The effect of treatment with a non-invasive foot worn biomechanical device on subjective and objective measures in patients with knee osteoarthritis- A retrospective analysis on a UK population

The effect of treatment with a non-invasive foot worn biomechanical device on subjective and objective measures in patients with knee osteoarthritis- A retrospective analysis on a UK population | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research article The effect of treatment with a non-invasive foot worn biomechanical device on subjective and objective measures in patients with knee osteoarthritis- A retrospective analysis on a UK population Christopher Miles, Andrew Greene This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-16291/v3 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 16 Jun, 2020 Read the published version in BMC Musculoskeletal Disorders → Version 3 posted 4 You are reading this latest preprint version Show more versions Abstract Background: Osteoarthritis is a major cause of pain and disability worldwide, therefore ways of treating this condition are paramount to a successful health system. The purpose of the study was to investigate the changes in spatial-temporal gait parameters and clinical measurements following treatment with a non-invasive foot-worn biomechanical device on patients with knee osteoarthritis within the UK. Methods: A retrospective analysis was carried out on 455 patients with knee osteoarthritis. All patients were evaluated using a computerized gait test and two self-assessment questionnaires (WOMAC and SF-36) at baseline and after 3 and 6 months of treatment. The biomechanical device is a shoe-like device with convex pods under the sole that have the capability of changing foot centre of pressure and training neuromuscular control. The device was individually calibrated for each patient to minimise symptoms whilst walking and train neuromuscular control. Patients used the device for short periods during activities of daily living. Repeated measures statistical analyses were performed to compare differences over time. Results: After 6 months of treatment significant improvements were seen in all gait parameters (p<0.01). Specifically, gait velocity, step length and single limb support of the more symptomatic knee improved by 13%, 7.8% and 3%, respectively. These were supported by significant improvements in pain, function and quality of life (48.6%, 45.7% and 22% respectively; p<0.001). A sub-group analysis revealed no baseline differences between those who were recommended joint replacement and those who were not. Both groups improved significantly over time (p<0.05 for all). Conclusions: Our results suggest that the personalised biomechanical treatment can improve gait patterns, pain, function and quality of life. It may provide an additional solution to managing UK patients suffering from knee osteoarthritis but needs to be tested in a controlled setting first. Orthopedics Knee osteoarthritis Gait Pain Function Biomechanical treatment Figures Figure 1 Figure 2 Figure 3 Background Osteoarthritis (OA) is a major cause of pain and locomotor disability worldwide. The knee is the most commonly affected weight-bearing joint with 4.11 million people having knee OA in England (1). With an aging population and a rise in obesity being leading risk factors (2), it is estimated that by 2020, the number of people suffering from knee OA will rise to 6.5 million (1). The condition leads to social, psychological and economical burdens with substantial financial consequences (3). Therefore, cost-effective and non-invasive ways of treating and managing this condition more effectively are paramount to a successful health system. Currently, the National Institute of Clinical Excellence (NICE) guidelines outline core treatments such as education and exercise as first line care, progressing to more advanced biomechanical modalities such as valgus knee braces and orthotics in some cases (4). Total knee replacement (TKR) is the most common treatment for end-stage knee OA and appears to be increasing over-time (5) with studies estimating that the rates of TKA will reach 119,000 procedures per year by 2035 (6). TKR’s have revolutionised the care of patients with knee OA and are considered an effective intervention for the treatment of chronic knee pain and disability (7). However, as well as the associated issues of surgical intervention, there is also evidence based on using patient reported outcome measures (PROM’s), that some patients experience chronic knee pain, functional disability, and poor quality of life after TKR (8). It is suggested approximately 18% of patients report the outcomes of their surgery as only fair or poor, with a small proportion of these experiencing complications (9). One plausible explanation is related to a poor patient selection process. Although the NHS is trying to optimise the selection criteria for TKR, ultimately it is a shared decision between the physician and the patient. There is currently no objective marker that accurately identifies the functional severity of a patient. In addition, patients following TKR often continue to have altered muscular activity, a possible contributor to symptoms remaining unaddressed. One factor that has been heavily researched over the past few decades is the effect of lower limb biomechanics upon the development and progression of the disease (10, 11). Patients with knee OA often present changes in spatial-temporal gait parameters including a reduction in gait velocity, step length and single limb support phases. Moreover, these changes were found to correlate with the levels of pain and functional disability (12, 13). External knee adductor moment (KAM) and knee adductor angular impulse (KAAI) have been suggested as the surrogate kinetic variables for expressing medial joint forces and overall cumulative loading of the knee throughout the stance phase respectively (11, 14, 15). Neuromuscular changes related to knee osteoarthritis such as muscle weakness and altered muscle activation have also been widely acknowledged as contributing factors to the development of OA (11, 16-19). Symptomatic knee OA has been shown to be influenced by both biomechanical and neuromuscular treatments, which has led to conservative treatments currently available largely aim to influence either one of these factors (20-27). Interventions typically attempt to manipulate the KAM and KAAI loads transmitted through the joint, or improve the neuromuscular deficits seen within the pathology by muscle strengthening and proprioceptive exercises (28, 29). However, these modalities often occur in isolation and can reduce effect in time, which may bring into question their effectiveness, leading to further deterioration of symptoms and eventually surgery (22, 30, 31). For the past decade, a personalised non-invasive biomechanical treatment for patients with knee OA has been available in the UK. In essence, it is a specially made shoe-like device which provides the platform to fit two convex pods under the sole. One is located under the anterior part of the sole and the other under the posterior, both attached using special rails and screws (Figure 1). This foot-worn device has the capability of changing foot centre of pressure and training neuromuscular control. The biomechanical device is individually calibrated to each patient based on their gait patterns and clinical symptoms. The patient then receives a home-based treatment plan and is asked to return to the clinic for follow-up appointments to assess progress and re-adjust the pods calibration if needed. There is extensive evidence about the effect of this treatment on clinical outcomes of patients with knee OA is promising (31-35), albeit no research is yet published on UK populations. Some cultural differences are associated with the prevalence of knee OA (36, 37) and although it is reasonable to assume that the clinical effect will be the same with regards to alleviation in symptoms (31, 34, 38), it is important to validate this treatment in new populations. Therefore, this study aimed to investigate the changes in spatial-temporal gait parameters, gait metrics of severity and clinical measurements (pain, function and quality of life) following treatment with a non-invasive foot-worn biomechanical device on patients with knee OA within the UK. We hypothesize that this treatment will have similar effect on the UK population as was described on other populations within previous studies (31-34). Methods A retrospective chart review analysis was carried out to examine the effect of the biomechanical treatment upon spatial-temporal gait parameters, levels of pain and function, along with perceptions of quality of life in patients suffering from knee OA. The protocol was approved by the University of Roehampton Ethics Committee and all participants provided consent for their data to be used within in the study. A search for eligible data was conducted on the companies’ database providing the biomechanical treatment between 2009 and 2017. The treatment has been available in the UK since 2009 via private clinics that were operated by the company. It is positioned to treat primary-care patients that have usually failed to respond to traditional modalities (physiotherapy/medications) that were looking for a solution to their MSK condition. Figure 2 represents the data reduction flow chart and the eligibility for the study against the inclusion/exclusion criteria. Four hundred and fifty-five patients, 247 females (54%) and 208 males (46%) with symptomatic knee OA participated in this study. Mean (SD) age was 61.6 (8.7) years and 62.9 (10.3) years, respectively (Table 1). All patients completed both computerised gait analysis and validated PROM’s at initial consultation and at 3 and 6 months after commencing treatment. The OptoGait system (Version 1.11) was used by trained physiotherapists to measure spatial-temporal gait parameters at each data collection point (39). It works by detecting the interruption between the transmitting and a receiving LED (light emitting diode) bars. This interruption produces quantifiable data that can highlight differences between normal to pathological gait such as in knee OA (13, 40). Patients walked at a self-selected speed over a 4m measurement area, with 2 metres before and after to allow for constant velocity walking speed during data capture. Each gait test included 4 lengths in which the mean values were calculated for each parameter. The parameters recorded include velocity (cm/s), step length (cm) and single-limb support (SLS) phase (% gait cycle). Step length and SLS was calculated for the less and more symptomatic limbs respectively. For patients with bilateral OA, the more symptomatic limb was determined by the lower SLS at baseline. For patients with unilateral OA, the more symptomatic limb was the limb that was reported with OA. All gait assessments were conducted in barefoot at each data collection point and occurred within one of the biomechanical treatments’ clinics (London, Birmingham or Manchester). Table 1. Patient Characteristics Total patients: 455 Male (% of total) 208 (46%) Female (% of total) 247 (54%) Age (years) 62.2 (9.5) Unilateral vs Bilateral knee OA (%) 204 (45%) vs 251 (55%) Sub-group data: Group Not recommended surgery Recommended surgery Number of patients (%) 363 (80%) 92 (20%) Duration of symptoms (months) 67 83 The Knee Osteoarthritis Function Grade (KOFG) was used to classify patients’ and assess improvements in gait over the treatment period. It is a validated classification tool utilising cadence and stride length from the spatial-temporal gait analysis as predictor variables to assess changes in functional severity (13). The KOFG is a four-grade scale with 1 being the best function and 4 the worst function. According to the model, a shorter stride length with lower cadence is indicative of a higher functional severity grade disease (more severe knee OA), while a longer stride length with higher cadence is indicative of a lower functional severity grade of disease (less severe knee OA). After the completion of the baseline measurements, the biomechanical devices (Apos System, Apos Medical Assets Ltd. Tel-Aviv, Israel; Figure 1) were individually calibrated to each patient by a physiotherapist certified in the treatment methodology. Patients wear a pair of devices regardless of whether bilateral or unilateral symptoms. The principle of the calibration is to reduce pain in the knee during walking. From a biomechanical perspective, shifting the elements on the shoe changes the foot’s centre of pressure (COP) during gait with the goal to re-orientate the GRF vector and to reduce the loads in the affected area of the joint while walking (43-45). Previous studies have shown that shifting the posterior pod laterally causes a reduction in the knee adduction moment, which is an indicator for knee OA severity, and alters muscle activation patterns. In addition, the convex nature of the elements induces a level of controlled perturbation and proprioceptive training causing muscles in the lower limb to work differently (43-47). The combination of altered forces and moments acting on the affected joint as a result of the device set-up, combined with controlled perturbation allows a neuromuscular training response to occur (38, 48). The treatment is undertaken whilst going about daily activities to induce multiple functional repetitions and promotes implementation of new motor patterns and better neuromuscular control. Patients with knee OA that have been previously treated with this biomechanical device have shown reductions in knee adduction and flexion moments during barefoot walking, which were accompanied by significant reductions in pain and subsequent improvements in function and quality of life (31, 38, 48). Previous studies have also suggested a positive clinical effect for the device when addressing other musculoskeletal conditions such as degenerative meniscal tear, post total knee replacement, hip OA, post total hip replacement and in patients with chronic non-specific low back pain (49-54). All patients received instructions to wear the biomechanical devices during walking in his/her daily routine (at home/work), for half an hour a day at the start of the treatment, gradually increasing (+10 min/week) up to 3 hours/day after 3 months. Patients undertook follow-up assessment and re-calibration of the device approximately 3, 12, and 24 weeks after commencing the treatment in-order to optimise the pain alleviating characteristics of the device and progress the convexity to induce further neuromuscular challenges as required. Typically, patients commence treatment whilst presenting moderate-severe symptoms and often in the advanced stages of the disease. The intervention is often sought after they have explored other non-surgical treatment modalities such as traditional physiotherapy, knee joint injections and other non-invasive treatments. Despite the apparent ineffectiveness of these treatment modalities for the patient to this point, patients are often reticent to abandon traditional care measures currently in place. To ensure compliance with the current study, patients were allowed to continue with traditional care in conjunction to the intervention, as they saw fit. Statistical analysis Data was analysed with SPSS software version 23.0 with significance levels set at p<0.05. Data is presented as mean and standard deviations for gait spatial-temporal parameters and