Inpatient Rehabilitation Facility Ownership Type Yields Mixed Performances on Quality Measures.

OBJECTIVE: To evaluate the effects of inpatient rehabilitation facility (IRF) ownership type on IRF-Quality Reporting Program (IRF-QRP) measures. DESIGN: Cross-sectional, observational design. SETTING: We used 2 Centers for Medicare and Medicare publicly-available, facility-level data sources: (1) IRF compare files and (2) IRF rate setting files - final rule. Data from 2021 were included. PARTICIPANTS: The study sample included 1092 IRFs (N=1092). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: We estimated the effects of IRF ownership type, defined as for-profit and nonprofit, on 15 IRF-QRP measures using general linear models. Models were adjusted for the following facility-level characteristics: (1) Centers for Medicare and Medicaid census divisions; (2) number of discharges; (3) teaching status; (4) freestanding vs hospital unit; and (5) estimated average weight per discharge. RESULTS: Ownership type was significantly associated with 9 out of the fifteen IRF-QRP measures. Nonprofit IRFs performed better with having lower readmissions rates within stay and 30-day post discharge. For-profit IRFs performed better for all the functional measures and with higher rates of returning to home and the community. Lastly, for-profit IRFs spent more per Medicare beneficiary. CONCLUSIONS: Ideally, IRF performance would not vary based on ownership type. However, we found that ownership type is associated with IRF-QRP performance scores. We suggest that future studies investigate how ownership type affects patient-level outcomes and the longitudinal effect of ownership type on IRF-QRP measures.

Intranasally applied human olfactory mucosa neural progenitor cells migrate to damaged brain regions.

Aim: To determine if intranasally administered olfactory mucosa progenitor cells (OMPCs) migrate to damaged areas of brain. Materials & methods: Rowett Nude (RNU) adult rats were injured using the Marmarou model then 2 weeks later received intranasally-delivered human OMPC. After 3 weeks, rats were sacrificed and brain sectioned. The mean distances from the human OMPCs to markers for degenerative neuronal cell bodies (p-c-Jun+), axonal swellings on damaged axons (ß-APP+) and random points in immunostained sections were quantified. One-way ANOVA was used to analyze data. Results: The human OMPCs were seen in specific areas of the brain near degenerating cell bodies and damaged axons. Conclusion: Intranasally delivered human OMPC selectively migrate to brain injury sites suggesting a possible noninvasive stem cell delivery for brain injury.

Phase IIB Randomized Trial on the Use of 4-Aminopyridine in Guillain-Barré Syndrome.

OBJECTIVE: To determine the safety and efficacy of orally delivered 4-aminopyridine (4-AP) in persons with Guillain-Barré Syndrome (GBS) >6 months from initial diagnosis. DESIGN: A randomized, double-blind, placebo-controlled, crossover study. SETTING: Tertiary care clinical outpatient program. PARTICIPANTS: Nineteen participants enrolled (14 male, 5 female; N=19), neurologic impairment secondary to GBS and functional loss on the FIM motor score (stable for ≥12mo) and >3.0 but <5.0 on the American Spinal Injury motor scale. Twelve participants (mean age, 59y; range, 23-77y) completed the study. INTERVENTIONS: A 4-AP dose-escalation study with 8 weeks in each period with a 3-week washout period, followed by 3 months open-label follow-up. MAIN OUTCOME MEASURES: FIM motor score was the primary outcome measure; also evaluated were the American Spinal Injury motor strength score (all limbs), handheld dynamometer, 6-minute walk test, Medical Outcomes Study 12-Item Short Form, Center for Epidemiological Studies Depression scale, Positive and Negative Affect Schedule, pain, GBS disability scale, Jepsen-Taylor Hand Function Test, Minnesota Manual Dexterity Test and Minnesota Rate of Manipulation Test, Get Up and Go Test, McGill Pain Inventory, Craig Handicap Assessment and Reporting Technique, and participant self-evaluation. RESULTS: Seven participants discontinued the study prematurely: 3 because of adverse events, 3 because of travel difficulties or relocation, and 1 because of pretreatment laboratory abnormalities. After removing 3 participants with maximum FIM scores, 4-AP arm trended superior to placebo (P=.065). Patients subjectively could always tell when they were on the active agent usually by tingling sensations or a sense of wellness. No statistically significant differences were found for other outcome measures although there were strong trends. CONCLUSIONS: This study demonstrates the safety of 4-AP in the patient population with GBS as the predominate goal of the study. A trend toward improved function after treatment was noted with most patients electing to stay on the medication after the trial.

