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1.  The epidemiology of hospital treated traumatic brain injury in Scotland 
BMC Neurology  2014;14:2.
Traumatic Brain Injury (TBI) is an important global public health problem made all the more important by the increased likelihood of disability following a hospital admission for TBI. Understanding those groups most at risk will help inform interventions designed to prevent causes of TBI, such as falls prevention measures. This study identifies the rate of hospitalisation episodes of TBI in Scotland, explores causes of TBI admissions, and trends in hospitalisation episodes by age and gender over a twelve year period using routinely collected hospital data.
A retrospective analysis of routine hospital episode data identified records relating to TBI for the twelve years between 1998 and 2009. Descriptive and joinpoint regression analysis were used, average annual percentage changes (AAPC) and annual percentage change (APC) in rates were calculated.
Between 1998 and 2009 there were 208,195 recorded episodes of continuous hospital care in Scotland as a result of TBI. Almost half (47%) of all TBIs were the result of falls, with marked peaks observed in the very young and the oldest groups. The AAPC of hospitalization episode rates over the study period for boys and girls aged 0-14 were -4.9% (95% CI -3.5 to-6.3) and -4.7% (95% CI -2.6 to -6.8) respectively. This reduction was not observed in older age groups. In women aged 65 and over there was an APC of 3.9% (95% CI 1.2 to 6.6) between 2004 and 2009.
Hospitalisation for TBI is relatively common in Scotland. The rise in the age-adjusted rate of hospitalisation episodes observed in older people indicates that reduction of TBI should be a public health priority in countries with an ageing population. Public health interventions such as falls prevention measures are well advised and evaluations of such interventions should consider including TBI hospitalisation as an alternative or supplementary outcome measure to fractured neck of femur. Further research is needed to advance understanding of the associations of risk factors with increased incidence of TBI hospital episodes in the elderly population.
PMCID: PMC3893436  PMID: 24386897
Traumatic brain injury; Accidental falls; Patient admissions; Epidemiology; Scotland; Trends
2.  Intracranial pressure monitoring and outcomes after traumatic brain injury 
Canadian Journal of Surgery  2000;43(6):442-448.
Uncontrolled intracranial hypertension after traumatic brain injury (TBI) contributes significantly to the death rate and to poor functional outcome. There is no evidence that intracranial pressure (ICP) monitoring alters the outcome of TBI. The objective of this study was to test the hypothesis that insertion of ICP monitors in patients who have TBI is not associated with a decrease in the death rate.
Study of case records.
The data files from the Ontario Trauma Registry from 1989 to 1995 were examined. Included were all cases with an Injury Severity Score (ISS) greater than 12 from the 14 trauma centres in Ontario. Cases identifying a Maximum Abbreviated Injury Scale score in the head region (MAIS head) greater than 3 were selected for further analysis. Logistic regression analyses were conducted to investigate the relationship between ICP and death.
Of 9001 registered cases of TBI, an MAIS head greater than 3 was recorded in 5507. Of these patients, 541 (66.8% male, mean age 34.1 years) had an ICP monitor inserted. Their average ISS was 33.4 and 71.7% survived. There was wide variation among the institutions in the rate of insertion of ICP monitors in these patients (ranging from 0.4% to over 20%). Univariate logistic regression indicated that increased MAIS head, ISS, penetrating trauma and the insertion of an ICP monitor were each associated with an increased death rate. However, multivariate analyses controlling for MAIS head, ISS and injury mechanism indicated that ICP monitoring was associated with significantly improved survival (p < 0.015).
ICP monitor insertion rates vary widely in Ontario’s trauma hospitals. The insertion of an ICP monitor is associated with a statistically significant decrease in death rate among patients with severe TBI. This finding strongly supports the need for a prospective randomized trial of management protocols, including ICP monitoring, in patients with severe TBI.
PMCID: PMC3695200  PMID: 11129833
3.  Comparison of SNOMED CT versus Medcin Terminology Concept Coverage for Mild Traumatic Brain Injury 
Traumatic Brain Injury (TBI) is a “signature” injury of the current wars in Iraq and Afghanistan. Structured electronic data regarding TBI findings is important for research, population health and other secondary uses but requires appropriate underlying standard terminologies to ensure interoperability and reuse. Currently the U.S. Department of Veterans Affairs (VA) uses the terminology SNOMED CT and the Department of Defense (DOD) uses Medcin.
We developed a comprehensive case definition of mild TBI composed of 68 clinical terms. Using automated and manual techniques, we evaluated how well the mild TBI case definition terms could be represented by SNOMED CT and Medcin, and compared the results. We performed additional analysis stratified by whether the concepts were rated by a TBI expert panel as having High, Medium, or Low importance to the definition of mild TBI.
SNOMED CT sensitivity (recall) was 90% overall for coverage of mild TBI concepts, and Medcin sensitivity was 49%, p < 0.001 (using McNemar’s chi square). Positive predictive value (precision) for each was 100%. SNOMED CT outperformed Medcin for concept coverage independent of import rating by our TBI experts.