questionnaires (WOMAC/SF-36), followed by a 95% confidence interval (CI) for all time periods. The Kolmogorov-Smirnov non-parametric test was used to establish the normal distribution of spatial-temporal parameters and therefore use parametric statistical tests. To assess for the potentially confounding effects of age and gender in the WOMAC and SF-36 scores, analysis of covariance was conducted. WOMAC and SF-36 were compared using the non-parametric equivalent methods of Kruskal–Wallis test to compare all three groups, and Mann–Whitney U-tests for pairwise comparisons. Repeated measure ANOVA’s were performed for the differences between the outcomes, measured at baseline, 3 and 6 months into treatment, as well as sub-group analysis of patients that were recommended surgery and patients that were not recommended surgery. Multiple linear regression analysis was used to address the percentages changes after 6 months. The WOMAC and SF-36 scores were the dependent variables, with the gait parameters used as independent variables. Because age is typically related to PCS and gender to MCS, the linear regression models initially included age and gender. Interaction terms were also included in the regression model. To adjust for the potentially confounding effects of socio-demographic factors (age and sex) in the SF-36 and WOMAC scores, analysis of covariance was conducted. All reported p-values are from two-sided tests. In addition, we calculated the Outcome Measures in Rheumatology Clinical Trials (OMERACT)-Osteoarthritis Research Society International (OARSI) responder criteria for clinically significant improvement for each of the patients (55). These stipulate either an improvement in total, pain or in function WOMAC sub-scales of at least 50% with a decrease of 2 cm on the visual analogue-scale for pain or function, or an improvement in both pain and function of at least 20% with a decrease of 1 cm on the VAS (55). The correlation between gait changes and questionnaire improvement was calculated (i.e. the difference between baseline and 6 months). KOFG descriptive statistics was calculated to reflect changes over time. KOFG is a categorical data and was analysed using Chi-square test to compare proportions of various scores of the study. Results All spatial-temporal gait parameters significantly improved following 3 months of treatment (all less than p<0.01). There were also further significant improvements in all parameters between 3 and 6 months of treatment (All less than p<0.01), except SLS on both sides (p= 0.554 and 0.452). After 6 months of treatment, all parameters significantly improved compared to baseline. Specifically, gait velocity, step length and SLS of the more symptomatic knee improved by 13%, 7.8% and 3% respectively (p<0.01). The changes in gait over the time intervals are summarised in Table 2. Table 2. Spatial-temporal parameter changes in knee OA patients after 3 and 6 months of treatment. Results are presented as mean (SD) [95% CI] Baseline 3 months 6 months P-value Velocity (cm/s) 91.88 (20.68) [89.97 - 93.78] 102.69 (19.19) [100.92 -104.46] 104 (19.12) [102.23 - 105.76] <0.001 Step length- more symptomatic limb (cm) 53.96 (8.8) [53.15 – 54.78] 57.70 (8.36) [56.93 -58.48] 58.15 (8.36) [57.384 – 58.93] 0.001 Step length- less symptomatic limb (cm) 54.07 (9.0) [53.24 – 54.9] 57.86 (8.63) [57.06 – 58.66] 58.34 (8.44) [57.564 – 59.12] <0.001 Single limb support- more symptomatic limb (% GC * ) 36.55 (2.42) [36.32 – 36.79] 37.68 (2.10) [37.49 – 37.88] 37.72 (2.09) [37.53 -37.92] <0.001 Single limb support- less symptomatic limb (% GC * ) 38.34 (2.06) [38.15 - 38.53] 38.53 (1.99) [38.34 – 38.71] 38.56 (1.93) [38.39 – 38.74] 0.003 N=455; *GC Gait Cycle; P-value was set to P < 0.05. Repeated measure ANOVA’s were performed for the differences between the outcomes, measured at baseline, 3 and 6 months into treatment. Significant differences were found between baseline and 3 months and baseline and 6 months. There was a significant improvement in KOFG between baseline and 3 months follow-up (p<0.001), with retained improvements at 6 months. Table 3 displays the changes in classification over the 6 months of treatment. It shows a shift from more severe functional grades to less severe levels over time (improved functional outcomes). More specifically, at baseline two thirds (71%) of the patients were classified with grade 1 and 2 (i.e. mild-moderate functional limitation) and a third of the patients (29%) were classified with grade 3 and 4 (i.e. moderate-severe functional severity). After 6 months of treatment 86% of the patients were with a functional classification grade 1 & 2 and 14% with grade 3 and 4 respectively. Table 3. Knee Osteoarthritis Functional Grade (KOFG) * changes in patients after 3 and 6 months of treatment. Values are presented as n (%). Baseline 3 months 6 months Grade 1 117 (25.71%) 190 (41.76%) 197 (43.29%) Grade 2 207 (45.49%) 193 (42.42%) 196 (43.07%) Grade 3 95 (20.88%) 62 (13.63%) 52 (11.43%) Grade 4 36 (7.91%) 10 (2.19%) 10 (2.19%) Descriptive statistics of patient's grade distribution over time. The average grade was 2.1 at baseline, 1.8 at 3 months and 1.7 at 6 months. Significant differences were found in paired T-test between baseline and 3 months (p<0.001) and between baseline and 6 months (p<0.001). There were no significant differences in mean grade score between 3 and 6 months (p=0.01) *Grade 1- least severe, Grade 4- most severe Following 6 months of treatment, all patients’ self-evaluation questionnaires improved significantly. All WOMAC subscales significantly improved following 3 months of treatment, with further improvements at 6 months (p<0.001). WOMAC Total, along with pain, function and stiffness subscales improved by 46.2%, 48.6%, 45.7% and 43.4% respectively (p<0.001 for all). 67% of the patients met the OMERACT-OARSI criteria (307/455 significantly improved). Table 4 displays the absolute changes from baseline to 6 months. Table 4. Patient reported outcome measures (PROM’s) changes in knee OA patients after 3 and 6 months of treatment. Results are presented as mean (SD) [95% CI] Baseline 3 months 6 months P-value * WOMAC ** Total 41.40 (19.68) [39.58 – 43.21] 25.32 (19.13) [23.56 – 27.08] 22.28 (18.13) [20.61 – 23.96] <0.001 Pain subscale 46.71 (18.86) [44.97 – 48.44] 27.42 (19.72) [25.60 – 29.24] 23.99 (18.94) [22.25 – 25.74] <0.001 Function subscale 38.97 (21.56) [36.98 – 40.96] 24.07 (19.78) [22.25 - 25.9] 21.16 (18.50) [19.45 – 22.86] <0.001 Stiffness subscale 48.74 (25.92) [46.35 – 51.13] 30.71 (25.92) [28.48 – 32.95] 27.59 (23.15) [25.45 – 29.72] <0.001 SF-36 *** Total 53.49 (16.08) [52.01 – 54.97] 62.60 (16.57) [61.08 – 64.13] 65.22 (16.87) [63.67 – 66.78] <0.001 Physical Component Summary (PCS) 45.67 (18.36) [43.98 – 47.36] 57.71 (19.85) [55.88 – 59.54] 61.37 (20.04) [59.52 – 63.21] <0.001 Mental Component Summary (MCS) 64.02 (19.49) [62.23 – 65.82] 72.30 (18.18) [70.63 – 73.98] 73.64 (18.12) [71.97 – 75.31] <0.001 *P-value was set to P < 0.05. **Western Ontario and McMaster Universities Index (WOMAC Index). The WOMAC questionnaire includes 24 questions in a Visual Analogue Scale (VAS) format (0 = no pain/stiffness/difficulty, 100 = severe pain/stiffness/difficulty). ***SF-36 Health Survey includes 36 questions. Results range between 0–100 (0 = poor quality of life, 100 = high quality of life). Repeated measure ANOVA’s were performed for the differences between the outcomes, measured at baseline, 3 and 6 months into treatment. Significant differences were found between baseline and 3 months and baseline and 6 months. All SF-36 subscales also significantly improved following 3 months of treatment (p<0.001). There were also further significant improvements between 3- and 6-month time intervals, except for the MCS (p= 0.068). After 6 months of treatment all subscales had significantly improved (p<0.001). Specifically, SF-36 Total, PCS and MCS improved by 11.73, 15.7, and 9.62 points, or 22%, 34% and 15% respectively compared to baseline (See Table 4). These improvements also met minimal clinical important differences (MCID) for clinical significance of 7.8 points (56). A correlation analysis between gait and questionnaire improvement was calculated. First, a new parameter was calculated for each measurement. This was the difference between baseline and 6 months. Second, a correlation calculation between the changes in gait measures and the changes in questionnaires was calculated. A significant correlation was found between the changes in gait parameters and the changes in questionnaires (p<0.05 for all). More specifically, the correlation between the changes in gait velocity and the changes in pain, function, PCS and MCS was -0.30, -0.29, 0.33 and 0.20 respectively. A sub-analysis was carried out on patients that had already been recommended knee joint replacement surgery (surgery recommended group) prior to commencing treatment (20%, 92 patients). There were no significant differences in any baseline measures (WOMAC, SF-36 or gait parameters) between this cohort and the rest of the patients, apart from duration of symptoms prior to commencing treatment (no surgery recommended group: 67 months vs surgery recommended group: 83 months, p=0.013). Both groups improved significantly over time (p<0.05), meeting the MCID in all outcome measures. Despite improvements in all variables of both groups at 6 months, the recommended surgery group displayed higher WOMAC pain and stiffness subscales (p=0.027, and p=0.019, see Figure 3), and lower SLS in both the more and less symptomatic sides (p=0.04 and p=0.028). Discussion The purpose of this study was to investigate the changes in spatial-temporal gait parameters and clinical measurements following treatment with a non-invasive foot-worn biomechanical device on patients with knee osteoarthritis within the UK. Following 3 months of treatment, patients demonstrated significant improvements in both gait and PROM’s, with maintained or further improvements occurring in all parameters after 6 months. The results suggest that most improvements occurred by 3 months, but further improvements occur between 3 and 6 months, apart from SLS in gait and MCS subscale of SF-36. This supports previous work which found that the largest improvements occurred within the initial few months of treatment and are then maintained (32). The improvements in WOMAC scores meet the OMERACT-OARSI guidelines for clinical response to treatment in 67% of the patients, signifying true positive impacts felt by patients (55). The thresholds for minimal clinical importance differences (MCID) within SF-36 were also met, suggesting improvements in quality of life following treatment (56). In addition, these improvements in self-evaluation questionnaires correlated with the significant improvements in gait. PROM’s along-with radiographic findings have historically been used to track knee OA outcomes and are leading predictors in guiding the decision upon joint replacement surgery (57). However, the low correlation between radiographic findings and patient symptoms has since become more acknowledged (58), and therefore the importance of more objective and functional measures to evaluate patient symptoms has become apparent. Previous research has proposed spatial-temporal parameters are a good indicator for functional severity (12, 58), with a recent meta-analysis suggesting that stride duration and cadence provided a better reflection of knee OA severity than kinematic and kinetic measures (59). Using the patients’ cadence and stride lengths as predictor variables for knee OA severity forms the basis of the validated Knee Osteoarthritis Functional Grade or KOFG (13), which in a follow-up study was also validated as a classification tool to measure treatment effect (60). A combination of spatial-temporal parameters objectively classifies patients with knee OA according to functional disease severity, which have been shown to correlate with radiographic evaluation, the level of pain, function and rate of TKR. The benefit of this tool is the ability to quantify the severity of disease and to assess the impact of an intervention, rather than just stating the change in gait analysis parameters (60). The model suggests that a shorter stride length with lower cadence is indicative of a higher functional severity grade (more severe knee OA), while a longer stride length with higher cadence is indicative of a lower functional severity grade (less severe knee OA). Within this current study, there was a significant improvement in KOFG between baseline and 3 months follow-up (p<0.001), with retained improvement at 6 months. The shift from more severe to less severe KOFG suggest patients not only improvement in symptoms, but actually move away from measures associated with increased rates of TKR (13, 60). The present study also examined whether there were any differences in the sub-group of patients (20%) that had already been offered joint replacement surgery (TKR/PKR) prior to commencing treatment. Interestingly, aside from the duration of symptoms, there were no significant differences between cohorts at baseline, suggesting that those patients that had been recommended surgery as a suitable option for their condition, displayed the same characteristics as those that have not had surgical recommendation (Figure 3). Research reports most patients that are suitable for TKR have WOMAC baseline scores between 40s to 50’s (57), which could indicate that the cohorts analysed within this study are representative of this population. Furthermore, significant improvements seen across both groups (Figure 3) suggests these populations can respond well to this treatment in levels of pain, function and quality of life measures. Differences between these two groups were seen at 6 months, including significantly higher WOMAC pain and stiffness subscales (p=0.027, and p=0.019), and significantly lower SLS in both the more and less symptomatic sides (p=0.04 and p=0.028) in the recommended surgery group. The reduction of improvements within this group could be explained by significantly longer durations of symptoms experienced by the patients, suggesting more chronicity of the condition. Previous studies have investigated the durations of symptoms and their relationship to clinical improvements and have suggested that optimising the timing that patients access relevant treatments could be key to optimising outcomes (61). Despite this, the overall improvements in both groups are marked and suggestive that the treatment could be an effective alternative for a number of patients that would otherwise have progressed to surgery. Researchers have presented several theories explaining how this treatment works to improve symptoms in patients with knee OA. Studies have shown that the biomechanical device can reduce the external loads acting on the body to “unload” the painful area, which is said to be important when treating this condition (43, 44). It has been shown to reduce the 1 st and 2 nd peak KAM and KAAI by 8.4%, 12.7 % and 13% after 9 months of treatment respectively (38). An important factor to note with the improvements in biomechanical variables seen with the device is that they remained, even when the patient was not wearing the device. This suggests that a motor learning effect occurs as a result of the neuromuscular retraining received from the treatment (46). Neuromuscular training is delivered by a controlled level of perturbation via the convex nature of the elements (46, 47). The combined features of the biomechanical