Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial.

BACKGROUNDCOVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined.METHODSThis secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low posttransfusion antibody levels was established by 2 methods: (i) analyzing virus neutralization-equivalent anti-Spike receptor-binding domain immunoglobulin G (anti-S-RBD IgG) responses in donors or (ii) receiver operating characteristic (ROC) curve analysis.RESULTSSARS-CoV-2 anti-S-RBD IgG antibody was volume diluted 21.3-fold into posttransfusion seronegative recipients from matched donor units. Virus-specific antibody delivered was approximately 1.2 mg. The high-antibody recipients transfused early (symptom onset within 5 days) had no hospitalizations. A CCP-recipient analysis for antibody thresholds correlated to reduced hospitalizations found a statistical significant association between early transfusion and high antibodies versus all other CCP recipients (or control plasma), with antibody cutoffs established by both methods-donor-based virus neutralization cutoffs in posttransfusion recipients (0/85 [0%] versus 15/276 [5.6%]; P = 0.03) or ROC-based cutoff (0/94 [0%] versus 15/267 [5.4%]; P = 0.01).CONCLUSIONIn unvaccinated, seronegative CCP recipients, early transfusion of plasma units in the upper 30% of study donors' antibody levels reduced outpatient hospitalizations. High antibody level plasma units, given early, should be reserved for therapeutic use.TRIAL REGISTRATIONClinicalTrials.gov NCT04373460.FUNDINGDepartment of Defense (W911QY2090012); Defense Health Agency; Bloomberg Philanthropies; the State of Maryland; NIH (3R01AI152078-01S1, U24TR001609-S3, 1K23HL151826NIH); the Mental Wellness Foundation; the Moriah Fund; Octapharma; the Healthnetwork Foundation; the Shear Family Foundation; the NorthShore Research Institute; and the Rice Foundation.

Eye movement as a simple, cost-effective tool for people who stutter: A case study.

BACKGROUND:  Access to services remains the biggest barrier to helping the most vulnerable in the South African Stuttering Community. This novel stuttering therapy, harnessing an unconscious link between eye and tongue movement, may provide a new therapeutic approach, easily communicated and deliverable online. OBJECTIVES:  This study provides both objective and subjective assessments of the feasibility of this intervention. Assessment tools holistically address all components of stuttering in line with comprehensive treatment approaches: core behaviours, secondary behaviours, anticipation and reactions. METHOD:  On receipt of ethical approval, this single-subject case design recruited one adult (21-year-old) male with a developmental stutter (DS). The participant gave informed consent and completed four scheduled assessments: baseline, after 5-week training, 3 months post-intervention and 24 months post-completion. The study used objective assessment tools: Stuttering Severity Instrument-4 (SSI-4); Subjective-assessment tools: SSI-4 clinical use self-report tool (CUSR); Overall Assessment of Speaker's Experience of Stuttering (OASES-A); Premonitory Awareness in Stuttering (PAiS) and Self-Report Stuttering Severity* (SRSS) (*final assessment). RESULTS:  The participant's scores improved across all assessment measures, which may reflect a holistic improvement. The participant reported that the tool was very useful. There were no negative consequences. CONCLUSION:  This case report indicates that this innovative treatment may be feasible. No adverse effects were experienced, and the treatment only benefited the participant. The results justify the design of a pilot randomised feasibility clinical trial.Contribution: The results indicate that this is a needed breakthrough in stuttering therapy as the instructions can be easily translated into any language. It can also be delivered remotely reducing accessibility barriers.

Dynamics of inflammatory responses after SARS-CoV-2 infection by vaccination status in the USA: a prospective cohort study.

