Upper limb sensorimotor recovery in Asian stroke survivors: a study protocol for the development and implementation of a Technology-Assisted dIgitaL biOmaRker (TAILOR) platform.

Background: Stroke is a leading cause of lifelong disability worldwide, partially driven by a reduced ability to use the upper limb in daily life causing increased dependence on caregivers. However, post-stroke functional impairments have only been investigated using limited clinical scores, during short-term longitudinal studies in relatively small patient cohorts. With the addition of technology-based assessments, we propose to complement clinical assessments with more sensitive and objective measures that could more holistically inform on upper limb impairment recovery after stroke, its impact on upper limb use in daily life, and on overall quality of life. This paper describes a pragmatic, longitudinal, observational study protocol aiming to gather a uniquely rich multimodal database to comprehensively describe the time course of upper limb recovery in a representative cohort of 400 Asian adults after stroke. Particularly, we will characterize the longitudinal relationship between upper limb recovery, common post-stroke impairments, functional independence and quality of life. Methods: Participants with stroke will be tested at up to eight time points, from within a month to 3 years post-stroke, to capture the influence of transitioning from hospital to community settings. We will perform a battery of established clinical assessments to describe the factors most likely to influence upper limb recovery. Further, we will gather digital health biomarkers from robotic or wearable sensing technology-assisted assessments to sensitively characterize motor and somatosensory impairments and upper limb use in daily life. We will also use both quantitative and qualitative measures to understand health-related quality of life. Lastly, we will describe neurophysiological motor status using transcranial magnetic stimulation. Statistics: Descriptive analyses will be first performed to understand post-stroke upper limb impairments and recovery at various time points. The relationships between digital biomarkers and various domains will be explored to inform key aspects of upper limb recovery and its dynamics using correlation matrices. Multiple statistical models will be constructed to characterize the time course of upper limb recovery post-stroke. Subgroups of stroke survivors exhibiting distinct recovery profiles will be identified. Conclusion: This is the first study complementing clinical assessments with technology-assisted digital biomarkers to investigate upper limb sensorimotor recovery in Asian stroke survivors. Overall, this study will yield a multimodal data set that longitudinally characterizes post-stroke upper limb recovery in functional impairments, daily-life upper limb use, and health-related quality of life in a large cohort of Asian stroke survivors. This data set generates valuable information on post-stroke upper limb recovery and potentially allows researchers to identify different recovery profiles of subgroups of Asian stroke survivors. This enables the comparisons between the characteristics and recovery profiles of stroke survivors in different regions. Thus, this study lays out the basis to identify early predictors for upper limb recovery, inform clinical decision-making in Asian stroke survivors and establish tailored therapy programs. Clinical trial registration: ClinicalTrials.gov, identifier: NCT05322837.

Thwarting Instant Messaging Phishing Attacks: The Role of Self-Efficacy and the Mediating Effect of Attitude towards Online Sharing of Personal Information.

CONTEXT: The cause of cybercrime phishing threats in Malaysia is a lack of knowledge and awareness of phishing. OBJECTIVE: The effects of self-efficacy (the ability to gain anti-phishing knowledge) and protection motivation (attitude toward sharing personal information online) on the risk of instant messaging phishing attacks (phishing susceptibility) are investigated in this study. The protection motivation theory (PMT) was tested in the context of attitudes toward sharing personal information online with a view to improving interventions to reduce the risk of phishing victimisation. METHODS: Data were collected using non-probability purposive sampling. An online survey of 328 Malaysian active instant messaging users was collected and analysed in SmartPLS version 4.0.8.6 using partial least squares structural equation modelling. RESULTS: The results showed that a person's cognitive factor (either high or low self-efficacy) affected their chance of being a victim of instant message phishing. A higher level of self-efficacy and a negative attitude towards sharing personal information online were significant predictors of phishing susceptibility. A negative attitude towards sharing personal information online mediated the relationship between high levels of self-efficacy and phishing susceptibility. A higher level of self-efficacy led to the formation of negative attitudes among internet users. Attitudes toward the sharing of personal information online are critical because they allow phishing attempts to exist and succeed. CONCLUSIONS: The findings give government agencies more information on how to organise anti-phishing campaigns and awareness programmes; awareness and education can improve one's ability to acquire anti-phishing knowledge (self-efficacy).

