Rusk Rehabilitation

Helen J. Hislop, Ph.D., James Perrine; The Isokinetic Concept of Exercise, Physical Therapy, Volume 47, Issue 2, 1 February 1967, Pages 114–117, https://do

Sixty higher‐level outpatients with traumatic brain injury (TBI), all at least 1 year post‐injury, were randomly assigned to either conventional group neuropsychological rehabilitation or an innovative group treatment focused on the treatment of problem‐solving deficits. Incorporating strategies for addressing underlying emotional self‐regulation and logical thinking/reasoning deficits, the innovative treatment is unique in its attention to both motivational, attitudinal, and affective processes and problem‐solving skills in persons with TBI. Participants in the innovative group improved in problem solving as assessed using a variety of measures, including (1) executive function, (2) problem‐solving self‐appraisal, (3) self‐appraised emotional self‐regulation and clear thinking, and (4) objective observer ratings of roleplayed scenarios. These improvements were maintained at follow‐up. Baseline performance on timed attention tasks was related to improvement; individuals who processed the most slowly benefited the most. These participants did not show improvements on timed attention tasks, but did improve on problem‐solving measures. Such findings are consistent with successful compensatory strategy use—the person may still have deficits and symptoms, but now has effective strategies for reducing their impact on daily functioning.

Ben-Yishay, Yehuda PhD; Silver, Saralyn M. MA, CRC; Piasetsky, Eugene PhD; Rattok, Jack MAAuthor Information

Conventional imaging is unable to detect damage that accounts for permanent cognitive impairment in patients with mild traumatic brain injury (mTBI). While diffusion tensor imaging (DTI) can help to detect diffuse axonal injury (DAI), it is a limited indicator of tissue complexity. It has also been suggested that the thalamus may play an important role in the development of clinical sequelae in mTBI. The purpose of this study was to determine if diffusional kurtosis imaging (DKI), a novel quantitative magnetic resonance imaging (MRI) technique, can provide early detection of damage in the thalamus and white matter (WM) of mTBI patients, and can help ascertain if thalamic injury is associated with cognitive impairment. Twenty-two mTBI patients and 14 controls underwent MRI and neuropsychological testing. Mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) were measured in the thalamus and several WM regions classically identified with DAI. Compared to controls, patients examined within 1 year after injury exhibited variously altered DTI- and DKI-derived measures in the thalamus and the internal capsule, while in addition to these regions, patients examined more than 1 year after injury also showed similar differences in the splenium of the corpus callosum and the centrum semiovale. Cognitive impairment was correlated with MK in the thalamus and the internal capsule. These findings suggest that combined use of DTI and DKI provides a more sensitive tool for identifying brain injury. In addition, MK in the thalamus might be useful for early prediction of permanent brain damage and cognitive outcome.

PRIMARY OBJECTIVE: To explore whether baseline diffusion tensor imaging (DTI) metrics are predictive of cognitive functioning 6 months post-injury in patients with mild traumatic brain injury (MTBI). RESEARCH DESIGN: Seventeen patients with MTBI and 29 sex- and age-matched healthy controls were studied. METHODS AND PROCEDURES: Participants underwent an MRI protocol including DTI, at an average of 4.0 (range: 1-10) days post-injury. Mean diffusivity (MD) and fractional anisotropy (FA) were measured in the following white matter (WM) regions: centra semiovale, the genu and the splenium of the corpus callosum and the posterior limb of the internal capsule. Participants underwent neuropsychological (NP) testing at baseline and at 6-month follow-up. Least squares regression analysis was used to evaluate the association of MD and FA with each NP test score at baseline and follow-up. MAIN OUTCOMES AND RESULTS: Compared to controls, average MD was significantly higher (p = 0.02) and average FA significantly lower (p = 0.0001) in MTBI patients. At the follow-up, there was a trend toward a significant association between baseline MD and response speed (r = -0.53, p = 0.087) and a positive correlation between baseline FA and Prioritization form B (r = 0.72, p = 0.003). CONCLUSIONS: DTI may provide short-term non-invasive predictive markers of cognitive functioning in patients with MTBI.

ABSTRACT Penicillium expansum, P. digitatum, and P. italicum acidify the ambient environments of apple and citrus fruit during decay development. They use two mechanisms for this: the production of organic acids, mainly citric and gluconic, and NH(4)(+) utilization associated with H(+) efflux. Exposure of P. expansum and P. digitatum hyphae to pH 5.0 increased their citric acid production, compared with the production of organic acids at acidic ambient pH. In decayed fruit, both pathogens produced significant amounts of citric and gluconic acids in the decayed tissue and reduced the host pH by 0.5 to 1.0 units. Ammonium depletion from the growth medium or from the fruit tissue was directly related to ambient pH reduction. Analysis of transcripts encoding the endopolygalacturonase gene, pepg1, from P. expansum accumulated under acidic culture conditions from pH 3.5 to 5.0, suggesting that the acidification process is a pathogenicity enhancing factor of Penicillium spp. This hypothesis was supported by the finding that cultivars with lower pH and citric acid treatments to reduce tissue pH increased P. expansum development, presumably by increasing local pH. However, organic acid treatment could not enhance decay development in naturally acidic apples. Conversely, local alkalinization with NaHCO(3) reduced decay development. The present results further suggest that ambient pH is a regulatory cue for processes linked to pathogenicity of postharvest pathogens, and that specific genes are expressed as a result of the modified host pH created by the pathogens.

