Objective
To compare the efficacy of infliximab (IFX) versus adalimumab (ADA) as a first‐line biologic drug over 1 year of treatment in a large series of patients with refractory uveitis due to ...Behçet's disease (BD).
Methods
We conducted an open‐label multicenter study of IFX versus ADA for BD‐related uveitis refractory to conventional nonbiologic treatment. IFX or ADA was chosen as the first‐line biologic agent based on physician and patient agreement. Patients received 3–5 mg/kg intravenous IFX at 0, 2, and 6 weeks and every 4–8 weeks thereafter, or 40 mg subcutaneous ADA every other week without a loading dose. Ocular parameters were compared between the 2 groups.
Results
The study included 177 patients (316 affected eyes), of whom 103 received IFX and 74 received ADA. There were no significant baseline differences between treatment groups in main demographic features, previous therapy, or ocular sign severity. After 1 year of therapy, we observed an improvement in all ocular parameters in both groups. However, patients receiving ADA had significantly better outcomes in some parameters, including improvement in anterior chamber inflammation (92.31% versus 78.18% for IFX; P = 0.06), improvement in vitritis (93.33% versus 78.95% for IFX; P = 0.04), and best‐corrected visual acuity (mean ± SD 0.81 ± 0.26 versus 0.67 ± 0.34 for IFX; P = 0.001). A nonsignificant difference was seen for macular thickness (mean ± SD 250.62 ± 36.85 for ADA versus 264.89 ± 59.74 for IFX; P = 0.15), and improvement in retinal vasculitis was similar between the 2 groups (95% for ADA versus 97% for IFX; P = 0.28). The drug retention rate was higher in the ADA group (95.24% versus 84.95% for IFX; P = 0.042).
Conclusion
Although both IFX and ADA are efficacious in refractory BD‐related uveitis, ADA appears to be associated with better outcomes than IFX after 1 year of follow‐up.
The G protein-coupled receptors form the most abundant family of membrane proteins and are crucial physiologic players in the homeostatic equilibrium, which we define as health. They also participate ...in the pathogenesis of many diseases and are frequent targets of therapeutic intervention. Considering their importance, it is not surprising that different mechanisms regulate their function, including desensitization, resensitization, internalization, recycling to the plasma membrane, and degradation. These processes are modulated in a highly coordinated and specific way by protein kinases and phosphatases, ubiquitin ligases, protein adaptors, interaction with multifunctional complexes, molecular motors, phospholipid metabolism, and membrane distribution. This review describes significant advances in the study of the regulation of these receptors by phosphorylation and endosomal traffic (where signaling can take place); we revisited the bar code hypothesis and include two additional observations: 1) that different phosphorylation patterns seem to be associated with internalization and endosome sorting for recycling or degradation, and 2) that, surprisingly, phosphorylation of some G protein-coupled receptors appears to be required for proper receptor insertion into the plasma membrane. SIGNIFICANCE STATEMENT: G protein-coupled receptor phosphorylation is an early event in desensitization/signaling switching, endosomal traffic, and internalization. These events seem crucial for receptor responsiveness, cellular localization, and fate (recycling/degradation) with important pharmacological/therapeutic implications. Phosphorylation sites vary depending on the cells in which they are expressed and on the stimulus that leads to such covalent modification. Surprisingly, evidence suggests that phosphorylation also seems to be required for proper insertion into the plasma membrane for some receptors.
