The Center for Medicare and Medicaid Innovation under the Centers for Medicare and Medicaid Services has invited institutions to demonstrate ways to bundle services into a 90-day episode of acute ...care that will lower costs and hospital re-admission rates. While these goals are laudable, they overlook the need for and value attained in postacute treatment. This article argues for elimination of the diagnosis of stroke from the proposed demonstration project due to misaligned financial incentives that will severely compromise patient outcomes.
We described recently a subacute serum autoantibody response toward glial fibrillary acidic protein (GFAP) and its breakdown products 5-10 days after severe traumatic brain injury (TBI). Here, we ...expanded our anti-GFAP autoantibody (AutoAbGFAP) investigation to the multicenter observational study Transforming Research and Clinical Knowledge in TBI Pilot (TRACK-TBI Pilot) to cover the full spectrum of TBI (Glasgow Coma Scale 3-15) by using acute (<24 h) plasma samples from 196 patients with acute TBI admitted to three Level I trauma centers, and a second cohort of 21 participants with chronic TBI admitted to inpatient TBI rehabilitation. We find that acute patients self-reporting previous TBI with loss of consciousness (LOC) (n = 43) had higher day 1 AutoAbGFAP (mean ± standard error: 9.11 ± 1.42; n = 43) than healthy controls (2.90 ± 0.92; n = 16; p = 0.032) and acute patients reporting no previous TBI (2.97 ± 0.37; n = 106; p < 0.001), but not acute patients reporting previous TBI without LOC (8.01 ± 1.80; n = 47; p = 0.906). These data suggest that while exposure to TBI may trigger the AutoAbGFAP response, circulating antibodies are elevated specifically in acute TBI patients with a history of TBI. AutoAbGFAP levels for participants with chronic TBI (average post-TBI time 176 days or 6.21 months) were also significantly higher (15.08 ± 2.82; n = 21) than healthy controls (p < 0.001). These data suggest a persistent upregulation of the autoimmune response to specific brain antigen(s) in the subacute to chronic phase after TBI, as well as after repeated TBI insults. Hence, AutoAbGFAP may be a sensitive assay to study the dynamic interactions between post-injury brain and patient-specific autoimmune responses across acute and chronic settings after TBI.
One of the major barriers that have restricted successful use of chimeric antigen receptor (CAR) T cells in the treatment of solid tumors is an unfavorable tumor microenvironment (TME). We engineered ...CAR-T cells targeting carbonic anhydrase IX (CAIX) to secrete anti-PD-L1 monoclonal antibody (mAb), termed immune-restoring (IR) CAR G36-PDL1. We tested CAR-T cells in a humanized clear cell renal cell carcinoma (ccRCC) orthotopic mouse model with reconstituted human leukocyte antigen (HLA) partially matched human leukocytes derived from fetal CD34+ hematopoietic stem cells (HSCs) and bearing human ccRCC skrc-59 cells under the kidney capsule. G36-PDL1 CAR-T cells, haploidentical to the tumor cells, had a potent antitumor effect compared to those without immune-restoring effect. Analysis of the TME revealed that G36-PDL1 CAR-T cells restored active antitumor immunity by promoting tumor-killing cytotoxicity, reducing immunosuppressive cell components such as M2 macrophages and exhausted CD8+ T cells, and enhancing T follicular helper (Tfh)-B cell crosstalk.
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•Developed immune-restoring anti-CAIX CAR-T cells secreting anti-PD-L1 mAb•A humanized ccRCC orthotopic mouse model recapitulates ccRCC patient TME•G36-PDL1 IR CAR-T shows superior antitumor efficacy in a humanized mouse model•G36-PDL1 IR CAR-T promotes tumor killing by reversing immunosuppressive TME
Immunology; Cancer; Transcriptomics
To explore the rates of suicidal ideation (SI) in a sample of community-dwelling adults with traumatic brain injury (TBI) and to assess the relationship between SI and demographic and injury ...characteristics, pre- and postinjury psychiatric history, and psychosocial functioning.
Data were collected from a cohort study focused on health, psychosocial functioning, and community integration post-TBI (N = 356). Participants were individuals with mild to severe TBI living in the community.
The Beck Depression Inventory II (BDI-II) was used to assess SI. Psychiatric functioning was assessed using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV) Axis I disorders (SCID-I), and psychosocial functioning was assessed using the Life-3, the Flanagan Scale of Unmet Needs, and the Bigelow Quality of Life Questionnaire.
There were no differences in SI endorsement based on gender, age, race, income, education, injury severity, or length of time since injury. Those who met current criteria for a psychiatric diagnosis of depression, anxiety, or posttraumatic stress disorder reported SI more frequently. Those with SI reported significantly lower psychosocial functioning.
Individuals with TBI from all demographic groups and with injuries of varying severity are at risk for SI and thus for emotional distress and suicidal behavior. Screening for SI is indicated in all individuals with TBI, particularly those with a history of premorbid substance misuse and concurrent mood and anxiety disorders. The importance of interventions to maximize social support and reduce social isolation is discussed.
