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Introduction: Innovative motor therapies have attempted to reduce upper extremity impairment after stroke but have not made substantial improvement as over 50% of people post-stroke continue to have sensorimotor deficits affecting their self-care and participation in daily activities. Intervention studies have focused on the role of increased dosing, however recent studies have indicated that timing of rehabilitation interventions may be as important as dosing and importantly, that dosing and timing interact in mediating effectiveness. This study is designed to empirically test dosing and timing.Methods and Analysis: In this single-blinded, interventional study, subjects will be stratified on two dimensions, impairment level (Fugl-Meyer Upper Extremity Assessment (FM) and presence or absence of Motor Evoked Potentials (MEPs) as follows; (1) Severe, FM score 10–19, MEP+, (2) Severe, FM score 10–19, MEP–, (3) Moderate, FM score 20–49, MEP+, (4) Moderate, FM score 20–49, MEP–. Subjects not eligible for TMS will be assigned to either group 2 (if severe) or group 3 (if moderate). Stratified block randomization will then be used to achieve a balanced assignment. Early Robotic/VR Therapy (EVR) experimental group will receive in-patient usual care therapy plus an extra 10 h of intensive upper extremity therapy focusing on the hand using robotically facilitated rehabilitation interventions presented in virtual environments and initiated 5–30 days post-stroke. Delayed Robotic/VR Therapy (DVR) experimental group will receive the same intervention but initiated 30–60 days post-stroke. Dose-matched usual care group (DMUC) will receive an extra 10 h of usual care initiated 5–30 days post-stroke. Usual Care Group (UC) will receive the usual amount of physical/occupational therapy.Outcomes: There are clinical, neurophysiological, and kinematic/kinetic measures, plus measures of daily arm use and quality of life. Primary outcome is the Action Research Arm Test (ARAT) measured at 4 months post-stroke.Discussion: Outcome measures will be assessed to determine whether there is an early time period in which rehabilitation will be most effective, and whether there is a difference in the recapture of premorbid patterns of movement vs. the development of an efficient, but compensatory movement strategy.Ethical Considerations: The IRBs of New Jersey Institute of Technology, Rutgers University, Northeastern University, and Kessler Foundation reviewed and approved all study protocols. Study was registered in https://ClinicalTrials.gov (NCT03569059) prior to recruitment. Dissemination will include submission to peer-reviewed journals and professional presentations.

Purpose: Rett syndrome (RTT) is a rare neurodevelopmental disorder that mainly affects girls and women. Trofinetide is approved for the treatment of RTT in adults and children aged ≥2 years. To gain insight into experiences with RTT and effects of trofinetide treatment at different stages of RTT, interviews with caregivers of individuals with RTT were conducted upon their exit from the open-label trofinetide trials., Methods: Interviews were conducted with caregivers of participants in the LILAC/LILAC-2 open-label extension trials of the phase 3 LAVENDER trial in participants aged 5 to 20 years, and in DAFFODIL, an open-label trial in participants aged 2 to 4 years. Caregivers were asked about the RTT effects, experiences with trofinetide, meaningfulness of treatment effects, and satisfaction. Qualitative thematic analysis was performed., Findings: Caregivers of 33 participants from the open-label trials were interviewed, including 26 from LILAC/LILAC-2 (mean age, 12.3 years) and 7 from DAFFODIL (mean age, 4.5 years). The most commonly reported effects of RTT in LILAC/LILAC-2 were no verbal communication (24/26 [92.3%]), unable to use hands (15/26 [57.7%]), repetitive hand movements (15/26 [57.7%]), unable to walk (15/26 [57.7%]), and seizures (14/26 [53.8%]). In DAFFODIL, the most commonly reported effects of RTT were no verbal communication (7/7 [100%]), impaired balance (4/7 [57.1%]), unable to use hands (3/7 [42.9%]), repetitive hand movements (3/7 [42.9%]), mood disturbance (3/7 [42.9%]), constipation (3/7 [42.9%]), and limited ability to use hands (3/7 [42.9%]). Caregivers most commonly reported improvements in hand use (11/26 [42.3%]), engagement with others (11/26 [42.3%]), eye gaze (8/26 [30.8%]), use of the Tobii eye tracking device (7/26 [26.9%]), and attention/focus/concentration (7/26 [26.9%]) in LILAC/LILAC-2. In DAFFODIL, caregivers reported improvements in new words (5/7 [71.4%]), hand use (4/7 [57.1%]), and eye contact (4/7 [57.1%]). Nearly all (31/32) caregivers were very satisfied or satisfied with trofinetide., Implications: Caregivers of participants in open-label trofinetide trials reported improvements in RTT with meaningful impact in areas of motor function, communication, and engagement., Competing Interests: Declaration of competing interest Amy M. Barrett, Oyebimpe Olayinka-Amao, and Susan Martin are employees of RTI Health Solutions, which was contracted by Acadia Pharmaceuticals Inc. to conduct the interviews and perform the analyses. Dilesh Doshi and James M. Youakim are employees of Acadia Pharmaceuticals Inc. and hold stock in Acadia Pharmaceuticals Inc. Kathie M. Bishop is a former employee of Acadia Pharmaceuticals Inc., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Claudin 18.2 (CLDN18.2) is a surface membrane protein that is crucial for maintaining tight junctions in gastric mucosal cells and is highly expressed in gastric, esophageal, and pancreatic cancers. Thus, CLDN18.2 is suited for exploration as a clinical target for chimeric antigen receptor T-cell (CAR-T) therapy in these indications. Although CAR-T therapies show promise, a challenge faced in their development for solid tumors is the immunosuppressive tumor microenvironment, which is often characterized by the presence of immune and stromal cells secreting high levels of TGFβ. The addition of TGFβ armoring can potentially expand CAR-T activity in solid tumors. We report on the preclinical development of a CLDN18.2-targeting CAR-T therapy showing effectiveness in patient models with CLDN18.2-positive gastric, esophageal, and pancreatic tumors., Experimental Design: The lead lentivirus product contains a unique single-chain variable fragment; CD28 and CD3z costimulatory and signaling domains; and dominant-negative TGF-β receptor armoring, enhancing targeting and safety and counteracting suppression. We developed a shortened cell manufacturing process to enhance the potency of the final product AZD6422., Results: AZD6422 exhibited significant antitumor activity and tolerability in multiple patient-derived tumor xenograft models with various CLDN18.2 and TGF-β levels, as determined by IHC. The efficacy of armored CAR-T cells in tumor models with elevated TGFβ was increased in vitro and in vivo. In vitro restimulation assays established greater persistence and cytolytic function of AZD6422 compared with a traditionally manufactured CAR-T., Conclusions: AZD6422 was safe and efficacious in patient-derived, CLDN18.2-positive murine models of gastrointestinal cancers. Our data support further clinical development of AZD6422 for patients with these cancers., (©2024 The Authors; Published by the American Association for Cancer Research.)

Introduction: There is a lack of cognitive tools to predict disease progression in mild cognitive impairment (MCI) and Alzheimer's disease (AD)., Methods: We assessed patients with MCI, AD, and cognitively healthy controls (cHC) using NIH toolbox assessments for attention/concentration and executive functioning and overall cognitive decline by the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog)., Results: Among 183 participants over a median follow-up of 540 days, both between- and within-subjects variance in NIH toolbox and ADAS-Cog assessments increased from cHC to MCI to AD patients. Among patients with AD, pattern comparison processing speed (PCPS) and dimensional change card sort tests (DCCS) declined at 3 and 6 months prior to global cognitive decline (p=0.008 & 0.0012). A 5-point decrease in either PCPS or DCCS increased risk of global cognitive decline (HR 1.32 (1.08-1.60) and 1.62 (1.16-2.26))., Discussion: Testing for cognitive domains of attention/concentration and executive functioning may predict subsequent global cognitive, and functional decline.