device allow for repetitive perturbations with diminished pain throughout the gait cycle. Patients wearing the devices for prescribed periods every day means that they gain high repetitions of closed kinetic chain, functional exercises and improved levels of compliance said to be advantageous for motor learning (62-64). This combination of key rehabilitation principles allows the patient to reacquire improved neuromuscular control, thus avoiding pathological patterns previously utilised whilst in pain (31). Given knee OA is a chronic degenerative condition, symptoms deteriorate over time at varying rates (65). Currently, interventions are directed to the end-stages of the disease and therefore can often be ineffective and palliative in nature (66). Whilst the literature reports that the number of patients progressing to having joint replacement surgery is growing (6), approximately 20-40% of those completed are considered inappropriate. These were classified due to having only slight or moderate symptoms, or not severe enough radiographic findings and therefore TKR deemed unnecessary (67, 68). A paradigm shift is needed to focus efforts on treating patients at high-risk earlier in the disease progression (66), or utilising more specialist modalities that can help minimise this potentially inappropriate flow to surgery. The results of this study display a combination of improvements in both subjective PROM’s and objective spatial-temporal gait parameters which are promising and may indicate that the biomechanical device used in this study has the ability to be an effective modality in managing this chronic condition, however further studies in a controlled setting are required. This study has some limitations. Firstly, the study was a retrospective analysis of patients from the centres database and therefore had no control group. However, a previous study has demonstrated comparable positive effects of this treatment compared to a control group in a double-blind study (31). In addition, patients were allowed to continue with traditional care, and we cannot determine that other treatment did not affect the results of this study. Patients are usually characterised with a moderate-severe knee OA and commence the current treatment after trying traditional care with little to no success. The treatment is often undertaken as one final attempt to address the condition non-invasively prior to the need for a surgical intervention. As a result, we believe most of the clinical effect seen in this study can be attributed to the biomechanical device and treatment plan as opposed to any adjunctive or continued treatment modalities. Potentially, a combined approach of exercise therapy utilised alongside the biomechanical treatment may yield further superior effects compared to the device alone and this should be investigated in a controlled setting in the future. Secondly, this study had a relatively short follow-up duration of 6 months for this cohort. Long-term follow-up would give more insight into the lasting effects of the treatment. However, it reflects previous research on the treatment on different populations with similar improvements in gait and PROM’s (33-35, 69). Therefore, it could be assumed that the improvements can be maintained with the high compliance rates in the treatment (32). Nevertheless, future research should continue to investigate the long-term clinical effect of the treatment, in prospective, randomised control trial (RCT) design whilst tracking decay rates for joint replacement surgeries. Promisingly, preliminary data from an RCT on the effect of this treatment displays comparable improvements to this study (70). Lastly, this study did not monitor the overall activity level of the patients in general and this compliance to the treatment plan in specifics. We cannot confirm the usage time of the device at home other than when the patients returned to the clinic for a follow-up appointment and reported that they have been using the device daily. Future studies should enforce methods to monitor compliance to the treatment plan at home. Conclusions The examined non-invasive biomechanical treatment led to a significant improvement in gait patterns, pain, function and quality of life for UK patients suffering with knee OA, although further studies in a controlled setting are required to investigate its clinical effect further. It appears to create a comparable response between patients that have already been recommended knee joint replacement surgery and those that have not been recommended, therefore potentially providing an alternative solution for this population. If these results can be retained in the longer term, it could hypothetically delay or even avoid the need for surgery in many cases which provides an area for examination in future trials. Whilst further studies in controlled settings are required in order to fully understand the clinical effect of this treatment, this study suggests that it may provide positive clinical implications for patients, with the potential to provide a sustainable modality for healthcare systems to manage knee OA patients effectively in the community setting. List Of Abbreviations OA - Osteoarthritis NICE - National Institute of Clinical Excellence (NICE) TKR - Total knee replacement (TKR) PROM's - patient reported outcome measures (PROM’s), KAM - knee adductor moment (KAM) KAAI - knee adductor angular impulse (KAAI) LED - light emitting diode (LED) SLS - single-limb support (SLS) KOFG - Knee Osteoarthritis Function Grade (KOFG) VAS - visual analogue scale (VAS) PCS - Physical Component Summary (PCS) MCS - Mental Component Summary (MCS) COP - Center of pressure (COP) OMERACT-OARSI - Outcome Measures in Rheumatology Clinical Trials (OMERACT)-Osteoarthritis Research Society International (OARSI) Declarations Ethics approval and consent to participate The protocol was approved by the University of Roehampton Ethics Committee and all participants provided written consent for their data to be used within the study Consent for publication N/A Availability of data and materials All data requests will be reviewed and addressed by the authors Competing interests None to declare Funding This study was not funded in any way Authors' contributions All authors take full responsibility for the entire manuscript content, integrity of the data and the accuracy of the data analysis. Study Concept and Design: CM, AG. Acquisition of data: CM Analysis and Interpretation of Data: CM Drafting of the Manuscript: CM Critical Revision of the Manuscript for Important Intellectual Content: AG Acknowledgements The authors would like to thank Apos Medical UK Ltd for allowing access to the data. The authors would also like to thank Dr..Ornit Cohen for her statistical analysis support. References Osteoarthritis in General Practice. www.arthritisresearchuk.org2013 [ Arden N, Nevitt MC. Osteoarthritis: epidemiology. Best Pract Res Clin Rheumatol. 2006;20(1):3-25. Gupta S, Hawker GA, Laporte A, Croxford R, Coyte PC. The economic burden of disabling hip and knee osteoarthritis (OA) from the perspective of individuals living with this condition. Rheumatology (Oxford). 2005;44(12):1531-7. NICE. Osteoarthritis: care and management (CG177). https://www.nice.org.uk/guidance/cg177 [ Carr AJ, Robertsson O, Graves S, Price AJ, Arden NK, Judge A, et al. Knee replacement. 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The influence of sagittal center of pressure offset on gait kinematics and kinetics. J Biomech. 2010;43(5):969-77. Haim A, Wolf A, Rubin G, Genis Y, Khoury M, Rozen N. Effect of center of pressure modulation on knee adduction moment in medial compartment knee osteoarthritis. J Orthop Res. 2011;29(11):1668-74. Debbi EM, Wolf A, Haim A. Detecting and quantifying global instability during a dynamic task using kinetic and kinematic gait parameters. J Biomech. 2012;45(8):1366-71. Goryachev Y, Debbi EM, Haim A, Rozen N, Wolf A. Foot center of pressure manipulation and gait therapy influence lower limb muscle activation in patients with osteoarthritis of the knee. J Electromyogr Kinesiol. 2011;21(5):704-11. Debbi EM, Wolf A, Goryachev Y, Rozen N, Haim A. Alterations in sagittal plane knee kinetics in knee osteoarthritis using a biomechanical therapy device. Ann Biomed Eng. 2015;43(5):1089-97. Segal G, Bar-Ziv Y, Velkes S, Benkovich V, Stanger G, Debbi EM, et al. A non-invasive biomechanical device and treatment for patients following total hip arthroplasty: results of a 6-month pilot investigation. J Orthop Surg Res. 2013;8:13. Elbaz A, Mirovsky Y, Mor A, Enosh S, Debbi E, Segal G, et al. A novel biomechanical device improves gait pattern in patient with chronic nonspecific low back pain. Spine (Phila Pa 1976). 2009;34(15):E507-12. Barzilay Y, Segal G, Lotan R, Regev G, Beer Y, Lonner BS, et al. Patients with chronic non-specific low back pain who reported reduction in pain and improvement in function also demonstrated an improvement in gait pattern. Eur Spine J. 2015. Solomonow-Avnon D, Haim A, Levin D, Elboim-Gabyzon M, Rozen N, Peled E, et al. Reduction of hip joint reaction force via medio-lateral foot center of pressure manipulation in bilateral hip osteoarthritis patients. J Orthop Res. 2016. Elbaz A, Beer Y, Rath E, Morag G, Segal G, Debbi EM, et al. A unique foot-worn device for patients with degenerative meniscal tear. 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Cite Share Download PDF Status: Published Journal Publication published 16 Jun, 2020 Read the published version in BMC Musculoskeletal Disorders → Version 3 posted Submission checks completed at journal 29 May, 2020 Editorial decision: Accept 28 May, 2020 Editor assigned by journal 26 May, 2020 Editor invited by journal 26 May, 2020 You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-16291","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":624070,"identity":"ee4b1832-34aa-4851-b900-48477adbb107","order_by":0,"name":"Christopher Miles","email":"data:image/png;base64,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","orcid":"","institution":"University of Roehampton","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Christopher","middleName":"","lastName":"Miles","suffix":""},{"id":624071,"identity":"b72c114b-dd8e-4cda-bd19-57e8d86e3c25","order_by":1,"name":"Andrew Greene","email":"","orcid":"","institution":"University of Roehampton","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Andrew","middleName":"","lastName":"Greene","suffix":""}],"badges":[],"createdAt":"2020-03-03 11:53:27","currentVersionCode":3,"declarations":"","doi":"10.21203/rs.3.rs-16291/v3","doiUrl":"https://doi.org/10.21203/rs.3.rs-16291/v3","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12891-020-03382-3","type":"published","date":"2020-06-16T12:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":1257916,"identity":"2b02a6ab-79b4-4281-8fbb-13932750fb5d","added_by":"auto","created_at":"2020-06-04 18:51:34","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":210767,"visible":true,"origin":"","legend":"The biomechanical device","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-16291/v3/1.png"},{"id":1257917,"identity":"2b3239ae-cd62-4d87-a4d7-730c418a6507","added_by":"auto","created_at":"2020-06-04 18:51:34","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":87189,"visible":true,"origin":"","legend":"Flow chart of study screening and inclusion.","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-16291/v3/2.png"},{"id":1257918,"identity":"a17e2295-7f41-43d4-b07f-1e8671b78d06","added_by":"auto","created_at":"2020-06-04 18:51:34","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":10778,"visible":true,"origin":"","legend":"Comparison of WOMAC changes between patients that had been recommended for knee joint replacement surgery (Total Knee Replacement/Partial Knee Replacement, TKR/PKR respectively) and patients that were not.","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-16291/v3/3.png"},{"id":13537118,"identity":"4ce0da7d-3002-4ed4-bf01-916ac218c104","added_by":"auto","created_at":"2021-09-17 01:34:56","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":556043,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-16291/v3/a4876cf2-945d-4ad8-824e-e21407971c08.pdf"}],"financialInterests":"","formattedTitle":"The effect of treatment with a non-invasive foot worn biomechanical device on subjective and objective measures in patients with knee osteoarthritis- A retrospective analysis on a UK population","fulltext":[{"header":"Background","content":"\u003cp\u003eOsteoarthritis (OA) is a major cause of pain and locomotor disability worldwide. The knee is the most commonly affected weight-bearing joint with 4.11 million people having knee OA in England (1). With an aging population and a rise in obesity being leading risk factors (2), it is estimated that by 2020, the number of people suffering from knee OA will rise to 6.5 million (1). The condition leads to social, psychological and economical burdens with substantial financial consequences (3). Therefore, cost-effective and non-invasive ways of treating and managing this condition more effectively are paramount to a successful health system.\u003c/p\u003e\n\u003cp\u003eCurrently, the National Institute of Clinical Excellence (NICE) guidelines outline core treatments such as education and exercise as first line care, progressing to more advanced biomechanical modalities such as valgus knee braces and orthotics in some cases (4). Total knee replacement (TKR) is the most common treatment for end-stage knee OA and appears to be increasing over-time (5) with studies estimating that the rates of TKA will reach 119,000 procedures per year by 2035 (6). TKR\u0026rsquo;s have revolutionised the care of patients with knee OA and are considered an effective intervention for the treatment of chronic knee pain and disability (7). However, as well as the associated issues of surgical intervention, there is also evidence based on using patient reported outcome measures (PROM\u0026rsquo;s), that some patients experience chronic knee pain, functional disability, and poor quality of life after TKR (8). It is suggested approximately 18% of patients report the outcomes of their surgery as only fair or poor, with a small proportion of these experiencing complications (9). One plausible explanation is related to a poor patient selection process. Although the NHS is trying to optimise the selection criteria for TKR, ultimately it is a shared decision between the physician and the patient. There is currently no objective marker that accurately identifies the functional severity of a patient. In addition, patients following TKR often continue to have altered muscular activity, a possible contributor to symptoms remaining unaddressed.\u003c/p\u003e\n\u003cp\u003eOne factor that has been heavily researched over the past few decades is the effect of lower limb biomechanics upon the development and progression of the disease (10, 11). Patients with knee OA often present changes in spatial-temporal gait parameters including a reduction in gait velocity, step length and single limb support phases. Moreover, these changes were found to correlate with the levels of pain and functional disability (12, 13). External knee adductor moment (KAM) and knee adductor angular impulse (KAAI) have been suggested as the surrogate kinetic variables for expressing medial joint forces and overall cumulative loading of the knee throughout the stance phase respectively (11, 14, 15). Neuromuscular changes related to knee osteoarthritis such as muscle weakness and altered muscle activation have also been widely acknowledged as contributing factors to the development of OA (11, 16-19).