Cardiovascular Disease After Hematopoietic Stem Cell Transplantation in Adults: JACC: CardioOncology State-of-the-Art Review.

The use of hematopoietic cell transplantation (HCT) has expanded in the last 4 decades to include an older and more comorbid population. These patients face an increased risk of cardiovascular disease after HCT. The risk varies depending on several factors, including the type of transplant (autologous or allogeneic). Many therapies used in HCT have the potential to be cardiotoxic. Cardiovascular complications after HCT include atrial arrhythmias, heart failure, myocardial infarction, and pericardial effusions. Before HCT, patients should undergo a comprehensive cardiovascular assessment, with ongoing surveillance tailored to their individual level of cardiovascular risk. In this review, we provide an overview of cardiotoxicity after HCT and outline our approach to risk assessment and ongoing care.

Motor imagery drives the effects of combined action observation and motor imagery on corticospinal excitability for coordinative lower-limb actions.

Combined action observation and motor imagery (AOMI) facilitates corticospinal excitability (CSE) and may potentially induce plastic-like changes in the brain in a similar manner to physical practice. This study used transcranial magnetic stimulation (TMS) to explore changes in CSE for AOMI of coordinative lower-limb actions. Twenty-four healthy adults completed two baseline (BLH, BLNH) and three AOMI conditions, where they observed a knee extension while simultaneously imagining the same action (AOMICONG), plantarflexion (AOMICOOR-FUNC), or dorsiflexion (AOMICOOR-MOVE). Motor evoked potential (MEP) amplitudes were recorded as a marker of CSE for all conditions from two knee extensor, one dorsi flexor, and two plantar flexor muscles following TMS to the right leg representation of the left primary motor cortex. A main effect for experimental condition was reported for all three muscle groups. MEP amplitudes were significantly greater in the AOMICONG condition compared to the BLNH condition (p = .04) for the knee extensors, AOMICOOR-FUNC condition compared to the BLH condition (p = .03) for the plantar flexors, and AOMICOOR-MOVE condition compared to the two baseline conditions for the dorsi flexors (ps ≤ .01). The study findings support the notion that changes in CSE are driven by the imagined actions during coordinative AOMI.

Chronic kidney disease and transvenous cardiac implantable electronic device infection-is there an impact on healthcare utilization, costs, disease progression, and mortality?

AIMS: Cardiac implantable electronic device (CIED) infections are a burden to hospitals and costly for healthcare systems. Chronic kidney disease (CKD) increases the risk of CIED infections, but its differential impact on healthcare utilization, costs, and outcomes is not known. METHODS AND RESULTS: This retrospective analysis used de-identified Medicare Fee-for-Service claims to identify patients implanted with a CIED from July 2016 to December 2020. Outcomes were defined as hospital days and costs within 12 months post-implant, post-infection CKD progression, and mortality. Generalized linear models were used to calculate results by CKD and infection status while controlling for other comorbidities, with differences between cohorts representing the incremental effect associated with CKD. A total of 584 543 patients had a CIED implant, of which 26% had CKD and 1.4% had a device infection. The average total days in hospital for infected patients was 23.5 days with CKD vs. 14.5 days (P < 0.001) without. The average cost of infection was $121 756 with CKD vs. $55 366 without (P < 0.001), leading to an incremental cost associated with CKD of $66 390. Infected patients with CKD were more likely to have septicaemia or severe sepsis than those without CKD (11.0 vs. 4.6%, P < 0.001). After infection, CKD patients were more likely to experience CKD progression (hazard ratio 1.26, P < 0.001) and mortality (hazard ratio 1.89, P < 0.001). CONCLUSION: Cardiac implantable electronic device infection in patients with CKD was associated with more healthcare utilization, higher cost, greater disease progression, and greater mortality compared to patients without CKD.

A Modular Communicative Leadless Pacing-Defibrillator System.

