Πέμπτη 19 Νοεμβρίου 2020

Joint hemorrhage accelerates cartilage degeneration in a rat immobilized knee model

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Abstract

Background

Joint hemorrhage is caused by trauma, ligament reconstruction surgery, and bleeding disorders such as hemophilia. Recurrence of hemorrhage in the joint space induces hemosiderotic synovitis and oxidative stress, resulting in both articular cartilage degeneration and arthropathy. Joint immobilization is a common treatment option for articular fractures accompanied by joint hemorrhage. Although joint hemorrhage has negative effects on the articular cartilage, there is no consensus on whether a reduction in joint hemorrhage would effectively prevent articular cartilage degeneration. The purpose of this study was to investigate the effect of joint hemorrhage combined with joint immobilization on articular cartilage degeneration in a rat immobilized knee model.

Methods

The knee joints of adult male rats were immobilized at the flexion using an internal fixator from 3 days to 8 weeks. The rats were randomly divided into the following groups: immobilized blood injection (Im-B) and immobilized-normal saline injection (Im-NS) groups. The cartilage was evaluated in two areas (contact and non-contact areas). The cartilage was used to assess chondrocyte count, Modified Mankin score, and cartilage thickness. The total RNA was extracted from the cartilage in both areas, and the expression of metalloproteinase (MMP)-8, MMP-13, interleukin (IL)-1β, and tumor necrosis factor (TNF)-α was measured by quantitative real-time polymerase chain reaction.

Results

The number of chondrocytes in the Im-B group significantly decreased in both areas, compared with that in the Im-NS group. Modified Mankin score from 4 to 8 weeks of the Im-B group was significantly higher than that of the Im-NS group only in the contact area. The expression of MMP-8 and MMP-13 from 2 to 4 weeks and TNF-α from 2 to 8 weeks significantly increased in the Im-B group compared with those in the Im-NS group, but there was no significant difference in IL-1β expression.

Conclusions

The results showed that joint hemorrhage exacerbated immobilization-induced articular cartilage degeneration. Drainage of a joint hemorrhage or avoidance of loading may help prevent cartilage degeneration during joint immobilization with a hemorrhage.

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Abuse and Misuse of Pregabalin and Gabapentin: A Systematic Review Update

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Abstract

Background

A 2017 systematic review (SR) identified 59 studies examining gabapentinoid (pregabalin and gabapentin) misuse/abuse. Evidence of gabapentinoid misuse/abuse has since grown substantially.

Objective

Update previous SR and describe new insights regarding gabapentinoid abuse.

Methods

A SR of PubMed was conducted to identify studies published from 7/29/2016–8/31/2020. Four searches were performed using the following terms: "gabapentin [MeSH] OR pregabalin [MeSH] OR gabapentinoid" AND one of the following substance misuse/abuse-related terms: "substance-related disorders [MeSH]", "overdose", "abuse", or "misuse". Clinicaltrials.gov and the Cochrane Library database were searched to identify ongoing studies or similar SRs. Reference lists of included studies were reviewed to identify additional literature. All studies with novel data related to pregabalin and/or gabapentin abuse, misuse, or overdose conducted during the study period were included. Articles not written in English, review articles, and animal studies were excluded.

Results

Fifty-five studies were included (29 [52.7%] from North America, 17 [30.9%] Europe, 6 [10.9%] Asia, and 3 [5.5%] Australia). Forty-six observational studies and 10 case reports/series were included (one manuscript included both). Twenty (36.4%) studied gabapentin only, 18 (32.7%) pregabalin only, and 17 (30.9%) both pregabalin/gabapentin. These studies corroborate findings from the previous SR that gabapentinoids are increasingly abused or misused to self-medicate, that gabapentinoids can produce desirable effects alone but are often used concomitantly with other drugs, and that opioid use disorder is the greatest risk factor for gabapentinoid abuse. While the original SR identified the largest studies having been published in Europe, this review identified several more generalisable US studies that have subsequently been conducted. The most concerning finding was increased evidence of associated patient harm, including increased hospital utilisation and opioid -related overdose mortality risk.

Conclusion

Evidence suggests that gabapentinoid misuse/abuse represents a growing trend that is causing significant patient harm. Prescribers should exercise appropriate caution with use in high-risk populations and monitor for signs of misuse or abuse.

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The ground state of the lithium atom in dense plasmas using variational Monte Carlo method

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Abstract

In this paper, the variational quantum Monte Carlo method is applied to investigate the ground state of the lithium atom. Moreover, the energy eigenvalues of the lithium atom in dense plasma are also investigated by using the Debye–Hückel model and the exponential cosine screened Coulomb potential model. The calculations are carried out by using trial wave functions in the form of the Slater determinant wave function multiplied by a correlation function due to the interaction between the electrons. Three types of correlation functions are used—with two, three and four variational parameters—one of which satisfies the well-known cusp conditions. Interesting results are obtained in comparison with results obtained by using other trial wave functions.

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Validation of novel patient-centred juvenile idiopathic arthritis-specific patient-reported outcome and experience measures (PROMs/PREMs)

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Abstract

Background

Measuring the outcomes that matter to children and young people (CYP) with juvenile idiopathic arthritis (JIA), is a necessary precursor to patient-centred improvements in quality of clinical care. We present a two-centre validation of novel JIA patient-reported outcome and experience measures (PROM and PREM) developed as part of the CAPTURE-JIA project.

Methods

CYP with JIA were recruited from paediatric rheumatology clinics, completing the CAPTURE-JIA PROM and PREM, CHAQ and CHU 9D. A subset participated in face-to-face interviews and completed the PROM/PREM 1 week later. The OMERACT filter was applied and the three domains of validation assessed. Truth assessments included cognitive interviewing, sensitivity analysis and Spearman's correlations. Discrimination assessments included specificity and reliability testing. Feasibility was assessed using time to form completion and proportion of missing data.

