Concomitant Tricuspid Repair in Patients with Degenerative Mitral Regurgitation.

BACKGROUND: Tricuspid regurgitation is common in patients with severe degenerative mitral regurgitation. However, the evidence base is insufficient to inform a decision about whether to perform tricuspid-valve repair during mitral-valve surgery in patients who have moderate tricuspid regurgitation or less-than-moderate regurgitation with annular dilatation. METHODS: We randomly assigned 401 patients who were undergoing mitral-valve surgery for degenerative mitral regurgitation to receive a procedure with or without tricuspid annuloplasty (TA). The primary 2-year end point was a composite of reoperation for tricuspid regurgitation, progression of tricuspid regurgitation by two grades from baseline or the presence of severe tricuspid regurgitation, or death. RESULTS: Patients who underwent mitral-valve surgery plus TA had fewer primary-end-point events than those who underwent mitral-valve surgery alone (3.9% vs. 10.2%) (relative risk, 0.37; 95% confidence interval [CI], 0.16 to 0.86; P = 0.02). Two-year mortality was 3.2% in the surgery-plus-TA group and 4.5% in the surgery-alone group (relative risk, 0.69; 95% CI, 0.25 to 1.88). The 2-year prevalence of progression of tricuspid regurgitation was lower in the surgery-plus-TA group than in the surgery-alone group (0.6% vs. 6.1%; relative risk, 0.09; 95% CI, 0.01 to 0.69). The frequencies of major adverse cardiac and cerebrovascular events, functional status, and quality of life were similar in the two groups at 2 years, although the incidence of permanent pacemaker implantation was higher in the surgery-plus-TA group than in the surgery-alone group (14.1% vs. 2.5%; rate ratio, 5.75; 95% CI, 2.27 to 14.60). CONCLUSIONS: Among patients undergoing mitral-valve surgery, those who also received TA had a lower incidence of a primary-end-point event than those who underwent mitral-valve surgery alone at 2 years, a reduction that was driven by less frequent progression to severe tricuspid regurgitation. Tricuspid repair resulted in more frequent permanent pacemaker implantation. Whether reduced progression of tricuspid regurgitation results in long-term clinical benefit can be determined only with longer follow-up. (Funded by the National Heart, Lung, and Blood Institute and the German Center for Cardiovascular Research; ClinicalTrials.gov number, NCT02675244.).

A Randomized Trial of Mesenchymal Stromal Cells for Moderate to Severe Acute Respiratory Distress Syndrome from COVID-19.

Rationale: There are limited therapeutic options for patients with coronavirus disease (COVID-19)-related acute respiratory distress syndrome with inflammation-mediated lung injury. Mesenchymal stromal cells offer promise as immunomodulatory agents. Objectives: Evaluation of efficacy and safety of allogeneic mesenchymal cells in mechanically-ventilated patients with moderate or severe COVID-19-induced respiratory failure. Methods: Patients were randomized to two infusions of 2 million cells/kg or sham infusions, in addition to the standard of care. We hypothesized that cell therapy would be superior to sham control for the primary endpoint of 30-day mortality. The key secondary endpoint was ventilator-free survival within 60 days, accounting for deaths and withdrawals in a ranked analysis. Measurements and Main Results: At the third interim analysis, the data and safety monitoring board recommended that the trial halt enrollment as the prespecified mortality reduction from 40% to 23% was unlikely to be achieved (n = 222 out of planned 300). Thirty-day mortality was 37.5% (42/112) in cell recipients versus 42.7% (47/110) in control patients (relative risk [RR], 0.88; 95% confidence interval, 0.64-1.21; P = 0.43). There were no significant differences in days alive off ventilation within 60 days (median rank, 117.3 [interquartile range, 60.0-169.5] in cell patients and 102.0 [interquartile range, 54.0-162.5] in control subjects; higher is better). Resolution or improvement of acute respiratory distress syndrome at 30 days was observed in 51/104 (49.0%) cell recipients and 46/106 (43.4%) control patients (odds ratio, 1.36; 95% confidence interval, 0.57-3.21). There were no infusion-related toxicities and overall serious adverse events over 30 days were similar. Conclusions: Mesenchymal cells, while safe, did not improve 30-day survival or 60-day ventilator-free days in patients with moderate and/or severe COVID-19-related acute respiratory distress syndrome.

A psychometric evaluation of a new social subscale for the Common Misconceptions about Traumatic Brain Injury (CM-TBI) questionnaire: toward the CM-TBI-II.