Safety and feasibility of minocycline in treatment of acute traumatic brain injury.

BACKGROUND: Minocycline is a pleomorphic neuroprotective agent well studied in animal models of traumatic brain injury (TBI) and brain ischemia. METHODS: To test the hypothesis that administration of minocycline in moderate to severe TBI (Glasgow Coma Score 3-12). Fifteen patients were enrolled in a two-dose escalation study of minocycline to evaluate the safety of twice the recommended antibiotic dosage; tier 1 n = 7 at a loading dose of 800 mg followed by 200 mg twice a day (BID) for 7 days; tier 2 n = 8 at a loading dose of 800 mg followed by 400 mg BID for 7 days. RESULTS: The mean initial GCS was 5.6 for Tier 1 patients and 5.4 for Tier 2. The Disability Rating Scale (DRS) had a trend towards improvement with the higher dose 12.5 SD ± 7.7 (N = 5) for Tier 1 at 4 weeks and 8.5 SD ± 9.9 at week 12 (N = 5), whereas for Tier 2 it was 9.7 ± 6.9 (N = 6) for week 4 and 6.0 SD ± 6.1 (N = 7) for week 12 (p = .251 repeated measures ANOVA). Liver function tests increased but resolved after the first week and there were no infections. CONCLUSIONS: Minocycline was safe for moderate to severe TBI at a dose twice that as recommended for treatment of infection. The higher dose did trend towards an improved outcome.

Baclofen Solution for Low-Volume Therapeutic Delivery.

OBJECTIVES: Baclofen is a zwitterion molecule where increased ions in the excipient increase the solubility. We developed baclofen in a stable solution similar to cerebrospinal fluid (CSF) without bicarbonate and proteins to improve the solubility of the baclofen and to reduce the potential toxicity to the central nervous system (CNS) and subarachnoid space. The objective is to develop a solution of baclofen wherein baclofen is solubilized in a multivalent physiological ion solution such as artificial cerebrospinal fluid (aCSF) at a concentration from 2 mg/cc to 10 mg/cc. METHODS: First, to determine the solubility of Baclofen in aCSF, solubility was determined at six different pH levels at 37°C, by the addition of aCSF to a known amount of Baclofen. The final concentrations were confirmed by high performance liquid chromatography (HPLC) analysis. Second, the stability of Baclofen at 4 mg/cc investigated in a test manufacturing batch utilizing standard methods of production of 1500 20 cc vials inverted for 18 months at 25°C at 60% humidity. The stability and purity of the baclofen was verified at 18 months by HPLC analysis. RESULTS: Baclofen was initially soluble between pH of 6-8 above 7 mg/cc but fell back to 6.3-5.8 mg/cc level with time. Baclofen produced in vials with inversion were noted to be stable at 4 mg/cc at 18 months with less than 2% breakdown of the baclofen in solution. CONCLUSION: Baclofen is much more soluble in artificial CSF than normal saline. The artificial CSF may also be less toxic to the subarachnoid space than saline.

Treatment of severe tetanus with intrathecal baclofen via implantable infusion device: a case report.

