Contextualized Treatment in Traumatic Brain Injury Inpatient Rehabilitation: Effects on Outcomes During the First Year after Discharge

Objective To evaluate the effect of providing a greater percentage of therapy as contextualized treatment on acute traumatic brain injury (TBI) rehabilitation outcomes. Design Propensity score methods are applied to the TBI-Practice-Based Evidence (TBI-PBE) database, a database consisting of multi-site, prospective, longitudinal observational data. Setting Acute inpatient rehabilitation. Participants Patients enrolled in the TBI-PBE study (n=1843), aged 14 years or older, who sustained a severe, moderate, or complicated mild TBI, receiving their first IRF admission in the US, and consented to follow-up 3 and 9 months post discharge from inpatient rehabilitation. Interventions Not applicable. Main Outcome Measures Participation Assessment with Recombined Tools-Objective- -17, FIMTM Motor and Cognitive scores, Satisfaction with Life Scale and Patient Health Questionnaire-9. Results Increasing the percentage of contextualized treatment during inpatient TBI rehabilitation leads to better outcomes, specifically in regard to community participation. Conclusions Increasing the proportion of treatment provided in the context of real-life activities appears to have a beneficial impact on outcome. Although the effect sizes are small, the results are consistent with other studies supporting functional-based interventions effecting better outcomes. Furthermore, any positive findings, regardless of size or strength, are endorsed as important by consumers (survivors of TBI). While the findings do not imply that decontextualized treatment should not be used, when the therapy goal can be addressed with either approach, the findings suggest that better outcomes may result if the contextualized approach is used

Impact of Level of Effort on the Effects of Compliance with the 3-Hour Rule

Objective To determine if patients’ level of effort (LOE) in therapy sessions during traumatic brain injury (TBI) rehabilitation modifies the effect of compliance with the 3-Hour Rule of the Centers for Medicare & Medicaid Services. Design Propensity score methodology applied to the TBI-Practice-Based Evidence (TBI-PBE) database, consisting of multi-site, prospective, longitudinal observational data. Setting Acute inpatient rehabilitation facilities (IRF). Participants Patients (n=1820) who received their first IRF admission for TBI in the US and were enrolled for 3 and 9 month follow-up. Main Outcome Measures Participation Assessment with Recombined Tools-Objective-17, FIMTM Motor and Cognitive scores, Satisfaction with Life Scale, and Patient Health Questionnaire-9. Results When the full cohort was examined, no strong main effect of compliance with the 3-Hour Rule was identified and LOE did not modify the effect of compliance with the 3-Hour Rule. In contrast, LOE had a strong positive main effect on all outcomes, except depression. When the sample was stratified by level of disability, LOE modified the effect of compliance, particularly on the outcomes of participants with less severe disability. For these patients, providing 3 hours of therapy for 50%+ of therapy days in the context of low effort resulted in poorer performance on select outcome measures at discharge and up to 9 months post discharge compared to patients with <50% of 3-hr therapy days. Conclusions LOE is an active ingredient in inpatient TBI rehabilitation, while compliance with the 3-Hour Rule was not found to have a substantive impact on the outcomes. The results support matching time in therapy during acute TBI rehabilitation to patients’ LOE in order to optimize long-term benefits on outcomes

Expression of a Mutant p53 Results in an Age-Related Demographic Shift in Spontaneous Lung Tumor Formation in Transgenic Mice

