Important Determinants Of Functional Outcome Research Articles

Brain Volume: An Important Determinant of Functional Outcome After Acute Ischemic Stroke

ObjectiveTo determine whether brain volume is associated with functional outcome after acute ischemic stroke (AIS). Patients and MethodsThis study was conducted between July 1, 2014, and March 16, 2019. We analyzed cross-sectional data of the multisite, international hospital-based MRI-Genetics Interface Exploration study with clinical brain magnetic resonance imaging obtained on admission for index stroke and functional outcome assessment. Poststroke outcome was determined using the modified Rankin Scale score (0-6; 0 = asymptomatic; 6 = death) recorded between 60 and 190 days after stroke. Demographic characteristics and other clinical variables including acute stroke severity (measured as National Institutes of Health Stroke Scale score), vascular risk factors, and etiologic stroke subtypes (Causative Classification of Stroke system) were recorded during index admission. ResultsUtilizing the data from 912 patients with AIS (mean ± SD age, 65.3±14.5 years; male, 532 [58.3%]; history of smoking, 519 [56.9%]; hypertension, 595 [65.2%]) in a generalized linear model, brain volume (per 155.1 cm3) was associated with age (β −0.3 [per 14.4 years]), male sex (β 1.0), and prior stroke (β −0.2). In the multivariable outcome model, brain volume was an independent predictor of modified Rankin Scale score (β −0.233), with reduced odds of worse long-term functional outcomes (odds ratio, 0.8; 95% CI, 0.7-0.9) in those with larger brain volumes. ConclusionLarger brain volume quantified on clinical magnetic resonance imaging of patients with AIS at the time of stroke purports a protective mechanism. The role of brain volume as a prognostic, protective biomarker has the potential to forge new areas of research and advance current knowledge of the mechanisms of poststroke recovery.

Rich-Club Organization: An Important Determinant of Functional Outcome After Acute Ischemic Stroke.

Objective: To determine whether the rich-club organization, essential for information transport in the human connectome, is an important biomarker of functional outcome after acute ischemic stroke (AIS).Methods: Consecutive AIS patients (N = 344) with acute brain magnetic resonance imaging (MRI) (<48 h) were eligible for this study. Each patient underwent a clinical MRI protocol, which included diffusion weighted imaging (DWI). All DWIs were registered to a template on which rich-club regions have been defined. Using manual outlines of stroke lesions, we automatically counted the number of affected rich-club regions and assessed its effect on the National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS; obtained at 90 days post-stroke) scores through ordinal regression.Results: Of 344 patients (median age 65, inter-quartile range 54–76 years) with a median DWI lesion volume (DWIv) of 3cc, 64% were male. We established that an increase in number of rich-club regions affected by a stroke increases the odds of poor stroke outcome, measured by NIHSS (OR: 1.77, 95%CI 1.41–2.21) and mRS (OR: 1.38, 95%CI 1.11–1.73). Additionally, we demonstrated that the OR exceeds traditional markers, such as DWIv (ORNIHSS 1.08, 95%CI 1.06–1.11; ORmRS 1.05, 95%CI 1.03–1.07) and age (ORNIHSS 1.03, 95%CI 1.01–1.05; ORmRS 1.05, 95%CI 1.03–1.07).Conclusion: In this proof-of-concept study, the number of rich-club nodes affected by a stroke lesion presents a translational biomarker of stroke outcome, which can be readily assessed using standard clinical AIS imaging protocols and considered in functional outcome prediction models beyond traditional factors.

Effect of Pretreatment Blood Pressure on Outcomes in Thrombolysed Acute Ischemic Stroke Patients: A Systematic Review and Meta-analysis