BACKGROUND: Cytokines and chemokines play a critical role in the response to infection and vaccination. We aimed to assess the longitudinal association of COVID-19 vaccination with cytokine and chemokine concentrations and trajectories among people with SARS-CoV-2 infection. METHODS: In this longitudinal, prospective cohort study, blood samples were used from participants enrolled in a multi-centre randomised trial assessing the efficacy of convalescent plasma therapy for ambulatory COVID-19. The trial was conducted in 23 outpatient sites in the USA. In this study, participants (aged ≥18 years) were restricted to those with COVID-19 before vaccination or with breakthrough infections who had blood samples and symptom data collected at screening (pre-transfusion), day 14, and day 90 visits. Associations between COVID-19 vaccination status and concentrations of 21 cytokines and chemokines (measured using multiplexed sandwich immunoassays) were examined using multivariate linear mixed-effects regression models, adjusted for age, sex, BMI, hypertension, diabetes, trial group, and COVID-19 waves (pre-alpha or alpha and delta). FINDINGS: Between June 29, 2020, and Sept 30, 2021, 882 participants recently infected with SARS-CoV-2 were enrolled, of whom 506 (57%) were female and 376 (43%) were male. 688 (78%) of 882 participants were unvaccinated, 55 (6%) were partly vaccinated, and 139 (16%) were fully vaccinated at baseline. After adjusting for confounders, geometric mean concentrations of interleukin (IL)-2RA, IL-7, IL-8, IL-15, IL-29 (interferon-λ), inducible protein-10, monocyte chemoattractant protein-1, and tumour necrosis factor-α were significantly lower among the fully vaccinated group than in the unvaccinated group at screening. On day 90, fully vaccinated participants had approximately 20% lower geometric mean concentrations of IL-7, IL-8, and vascular endothelial growth factor-A than unvaccinated participants. Cytokine and chemokine concentrations decreased over time in the fully and partly vaccinated groups and unvaccinated group. Log10 cytokine and chemokine concentrations decreased faster among participants in the unvaccinated group than in other groups, but their geometric mean concentrations were generally higher than fully vaccinated participants at 90 days. Days since full vaccination and type of vaccine received were not correlated with cytokine and chemokine concentrations. INTERPRETATION: Initially and during recovery from symptomatic COVID-19, fully vaccinated participants had lower concentrations of inflammatory markers than unvaccinated participants suggesting vaccination is associated with short-term and long-term reduction in inflammation, which could in part explain the reduced disease severity and mortality in vaccinated individuals. FUNDING: US Department of Defense, National Institutes of Health, Bloomberg Philanthropies, State of Maryland, Mental Wellness Foundation, Moriah Fund, Octapharma, HealthNetwork Foundation, and the Shear Family Foundation.

Transfusion reactions associated with COVID-19 convalescent plasma in outpatient clinical trials.

BACKGROUND: COVID-19 convalescent plasma (CCP) is an important therapeutic option for outpatients at high risk of hospitalization from SARS-CoV-2 infection. We assessed the safety of outpatient CCP transfusions administered during clinical trials. STUDY DESIGN AND METHODS: We analyzed data pertaining to transfusion-related reactions from two randomized controlled trials in the U.S. that evaluated the efficacy of CCP versus control plasma in various ambulatory settings. Multivariable logistic regression was used to assess whether CCP was associated with transfusion reactions, after adjusting for potential confounders. RESULTS: The combined study reported 79/1351 (5.9%) adverse events during the transfusion visit, with the majority 62/1351 (4.6%) characterized by mild, allergic-type findings of urticaria, and/or pruritus consistent with minor allergic transfusion reactions; the other reported events were attributed to the patients' underlying disease, COVID-19, or vasovagal in nature. We found no difference in the likelihood of allergic transfusion reactions between those receiving CCP versus control plasma (adjusted odds ratio [AOR], 0.75; 95% CI, 0.43-1.31). Risk of urticaria and/or pruritus increased with a pre-existing diagnosis of asthma (AOR, 2.33; 95% CI, 1.16-4.67). We did not observe any CCP-attributed antibody disease enhancement in participants with COVID-19 or increased risk of infection. There were no life-threatening severe transfusion reactions and no patients required hospitalization related to transfusion-associated complications. DISCUSSION: Outpatient plasma administration was safely performed for nearly 1400 participants. CCP is a safe therapeutic option for outpatients at risk of hospitalization from COVID-19.

Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial.

BACKGROUND: The COVID-19 convalescent plasma (CCP) viral specific antibody levels that translate into recipient post-transfusion antibody levels sufficient to prevent disease progression is not defined. METHODS: This secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low post-transfusion antibody levels was established by two methods: 1) analyzing virus neutralization-equivalent anti-S-RBD IgG responses in donors or 2) receiver operating characteristic (ROC) analysis. RESULTS: SARS-CoV-2 anti-S-RBD IgG antibody was diluted by a factor of 21.3 into post-transfusion seronegative recipients from matched donor units. Viral specific antibody delivered approximated 1.2 mg. The high antibody recipients transfused early (symptom onset within 5 days) had no hospitalizations. A CCP recipient analysis for antibody thresholds correlated to reduced hospitalizations found a significant association with Fisher's exact test between early and high antibodies versus all other CCP recipients (or control plasma) with antibody cutoffs established by both methods-donor virus neutralization-based cutoff: (0/85; 0% versus 15/276; 5.6%) p=0.03 or ROC based cutoff: (0/94; 0% versus 15/267; 5.4%) p=0.01. CONCLUSION: In unvaccinated, seronegative CCP recipients, early transfusion of plasma units corresponding to the upper 30% of all study donors reduced outpatient hospitalizations. These high antibody level plasma units, given early, should be reserved for therapeutic use.Trial registration: NCT04373460. FUNDING: Defense Health Agency and others.

To assess the effects of cross-education on strength and motor function in post stroke rehabilitation: a systematic literature review and meta-analysis.

BACKGROUND: Cross-education refers to the increase in motor output of the untrained limb following unilateral training of the opposite limb. Cross education has been shown to be beneficial in clinical settings. OBJECTIVES: This systematic literature and meta-analysis aims to assess the effects of cross-education on strength and motor function in post stroke rehabilitation. DATA SOURCES: MEDLINE, CINAHL, Cochrane Library, PubMed, PEDro, Web of Science, ClinicalTrails.gov and Cochrane Central registers were searched up to 1st October 2022. STUDY SELECTION: Controlled trials using unilateral training of the less affected limb in individuals diagnosed with stroke and English language. DATA SYNTHESIS: Methodological quality was assessed using Cochrane Risk-of-Bias tools. Quality of evidence was evaluated using Grading of Recommendations Assessment, Development and Evaluation. Meta-analyses were performed using RevMan 5.4.1. RESULTS: Five studies capturing 131 participants were included in the review and three studies capturing 95 participants were included in the meta-analysis. Cross education was shown to have a statistically and clinically significant effect on upper limb strength (p < 0.003; SMD 0.58; 95% CI 0.20-0.97; n = 117) and upper limb function (p = 0.04; SMD 0.40; 95% CI 0.02-0.77; n = 119). LIMITATIONS: Small number of studies, with all studies identified as having some risk of bias. Quality of evidence graded 'low' due to limitations and imprecision. CONCLUSION: Cross education may be beneficial in improving strength and motor function in the more affected upper limb post stroke. Further studies are needed as the research into the benefits of cross education in stroke rehabilitation is still limited. Systematic Review Registration Number: PROSPERO (CRD42020219058).

What are the effects of pilates in the post stroke population? A systematic literature review & meta-analysis of randomised controlled trials.