OBJECTIVE: Existing TBI misconception measures are critiqued for failing to measure postinjury social experiences. This study developed a social subscale for the Common Misconceptions about TBI (CM-TBI) questionnaire for use in the general public. METHODS: Seven experts independently review items drawn from the literature. Shortlisted items were administered online to 158 adults (aged ≥18 years; 51% postschool educated; 60% no TBI experience), the CM-TBI, and a measure of construct validity (a published TBI-adaptation of the Community Attitudes Towards the Mentally Ill; CAMI-TBI). One week later, the new items were redeployed (n = 46). RESULTS: Expert review and iterative correlations identified a 10-item social subscale (internal consistency, test-retest reliability, α's>.80). When added to the CM-TBI (ie. CM-TBI-II), the internal consistency was .71. The social subscale was significantly correlated with CAMI-TBI measures (p's <.05, r's > .3). There was no significant difference on the social subscale for education subgroups (school vs post-school, p = 0.056) or previous TBI experience; but there was a difference for the CM-TBI-II (post-school>school; Cohen's d = 7.83, large effect). CONCLUSION: This study found strong preliminary psychometric support for a new social subscale, administered as the CM-TBI-II. This subscale shows promise as a measure of misconceptions about social functioning post-TBI. The CM-TBI-II could support evaluations of programs aiming to improve social engagement and community participation for people with TBI.

Factor structure of the modified Rivermead Post-concussion Symptoms Questionnaire (mRPQ): an exploratory analysis with healthy adult simulators.

OBJECTIVE: Persistent postconcussion symptoms (PPCS) are challenging to diagnose. An improved diagnostic process could consider typical and atypical postconcussion symptoms. This study examined the structure of a modified Rivermead Post-concussion Symptoms Questionnaire (mRPQ) with both symptom types. METHOD: 298 adult volunteers were randomized into groups: honest responders, mild traumatic brain injury (mTBI) simulators (MS), and biased mTBI simulators (BMS). Both mTBI simulating groups were coached about mTBI and primed about the simulation context (compensation evaluation). The BMS group was also encouraged to bias (exaggerate) symptoms. The participants completed an online battery of tests, including the mRPQ. RESULTS: An exploratory factor analysis of the mRPQ (full sample) revealed a three-factor solution, including a separate dimension for atypical symptoms (all item loadings >0.45, ~4% of explained variance). The overall and group analyses of the standard RPQ items (typical symptoms) found a one- or two-factor solution, as did the analyses of atypical symptoms. CONCLUSIONS: Consistent with prior RPQ research, a unidimensional or bifactor structure was measurable from standard RPQ symptoms. Whilst this study did not find support for domain-level symptom scores for either typical or atypical symptoms, the findings support the use of an overall atypical symptoms score.

Ratings of the reasons for and against the disclosure of an Alzheimer's disease diagnosis: has anything changed in the past 20 years?

OBJECTIVES: The disclosure of an Alzheimer's disease diagnosis poses challenges for health care professionals, patients, and their families. Past research has shown that people favour disclosure, but it is uncertain if this situation has changed. METHOD: We used a cross-sectional online survey to explore disclosure preferences in a sample of young adults (n = 229; 66.7% aged 18 - 25 years, 79.5% Australian born). Factors contributing to preferences were also examined (knowledge, experience, close experience, age, relationship to diagnosis recipient). Established measures were used to assess knowledge (the Alzheimer's Disease Knowledge Test) and preferences (the Reasons for Wanting to Know Questionnaire). RESULTS: Most (95%) but not all participants favoured disclosure, whilst recognising as important at least one reason against it. Only age was a significant determinant of preferences (older people were more likely to prefer disclosure). Those against disclosure cited the fear of suicide as a key reason. CONCLUSION: The right to know remains a primary reason for preferring disclosure. Health care professionals should use pre-diagnostic interviewing to discuss overall preference and the underpinning reasons both for and against disclosure. Focus should be on developing a person-centred approach that responds to concerns, with further research to evaluate this approach.

Understanding the Sociocognitive Determinants Underlying Intentions to Exercise for Postconcussion Symptom Relief: An Application of the Theory of Planned Behavior.