BackgroundBlood pressure (BP) is an important determinant of functional outcome in acute ischemic stroke (AIS) patients treated with intravenous tissue plasminogen activator (IV-tPA). Current guidelines recommend a BP target of 185/110 mmHg before IV-tPA bolus and maintaining it at less than 180/105 mmHg for the first 24 hours. However, the effect of blood pressure on various outcome measures after systemic thrombolysis remains unclear. MethodsFollowing a systematic search of Medline and EMBASE, all observational studies reporting effect of pretreatment BP on 90-day functional outcome as measured by the modified Rankin Scale (mRS) and/ or incidence of symptomatic intracranial hemorrhage (sICH) in AIS patients receiving thrombolytic therapy were included. ResultsOf 2181 studies screened, 26 studies, involving 38,937 subjects, met inclusion criteria. Higher prethrombolysis systolic BP was significantly-associated with poorer 90-day functional outcome (Mean difference 3.87 mmHg; 95% confidence interval [CI] 1.18-6.56) and increased incidence of sICH (Mean difference 5.31; 95% CI 2.22-8.40). When studies were stratified by different cut-offs for functional outcome (mRS 0-1 versus 0-2) and definitions of sICH used (Randomized controlled trials or SITS-MOST), there was no significant difference in mean difference between the subgroups. ConclusionsOur data showed that higher prethrombolysis SBP was associated with poorer outcomes in thrombolysed acute ischemic stroke patients. This may suggest that more aggressive lowering of BP below the current recommendations prior to thrombolysis could be beneficial. The effect of early BP trends after tPA infusion could not be evaluated due to limited available data. Ongoing randomized clinical trials, like ENCHANTED, may provide further insights into the current guidelines and optimal BP levels.

Psychiatric disability as mediator of the neurocognition-functioning link in schizophrenia spectrum disorders: SEM analysis using the Evaluation of Cognitive Processes involved in Disability in Schizophrenia (ECPDS) scale

The functional outcome in schizophrenia spectrum disorders is affected by multiple factors such as cognitive performance and clinical symptoms. Psychiatric disability may be another important determinant of functional outcome. The purpose of this study was to test whether schizophrenia symptoms and psychiatric disability mediated the association between cognition and functioning.Between April 2013 and July 2017, we included 108 community-dwelling adults with stable schizophrenia spectrum disorder in a multicenter study. Psychiatric disability was assessed with the Evaluation of Cognitive Processes involved in Disability in Schizophrenia (ECPDS) scale by relatives of patients. ECPDS focused on the broad array of motivational, neurocognitive, sociocognitive, and metacognitive impairments that result in activity restrictions. We used a battery of tests to assess seven cognition domains (processing speed, attention/vigilance, working, verbal and visual memory, reasoning and problem solving, and executive functioning) and cross-sectional structural equation modeling (SEM) for the mediation analyses. We estimated the one-year temporal stability of ECPDS scores in 45 participants.The model provided showed good fit and explained 43.9% of the variance in functioning. The effect of neurocognition on functioning was fully mediated by symptoms (proportion mediated: 36.5%) and psychiatric disability (proportion mediated: 31.3%). The ECPDS score had acceptable one-year temporal stability.The ECPDS scale has satisfactory psychometric properties, and shows significant convergence with neurocognition and functioning, suggesting a role for this tool in the routine evaluation of cognitive remediation needs. Our model validates psychiatric disability as a crucial step from cognitive impairment to restricted participation in life situations.

The Importance of Social Cognition in Improving Functional Outcomes in Schizophrenia.

Social cognition has become recognized as an important driver of functional outcomes and overall recovery in patients with schizophrenia, mediating the relationship between neurocognition and social functioning. Since antipsychotic therapy targeting remission of clinical symptoms has been shown to have a limited impact on social cognition, there has been an increasing drive to develop therapeutic strategies to specifically improve social cognition in schizophrenia. We sought to review current evidence relating to social cognition in schizophrenia and its clinical implications, including interventions designed to target the core domains of social cognition (emotion processing, theory of mind, attributional bias, and social perception) as a means of improving functional outcomes and thereby increasing the likelihood of recovery. Relevant articles were identified by conducting a literature search in PubMed using the search terms “schizophrenia” AND “cognition” AND “social functioning,” limited to Title/, over a time period of the past 10 years. Current evidence demonstrates that schizophrenia is associated with impairments in all four core domains of social cognition, during the pre-first-episode, first-episode, early, and chronic phases of the disease, and that such impairments are important determinants of functional outcome. Interventions targeting the four core domains of social cognition comprise psychosocial approaches (social cognition training programs) and pharmacological therapies. Social cognition training programs targeting multiple and specific core domains of social cognition have shown promise in improving social cognition skills, which, in some cases, has translated into improvements in functional outcomes. Use of some psychosocial interventions has additionally resulted in improvements in clinical symptoms and/or quality of life. Pharmacological therapies, including oxytocin and certain antipsychotics, have yielded more mixed results, due in part to the confounding impact of factors including variation in receptor genetics, bioavailability, pharmacokinetics, and drug–drug interactions, and inconsistencies between study designs and medication dosages. Additional research is required to advance our understanding of the role of social cognition in schizophrenia, and to further establish the utility of targeted interventions in this setting.

