Effect of load on preferred speed and cost of transport.

Horses have a tendency to utilize a relatively narrow set of speeds near the middle of a much broader range they are capable of using within a particular gait, i.e., a preferred speed. Possible explanations for this behavior include minimizing musculoskeletal stresses and maximizing metabolic economy. If metabolic economy (cost of transport, CT) and preferred speeds are linked, then shifts in CT should produce shifts in preferred speed. To test this hypothesis, preferred speed was measured in trotting horses (n = 7) unloaded on the level and loaded with 19% of their body weight on the level. The preferred speed on the level was 3.33 +/- 0.09 (SE) m/s, and this decreased to 3.13 +/- 0.11 m/s when loaded. In both conditions (no load and load), the rate of O2 consumption (n = 3) was a curvilinear function of speed that produced a minimum CT (i.e., speed at which trotting is most economical). When unloaded, the speed at which CT was minimum was very near the preferred speed. With a load, CT decreased and the minimum was also near the preferred speed of horses while carrying a load.

Assessing traumatic brain injury outcome measures for long-term follow-up of community-based individuals.

OBJECTIVES: To determine which outcome measures are best and least suited for assessing long-term functional outcome of individuals with traumatic brain injury (TBI) in the community. DESIGN: Survey of participants in the community an average of 5 years after TBI. A battery of outcome measures was given. SETTING: Community in northern California after inpatient rehabilitation. PARTICIPANTS: Forty-eight adult individuals with prior moderate to severe TBI. All subjects had received inpatient rehabilitation 2 to 9 years previously and could be reached for telephone interview. MAIN OUTCOME MEASURES: The Community Integration Questionnaire, Neurobehavioral Functioning Inventory (NFI), Patient Competency Rating Scale (PCRS), Level of Cognitive Functioning Scale (LCFS), FIM instrument, Functional Assessment Measure (FIM+FAM), Supervision Rating Scale (SRS), Disability Rating Scale (DRS), Revised Craig Handicap Assessment and Reporting Technique (R-CHART), and Glasgow Outcome Scale (GOS). The number of maximal scores on each of the surveys was studied to determine which instruments continued to reveal deficits years after TBI. RESULTS: Most individuals obtained maximum scores, ie, functional independence, on these scales: LCFS, FIM motor subscale and total score, R-CHART physical independence subscale, FIM+FAM, GOS, and the SRS. Measures with the fewest maximum scores (<36%, measuring deficits still extant in the group) were the R-CHART cognition subscale and the NFI memory/attention and communication subscales, and employment subscales. Items, subscales, and total scores that showed good variability and correlated most highly and frequently with other scales also demonstrating good variability were the PCRS, the DRS and FIM+FAM employment items, the R-CHART cognition subscale, and the NFI motor, memory/attention, communication, and depression subscales (the R-CHART cognition subscale and NFI memory/attention subscale were highly correlated with the PCRS;.84,.83). CONCLUSIONS: Measures that appeared to contribute little to assessing functional status of a TBI sample years postinjury were the FIM, FIM+FAM, SRS, GOS, and LCFS. Measures that showed a range of deficits across participants were DRS employability, the NFI, PCRS, and the R-CHART cognition subscale.

Is hypercholesterolemia a risk factor and should it be treated in the elderly?

PURPOSE: The 1993 National Cholesterol Education Program guidelines recommend cholesterol screening for elderly patients with and without known coronary heart disease. This review summarizes clinical trial evidence from the medical literature that addresses cholesterol treatment in the elderly. DATA SOURCES: References were obtained from a MEDLINE search, bibliographies, metaanalyses, and review articles. STUDY INCLUSION AND EXCLUSION CRITERIA: Randomized, controlled clinical trials, including all lipid intervention trials with elderly participants or subgroup analyses of the elderly designed to measure major cardiovascular disease endpoints, were selected. DATA EXTRACTION METHODS: A MEDLINE search of all clinical trials using key search terms yielded 1360 references. Journal titles and abstracts were reviewed for all references by one of us (K.M.H.). A full journal review was undertaken for 41 references to clinical trials. Five clinical trials fulfilled all criteria and represented unique data. DATA SYNTHESIS: A MEDLINE search (from 1966 to January 2000) and bibliography reviews yielded five important clinical trials with analyses of elderly participants. Data are presented in text form and a summary table. MAJOR CONCLUSIONS: Clinical trial evidence supports treating hyperlipidemia in elderly persons for secondary prevention of coronary heart disease. Evidence from four secondary prevention trials demonstrated that major coronary heart disease risk decreased by 25% to 30% in elderly subjects treated for 5 years. Unanswered questions include cholesterol treatment for primary prevention in the elderly, gender effect, and benefit of treatment in persons older than 70.