Objective: To assess safety and mobility outcomes utilizing the Indego powered exoskeleton in indoor and outdoor walking conditions with individuals previously diagnosed with a spinal cord injury (SCI). Methods: We conducted a multicenter prospective observational cohort study in outpatient clinics associated with 5 rehabilitation hospitals. A convenience sample of nonambulatory individuals with SCI (N = 32) completed an 8-week training protocol consisting of walking training 3 times per week utilizing the Indego powered exoskeleton in indoor and outdoor conditions. Participants were also trained in donning/doffing the exoskeleton during each session. Safety measures such as adverse events (AEs) were monitored and reported. Time and independence with donning/doffing the exoskeleton as well as walking outcomes to include the 10-meter walk test (10MWT), 6-minute walk test (6MWT), Timed Up & Go test (TUG), and 600-meter walk test were evaluated from midpoint to final evaluations. Results: All 32 participants completed the training protocol with limited device-related AEs, which resulted in no interruption in training. The majority of participants in this trial were able to don and doff the Indego independently. Final walking speed ranged from 0.19 to 0.55 m/s. Final average indoor and outdoor walking speeds among all participants were 0.37 m/s (SD = 0.08, 0.09, respectively), after 8 weeks of training. Significant (p < .05) improvements were noted between midpoint and final gait speeds in both indoor and outdoor conditions. Average walking endurance also improved among participants after training. Conclusion: The Indego was shown to be safe for providing upright mobility to 32 individuals with SCIs who were nonambulatory. Improvements in speed and independence were noted with walking in indoor and outdoor conditions as well as with donning/doffing the exoskeleton.

Microglia are known as resident immune cells in the brain. β-amyloid (Aβ) plaques in the brain of Alzheimer’s disease (AD) are surrounded by microglia, but whether and how microglia affect the formation and maintenance of plaques remains controversial. We depleted microglia by injecting diphtheria toxin (DT) in CX 3 CR1 CreER/+ :R26 DTR/+ (CX 3 CR1-iDTR) mice crossed with APPswe/PSEN1dE9 (APP/PS1) mice. Intravital time-lapse imaging was performed to examine changes in the number and size of Congo Red-labeled amyloid plaques over 1–2 weeks. We also examined spine density and shaft diameter of dendrites passing through plaques in a PSAPP mouse model of AD (PS1 M146L line 6.2 × Tg2576) crossed with Thy1 YFP H-line mice. We found that DT administration to CX 3 CR1-iDTR mice efficiently ablated microglia within one week and that microglia repopulated in the second week after DT administration. Microglia depletion didn’t affect the number of amyloid plaques, but led to ~13% increase in the size of Aβ plaques within one week. Moreover, microglia repopulation was associated with the stabilization of plaque size during the second week. In addition, we found dendritic spine loss and shaft atrophy in the distal parts of dendrites passing through plaques. Our results demonstrate the important role of microglia in limiting the growth of Aβ plaques and plaque-associated disruption of neuronal connection.

Cognitive Remediation (CR) is a relatively new treatment technique for alleviating residual cognitive deficits following traumatic brain injury. This is a promising yet still changing technique. The future of CR as a rational and systematic endeavor requires the incorporation of important new ideas that have been emerging in allied fields. For example, the emerging field of instructional psychology has contributed relevant concepts such as scaffolding, metacognition, and generalization. It is furthermore argued that the issues of awareness, self-concept, and self-efficacy are vital to the process of CR intervention, and an integrative (holistic) approach to the remedial endeavor is thus indicated.

The node of Ranvier is a distinct domain of myelinated axons that is highly enriched in sodium channels and is critical for impulse propagation. During development, the channel subtypes expressed at the node undergo a transition from Nav1.2 to Nav1.6. Specialized junctions that form between the paranodal glial membranes and axon flank the nodes and are candidates to regulate their maturation and delineate their boundaries. To investigate these roles, we characterized node development in mice deficient in contactin-associated protein (Caspr), an integral junctional component. Paranodes in these mice lack transverse bands, a hallmark of the mature junction, and exhibit progressive disruption of axon-paranodal loop interactions in the CNS. Caspr mutant mice display significant abnormalities at central nodes; components of the nodes progressively disperse along axons, and many nodes fail to mature properly, persistently expressing Nav1.2 rather than Nav1.6. In contrast, PNS nodes are only modestly longer and, although maturation is delayed, eventually all express Nav1.6. Potassium channels are aberrantly clustered in the paranodes; these clusters are lost over time in the CNS, whereas they persist in the PNS. These findings indicate that interactions of the paranodal loops with the axon promote the transition in sodium channel subtypes at CNS nodes and provide a lateral diffusion barrier that, even in the absence of transverse bands, maintains a high concentration of components at the node and the integrity of voltage-gated channel domains.