Effects of Malunited Fractured Distal End of Radius on the Morphometric Parameters of Distal Radioulnar Joint in Old Age Group

Background: Fifteen per cent of all upper limb fractures occur in distal end of the radius. Occurrence of such fracture has increased in last 50 years. Normal values of four radiographic distal radius parameters are commonly used for accurately evaluating malunions i.e., a radial length of 11to 12 mm, a radial inclination of 22 o to 23 o, an ulnar variance of ±1mm and a palmar inclination of approximately 11 o to12 o. Our clinical practice is based on western figure due to the absence of the local database. Methods: Study was carried out on seventeen elderly (>50yr) females. Invariably the patients have a unilateral radial fracture belonging to universal classification type-Π. Results: Data of normal and malunited distal radius for each parameter were compared. In old age mean differences showed by radial length, radial inclination, ulnar variance and palmar tilt were 2.47 mm, 9.36 o, 1.85 mm and 5.59 o respectively. Conclusion: Most of our patients with radial shortening and increased dorsal tilt have pain and diminished grip strength, therefore restoration of radial length has been considered the most important determinant of functional outcome.

Free thyroxine levels are associated with cognitive abilities in subjects with early psychosis

IntroductionSubjects with a psychotic disorder show mild to moderate cognitive impairment, which is an important determinant of functional outcome. The underlying biological process of cognitive impairment in psychosis is unclear. We aimed to explore whether hypothalamic–pituitary–thyroid axis hormones or thyroid autoimmunity modulate cognitive functioning in subjects with early psychosis. MethodsWe studied 70 patients with a psychotic disorder (<3years of illness) and a control group of 37 healthy subjects (HS). Plasma levels of thyroid-stimulating hormone (TSH), free thyroxine (FT4) and thyroid-peroxidase (TPO-Abs) and thyroglobulin antibodies (TG-Abs) were determined. Cognitive assessment was performed with the MATRICS Cognitive Consensus Cognitive Battery. We also explored the relationship between thyroid variables and cognition in three subgroups of psychotic patients: psychosis not otherwise specified, affective psychosis (bipolar disorder or schizoaffective disorder) and non-affective psychosis (schizophrenia or schizophreniphorm disorder). ResultsIn patients with early psychosis, higher FT4 levels (but not TSH or thyroid antibodies) were associated with better cognitive performance in attention/vigilance and overall cognition. The relationship between FT4 levels and the attention/vigilance domain remained significant in a multivariate analysis after adjusting for education level, age, gender, substance use, and benzodiazepine and antipsychotic treatments. We did not find a significant association between FT4 and cognitive performance in HS. In the exploratory analysis by psychotic subtypes, subjects with affective psychosis had increased FT4 levels and better cognitive profile than those with non-affective psychosis. ConclusionsOur study suggests that FT4 levels are associated with cognitive abilities (attention/vigilance and overall cognition) in individuals with early psychosis.

Prognostic value of computed tomography classification systems for intra-articular calcaneus fractures.

There are several published computed tomography (CT) classification systems for calcaneus fractures, each validated by a different standard. The goal of this study was to measure which system would best predict clinical outcomes as measured by a widely used and validated musculoskeletal health status questionnaire. Forty-nine patients with isolated intra-articular joint depression calcaneus fractures more than 2 years after treatment were identified. All had preoperative CT studies and were treated with open reduction and plate fixation using a lateral extensile approach. Four different blinded reviewers classified injuries according to the CT classification systems of Crosby and Fitzgibbons, Eastwood, and Sanders. Functional outcomes evaluated with a Musculoskeletal Functional Assessment (MFA). The mean follow-up was 4.3 years. The mean MFA score was 15.7 (SD = 11.6), which is not significantly different from published values for midfoot injuries, hindfoot injuries, or both, 1 year after injury (mean = 22.1, SD = 18.4). The classification systems of Crosby and Fitzgibbons, Eastwood, and Sanders, the number of fragments of the posterior facet, and payer status were not significantly associated with outcome as determined by the MFA. The Sanders classification trended toward significance. Anterior process comminution and surgeon's overall impression of severity were significantly associated with functional outcome. The amount of anterior process comminution was an important determinant of functional outcome with increasing anterior process comminution significantly associated with worsened functional outcome (P = .04). In addition, the surgeon's overall impression of severity of injury was predictive of functional outcome (P = .02), as determined by MFA. Level III, comparative series.