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (ICD) is associated with fewer lead-related complications than a transvenous ICD; however, the subcutaneous ICD cannot provide bradycardia and antitachycardia pacing. Whether a modular pacing-defibrillator system comprising a leadless pacemaker in wireless communication with a subcutaneous ICD to provide antitachycardia and bradycardia pacing is safe remains unknown. METHODS: We conducted a multinational, single-group study that enrolled patients at risk for sudden death from ventricular arrhythmias and followed them for 6 months after implantation of a modular pacemaker-defibrillator system. The safety end point was freedom from leadless pacemaker-related major complications, evaluated against a performance goal of 86%. The two primary performance end points were successful communication between the pacemaker and the ICD (performance goal, 88%) and a pacing threshold of up to 2.0 V at a 0.4-msec pulse width (performance goal, 80%). RESULTS: We enrolled 293 patients, 162 of whom were in the 6-month end-point cohort and 151 of whom completed the 6-month follow-up period. The mean age of the patients was 60 years, 16.7% were women, and the mean (±SD) left ventricular ejection fraction was 33.1±12.6%. The percentage of patients who were free from leadless pacemaker-related major complications was 97.5%, which exceeded the prespecified performance goal. Wireless-device communication was successful in 98.8% of communication tests, which exceeded the prespecified goal. Of 151 patients, 147 (97.4%) had pacing thresholds of 2.0 V or less, which exceeded the prespecified goal. The percentage of episodes of arrhythmia that were successfully terminated by antitachycardia pacing was 61.3%, and there were no episodes for which antitachycardia pacing was not delivered owing to communication failure. Of 162 patients, 8 died (4.9%); none of the deaths were deemed to be related to arrhythmias or the implantation procedure. CONCLUSIONS: The leadless pacemaker in wireless communication with a subcutaneous ICD exceeded performance goals for freedom from major complications related to the leadless pacemaker, for communication between the leadless pacemaker and subcutaneous ICD, and for the percentage of patients with a pacing threshold up to 2.0 V at a 0.4-msec pulse width at 6 months. (Funded by Boston Scientific; MODULAR ATP ClinicalTrials.gov NCT04798768.).

Development and Validation of the Combined Action Observation and Motor Imagery Ability Questionnaire.

Combined use of action observation and motor imagery (AOMI) is an increasingly popular motor-simulation intervention, which involves observing movements on video while simultaneously imagining the feeling of movement execution. Measuring and reporting participant imagery-ability characteristics are essential in motor-simulation research, but no measure of AOMI ability currently exists. Accordingly, the AOMI Ability Questionnaire (AOMI-AQ) was developed to address this gap in the literature. In Study 1, two hundred eleven participants completed the AOMI-AQ and the kinesthetic imagery subscales of the Movement Imagery Questionnaire-3 and Vividness of Motor Imagery Questionnaire-2. Following exploratory factor analysis, an 8-item AOMI-AQ was found to correlate positively with existing motor-imagery measures. In Study 2, one hundred seventy-four participants completed the AOMI-AQ for a second time after a period of 7-10 days. Results indicate a good test-retest reliability for the AOMI-AQ. The new AOMI-AQ measure provides a valid and reliable tool for researchers and practitioners wishing to assess AOMI ability.

The self-reported driving and pedestrian behaviour of adults with developmental coordination disorder.

BACKGROUND: Developmental coordination disorder (DCD) affects movement coordination, but little is known about how the condition impacts the behaviours of car drivers and pedestrians. AIMS: This study examined the self-reported driving and pedestrian behaviours of adults with Developmental Coordination Disorder (DCD). METHODS AND PROCEDURES: One hundred and twenty-eight participants (62 adults with DCD vs. 66 TD adults) responded to an online survey asking them about their perceptions of confidence and self-reported driving and pedestrian behaviours in the real-world. OUTCOMES AND RESULTS: Results suggested that adults with DCD felt less confident and reported more lapses in attention (e.g., forgetting where their car was parked) and errors (e.g., failing to check their mirrors prior to a manoeuvre) when driving compared to typically developed (TD) adults. Adults with DCD also reported feeling less confident and reported less adherence to road traffic laws (e.g., not waiting for a green crossing signal before crossing the road) when walking as pedestrians. CONCLUSIONS AND IMPLICATIONS: These results offer some much-needed insight into the behaviours of those with DCD outside of the laboratory environment and underline the need for research investigating the driving and pedestrian behaviours of individuals with DCD in 'real-world' contexts.

No increase in corticospinal excitability during motor simulation provides a platform to explore the neurophysiology of aphantasia.

This scientific commentary refers to 'Explicit and implicit motor simulations are impaired in individuals with aphantasia', by Dupont  et al. (https://doi.org/10.1093/braincomms/fcae072) in Brain Communications.

Apixaban for Stroke Prevention in Subclinical Atrial Fibrillation.

