Effectiveness and mechanism of action of rTMS combined with quadriceps strength training in individuals with knee osteoarthritis: study protocol for a randomized controlled trial.

BACKGROUND: Quadriceps training is necessary in function and activity of daily living for patients with knee osteoarthritis (KOA). However, it did not reduce the rate of surgical treatment for end-stage KOA in the long term. This may be related to brain structure changes and maladaptive plasticity in KOA patients. Transcranial Magnetic Stimulation (TMS) could enhance the functional connectivity of brain regions and improves maladaptive plasticity. However, the synergistic effect of the combination of the two for treat KOA is still unclear. Therefore, the purpose of this study is to investigate whether the High-Frequency rTMS combined with quadriceps strength training can improve the pain and function in KOA more effectively than quadriceps training alone and explore the mechanism of action. METHODS: This study is an assessor-blind, sham-controlled, randomized controlled trial involving 12 weeks of intervention and 6 months follow-up. 148 participants with KOA will receive usual care management and be randomized into four subgroups equally, including quadriceps strength training, high-frequency rTMS training, sham rTMS and quadriceps strength training, high-frequency rTMS and quadriceps strength training. The rehabilitation interventions will be carried out 5 days per week for a total of 12 weeks. All outcomes will be measured at baseline, 4 weeks, 8 weeks, and 12 weeks during the intervention and 1 month, 3 months and 6 months during the follow-up period. The effectiveness outcomes will be included visual analog scale, isokinetic knee muscle strength, Knee Injury and Osteoarthritis Outcome score and 36-Item Short-Form Health Survey score; The act mechanism outcomes will be included motor evoked potential, grey matter density, white matter, subcortical nuclei volumes, cortical thickness and functional connectivity by MRI. Two-way of variance with repeated measures will be used to test the group and time effect for outcome measures. DISCUSSION: The study will be the first protocol to examine whether there are synergistic effects following high-frequency rTMS combined with quadriceps strength training for treat KOA and clarify the mechanism of action. High-frequency rTMS can be added into the training program for KOA patients if it is proven effective. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300067617. Registered on Jan.13,2023.

Synergy-based functional electrical stimulation and robotic-assisted for retraining reach-to-grasp in stroke: a study protocol for a randomized controlled trial.

BACKGROUND: Stroke survivors have long-term upper limb impairment, which impacts the quality of life (QOL) and social reintegration, but there is lack of effective therapeutic strategies and novel technologies. Customized multi-muscle functional electrical stimulation (FES) based on the muscle synergy of healthy adults and robotic-assisted therapy (RAT) have been proved efficacy respectively. Synergy-based FES combined with RAT can be a novel and more effective therapy for upper limb recovery of stroke survivors from the perspective of synergistic enhancement. However, few studies have examined the effectiveness of combined synergy-based FES and RAT, especially for motor control evaluated by reach-to-grasp (RTG) movements. The main objective of the following research protocol is to evaluate the effectiveness and efficacy, as well as adoptability, of FES-RAT and FES or RAT rehabilitation program for upper limb function improvement after stroke. METHODS: This will be an assessor-blinded randomized controlled trial involving a 12-week intervention and a 6-month follow-up. Stratified randomization will be used to equally and randomly assign 162 stroke patients into the FES + conventional rehabilitation program (CRP) group, RAT + CRP group and FES-RAT + CRP group. Interventions will be provided in 5 sessions per week, with a total of 60 sessions. The primary outcome measurements will include the Fugl-Meyer Assessment and Biomechanical Assessment of RTG movements. The secondary outcome measurements will include quality of life and brain neuroplasticity assessments by MRI. Evaluations will be performed at five time points, including at baseline, 6 weeks and 12 weeks from the start of treatment, and 3 months and 6 months following the end of treatment. A two-way analysis of variance with repeated measures will be applied to examine the main effects of the group, the time factor and group-time interaction effects. DISCUSSION: The results of the study protocol will provide high quality evidence for integrated synergy-based FES and RAT, and synergy-based FES alone and guide the design of more effective treatment methods for stroke rehabilitation. TRIAL REGISTRATION: ChiCTR2300071588.

Effectiveness and brain mechanism of multi-target transcranial alternating current stimulation (tACS) on motor learning in stroke patients: study protocol for a randomized controlled trial.

BACKGROUND: Transcranial alternating current stimulation (tACS) has proven to be an effective treatment for improving cognition, a crucial factor in motor learning. However, current studies are predominantly focused on the motor cortex, and the potential brain mechanisms responsible for the therapeutic effects are still unclear. Given the interconnected nature of motor learning within the brain network, we have proposed a novel approach known as multi-target tACS. This study aims to ascertain whether multi-target tACS is more effective than single-target stimulation in stroke patients and to further explore the potential underlying brain mechanisms by using techniques such as transcranial magnetic stimulation (TMS) and magnetic resonance imaging (MRI). METHODS: This study employs a double-blind, sham-controlled, randomized controlled trial design with a 2-week intervention period. Both participants and outcome assessors will remain unaware of treatment allocation throughout the study. Thirty-nine stroke patients will be recruited and randomized into three distinct groups, including the sham tACS group (SS group), the single-target tACS group (ST group), and the multi-target tACS group (MT group), at a 1:1:1 ratio. The primary outcomes are series reaction time tests (SRTTs) combined with electroencephalograms (EEGs). The secondary outcomes include motor evoked potential (MEP), central motor conduction time (CMCT), short interval intracortical inhibition (SICI), intracortical facilitation (ICF), magnetic resonance imaging (MRI), Box and Block Test (BBT), and blood sample RNA sequencing. The tACS interventions for all three groups will be administered over a 2-week period, with outcome assessments conducted at baseline (T0) and 1 day (T1), 7 days (T2), and 14 days (T3) of the intervention phase. DISCUSSION: The study's findings will determine the potential of 40-Hz tACS to improve motor learning in stroke patients. Additionally, it will compare the effectiveness of multi-target and single-target approaches, shedding light on their respective improvement effects. Through the utilization of techniques such as TMS and MRI, the study aims to uncover the underlying brain mechanisms responsible for the therapeutic impact. Furthermore, the intervention has the potential to facilitate motor learning efficiency, thereby contributing to the advancement of future stroke rehabilitation treatment. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300073465. Registered on 11 July 2023.