CONTEXT: This study investigated individual sociocognitive factors from the theory of planned behavior and their relationship to exercise for postconcussion recovery. DESIGN AND METHODS: Four hundred and fifty-nine Australian adults, two-thirds of whom had no concussion history (66%), completed an online survey of their beliefs and attitudes toward exercise for postconcussion recovery. Secondary questions evaluated program design features that could affect engagement (eg, session frequency). RESULTS: Structured equation modeling found that subjective norms were the strongest significant predictor of intention to participate in exercise for postconcussion recovery. Perceived behavioral control was also a significant predictor of intention to participate but to a lesser extent. Attitude did not predict participation intention. The design features identified as key were personalization and being supervised during the program. CONCLUSIONS: This study found that people's intention to participate in a program of exercise postconcussion recovery is shaped by individual psychological factors and identified program design features that could be adjusted for increased engagement. Program success could be maximized through strategies such as supporting individuals to have a stronger sense of control over their participation through the choice of session timing or frequency and harnessing the influence of significant others via supportive messaging from key professionals.

Exercise Parameters for Postconcussion Symptom Rehabilitation: A Systematic Review.

CONTEXT: Exercise rehabilitation for postconcussion symptoms (PCS) has shown some benefits in adolescent athletes; but a synthesis of evidence on exercise per se has been lacking. OBJECTIVE: This systematic review aimed to determine if unimodal exercise interventions are useful to treat PCS and if so, to identify a set of clearly defined and effective exercise parameters for further research. EVIDENCE ACQUISITION: Relevant health databases and clinical trial registries were searched from inception to June 2022. The searches used a combination of subject headings and keywords related to mild traumatic brain injury (mTBI), PCSs, and exercise. Two independent reviewers screened and appraised the literature. The Cochrane Collaboration's Risk of Bias-2 tool for randomized controlled trials was used to assess methodological quality of studies. EVIDENCE SYNTHESIS: Seven studies were included in the review. Four studies were assessed to have a low overall risk of bias, 2 with low risk and 1 with some concerns. Participants in the studies comprised mostly adolescents with sports-related concussion. The review found exercise to be more beneficial than control conditions in 2 studies investigating acute PCS and 2 studies investigating persistent PCS. Within-group differences showing symptom improvement over time were observed in all 7 studies. In general, the review found support for programmatic exercise that commences after an initial period of rest for 24 to 48 hours. Recommendations for exercise parameters that can be explored in subsequent research include progressive aerobic exercise starting from 10 to 15 minutes at least 4 times a week, at a starting intensity of 50% HR of the subsymptom threshold, with length of program depending on recovery. CONCLUSION: The evidence in support of exercise rehabilitation for PCSs is moderate based on the small pool of eligible studies. Further research can be guided by the exercise parameters identified in this review.

Public awareness of legal decision-making capacity and planning instruments in dementia: implications for health care practitioners.

The protection of a person facing difficulties with legal decision-making can be challenging; however, estate planning documents (EPDs) can offer safeguards. Little is known about the community awareness of EPDs and their perceived importance, including for people with dementia. Two-hundred and thirty adults read a mild dementia vignette, proposed a diagnosis for the vignette character (VC), and rated the VC's legal decision-making capacity (DMC). The effect on ratings about DMC under different conditions was explored (e.g., variation of VC characteristics and the decision). Awareness, and the personal importance, of EPDs were assessed. DMC was affected by the variations in the VC's age, diagnosis, and the decision, as high- or low-stakes, but not VC sex. Awareness of EPDs was low; however, planning importance was increased for dementia. Although the public understand that dementia affects DMC, they require further information about EPDs to validly enact them, thereby reducing potential vulnerability.

Traumatic Brain Injury Rehabilitation: An Exercise Immunology Perspective.

Traumatic brain injury (TBI) is the largest cause of death and disability globally. The physical and psychosocial consequences after TBI can persist for prolonged periods, and lead to increased health care and economic burden. Exercise has shown promise over recent years as a mode of rehabilitation that alleviates multiple TBI symptoms; but there is a lack of controlled large-scale studies and limited research into the underlying mechanisms. This critical review draws from animal and human studies on exercise immunology to speculate on possible mechanisms that could underlie beneficial outcomes of exercise after TBI. The anti-inflammatory role of exercise, protective role offered by pre-injury exercise, and the need for more objective studies on biomarker analysis are expected to be useful considerations to develop optimal post-TBI exercise rehabilitation programs. Future studies can consider investigating the specific immunological processes induced by exercise in consideration of individual differences and non-aerobic exercise modalities.