BACKGROUND: Subclinical atrial fibrillation is short-lasting and asymptomatic and can usually be detected only by long-term continuous monitoring with pacemakers or defibrillators. Subclinical atrial fibrillation is associated with an increased risk of stroke by a factor of 2.5; however, treatment with oral anticoagulation is of uncertain benefit. METHODS: We conducted a trial involving patients with subclinical atrial fibrillation lasting 6 minutes to 24 hours. Patients were randomly assigned in a double-blind, double-dummy design to receive apixaban at a dose of 5 mg twice daily (2.5 mg twice daily when indicated) or aspirin at a dose of 81 mg daily. The trial medication was discontinued and anticoagulation started if subclinical atrial fibrillation lasting more than 24 hours or clinical atrial fibrillation developed. The primary efficacy outcome, stroke or systemic embolism, was assessed in the intention-to-treat population (all the patients who had undergone randomization); the primary safety outcome, major bleeding, was assessed in the on-treatment population (all the patients who had undergone randomization and received at least one dose of the assigned trial drug, with follow-up censored 5 days after permanent discontinuation of trial medication for any reason). RESULTS: We included 4012 patients with a mean (±SD) age of 76.8±7.6 years and a mean CHA2DS2-VASc score of 3.9±1.1 (scores range from 0 to 9, with higher scores indicating a higher risk of stroke); 36.1% of the patients were women. After a mean follow-up of 3.5±1.8 years, stroke or systemic embolism occurred in 55 patients in the apixaban group (0.78% per patient-year) and in 86 patients in the aspirin group (1.24% per patient-year) (hazard ratio, 0.63; 95% confidence interval [CI], 0.45 to 0.88; P = 0.007). In the on-treatment population, the rate of major bleeding was 1.71% per patient-year in the apixaban group and 0.94% per patient-year in the aspirin group (hazard ratio, 1.80; 95% CI, 1.26 to 2.57; P = 0.001). Fatal bleeding occurred in 5 patients in the apixaban group and 8 patients in the aspirin group. CONCLUSIONS: Among patients with subclinical atrial fibrillation, apixaban resulted in a lower risk of stroke or systemic embolism than aspirin but a higher risk of major bleeding. (Funded by the Canadian Institutes of Health Research and others; ARTESIA ClinicalTrials.gov number, NCT01938248.).

Guidelines for reporting action simulation studies (GRASS): Proposals to improve reporting of research in motor imagery and action observation.

Researchers from multiple disciplines have studied the simulation of actions through motor imagery, action observation, or their combination. Procedures used in these studies vary considerably between research groups, and no standardized approach to reporting experimental protocols has been proposed. This has led to under-reporting of critical details, impairing the assessment, replication, synthesis, and potential clinical translation of effects. We provide an overview of issues related to the reporting of information in action simulation studies, and discuss the benefits of standardized reporting. We propose a series of checklists that identify key details of research protocols to include when reporting action simulation studies. Each checklist comprises A) essential methodological details, B) essential details that are relevant to a specific mode of action simulation, and C) further points that may be useful on a case-by-case basis. We anticipate that the use of these guidelines will improve the understanding, reproduction, and synthesis of studies using action simulation, and enhance the translation of research using motor imagery and action observation to applied and clinical settings.

Synchronous action observation and motor imagery may not always represent the optimal form of action simulation: a commentary on Eaves et al. (2022).

(Eaves et al., Psychological Research Psychologische Forschung, 2022) summary review, showing positive behavioural effects of AOMI interventions, is a welcome addition to the field. Several recent studies, however, have reported that AOMI may be no more beneficial than independent MI, and, for some tasks, may add no benefit beyond that obtained via physical practice. We discuss evidence to balance the narrative but support the pragmatic reasons why AOMI remains a suitable and appealing form of action simulation. We propose that further research interrogation of the discrete AOMI states through a more continuum-based approach could address some of the inconsistent data seen in AOMI research.

Protocol of the process evaluation of cluster randomised control trial for estimating the effectiveness and cost-effectiveness of a complex intervention to increase care home staff influenza vaccination rates compared to usual practice (FluCare).

