The document summarizes an international workshop on comparative effectiveness research in traumatic brain injury (TBI). The workshop had two main outcomes: 1) It initiated a process of re-orienting clinical research in TBI away from randomized controlled trials, which have not led to major advances, and toward other approaches like comparative effectiveness research and systems biology. 2) It provided ideas for potential collaboration between the European Commission and NIH to stimulate research in TBI.
Autologous Bone Marrow Mononuclear Cell Therapy for Autism: An Open Label Pro...DrAlokSharma
Autism spectrum disorders (ASD) are a group of heterogeneous neurodevelopmental disorders characterized by
deficits in verbal and nonverbal communication, social
interaction, and presence of stereotypical repetitive behavior.
This document discusses telemedicine, including its history, current uses, and future potential. It explores telemedicine across technical, clinical, human, and economic dimensions. Key points covered include how telemedicine has improved healthcare access and outcomes in various medical specialties. Challenges addressed relate to technology needs, user training, and the need for more rigorous cost-benefit analyses. The conclusion is that telemedicine's benefits now outweigh challenges as the field continues to evolve through improved collaboration and mobile technologies.
Radiotherapy for painful bone metastasesbigsky_2009
This document discusses radiotherapy treatment options for painful bone metastases. It summarizes that pain from bone metastases is commonly treated successfully with local external beam irradiation. There is controversy around whether single dose treatments requiring one visit or fractionated courses requiring multiple visits are more effective. While many radiotherapists still use fractionated regimens, the evidence shows that single fractions are as effective in relieving pain from bone metastases. For widespread bone metastases, hemibody irradiation should be considered to avoid repeated local treatments, though it is more toxic.
This document summarizes a study comparing outcomes of general versus spinal anesthesia for total hip arthroplasty. The study found higher odds of adverse events, such as prolonged ventilation and unplanned intubation, with general anesthesia. While many studies have found improved outcomes with spinal anesthesia, it remains underutilized. The interpretation of such database studies is limited as they cannot prove causality. A large prospective randomized trial would be needed to definitively compare the techniques.
Objectives: To describe the pattern of clavicle fractures and to evaluate the results of surgical treatment for clavicle fractures. Patients and methods: This retrospective study included 38 cases of clavicle fractures who were treated by open reduction internal fi xation at Hanoi Medical University Hospital between January 2008 and June 2013.
Results: The ratio of male to female was 1.5/1. Average age was 42.0 years. Simple fractures (no intermediate fragments) are most common with 65.8% of patients. Middle third fractures accounted for
92.1% of patients. Bone union rate was 100%. The surgical results were excellent in 94.7% and good in 5.3% of cases according to Constant Score.
I apologize, upon further reflection I do not feel comfortable advising how to hide or omit negative data. As researchers, our goal should be to accurately and transparently report both positive and negative findings.
This study analyzed data from a clinical trial of once-weekly teriparatide therapy for osteoporosis. It found that two thresholds - the least significant change (LSC) criterion and achieving a bone mineral density above -2.5 standard deviations from the young adult mean - were useful indicators of treatment success. Using these thresholds, the study found treatment success rates of 79.2% for the lumbar spine and 44.1% for the femoral neck at 72 weeks of teriparatide therapy. Achieving the treatment success thresholds, especially at the femoral neck, was associated with a lower incidence of vertebral fractures.
This meta-analysis reviewed 22 randomized controlled trials involving 1014 patients to determine the effectiveness of low-level laser therapy (LLLT) for pain relief in various joint areas. The average methodological quality score of the trials was 7.96 out of 10. The analysis found that 11 trials reported positive effects of LLLT for pain relief while 11 reported negative effects. However, when pooling the results, the mean weighted difference in pain reduction on a visual analogue scale was 13.96 mm in favor of the active LLLT groups, indicating LLLT provides statistically significant pain relief for joints. Restricting the analysis to trials using energy doses within previously suggested therapeutic windows produced even greater mean pain relief of 19.88-21
Autologous Bone Marrow Mononuclear Cell Therapy for Autism: An Open Label Pro...DrAlokSharma
Autism spectrum disorders (ASD) are a group of heterogeneous neurodevelopmental disorders characterized by
deficits in verbal and nonverbal communication, social
interaction, and presence of stereotypical repetitive behavior.
This document discusses telemedicine, including its history, current uses, and future potential. It explores telemedicine across technical, clinical, human, and economic dimensions. Key points covered include how telemedicine has improved healthcare access and outcomes in various medical specialties. Challenges addressed relate to technology needs, user training, and the need for more rigorous cost-benefit analyses. The conclusion is that telemedicine's benefits now outweigh challenges as the field continues to evolve through improved collaboration and mobile technologies.
Radiotherapy for painful bone metastasesbigsky_2009
This document discusses radiotherapy treatment options for painful bone metastases. It summarizes that pain from bone metastases is commonly treated successfully with local external beam irradiation. There is controversy around whether single dose treatments requiring one visit or fractionated courses requiring multiple visits are more effective. While many radiotherapists still use fractionated regimens, the evidence shows that single fractions are as effective in relieving pain from bone metastases. For widespread bone metastases, hemibody irradiation should be considered to avoid repeated local treatments, though it is more toxic.
This document summarizes a study comparing outcomes of general versus spinal anesthesia for total hip arthroplasty. The study found higher odds of adverse events, such as prolonged ventilation and unplanned intubation, with general anesthesia. While many studies have found improved outcomes with spinal anesthesia, it remains underutilized. The interpretation of such database studies is limited as they cannot prove causality. A large prospective randomized trial would be needed to definitively compare the techniques.
Objectives: To describe the pattern of clavicle fractures and to evaluate the results of surgical treatment for clavicle fractures. Patients and methods: This retrospective study included 38 cases of clavicle fractures who were treated by open reduction internal fi xation at Hanoi Medical University Hospital between January 2008 and June 2013.
Results: The ratio of male to female was 1.5/1. Average age was 42.0 years. Simple fractures (no intermediate fragments) are most common with 65.8% of patients. Middle third fractures accounted for
92.1% of patients. Bone union rate was 100%. The surgical results were excellent in 94.7% and good in 5.3% of cases according to Constant Score.
I apologize, upon further reflection I do not feel comfortable advising how to hide or omit negative data. As researchers, our goal should be to accurately and transparently report both positive and negative findings.
This study analyzed data from a clinical trial of once-weekly teriparatide therapy for osteoporosis. It found that two thresholds - the least significant change (LSC) criterion and achieving a bone mineral density above -2.5 standard deviations from the young adult mean - were useful indicators of treatment success. Using these thresholds, the study found treatment success rates of 79.2% for the lumbar spine and 44.1% for the femoral neck at 72 weeks of teriparatide therapy. Achieving the treatment success thresholds, especially at the femoral neck, was associated with a lower incidence of vertebral fractures.
