Liver transplantation is the definitive treatment for individuals with end-stage liver disease. However, a range of medical and physical complications frequently arise following transplantation, which can hinder a patient's overall recovery. Post-operative rehabilitation is often necessary to support and enhance functional outcomes. This review explores the role of early mobilization and inpatient rehabilitation, outlines the rehabilitation process, defines the role of the physiatrist and the interdisciplinary rehabilitation team, and examines the potential functional gains for liver transplant recipients who undergo inpatient rehabilitation.

Importance:Ischemic stroke remains a leading cause of disability worldwide. Preliminary studies have suggested that noninvasive, frequency-tuned, low-intensity electromagnetic network targeting field (ENTF) stimulation may have recovery benefit for patients with stroke. Objective:To evaluate the safety and effectiveness of ENTF therapy in reducing global disability among patients in the subacute ischemic stroke phase with moderate to severe disability and upper-extremity impairment. Design, Setting, and Participants:This multicenter, double-blind, sham-controlled, randomized clinical trial was conducted at 15 US-based acute care and inpatient rehabilitation facilities from December 2021 to November 2023. Participants were enrolled 4 to 21 days after a stroke and had a baseline modified Rankin Scale (mRS) score of 3 or 4 (moderate or moderately severe global disability) and Fugl-Meyer Assessment for Upper Extremity score of 10 to 45 (higher scores indicating better arm function). Target sample size was 150 participants. Participants were randomly allocated to receive either active or sham ENTF stimulation. Modified intention-to-treat approach was used in primary efficacy and safety analyses. Intervention:Participants allocated to the active or sham ENTF stimulation were treated with a proprietary brain-computer interface-based stimulation device paired with an evidence-based, functional, repetitive, home-based physical and occupational exercise regimen for 45 one-hour sessions, 5 times per week within the first 90 days after a stroke. Main Outcomes and Measures:The primary end point was change in global disability, assessed with the mRS (score range: 0 [indicating normal or no symptoms] to 6 [indicating death]), from baseline to day 90. Secondary end points were change from baseline to day 90 in upper-limb impairment, arm motor function, gait speed, hand function, and physical and functional limitations as well as day-90 health-related quality of life, each of which was assessed with a specific metric. Results:The trial was stopped early after enrollment of 100 participants (50 in active group, 50 in sham group) when a promising zone threshold was not attained at planned interim analysis of the first 78 evaluable participants. Participants had a mean age of 59.0 (12.5) years and included 66 males (67.3%). The median (IQR) time from stroke to first ENTF treatment was 14 (12-19) days. Study groups were similar in age, sex, and baseline mRS scores, but imbalances were noted with participants in the active, compared with the sham, group having more right-hemisphere strokes (31 of 49 [63.3%] vs 22 of 49 [44.9%]), more severe upper-extremity impairment (Shoulder Abduction Finger Extension score <5; 31 of 49 [63.3%] vs 24 of 49 [49.0%]), and fewer small-vessel infarcts (14 of 49 [28.6%] vs 21 of 49 [42.9%]). For the primary outcome, the mean (SD) disability reduction on mRS at day 90 was not statistically significantly higher in the active group than in the sham group (-1.96 [0.12] vs -1.72 [0.12]), including mRS score of 0 to 1 attained in 12 participants (26.0%) vs 5 participants (10.0%) (odds ratio, 2.99; 95% CI, 0.96-9.30; P = .05). Point estimates for secondary outcomes favored the active group, although the differences were not statistically significant, in the prespecified analysis. No ENTF device-related serious adverse events were noted. Conclusion and Relevance:This trial found that ENTF therapy is safe. Although the difference between groups was not statistically significant, ENTF therapy may reduce global disability in patients with severe baseline disability after ischemic stroke. These results warrant confirmation in a higher powered pivotal trial of ENTF therapy. Trial Registration:ClinicalTrials.gov Identifier NCT05044507.

Ischemic stroke remains a leading cause of disability worldwide. Preliminary studies have suggested that noninvasive, frequency-tuned, low-intensity electromagnetic network targeting field (ENTF) stimulation may have recovery benefit for patients with stroke. To evaluate the safety and effectiveness of ENTF therapy in reducing global disability among patients in the subacute ischemic stroke phase with moderate to severe disability and upper-extremity impairment. This multicenter, double-blind, sham-controlled, randomized clinical trial was conducted at 15 US-based acute care and inpatient rehabilitation facilities from December 2021 to November 2023. Participants were enrolled 4 to 21 days after a stroke and had a baseline modified Rankin Scale (mRS) score of 3 or 4 (moderate or moderately severe global disability) and Fugl-Meyer Assessment for Upper Extremity score of 10 to 45 (higher scores indicating better arm function). Target sample size was 150 participants. Participants were randomly allocated to receive either active or sham ENTF stimulation. Modified intention-to-treat approach was used in primary efficacy and safety analyses. Participants allocated to the active or sham ENTF stimulation were treated with a proprietary brain-computer interface–based stimulation device paired with an evidence-based, functional, repetitive, home-based physical and occupational exercise regimen for 45 one-hour sessions, 5 times per week within the first 90 days after a stroke. The primary end point was change in global disability, assessed with the mRS (score range: 0 [indicating normal or no symptoms] to 6 [indicating death]), from baseline to day 90. Secondary end points were change from baseline to day 90 in upper-limb impairment, arm motor function, gait speed, hand function, and physical and functional limitations as well as day-90 health-related quality of life, each of which was assessed with a specific metric. The trial was stopped early after enrollment of 100 participants (50 in active group, 50 in sham group) when a promising zone threshold was not attained at planned interim analysis of the first 78 evaluable participants. Participants had a mean age of 59.0 (12.5) years and included 66 males (67.3%). The median (IQR) time from stroke to first ENTF treatment was 14 (12-19) days. Study groups were similar in age, sex, and baseline mRS scores, but imbalances were noted with participants in the active, compared with the sham, group having more right-hemisphere strokes (31 of 49 [63.3%] vs 22 of 49 [44.9%]), more severe upper-extremity impairment (Shoulder Abduction Finger Extension score <5; 31 of 49 [63.3%] vs 24 of 49 [49.0%]), and fewer small-vessel infarcts (14 of 49 [28.6%] vs 21 of 49 [42.9%]). For the primary outcome, the mean (SD) disability reduction on mRS at day 90 was not statistically significantly higher in the active group than in the sham group (−1.96 [0.12] vs −1.72 [0.12]), including mRS score of 0 to 1 attained in 12 participants (26.0%) vs 5 participants (10.0%) (odds ratio, 2.99; 95% CI, 0.96-9.30; P = .05). Point estimates for secondary outcomes favored the active group, although the differences were not statistically significant, in the prespecified analysis. No ENTF device–related serious adverse events were noted. This trial found that ENTF therapy is safe. Although the difference between groups was not statistically significant, ENTF therapy may reduce global disability in patients with severe baseline disability after ischemic stroke. These results warrant confirmation in a higher powered pivotal trial of ENTF therapy. ClinicalTrials.gov Identifier NCT05044507