SNOMED CT was significantly better able to represent mild TBI concepts than Medcin. This finding may inform data gathering, management and sharing, and data exchange strategies between the VA and DOD for active duty soldiers and veterans with mild TBI. Since mild TBI is an important condition in the civilian population as well, the current study results may be useful also for the general medical setting.
PMCID: PMC3243122  PMID: 22195156
4.  Direct cost associated with acquired brain injury in Ontario 
BMC Neurology  2012;12:76.
Acquired Brain Injury (ABI) from traumatic and non traumatic causes is a leading cause of disability worldwide yet there is limited research summarizing the health system economic burden associated with ABI. The objective of this study was to determine the direct cost of publicly funded health care services from the initial hospitalization to three years post-injury for individuals with traumatic (TBI) and non-traumatic brain injury (nTBI) in Ontario Canada.
A population-based cohort of patients discharged from acute hospital with an ABI code in any diagnosis position in 2004 through 2007 in Ontario was identified from administrative data. Publicly funded health care utilization was obtained from several Ontario administrative healthcare databases. Patients were stratified according to traumatic and non-traumatic causes of brain injury and whether or not they were discharged to an inpatient rehabilitation center. Health system costs were calculated across a continuum of institutional and community settings for up to three years after initial discharge. The continuum of settings included acute care emergency departments inpatient rehabilitation (IR) complex continuing care home care services and physician visits. All costs were calculated retrospectively assuming the government payer’s perspective.
Direct medical costs in an ABI population are substantial with mean cost in the first year post-injury per TBI and nTBI patient being $32132 and $38018 respectively. Among both TBI and nTBI patients those discharged to IR had significantly higher treatment costs than those not discharged to IR across all institutional and community settings. This tendency remained during the entire three-year follow-up period. Annual medical costs of patients hospitalized with a brain injury in Ontario in the first follow-up year were approximately $120.7 million for TBI and $368.7 million for nTBI. Acute care cost accounted for 46-65% of the total treatment cost in the first year overwhelming all other cost components.
The main finding of this study is that direct medical costs in ABI population are substantial and vary considerably by the injury cause. Although most expenses occur in the first follow-up year ABI patients continue to use variety of medical services in the second and third year with emphasis shifting over time from acute care and inpatient rehabilitation towards homecare physician services and long-term institutional care. More research is needed to capture economic costs for ABI patients not admitted to acute care.
PMCID: PMC3518141  PMID: 22901094
5.  Postinjury employment as a surrogate for functional outcomes: a quality indicator for trauma systems 
Return to work may be easily monitored as a surrogate of long-term functional outcome for benchmarking and performance improvement of trauma systems. We hypothesized that employment rates among survivors of traumatic brain injury (TBI) decrease following injury and remain depressed for an extended period of time. Data were obtained from a statewide surveillance system of 3522 TBI patients (aged >15 years) who were discharged alive from acute care hospitals and followed yearly using telephone interviews (1996–1999). The study population consisted of patients with severe TBI (head abbreviated injury score 3, 4, or 5) and complete follow-up for 3 years postinjury (n = 572). Patients were mostly young males (43 ± 19 years, 65% male) with blunt TBI (92%). The preinjury employment rate was 67%, which declined to 52% (P < 0.001) in the first year and slowly rose in subsequent years but never reached the preinjury level (54% in year 2, P < 0.001; 57% in year 3, P = 0.001). Increasing severity of TBI was associated with a lower employment rate. Patients who remained employed worked the same number of hours as they did before the injury (47.8 ± 10.5 hours). Female employment rates rose similar to rates for males. However, women who were employed full-time before TBI were more likely to work part-time after TBI than men (50% vs 24%, P < 0.001). In conclusion, survivors of severe injury do not attain preinjury employment levels for several years. Once validated in other studies, postinjury employment may be used as an indicator to monitor functional outcomes in trauma registries.
PMCID: PMC2943447  PMID: 20944755
6.  Spatial Epidemiology: Current Approaches and Future Challenges 
Environmental Health Perspectives  2004;112(9):998-1006.
Spatial epidemiology is the description and analysis of geographic variations in disease with respect to demographic, environmental, behavioral, socioeconomic, genetic, and infectious risk factors. We focus on small-area analyses, encompassing disease mapping, geographic correlation studies, disease clusters, and clustering. Advances in geographic information systems, statistical methodology, and availability of high-resolution, geographically referenced health and environmental quality data have created unprecedented new opportunities to investigate environmental and other factors in explaining local geographic variations in disease. They also present new challenges. Problems include the large random component that may predominate disease rates across small areas. Though this can be dealt with appropriately using Bayesian statistics to provide smooth estimates of disease risks, sensitivity to detect areas at high risk is limited when expected numbers of cases are small. Potential biases and confounding, particularly due to socioeconomic factors, and a detailed understanding of data quality are important. Data errors can result in large apparent disease excess in a locality. Disease cluster reports often arise nonsystematically because of media, physician, or public concern. One ready means of investigating such concerns is the replication of analyses in different areas based on routine data, as is done in the United Kingdom through the Small Area Health Statistics Unit (and increasingly in other European countries, e.g., through the European Health and Environment Information System collaboration). In the future, developments in exposure modeling and mapping, enhanced study designs, and new methods of surveillance of large health databases promise to improve our ability to understand the complex relationships of environment to health.
