Orientador: Yvens Barbosa Fernandes, Sebastião Araujo / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-08T19:37:05Z (GMT). No. of bitstreams: 1 Pasini_RenataLenize_M.pdf: 1921410 bytes, checksum: 17bcb0d3a217f0284da26d92e3b8a5da (MD5) Previous issue date: 2007 / Resumo: A traqueostomia é um procedimento comumente realizado em pacientes dependentes da ventilação mecânica (VM), internados em Unidade de Terapia Intensiva (UTI). Alguns autores acreditam que a realização precoce desse procedimento em tais pacientes diminui o tempo de dependência do aparelho ventilatório, bem como apresenta outros benefícios associados. Entretanto, o período mais adequado para a realização do procedimento ainda não se encontra bem estabelecido para pacientes com traumatismo craniencefálico (TCE), o que justificou a realização do presente estudo, cujo objetivo foi avaliar a influência da traqueostomia no tempo de ventilação mecânica e tempo de internação hospitalar de pacientes com TCE. Foi realizado um estudo prospectivo e não intervencionista, em que foram avaliados 33 pacientes com TCE de moderado a grave, cuja pontuação na escala de coma de Glasgow (ECG) foi = 10, com idade entre 14 e 80 anos e necessidade de traqueostomia. Os pacientes foram distribuídos em três grupos determinados a partir do momento da realização da traqueostomia: traqueostomia precoce (TP), realizada até o 6º dia de VM; traqueostomia intermediária (TI), realizada entre o 7° e 11° dias de VM; e a traqueostomia tardia (TT), realizada após o 12° dia de VM. Dos 33 pacientes avaliados, 28 eram do sexo masculino, com idade média de 30,7 ± 14,0 anos para a TP; 39,0 ± 18,4 anos para a TI e 37,7 ± 18,4 anos para a TT. No grupo submetido à traqueostomia precoce houve redução do tempo de ventilação mecânica e tendência a uma diminuição do tempo de internação hospitalar. O momento de realização da traqueostomia não influenciou na incidência de infecção pulmonar e mortalidade / Abstract: Tracheostomy has been performed frequently in ventilator-dependent patients in intensive care unit (ICU). Some authors believe that early tracheostomy can reduce mechanical ventilation (MV) time and can provide other associated benefits. However, its influence on weaning from MV is not clear in pacients with traumatic brain injury (TBI). The aim of this study was to evaluate the influence of tracheostomy on MV weaning in TBI patients. It was a prospective and non interventional study; including 33 patients with TBI (GCS < 10), aging between 14 and 80 years and that were submitted to a tracheostomy. The patients had been distributed into three groups: early tracheostomy (ET) (performed until 6th day of MV); intermediate tracheostomy (IT) (performed from the 7th to 11th day of MV) and late tracheostomy (LT) (performed after the 12th day of MV). Of the 33 evaluated patients, 28 were male and 5 female, aging 30.7 ± 14.0 years in ET group; 39.0 ± 18.4 years in IT group; and 37.7 ± 18.4 years in LT group. In the ET group, those patients with lower GCS and higher APACHE II at admission have shown a lesser hospital length of stay (HLOS); the IT group has shown a lesser HLOS in younger individuals and with lower APACHE II values. Regarding total MV time (orotracheal tube + tracheostomy), ET group has shown a lesser average time in relation to the other groups. However weaning times with tracheostomy alone were not different between groups. Also, pulmonary infection incidences have not been different between groups. Early tracheostomy can reduce total MV time and HLOS in patients with severe TBI, but it appears to have no influence on weaning time, incidence of pulmonary infection and mortality / Mestrado / Ciencias Biomedicas / Mestre em Ciências Médicas

