Do etoricoxib and indometacin have similar effects and safety for gouty arthritis? A meta-analysis of randomized controlled trials

Tzu-Min Lin,1,2,* Jia-En Chi,1,3,* Chi-Ching Chang,2,4,* Yi-No Kang1 1Center for Evidence-Based Medicine, Department of Education, Taipei Medical University Hospital, Taipei, Taiwan, Republic of China; 2Division of Rheumatology, Immunology and Allergy, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan, Republic of China; 3School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, Republic of China; 4Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, Republic of China *These authors contributed equally to this work Background: Gout, a common medical condition that causes pain, can be treated by painkillers and anti-inflammatories. Indometacin and etoricoxib are two such drugs. However, no synthesized evidence exists comparing etoricoxib with indometacin in treating patients with gout.Methods: We searched PubMed, Embase, Ovid MEDLINE, Web of Science, ScienceDirect, and the Cochrane Library without restrictions on language or publication date for potential randomized clinical trials comparing etoricoxib with indometacin for gout. The meta-analysis was conducted using a random-effects model.Results: Search results yielded 313 references from six electronic databases, four of which met the eligibility criteria. These four were randomized clinical trials, and they involved a total of 609 patients with gouty arthritis. No significant differences were observed in pain score change, tenderness, or swelling between etoricoxib and indometacin; the mean differences were −0.05 (95% CI, −0.21 to 0.10), −0.06 (95% CI, −0.18 to 0.05), and −0.04 (95% CI, −0.17 to 0.09). However, the pooled data revealed that significantly fewer overall adverse events occurred in the etoricoxib group (n=105, 33.5%) than in the indometacin group (n=130, 44.1%) and the risk ratio was 0.77 (95% CI, 0.62–0.94).Conclusion: Our meta-analysis revealed that etoricoxib and indometacin have similar effects on pain relief. However, etoricoxib has a significantly lower risk of adverse events than does indometacin, especially digestive system-related adverse events. Keywords: gout, etoricoxib, indometacin&nbsp

Occupational noise exposure is associated with hypertension in China: Results from project ELEFANT

OBJECTIVES: We investigated the association between occupational noise exposure and the risk of elevated blood pressure and hypertension by stage in young adults. METHODS: We utilized 124,286 young adults (18-40 years) from the Project ELEFANT study. We categorized occupational noise exposure as high (75 dBA noise exposure for more than 4 hours per day) or low, and measured blood pressure (mmHg) and categorized participants by hypertension stage (normal, elevated, Stage 1, Stage 2). We applied adjusted logistic regression models to identify associations with hypertension risk, and we further examined the noise-BMI, noise-gender, and noise-residence interactions on hypertension risk in separate models. RESULTS: High occupational noise exposure was associated with increases in blood pressure among participants with elevated blood pressure (Estimate = 0.23, 95% CI: 1.09, 1.46, p = 0.0009), in Stage 1 hypertension (Estimate = 0.15, 95% CI: 1.06, 1.25, p = 0.0008), and in Stage 2 hypertension (Estimate = 0.41 95% CI: 1.31, 1.73, p<0.0001). Likewise, noise exposure-BMI interaction was consistently positively associated with increases in blood pressure in participants with elevated blood pressure (Estimate = 0.71, 95% CI: 1.55, 2.69, p<0.0001), in Stage 1 hypertension (Estimate = 0.78, 95% CI: 1.82, 2.61, p<0.0001), and in Stage 2 hypertension (Estimate = 2.06, 95% CI: 5.64, 10.81, p<0.0001). The noise exposure-male interaction showed higher risk for hypertension compared to the noise exposure-female interaction in participants with elevated blood pressure (Estimate = 1.24, 95% CI: 2.56, 4.71, p<0.0001), Stage 1 (Estimate = 1.67, 95% CI: 4.34, 6.42, p<0.0001) and Stage 2 hypertension (Estimate = 1.70, 95% CI: 3.86, 7.77, p<0.0001). Finally, we found that noise exposure-urban interaction was consistently associated with an increase in blood pressure in elevated blood pressure (Estimate = 0.32, 95% CI: 1.19, 1.62, p<0.0001) and in Stage 2 hypertension (Estimate = 0.44, 95% CI: 1.31, 1.80, p<0.0001)

On Justification, Idealization, and Discursive Purchase

Conceptions of acceptability-based moral or political justification take it that authoritative acceptability, widely conceived, constitutes, or contributes to, validity, or justification. There is no agreement as to what bar for authoritativeness such justification may employ. The paper engages the issue in relation to (i) the level of idealization that a bar for authoritativeness, ψ, imparts to a standard of acceptability-based justification, S, and (ii) the degree of discursive purchase of the discursive standing that S accords to people when it builds ψ. I argue that (i) and (ii) are interdependent: high idealization values entail low discursive purchase, while high degrees of purchase require low idealization values. I then distinguish between alethic conceptions of justification that prioritize ends that commit to high idealization values, and recognitive conceptions that favor high discursive purchase. On this basis, I argue for a moderately recognitivist constraint on idealization. To render the recognitive discursive minimum available to relevant people at the site of justification, S should set ψ low enough so that it is a genuine option for actual people to reject relevant views in ways that S recognizes as authoritative. (The Appendix applies this to a Forst-type view of reciprocity of reasons to draw out some limitations of this view.) [Draft available from author on request.