OBJECTIVE: Severe tetanus remains a serious issue in less developed countries, leading to prolonged hospitalization due to prolonged neuromuscular contraction of muscles. We present a case of severe tetanus in the United States that was successfully managed with intrathecal baclofen. CASE REPORT: A 42-year-old male without tetanus vaccination history presented to the emergency department with intractable jaw pain and worsening diffuse muscle contractures due to severe generalized tetanus requiring prolonged paralysis and ventilator support. After 14 days of continuous neuromuscular treatment with benzodiazepines, vecuronium, propofol, and magnesium sulfate, a baclofen pump trial was performed 14 days post-admission as an alternative to prolonged neuromuscular blockade. After demonstrable improvement in spasms and paroxysmal contractures due to intrathecal baclofen (ITB), a baclofen pump was implanted on hospital day 17. The catheter was threaded to T4 for maximal effect of intrathecal baclofen on the upper and lower extremities at an initial rate of 100 µg/day. ITB was titrated upward, the vecuronium was slowly weaned, and the patient was weaned off a ventilator by day 14 of ITB treatment. At an ITB dose of 450 µg/day, propofol was discontinued. ITB was continued over the next four weeks and eventually weaned over the next two weeks. The ITB pump was removed eight weeks after placement, and the patient was successfully discharged to home. CONCLUSION: Due to prolonged muscle weakness associated with long-term use of paralytic agents and sedation, early ITB trial and pump placement should be considered as an alternative in the treatment of severe tetanus to shorten length of stay and improve the functional outcome of the patient.

Acute management of acquired brain injury part I: an evidence-based review of non-pharmacological interventions.

PRIMARY OBJECTIVE: To review the literature on non-pharmacological interventions used in acute settings to manage elevated intracranial pressure (ICP) and minimize cerebral damage in patients with acquired brain injury (ABI). MAIN OUTCOMES: A literature search of multiple databases (CINAHL, EMBASE, MEDLINE and PSYCHINFO) and hand-searched articles covering the years 1980-2008 was performed. Peer reviewed articles were assessed for methodological quality using the PEDro scoring system for randomized controlled trials (RCTs) and the Downs and Black tool for RCTs and non-randomized trials. Levels of evidence were assigned and recommendations made. RESULTS: Five non-invasive interventions for acute ABI management were assessed: adjusting head posture, body rotation (continuous rotational therapy and prone positioning), hyperventilation, hypothermia and hyperbaric oxygen. Two invasive interventions were also reviewed: cerebrospinal fluid (CSF) drainage and decompressive craniectomy (DC). CONCLUSIONS: There is a paucity of information regarding non-pharmacological acute management of patients with ABI. Strong levels of evidence were found for only four of the seven interventions (decompressive craniectomy, cerebrospinal fluid drainage, hypothermia and hyperbaric oxygen) and only for specific components of their use. Further research into all interventions is warranted.

Acute management of acquired brain injury part II: an evidence-based review of pharmacological interventions.

PRIMARY OBJECTIVE: To review the research literature on pharmacological interventions used in the acute phase of acquired brain injury (ABI) to manage ICP and improve neural recovery. MAIN OUTCOMES: A literature search of multiple databases (CINAHL, EMBASE, MEDLINE and PSYCHINFO) and hand searched articles covering the years 1980-2008 was performed. Peer reviewed articles were assessed for methodological quality using the PEDro scoring system for randomized controlled trials (RCTs) and the Downs and Black tool for RCTs and non-randomized trials. Levels of evidence were assigned and recommendations were made. RESULTS: In total, 11 pharmacological interventions used in the acute management of ABI were evaluated. These included propofol, barbiturates, opioids, midazolam, mannitol, hypertonic saline, corticosteroids, progesterone, bradykinin antagonists, dimethyl sulphoxide and cannabinoids. Of these interventions, corticosteroids were found to be contraindicated and cannabinoids were reported as ineffective. The other nine interventions demonstrated some benefit for treatment of acute ABI. However, rarely did these benefits result in improved long-term patient outcomes. CONCLUSIONS: Substantial research has been devoted to evaluating the use of pharmacological interventions in the acute management of ABI. However, much of this research has focused on the application of individual interventions in small single-site trials. Future research will need to establish larger patient samples to evaluate the benefits of combined interventions within specific patient populations.

Acute management of acquired brain injury Part III: an evidence-based review of interventions used to promote arousal from coma.