This meta-analysis reviewed 22 randomized controlled trials involving 1014 patients to determine the effectiveness of low-level laser therapy (LLLT) for pain relief in various joint areas. The average methodological quality score of the trials was 7.96 out of 10. The analysis found that 11 trials reported positive effects of LLLT for pain relief while 11 reported negative effects. However, when pooling the results, the mean weighted difference in pain reduction on a visual analogue scale was 13.96 mm in favor of the active LLLT groups, indicating LLLT provides statistically significant pain relief for joints. Restricting the analysis to trials using energy doses within previously suggested therapeutic windows produced even greater mean pain relief of 19.88-21
This document summarizes research on using stem cells to treat malignant brain tumors. It discusses the limitations of current standard treatments and emerging stem cell therapies. While preclinical studies show neural stem cells can target brain tumors, clinical trials have shown dismal efficacy. The document reviews that a small fraction of applied stem cells reach tumors, while most cannot. It proposes training stem cells in a native tissue environment to help them move through barriers and target tumors. Specifically, it presents data validating an engineered tissue graft culture platform can produce stem cells with better distribution for targeting tumors than standard culture methods.
MEDICAL IMAGING MUTIFRACTAL ANALYSIS IN PREDICTION OF EFFICIENCY OF CANCER TH...csandit
Multifractal analysis of breast tumor tissue prior to chemotherapy can predict chemotherapy response with high accuracy. It was shown to distinguish histological images of different response groups with over 82% accuracy for pathological complete response and progressive/stable disease. The maximum of the multifractal spectrum parameter f(α)max provided the most important predictive value, suggesting it may detect unknown structural clues related to drug resistance. Further investigation of f(α)max could help characterize its predictive potential.
This study developed a machine learning classifier to analyze early frame amyloid PET scans and measure neurodegeneration related to Alzheimer's disease. The classifier produced scores that strongly correlated with scores from an FDG PET classifier, indicating it can detect disease progression. Early frame amyloid scans had lower cortical but higher subcortical signals compared to FDG PET. Nonetheless, the amyloid PET classifier achieved similar performance to FDG PET at differentiating disease stages. This suggests early frame amyloid PET can provide a measure of neurodegeneration without an additional scan, useful for clinical trials and diagnosis.
This study analyzed 66 patients with mandibular fractures to determine patterns and epidemiology in Lucknow, India. The highest percentage of fractures occurred in patients ages 21-30, who were predominantly male. Road traffic accidents were the primary cause, with the parasymphysis as the most common fracture site. The most frequent fracture combination involved the parasymphysis and subcondyle. While most fractures occurred singly, the number of fracture sites correlated with younger and older age groups.
Thank You for referencing this work, if you find it useful!
Citation of a related scientific book:
Wac, K., Wulfovich, S. (2021). Quantifying Quality of Life, Series: Health Informatics, Springer Nature, Cham, Switzerland. The talk details:
Katarzyna Wac, “Remote quality of life assessment: ‘What is always speaking silently is the body'”. Digital Health Connect Conference, Sion, Switzerland
Video: https://www.digitalhealthconnect.ch/en/
This document summarizes a research study that used texture analysis of knee MRI images to diagnose osteoporosis. The study selected MRI images of 40 female patients aged 50-59, with 20 patients taking osteoporosis medication and 20 not taking medication. Regions of interest on the images were analyzed using MATLAB to obtain mean texture values. Statistical t-tests found significant differences between the medication and non-medication groups, indicating texture analysis can detect osteoporosis from medical images.
- A study was conducted at Green Pastures Hospital in Nepal to assess woundcare practices for pressure ulcers in leprosy patients and evaluate knowledge of wound prevention and treatment.
- A review of patient records from 2009-2014 showed reductions in ulcer healing time, readmissions for ulcers, and severe ulcers requiring surgery, suggesting improved care. However, current woundcare practices did not fully follow protocols.
- Focus groups and interviews with patients and staff found generally good knowledge of leprosy, ulcer causes, and prevention measures, but identified opportunities to strengthen woundcare and self-care management.
Analytical Study of Clinicopathological Data of Saudi Patients with Osteoarth...Prof. Hesham N. Mustafa
SUMMARY: Knee osteoarthritis (OA) is a common disabling disease. Epidemiological studies have revealed various risk
factors for OA, including sex, aging, obesity, occupational illnesses, and chronic diseases. Here we evaluate the clinical, pathological,
and radiological findings of knee OA in a subset of Saudi patients who were subjected to total knee replacement (TKA). The study
population included 30 Saudi patients with knee OA who were operated by TKA (from June 2014 to December 2015) in the Department
of Orthopedics, Faculty of Medicine, King Abdulaziz University, Saudi Arabia. Patient’s clinical and radiological data were collected
from the hospital files. Pathological examination of the excised superior articular surface of tibia and femoral condyles were done.
Pearson Chi-squared analysis was used to test for differences between the variables in associated risk factors. There were more women
than men. Sixty per cent of patients were older than 60 years [mean age, 59.2 (females) and 61.7 (men) years-old]. All patients exceeded
obesity class 1, with females being more obese than males. Pathological examination of the superior articular surface of tibia and femoral
condyles showed high score lesions, which was more apparent in females than in males. Radiological findings showed that most lesions
were high grade. The findings of this study will help to understand the pathogenesis of OA and improve treatment decision making
relevant to TKA in knee OA in Saudi Arabia and elsewhere.
KEY WORDS: Osteoarthritis; Knee; Arthroplasty.
Union Rate of Tibiotalocalcaneal Nail with Internal or External Bone Stimulat...skisnfeet
This study compared the union rates of tibiotalocalcaneal (TTC) arthrodesis using an intramedullary nail with either internal or external bone stimulation. The study found that the union rates were similar between internal (53%) and external (57%) bone stimulation. Additionally, the rates of successful fusion capable of independent ambulation were similar between internal (81%) and external (83%) groups. While time to partial weight bearing was slightly faster with internal stimulation, there were no other significant differences in outcomes between the two bone stimulation methods.
Meta analysis of clinical efficacy of pulsed radio frequencyPainezee Specialist
This meta-analysis reviewed 25 controlled clinical trials involving 1332 patients to evaluate the efficacy of pulsed radio frequency energy (PRFE) therapy for postoperative pain and edema, nonpostoperative pain and edema, and wound healing. A vote-counting method found more positive outcomes than neutral or negative outcomes for each clinical application. A statistical combination of P-values also found statistically significant improvements in pain, edema reduction, and wound healing outcomes. The analysis provides strong statistical evidence that PRFE therapy is an effective treatment for postoperative and nonpostoperative pain and edema as well as for wound healing applications.
Sampling-Based Approach to Determining Outcomes of Patients Lost to Follow-Up...elvingeng
This study developed a sampling-based approach to account for patients lost to follow-up in antiretroviral therapy (ART) scale-up programs in Africa. Researchers evaluated over 3,600 HIV-infected adults starting ART in Uganda and tracked a sample of 128 patients lost to follow-up, finding the vital status of 111. Incorporating deaths from these tracked patients into survival estimates significantly increased the corrected mortality rates compared to estimates ignoring lost patients. This sampling method provides a feasible way to determine outcomes of lost patients and better evaluate ART program impact in resource-limited settings.
This study examined whether priming different dimensions of mortality awareness (legacy, fearfulness, disengagement) could influence intentions to increase or decrease alcohol consumption. The study found that priming mortality legacy awareness was associated with greater intentions to reduce drinking than the other conditions. Recalling past alcohol use may act as an intervention itself, as there were no differences between the intervention conditions and the control. Raising mortality legacy awareness could be an effective public health approach to increase preventative health behaviors.