Postconcussion discharge advice does not improve concussion knowledge in a community sample.

OBJECTIVE: Poor concussion knowledge in the community has been linked to reduced injury identification. This study investigated if concussion knowledge could be improved by providing standard postinjury advice (written brochure). METHODS: This study was a prospective, controlled study, with random allocation of 199 Australian adults to receive either a concussion information (CI, n=101), or non-CI (n=98). All participants completed the Rosenbaum Concussion Knowledge and Attitudes Survey on three occasions: pre-education and posteducation, and 1 week later. RESULTS: A 2 (condition) × 3 (occasion) mixed analysis of variance with concussion knowledge as the dependent variable did not find a statistically significant interaction (p>0.05). This result was unchanged: (1) with the covariate addition of background education and; (2) in a subgroup analysis (individuals with initially 'low' self-rated knowledge). Some key misconceptions about concussion were identified. CONCLUSION: The community knowledge of concussion was not significantly improved by the concussion advice. Since injury recognition relies ton an extent on community knowledge, the identified misconceptions should be addressed. This could occur via public health messaging. In clinical settings and for future research, the next steps should also include regular updating of concussion information to keep pace with advances in the field.

Research Letter: Concussion Knowledge Is Difficult to Predict From Self-Reported Exposure, Sports Participation, and Education.

OBJECTIVES: Increasing concussion knowledge could contribute to improving injury outcomes. Understanding the predictors of concussion knowledge could determine the areas of educational need. This study examined whether individual factors, prior brain injury, prior concussion education, and contact-sports participation predicted concussion knowledge. DESIGN AND SETTING: Cross-sectional study with recruitment of community volunteers. PARTICIPANTS: An online survey was completed by 525 adults, 443 of whom provided useable responses. MAIN MEASURES: The respondents provided background information and completed the Concussion Knowledge Index from the Rosenbaum Concussion Knowledge and Attitudes Survey (RoCKAS). RESULTS: On average, the participants answered 19.8 out of 25 items correctly. A multiple regression model with demographic, injury, and sport-related variables did not significantly predict concussion knowledge. CONCLUSION: This community sample had higher than expected concussion knowledge (restricted range), but some important misconceptions were still present. The model reflecting a combination of self-reported factors did not predict concussion knowledge. The implications for concussion education are discussed, including the need for targeted education to address specific misconceptions.

Quality of life, community integration, service needs and clinical outcomes of people with traumatic brain injury in urban, regional and remote areas of Queensland, Australia.

OBJECTIVE: To understand and explore the traumatic brain injury (TBI) outcomes for people returning to urban versus rural communities post-injury, and if geographical location plays a role in those outcomes. DESIGN: Cross-sectional mail-out survey of TBI patients, using standardised, quantitative measures. SETTING: Data were drawn from three Accessibility Remoteness Index of Australia (ARIA) areas in Queensland to model the contribution of these areas and other factors to TBI outcomes. PARTICIPANTS: Using hospital records, 662 people with mild to severe TBI were identified. These people were sent a survey, postdischarge. Usable surveys were returned by 91 individuals, 6- to 18-months post-injury. Location was coded using the ARIA (urban n = 22, rural n = 43, remote n = 26). MAIN OUTCOME MEASURES: TBI-related symptoms, quality of life, service obstacles, unmet needs, mental health and community integration. RESULTS: No group differences in TBI outcomes due to location were found. While the participant's gender, age, and injury severity were significant independent predictors of five of the six outcomes, location did not play a role. CONCLUSION: Consistent with previous findings, geographical remoteness did not affect self-reported TBI outcomes. Older people, women and those with severe TBI had worse outcomes and required additional supports, and men require community integration assistance. An Australia-wide study with regular follow-ups is strongly recommended to support direct regional comparisons and improve service planning.

Developing and piloting the Consumer Experience of Capacity Assessment Tool (CECAT).

Autonomy in personal decision-making (DM) is a fundamental human right. Yet, DM can be impaired for many reasons, including poor health. If impairments are suspected, they may be formally investigated via a capacity assessment. The 'consumer' experience of such assessments is largely unexplored. The Consumer Experience of Capacity Assessment Tool (CECAT) was developed to address this gap. Fifteen individuals pilot tested the CECAT. The CECAT was found to be quick to complete, and easily understood. The results showed a wide range of perceptions about capacity assessment and suggestions for improvement (e.g., better communication to consumers about what to expect). With further development, the CECAT could be adopted as a standardised method for understanding the consumer experience of capacity assessment. This perspective could then be integrated into future capacity assessment guidelines so that appropriate human rights-based approaches are incorporated into capacity assessments.

