The purpose of this study was to evaluate the effect of various non-operative modalities of treatment (transcutaneous electrical nerve stimulation (TENS); neuromuscular electrical stimulation (NMES); insoles and bracing) on the pain of osteoarthritis (OA) of the knee. We conducted a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify the therapeutic options which are commonly adopted for the management of osteoarthritis (OA) of the knee. The outcome measurement tools used in the different studies were the visual analogue scale and The Western Ontario and McMaster Universities Arthritis Index pain index: all pain scores were converted to a 100-point scale. A total of 30 studies met our inclusion criteria: 13 on insoles, seven on TENS, six on NMES, and four on bracing. The standardised mean difference (SMD) in pain after treatment with TENS was 1.796, which represented a significant reduction in pain. The significant overall effect estimate for NMES on pain was similar to that of TENS, with a SMD of 1.924. The overall effect estimate of insoles on pain was a SMD of 0.992. The overall effect of bracing showed a significant reduction in pain of 1.34. Overall, all four non-operative modalities of treatment were found to have a significant effect on the reduction of pain in OA of the knee. This study shows that non-operative physical modalities of treatment are of benefit when treating OA of the knee. However, much of the literature reviewed evaluates studies with follow-up of less than six months: future work should aim to evaluate patients with longer follow-up.

BackgroundProgress in clinical trials in infectious disease, autoimmunity, and cancer is stymied by a dearth of successful whole cell biomarkers for peripheral blood lymphocytes (PBLs). Successful biomarkers could help to track drug effects at early time points in clinical trials to prevent costly trial failures late in development. One major obstacle is the inaccuracy of Ficoll density centrifugation, the decades-old method of separating PBLs from the abundant red blood cells (RBCs) of fresh blood samples.Methods and FindingsTo replace the Ficoll method, we developed and studied a novel blood-based magnetic separation method. The magnetic method strikingly surpassed Ficoll in viability, purity and yield of PBLs. To reduce labor, we developed an automated platform and compared two magnet configurations for cell separations. These more accurate and labor-saving magnet configurations allowed the lymphocytes to be tested in bioassays for rare antigen-specific T cells. The automated method succeeded at identifying 79% of patients with the rare PBLs of interest as compared with Ficoll's uniform failure. We validated improved upfront blood processing and show accurate detection of rare antigen-specific lymphocytes.ConclusionsImproving, automating and standardizing lymphocyte detections from whole blood may facilitate development of new cell-based biomarkers for human diseases. Improved upfront blood processes may lead to broad improvements in monitoring early trial outcome measurements in human clinical trials.

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