Efficient retrovirus-mediated transfer of the multidrug resistance 1 gene into autologous human long-term repopulating hematopoietic stem cells.

Pre-clinical studies indicate that efficient retrovirus-mediated gene transfer into hematopoietic stem cells and progenitor cells can be achieved by co-localizing retroviral particles and target cells on specific adhesion domains of fibronectin. In this pilot study, we used this technique to transfer the human multidrug resistance 1 gene into stem and progenitor cells of patients with germ cell tumors undergoing autologous transplantation. There was efficient gene transfer into stem and progenitor cells in the presence of recombinant fibronectin fragment CH-296. The infusion of these cells was associated with no harmful effects and led to prompt hematopoietic recovery. There was in vivo vector expression, but it may have been limited by the high rate of aberrant splicing of the multidrug resistance 1 gene in the vector. Gene marking has persisted more than a year at levels higher than previously reported in humans.

Characteristics of the Functional Independence Measure in traumatic spinal cord injury.

OBJECTIVES: The characteristics of the Functional Independence Measure (FIM) were examined for spinal cord injury (SCI) in regard to norms over time by level and completeness of injury, differential benefit of motor and cognition subscales, and "ceiling effect" after rehabilitation discharge. DESIGN: Descriptive study of raw FIM data collected prospectively at admission and discharge from acute inpatient rehabilitation, and at 1, 2, and 5 years after injury. SETTING: National Database of the 18 Spinal Cord Injury Model Systems. SUBJECTS: Persons with SCI, age 16 and over, with functionally complete injuries at inpatient rehabilitation admission (ASIA grades A, B, or C), admitted to Model System an average of 8 days after injury (standard deviation = 13, median = 1 day). Maximum sample sizes for which data were available were: at rehabilitation admission, 3,971 cases; at discharge, 4,033; at year 1 postinjury, 903; 2 years, 712; and 5 years, 570. OUTCOME MEASURES: The FIM motor and cognition subscales. RESULTS: There is a substantial ceiling effect of the FIM cognition items even by inpatient rehabilitation discharge, ie, 80% to 90% of the cases average 6 to 7 (independent or modified independence) across the 5 FIM cognition items. At 1 year 89% to 97% of cases were rated independent. FIM motor items were consistent with level of injury and neurologic status. Motor items (excluding locomotion items) were highly intercorrelated (correlations range from .58 to .92 for self care, sphincter control, and mobility items). Trends over years 1, 2, and 5 were stable for both motor and cognition subscales. FIM motor gains were greatest between admission and discharge and gains continued through 1 year after injury, but at a much-decreased rate. CONCLUSIONS: The cognition items are not informative for detecting changes over time in SCI; at best, these items could serve as a crude cognition screening assessment. Motor items, in contrast, appear to reflect well the functional status of individuals. High correlations among several of the motor items suggest item redundancy. FIM motor scores illustrated the improvements in neurologic and ASIA scores in appropriate cases. Individuals with ASIA impairment grades of B or C at admission make the most gains in FIM motor scores.

Follow-up study of individuals with high tetraplegia (C1-C4) 14 to 24 years postinjury.