To examine the predictive validity of a brief neuropsychologic test battery consisting of the Galveston Orientation and Amnesia Test, the California Verbal Learning Test-II, Trail-Making Test (TMT), ...Symbol Digit Modalities Test, grooved pegboard, phonemic and categorical word generation tasks, the Wechsler Test of Adult Reading (WTAR), and the Wisconsin Card Sorting Test-64 relative to functional outcome at 1 year in persons with traumatic brain injury.
Inception cohort study. Follow-up period of 12 months.
Seven Traumatic Brain Injury Model System centers. Neuropsychologic testing was conducted during the acute inpatient rehabilitation stay and functional outcome measures were obtained at 1-year outpatient follow-up.
Adults (N=174) who met criteria for admission to inpatient brain injury rehabilitation.
Not applicable.
FIM instrument, Disability Rating Scale, Supervision Rating Scale, Satisfaction With Life Scale (SWLS), and Glasgow Outcome Scale-Extended.
Multiple regression analyses revealed that performance on the neuropsychologic test battery was predictive of outcome at 1 year postinjury for all outcome measures, except FIM motor scores and the SWLS. Cognitive performance using this battery was found to predict 1-year outcomes above and beyond functional variables and injury severity variables collected during inpatient rehabilitation, thereby indicating incremental validity for this test battery. Individual tests that were found to be significant predictors of 1-year outcomes included the WTAR and TMT part B.
These findings support the clinical utility and ecological validity of this battery with respect to level of disability, functional independence, and supervision required.
Role and impact of cognitive rehabilitation Dams-O'Connor, Kristen; Gordon, Wayne A
The Psychiatric clinics of North America,
12/2010, Letnik:
33, Številka:
4
Journal Article
Recenzirano
Cognitive rehabilitation interventions are theoretically based and empirically validated treatments designed to ameliorate the cognitive, behavioral, and emotional impairments commonly experienced by ...individuals with traumatic brain injury (TBI). Cognitive rehabilitation can play many roles in facilitating recovery after TBI, such as improving impaired cognitive functions, increasing awareness of injury-related deficits, improving mood, facilitating vocational and community involvement, and reducing the probability of secondary disability. The considerable evidence documenting the impact of cognitive rehabilitation on improving the day-to-day function of individuals with TBI is described.
The primary objective was to examine specific aspects of sexual functioning (frequency, desired frequency, importance, and satisfaction) and their relationship to fatigue in individuals with ...traumatic brain injury (TBI) compared with those without brain injury. The relationship of demographic variables, emotional well-being, and health-related quality of life to sexual functioning was also explored.
200 community-dwelling adults with self-reported mild-to-severe TBI and 83 individuals without brain injury.
Participation Objective, Participation Subjective, Fatigue Assessment Instrument, Global Fatigue Index, Beck Depression Inventory, and SF-36 Health Survey.
Data were collected through administration of self-report measures and interviews as part of a larger study of post-TBI fatigue.
Several aspects of sexual activity (frequency, desired frequency, and importance) were closely related to specific features of fatigue among individuals with TBI. Women with TBI reported lower frequency and lower importance of sex than men. In individuals without brain injury, the impact of fatigue was limited to the frequency of sexual activity with no sex differences observed.
Fatigue plays a different role in the subjective experience of sexual activity for men and women with TBI than for those without brain injuries. Fatigue and sex should be taken into account in future research and interventions focused on sexual function after TBI.
China's one-child-per-couple policy, introduced in 1979, led to profound demographic changes for nearly a quarter of the world's population. Several decades later, the consequences include decreased ...fertility rates, population aging, decreased household sizes, changes in family structure, and imbalanced sex ratios. The epidemiology of communicable diseases may have been affected by these changes since the transmission dynamics of infectious diseases depend on demographic characteristics of the population. Of particular interest is influenza because China and Southeast Asia lie at the center of a global transmission network of influenza. Moreover, changes in household structure may affect influenza transmission. Is it possible that the pronounced demographic changes that have occurred in China have affected influenza transmission?
To address this question, we developed a continuous-time, stochastic, individual-based simulation model for influenza transmission. With this model, we simulated 30 years of influenza transmission and compared influenza transmission rates in populations with and without the one-child policy control. We found that the average annual attack rate is reduced by 6.08% (SD 2.21%) in the presence of the one-child policy compared to a population in which no demographic changes occurred. There was no discernible difference in the secondary attack rate, -0.15% (SD 1.85%), between the populations with and without a one-child policy. We also forecasted influenza transmission over a ten-year time period in a population with a two-child policy under a hypothesis that a two-child-per-couple policy will be carried out in 2015, and found a negligible difference in the average annual attack rate compared to the population with the one-child policy.
This study found that the average annual attack rate is slightly lowered in a population with a one-child policy, which may have resulted from a decrease in household size and the proportion of children in the population.
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