Background: Trofinetide was approved for the treatment of Rett syndrome (RTT) in patients aged ≥2 years based on the results of the 12-week, randomized, phase 3 LAVENDER study. In LILAC, a 40-week, open-label extension study of LAVENDER, trofinetide continued to improve the symptoms of RTT, with a similar safety profile as LAVENDER. Here, we report long-term safety and efficacy results of LILAC-2, a 32-month, open-label extension study., Methods: Females aged 5-22 years who completed LILAC were eligible to enter LILAC-2. Safety and tolerability were assessed with the incidence of adverse events (AEs). Efficacy was assessed with Rett Syndrome Behaviour Questionnaire (RSBQ) and Clinical Global Impression-Improvement (CGI-I) scores. Caregiver interviews explored the patient's experience with RTT and the efficacy of trofinetide during study participation., Findings: In total, 77 participants were enrolled in LILAC-2. The most common AEs were diarrhea (53.2%), COVID-19 (27.3%), and vomiting (19.5%). The mean (standard error [SE]) change in RSBQ score from LAVENDER baseline to week 104 of LILAC-2 was -11.8 (2.45). The mean (SE) CGI-I score from LILAC baseline to week 12 of LILAC-2 was 3.1 (0.10). Most caregivers (96%; n = 24/25) were satisfied or very satisfied with the benefits of trofinetide., Conclusions: Long-term treatment with trofinetide continued to improve RTT symptoms, without new safety concerns. Caregivers reported satisfaction with trofinetide related to improvements that were meaningful for their child and themselves., Funding: The study was supported by Acadia Pharmaceuticals (San Diego, CA, USA). This study was registered at ClinicalTrials.gov: NCT04776746., Competing Interests: Declaration of interests A.K.P. is co-editor of Translational Science of Rare Diseases, received research funding from the National Institutes of Health, and is a consultant for Acadia Pharmaceuticals, Anavex Life Sciences, AveXis, and GW Pharmaceuticals, as well as advisor to the International Rett Syndrome Foundation. J.L.N. has received research funding from the International Rett Syndrome Foundation, the National Institutes of Health, and the Rett Syndrome Research Trust; has received personal consultancy fees from Acadia Pharmaceuticals, Analysis Group, AveXis, F. Hoffmann-La Roche, GW Pharmaceuticals, Myrtelle, Neurogene, Newron Pharmaceuticals, Signant Health, and Taysha Gene Therapies; has received personal consultancy fees for the preparation of CME activities for Medscape and the Peer Review Institute; serves on the scientific advisory board of Alcyone Therapeutics; is a scientific co-founder of LizarBio Therapeutics; and was a member of a data safety monitoring board for clinical trials conducted by Ovid Therapeutics. T.A.B. has received research funding from the GRIN2B Foundation, the International Foundation for CDKL5 Research, the Loulou Foundation, the National Institutes of Health, and the Simons Foundation; has received consultancy fees from Alcyone Therapeutics, GRIN Therapeutics, the International Rett Syndrome Foundation, Marinus Pharmaceuticals, Neurogene, Takeda, Taysha Gene Therapies, Ultragenyx, and Zogenix/UCB Pharma; and has participated in clinical trials with Acadia Pharmaceuticals, GW Pharmaceuticals, Marinus Pharmaceuticals, Ovid Therapeutics, and Rett Syndrome Research Trust; all remuneration has been made to his department. E.M.B.-K. has received funding from Acadia Pharmaceuticals, Alcobra, AMO Pharma, Asuragen, AveXis, Biogen, BioMarin, Cydan Development, EryDel, ESCAPE Bio, Fulcrum Therapeutics, GeneTx, GW Pharmaceuticals, Healx, Ionis Pharmaceuticals, Jaguar Health, Lumos Pharma, Marinus Pharmaceuticals, Neuren Pharmaceuticals, Neurogene, Neurotrope, Novartis, Orphazyme, Ovid Therapeutics, REGENXBIO, Retrophin, Roche, Seaside Therapeutics, Taysha Gene Therapies, Tetra Therapeutics, Ultragenyx, Vtesse/Sucampo/Mallinckrodt Pharmaceuticals, Yamo Pharmaceuticals, and Zynerba Pharmaceuticals to consult on trial design or run clinical or lab validation trials in genetic neurodevelopmental or neurodegenerative disorders, all of which have been directed to Rush University Medical Center in support of rare disease programs. D.G.G. has received personal compensation and research support from Acadia Pharmaceuticals, Neuren Pharmaceuticals, and Newron Pharmaceuticals. E.D.M. has received research support from the Eagles Autism Foundation, the International CDKL5 Research Foundation, the International Rett Syndrome Foundation, the Loulou Foundation, the National Institute of Child Health and Human Development, the National Institute of Neurological Disorders and Stroke, the Penn Orphan Disease Center, and the Rett Syndrome Research Trust; has been a site principal investigator for trials from Acadia Pharmaceuticals, GW Pharmaceuticals, Marinus Pharmaceuticals, Stoke Therapeutics, Takeda, and Zogenix; and has received personal compensation for consulting from Acadia Pharmaceuticals and Stoke Therapeutics. A.M.B. is an employee of RTI Health Solutions, which received funding from Acadia Pharmaceuticals for the design, conduct, and analysis of the qualitative interviews. D.A. and J.M.Y. are employees of and stakeholders in Acadia Pharmaceuticals. K.M.B. was an employee of Acadia Pharmaceuticals while LILAC-2 was conducted., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Behavioral neurology & neuropsychiatry (BNNP) is a field that seeks to understand brain-behavior relationships, including fundamental brain organization principles and the many ways that brain structures and connectivity can be disrupted, leading to abnormalities of behavior, cognition, emotion, perception, and social cognition. In North America, BNNP has existed as an integrated subspecialty through the United Council for Neurologic Subspecialties since 2006. Nonetheless, the number of behavioral neurologists across academic medical centers and community settings is not keeping pace with increasing clinical and research demand. In this commentary, we provide a brief history of BNNP followed by an outline of the current challenges and opportunities for BNNP from the behavioral neurologist's perspective across clinical, research, and educational spheres. We provide a practical guide for promoting BNNP and addressing the shortage of behavioral neurologists to facilitate the continued growth and development of the subspecialty. We also urge a greater commitment to recruit trainees from diverse backgrounds so as to dismantle persistent obstacles that hinder inclusivity in BNNP-efforts that will further enhance the growth and impact of the subspecialty. With rapidly expanding diagnostic and therapeutic approaches across a range of conditions at the intersection of neurology and psychiatry, BNNP is well positioned to attract new trainees and expand its reach across clinical, research, and educational activities., Competing Interests: J.R.B. has received honoraria for continuing medical education (CME) lectures in behavioral neurology & neuropsychiatry (BNNP) and from Novo Nordisk. He has received funding from the National Institutes of Health (NIH), Dementia Alliance of North Carolina, and Alzheimer’s Association for work unrelated to this project. S.J.H. has received honoraria for CME lectures in BNNP. She has received funding from the Sidney R. Baer Jr. Foundation unrelated to this project. S.B. is a partner in and author for Brain Educators LLC, a neuropsychiatry education publisher. He has received honoraria for CME lectures in BNNP and receives a stipend as a psychiatry director of the American Board of Psychiatry and Neurology. B.F.B. receives author royalties from Cambridge University Press; honoraria for scientific advisory board activities for the Tau Consortium, funded by the Rainwater Charitable Foundation; and institutional research grant support from NIH and for clinical trials from Alector, Biogen, Transposon, Cognition Therapeutics, EIP Pharma, and GE Healthcare—all unrelated to this project. A.E.B. receives author royalties from Oxford University Press and Elsevier; investigator-initiated grants from the Alzheimer’s Association, VoxNeuro, and Bristol Myers Squibb; and consulting honorarium from Eli Lilly—all unrelated to this project. M.D.G. has consulted for Gerson Leherman Group and Reata Pharmaceuticals and receives research support from NIH, the National Institute of Neurological Disorders and Stroke (NINDS), and the Michael J. Homer Family Fund. A.E.H. receives honoraria from the American Heart Association as editor-in-chief of Stroke , and from Elsevier as associate editor of PracticeUpdate Neurology , unrelated to this project. S.K.H. has received honoraria for CME lectures from the American Academy of Neurology (AAN) and the Lewy Body Dementia Association. She has received research funding from NIH and the Michael J. Fox Foundation for Parkinson’s Research. I.K. receives funding from NIH and NINDS. J.D.S. is site principal investigator for Biohaven Pharmaceuticals clinical trials NCT03701399, NCT02960893, and NCT03952806; receives royalties from Oxford University Press, Elsevier, MacKeith Press, and Springer; and is the inventor of the Brief Ataxia Rating Scale, Cerebellar Cognitive Affective/Schmahmann Syndrome Scale, Patient Reported Outcome Measure of Ataxia, and Cerebellar Neuropsychiatry Rating Scale, which are licensed to the General Hospital Corporation. C.C.W. has received honoraria for creating educational content for the AAN. R.H.H. is a paid member of the board of trustees for the McKnight Brain Research Foundation and has received funding from NIH, the Department of Defense, and the Chan Zuckerberg Initiative for work unrelated to this project. D.L.P. has received honoraria for CME lectures in BNNP, royalties from Springer for a functional movement disorder textbook, and honoraria from Elsevier for a functional neurological disorder textbook, and is a paid member of the Brain and Behavior editorial board. He has received funding from NIH and the Sidney R. Baer Jr. Foundation unrelated to this project. The remaining authors declare no conflicts of interest., (Copyright © 2024 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Background: With the COVID-19 pandemic came rapid uptake in virtual oncology care. During this, sociodemographic inequities in access to virtual visits (VVs) have become apparent. To better understand these issues, we conducted a qualitative study to describe the perceived usability and acceptability of VVs among Black adults diagnosed with cancer., Methods: Adults who self-identified as Black and had a diagnosis of prostate, multiple myeloma, or head and neck cancer were recruited from 2 academic medical centers, and their community affiliates to participate in a semi-structured interview, regardless of prior VV experience. A patient and family advisory board was formed to inform all components of the study. Interviews were conducted between September 2, 2021 and February 23, 2022. Transcripts were organized topically, and themes and subthemes were determined through iterative and interpretive immersion/crystallization cycles., Results: Of the 49 adults interviewed, 29 (59%) had participated in at least one VV. Three overarching themes were derived: (1) VVs felt comfortable and convenient in the right contexts; (2) the technology required for VVs with video presented new challenges, which were often resolved by an audio-only telephone call; and (3) participants reported preferring in-person visits, citing concerns regarding gaps in nonverbal communication, trusting providers, and distractions during VV., Conclusion: While VVs were reported to be acceptable in specific circumstances, Black adults reported preferring in-person care, in part due to a perceived lack of interpersonal connectedness. Nonetheless, retaining reimbursement for audio-only options for VVs is essential to ensure equitable access for those with less technology savvy and/or limited device/internet capabilities., (© The Author(s) 2023. Published by Oxford University Press.)