PMCID: PMC1247193  PMID: 15198920
disease clusters; disease mapping; environmental pollution; epidemiology; geographic studies; methods
7.  Regional variations in the use of home care services in Ontario, 1993/95 
BACKGROUND: Although regional variations in the use of many health care services have been reported, little attention has been devoted to home care practices. Given the dramatic shift in care settings from hospitals to private homes, it is important to determine the extent to which home care practices vary by geographic region. METHODS: Data from the Canadian Institute for Health Information and the Ontario Home Care Administration System database were used to assess regional variations in rates of home care use following inpatient care and same-day surgery for the fiscal years 1993, 1994 and 1995. Various measures of regional variation were employed. RESULTS: Of the 2,870,695 inpatient separations and 1,803,307 same-day surgery separations during the study period, 359,972 and 64,541, respectively, were followed by home care. The rate of home care use per 100 separations was 12.5 for inpatients and 3.6 for same-day surgery patients. There was a a 3.5-fold regional variation in the rates of home care use following inpatient care and a 7-fold variation in rates of use following same-day surgery. Additional home care funding to attain calculated target rates was estimated to be $48.9 million (30% of expenditures for patients recently discharged from hospital over the study period). For a 20% increase in service provision it was estimated that an additional injection of $42.2 million is required. INTERPRETATION: The wide regional variations in rates of home care use highlight the importance of modifying home care funding to ensure that all residents of Ontario have equal access to services. To achieve this our estimates suggest that a substantial increase in home care funding is warranted.
PMCID: PMC1230537  PMID: 10478160
8.  Using GIS technology to identify areas of tuberculosis transmission and incidence 
Currently in the U.S. it is recommended that tuberculosis screening and treatment programs be targeted at high-risk populations. While a strategy of targeted testing and treatment of persons most likely to develop tuberculosis is attractive, it is uncertain how best to accomplish this goal. In this study we seek to identify geographical areas where on-going tuberculosis transmission is occurring by linking Geographic Information Systems (GIS) technology with molecular surveillance.
This cross-sectional analysis was performed on data collected on persons newly diagnosed with culture positive tuberculosis at the Tarrant County Health Department (TCHD) between January 1, 1993 and December 31, 2000. Clinical isolates were molecularly characterized using IS6110-based RFLP analysis and spoligotyping methods to identify patients infected with the same strain. Residential addresses at the time of diagnosis of tuberculosis were geocoded and mapped according to strain characterization. Generalized estimating equations (GEE) analysis models were used to identify risk factors involved in clustering.
Evaluation of the spatial distribution of cases within zip-code boundaries identified distinct areas of geographical distribution of same strain disease. We identified these geographical areas as having increased likelihood of on-going transmission. Based on this evidence we plan to perform geographically based screening and treatment programs.
Using GIS analysis combined with molecular epidemiological surveillance may be an effective method for identifying instances of local transmission. These methods can be used to enhance targeted screening and control efforts, with the goal of interruption of disease transmission and ultimately incidence reduction.
PMCID: PMC529461  PMID: 15479478
9.  Neuroinformatics challenges to the structural, connectomic, functional and electrophysiological multimodal imaging of human traumatic brain injury 
Throughout the past few decades, the ability to treat and rehabilitate traumatic brain injury (TBI) patients has become critically reliant upon the use of neuroimaging to acquire adequate knowledge of injury-related effects upon brain function and recovery. As a result, the need for TBI neuroimaging analysis methods has increased in recent years due to the recognition that spatiotemporal computational analyses of TBI evolution are useful for capturing the effects of TBI dynamics. At the same time, however, the advent of such methods has brought about the need to analyze, manage, and integrate TBI neuroimaging data using informatically inspired approaches which can take full advantage of their large dimensionality and informational complexity. Given this perspective, we here discuss the neuroinformatics challenges for TBI neuroimaging analysis in the context of structural, connectivity, and functional paradigms. Within each of these, the availability of a wide range of neuroimaging modalities can be leveraged to fully understand the heterogeneity of TBI pathology; consequently, large-scale computer hardware resources and next-generation processing software are often required for efficient data storage, management, and analysis of TBI neuroimaging data. However, each of these paradigms poses challenges in the context of informatics such that the ability to address them is critical for augmenting current capabilities to perform neuroimaging analysis of TBI and to improve therapeutic efficacy.
