Synergistic efficacy of repetitive peripheral magnetic stimulation on central intermittent theta burst stimulation for upper limb function in patients with stroke: a double-blinded, randomized controlled trial.

BACKGROUND: Non-invasive techniques such as central intermittent theta burst stimulation (iTBS) and repetitive peripheral magnetic stimulation (rPMS) have shown promise in improving motor function for patients with stroke. However, the combined efficacy of rPMS and central iTBS has not been extensively studied. This randomized controlled trial aimed to investigate the synergistic effects of rPMS and central iTBS in patients with stroke. METHOD: In this study, 28 stroke patients were randomly allocated to receive either 1200 pulses of real or sham rPMS on the radial nerve of the affected limb, followed by 1200 pulses of central iTBS on the ipsilesional hemisphere. The patients received the intervention for 10 sessions over two weeks. The primary outcome measures were the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) and the Action Research Arm Test (ARAT). Secondary outcomes for activities and participation included the Functional Independence Measure-Selfcare (FIM-Selfcare) and the Stroke Impact Scale (SIS). The outcome measures were assessed before and after the intervention. RESULTS: Both groups showed significant improvement in FMA-UE and FIM-Selfcare after the intervention (p < 0.05). Only the rPMS + iTBS group had significant improvement in ARAT-Grasp and SIS-Strength and activity of daily living (p < 0.05). However, the change scores in all outcome measures did not differ between two groups. CONCLUSIONS: Overall, the study's findings suggest that rPMS may have a synergistic effect on central iTBS to improve grasp function and participation. In conclusion, these findings highlight the potential of rPMS as an adjuvant therapy for central iTBS in stroke rehabilitation. Further large-scale studies are needed to fully explore the synergistic effects of rPMS on central iTBS. TRIAL REGISTRATION: This trial was registered under ClinicalTrials.gov ID No.NCT04265365, retrospectively registered, on February 11, 2020.

Myoelectric, Myo-Oxygenation, and Myotonometry Changes during Robot-Assisted Bilateral Arm Exercises with Varying Resistances.

Robot-assisted bilateral arm training has demonstrated its effectiveness in improving motor function in individuals post-stroke, showing significant enhancements with increased repetitions. However, prolonged training sessions may lead to both mental and muscle fatigue. We conducted two types of robot-assisted bimanual wrist exercises on 16 healthy adults, separated by one week: long-duration, low-resistance workouts and short-duration, high-resistance exercises. Various measures, including surface electromyograms, near-infrared spectroscopy, heart rate, and the Borg Rating of Perceived Exertion scale, were employed to assess fatigue levels and the impacts of exercise intensity. High-resistance exercise resulted in a more pronounced decline in electromyogram median frequency and recruited a greater amount of hemoglobin, indicating increased muscle fatigue and a higher metabolic demand to cope with the intensified workload. Additionally, high-resistance exercise led to increased sympathetic activation and a greater sense of exertion. Conversely, engaging in low-resistance exercises proved beneficial for reducing post-exercise muscle stiffness and enhancing muscle elasticity. Choosing a low-resistance setting for robot-assisted wrist movements offers advantages by alleviating mental and physiological loads. The reduced training intensity can be further optimized by enabling extended exercise periods while maintaining an approximate dosage compared to high-resistance exercises.

The effects of high versus low frequency of combined physical and cognitive training on cognitive function in older adults with cognitive decline: a quasi-experimental study.

BACKGROUND: The effects of combined training can be affected by training characteristics such as frequency, session length, and duration. No empirical studies to date have directly compared how combined physical and cognitive training offered at different training frequencies affects cognitive function for older adults with cognitive decline. This study investigated the impact of training frequency on cognitive outcomes after combined physical and cognitive training for older adults with cognitive decline. METHODS: A quasi-experimental study was conducted in community facilities and day care centers. The study assigned 89 older adults with cognitive decline into high-frequency (HF) or low-frequency (LF) training groups. The participants received 90- to 105-min training sessions, one (LF) or three (HF) times a week, for 12 weeks. Outcome measures were the Montreal Cognitive Assessment, Word List subtest of the Wechsler Memory Scale, Digit Symbol Substitution Test (DSST), and Stroop Color Word Test. RESULTS: The HF group demonstrated greater improvement in immediate memory measured by the WL-IM (F = 8.7, P = 0.004) and in executive function measured by the SCWT (F = 5.89, P = 0.017) than the LF group. Compared with the HF group, the LF group showed a great improvement in delayed memory measured by the WL-DM (F = 9.62, P = 0.003). The HF and LF groups both increased in processing speed and global cognitive function. CONCLUSIONS: Our study indicated that the different training frequency of combined physical and cognitive training may result in benefits on different cognitive functions in older adults with cognitive decline. These findings may assist clinical practitioners in choosing appropriate training frequencies based on various intervention purposes for the elderly with cognitive decline. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03619577 (08/08/2018).