Background:Assisted walking exercise programs are widely recommended in rehabilitation guidelines for stroke survivors. However, most evidence supporting these programs primarily focuses on ambulatory stroke survivors or those dependent ambulatory in acute and subacute stages. There is a notable gap in the application of walking exercise programs for chronic dependent ambulatory stroke survivors despite potential benefits in reducing sedentary behavior and improving rehabilitation outcomes. Thus, this literature review aims to summarize the existing evidence on the feasibility and efficacy of assisted walking exercise programs for chronic stroke survivors who are dependent ambulators. Methods:Six major databases were searched for clinical trials related to assisted walking exercise and chronic dependent ambulatory stroke. Results:Seven studies (evidence with low- to moderate-quality) involving 91 chronic dependent ambulatory stroke subjects are included in this review. Conclusions:These studies indicated that assisted walking exercise is feasible to perform by chronic dependent ambulatory stroke survivors and can induce continued motor recovery and functional improvement. However, the mixed and limited evidence from existing research underscores the need for future high-quality randomized controlled trials with standardized designs and outcome measures to establish evidence-based walking programs for this population.

Fluctuating arterial blood pressure during high-intensity interval exercise (HIIE) may challenge dynamic cerebral autoregulation (dCA), specifically after stroke after an injury to the cerebrovasculature. We hypothesized that dCA would be attenuated at rest and during a sit-to-stand transition immediately after and 30 min after HIIE in individuals poststroke compared with age- and sex-matched control subjects (CON). HIIE switched every minute between 70% and 10% estimated maximal watts for 10 min. Mean arterial pressure (MAP) and middle cerebral artery blood velocity (MCAv) were recorded. dCA was quantified during spontaneous fluctuations in MAP and MCAv via transfer function analysis. For sit-to-stand, time delay before an increase in cerebrovascular conductance index (CVCi = MCAv/MAP), rate of regulation, and % change in MCAv and MAP were measured. Twenty-two individuals poststroke (age 60 ± 12 yr, 31 ± 16 mo) and twenty-four CON (age 60 ± 13 yr) completed the study. Very low frequency (VLF) gain (P = 0.02, η2 = 0.18) and normalized gain (P = 0.01, η2 = 0.43) had a group × time interaction, with CON improving after HIIE whereas individuals poststroke did not. Individuals poststroke had lower VLF phase (P = 0.03, η2 = 0.22) after HIIE compared with CON. We found no differences in the sit-to-stand measurement of dCA. Our study showed lower dCA during spontaneous fluctuations in MCAv and MAP following HIIE in individuals poststroke compared with CON, whereas the sit-to-stand response was maintained.NEW & NOTEWORTHY This study provides novel insights into poststroke dynamic cerebral autoregulation (dCA) following an acute bout of high-intensity interval exercise (HIIE). In people after stroke, dCA appears attenuated during spontaneous fluctuations in mean arterial pressure (MAP) and middle cerebral artery blood velocity (MCAv) following HIIE. However, the dCA response during a single sit-to-stand transition after HIIE showed no significant difference from controls. These findings suggest that HIIE may temporarily challenge dCA after exercise in individuals with stroke.