This document summarizes and critiques a study on the epidemiology of glioma and its section on cellular phones. It finds deficiencies in the studies cited by the section. In particular, it notes that incidence time trend studies failed to account for late cancer reporting, changing phone use over time, and missing cancer cases. Cohort studies are unable to determine cancer risks for rare diseases. While one case-control study found increased glioma risks, other relevant case-control studies were not cited that also found increasing risks with greater phone use. In conclusion, the evidence does not support the conclusion that phone use is unrelated to glioma risk.
This document summarizes research on chronic post-surgical pain (CPSP) over the past 10 years. It finds that CPSP is a significant problem affecting large numbers of patients. While studies of CPSP have improved, definition and measurement issues remain. Recent research has focused on risk factors in hopes of prevention. Severe acute post-operative pain emerges as an influential risk factor. Further research is still needed to better understand mechanisms and improve treatment of CPSP.
Oral cancer is caused by genetic mutations from exposure to toxins like tobacco and develops when genes controlling cell growth mutate, causing uncontrolled proliferation. Gene therapy aims to improve cancer treatment by replacing defective genes or manipulating existing genes. It involves transferring therapeutic genes using viruses as vectors to treat the disease. While gene therapy holds promise for cancer treatment, challenges remain as host immune responses and insertional mutagenesis could reduce its effectiveness.
Terrando et al-2015-anesthesia_&_analgesiasamirsharshar
This article summarizes discussions from a workshop on perioperative neurotoxicity in the elderly. The workshop included presentations on:
1) Preclinical evidence that surgery and anesthesia can cause neuroinflammation and cognitive impairment in rodent models, especially in vulnerable populations like the elderly.
2) Emerging human biomarkers like CSF tau levels that show potential to objectively measure postoperative neuronal injury and predict cognitive outcomes.
3) Preliminary clinical studies finding associations between postoperative cytokines, blood-brain barrier disruption, and delirium; however, interventions like glucocorticoids have not proven effective yet.
4) The need for standardized nomenclature and consideration of preexisting patient vulnerabilities in clinical studies to help resolve
This study investigated the efficacy of pulsed electromagnetic field therapy (PEMF) in reducing delayed onset muscle soreness (DOMS) in marathon runners. A double-blind randomized controlled trial assigned 133 marathon runners to either an active PEMF device or placebo device to use for 20 minutes, 4 times per day for 5 days after a marathon. The primary outcome was thigh pain assessed using a visual analog scale during squats. Subjects using the active PEMF device had significantly lower pain scores compared to the placebo group, indicating PEMF reduced DOMS in marathon runners.
This randomized, double-blind pilot study examined the effects of pulsed electromagnetic field (PEMF) therapy on pain in patients with early knee osteoarthritis. 34 patients were randomly assigned to either an active PEMF device group (n=15) or a sham device group (n=19). The PEMF signal was designed to modulate the calcium/calmodulin dependent nitric oxide signaling pathway. Results showed a 50% reduction in pain scores from baseline in the active group starting on day 1 and persisting to day 42, while no significant reduction was seen in the sham group. The overall decrease in pain was nearly threefold greater in the active group. The rapid and sustained pain relief seen with PEMF therapy suggests it may reduce inflammation
Description of Different Phases of Brain Tumor Classificationasclepiuspdfs
The proposed approach makes contributions in various stages in the development of a computer-aided diagnosis (CAD) system of brain diseases, namely image preprocessing, intermediate processing, detection, segmentation, feature extraction, and classification. Literature study incorporates many important ideas for abnormalities detection and analysis with their advantages and disadvantages. Literature studies have pointed out the needs of dividing task and appropriate ways for accurate abnormality characterization to provide a proper clinical diagnosis.
Challenges of Harnessing the Informatics Landscape to Promote Health Behavior...AmericanLegacyFoundation
The document discusses the challenges of using informatics and technology to promote public health and behavior change, noting that while tools now exist to accelerate scientific discovery and intervention delivery, traditional research methods have not adapted sufficiently. It argues for moving beyond single-level interventions and randomized controlled trials to approaches like just-in-time adaptive interventions and learning health systems integrated across multiple levels to achieve population impact.
1 The Outcomes of Neural Stem Cell Transplantation and .docxaulasnilda
1
The Outcomes of Neural Stem Cell Transplantation and Localized Drug Therapy on Patients
Suffering from Traumatic Brain Injury
John Doe
Panther ID: 1212121
Assignment #3
Florida International University
2
Method
Traumatic Brain Injury (TBI) is a resonating issue here in the U.S. and it comes as no
surprise that it has increased in awareness as one of the nation’s most prevalent injury related
deaths within the last 15 years (American Speech-Language-Hearing Association [ASHA],
2009). It is an illness of great importance due to its association of injuries related to military
combat operations, both the Department of Defense (DoD) and Veteran Affairs (VA) are
recognized leaders in TBI care and are in constant joint health practices with research based
universities such as The University of Miami Miller School of Medicine and The University of
Michigan Health System [UMHS] (Dennis, 2013). My methods paper will incorporate a holistic
overview of the overall effectiveness of Neural Stem Cell (NSC) engraftment on TBI patients
based on publications reported within scholarly journals. The overall efficacy of treatment will
be compared to many control groups that serve as a basis to see if NSC outcomes lessen or
diminish possible injuries, as a disclaimer, findings within TBI based research do not support nor
condone that there is a cure to secondary injuries such as comas, neuronal cell death, loss of
motor or cognitive function, paralysis, or even death due to TBI. Simply put, this research paper
will look at collaborative efforts that a controlled laboratory setting has made in regards to
ameliorating TBI conditions in either acute or severe injuries and review the success of treatment
in the hopes that it can serve patients and their respective loved ones in finding more adequate
treatment platforms that can efficiently save lives in the long run.
Research Method & Design Appropriateness
According to Martyn Shuttleworth (2008), the top three most widely used research
methods are Experimental Research Methods, Opinion Based Research Methods, and
Observational Research Methods. There are a myriad of factors to take into account and evaluate
3
when choosing the correct research method. Every experimental design must make compromises
and generalizations, so each individual researcher must minimize these, but, also do it while
being realistic (Shuttleworth, 2008).
Experimental Research Methods is a more straightforward experiment that involves the
standard practice of manipulating quantitative data and independent variables to generate
statistically analyzable data. The results generated can be quantified using a testable hypothesis,
with statistical information giving a clear and unambiguous picture (Shuttleworth, 2008).
Opinion Based Research Methods generally involve designing an experiment and collecting
numerical data that that can be repr.