Dual task measures in older adults with and without cognitive impairment: response to simultaneous cognitive-exercise training and minimal clinically important difference estimates.

BACKGROUND: Responsiveness and minimal clinically important difference (MCID) are critical indices to understand whether observed improvement represents a meaningful improvement after intervention. Although simultaneous cognitive-exercise training (SCET; e.g., performing memory tasks while cycling) has been suggested to enhance the cognitive function of older adults, responsiveness and MCID have not been established. Hence, we aimed to estimate responsiveness and MCIDs of two dual task performance involving cognition and hand function in older adults with and without cognitive impairment and to compare the differences in responsiveness and MCIDs of the two dual task performance between older adults with and without cognitive impairment. METHODS: A total of 106 older adults completed the Montreal Cognitive Assessment and two dual tasks before and after SCET. One dual task was a combination of Serial Sevens Test and Box and Block Test (BBT), and the other included frequency discrimination and BBT. We used effect size and standardized response mean to indicate responsiveness and used anchor- and distribution-based approaches to estimating MCID ranges. When conducting data analysis, all participants were classified into two cognitive groups, cognitively healthy (Montreal Cognitive Assessment ≥ 26) and cognitively impaired (Montreal Cognitive Assessment < 26) groups, based on the scores of the Montreal Cognitive Assessment before SCET. RESULTS: In the cognitively healthy group, Serial Seven Test performance when tasked with BBT and BBT performance when tasked with Serial Seven Test were responsive to SCET (effect size = 0.18-0.29; standardized response mean = 0.25-0.37). MCIDs of Serial Seven Test performance when tasked with BBT ranged 2.09-2.36, and MCIDs of BBT performance when tasked with Serial Seven Test ranged 3.77-5.85. In the cognitively impaired group, only frequency discrimination performance when tasked with BBT was responsive to SCET (effect size = 0.37; standardized response mean = 0.47). MCIDs of frequency discrimination performance when tasked with BBT ranged 1.47-2.18, and MCIDs of BBT performance when tasked with frequency discrimination ranged 1.13-7.62. CONCLUSIONS: Current findings suggest that a change in Serial Seven Test performance when tasked with BBT between 2.09 and 2.36 corrected number (correct responses - incorrect responses) should be considered a meaningful change for older adults who are cognitively healthy, and a change in frequency discrimination performance when tasked with BBT between 1.47 and 2.18 corrected number (correct responses - incorrect responses) should be considered a meaningful change for older adults who are cognitively impaired. Clinical practitioners may use these established MCIDs of dual tasks involving cognition and hand function to interpret changes following SCET for older adults with and without cognitive impairment. TRIAL REGISTRATION: NCT04689776, 30/12/2020.

Comparative effects of EMG-driven robot-assisted therapy versus task-oriented training on motor and daily function in patients with stroke: a randomized cross-over trial.

BACKGROUND: Robot-assisted hand training has shown positive effects on promoting neuromuscular control. Since both robot-assisted therapy and task-oriented training are often used in post-stroke rehabilitation, we raised the question of whether two interventions engender differential effects in different domains. METHODS: The study was conducted using a randomized, two-period crossover design. Twenty-four chronic stroke survivors received a 12-session robot-assisted intervention followed by a 12-session task-oriented intervention or vice versa. A 1-month washout period between each intervention was implemented. Outcome measures were evaluated before the intervention, after the first 12-session intervention, and after the second 12-session intervention. Clinical assessments included Fugl-Meyer Assessment for Upper Extremity, Wolf Motor Function Test, Action Research Arm Test and Motor Activity Log. RESULTS: Our findings suggested that EMG-driven robot-assisted therapy was as effective as task-oriented training in terms of improving upper limbs functional performance in activity domain, and robot-assisted therapy was more effective in improving movement duration during functional tasks. Task-oriented training showed better improvement in body function domain and activity and participation domain, especially in improving spontaneous use of affected arm during daily activities. CONCLUSIONS: Both intervention protocol had their own advantages in different domains, and robot-assisted therapy may save manpower and be considered as an alternative intervention to task-oriented training. Combining the two approaches could yield results greater than either alone, which awaits further study. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03624153. Registered on 9th August 2018, https://clinicaltrials.gov/ct2/show/NCT03624153 .