Can Adults Recognize Concussion Symptoms? A Critical Review of Empirical Research Using the Rosenbaum Concussion Knowledge and Attitudes Survey.

OBJECTIVE: The correct identification of concussion symptoms is vital for mild traumatic brain injury recognition, diagnosis, and injury management. Numerous surveys of symptom recognition have been conducted, including with athletes at-risk for injury. This critical, methodologically focused review aimed to: (1) discover which concussion symptoms are recognized, and (2) provide recommendations for future research. DATA SOURCES: A quasi-systematic literature search was conducted to identify studies that used the Rosenbaum Concussion Knowledge and Attitudes Survey. STUDY SELECTION: Eighty-five publications were identified, 8 of which were retained after screening. DATA EXTRACTION: The identification of individual concussion symptoms was coded as good (a correct response by >90% of the sample), moderate (a correct response by 75%-90% of the sample), or poor (a correct response by <75% of the sample). DATA SYNTHESIS: The pooled data comprised responses from more than 2000 individuals, most of whom were male, young adult, sport players. Overall, there was good recognition of 3 concussion symptoms (headaches, dizziness, and confusion), poor recognition of sleep disturbances, nausea, and loss of consciousness, and misattribution to concussion of 2 distractor symptoms (weakness of neck range of motion, difficulty speaking). The methodological evaluation revealed significant variability in symptom measurement. CONCLUSIONS: The identified trends for concussion symptom recognition must be regarded as tentative because of the significant methodological variation in the reviewed studies. This variability affected the number, wording, and classification of items, and it restricted the data synthesis. This problem must be addressed in future research and recommendations are provided.

Maternal interactive beliefs and style as predictors of language development in preterm and full term children.

Previous research has shown that the quality of mother-child interactions between pre-term children and their mothers tends to be poorer than that of full-term children and their mothers (Forcada-Guex, Pierrehumbert, Borghini, Moessinger & Muller-Nix, 2006). Mothers of pre-term children are less responsive and more intrusive in interactions with their children than mothers of full-term children (Forcada-Guex et al., 2006; Ionio, Lista, Mascheroni, Olivari, Confalonieri, Mastrangelo, Brazzoduro, Balestriero, Banfi, Bonanomi, Bova, Castoldi, Colombo, Introvini & Scelsa, 2017; Laing, McMahon, Ungerer, Taylor, Badawi & Spence, 2010). The current research explored differences between mothers of pre-term and full-term children in terms of interactive beliefs and style, and the potential for language development to be differentially predicted by maternal interactive beliefs and styles in pre-term versus full-term children. Independent t-tests were conducted to compare pre-term and full-term groups in relation to the measures of maternal interactive beliefs and styles. A series of multiple regression analyses were then performed separately for each group to examine the shared and unique contributions of maternal interactive beliefs and styles on full-term versus pre-term children's language development. The results showed that mothers of pre-term children were more intrusive-directive than mothers of full-term children; in contrast, mothers of full-term children were more responsive and supportive-directive in interactions with their children. Moreover, predictors of language development were different in full-term versus pre-term children; in full-term children, maternal supportive beliefs and responsiveness were significant predictors of language development evaluated by both the Bayley Scales of Infant and Toddler Development and the MacArthur Communicative Development Inventory; in the pre-term group, maternal supportive and directive beliefs, as well as supportive and intrusive directiveness, were significant predictors, with the latter being negatively associated with language development indicators. This research can shed light on how to prevent language delay in children and improve mother-child interactions that contribute to language development, which may in turn improve language development in vulnerable children, children born pre-term in particular.

Two-Year Outcomes of Surgical Treatment of Severe Ischemic Mitral Regurgitation.