The present study is a cross-validation of the Validity-10 embedded symptom validity indicator from the Neurobehavioral Symptom Inventory (NSI) for the detection of questionable response validity during evaluation for mild traumatic brain injury (TBI). The sample and data derived from a three-site Veterans Affairs (VA) parent study to validate the TBI Clinical Reminder, a routine set of questions asked of all recently returned veterans at VA facilities to screen for history of TBI. In the parent study, veterans recently returned from Iraq and Afghanistan underwent an evaluation for TBI with a physician and completed an assessment battery including neuropsychological tests of cognitive performance and indicators of symptom and performance validity, psychiatric assessment measures, a structured interview for post-traumatic stress disorder (PTSD), and various behavioral health questionnaires. The present study estimated the test operating characteristics of Validity-10, using NSI results gathered during the physician evaluation to compute Validity-10 scores, and using results on several other measures of symptom and performance validity from the assessment battery as criteria for questionable response validity. Only individuals who had positive screen results for TBI on the TBI Clinical Reminder prior to full evaluation were included in the present sample. Sensitivity of Validity-10 to questionable validity was moderately high (.60 - .70) to excellent (.90 - 1.00) at high levels of specificity (> .80). Effects of different base rates of and different criteria for questionable validity on the utility of Validity-10 were explored as well. Chi-square analyses to determine the effect of PTSD symptoms on the utility of Validity-10 demonstrated overall classification accuracy in general, and false positive rate in particular, were relatively poorer when used with individuals who reported significant PTSD symptoms. Overall, these findings support the use of Validity-10 (at cut score Validity-10 ≥ 19) to identify those veterans being evaluation for mild TBI in the VA system who should be referred for comprehensive secondary evaluation by a clinical neuropsychologist using multiple forms of symptom and performance validity testing. Further studies of the effects of PTSD symptoms on the accuracy of Validity-10 for this purpose are recommended.

Abstract Traumatic brain injury (TBI) is often the leading cause of death and the most common cause of permanent disability in children and young adults. The hospital admission rates as well as the incidence and mortality rates of TBI vary enormously in different countries and populations. Even though alcohol misuse is a well-known modifiable risk factor for TBI and other injuries, few studies have been carried out on drinking patterns in relation to TBI, alcohol's role in recurrent brain injuries as well as TBI in relation to alcohol use in children and adolescents. The Northern Finland 1966 Birth Cohort was used to study the epidemiology and recurrence of TBI as well as alcohol use by children with TBI by the age of 14 years and those who sustained TBI later in life. The role of parents' alcohol misuse on children's TBI was also studied. The incidence of TBI in the whole study population was 118/100 000 person-years (PY), and the pediatric incidence of TBI (children aged under 16 years) was 130/100 000 PY. Up to the age of 10 years, the occurrence of TBI did not differ by gender, but after that age, boys and men had a higher incidence compared to girls and women. Mortality from TBI in the whole study population was 14/100 000 PY. Parental alcohol misuse and male gender were significant risk factors for the occurrence of TBI in childhood. Drinking to intoxication at the age of 14 years was a more common habit of TBI subjects than controls, especially among girls. Frequent alcohol drinking and drunkenness reported at the age of 14 years as well as male gender were independent predictors of TBI later in life. An alcohol-related first TBI and urban place of birth were found to be significant risk factors for recurrent TBI. A significant positive correlation between first and recurrent TBIs with respect to alcohol involvement was observed. Alcohol drinking and parental alcohol misuse should be recognized among children and adolescents with acute TBI. Because alcohol drinking predicts the recurrence of TBI, a brief intervention focused on drinking habits is needed as an immediate preventive measure.