PMCID: PMC3935464  PMID: 24616696
neuroinformatics; traumatic brain injury; neuroanatomy; connectomics; rehabilitation; MRI; DTI
10.  The Diagnosis of Traumatic Brain Injury on the Battlefield 
The conflicts in Iraq and Afghanistan have placed an increased awareness on traumatic brain injury (TBI). Various publications have estimated the incidence of TBI for our deployed servicemen, however all have been based on extrapolations of data sets or subjective evaluations due to our current method of diagnosing a TBI. Therefore it has been difficult to get an accurate rate and severity of deployment related TBIs, or the incidence of multiple TBIs our service members are experiencing. As such, there is a critical need to develop a rapid objective method to diagnose TBI on the battlefield. Because of the austere environment of the combat theater the ideal diagnostic platform faces numerous logistical constraints not encountered in civilian trauma centers. Consequently, a simple blood test to diagnosis TBI represents a viable option for the military. This perspective will provide information on some of the current options for TBI biomarkers, detail concerning battlefield constraints, and a possible acquisition strategy for the military. The end result is a non-invasive TBI diagnostic platform capable of providing much needed advances in objective triage capabilities and improved clinical management of in-Theater TBI.
PMCID: PMC3373009  PMID: 22701447
TBI; military; biomarkers; diagnosis; concussion
11.  Epidemiology of traumatic brain injury in Austria 
Traumatic brain injury (TBI) is an important cause of preventable deaths. The goal of this study was to provide data on epidemiology of TBI in Austria.
Data on all hospital discharges, outpatients, and extra- as well as in-hospital deaths due to TBI were collected from various sources for the years 2009–2011. Population data (number of male/female people per age-group, population of Austrian cities, towns, and villages) for 2009–2011 were collected from the national statistical office. Incidence, case fatality rate(s) (CFR), and mortality rate(s) (MR) were calculated for the whole population and for age groups.
Incidence (303/100,000/year), CFR (3.6 %), and MR (11/100,000/year) of TBI in Austria are comparable with those from other European countries. We found a high rate of geriatric TBI. The ratio between male and female cases was 1.4:1 for all cases, and was 2.2:1 for fatal cases. The most common mechanism was falls; traffic accidents accounted for only 7 % of the cases. Males died more frequently from traffic accidents and suicides, and females died more frequently from falls. CFRs and MRs increased with increasing age. CFRs were higher in patients from less populated areas, and MRs were lower in cases who lived closer to hospitals that admitted TBI.
The high rate of geriatric TBI warrants better prevention of falls in this age group.
PMCID: PMC3904034  PMID: 24249325
Traumatic brain injury; Epidemiology; Outcome; Severity; Age; Sex; Geographical factors; Trauma; Schädelhirntrauma; Epidemiologie; Altersgruppen; Geschlecht; Unfallmechanismus; Geografische Faktoren
12.  Geriatric Traumatic Brain Injury in China 
Traumatic brain injury (TBI) is one of the major causes of morbidity and mortality in China. The elderly population has the higher rates of TBI-related hospitalization and death. Traffic accidents are the major cause for TBI in all age groups except in the group of 75 years and older, in which stumbles occurred in nearly half of those who suffered TBI. Older age is known to negatively influence outcome after TBI. To date, investigators have identified a panel of prognostic factors that include initial Glasgow Coma Scale score, comorbidities, cerebrospinal fluid leakage, associated extracranial lesions, and other factors such as cerebral perfusion pressure on recovery after injury. However, these aspects remain understudied in elderly patients with TBI. In the absence of complete clinical data, predicting outcomes and providing good care of the elderly population with TBI remain limited. To address this significant public health issue, a refocusing of research efforts is justified to prevent TBI in this population and to develop unique care strategies for achieving better clinical outcomes of the patients with TBI.
PMCID: PMC3758510  PMID: 24014155
Traumatic brain injury; Geriatric; Trauma; Injury; Epidemiology; Outcomes
13.  Older adults with acquired brain injury: a population based study 
BMC Geriatrics  2013;13:97.
Acquired brain injury (ABI), which includes traumatic (TBI) and non-traumatic brain injury (nTBI), is a leading cause of death and disability worldwide. The objective of this study was to examine the trends, characteristics, cause of brain injury, and discharge destination of hospitalized older adults aged 65 years and older with an ABI diagnosis in a population with universal access to hospital care. The profile of characteristics of patients with TBI and nTBI causes of injury was also compared.
A population based retrospective cohort study design with healthcare administrative databases was used. Data on acute care admissions were obtained from the Discharge Abstract Database and patients were identified using the International Classification of Diseases – Version 10 codes for Ontario, Canada from April 1, 2003 to March 31, 2010. Older adults were examined in three age groups – 65 to 74, 75 to 84, and 85+ years.
From 2003/04 to 2009/10, there were 14,518 episodes of acute care associated with a TBI code and 51, 233 episodes with a nTBI code. Overall, the rate of hospitalized TBI and nTBI episodes increased with older age groups. From 2007/08 to 2009/10, the percentage of patients that stayed in acute care for 12 days or more and the percentage of patients with delayed discharge from acute care increased with age. The most common cause of TBI was falls while the most common type of nTBI was brain tumours. The percentage of patients discharged to long term care and complex continuing care increased with age and the percentage discharged home decreased with age. In-hospital mortality also increased with age. Older adults with TBI and nTBI differed significantly in demographic and clinical characteristics and discharge destination from acute care.