Enhancing production of herpes simplex virus type 1 in oral epithelial cells by co-infection with Aggregatibacter actinomycetemcomitans.

BACKGROUND/PURPOSE: The association between herpetic/bacterial co-infection and periodontal diseases has been reported. However, how interactions between herpesviruses and periodontal bacteria dampen periodontal inflammation is still unclear. This study determined effects of co-infection with oral bacteria, including Streptococcus sanguinis, Fusobacterium nucleatum or Aggregatibacter actinomycetemcomitans, in herpes simplex virus type 1 (HSV-1)-infected oral epithelial cells. METHODS: Cell viability was determined by detection the activity of mitochondrial dehydrogenase. Viral production was measured using the plaque assay. Levels of bacterial and viral DNA were determined by real-time polymerase chain reaction. Secretion of interleukin (IL)-6 and IL-8 was measured using the enzyme-linked immunosorbent assay. RESULTS: Viability was not further reduced by bacterial co-infection in HSV-1-infected cells. Co-infection with HSV-1 and S. sanguinis or F. nucleatum reduced the viral yield whereas co-infection with HSV-1 and A. actinomycetemcomitans significantly enhanced the viral yield in oral epithelial cells. The enhancing effect of A. actinomycetemcomitans was not affected by bacterial heat-inactivation. Co-infection with HSV-1/A. actinomycetemcomitans increased intracellular levels of both viral and bacterial DNA. Secretion of IL-6 and IL-8 stimulated by A. actinomycetemcomitans infection was partly reduced by co-infection with HSV-1 in oral epithelial cells. CONCLUSION: In contrast to S. sanguinis and F. nucleatum, A. actinomycetemcomitans enhanced the yield of HSV-1. Either HSV-1 or A. actinomycetemcomitans may be benefited from co-infection, in aspects of increases in production of viral and bacterial DNA as well as reductions in cytokine secretion. These findings echoed with previous clinical studies showing co-infection of HSV and A. actinomycetemcomitans in patients with aggressive periodontitis.

Topographical Distribution and Phenotype of Resident Meibomian Gland Orifice Immune Cells (MOICs) in Mice and the Effects of Topical Benzalkonium Chloride (BAK).

Meibomian gland orifices (MGOs) are located along the eyelid margin and secrete meibum into the tear film. The profile of resident innate immune cells (ICs) at this site is not well understood. The distribution and phenotype of resident ICs around MGOs in mice was investigated and herein defined as MGO-associated immune cells (MOICs). The effect of topical 0.1% benzalkonium chloride (BAK) on MOICs was also assessed. Eyelids from healthy CD11ceYFP and Cx3cr1gfp/gfp mice aged three or seven months were compared. ICs were identified as CD11c+, Cx3cr1+, and MHC-II+ using four-colour immunostaining and confocal microscopy. MOIC density was variable but clustered around MGOs. There were more CD11c+ MOICs in three-month-old compared with seven-month-old mice (three-month-old: 893 ± 449 cells/mm2 vs. seven-month-old: 593 ± 493 cells/mm2, p = 0.004). Along the eyelid margin, there was a decreasing gradient of CD11c+ MOIC density in three-month-old mice (nasal: 1003 ± 369 cells/mm2, vs. central: 946 ± 574 cells/mm2, vs. temporal: 731 ± 353 cells/mm2, p = 0.044). Cx3cr1-deficient mice had two-fold fewer MHC-II+ MOICs, suggesting a role for Cx3cr1 receptor signaling in meibomian gland surveillance. CD11c+ MOIC density was lower in BAK-exposed eyes compared to saline-treated controls, suggesting a change in homeostasis. This study provides novel insight into resident ICs located at MGOs, and their contribution to MG homeostasis.

Baseline Global Cognitive Function Affects Cognitive and Functional Outcomes of Combined Physical and Cognitive Training Among Older Adults With Cognitive Decline.