Determinants of functional outcome in hip fracture patients: the role of specific neuropsychiatric symptoms

Background: The correlation between single neuropsychiatric symptoms and functional outcome in hip fracture patients is little investigated in the literature, and it is not yet established which neuropsychiatric symptoms are the most important determinants of functional outcome. Aim: To determine which neuropsychiatric symptoms are the most important determinants of functional outcome. Methods: This prospective study was carried out in 204 consecutive patients with primary diagnosis of hip fracture admitted to our Rehabilitation Unit for a course of rehabilitation. Neuropsychiatric symptoms were assessed at admission with the Neuropsychiatric Inventory (NPI). Outcome measures of rehabilitation were: final score, efficiency and effectiveness in motor-Functional Independence Measure (motor-FIM), and discharge destination. Pearson's correlation coefficients were used to assess the relationship between NPI variables and the outcome measures, while backward stepwise regression was used to identify determinants of the outcome measures. Results: Pearson's correlation showed that night-time behavior disturbances were related to all outcome measures, while agitation, depression, elation, apathy, disinhibition and irritability were significantly related to motor-FIM outcomes. At multivariate regression analysis agitation was the only determinant of final motor-FIM score, while irritability was the only determinant of efficiency and effectiveness in motor-FIM score. No neuropsychiatric symptom was a determinant of discharge destination. Conclusions: This study highlights that in hip fracture patients there are relationships between specific neuropsychiatric symptoms and functional outcome. Among the neuropsychiatric symptoms, irritability and agitation are the most important. They are associated to poor functional outcome and are the only determinants of motor-FIM outcome measures.Implications for RehabilitationRelationships between specific neuropsychiatric symptoms and functional outcome have not been clearly described in hip fracture patients.Irritability and agitation have been shown to have the strongest relationship with poor functional outcomes.Appropriate identification, assessment and treatment of neuropsychiatric symptoms may be useful to physicians for the management of hip fracture patients.

EPA-1408 – Cognitive Remediation in Early Psychosis and in At-risk Mental States – Approaches and Efficacy

Cognitive impairments have a high prevalence in schizophrenia, and are important determinants of functional outcome and treatment responsiveness. They are well-documented in chronic schizophrenia patients but are already apparent before the onset of the disorder and are predictive of transition to psychosis. Cognitive Remediation approaches have proved to be effective in enhancing cognitive functions and functional outcome in multi-episode schizophrenia patients. Recent studies suggest that younger people with an early course of illness are even more likely to benefit from these interventions. Therefore, Cognitive Remediation approaches may be especially appropriate for early intervention in psychosis. However, there is still a paucity of studies that evaluated Cognitive Remediation in early psychosis patients and in those symptomatically at-risk for psychosis. Moreover, several approaches are summarized under the umbrella term Cognitive Remediation. Consequently, they differ in content, setting, and practical application. Therefore, it remains rather unclear which type of therapy works best for the specific treatment needs of these patients. Against this background, this presentation will summarize and critically discuss current CRT approaches and their efficacy in early psychosis and in at-risk mental states with regard to cognitions, symptom levels, and functional outcome. Furthermore, we will present novel treatments and study designs specifically developed for early intervention in psychosis.

Reconstruction of the thumb amputation at the carpometacarpal joint level by groin flap and second toe transfer