Retinal and choroidal neovascularization are a major cause of significant visual impairment, worldwide. Understanding the various factors involved in the accompanying physiopathology is vital for development of novel treatments, and most important, for preserving patient vision. The intraocular use of anti-vascular endothelial growth factor therapeutics has improved management of the retinal and choroidal neovascularization but some patients do not respond, suggesting other vascular mediators may also contribute to ocular angiogenesis. Several recent studies examined possible new targets for future anti-angiogenic therapies. Potential targets of retinal and choroidal neovascularization therapy include members of the platelet-derived growth factor family, vascular endothelial growth factor sub-family, epidermal growth factor family, fibroblast growth factor family, transforming growth factor-β superfamily (TGF-β1, activins, follistatin and bone morphogenetic proteins), angiopoietin-like family, galectins family, integrin superfamily, as well as pigment epithelium derived factor, hepatocyte growth factor, angiopoietins, endothelins, hypoxia-inducible factors, insulin-like growth factors, cytokines, matrix metalloproteinases and their inhibitors and glycosylation proteins. This review highlights current antiangiogenic therapies under development, and discusses future retinal and choroidal pro- and anti-angiogenic targets as wells as the importance of developing of new drugs.

In Brief PURPOSE: To assess the effects of horticultural therapy (HT) on mood state and heart rate (HR) in patients participating in an inpatient cardiac rehabilitation program. METHODS: Cardiac rehabilitation inpatients (n = 107) participated in the study. The HT group consisted of 59 subjects (34 males, 25 females). The control group, which participated in patient education classes (PECs), consisted of 48 subjects (31 males, 17 females). Both HT sessions and PEC are components of the inpatient rehabilitation program. Each group was evaluated before and after a class in their respective modality. Evaluation consisted of the completion of a Profile of Mood States (POMS) inventory, and an HR obtained by pulse oximetry. RESULTS: Changes in the POMS total mood disturbance (TMD) score and HR between preintervention and postintervention were compared between groups. There was no presession difference in either TMD score (16 ± 3.6 and 19.0 ± 3.2, PEC and HT, respectively)or HR (73.5 ± 2.5 and 79 ± 1.8, PEC and HT, respectively). Immediately following the intervention, the HT TMD was significantly reduced (post-TMD = 1.6 ± 3.2, P < .001), while PEC TMD was not significantly changed (TMD = 17.0 ± 28.5). After intervention, HR fell in HT by 4 ± 9.6 bpm (P < .001) but was unchanged in PEC. CONCLUSION: These findings indicate that HT improves mood state, suggesting that it may be a useful tool in reducing stress. Therefore, to the extent that stress contributes to coronary heart disease, these findings support the role of HT as an effective component of cardiac rehabilitation. Following a session of horticultural therapy, inpatient cardiac rehabilitation subjects demonstrated a significant increase in the "Profile of Mood State" score and a reduced heart rate. These data indicate that horticultural therapy can improve mood and reduce stress and support its the role as an effective component of cardiac rehabilitation.

The effect of the serine/glycine-free diet (-SG diet) on colorectal cancer (CRC) remains unclear; meanwhile, programmed death-1 (PD-1) inhibitors are less effective for most CRC patients. Here, we demonstrate that the -SG diet inhibits CRC growth and promotes the accumulation of cytotoxic T cells to enhance antitumor immunity. Additionally, we also identified the lactylation of programmed death-ligand 1 (PD-L1) in tumor cells as a mechanism of immune evasion during cytotoxic T cell-mediated antitumor responses, and blocking the PD-1/PD-L1 signaling pathway is able to rejuvenate the function of CD8+ T cells recruited by the -SG diet, indicating the potential of combining the -SG diet with immunotherapy. We conducted a single-arm, phase I study (ChiCTR2300067929). The primary outcome suggests that the -SG diet is feasible and safe for regulating systemic immunity. Secondary outcomes include patient tolerability and potential antitumor effects. Collectively, our findings highlight the promising therapeutic potential of the -SG diet for treating solid tumors.

OBJECTIVES: This study examined whether pretreatment self-efficacy and pre- to post-treatment changes in self-efficacy predict post-treatment tender point index, disease severity, pain, and physical activity. METHODS: One hundred nine subjects with fibromyalgia were assessed before and after a 6-week training intervention. Measures included tender point index, physician ratings of disease severity, the visual analog scale for pain, the Physical Activities subscale of the Arthritis Impact Measurement Scales, and the Arthritis Self-Efficacy Scale. RESULTS: Pretreatment self-efficacy significantly predicted post-treatment physical activity, with higher self-efficacy associated with better physical activity outcome. Changes in self-efficacy significantly predicted post-treatment tender point index, disease severity, and pain; improvements in self-efficacy were associated with better outcomes on each measure. CONCLUSIONS: Higher levels of self-efficacy are associated with better outcome, and may mediate the effectiveness of rehabilitation-based treatment programs for fibromyalgia.