\u003c/p\u003e\n\u003cp\u003eSymptomatic knee OA has been shown to be influenced by both biomechanical and neuromuscular treatments, which has led to conservative treatments currently available largely aim to influence either one of these factors (20-27). Interventions typically attempt to manipulate the KAM and KAAI loads transmitted through the joint, or improve the neuromuscular deficits seen within the pathology by muscle strengthening and proprioceptive exercises (28, 29).\u0026nbsp; However, these modalities often occur in isolation and can reduce effect in time, which may bring into question their effectiveness, leading to further deterioration of symptoms and eventually surgery (22, 30, 31).\u003c/p\u003e\n\u003cp\u003eFor the past decade, a personalised non-invasive biomechanical treatment for patients with knee OA has been available in the UK. In essence, it is a specially made shoe-like device which provides the platform to fit two convex pods under the sole. One is located under the anterior part of the sole and the other under the posterior, both attached using special rails and screws (Figure 1). This foot-worn device has the capability of changing foot centre of pressure and training neuromuscular control. The biomechanical device is individually calibrated to each patient based on their gait patterns and clinical symptoms. The patient then receives a home-based treatment plan and is asked to return to the clinic for follow-up appointments to assess progress and re-adjust the pods calibration if needed.\u003c/p\u003e\n\u003cp\u003eThere is extensive evidence about the effect of this treatment on clinical outcomes of patients with knee OA is promising (31-35), albeit no research is yet published on UK populations. Some cultural differences are associated with the prevalence of knee OA (36, 37) and although it is reasonable to assume that the clinical effect will be the same with regards to alleviation in symptoms (31, 34, 38), it is important to validate this treatment in new populations. Therefore, this study aimed to investigate the changes in spatial-temporal gait parameters, gait metrics of severity and clinical measurements (pain, function and quality of life) following treatment with a non-invasive foot-worn biomechanical device on patients with knee OA within the UK. We hypothesize that this treatment will have similar effect on the UK population as was described on other populations within previous studies (31-34).\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eA retrospective chart review analysis was carried out to examine the effect of the biomechanical treatment upon spatial-temporal gait parameters, levels of pain and function, along with perceptions of quality of life in patients suffering from knee OA. The protocol was approved by the University of Roehampton Ethics Committee and all participants provided consent for their data to be used within in the study. A search for eligible data was conducted on the companies\u0026rsquo; database providing the biomechanical treatment between 2009 and 2017.\u0026nbsp;The treatment has been available in the UK since 2009 via private clinics that were operated by the company. It is positioned to treat primary-care patients that have usually failed to respond to traditional modalities (physiotherapy/medications) that were looking for a solution to their MSK condition.\u0026nbsp;Figure 2 represents the data reduction flow chart and the eligibility for the study against the inclusion/exclusion criteria.\u003c/p\u003e\n\u003cp\u003eFour hundred and fifty-five patients, 247 females (54%) and 208 males (46%) with symptomatic knee OA participated in this study. \u0026nbsp;Mean (SD) age was 61.6 (8.7) years and 62.9 (10.3) years, respectively (Table 1). All patients completed both computerised gait analysis and validated PROM\u0026rsquo;s at initial consultation and at 3 and 6 months after commencing treatment. The OptoGait system (Version 1.11) was used by trained physiotherapists to measure spatial-temporal gait parameters at each data collection point (39). It works by detecting the interruption between the transmitting and a receiving LED (light emitting diode) bars.\u0026nbsp;This interruption produces quantifiable data that can highlight differences between normal to pathological gait such as in knee OA (13, 40). Patients walked at a self-selected speed over a 4m measurement area, with 2 metres before and after to allow for constant velocity walking speed during data capture. Each gait test included 4 lengths in which the mean values were calculated for each parameter. The parameters recorded include velocity (cm/s), step length (cm) and single-limb support (SLS) phase (% gait cycle). Step length and SLS was calculated for the less and more symptomatic limbs respectively. For patients with bilateral OA, the more symptomatic limb was determined by the lower SLS at baseline. For patients with unilateral OA, the more symptomatic limb was the limb that was reported with OA. All gait assessments were conducted in barefoot at each data collection point and occurred within one of the biomechanical treatments\u0026rsquo; clinics (London, Birmingham or Manchester).\u003c/p\u003e\n\u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style=\"font-family: Helvetica; font-size: 13px; color: rgb(0, 0, 0);\"\u003eTable 1.\u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u0026nbsp;Patient Characteristics\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"width:450.8pt;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 184.3pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 12.65pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cstrong\u003eTotal patients:\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 266.5pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 12.65pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e455\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 184.3pt;border: none;padding: 0in 5.4pt;height: 13.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003eMale (% of total)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 266.5pt;border: none;padding: 0in 5.4pt;height: 13.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e208 (46%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 184.3pt;border: none;padding: 0in 5.4pt;height: 12.65pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003eFemale (% of total)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 266.5pt;border: none;padding: 0in 5.4pt;height: 12.65pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e247 (54%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 184.3pt;border: none;padding: 0in 5.4pt;height: 13.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003eAge (years)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 266.5pt;border: none;padding: 0in 5.4pt;height: 13.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e62.2 (9.5)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 184.3pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1.5pt double windowtext;padding: 0in 5.4pt;height: 12.65pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003eUnilateral vs Bilateral knee OA (%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 266.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1.5pt double windowtext;padding: 0in 5.4pt;height: 12.65pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e204 (45%) vs 251 (55%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 184.3pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 13.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cstrong\u003eSub-group data:\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"border:none;border-bottom:solid windowtext 1.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 184.3pt;border: none;padding: 0in 5.4pt;height: 21.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003eGroup\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141.75pt;border: none;padding: 0in 5.4pt;height: 21.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cu\u003eNot recommended surgery\u003c/u\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124.75pt;border: none;padding: 0in 5.4pt;height: 21.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cu\u003eRecommended surgery\u003c/u\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 184.3pt;border: none;padding: 0in 5.4pt;height: 12.65pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003eNumber of patients (%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141.75pt;border: none;padding: 0in 5.4pt;height: 12.65pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e363 (80%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124.75pt;border: none;padding: 0in 5.4pt;height: 12.65pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e92 (20%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 184.3pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 12.65pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003eDuration of symptoms (months)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 12.65pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e67\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 12.65pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"font-family: Helvetica; font-size: 13px; color: rgb(0, 0, 0);\"\u003e83\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003eThe Knee Osteoarthritis Function Grade (KOFG) was used to classify patients\u0026rsquo; and assess improvements in gait over the treatment period. It is a validated classification tool utilising cadence and stride length from the spatial-temporal gait analysis as predictor variables to assess changes in functional severity (13). The KOFG is a four-grade scale with 1 being the best function and 4 the worst function. According to the model, a shorter stride length with lower cadence is indicative of a higher functional severity grade disease (more severe knee OA), while a longer stride length with higher cadence is indicative of a lower functional severity grade of disease (less severe knee OA).\u003c/p\u003e\n\u003cp\u003eAfter the completion of the baseline measurements, the biomechanical devices (Apos System, Apos Medical Assets Ltd. Tel-Aviv, Israel; Figure 1) were individually calibrated to each patient by a physiotherapist certified in the treatment methodology. Patients wear a pair of devices regardless of whether bilateral or unilateral symptoms. The principle of the calibration is to reduce pain in the knee during walking.\u0026nbsp; From a biomechanical perspective, shifting the elements on the shoe changes the foot\u0026rsquo;s centre of pressure (COP) during gait with the goal to re-orientate the GRF vector and to reduce the loads in the affected area of the joint while walking (43-45). Previous studies have shown that shifting the posterior pod laterally causes a reduction in the knee adduction moment, which is an indicator for knee OA severity, and alters muscle activation patterns. In addition, the convex nature of the elements induces a level of controlled perturbation and proprioceptive training causing muscles in the lower limb to work differently (43-47). The combination of altered forces and moments acting on the affected joint as a result of the device set-up, combined with controlled perturbation allows a neuromuscular training response to occur (38, 48).\u003c/p\u003e\n\u003cp\u003eThe treatment is undertaken whilst going about daily activities to induce multiple functional repetitions and promotes implementation of new motor patterns and better neuromuscular control. Patients with knee OA that have been previously treated with this biomechanical device have shown reductions in knee adduction and flexion moments during barefoot walking, which were accompanied by significant reductions in pain and subsequent improvements in function and quality of life (31, 38, 48). Previous studies have also suggested a positive clinical effect for the device when addressing other musculoskeletal conditions such as degenerative meniscal tear, post total knee replacement, hip OA, post total hip replacement and in patients with chronic non-specific low back pain (49-54).\u003c/p\u003e\n\u003cp\u003eAll patients received instructions to wear the biomechanical devices during walking in his/her daily routine (at home/work), for half an hour a day at the start of the treatment, gradually increasing (+10 min/week) up to 3 hours/day after 3 months. Patients undertook follow-up assessment and re-calibration of the device approximately 3, 12, and 24 weeks after commencing the treatment in-order to optimise the pain alleviating characteristics of the device and progress the convexity to induce further neuromuscular challenges as required. Typically, patients commence treatment whilst presenting moderate-severe symptoms and often in the advanced stages of the disease.\u0026nbsp; The intervention is often sought after they have explored other non-surgical treatment modalities such as traditional physiotherapy, knee joint injections and other non-invasive treatments. Despite the apparent ineffectiveness of these treatment modalities for the patient to this point, patients are often reticent to abandon traditional care measures currently in place.\u0026nbsp; To ensure compliance with the current study, patients were allowed to continue with traditional care in conjunction to the intervention, as they saw fit.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData was analysed with SPSS software version 23.0 with significance levels set at p\u0026lt;0.05.\u0026nbsp; Data is presented as mean and standard deviations for gait spatial-temporal parameters and questionnaires (WOMAC/SF-36), followed by a 95% confidence interval (CI) for all time periods. The Kolmogorov-Smirnov non-parametric test was used to establish the normal distribution of spatial-temporal parameters and therefore use parametric statistical tests. To assess for the potentially confounding effects of age and gender in the WOMAC and SF-36 scores, analysis of covariance was conducted.\u003c/p\u003e\n\u003cp\u003eWOMAC and SF-36 were compared using the non-parametric equivalent methods of Kruskal\u0026ndash;Wallis test to compare all three groups, and Mann\u0026ndash;Whitney U-tests for pairwise comparisons. Repeated measure ANOVA\u0026rsquo;s were performed for the differences between the outcomes, measured at baseline, 3 and 6 months into treatment, as well as sub-group analysis of patients that were recommended surgery and patients that were not recommended surgery. Multiple linear regression analysis was used to address the percentages changes after 6 months. The WOMAC and SF-36 scores were the dependent variables, with the gait parameters used as independent variables. Because age is typically related to PCS and gender to MCS, the linear regression models initially included age and gender. Interaction terms were also included in the regression model. To adjust for the potentially confounding effects of socio-demographic factors (age and sex) in the SF-36 and WOMAC scores, analysis of covariance was conducted. All reported p-values are from two-sided tests.\u003c/p\u003e\n\u003cp\u003eIn addition, we calculated the Outcome Measures in Rheumatology Clinical Trials (OMERACT)-Osteoarthritis Research Society International (OARSI) responder criteria for clinically significant improvement for each of the patients (55). These stipulate either an improvement in total, pain or in function WOMAC sub-scales of at least 50% with a decrease of 2 cm on the visual analogue-scale for pain or function, or an improvement in both pain and function of at least 20% with a decrease of 1 cm on the VAS (55).