ObjectiveTo estimate the cost-effectiveness of adalimumab plus methotrexate (MTX) versus MTX monotherapy in early, aggressive rheumatoid arthritis (RA) when explicitly modelling short-term (reversible) and long-term (irreversible, ie, joint damage) disease activity and physical function.MethodsA microsimulation model was developed to unify, in a single cost-effectiveness model, measures of reversible and irreversible disease activity and physical function based on data from the PREMIER trial. Short term, reversible disease activity was modelled using DAS28 variables, including swollen joint counts, tender joint counts, C reactive protein concentration and pain. The DAS28 variables were then used in a logistic regression to predict short-term American College of Rheumatology (ACR) responses, which informed treatment continuation and switches. Long term, irreversible, radiographically documented joint damage was modelled using modified Total Sharp Score (mTSS). The model then linked both short-term disease activity and mTSS to the Health Assessment Questionnaire score, which was used to calculate direct and indirect costs, and quality adjusted life-years (QALYs).ResultsWhen both reversible and irreversible effects of therapy were included, combination therapy was estimated to produce 6-month 50% ACR responses in 75% of patients versus 54% in MTX monotherapy. Compared to MTX monotherapy, combination therapy resulted in 2.68 and 3.04 discounted life years and QALYs gained, respectively. Combination therapy also resulted in a net increase in direct costs of £106 207 for a resulting incremental cost/QALY gain of £32 425. When indirect costs were included in the analysis, the ICER (incremental cost-effectiveness ratio) decreased to £27 238. Disregarding irreversible effects increased the incremental cost-effectiveness ratio to £78 809 (when only direct costs were included).ConclusionsStarting with adalimumab plus MTX combination therapy in early, aggressive RA is cost-effective when irreversible damage is adequately considered.

Context: Limited dorsiflexion (DF) range of motion (ROM) is commonly observed in both the athletic and general populations and is a predisposing factor for lower extremity injury. Graston Technique® (GT) is a form of instrument-assisted soft tissue mobilization (IASTM), used commonly to increase ROM. Evidence of the long-term effects of GT on ROM is lacking, particularly comparing the full GT protocol versus IASTM alone. Objective: To evaluate the effectiveness of 6 sessions of the GT or IASTM compared with a control (CON) group for increasing closed-chain DF ROM. Design: Cohort design with randomization. Setting: Athletic training clinic. Patients or Other Participants: A total of 23 physically active participants (37 limbs) with <34° of DF. Participants’ limbs were randomly allocated to the GT, IASTM, or CON group. Intervention: Participants’ closed-chain DF ROM (standing and kneeling) were assessed at baseline and 24–48 hours following their sixth treatment. Participants in the CON group were measured at baseline and 3 weeks later. The intervention groups received 6 treatments during a 3-week period, whereas the CON group received no treatment. The GT group received a warm-up, instrument application, stretching, and strengthening of the triceps surae. The IASTM group received a warm-up and instrument application. Main Outcome Measures: Closed-chain DF was assessed with a digital inclinometer in standing and kneeling. Results: A significant difference between groups was found in the standing position (P = .03) but not in kneeling (P = .15). Post hoc testing showed significant improvements in DF in standing following the GT compared with the control (P = .02). Conclusions: The GT significantly increases ankle DF following 6 treatments in participants with DF ROM deficits; however, no differences were found between GT and IASTM. The GT may be an effective intervention for clinicians to consider when treating patients with DF deficits.

Aggresome formation, a cellular response to misfolded protein aggregates, is linked to cancer and neurodegenerative disorders. Previously we showed that Gag-v-ErbA (v-ErbA), a retroviral variant of the thyroid hormone receptor (TRα1), accumulates in and sequesters TRα1 into cytoplasmic foci. Here, we show that foci represent v-ErbA targeting to aggresomes. v-ErbA colocalizes with aggresomal markers, proteasomes, hsp70, HDAC6, and mitochondria. Foci have hallmark characteristics of aggresomes: formation is microtubule-dependent, accelerated by proteasome inhibitors, and they disrupt intermediate filaments. Proteasome-mediated degradation is critical for clearance of v-ErbA and T3-dependent TRα1 clearance. Our studies highlight v-ErbA’s complex mode of action: the oncoprotein is highly mobile and trafficks between the nucleus, cytoplasm, and aggresome, carrying out distinct activities within each compartment. Dynamic trafficking to aggresomes contributes to the dominant negative activity of v-ErbA and may be enhanced by the viral Gag sequence. These studies provide insight into novel modes of oncogenesis across multiple cellular compartments.

Context Dry cupping therapy is a noninvasive treatment commonly used to reduce pain and promote the healing process in various populations, including those with nonspecific neck pain; however, no data are available to support most of this method's true physiological benefits. Objective To determine if dry cupping therapy decreased pain and increased subcutaneous blood flow compared with sham cupping and control conditions. Design Controlled laboratory study. Setting Laboratory. Patients or Other Participants A total of 32 participants (age = 22.5 ± 2.8 years, height = 173.3 ± 10.1 cm, mass = 76.6 ± 18.7 kg) with self-reported nonspecific neck pain. Intervention(s) We used dry cupping and sham cupping interventions and a control condition. For the dry cupping intervention, 1 stationary cup was placed directly over the most painful area for 8 minutes. The sham cupping intervention followed the same procedures as the dry cupping intervention except a sham cup was applied. For the control condition, participants received no treatment. Main Outcome Measure(s) Subjective pain intensity (visual analog scale); pain-pressure threshold; subcutaneous hemodynamics, including superficial and deep oxygenated, deoxygenated, and total hemoglobin levels; and tissue saturation index;. Results We observed differences in the visual analog scale score and the superficial and deep oxygenated and total hemoglobin levels (P values ≤ .002) immediately postintervention compared with baseline. Post hoc tests revealed that the dry cupping group had less pain than the sham cupping and control groups and higher superficial and deep oxygenated and total hemoglobin levels (P values ≤ .008). No differences were found between baseline and 24 hours postintervention. Conclusions A single session of dry cupping therapy may be an effective short-term treatment method for immediately reducing pain and increasing oxygenated and total hemoglobin levels in patients with nonspecific neck pain.