BACKGROUND: In a randomized trial comparing mitral-valve repair with mitral-valve replacement in patients with severe ischemic mitral regurgitation, we found no significant difference in the left ventricular end-systolic volume index (LVESVI), survival, or adverse events at 1 year after surgery. However, patients in the repair group had significantly more recurrences of moderate or severe mitral regurgitation. We now report the 2-year outcomes of this trial. METHODS: We randomly assigned 251 patients to mitral-valve repair or replacement. Patients were followed for 2 years, and clinical and echocardiographic outcomes were assessed. RESULTS: Among surviving patients, the mean (±SD) 2-year LVESVI was 52.6±27.7 ml per square meter of body-surface area with mitral-valve repair and 60.6±39.0 ml per square meter with mitral-valve replacement (mean changes from baseline, -9.0 ml per square meter and -6.5 ml per square meter, respectively). Two-year mortality was 19.0% in the repair group and 23.2% in the replacement group (hazard ratio in the repair group, 0.79; 95% confidence interval, 0.46 to 1.35; P=0.39). The rank-based assessment of LVESVI at 2 years (incorporating deaths) showed no significant between-group difference (z score=-1.32, P=0.19). The rate of recurrence of moderate or severe mitral regurgitation over 2 years was higher in the repair group than in the replacement group (58.8% vs. 3.8%, P<0.001). There were no significant between-group differences in rates of serious adverse events and overall readmissions, but patients in the repair group had more serious adverse events related to heart failure (P=0.05) and cardiovascular readmissions (P=0.01). On the Minnesota Living with Heart Failure questionnaire, there was a trend toward greater improvement in the replacement group (P=0.07). CONCLUSIONS: In patients undergoing mitral-valve repair or replacement for severe ischemic mitral regurgitation, we observed no significant between-group difference in left ventricular reverse remodeling or survival at 2 years. Mitral regurgitation recurred more frequently in the repair group, resulting in more heart-failure-related adverse events and cardiovascular admissions. (Funded by the National Institutes of Health and Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00807040.).

Rate Control versus Rhythm Control for Atrial Fibrillation after Cardiac Surgery.

BACKGROUND: Atrial fibrillation after cardiac surgery is associated with increased rates of death, complications, and hospitalizations. In patients with postoperative atrial fibrillation who are in stable condition, the best initial treatment strategy--heart-rate control or rhythm control--remains controversial. METHODS: Patients with new-onset postoperative atrial fibrillation were randomly assigned to undergo either rate control or rhythm control. The primary end point was the total number of days of hospitalization within 60 days after randomization, as assessed by the Wilcoxon rank-sum test. RESULTS: Postoperative atrial fibrillation occurred in 695 of the 2109 patients (33.0%) who were enrolled preoperatively; of these patients, 523 underwent randomization. The total numbers of hospital days in the rate-control group and the rhythm-control group were similar (median, 5.1 days and 5.0 days, respectively; P=0.76). There were no significant between-group differences in the rates of death (P=0.64) or overall serious adverse events (24.8 per 100 patient-months in the rate-control group and 26.4 per 100 patient-months in the rhythm-control group, P=0.61), including thromboembolic and bleeding events. About 25% of the patients in each group deviated from the assigned therapy, mainly because of drug ineffectiveness (in the rate-control group) or amiodarone side effects or adverse drug reactions (in the rhythm-control group). At 60 days, 93.8% of the patients in the rate-control group and 97.9% of those in the rhythm-control group had had a stable heart rhythm without atrial fibrillation for the previous 30 days (P=0.02), and 84.2% and 86.9%, respectively, had been free from atrial fibrillation from discharge to 60 days (P=0.41). CONCLUSIONS: Strategies for rate control and rhythm control to treat postoperative atrial fibrillation were associated with equal numbers of days of hospitalization, similar complication rates, and similarly low rates of persistent atrial fibrillation 60 days after onset. Neither treatment strategy showed a net clinical advantage over the other. (Funded by the National Institutes of Health and the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT02132767.).

Intramyocardial Injection of Mesenchymal Precursor Cells and Successful Temporary Weaning From Left Ventricular Assist Device Support in Patients With Advanced Heart Failure: A Randomized Clinical Trial.