OBJECTIVE: Stroke is a leading cause of death and disability worldwide. Pilates, a programme of mind-body exercises is theorised to have beneficial effects on strength, postural control, balance, proprioception, coordination and gait in people with deficits due to a neurological condition. However, the evidence of pilates in stroke patients has never been systemised. The objectives of this systematic literature review are to investigate the effects of pilates in post stroke individuals and compare this intervention to other forms of exercise, standard care and/or physiotherapy. DATA SOURCES: A comprehensive search was conducted in the following databases: Pubmed (including MEDline), Web of Science, the Cochrane library, Science Direct, Embase and PEDro. STUDY SELECTION: Studies were selected, screened, filtered and reviewed in detail to identify those that met the inclusion criteria. DATA EXTRACTION: Data was extracted to a table with specific headings for analysis and studies were rated using the Physiotherapy Evidence Database (PEDro) scale. DATA SYNTHESIS: Data from a total of 5 included studies with 122 participants was pooled and analysed using the Revman 5 software. Significant findings were found in favour of the pilates intervention groups on balance (P<0.00001), quality of Life (P=0.0002), and gait parameters (P=0.001), when results from the studies were combined and analysed. CONCLUSIONS: This review found moderate evidence for pilates exercises improving balance in post stroke individuals and limited evidence for improvements in quality of life, cardiopulmonary function and gait. Future studies should examine long term follow up, home programmes and comparisons with other forms of exercise in post stroke patients.

Transfusing Convalescent Plasma as Post-Exposure Prophylaxis Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Double-Blinded, Phase 2 Randomized, Controlled Trial.

BACKGROUND: The efficacy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent plasma (CCP) for preventing infection in exposed, uninfected individuals is unknown. CCP might prevent infection when administered before symptoms or laboratory evidence of infection. METHODS: This double-blinded, phase 2 randomized, controlled trial (RCT) compared the efficacy and safety of prophylactic high titer (≥1:320 by Euroimmun ELISA) CCP with standard plasma. Asymptomatic participants aged ≥18 years with close contact exposure to a person with confirmed coronavirus disease 2019 (COVID-19) in the previous 120 hours and negative SARS-CoV-2 test within 24 hours before transfusion were eligible. The primary outcome was new SARS-CoV-2 infection. RESULTS: In total, 180 participants were enrolled; 87 were assigned to CCP and 93 to control plasma, and 170 transfused at 19 sites across the United States from June 2020 to March 2021. Two were excluded for screening SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) positivity. Of the remaining 168 participants, 12/81 (14.8%) CCP and 13/87 (14.9%) control recipients developed SARS-CoV-2 infection; 6 (7.4%) CCP and 7 (8%) control recipients developed COVID-19 (infection with symptoms). There were no COVID-19-related hospitalizations in CCP and 2 in control recipients. Efficacy by restricted mean infection free time (RMIFT) by 28 days for all SARS-CoV-2 infections (25.3 vs 25.2 days; P = .49) and COVID-19 (26.3 vs 25.9 days; P = .35) was similar for both groups. CONCLUSIONS: Administration of high-titer CCP as post-exposure prophylaxis, although appearing safe, did not prevent SARS-CoV-2 infection. CLINICAL TRIALS REGISTRATION: NCT04323800.

Sensory substitution for orthopaedic gait rehabilitation: A systematic review and meta-analysis for clinical practice guideline development.

Introduction: Sensory Substitution is a biofeedback intervention whereby at least sensory system is utilised to supplement environmental information which is traditionally gathered by another sense. Objective: To present an evidence-based overview of the feasibility and effectiveness of wearable Sensory Substitution devices on gait outcomes in orthopaedic patient populations. Methods: This Systematic Review and Meta-Analysis was reported according to the PRISMA 2020 statement. PubMed, the Cochrane Library, Web of science and PEDro were searched for relevant published literature. Inclusion criteria limited the search strictly to patients diagnosed with an orthopaedic condition and who were randomly grouped to a Sensory Substitution intervention or conventional therapy/training or an equivalent placebo intervention. Results: Nine Randomised Controlled Trials and three Crossover Trials investigating the effectiveness of Sensory Substitution supplemented gait training were identified and included participants with a variety of orthopaedic conditions. Meta-Analyses revealed positive findings of feasibility as well as statistical and clinical effect of the interventions in improving measures of gait speed, weight-bearing control, measures of functionality and subjective self-reporting. Meta-Analyses also revealed the interventions effects were not significant in the management of pain and retention of gait speed. Negatively reinforced Sensory Substitution biofeedback was statistically and clinically effective, whilst positively reinforced biofeedback was not. Conclusion: For orthopaedic patient populations to improve gait speed, weight-bearing control, functionality, pain and self-report measures, the authors recommend a Sensory Substitution supplemented gait training programme with negative biofeedback on performance. The intervention should be undertaken for 20 min per day, 3 days per week for 5 weeks. The intervention should coincide with structured analgesia administration to facilitate effective pain management. Limitations of the data included some low sample sizes and large age-ranges. No financial support was provided for this study.