BACKGROUND: Influenza (flu) vaccination rates in UK care home staff are extremely low. Less than 40% of staff in care homes are vaccinated for influenza (flu), presenting risks to the health of frail residents and potential staff absence from cross-infection. Staff often do not perceive a need for vaccination and are unaware they are entitled to free flu vaccination. The FluCare study, a cluster randomised control trial (RCT), uses behavioural interventions to address barriers. Videos, posters, and leaflets are intended to raise awareness of flu vaccination benefits and debunk myths. On-site staff vaccination clinics increase accessibility. Financial incentives to care homes for improved vaccination rates and regular monitoring influence the environment. This paper outlines the planned process evaluation which will describe the intervention's mechanisms of action, explain any changes in outcomes, identify local adaptations, and inform design of the implementation phase. METHODS/DESIGN: A mixed method process evaluation to inform the interpretation of trial findings. OBJECTIVES: • Describe the intervention as delivered in terms of dose and fidelity, including adaptations and variations across care homes. • Explore the effects of individual intervention components on primary outcomes. • Investigate the mechanisms of impact. • Describe the perceived effectiveness of relevant intervention components (including videos, leaflets, posters, and flu clinics) from participant perspectives (care home manager, care home staff, flu clinic providers). • Describe the characteristics of care homes and participants to assess reach. A purposive sample of twenty care homes (ten in the intervention arm, ten in the control arm) for inclusion in the process evaluation. Data will include (1) study records including care home site profiles, (2) responses to a mechanism of action questionnaire, and (3) semi-structured interviews with care home staff and clinic providers. Quantitative data will be descriptively reported. Interview data will be thematically analysed and then categories mapped to the Theoretical Domains Framework. DISCUSSION: Adopting this systematic and comprehensive process evaluation approach will help ensure data is captured on all aspects of the trial, enabling a full understanding of the intervention implementation and RCT findings. TRIAL REGISTRATION: ISRCTN ISRCTN22729870. Registered on 24 August 2022.

Design and rationale of the MODULAR ATP global clinical trial: A novel intercommunicative leadless pacing system and the subcutaneous implantable cardioverter-defibrillator.

Background: The subcutaneous implantable cardioverter-defibrillator (S-ICD) has demonstrated safety and efficacy for the treatment of malignant ventricular arrhythmias. However, a limitation of the S-ICD lies in the inability to either pace-terminate ventricular tachycardia or provide prolonged bradycardia pacing support. Objective: The rationale and design of a prospective, single-arm, multinational trial of an intercommunicative leadless pacing system integrated with the S-ICD will be presented. Methods: A technical description of the modular cardiac rhythm management (mCRM) system (EMPOWER leadless pacemaker and EMBLEM S-ICD) and the implantation procedure is provided. MODULAR ATP (Effectiveness of the EMPOWER™ Modular Pacing System and EMBLEM™ Subcutaneous ICD to Communicate Antitachycardia Pacing) is a multicenter, international trial enrolling up to 300 patients at risk of sudden cardiac death at up to 60 centers trial design. The safety endpoint of freedom from major complications related to the mCRM system or implantation procedure at 6 months and 2 years are significantly higher than 86% and 81%, respectively, and all-cause survival is significantly >85% at 2 years. Results: Efficacy endpoints are that at 6 months mCRM communication success is significantly higher than 88% and the percentage of subjects with low and stable thresholds is significantly higher than 80%. Substudies to evaluate rate-responsive features and performance of the pacing module are also described. Conclusion: The MODULAR ATP global clinical trial will prospectively test the safety and efficacy of the first intercommunicating leadless pacing system with the S-ICD. This trial will allow for robust validation of device-device communication, pacing performance, rate responsiveness, and system safety.

Panhematopoietic RNA barcoding enables kinetic measurements of nucleate and anucleate lineages and the activation of myeloid clones following acute platelet depletion.

BACKGROUND: Platelets and erythrocytes constitute over 95% of all hematopoietic stem cell output. However, the clonal dynamics of HSC contribution to these lineages remains largely unexplored. RESULTS: We use lentiviral genetic labeling of mouse hematopoietic stem cells to quantify output from all lineages, nucleate, and anucleate, simultaneously linking these with stem and progenitor cell transcriptomic phenotypes using single-cell RNA-sequencing. We observe dynamic shifts of clonal behaviors through time in same-animal peripheral blood and demonstrate that acute platelet depletion shifts the output of multipotent hematopoietic stem cells to the exclusive production of platelets. Additionally, we observe the emergence of new myeloid-biased clones, which support short- and long-term production of blood cells. CONCLUSIONS: Our approach enables kinetic studies of multi-lineage output in the peripheral blood and transcriptional heterogeneity of individual hematopoietic stem cells. Our results give a unique insight into hematopoietic stem cell reactivation upon platelet depletion and of clonal dynamics in both steady state and under stress.

Age and adult attachment style predict psychological distress in the Singapore general population during COVID-19.

