Predicting long-term outcome after acute ischemic stroke: a simple index works in patients from controlled clinical trials

Background and Purpose—An early and reliable prognosis for recovery in stroke patients is important for initiation of individual treatment and for informing patients and relatives. We recently developed and validated models for predicting survival and functional independence within 3 months after acute stroke, based on age and the National Institutes of Health Stroke Scale score assessed within 6 hours after stroke. Herein we demonstrate the applicability of our models in an independent sample of patients from controlled clinical trials. Methods—The prognostic models were used to predict survival and functional recovery in 5419 patients from the Virtual International Stroke Trials Archive (VISTA). Furthermore, we tried to improve the accuracy by adapting intercepts and estimating new model parameters. Results—The original models were able to correctly classify 70.4% (survival) and 72.9% (functional recovery) of patients. Because the prediction was slightly pessimistic for patients in the controlled trials, adapting the intercept improved the accuracy to 74.8% (survival) and 74.0% (functional recovery). Novel estimation of parameters, however, yielded no relevant further improvement. Conclusions—For acute ischemic stroke patients included in controlled trials, our easy-to-apply prognostic models based on age and National Institutes of Health Stroke Scale score correctly predicted survival and functional recovery after 3 months. Furthermore, a simple adaptation helps to adjust for a different prognosis and is recommended if a large data set is available. (Stroke. 2008;39:000-000.

Symptomatic and Functional recovery: Does symptom severity affect the recovery of executive functioning in people with a psychotic disorder?

Background:Recovery in psychotic disorder patients is a multidimensional concept that can include personal, symptomatic, societal and functional recovery. Here we define Functional Recovery (FR) as recovery or compensation after the loss or impairment of skills in different cognitive functions. Some of the most impaired cognitive functions in psychosis are the executive functions, whose impairment in people with a psychotic disorder can produce problems that are difficult to overcome, partly because treatment often focuses only on Symptomatic Recovery (SR). Although symptom severity may be a risk factor for longstanding impairments of executive functioning, the association is not always found. To date, there has been little research on the association between the 2.MethodThis study is part of the UP’S study, a longitudinal cohort study of patients with a psychotic disorder. The Behaviour Rating Inventory of Executive Functioning Adult version (BRIEF-A) was used to measure FR at baseline and after 1 year. SR was measured using the Positive and Negative Symptom Scale-Remission (PANSS-R), also at baseline and 1 year? At both time points, correlations were computed as cross-sectional analyses. For the longitudinal analysis, the difference scores were used to calculate generalized linear models. Model selection was based on the Wald-Chi square test.Results323 people were included for the baseline assessment of the UP’S study, 163 of whom had completed the T1 follow-up measurement at the time of this study. We found a moderate association between PANSS-R baseline scores and BRIEF-A baseline scores (β=3.76). While there was also an association between the PANSS-R score at baseline and the BRIEF-A difference scores (β=1.67), we found no association between the PANSS-R difference scores and the BRIEF-A differences scores.ConclusionOur finding that less overall symptom severity was associated with 1 year improvement in executive functioning suggests that symptom severity could be a way of improving executive functioning over a year. However, as no link was found within the year between changes in symptoms and changes in executive functioning, it is possible that symptom severity does not have an immediate effect on executive functioning, but that its effect is delayed. This leaves scope for targeted interventions to improve executive functioning, and thus functional recovery

Regularized pointwise map recovery from functional correspondence

The concept of using functional maps for representing dense correspondences between deformable shapes has proven to be extremely effective in many applications. However, despite the impact of this framework, the problem of recovering the point-to-point correspondence from a given functional map has received surprisingly little interest. In this paper, we analyse the aforementioned problem and propose a novel method for reconstructing pointwise correspondences from a given functional map. The proposed algorithm phrases the matching problem as a regularized alignment problem of the spectral embeddings of the two shapes. Opposed to established methods, our approach does not require the input shapes to be nearly-isometric, and easily extends to recovering the point-to-point correspondence in part-to-whole shape matching problems. Our numerical experiments demonstrate that the proposed approach leads to a significant improvement in accuracy in several challenging cases

Recovery: What does this mean to patients with low back pain?