Transcranial direct current stimulation combined with bodyweight support-tai chi footwork for motor function of stroke survivors: a study protocol of randomised controlled trial.

INTRODUCTION: Our previous studies have proposed the bodyweight support-t'ai chi (BWS-TC) footwork training for stroke survivors with severe motor dysfunction and fear of falling, and have proven its positive effects for motor function. Transcranial direct current stimulation (tDCS) provides a non-invasive and safe way to modulate neuronal activity and provoke neuroplastic changes and to improve the motor function of stroke survivors. However, it is unclear whether the integration of BWS-TC and tDCS has synergistic effects on improving motor function of the stroke survivors. METHODS AND ANALYSIS: This study will be an assessor-blinded randomised controlled trial involving 12-week intervention and 6-month follow-up. One hundred and thirty-five individuals with stroke will be randomly divided in a ratio of 1:1:1 into three groups. Control group A, control group B and intervention group C will receive tDCS and conventional rehabilitation programmes (CRPs), BWS-TC and CRP, tDCS-BWS-TC and CRP for 12 weeks, respectively. The primary outcome measures will include the efficacy (Fugl-Meyer Assessment), acceptability and safety of these interventions. The secondary outcome measures will include balance ability (ie, limits of stability and modified clinical test of sensory integration), walking function, brain structure and function, risk of falling, Barthel Index and 36-Item Short Form Survey. All outcomes will be assessed at baseline, 6 and 12 weeks during intervention, and 1, 3 and 6 months during the follow-up period. Two-way analysis of variance with repeated measures will be applied to examine the main effects of the group and the time factor and group-time interaction effects for all outcome measures. ETHICS AND DISSEMINATION: Ethics approval was obtained from the ethics committee of the Shanghai Seventh People's Hospital (2021-7th-HIRB-017). The results of the study will be published in a peer-reviewed journal and presented at scientific conferences. TRIAL REGISTRATION NUMBER: ChiCTR2200059329.

Dynamic Patterns of Symptoms and Functioning in Predicting Deliberate Self-harm in Patients with First-Episode Schizophrenia-Spectrum Disorders Over 3 Years.

OBJECTIVES: Patients with schizophrenia have a significant risk of self-harm. We aimed to explore the dynamic relationship between symptomatology, functioning and deliberate self-harm (DSH) and evaluate the feasibility of developing a self-harm risk prediction tool for patients with first-episode schizophrenia (FES). METHODS: Patients with FES (n = 1234) were followed up for 36 months. Symptomatology, functioning, treatment adherence and self-harm information were obtained monthly over the follow-up period. A time-varying vector autoregressive (VAR) model was used to study the contribution of clinical variables to self-harm over the 36th month. Random forest models for self-harm were established to classify the individuals with self-harm and predict future self-harm events. RESULTS: Over a 36-month period, 187 patients with FES had one or more self-harm events. The depressive symptoms contributed the most to self-harm prediction during the first year, while the importance of positive psychotic symptoms increased from the second year onwards. The random forest model with all static information and symptom instability achieved a good area under the receiver operating characteristic curve (AUROC = 0.77 ± 0.023) for identifying patients with DSH. With a sliding window analysis, the averaged AUROC of predicting a self-event was 0.65 ± 0.102 (ranging from 0.54 to 0.78) with the best model being 6-month predicted future 6-month self-harm for month 11-23 (AUROC = 0.7). CONCLUSIONS: Results highlight the importance of the dynamic relationship of depressive and positive psychotic symptoms with self-harm and the possibility of self-harm prediction in FES with longitudinal clinical data.

Prevalence and predictors of medication non-adherence among Chinese patients with first-episode psychosis.

Medication non-adherence is one of the major obstacles to recovery in first-episode psychosis (FEP). This study aimed to identify the predictors and rates of medication non-adherence in the first and second year after the start of treatment (baseline) in urban Chinese FEP patients. Relevant information on medication non-adherence and potential baseline predictors, including demographic variables, clinical measures, violence/suicide attempts, stressful life experiences, intervention received, and follow-up attendance, were collected from case records of 1400 FEP patients in Hong Kong. The non-adherence rate was 16.2% in year 1 and 15.4% in year 2. Regression analyses revealed the predictors for non-adherence in year 1 were no hospitalization at baseline, non-schizophrenia diagnosis, and more years of education. Predictors of non-adherence in year 2 included acute/subacute onset and older age of onset. Predictors common in both years were defaulting from psychiatric follow-up during baseline, standard psychiatric care (no early intervention), and lower positive symptoms severity at baseline. In assessing non-adherence risk and for planning phase-specific early interventions for FEP, particularly in a Chinese context, healthcare professionals should consider the common and specific predictors for non-adherence identified in the first and second years of treatment and should not overlook patients with less clinically severe symptoms.