Feature editor: Debjani Mukherjee, PhD, HEC-C “While informed consent is necessary in most but not all cases, in no case is it sufficient for ethical clinical research.”1 Although the United States often prioritizes respect for autonomy and informed choices, the requirements also underscore the importance of social justice and avoiding societal harms. For clinical researchers working with people with disabilities, who have often been marginalized and may be deemed “vulnerable,” the importance of fairness, respect, and a favorable risk–benefit ratio must be carefully weighed. In my former role at the Shirley Ryan AbilityLab (formerly the Rehabilitation Institute of Chicago), I was the ethics leader as we transitioned to a translational research hospital, and we held many educational sessions and engaged in discussions about conducting ethical clinical research. The process of having these discussions with various stakeholders, and weighing options, is an important part that goes beyond the work that institutional review boards engage in after a project has already been conceived of and is ready to enroll. As a rehabilitation researcher, how do you interpret this framework? How do these requirements impact the design and implementation of your research? Have you experienced or observed missteps and/or dilemmas? Please share any recommendations you have for conducting ethical clinical rehabilitation research. The first respondent is Sarah Eickmeyer, MD who is an Associate Professor of Rehabilitation Medicine at the University of Kansas Medical Center and Medical Director of Acute Inpatient Rehabilitation. She addresses the requirements drawing on examples from her expertise in stroke rehabilitation research. The second respondent is Elissa Larkin, MS, CCC-SLP who is a Research Speech-Language Pathologist in the Center for Aphasia Research and Treatment and a Clinical Bioethicist at the Shirley Ryan AbilityLab. She focuses on communication access as a key ethical issue in clinical research. The next piece is by Michael W. O'Dell, MD who is Professor Emeritus of Clinical Rehabilitation Medicine at Weill Cornell Medical College. He draws on his decades of experiences as an expert in neurorehabilitation and focuses on the requirements as they relate to people with neurological impairments. The last essay is by Scott A. Barbuto, MD, PhD who is an Assistant Professor of Rehabilitation and Regenerative Medicine at Columbia University Medical Center. He responds to the ethical requirements from his experiences as a researcher conducting clinical trials. All of the commentaries add to a rich discussion of what it means to consider the ethical requirements of clinical rehabilitation research. The importance of scientific validity, access, communication, weighing risks and benefits, and the responsibilities of the investigator are all woven throughout the essays. These considerations are important for all stages of the research process from the generation of ideas and hypotheses to dissemination of results. Finally, a note on the use of terms. Emanuel, Wendler, and Grady used the term “subjects” in their article, and the preferred term for this journal is “participants.” In many fields, what we call individuals who agree to voluntarily engage in the research process has shifted from a focus of being the subject of scientific inquiry to (ideally) being an active partner. In that spirit, we use the term participant throughout this article except when referring to the Emanuel, Wendler, and Grady article. As always, I welcome your comments at [email protected]. Sarah Eickmeyer MD University of Kansas Medical Center Emanuel, Wendler, and Grady outline several ethical requirements in a framework for clinical research.1 Because the objective of clinical research is to develop generalizable knowledge to improve health while minimizing exploitation, these additional requirements provide guidance to develop and evaluate clinical studies. As a rehabilitation researcher and clinician, I interpret these requirements considering potential conflicts while performing clinical research. A key tenet as a rehabilitation physician is to avoid exploitation of vulnerable populations, most notably the persons with disabilities whom we serve. The first requirement is value, referring to interventions that could lead to improvements in health or well-being or could generate important knowledge about human biological systems.1 Importantly, interventions that could never be practically implemented, even if effective, should be avoided because they do not add value. As a rehabilitation researcher, I must consider the cost and finite resources available to the study population. For example, people with significant disability may represent a socially disadvantaged group with limited resources and/or insurance if they cannot return to work after the disabling event. The affordability of high-tech interventions in rehabilitation must be considered. The availability of innovative rehabilitation solutions in a limited number of specialty clinics may not add value to the entire population. If the new therapeutic trial is only available in urban cities, entire populations in rural communities are left disadvantaged. Social justice for persons with disabilities must be at the forefront of rehabilitation researchers' considerations when designing clinical research trials. The second consideration is scientific validity or conducting research in a methodologically rigorous manner.1 Sufficient power must exist to definitively test the hypothesis and conduct data analysis. The authors posit that underpowered studies that cannot enroll a sufficient number of participants cannot generate scientific knowledge and thus are unethical. In clinical rehabilitation research, it can be difficult to enroll individuals with disability, especially if they rely on other people or services for transportation, need physical assistance to access research spaces, or must travel long distances for specialty care and access to clinical trials. Smaller studies may be necessary and valid, if well designed, and may provide pilot data to extend the study to multiple sites to ultimately enroll a sufficient number of people. Research networks like StrokeNet2 can be valuable ways to pool resources and limited numbers of eligible participants across regions or states. The next requirement is fair “subject” selection, referring to recruitment strategies that support the scientific goals of the study, not vulnerability, privilege, or other unrelated factors.1 In rehabilitation research, the vulnerability of participants must be considered, especially if groups are compromised in their ability to protect themselves. People with disabilities are a vulnerable population and must be recruited carefully to avoid potential exploitation. For example, in research involving stroke recovery of fine and gross motor function, I must also consider participants' cognition and communication impairments. Clinical studies involving stroke must ensure that the participants are able to understand the risks and benefits of the study before enrolling. Family members and caregivers can also be involved in the informed consent process, but the participant's assent must also be considered. Similarly, recent efforts to increase diversity in clinical trial enrollment outside of rehabilitation must also include people with disabilities who represent a growing segment of the population,3 to maximize the benefits, values and generalizability of results. A favorable risk–benefit ratio ensures that potential risks to participants are minimized, and potential benefits are maximized, such that the benefits outweigh the risks for potential clinical research participants.1 The authors state that, although clinical research participants may benefit from health services received during research, the purpose of clinical research is not the provision of health services. However, rehabilitation interventions like physical, occupational, and speech therapy are limited by insurance and financial resources. Is it ethical to offer rehabilitation research studies if the health benefit is an extension of ongoing therapy that was limited by insurance caps on therapy days? Often, clinical trials in rehabilitation offer a way to continue therapy without cost to the participant when traditional therapy days have been depleted under insurance benefits. In general, the risks to ongoing therapeutic interventions are low and the potential benefits of supervised exercise or therapy are high, therefore likely justifying this risk–benefit ratio. Independent review of clinical research is a requirement that helps minimize the potential impact of conflicts of interest that may distort the judgment of clinical researchers.1 As a rehabilitation researcher and clinician, enrolling my own patients into clinical trials leads to inherent bias. I am both committed to the well-being of my patients and the completion of high-quality research. If a patient may benefit from a research intervention but must be excluded to maintain the integrity of the study, an independent review will ensure that a clear and ethical decision is made. For example, in a recent clinical trial a potential participant was excluded due to the diagnosis of alcohol use disorder. Clinicians involved in the care of the patient, myself included, desired that he should benefit from the research intervention. However, independent review of the eligibility requirements ultimately determined that he must be excluded to maintain the integrity of the research. Regarding informed consent, participation in research must be consistent with participants' values, interests, and preferences.1 Individuals must understand the risks, benefits, and alternatives to participation and be allowed to make an uncoerced decision to participate. In rehabilitation research, we often encounter potential participants with cognitive impairment who are unable to make their own decisions and require informed consent from a proxy decision maker. I agree with the authors that respect for persons means ensuring that research participation is consistent with their interests and values and should include the participants' assent if possible. As with all decisions involving vulnerable populations, caution must be exercised to avoid exploitation. Finally, respect for potential and enrolled participants must be maintained, whether or not they decide to enroll in the clinical research.1 As a rehabilitation researcher and clinician, I cannot let a person's decision to participate in research cloud my judgment or ongoing medical care. My own personal excitement for stroke recovery research may influence my patients' decision to enroll in research studies at our institution. However, if people decline to enroll or change their mind, that is their right and they must still be treated with respect by all members of the rehabilitation team. Just as we partner with our patients to make decisions in their health care, we also partner with our patients if they choose to