Large numbers of individuals who have been infected with SARS-CoV-2, the virus responsible for COVID-19, continue to experience a constellation of symptoms long past the time that they have recovered from the acute stages of their illness. Often referred to as "long COVID," these symptoms, which can include fatigue, shortness of breath, palpitations, cognitive dysfunction ("brain fog"), sleep disorders, fevers, gastrointestinal symptoms, anxiety, depression, and others, can persist for months and can range from mild to incapacitating. Although still being defined, these effects can be collectively referred to as postacute sequelae of SARS-CoV-2 infection (PASC).1 The magnitude of this problem is not yet known, but given the millions of individuals worldwide who have had, or will have, COVID-19, the societal impacts are likely to be profound and long lasting.2-5 It is widely acknowledged that systematic study is needed to develop an evidence-based approach for caring for patients with PASC. At present, there is a dearth of rigorous scientific evidence regarding effective assessment and treatment of PASC that prevents the creation of evidence-based clinical guidelines. However, the U.S. health system is currently seeing an increase in the number of patients presenting with PASC, and there is an urgent need for clinical guidance in treating these patients. The goal of this, and future statements, is to provide practical guidance to clinicians in the assessment and treatment of patients presenting with PASC. This Consensus Guidance Statement on fatigue is the first of a series focused on the most prominent PASC symptoms. The American Academy of Physical Medicine and Rehabilitation (AAPM&R) Multi-Disciplinary PASC Collaborative ("PASC Collaborative") was created, in part, to develop expert recommendations and guidance from established PASC centers with extensive experience in managing patients with PASC. The PASC Collaborative is following an iterative, development approach to achieve consensus on assessment and treatment recommendations for a series of Consensus Guidance Statements focused on the most prominent PASC symptoms. These statements were developed by a diverse team of experts, with input from patient representatives with a history of PASC, and integrate current experience and expertise with available evidence to provide tools to clinicians treating patients. There is an intentional focus on health equity as disparities in care and outcomes are critically important to address. Beyond patient care, the hope is that a broadened understanding of current patient care practices will help identify areas of future research. A full description of the methodology is also published in this issue.6 We acknowledge that the definition of PASC is evolving, and there are various factors that contribute to diagnosis. The PASC Collaborative sought input from patient representatives with a history of PASC and patient-led research initiatives to inform recommendations. For example, previous literature has suggested that PASC be defined as the continuation of symptoms beyond 3 or 4 weeks from the onset of acute infection.7 Other definitions of PASC include symptoms lasting longer than 3 months.8 Based on feedback of patient representatives that earlier evaluation, diagnosis, and management can improve access to beneficial interventions, for the purpose of this Consensus Guidance Statement, we recommend expanded assessment if symptoms are not improving 1 month after acute symptom onset. These Consensus Guidance Statements are intended to reflect current practice in patient assessment, testing, and treatments. They should not preclude clinical judgment and must be applied in the context of the specific patient, with adjustments for patient preferences, comorbidities, and other factors. Fatigue is a feeling of weariness, tiredness, or lack of energy. It can be physical, cognitive, or emotional, mild to severe, intermittent to persistent, and affect a person's energy, motivation, and concentration. Fatigue can negatively affect an individual's sense of well-being and quality of life and generally lacks objective markers. Fatigue during an acute viral illness is common; however individuals with PASC are often presenting with long lasting and debilitating fatigue after recovery from their acute viral illness.5 Further discussion on the definition and impact of fatigue can be found in the Institute of Medicine's 2015 report on chronic fatigue syndrome (Chapter 4).9 Individuals are seeking care from their clinicians for fatigue following COVID-19. Among nonhospitalized adults with a history of COVID-19 and enrolled in an integrated health system in Georgia, approximately two thirds had at least one outpatient medical encounter between 1 and 6 months after their diagnosis.10 Approximately two thirds of these patients received a new primary diagnosis, with fatigue being one of the most common based on International Classification of Diseases, Tenth Revision codes.10 In another study describing the long-term health consequences for individuals hospitalized with COVID-19, the most common symptoms were fatigue or muscle weakness (63%) and sleep difficulties (26%).11 Anxiety and depression were also common, reported by 23% of patients. Greater than 20% of patients had performances on the 6-minute walk test below the lower-limit of normal.11 The Patient Led Research Collaborative, a self-organized group of individuals with PASC who conduct patient-led research around the long COVID experience, conducted a study of self-reported symptoms of individuals enrolled in support groups for PASC.12 A majority (96%) of individuals who completed the survey self-identified as having PASC reported symptoms beyond 90 days. The most common early symptoms were fatigue, cough, shortness of breath, headaches, muscle aches, chest tightness, and sore throat. The most frequent symptoms reported after 6 months were fatigue, postexertional malaise, and cognitive dysfunction. Greater than 85% of individuals experienced relapses of their symptoms, with exercise, physical or mental activity, and stress being the main triggers. In addition, 42.5% reported requiring a reduced work schedule compared to pre-illness and 22.3% were not working at the time of survey because of their health conditions.12 Fatigue is among the most common persistent symptoms following COVID-19 in both individuals that have been hospitalized (p = 24.6%, confidence interval [CI] 20.11-29.72) and those that have not been hospitalized (p = 37.1%, CI 26.54-49.06).13 Although fatigue likely improves over time, it can persist beyond 6 months.2, 5, 7 As noted in the PASC Collaborative methodology,6 the recommendations that follow are based on expert consensus. Specific guidance recommendations that have been approved by consensus will be noted in the tables and recommendations will be followed by additional discussion (Table 1). The following basic lab workup should be considered in new patients or those without lab workup in the 3 months before visit including complete blood count with differential, chemistries including renal and hepatic function tests, thyroid stimulating hormone, c-reactive protein or erythrocyte sedimentation rate, and creatinine kinase. Other laboratory tests may be considered based on the results of these tests or if there is specific concern for comorbid conditions as outlined in Table 2. It is not unusual for individuals to have persistent and fluctuating fatigue during their recovery from acute COVID-19 disease, particularly in the first 1 to 2 months. This fatigue can involve both physical and cognitive components. This document focuses on physical fatigue and a subsequent Consensus Guidance Statement will focus on cognitive issues. Additional assessment and management of post-COVID fatigue should be considered if a patient is not continuing to improve after the initial 4 weeks beyond symptom onset, if symptoms are severe, or if the patient is experiencing negative impacts on quality of life. In cases of mild fatigue that is not functionally limiting, it can be monitored for improvement as part of the natural recovery from COVID-19. Symptoms: Chest pains, palpitations, sweating, nausea, fatigue, leg swelling, shortness of breath - at rest/on exertion/lying flat/waking up at night, dizziness on standing, feeling faint/fainting Signs: Pallor, tachypnea, tachycardia, diaphoresis, pulmonary rales, lower extremity edema, hypotensive sitting/standing - orthostatic hypotension, presyncopal/syncopal, poor activity tolerance/endurance Symptoms: Shortness of breath – at rest/on exertion, cough, wheeze, fatigue, poor activity tolerance Signs: Tachypnea, tachycardia, cough, hypoxia/low pulse oximeter, pulmonary wheezes/rhonchi/"Velcro" rales, poor activity tolerance/endurance Symptoms: Palpitations, fatigue, dizziness, weight gain/loss, sense of chills/fever, irregular menstrual cycle, poor diabetic control, excessive thirst/urination Signs: Tachycardia, poor activity tolerance, weight gain/loss, low/elevated temperature, elevated finger-stick/urine glucose, ketotic (fruity) breath Symptoms: Rash, joint/muscle pain and stiffness, fever, mouth sores/ulcers, cold/pale/blue/red fingers, sharp chest pain, numbness/tingling/burning in fingers/toes, blurry/decreased vision Signs: Rash, arthropathy – swelling/warmth/decreased ROM, myopathy – tenderness/weakness, fever, Raynaud's phenomena, pleuritic pain on deep breathing, altered sensation, decreased visual acuity Symptoms: Anxiety, irritability, chest tightness, low frustration tolerance, depression, fatigue, mood swings, palpitations, change in memory/recall Signs: flat affect/low mood, emotional lability that is, crying/laughing inappropriately, limited impulse control, psychosis Symptoms: Poor sleep - hard to fall asleep/wakes frequently/wakes early, nonrestorative/refreshing sleep - "tired" on waking, snoring, frequent urination at night, bad dreams/nightmares, falls asleep during the day, morning headaches Signs: Snoring, restless legs, observed apneic episodes, hypertension, arrhythmias, narcolepsy, congestive heart failure, impaired neurocognition, poorly controlled mood disorder In patients presenting with fatigue, it is important to consider the evaluation of fatigue and diminished activity tolerance as related but distinct conditions. As these two symptoms may intersect, the differential etiologies of fatigue should be considered in conjunction with a separate differential for lowered activity tolerance. When evaluating the etiology of fatigue, the following should be considered as central or contributing factors: sleep disorders, endocrine disorders, nutritional disorders, chronic infectious disorders, autoimmune/inflammatory disorders, cardiac disorders, respiratory disorders, psychiatric disorders, malignancies, drug reactions, and adult-onset metabolic disorders (See Table 2). Diminished activity tolerance is the inability or reduced ability to perform physical activity at the normally expected frequency, intensity level, or duration for people of that age, size, gender, and muscle mass. Individuals may experience unusually severe postexercise pain, fatigue, nausea, vomiting, or other negative effects. When evaluating the etiology of diminished activity tolerance, the following disorders or system dysfunctions should be considered as central or contributing factors: pulmonary, cardiovascular, and/or neuromuscular systems. The presentation of fatigue in individuals with PASC may appear similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS is a complex syndrome that often occurs following viral illness. A 2015 Institute of Medicine report on ME/CFS created specific diagnostic criteria as outlined in Table 3.9 The specific pathophysiology behind ME/CFS has yet to be discovered. The Centers for Disease Control and Prevention has developed treatment recommendations for ME/CFS that have been used to help develop the current treatment recommendations for PASC-related fatigue.18 However, more data are needed to understand if and in which individuals PASC-related fatigue is a manifestation of ME/CFS and in which individuals PASC-related fatigue represents a distinct process. Finally, it is important to note that the etiology of fatigue may be multifactorial in individuals with PASC and there may not be one unifying cause of PASC-related fatigue. As with any treatment plan, clinicians treating patients with PASC-related fatigue are encouraged to discuss the unknowns of PASC treatments, as well as the pros and cons of any therapeutic approach. It may also be helpful to discuss that despite the unknown time course of post-COVID symptoms, it is the experience of established PASC centers that fatigue tends to slowly improve over time. As treatment is initiated, patients should be followed for their response to treatment and impact of treatment on level of function. As with the PASC patient assessment, therapeutic options vary and should be customized based on