Copyright © 2009, American College of Rheumatology. This article is freely available through the publisher’s link below.Objective - To explore patients' perceptions of recovery from low back pain, about which little is known. Methods - A qualitative study was conducted in which 36 participants, either recovered or unrecovered from low back pain, participated in focus groups. Interviews were audiorecorded and transcribed verbatim. Framework analysis was used to identify emergent themes and domains of recovery. Results - Patients' views of recovery encompassed a range of factors that can be broadly classified into the domains of symptom attenuation, improved capacity to perform a broad scope of self-defined functional activities, and achievement of an acceptable quality of life. An interactive model is proposed to describe the relationships between these domains, cognitive appraisal of the pain experience, and self-rated recovery. Pain attenuation alone was not a reliable indicator of recovery. Conclusion - The construct of recovery for typical back pain patients seeking primary care is more complex than previously recognized and is a highly individual construct, determined by appraisal of the impact of symptoms on daily functional activities as well as quality of life factors. These findings will be valuable for reassessing how to optimize measures of recovery from low back pain by addressing the spectrum of factors patients consider meaningful

Polycistronic Delivery of IL-10 and NT-3 Promotes Oligodendrocyte Myelination and Functional Recovery in a Mouse Spinal Cord Injury Model.

One million estimated cases of spinal cord injury (SCI) have been reported in the United States and repairing an injury has constituted a difficult clinical challenge. The complex, dynamic, inhibitory microenvironment postinjury, which is characterized by proinflammatory signaling from invading leukocytes and lack of sufficient factors that promote axonal survival and elongation, limits regeneration. Herein, we investigated the delivery of polycistronic vectors, which have the potential to coexpress factors that target distinct barriers to regeneration, from a multiple channel poly(lactide-co-glycolide) (PLG) bridge to enhance spinal cord regeneration. In this study, we investigated polycistronic delivery of IL-10 that targets proinflammatory signaling, and NT-3 that targets axonal survival and elongation. A significant increase was observed in the density of regenerative macrophages for IL-10+NT-3 condition relative to conditions without IL-10. Furthermore, combined delivery of IL-10+NT-3 produced a significant increase of axonal density and notably myelinated axons compared with all other conditions. A significant increase in functional recovery was observed for IL-10+NT-3 delivery at 12 weeks postinjury that was positively correlated to oligodendrocyte myelinated axon density, suggesting oligodendrocyte-mediated myelination as an important target to improve functional recovery. These results further support the use of multiple channel PLG bridges as a growth supportive substrate and platform to deliver bioactive agents to modulate the SCI microenvironment and promote regeneration and functional recovery. Impact statement Spinal cord injury (SCI) results in a complex microenvironment that contains multiple barriers to regeneration and functional recovery. Multiple factors are necessary to address these barriers to regeneration, and polycistronic lentiviral gene therapy represents a strategy to locally express multiple factors simultaneously. A bicistronic vector encoding IL-10 and NT-3 was delivered from a poly(lactide-co-glycolide) bridge, which provides structural support that guides regeneration, resulting in increased axonal growth, myelination, and subsequent functional recovery. These results demonstrate the opportunity of targeting multiple barriers to SCI regeneration for additive effects

Behavioral Recovery and Early Decision Making in Patients with Prolonged Disturbance in Consciousness after Traumatic Brain Injury