participate in clinical research. In rehabilitation we value the long-term relationships we develop with patients and must be careful to maintain trust and respect in the relationship to optimize access to rehabilitation care over time. These seven ethical requirements for clinical research provide a framework to ensure that clinical research proceeds in a valid, fair, and safe manner. In rehabilitation research, the additional considerations for a potentially vulnerable population of people with disabilities will ensure that we avoid exploitation and maximize the benefits for the people we serve. Elissa Larkin MS, CCC SLP Shirley Ryan Ability Lab As a clinician and rehabilitation researcher, I have had many humbling and enlightening experiences during which individuals with communication disabilities have educated me about the inequities they face. These experiences have shaped my understanding of the critical role of communication access in conducting ethical research. I will reflect on Emanuel and colleagues' framework for ethical clinical research as it relates to participants with communication difficulties. Clinically I have worked with individuals with a variety of developmental and neurogenic communication disabilities, but the majority of my experience as a researcher has been with individuals with aphasia. Aphasia is a language disorder caused by damage to the language areas and networks in the brain, and conservative estimates indicate there are currently more than 2.5 million people living with aphasia in the United States.1 Aphasia can affect any of the four language modalities (speaking, understanding, reading, and writing) to varying degrees depending on the type and extent of a person's injury. Aphasia is a helpful example to consider in relation to communication practices within clinical research because it encourages consideration of the varied communication needs a research participant may have. From a disability rights perspective, people with communication disabilities like aphasia experience issues of communication access. The concept of access within the disability rights movement has been key to shifting the locus of the “problem” from within the individual with a disability to the environment with which that individual engages.2 Historically, however, American society has promoted access by providing accommodations primarily in the physical sense, that is, by making physical environments accessible with accommodations such as ramps and curb cutouts. The concept of communication access is not as familiar, nor as regularly applied. In an analysis of the experiences of people with complex communication needs, Collier and colleagues defined communication access as “having the means, supports and opportunities to communicate effectively, meaningfully, accurately and authentically in order to get equal uncompromised access to goods and services.”.3 For many individuals with communication disabilities, such access depends on accommodations provided in the communication environment. Examples of communication accommodations include environmental setup and communication tools made available during interactions (e.g., limiting background noise, pen and paper within reach) and the practices of communication partners (e.g., slowed rate of speech, body language, varied question and answer formats). In the context of a clinical research relationship, the communication partners are the research staff who interact with a participant with a communication disability at any point during the course of their recruitment, consent, participation, and follow-up. When viewed through the lens of communication access, four of the seven ethical requirements outlined in the suggested framework contain opportunities for expansion: scientific value, fair participant selection, informed consent, and respect for potential and enrolled participants. Returning to the illustrative experiences of people with aphasia, their exclusion from research opportunities is common. For example, a 2018 systematic review of treatment interventions for post-stroke depression in aphasia had to exclude 62% of otherwise relevant studies (198 out of 320) due to inadequate description or no mention of participants with aphasia within the sample.4 An estimated 34% of stroke survivors have aphasia,5 so their exclusion affects how representative stroke research samples are and thereby their applicability and generalizability, which may ultimately compromise studies' scientific value. Further, excluding people with communication disabilities from research opportunities constitutes an unfair method of participant selection, particularly in cases where the wider population of individuals with aphasia may benefit from the research. While it is true that people with communication disabilities may be more susceptible to the risk of non- or limited comprehension of complex concepts, both the literature and my own direct experiences as a clinical researcher show that appropriate communication accommodations allow people with varied communication disabilities to communicate effectively and participate meaningfully as research participants. Implementing appropriate communication accommodations for participants serves to reduce vulnerabilities associated with communication challenges and promote participants' autonomy. Due to the wide variety of communication abilities a clinical researcher may encounter, adjusting communication practices to the unique needs of each participant may seem daunting. In truth, as stated earlier, this is a less familiar concept for many of us, and even fewer researchers may have experience or education on how to adapt communication during the research process. Thankfully, there is a growing evidence base and an increasing number of educational tools and tutorials available for those who seek to build their knowledge and skills in this area. Additionally, having a communication expert such as a Speech-Language Pathologist on your research team or as a consultant can help ensure participant communication needs are appropriately accommodated. One practice our team utilizes is that of talking through complex information such as details of a consent form using a simplified parallel “aphasia-friendly information sheet” with larger print, and key concepts highlighted and described with simpler language and pictorial representations. Such tools can make information accessible not only for those with communication disabilities, but also for potential research participants with different levels of health literacy. When researchers provide information to participants with communication disabilities in multiple modalities (e.g., written, verbal, pictorial) and give participants both ample time and supported methods for asking questions and expressing their opinions, it is not only respectful but can be empowering. It is widely accepted that clinical researchers should inform participants of newly learned information both during and at the conclusion of a scientific study. However, it should also be explicitly stated that such information must be provided in the most comprehensible manner possible to support adequate communication access. With that last point in mind, I'll close where I began; with a story of a person with a communication disability who helped me challenge my assumptions and adapt my communication practices to his unique needs. I was recently recruiting for a research study working with people with a range of communication disabilities including aphasia and dysarthria (or speech difficulties) related to cerebral palsy. A colleague referred a community member with cerebral palsy who had expressed interest. I first spoke with this person by video conference (allowing us to use both auditory and visual communication aids), and then emailed both the formal consent form and our simplified accompanying information sheet, so that the participant would have time to review the details before we completed the consent process. I thought this was a sufficiently supportive way to accommodate the individual's communication needs. However, after receiving my email the participant called me back and asked if we could have another video conference to go through the information together. “I don't read too good,” he shared bravely. Once again, I was humbled as I realized I had made an assumption about this individual's literacy level. I was so focused on the more evident speech difficulty, that I did not utilize my best practices training to evaluate and implement adaptations to support his comprehension. I share this to highlight the complexity and subtleties of each individual's communication needs, and to underscore the importance of consistent practices to first inquire about a person's best methods of expressing and understanding information to inform communication accommodations. No matter our background, a first step of humble inquiry in partnership with our research participants can promote consistent communication access within clinical research. Michael W. O'Dell MD Weill Cornell Medical College I have admired and reflected upon the 2000 Emanuel and colleagues' article, “What Makes Clinical Research Ethical?”1 for years, having initially read it during a medical student ethics course at Weill Cornell Medicine. I have since frequently used the article to help frame discussions surrounding research ethics for residents and faculty in The Department of Rehabilitation Medicine at New York-Presbyterian Hospital—Columbia and Cornell. I have worked as an active researcher in all facets of neurorehabilitation over the past three decades—research education, study design and peer-review, clinical trials procurement and management, participant recruitment, data analysis and manuscript composition and publication. Upon reflection of these seven requirements, I would like to focus on four—fair participant (subject) selection, informed consent, scientific validity (specifically outcomes assessment) and balancing risk and benefit. Regarding fair participant selection, depending on the research intervention, those who stand to benefit the most will likely be the most difficult to identify, recruit and retain.2 Persons with greatest degrees of weakness, spasticity, aphasia, cognitive deficit, and locomotors or self-care limitations are probably those individuals who are physically unable to travel, lack internet or computer access (at home or in a long-term care facility); have difficulty understanding, affording or using a keyboard or mouse, or are in general unfamiliar with computers due to lesser education or more advanced age.2 The later issue of age maybe reflected by the consistently younger age of participants in stroke rehabilitation and recovery trials compared with the general stroke population. To be sure, there are success stories in recruiting “hard to find” participants in neurorehabilitation research, such as the recent clinical trial of amantadine for severe disorders of consciousness where many of the participants were based at long term care facilities.3 Other