IMPORTANCE: Baseline global cognitive function may affect cognitive and functional outcomes during combined physical and cognitive training; however, how it influences the effects of combined training remains uncertain. OBJECTIVE: To determine the impact of baseline global cognitive function on cognitive and functional outcomes after combined physical and cognitive training among older adults with cognitive decline. DESIGN: Observational. SETTING: Local communities and senior centers. PARTICIPANTS: Older adults with mild cognitive decline (MCD; n = 51) and moderate to severe cognitive decline (MSCD; n = 40). INTERVENTION: Participants received 45 to 55 min of physical exercise training followed by 45 to 55 min of cognitive training in one session per week for 12 wk. Outcomes and Measures: Montreal Cognitive Assessment (MoCA), Lawton-Brody Instrumental Activities of Daily Living Scale (Lawton-Brody IADL), Word Recall Test (WRT), Stroop Color and Word Test (SCWT), Digital Symbol Substitution Test (DSST), and Trail Making Test (TMT) scores were assessed and compared between the MCD and MSCD groups. RESULTS: Significant interaction effects were found for the WRT, SCWT, MoCA, and Lawton-Brody IADL. WRT and SCWT scores significantly improved in the MCD group, whereas MoCA and Lawton-Brody IADL scores significantly improved in the MSCD group. DSST scores increased among all participants, but TMT scores improved only in the MCD group. CONCLUSIONS AND RELEVANCE: Older adults' baseline global cognitive function affected cognitive and instrumental activities of daily living (IADL) outcomes regarding combined training. High-level cognitive function, including inhibition and shifting abilities and working memory capacity, improved among older adults with MCD, whereas general cognitive function and IADLs improved among older adults with MSCD. What This Article Adds: Findings revealed domain-specific changes with respect to baseline cognitive function, which may help to refine current combined training protocols and facilitate development of personalized combined training programs for older adults with cognitive impairments.

Role of Self-efficacy in the Predictive Relationship of Motor Ability to Functional Performance After Task-Related Training in Stroke: A Secondary Analysis of Longitudinal Data.

OBJECTIVE: To determine whether self-efficacy (SE) mediates or moderates the relationship between motor ability at pretest and functional use of the affected arm at posttest in task-related training for stroke. DESIGN: Retrospective, observational cohort study. SETTING: Outpatient rehabilitation settings. PARTICIPANTS: Eighty patients with chronic stroke (N=80). INTERVENTIONS: The training was delivered to the participants for 60-90 min/session, 3-5 sessions/wk for 4-6 weeks. The training involved specific robot-assisted, mirror, or combined therapy, followed by functional task practice for approximately 30 minutes in each session. MAIN OUTCOME MEASURES: The outcome measure was the perceived amount of functional arm use and quality of movement evaluated by the Motor Activity Log (MAL) at posttest. The predictor was scores on the Fugl-Meyer Assessment (FMA)-Upper Extremity subscale at pretest. The tested mediator and moderator were scores on the Stroke Self-Efficacy Questionnaire (SSEQ) at pretest and posttest. RESULTS: The SSEQ scores at pretest and posttest moderated the predictive relationship of pretest FMA to posttest MAL. The interaction between pretest FMA and SSEQ accounted for an additional 3.14%-5.37% of the variance in the posttest MAL. The predictive relationship between FMA and MAL was its greatest when the SSEQ was high, with a less amplified positive relationship at low levels of SSEQ. CONCLUSIONS: The results suggest the evaluation of SE at pretest for a better prediction of an individual patient's functional arm use after an intervention and recommend aiming at SE during training to make the most of motor ability transferred to functional use. Future research may compare the effectiveness of task-related training with and without SE building to verify the findings of this study.

Corneal immune cell morphometry as an indicator of local and systemic pathology: A review.

The corneal epithelium contains a population of resident immune cells commonly referred to as dendritic cells (DCs), or Langerhans cells. A unique advantage of the transparent cornea being situated at the surface of the eye is that these cells can be readily visualised using in vivo confocal microscopy. Over the past decade, interest in the involvement of corneal DCs in a range of ocular and systemic diseases has surged. For most studies, the number of corneal DCs has been the main outcome of interest. However, more recently attention has shifted towards understanding how DC morphology may provide insights into the inflammatory status of the cornea, and in some cases, the health of the peripheral nervous system. In this review, we provide examples of recent methodologies that have been used to classify and measure corneal DC morphology and discuss how this relates to local and systemic inflammatory conditions in humans and rodents.

Augmented efficacy of intermittent theta burst stimulation on the virtual reality-based cycling training for upper limb function in patients with stroke: a double-blinded, randomized controlled trial.