Teasing Apart the Impact of Illness and IQ on Functional Neuroimaging Findings in Schizophrenia

Schizophrenia is a major psychiatric disorder associated with cognitive impairment. Functional brain imaging (fMRI) studies of schizophrenia patients reveal a complex pattern of brain differences in the prefrontal cortex. Both decreased (hypofrontality) and increased (hyperfrontality) activity have been reported in patients – inconsistencies that this paper argues could be explained by differences in IQ between patients and healthy controls. This study demonstrates a novel method to tease apart IQ and schizophrenia effects on brain activity. Twelve schizophrenia patients were matched to twelve healthy controls matched to patients’ estimated (premorbid) IQ before their illness, and twelve healthy controls matched to patients’ measured current IQ. All participants performed an executive function event-related fMRI task. Schizophrenia patients’ mean behavioral scores fell numerically between those of both control groups, and did not differ significantly from either group. Two distinct patterns of brain activity were found that were consistent with an effect due to either IQ impairment or schizophrenia diagnosis. Schizophrenia patients’ relatively reduced activity in middle/superior frontal (BA6/BA8) regions was related to their schizophrenia diagnosis, whereas their relatively increased activity in inferior frontal (BA44/45) and left middle frontal (BA8/9) regionsrelated instead to their current IQ impairment. These findings indicate that some fMRI differences reported in schizophrenia patients are artefacts of IQ matching. After removing the IQ confounds, schizophrenia was associated with lateral frontal hypoactivations and medial frontal failure of deactivation. This paper proposes a method to address IQ matching-related issues when studying populations where their illness involves cognitive deterioration

Exploring the context of sedentary behaviour in older adults (what, where, why, when and with whom)

BACKGROUND: Older adults are the most sedentary segment of the population. Little information is available about the context of sedentary behaviour to inform guidelines and intervention. There is a dearth of information about when, where to intervene and which specific behaviours intervention should target. The aim of this exploratory study was to obtain objective information about what older adults do when sedentary, where and when they are sedentary and in what social context. METHODS: The study was a cross-sectional data collection. Older adults (Mean age = 73.25, SD ± 5.48, median = 72, IQR = 11) volunteers wore activPAL monitors and a Vicon Revue timelapse camera between 1 and 7 days. Periods of sedentary behaviour were identified using the activPAL and the context extracted from the pictures taken during these periods. Analysis of context was conducted using the Sedentary Behaviour International Taxonomy classification system. RESULTS: In total, 52 days from 36 participants were available for analysis. Participants spent 70.1 % of sedentary time at home, 56.9 % of sedentary time on their own and 46.8 % occurred in the afternoon. Seated social activities were infrequent (6.9 % of sedentary bouts) but prolonged (18 % of sedentary time). Participants appeared to frequently have vacant sitting time (41 % of non-screen sedentary time) and screen sitting was prevalent (36 % of total sedentary time). CONCLUSIONS: This study provides valuable information to inform future interventions to reduce sedentary behaviour. Interventions should consider targeting the home environment and focus on the afternoon sitting time, though this needs confirmation in a larger study. Tackling social isolation may also be a target to reduce sedentary time

Cysteine oxidation targets peroxiredoxins 1 and 2 for exosomal release through a novel mechanism of redox-dependent secretion

Non-classical protein secretion is of major importance as a number of cytokines and inflammatory mediators are secreted via this route. Current evidence indicates that there are several mechanistically distinct methods of non-classical secretion. We have recently shown that peroxiredoxin (Prdx) 1 and Prdx2 are released by various cells upon exposure to inflammatory stimuli such as LPS or TNF-α. The released Prdx then acts to induce production of inflammatory cytokines. However, Prdx1 and 2 do not have signal peptides and therefore must be secreted by alternative mechanisms as has been postulated for the inflammatory mediators IL-1β and HMGB1. We show here that circulating Prdx1 and 2 are present exclusively as disulphide-linked homodimers. Inflammatory stimuli also induce in vitro release of Prdx1 and 2 as disulfide-linked homodimers. Mutation of cysteines Cys51 or Cys172 (but not Cys70) in Prdx2, and Cys52 or Cys173 (but not Cys71 or Cys83) in Prdx1 prevented dimer formation and this was associated with inhibition of their TNF-α-induced release. Thus, the presence and oxidation of key cysteine residues in these proteins are a prerequisite for their secretion in response to TNF-α and this release can be induced with an oxidant. In contrast, the secretion of the nuclear-associated danger signal HMGB1 is independent of cysteine oxidation, as shown by experiments with a cysteine-free HMGB1 mutant. Release of Prdx1 and 2 is not prevented by inhibitors of the classical secretory pathway; instead, both Prdx1 and 2 are released in exosomes from both HEK cells and monocytic cells. Serum Prdx1 and 2 are also associated with the exosomes. These results describe a novel pathway of protein secretion mediated by cysteine oxidation that underlines the importance of redox-dependent signalling mechanisms in inflammation

Constraining parameter space in type-II two-Higgs doublet model in light of a 126 GeV Higgs boson

We explore the implications of a 126 GeV Higgs boson indicated by the recent LHC results for two-Higgs doublet model (2HDM). Identifying the 126 GeV Higgs boson as either the lighter or heavier of CP even neutral Higgs bosons in 2HDM, we examine how the masses of Higgs fields and mixing parameters can be constrained by the theoretical conditions and experimental constraints. The theoretical conditions taken into account are the vacuum stability, perturbativity and unitarity required to be satisfied up to a cut-off scale. We also show how bounds on the masses of Higgs bosons and mixing parameters depend on the cut-off scale. In addition, we investigate whether the allowed regions of parameter space can accommodate particularly the enhanced di-photon signals, ZZ* and WW* decay modes of the Higgs boson, and examine the prediction of the signal strength of Z{\gamma} decay mode for the allowed regions of the parameter space.Comment: To be published in JHEP, 20 pages, 11 figures, Figures and results are updated for the recent LHC result