OBJECTIVE: To determine the life circumstances and psychosocial status of individuals with respirator-assisted and respirator-independent high tetraplegia an average of 19 years after spinal cord injury. DESIGN: Survey data were analyzed separately for ventilator-assisted and ventilator-independent groups. SETTING: Three spinal cord injury rehabilitation centers in California, Colorado, and Texas. SUBJECTS: Eighty-two individuals with CI-C4 tetraplegia between 14 and 24 years postinjury who had received acute inpatient rehabilitation. MAIN OUTCOME MEASURES: Demographics, health care utilization patterns, activities of daily living (Katz Level of Free Time Activities Scale), self esteem (Rosenberg Self Esteem Scale), quality of life, and employment. RESULTS: Self esteem and quality of life were, reported as high. Most subjects had some form of health care insurance. More than 90% lived in private homes. Approximately one third of cases had at least a college degree, yet only one quarter reported being employed. One fifth of individuals were married. Almost half of ventilator-independent cases and one quarter of ventilator-assisted cases lived in households with income of less than $20,000 per year. Mean hospital days in the past year were 11 for the ventilator-independent group and 6 for the ventilator-assisted group. The latter group required more nursing level care, significantly more hours of care, and more paid attendants over the year. Ninety-five percent of individuals reported being "glad to be alive." CONCLUSIONS: Assistance in the areas of socialization, financial status, personal assistance services, transportation, and entry into competitive employment were defined as needed. Quality of life was higher than expected, considering the substantial physical limitations of the group. The sample was almost unanimously glad to be alive, including all ventilator-assisted individuals.

The Community Integration Questionnaire revisited: an assessment of factor structure and validity.

OBJECTIVE: To investigate the factor structure and concurrent validity of the Community Integration Questionnaire (CIQ), using a large sample of persons with traumatic brain injury (TBI). DESIGN: Principal components analysis with varimax rotation was performed on CIQ items completed through interview with patients at 1 year after injury. Correlational analyses compared CIQ scores to scores on other widely used outcome measures. SETTING: Outpatient clinics affiliated with four TBI Model System rehabilitation centers funded by the National Institute on Disability and Rehabilitation Research. PARTICIPANTS: Three hundred twelve patients with medically documented TBI who were enrolled in the TBI Model Systems Project. The majority of patients were Caucasian males with severe TBI. MAIN OUTCOME MEASURES: CIQ; Functional Independence Measure (FIM); Functional Assessment Measure (FAM); Disability Rating Scale (DRS). RESULTS: Three factors emerged: Home Competency, Social Integration, and Productive Activity. The financial management item was moved from Social Integration to Home Competency, and the travel item was moved from Productive Activity to Social Integration. Each CIQ scale score showed significant correlations in the expected direction with the FIM+FAM and DRS items. CONCLUSIONS: The results provide further evidence for the validity of the CIQ and improve the scoring system. The factor structure is clinically and theoretically meaningful. The subscale and total scores show significant relationships with other widely used measures of outcome. Future research should focus on increasing the range of questions, accounting for changes from preinjury functioning, and obtaining normative data on the new factors.

Premorbid history and traumatic brain injury.

The literature is replete with studies investigating predictors of outcomes in traumatic brain injury. Few, however, have addressed the pre morbid life events and behaviors that may significantly impact the physical, behavioral, cognitive, and/or psychosocial and vocational status of individuals after a traumatic brain injury (TBI). Findings of studies on premorbid history are reviewed and data are presented on a sample of 82 cases on which premorbid psychosocial information, severity of initial injury and outcome status were obtained. Cases were dichotomized into groups at high risk and at low risk for TBI, based on premorbid history. High risk and low risk groups were comparable in the severity of initial injury. Outcomes were defined by the Functional Independence Measure and the Disability Rating Scale scores at 1 year after injury. No differences were found in FIMTM or DRS scores between those with and without premorbid learning disability, psychiatric history, incarcerations, arrests, academic difficulties, or substance abuse. Explanations for the lack of significant differences are discussed. Based on experience in completing this study, a screening tool incorporating documentation of a number of pre morbid factors that might impact status at outcome is presented.

Establishing a national traumatic brain injury information system based upon a unified data set.

In alliance with payers and persons with disabilities, rehabilitation professionals can create an outcome data system for traumatic brain injury (TBI) that will provide the knowledge necessary to improve the effectiveness and cost-effectiveness of rehabilitation programs. A nationwide TBI data system is needed to identify reasonably homogeneous subgroups given different treatments whose outcomes can be meaningfully compared. The advantages of a national outcome data system for gathering and analyzing this information include large sample sizes, objective assessment, measurement across the whole continuum of care, and adequate severity adjusters. Proposed methods and content for such a database are described, for reflecting general functional levels of clients along the continuum of care: acute care, TBI rehabilitation programs, and the community. Tools proposed are brief, have proven reliability and validity, and measure characteristics common to traumatically brain injured individuals. Possible data analysis approaches for a National Information System (database) dedicated to TBI are described for discussion within the rehabilitation community.