\u003c/p\u003e\n\u003cp\u003eThe correlation between gait changes and questionnaire improvement was calculated (i.e. the difference between baseline and 6 months).\u003c/p\u003e\n\u003cp\u003eKOFG descriptive statistics was calculated to reflect changes over time. KOFG is a categorical data and was analysed using Chi-square test to compare proportions of various scores of the study.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cspan lang=\"EN-GB\"\u003eAll spatial-temporal gait parameters significantly improved following 3 months of treatment (all less than p\u0026lt;0.01). There were also further significant improvements in all parameters between 3 and 6 months of treatment (All less than p\u0026lt;0.01), except SLS on both sides (p= 0.554 and 0.452). After 6 months of treatment, all parameters significantly improved compared to baseline. Specifically, gait velocity, step length and SLS of the more symptomatic knee improved by 13%, 7.8% and 3% respectively (p\u0026lt;0.01). The changes in gait over the time intervals are summarised in Table 2. \u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style=\"font-family: Helvetica; font-size: 13px; color: rgb(0, 0, 0);\"\u003eTable 2.\u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e Spatial-temporal parameter changes in knee OA patients after 3 and 6 months of treatment. Results are presented as mean (SD) [95% CI]\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 139.95pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79.8pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003eBaseline\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.7pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e3 months\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e6 months\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.45pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003eP-value\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 139.95pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003eVelocity (cm/s)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e91.88 (20.68)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e[89.97 - 93.78]\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.7pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e102.69 (19.19)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e[100.92 -104.46]\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e104 (19.12)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e[102.23 - 105.76]\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.45pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 139.95pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003eStep length- more symptomatic limb (cm)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e53.96 (8.8)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e[53.15 \u0026ndash; 54.78]\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.7pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e57.70 (8.36)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e[56.93 -58.48]\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e58.15 (8.36)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e[57.384 \u0026ndash; 58.93]\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.45pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e0.001\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 139.95pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003eStep length- less symptomatic limb (cm)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e54.07 (9.0)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e[53.24 \u0026ndash; 54.9]\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.7pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e57.86 (8.63)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e[57.06 \u0026ndash; 58.66]\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e58.34 (8.44)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e[57.564 \u0026ndash; 59.12]\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.45pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 139.95pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003eSingle limb support- more symptomatic limb (% GC\u003csup\u003e*\u003c/sup\u003e)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e36.55 (2.42)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e[36.32 \u0026ndash; 36.79]\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.7pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e37.68 (2.10)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e[37.49 \u0026ndash; 37.88]\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e37.72 (2.09)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e[37.53 -37.92]\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.45pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 139.95pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003eSingle limb support- less symptomatic limb (% GC\u003csup\u003e*\u003c/sup\u003e)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79.8pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e38.34 (2.06)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e[38.15 - 38.53]\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.7pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e38.53 (1.99)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e[38.34 \u0026ndash; 38.71]\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e38.56 (1.93)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e[38.39 \u0026ndash; 38.74]\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.45pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e0.003\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003eN=455; *GC Gait Cycle; P-value was set to P \u0026lt; 0.05.\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003eRepeated measure ANOVA\u0026rsquo;s were performed for the differences between the outcomes, measured at baseline, 3 and 6 months into treatment. Significant differences were found between baseline and 3 months and baseline and 6 months.\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003cstrong\u003e\u003cspan style=\"font-family: Helvetica; font-size: 13px; color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003cbr\u003e \u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\u003cbr\u003e\n\u003cp\u003e\u003cspan lang=\"EN-GB\"\u003eThere was a significant improvement in KOFG between baseline and 3 months follow-up (p\u0026lt;0.001), with retained improvements at 6 months. Table 3 displays the changes in classification over the 6 months of treatment. It shows a shift from more severe functional grades to less severe levels over time (improved functional outcomes). More specifically, at baseline two thirds (71%) of the patients were classified with grade 1 and 2 (i.e. mild-moderate functional limitation) and a third of the patients (29%) were classified with grade 3 and 4 (i.e. moderate-severe functional severity). After 6 months of treatment 86% of the patients were with a functional classification grade 1 \u0026amp; 2 and 14% with grade 3 and 4 respectively.\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;margin-bottom:.0001pt;text-align:justify;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style=\"font-family: Helvetica; font-size: 13px; color: rgb(0, 0, 0);\"\u003eTable 3.\u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e Knee Osteoarthritis Functional Grade (KOFG)\u003csup\u003e*\u003c/sup\u003e changes in patients after 3 and 6 months of treatment. Values are presented as n (%).\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 110.35pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;margin-bottom:.0001pt;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110.35pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;margin-bottom:.0001pt;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003eBaseline\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110.35pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;margin-bottom:.0001pt;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e3 months\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110.35pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;margin-bottom:.0001pt;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e6 months\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 110.35pt;border: none;padding: 0in 5.4pt;height: 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;margin-bottom:.0001pt;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003eGrade 1\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110.35pt;border: none;padding: 0in 5.4pt;height: 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;margin-bottom:.0001pt;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e117 (25.71%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110.35pt;border: none;padding: 0in 5.4pt;height: 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;margin-bottom:.0001pt;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e190 (41.76%)\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110.35pt;border: none;padding: 0in 5.4pt;height: 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;margin-bottom:.0001pt;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026nbsp;197 (43.29%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 110.35pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;margin-bottom:.0001pt;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003eGrade 2\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110.35pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;margin-bottom:.0001pt;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e207 (45.49%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110.35pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;margin-bottom:.0001pt;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e193 (42.42%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110.35pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;margin-bottom:.0001pt;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e196 (43.07%)\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 110.35pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;margin-bottom:.0001pt;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003eGrade 3\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110.35pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;margin-bottom:.0001pt;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e95 (20.88%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110.35pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;margin-bottom:.0001pt;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e62 (13.63%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110.35pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;margin-bottom:.0001pt;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e52 (11.43%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 110.35pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;margin-bottom:.0001pt;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003eGrade 4\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110.35pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;margin-bottom:.0001pt;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e36 (7.91%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110.35pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;margin-bottom:.0001pt;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e10 (2.19%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110.35pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;margin-bottom:.0001pt;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e10 (2.19%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 441.4pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 26.15pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;margin-bottom:.0001pt;line-height:200%;'\u003e\u003cspan style=\"font-family: Helvetica; font-size: 13px; color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 200%;\"\u003eDescriptive statistics of patient\u0026#39;s grade distribution over time. The average grade was 2.1 at baseline, 1.8 at 3 months and 1.7 at 6 months. Significant differences were found in paired T-test between baseline and 3 months (p\u0026lt;0.001) and between baseline and 6 months (p\u0026lt;0.001). There were no significant differences in mean grade score between 3 and 6 months (p=0.01) *Grade 1- least severe, Grade 4- most severe\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\u003cbr\u003e\n\u003cp\u003eFollowing 6 months of treatment, all patients\u0026rsquo; self-evaluation questionnaires improved significantly. All WOMAC subscales significantly improved following 3 months of treatment, with further improvements at 6 months (p\u0026lt;0.001). WOMAC Total, along with pain, function and stiffness subscales improved by 46.2%, 48.6%, 45.7% and 43.4% respectively (p\u0026lt;0.001 for all). 67% of the patients met the OMERACT-OARSI criteria (307/455 significantly improved). Table 4 displays the absolute changes from baseline to 6 months.\u003c/p\u003e\n\u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style=\"font-family: Helvetica; font-size: 13px; color: rgb(0, 0, 0);\"\u003eTable 4.