history, comorbidities, and treatment response to date. It is important to note that if specific etiologies of fatigue are identified (see Table 2), they should be addressed as part of the treatment plan (Table 4, Recommendation #4). The current recommendations are based on the experience of the PASC Collaborative clinics and have helped to alleviate symptoms in cases in which specific contributing etiologies have not been identified or, despite addressing, symptoms persist. Additional details on techniques used by clinicians are summarized next. As treatment efficacy of therapeutic options emerges, these recommendations will be reviewed and revised on a periodic basis. An individually titrated, symptom-guided program of return to activity is recommended for patients presenting with fatigue. The goal of a rehabilitation program is to restore patients to previous levels of activity and improve quality of life. Until those goals have been achieved, the rehabilitation program should not focus on high intensity aerobic exercises or heavy weightlifting to build strength and endurance. If the rehabilitation program is advanced too quickly or is too intense, it may worsen symptoms and lead to postexertional malaise (PEM), a diagnostic criterion of ME/CFS.9 The titrated approach encourages patients to perform activities at a submaximal level to avoid exacerbation of fatigue and PEM. Activity should be adjusted in response to symptoms that develop during or after activity. Before starting this program, it is crucial for the clinician to educate the patient on recognizing perceived exertion and the use of other metrics such as heart rate or exertion scales (such as the Borg Rating of Perceived Exertion Scale) that can guide the individual toward submaximal exertional activities. Smartphones and activity trackers may also be effective methods to monitor duration and intensity of activity.19 We also recommend educating patients on energy conservation strategies to aid in recovery. One framework is the "Four Ps": Pacing, Prioritizing, Positioning, and Planning.23 Pacing is the concept of avoiding the push and crash cycle that is common in post-COVID recovery. Ways to achieve optimal pacing include keeping activity to reasonable, and often shorter, durations (or alternatively, giving more time to complete activities to avoid rushing) and including scheduled rest breaks with activities. Patients should pay attention to their body and avoid or moderate activities that lead to the need for prolonged recovery periods. Prioritizing encourages a patient to focus and decide on which activities need to get done on specific days and which activities can be postponed (or are unnecessary to do at all) to avoid overexertion and crashing. Positioning is modifying activities to make them easier to perform. For example, it may be possible for the patient to sit during an activity or have a workspace at a comfortable height with all necessary equipment within easy reach. Another example would be the use of a shower chair or bench rather than standing for showering. Planning encourages the patient to plan the day or week to avoid overexertion and to recognize energy windows. Energy windows are periods during the day when patients have more energy to complete tasks. Patients are often aware of their optimal energy window, which may vary throughout the week. Asking patients to keep a diary of good days, bad days, and energy windows is helpful for optimizing timing of therapy and activities. As such, it is important for patients to plan rest breaks. Other elements of planning include determining steps for completion of tasks and preparing for tasks ahead of time. Daily routines may also be helpful. Finally, planning may consist of return to previous activities. In to work may be of concern to individuals with PASC-related fatigue. We recommend patients work with their and to a specific plan for return to activities. Patients should be on to if are needed or in a limited as long as it not worsen symptoms or lead to PEM. of possible include working a limited number of working from work activities of medical equipment aid to increase additional breaks throughout the day, and the work the patient to These activities and return to work should be advanced as the patient When to rehabilitation can be helpful in the return activities and with At this time there are scientific data to support the of one specific for the management of PASC-related fatigue. nutritional recommendations should reflect the individual health a including and and limited of of and the of is also COVID-19 is with a response and PASC has been to be related to of this There has been in the between and chronic related fatigue. and and specific high in and have been suggested to have and research is syndrome with has also been suggested to a in PASC It is that individuals may not in to be a of reduced activity of the which breaks to an of in the body and include or low blood irregular and other conditions and are similar to those reported by individuals with PASC. Although there are current scientific the of a low of limited and other in PASC, have suggested improvement in It is that following have also been recommendations have been for individuals with and similar recommendations may be beneficial for PASC-related fatigue. These include but often - 3 to 4 with a low complex in to support energy and a including and There is currently not evidence to support the use of specific nutritional to help including or Fatigue related to dysfunction in individuals with PASC, orthostatic syndrome can be addressed with and and frequent are and with high and complex may help blood and symptoms. Fatigue to muscle in the context of weight is reported in PASC and can be with and protein There is a in the use of and to improve PASC-related fatigue. clinics do not use use when management has been and comorbid conditions have been patients often in and for and that may be helpful of these is needed for patient that have been suggested to alleviate chronic fatigue in other of chronic illness and include 3 and These have been suggested to support the help with and improve fatigue. It is important to note that there was consensus on the use of these and they should be considered on a recognizing the limited scientific there to be of the of the of lack of and possible effects. There are that are used for fatigue in other individuals with and that PASC clinics for PASC-related and have been used by PASC clinics for the treatment of Other that have been suggested in the treatment of ME/CFS include and are limited and evidence for these not or is of these have from the and for use in other with fatigue, but there are currently clinical their use in the PASC It is important to note that of these were recommended consensus and should be considered on a basis. There also can be effects and with of these that need to be considered to The use of has also been reported by patient to improve fatigue. Although there has not been evidence to support use in PASC-related fatigue, there is evidence that use in In the context of PASC, it is important to focus on health health and of health with the following clinicians are encouraged to the and in of SARS-CoV-2 Fatigue for guidance the of health equity with the evaluation and treatment of individuals with PASC. The health equity as of and or in health among groups defined or defined a health as of health that is with and/or and that health disparities affect groups of people who have experienced to health based on their or mental cognitive, or physical or or other to or There has been an of are contributing to health and are the factors that health and involve the in which people are and and the of and the conditions of For example, the and can include and an individual's level of and access to and other factors. care in individuals with PASC, we need to are available for those to physical and mental of include access to and/or in a the individual or for with a and and and care, and medical and mental health care that are all to the of those from When and that support health are poor health outcomes can be health disparities can be and the of the between and health in acute COVID-19 is well the of with PASC is As more data there will likely be evidence of health disparities in care and treatment options because of differential of health of testing, limited clinical and lack of and in of fatigue may be reported more in adults and in COVID-19 symptoms may be more severe in and the is a cause of fatigue because of a of and factors. In addition, people who identify with or groups may have a level of chronic fatigue that should be considered in the assessment and treatment and groups may also be at a of chronic that may increase levels of chronic fatigue. For example, individuals with lower and adults are at of which the of body and are also related to more severe consequences of Finally, those with lower may not be to access treatments. For example, they may not have the ability to get time from work to pacing recommendations or to access therapy encounter a range of to health care to and/or factors such as gender, and The and between the health care and must be by in are that are support or focused as the of that are and and consider the of and individual have a in health health and improving a deep understanding of of diverse and that with the and the of that support the health of all individuals in the PASC may have or health In addition, debilitating and symptoms with ability to work and to for and their The in have in their and to pay and health in care we recommend assessment and treatment that including and as they can be helpful for and the on individuals with limited energy from PASC or who have other the of expanded during the and have been noted to be in access for various such as and the In addition, individuals should be to when including for other and on and for work or and to PASC support PASC-related fatigue individuals and Individuals with PASC-related fatigue can experience severe and The pathophysiology fatigue after COVID-19 still research to understand this constellation of symptoms, the cause of fatigue is likely multifactorial and may be specific to the The goal of this PASC Collaborative Consensus Guidance Statement is to a and systematic approach to the evaluation and treatment of patients presenting with PASC. The recommendations a consensus of of centers focused on the treatment of individuals with PASC. The recommendations are based on the most current available from evidence in similar and the clinical experience of treating of patients with PASC-related fatigue. The of this Multi-Disciplinary Consensus Guidance Statement was developed in with the PASC Multi-Disciplinary Collaborative, of PASC who to the development of the consensus statements individuals working in their or from their expertise in the assessment and treatment of PASC in their expert The and by Collaborative are their and do not reflect the of any We would also to acknowledge and a to and for their in the of the PASC Collaborative and the of this The work of the is by without received an for on the care of PASC Patients from is a by for and received for a presentation on of COVID-19 at Medicine equity and in sequelae of SARS-CoV-2 infection Fatigue individuals who identify as and and/or who are or in and other who have in and and other Before the COVID-19 people with were reduced access to physical and emotional to and decreased access to health the was impaired by necessary health such as and a that not As a individuals with PASC-related fatigue for and research as a chronic The has established to the of should with the with a that access and prevents in areas of life care and The Rehabilitation of access for individuals with the of and for that When clinicians should for patients with PASC-related fatigue to a health medical equipment or for and or an emotional support for should include options for those who are and Although has access for who are clinicians must consider options such as for those who do not have access to access or the to who have from another in to in the who identify with a in is or Physical and factors that fatigue of blood for severe in or during a can affect those to various For individuals with PASC-related fatigue, practices such as may increase symptoms. also physical affect and/or ability to in rehabilitation Although nutritional natural and practices may have for or to fatigue, clinical regarding their use for PASC-related fatigue should be considered in conjunction with an experienced and if should be used in a with evidence-based This is in the to provide additional for clinicians who are treating patients for PASC-related fatigue. This is not intended to be a but rather to provide clinical as they to health health and of The literature that all groups and access to care these may or may not be for a specific individual with those who identify with more than one or often levels of and