Agreement between persons with traumatic brain injury and their relatives regarding psychosocial outcome using the Community Integration Questionnaire.

OBJECTIVE: To extend psychometric research on the Community Integration Questionnaire (CIQ) by comparing patients' reports with those of family members. DESIGN: Reports on community integration were obtained from family members and patients 1 year after brain injury. Kappa reliability coefficients were used to examine agreement for individual items on the questionnaire. Total scores for the three CIQ scales were compared between groups using independent samples t tests. SETTING: Outpatient clinics affiliated with the four NIDRR traumatic brain injury Model System rehabilitation centers. PARTICIPANTS: CIQ data were obtained for 259 adult patients with traumatic brain injury. For 122 cases, patients and family members provided corresponding data. In 101 cases, only self-reported data were available. In 36 cases, information was provided solely by family members. All patients received inpatient rehabilitation and were at least 16 years of age. The full range of brain injury severity was represented. MAIN OUTCOME MEASURE: The 15-item CIQ, comprised of three scales, Home Integration, Productive Activity, and Social Integration. RESULTS: Analysis of kappa values found "moderate" to "almost perfect" agreement levels for all 15 items. Almost-perfect ratings were found for three of the four items on the Productive Activity Scale. Comparisons were made between scale scores derived from patients and families. The Home Integration scale showed differences, with patient scores higher than those reported by family members (t = 3.51, p < .01). However, the difference in scores was attributable to small discrepancies on two items and was not considered clinically meaningful. The Total CIQ score also showed a difference, with patients reporting significantly higher levels of integration relative to family members (t = 2.30, p < .05). This difference was also attributable to discrepancies on two items of the Home Integration Scale. CONCLUSIONS: The results have important implications for researchers who may be limited to one source of data. The hypothesis that patients and family members have very different perspectives of patients' community activities was not supported. Rather, similar ratings of individual activities were given with two exceptions, meal preparation and housekeeping. More research is needed to delineate relationships between agreement ratings and outcome categories.

Outcomes evaluation in TBI Rehabilitation. Part I: overview and system principles.

Questions of how to measure outcomes are commonly heard in rehabilitation today. In this supplement we review the current state of the art of outcomes measurement in traumatic brain injury rehabilitation, discuss key issues, and identify steps that need to be taken. The underlying question is not simply that of outcomes measurement but how to infer effective and cost-effective treatment. The validity of such inferences rests on multiple features of the entire clinical information system. Requirements for valid, feasible, outcome-oriented clinical data systems are described. Effectiveness is inferred from variations in outcomes experienced by similar persons who received differing interventions. Outcome data systems need large sample sizes and technically adequate severity adjusters. A nationwide TBI data system is needed to identify reasonably homogeneous subgroups in different programs whose outcomes can be meaningfully compared. In alliance with payors and persons with disabilities, rehabilitation professionals can create outcome data systems that will provide the knowledge necessary to improve the effectiveness and cost-effectiveness of rehabilitation programs.

Outcomes evaluation in TBI Rehabilitation. Part II: measurement tools for a nationwide data system.

In Part II we address tools for describing general functional levels of clients in acute care, in traumatic brain injury (TBI) rehabilitation programs, and in the community. Tools must be brief, have proven reliability, and measure characteristics common to moderately and severely brain-injured individuals. Possible components of a uniform dataset dedicated to TBI are described.

Family stressors in traumatic brain injury: a two-year follow-up.

A review of the literature suggests that psychosocial disability in traumatic brain-injured (TBI) individuals and distress in families continues long after the initial injury. In this study the relationship of family stress to a number of factors was studied longitudinally. Caregivers of 51 TBI inpatients were interviewed at rehabilitation admission and by phone at 6, 12, and 24 months postinjury. Caregivers' most common complaints about their relatives were a lack of involvement in leisure activities, fatigue, slowness, and forgetfulness. Increasingly severe temper outbursts, anxiety, and self-centeredness were reported over time. Aggressiveness was reported by caregivers as moderate or severe in 31% of cases by 2 years postinjury. Of all complaints, only reports of inappropriate social behavior decreased over time. Despite caregivers' increasing complaints about their relatives, there were no trends toward greater self-reported stress over time. At the 2-year assessment, stress was significantly higher for caregivers of those with an at risk psychosocial history, and for those without sufficient funds for services. Caregivers reporting financial strain increased 22% from rehabilitation admission. Forty-seven percent of caregivers had altered or given up their jobs at 1 year postinjury, and 33% at 2 years postinjury. Although self-perceived measurements of stress did not increase over time, caregivers reported notable increases in medication use and substance use, and decreases in employment and financial status over the 2-year time period. When spouse and parent caregiver responses were compared, spouses reported a consistently greater number of behavioral problems, which increased in severity over time. Those behaviors associated with mood disturbances predominated.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of the methemoglobinemia associated with sulofenur.