\u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e Patient reported outcome measures (PROM\u0026rsquo;s) changes in knee OA patients after 3 and 6 months of treatment. Results are presented as mean (SD) [95% CI]\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 146.45pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80.1pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003eBaseline\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e3 months\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e6 months\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.8pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003eP-value\u003csup\u003e*\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 146.45pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 200%;\"\u003eWOMAC\u003c/span\u003e\u003c/strong\u003e\u003csup\u003e\u003cspan style=\"line-height: 200%;\"\u003e**\u003c/span\u003e\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80.1pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New 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Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e[20.61 \u0026ndash; 23.96]\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 146.45pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003ePain subscale\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80.1pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e46.71 (18.86)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e[44.97 \u0026ndash; 48.44]\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e27.42 (19.72)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e[25.60 \u0026ndash; 29.24]\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New 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top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e38.97 (21.56)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e[36.98 \u0026ndash; 40.96]\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New 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Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e[19.45 \u0026ndash; 22.86]\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 146.45pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003eStiffness subscale\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80.1pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e48.74 (25.92)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e[46.35 \u0026ndash; 51.13]\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e30.71 (25.92)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e[28.48 \u0026ndash; 32.95]\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e27.59 (23.15)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e[25.45 \u0026ndash; 29.72]\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 146.45pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 200%;\"\u003eSF-36\u003c/span\u003e\u003c/strong\u003e\u003csup\u003e\u003cspan style=\"line-height: 200%;\"\u003e***\u003c/span\u003e\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80.1pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 146.45pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003eTotal\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80.1pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e53.49 (16.08)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e[52.01 \u0026ndash; 54.97]\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e62.60 (16.57)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e[61.08 \u0026ndash; 64.13]\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e65.22 (16.87)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e[63.67 \u0026ndash; 66.78]\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 146.45pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003ePhysical Component Summary (PCS)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80.1pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e45.67 (18.36)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e[43.98 \u0026ndash; 47.36]\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e57.71 (19.85)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e[55.88 \u0026ndash; 59.54]\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e61.37 (20.04)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e[59.52 \u0026ndash; 63.21]\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 146.45pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003eMental Component Summary (MCS)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80.1pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e64.02 (19.49)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e[62.23 \u0026ndash; 65.82]\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e72.30 (18.18)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e[70.63 \u0026ndash; 73.98]\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e73.64 (18.12)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e[71.97 \u0026ndash; 75.31]\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.8pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin:0in;margin-bottom:.0001pt;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 13px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e*P-value was set to\u0026nbsp;P\u0026nbsp;\u0026lt;\u0026nbsp;0.05. \u0026nbsp;\u0026nbsp;**Western Ontario and McMaster Universities Index (WOMAC Index). The WOMAC questionnaire includes 24 questions in a Visual Analogue Scale (VAS) format (0 = no pain/stiffness/difficulty, 100 = severe pain/stiffness/difficulty). ***SF-36 Health Survey includes 36 questions. Results range between 0\u0026ndash;100 (0 = poor quality of life, 100 = high quality of life).\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 13px; font-family: Helvetica;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003eRepeated measure ANOVA\u0026rsquo;s were performed for the differences between the outcomes, measured at baseline, 3 and 6 months into treatment. Significant differences were found between baseline and 3 months and baseline and 6 months.\u003c/span\u003e\u003cstrong\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\u003cbr\u003e\n\u003cp\u003eAll SF-36 subscales also significantly improved following 3 months of treatment (p\u0026lt;0.001). There were also further significant improvements between 3- and 6-month time intervals, except for the MCS (p= 0.068). After 6 months of treatment all subscales had significantly improved (p\u0026lt;0.001). Specifically, SF-36 Total, PCS and MCS improved by 11.73, 15.7, and 9.62 points, or 22%, 34% and 15% respectively compared to baseline (See Table 4). These improvements also met minimal clinical important differences (MCID) for clinical significance of 7.8 points (56).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA correlation analysis between gait and questionnaire improvement was calculated. First, a new parameter was calculated for each measurement. This was the difference between baseline and 6 months. Second, a correlation calculation between the changes in gait measures and the changes in questionnaires was calculated. A significant correlation was found between the changes in gait parameters and the changes in questionnaires (p\u0026lt;0.05 for all). More specifically, the correlation between the changes in gait velocity and the changes in pain, function, PCS and MCS was -0.30, -0.29, 0.33 and 0.20 respectively.\u003c/p\u003e\n\u003cp\u003eA sub-analysis was carried out on patients that had already been recommended knee joint replacement surgery (surgery recommended group) prior to commencing treatment (20%, 92 patients).\u0026nbsp; There were no significant differences in any baseline measures (WOMAC, SF-36 or gait parameters) between this cohort and the rest of the patients, apart from duration of symptoms prior to commencing treatment (no surgery recommended group: 67 months vs surgery recommended group: 83 months, p=0.013). Both groups improved significantly over time (p\u0026lt;0.05), meeting the MCID in all outcome measures. Despite improvements in all variables of both groups at 6 months, the recommended surgery group displayed higher WOMAC pain and stiffness subscales (p=0.027, and p=0.019, see Figure 3), and lower SLS in both the more and less symptomatic sides (p=0.04 and p=0.028).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe purpose of this study was to investigate the changes in spatial-temporal gait parameters and clinical measurements following treatment with a non-invasive foot-worn biomechanical device on patients with knee osteoarthritis within the UK. Following 3 months of treatment, patients demonstrated significant improvements in both gait and PROM\u0026rsquo;s, with maintained or further improvements occurring in all parameters after 6 months. The results suggest that most improvements occurred by 3 months, but further improvements occur between 3 and 6 months, apart from SLS in gait and MCS subscale of SF-36. This supports previous work which found that the largest improvements occurred within the initial few months of treatment and are then maintained (32). The improvements in WOMAC scores meet the OMERACT-OARSI guidelines for clinical response to treatment in 67% of the patients, signifying true positive impacts felt by patients (55). The thresholds for minimal clinical importance differences (MCID) within SF-36 were also met, suggesting improvements in quality of life following treatment (56). In addition, these improvements in self-evaluation questionnaires correlated with the significant improvements in gait.\u003c/p\u003e\n\u003cp\u003ePROM\u0026rsquo;s along-with radiographic findings have historically been used to track knee OA outcomes and are leading predictors in guiding the decision upon joint replacement surgery (57). However, the low correlation between radiographic findings and patient symptoms has since become more acknowledged (58), and therefore the importance of more objective and functional measures to evaluate patient symptoms has become apparent. Previous research has proposed spatial-temporal parameters are a good indicator for functional severity (12, 58), with a recent meta-analysis suggesting that stride duration and cadence provided a better reflection of knee OA severity than kinematic and kinetic measures (59).\u003c/p\u003e\n\u003cp\u003eUsing the patients\u0026rsquo; cadence and stride lengths as predictor variables for knee OA severity forms the basis of the validated Knee Osteoarthritis Functional Grade or KOFG (13), which in a follow-up study was also validated as a classification tool to measure treatment effect (60).\u0026nbsp; A combination of spatial-temporal parameters objectively classifies patients with knee OA according to functional disease severity, which have been shown to correlate with radiographic evaluation, the level of pain, function and rate of TKR.\u0026nbsp; The benefit of this tool is the ability to quantify the severity of disease and to assess the impact of an intervention, rather than just stating the change in gait analysis parameters (60). The model suggests that a shorter stride length with lower cadence is indicative of a higher functional severity grade (more severe knee OA), while a longer stride length with higher cadence is indicative of a lower functional severity grade (less severe knee OA). Within this current study, there was a significant improvement in KOFG between baseline and 3 months follow-up (p\u0026lt;0.001), with retained improvement at 6 months. The shift from more severe to less severe KOFG suggest patients not only improvement in symptoms, but actually move away from measures associated with increased rates of TKR (13, 60).\u003c/p\u003e\n\u003cp\u003eThe present study also examined whether there were any differences in the sub-group of patients (20%) that had already been offered joint replacement surgery (TKR/PKR) prior to commencing treatment. Interestingly, aside from the duration of symptoms, there were no significant differences between cohorts at baseline, suggesting that those patients that had been recommended surgery as a suitable option for their condition, displayed the same characteristics as those that have not had surgical recommendation (Figure 3). Research reports most patients that are suitable for TKR have WOMAC baseline scores between 40s to 50\u0026rsquo;s (57), which could indicate that the cohorts analysed within this study are representative of this population. Furthermore, significant improvements seen across both groups (Figure 3) suggests these populations can respond well to this treatment in levels of pain, function and quality of life measures. Differences between these two groups were seen at 6 months, including significantly higher WOMAC pain and stiffness subscales (p=0.027, and p=0.019), and significantly lower SLS in both the more and less symptomatic sides (p=0.04 and p=0.028) in the recommended surgery group. The reduction of improvements within this group could be explained by significantly longer durations of symptoms experienced by the patients, suggesting more chronicity of the condition. Previous studies have investigated the durations of symptoms and their relationship to clinical improvements and have suggested that optimising the timing that patients access relevant treatments could be key to optimising outcomes (61). Despite this, the overall improvements in both groups are marked and suggestive that the treatment could be an effective alternative for a number of patients that would otherwise have progressed to surgery.\u003c/p\u003e\n\u003cp\u003eResearchers have presented several theories explaining how this treatment works to improve symptoms in patients with knee OA. Studies have shown that the biomechanical device can reduce the external loads acting on the body to \u0026ldquo;unload\u0026rdquo; the painful area, which is said to be important when treating this condition (43, 44). It has been shown to reduce the 1\u003csup\u003est\u003c/sup\u003e and 2\u003csup\u003end\u003c/sup\u003e peak KAM and KAAI by 8.4%, 12.7 % and 13% after 9 months of treatment respectively (38). An important factor to note with the improvements in biomechanical variables seen with the device is that they remained, even when the patient was not wearing the device. This suggests that a motor learning effect occurs as a result of the neuromuscular retraining received from the treatment (46). Neuromuscular training is delivered by a controlled level of perturbation via the convex nature of the elements (46, 47). The combined features of the biomechanical device allow for repetitive perturbations with diminished pain throughout the gait cycle. Patients wearing the devices for prescribed periods every day means that they gain high repetitions of closed kinetic chain, functional exercises and improved levels of compliance said to be advantageous for motor learning (62-64). This combination of key rehabilitation principles allows the patient to reacquire improved neuromuscular control, thus avoiding pathological patterns previously utilised whilst in pain (31).\u003c/p\u003e\n\u003cp\u003eGiven knee OA is a chronic degenerative condition, symptoms deteriorate over time at varying rates (65). Currently, interventions are directed to the end-stages of the disease and therefore can often be ineffective and palliative in nature (66). Whilst the literature reports that the number of patients progressing to having joint replacement surgery is growing (6), approximately 20-40% of those completed are considered inappropriate. These were classified due to having only slight or moderate symptoms, or not severe enough radiographic findings and therefore TKR deemed unnecessary (67, 68). A paradigm shift is needed to focus efforts on treating patients at high-risk earlier in the disease progression (66), or utilising more specialist modalities\u0026nbsp; that can help minimise this potentially inappropriate flow to surgery. The results of this study display a combination of improvements in both subjective PROM\u0026rsquo;s and objective spatial-temporal gait parameters which are promising and may indicate that the biomechanical device used in this study has the ability to be an effective modality in managing this chronic condition, however further studies in a controlled setting are required.\u003c/p\u003e\n\u003cp\u003eThis study has some limitations. Firstly, the study was a retrospective analysis of patients from the centres database and therefore had no control group. However, a previous study has demonstrated comparable positive effects of this treatment compared to a control group in a double-blind study (31). In addition, patients were allowed to continue with traditional care, and we cannot determine that other treatment did not affect the results of this study. Patients are usually characterised with a moderate-severe knee OA and commence the current treatment after trying traditional care with little to no success. The treatment is often undertaken as one final attempt to address the condition non-invasively prior to the need for a surgical intervention. As a result, we believe most of the clinical effect seen in this study can be attributed to the biomechanical device and treatment plan as opposed to any adjunctive or continued treatment modalities. Potentially, a combined approach of exercise therapy utilised alongside the biomechanical treatment may yield further superior effects compared to the device alone and this should be investigated in a controlled setting in the future.