challenges such as the high prevalence of mood disorders, an overly nihilistic view of the prognosis and outcomes of neurological disease and injury and an inherent distrust of research and the medical system may quell enthusiasm to seek out clinical trials, further reducing access.2, 4 In stroke rehabilitation and recovery research, specifically, the near universal exclusion of hemorrhagic strokes, ostensibly to minimize medical complications or maximize sample homogeneity, possibly limits access to nearly 13% of persons with stroke.5 Researchers and funders alike should provide clear justification as to why persons with hemorrhagic strokes should be excluded from a given stroke recovery research protocol. In addition, they must be more aggressive in exploring innovative recruiting strategies such as field-based, mobile research screening and treatment units, assigning scribes to assist participants unfamiliar with using computer and other technologies, and hiring persons with disabilities as part of our research teams, including as principal investigator (PI),2 to help develop novel identification and recruiting approaches.2, 4 Clinical research in neurorehabilitation nearly guarantees interaction with participants having deficits in cognition and language. Most research protocols allow the designation of a surrogate to provide informed consent, but this does not absolve the PI from independently assessing the wishes of the participant to guard against coercion.2 Deficits in cognition and language are not black and white but infinite shades of gray. The PI must balance whether cognitive deficits might be severe enough to undermine fully informed consent on the one hand or not so severe as to inappropriately exclude an individual from the opportunity to participate in research on the other hand. Cognitive and language deficits also pose a scientific validity dilemma with regards to outcome assessment. Many endpoints in neurorehabilitation clinical trials are questionnaires or at least partially language based. Even in botulinum toxin trials, where the motor-based Modified Ashworth Score (MAS) usually serves as the primary outcome, nearly all secondary and tertiary outcomes are heavily language-dependent.6 Other outcome approaches, such as goal attainment scaling, can be quite long and complex requiring high degrees of concentration, short-term memory and executive function. In lieu of exclusion, alternative or novel outcome assessment strategies in persons with language deficits have been proposed,7 but rarely implemented. I was unable to identify significant discussions on strategies to accommodate persons with cognitive deficits in neurorehabilitation research. Finally, independence may be among the dearest of all human experiences and its forfeit among its gravest of all losses. Given that, what is any given “person” willing to sacrifice to become a “participant” and potentially regain a degree of that independence? What risk would someone assuming “to walk,” “to communicate,” “to remember,” or “to see one's loved one resume consciousness”? How much greater risk might one tolerate for “walking normally” rather than “walking better” rather than simply “walk” and how does an investigator temper his or her confidence in conveying those benefits proportional to the risk of experimental phase II surgery, drugs, or biological therapy. The nature of many research endpoints in neurorehabilitation go directly to the essence of what it means to be human: independence, individuality, and self-determination. Therefore, investigators must be precise in their ability to quantify both the risk and present the potential realistic benefit of their research in order to achieve the proportionality to which Dr. Emanuel refers. In summary, neurorehabilitation researchers face special challenges by virtue of the populations they seek to recruit and study and the nature and personal importance of the impairments they seek to ameliorate. A keen sense of the ethical nature of their work is of equal importance to a familiarity with basic science, research design and statistics. Dr O'Dell reports participating on an advisory board for Merz. All other authors have no disclosures. Scott Barbuto MD, PhD University of Kansas Medical Center With the prospect of changing lives for the better, clinical research is a uniquely rewarding field. Yet, it does not come without challenges, one of which is how to conduct trials ethically where individuals are treated with the respect they deserve. In the classic article, “What Makes Clinical Research Ethical,” seven ethical requirements are outlined: (1) value, (2) scientific validity, (3) fair subject selection, (4) favorable risk–benefit ratio, (5) independent review, (6) informed consent, and (7) respect for potential and enrolled participants.1 In this commentary, I will address each requirement from the perspective of a clinician trained in rehabilitation medicine who routinely conducts clinical trials. I hope the examples provided and questions raised from my own research will offer insight on how to perform ethical research in physical medicine. This principle seems simple enough to understand. Of course, clinical research should be of some value if it is to be conducted. Yet, there are nuances to this ethical principle, especially in the context of rehabilitation medicine, that are easy to overlook. First, one of the easiest ways for clinical research to lose value is the selection of the wrong outcome measure. As my mentor frequently said, “you can't study something if you can't measure it.” In rehabilitation medicine, where much of what we want to study is difficult to measure, it is easier than expected to make this error. Second, for research to be of value, the results must be disseminated. With chronic disabilities that are notoriously difficult to treat, negative trials are commonplace, and unfortunately, it is still difficult to publish negative results. This recently happened to me. When we found out that delayed speech therapy did not lead to poorer outcomes in COVID patients, we had to submit our findings to more than five journals. It would have been easy to give up on publication, but then would the work we did be ethical if no one knew about it? For research to be ethical, accepted scientific principles and methods must be used. When I first started performing clinical research, I made a mistake in this regard. I thought, since I was conducting research that would take over a year to finish, I should measure everything and anything. I checked if my aerobic program impacted sleep, fatigue, memory, disability, depression, gait, balance, and ataxia. Even though I only had one primary outcome, reviewers still called my work the dreaded “fishing expedition.” I had measured too many things with not enough participants, making my study of limited value. I also subjected the participants to multiple surveys and ultimately, wasted some of their time. Were my participants treated unethically? If you asked them, I bet they would answer no, but ultimately any sloppy research should be considered unethical. This principle prevents conducting risky research on vulnerable populations. I think everyone would agree using money to solicit research participants from poor areas is unethical. Yet, in addition to the wrongful inclusion of participants, this principle also relates to the exclusion of individuals from research. For example, I work in Harlem where many potential research participants only speak Spanish. In order to recruit these individuals, I need to have consent forms, questionnaires, and any written documents printed in Spanish. Moreover, since I do not speak Spanish fluently, I need to use an interpreter for all interactions. It would obviously be easier to exclude participants where English is not their first language, but is that ethical? One study found that 40% of researchers exclude individuals who are not proficient in English, making this topic a real ethical concern.2 When starting out in research, I thought this meant that the benefits of the research must outweigh the risks. Yet, with this definition, how could anyone conduct a dose-finding trial on healthy individuals? Participants would receive no benefit, and there are always potential side effects to any treatment. As I was explained, this principle proclaims that researchers have a burden to maximize benefits and minimize risks. For me, this meant having individuals perform balance training in a safe environment, minimizing injury from falls. It also meant conducting a trial without a placebo control group, even though having an active control lessens the difference I see between groups. This principle states that enrolled participants must know: (1) the purpose of the research, (2) its procedures, and (3) the potential risks, benefits, and alternatives, so that they can make an informed, voluntary decision regarding participation. Although it is the one component everyone thinks of when discussing research ethics, there is no standardized approach to how informed consent is conducted.3 For my own research, I almost always carry out the informed consent process. The reason is that I know my research best, so I am the best to answer questions and explain the procedures. However, there is one circumstance in which I have a research assistant perform informed consent: when the potential participant is my own patient. Given the power dynamics in a doctor-patient relationship, it is reasonable to believe that any potential participant would feel compelled to join a study in which their own physician wished them to do so. Thus, I remove myself from this situation to ensure that my patient feels no pressure to participate. This principle ensures that participants have protected privacy and are informed of any new risks, benefits, and results. It also means that enrolled participants have the right to withdraw from the research at any time, which is where I would like to comment. Working with individuals with a rare disease, I must admit it is frustrating to have participants withdraw from the study, especially when it is so hard to recruit them. Like many rehabilitation researchers, I also use exercise as a treatment where compliance to training and study retention is notoriously low.4 Luckily, however, I have not had many participants drop-out of my studies. I attribute this to two things: (1) I speak with my participants every 2 weeks to discuss training, which helps build rapport with them, and (2) I am very detailed in my informed consent process so that individuals know exactly what to expect when they enroll. Therefore, even though ethics allows for participant withdrawal, having good ethical practices may actually help with study retention. In summary, good ethical research requires constant self-evaluation. There are gray areas in the field, which sometimes make you question your practices. But, there is always help in this regard and I have found that the best practice is to ask your Institutional Review Board for help whenever questions arise.