A new class of antineoplastic agents, the diarylsulfonylureas entered clinical trials with the testing of Sulofenur (LY186641). Phase I trials and preclinical studies showed the dose limiting toxicity to be methemoglobinemia. We studied the incidence of methemoglobinemia, sulfhemoglobinemia and cytochrome b5 reductase deficiency in nine consecutive patients enrolled in a phase II trials using Sulofenur. The specific Malloy method as well as clinically standard co-oximeter measurements were used to determine methemoglobin levels and marked discrepancies were noted. One patient with symptomatic methemoglobinemia had enzyme levels and family history consistent with a heterozygous state for a cytochrome b5 reductase deficiency. We conclude that the clinical incidence of methemoglobinemia will be overestimated by co-oximeter measurements but that Sulofenur does produce clinically significant methemoglobinemia in cytochrome b5 reductase deficient patients.

Studies of the retention mechanism of the brain perfusion imaging agent 99mTc-bicisate (99mTc-ECD).

The structure-activity relationship in a series of analogues of 99mTc-bicisate (99mTc-N,N'-1,2-ethylenediylbis-L-cysteine diethyl ester dihydrochloride, RP-217) is described using in vivo studies in rodent and primate models and in vitro studies in rodent and primate brain tissue. All analogues investigated were 99mTc-diamine dithiol diesters, which were neutral and lipophilic and had modified brain uptake indexes (> or = 40) suggesting adequate first-pass extraction. All analogues were poorly retained by the rodent brain. In contrast, the stereochemistry and structure of the 99mTc-complexes affected their brain retention in primates. All compounds that demonstrated selective primate brain retention were L-diesters that were metabolized in primate brain tissue to nonlypophilic complexes resulting from ester hydrolysis. Unretained complexes were not metabolized in primate brain tissue. More extensive studies were performed with 99mTc-bicisate, which demonstrated poor brain retention in several nonprimate species (i.e., dogs, ferrets, pigs, and rodents). In rodent and nonhuman primate tissue, 99mTc-bicisate was rapidly metabolized to a monoacid ester (99mTc-N,N'-1,2-ethylenediylbis-L-cysteine monoethyl ester). Therefore, brain metabolism of 99mTc-bicisate results in the formation of an acid product(s) that is selectively trapped in primate brain.

The role of single photon emission computed tomography brain imaging with 99mTc-bicisate in the localization and definition of mechanism of ischemic stroke.

99mTc-bicisate (99mTc-ECD) is a new brain perfusion imaging agent formulated from a radiochemically stable kit (Neurolite). A multicenter trial was conducted to determine the sensitivity and specificity of single photon emission computed tomography (SPECT) imaging with 99mTc-bicisate in the localization of ischemic stroke; 170 subjects were enrolled, 128 patients with stroke and 42 controls. Imaging results from 148 subjects (107 stroke patients and 41 controls) were considered evaluable. In the evaluable subjects, SPECT brain imaging with 99mTc-bicisate (21.0 +/- 2.5 mCi) was interpreted without clinical information and was compared with a final assessment using all clinical, diagnostic, and laboratory procedures except the 99mTc-bicisate SPECT results. 99mTc-bicisate was safe and well-tolerated. SPECT imaging with 99mTc-bicisate demonstrated a specificity of 98% and a sensitivity of 86% for localization of strokes (kappa, 0.75; 95% confidence interval, 0.64-0.86). Results were unchanged over time and were similar for all stroke mechanisms except for lacunar disease (sensitivity, 58%). In a secondary analysis, a normal image or small, deep (e.g., subcortical) perfusion defect was highly predictive of a lacunar mechanism. Defects involving the cortical surface were strongly associated with nonlacunar mechanisms. SPECT imaging with 99mTc-bicisate is a sensitive marker in the localization of perfusion defects associated with ischemic stroke and may assist in the determination of the underlying mechanism of a stroke.