Background: Arthrofibrosis can limit function and return to sport after anterior cruciate ligament (ACL) reconstruction. Previously reported risk factors for developing arthrofibrosis after ACL reconstruction include female sex, age <18 years, time from injury to surgery <28 days, concomitant meniscal repair, prolonged immobilization, and genetic factors. There is a lack of evidence regarding whether race plays a significant role., Hypothesis: The risk of undergoing manipulation under anesthesia (MUA) and/or lysis of adhesions (LOA) after primary ACL reconstruction with bone-patellar tendon-bone (BTB) autograft in female basketball players is higher in African American players than in White players., Study Design: Case-control study; Level of evidence, 3., Methods: Using a computerized relational database, the authors identified competitive female basketball players who underwent primary ACL reconstruction with BTB autograft by the senior author over a 13-year period. Data previously entered from examinations and surgical findings were reviewed retrospectively. Univariate statistics and multivariable logistic regression were used to assess the relationship between undergoing subsequent MUA and/or LOA and study predictors., Results: A total of 186 knees (114 African American knees and 72 White knees) met inclusion criteria. The overall rate of MUA and/or LOA was 8.6%. Thirteen African American knees (11.4%) and 3 White knees (4.2%) underwent MUA and/or LOA for treatment of arthrofibrosis. No study predictor was found to have a statistically significant relationship with the rate of MUA and/or LOA on univariate analysis. However, when controlling for body mass index and previously described risk factors (age <18 years, time from injury to surgery ≤28 days, and concomitant meniscal repair) in the logistic regression model, the authors found that MUA and/or LOA was more likely in African American (odds ratio, 4.01 [95% CI, 1.01-15.92]; P = .049) than in White female players and in patients who underwent ACL reconstruction within 28 days of injury (odds ratio, 4.01 [95% CI, 1.18-13.57]; P = .026) compared with those with surgery delayed beyond 28 days., Conclusion: In female basketball players, the present study found a statistically significantly increased risk for undergoing MUA and/or LOA after primary ACL reconstruction with BTB autograft in African American females compared with White females and in patients who underwent ACL reconstruction within 28 days of injury., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: R.M.C. has received support for education from Alon Medical Technology, Medical Device Business Services, and Stryker. A.M.B. has received support for education from Alon Medical Technology. W.J.F. has received support for education from Alon Medical Technology, Arthrex, and Smith & Nephew and a grant from Arthrex. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Background: The expansion of telemedicine associated with the COVID-19 pandemic has influenced outpatient medical care. The objective of our study was to determine the impact of telemedicine on post-acute stroke clinic follow-up., Methods: We retrospectively evaluated the impact of telemedicine in Emory Healthcare, an academic healthcare system of comprehensive and primary stroke centers in Atlanta, Georgia, on post-hospital stroke clinic follow-up. We compared the frequency of 90-day follow-up in a centralized subspecialty stroke clinic among patients hospitalized before the local COVID-19 pandemic (January 1, 2019- February 28, 2020), during (March 1- April 30, 2020) and after telemedicine implementation (May 1- December 31, 2020). A comparison was made across hospitals less than 1 mile, 10 miles, and 25 miles from the stroke clinic., Results: Of 1096 ischemic stroke patients discharged home or to a rehab facility during the study period, 342 (31%) had follow-up in the Emory Stroke Clinic (comprehensive stroke center 46%, primary stroke center 10 miles away 18%, primary stroke center 25 miles away 14%). Overall, 90-day follow-up increased from 19% to 41% after telemedicine implementation (p<0.001) with telemedicine appointments amounting for up to 28% of all follow-up visits. In multivariable analysis, factors associated with teleneurology follow-up (vs no follow-up) included discharge from the comprehensive stroke center, thrombectomy treatment, private insurance, private transport to the hospital, NIHSS 0-5 and history of dyslipidemia., Conclusions: Despite telemedicine implementation at an academic healthcare network successfully increasing post-stroke discharge follow-up in a centralized subspecialty stroke clinic, the majority of patients did not complete 90-day follow-up during the COVID-19 pandemic., Competing Interests: Declaration of Competing Interest There were no unusual circumstances surrounding the research, nor were there deviations from standard procedures or format. There is no funding or financial support to disclose., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: Spatial neglect remains an underdiagnosed and undertreated consequence of stroke that imposes significant disability. A growing appreciation of brain networks involved in spatial cognition is helping us to develop a mechanistic understanding of different therapies under development., Areas Covered: This review focuses on neuromodulation of brain networks for the treatment of spatial neglect after stroke, using evidence-based approaches including 1) Cognitive strategies that are more likely to impact frontal lobe executive function networks; 2) Visuomotor adaptation, which may depend on the integrity of parietal and parieto- and subcortical-frontal connections and the presence of a particular subtype of neglect labeled Aiming neglect; 3) Non-invasive brain stimulation that may modulate relative levels of activity of the two hemispheres and depend on corpus callosum connectivity; and 4) Pharmacological modulation that may exert its effect primarily via right-lateralized networks more closely involved in arousal., Expert Opinion: Despite promising results from individual studies, significant methodological heterogeneity between trials weakened conclusions drawn from meta-analyses. Improved classification of spatial neglect subtypes will benefit research and clinical care. Understanding the brain network mechanisms of different treatments and different types of spatial neglect will make possible a precision medicine treatment approach.

Objective: To determine the maximum permissible number of missed items on the 10-item Catherine Bergego Scale administered after the Kessler Foundation Neglect Assessment Process (KF-NAP). Secondary objectives were to determine the frequency, characteristics, and most commonly cited reasons reported for missed items., Design: Retrospective diagnostic accuracy study., Setting: Sixteen inpatient rehabilitation facilities in the United States., Participants: A consecutive clinical sample of 4256 patients (N=4256) with stroke or other neurologic deficits who were assessed for spatial neglect with the KF-NAP., Interventions: Not applicable., Main Outcome Measures: Catherine Bergego Scale via KF-NAP., Results: The majority (69.7%) of patients had at least 1 missed item on their KF-NAP. Among those with missed items, it was most common to have 2 missed items (51.4%), and few had more than 3 missed items (11.3%). The most commonly missed items were Collisions (37.2%), Cleaning After Meals (36.1%), Meals (34.0%), and Navigation (19.7%). The most commonly reported reasons for missed items included time constraints, cognitive or communication deficits, and behavior or refusal of the therapy session. These reasons were reported for nearly all item types. Item-specific reasons were also commonly reported, such as a lack of a needed resource for task completion or low functional status of the patient. Prorated scoring of measures with up to 3 missed items maintained an acceptable level of concordance with complete measures (Lin's Concordance Correlation Coefficient=0.96, 95% CI, 0.9478-0.9626) for the combination of 3 missed items with lowest concordance., Conclusions: Clinicians should make every effort to capture all items on the KF-NAP. However, missed items occur in the majority of cases because of patient factors and barriers inherent to the inpatient hospital setting. When missed items are necessary, clinicians can confidently interpret a prorated score when 7 or more items are scored., (Copyright © 2022 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Evolution in response to a change in ecology often coincides with various morphological, physiological, and behavioral traits. For most organisms little is known about the genetic and functional relationship between evolutionarily derived traits, representing a critical gap in our understanding of adaptation. The Mexican tetra, Astyanax mexicanus, consists of largely independent populations of fish that inhabit at least 30 caves in Northeast Mexico, and a surface fish population, that inhabit the rivers of Mexico and Southern Texas. The recent application of molecular genetic approaches combined with behavioral phenotyping have established A. mexicanus as a model for studying the evolution of complex traits. Cave populations of A. mexicanus are interfertile with surface populations and have evolved numerous traits including eye degeneration, insomnia, albinism, and enhanced mechanosensory function. The interfertility of different populations from the same species provides a unique opportunity to define the genetic relationship between evolved traits and assess the co-evolution of behavioral and morphological traits with one another. To define the relationships between morphological and behavioral traits, we developed a pipeline to test individual fish for multiple traits. This pipeline confirmed differences in locomotor activity, prey capture, and startle reflex between surface and cavefish populations. To measure the relationship between traits, individual F2 hybrid fish were characterized for locomotor behavior, prey-capture behavior, startle reflex, and morphological attributes. Analysis revealed an association between body length and slower escape reflex, suggesting a trade-off between increased size and predator avoidance in cavefish. Overall, there were few associations between individual behavioral traits, or behavioral and morphological traits, suggesting independent genetic changes underlie the evolution of the measured behavioral and morphological traits. Taken together, this approach provides a novel system to identify genetic underpinnings of naturally occurring variation in morphological and behavioral traits., (© 2022 The Authors. Evolution & Development published by Wiley Periodicals LLC.)

We examined whether number of prism adaptation treatment (PAT) sessions in regular clinical practice would predict spatial neglect (SN) improvement and rehabilitation outcomes. We reviewed clinical records from 16 U.S. rehabilitation hospitals where neurological patients were assessed for SN using the Catherine Bergego Scale (CBS) and if SN was detected, and may have received PAT. Multiple linear regression was used to predict CBS Change (indicating SN improvement) in 520 patients who received PAT while considering age, sex, diagnosis, time post diagnosis, CBS at baseline, neglected side of space, and length of stay. Another set of regression models including the same variables and adding Function Independent Measure (FIM®) at admission was used to predict FIM Gains (indicating rehabilitation outcomes) in 1720 patients receiving PAT or not. We found that greater number of PAT sessions predicted greater CBS Change, especially in patients with moderate-to-severe neglect. Number of PAT sessions also positively correlated with Total FIM, Motor FIM, and Cognitive FIM Gains regardless of SN severity classification at baseline. Furthermore, number of PAT sessions predicted CBS Change and FIM Gains among patients completing ≤8 PAT sessions but not among patients with ≥8 sessions, who however, showed greater CBS Change with increased PAT frequency (i.e., fewer days between two consecutive sessions). Receiving more once-daily PAT sessions predicted greater improvement in SN and rehabilitation outcomes. Receiving PAT at a higher frequency for 8 or more sessions predicted better SN improvement. Thus, dosage matters. The study provides practice-based evidence that PAT is appropriate for inpatient rehabilitation.