PRIMARY OBJECTIVE: To review the literature regarding techniques used to promote arousal from coma following an acquired brain injury. MAIN OUTCOMES: A literature search of multiple databases (CINAHL, EMBASE, MEDLINE and PsycINFO) and hand searched articles covering the years 1980-2008 was performed. Peer reviewed articles were assessed for methodological quality using the PEDro scoring system for randomized controlled trials and the Downs and Black tool for RCTs and non-randomized trials. Levels of evidence were assigned and recommendations were made. RESULTS: Research into coma arousal has generally focused on the stimulation of neural pathways responsible for arousal. These pathways have been targeted using pharmacological and non-pharmacological techniques. This review reports the evidence surrounding agents targeting dopamine pathways (amantadine, bromocriptine and levodopa), sensory stimulation, music therapy and median nerve electrical stimulation. Each of these interventions has shown some degree of benefit in improving consciousness, but further research is necessary. CONCLUSIONS: Despite numerous studies, strong evidence was only found for one intervention (Amantadine use in children) and this was based on a single study. However, each of the interventions showed promise in some aspect of arousal and warrant further study. More methodologically rigorous study is needed before any definitive conclusions can be drawn.

Impact of early administration of sertraline on cognitive and behavioral recovery in the first year after moderate to severe traumatic brain injury.

OBJECTIVE: To assess the efficacy of sertraline administered in the first 3 months after moderate to severe traumatic brain injury (TBI) in improving cognitive and behavioral outcomes. DESIGN: Double-blind, randomized controlled trial. SETTING: Academic medical center. PARTICIPANTS: Ninety-nine individuals randomized to placebo (n = 50) or sertraline 50 mg (n = 49) conditions. There were no group differences in age, gender, education, or severity of injury. INTERVENTIONS: Participants were enrolled an average of 21 days after injury (none > 8 weeks), followed by oral administration of placebo or sertraline 50 mg for 3 months. MAIN OUTCOME MEASURES: Wechsler Memory Scale-Third Edition Logical Memory, Trail Making Test, Wechsler Adult Intelligence Scale-Third Edition Working Memory Index, Symbol-Digit Modalities Test, Wisconsin Card Sorting Test (64-item), Neurobehavioral Functioning Inventory administered 3, 6, and 12 months after the onset of injury. RESULTS: Early administration of sertraline did not result in improved cognitive functioning during the year after injury compared with placebo administration. Those receiving placebo performed marginally better than the treatment group on a measure of executive function, but this appeared to be inauthentic. The treatment group followed expected recovery patterns based on existing literature. The placebo group performed better than expected on some measures, primarily due to differential dropout. CONCLUSIONS: Sertraline does not appear to prevent development of cognitive and behavioral problems following TBI, although this does not negate evidence for the treatment (as opposed to prophylactic) role of sertraline to address emotional and neurobehavioral problems in individuals with TBI.

Prophylaxis for venous thromboembolism during rehabilitation for traumatic brain injury: a multicenter observational study.

BACKGROUND: Deep venous thrombosis (DVT) is a major cause of mortality and morbidity after traumatic brain injury (TBI). There is no consensus regarding appropriate screening, prophylaxis, or treatment during acute rehabilitation. METHODS: This prospective observational study evaluated prophylactic anticoagulation during rehabilitation in patients with TBI aged 16 years or older admitted to 12 TBI Model Systems rehabilitation centers (July 2004-December 2007). After propensity score stratification within center, the odds ratio associated with incidence of symptomatic DVT or pulmonary embolism (PE) for patients who did and did not receive prophylactic anticoagulation was estimated using conditional logistic regression in patients who were not screened for DVT on rehabilitation admission or who screened negative; the analysis was repeated in these two subgroups. RESULTS: Patients with identified DVTs at rehabilitation admission (n = 266) were excluded, leaving 1,897 patients: 1,002 screened negative, 895 unscreened; 932 received prophylactic anticoagulation, and 965 did not. Symptomatic DVT/PE was detected in 32 patients (15 of 932 [1.6%] with prophylaxis, 17 of 965 [1.8%] without). After propensity score adjustment, the odds ratio (95% confidence interval) for symptomatic DVT/PE with prophylaxis versus no prophylaxis was 0.80 (0.33-1.94) in the full analytic population and 0.46 (0.12-1.84) in the screened-negative subgroup. The only probable venous thromboembolism-related death occurred in the prophylactic anticoagulation group. Fewer new/expanded intracranial hemorrhages occurred among patients who received prophylactic anticoagulation. CONCLUSIONS: Prophylactic anticoagulation during rehabilitation seemed safe for TBI patients whose physicians deemed it appropriate, but did not conclusively reduce venous thromboembolism. Given the number of DVTs present before rehabilitation, screening and prophylaxis during acute care may be more important.