1 The Outcomes of Neural Stem Cell Transplantation and .docxjeremylockett77
1
The Outcomes of Neural Stem Cell Transplantation and Localized Drug Therapy on Patients
Suffering from Traumatic Brain Injury
John Doe
Panther ID: 1212121
Assignment #3
Florida International University
2
Method
Traumatic Brain Injury (TBI) is a resonating issue here in the U.S. and it comes as no
surprise that it has increased in awareness as one of the nation’s most prevalent injury related
deaths within the last 15 years (American Speech-Language-Hearing Association [ASHA],
2009). It is an illness of great importance due to its association of injuries related to military
combat operations, both the Department of Defense (DoD) and Veteran Affairs (VA) are
recognized leaders in TBI care and are in constant joint health practices with research based
universities such as The University of Miami Miller School of Medicine and The University of
Michigan Health System [UMHS] (Dennis, 2013). My methods paper will incorporate a holistic
overview of the overall effectiveness of Neural Stem Cell (NSC) engraftment on TBI patients
based on publications reported within scholarly journals. The overall efficacy of treatment will
be compared to many control groups that serve as a basis to see if NSC outcomes lessen or
diminish possible injuries, as a disclaimer, findings within TBI based research do not support nor
condone that there is a cure to secondary injuries such as comas, neuronal cell death, loss of
motor or cognitive function, paralysis, or even death due to TBI. Simply put, this research paper
will look at collaborative efforts that a controlled laboratory setting has made in regards to
ameliorating TBI conditions in either acute or severe injuries and review the success of treatment
in the hopes that it can serve patients and their respective loved ones in finding more adequate
treatment platforms that can efficiently save lives in the long run.
Research Method & Design Appropriateness
According to Martyn Shuttleworth (2008), the top three most widely used research
methods are Experimental Research Methods, Opinion Based Research Methods, and
Observational Research Methods. There are a myriad of factors to take into account and evaluate
3
when choosing the correct research method. Every experimental design must make compromises
and generalizations, so each individual researcher must minimize these, but, also do it while
being realistic (Shuttleworth, 2008).
Experimental Research Methods is a more straightforward experiment that involves the
standard practice of manipulating quantitative data and independent variables to generate
statistically analyzable data. The results generated can be quantified using a testable hypothesis,
with statistical information giving a clear and unambiguous picture (Shuttleworth, 2008).
Opinion Based Research Methods generally involve designing an experiment and collecting
numerical data that that can be repr ...
This document summarizes research on using stem cells to treat malignant brain tumors. It discusses the limitations of current standard treatments and emerging stem cell therapies. While preclinical studies show neural stem cells can target brain tumors, clinical trials have shown dismal efficacy. The document reviews that a small fraction of applied stem cells reach tumors, while most cannot. It proposes training stem cells in a native tissue environment to help them move through barriers and target tumors. Specifically, it presents data validating an engineered tissue graft culture platform can produce stem cells with better distribution for targeting tumors than standard culture methods.
MEDICAL IMAGING MUTIFRACTAL ANALYSIS IN PREDICTION OF EFFICIENCY OF CANCER TH...csandit
Multifractal analysis of breast tumor tissue prior to chemotherapy can predict chemotherapy response with high accuracy. It was shown to distinguish histological images of different response groups with over 82% accuracy for pathological complete response and progressive/stable disease. The maximum of the multifractal spectrum parameter f(α)max provided the most important predictive value, suggesting it may detect unknown structural clues related to drug resistance. Further investigation of f(α)max could help characterize its predictive potential.
This study developed a machine learning classifier to analyze early frame amyloid PET scans and measure neurodegeneration related to Alzheimer's disease. The classifier produced scores that strongly correlated with scores from an FDG PET classifier, indicating it can detect disease progression. Early frame amyloid scans had lower cortical but higher subcortical signals compared to FDG PET. Nonetheless, the amyloid PET classifier achieved similar performance to FDG PET at differentiating disease stages. This suggests early frame amyloid PET can provide a measure of neurodegeneration without an additional scan, useful for clinical trials and diagnosis.
This study analyzed 66 patients with mandibular fractures to determine patterns and epidemiology in Lucknow, India. The highest percentage of fractures occurred in patients ages 21-30, who were predominantly male. Road traffic accidents were the primary cause, with the parasymphysis as the most common fracture site. The most frequent fracture combination involved the parasymphysis and subcondyle. While most fractures occurred singly, the number of fracture sites correlated with younger and older age groups.
Thank You for referencing this work, if you find it useful!
Citation of a related scientific book:
Wac, K., Wulfovich, S. (2021). Quantifying Quality of Life, Series: Health Informatics, Springer Nature, Cham, Switzerland. The talk details:
Katarzyna Wac, “Remote quality of life assessment: ‘What is always speaking silently is the body'”. Digital Health Connect Conference, Sion, Switzerland
Video: https://www.digitalhealthconnect.ch/en/
This document summarizes a research study that used texture analysis of knee MRI images to diagnose osteoporosis. The study selected MRI images of 40 female patients aged 50-59, with 20 patients taking osteoporosis medication and 20 not taking medication. Regions of interest on the images were analyzed using MATLAB to obtain mean texture values. Statistical t-tests found significant differences between the medication and non-medication groups, indicating texture analysis can detect osteoporosis from medical images.
- A study was conducted at Green Pastures Hospital in Nepal to assess woundcare practices for pressure ulcers in leprosy patients and evaluate knowledge of wound prevention and treatment.
- A review of patient records from 2009-2014 showed reductions in ulcer healing time, readmissions for ulcers, and severe ulcers requiring surgery, suggesting improved care. However, current woundcare practices did not fully follow protocols.
- Focus groups and interviews with patients and staff found generally good knowledge of leprosy, ulcer causes, and prevention measures, but identified opportunities to strengthen woundcare and self-care management.
Analytical Study of Clinicopathological Data of Saudi Patients with Osteoarth...Prof. Hesham N. Mustafa
SUMMARY: Knee osteoarthritis (OA) is a common disabling disease. Epidemiological studies have revealed various risk
factors for OA, including sex, aging, obesity, occupational illnesses, and chronic diseases. Here we evaluate the clinical, pathological,
and radiological findings of knee OA in a subset of Saudi patients who were subjected to total knee replacement (TKA). The study
population included 30 Saudi patients with knee OA who were operated by TKA (from June 2014 to December 2015) in the Department
of Orthopedics, Faculty of Medicine, King Abdulaziz University, Saudi Arabia. Patient’s clinical and radiological data were collected
from the hospital files. Pathological examination of the excised superior articular surface of tibia and femoral condyles were done.
Pearson Chi-squared analysis was used to test for differences between the variables in associated risk factors. There were more women
than men. Sixty per cent of patients were older than 60 years [mean age, 59.2 (females) and 61.7 (men) years-old]. All patients exceeded
obesity class 1, with females being more obese than males. Pathological examination of the superior articular surface of tibia and femoral
condyles showed high score lesions, which was more apparent in females than in males. Radiological findings showed that most lesions
were high grade. The findings of this study will help to understand the pathogenesis of OA and improve treatment decision making
relevant to TKA in knee OA in Saudi Arabia and elsewhere.
KEY WORDS: Osteoarthritis; Knee; Arthroplasty.
Union Rate of Tibiotalocalcaneal Nail with Internal or External Bone Stimulat...skisnfeet
This study compared the union rates of tibiotalocalcaneal (TTC) arthrodesis using an intramedullary nail with either internal or external bone stimulation. The study found that the union rates were similar between internal (53%) and external (57%) bone stimulation. Additionally, the rates of successful fusion capable of independent ambulation were similar between internal (81%) and external (83%) groups. While time to partial weight bearing was slightly faster with internal stimulation, there were no other significant differences in outcomes between the two bone stimulation methods.