Introduction: Spatial neglect, a neurocognitive disorder of lateralized spatial attention, is prevalent among stroke survivors especially in inpatient rehabilitation facilities (IRFs). The ultimate goal of the project was to improve spatial neglect care in inpatient rehabilitation and trained as many OTs as possible using both tools in their regular practices as the means to achieve our overall objective. Therefore, we conducted a project aimed at implementing two evidence-based protocols, one for assessment (KF-NAP®) and the other for treatment (KF-PAT®), and share the implementation process, which included barriers and facilitators identified during and after the process, and implementation outcomes., Methods: Sixteen IRFs were involved. The Knowledge-To-Action Cycle was used to describe the process of knowledge inquiry (training), translating knowledge (implementation) and evaluating the use of knowledge in clinical practice (outcomes). Barriers and strategies were reported using the Consolidated Framework for Implementation Research and identified through a survey, after the study concluded., Results: Thirty-two therapists at the participating sites were trained to some level of the KF-NAP and KF-PAT. Throughout the project and also once after it finished, different barriers were identified by researchers and clinicians, who then determined together actions to eliminate or minimize the barriers. For example, multiple sites reported: "not having time to train other staff at their hospital due to high patient volume and other responsibilities.", Discussion: The project shared our implementation process which demonstrated the importance of using implementation methods and incorporating a researcher-clinician partnership, not only for knowledge generation but also knowledge translation. Frequent communications and exchanging information with stakeholders at different levels, may be determinant to the success of each implementation phase. Further research is needed., Competing Interests: The KF-NAP and KF-PAT are registered trademarks of Kessler Foundation in the United States. JM and PC are employees of Kessler Foundation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hreha, Barrett, Gillen, Gonzalez-Snyder, Masmela and Chen.)

Animal and human literature supports spatial-motor "Aiming" bias, a frontal-subcortical syndrome, as a core deficit in spatial neglect. However, spatial neglect treatment studies rarely assess Aiming errors. Two knowledge gaps result: spatial neglect rehabilitation studies fail to capture the impact on motor-exploratory aspects of functional disability. Also, across spatial neglect treatment studies, discrepant treatment effects may also result from sampling different proportions of patients with Aiming bias. We review behavioural evidence for Aiming spatial neglect, and demonstrate the importance of measuring and targeting Aiming bias for treatment, by reviewing literature on Aiming spatial neglect and prism adaptation treatment, and presenting new preliminary data on bromocriptine treatment. Finally, we review neuroanatomical and network disruption that may give rise to Aiming spatial neglect. Because Aiming spatial neglect predicts prism adaptation treatment response, assessment may broaden the ability of rehabilitation research to capture functionally-relevant disability. Frontal brain lesions predict both the presence of Aiming spatial neglect, and a robust response to some spatial neglect interventions. Research is needed that co-stratifies spatial neglect patients by lesion location and Aiming spatial neglect, to personalize spatial neglect rehabilitation and perhaps even open a path to spatial retraining as a means of promoting better mobility after stroke.

Background: Multi-site studies in stroke rehabilitation are important for determining whether a technology and/or treatment can be successfully administered by sites other than the originating site and with similar positive outcomes. This study is the first multi-site clinical trial of a novel intervention for post-stroke upper limb rehabilitation called contralaterally controlled functional electrical stimulation (CCFES). Previous pilot and single-site studies showed positive effects of CCFES on upper limb impairment and hand dexterity in stroke survivors. The main purpose of this study is to confirm and demonstrate the efficacy of CCFES in a larger group of most likely responders across multiple clinical sites., Methods: Up to 129 stroke survivors with moderate to severe upper extremity hemiparesis at 4 clinical trial sites will be randomized to CCFES, cyclic neuromuscular electrical stimulation (cNMES), or task-oriented-training (TOT). Participants will receive 12 weeks of group-specific therapy. Blinded assessments of upper limb impairment and activity limitation, quality of life, and neurophysiology will be used to compare outcomes at baseline, after treatment, and up to 6 months post-treatment. The primary endpoint is change in dexterity from baseline to 6 months post-treatment., Discussion: Loss of hand function following stroke is a major rehabilitation problem affecting millions of people per year globally. More effective rehabilitation therapies are needed to restore hand function in these individuals. This study will determine whether CCFES therapy produces greater improvements in upper extremity function than cNMES or TOT, and will begin to elucidate the different mechanisms underlying each of the three treatments. This multi-site study is a critical step in advancing a novel method of rehabilitation toward clinical translation and widespread dissemination., Trial Registration: ClinicalTrials.gov NCT03574623 . Registered prior to first enrollment; July 2, 2018., (© 2022. The Author(s).)

Objective: Spatial Neglect is prevalent among stroke survivors, yet few treatments have evidence supporting efficacy. This study examines the feasibility of Prism Adaptation Treatment (PAT) within an inpatient rehabilitation facility and the degree by which PAT improves symptoms of spatial neglect and functional independence among sub-acute survivors of right hemispheric stroke., Design: In this retrospective cohort study, 37 right hemispheric stroke patients were identified as having received at least 4 PAT sessions during their inpatient stay. Spatial neglect and functional independence levels of patients in the PAT cohort were compared to a matched active control group comprised of rehabilitation patients receiving alternative therapies to address neglect admitted during the same time period., Results: Most patients received the full recommended 10 sessions of PAT (average sessions completed = 8.6). A higher percentage of severe neglect patients receiving PAT (69%) displayed clinically significant gains on FIM (≥22 points) compared to those receiving alternative treatments (6%). Patients with mild or moderate neglect in the PAT cohort did not exhibit greater benefit than controls., Conclusion: Provision of PAT for treatment of spatial neglect in right hemispheric stroke patients was feasible during the inpatient rehabilitation admission. Patients with severe neglect showed the most benefit from PAT., Clinical Trial Registration: This study was registered as a retrospective observational study on Itab Clinical Trials.gov. NCT04977219., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gillen, Harmon, Weil, Fusco-Gessick, Novak and Barrett.)

Background and Purpose: Delirium, an acute reduction in cognitive functioning, hinders stroke recovery and contributes to cognitive decline. Right-hemisphere stroke is linked with higher delirium incidence, likely, due to the prevalence of spatial neglect (SN), a right-brain disorder of spatial processing. This study tested if symptoms of delirium and SN after right-hemisphere stroke are associated with abnormal function of the right-dominant neural networks specialized for maintaining attention, orientation, and arousal., Methods: Twenty-nine participants with right-hemisphere ischemic stroke undergoing acute rehabilitation completed delirium and SN assessments and functional neuroimaging scans. Whole-brain functional connectivity of 4 right-hemisphere seed regions in the cortical-subcortical arousal and attention networks was assessed for its relationship to validated SN and delirium severity measures., Results: Of 29 patients, 6 (21%) met the diagnostic criteria for delirium and 16 (55%) for SN. Decreased connectivity of the right basal forebrain to brain stem and basal ganglia predicted more severe SN. Increased connectivity of the arousal and attention network regions with the parietal, frontal, and temporal structures in the unaffected hemisphere was also found in more severe delirium and SN., Conclusions: Delirium and SN are associated with decreased arousal network activity and an imbalance of cortico-subcortical hemispheric connectivity. Better understanding of neural correlates of poststroke delirium and SN will lead to improved neuroscience-based treatment development for these disorders. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03349411.

Background and Purpose: Delirium portends worse outcomes after intracerebral hemorrhage (ICH), but it is unclear if symptom resolution or postacute care intensity may mitigate its impact. We aimed to explore differences in outcome associated with delirium resolution before hospital discharge, as well as the potential mediating role of postacute discharge site., Methods: We performed a single-center cohort study on consecutive ICH patients over 2 years. Delirium was diagnosed according to DSM-5 criteria and further classified as persistent or resolved based on delirium status at hospital discharge. We determined the impact of delirium on unfavorable 3-month outcome (modified Rankin Scale score, 4-6) using logistic regression models adjusted for established ICH predictors, then used mediation analysis to examine the indirect effect of delirium via postacute discharge site., Results: Of 590 patients (mean age 70.5±15.5 years, 52% male, 83% White), 59% (n=348) developed delirium during hospitalization. Older age and higher ICH severity were delirium risk factors, but only younger age predicted delirium resolution, which occurred in 75% (161/215) of ICH survivors who had delirium. Delirium was strongly associated with unfavorable outcome, but patients with persistent delirium fared worse (adjusted odds ratio [OR], 7.3 [95% CI, 3.3-16.3]) than those whose delirium resolved (adjusted OR, 3.1 [95% CI, 1.8-5.5]). Patients with delirium were less likely to be discharged to inpatient rehabilitation than skilled nursing facilities (adjusted OR, 0.31 [95% CI, 0.17-0.59]), and postacute care site partially mediated the relationship between delirium and functional outcome in ICH survivors, leading to a 25% reduction in the effect of delirium (without mediator: adjusted OR, 3.0 [95% CI, 1.7-5.6]; with mediator: adjusted OR, 2.3 [95% CI, 1.2-4.3])., Conclusions: Acute delirium resolves in most patients with ICH by hospital discharge, which was associated with better outcomes than in patients with persistent delirium. The impact of delirium on outcomes may be further mitigated by postacute rehabilitation.