How do I implement an outpatient program for the administration of convalescent plasma for COVID-19?

Convalescent plasma, collected from donors who have recovered from a pathogen of interest, has been used to treat infectious diseases, particularly in times of outbreak, when alternative therapies were unavailable. The COVID-19 pandemic revived interest in the use of convalescent plasma. Large observational studies and clinical trials that were executed during the pandemic provided insight into how to use convalescent plasma, whereby high levels of antibodies against the pathogen of interest and administration early within the time course of the disease are critical for optimal therapeutic effect. Several studies have shown outpatient administration of COVID-19 convalescent plasma (CCP) to be both safe and effective, preventing clinical progression in patients when administered within the first week of COVID-19. The United States Food and Drug Administration expanded its emergency use authorization (EUA) to allow for the administration of CCP in an outpatient setting in December 2021, at least for immunocompromised patients or those on immunosuppressive therapy. Outpatient transfusion of CCP and infusion of monoclonal antibody therapies for a highly transmissible infectious disease introduces nuanced challenges related to infection prevention. Drawing on our experiences with the clinical and research use of CCP, we describe the logistical considerations and workflow spanning procurement of qualified products, infrastructure, staffing, transfusion, and associated management of adverse events. The purpose of this description is to facilitate the efforts of others intent on establishing outpatient transfusion programs for CCP and other antibody-based therapies.

Early Outpatient Treatment for Covid-19 with Convalescent Plasma.

BACKGROUND: Polyclonal convalescent plasma may be obtained from donors who have recovered from coronavirus disease 2019 (Covid-19). The efficacy of this plasma in preventing serious complications in outpatients with recent-onset Covid-19 is uncertain. METHODS: In this multicenter, double-blind, randomized, controlled trial, we evaluated the efficacy and safety of Covid-19 convalescent plasma, as compared with control plasma, in symptomatic adults (≥18 years of age) who had tested positive for severe acute respiratory syndrome coronavirus 2, regardless of their risk factors for disease progression or vaccination status. Participants were enrolled within 8 days after symptom onset and received a transfusion within 1 day after randomization. The primary outcome was Covid-19-related hospitalization within 28 days after transfusion. RESULTS: Participants were enrolled from June 3, 2020, through October 1, 2021. A total of 1225 participants underwent randomization, and 1181 received a transfusion. In the prespecified modified intention-to-treat analysis that included only participants who received a transfusion, the primary outcome occurred in 17 of 592 participants (2.9%) who received convalescent plasma and 37 of 589 participants (6.3%) who received control plasma (absolute risk reduction, 3.4 percentage points; 95% confidence interval, 1.0 to 5.8; P = 0.005), which corresponded to a relative risk reduction of 54%. Evidence of efficacy in vaccinated participants cannot be inferred from these data because 53 of the 54 participants with Covid-19 who were hospitalized were unvaccinated and 1 participant was partially vaccinated. A total of 16 grade 3 or 4 adverse events (7 in the convalescent-plasma group and 9 in the control-plasma group) occurred in participants who were not hospitalized. CONCLUSIONS: In participants with Covid-19, most of whom were unvaccinated, the administration of convalescent plasma within 9 days after the onset of symptoms reduced the risk of disease progression leading to hospitalization. (Funded by the Department of Defense and others; CSSC-004 ClinicalTrials.gov number, NCT04373460.).

Adaptive immune responses in vaccinated patients with symptomatic SARS-CoV-2 Alpha infection.

