Transcranial direct current stimulation for knee osteoarthritis: a single-blind randomized sham-controlled trial

ObjectiveTo evaluate the effects of transcranial direct current stimulation on pain and other symptoms of knee osteoarthritis.MethodsWe performed a single-blind randomized sham-controlled trial with two parallel arms in an outpatient clinic of physical medicine and rehabilitation at a teaching hospital. We randomized 54 patients, 30–70 years of age, with knee osteoarthritis into two groups. They had morning stiffness ≤ 30 min, knee pain ≥ 3 months, joint crepitus, and Kellgren-Lawrence grade 1 or 2 on radiographs. For the active stimulation we administered 2 mA current, 20 min for each session and for the sham group 30 s stimulation and 20 min no current. Using the 10/20 International EEG system, the anode was fixed over the contralateral primary motor cortex (C3 or C4), and the cathode was placed on the ipsilateral supraorbital region (Fp1 or Fp2), with respect to the included knee. The program was repeated once daily over 5 consecutive days. Both groups received acetaminophen. We assessed the patients before and after the interventions, and three months post-intervention. The primary outcome was knee pain on the visual analog scale, and the secondary outcome was the Knee injury and Osteoarthritis Outcome Score.ResultsThere was a statistically significant reduction in the intensity of pain within sham and active groups (both p < 0.001), but no significant difference between the groups (p = 0.226). Analyses of the Knee injury and Osteoarthritis Outcome Scores showed no clinically important changes.ConclusionsTranscranial direct current stimulation does not reduce knee pain, does not abate other symptoms, and does not restore knee function in patients with knee osteoarthritis. The pain reduction in our study could be attributed to either placebo or the acetaminophen effect.     

Randomized clinical trial comparing of transcranial direct current stimulation (tDCS) and transcutaneous electrical nerve stimulation (TENS) in knee osteoarthritis

BackgroundDue to the limitations of pharmacological and surgical management of knee osteoarthritis (OA), several non-pharmacologic approaches including transcutaneous electrical nerve stimulation (TENS) and transcranial direct current stimulation (tDCS) have been introduced, with promising results.ObjectiveWe aimed to investigate and compare the therapeutic effects of TENS and tDCS for the treatment of patients with knee OA.MethodsIn this double-blinded randomized controlled trial, a total of 40 adult patients with knee OA were randomly allocated to either the TENS or the tDCS group. Patients in either group received 6 sessions of the TENS or tDCS for 2 weeks. Knee strengthening exercises were performed twice daily for the entire treatment period. Patients were evaluated using the visual analogue scale (VAS) and Western Ontario and McMaster Universities (WOMAC).ResultsSignificant improvement was observed in all outcomes in both TENS and tDCS groups at each follow up compared to baseline although the early improvement (first follow-up) in the WOMAC index was not significant in the TENS group. Based on the within-subject analysis, the behavior of two treatment groups did not differ regarding the changes in the course of the VAS, WOMAC score and its subscales, i.e. stiffness, pain and function (p = 0.263, 0.051, 0.198, 0.075, and 0.146, respectively).ConclusionsBased on the results of this study, the effect of tDCS and TENS was not significantly different on pain and function of patients with knee OA.     

Pre-treatment attentional processing speed and antidepressant response to transcranial direct current stimulation: Results from an international randomized controlled trial

Background

Transcranial direct current stimulation (tDCS) has promising antidepressant effects, however, clinical trials have shown variable efficacy. Pre-treatment neurocognitive functioning has previously been identified as an inter-individual predictor of tDCS antidepressant efficacy.

Transcranial direct current stimulation during treadmill training in children with cerebral palsy: A randomized controlled double-blind clinical trial

Impaired gait constitutes an important functional limitation in children with cerebral palsy (CP). Treadmill training has achieved encouraging results regarding improvements in the gait pattern of this population. Moreover, transcranial direct current stimulation (tDCS) is believed to potentiate the results achieved during the motor rehabilitation process. The aim of the present study was to determine the effect of the administration of tDCS during treadmill training on the gait pattern of children with spastic diparetic CP. A double-blind randomized controlled trial was carried out involving 24 children with CP allocated to either an experimental group (active anodal tDCS [1 mA] over the primary motor cortex of the dominant hemisphere) or control group (placebo tDCS) during ten 20-min sessions of treadmill training. The experimental group exhibited improvements in temporal functional mobility, gait variables (spatiotemporal and kinematics variables). The results were maintained one month after the end of the intervention. There was a significant change in corticospinal excitability as compared to control group. In the present study, the administration of tDCS during treadmill training potentiated the effects of motor training in children with spastic diparetic CP.     