Abstract Objective The purpose of this study was to evaluate interrater reliability in the diagnosis of myofascial trigger points (MTrPs) in the tibialis anterior, peroneus brevis, and extensor ...digitorum longus muscles. Methods A reliability research study was performed. Three physical therapists with clinical experience in myofascial pain functioned as raters and randomly and bilaterally evaluated the ankles of 40 subjects in the Madrid public health care system. The absence or presence of MTrPs, nodules in taut bands, patterns of referred pain, local twitch response (LTR), and jump-sign were evaluated. Results We calculated the pairwise interrater agreement and κ-value concordance of the presence or absence of trigger points (55%-85%; κ = 0.12-0.60), palpable nodules in taut bands (63%-90%; κ = 0.24-0.60), referred pain (63%-85%; κ = 0.20-0.54), and jump sign (62%-89%; κ = 0.15-0.72) in the 3 studied muscles. The LTR could only be evaluated in the tibialis anterior (43%-70%; κ = 0.05-0.21), and evaluation was not possible for the other muscles. Conclusions Three blinded raters were able to reach acceptable pairwise interrater agreement (percentage of agreement value ≥70%) for the presence or absence of MTrPs and LTR in the tibialis anterior, as well as for nodules in taut bands, referred pain, and the jump sign for the extensor digitorum longus. The peroneus brevis showed a wide percentage of agreement value, ranging from 31% to 82%. The results of this study showed that expert raters can agree, with slight-to-moderate concordance, with regard to the clinical testing of muscle trigger points by direct palpation of the 3 muscles studied: the tibialis anterior, the extensor digitorum longus, and the peroneus brevis. Interrater reliability seems to be muscle dependent, especially with regard to the depth of the muscle.
Abstract Objective The purpose of this study was to quantify the cross-sectional area (CSA) of the peroneus brevis, the peroneus longus, and connective tissue; to compare these measures in ...participants with and without lateral ankle sprains (LAS); and to determine the intraexaminer reliability of the protocol used to acquire these measures. Methods A cross-sectional case-control study was undertaken. B-mode ultrasound imaging was performed to measure the resting CSA and circular perimeter of the muscles and connective tissue and the total area and ratio between the CSA of the peroneus longus and the peroneus brevis. The imaging was performed for 56 feet, 28 with LAS and 28 without LAS (the mean numbers ± SD of total LAS, grade-I LAS and grade-II LAS were 4.1 ± 3.6, 2.71 ± 3.2, and 1.39 ± 0.9, respectively). A univariate correlation analysis using Pearson ( r ) and the Kendall tau_b (τB ) coefficients was performed to evaluate the ultrasound imaging measurements (α = 0.05). Results Statistically significant differences ( P < .05) were observed between the 2 groups, with a moderate negative correlation for the circular perimeter of the peroneus longus ( P = .001; r = −0.444) and a weak association for the CSA of the peroneus longus ( P = .002; τB = − 0.349), the ratio between the CSA of the peroneus longus and the peroneus brevis ( P = .008; τB = −0.293), and the circular perimeter of connective tissue ( P = .013; τB = −0.277). Conclusions The peroneus longus CSA is reduced in participants with LAS compared with that in participants without LAS. The intraexaminer reliability of the ultrasonography protocol was excellent when quantifying the peroneus brevis and the peroneus longus muscle tissues and acceptable when quantifying connective tissue.
High demand of flexor hallucis longus (FHL) in the positions of extreme flexion of the ankle and toes is required in the dance. The aim was to investigate the effects of single-shot of ...ultrasound-guided percutaneous neuromodulation (PNM) vs. single-shot of transcutaneous electrical nerve stimulation (TENS) in performance of the FHL muscle in professional dancers.
Thirty-two female healthy dancers were divided into two groups: TENS group and PNM group. The stimulation interventions consisted in the application of a square wave biphasic electrical current for a total of 1.5 mins. Range of motion (ROM) of first metatarsophalangeal joint, balance test, and unilateral heel raise fatigue test were performed in dominance limb.
There were no differences between both groups in the baseline measurements. Compared to their baseline values, the TENS group statistically improved balance (p < 0.01, d = 0.6), ROM (p < 0.001, d = 0.3), and endurance (p = 0.04, d = 0.5). The PNM group only statistically improved balance and endurance (p < 0.001), with a large effect size for both test (d = 0.8 and d = 2.24, respectively). After interventions, there were no significant differences between TENS and PNM groups for all variables. However, PNM was qualitatively more effective because the percentage change in mean was greater and effect size was large for the balance test and endurance test.
Simple single-shot procedure with percutaneous or TENS provided immediate performance improvement of FHL muscle in dancers, being PNM the more effective intervention.
The objectives of this study were to evaluate the effects of an ultrasound (US)-guided percutaneous neuromodulation (PNM) intervention on the sciatic nerve, regarding pain, hip range of motion (ROM), ...balance, and functionality in patients with chronic low back pain (LBP); and to determine the optimal anatomical location of sciatic nerve stimulation to obtain therapeutic benefits in such patients.