Benchmarks for protective immunity from infection or severe disease after SARS-CoV-2 vaccination are still being defined. Here, we characterized virus neutralizing and ELISA antibody levels, cellular immune responses, and viral variants in 4 separate groups: healthy controls (HCs) weeks (early) or months (late) following vaccination in comparison with symptomatic patients with SARS-CoV-2 after partial or full mRNA vaccination. During the period of the study, most symptomatic breakthrough infections were caused by the SARS-CoV-2 Alpha variant. Neutralizing antibody levels in the HCs were sustained over time against the vaccine parent virus but decreased against the Alpha variant, whereas IgG titers and T cell responses against the parent virus and Alpha variant declined over time. Both partially and fully vaccinated patients with symptomatic infections had lower virus neutralizing antibody levels against the parent virus than the HCs, similar IgG antibody titers, and similar virus-specific T cell responses measured by IFN-γ. Compared with HCs, neutralization activity against the Alpha variant was lower in the partially vaccinated infected patients and tended to be lower in the fully vaccinated infected patients. In this cohort of breakthrough infections, parent virus neutralization was the superior predictor of breakthrough infections with the Alpha variant of SARS-CoV-2.

Randomized controlled trial transfusing convalescent plasma as post-exposure prophylaxis against SARS-CoV-2 infection.

BACKGROUND: The efficacy of SARS-CoV-2 convalescent plasma (CCP) for preventing infection in exposed, uninfected individuals is unknown. We hypothesized that CCP might prevent infection when administered before symptoms or laboratory evidence of infection. METHODS: This double-blinded, phase 2 randomized, controlled trial (RCT) compared the efficacy and safety of prophylactic high titer (≥1:320) CCP with standard plasma. Asymptomatic participants aged ≥18 years with close contact exposure to a person with confirmed COVID-19 in the previous 120 hours and negative SARS-CoV-2 test within 24 hours before transfusion were eligible. The primary outcome was development of SARS-CoV-2 infection. RESULTS: 180 participants were enrolled; 87 were assigned to CCP and 93 to control plasma, and 170 transfused at 19 sites across the United States from June 2020 to March 2021. Two were excluded for SARS-CoV-2 RT-PCR positivity at screening. Of the remaining 168 participants, 12/81 (14.8%) CCP and 13/87 (14.9%) control recipients developed SARS-CoV-2 infection; 6 (7.4%) CCP and 7 (8%) control recipients developed COVID-19 (infection with symptoms). There were no COVID-19-related hospitalizations in CCP and 2 in control recipients. There were 28 adverse events in CCP and 58 in control recipients. Efficacy by restricted mean infection free time (RMIFT) by 28 days for all SARS-CoV-2 infections (25.3 vs. 25.2 days; p=0.49) and COVID-19 (26.3 vs. 25.9 days; p=0.35) were similar for both groups. CONCLUSION: In this trial, which enrolled persons with recent exposure to a person with confirmed COVID-19, high titer CCP as post-exposure prophylaxis appeared safe, but did not prevent SARS-CoV-2 infection. TRIAL REGISTRATION: Clinicaltrial.gov number NCT04323800 .

Randomized Controlled Trial of Early Outpatient COVID-19 Treatment with High-Titer Convalescent Plasma.

BACKGROUND: The efficacy of polyclonal high titer convalescent plasma to prevent serious complications of COVID-19 in outpatients with recent onset of illness is uncertain. METHODS: This multicenter, double-blind randomized controlled trial compared the efficacy and safety of SARS-CoV-2 high titer convalescent plasma to placebo control plasma in symptomatic adults ≥18 years positive for SARS-CoV-2 regardless of risk factors for disease progression or vaccine status. Participants with symptom onset within 8 days were enrolled, then transfused within the subsequent day. The measured primary outcome was COVID-19-related hospitalization within 28 days of plasma transfusion. The enrollment period was June 3, 2020 to October 1, 2021. RESULTS: A total of 1225 participants were randomized and 1181 transfused. In the pre-specified modified intention-to-treat analysis that excluded those not transfused, the primary endpoint occurred in 37 of 589 (6.3%) who received placebo control plasma and in 17 of 592 (2.9%) participants who received convalescent plasma (relative risk, 0.46; one-sided 95% upper bound confidence interval 0.733; P=0.004) corresponding to a 54% risk reduction. Examination with a model adjusting for covariates related to the outcome did not change the conclusions. CONCLUSION: Early administration of high titer SARS-CoV-2 convalescent plasma reduced outpatient hospitalizations by more than 50%. High titer convalescent plasma is an effective early outpatient COVID-19 treatment with the advantages of low cost, wide availability, and rapid resilience to variant emergence from viral genetic drift in the face of a changing pandemic. Trial Registration: ClinicalTrials.gov number, NCT04373460.