Utilizing transcranial direct current stimulation to enhance laparoscopic technical skills training: A randomized controlled trial

BackgroundTranscranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that delivers constant, low electrical current resulting in changes to cortical excitability. Prior work suggests it may enhance motor learning giving it the potential to augment surgical technical skill acquisition.ObjectivesThe aim of this study was to test the efficacy of tDCS, coupled with motor skill training, to accelerate laparoscopic skill acquisition in a pre-registered (NCT03083483), double-blind and placebo-controlled study. We hypothesized that relative to sham tDCS, active tDCS would accelerate the development of laparoscopic technical skills, as measured by the Fundamentals of Laparoscopic Surgery (FLS) Peg Transfer task quantitative metrics.MethodsIn this study, sixty subjects (mean age 22.7 years with 42 females) were randomized into sham or active tDCS in either bilateral primary motor cortex (bM1) or supplementary motor area (SMA) electrode configurations. All subjects practiced the FLS Peg Transfer Task during six 20-min training blocks, which were preceded and followed by a single trial pre-test and post-test. The primary outcome was changes in laparoscopic skill performance over time, quantified by group differences in completion time from pre-test to post-test and learning curves developed from a calculated score accounting for errors.ResultsLearning curves calculated over the six 20-min training blocks showed significantly greater improvement in performance for the bM1 group than the sham group (t = 2.07, p = 0.039), with the bM1 group achieving approximately the same amount of improvement in 4 blocks compared to the 6 blocks required of the sham group. The SMA group also showed greater mean improvement than sham, but exhibited more variable learning performance and differences relative to sham were not significant (t = 0.85, p = 0.400). A significant main effect was present for pre-test versus post-test times (F = 133.2, p < 0.001), with lower completion times at post-test, however these did not significantly differ for the training groups.ConclusionLaparoscopic skill training with active bilateral tDCS exhibited significantly greater learning relative to sham. The potential for tDCS to enhance the training of surgical skills, therefore, merits further investigation to determine if these preliminary results may be replicated and extended.     

Repetitive transcranial magnetic stimulation (rTMS) versus transcranial direct current stimulation (tDCS) in the management of patients with fibromyalgia: A randomized controlled trial

ObjectivesThe aim of this study was to compare the effects of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) on pain and quality of life in patients with fibromyalgia.MethodsThirty participants were randomized into two groups of 15 patients, to receive 3 sessions of either high-frequency (10 Hz) rTMS or 2 mA, 20 min anodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex (DLPFC) over 1 week. Pain was assessed using a Visual Analog Scale (VAS) before treatment, immediately after treatment, 6 and 12 weeks later. Quality of life was evaluated using the Revised Fibromyalgia Impact Questionnaire (FIQR) and psychiatric symptoms were measured using the Depression Anxiety Stress Scale-21 Item (DASS-21) before treatment, and 6 and 12 weeks after treatment.ResultsFor the VAS there was a significant time-group interaction, showing that the behavior of two groups differed regarding changes of VAS in favor of the RTMS group (df = 1.73, F = 4.80, p = <0.016). Time-group interaction effect on DASS-21 and FIQR was not significant. 66.6% of patients in rTMS group and 26.6% of patients in tDCS group experienced at least a 30% reduction of VAS from baseline to last follow-up (p = 0.028).DiscussionWith the methodology used in this study, both rTMS and tDCS were safe modalities and three sessions of rTMS over DLPFC had greater and longer lasting analgesic effects compared to tDCS in patients with FM. However, considering the limitations of this study, further studies are needed to explore the most effective modality.     