IntroductionTraumatic loss of thumb at the carpometacarpal (CMC) joint level is very disabling to an individual. Pollicisation is the recommended technique of reconstruction for loss of thumb at this level. On occasions, injury to the rest of the hand or amputation of additional fingers may make pollicisation an impossible option. Microsurgical transfer of second toe is an option in such situations. Although many large series of toe transfers are available in the literature, no series deals exclusively with this subset of patients. Materials and methodsEight patients who had amputation of the thumb at or proximal to the CMC joint level were reconstructed by second toe transfer by us in the period 2002–2011. All had preliminary groin flap cover in the area of the thumb during the acute stage of treatment. Second toe with the metatarsal was transferred for thumb reconstruction after a mean duration of 3 months after flap cover. Patients were assessed for their ability to pinch, hold large objects and opposition achieved by Kapandji score. Average follow up is 4 years and 6 months with a minimum of 1 year. ResultsAll toe transfers survived. They reached their maximum functional potential by 1 year. All patients actively used the reconstructed thumb for day to day activities. Pinch was possible in all patients except two patients who did not have any fingers. Six of them registered grip strength of at least 50% of the opposite hand. When fingers were present, opposition was possible in all patients with Kapandji scores ranging from 5 to 8. Extent of usage was less in patients who did not have good function in other fingers. ConclusionSecond toe transfer is a viable option for reconstruction of thumb loss at or proximal to the CMC joint level. Proper planning of the preliminary flap cover determines the length of the thumb reconstruction. Strategic position of the transferred toe of adequate length and the functional status of the other fingers are important determinants of functional outcome.

The influence of social interaction on cognitive training for schizophrenia.

In addition to the core features of the condition, individuals with schizophrenia typically exhibit deficits in cognitive functions (Barnett et al., 2010). Such impairments are known to be important determinants of functional outcome (Green et al., 2000; Harvey et al., 2003) and their magnitude is associated with the level of self-care, utilization of hospital services, and burden placed on caregivers (Davidson and Keefe, 1995; Sevy and Davidson, 1995; Martens and Addington, 2001). The cognitive features of schizophrenia are poorly treated with antipsychotics (Liberman, 1994). Cognitive training offers a more promising option. Training interventions have been associated with cognitive improvements including information processing, verbal learning, and executive function (Medalia et al., 1998; Bellucci et al., 2003; McGurk et al., 2005; Sartory et al., 2005). The most recent meta-analysis found that, for individuals with schizophrenia, cognitive training improves cognitive function, psychosocial function, and psychiatric symptom severity (effect sizes of 0.45, 0.42, and 0.18 respectively; Wykes et al., 2011). Such findings highlight the promise of training programs in treating the cognitive symptoms of schizophrenia.

Effects of modafinil on cognitive functions in first episode psychosis

Cognitive impairments are important determinants of functional outcome in psychosis, which are inadequately treated by antipsychotic medication. Modafinil is a wake-promoting drug that has been shown to improve attention, memory and executive function in the healthy population and in patients with schizophrenia. We aimed to establish modafinil's role in the adjunctive treatment of cognitive impairments in the first episode of psychosis, a time when symptoms may be more malleable than at chronic stages of the disease. Forty patients with a first episode of psychosis participated in a randomised, double-blind, placebo-controlled crossover design study assessing the effects of a single dose of 200mg modafinil on measures of executive functioning, memory, learning, impulsivity and attention. Modafinil improved verbal working memory (d = 0.24, p = 0.04), spatial working memory errors (d = 0.30, p = 0.0004) and strategy use (d = 0.23, p = 0.03). It also reduced discrimination errors in a task testing impulsivity. Modafinil showed no effect on impulsivity measures, sustained attention, attentional set-shifting, learning or fluency. Modafinil selectively enhances working memory in first episode psychosis patients, which could have downstream effects on patients' social and occupational functioning.

Effects of Modafinil on Emotional Processing in First Episode Psychosis

Emotional impairments are important determinants of functional outcome in psychosis, and current treatments are not particularly effective. Modafinil is a wake-promoting drug that has been shown to improve emotion discrimination in healthy individuals and attention and executive function in schizophrenia. We aimed to establish whether modafinil might have a role in the adjuvant treatment of emotional impairments in the first episode of psychosis, when therapeutic endeavor is arguably most vital. Forty patients with a first episode of psychosis participated in a randomized, double-blind, placebo-controlled crossover design study testing the effects of a single dose of 200 mg modafinil on neuropsychological performance. Emotional functions were evaluated with the emotional face recognition test, the affective go-no go task, and the reward and punishment learning test. Visual analogue scales were used throughout the study to assess subjective mood changes. Modafinil significantly improved the recognition of sad facial expressions (z = 2.98, p = .003). In contrast, there was no effect of modafinil on subjective mood ratings, on tasks measuring emotional sensitivity to reward or punishment, or on interference of emotional valence on cognitive function, as measured by the affective go-no go task. Modafinil improves the analysis of emotional face expressions. This might enhance social function in people with a first episode of psychosis.