Commentary on model systems of care in neurotrauma: clinical perspectives and future directions.

The first section of this article discusses the principal clinical components of a model system of care for traumatic brain injury (TBI) or spinal cord injury (SCI). The next section, "The Future of Model Systems", addresses the advantages of such a system, as related to the changing health care climate and predicted future directions of health care in the United States. The need for innovative approaches to rehabilitation is upon us. In addressing this need, the last section, "Recommendations for Change", outlines cost-effective measures for providing rehabilitation services to our clientele.

Brain injury: analysis of outcome in a post-acute rehabilitation system. Part 1: General analysis.

During the past decade the rehabilitation field has developed new, non-hospital based programmes of cognitive, behavioural, social, educational and vocational treatments to address the higher order cognitive, behavioural and social deficits following brain injury. These new arrays of programmes are referred to under the term 'post-acute' rehabilitation. No comprehensive, methodologically sound study of the effects of these new treatments has been made to date. This paper reports data from brain-injured patients who underwent treatment within a co-ordinated system of post-acute brain-injury rehabilitation programmes. This system consists of a continuum of neurobehavioural, residential, day treatment and community and home programmes, and provides overt components of medical and rehabilitation care: behavioural management; activities of daily living, self-management, substance-abuse, social, academic and vocational skills training; counselling; and family education. The changes in function during the course of treatment by this post-acute sequence of rehabilitation have been obtained and are reported here. A defined total population of N = 192 is examined, with exclusions for appropriate causes (e.g. patients seen only for evaluation) producing a study population of N = 173; of these, follow-up was achieved in 145 cases, a follow-up rate of 83.8%. Time from date of injury to data of admission, severity of deficit at time of admission to programme, and other appropriate independent variables are used to characterize the population. A single-blind interview methodology was employed in obtaining dependent measures of outcome at 6, 12, or 24 month periods post-discharge. Measures of outcome included residential status, level of productivity activity and hours per day of attendant care or supervision required. Dependent variables were analysed for the total study population and a subgroup greater than 1 year from date of injury at entry to treatment and not from a treatment facility. Results are presented in terms of the percentage change in dependent measures from the point of admission to follow-up. Appropriate parametric and non-parametric statistical analyses of significance have been carried out. The results document substantial improvements in function during the post-acute rehabilitation of this population and such improvements are unlikely to be the result of spontaneous improvement alone.

Brain injury: analysis of outcome in a post-acute rehabilitation system. Part 2: Subanalyses.

The basic findings of brain-injured patients who underwent treatment within a co-ordinated system of post-acute brain-injury rehabilitation programmes have already been reported. The changes in function during the course of treatment by this post-acute sequence of rehabilitation were obtained and reported. A defined total population of N = 192 was examined, with exclusions for appropriate causes (e.g. patients seen only for evaluation) producing a study population of N = 173; of these, follow-up was achieved in 145 cases, a follow-up rate of 83.8%. Time from date of injury to date of admission, severity of deficit at time of admission to programme, and other appropriate independent variables were used to characterize the population. A single-blind interview methodology was employed in obtaining dependent measures of outcome at 6, 12 or 24 month periods post-discharge. Measures of outcome included residential status, level of productivity activity, and hours per day of attendant care or supervision required. In the work reported in this paper dependent variables are analysed for various subgroups of the total population. The subgroups analysed are: patients with traumatic brain injury only; mild moderate and severe grades of disability; and comparisons of outcomes at 6 months, 1 year, and 2 years post-discharge from treatment. The results are presented in terms of percentage change in dependent measures from point of admission to follow-up. Appropriate parametric and non-parametric statistical analyses of significance are carried out. Additionally, an analysis of cost associated with treatment, and some analysis of cost-benefit is provided. The results document substantial improvements in function during post-acute rehabilitation for both traumatic brain injury and brain dysfunction of other etiologies. Significant improvements are seen to occur in all grades of severity of dysfunction examined, and such improvements are robust and persist without evidence of decrement over the 2-year follow-up period. In addition, economic considerations suggest the potential for the recouping of costs of treatment within a reasonable period of time.