A self-directed upper limb program during early post-stroke rehabilitation: A qualitative study of the perspective of nurses, therapists and stroke survivors.

INTRODUCTION: This study aimed to explore the perspective of nurses, therapists and stroke survivors on the performance of upper limb self-exercise and use outside therapy during early inpatient stroke rehabilitation. METHODS: A descriptive qualitative approach was used in focus groups with nurses (n = 21) and therapists (n = 8), as well as in-depth semi-structured interviews with stroke survivors (n = 8) who were undergoing subacute inpatient stroke rehabilitation. Inductive thematic analysis of data was performed according to participant group. RESULTS: Nurses and therapists perceived that stroke survivors played a central role in determining the success of a self-directed upper limb program. Nurses perceived that stroke survivors needed a lot of prompting to be motivated to perform self-directed upper limb therapy outside therapy. Therapists perceived that not all stroke survivors would be able to perform self-directed upper limb therapy and deemed it important to consider stroke survivor factors before commencing a program. Although some stroke survivors expressed initial reservations with performing self-practice, many indicated that they would participate in the self-directed upper limb program because they wanted to recover faster. CONCLUSION: A difference between the perspective of nurses/therapists and stroke survivors towards self-directed upper limb performance outside therapy was found. Deeper stroke survivor engagement and a shift in rehabilitation culture to encourage stroke survivor autonomy are important considerations for a self-directed upper limb program. Teamwork amongst healthcare professionals and families is essential to support stroke survivors to participate in a self-directed upper limb program during early inpatient stroke rehabilitation.

A Self-Empowered Upper Limb Repetitive Engagement Program to Improve Upper Limb Recovery Early Post-Stroke: Phase II Pilot Randomized Controlled Trial.

Background. Time outside therapy provides an opportunity to increase upper limb (UL) use during post-stroke hospitalization. Objective. To determine if a self-directed UL program outside therapy (Self-Empowered UL Repetitive Engagement, SURE) was feasible and to explore the potential effect of the SURE program on UL use and recovery. Methods. Twenty-three patients from an inpatient rehabilitation center who were ≤21 days post-stroke and had a Fugl Meyer UL (FMUL) score ≤50 and a positive motor evoked potential (MEP+) response were randomized (stratified by impairment) to either experimental group (SURE: individualized, UL self-exercise and use outside therapy for 6 hours/week for 4 weeks) or control group (education booklet). Feasibility was evaluated by program adherence, dropout rate, adverse events, and satisfaction. Potential effect was measured by paretic UL use via accelerometry weekly during the intervention, FMUL and Action Research Arm Test (ARAT) at baseline (Week 0), post-intervention (Week 4), and follow-up (Week 8 and Week 16). Results. Adherence to SURE was high: 87% program completion (mean 313±75 repetitions/day). There were no dropouts, no adverse events related to SURE, and patient satisfaction averaged 7.8/10. Experimental participants achieved an additional hour of UL use daily (range: .3-1.2 hours/day) compared to control. Significant improvements in FMUL and ARAT were observed in both groups from Week 0 to Week 4 and to Week 8 (P ≤ .002), which were maintained to Week 16. There were no differences between groups (P ≥ .119). Conclusions. SURE was a feasible self-directed program that increased UL use in MEP+ individuals with moderate-severe impairment early post-stroke. Further studies with larger sample sizes and potentially higher dose are required to determine efficacy.

Factors Influencing Paretic Upper Limb Use During First 4 Weeks After Stroke: A Cross-Sectional Accelerometry Study.