Purpose of Review: Up to 80% of survivors of right brain stroke leave acute care without being diagnosed with a major invisible disability. Studies indicate that a generic cognitive neurologic evaluation does not reliably detect spatial neglect, nor does it identify unawareness of deficit after right brain stroke; this article reviews the symptoms, clinical presentation, and management of these two cognitive disorders occurring after right brain stroke., Recent Findings: Stroke and occupational therapy practice guidelines stress a quality standard for spatial neglect assessment and treatment to reduce adverse outcomes for patients, their families, and society. Neurologists may attribute poor outcomes associated with spatial neglect to stroke severity. However, people with spatial neglect are half as likely to return to home and community, have one-third the community mobility, and require 3 times as much caregiver supervision compared with similar stroke survivors. Multiple randomized trials support a feasible first-line rehabilitation approach for spatial neglect: prism adaptation therapy; more than 20 studies reported that this treatment improves daily life independence. Evidence-based treatment of anosognosia is not as developed; however, treatment for this problem is also available., Summary: This article guides neurologists' assessment of right brain cognitive disorders and describes how to efficiently assemble and direct a treatment team to address spatial neglect and unawareness of deficit., (Copyright © 2021 American Academy of Neurology.)

Objective: To determine whether prism adaptation treatment (PAT) integrated into the standard of care improves rehabilitation outcome in patients with spatial neglect (SN)., Design: Retrospective matched control study based on information extracted from June 2017-September 2019., Setting: Inpatient rehabilitation., Participants: Patients from 14 rehabilitation hospitals scoring >0 on the Catherine Bergego Scale (N=312). The median age was 69.5 years, including 152 (49%) female patients and 275 (88%) patients with stroke., Interventions: Patients were matched 1:1 by age (±5 years), FIM score at admission (±2 points), and SN severity using the Catherine Bergego Scale (±2 points) and classified into 2 groups: treated (8-12 daily sessions of PAT) vs untreated (no PAT)., Main Outcome Measures: FIM and its minimal clinically important difference (MCID) were the primary outcome variables. Secondary outcome was home discharge., Results: Analysis included the 312 matched patients (156 per group). FIM scores at discharge were analyzed using repeated-measures analyses of variance. The treated group showed reliably higher scores than the untreated group in Total FIM, F =5.57, P =.020, partial η 2 =0.035, and Cognitive FIM, F =19.20, P <.001, partial η 2 =0.110, but not Motor FIM, F =0.35, P =.553, partial η 2 = 0.002. We used conditional logistic regression to examine the odds ratio of reaching MCID in each FIM score and of returning home after discharge. No reliable difference was found between groups in reaching MCID or home discharge., Conclusions: Patients with SN receiving PAT had better functional and cognitive outcomes, suggesting that integrating PAT into the standard of care is beneficial. However, receiving PAT may not determine home discharge., (© 2021 The Authors.)

Objective: To evaluate the effect of intensive rehabilitation on the modified Rankin Scale (mRS), a measure of activities limitation commonly used in acute stroke studies, and to define the specific changes in body structure/function (motor impairment) most related to mRS gains., Methods: Patients were enrolled >90 days poststroke. Each was evaluated before and 30 days after a 6-week course of daily rehabilitation targeting the arm. Activity gains, measured using the mRS, were examined and compared to body structure/function gains, measured using the Fugl-Meyer (FM) motor scale. Additional analyses examined whether activity gains were more strongly related to specific body structure/function gains., Results: At baseline (160 ± 48 days poststroke), patients (n = 77) had median mRS score of 3 (interquartile range, 2-3), decreasing to 2 [2-3] 30 days posttherapy ( p < 0.0001). Similarly, the proportion of patients with mRS score ≤2 increased from 46.8% at baseline to 66.2% at 30 days posttherapy ( p = 0.015). These findings were accounted for by the mRS score decreasing in 24 (31.2%) patients. Patients with a treatment-related mRS score improvement, compared to those without, had similar overall motor gains (change in total FM score, p = 0.63). In exploratory analysis, improvement in several specific motor impairments, such as finger flexion and wrist circumduction, was significantly associated with higher likelihood of mRS decrease., Conclusions: Intensive arm motor therapy is associated with improved mRS in a substantial fraction (31.2%) of patients. Exploratory analysis suggests specific motor impairments that might underlie this finding and may be optimal targets for rehabilitation therapies that aim to reduce activities limitations., Clinical Trial: Clinicaltrials.gov identifier: NCT02360488., Classification of Evidence: This study provides Class III evidence that for patients >90 days poststroke with persistent arm motor deficits, intensive arm motor therapy improved mRS in a substantial fraction (31.2%) of patients., (© 2021 American Academy of Neurology.)

Objective: To identify barriers and facilitators to achieving optimal inpatient rehabilitation outcome among individuals with spatial neglect (SN)., Design: Cross-sectional, semistructured focus group discussions., Setting: Rehabilitation hospitals., Participants: A total of 15 occupational therapists and 14 physical therapists treating patients with SN on 3 campuses of a rehabilitation hospital system (N=29). Six focus group sessions were conducted and audio-recorded for transcription., Interventions: Not applicable., Main Outcome Measures: Not applicable., Results: Participants identified several patient-related characteristics that posed barriers to treatment, including the symptoms of SN itself, cognitive issues, physical weakness, comorbidities, and reduced therapy engagement. Supportive family members were considered a key facilitator, but lack of preparedness to assume caregiving roles, poor understanding of SN and rehabilitation goals, and inadequate levels of involvement were family-related barriers to successful treatment. Participants expressed that having resources and technologies available at their center to support SN treatment facilitated positive outcomes and perceived limited staff knowledge and skills and poor interclinician communication as barriers to treatment. At the health care system level, barriers included a lack of responsive measures of SN progress and insurer-related issues. Strong continuity of care between transitions was considered an important factor for enabling effective treatment., Conclusions: Barriers and facilitators to the current practice of SN care were identified from occupational and physical therapists' point of view. Opportunities exist to promote identified facilitators and minimize barriers to improve SN rehabilitation. The present study makes a unique contribution in identifying specific needs for innovative interventions that involve family support and training, promotion of interdisciplinary collaboration, development of interprofessional vocabulary, and continuous treatment and follow-up assessment for SN through care transitions., (© 2021 The Authors.)

Resistance to antibody-drug conjugates (ADCs) has been observed in both preclinical models and clinical studies. However, mechanisms of resistance to pyrrolobenzodiazepine (PBD)-conjugated ADCs have not been well characterized and thus, this study was designed to investigate development of resistance to PBD dimer warheads and PBD-conjugated ADCs. We established a PBD-resistant cell line, 361-PBDr, by treating human breast cancer MDA-MB-361 cells with gradually increasing concentrations of SG3199, the PBD dimer released from the PBD drug-linker tesirine. 361-PBDr cells were over 20-fold less sensitive to SG3199 compared with parental cells and were cross-resistant to other PBD warhead and ADCs conjugated with PBDs. Proteomic profiling revealed that downregulation of Schlafen family member 11 (SLFN11), a putative DNA/RNA helicase, sensitizing cancer cells to DNA-damaging agents, was associated with PBD resistance. Confirmatory studies demonstrated that siRNA knockdown of SLFN11 in multiple tumor cell lines conferred reduced sensitivity to SG3199 and PBD-conjugated ADCs. Treatment with EPZ011989, an EZH2 inhibitor, derepressed SLFN11 expression in 361-PBDr and other SLFN11-deficient tumor cells, and increased sensitivity to PBD and PBD-conjugated ADCs, indicating that the suppression of SLFN11 expression is associated with histone methylation as reported. Moreover, we demonstrated that combining an ataxia telangiectasia and Rad3-related protein (ATR) inhibitor, AZD6738, with SG3199 or PBD-based ADCs led to synergistic cytotoxicity in either resistant 361-PBDr cells or cells that SLFN11 was knocked down via siRNA. Collectively, these data provide insights into potential development of resistance to PBDs and PBD-conjugated ADCs, and more importantly, inform strategy development to overcome such resistance., (©2021 American Association for Cancer Research.)

Objective: To derive and validate a comorbidity-based delirium risk index (DRI) to predict postoperative delirium., Data Source/study Setting: Data of 506 438 hip fracture repair surgeries from 2006 to 2016 were collected to derive DRI and perform internal validation from the Premier Healthcare Database, which provided billing information on 20-25 percent of hospitalizations in the USA. Additionally, data of 1 130 569 knee arthroplasty surgeries were retrieved for external validation., Study Design: Thirty-six commonly seen comorbidities were evaluated by logistic regression with the outcome of postoperative delirium. The hip fracture repair surgery cohort was separated into a training dataset (60 percent) and an internal validation (40 percent) dataset. The least absolute shrinkage and selection operator (LASSO) procedure was applied for variable selection, and weights were assigned to selected comorbidities to quantify corresponding risks. The newly developed DRI was then compared to the Charlson-Deyo Index for goodness-of-fit and predictive ability, using the Akaike information criterion (AIC), Bayesian information criterion (BIC), area under the ROC curve (AUC) for goodness-of-fit, and odds ratios for predictive performance. Additional internal validation was performed by splitting the data by four regions and in 4 randomly selected hospitals. External validation was conducted in patients with knee arthroplasty surgeries., Data Collection: Hip fracture repair surgeries, knee arthroplasty surgeries, and comorbidities were identified by using ICD-9 codes. Postoperative delirium was defined by using ICD-9 codes and analyzing billing information for antipsychotics (specifically haloperidol, olanzapine, and quetiapine) typically recommended to treat delirium., Principal Findings: The derived DRI includes 14 comorbidities and assigns comorbidities weights ranging from 1 to 6. The DRI outperformed the Charlson-Deyo Comorbidity Index with better goodness-of-fit and predictive performance., Conclusions: Delirium risk index is a valid comorbidity index for covariate adjustment and risk prediction in the context of postoperative delirium. Future work is needed to test its performance in different patient populations and varying definitions of delirium., (© 2020 Health Research and Educational Trust.)