Aortic Valve Replacement in 8 Adults with Anomalous Aortic Origin of Coronary Artery.

Patients with anomalous origin of a coronary artery during aortic valve replacement (AVR) are at risk of coronary compromise. Large case series are lacking. In this retrospective study, we review our experience with this condition. From August 2014 through June 2016, 8 adult patients (mean age, 74 ± 17.5 yr; age range, 33-86 yr; 5 men) with anomalous aortic origin of a coronary artery underwent surgical or transcatheter AVR at our institution. Six patients had aortic stenosis; 2 had aortic insufficiency, one of whom had an associated aortic root aneurysm. In 7 patients, the left anomalous coronary artery originated from the right aortic sinus, and in one, the right coronary artery arose from the left cusp. The anatomic course was revealed by means of 3-dimensional computed tomographic angiography. No patient underwent primary aortic reimplantation of the anomalous artery. Two had the artery mobilized from encircling the annulus too closely and then underwent coronary artery bypass grafting. Two high-risk patients underwent transcatheter AVR. After surgical AVR, 2 patients had perioperative myocardial infarction caused by coronary compression, so percutaneous coronary intervention was performed. One patient died of sepsis 3 months after discharge from the hospital. In our patients, AVR sometimes led to severe perioperative complications. Successful AVR depended on 3-dimensional computed tomographic angiographic findings, individual anatomic variations, and appropriate treatment choices.

Unilateral dorsiflexor strengthening with mirror therapy to improve motor function after stroke: A pilot randomized study.

BACKGROUND: Independently, cross-education, the performance improvement of the untrained limb following unilateral training, and mirror therapy have shown to improve lower limb functioning poststroke. Mirror therapy has shown to augment the cross-education effect in healthy populations. However, this concept has not yet been explored in a clinical setting. OBJECTIVES: This study set out to investigate the feasibility and potential efficacy of applying cross-education combined with mirror therapy compared with cross-education alone for lower limb recovery poststroke. METHODS: Thirty-one chronic stroke participants (age 61.7 ± 13.3) completed either a unilateral strength training (ST; n = 15) or unilateral strength training with mirror-therapy (MST; n = 16) intervention. Both groups isometrically strength trained the less-affected ankle dorsiflexors three times per week for 4 weeks. Only the MST group observed the mirror reflection of the training limb. Patient eligibility, compliance, treatment reliability, and outcome measures were assessed for feasibility. Maximal voluntary contraction (MVC; peak torque, rate of torque development, and average torque), 10-m walk test, timed up and go (TUG), Modified Ashworth Scale (MAS), and the London Handicap Scale (LHS) were assessed at pretraining and posttraining. RESULTS: Treatment and assessments were well tolerated without adverse effects. No between group differences were identified for improvement in MVC, MAS, TUG, or LHS. Only the combined treatment was associated with functional improvements with the MST group showing an increase in walking velocity. CONCLUSION: Cross-education plus mirror therapy may have potential for improving motor function after stroke. This study demonstrates the feasibility of the combination treatment and the need for future studies with larger sample sizes to investigate the effectiveness of the treatment.

Unilateral Strength Training and Mirror Therapy in Patients With Chronic Stroke: A Pilot Randomized Trial.