Concussion is an injury that disproportionately affects children and adolescents and has the potential to negatively impact school performance. Currently, a significant proportion of youth with concussion go unreported due to a lack of effective concussion surveillance procedures. Additionally, many individuals who have daily contact with youth (e.g., parents, teachers) lack training in how to assess or manage a concussion. Schools may be the ideal setting to address both of these problems as they have a high level of access to students and employ personnel (e.g., school psychologists, nurses, social workers, counselors) with experience in assessment and intervention. What is not known is how to best design a school-based concussion management (SBCM) procedure in order to facilitate concussion surveillance and management. Accordingly, the overall purpose of this study was to identify and describe factors (i.e., provider implementation characteristics, concussion referral communication) which may inform the design and implementation of SBCM programming. Examining the relationship between relevant SBCM outcomes and factors associated with strong school programming may help build the foundation for future SBCM procedures. Factors that influence program fidelity and outcomes are called school programming implementation characteristics and they reside at multiple levels (i.e., community, school, climate, program, provider) and are positively related to successful outcomes across varied programming. This exploratory study which utilized secondary analysis of existing data focused on the provider level with the primary aim of identifying and describing student services personnel (SSP; n = 144) implementation characteristics. Indicators of provider implementation characteristics consisted of their beliefs, training, and experiences in order to quantify how these characteristics predict perceptions of the impact of concussion on academics, perception of current informal procedures, and the number of students with concussions served. The independent variables primarily under investigation in this study (role, career experience, recent concussion experience, and training subscale) align with empirically supported personnel implementation characteristics. The second aim of this study was to explore pre-existing communication patterns between SSP utilizing the independent variable referral source. It is of note that the school district from which the data were collected had no formal SBCM programming; therefore, all SSP implementation characteristics examined were viewed as baseline characteristics. Results indicated that as all SSP groups (i.e., school psychologists, nurses, counselors, social workers) perceive a need for SBCM as indicated by dissatisfaction with current procedures and agreement that concussion can negatively impact student performance. Although all groups indicated that they did not believe current concussion procedures to be effective, school psychologists and nurses reported the highest levels of dissatisfaction Additionally, nurses were found to have the highest levels of training in concussion assessment and management, and received significantly more concussion referrals per year when compare to the other SSP. These findings suggest that nurses may be effective in delivering concussion related service and establishing effective concussion surveillance procedures. Although more research is needed, this study represents the first step in bridging the gap between experimental concussion research and the successful delivery of these innovations through SBCM programming in order to help students recover from a concussion.

Fundação de Amparo a Pesquisa no Estado do Rio Grande do Sul / This study presents an analysis on the effects of creatine supplementation on parameters of susceptibility to seizures induced by subconvulsant dose of pentylenetetrazol (PTZ) in an experimental rat model of traumatic brain injury (TBI). TBI is an acute neurological event that can lead to chronic neurological disease, such as epilepsy. Given the magnitude of the problem, various forms of therapy is being tested, but many have failed and yet, few take into account the susceptibility to seizures as an outcome and concentrate on a very early period of injury, getting away from the reality of patients in underdeveloped countries. Creatine is an interesting compound to be evaluated for this purpose, since it has neuromodulatory properties and may regulate synaptic plasticity in developing neurons. Thus, it became interesting to investigate whether there is any effect of creatine in this scenario. To this, creatine supplementation was held by gavage in rats subjected to fluid percussion TBI model and this supplementation began one week after TBI, once a day for four weeks. PTZ test was performed two hours after the last dose of creatine. Furthermore a similar protocol was performed to verify the persistence of the effect and secondly, to verify the acute effect of creatine, just before the PTZ test. Latency for myoclonic and tonic clonic seizures, total time of generalized seizure as the clinical severity through the scale of Racine were measured and also epileptiform discharges and spindle activity before and after the administration of PTZ were quantified. As main results, it was found a decreased susceptibility to seizures in rats supplemented by a month, and the effect remained even if there was withdrawal of creatine for a week, however, this effect was not observed in the single dose of the compound. Still, a positive correlation between epileptiform discharges and spindle activity was found, both reduced in animals supplemented continuously. Thus, creatine is presented as a candidate to be tested in studies with TBI, with the purpose of reducing the susceptibility to seizures. / Este trabalho apresenta uma análise dos efeitos da suplementação de creatina sobre parâmetros de suscetibilidade à crise epiléptica induzida por pentilenotetrazol (PTZ) em dose subconvulsivante, por modelo experimental de traumatismo cranioencefálico (TCE) em ratos. O traumatismo cranioencefálico (TCE) é um evento neurológico agudo que