Results

Eighty-two CYP and their families were recruited; ten cognitive interviews and fifteen PROM/PREM test/retests were conducted. Truth: CYP and parents understood the PROM/PREM and felt important areas were covered. PROM criteria had high sensitivities (> 70%) against similar items on the CHU 9D, with the exception of fatigue (58%). Correlations between similar PROM and CHU 9D criteria were moderate to very strong (coefficients 0.40–0.82.) Discrimination: high specificities (> 70%) on corresponding PROM and CHU 9D domains. Feasibility: median completion times for PROM 60 s (IQR 38–75) and PREM 49 s (IQR 30–60) respectively.

Conclusion

The CAPTURE-JIA PROM and PREM are valid and feasible in UK paediatric rheumatology clinics. Embedding routine collection into clinical care would be a major step towards improving quality of care.

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EndoPil: A Magnetically Actuated Swallowable Capsule for Weight Management: Development and Trials

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Abstract

Intragastric balloons (IGBs), by occupying the stomach space and prolonging satiety, is a promising method to treat obesity and consequently improves its associated comorbidities, e.g. coronary heart disease, diabetes, and cancer. However, existing IGBs are often tethered with tubes for gas or liquid delivery or require endoscopic assistance for device delivery or removal, which are usually uncomfortable, costly, and may cause complications. This paper presents a novel tetherless, magnetically actuated capsule (EndoPil) which can deploy an IGB inside the stomach after being swallowed and being activated by an external magnet. The external magnet attracts a small magnet inside the EndoPil to open a valve, triggering the chemical reaction of citric acid and potassium bicarbonate to produce carbon dioxide gas, which inflates a biocompatible balloon (around 120 mL). A prototype, 13 mm in diameter and 35 mm in length, was developed. Simulations and bench-top tests wer e conducted to test the force capability of the magnetic actuation mechanism, the required force to activate the valve, and the repeatability of balloon inflation. Experiments on animal and human were successfully conducted to demonstrate the safety and feasibility of inflating a balloon inside the stomach by an external magnet.

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Neck Muscle and Head/Neck Kinematic Responses While Bracing Against the Steering Wheel During Front and Rear Impacts

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Abstract

Drivers often react to an impending collision by bracing against the steering wheel. The goal of the present study was to quantify the effect of bracing on neck muscle activity and head/torso kinematics during low-speed front and rear impacts. Eleven seated subjects (3F, 8 M) experienced multiple sled impacts (Δv = 0.77 m/s; apeak = 19.9 m/s2, Δt = 65.5 ms) with their hands on the steering wheel in two conditions: relaxed and braced against the steering wheel. Electromyographic activity in eight neck muscles (sternohyoid, sternocleidomastoid, splenius capitis, semispinalis capitis, semispinalis cervicis, multifidus, levator scapulae, and trapezius) was recorded unilaterally with indwelling electrodes and normalized by maximum voluntary contraction (MVC) levels. Head and torso kinematics (linear acceleration, angular velocity, angular rotation, and retraction) were measured with sen sors and motion tracking. Muscle and kinematic variables were compared between the relaxed and braced conditions using linear mixed models. We found that pre-impact bracing generated only small increases in the pre-impact muscle activity (< 5% MVC) when compared to the relaxed condition. Pre-impact bracing did not increase peak neck muscle responses during the impacts; instead it reduced peak trapezius and multifidus muscle activity by about half during front impacts. Bracing led to widespread changes in the peak amplitude and timing of the torso and head kinematics that were not consistent with a simple stiffening of the head/neck/torso system. Instead pre-impact bracing served to couple the torso more rigidly to the seat while not necessarily coupling the head more rigidly to the torso.

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Efficacy of Liraglutide to Prevent Weight Regain After Retrieval of an Adjustable Intra-gastric Balloon—a Case-Matched Study

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Abstract

Purpose

Weight regain after balloon retrieval is a concern with all intra-gastric balloons (IGBs). The aim of this study was to evaluate the efficacy of liraglutide, a glucagon-like peptide-1 (GLP-1) agonist, to prevent weight regain following IGB retrieval.

Materials and Methods

This was a case-matched study of patients undergoing Spatz3 adjustable IGB (Spatz FGIA, Inc. NY, USA) at three outpatient clinics in Brazil between November 2015 and January 2019. Seventy-seven patients that opted to take liraglutide following IGB retrieval (IGB-L) were matched 1:1 to 198 patients that declined the medication—IGB-Alone (IGB-A). Propensity score adjustment was performed at the time of balloon retrieval on factors known to influence the choice of liraglutide. Weight and percent body fat (%BF) was measured at baseline and 9 months after IGB retrieval. % BF is defined as the total mass of fat divided by total body mass, multiplied by 100. The primary outcome was weight regain, and the secondary outcome was change in %BF 9 months after IGB retrieval.

Results

Propensity score matching yielded 53 matched pairs. Weight regain to the starting point was not observed in either group. There was significantly less weight regain in IGB-L compared to IGB-A, − 1.15 ± 0.94 kg versus − 0.66 ± 0.99 kg (p = 0.010) 9 months after balloon retrieval. Additionally, %BF decline in IGB-L was superior to IGB-A − 10.83 ± 1.50 versus − 7.94 ± 2.02 (p < 0.01). There was no difference in weight regain or decline in %BF based on liraglutide dose.

Conclusion

Liraglutide has an additive benefit with respect to efficacy and a reduction in body fat when commenced after IGB retrieval. Future randomized control studies will be needed to determine the optimal dose and duration of liraglutide to achieve superior outcomes.

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