This study showed an increased rate of acute care admissions for both TBI and nTBI with age. It also provided additional support for falls prevention strategies to prevent injury leading to cognitive disability with costly human and economic consequences. Implications for increased numbers of people with ABI are discussed.
PMCID: PMC3849645  PMID: 24060144
Brain injury; Epidemiology; Outcomes
14.  Nutritional Support for Patients Sustaining Traumatic Brain Injury: A Systematic Review and Meta-Analysis of Prospective Studies 
PLoS ONE  2013;8(3):e58838.
In traumatic brain injury (TBI), the appropriate timing and route of feeding, and the efficacy of immune-enhancing formulae have not been well established. We performed this meta-analysis aiming to compare the effects of different nutritional support modalities on clinical outcomes of TBI patients.
We systematically searched Pubmed, Embase, and the Cochrane Library until October, 2012. All randomized controlled trials (RCTs) and non-randomized prospective studies (NPSs) that compared the effects of different routes, timings, or formulae of feeding on outcomes in TBI patients were selected. The primary outcomes included mortality and poor outcome. The secondary outcomes included the length of hospital stay, the length of ventilation days, and the rate of infectious or feeding-related complications.
13 RCTs and 3 NPSs were included. The pooled data demonstrated that, compared with delayed feeding, early feeding was associated with a significant reduction in the rate of mortality (relative risk [RR] = 0.35; 95% CI, 0.24–0.50), poor outcome (RR = 0.70; 95% CI, 0.54–0.91), and infectious complications (RR = 0.77; 95% CI, 0.59–0.99). Compared with enteral nutrition, parenteral nutrition showed a slight trend of reduction in the rate of mortality (RR = 0.61; 95% CI, 0.34–1.09), poor outcome (RR = 0.73; 95% CI, 0.51–1.04), and infectious complications (RR = 0.89; 95% CI, 0.66–1.22), whereas without statistical significances. The immune-enhancing formula was associated with a significant reduction in infection rate compared with the standard formula (RR = 0.54; 95% CI, 0.35–0.82). Small-bowel feeding was found to be with a decreasing rate of pneumonia compared with nasogastric feeding (RR = 0.41; 95% CI, 0.22–0.76).
After TBI, early initiation of nutrition is recommended. It appears that parenteral nutrition is superior to enteral nutrition in improving outcomes. Our results lend support to the use of small-bowel feeding and immune-enhancing formulae in reducing infectious complications.
PMCID: PMC3602547  PMID: 23527035
15.  Predicting Progressive Hemorrhagic Injury after Traumatic Brain Injury: Derivation and Validation of a Risk Score Based on Admission Characteristics 
Journal of Neurotrauma  2012;29(12):2137-2142.
Previous studies have demonstrated that patients with traumatic brain injury (TBI) who also have progressive hemorrhagic injury (PHI), have a higher risk of clinical deterioration and worse outcomes than do TBI patients without PHI. Therefore, the early prediction of PHI occurrence is useful to evaluate the status of patients with TBI and to improve outcomes. The objective of this study was to develop and validate a prognostic model that uses information available at admission to determine the likelihood of PHI after TBI. Retrospectively collected data were used to develop a PHI prognostic model with a logistic regression analysis. The prediction model was validated in 114 patients from a separate hospital. Eight independent prognostic factors were identified: age ≥57 years (5 points), intra-axial bleeding/brain contusion (4 points), midline shift≥5 mm (6 points), platelet (PLT) count<100×109/L (10 points), PLT count≥100 but <150×109/L (4 points), prothrombin time>14 sec (7 points), D-dimer≥5 mg/L (12 points), and glucose≥10 mmol/L (10 points). Each patient was assigned a number of points proportional to the regression coefficient. We calculated risk scores for each patient and defined three risk groups: low risk (0–13 points), intermediate risk (14–22 points), and high risk (23–54 points). In the development cohort, the PHI rates after TBI for these three groups were 10.3%, 47.3%, and 85.2%, respectively. In the validation cohort, the corresponding PHI rates were 10.9%, 47.3%, and 86.9%. The C-statistic for the point system was 0.864 (p=0.509 by the Hosmer-Lemeshow test) in the development cohort, and 0.862 (p=0.589 by the Hosmer-Lemeshow test) in the validation cohort. In conclusion, a relatively simple risk score using admission predictors accurately predicted the risk for PHI after TBI.