BACKGROUND: Virtual reality and arm cycling have been reported as effective treatments for improving upper limb motor recovery in patients with stroke. Intermittent theta burst stimulation (iTBS) can increase ipsilesional cortical excitability, and has been increasingly used in patients with stroke. However, few studies examined the augmented effect of iTBS on neurorehabilitation program. In this study, we investigated the augmented effect of iTBS on virtual reality-based cycling training (VCT) for upper limb function in patients with stroke. METHODS: In this randomized controlled trial, 23 patients with stroke were recruited. Each patient received either 15 sessions of iTBS or sham stimulation in addition to VCT on the same day. Outcome measures were assessed before and after the intervention. Primary outcome measures for the improvement of upper limb motor function and spasticity were Fugl-Meyer Assessment-Upper Extremity (FMA-UE) and Modified Ashworth Scale Upper-Extremity (MAS-UE). Secondary outcome measures for activity and participation were Action Research Arm Test (ARAT), Nine Hole Peg Test (NHPT), Box and Block Test (BBT) and Motor Activity Log (MAL), and Stroke Impact Scale (SIS). Wilcoxon signed-rank tests were performed to evaluate the effectiveness after the intervention and Mann-Whitney U tests were conducted to compare the therapeutic effects between two groups. RESULTS: At post-treatment, both groups showed significant improvement in FMA-UE and ARAT, while only the iTBS + VCT group demonstrated significant improvement in MAS-UE, BBT, NHPT, MAL and SIS. The Mann-Whitney U tests revealed that the iTBS + VCT group has presented greater improvement than the sham group significantly in MAS-UE, MAL-AOU and SIS. However, there were no significant differences in the changes of the FMA-UE, ARAT, BBT, NHPT and MAL-QOM between groups. CONCLUSIONS: Intermittent TBS showed augmented efficacy on VCT for reducing spasticity, increasing actual use of the affected upper limb, and improving participation in daily life in stroke patients. This study provided an integrated innovative intervention, which may be a promising therapy to improve upper limb function recovery in stroke rehabilitation. However, this study has a small sample size, and thus a further larger-scale study is warranted to confirm the treatment efficacy. Trial registration This trial was registered under ClinicalTrials.gov ID No. NCT03350087, retrospectively registered, on November 22, 2017.

Effects of epigallocatechin-3-gallate and acyclovir on herpes simplex virus type 1 infection in oral epithelial cells.

BACKGROUND/PURPOSE: Herpes simplex virus type 1 (HSV-1) is the pathogenic agent of human diseases, including gingivostomatitis and herpes labialis. The anti-viral activities of the tea polyphenol, epigallocatechin-3-gallate (EGCG), have been demonstrated. This study examined the combined effects of EGCG and the antiviral drug, acyclovir (ACV), on infection of HSV-1 in oral epithelial cells. METHODS: Cell viability was examined using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide. Viral yields were determined using the plaque assay. Viral proteins were detected using Western blotting analysis or confocal laser scanning microscopy. Viral DNA was detected using the real-time polymerase chain reaction. RESULTS: Cytotoxic effects of HSV-1 on the viability of oral epithelial cells were evidently reduced in the presence of EGCG (25 µg/ml) or/and ACV (50 µg/ml). Viral yields were also significantly reduced by treatment of cells with EGCG or/and ACV. Expression of viral immediate early protein, infected cell protein 0 (ICP0), was greatly inhibited when cells were treated with EGCG. Combined effects of EGCG and ACV were more evident for the expression of viral thymidine kinase, ICP5 and glycoprotein D. EGCG, but not ACV, significantly reduced the levels of viral particles and viral DNA during viral entry phase. However, at 20 h post infection, the intracellular viral DNA was evidently reduced in HSV-1 infected cells treated with EGCG and ACV. Moreover, the stimulatory effects of HSV-1 on phosphorylation of c-Jun N-terminal kinase could be reduced by ACV. CONCLUSION: The results demonstrated the additive effects of EGCG and ACV on HSV-1 infection in oral epithelial cells.

Stimulatory effects of Porphyromonas gingivalis GroEL protein on interleukin-6 and interleukin-8 in human osteoblasts.

BACKGROUND/PURPOSE: Porphyromonas gingivalis is an oral pathogen associated with periodontal diseases. P. gingivalis GroEL protein is a stimulator of inflammatory cytokines in macrophages. This study inspected effects of P. gingivalis GroEL protein on production of interleukin (IL)-6 and IL-8 by human osteoblasts. METHODS: Viability of GroEL-treated osteoblasts was analyzed with 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide. Secretion of IL-6 and IL-8 was analyzed using the enzyme-linked immunosorbent assay. Levels of mRNA were analyzed using the reverse transcription and real-time polymerase chain reaction. The antioxidant (curcumin), the p38 mitogen-activated protein kinase (MAPK) inhibitor (SB203580) and the c-Jun N-terminal kinase (JNK) inhibitor (SP600125) were employed to elucidate possible signaling pathways involved. RESULTS: Treatment with GroEL did not affect morphology and viability of osteoblasts. GroEL significantly induced the secretion of IL-6 and IL-8 by osteoblasts in a concentration-dependent pattern. Moreover, the mRNA levels of IL-6 and IL-8 were stimulated by GroEL. The application of SP600125 (10 µM) significantly suppressed the induction of IL-6 and IL-8 by GroEL-treated cells. However, curcumin (20 µM) and SB203580 (20 µM) only down-regulated the stimulatory effects of GroEL on IL-6. CONCLUSION: GroEL protein stimulated the inflammatory reaction of osteoblasts, probably through the activation of p38 MAPK or JNK pathway. The findings suggest that P. gingivalis GroEL may influence the immune functions of osteoblasts and endanger the periodontal health.