Meta analysis of clinical efficacy of pulsed radio frequencyPainezee Specialist
This meta-analysis reviewed 25 controlled clinical trials involving 1332 patients to evaluate the efficacy of pulsed radio frequency energy (PRFE) therapy for postoperative pain and edema, nonpostoperative pain and edema, and wound healing. A vote-counting method found more positive outcomes than neutral or negative outcomes for each clinical application. A statistical combination of P-values also found statistically significant improvements in pain, edema reduction, and wound healing outcomes. The analysis provides strong statistical evidence that PRFE therapy is an effective treatment for postoperative and nonpostoperative pain and edema as well as for wound healing applications.
Sampling-Based Approach to Determining Outcomes of Patients Lost to Follow-Up...elvingeng
This study developed a sampling-based approach to account for patients lost to follow-up in antiretroviral therapy (ART) scale-up programs in Africa. Researchers evaluated over 3,600 HIV-infected adults starting ART in Uganda and tracked a sample of 128 patients lost to follow-up, finding the vital status of 111. Incorporating deaths from these tracked patients into survival estimates significantly increased the corrected mortality rates compared to estimates ignoring lost patients. This sampling method provides a feasible way to determine outcomes of lost patients and better evaluate ART program impact in resource-limited settings.
This study examined whether priming different dimensions of mortality awareness (legacy, fearfulness, disengagement) could influence intentions to increase or decrease alcohol consumption. The study found that priming mortality legacy awareness was associated with greater intentions to reduce drinking than the other conditions. Recalling past alcohol use may act as an intervention itself, as there were no differences between the intervention conditions and the control. Raising mortality legacy awareness could be an effective public health approach to increase preventative health behaviors.
This document summarizes and critiques a study on the epidemiology of glioma and its section on cellular phones. It finds deficiencies in the studies cited by the section. In particular, it notes that incidence time trend studies failed to account for late cancer reporting, changing phone use over time, and missing cancer cases. Cohort studies are unable to determine cancer risks for rare diseases. While one case-control study found increased glioma risks, other relevant case-control studies were not cited that also found increasing risks with greater phone use. In conclusion, the evidence does not support the conclusion that phone use is unrelated to glioma risk.
This document summarizes research on chronic post-surgical pain (CPSP) over the past 10 years. It finds that CPSP is a significant problem affecting large numbers of patients. While studies of CPSP have improved, definition and measurement issues remain. Recent research has focused on risk factors in hopes of prevention. Severe acute post-operative pain emerges as an influential risk factor. Further research is still needed to better understand mechanisms and improve treatment of CPSP.
Oral cancer is caused by genetic mutations from exposure to toxins like tobacco and develops when genes controlling cell growth mutate, causing uncontrolled proliferation. Gene therapy aims to improve cancer treatment by replacing defective genes or manipulating existing genes. It involves transferring therapeutic genes using viruses as vectors to treat the disease. While gene therapy holds promise for cancer treatment, challenges remain as host immune responses and insertional mutagenesis could reduce its effectiveness.
Terrando et al-2015-anesthesia_&_analgesiasamirsharshar
This article summarizes discussions from a workshop on perioperative neurotoxicity in the elderly. The workshop included presentations on:
1) Preclinical evidence that surgery and anesthesia can cause neuroinflammation and cognitive impairment in rodent models, especially in vulnerable populations like the elderly.
2) Emerging human biomarkers like CSF tau levels that show potential to objectively measure postoperative neuronal injury and predict cognitive outcomes.
3) Preliminary clinical studies finding associations between postoperative cytokines, blood-brain barrier disruption, and delirium; however, interventions like glucocorticoids have not proven effective yet.
4) The need for standardized nomenclature and consideration of preexisting patient vulnerabilities in clinical studies to help resolve
This study investigated the efficacy of pulsed electromagnetic field therapy (PEMF) in reducing delayed onset muscle soreness (DOMS) in marathon runners. A double-blind randomized controlled trial assigned 133 marathon runners to either an active PEMF device or placebo device to use for 20 minutes, 4 times per day for 5 days after a marathon. The primary outcome was thigh pain assessed using a visual analog scale during squats. Subjects using the active PEMF device had significantly lower pain scores compared to the placebo group, indicating PEMF reduced DOMS in marathon runners.
This randomized, double-blind pilot study examined the effects of pulsed electromagnetic field (PEMF) therapy on pain in patients with early knee osteoarthritis. 34 patients were randomly assigned to either an active PEMF device group (n=15) or a sham device group (n=19). The PEMF signal was designed to modulate the calcium/calmodulin dependent nitric oxide signaling pathway. Results showed a 50% reduction in pain scores from baseline in the active group starting on day 1 and persisting to day 42, while no significant reduction was seen in the sham group. The overall decrease in pain was nearly threefold greater in the active group. The rapid and sustained pain relief seen with PEMF therapy suggests it may reduce inflammation
Description of Different Phases of Brain Tumor Classificationasclepiuspdfs
The proposed approach makes contributions in various stages in the development of a computer-aided diagnosis (CAD) system of brain diseases, namely image preprocessing, intermediate processing, detection, segmentation, feature extraction, and classification. Literature study incorporates many important ideas for abnormalities detection and analysis with their advantages and disadvantages. Literature studies have pointed out the needs of dividing task and appropriate ways for accurate abnormality characterization to provide a proper clinical diagnosis.
Challenges of Harnessing the Informatics Landscape to Promote Health Behavior...AmericanLegacyFoundation
The document discusses the challenges of using informatics and technology to promote public health and behavior change, noting that while tools now exist to accelerate scientific discovery and intervention delivery, traditional research methods have not adapted sufficiently. It argues for moving beyond single-level interventions and randomized controlled trials to approaches like just-in-time adaptive interventions and learning health systems integrated across multiple levels to achieve population impact.
1 The Outcomes of Neural Stem Cell Transplantation and .docxaulasnilda
1
The Outcomes of Neural Stem Cell Transplantation and Localized Drug Therapy on Patients
Suffering from Traumatic Brain Injury
John Doe
Panther ID: 1212121
Assignment #3
Florida International University
2
Method
Traumatic Brain Injury (TBI) is a resonating issue here in the U.S. and it comes as no
surprise that it has increased in awareness as one of the nation’s most prevalent injury related
deaths within the last 15 years (American Speech-Language-Hearing Association [ASHA],
2009). It is an illness of great importance due to its association of injuries related to military
combat operations, both the Department of Defense (DoD) and Veteran Affairs (VA) are
recognized leaders in TBI care and are in constant joint health practices with research based
universities such as The University of Miami Miller School of Medicine and The University of
Michigan Health System [UMHS] (Dennis, 2013). My methods paper will incorporate a holistic
overview of the overall effectiveness of Neural Stem Cell (NSC) engraftment on TBI patients
based on publications reported within scholarly journals. The overall efficacy of treatment will
be compared to many control groups that serve as a basis to see if NSC outcomes lessen or
diminish possible injuries, as a disclaimer, findings within TBI based research do not support nor
condone that there is a cure to secondary injuries such as comas, neuronal cell death, loss of
motor or cognitive function, paralysis, or even death due to TBI. Simply put, this research paper
will look at collaborative efforts that a controlled laboratory setting has made in regards to
ameliorating TBI conditions in either acute or severe injuries and review the success of treatment
in the hopes that it can serve patients and their respective loved ones in finding more adequate
treatment platforms that can efficiently save lives in the long run.