Impact of early administration of sertraline on depressive symptoms in the first year after traumatic brain injury.

The potential for sertraline administered in the first 3 months after moderate to severe traumatic brain injury (TBI) to decrease the incidence of depression in the first year after injury was assessed in a double-blinded randomized control trial. Subjects were enrolled an average of 21 days after injury (none >8 weeks) followed by oral administration of placebo (50 subjects) or sertraline 50 mg (49 subjects) for 3 months. Subjects were not depressed at the time of study initiation. Outcome was assessed using the Hamilton Depression Rating Scale (HDRS) and the Depression Scale of the Neurobehavioral Functioning Inventory (NFI). Based on intent-to-treat and efficacy subset analyses, those receiving placebo exhibited significantly greater depressive symptoms than those receiving sertraline during the first 3 months after injury while receiving placebo/drug (10% of placebo group achieving a score of 6 or greater on the HDRS, 0% of the sertraline group; p < 0.023.). There was no significant difference in depressive symptoms during the remainder of the year between the two groups. Sertraline is effective in diminishing depressive symptoms even among those not clinically depressed while the medication is being taken. However, the results do not support the idea that administration early in recovery diminishes the expression of depressive symptoms after the drug is stopped. There is no basis from this study to assume that sertraline administered early in recovery after TBI, when neurotransmitter functioning is often altered, has ongoing effects on the serotonin system after sertraline is discontinued.

A preliminary assessment of the benefits of the addition of botulinum toxin a to a conventional therapy program on the function of people with longstanding stroke.

OBJECTIVE: To determine if botulinum toxin type A (BTX-A) combined with therapy can facilitate improved upper-extremity (UE) functional status versus therapy alone. DESIGN: Double-blind randomized crossover trial. SETTING: Tertiary care outpatient rehabilitation center. PARTICIPANTS: Convenience sample of 21 men and women (ages 19-80 y) with stroke more than 6 months after insult who had tone greater than 3 on the Ashworth Scale for 2 joints in the involved UE. INTERVENTION: Subjects were consecutively recruited and randomized to a double-blind crossover trial. Subjects received either BTX-A combined with a defined therapy program or placebo injection combined with a therapy program in two 12-week sessions. MAIN OUTCOME MEASURES: The primary functional outcome measure was the Motor Activity Log (MAL). Subjects were also assessed on physiologic measures including tone (Ashworth Scale), range of motion, and motor strength. RESULTS: Improvements were noted in the functional status of the subjects in both arms of the study as measured by the MAL. All subjects had a significant change in functional status on MAL with therapy (P<.05). The use of BTX-A combined with therapy as compared with therapy only improved the functional status of the subjects on the MAL Quality of Movement subscale (P=.0180, t test) and showed a trend toward significance in the Amount of Use subscale (P=.0605, analysis of variance). Six weeks after treatment, the BTX-A combined with therapy decreased the Ashworth score statistically (P=.0271), but the therapy alone group decreased a similar amount at 6 weeks (P=.0117), indicating that most of the physiologic tone change could be attributed to therapy. After each 12-week period, tone had largely returned to baseline (P>.05). CONCLUSION: A focused therapy program showed the most improvement in function in this defined stroke population. BTX-A combined with a focused traditional therapy program slightly enhanced the functional status of stroke subjects beyond that obtained with therapy alone 12 weeks after injection.

Global white matter analysis of diffusion tensor images is predictive of injury severity in traumatic brain injury.