The coronavirus outbreak has led to abrupt changes in people's daily lives as many state governments have restricted individuals' movements in order to slow the spread of the virus. We conducted a natural experiment in the United States of America in April 2020, in which we compare responses from states with "stay-at-home orders" (3 states) and no such orders (6 states). We surveyed 458 participants (55.6% female, age range 25-64, M age = 36.5) and examined the effects of these government-imposed restrictions on social, mental, physical, and financial well-being as well as the mediating role of resilience. Structural equation modeling reveals that resilience buffers stay-at-home orders' potential side-effects on well-being. Specifically, individuals living in states with stay-at-home orders report lower functional well-being than individuals living in states without such orders, which negatively relates to resilience. Resilience in turn is associated with higher social, mental, physical, and financial well-being. Thus, resilience can be seen as an effective means of buffering stay-at-home orders' potential negative effects on the components of well-being. Our results indicate the central role of resilience, which is crucial in dampening the effects of stay-at-home orders on well-being. Following our results, governments and policymakers should focus their efforts on strengthening individuals' resilience, which is a key predictor of social, mental, financial, and physical well-being., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Barrett, Hogreve and Brüggen.)

Background: Delirium is well studied in the acute care setting, but there is limited understanding of its impact in the postacute care setting, particularly in the inpatient rehabilitation facility (IRF)., Objective: To investigate the prevalence and related outcomes of delirium in the IRF setting, particularly patients' transfers to acute care hospitals., Design: Retrospective cohort study., Setting: A freestanding IRF., Participants: Patients discharged from an IRF between January 2016 and December 2016 (12 months)., Interventions: Not applicable., Main Outcome Measures: Transfer to acute care hospitals, motor and cognitive Functional Independence Measures (FIM), length of stay, discharge disposition., Results: A total of 1567 patients (53.9% female, mean age 72.9 ± 13.9) were included in the analysis. Positive scores were found among 142 (9.1%) patients on a 3-Minute Diagnostic Interview for Confusion Assessment Method (3D-CAM), indicating delirium on admission. Fifty-nine (3.8%) were unscorable on 3D-CAM. Twice as many delirium patients were transferred to acute care hospitals compared to non-delirium patients (22.5% vs. 10.8%, P < .001). Multivariate logistic regression showed that, for patients with 3D-CAM positive scores, there was an increased risk of transfers to acute care hospitals at an odds ratio of 1.61 (1.03-2.53, P = .04) after adjusting for age, gender, neurological diagnosis, and motor FIM score. The delirium group also showed lower gains in motor function, increased lengths of stay, and reduced discharges to home when compared to the non-delirium group (P < .001)., Conclusions: This study finds that delirium on admission to an IRF is associated with worsened outcomes related to function, length of stay, discharge status, and transfer to acute care hospitals. Positive delirium screening is an independent predictor for transfer to acute care hospitals from an IRF. Early identification of delirium is recommended in order to mitigate preventable transfers., (© 2019 American Academy of Physical Medicine and Rehabilitation.)

Background: Intensive, adaptable and engaging telerehabilitation is needed to enhance recovery and maximize outcomes. Such services may be provided under early supported discharge, or later for chronic populations. A novel virtual reality game-based telerehabilitation system was designed for individuals post-stroke to enhance their bimanual upper extremity motor function, cognition, and wellbeing., Objectives: To evaluate the feasibility of novel therapeutic game controller and telerehabilitation system for home use., Methods: Individuals chronic post-stroke and their caregivers were recruited (n = 8 + 8) for this feasibility study. One was a screen failure and seven completed 4 weeks (20 sessions) of home-based therapy with or without remote monitoring. Standardized clinical outcome measures were taken pre- and post-therapy. Game performance outcomes were sampled at every session, while participant and caregiver subjective evaluations were done weekly., Results: There was a 96% rate of compliance to protocol, resulting in an average of 13,000 total arm repetitions/week/participant. Group analysis showed significant ( p <.05) improvements in grasp strength (effect size [ES] = 0.15), depression (Beck Depression Inventory II, ES = 0.75), and cognition (Neuropsychological Assessment Battery for Executive Function, ES = 0.46). Among the 49 outcome variables, 36 variables (73.5%) improved significantly ( p = .001, binomial sign test). Technology acceptance was very good with system rating by participants at 3.7/5 and by caregivers at 3.5/5., Conclusions: These findings indicate the feasibility and efficacy of the system in providing home-based telerehabilitation. The BrightBrainer system needs to be further evaluated in randomized control trials and with individuals early post-stroke.

Context: Physician burnout is a national problem that has gained increasing attention among the medical community. Many organizations like the American Medical Association, American College of Physicians, and the National Academy of Medicine are taking action., Evidence Acquisition: Endocrinologists and other members of the endocrine community are not immune to burnout. Approximately 47% of endocrinologists report feeling burnt out or have experienced symptoms of burnout, and this number is rising., Evidence Synthesis: The consequences of burnout include personal factors such as stress, depression, and risk of suicide as well as organizational impacts like decreased quality of care, increased clinical errors, reduced empathy for patients, decreased patient satisfaction, and higher turnover rates, with some physicians leaving practice altogether. Burnout has substantial economic impacts at an organizational level, and high costs are associated with replacing, recruiting, and retraining endocrinologists. Endocrinologists identified feeling a lack of respect from administration, excessive bureaucratic tasks, increased computerization, emphasis on profit that has contributed to loss of control over schedules, and insufficient compensation as top contributors to burnout. One strategy to address burnout is to focus on the promotion of joy in work. Joy in work is guided by 4 key themes: meaning, camaraderie, choice, and equity. Each of these themes can be implemented through cocreating solutions. We discuss how each theme can be addressed among endocrine practices., Conclusion: Ultimately, initiatives need to be implemented across the endocrinology community to cultivate joy and reduce burnout., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: This study examined lexical and neuroanatomic correlates of reading errors in individuals with spatial neglect, defined as a failure to respond to stimuli in the side of space opposite a brain lesion, causing functional disability., Method: One-hundred and ten participants with left spatial neglect after right-hemisphere stroke read aloud a list of 36 words. Reading errors were scored as "contralesional" (error in the left half of the word) or as "other." The influence of lexical processing on neglect dyslexia was studied with a stepwise regression using word frequency, orthographic neighborhood (number of same length neighbors that differ by 1 letter), bigram and trigram counts (number of words with the same 2- and 3-letter combinations), length, concreteness, and imageability as predictors. MRI/CT images of 92 patients were studied in a voxelwise lesion-symptom analysis (VLSM)., Results: Longer length and more trigram neighbors increased, while higher concreteness reduced, the rate of contralesional errors. VLSM revealed lesions in the inferior temporal sulcus, middle temporal and angular gyri, precuneus, temporal pole, and temporo-parietal white matter associated with the rate of contralesional errors., Conclusions: Orthographic competitors may decrease word salience, while semantic concreteness may help constrain the selection of available word options when it is based on degraded information from the left side of the word. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Objectives: Poststroke delirium may be underdiagnosed due to the challenges of disentangling delirium symptoms from underlying neurologic deficits. We aimed to determine the prevalence of individual delirium features and the frequency with which they could not be assessed in patients with intracerebral hemorrhage., Design: Prospective observational cohort study., Setting: Neurocritical Care and Stroke Units at a university hospital., Patients: Consecutive patients with intracerebral hemorrhage from February 2018 to May 2018., Interventions: None., Measurements and Main Results: An attending neurointensivist performed 257 total daily assessments for delirium on 60 patients (mean age 68.0 [SD 18.4], 62% male, median intracerebral hemorrhage score 1.5 [interquartile range 1-2], delirium prevalence 57% [n = 34]). Each assessment included the Confusion Assessment Method for the ICU, Intensive Care Delirium Screening Checklist, a focused bedside cognitive examination, chart review, and nurse interview. We characterized individual symptom prevalence and established delirium diagnoses using Diagnostic and Statistical Manual of Mental Disorders, fifth edition criteria, then compared performance of the Confusion Assessment Method for the ICU and Intensive Care Delirium Screening Checklist against reference-standard expert diagnosis. Symptom fluctuation (61% of all assessments), psychomotor changes (46%), sleep-wake disturbances (46%), and impaired arousal (37%) had the highest prevalence and were never rated "unable to assess," while inattention (36%), disorientation (27%), and disorganized thinking (18%) were also common but were often rated 'unable to assess' (32%, 43%, and 44% of assessments, respectively), most frequently due to aphasia (32% of patients). Including nonverbal assessments of attention decreased the frequency of 'unable to assess' ratings to 11%. Since the Intensive Care Delirium Screening Checklist may be positive without the presence of symptoms that require verbal assessment, it was more accurate (sensitivity = 77%, specificity = 97%, area under the receiver operating characteristic curve, 0.87) than the Confusion Assessment Method for the ICU (sensitivity = 41%, specificity = 88%, area under the receiver operating characteristic curve, 0.64)., Conclusions: Delirium is common after intracerebral hemorrhage, but severe neurologic deficits may confound its assessment and lead to underdiagnosis. The Intensive Care Delirium Screening Checklist's inclusion of nonverbal features may make it more accurate than the Confusion Assessment Method for the ICU in patients with neurologic deficits, but novel tools designed for such patients may be warranted.