Importance: Left ventricular assist device (LVAD) therapy improves myocardial function, but few patients recover sufficiently for explant, which has focused attention on stem cells to augment cardiac recovery. Objective: To assess efficacy and adverse effects of intramyocardial injections of mesenchymal precursor cells (MPCs) during LVAD implant. Design, Setting, and Participants: A randomized phase 2 clinical trial involving patients with advanced heart failure, undergoing LVAD implant, at 19 North American centers (July 2015-August 2017). The 1-year follow-up ended August 2018. Interventions: Intramyocardial injections of 150 million allogeneic MPCs or cryoprotective medium as a sham treatment in a 2:1 ratio (n = 106 vs n = 53). Main Outcomes and Measures: The primary efficacy end point was the proportion of successful temporary weans (of 3 planned assessments) from LVAD support within 6 months of randomization. This end point was assessed using a Bayesian analysis with a predefined threshold of a posterior probability of 80% to indicate success. The 1-year primary safety end point was the incidence of intervention-related adverse events (myocarditis, myocardial rupture, neoplasm, hypersensitivity reactions, and immune sensitization). Secondary end points included readmissions and adverse events at 6 months and 1-year survival. Results: Of 159 patients (mean age, 56 years; 11.3% women), 155 (97.5%) completed 1-year of follow-up. The posterior probability that MPCs increased the likelihood of successful weaning was 69%; below the predefined threshold for success. The mean proportion of successful temporary weaning from LVAD support over 6 months was 61% in the MPC group and 58% in the control group (rate ratio [RR], 1.08; 95% CI, 0.83-1.41; P = .55). No patient experienced a primary safety end point. Of 10 prespecified secondary end points reported, 9 did not reach statistical significance. One-year mortality was not significantly different between the MPC group and the control group (14.2% vs 15.1%; hazard ratio [HR], 0.89; 95%, CI, 0.38-2.11; P = .80). The rate of serious adverse events was not significantly different between groups (70.9 vs 78.7 per 100 patient-months; difference, -7.89; 95% CI, -39.95 to 24.17; P = .63) nor was the rate of readmissions (0.68 vs 0.75 per 100 patient-months; difference, -0.07; 95% CI, -0.41 to 0.27; P = .68). Conclusions and Relevance: Among patients with advanced heart failure, intramyocardial injections of mesenchymal precursor cells, compared with injections of a cryoprotective medium as sham treatment, did not improve successful temporary weaning from left ventricular assist device support at 6 months. The findings do not support the use of intramyocardial mesenchymal stem cells to promote cardiac recovery as measured by temporary weaning from device support. Trial Registration: clinicaltrials.gov Identifier: NCT02362646.

Graded Combined Aerobic Resistance Exercise (CARE) to Prevent or Treat the Persistent Post-concussion Syndrome.

PURPOSE OF REVIEW: To review the growing body of indirect and direct evidence that suggests that exercise can be helpful for children, adolescents, and adults with persistent symptoms following a mild traumatic brain injury (mTBI). RECENT FINDINGS: The direct evidence shows that graded exercise assessments are safe, and that aerobic exercise interventions are associated with improvement of multiple symptoms and other benefits, including earlier return-to-sport. The indirect evidence supports this approach via studies that reveal the potential mechanisms, and show benefits for related presentations and individual symptoms, including headaches, neck pain, vestibular problems, sleep, stress, anxiety, and depression. We document the forms of exercise used for the post-acute management of mTBI, highlight the knowledge gaps, and provide future research directions. We recommend trialing a new approach that utilizes a graduated program of individually prescribed combined aerobic resistance exercises (CARE) if mTBI symptoms persist. This program has the potential to improve patient outcomes and add to the management options for providers.

Psychological Predictors of Postconcussive Symptoms Following Traumatic Injury.

OBJECTIVE: To determine the contribution of demographics, injury type, pain, and psychological factors on postconcussive symptoms. SETTING AND PARTICIPANTS: Recently injured (n = 54) and noninjured (n = 184) adults were recruited from a hospital emergency department or the community. Thirty-eight individuals met the diagnostic criteria for a mild traumatic brain injury and 16 individuals received treatment for a minor traumatic non-brain injury. MAIN MEASURES: Standardized tests were administered to assess 4 postconcussion symptom types and theorized predictors including a "physiogenic" variable (injury type) and "psychogenic" variables (symptoms of anxiety, depression, and stress) within 1 month of the injury. RESULTS: In the injured sample, after controlling for injury type, demographics, and pain (chronic and current), a hierarchical regression analysis revealed that the combination of psychological symptoms predicted affective (F10,42 = 2.80, P = .009, Rchange = 0.27) but not other postconcussion symptoms types. Anxiety (ß = .48), stress (ß = .18), and depression (ß = -.07) were not statistically significant individual predictors (P > .05). Cognitive and vestibular postconcussion symptoms were not predicted by the modeled factors, somatic sensory postconcussion symptoms were predicted by demographic factors only, and the pattern of predictors for the symptom types differed for the samples. CONCLUSIONS: Traditional explanatory models do not account for these findings. The predictors are multifactorial, different for injured versus noninjured samples, and symptom specific.