OBJECTIVE: Determine incidence of posttraumatic seizure (PTS) following traumatic brain injury (TBI) among individuals with moderate-to-severe TBI requiring rehabilitation and surviving at least 5 years. METHODS: Using the prospective TBI Model Systems National Database, we calculated PTS incidence during acute hospitalization, and at years 1, 2, and 5 postinjury in a continuously followed cohort enrolled from 1989 to 2000 (n = 795). Incidence rates were stratified by risk factors, and adjusted relative risk (RR) was calculated. Late PTS associations with immediate (<24 h), early (24 h-7 day), or late seizures (>7 day) versus no seizure prior to discharge from acute hospitalization was also examined. RESULTS: PTS incidence during acute hospitalization was highest immediately (<24 h) post-TBI (8.9%). New onset PTS incidence was greatest between discharge from inpatient rehabilitation and year 1 (9.2%). Late PTS cumulative incidence from injury to year 1 was 11.9%, and reached 20.5% by year 5. Immediate/early PTS RR (2.04) was increased for those undergoing surgical evacuation procedures. Late PTS RR was significantly greater for individuals who self-identified as a race other than black/white (year 1 RR = 2.22), and for black individuals (year 5 RR = 3.02) versus white individuals. Late PTS was greater for individuals with subarachnoid hemorrhage (year 1 RR = 2.06) and individuals age 23-32 (year 5 RR = 2.43) and 33-44 (year 5 RR = 3.02). Late PTS RR years 1 and 5 was significantly higher for those undergoing surgical evacuation procedures (RR: 3.05 and 2.72, respectively). SIGNIFICANCE: In this prospective, longitudinal, observational study, PTS incidence was similar to that in studies published previously. Individuals with immediate/late seizures during acute hospitalization have increased late PTS risk. Race, intracranial pathologies, and neurosurgical procedures also influenced PTS RR. Further studies are needed to examine the impact of seizure prophylaxis in high-risk subgroups and to delineate contributors to race/age associations on long-term seizure outcomes.