Automatic identification of brain lesions from magnetic resonance imaging (MRI) scans of stroke survivors would be a useful aid in patient diagnosis and treatment planning. It would also greatly facilitate the study of brain-behavior relationships by eliminating the laborious step of having a human expert manually segment the lesion on each brain scan. We propose a multi-modal multi-path convolutional neural network system for automating stroke lesion segmentation. Our system has nine end-to-end UNets that take as input 2-dimensional (2D) slices and examines all three planes with three different normalizations. Outputs from these nine total paths are concatenated into a 3D volume that is then passed to a 3D convolutional neural network to output a final lesion mask. We trained and tested our method on datasets from three sources: Medical College of Wisconsin (MCW), Kessler Foundation (KF), and the publicly available Anatomical Tracings of Lesions After Stroke (ATLAS) dataset. To promote wide applicability, lesions were included from both subacute (1 to 5 weeks) and chronic ( >  3 months) phases post stroke, and were of both hemorrhagic and ischemic etiology. Cross-study validation results (with independent training and validation datasets) were obtained to compare with previous methods based on naive Bayes, random forests, and three recently published convolutional neural networks. Model performance was quantified in terms of the Dice coefficient, a measure of spatial overlap between the model-identified lesion and the human expert-identified lesion, where 0 is no overlap and 1 is complete overlap. Training on the KF and MCW images and testing on the ATLAS images yielded a mean Dice coefficient of 0.54. This was reliably better than the next best previous model, UNet, at 0.47. Reversing the train and test datasets yields a mean Dice of 0.47 on KF and MCW images, whereas the next best UNet reaches 0.45. With all three datasets combined, the current system compared to previous methods also attained a reliably higher cross-validation accuracy. It also achieved high Dice values for many smaller lesions that existing methods have difficulty identifying. Overall, our system is a clear improvement over previous methods for automating stroke lesion segmentation, bringing us an important step closer to the inter-rater accuracy level of human experts., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Spatial neglect commonly follows right hemisphere stroke. It is defined as impaired contralesional stimulus detection, response, or action, causing functional disability. While prism adaptation treatment is highly promising to promote functional recovery of spatial neglect, not all individuals respond. Consistent with a primary effect of prism adaptation on spatial movements, we previously demonstrated that functional improvement after prism adaptation treatment is linked to frontal lobe lesions. However, that study was a treatment-only study with no randomised control group. The current study randomised individuals with spatial neglect to receive 10 days of prism adaptation treatment or to receive only standard care (control group). Replicating our earlier results, we found that the presence of frontal lesions moderated response to prism adaptation treatment: among prism-treated patients, only those with frontal lesions demonstrated functional improvements in their neglect symptoms. Conversely, among individuals in the standard care control group, the presence of frontal lesions did not modify recovery. These results suggest that further research is needed on how frontal lesions may predict response to prism adaptation treatment. Additionally, the results help elucidate the neural network involved in spatial movement and could be used to aid decisions about treatment.

Better understanding of cerebral blood flow (CBF) perfusion in stroke recovery can help inform decisions about optimal timing and targets of restorative treatments. In this study, we examined the relationship between cerebral perfusion and recovery from stroke-induced reading deficits. Left stroke patients were tested with a noninvasive CBF measure (arterial spin labeling) <5 weeks post-stroke, and a subset had follow up testing >3 months post-stroke. We measured blood flow perfusion within the left and right sides of the brain, in areas surrounding the lesion, and areas belonging to the reading network. Two hypotheses were tested. The first was that recovery of reading function depends on increased perfusion around the stroke lesion. This hypothesis was not supported by our findings. The second hypothesis was that increased perfusion of intact areas within the reading circuit is tightly coupled with recovery. Our findings are consistent with this hypothesis. Specifically, higher perfusion in the left reading network measured during the subacute stroke period predicted better reading ability and phonology competence in the chronic period. In contrast, higher perfusion of the right homologous regions was associated with decreased reading accuracy and phonology competence in the subacute and chronic periods. These findings suggest that recovery of reading and language competence may rely on improved blood flow in the reading network of the language-dominant hemisphere., (© 2019 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

Antibody-drug conjugates (ADCs) containing pyrrolobenzodiazepine (PBD) dimers are currently being evaluated in human oncology clinical trials with encouraging results. To further improve the therapeutic window, next-generation PBD drug-linker design has focused on the inclusion of additional tumor-selective triggers and use of lower-potency PBDs. β-Glucuronidase is a well-known target for discovery prodrugs due to increased presence in tumor cells and microenvironment. In this study, a β-glucuronidase cleavable cap was investigated at the PBD N10-position and compared with corresponding free imine ADCs. SG3600 (glucuronide) ADCs showed in vitro and in vivo efficacy/tolerability comparable to SG3400 (imine) ADCs, and good 50% inhibitory concentration differentials were observed in vitro between control non-antigen-targeted ADCs and targeted ADCs. Dependence on β-glucuronidase for SG3600 activity was demonstrated through CRISPRCas9 knockdown studies and addition of exogenous β-glucuronidase. SG3600 showed better serum stability, improved conjugation efficiency and was able to reach high drug-to-antibody ratio without aggregation., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Importance: Many patients receive suboptimal rehabilitation therapy doses after stroke owing to limited access to therapists and difficulty with transportation, and their knowledge about stroke is often limited. Telehealth can potentially address these issues., Objectives: To determine whether treatment targeting arm movement delivered via a home-based telerehabilitation (TR) system has comparable efficacy with dose-matched, intensity-matched therapy delivered in a traditional in-clinic (IC) setting, and to examine whether this system has comparable efficacy for providing stroke education., Design, Setting, and Participants: In this randomized, assessor-blinded, noninferiority trial across 11 US sites, 124 patients who had experienced stroke 4 to 36 weeks prior and had arm motor deficits (Fugl-Meyer [FM] score, 22-56 of 66) were enrolled between September 18, 2015, and December 28, 2017, to receive telerehabilitation therapy in the home (TR group) or therapy at an outpatient rehabilitation therapy clinic (IC group). Primary efficacy analysis used the intent-to-treat population., Interventions: Participants received 36 sessions (70 minutes each) of arm motor therapy plus stroke education, with therapy intensity, duration, and frequency matched across groups., Main Outcomes and Measures: Change in FM score from baseline to 4 weeks after end of therapy and change in stroke knowledge from baseline to end of therapy., Results: A total of 124 participants (34 women and 90 men) had a mean (SD) age of 61 (14) years, a mean (SD) baseline FM score of 43 (8) points, and were enrolled a mean (SD) of 18.7 (8.9) weeks after experiencing a stroke. Among those treated, patients in the IC group were adherent to 33.6 of the 36 therapy sessions (93.3%) and patients in the TR group were adherent to 35.4 of the 36 assigned therapy sessions (98.3%). Patients in the IC group had a mean (SD) FM score change of 8.36 (7.04) points from baseline to 30 days after therapy (P < .001), while those in the TR group had a mean (SD) change of 7.86 (6.68) points (P < .001). The covariate-adjusted mean FM score change was 0.06 (95% CI, -2.14 to 2.26) points higher in the TR group (P = .96). The noninferiority margin was 2.47 and fell outside the 95% CI, indicating that TR is not inferior to IC therapy. Motor gains remained significant when patients enrolled early (<90 days) or late (≥90 days) after stroke were examined separately., Conclusions and Relevance: Activity-based training produced substantial gains in arm motor function regardless of whether it was provided via home-based telerehabilitation or traditional in-clinic rehabilitation. The findings of this study suggest that telerehabilitation has the potential to substantially increase access to rehabilitation therapy on a large scale., Trial Registration: ClinicalTrials.gov identifier: NCT02360488.

Purpose: We sought to examine the pharmacodynamic activation of the DNA damage response (DDR) pathway in tumors following anticancer treatment for confirmation of target engagement., Experimental Design: We evaluated the time course and spatial activation of 3 protein biomarkers of DNA damage recognition and repair (γH2AX, pS343-Nbs1, and Rad51) simultaneously in a quantitative multiplex immunofluorescence assay (IFA) to assess DDR pathway activation in tumor tissues following exposure to DNA-damaging agents., Results: Because of inherent biological variability, baseline DDR biomarker levels were evaluated in a colorectal cancer microarray to establish clinically relevant thresholds for pharmacodynamic activation. Xenograft-bearing mice and clinical colorectal tumor biopsies obtained from subjects exposed to DNA-damaging therapeutic regimens demonstrated marked intratumor heterogeneity in the timing and extent of DDR biomarker activation due, in part, to the cell-cycle dependency of DNA damage biomarker expression., Conclusions: We have demonstrated the clinical utility of this DDR multiplex IFA in preclinical models and clinical specimens following exposure to multiple classes of cytotoxic agents, DNA repair protein inhibitors, and molecularly targeted agents, in both homologous recombination-proficient and -deficient contexts. Levels exceeding 4% nuclear area positive (NAP) γH2AX, 4% NAP pS343-Nbs1, and 5% cells with ≥5 Rad51 nuclear foci indicate a DDR activation response to treatment in human colorectal cancer tissue. Determination of effect-level cutoffs allows for robust interpretation of biomarkers with significant interpatient and intratumor heterogeneity; simultaneous assessment of biomarkers induced at different phases of the DDR guards against the risk of false negatives due to an ill-timed biopsy., (©2019 American Association for Cancer Research.)

Purpose of Review: Spatial neglect is asymmetric orienting and action after a brain lesion, causing functional disability. It is common after a stroke; however, it is vastly underdocumented and undertreated. This article addresses the implementation gap in identifying and treating spatial neglect, to reduce disability and improve healthcare costs and burden., Recent Findings: Professional organizations published recommendations to implement spatial neglect care. Physicians can lead an interdisciplinary team: functionally relevant spatial neglect assessment, evidence-based spatial retraining, and integrated spatial and vision interventions can optimize outcomes. Research also strongly suggests spatial neglect adversely affects motor systems. Spatial neglect therapy might thus "kick-start" rehabilitation and improve paralysis recovery. Clinicians can implement new techniques to detect spatial neglect and lead interdisciplinary teams to promote better, integrated spatial neglect care. Future studies of brain imaging biomarkers to detect spatial neglect, and real-world applicability of prism adaptation treatment, are needed.