To date, there is increasing evidence to suggest that age and adult attachment styles, such as secure, anxious and avoidant attachment are predictive or protective for psychological distress. The study aimed to investigate the extent to which age and adult attachment style, measured by the Attachment Style Questionnaire, predicted psychological distress, measured by the Kessler 10 Psychological Distress Scale, in the Singapore general population during COVID-19. Ninety-nine residents of Singapore (44 females, 52 males, 3 prefer not to state their gender) aged between 18 and 66 completed an online survey, which collected information on age, adult attachment styles and levels of psychological distress. Multiple regression analysis was performed to study the influence of predictive factors on psychological distress. The study identified 20.2%, 13.1% and 14.1% of participants reporting psychological distress at the mild, moderate and severe levels, respectively. The study also reported that age and psychological distress were negatively correlated, and that psychological distress was negatively correlated with both anxious and avoidant attachment styles. It was concluded that age and adult attachment style significantly predicted psychological distress in the Singapore general population during COVID-19. Further studies exploring other variables and risk factors are required to further consolidate these results. At the global level, these findings may help countries predict residents' reactions to future outbreaks and help them prepare strategies and approaches to address these situations.

Prevalence of SARS-CoV-2 Viremia in Presymptomatic Blood Donors in the Delta and Omicron Variant Eras.

Presymptomatic plasma samples from 1596 donors reporting coronavirus disease 2019 infection or symptoms after blood donation were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and anti-S and anti-N antibodies. Prior infection and vaccination both protected from developing SARS-CoV-2 RNAemia and from symptomatic infection. RNAemia rates did not differ in the Delta and Omicron variant eras.

Combined action observation and motor imagery improves learning of activities of daily living in children with Developmental Coordination Disorder.

Developmental coordination disorder (DCD) is characterised by poor motor coordination, which interferes with the ability to execute activities of daily living (ADLs). Combined action observation and motor imagery (AOMI) involves observing movement videos whilst imagining simultaneously the sensations of executing the same movement. Laboratory-based research indicates that AOMI can help improve movement coordination in children with DCD, but no previous research had investigated the efficacy of AOMI interventions for learning ADLs. This study investigated the efficacy of a home-based, parent-led, AOMI intervention for learning ADLs in children with DCD. Children with confirmed (n = 23) or suspected (n = 5) DCD (total sample n = 28), aged 7-12 years, were assigned to either an AOMI intervention or a control intervention (both n = 14). Participants attempted the following ADLs at pre-test (week 1), post-test (week 4), and retention test (week 6): shoelace tying, cutlery use, shirt buttoning, and cup stacking. Task completion times and movement techniques were recorded. The AOMI intervention produced significantly faster task completion times than the control intervention at post-test for shoelace tying, and significantly improved movement techniques for shoelace tying and cup stacking. Importantly, for children who could not tie shoelaces at pre-test (n = 9 per group), 89% of those following the AOMI intervention learnt the skill successfully by the end of the study, compared to only 44% of those following the control intervention. The findings indicate that home-based, parent-led, AOMI interventions can aid the learning of complex ADLs in children with DCD, and may be particularly effective for facilitating the learning of motor skills that do not currently exist within these children's motor repertoire.

A tool for measuring mental workload during prosthesis use: The Prosthesis Task Load Index (PROS-TLX).

When using a upper-limb prosthesis, mental, emotional, and physical effort is often experienced. These have been linked to high rates of device dissatisfaction and rejection. Therefore, understanding and quantifying the complex nature of workload experienced when using, or learning to use, a upper-limb prosthesis has practical and clinical importance for researchers and applied professionals. The aim of this paper was to design and validate a self-report measure of mental workload specific to prosthesis use (The Prosthesis Task Load Index; PROS-TLX) that encapsulates the array of mental, physical, and emotional demands often experienced by users of these devices. We first surveyed upper-limb prosthetic limb users who confirmed the importance of eight workload constructs taken from published literature and previous workload measures. These constructs were mental demands, physical demands, visual demands, conscious processing, frustration, situational stress, time pressure and device uncertainty. To validate the importance of these constructs during initial prosthesis learning, we then asked able-bodied participants to complete a coin-placement task using their anatomical hand and then using a myoelectric prosthesis simulator under low and high mental workload. As expected, using a prosthetic hand resulted in slower movements, more errors, and a greater tendency to visually fixate the hand (indexed using eye-tracking equipment). These changes in performance were accompanied by significant increases in PROS-TLX workload subscales. The scale was also found to have good convergent and divergent validity. Further work is required to validate whether the PROS-TLX can provide meaningful clinical insights to the workload experienced by clinical users of prosthetic devices.