Heart transplantation is a definitive treatment option for patients with end-stage heart failure. Medical and functional complications are common after this procedure, and rehabilitation is often needed postoperatively. Physiatrists caring for persons who have received a donor heart must appreciate the surgical background, the physiologic changes expected, as well as the potential medical complications for which they are at risk after heart transplantation. This review summarizes various topics in heart transplantation including the history of the procedure, exercise physiology and functional outcomes, postoperative medical therapy, medical complications, and special considerations for inpatient rehabilitation in this patient population.

Heart transplantation is considered definitive treatment for patients with end-stage heart failure. Unfortunately, medical and functional complications are common after heart transplantation for a variety of reasons, and these may impact the patients' functional recovery. Rehabilitation is often needed post-operatively to improve functional outcomes. This review article aims to discuss the transplanted heart exercise physiology that may affect the rehabilitation process and provide an overview of the functional benefits of inpatient rehabilitation for cardiac and surgical specialties who may be less familiar with post-acute care rehabilitation options for their patients.

Communication challenges in persons with aphasia may negatively affect their health care. Building effective communication skills is critical for health professional student education, yet communication skills for interacting with persons with aphasia are often not taught or practiced within health care education. A review of the literature found that research is limited but does demonstrate evidence-based training can improve skills for health professional students. Through utilization of workshops, seminars, and standardized patients, medical students and other health professional students can build confidence and skills in successful communication for future encounters with persons with aphasia.

Bone loss leading to fragility fracture is a highly prevalent late effect in hematopoietic stem-cell transplant patients, who are affected 8–9 times more than the general population, particularly for vertebral compression fractures. Spinal interventions such as lumbar epidural steroid injections and vertebral augmentation may be helpful for providing pain relief and improved function, quality of life and return to ambulation. However, interventional procedures should be approached with caution in these patients. Our study found that there is a paucity of scientific studies addressing the risks of spinal injections in these patients and there is no absolute recommendation specific to spinal injections in patients receiving immunosuppressive agents or who have a history of solid organ or hematopoietic stem cell transplant. It is imperative to consider proper timing of the intervention to minimize risks while optimizing the benefits of the intervention combined with a well-defined post-transplant rehabilitation plan. Moreover, the decision to proceed with spinal interventions should be done case by case and with caution. Therefore, this article reports the case of a multidisciplinary treatment for a vertebral compression fracture in a patient with a hematopoietic stem-cell transplant, in particular discussing safety appropriateness in interventional pain management and rehabilitation considerations for this condition in this patient population.