Responsiveness and minimal clinically important difference of TNO-AZL Preschool Children Quality of Life in children with cerebral palsy.

PURPOSE: To examine the responsiveness and minimal clinically important difference (MCID) of the TNO-AZL (Netherlands Organization for Applied Scientific Research Academic Medical Centre) Preschool Children Quality of Life (TAPQOL) in children with cerebral palsy (CP). METHODS: Ninety-seven children with CP (60 males, 37 females; aged 1-6 years) and their caregivers were recruited from the rehabilitation programs of Chang Gung Memorial Hospital in Taiwan for this 6-month longitudinal follow-up study. The Functional Independence Measure for Children (WeeFIM) and TAPQOL outcomes were measured at baseline and at a 6-month follow-up. Responsiveness was examined using the standardized response mean (SRM). The distribution-based and anchor-based MCID were determined. The TAPQOL outcomes include physical functioning (PF), social functioning (SF), cognitive functioning (CF), and emotional functioning (EF) domains. RESULTS: The responsiveness of the TAPQOL for all of TAPQOL domains was marked (SRM = 1.12-1.54). The anchor-based MCIDs of TAPQOL for PF, SF, CF, EF, and total domains were 1.25, 3.28, 2.93, 2.25, and 1.73, respectively, which were similar to the distribution-based MCID values of TAPQOL, except in the PF domain. The distribution-based MCIDs of TAPQOL in various domains were 2.85-3.73 when effect size (ES) was 0.2, 7.13-9.32 when ES was 0.5, and 11.40-14.91 when ES was 0.8. CONCLUSIONS: TAPQOL is markedly responsive to detect change in children with CP. The caregivers perceived the minimally important change in HRQOL of their children at a relatively low treatment efficacy. Researchers and clinicians can utilize TAPQOL data to determine whether changes in TAPQOL scores indicate clinically meaningful effects post-treatment and at the follow-up.

Predicting clinically significant motor function improvement after contemporary task-oriented interventions using machine learning approaches.

BACKGROUND: Accurate prediction of motor recovery after stroke is critical for treatment decisions and planning. Machine learning has been proposed to be a promising technique for outcome prediction because of its high accuracy and ability to process large volumes of data. It has been used to predict acute stroke recovery; however, whether machine learning would be effective for predicting rehabilitation outcomes in chronic stroke patients for common contemporary task-oriented interventions remains largely unexplored. This study aimed to determine the accuracy and performance of machine learning to predict clinically significant motor function improvements after contemporary task-oriented intervention in chronic stroke patients and identify important predictors for building machine learning prediction models. METHODS: This study was a secondary analysis of data using two common machine learning approaches, which were the k-nearest neighbor (KNN) and artificial neural network (ANN). Chronic stroke patients (N = 239) that received 30 h of task-oriented training including the constraint-induced movement therapy, bilateral arm training, robot-assisted therapy and mirror therapy were included. The Fugl-Meyer assessment scale (FMA) was the main outcome. Potential predictors include age, gender, side of lesion, time since stroke, baseline functional status, motor function and quality of life. We divided the data set into a training set and a test set and used the cross-validation procedure to construct machine learning models based on the training set. After the models were built, we used the test data set to evaluate the accuracy and prediction performance of the models. RESULTS: Three important predictors were identified, which were time since stroke, baseline functional independence measure (FIM) and baseline FMA scores. Models for predicting motor function improvements were accurate. The prediction accuracy of the KNN model was 85.42% and area under the receiver operating characteristic curve (AUC-ROC) was 0.89. The prediction accuracy of the ANN model was 81.25% and the AUC-ROC was 0.77. CONCLUSIONS: Incorporating machine learning into clinical outcome prediction using three key predictors including time since stroke, baseline functional and motor ability may help clinicians/therapists to identify patients that are most likely to benefit from contemporary task-oriented interventions. The KNN and ANN models may be potentially useful for predicting clinically significant motor recovery in chronic stroke.