OBJECTIVE: This study aimed to investigate factors related to paretic upper limb use within the first 4 wks after stroke. DESIGN: Sixty inpatients within 4 wks of first-time stroke were stratified by severity defined by Fugl-Meyer Upper Limb scores: severe = 0-22, moderate = 23-50, and mild = 51-66. All wore a wrist accelerometer on the paretic upper limb (24 hrs). Factors investigated were the following measures: upper limb motor impairment; mobility; balance; functional independence; sensory impairment; cognitive function; social factors; environmental restriction; and knowledge. Individual and multivariate quantile regression analyses were performed. RESULTS: Upper limb motor impairment, mobility, balance, functional independence, self-efficacy, and knowing how to use the paretic upper limb were significantly related to upper limb use across the three impairment groups (pseudo R2 = 0.079-0.492, P < 0.02). Multivariate regression showed the only significant factor in moderate and mild group was Fugl-Meyer Upper Limb score (moderate pseudo R2 = 0.55, mild pseudo R2 = 0.54, P < 0.001). For the severe group, Fugl-Meyer upper limb score and step count were significant (severe pseudo R2 = 0.47, P ≤ 0.030). CONCLUSIONS: Upper limb motor impairment is significantly associated with paretic upper limb use across three impairment groups and step count with the severe group. Strategies to improve upper limb motor impairment and increase mobility may be required to increase upper limb use.

Upper limb use differs among people with varied upper limb impairment levels early post-stroke: a single-site, cross-sectional, observational study.

Background: There is limited knowledge on the upper limb (UL) use early post-stroke by impairment levels.Objectives: To 1) To characterize paretic UL use in people with different UL impairment levels early post-stroke during and outside therapy; 2) compare UL use in people early post-stroke to age-matched controls.Methods: A prospective cross-sectional study of inpatients with first-time stroke ≤4-weeks (n=60, 61±12 years) categorized by Fugl-Meyer UL score for impairment subgroups: mild (51-66), moderate (23-50) and severe (0-22) was conducted. Age-matched, community-dwelling individuals without a history of stroke were recruited (n=30, 60±11 years). Bilateral wrist-worn accelerometers measured the duration of paretic UL use and use the ratio of paretic/non-paretic and non-dominant/dominant UL.Results: Sixty-three percent of stroke participants with mild impairment used their paretic UL >6 h/day (median (IQR): 6.7(3.3); use ratio 0.9(0.3)). Those with moderate impairment demonstrated wide variation of use; 13.3% achieving >6 h use/day (median (IQR): 4.5(3.8); use ratio 0.5(0.2)). People with severe impairment demonstrated limited use. None achieved >6 h/day of use (median (IQR): 1.7(0.7); use ratio 0.3(0.2)). Paretic UL use and use ratio were greater during therapy compared to outside therapy in moderate and severe groups (p<.002). Age-matched controls used their non-dominant UL for 8.7(3.0) hours, significantly more than all stroke participants (p<.002).Conclusions: Patterns of UL use differed by severity of impairment. Moderate and severe groups used their paretic UL more during therapy, inferring that it is possible to increase paretic use despite motor impairment. Future research stratifying by impairment across multinational sites is warranted to generalize findings.

An accelerometry and observational study to quantify upper limb use after stroke during inpatient rehabilitation.

OBJECTIVES: The objectives of the study are to characterize paretic upper limb (UL) use in people with different levels of impairment 4 weeks poststroke and to compare accelerometry and direct observational approaches. METHODS: Twelve stroke inpatients (five mild, three moderate, and four severe UL impairment) were recruited from a rehabilitation hospital. UL use was measured using accelerometry (24 hr) and direct observation (12 hr of behavioural mapping). Accelerometry variables included duration of use, use ratio, magnitude ratio, bilateral magnitude, and variation ratio. Direct observation recorded the duration of use and type of UL movement (e.g., functional vs. non-functional). RESULTS: From accelerometry data, people with mild, moderate, and severe UL impairments used their paretic UL 59%, 45%, and 22% of a 24 hr-day, respectively. People with severe UL impairment had the lowest paretic UL use duration (median 1.49 hr/day), magnitude ratio, and variation ratio compared with people with mild and moderate UL impairment. From 12 hr of observational data, people with mild impairment were using their UL for 37.8% of the observed time, whereas the people with moderate and severe impairment were using their UL 15.8% and 4.9%, respectively. UL movements for the mild cohort were mainly functional, whereas UL movements of the moderate and severe cohorts were mainly non-functional. UL movements were predominantly active for the mild and moderate cohorts but passive for the severe cohort. Duration of paretic UL use from accelerometry and observation data were highly correlated (ICC > 0.8), but the absolute percentage error between methods ranged from 34.2% to 42.7%. CONCLUSIONS: Paretic UL use within the first 4 weeks poststroke differs across levels of impairment in this exploratory study. Accelerometry and observation findings of paretic UL use were correlated and may be needed in different situations as they capture different information.