Emotional experience predicts social adjustment independent of neurocognition and social cognition in schizophrenia

BackgroundEmotional abnormalities are prominent features of schizophrenia. While the capacity for emotions is essential to social adaptation, little is known about the role of emotional experience in the social dysfunction observed in schizophrenia. ObjectiveThis study examined the contribution of emotional experience, neurocognition, and social cognition to functional outcome in schizophrenia. MethodSelf-reported emotional experience (anhedonia, affect intensity, and emotion frequency) was assessed in 33 stable schizophrenic/schizoaffective patients and 33 healthy controls. Symptoms, neurocognition, social cognition, and functional outcome were also assessed. ResultsPatients and controls exhibited good internal reliability on all self-report scales, except for negative affect intensity. Patients reported equally intense but less frequent positive emotions, more intense and frequent negative emotions, and more anhedonia. Results of hierarchical regression analyses showed that emotional experience accounted for significant amounts of variance of social adjustment independent of neurocognition and social cognition. ConclusionThese data show that emotional experience can be reliably assessed and is an important determinant of functional outcome in schizophrenia.

Determinants of functional outcome after revascularization for critical limb ischemia: An analysis of 1000 consecutive vascular interventions

When reporting standards for successful lower extremity revascularization were established, it was assumed that arterial reconstruction, patency, and limb salvage would correlate with the ultimate goal of therapy: improved functional performance. In reality, factors determining improvement of ambulation and maintenance of independent living status after revascularization have been poorly studied. The purpose of this study was to assess the important determinants of functional outcome for patients after intervention for critical limb ischemia. The results of 1000 revascularized limbs from 841 patients were studied. Indications were rest pain, 41.1%; ischemic ulceration, 35.6%; gangrene, 23.3%; infrainguinal, 70.9%; aortoiliac, 24.2%; and both, 4.9%. Treatment was by endovascular intervention, 35.5%; open surgery, 61.7%; and both, 2.8%. Patient were mean age of 68 +/- 12 years, and 56.6% were men, 74.7% were white, 54.2% had diabetes mellitus, 67% were smokers, 13.4% had end-stage renal disease and were on dialysis, and 36% had prior vascular surgery. Patients were treated with conventional therapy by fellowship-trained vascular specialists at a single center and were analyzed according to the type of intervention, the arterial level treated, age, race, gender, presentation, the presence of diabetes, smoking history, end-stage renal disease, coronary disease, hypertension, hyperlipidemia, obesity, chronic obstructive pulmonary disease, previous stroke, dementia, prior vascular surgery, preoperative ambulatory status, limb loss <or=1 year of treatment, and independent living status. The technical outcomes of reconstruction patency and limb salvage as well as the functional outcomes of survival, maintenance of ambulation, and independent living status were measured for each variable using Kaplan-Meier life-table analysis, and differences were assessed using the log-rank test. A Cox proportional hazards model was used to assess independent predictors of outcome and obtain adjusted hazard ratios and 95% confidence intervals. At 5 years, 72.4% of the entire cohort had a patent reconstruction and 72.1% had an intact limb. Overall 5-year functional outcomes were 41.9% for survival, 70.6% for maintenance of ambulation, and 81.3% for independent living status. Outcome was not significantly affected by the type of treatment (endovascular or open surgery) or by the level of disease treated (aortoiliac, infrainguinal, or both). The most important independent, statistically significant predictors of particularly poor functional outcome were impaired ambulatory ability at the time of presentation (70% 5-year mortality, hazard ratio, 3.34; 39.5% failure to eventually ambulate, hazard ratio, 2.83; 30% loss of independent living status, hazard ratio, 7.97), and the presence of dementia (73% late mortality, hazard ratio, 1.57; 41.2% failure to eventually ambulate, hazard ratio, 2.20; 46.4% loss of independent living status, hazard ratio, 5.44). These factors were even more predictive than limb amputation alone. Functional outcome for patients undergoing intervention for critical limb ischemia is not solely determined by the traditional measures of reconstruction patency and limb salvage, but also by certain intrinsic patient comorbidities at the time of presentation. These findings question the benefit of our current approach to critical limb ischemia in functionally impaired, chronically ill patients--patients who undoubtedly will be more prevalent as our population ages.