Timing-dependent effects of transcranial direct current stimulation with mirror therapy on daily function and motor control in chronic stroke: a randomized controlled pilot study.

BACKGROUND: The timing of transcranial direct current stimulation (tDCS) with neurorehabilitation interventions may affect its modulatory effects. Motor function has been reported to be modulated by the timing of tDCS; however, whether the timing of tDCS would also affect restoration of daily function and upper extremity motor control with neurorehabilitation in stroke patients remains largely unexplored. Mirror therapy (MT) is a potentially effective neurorehabilitation approach for improving paretic arm function in stroke patients. This study aimed to determine whether the timing of tDCS with MT would influence treatment effects on daily function, motor function and motor control in individuals with chronic stroke. METHODS: This study was a double-blinded randomized controlled trial. Twenty-eight individuals with chronic stroke received one of the following three interventions: (1) sequentially combined tDCS with MT (SEQ), (2) concurrently combined tDCS with MT (CON), and (3) sham tDCS with MT (SHAM). Participants received interventions for 90 min/day, 5 days/week for 4 weeks. Daily function was assessed using the Nottingham Extended Activities of Daily Living Scale. Upper extremity motor function was assessed using the Fugl-Meyer Assessment Scale. Upper extremity motor control was evaluated using movement kinematic assessments. RESULTS: There were significant differences in daily function between the three groups. The SEQ group had greater improvement in daily function than the CON and SHAM groups. Kinematic analyses showed that movement time of the paretic hand significantly reduced in the SEQ group after interventions. All three groups had significant improvement in motor function from pre-intervention to post-intervention. CONCLUSION: The timing of tDCS with MT may influence restoration of daily function and movement efficiency of the paretic hand in chronic stroke patients. Sequentially applying tDCS prior to MT seems to be advantageous for enhancing daily function and hand movement control, and may be considered as a potentially useful strategy in future clinical application. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02827864 . Registered on 29th June, 2016.

Psychometric Evaluation of an ICF-Based Instrumental Activities of Daily Living Assessment With Older Adults With Cognitive Decline.

IMPORTANCE: Identifying cognitive or physical limitations that contribute to difficulties in instrumental activities of daily living (IADLs) is critical for adequate intervention with community-dwelling older adults with cognitive decline. OBJECTIVE: To establish the validity and responsiveness of an IADL scale based on the International Classification of Functioning, Disability and Health (the ICF-IADL) with respect to both cognitive and physical limitations. DESIGN: Cross-sectional study. SETTING: Multiple community care and senior centers. PARTICIPANTS: Eighty-two older adults. INTERVENTION: Combination of physical exercise and cognitive training. MEASURES: Five criterion measures-Lawton IADL Scale, Montreal Cognitive Assessment (MoCA), Digit Symbol Substitution Test (DSS), Word Lists Test (WLT), and Timed Up and Go Test (TUG). RESULTS: The ICF-IADL's three summary scales-Disability Index (DI), Cognitive Disability Index (CDI), and Physical Disability Index (PDI)-had good concurrent validity with the Lawton IADL Scale. The DI and CDI had moderate to good associations with the MoCA. The DI's and CDI's predictive validity for scores on the Lawton IADL Scale, MoCA, and TUG was moderate to good and that of the PDI was fair. Responsiveness was large for the DI, moderate for the CDI, and small for the PDI. CONCLUSIONS AND RELEVANCE: The ICF-IADL can be used to measure disability in IADLs related to cognitive and physical limitations. The DI and CDI were better than the PDI in predicting outcomes in general cognitive function and dynamic balance and were more responsive to change after intervention than the PDI. WHAT THIS ARTICLE ADDS: The ICF-IADL addresses both cognitive and physical limitations and can be a valid assessment of IADLs. Occupational therapists can use it to determine difficulties in IADLs and causes of those difficulties, guide treatment planning, and monitor intervention effectiveness with community-dwelling older adults with cognitive decline.

Intermittent theta burst stimulation enhances upper limb motor function in patients with chronic stroke: a pilot randomized controlled trial.