Background: As medicinal and recreational marijuana use broadens across the United States, knowledge of its effects on the body will become increasingly important to all health care providers, including surgeons., Data Sources: We performed a literature review of Pubmed for articles discussing the basic science related to cannabinoids, as well as articles regarding cannabinoid medications, and cannabis use in surgical patients., Conclusions: The primary components in the cannabis plant, tetrahydrocannabinol (THC) and cannabidiol (CBD), have been made available in numerous forms and formulations to treat multiple medical conditions, and recreational access to marijuana is increasing. Of particular importance to the surgeon may be their effects on prolonging intestinal motility, decreasing inflammation, increasing hunger, mitigating pain, and reducing nausea and vomiting. Perioperative use of medicinal or recreational marijuana will become increasingly prevalent, and the surgeon should be aware of the positive and negative effects of these cannabinoids., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Emerging research suggests spatial neglect after right stroke is linked to dysfunctional attention and motor networks. Advanced functional connectivity analysis clarified brain network recovery, however we need to know how networks participate in adaptive motor performance. We need to verify network changes associated with validated functional measures and spatial-motor performance in spatial neglect, especially in patients with large brain lesions and significant disability. This study tested whether disability-relevant spatial neglect associates with different patterns of resting state functional connectivity between motor, dorsal and ventral attention networks (MN, DAN and VAN). Right stroke patients had spatial neglect (n = 8) or not (n = 10) on the Behavioural Inattention Test-conventional. Spatial neglect patients had weaker intranetwork VAN connectivity, and reduced internetwork connectivity between VAN and left frontal eye field (DAN), and between VAN and the left primary motor area (MN). These network impairments might explain the co-occurrence of attention and motor deficits in spatial neglect, and open a path to assessing functional connectivity in clinical trials of combined spatial retraining and motor rehabilitation after stroke., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Spatial neglect is asymmetric attention, orienting, and action causing functional disability. It is linked to higher-order cortical sensory processing; however, spatial motor "Aiming" processing is critical to fundamental, adaptive environmental movement and daily life function. The cingulate cortex, in particular the anterior cingulate and anterior midcingulate cortex, is strongly linked to spatial Aiming deficits and likely to predict daily life disability in spatial neglect. The authors review the impact and mechanisms of spatial neglect and then describe specific symptoms associated with spatial neglect that are theoretically linked to cingulate cortical functions or associated with lesions extending to cingulate regions in a well-characterized spatial neglect cohort. The treatment implications for a link between cingulate cortex spatial Aiming neglect and therapies that improve spatial action, arousal, and persistence are discussed. Clinicians may want to consider theoretically motivated treatments targeted at specific symptoms as well as use treatments supported for spatial neglect based on unselected and uncharacterized groups., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Delirium is an acute and fluctuating disturbance in cognition attention and awareness that is often a reflection of abnormal physiological condition of an individual. Delirium is highly prevalent among an older population and is associated with high mortality, poor medical and functional outcomes, and high healthcare cost. Delirium often has iatrogenic triggers, and it has been recognized as a quality indicator of healthcare organizations. Despite its high prevalence and significance, more than 50% of the delirium cases are underrecognized by healthcare professionals and remained untreated. Most patients in inpatient rehabilitation facilities are older adults with multiple risk factors for delirium including operation, intensive care stay, multiple co-morbidities, and impaired mobility. Early detection, intervention, and primary prevention of delirium will allow patients to avoid additional morbidities and reach their maximum functional potential during their rehabilitation stay. After the systematic implementation of delirium screening in our inpatient rehabilitation facility, we found that 10.3% of patients were screened positive for delirium at admission. This review discusses the systematic implementation of screening and intervention for delirium as well as the epidemiology of delirium to increase the awareness and guide clinical practice for clinicians in inpatient rehabilitation facilities.

Objective: Spatial neglect (SN) constitutes a substantial barrier to functional recovery after acquired brain injury. However, because of its multimodal nature, no single test can capture all the signs of SN. To provide a clinically feasible solution, we used conventional neuropsychological tests as well as the Catherine Bergego Scale (CBS) via the Kessler Foundation Neglect Assessment Process (KF-NAP). The goal was to add evidence that a global approach should detect better even subtle signs of SN., Method: Fourteen individuals with lesions located in the right cerebral hemisphere participated in the study. Participants were assessed with a comprehensive battery of neuropsychological tests, comprising a set of visuospatial tests to evaluate several spatial domains. In addition, patients underwent functional assessment with the Barthel Index, the Functional Independence Measure (FIM), and the CBS via KF-NAP., Results: The CBS via KF-NAP was associated with the visuospatial paper-based tests (p = .004) as well as the Motor FIM (p = .003), and was more sensitive than the Behavioral Inattention Test-Conventional in detecting SN (p = .014)., Conclusions: We showed that the CBS via KF-NAP was able: (a) to detect functional impairment, especially motor, related to SN; (b) to selectively measures spatial rather than nonspatial dysfunctions; and (c) to be highly sensitive in detecting SN signs especially in those patients with mild severity, covering several aspects of SN manifestations. The patient's SN diagnosis based on the CBS via KF-NAP is clinically important and directly relevant to care planning and goal setting. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Spatial neglect is a disorder of attention, perception, and processing of stimuli in contralesional space. The heterogeneous behaviors involve diverse neuroanatomical mechanisms. Anecdotal evidence suggests that neural circuitry of active spatial perception may differ from that used to encode spatial memory. These differences can escape detection by conventional assessments, thereby leading to missed diagnoses. We present a case, in an artist who demonstrates selective impairment in a contralesional space during active Where spatial perception. His performance is better when asked to draw entirely from memory. This case highlights the variability in neglect, importance for comprehensive testing, and encourages further investigation.

The objective of this study was to assess the current use of patient-centered psychosocial assessments for the evaluation of children with central precocious puberty (CPP). Studies evaluating the psychosocial impact of CPP were identified through searches of the PubMed and Cochrane Library databases, ClinicalTrials.gov, a drug prescribing information database, and regulatory websites. Studies were screened using prespecified inclusion and exclusion criteria. Potentially relevant patient-centered outcome assessments (including patient-, parent- or observer-reported measures) used in the identified studies were evaluated in detail for their relevance in CPP. Of the 467 studies identified, 15 met the inclusion criteria. Frequently assessed concepts included depression and anxiety, behavior and behavioral problems, body image and self-esteem and personality type/characteristics. Among the assessments used in the identified studies, the Child Behavior Checklist, Pediatric Quality of Life Inventory (PedsQL), SF-10 for Children and Child Health Questionnaire were comprehensively evaluated. The PedsQL showed promise as a patient-centered outcome measure in CPP. Although there is a lack of validated tools measuring psychosocial health and health-related quality of life in patients with CPP, the PedsQL captures issues seen in this patient population and is relatively easy to administer. Further studies using this and other tools in children with CPP are needed.

Delirium is an acute attention and cognitive dysfunction, adversely affecting functional outcomes and mortality. As many as half of hospitalized right brain stroke survivors may develop delirium. Further, about 50% of right stroke patients experience spatial neglect, impairing safety and recovery. In this review we explore the brain mechanisms, which may explain the high incidence of delirium and spatial neglect after right-brain stroke. We suggest that brain networks for spatial attention and arousal, composed of ascending projections from the midbrain nuclei and integrating dorsal and ventral cortical and limbic components, may underlie impairments in delirium and spatial neglect. We propose that lateralized deficits in spatial neglect may arise because cortical and limbic components of these functional networks are disproportionally impaired by right-brain strokes, and that spatial neglect may lower the threshold for developing delirium. An improved understanding of the brain basis of delirium and spatial neglect could provide a critical biomarker for initiating preventive care in stroke patients at high risk of hospital morbidity and loss of independence., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The purpose of this study is to compare failure rate and functional outcome in young, active patients (< 25 years) with two-incision (rear-entry) versus transtibial (all-endoscopic) anterior cruciate ligament (ACL) reconstructions.Utilizing a computerized relational database (Access 2007, Microsoft Inc., Redmond, WA), 480 patients were identified that underwent ACL reconstruction, using a bone-patellar-tendon-bone autograft, by a single surgeon between January 2000 and December 2010 via a transtibial or two-incision technique. Totally, 377 (78.6%) of these patients were less than 25 years of age. Data for each patient were collected at their initial clinic visit, at the time of surgery, and at each follow-up clinic visit and entered into the computerized relational database. Overall, 274 patients (72.7%) underwent ACL reconstruction with a transtibial technique, and 103 patients (27.3%) underwent reconstruction with a two-incision technique. Failures were identified as a 2+ Lachman, 1+ or greater pivot shift, or a KT-1000 arthrometer difference of five or more.In patients < 25 years of age, there were 10 failures (9.7%) out of 103 patients undergoing a two-incision reconstruction and 28 failures (10.2%) out of 274 patients undergoing a transtibial reconstruction ( p  = 1.000). There was no statistical significance between the failure rate in the two different groups in regards to gender, meniscal tear, activity level, or any other factor that was analyzed.Our study showed no statistical difference between the two-incision technique and the transtibial technique for ACL reconstruction using bone-patellar-tendon-bone autograft with an overall 10.1% failure rate in young, active patients (< 25 years of age). The level of evidence is level IV., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)