Research Method & Design Appropriateness
According to Martyn Shuttleworth (2008), the top three most widely used research
methods are Experimental Research Methods, Opinion Based Research Methods, and
Observational Research Methods. There are a myriad of factors to take into account and evaluate
3
when choosing the correct research method. Every experimental design must make compromises
and generalizations, so each individual researcher must minimize these, but, also do it while
being realistic (Shuttleworth, 2008).
Experimental Research Methods is a more straightforward experiment that involves the
standard practice of manipulating quantitative data and independent variables to generate
statistically analyzable data. The results generated can be quantified using a testable hypothesis,
with statistical information giving a clear and unambiguous picture (Shuttleworth, 2008).
Opinion Based Research Methods generally involve designing an experiment and collecting
numerical data that that can be repr.
1 The Outcomes of Neural Stem Cell Transplantation and .docxjeremylockett77
1
The Outcomes of Neural Stem Cell Transplantation and Localized Drug Therapy on Patients
Suffering from Traumatic Brain Injury
John Doe
Panther ID: 1212121
Assignment #3
Florida International University
2
Method
Traumatic Brain Injury (TBI) is a resonating issue here in the U.S. and it comes as no
surprise that it has increased in awareness as one of the nation’s most prevalent injury related
deaths within the last 15 years (American Speech-Language-Hearing Association [ASHA],
2009). It is an illness of great importance due to its association of injuries related to military
combat operations, both the Department of Defense (DoD) and Veteran Affairs (VA) are
recognized leaders in TBI care and are in constant joint health practices with research based
universities such as The University of Miami Miller School of Medicine and The University of
Michigan Health System [UMHS] (Dennis, 2013). My methods paper will incorporate a holistic
overview of the overall effectiveness of Neural Stem Cell (NSC) engraftment on TBI patients
based on publications reported within scholarly journals. The overall efficacy of treatment will
be compared to many control groups that serve as a basis to see if NSC outcomes lessen or
diminish possible injuries, as a disclaimer, findings within TBI based research do not support nor
condone that there is a cure to secondary injuries such as comas, neuronal cell death, loss of
motor or cognitive function, paralysis, or even death due to TBI. Simply put, this research paper
will look at collaborative efforts that a controlled laboratory setting has made in regards to
ameliorating TBI conditions in either acute or severe injuries and review the success of treatment
in the hopes that it can serve patients and their respective loved ones in finding more adequate
treatment platforms that can efficiently save lives in the long run.
Research Method & Design Appropriateness
According to Martyn Shuttleworth (2008), the top three most widely used research
methods are Experimental Research Methods, Opinion Based Research Methods, and
Observational Research Methods. There are a myriad of factors to take into account and evaluate
3
when choosing the correct research method. Every experimental design must make compromises
and generalizations, so each individual researcher must minimize these, but, also do it while
being realistic (Shuttleworth, 2008).
Experimental Research Methods is a more straightforward experiment that involves the
standard practice of manipulating quantitative data and independent variables to generate
statistically analyzable data. The results generated can be quantified using a testable hypothesis,
with statistical information giving a clear and unambiguous picture (Shuttleworth, 2008).
Opinion Based Research Methods generally involve designing an experiment and collecting
numerical data that that can be repr ...
Clinico-Demographic Profile of Traumatic Spinal Injury in a Tertiary HospitalLemuelJohnTonogan
As of today, there has been a limited number of studies about the demographic profile of traumatic spinal injuries in our locality and our country. The objective of this study is to determine the clinico-demographic profile of patients with traumatic spinal injury admitted in our institution for the past 10 years. A chart review of 73 patients who satisfied the inclusion criteria with traumatic spinal injuries were reviewed. Traumatic spinal injury in the locality mostly affects ages 46-60 years with a mean age of 53.5. Males were most commonly affected, married and unemployed secondary to fall and motor vehicular accidents. The cervical spine is the most commonly affected area, resulting to an incomplete paraplegia with ASIA D score in most cases. These patients were mostly managed conservatively and improved upon discharge. Strict implementation of traffic rules and fall prevention should be emphasized by the government and the locality, and also increase the awareness of patients at risk for traumatic spinal injuries and its debilitating consequences.
This document summarizes recent research on treatments for acute spinal cord injuries. It discusses approaches such as neuroprotection, regeneration, transplantation, and rehabilitation that have been areas of focus. For neuroprotection, it reviews studies on methylprednisolone and other anti-inflammatory strategies. For regeneration, it discusses inhibiting glial scar formation and replacing damaged cells through transplantation of Schwann cells, olfactory ensheathing cells, and neural stem cells. However, it notes that while animal studies show promise for many of these approaches, there remain limitations and no proven therapies currently exist for acute spinal cord injuries.
The 2016 World Health Organization classification of tumors of the central nervous system broadly employs genetic alterations for diagnostic criteria including isocitrate dehydrogenase-1 (IDH1) mutation or IDH2 mutation, and 1p/19q codeletion,[1] with the goal of creating more homogeneous disease categories with greater prognostic value.[2-5] Molecular diagnostics is becoming an increasingly important aspect of clinical oncologic neuropathology practice.
5The Application of Clinical Systems to the Stud.docxblondellchancy
5
The Application of Clinical Systems to the Study of Traumatic Brain Injury
G.G.
Walden University
NURS 6051, Section 49, Transforming Nursing and Healthcare
April 25, 2019
The Application of Clinical Systems to the Study of Traumatic Brain Injury
An area of research that has always sparked a keen interest in me revolves around rehabilitation medicine. I used to volunteer at TIRR Memorial Hermann, a nationally known rehab facility that deals with patients in recovery from significant injuries. Their patient population includes persons recovering from a stroke, spinal cord injury, traumatic brain injury, and a multitude of other less common illnesses. Because of that passion, I am interested in how nursing technology has evolved to help patients recovering from traumatic brain injuries (TBI). This paper will summarize a brief literature search of five articles that apply clinical systems to TBI recovery.
Informatics Database
Caban and associates (2016) studied whether building a large-scale informatics database would facilitate collection of standardized clinical data and obtain trends of the longitudinal outcomes of service members diagnosed with mild TBI. The article written as a result of this study mentioned how the detailed clinical guidelines for treating mild TBI rely too heavily on behavior observations and subjective recollections (Caban et. al., 2016). Knowing there was a need for an informatics database, these researchers created one using a combination of several other electronic health records systems. This database will improve outcomes in TBI because it will provide immediate concrete information that is objective and can be used to determine treatment paths for new TBI patients.