BACKGROUND: Intermittent theta burst stimulation (iTBS) is a form of repetitive transcranial stimulation that has been used to enhance upper limb (UL) motor recovery. However, only limited studies have examined its efficacy in patients with chronic stroke and therefore it remains controversial. METHODS: This was a randomized controlled trial that enrolled patients from a rehabilitation department. Twenty-two patients with first-ever chronic and unilateral cerebral stroke, aged 30-70 years, were randomly assigned to the iTBS or control group. All patients received 1 session per day for 10 days of either iTBS or sham stimulation over the ipsilesional primary motor cortex in addition to conventional neurorehabilitation. Outcome measures were assessed before and immediately after the intervention period: Modified Ashworth Scale (MAS), Fugl-Meyer Assessment Upper Extremity (FMA-UE), Action Research Arm Test (ARAT), Box and Block test (BBT), and Motor Activity Log (MAL). Analysis of covariance was adopted to compare the treatment effects between groups. RESULTS: The iTBS group had greater improvement in the MAS and FMA than the control group (η2 = 0.151-0.233; p < 0.05), as well as in the ARAT and BBT (η2 = 0.161-0.460; p < 0.05) with large effect size. Both groups showed an improvement in the BBT, and there were no significant between-group differences in MAL changes. CONCLUSIONS: The iTBS induced greater gains in spasticity decrease and UL function improvement, especially in fine motor function, than sham TBS. This is a promising finding because patients with chronic stroke have a relatively low potential for fine motor function recovery. Overall, iTBS may be a beneficial adjunct therapy to neurorehabilitation for enhancing UL function. Further larger-scale study is warranted to confirm the findings and its long-term effect. TRIAL REGISTRATION: This trial was registered under ClinicalTrials.gov ID No. NCT01947413 on September 20, 2013.

The Active Ingredient of Cognitive Restoration: A Multicenter Randomized Controlled Trial of Sequential Combination of Aerobic Exercise and Computer-Based Cognitive Training in Stroke Survivors With Cognitive Decline.

OBJECTIVE: To investigate the efficacy of a sequential combination of aerobic exercise and cognitive training on cognitive function and other health-related outcomes in stroke survivors with cognitive decline. DESIGN: Intervention study and randomized controlled trial. SETTING: Hospital-based rehabilitation units. PARTICIPANTS: Survivors of stroke with cognitive decline (N=30) were randomized to sequential combination training (SEQ) (n=15) or an active control (n=15) group. INTERVENTIONS: The SEQ group received 30 minutes of aerobic exercise, followed by 30 minutes of computerized cognitive training. The control group received 30 minutes of nonaerobic physical exercise, followed by 30 minutes of unstructured mental activities. MAIN OUTCOME MEASURES: The primary outcome measure was cognitive function. Secondary outcome measures included physical function, social participation, and quality of life. RESULTS: Compared with the control group, the SEQ group had significantly improved Montreal Cognitive Assessment scores (P=.03) and Wechsler Memory Scale span scores (P=.012) after training. The endurance and mobility level measured by the 6-minute walk test (P=.25) was also enhanced in the SEQ group relative to the control group. However, the transfer of sequential training to social participation (Community Integration Questionnaire) and quality of life (EuroQoL questionnaire) was limited (P>.05 for both). CONCLUSIONS: Aerobic exercise combined with computerized cognitive training has better effects on the cognitive functional status of survivors of stroke than an active control. The cognitive functional status of stroke survivors was better after participation in aerobic exercise combined with computerized training than after active control therapy, demonstrating the clinical significance of this combination therapy.

Low Persistence of Antithrombotic Agents is Associated with Poor Outcomes after First-ever Acute Ischemic Stroke.

OBJECTIVE: This study investigated the time-trend persistence with antithrombotic agents (AT) and assessed the impact of AT persistence on outcome events and adverse events (AE) within two years after first-ever acute ischemic stroke (IS). METHODS: Using Taiwan's National Health Insurance claims dataset, 7,341 IS subjects hospitalized between 2001 and 2005 with AT prescribed at discharge and survived at least 3 months were followed up for 2 years. Time-trends of AT usage were analyzed. Medication persistence was assessed as the proportion of days covered (PDC) for filled prescription, and categorized into low, intermediate and high persistence. Multivariate logistic regression analysis and multivariate Cox proportional hazard regression models were performed to identify factors associated with AT persistence and its impact on vascular outcomes. RESULTS: AT persistence rates declined sharply from 81% to 52% during the first 6 months. In addition to patient and facility-level characteristics, occurrence of AE (e.g., GI bleeding/ulceration, fractures/ major trauma, and iatrogenic/unspecific illness) was inversely related to AT persistence. Compared with patients with low persistence, the composite risk of recurrent stroke, cardiovascular disease, or death from any cause was significantly lower in patients with intermediate (Hazard Ratio [HR] 0.64, 0.57-0.71) or high AT persistence (0.74, 0.66-0.83).