PMCID: PMC3419842  PMID: 22568757
prognostic model; progressive hemorrhagic injury; risk score; traumatic brain injury; validation
16.  Traumatic Brain Injury in Older Adults: Epidemiology, Outcomes, and Future Implications 
Traumatic brain injury (TBI) is a significant problem in older adults. In persons aged 65 and older, TBI is responsible for more than 80,000 emergency department visits each year; three-quarters of these visits result in hospitalization as a result of the injury. Adults aged 75 and older have the highest rates of TBI-related hospitalization and death. Falls are the leading cause of TBI for older adults (51%), and motor vehicle traffic crashes are second (9%). Older age is known to negatively influence outcome after TBI. Although geriatric and neurotrauma investigators have identified the prognostic significance of preadmission functional ability, comorbidities, sex, and other factors such as cerebral perfusion pressure on recovery after illness or injury, these variables remain understudied in older adults with TBI. In the absence of good clinical data, predicting outcomes and providing care in the older adult population with TBI remains problematic. To address this significant public health issue, a refocusing of research efforts on this population is justified to prevent TBI in the older adult and to discern unique care requirements to facilitate best patient outcomes.
PMCID: PMC2367127  PMID: 17038079
traumatic brain injury; head injury; geriatric; trauma; injury; epidemiology; outcomes; functional status
17.  Traumatic brain injury, paraquat exposure, and their relationship to Parkinson disease 
Neurology  2012;79(20):2061-2066.
Traumatic brain injury (TBI) increased risk of Parkinson disease (PD) in many but not all epidemiologic studies, giving rise to speculations about modifying factors. A recent animal study suggested that the combination of TBI with subthreshold paraquat exposure increases dopaminergic neurodegeneration. The objective of our study was to investigate PD risk due to both TBI and paraquat exposure in humans.
From 2001 to 2011, we enrolled 357 incident idiopathic PD cases and 754 population controls in central California. Study participants were asked to report all head injuries with loss of consciousness for >5 minutes. Paraquat exposure was assessed via a validated geographic information system (GIS) based on records of pesticide applications to agricultural crops in California since 1974. This GIS tool assesses ambient pesticide exposure within 500 m of residences and workplaces.
In logistic regression analyses, we observed a 2-fold increase in risk of PD for subjects who reported a TBI (adjusted odds ratio [AOR] 2.00, 95% confidence interval [CI] 1.28–3.14) and a weaker association for paraquat exposures (AOR 1.36, 95% CI 1.02–1.81). However, the risk of developing PD was 3-fold higher (AOR 3.01, 95% CI 1.51–6.01) in study participants with a TBI and exposure to paraquat than those exposed to neither risk factor.
While TBI and paraquat exposure each increase the risk of PD moderately, exposure to both factors almost tripled PD risk. These environmental factors seem to act together to increase PD risk in a more than additive manner.
PMCID: PMC3511918  PMID: 23150532
18.  Risk for late-life re-injury, dementia and death among individuals with traumatic brain injury: a population-based study 
To determine the association of self-reported traumatic brain injury (TBI) with loss of consciousness (LOC) with late-life re-injury, dementia diagnosis and mortality.
Ongoing longitudinal population-based prospective cohort study.
Seattle-area integrated health system.
4225 dementia-free individuals age 65 and older were randomly selected and enrolled between 1994 and 2010. Participants were seen every 2 years, with mean (range) follow-up of 7.4 (0–16) years. 606 (14%) participants reported a lifetime history of TBI with LOC at enrolment. 3466 participants provided information regarding lifetime history of TBI and completed at least one follow-up visit.
Main outcome measures
Self-reported TBI with LOC after study entry, incident all-cause dementia and Alzheimer’s disease (AD), and all-cause mortality.
There were 25 567 person-years of follow-up. History of TBI with LOC reported at study enrolment was associated with increased risk for TBI with LOC during follow-up, with adjusted HRs ranging from 2.54 (95% CI 1.42 to 4.52) for those reporting first injury before age 25 to 3.79 (95% CI 1.89 to 7.61) for those with first injury after age 55. History of TBI with LOC was not associated with elevated risk for developing dementia or AD. There was no association between baseline history of TBI with LOC and mortality, though TBI with LOC since the previous study visit (‘recent TBI’) was associated with increased mortality (HR 2.12, 95% CI 1.62 to 2.78).
Individuals aged 65 or older who reported a history of TBI with LOC at any time in their lives were at elevated risk of subsequent re-injury. Recent TBI with LOC sustained in older adulthood was associated with increased risk for mortality. Findings support the need for close clinical monitoring of older adults who sustain a TBI with LOC.
PMCID: PMC3752841  PMID: 23172868
19.  Elevation of MMP-3 and MMP-9 in CSF and Blood in Patients with Severe Traumatic Brain Injury 
Neurosurgery  2009;65(4):702-708.
Traumatic brain injury (TBI) causes elevation of matrix metalloproteinases (MMPs), which are associated with neuroinflammation, blood-brain barrier (BBB) disruption, hemorrhage and cell death. We hypothesized that patients with TBI have an increase in MMPs in the ventricular cerebrospinal fluid (CSF) and plasma.