OBJECTIVE: The aim of the study was to investigate the feasibility and potential effectiveness of mirror-aided cross-education compared with cross-education alone in poststroke upper limb recovery. DESIGN: A pilot randomized controlled parallel group study was carried out. Thirty-two patients with chronic stroke followed a 4-wk isometric strength training program performed with the less-affected upper limb three times per week. Participants in the mirror and strength training group observed the reflection of the exercising arm in the mirror. Participants in the strength training only group exercised without a mirror entirely. Participant compliance, adverse effects, and suitability of outcome measures assessed feasibility. Effectiveness outcomes included maximal isometric strength measured with the Biodex Dynamometer, the Modified Ashworth Scale, and the Chedoke Arm and Hand Activity Inventory. RESULTS: Compliance was high with no adverse effects. The use of the Biodex Dynamometer must be reviewed. Mirror therapy did not augment the cross-education effect (P > 0.05) in patients with chronic stroke when training isometrically. CONCLUSIONS: This pilot trial established the feasibility of a randomized controlled trial comparing mirror-aided cross-education with cross-education alone for poststroke upper limb recovery. Mirror therapy did not augment cross-education when training isometrically. However, results indicate that the combination of interventions should be investigated further applying an altered training protocol.

Peak torque, rate of torque development and average torque of isometric ankle and elbow contractions show excellent test-retest reliability.

BACKGROUND: Peak Torque (PT), Rate of Torque Development (RTD) and Average Torque (AT) over a single contraction assess the three components of muscle function during isometric contractions. Surprisingly, AT has never been reported or its reliability confirmed. OBJECTIVES: This study aims to establish protocol reliability for ankle dorsiflexion and elbow extension isometric muscle function (PT, RTD, AT) in healthy participants using the Biodex System 3 Dynamometer. METHODS: Twelve participants (6 male, 6 female, mean age 39 . 8 ± 16 . 0 years) performed four maximal isometric contractions on two occasions. Intraclass Correlation Coefficient (ICC), Typical Error (TE) and Coefficient of Variation (CV) for PT, RTD and AT were reported. RESULTS: The ICC for all strength parameters varied from 0.98-0.92. TE for ankle dorsiflexion PT was 1.38 Nm, RTD 7.43 Nm/s and AT 1.33 Nm, CV varied from 6 . 26 ± 6 . 25 % to 11 . 72 ± 8 . 27 % . For elbow extension, TE was 3.36 Nm for PT, 14.87 Nm/s for RTD and 3.03 Nm for AT, CV varied from 5 . 97 ± 4 . 52 % to 18 . 46 ± 14 . 78 % . CONCLUSION: Maximal isometric ankle dorsiflexion and elbow extension PT, RTD and AT can be evaluated with excellent reliability when following the described protocol. This testing procedure, including the application of AT, can be confidently applied in research, exercise or clinical settings.

Mirror therapy and treadmill training for a patient with chronic stroke: A case report.

INTRODUCTION: A large proportion of patients with chronic stroke have permanent lower limb functional disability leading to reduced levels of independent mobility. Individually, both mirror therapy and treadmill training have been shown to improve aspects of lower limb functioning in patients with stroke. This case report examined whether a new combination of both interventions would lead to improvements in lower limb functional disability for a patient with chronic stroke. CASE DESCRIPTION: The participant was a 50-year-old female who had a left middle cerebral artery infarction (47 months' post stroke). Due to hemiparesis, she had lower limb motor impairment and gait deficits. INTERVENTION: The participant engaged in a combination of mirror therapy and treadmill training for 30 minutes per day, 3 days per week, for 4 weeks. OUTCOMES: Modified Ashworth Scale, Fugl-Meyer Assessment-Lower Extremity and the 10 m Walk Test demonstrated clinically meaningful change. The 6 Minute Walk Test did not demonstrate meaningful change. DISCUSSION: The positive outcomes from this new combination therapy for this participant are encouraging given the relatively small dose of training and indicate the potential benefit of mirror therapy as an adjunct to treadmill training for enhancing lower limb muscle tone, motor function and walking velocity in patients with chronic stroke.