The extent of behavioral recovery that occurs in patients with traumatic disorders of consciousness (DoC) following discharge from the acute care setting has been under-studied and increases the risk of overly pessimistic outcome prediction. The aim of this observational cohort study was to systematically track behavioral and functional recovery in patients with prolonged traumatic DoC following discharge from the acute care setting. Standardized behavioral data were acquired from 95 patients in a minimally conscious (MCS) or vegetative state (VS) recruited from 11 clinic sites and randomly assigned to the placebo arm of a previously completed prospective clinical trial. Patients were followed for 6 weeks by blinded observers to determine frequency of recovery of six target behaviors associated with functional status. The Coma Recovery Scale-Revised and Disability Rating Scale were used to track reemergence of target behaviors and assess degree of functional disability, respectively. Twenty percent (95% confidence interval [CI]: 13-30%) of participants (mean age 37.2; median 47 days post-injury; 69 men) recovered all six target behaviors within the 6 week observation period. The odds of recovering a specific target behavior were 3.2 (95% CI: 1.2-8.1) to 7.8 (95% CI: 2.7-23.0) times higher for patients in MCS than for those in VS. Patients with preserved language function ("MCS+") recovered the most behaviors (p ≤ 0.002) and had the least disability (p ≤ 0.002) at follow-up. These findings suggest that recovery of high-level behaviors underpinning functional independence is common in patients with prolonged traumatic DoC. Clinicians involved in early prognostic counseling should recognize that failure to emerge from traumatic DoC before 28 days does not necessarily portend unfavorable outcome

Symptomatic and Functional Recovery:Does symptom severity affect the recovery of executive functioning in people with psychotic disorders?

Background: Recovery in psychotic disorder patients is a multidimensional concept that can include personal, symptomatic, societal and functional recovery. Here we define Functional Recovery (FR) as recovery or compensation after the loss or impairment of skills in different cognitive functions. Some of the most impaired cognitive functions in psychosis are the executive functions, whose impairment in people with a psychotic disorder can produce problems that are difficult to overcome, partly because treatment often focuses only on Symptomatic Recovery (SR). Although symptom severity may be a risk factor for longstanding impairments of executive functioning, the association is not always found. To date, there has been little research on the association between the 2. MethodThis study is part of the UP’S study, a longitudinal cohort study of patients with a psychotic disorder. The Behaviour Rating Inventory of Executive Functioning Adult version (BRIEF-A) was used to measure FR at baseline and after 1 year. SR was measured using the Positive and Negative Symptom Scale-Remission (PANSS-R), also at baseline and 1 year? At both time points, correlations were computed as cross-sectional analyses. For the longitudinal analysis, the difference scores were used to calculate generalized linear models. Model selection was based on the Wald-Chi square test. Results323 people were included for the baseline assessment of the UP’S study, 163 of whom had completed the T1 follow-up measurement at the time of this study. We found a moderate association between PANSS-R baseline scores and BRIEF-A baseline scores (β=3.76). While there was also an association between the PANSS-R score at baseline and the BRIEF-A difference scores (β=1.67), we found no association between the PANSS-R difference scores and the BRIEF-A differences scores. ConclusionOur finding that less overall symptom severity was associated with 1 year improvement in executive functioning suggests that symptom severity could be a way of improving executive functioning over a year. However, as no link was found within the year between changes in symptoms and changes in executive functioning, it is possible that symptom severity does not have an immediate effect on executive functioning, but that its effect is delayed. This leaves scope for targeted interventions to improve executive functioning, and thus functional recovery

Co-transplantation of Human Embryonic Stem Cell-derived Neural Progenitors and Schwann Cells in a Rat Spinal Cord Contusion Injury Model Elicits a Distinct Neurogenesis and Functional Recovery

Co-transplantation of neural progenitors (NPs) with Schwann cells (SCs) might be a way to overcome low rate of neuronal differentiation of NPs following transplantation in spinal cord injury (SCI) and the improvement of locomotor recovery. In this study, we initially generated NPs from human embryonic stem cells (hESCs) and investigated their potential for neuronal differentiation and functional recovery when co-cultured with SCs in vitro and co-transplanted in a rat acute model of contused SCI. Co-cultivation results revealed that the presence of SCs provided a consistent status for hESC-NPs and recharged their neural differentiation toward a predominantly neuronal fate. Following transplantation, a significant functional recovery was observed in all engrafted groups (NPs, SCs, NPs+SCs) relative to the vehicle and control groups. We also observed that animals receiving co-transplants established a better state as assessed with the BBB functional test. Immunohistofluorescence evaluation five weeks after transplantation showed invigorated neuronal differentiation and limited proliferation in the co-transplanted group when compared to the individual hESC-NPs grafted group. These findings have demonstrated that the co-transplantation of SCs with hESC-NPs could offer a synergistic effect, promoting neuronal differentiation and functional recovery