Individuals With Chronic Traumatic Brain Injury Improve Walking Speed and Mobility With Intensive Mobility Training

Objective

To determine the feasibility and impact of different dosages of Intensive Mobility Training (IMT) on mobility, balance, and gait speed in individuals with chronic traumatic brain injury (TBI).

Design

Prospective, single group design with 3-month follow-up.

Setting

University research laboratory.

Participants

Volunteer sample of participants with chronic TBI (N=10; ≥3mo post-TBI; able to ambulate 3.05m with or without assistance; median age, 35.4y; interquartile range, 23.5–46y; median time post-TBI, 9.91y; interquartile range, 6.3–14.2y). Follow-up data were collected for all participants.

Interventions

Twenty days (5d/wk for 4wk), with 150min/d of repetitive, task-specific training equally divided among balance; gait training; and strength, coordination, and range.

Main Outcome Measures

Pain and fatigue were recorded before and after each session to assess feasibility. Treatment outcomes were assessed before training (pre), after 10 sessions (interim), after 20 sessions (post), and at 3-months follow-up and included the Berg Balance Scale and gait speed.

Results

Participants averaged 150.1±2.7 minutes per session. Median presession and postsession pain scores were 0 (out of 10) for 20 sessions; median presession fatigue scores ranged from 0 to 2.5 (out of 10); and postsession scores ranged from 3 to 5.5 (out of 10). Four outcome measures demonstrated significant improvement from the pretest to interim, with 7 out of 10 participants exceeding the minimal detectable change (MDC) for fast walking speed. At the posttest, 2 additional measures were significant, with more participants exceeding the MDCs. Changes in fast walking speed and Timed Up and Go test were significant at follow-up.

Conclusions

Limited fluctuations in pain and fatigue scores indicate feasibility of IMT in this population. Participants demonstrated improvements in walking speed, mobility, and balance postintervention and maintained gains in fast walking speed and mobility at 3 months.     

Quantitative CT improves outcome prediction in acute traumatic brain injury

The admission noncontrast head computed tomography (CT) scan has been demonstrated to be one of several key early clinical and imaging features in the challenging problem of prediction of long-term outcome after acute traumatic brain injury (TBI). In this study, we employ two novel approaches to the problem of imaging classification and outcome prediction in acute TBI. First, we employ the novel technique of quantitative CT (qCT) image analysis to provide more objective, reproducible measures of the abnormal features of the admission head CT in acute TBI. We show that the incorporation of quantitative, rather than qualitative, CT features results in a significant improvement in prediction of the 6-month Extended Glasgow Outcome Scale (GOS-E) score over a wide spectrum of injury severity. Second, we employ principal components analysis (PCA) to demonstrate the interdependence of certain predictive variables. Relatively few prior studies of outcome prediction in acute TBI have used a multivariate approach that explicitly takes into account the potential covariance among clinical and CT predictive variables. We demonstrate that several predictors, including midline shift, cistern effacement, subdural hematoma volume, and Glasgow Coma Scale (GCS) score are related to one another. Rather than being independent features, their importance may be related to their status as surrogate measures of a more fundamental underlying clinical feature, such as the severity of intracranial mass effect. We believe that objective computational tools and data-driven analytical methods hold great promise for neurotrauma research, and may ultimately have a role in image analysis for clinical care.     

Safety Practices in Relation to Home Ownership Among Urban Mexican Immigrant Families

We examined home safety hazards, comparing renter- to owner-occupied housing among urban, immigrant Mexican families. Methods: Interviews and home inspections were conducted among urban, Spanish-speaking immigrant families with children. We estimated weighted hazard prevalence and used logistic regression to compare owner- and renter-occupied homes. Of 313 eligible households, 250 (80%) enrolled. Respondents were predominantly Mexican-born (99%), low income (72.6%) and lower education (92.3%). Most homes had fire, burn, fall, poisoning, electrocution and fire escape hazards, including high tap water temperatures (76.4%; 95% CI: 69.0, 83.7%), no working smoke alarms (60.0%; 51.3, 68.8%), slippery bathtub/shower surfaces (58.7%; 49.9, 67.5%), blocked fire escape routes (55.9%; 47.2, 64.5%) and child-accessible medications (71.0%; 60.1, 81.3%). After adjustment for sociodemographics, fire escape (OR = 8.8; 95% CI: 2.8, 27.7), carbon monoxide poisoning (OR = 2.9; 1.4, 6.2) and drowning (OR = 3.5; 1.3, 9.4) hazards were more likely in owner- than renter-occupied homes. Housing age and type explained most differences. Many urban, immigrant Spanish-speaking families live in unsafe homes. For this population, housing safety programs should be targeted based on housing age and type rather than tenure.     