Purpose: Physical activity within the hospital poststroke is recommended for cardiovascular and musculoskeletal health, but no studies have examined cerebrovascular health. We hypothesized that individuals who walked farther distances (FARhigh) during the acute phase of stroke recovery in a hospital setting would have a higher resting middle cerebral artery blood velocity (MCAv) and a greater cerebrovascular response (CVR) to moderate-intensity exercise at 3 months poststroke, compared with individuals who walked shorter distances (FARlow). Methods: At 3 months poststroke, we recorded 90 seconds of resting baseline (BL) MCAv, followed by 6 minutes of moderate-intensity exercise. We calculated CVR as the change in MCAv from BL to steady-state exercise. We retrospectively collected the farthest distance walked within the hospital poststroke from the electronic medical record. Participants were classified as FARhigh or FARlow based on the average farthest walking distance. Results: Twenty participants completed the study, aged 63 (15) years. Baseline MCAv was not different between groups (P = .07). In comparison with FARlow, we report a higher CVR in FARhigh's ipsilesional ( = 7.38 [5.42] vs = 2.19 [3.53], P = .02)and contralesional hemispheres ( = 8.15 [6.37] vs = 2.06 [4.76], P = .04). Conclusions: Physical activity during the hospital stay poststroke may support cerebrovascular health after discharge. Prospective studies are needed to support this finding.

INTRODUCTION:Obesity is a risk factor for many adverse health outcomes. However for some cardiac conditions and cancers, evidence of an "obesity paradox" seems to exist where an elevated body mass index (BMI) is linked to protective effects in mortality and functional outcomes. Within the stroke rehabilitation literature, there are conflicting findings on this phenomenon possibly due to unaccounted for variables, such as comorbid medical conditions.OBJECTIVE:To investigate the association between BMI and functional gains made in acute inpatient stroke rehabilitation, and the effects of multiple confounding variables.DESIGN:Retrospective cohort study.SETTING:Tertiary academic hospital.PATIENTS:Three hundred ninety-two adults following a recent ischemic (82%) or hemorrhagic (18%) stroke with a mean age 62.9 years.INTERVENTIONS:Acute inpatient rehabilitation.MAIN OUTCOME MEASURES:Functional Independence Measure (FIM) score and BMI.RESULTS:A significant association was found between motor FIM score gains and elevated BMI when BMI was treated as a continuous variable (p < .05). However, this association disappeared when patient factors and comorbid conditions were taken into account and when BMI was conceptualized categorically (underweight [BMI <18.5], normal [BMI 18.5-24.9], overweight [BMI 25.0-29.9], obese [BMI 30.0-39.9], and severely obese [BMI ≥40.0]). Advanced age, higher motor function on admission, and a diagnosis of diabetes were all significantly associated with decreased motor FIM gains.CONCLUSIONS:The results from this study provide insufficient evidence to support the "obesity paradox" once patient factors and comorbid conditions are taken into account. Diabetes was the single comorbidity tracked that showed a significant association with change in motor function (p = .01). Further studies might explore how the unique interventions of rehabilitation physicians and ancillary health professionals might mitigate the functional debility associated with diabetes and obesity in stroke patients.

Objective: To describe functional outcomes following discharge from an acute inpatient rehabilitation facility (IRF) in patients following epilepsy surgery, comparing laser interstitial thermal therapy (LITT) versus surgical resection for epilepsy. Design: Retrospective case series. Setting: Academic tertiary hospital. Participants: Eight patients who received LITT (n = 3) or surgical resection (n = 5) for epilepsy. Interventions: Acute inpatient rehabilitation. Main Outcome Measures: Functional independence measure (FIM), seizure incidence, discharge destination. Level of Evidence: IV. Results: The epilepsy cohort demonstrated a FIM change of 38.88 (vs. national average 29.55), average length of stay (LOS) of 15.13 days (vs. 13.38 days), and LOS efficiency was 3.4 (vs. 2.68). No patients in the epilepsy cohort were discharged to acute care hospital compared to a national average of 9.82%. Eighty-seven percent in the epilepsy cohort discharged to home (vs. 77%) and 12.5% to skilled nursing facility (vs. 11.90%). Between the subset who received LITT and those who received surgical resection, there was no statistically significant change in mean total FIM change (43.7 vs. 36), FIM efficiency (5.3 vs. 2.2), or FIM change in subset measures of memory (0.5 vs. 0.25) or problem solving (0 vs. 0.8). There was no statistical significance between groups in adverse events, including seizure. Conclusions: Outcome measures in this population appear to be consistent with national outcome measures for other IRF diagnoses. This suggests that acute inpatient rehabilitation should be considered after patients undergo surgical intervention for epilepsy. However, a larger sample size and controlled studies are necessary before generalizations can be made. In addition, no statistically significant functional difference was seen between patients who underwent LITT or surgical resection.

Background The primary aim of this study was to characterize the middle cerebral artery blood velocity (MCAv) dynamic response to an acute bout of exercise in humans at 3‐ and 6‐months poststroke. As a secondary objective, we grouped individuals according to the MCAv dynamic response to the exercise bout as responder or nonresponder. We tested whether physical activity, aerobic fitness, and exercise mean arterial blood pressure differed between groups. Methods and Results Transcranial Doppler ultrasound measured MCAv during a 90‐second baseline followed by a 6‐minute moderate intensity exercise bout. Heart rate, mean arterial blood pressure, and end‐tidal CO2 were additional variables of interest. The MCAv dynamic response variables included the following: baseline, time delay, amplitude, and time constant. Linear mixed model revealed no significant differences in our selected outcomes between 3‐ and 6‐months poststroke. Individuals characterized as responders demonstrated a faster time delay, higher amplitude, and reported higher levels of physical activity and aerobic fitness when compared with the nonresponders. No between‐group differences were identified for baseline, time constant, or exercise mean arterial blood pressure. In the nonresponders, we observed an immediate rise in MCAv following exercise onset followed by an immediate decline to near baseline values, while the responders showed an exponential rise until steady state was reached. Conclusions The MCAv dynamic response profile has the potential to provide valuable information during an acute exercise bout following stroke. Individuals with a greater MCAv response to the exercise stimulus reported statin use and regular participation in exercise.