BACKGROUND:Mutations in the P53 gene are among the most common genetic abnormalities in human lung cancer. Codon 273 in the sequence-specific DNA binding domain is one of the most frequently mutated sites. METHODOLOGY:To investigate the role of mutant p53 in lung tumorigenesis, a lung specific p53(273H) transgenic mouse model was developed. Rates of lung cancer formation in the transgenic animals and their littermates were evaluated by necropsy studies performed in progressive age cohorts ranging from 4 to 24 months. In order to establish the influence of other common genetic abnormalities in lung tumor formation in the animals, K-Ras gene mutation and p16INK4a (p16) promoter methylation were evaluated in a total of 281 transgenic mice and 189 non-transgenic littermates. PRINCIPAL FINDINGS:At the age extremes of 4-12 and 22-24 months no differences were observed, with very low prevalence of tumors in animals younger than 12 months, and a relatively high prevalence at age 22 months or older. However, the transgenic mice had a significant higher lung tumor rate than their non-transgenic counterparts during the age of 13-21 months, suggesting an age-related shift in lung tumor formation induced by the lung-specific expression of the human mutant p53. Histopathology suggested a more aggressive nature for the transgenic tumors. Older mice (>13 months) had a significantly higher rate of p16 promoter methylation (17% v 82%). In addition, an age related effect was observed for K-Ras codons 12 or 13 mutations, but not for codon 61 mutations. CONCLUSIONS/SIGNIFICANCE:These results would suggest that the mutant p53(273H) contributes to an acceleration in the development of spontaneous lung tumors in these mice. Combination with other genetic and epigenetic alterations occurring after the age of 13 months is intimately linked to its oncogenic potential

Advanced Therapy in Traumatic Brain Injury Inpatient Rehabilitation: Effects on Outcomes During the First Year after Discharge

Objective To use causal inference methods to determine if receipt of a greater proportion inpatient rehabilitation treatment focused on higher level functions, e.g. executive functions, ambulating over uneven surfaces (Advanced Therapy, AdvTx) results in better rehabilitation outcomes. Design A cohort study using propensity score methods applied to the TBI-Practice-Based Evidence (TBI-PBE) database, a database consisting of multi-site, prospective, longitudinal observational data. Setting Acute inpatient rehabilitation (IRF). Participants Patients enrolled in the TBI-PBE study (n=1843), aged 14 years or older, who sustained a severe, moderate, or complicated mild TBI, receiving their first IRF admission to one of 9 sites in the US, and consented to follow-up 3 and 9 months post discharge from inpatient rehabilitation. Interventions Not applicable. Main Outcome Measures: Participation Assessment with Recombined Tools-Objective-17, FIMTM Motor and Cognitive scores, Satisfaction with Life Scale, and Patient Health Questionnaire-9. Results Controlling for measured potential confounders, increasing the percentage of AdvTx during inpatient TBI rehabilitation was found to be associated with better community participation, functional independence, life satisfaction, and decreased likelihood of depression during the year following discharge from inpatient rehabilitation. Participants who began rehabilitation with greater disability experienced larger gains on some outcomes than those who began rehabilitation with more intact abilities. Conclusions Increasing the proportion of treatment targeting higher level functions appears to have no detrimental and a small, beneficial effect on outcome. Caution should be exercised when inferring causality given that a large number of potential confounders could not be completely controlled with propensity score methods. Further, the extent to which unmeasured confounders influenced the findings is not known and could be of particular concern due to the potential for the patient’s recovery trajectory to influence therapists’ decisions to provide a greater amount AdvTx

Breastfeeding History and Risk of Stroke Among Parous Postmenopausal Women in the Women\u27s Health Initiative

