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Background: Knee osteoarthritis (KOA) affects 22.9% of individuals over the age of 40 and causes significant pain and disability. Pain is the most prevalent and troublesome symptom of KOA leading patients to seek medical interventions for relief. Knee osteoarthritis pain has both peripheral and central mechanisms that vary by individual. Non-pharmacological pain management strategies such as walking is the first step in reducing KOA pain. However, initiation of a walking regime can induce knee pain for some and the mechanism by which habitual walking reduces KOA pain is unclear. Purpose: The purpose of this study was to use a discovery proteomics approach and quantitative sensory testing (QST) to determine the molecular changes that occur after habitual walking and their relationship to pain sensitivity. Research Design and Study Sample: We conducted a pre-test/post-test study using QST to measure neurophysiological parameters at the knee and contralateral forearm and examined platelet protein signatures before and after 6 weeks of walking 3 days per week for 30 minutes among six adults with KOA and six healthy controls. Results: Knee pain sensitivity did not change significantly after 6 weeks of walking among either KOA or healthy participants. However, forearm pressure pain sensitivity decreased for both groups after walking, indicating reduction in central pain pathways. Protein signatures showed downregulation of immune and inflammatory, pathways among KOA participants after walking which were upregulated in healthy controls. Conclusion: These differences may contribute differences in centralized pain thresholds seen between KOA and healthy participants.

BACKGROUND: Knee osteoarthritis affects nearly 30% of adults aged 60 or older and causes significant pain and disability. Walking is considered a “gold standard” treatment option for reducing knee osteoarthritis pain and maintaining joint mobility but does not reduce pain for all adults with knee osteoarthritis pain and may induce pain—particularly when starting a walking routine. The mechanism by which walking is helpful for knee osteoarthritis pain is unclear. Quantitative sensory testing has revealed that knee osteoarthritis pain has both peripheral and central components, which vary by individual. OBJECTIVE: This study’s purpose was to better understand the mechanisms underlying the value of walking for knee pain. METHODS: We conducted a pretest/posttest study using quantitative sensory testing to measure neurophysiological parameters and examined systemic protein signatures. Adults with knee osteoarthritis and healthy controls underwent quantitative sensory testing and blood draw for platelet proteomics before and after a 30-min walk at 100 steps/minute. RESULTS: A single 30-min walk moderately increased pressure pain sensitivity at the affected knee among persons with knee osteoarthritis. Healthy adults showed no difference in pain sensitivity. Protein signatures among participants with knee osteoarthritis indicated changes in inflammatory and immune pathways, including the complement system and SAA1 protein that coincided with changes in pain with walking and differed from healthy participants. DISCUSSION: One goal of developing individualized interventions for knee osteoarthritis pain is to elucidate the mechanisms by which self-management interventions affect pain. The addition of therapies that target the complement system or SAA1 expression may improve the pain sensitivity after a moderate walk for adults with knee osteoarthritis.

Retrospective data showed that when we administered ledipasvir/sofosbuvir (LDV/SOF) to patients with hepatitis B and C coinfection, there was a modest reduction in hepatitis B surface antigen (HBsAg). Therefore, we hypothesize that similar HBsAg reduction can be seen in hepatitis B virus (HBV) monoinfected subjects. Primary and secondary efficacy endpoints are the decline in HBsAg and HBV DNA at Week 12 from baseline, respectively. We conducted an open-label Phase 2 pilot study to evaluate the safety, tolerability, and antiviral activity of LDV and/or SOF for HBV. Eligible subjects were either suppressed on antivirals (Group B) or inactive chronic HBV (Group A, C, D). Group A and B received LDV/SOF. Group C and D received SOF 400 mg and LDV 90 mg, respectively. All subjects completed the study, and all related adverse events (AEs) were mild. No discontinuations due to AEs or hepatitis flare occurred. At Week 12, HBsAg decline (log