Patients with TBI and a ventricular catheter were entered into the study. Samples of CSF and plasma were collected at the time of catheter placement, and 24 and 72 hrs after admission. Seven TBI patients were entered into the study with six having complete data for analysis. Only patients that had a known time of insult that fell within a six hour window from initial insult to ventriculostomy were accepted into the study. Control CSF came from ventricular fluid in patients undergoing shunt placement for normal pressure hydrocephalus (NPH). Both MMP-2 and MMP-9 were measured with gelatin zymography and MMP-3 with Western immunoblotting.
We found a significant elevation in the levels of the latent form of MMP-9 (92-kDa) in the CSF obtained at the time of arrival (TOA) (p<0.05). Elevated levels of MMP-2 were detected in plasma at 72 hours, but not in the CSF. Using albumin from both CSF and blood, we calculated the MMP-9 index, which was significantly elevated in the CSF, indicating endogenous MMP production. Western immunoblots showed increased levels of MMP-3 in CSF at all times measured, while MMP-3 was not detected in the CSF of NPH.
We show that MMPs are elevated in CSF of TBI patients. Although the number of patients was small, the results were robust and clearly demonstrated elevations of MMP-3 and MMP-9 in ventricular CSF in TBI patients compared to controls. While these preliminary results will need to be replicated, we propose that MMPs may be important in BBB opening and hemorrhage secondary to brain injury in patients.
PMCID: PMC2764327  PMID: 19834375
Traumatic brain injury; matrix metalloproteinases; cerebrospinal fluid; ventriculostomy
20.  Assessing gait impairment following experimental traumatic brain injury in mice 
Journal of neuroscience methods  2008;176(1):34-44.
Although gait disturbance is frequently documented among patients with traumatic brain injury (TBI), gait data from animal models of TBI are lacking. To determine the effect of TBI on gait function in adult mice, we assessed gait changes following unilateral controlled cortical impact (CCI) using a computer-assisted automated gait analysis system. Three days after CCI, intensity, area or width of paw contact were significantly decreased in forepaw(s) while the relative paw placement between the fore and hindpaws altered, suggesting that TBI affected sensorimotor status and reduced inter-limb coordination. Similar to TBI patients, CCI decreased gait velocity and stride length, and prolonged stance and swing phase in mice. Following CCI, step pattern was also changed with increasing use in the ipsilateral-diagonal limb sequence. Our results indicate that gait analysis provides great insight into both spatial and temporal aspects of limb function changes during overground locomotion in quadruped species with head injury that are valuable for the purpose of treatment and rehabilitation. Our study also provides additional functional validation for the established mouse CCI model that is relevant to human head injury.
PMCID: PMC2588469  PMID: 18805438
controlled cortical impact; catwalk; motor function; corticospinal tract; and neuroplasticity
21.  Blast-Related Brain Injury: Imaging for Clinical and Research Applications: Report of the 2008 St. Louis Workshop 
Journal of Neurotrauma  2009;26(12):2127-2144.
Blast-related traumatic brain injury (bTBI) and post-traumatic stress disorder (PTSD) have been of particular relevance to the military and civilian health care sectors since the onset of the Global War on Terror, and TBI has been called the “signature injury” of this war. Currently there are many questions about the fundamental nature, diagnosis, and long-term consequences of bTBI and its relationship to PTSD. This workshop was organized to consider these questions and focus on how brain imaging techniques may be used to enhance current diagnosis, research, and treatment of bTBI. The general conclusion was that although the study of blast physics in non-biological systems is mature, few data are presently available on key topics such as blast exposure in combat scenarios, the pathological characteristics of human bTBI, and imaging signatures of bTBI. Addressing these gaps is critical to the success of bTBI research. Foremost among our recommendations is that human autopsy and pathoanatomical data from bTBI patients need to be obtained and disseminated to the military and civilian research communities, and advanced neuroimaging used in studies of acute, subacute, and chronic cases, to determine whether there is a distinct pathoanatomical signature that correlates with long-term functional impairment, including PTSD. These data are also critical for the development of animal models to illuminate fundamental mechanisms of bTBI and provide leads for new treatment approaches. Brain imaging will need to play an increasingly important role as gaps in the scientific knowledge of bTBI and PTSD are addressed through increased coordination, cooperation, and data sharing among the academic and military biomedical research communities.
PMCID: PMC2824226  PMID: 19508154
animal models of blast-related injury; blast physics; blast-related traumatic brain injury; brain imaging; post-traumatic stress disorder
22.  A GIS-based spatiotemporal analysis of violent trauma hotspots in Vancouver, Canada: identification, contextualisation and intervention 
BMJ Open  2014;4(2):e003642.
In 2002, the WHO declared interpersonal violence to be a leading public health problem. Previous research demonstrates that urban spaces with a high incidence of violent trauma (hotspots) correlate with features of built environment and social determinants. However, there are few studies that analyse injury data across the axes of both space and time to characterise injury–environment relationships. This paper describes a spatiotemporal analysis of violent injuries in Vancouver, Canada, from 2001 to 2008.
Using geographic information systems, 575 violent trauma incidents were mapped and analysed using kernel density estimation to identify hotspot locations. Patterns between space, time, victim age and sex and mechanism of injury were investigated with an exploratory approach.