Exposure of Research Personnel to Carbon Dioxide during Euthanasia Procedures

CO₂ is one of the most commonly used euthanasia agents for laboratory animals. Considerable research has gone into the effect of the agent on animals, but little has been done to examine potential human exposure during these procedures. In this study, we examine the CO₂ concentrations to which personnel are exposed while euthanizing rodents with CO₂. To examine the environmental levels of CO₂ generated during euthanasia, we examined several variables including flow rate, inclusion of a cage in the euthanasia chamber, inversion of the euthanasia chamber, chamber size, distance from the euthanasia chamber, and room size. Under all conditions, CO₂ concentrations in the room temporarily increased significantly to 600 to 4000 ppm. The results of this study show that, under several testing scenarios, occupational levels of CO₂ did not exceed governmentally mandated allowable exposure limits during routine rodent euthanasia procedures.Abbreviations: STEL, short-term exposure limit; TWA, time-weighted averageCO₂ is one of the most commonly used euthanasia agents in laboratory animal facilities. Euthanasia typically is performed by using a compressed gas cylinder to supply CO₂ to a small chamber. Considerable research has gone into the CO₂ effect on animals, but little has been done to examine the potential effects of human exposure. To protect workers exposed to CO₂, several organizations have set CO₂ exposure levels with which employers must comply. The Occupational Safety and Health Administration has set a permissible exposure limit,¹⁹ American Conference of Governmental Industrial Hygienists set a threshold limit value,² and the National Institute of Safety and Health⁷ has a recommended exposure limit. Normal atmospheric CO₂ is approximately 300 to 500 ppm. These 3 entities have all set the time-weighted average (TWA) for CO₂ as 5000 ppm and short-term exposure limit (STEL) is 30,000 ppm. TWA is an average exposure over 8 h, and STEL is the maximal exposure, typically over a 15-min interval. The National Institute of Safety and Health considers 40,000 ppm to be immediately dangerous to life.¹⁶Rooms dedicated for euthanasia typically are small, and in some institutions, dedicated personnel are responsible for overseeing all euthanasia activities. This is especially evident during rodent colony health surveillance, in which rodent CO₂ euthanasia may involve several days. This situation potentially can place employees at risk for both exposures to STEL and TWA limits. To our knowledge, there are no reports of CO₂ over-exposure incidents in animal care facilities. However, there are multiple incidents of CO₂ mortality and morbidity in other settings, including a research laboratory.^3,8 Events are commonly associated with CO₂ gas-line leaks in restaurants and manufacturing facilities¹ and pooling of CO₂ during fermentation processes in basements or low areas. One case report involved 25 people at an ice factory who required hospitalization when the discharge valve of a truck containing liquid CO₂ was knocked open in an enclosed environment.¹⁰ These events warn us that exposure to harmful and potentially lethal CO₂ levels can occur.The current study examined personnel CO₂ exposure in an animal research facility during mock mice euthanasia procedures. We hypothesized that the CO₂ room concentrations depend on gas flow rate, room size, room ventilation, chamber position, and chamber size. We also hypothesized that CO₂ room concentrations remain below 5000 ppm.     

“Hot” Unstable Angina—Is it Worse than Subacute Unstable Angina? Results from the GUARANTEE Registry

Abstract. Background and Methods: Because time to presentation to the hospital affects time to treatment and is known to be important in acute myocardial infarction, we evaluated this variable in patients with unstable angina/non-ST segment elevation myocardial infarction (UA/NSTEMI). Among 2909 consecutive patients with UA/NSTEMI admitted to 35 hospitals in 6 geographic regions of the United States, we compared patients with acute (onset of pain <12 hours before admission) and subacute (onset >12 hours) unstable angina. Results: Patients with hot (acute) unstable angina presented more often to the emergency department and were subsequently admitted more often to an intensive care unit. Hospital administration of medications did not differ between the two groups, with the exception of heparin, which was paradoxically used more often in subacute patients (p<0.001). All cardiac invasive procedures were undertaken less often in the acute patients (catheterization, 41.4% vs. 58.7%, p=0.001; percutaneous coronary intervention, 11.3% vs. 21.1%, p=0.001; coronary artery bypass grafting, 5.6% vs. 12.0%, p=0.001). A greater percentage of acute patients were found to have no significant coronary artery disease at cardiac catheterization (20.1% vs. 15.0%, p=0.006). Mortality did not differ between the two groups; however, the composite endpoint of death and MI favored the acute patients (1.3% vs. 2.2%, p=0.032). Conclusions: Contrary to our initial hypothesis, hot UA patients tended to be at lower risk than patients with subacute presentation, highlighting the fact that patients with UA/NSTEMI remain at high risk even after the initial 12-hour period.     

Pharmacologically regulated Fas-mediated death of adoptively transferred T cells in a nonhuman primate model

Conditional suicide genes derived from pathogens have been developed to confer drug sensitivity and enhance safety of cell therapy, but this approach is limited by immune responses to the transgene product. We examined a strategy to regulate survival of transferred cells based on induction of apoptosis through oligomerization of a modified human Fas receptor by a bivalent drug (AP1903). Three macaques (Macaca nemestrina) received autologous T cells retrovirally engineered to express a Fas suicide-construct (LV'VFas). High levels of transduced cells were present in blood following cell transfer, but LV'VFas(+) cells declined rapidly after AP1903 administration. A small fraction of LV'VFas(+) cells resisted elimination by AP1903, in part due to insufficient levels of transgene expression in resting T cells, because reactivation of these cells in vitro enhanced sensitivity to AP1903. An immune response to the transgene product was observed, but epitope mapping indicated the response was directed to discrete components of human LV'VFas that were variant with the corresponding macaque sequences. These data demonstrate that chemically induced dimerization can be used to regulate survival of adoptively transferred T cells in vivo.