Community dysfunction in schizophrenia: Rate-limiting factors

The purpose of the present study was to investigate the impact of cognitive functioning, psychopathology, and severity of extrapyramidal side effects on community outcome in a group of Greek outpatients with schizophrenia. Participants were 40 outpatients with schizophrenia (25 men). Social adjustment was assessed with the Quality of Life Scale (QLS). Severity of symptoms of schizophrenia was measured with the Positive and Negative Syndrome Scale (PANNS), and extrapyramidal symptoms with the Extrapyramidal Symptom Rating Scale (ESRS). Finally, a battery of neuropsychological tests was administered in order to assess the following cognitive domains: executive functioning/set shifting, executive functioning/inhibition, fluency, verbal memory, visual memory, working memory, attention, visuospatial ability, and psychomotor speed/visual scanning. Total scores on the QLS were significantly correlated with negative symptoms, parkinsonism, and performance on the fluency tasks. Interpersonal relations subscale was significantly related with negative symptoms and fluency. No significant relationship was found between the Instrumental Role Functioning subscale and the PANSS, ESRS, or any cognitive domain. Scores on the Intrapsychic Foundation subscale were significantly correlated with negative symptoms and fluency. Finally, scores on the Common Objects and Activities subscale were significantly related with severity of negative symptoms, parkinsonism and visual memory. Our findings suggest that severity of negative symptoms, cognitive dysfunction, especially performance on fluency tasks and visual memory, as well as parkinsonism, are important determinants of functional outcome in schizophrenia.

Differential gene expression profiling of short and long term denervated muscle

Skeletal muscle function and viability are dependent upon intact innervation. Peripheral nerve injury and muscle denervation cause muscle atrophy. Time to re-innervation is one of the most important determinants of functional outcome. While short-term denervation can result in nearly fully reversible changes in muscle mass, prolonged denervation leads to irreversible muscle impairment from profound atrophy, myocyte death and fibrosis. We performed transcriptional profiling to identify genes that were altered in expression in short-term (1 month) and long-term (3 month) denervated muscle and validated the microarray data by RT-PCR and Western blotting. Genes controlling cell death, metabolism, proteolysis, stress responses and protein synthesis/translation were altered in expression in the denervated muscle. A differential pattern of expression of genes encoding cell cycle regulators and extracellular matrix components was identified that correlated with the development of irreversible post-denervation changes. Genes encoding mediators of protein degradation were differentially expressed between 1 and 3 month denervated muscle suggesting different signaling networks are recruited over time to induce and maintain muscle atrophy. Understanding of the timing and type of pathological processes that are triggered by denervation may allow the design of interventions that delay or protect muscle from loss of nerve function.

Recovery from psychosis in schizophrenia and schizoaffective disorder: symptoms and neurocognitive rate-limiters for the development of social behavior skills

Neurocognitive deficits are believed to be important predictors of functional outcome in chronic psychotic disorders, but few supporting studies have utilized prospective designs and adequate control. The aim of this study was to estimate the relative influence of symptoms and neurocognitive deficits on the development of social behavior skills in a cohort of individuals with schizophrenia or schizoaffective disorder recovering from acute symptom exacerbations. Forty-six individuals were recruited upon discharge from an inpatient unit and completed assessments of symptoms, neurocognitive function, and social behavior at 3-month intervals for 1 year. Correlational analyses and random regression models were used to model social behavioral capacities longitudinally. Social behavior improved modestly (10% improvements in ratings) over the follow-up period for the group as a whole. Disorganized and negative symptoms, as well as neurocognitive deficits in short-term and working memory predicted changes in social behavior over time. Individuals with better working memory function showed significantly greater abilities to recover social behavior skills, whereas those with working memory deficits showed no functional improvement over time. Both symptoms and neurocognitive deficits are important determinants of functional outcome in schizophrenia. It is proposed that clinicians should consider neurocognitive thresholds for treatment response when developing rehabilitation plans.

Axonal regeneration through acellular muscle grafts.

The management of peripheral nerve injury remains a major clinical problem. Progress in this field will almost certainly depend upon manipulating the pathophysiological processes which are triggered by traumatic injuries. One of the most important determinants of functional outcome after the reconstruction of a transected peripheral nerve is the length of the gap between proximal and distal nerve stumps. Long defects (> 2 cm) must be bridged by a suitable conduit in order to support axonal regrowth. This review examines the cellular and acellular elements which facilitate axonal regrowth and the use of acellular muscle grafts in the repair of injuries in the peripheral nervous system.