Alternate sessions of transcranial direct current stimulation (tDCS) reduce chronic pain in women affected by chikungunya. A randomized clinical trial

ContextThousands of people worldwide have been infected by the chikungunya virus (CHIKV), and the persistence of joint pain symptoms has been considered the main problem. Neuromodulation techniques such as transcranial direct current stimulation (tDCS) act on brain areas involved in the processing of chronic pain. It was previously demonstrated that tDCS for five consecutive days significantly reduced pain in the chronic phase of chikungunya (CHIK).ObjectiveTo analyze the effect of alternate tDCS sessions on pain and functional capacity in individuals affected by CHIK.MethodsIn a randomized clinical trial, 58 women in the chronic phase of CHIK were divided into two groups: active-tDCS (M1-S0, 2 mA, 20 min) and sham-tDCS. The Visual Analogue Scale (VAS) and the Brief Pain Inventory (BPI) were used to assess pain, while the Health Assessment Questionnaire (HAQ) assessed functional capacity. These scales were used before and after six sessions of tDCS in nonconsecutive days on the primary motor cortex, and at follow-up consultation 7 and 15 days after the last session. A repeated measures mixed-model ANOVA was used for comparison between groups (significant p-values < 0.05).ResultsA significant pain reduction (Z [3, 171] = 14.303; p < 0.0001) was observed in the tDCS group compared to the sham group; no significant difference in functional capacity was observed (Z [1.57] = 2.797; p = 0.1).ConclusionOur results suggest that six nonconsecutive sessions of active tDCS on M1 reduce pain in chronic CHIKV arthralgia.     

Efficacy of pre-supplementary motor area transcranial direct current stimulation for treatment resistant obsessive compulsive disorder: A randomized,double blinded,sham controlled trial

BackgroundA significant proportion of obsessive compulsive disorder (OCD) patients do not respond to specific serotonin reuptake inhibitors (SSRIs). There is a need to evaluate novel treatment options for OCD.ObjectiveIn this double blinded, randomized, sham controlled study, we investigated the efficacy of add-on transcranial direct current stimulation (tDCS) in reducing the symptoms in SSRI-resistant OCD patients by employing anodal pre-supplementary motor area (pre-SMA) stimulation.MethodTwenty-five patients with DSM-IV OCD having persistent symptoms despite adequate and stable treatment with at least one SSRI were randomly allocated to receive 20 min of verum (active) 2-mA tDCS or sham stimulation twice daily on 5 consecutive days [anode over Pre-SMA; cathode over right supra-orbital area]. Response to treatment was defined as at least 35% reduction in the Yale-Brown Obsessive-Compulsive Scale (YBOCS) total score along with a Clinical Global Impression – Improvement (CGI-I) score of 1 (very much improved) or 2 (much improved).ResultsThe response rate was significantly greater in the verum tDCS(4 out of 12) compared to sham-tDCS (0 out of 13) [Fisher's exact test, p = 0.04]. Repeated measures analysis of variance with tDCS type (verum vs. sham) as between subjects factor showed that there was a significant tDCS-type X time-point interaction with significantly greater reduction of YBOCS total score [F (1,22) = 4.95,p = 0.04,partial-η² = 0.18] in verum-tDCS group.ConclusionsThe results of this RCT suggest that tDCS may be effective in treating SSRI-resistant OCD. Future studies should examine the efficacy in larger samples of OCD and explore other potential target regions using randomized sham-controlled designs, in addition to examining the sustainability of the beneficial effects.Trial registrationClinical Trials Registry India (http://ctri.nic.in/Clinicaltrials/login.php): Registration Number- CTRI/2016/04/006837).     

Effects of transcranial direct current stimulation on experimental pain perception: A systematic review and meta-analysis

ObjectiveMany studies have examined the effectiveness of transcranial direct current stimulation (tDCS) on human pain perception in both healthy populations and pain patients. Nevertheless, studies have yielded conflicting results, likely due to differences in stimulation parameters, experimental paradigms, and outcome measures. Human experimental pain models that utilize indices of pain in response to well-controlled noxious stimuli can avoid many confounds present in clinical data. This study aimed to assess the robustness of tDCS effects on experimental pain perception among healthy populations.MethodsWe conducted three meta-analyses that analyzed tDCS effects on ratings of perceived pain intensity to suprathreshold noxious stimuli, pain threshold and tolerance.ResultsThe meta-analyses showed a statically significant tDCS effect on attenuating pain-intensity ratings to suprathreshold noxious stimuli. In contrast, tDCS effects on pain threshold and pain tolerance were statistically non-significant. Moderator analysis further suggested that stimulation parameters (active electrode size and current density) and experimental pain modality moderated the effectiveness of tDCS in attenuating pain-intensity ratings.ConclusionThe effectiveness of tDCS on attenuating experimental pain perception depends on both stimulation parameters of tDCS and the modality of experimental pain.SignificanceThis study provides some theoretical basis for the application of tDCS in pain management.     