Background and Purpose The primary aim was to characterize the middle cerebral artery blood velocity (MCAv) dynamic response to an acute bout of exercise at 3- and 6-months post stroke. As a secondary objective, we grouped individuals according to the MCAv dynamic response to the exercise bout as responder or non-responder. We tested whether physical activity, aerobic fitness and exercise mean arterial blood pressure (MAP) differed between groups. Methods Transcranial Doppler ultrasound measured MCAv during a 90-second baseline (BL) followed by a 6-minute moderate intensity exercise bout. Heart rate (HR), MAP and end tidal CO2 (PETCO2) were additional variables of interest. The MCAv dynamic response variables included: BL, time delay (TD), amplitude and time constant (τ). Results Individuals enrolled in the study at 3 months post-stroke and the follow up visit commenced at 6 months post-stroke. Linear mixed model revealed no significant differences in our selected outcomes across between 3- and 6-months post-stroke. Individuals characterized as responders demonstrated a faster TD, higher amplitude, reported higher levels of physical activity and aerobic fitness when compared to the non-responders. No between group differences were identified for BL,τ or exercise MAP. In the non-responders, we observed an immediate rise in MCAv following exercise onset followed by an immediate decline to near BL values while the responders showed an exponential rise until steady state was reached. Conclusions The MCAv dynamic response profile has the potential to provide valuable information during an acute exercise bout following stroke. Individuals with a greater MCAv response to the exercise stimulus reported regular participation in exercise than those who reported being sedentary. ### Competing Interest Statement SAB reports a patent pending (18KU028M-02). MA reports consulting for Stryker Neurovascular and Penumbra Inc. outside the submitted work. AW, AM, CK, SP, JW, SE, SB, and LL report no conflicts of interest. ### Clinical Trial This was an observational study and was not registered. ### Funding Statement Dr. Billinger was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (K01HD067318). Dr. Billinger received support from the Wohlgemuth Faculty Scholar Award. Dr. Whitaker and Ms. Morton were supported in part by T32HD057850 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Ms. Morton was also supported by a Student Scholarship in Cerebrovascular Disease and Stroke from the American Heart Association. Dr. Perdomo received partial support from the University of Kansas Alzheimer's Disease Center (P30AG035982) and from the National Institute on Aging Diversity Supplement to R01 AG058162. REDCap at University of Kansas Medical Center is supported by CTSA Award (UL1TR000001) from NCRR and NCATS awarded to the University of Kansas Medical Center for Frontiers: The Heartland Institute for Clinical and Translational Research. This work was supported by a CTSA grant from NCATS awarded to the University of Kansas for Frontiers: University of Kansas Clinical and Translational Science Institute (UL1TR002366) The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or NCATS. The Georgia Holland Research in Exercise and Cardiovascular Health (REACH) laboratory space was supported by the Georgia Holland Endowment Fund. ### Author Declarations All relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript. Yes All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The data are available upon request from the corresponding author.

Abstract Background and Purpose Chronic hyperglycemia contributes to cerebrovascular dysfunction by damaging blood vessels. Poor glucose control has been tied to impairments in cerebral blood flow, which may be particularly detrimental for people recovering from major cerebrovascular events such as acute ischemic stroke. In this secondary analysis, we explore for the first time the connection between chronic hyperglycemia before acute stroke and the cerebrovascular response (CVR) to exercise 3 and 6 month into the subacute recovery period. Methods We recorded middle cerebral artery velocity (MCAv) using transcranial Doppler ultrasound bilaterally at rest and during moderate‐intensity exercise in stroke patients at 3 (n = 19) and 6 (n = 12) months post‐stroke. We calculated CVR as the difference between MCAv during steady‐state exercise and resting MCAv. We obtained hemoglobin A1c levels (HbA1c; a measure of blood glucose over the prior 3 months) from the electronic medical record (EMR) and divided participants by HbA1c greater or less than 7%. Results Participants with high HbA1c (>7%) at the time of acute stroke had significantly lower CVR to exercise for both the stroke‐affected (p = .009) and non‐affected (p = .007) hemispheres at 3 months post‐stroke. These differences remained significant at 6 months post‐stroke (stroke‐affected, p = .008; non‐affected, p = .016). Conclusions Patients with chronic hyperglycemia before acute ischemic stroke demonstrated impaired cerebrovascular function during exercise months into the subacute recovery period. These findings highlight the importance of maintaining tight glucose control to reduce morbidity and improve recovery post‐stroke and could have implications for understanding cerebrovascular pathophysiology.

Physicians often overlook exercise as a treatment or prophylactic measure for many common diseases and ailments. It can be used to treat comorbidities including obesity, cardiovascular disease, chronic obstructive pulmonary disease, diabetes mellitus, osteoporosis, osteoarthritis, cancer, and low back pain. Education on the general physical activity guidelines as well as easy exercise prescription methods can improve the ability of physicians to prescribe exercise as a therapeutic option. In addition, identifying barriers to compliance with exercise and ways to overcome these barriers is also necessary in order to use therapeutic exercise effectively.

Background: In 2012, the Centers for Medicare and Medicaid Services began to reduce payments to qualifying hospitals for 30-day readmission rates that were higher than predicted for specific diagnoses. The process was broadened to include skilled nursing facilities in 2018. It is reasonable to expect future expansion will include acute inpatient rehabilitation facilities. A pre-intervention quality improvement project from 2017 identified that patients admitted to an acute inpatient rehabilitation facility (IRF) for the primary diagnosis of debility were readmitted within 30 days of discharge at a rate of 38%, which was nearly three times higher than the next most readmitted diagnosis. A literature review identified rapid primary care provider (PCP) outpatient follow up as a worthy intervention to reduce readmissions. Objectives: Over a six-month intervention period, we attempted to achieve a reduction in 30-day readmission rates in the debility population of an IRF by scheduling PCP follow-ups within seven business days after discharge. Results: Of those that received the intervention, 7% were readmitted (P=0.018). Of those who did not receive the intervention, 56% were readmitted. Conclusion: The adoption of PCP follow-up within seven business days of discharge may lower the 30-day readmission rate for patients admitted to IRF with a primary diagnosis of debility.

Background and Purpose: A major challenge for stroke rehabilitation and recovery research is the recruitment and retention of participants. Our prior challenges and successes have influenced our team to rethink our approach and the potential for large-scale stroke recruitment. Summary of Key Points: In this special interest article, we highlight how the adoption and implementation of recruitment strategies such as physician engagement and a streamlined “customer service” approach helped us improve our enrollment and maximize efficiency. Another positive outcome of enrollment was increased representation of those who identify as underrepresented minority or live in rural areas. Recommendations for Clinical Practice: Rethinking our recruitment processes and infrastructure allowed for greater interprofessional interactions, minimal burden for our stroke physician team members, and maximized enrollment into our stroke studies. Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A324).