Several patterns in space and time were identified and described, corresponding to distinct neighbourhood characteristics. Violent trauma hotspots were most prevalent in Vancouver's nightclub district on Friday and Saturday nights, with higher rates in the most socioeconomically deprived neighbourhoods. Victim sex, age and mechanism of injury also formed strong patterns. Three neighbourhood profiles are presented using the dual axis of space/time to describe the hotspot environments.
This work posits the value of exploratory spatial data analysis using geographic information systems in trauma epidemiology studies and further suggests that using both space and time concurrently to understand urban environmental correlates of injury provides a more granular or higher resolution picture of risk. We discuss implications for injury prevention and control, focusing on education, regulation, the built environment and injury surveillance.
PMCID: PMC3931990  PMID: 24556240
Epidemiology; Public Health; Statistics & Research Methods
23.  Enhancing Phylogeography by Improving Geographical Information from GenBank 
Journal of biomedical informatics  2011;44(Suppl 1):S44-S47.
Phylogeography is a field that focuses on the geographical lineages of species such as vertebrates or viruses. Here, geographical data, such as location of a species or viral host is as important as the sequence information extracted from the species. Together, this information can help illustrate the migration of the species over time within a geographical area, the impact of geography over the evolutionary history, or the expected population of the species within the area. Molecular sequence data from NCBI, specifically GenBank, provide an abundance of available sequence data for phylogeography. However, geographical data is inconsistently represented and sparse across GenBank entries. This can impede analysis and in situations where the geographical information is inferred, and potentially lead to erroneous results. In this paper, we describe the current state of geographical data in GenBank, and illustrate how automated processing techniques such as named entity recognition, can enhance the geographical data available for phylogeographic studies.
PMCID: PMC3199023  PMID: 21723960
Phylogeography; Databases; Nucleic Acid; Geographic Locations; Bioinformatics
24.  Executive Functions and Social Competence in Young Children 6 Months Following Traumatic Brain Injury 
Neuropsychology  2011;25(4):466-476.
This study examined the impact of traumatic brain injury (TBI) in young children on executive functions and social competence, and particularly on the role of executive functions as a predictor of social competence.
Data were drawn from a prospective, longitudinal study. Participants were children aged 3.0 to 6.11 years at time of injury. The initial sample included 23 with severe TBI, 64 with moderate TBI, and 119 with orthopedic injuries (OI). All participants were assessed at 3 and 6 months post injury. Executive functions were assessed using neuropsychological tests (Delayed Alternation task and Shape School) and parent ratings on the Behavior Rating Inventory of Executive Function and Child Behavior Questionnaire. Parents rated children’s social competence on the Adaptive Behavior Assessment System, Preschool and Kindergarten Behavior Scales, and Home and Community Social Behavior Scales.
Children with severe TBI displayed more negative outcomes than children with OI on neuropsychological tests and ratings of executive functions, and ratings of social competence (η2 ranged from 0.03 to 0.11). Neuropsychological tests of executive functions had significant but weak relationships with behavioral ratings of executive functions (ΔR2 ranged from .06 to .08). Behavioral ratings of executive functions were strongly related to social competence (ΔR2 ranged from .32 to .42), although shared rater and method variance likely contributed to these associations.
Severe TBI in young children negatively impacts executive functions and social competence. Executive functions may be an important determinant of social competence following TBI.
PMCID: PMC3125456  PMID: 21463038
Traumatic brain injury; Young children; Executive functions; Social competence
25.  The Spatial Distribution of Cancer Incidence in Fars Province: A GIS-Based Analysis of Cancer Registry Data 
Cancer is a major health problem in the developing countries. Variations of its incidence rate among geographical areas are due to various contributing factors. This study was performed to assess the spatial patterns of cancer incidence in the Fars Province, based on cancer registry data and to determine geographical clusters.
In this cross sectional study, the new cases of cancer were recorded from 2001 to 2009. Crude incidence rate was estimated based on age groups and sex in the counties of the Fars Province. Age-standardized incidence rates (ASR) per 100,000 was calculated in each year. Spatial autocorrelation analysis was performed in measuring the geographic patterns and clusters using geographic information system (GIS). Also, comparisons were made between ASRs in each county.
A total of 28,411 new cases were diagnosed with cancer during 2001-2009 in the Fars Province, 55.5% of which were men. The average age was 61.6 ± 0.5 years. The highest ASR was observed in Shiraz, which is the largest county in Fars. The Moran's Index of cancer was significantly clustered in 2004, 2005, and 2006 in total, men, and women. The type of spatial clustering was high-high cluster, that to indicate from north-west to south-east of Fars Province.
Analysis of the spatial distribution of cancer shows significant differences from year to year and between different areas. However, a clear spatial autocorrelation is observed, which can be of great interest and importance to researchers for future epidemiological studies, and to policymakers for applying preventive measures.
PMCID: PMC3843298  PMID: 24319551
Cancer; Iran; spatial analysis

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