\u003c/p\u003e\n\u003cp\u003eSecondly, this study had a relatively short follow-up duration of 6 months for this cohort. Long-term follow-up would give more insight into the lasting effects of the treatment. However, it reflects previous research on the treatment on different populations with similar improvements in gait and PROM\u0026rsquo;s (33-35, 69). Therefore, it could be assumed that the improvements can be maintained with the high compliance rates in the treatment (32).\u0026nbsp; Nevertheless, future research should continue to investigate the long-term clinical effect of the treatment, in prospective, randomised control trial (RCT) design whilst tracking decay rates for joint replacement surgeries. Promisingly, preliminary data from an RCT on the effect of this treatment displays comparable improvements to this study (70).\u003c/p\u003e\n\u003cp\u003eLastly, this study did not monitor the overall activity level of the patients in general and this compliance to the treatment plan in specifics. We cannot confirm the usage time of the device at home other than when the patients returned to the clinic for a follow-up appointment and reported that they have been using the device daily. Future studies should enforce methods to monitor compliance to the treatment plan at home.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe examined non-invasive biomechanical treatment led to a significant improvement in gait patterns, pain, function and quality of life for UK patients suffering with knee OA, although further studies in a controlled setting are required to investigate its clinical effect further. It appears to create a comparable response between patients that have already been recommended knee joint replacement surgery and those that have not been recommended, therefore potentially providing an alternative solution for this population. If these results can be retained in the longer term, it could hypothetically delay or even avoid the need for surgery in many cases which provides an area for examination in future trials. Whilst further studies in controlled settings are required in order to fully understand the clinical effect of this treatment, this study suggests that it may provide positive clinical implications for patients, with the potential to provide a sustainable modality for healthcare systems to manage knee OA patients effectively in the community setting.\u003c/p\u003e"},{"header":"List Of Abbreviations","content":"\u003cp\u003eOA - Osteoarthritis\u003c/p\u003e\n\u003cp\u003eNICE - National Institute of Clinical Excellence (NICE)\u003c/p\u003e\n\u003cp\u003eTKR - Total knee replacement (TKR)\u003c/p\u003e\n\u003cp\u003ePROM's - patient reported outcome measures (PROM\u0026rsquo;s),\u003c/p\u003e\n\u003cp\u003eKAM - knee adductor moment (KAM)\u003c/p\u003e\n\u003cp\u003eKAAI - knee adductor angular impulse (KAAI)\u003c/p\u003e\n\u003cp\u003eLED - light emitting diode (LED)\u003c/p\u003e\n\u003cp\u003eSLS - single-limb support (SLS)\u003c/p\u003e\n\u003cp\u003eKOFG - Knee Osteoarthritis Function Grade (KOFG)\u003c/p\u003e\n\u003cp\u003eVAS - visual analogue scale (VAS)\u003c/p\u003e\n\u003cp\u003ePCS - Physical Component Summary (PCS)\u003c/p\u003e\n\u003cp\u003eMCS - Mental Component Summary (MCS)\u003c/p\u003e\n\u003cp\u003eCOP - Center of pressure (COP)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;OMERACT-OARSI - Outcome Measures in Rheumatology Clinical Trials (OMERACT)-Osteoarthritis Research Society International (OARSI)\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cu\u003eEthics approval and consent to participate\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThe protocol was approved by the University of Roehampton Ethics Committee and all participants provided written consent for their data to be used within the study\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eConsent for publication\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eN/A\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eAvailability of data and materials\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eAll data requests will be reviewed and addressed by the authors\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eCompeting interests\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eNone to declare\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eFunding\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThis study was not funded in any way\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eAuthors' contributions\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eAll authors take full responsibility for the entire manuscript content, integrity of the data and the accuracy of the data analysis.\u003c/p\u003e\n\u003cp\u003eStudy Concept and Design: CM, AG.\u003c/p\u003e\n\u003cp\u003eAcquisition of data: CM\u003c/p\u003e\n\u003cp\u003eAnalysis and Interpretation of Data: CM\u003c/p\u003e\n\u003cp\u003eDrafting of the Manuscript: CM\u003c/p\u003e\n\u003cp\u003eCritical Revision of the Manuscript for Important Intellectual Content: AG\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eAcknowledgements\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank Apos Medical UK Ltd for allowing access to the data. The authors would also like to thank Dr..Ornit Cohen for her statistical analysis support.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eOsteoarthritis in General Practice.\u0026nbsp; \u003ca href=\"about:blank\"\u003ewww.arthritisresearchuk.org2013\u003c/a\u003e [\u003c/li\u003e\n\u003cli\u003eArden N, Nevitt MC. Osteoarthritis: epidemiology. Best Pract Res Clin Rheumatol. 2006;20(1):3-25.\u003c/li\u003e\n\u003cli\u003eGupta S, Hawker GA, Laporte A, Croxford R, Coyte PC. The economic burden of disabling hip and knee osteoarthritis (OA) from the perspective of individuals living with this condition. Rheumatology (Oxford). 2005;44(12):1531-7.\u003c/li\u003e\n\u003cli\u003eNICE. Osteoarthritis: care and management (CG177). \u003ca href=\"about:blank\"\u003ehttps://www.nice.org.uk/guidance/cg177\u003c/a\u003e [\u003c/li\u003e\n\u003cli\u003eCarr AJ, Robertsson O, Graves S, Price AJ, Arden NK, Judge A, et al. Knee replacement. 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Foot center of pressure manipulation and gait therapy influence lower limb muscle activation in patients with osteoarthritis of the knee. J Electromyogr Kinesiol. 2011;21(5):704-11.\u003c/li\u003e\n\u003cli\u003eDebbi EM, Wolf A, Goryachev Y, Rozen N, Haim A. Alterations in sagittal plane knee kinetics in knee osteoarthritis using a biomechanical therapy device. Ann Biomed Eng. 2015;43(5):1089-97.\u003c/li\u003e\n\u003cli\u003eSegal G, Bar-Ziv Y, Velkes S, Benkovich V, Stanger G, Debbi EM, et al. A non-invasive biomechanical device and treatment for patients following total hip arthroplasty: results of a 6-month pilot investigation. J Orthop Surg Res. 2013;8:13.\u003c/li\u003e\n\u003cli\u003eElbaz A, Mirovsky Y, Mor A, Enosh S, Debbi E, Segal G, et al. A novel biomechanical device improves gait pattern in patient with chronic nonspecific low back pain. 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Br J Sports Med. 2011;45(4):283-8.\u003c/li\u003e\n\u003cli\u003eRiddle DL, Jiranek WA, Hayes CW. Use of a validated algorithm to judge the appropriateness of total knee arthroplasty in the United States: a multicenter longitudinal cohort study. Arthritis Rheumatol. 2014;66(8):2134-43.\u003c/li\u003e\n\u003cli\u003eGhomrawi HM, Schackman BR, Mushlin AI. Appropriateness criteria and elective procedures--total joint arthroplasty. N Engl J Med. 2012;367(26):2467-9.\u003c/li\u003e\n\u003cli\u003eElbaz A, Mor A, Segal G, Aloni Y, Teo YH, Teo YS, et al. Patients with knee osteoarthritis demonstrate improved gait pattern and reduced pain following a non-invasive biomechanical therapy: a prospective multi-centre study on Singaporean population. J Orthop Surg Res. 2014;9:1.\u003c/li\u003e\n\u003cli\u003eReichenbach S, Heldner S, Lenz A, Felson D, Juni P. LB0002 Biomechanical therapy for osteoarthritis of the knee: a randomised controlled trial (BIOTOK). Annals of the Rheumatic diseases.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-musculoskeletal-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmsd","sideBox":"Learn more about [BMC Musculoskeletal Disorders](http://bmcmusculoskeletdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://author-welcome.nature.com/12891","title":"BMC Musculoskeletal Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Knee osteoarthritis; Gait; Pain; Function; Biomechanical treatment","lastPublishedDoi":"10.21203/rs.3.rs-16291/v3","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-16291/v3","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cem\u003eBackground:\u0026nbsp;\u003c/em\u003eOsteoarthritis is a major cause of pain and disability worldwide, therefore ways of treating this condition are paramount to a successful health system. The purpose of the study was to investigate the changes in spatial-temporal gait parameters and clinical measurements following treatment with a non-invasive foot-worn biomechanical device on patients with knee osteoarthritis within the UK. \u003c/p\u003e\u003cp\u003e\u003cem\u003eMethods:\u0026nbsp;\u003c/em\u003eA retrospective analysis was carried out on 455 patients with knee osteoarthritis. All patients were evaluated using a computerized gait test and two self-assessment questionnaires (WOMAC and SF-36) at baseline and after 3 and 6 months of treatment. The biomechanical device is a shoe-like device with convex pods under the sole that have the capability of changing foot centre of pressure and training neuromuscular control. The device was individually calibrated for each patient to minimise symptoms whilst walking and train neuromuscular control. Patients used the device for short periods during activities of daily living. Repeated measures statistical analyses were performed to compare differences over time.\u003c/p\u003e\u003cp\u003e\u003cem\u003eResults:\u003c/em\u003e\u0026nbsp;After 6 months of treatment significant improvements were seen in all gait parameters (p\u0026lt;0.01). Specifically, gait velocity, step length and single limb support of the more symptomatic knee improved by 13%, 7.8% and 3%, respectively. These were supported by significant improvements in pain, function and quality of life (48.6%, 45.7% and 22% respectively; p\u0026lt;0.001). A sub-group analysis revealed no baseline differences between those who were recommended joint replacement and those who were not. Both groups improved significantly over time (p\u0026lt;0.05 for all).\u003c/p\u003e\u003cp\u003e\u003cem\u003eConclusions:\u003c/em\u003e\u0026nbsp;Our results suggest that the personalised biomechanical treatment can improve gait patterns, pain, function and quality of life. It may provide an additional solution to managing UK patients suffering from knee osteoarthritis but needs to be tested in a controlled setting first.\u003c/p\u003e","manuscriptTitle":"The effect of treatment with a non-invasive foot worn biomechanical device on subjective and objective measures in patients with knee osteoarthritis- A retrospective analysis on a UK population","msid":"","msnumber":"","nonDraftVersions":[{"code":3,"date":"2020-06-04 18:51:33","doi":"10.21203/rs.3.rs-16291/v3","editorialEvents":[{"type":"communityComments","content":0},{"type":"checksComplete","content":"","date":"2020-05-29T12:00:00+00:00","index":"","fulltext":""},{"type":"decision","content":"Accept","date":"2020-05-28T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2020-05-27T00:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-05-26T23:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-musculoskeletal-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmsd","sideBox":"Learn more about [BMC Musculoskeletal Disorders](http://bmcmusculoskeletdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://author-welcome.nature.com/12891","title":"BMC Musculoskeletal Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":2,"date":"2020-05-04 14:39:35","doi":"10.21203/rs.3.rs-16291/v2","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor revision","date":"2020-05-26T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-05-23T12:00:00+00:00","index":2,"fulltext":"Recommendation: Accept without revision\nForm responses:\n---\n\nComments to Author:\n---\n* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I recommend additional statistical review**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests below**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please publish my name with my report.**\n"},{"type":"reviewerAgreed","content":"","date":"2020-05-05T12:00:00+00:00","index":2,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-05-03T12:00:00+00:00","index":1,"fulltext":"Recommendation: Accept without revision\nForm responses:\n---\n\nComments to Author:\n---\nPlease include all comments for the authors in this box rather than uploading your report as an attachment. Please only upload as attachments annotated versions of manuscripts, graphs, supporting materials or other aspects of your report which cannot be included in a text format.\nPlease overwrite this text when adding your comments to the authors.* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n"},{"type":"reviewerAgreed","content":"","date":"2020-05-01T12:00:00+00:00","index":1,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2020-04-28T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2020-04-21T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-04-20T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-04-20T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-musculoskeletal-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmsd","sideBox":"Learn more about [BMC Musculoskeletal Disorders](http://bmcmusculoskeletdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://author-welcome.nature.com/12891","title":"BMC Musculoskeletal Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2020-03-09 14:58:55","doi":"10.21203/rs.3.rs-16291/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2020-04-02T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-03-27T12:00:00+00:00","index":4,"fulltext":"Recommendation: Reviewer's comments unavailable pending editorial decision\n"},{"type":"editorInvitedReview","content":"","date":"2020-03-26T12:00:00+00:00","index":3,"fulltext":"Recommendation: Major revisions required\nForm responses:\n---\n\nComments to Author:\n---\nThe manuscript presents the results of a retrospective analysis investigating the changes in spatial-temporal gait parameters and clinical measurements following treatment with a non-invasive biomechanical device in patients with knee osteoarthritis.\n\nOverall, I have major concerns when it comes to the quality of evidence of the study and the conclusions made.\nIn the following I will briefly state my concern and I will not go into more details of the manuscript before these issues have been addressed and the interpretation of the results have been critically revised.\n\nWith the aim of investigating changes of a biomechanical device in patients with knee osteoarthritis the use of a randomised controlled trial would be the design to choose in order to answer the research question.\nInvestigating changes and concluding on the effect of an intervention on the chosen outcomes requires a control group. This is not the case in this study.\nHowever, data from a retrospective, uncontrolled, non-randomised study are presented. Therefore, I find it highly inappropriate and critical that the authors conclude: \"The examined non-invasive biomechanical treatment appears to provide an effective treatment that improves gait patterns, pain, function and quality of life for UK patients suffering with knee OA\"\nThe changes presented in this study are observational data and it is highly crucial that the conclusions drawn from these observations should be revised critically.