Background: Stroke is the third leading cause of death among US Hispanic and non-Hispanic black women aged 65 and older. One factor that may protect against stroke is breastfeeding. Few studies have assessed the association between breastfeeding and stroke and whether this association differs by race and ethnicity. Methods and Results: Data were taken from the Women\u27s Health Initiative Observational Study with follow-up through 2010; adjusted hazard ratios for stroke subsequent to childbirth were estimated with Cox regression models accounting for left and right censoring, overall and stratified by race/ethnicity. Of the 80 191 parous women in the Women\u27s Health Initiative Observational Study, 2699 (3.4%) had experienced a stroke within a follow-up period of 12.6 years. The average age was 63.7 years at baseline. Fifty-eight percent (n=46 699) reported ever breastfeeding; 83% were non-Hispanic white, 8% were non-Hispanic black, 4% were Hispanic, and 5% were of other race/ethnicity. After adjustment for nonmodifiable potential confounders, compared with women who had never breastfed, women who reported ever breastfeeding had a 23% lower risk of stroke (adjusted hazard ratio=0.77; 95% confidence interval 0.70-0.83). This association was strongest for non-Hispanic black women (adjusted hazard ratio=0.52; 95% confidence interval 0.37-0.71). Further, breastfeeding for a relatively short duration (1-6 months) was associated with a 19% lower risk of stroke (adjusted hazard ratios=0.81; 95% confidence interval 0.74-0.89). This association appeared stronger with longer breastfeeding duration and among non-Hispanic white and non-Hispanic black women (test for trend P \u3c 0.01). Conclusions: Study results show an association and dose-response relationship between breastfeeding and lower risk of stroke among postmenopausal women after adjustment for multiple stroke risk factors and lifestyle variables. Further investigation is warranted

Randomized pilot trial for the efficacy of the MMF07 foot massager and heat therapy for restless legs syndrome.

BackgroundRestless Legs Syndrome (RLS) is a sensorimotor condition with a wide range of severity. Symptoms negatively affect sleep and quality of life. Pharmacologic options are not universally effective and side effects are common. Objective data regarding non-pharmacologic treatment is limited. The study objective was to evaluate the efficacy of the MMF07 foot massager and heat therapy on the severity of RLS symptoms.MethodsIn this pilot randomized controlled trial, twenty-eight patients with diagnosed, bothersome RLS were randomized to four treatment arms: no active intervention (n = 7), foot massager (n = 8), heat therapy (n = 6), and foot massager plus heat therapy (n = 7). Participants completed the RLS Severity Scale, RLS Quality of Life questionnaire, and the Medical Outcomes Study Sleep scale at the baseline visit and at the 4-week follow up visit.ResultsFour weeks post randomization, participants in the massager group had significant improvement in the RLS severity score (average difference: -9.0, 95% CI: -16.3, -1.7, p = 0.017) and sleep scale (average difference: -22.0, 95% CI: -36.5, -7.5, p = 0.005) compared to the no intervention group. The heat alone group had a significant improvement in the sleep scale compared to the no-intervention group (average difference: -17.4, 95% CI: -32.5, -2.3, p = 0.026). Quality of life improved in the massage only group compared to control (average difference 25.3, 95% CI: -2.4, 53.0, p = 0.072).ConclusionsResults suggest that the MMF07 foot massage device and heat therapy may be feasible and effective treatment options to improve RSL symptoms

The role of perioperative sodium bicarbonate infusion affecting renal function after cardiothoracic surgery

Cardiac surgery associated acute kidney injury (CSA-AKI) is associated with poor outcomes including increased mortality, length of hospital stay and cost. The incidence of acute kidney injury (AKI) is reported to be between 3-30% depending on the definition of AKI. We designed a multicenter randomized controlled trial to test our hypothesis that a perioperative infusion of sodium bicarbonate during cardiac surgery will attenuate the postoperative rise in creatinine indicating renal injury when compared to a perioperative infusion with normal saline. An interim analysis was performed after data was available on the first 120 participants. A similar number of patients in the two treatment groups developed acute kidney injury (AKI), defined as an increase in serum creatinine the first 48 hours after surgery of 0.3 mg/dl or more. Specifically 14 patients (24%) who received sodium chloride (SC) and 17 patients (27%) who received sodium bicarbonate (SB) were observed to develop AKI post surgery, resulting in a relative risk of AKI of 1.1 (95% CI: 0.6-2.1, chi-square p-value=0.68) for patients receiving SB compared to those who received SC . The data safety monitoring board for the trial recommended closing the study early as there was only a 12% probability that the null hypothesis would be rejected. We therefore concluded that a perioperative infusion of sodium bicarbonate failed to attenuate the risk of CSA-AKI. <br/