pode levar à doença neurológica crônica, como a epilepsia. Devido a magnitude do problema, diversas formas terapêuticas vêm sendo testadas, porém muitas falharam e ainda, poucas levam em conta o desfecho da suscetibilidade à crises epilépticas, além de se concentrarem em um período muito precoce da patologia, ficando longe da realidade dos pacientes de países subdesenvolvidos. A creatina consiste num interessante composto a ser avaliado para esse fim, já que apresenta propriedades neuromodulatorias e de regulação da plasticidade sináptica em neurônios em desenvovlimento. Assim, tornou-se interessante investigar se existe algum efeito da creatina nesse cenário. Para isso, realizou-se suplementação de creatina por gavagem em ratos submetidos ao TCE por percussão de fluído, iniciada esta suplementação uma semana após o TCE, uma vez ao dia, por quatro semanas, sendo o teste com PTZ realizado duas horas após a última dose. Também foi realizado um protocolo semelhante para verificar se o efeito da creatina era duradouro e outro, para verificar o efeito agudo, logo antes do teste com PTZ. Foram mensurados o tempo de latência para crises mioclônica e tônico clônica generalizada, tempo total de crise generalizada, gravidade da crise através da escala de Racine, bem como quantificada as descargas epileptiformes e ondas de fuso antes e após a administração de PTZ. Como resultados principais, encontrou-se a diminuição da suscetibilidade à crises epilépticas nos ratos suplementados por um mês, e o efeito permaneceu mesmo quando houve retirada da creatina por uma semana adicional, porém, esse efeito não foi observado na administração única do composto. Também houve correlação positiva do aparecimento de descargas epileptiformes e atividades de fuso, ambas reduzidas nos animais suplementados continuamente. Assim, a creatina apresenta-se como substância candidata à testes em estudos com traumatismo cranioencefálico, com a finalidade de diminuir a suscetibilidade à crises epilépticas.

Traumatic brain injury (TBI) is the leading cause of death and disability among children and adolescents. Brain injury survivors are often left with persistent impairments that have the potential to impede daily functioning, delay or prevent the attainment of developmental milestones, and subsequently limit future productivity in adulthood. A shared goal of both neurorehabilitation and the educational system is to prepare youth for a productive adulthood with both systems of care having substantial, yet independent, literature bases regarding factors associated with productivity (e.g., engagement in employment or post-secondary education). It is currently assumed that because type of high school exiting (e.g., diploma, GED, dropout) is related to productivity for the general population, it also is related to productivity for adolescents with a serious TBI. It is possible that the factors outlined in the TBI literature account for the majority of the variance in this relationship and that exiting has no unique relationship with future productivity for this neurologically compromised population. As such, the purpose of this study was to explore the intersection of TBI and high school exiting. This study was a secondary analysis of the Traumatic Brain Injury Model Systems (TBIMS) database and featured a sample (n = 202) of 16 to 18-year-olds who were enrolled in high school when they sustained a moderate to severe TBI and subsequently attended inpatient neurorehabilitation. All participants in this study suffered their injuries between 4/1/2003 and 10/1/2010. The first aim of this study was to describe the rates of high school exiting for students with a moderate or severe TBI who attended inpatient neurorehabilitation and to examine group differences (e.g., race, insurance type, injury severity). Currently, there are no known data regarding rates for type of high school exiting (diploma, GED, dropout) or group differences for this population. This study found rates of 83% diploma, 5% GED, and 12% dropout. These rates are striking as they mirror data reported for the general student population. When examining group differences, several factors appeared to be more likely associated with earning a diploma (i.e., White, not receiving Medicaid, no pre-injury learning problem, no pre-injury learning problem, injury severity, higher motor functioning at rehabilitation discharge, acute length of stay) and others with GED (i.e., pre-injury learning problem, pre-injury substance use problem) or dropout (i.e., nonWhite, receiving Medicaid, pre-injury learning problem, lower cognitive functioning at rehabilitation discharge). In this study, variables associated with diploma were conceptualized as protective factors and variables associated with dropout conceptualized as risk factors. Findings from aim one (rates, group differences) are foundational data regarding high school exiting for students with a TBI. These data have the potential to provide normative reference, instill hope, spur collaboration between medicine and education, provide targets for intervention and policy, and serve as the foundation for future research. The second aim of this study was to examine if exiting type has a unique relationship with future productivity. Productivity was defined as hours per week engaged in post-secondary education and/or employment. Results indicated that exiting type (i.e., diploma) had a unique relationship with total productivity and educational productivity but not employment productivity after TBI. Employment productivity was better explained by several established predictors of productivity (race, pre-injury special education status, post-traumatic amnesia, functioning at rehabilitation discharge). The data from this study provide preliminary evidence that for students who attend inpatient neurorehabilitation after a serious TBI, earning a diploma is attainable, successful exiting can be promoted, and that earning a diploma is related to outcome (i.e., productivity). Overall, findings from this study provide foundational data that have the potential to aid in prognostication, serve as targets for intervention, and deserve further scientific inquiry.