Self-administered transcranial direct current stimulation for pain in older adults with knee osteoarthritis: A randomized controlled study

BackgroundKnee osteoarthritis (OA) is a leading cause of pain in older adults. Previous studies indicated clinic-based transcranial direct current stimulation (tDCS) was effective to reduce pain in various populations, but no published studies have reported the efficacy of home-based self-administered tDCS in older adults with knee OA using a randomized clinical study.ObjectiveThe purpose of this study was to evaluate the efficacy and feasibility of tDCS on clinical pain intensity in adults with knee OA pain.MethodsOne hundred twenty participants aged 50–85 years with knee OA pain were randomly assigned to receive fifteen daily sessions of 2 mA tDCS for 20 min (n = 60) or sham tDCS (n = 60) over 3 weeks with remote supervision via telehealth. Clinical pain intensity was measured by the Numeric Rating Scale and Western Ontario and McMaster Universities Osteoarthritis Index. Also, we collected data on the tDCS experience via a questionnaire.ResultsParticipants (68% female) had a mean age of 66 years. Active tDCS significantly reduced pain intensity compared to sham tDCS after completion of the fifteen daily sessions (Cohen's d = 1.20; p-value < 0.0001). Participants showed high levels of satisfaction with their tDCS experience, and there have been no adverse events.ConclusionWe demonstrated that home-based self-administered tDCS was feasible and reduced clinical pain intensity in older adults with knee OA, which can increase its accessibility. Future studies with multi-site randomized controlled trials are needed to validate our findings.Trial registrationClinicalTrials.gov Identifier NCT04016272.     

Concurrent conventional & high-definition transcranial direct current stimulation for treatment of schizophrenia with co-morbid obsessive-compulsive disorder: A case report

Non-invasive brain stimulation techniques such as conventional transcranial direct current stimulation (tDCS) and high definition tDCS (HD-tDCS) are increasingly being used as add-on treatment options in schizophrenia and obsessive-compulsive disorder (OCD). This is reporting of the use of a novel accelerated, symptom-specific, add-on tDCS (combining conventional and high definition) protocol in a patient with both schizophrenia and OCD. The intervention showed clinical utility by reducing both schizophrenia and OCD symptoms.     

Transcranial direct current stimulation (tDCS) for depression in pregnancy: A pilot randomized controlled trial

BackgroundDepression in pregnancy negatively affects maternal-child health. Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation treatment for depression, has not been evaluated in pregnancy.ObjectiveTo conduct a pilot randomized controlled trial (RCT) to evaluate tDCS for antenatal depression.MethodsIn this pilot RCT in Toronto, Ontario (October 2014 to December 2016), adult pregnant women 14–32 weeks gestation with major depressive disorder who had declined antidepressant medication were considered for inclusion. Participants were randomly assigned 1:1 to tDCS or sham-control. Active tDCS comprised 30-min sessions of 2 mAmp direct current delivered over the dorsolateral prefrontal cortex, 5 days per week, for 3 weeks. Sham was administered similarly, but with current turned off after 30 s. Main outcomes were feasibility, acceptability, and protocol adherence. Maternal Montgomery Asperg Depression Rating Scale (MADRS) was measured post-treatment and at 4 and 12 weeks postpartum.ResultsOf 20 women randomized, 16 completed treatment and provided data (124 tDCS, 122 sham sessions). Views of treatment were positive with no serious adverse events. Post-treatment estimated marginal mean MADRS scores were 11.8 (standard error, SE 2.66) for tDCS and 15.4 (SE 2.51) for sham (p = 0.34). At 4 weeks postpartum, 75.0% of tDCS women were remitted versus 12.5% sham-control (p = 0.04).ConclusionsResults support proceeding to a definitive RCT to evaluate tDCS for antenatal depression. The preliminary efficacy estimates immediately post-treatment and in the postpartum, are encouraging with respect to the potential use of tDCS to improve treatment rates in this population. The trial was registered at: clinical trials.gov (NCT02116127).     