\n\nAre there any data available on a comparable background population not receiving any intervention? If not, a suggestion could be to use the data to inform a coming large RCT study and describe the feasibility of the intervention. If so it would be highly relevant to include data on compliance and adverse events if available.\n\nIn its current form I can not recommend this manuscript to be published.\n* Are the methods appropriate and well described?: **No**\n* Does the work include the necessary controls?: **No**\n* Are the conclusions drawn adequately supported by the data shown?: **No**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I recommend additional statistical review**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* I agree to the open peer review policy of the journal. I understand that my name will be included on my report to the authors and, if the manuscript is accepted for publication, my named report including any attachments I upload will be posted on the website along with the authors' responses. I agree for my report to be made available under an Open Access Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/). I understand that any comments which I do not wish to be included in my named report can be included as confidential comments to the editors, which will not be published.: ** I agree to the open peer review policy of the journal**\n"},{"type":"editorInvitedReview","content":"","date":"2020-03-26T12:00:00+00:00","index":2,"fulltext":"Recommendation: Major revisions required\nForm responses:\n---\n\nComments to Author:\n---\nReview Comments for the Author(s)\nJournal: BMC Musculoskeletal Disorders\nManuscript Number: BMSD-D-20-00427\nTitle: The effect of a non-invasive biomechanical treatment on subjective and objective measures in patients with knee osteoarthritis- A retrospective analysis on a UK population\nOverview: This is a study analyzing the results after a non-invasive biomechanical device on patients with knee OA. In this paper, the authors show improved gait pattern, pain, function, and quality of life after 3 and 6 months.\n\nComments:\n1. Title\nIn the title \"a non-invasive biomechanical treatment\" should be described clearer and should include a footwear device.\n2. Abstract\nIn the title, the intervention has been describing as a non-invasive biomechanical treatment and at Line 37, it is a therapy and at Line 44 it is a personalized biomechanical intervention.\nIs it a treatment, therapy or intervention? Please be consistent throughout the whole manuscript.\nLines 32-33; …The biomechanical device was individually calibrated…, please describe the device (footwear device).\nLine 34, you say they train neuromuscular control, I can not find that in the manuscript, please add a part about this in the method section.\n3. Keywords\nThe keywords are suitable.\n4. Introduction and aim\nThe introduction is well written and concise; however, some parts need to be extended.\nLine 92, please describe what a personalized non-invasive biomechanical treatment is, and please state the hypothesis behind the intervention, and why the results should be different on a UK population?\nLine 95, you say, \"Therefore, this study aims to review the effect of this therapy on UK populations suffering with knee OA.\" Can you evaluate the effect of the therapy without a control group? In the abstract, on line 26 you say that the aim is …\" The purpose of the study was to investigate the changes in spatial-temporal gait parameters and clinical measurements following treatment with a non-invasive biomechanical device on patients with knee osteoarthritis within the UK.\". I think this aim is better, but in the result part, you report even more data. Please control that all your aims are clarified and clear and match the data you report in the result part.\n\n5. Methods\nStudy design and procedure\nLine 104, please describe that kind of database this is. What kind of patients are in the database (primary care, secondary care, etc.), have these patients search health care caused by their OA or are they asked for participation in a study?\na study? Is this a database own by the device company or by health care? Please describe this clear.\nParticipants\nFigure 1, Why did they need to have symptoms for at least 6 months? In the square for exclusion criteria, you wrote that 12 (significant OA in other lower limb joints), what is significant OA?\nLine 107-109, here you describe the patients, but I miss a table with baseline characteristics with, age, sex, BMI, unilateral/bilateral OA, OA other joints, education, comorbid conditions, joint history and joint-specific surgical history (all parameters that may affect the results of treatment in patients with OA), do you have this information?\nLine 111-122, please describe how the OptoGait system was used and how did it ( a trained physical therapist? the devising company? Etc.) and were the test was done, in one or five different gait laboratories? In which area in UK?\nLine 119-120, you say that step length and SLS were calculated for the less and more symptomatic limbs respectively, do they have bilateral OA, or why do they have symptoms from both knees?\nLine 141, Figure 2, it is unclear if the device can be put to all shoes or if the patients get new shoes? are the device/shoes for free or do the patients need to pay for them? How do you think this will affect your results? Please describe the device in the method and discuss it in the discussion part.\nLine 149, here you describe that the patients received instructions to wear the device, but did they have a dairy to double-check the compliance to the device? Were the patients told to do something in combination with the intervention, exercise? Do you have information about exercise and physical activity? Do they have devices on both shoes, or only on the feet with the affected knee? Please describe this part so detailed that someone else can redo the study.\n\nStatistical analysis\nLine 155, add a header for statistical analysis\nLine 165, you say that multiple linear regression was used to address the percentages changes after 6 months, is this correct? In the abstract you say that your aim is; \"The purpose of the study was to investigate the changes in spatial-temporal gait parameters and clinical measurements following treatment with a non-invasive biomechanical device on patients with knee osteoarthritis within the UK\", do you need to do a regression model to answer that aim?\nLine 171, you say that you adjust for age and sex as potential confounders, do you think you should adjust for more potentially confounders as BMI, earlier surgery to the knee?\n\nResults\nTable 1,\n- add SD [95% CI] in the table\n- add the number of patients in the table\n- under the table *GC Gait Cycle, I can´t find any * in the table\n- please add under the table how you get the p-value, and if it is a difference between baseline and 3 months or 6 months or both?\n- The difference between more and less symptomatic limb is very small, is this left and right knee or something else?\nTable 2\n- Please add the value for all variables (n, %)?\n- Please add a column with p-value and describe the method under the table now, the result is unclear\n- The * is missed in the table but is explained under the table\n\nLine 195, you write that WOMAC meets the OMERACT responder criteria, is this a part of your aim? In that case, add it to the aim and the method section. You can move lines 195-200 to the method section and only report the result in the result section.\nTable 3\n- Add SD [95% CI] in the table\n- The * is missed in the table but is explained under the table\n- Please add under the table how you get the p-value, and is a difference between baseline and 3 months or 6 months or both?\nLine 207-208, …These improvements also met minimal clinical….., add to aim if it is an aim to evaluate it and move the part to the method section and report only the result in the result section\nLine 210, you wrote about a correlation analysis, is this a part of the aim? Add it\nLine 217, …a sub-analysis was carried out…., is this a part of the aim? Add it, and explain in the introduction why this is interesting.\nLine 220, you described a difference between the two groups in duration of symptoms before the therapy, I can´t find this information somewhere else? Add a column of the subgroup (surgery group) to the table of baseline characteristics and this will be very clear.\nFigure 3, In the heading it says …changes between patients that had been recommended for knee joint replacement surgery (TKR/PKR respectively), but in the information text under the figure, it says No surgery recommended /Surgery recommended, which one is correct?\nDiscussion\nLine 229, …was to evaluate the clinical effect…Can you evaluate the effect of a study with no control group?\nLine 275, should it be Figure 3 instead of Table 3?\nLine 299, you wrote that compliance to the intervention is important, but I can not find any information about the compliance in the result part, do you have any information about that?\nLine 317, under limitation please discuss the placebo effect, regression to the mean and other potential limitations that the patients have met a physical therapist 4-5 times to calibrate the device, they have got an external device (how much does that affect the results? new shoes? Ect.\nConclusion\nOk.\n\n\n\n\n\n\n\n* Are the methods appropriate and well described?: **No**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I recommend additional statistical review**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests´below.**\n* I agree to the open peer review policy of the journal. I understand that my name will be included on my report to the authors and, if the manuscript is accepted for publication, my named report including any attachments I upload will be posted on the website along with the authors' responses. I agree for my report to be made available under an Open Access Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/). I understand that any comments which I do not wish to be included in my named report can be included as confidential comments to the editors, which will not be published.: ** I agree to the open peer review policy of the journal**\n"},{"type":"reviewerAgreed","content":"","date":"2020-03-23T12:00:00+00:00","index":4,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-03-19T12:00:00+00:00","index":3,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-03-19T12:00:00+00:00","index":1,"fulltext":"Recommendation: Accept after minor essential revisions\nForm responses:\n---\n\nComments to Author:\n---\nThank you for the opportunity to review your manuscript.\n\nI have the following comments:\n\nAbstract:\n- it remains unclear what kind of device you tested, so please specify this: is it a brace, a sleeve, etc?\n- your statement \"It may provide an additional solution to managing UK patients suffering from knee osteoarthritis.\" cannot be drawn form your uncontrolled study, so you should add to this: '... , but needs to be tested in a controlled setting first'\n\nIntroduction:\n- also in the last paragraph of the Introduction, your intervention is still quite vague ('personalised non-invasive biomechanical treatment'), so please specify this, as the reader so far has no clue what you studied.\n\nMethods:\n- this starts with a sentence including 'the effect of the biomechanical therapy', please specify this somewhat more, as suggested in the previous comment\n- Furthermore, add a paragraph on this intervention, including a Figure. What is it, what kind of material, what are the previous studies in which this devide has been tested?\n- Also, add some more information on your cohort; what kind of treatment do they usually receive in your centre (of were they untreated during your study?)? Because of your uncontrolled design, this is of particular interest.\n\nResults:\n- You state that \"The improvements in the WOMAC scores meet the Outcome Measures in Rheumatology Clinical Trials (OMERACT)-Osteoarthritis Research Society International (OARSI) responder criteria for clinically significant improvement \", but you used your mean improvements of your cohort in this. However, you should use these responder critiria only to test for each individual patient if he/she meet this criteria, and than you should state what % of your cohort did meet it (which you also did).\n\nDiscussion:\n-\"the biomechanical device used in this study has the ability to be an effective modality in managing this chronic condition\"--\u003e as stated for the Abstract, you should add this this device first needs to be tested in a controlled design (RCT). This also concerns the Conclusions.\n- what about the combination of neuromuscular and strengthening exercise therapy with your devide, would that lead to superior effects than your devide only?\n* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* I agree to the open peer review policy of the journal. I understand that my name will be included on my report to the authors and, if the manuscript is accepted for publication, my named report including any attachments I upload will be posted on the website along with the authors' responses. I agree for my report to be made available under an Open Access Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/). I understand that any comments which I do not wish to be included in my named report can be included as confidential comments to the editors, which will not be published.: ** I agree to the open peer review policy of the journal**\n"},{"type":"reviewerAgreed","content":"","date":"2020-03-17T12:00:00+00:00","index":2,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-03-12T12:00:00+00:00","index":1,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2020-03-06T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2020-03-05T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-03-03T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-03-02T12:00:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"","date":"2020-02-24T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-musculoskeletal-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmsd","sideBox":"Learn more about [BMC Musculoskeletal Disorders](http://bmcmusculoskeletdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://author-welcome.nature.com/12891","title":"BMC Musculoskeletal Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4126b4e0-618b-4bad-bb61-e0f522c4ac3b","owner":[],"postedDate":"June 4th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":113689,"name":"Orthopedics"}],"tags":[],"updatedAt":"2020-06-21T20:15:40+00:00","versionOfRecord":{"articleIdentity":"rs-16291","link":"https://doi.org/10.1186/s12891-020-03382-3","journal":{"identity":"bmc-musculoskeletal-disorders","isVorOnly":false,"title":"BMC Musculoskeletal Disorders"},"publishedOn":"2020-06-16 12:00:00","publishedOnDateReadable":"June 16th, 2020"},"versionCreatedAt":"2020-06-04 18:51:33","video":"","vorDoi":"10.1186/s12891-020-03382-3","vorDoiUrl":"https://doi.org/10.1186/s12891-020-03382-3","workflowStages":[]},"version":"v3","identity":"rs-16291","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-16291","identity":"rs-16291","version":["v3"]},"buildId":"FbvkV6FR0MCFSLy54lSbu","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}