Prognosis Calculator
In the article “The Aggressiveness of Neurotrauma Practitioners and the Influence of the IMPACT Prognostic Calculator,” researchers investigated how effective a prognosis calculator is improving outcomes for TBI patients. 154 medical professionals responded to a survey that specifically questioned them regarding the usefulness and effectiveness of the IMPACT prognosis calculator. The prognosis calculator is a clinical system that was created to assist with care planning for TBI patients. The calculator is supposed to provide an accurate estimate of the future prognosis of the patient so that doctors can know whether to use aggressive treatment strategies or not. Survey responses were collected using a research electronic data capture system and the responses were statistically analyzed using SPSS software (Letsinger, Rommel, Hirschi, Nirula, & Hawryluk, 2017). Although the IMPACT system is the most significant technological advances in modern TBI care, the results of this article reveal that physicians are not properly aware of the capabilities of this software (Lestinger et. al., 2017). Unfortunately, more medical professionals use it as a communication tool more than anything else.
Assistive Technology for Cognition
A ...
1 The Outcomes of Neural Stem Cell Transplantation and .docxhoney725342
1
The Outcomes of Neural Stem Cell Transplantation and Localized Drug Therapy on Patients
Suffering from Traumatic Brain Injury
John Doe
Panther ID: 12121212
Assignment #1
Florida International University
2
Introduction
TBI Trend and Growth
Traumatic Brain Injury (TBI) affects a wide variety of people nationwide. One constant
does remain; the human condition suffers, both internally and externally. Studies confirm that
caregivers of those who suffer from TBI may experience feelings of burden, distress, anxiety,
anger, and recurring depression (Brain Injury Association of America [BIAUSA], 2015). More
detrimental is the alarming number of deaths and disabilities caused by TBI, which contribute to
roughly 30% of ALL injury related deaths in the U.S. (Centers for Disease Control and
Prevention [CDCP], 2014). The effects of TBI can include impaired thinking or memory,
movement, sensation, or emotional function (CDCP, 2014). The ferocity and utter devastation of
those afflicted with this condition are severely hindered in life and in turn the negative prognosis
can have an enduring effect on relatives and even on a community as a whole. The proposed
study will review current literature and collective research models and data based on neural stem
cell transplantation on injured brains and their positive outcomes; as well as, the facilitation of
newly implemented procedures for localized drug therapy on their respective injury sites. Studies
are primarily collected in controlled laboratory setting and modeled on mice for efficacy of
desired treatment protocol. Study goals will also encompass current newly invested research at
the University of Miami Miller School of Medicine and the University of Michigan Medical
School so as to further support the indicated research listed above.
Background: Origins of TBI and Impact
TBI is primarily found in patients who suffer from penetrating head injuries that disrupt
the normal function of the brain. It is important to note that not all blows and bumps necessarily
result in TBI formation, but, is based on how serious head trauma is and can range from mild
3
(i.e. brief change in mental status) to severe (i.e. an extended period of unconsciousness or major
loss of cognitive and motor function) (CDCP, 2014). According to the CDCP (2014), most cases
of TBI result in mild symptoms, like concussions, but if left unchecked can result in serious
injury or even death in some cases. TBI has a very unpredictable form of recovery and many
factors can contribute to the ultimate outcome, such as, pre-morbid personality and oriented goal
direction of healthcare team and patient alike, length of coma, specific area of the brain or brain
stem damaged, family support, age the injury occurs, and care of specialized rehabilitation
services (BIAUSA, 2015).
General Problem Statement
The general problem is represented with the ...
This meta-analysis examined the influence of smoking on dental implant failure. The authors analyzed 19 relevant studies comprising over 10,000 implants. They found that smokers had over twice the odds of implant failure compared to non-smokers. Specifically, implants in the maxillary arch of smokers had over twice the odds of failure, while implants in the mandibular arch did not show a significant increased risk from smoking. This study revealed a significant relationship between smoking and risk of dental implant failure, particularly for implants located in the maxillary arch.
This document discusses evidence-based practice and how it applies to assessing clinical intervention studies. It begins by listing the learning objectives for Lecture c, which include explaining how evidence-based medicine can be applied to intervention studies. The document then discusses how the best evidence for assessing interventions comes from randomized controlled trials (RCTs) or systematic reviews of RCTs. It provides examples of RCTs and outlines key questions one should ask to critically appraise an intervention study, such as whether the results are valid and can be applied to patient care.
Rehabilitation for traumatic brain injury 2005Tláloc Estrada
This document summarizes a book titled "Rehabilitation for Traumatic Brain Injury" which contains chapters written by experts in various areas of brain injury rehabilitation. The book aims to provide a concise overview of the current state of knowledge in different aspects of traumatic brain injury rehabilitation, identify gaps in research, and recommend priorities for future research. It covers topics such as rehabilitation of specific cognitive impairments, special populations, medical interventions, and the role of neuroimaging in rehabilitation. The goal is for the book to serve as a resource for both researchers and practitioners working in the field of brain injury rehabilitation.
- Traumatic brain injury (TBI) poses a significant burden globally, especially in low- and middle-income countries (LMICs) where the majority of cases occur but research is limited.
- Research on TBI disproportionately focuses on high-income countries despite LMICs facing the greatest burden. Disparities exist between regions with high TBI burden and where research is conducted.
- Conducting high-quality clinical research on TBI in LMICs faces many challenges including limited health infrastructure, resources, follow-up data collection, and differences in appropriate treatment compared to guidelines from high-income settings. Increased international collaboration may help address gaps.
Medical Students in Global Neurosurgery: Rationale and RoleAhmad Ozair
Approximately 5 million essential neurosurgical cases are unmet each year, all in low- and middle-income countries (1). After the Lancet Commission on Global Surgery described the absence of global surgery from global health discourse in January 2014 (2), the field of neurosurgery quickly recognized the importance of increasing equity in care globally (3-5). Although existing initiatives in global neurosurgery have focused on neurosurgeons and trainees, medical students represent a promising group for sustainable long-term engagement. We characterize why medical students are fundamental to success, outline the importance of incorporating medical students, and delineate how to increase medical student interest and participation in global neurosurgery.
Effect of Transcranial Direct Current Stimulation (Tdcs) on the Consumption o...semualkaira
Migraine is a disorder that has a pulsating, unilateral character, which worsens with physical exertion and hinders the quality of life of people who suffer from it. Even though
there are several comorbidities related to the disease, pain control
is the main objective and neuromodulation can be used in patients
who have some drug intolerance or capacity for non-pharmacological management.
Effect of Transcranial Direct Current Stimulation (Tdcs) on the Consumption o...semualkaira
Migraine is a disorder that has a pulsating, unilateral character, which worsens with physical exertion and hinders the quality of life of people who suffer from it. Even though
there are several comorbidities related to the disease, pain control
is the main objective and neuromodulation can be used in patients
who have some drug intolerance or capacity for non-pharmacological management.
Whole body ct adult versus ped centers (iep)bahlinnm
1) The study analyzed over 30,000 pediatric trauma patients treated at level I or II adult or pediatric trauma centers to compare the use of whole body CT (WBCT) scans between facilities.
2) It found WBCT scans were used significantly more often on pediatric patients treated at adult trauma centers (31.4%) compared to pediatric centers (17.6%).
3) After adjusting for factors, pediatric patients treated at adult centers were 1.8 times more likely to receive a WBCT, increasing their radiation risk without improving outcomes, as mortality did not differ between the groups. The study concludes guidelines are needed to minimize unnecessary WBCT use across centers.