PURPOSE: The purpose of this study was to examine the effects of self-efficacy on self-report pain and physical activities among subjects with fibromyalgia (FM). In addition, descriptive statistics of the Arthritis Impact Measurement Scale (AIMS), a measure developed for use with arthritis patients, were reported. METHODS: Seventy-nine subjects with FM, as classified by the American College of Rheumatology (ACR) criteria, completed the Visual Analogue Scale for Pain, the AIMS, and the Arthritis Self-Efficacy Scale. A myalgic score was obtained during a tender point evaluation. Hierarchical multiple regression analyses were used to assess the effect of self-efficacy on self-report pain and physical activities measures after controlling for demographic variables (age, education, and symptom duration), disease severity (myalgic scores), and psychological distress (negative affect from the AIMS). RESULTS: Higher self-efficacy was associated with less pain and less impairment on the physical activities measure after controlling for demographic and disease severity measures. CONCLUSIONS: This study underscores the unique importance of self-efficacy in understanding pain and physical activities impairment.

Myelin sheaths include an extraordinary structure, the "paranodal axoglial junction" (PNJ), which attaches the sheath to the axon at each end of each myelin segment. Its size is enormous and its structure unique. Here we review past and current studies showing that this junction can serve multiple functions in maintaining reliable saltatory conduction. The present evidence points to three functions in particular. 1) It seals the myelin sheath to the axon to prevent major shunting of nodal action currents beneath the myelin sheath while still leaving a narrow channel interconnecting the internodal periaxonal space with the perinodal space. This pathway represents a potential route through which juxtaparanodal and internodal channels can influence nodal activity and through which nutrients, such as glucose, and other metabolites can diffuse to and from the internodal periaxonal space. 2) It serves as a mechanism for maintaining discrete, differentiated axolemmal domains at and around the node of Ranvier by acting as a barrier to the lateral movement of ion channel complexes within the axolemma, thus concentrating voltage-gated sodium channels at the node and segregating fast voltage-gated potassium channels to the juxtaparanode under the myelin sheath. 3) It attaches the myelin sheath to the axon on either side of the node and can thus maintain nodal dimensions in the face of mechanical stresses associated with stretch or other local factors that might cause disjunction. It is therefore the likely means for maintaining constancy of nodal surface area and electrical parameters essential for consistency in conduction.