Class of 2011 Abstract / OBJECTIVES: The overall purpose of this study was to describe comorbidities, charges, and mortality associated with inpatient, adult traumatic brain injury (TBI) cases in the United States (US) for the year 2007. METHODS: This was a retrospective cohort analysis of discharge records located in the National Emergency Department Sample (NEDS) of the Healthcare Cost and Utilization Project (HCUP). Descriptive statistics are provided for comorbidities, charges, and mortality. Logistic regression was performed to find characteristics associated with mortality while multiple regression was used to assess charges. Independent variables included age, injury severity, procedures used, location of TBI, and primary payer. RESULTS: A total of 639,698 TBI cases were found which were associated with 267,061 hospital admissions, over $17 billion in hospital charges, and 20,620 deaths in the year 2007.Most common comorbidities were essential hypertension, sprains and strains of the back, tobacco use, fluid and electrolyte disorders, and alcohol-related disorders. Characteristics associated with increased mortality and charges included New Injury Severity Score (NISS) over 10, involvement of a firearm, falls, motor vehicle traffic, and intubation. CONCLUSION: The current study gives the most current picture of inpatient adult TBI cases throughout the US. Future research is warranted to ensure that optimal outcomes are being attained in this vulnerable patient population.

Mild Traumatic Brain Injuries (mTBIs) are non-penetrating brain injuries that do not result in gross pathological lesions, yet they may cause a spectrum of cognitive and behavioral deficits. mTBI has been placed in the spotlight because of increased awareness of blast induced and sports-related concussions, but the underlying pathophysiological mechanisms are poorly understood. Several studies have implicated neuronal membrane poration and ion channel dysfunction as the primary mechanism of injury. We hypothesized that injury forces utilize mechanically-sensitive, transmembrane integrin proteins, which are coupled to the neuronal cytoskeleton (CSK) and distribute injury forces within the intracellular space, disrupting CSK organization and reducing intercellular neuronal functionality. To test this, magnetic beads were coated with adhesive protein, allowing them to bind to integrins in the neuronal membrane in vitro. To apply forces to the neurons via the bound beads, we built custom magnetic tweezers and demonstrated that focal adhesions (FACs) formed at the site of bead binding. We showed that the beads were coupled to the CSK via integrins by measuring the disparate adhesion of the soma and neurite to their underlying substrate. The soma also required more force to detach than neurites, correlating with the FAC density between each neuronal microcompartment and substrate. We then utilized the magnetic tweezers to test whether beads bound to integrins injured neurons more than beads that bound to neurons nonspecifically. Integrin-bound beads injured neurons more often and the injury was characterized by the formation of focal swellings along axons, reminiscent of Diffuse Axonal Injury. While integrin-bound beads initiated swellings throughout neurons, beads bound nonspecifically only caused local injury where beads were attached to neurons. To demonstrate the electrical dysfunction of integrin-mediated injury forces, we adapted Magnetic Twisting Cytometry to simultaneously apply injury forces to beads bound to multiple cells within neuronal networks in vitro. The formation of focal swellings resulted in reduced axonal electrical activity and decreased coordinated network activity. These data demonstrate that the mechanical insult associated with mTBI is propagated into neurons via integrins, initiating maladaptive CSK remodeling that is linked to impaired electrical function, providing novel insight into the underlying mechanisms of mTBI. / Engineering and Applied Sciences

Traumatic Brain Injury (TBI) is linked to a diverse range of diffuse pathological damage for which there is a severe lack of therapeutic options. A major limitation to drug development is the inability to identify causal mechanisms that link head trauma to the multitude of secondary injury cascades that underlie neuropathology. To elucidate these relationships, it is important to consider how physical forces are transmitted through the brain across multiple spatial scales ranging from the whole head to the sub-cellular level. In doing so, the mechanical behavior of the brain is typically characterized solely by its material properties and biological structure. Alternatively, forces transmitted through distinct cellular and extracellular structures have been shown