Factors affecting falls in community-dwelling individuals with stroke in Singapore after hospital discharge.

INTRODUCTION: This study aimed to investigate the factors affecting the incidence of falls among individuals with stroke living in the community one year after discharge from a rehabilitation hospital in Singapore. METHODS: A cross-sectional telephone survey of individuals with stroke living in the community was carried out one year after discharge. The interview covered aspects such as incidence and circumstances of fall, use of walking aids, and presence of environmental obstacles. Each participant's case record was retrospectively reviewed using discharge Fugl-Meyer (FM) assessment of the upper and lower limbs, functional independence measure (FIM) and Berg Balance Scale (BBS). RESULTS: A total of 126 individuals with stroke were interviewed. Overall, 24% fell in the year following their discharge. Factors associated with falls were longer length of hospital stay, lower BBS and lower-limb FM scores, and lower discharge FIM scores for the Bladder and Bowel Management, Transfer, Mobility, Communication, and Social Cognition domains (p < 0.05). The fallers were more likely to use walking aids, and required help with basic activities of daily living after discharge (p < 0.05). Multivariate logistic regression analysis revealed that only the Transfer domain was an independent factor for falls. CONCLUSION: Discharge FIM outcomes, especially for the Transfer domain, can be used to identify communitydwelling individuals with stroke who have a high fall risk after discharge. Identification of such individuals will enable early fall prevention management, which will in turn minimise fall events in the community.

Interleukin-21 enhances rituximab activity in a cynomolgus monkey model of B cell depletion and in mouse B cell lymphoma models.

Rituximab, a monoclonal antibody targeting CD20 on B cells, is currently used to treat many subtypes of B cell lymphomas. However, treatment is not curative and response rates are variable. Recombinant interleukin-21 (rIL-21) is a cytokine that enhances immune effector function and affects both primary and transformed B cell differentiation. We hypothesized that the combination of rIL-21 plus rituximab would be a more efficacious treatment for B cell malignancies than rituximab alone. We cultured human and cynomolgus monkey NK cells with rIL-21 and found that their activity was increased and proteins associated with antibody dependent cytotoxicity were up-regulated. Studies in cynomolgus monkeys modeled the effects of rIL-21 on rituximab activity against CD20 B cells. In these studies, rIL-21 activated innate immune effectors, increased ADCC and mobilized B cells into peripheral blood. When rIL-21 was combined with rituximab, deeper and more durable B cell depletion was observed. In another series of experiments, IL-21 was shown to have direct antiproliferative activity against a subset of human lymphoma cell lines, and combination of murine IL-21 with rituximab yielded significant survival benefits over either agent alone in xenogeneic mouse tumor models of disseminated lymphoma. Therefore, our results do suggest that the therapeutic efficacy of rituximab may be improved when used in combination with rIL-21.

Comparison of the ability of wild type and stabilized human IgG(4) to undergo Fab arm exchange with endogenous IgG(4)in vitro and in vivo.

Fab arm exchange by a stabilized anti-IL-31 IgG(4)S228P monoclonal antibody (mAb) was studied using physiologically relevant antibody concentrations and thiol exchange conditions, and directly compared to that of matched wild type IgG(4) (IgG(4)wt) and IgG(1) control antibodies. In vitro arm exchange between the test mAbs and a purified IgG(4)wt exchange partner was monitored using capillary isoelectric focusing and a size-exclusion peak shift assay. Arm exchange between the test mAbs and IgG exchange partners with unknown specificity was monitored using only the shift assay. Studies were performed using single isotype human and mouse mAbs, unfractionated human, mouse, and cynomolgus monkey IgG, and human serum as the sources of the exchange partners. In vitro studies using human serum demonstrated that anti-IL-31 IgG(4)S228P did not undergo significant Fab arm exchange with endogenous human IgG(4) whereas anti-IL-31 IgG(4)wt underwent rapid and extensive Fab arm exchange. The in vitro results were corroborated by in vivo studies in which mice were injected with a mixture of either form of the test mAb and an excess of non-specific human IgG(4) exchange partner.