Conventional clinical neuroimaging is insensitive to axonal injury in traumatic brain injury (TBI). Immunocytochemical staining reveals changes to axonal morphology within hours, suggesting potential for diffusion-weighted magnetic resonance (MR) in early diagnosis and management of TBI. Diffusion tensor imaging (DTI) characterizes the three-dimensional (3D) distribution of water diffusion, which is highly anisotropic in white matter fibers owing to axonal length. Recently, DTI has been used to investigate traumatic axonal injury (TAI), emphasizing regional analysis in more severe TBI. In the current study, we hypothesized that a global white matter (WM) analysis of DTI data would be sensitive to TAI across a spectrum of TBI severity and injury to scan interval. To investigate this, we compared WM-only histograms of a scalar, fractional anisotropy (FA), between 20 heterogeneous TBI patients recruited from Detroit Medical Center, including six mild TBI (GCS 13-15), and 14 healthy age-matched controls. FA histogram parameters were correlated with admission GCS and posttraumatic amnesia (PTA). In all cases, including mild TBI, patients' FA histograms were globally decreased compared with control histograms. The shape of the TBI histograms also differed from controls, being more peaked and skewed. The mean FA, kurtosis and skewness were highly correlated suggesting a common mechanism. FA histogram properties also correlated with injury severity indexed by GCS and PTA, with mean FA being the best predictor and duration of PTA (r = 0.64) being superior to GCS (r = 0.47). Therefore, in this heterogeneous sample, the FA mean accounted for 40% of the variance in PTA. Increased diffusion in the short axis dimension, likely reflecting dysmyelination and swelling of axons, accounted for most of the FA decrease. FA is globally deceased in WM, including mild TBI, possibly reflecting widespread involvement. FA changes appear to be correlated with injury severity suggesting a role in early diagnosis and prognosis of TBI.

Bias in magnitude estimation following left hemisphere injury.

There is a growing interest both in identifying the neural mechanisms of magnitude estimation and in identifying forms of bias that can explain aspects of behavioral syndromes like unilateral neglect. Magnitude estimation is associated with activation of temporo-parietal cortex in both cerebral hemispheres of normal subjects; however, it is unclear if and how left hemisphere lesions bias magnitude estimation because the infrequency of neglect and the presence of aphasia in these subjects confound examination. In contrast, we examined magnitude estimation using 12 different types of sensory stimuli that spanned five sensory domains in two patients with very different clinical presentations following unilateral left hemisphere stroke. One patient had neglect sub-acutely without aphasia. The other had aphasia chronically after a temporo-parietal lesion but not neglect. The neglect patient was re-examined 48 h after being treated with modafinil (Provigil) for decreased arousal. Both patients demonstrated bias in magnitude estimation relative to normal subjects (n=83). Alertness improved in the neglect patient after taking modafinil. His neglect also resolved and his magnitude estimates more closely resembled those of normal subjects. This is the first evidence, to our knowledge, that left hemisphere injury can bias magnitude estimation in a manner similar but not identical to that associated with right hemisphere injury.

Supportive care for patients with Guillain-Barré syndrome.

A multidisciplinary consensus group searched MEDLINE from 1966 to May 2003, extracted relevant references, and prepared recommendations on supportive care for Guillain-Barré syndrome. In the absence of randomized controlled trials, we agreed on recommendations by consensus based on observational studies and expert opinion. In the acute phase in bed-bound adult patients, the group recommended the use of heparin and graduated pressure stockings to prevent deep vein thrombosis, monitoring for blood pressure, pulse, autonomic disturbances, and respiratory failure, and the timely institution of artificial ventilation and tracheostomy. Pain management is difficult, but carbamazepine or gabapentin may help. The cautious use of narcotic analgesics may be needed. Disabled patients should be treated by a multidisciplinary rehabilitation team and should receive an assistive exercise program. Persistent fatigue following Guillain-Barré syndrome is common and may be helped by an exercise program. Because of a very small and possibly only theoretical increase in the risk of recurrence following immunization, the need for immunization should be reviewed on an individual basis. More research is needed to identify optimal methods for all aspects of supportive care.