The NIH Toolbox (NIHTB) Pattern Comparison Processing Speed Test was developed to assess processing speed within the NIHTB for the Assessment of Neurological Behavior and Function Cognition Battery (NIHTB-CB). This study highlights validation data collected in adults ages 18-85 on this measure and reports descriptive data, test-retest reliability, construct validity, and preliminary work creating a composite index of processing speed. Results indicated good test-retest reliability. There was also evidence for both convergent and discriminant validity; the Pattern Comparison Processing Speed Test demonstrated moderate significant correlations with other processing speed tests (i.e., WAIS-IV Coding, Symbol Search and Processing Speed Index), small significant correlations with measures of working memory (i.e., WAIS-IV Letter-Number Sequencing and PASAT), and non-significant correlations with a test of vocabulary comprehension (i.e., PPVT-IV). Finally, analyses comparing and combining scores on the NIHTB Pattern Comparison Processing Speed Test with other measures of simple reaction time from the NIHTB-CB indicated that a Processing Speed Composite score performed better than any test examined in isolation. The NIHTB Pattern Comparison Processing Speed Test exhibits several strengths: it is appropriate for use across the lifespan (ages, 3-85 years), it is short and easy to administer, and it has high construct validity.

With the ubiquity of mobile devices, the availability of mobile health (mHealth) applications for cardiovascular disease (CVD) has markedly increased in recent years. Older adults represent a population with a high CVD burden and therefore have the potential to benefit considerably from interventions that utilize mHealth. Traditional facility-based cardiac rehabilitation represents one intervention that is currently underutilized for CVD patients and, because of the unique barriers that older adults face, represents an attractive target for mHealth interventions. Despite potential barriers to mHealth adoption in older populations, there is also evidence that older patients may be willing to adopt these technologies. In this review, we highlight the potential for mHealth uptake for older adults with CVD, with a particular focus on mHealth cardiac rehabilitation (mHealth-CR) and evidence being generated in this field.