to influence physiological processes in multiple cell types through the transduction of mechanical forces into cellular chemical responses. As an essential component of various biological processes, these mechanotransduction events are regulated by mechanical cues directed through extracellular matrix (ECM) and cell adhesion molecules (CAM) to mechanosensitive intra-cellular structures such as focal adhesions (FAs). Using a series of in vitro models, we have implicated FAs in the cellular mechanism of traumatic axonal injury by showing that forces directed through these structures potentiate injury levels and, moreover, that inhibition of FA-mediated signaling pathways may be neuroprotective. In addition, we show that localizing trauma forces through specific brain ECM results in differential injury rates, further implicating mechanosensitive cell-ECM linkages in the mechanism of TBI. Therefore, we show that FAs play a major role in axonal injury at low strain magnitudes indicating that cellular mechanotransduction may be an important mechanism underlying the initiation of cell and sub-cellular injuries ultimately responsible for the diffuse pathological damage and clinical symptoms observed in diffuse axonal injury. Furthermore, since these mechanisms may present the earliest events in the complex sequelae associated with TBI, they also represent potential therapeutic opportunities. / Engineering and Applied Sciences

Objectives: The majority of individuals who sustain a mild traumatic brain injury (mTBI) will experience a full recovery within the first weeks or months post-injury. However, some individuals will experience ongoing difficulties, or persistent post-concussion symptoms (PCS), for years following the injury. To date, most researchers have attributed PCS to either neuropathological factors or to psychogenic factors. Lacking exploration has been the role of psychosocial variables and the consideration of PCS from a more holistic, or 'whole person', perspective. As such, the goal of the current study was to undertake an investigation of persistent PCS using a broad, neuropsychosocial framework. Specifically, this was done by investigating how (a) cognitive functioning, (b) susceptibility to anxiety while in the context of a stressful situation (i.e., anxiety susceptibility), and (c) multiple components of identity (including self-perception, TBI- related self-concept, and TBI-related social identity) influence the severity of persistent PCS. The main underlying assertion to this research is that there are multiple factors that underlie the experience of persistent PCS; a purely neuropathological or psychogenic perspective is not sufficient to understand the complex processes inherent in recovery after mTBI. Method: The sample consisted of 21 adults, between 20 and 65 years of age, who had sustained an mTBI at least one year earlier. Following a telephone interview to determine eligibility (and a separate telephone interview with a source of collateral information) the participants completed a number of standardized neuropsychological measures and self- report questionnaires during an in-person, one-on-one data collection session. Results: The only injury-related or demographic variable that had an influence on PCS was injury etiology, whereby individuals with sports related injuries reported significantly less PCS than did those who sustained non-sports related injuries (e.g., motor vehicle accidents). Cognitive functioning had no influence on PCS severity, nor did anxiety susceptibility. However, one's general propensity to experience anxiety (i.e., trait anxiety) was a significant predictor of PCS. Further, multiple aspects of identity influenced PCS with both current self-perception and TBI-related social identity being significant predictors of self-reported PCS severity. Conclusions: Despite the failure to find any impact of neuropsychological factors on PCS in the current study, other lines of research have demonstrated neuropathological changes associated with mTBI – some of which may be chronic. Therefore, cognitive functioning may not be a sufficiently sensitive indicator of possible neuropathology at more than one year post-injury. On the other hand, the current study demonstrates that psychological and psychosocial factors are highly relevant to recovery and outcome following mTBI, and are significant predictors of PCS severity. Overall, the results support the assertion that recovery after mTBI is complex and that there are multiple factors that underlie persistent PCS. Further, the study demonstrates the importance of conceptualizing the process of recovery from a broad, neuropsychosocial perspective. Implications for treatment interventions and future research are discussed. / Graduate