A randomized controlled trial of transcranial direct-current stimulation and cognitive training in children with fetal alcohol spectrum disorder

BackgroundThis study was a randomized double-blind sham-controlled trial examining the effects of transcranial direct current stimulation (tDCS) augmented cognitive training (CT) in children with Fetal Alcohol Spectrum Disorders (FASD). Prenatal alcohol exposure has profound detrimental effects on brain development and individuals with FASD commonly present with deficits in executive functions including attention and working memory. The most commonly studied treatment for executive deficits is CT, which involves repeated drilling of exercises targeting the impaired functions. As currently implemented, CT requires many hours and the observed effect sizes are moderate. Neuromodulation via tDCS can enhance brain plasticity and prior studies demonstrate that combining tDCS with CT improves efficacy and functional outcomes. TDCS-augmented CT has not yet been tested in FASD, a condition in which there are known abnormalities in neuroplasticity and few interventions.MethodsThis study examined the feasibility and efficacy of this approach in 44 children with FASD. Participants were randomized to receive five sessions of CT with either active or sham tDCS targeting the dorsolateral prefrontal cortex, a region of the brain that is heavily involved in executive functioning.ResultsThe intervention was feasible and well-tolerated in children with FASD. The tDCS group showed nominally significant improvement in attention on a continuous performance test compared to sham (p = .043). Group differences were observed at the third, fourth and fifth treatment sessions. There was no effect of tDCS on working memory (p = .911). Further, we found no group differences on a trail making task (p = .659) or on the verbal fluency test (p = .826). In the active tDCS group, a significant correlation was observed between improvement in attention scores and decrease in parent-reported attention deficits (p = .010).ConclusionsThese results demonstrate that tDCS-augmented CT is well tolerated in children with FASD and potentially offers benefits over and above CT alone.     

Efficacy of transcranial direct current stimulation on postoperative delirium in elderly patients undergoing lower limb major arthroplasty: A randomized controlled trial

BackgroundPostoperative delirium (POD) is a common and severe postoperative complication in elderly patients undergoing major surgery linked to increased morbidity and mortality. It is reported that transcranial direct current stimulation (tDCS) effectively enhances cognitive function and improves impaired consciousness.ObjectiveThis study aimed to evaluate the efficacy of tDCS on POD in elderly patients undergoing lower limb major arthroplasty, including total hip arthroplasty (THA) or total knee arthroplasty (TKA).MethodsPatients aged ≥65 years scheduled for THA or TKA were randomly assigned to receive 2 mA tDCS for 20 min active-tDCS (n = 61) or sham-tDCS (n = 61). The primary outcome was the incidence of POD during the first 3 postoperative days.ResultsAll 122 patients (median age, 70 years; 80 women [65.6%]) completed the trial. The incident delirium risk was 4.9% (n = 3) vs. 19.7% (n = 12) in active-tDCS and sham-tDCS groups, respectively (relative risk, 0.250; 95% CI, 0.074 to 0.842; P = 0.013). Compared to the sham-tDCS group, the anxiety and depression scores of patients in the active-tDCS group were lower at 2 h and one day after surgery (P < 0.001 for each), and pain scores of patients in the active-tDCS group were lower during the first three days after surgery (P < 0.05).ConclusionOne session of anodal tDCS over the left dorsolateral prefrontal cortex may decrease the incidence of POD in elderly patients undergoing lower limb major arthroplasty.     

Transcranial direct current stimulation improves tinnitus perception and modulates cortical electrical activity in patients with tinnitus: A randomized clinical trial