Thirty patients with chronic LBP were recruited and divided randomly into three groups. All patients received a single percutaneous electrical stimulation intervention on the sciatic nerve, with a different anatomical application location for each group (proximal, middle, and distal). Level of pain, hip passive ROM, dynamic balance, and Oswestry disability index were analyzed. All variables were calculated before the intervention, immediately postintervention, 48 hours and one week after the intervention, except the LBP questionnaire (before, and 48 hours and one week after the intervention).
All interventions decreased the level of pain and increased the ROM, balance, and functionality. Besides, these therapeutic effects were maintained during one week, regardless of the anatomical location of application.
The choice of an anatomical location of application of the US-guided PNM on the sciatic nerve by the physiotherapist does not influence the improvement of pain, ROM, balance, and function in patients with chronic LBP.
A cross-sectional area (CSA) and thickness reduction of the abductor hallucis (AbH) is shown in subjects with hallux valgus (HV). To date, other soft-tissue structures have not been researched in ...relation with HV. The aim of this study was to compare the CSA and thickness of the intrinsic plantar muscles and fascia (PF) between feet with and without HV. Therefore, a cross-sectional and case-control study was performed using B-mode with an iU22 Philips ultrasound system and a 5 to 17-MHz transducer. The CSA and thickness were measured for the AbH, flexor digitorum brevis (FDB) and flexor hallucis brevis (FHB), and also the thickness for the anterior, middle, and posterior PF portions. A convenience sample of 40 feet, 20 with HV and 20 without HV, was recruited from a clinical and research center. A multivariate regression analysis using linear regression was performed to evaluate the ultrasound imaging measurements (α = 0.05). Consequently, statistically significant differences were observed between the groups (P < 0.05) for the AbH and FHB thickness, and CSA reduction, and also the plantar fascia thickness increase in favor of the HV group. On the contrary, the FDB thickness and CSA did not show statistically significant differences (P ≥ 0.05). In conclusion, the CSA and thickness of the AbH and FHB intrinsic plantar muscles are reduced, whereas the thickness of the anterior, middle, and posterior PF portions are increased, in subjects with HV compared with those without HV.
According to the World Health Organization, the incidence of malignant neoplasms and endocrine, blood, and immune disorders will increase in the upcoming decades along with the demand of affordable ...treatments. In response to this need, the development of biosimilar drugs is increasing worldwide. The approval of biosimilars relies on the compliance with international guidelines, starting with the demonstration of similarity in their physicochemical and functional properties against the reference product. Subsequent clinical studies are performed to demonstrate similar pharmacological behavior and to diminish the uncertainty related to their safety and efficacy. Herein we present a comparability exercise between a biosimilar trastuzumab and its reference product, by using a hierarchical strategy with an orthogonal approach, to assess the physicochemical and biological attributes with potential impact on its pharmacokinetics, pharmacodynamics, and immunogenicity. Our results showed that the high degree of similarity in the physicochemical attributes of the biosimilar trastuzumab with respect to the reference product resulted in comparable biological activity, demonstrating that a controlled process is able to provide consistently the expected product. These results also constitute the basis for the design of subsequent delimited pharmacological studies, as they diminish the uncertainty of exhibiting different profiles.
Abstract
Foot problems are highly prevalent conditions, being a frequent reason for medical and podiatric consultation. The aim of this study was to compare the differences of quality of life (QoL) ...related to foot health in people with and without the presence of foot problems. A case–control study was carried out in an outpatient centre, where a clinician recorded data related to sociodemographic and clinical characteristics. In addition, self-reported data on foot health-related quality of life were recorded using the Spanish version of the Foot Health Status Questionnaire. The sample consisted of 498 participants (249 cases and 249 controls), with a median age of 30 years and an interquartile range of 23 years. The differences between the groups were statistically significant for gender, age, footwear, general health, foot health, and physical activity. Cases showed lower scores for the domain of footwear, physical activity and vitality compared to controls. Foot pathologies have a negative impact on quality of life related to foot health, and the domains of footwear, general health and physical activity seem to be the factors that are associated with the presence of alterations and foot deformities.
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