ObjectivesThis study aims to determine whether transcranial direct current stimulation (tDCS): a) is effective in the treatment of tinnitus by decreasing its annoyance and severity; b) modulates the cortical electrical activity of such individuals.MethodsA double-blind, placebo-controlled clinical trial was conducted with 24 patients with tinnitus, randomized into two groups: Group 1 (n = 12) received anodal tDCS over the left temporoparietal area (LTA) and cathodal tDCS over the right dorsolateral prefrontal cortex (DLPFC) and Group 2 (n = 12) received placebo intervention. Tinnitus perception using a visual analog scale (VAS) and the Tinnitus Handicap Inventory (THI) questionnaire, in addition to electroencephalogram (EEG) was measured with eyes opened and closed at baseline and after the intervention. For the treatment, patients were subjected to five consecutive sessions of tDCS with the anodal electrode over the LTA and cathodal electrode over the right DLPFC (7 × 5 cm, 2 mA for 20 min). tDCS was turned off after 30 s in the sham group.ResultsActive tDCS significantly improved tinnitus annoyance and severity. It was associated with decreased beta and theta EEG frequency bands with eyes opened and decreased alpha frequency with eyes closed. sLORETA identified changes in frequency bands in the frontal, temporoparietal, and limbic regions. Finally, there were negative correlations between baseline EEG frequency bands and tDCS-induced change in tinnitus annoyance and severity.ConclusionsThese results demonstrate that tDCS modulates the EEG activity and alleviates tinnitus perception. This effect may be related to baseline EEG activity.     

Motor cortex transcranial direct current stimulation effects on knee osteoarthritis pain in elderly subjects with dysfunctional descending pain inhibitory system: A randomized controlled trial

BackgroundAlthough evidence has indicated a positive effect of transcranial direct current stimulation (tDCS) on reducing pain, few studies have focused on the elderly population with knee osteoarthritis (KOA).ObjectiveTo evaluate whether tDCS reduces KOA pain in elderly individuals with a dysfunctional descending pain inhibitory system (DPIS).MethodsIn a double-blind trial, individuals ≥ 60 years with KOA pain and a dysfunctional DPIS, we randomly assigned patients to receive 15 daily sessions of 2 mA tDCS over the primary motor cortex (anode) and contralateral supraorbital area (cathode) (M1-SO) for 20 min or sham tDCS. Change in pain perception indexed by the Brief Pain Inventory (BPI) at the end of intervention was the primary outcome. Secondary outcomes included: disability, quantitative sensory testing, pain pressure threshold and conditioned pain modulation (CPM). Subjects were followed-up for 2 months.ResultsOf the 104 enrolled subjects, with mean (SD) age of 73.9 (8.01) years and 88 (84.6%) female, 102 finished the trial. In the intention-to-treat analysis, the active tDCS group had a significantly greater reduction in BPI compared to the sham group (difference, 1.59; 95% CI, 0.95 to 2.23; P < 0.001; Cohen’s d, 0.58); and, also a significantly greater improvement in CPM-pressure in the knee (P = 0.01) and CPM-pain in the hand (P = 0.01). These effects were not sustained at follow-up. The intervention was well tolerated, with no severe adverse effects.ConclusionM1-SO tDCS is associated with a moderate effect size in reducing pain in elderly patients with KOA after 15 daily sessions of stimulation. This intervention has also shown to modulate the DPIS.     

Feasibility and efficacy of remotely supervised cranial electrical stimulation for pain in older adults with knee osteoarthritis: A randomized controlled pilot study

Cranial electrical stimulation (CES) is a noninvasive brain stimulation technique that has been shown to improve pain. However, few studies have investigated the potential benefits associated with remotely supervised CES in older adults with knee osteoarthritis (OA). The aim of this study was to examine the feasibility and preliminary efficacy of remotely supervised CES via secure videoconferencing software on clinical pain severity, experimental pain sensitivity, and pain-related cortical response in older adults with knee OA. Thirty participants with symptomatic knee OA pain were randomly assigned to receive 10 daily sessions (60 min each) of remotely supervised CES (n = 15) or sham CES (n = 15) over two weeks. We measured clinical pain severity via a Numeric Rating Scale, experimental pain sensitivity (e.g., heat pain sensitivity, pressure pain sensitivity, and conditioned pain modulation) using quantitative sensory testing, and pain-related cortical response via functional near-infrared spectroscopy imaging. We also measured participant satisfaction with treatment using the Client Satisfaction Questionnaire. Active CES significantly reduced scores on the Numeric Rating Scale and increased heat pain threshold, pressure pain thresholds, and conditioned pain modulation. We also found significant changes in pain-related cortical hemodynamic activity after CES. Participants tolerated CES well without serious adverse effects and were satisfied with the treatment. Our findings demonstrate promising clinical efficacy of remotely supervised CES for older adults with knee OA.