Casemix, management, and mortality of patients receiving emergency neurosurge...Ahmad Ozair
This study characterized differences in casemix, management, and mortality of patients receiving emergency neurosurgery for traumatic brain injury (TBI) across countries with different levels of human development. The study included 1635 patients from 159 hospitals in 57 countries. Patients' ages, injury mechanisms, and procedures varied significantly between countries. Younger patients in lower HDI countries typically had mild TBI from assaults, while older patients in very high HDI countries usually had moderate or severe TBI from falls. Overall mortality was 18%, and after adjusting for casemix, mortality was higher in medium and high HDI countries compared to very high HDI countries. Significant between-hospital variation in mortality was also observed. This large, global study provides valuable
This document discusses methods for exploring between-study heterogeneity in meta-analyses, including subgroup analyses, meta-regression, and control-rate meta-regression. It provides examples of how these techniques can help identify sources of variability in treatment effects across studies and generate hypotheses. However, it also cautions that subgroup analyses and meta-regressions on patient-level covariates are prone to spurious findings due to multiple testing and ecological fallacy.
This document summarizes the neuroimmune response in the developing brain following traumatic brain injury (TBI). It discusses how the immune system plays a key role in normal brain development and how an immune response after TBI can disrupt this process. The immune response to TBI involves both the innate immune system through activation of microglia and infiltration of cells like neutrophils, as well as the adaptive immune system with lymphocytes migrating to the injury site. Younger patients are more susceptible to long-term effects of TBI due to the disruption of ongoing brain development by the neuroinflammatory response. Modulating this immune response may help enhance repair after pediatric TBI.
Optimizing Radiation Therapy for Paediatric Cancers: A Case Study of Medullob...Victor Ekpo
This document discusses optimization techniques for radiotherapy in treating childhood medulloblastoma. It reviews conventional radiotherapy, intensity-modulated radiotherapy (IMRT), and proton therapy. The major side effect of treatment is ototoxicity or hearing loss. Studies show proton therapy significantly reduces ototoxicity compared to IMRT or conventional radiotherapy. While all techniques are effective when combined with chemotherapy like cisplatin, proton therapy allows for best sparing of healthy tissue and lowest toxicity rates. The goal is optimizing treatment to cure medulloblastoma while minimizing negative effects on patients' quality of life.
The document discusses the Hereditary Neuropathy Foundation's (HNF) efforts to accelerate research for treatments for Charcot-Marie-Tooth (CMT) disease and related inherited neuropathies. Some key points:
- HNF submitted a large proposal to the NIH for $1.25M per year over 5 years to fund clinical trials and research to help translate existing preclinical research into therapies more quickly.
- Currently there are no effective treatments for CMT despite the discovery of the causal genes over 20 years ago. HNF's TRIAD program aims to increase collaboration between advocacy groups, academia, and industry to speed development of therapies.
- HNF is conducting studies to develop better
Similar to Ricerca clinica sul trauma cranico: report di un Workshop Internazionale sull'efficacia comparativa (20)
The document summarizes a study that investigated the effects of iron supplementation alone and in combination with vitamins on hematological status, oxidative stress, and erythrocyte membrane fluidity in anemic pregnant women. 164 anemic pregnant women were randomly assigned to receive placebo, iron alone, iron with folic acid, or iron with folic acid, retinol, and riboflavin for 2 months. The study found that supplementation significantly increased hemoglobin and ferritin levels and decreased oxidative stress markers in all treatment groups compared to placebo. Erythrocyte membrane fluidity also increased with supplementation.
Mitochondrial dysfunction and oxidative damage are thought to play a role in Parkinson's disease (PD) pathogenesis. Recent animal studies show that inhibiting mitochondrial complex I with rotenone closely mimics PD's biochemical and histological features. Several agents like creatine, coenzyme Q10, and acetyl-L-carnitine have shown benefits in animal models by modulating energy metabolism and reducing oxidative stress. These agents warrant further study as potential neuroprotective treatments for PD.
La conduzione del nervo surale dorsale in pazienti con carenza di vitamina B1...MerqurioEditore_redazione
This study investigated peripheral neuropathy in vitamin B12 deficient patients with megaloblastic anemia using dorsal sural nerve conduction studies and tibial sensory-evoked potentials. Dorsal sural nerve responses were absent in over half of patients but only one third had abnormalities on conventional nerve conduction studies. Patients with recordable dorsal sural nerves had prolonged latencies, reduced amplitudes, and slower conduction velocities compared to controls, suggesting dorsal sural nerve conduction is more sensitive for detecting early neuropathy. Over 70% of patients showed evidence of myelopathy on tibial sensory-evoked potentials and neurological examination.
DECLARATION OF HELSINKI - History and principlesanaghabharat01
This SlideShare presentation provides a comprehensive overview of the Declaration of Helsinki, a foundational document outlining ethical guidelines for conducting medical research involving human subjects.
- Video recording of this lecture in English language: https://youtu.be/Pt1nA32sdHQ
- Video recording of this lecture in Arabic language: https://youtu.be/uFdc9F0rlP0
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
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The skin is the largest organ and its health plays a vital role among the other sense organs. The skin concerns like acne breakout, psoriasis, or anything similar along the lines, finding a qualified and experienced dermatologist becomes paramount.
5-hydroxytryptamine or 5-HT or Serotonin is a neurotransmitter that serves a range of roles in the human body. It is sometimes referred to as the happy chemical since it promotes overall well-being and happiness.
It is mostly found in the brain, intestines, and blood platelets.
5-HT is utilised to transport messages between nerve cells, is known to be involved in smooth muscle contraction, and adds to overall well-being and pleasure, among other benefits. 5-HT regulates the body's sleep-wake cycles and internal clock by acting as a precursor to melatonin.
It is hypothesised to regulate hunger, emotions, motor, cognitive, and autonomic processes.
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
Mercurius is named after the roman god mercurius, the god of trade and science. The planet mercurius is named after the same god. Mercurius is sometimes called hydrargyrum, means ‘watery silver’. Its shine and colour are very similar to silver, but mercury is a fluid at room temperatures. The name quick silver is a translation of hydrargyrum, where the word quick describes its tendency to scatter away in all directions.
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Learning objectives:
1. Describe the organisation of respiratory center
2. Describe the nervous control of inspiration and respiratory rhythm
3. Describe the functions of the dorsal and respiratory groups of neurons
4. Describe the influences of the Pneumotaxic and Apneustic centers
5. Explain the role of Hering-Breur inflation reflex in regulation of inspiration
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7. Explain the role of peripheral chemoreceptors in regulation of respiration
8. Explain the regulation of respiration during exercise
9. Integrate the respiratory regulatory mechanisms
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Study Resources:
1. Chapter 42, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 36, Ganong’s Review of Medical Physiology, 26th edition
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The Nervous and Chemical Regulation of Respiration
Ricerca clinica sul trauma cranico: report di un Workshop Internazionale sull'efficacia comparativa
1. JOURNAL OF NEUROTRAUMA 29:32–46 (January 1, 2012)
ª Mary Ann Liebert, Inc. Original Articles
DOI: 10.1089/neu.2010.1599
Re-Orientation of Clinical Research in Traumatic
Brain Injury: Report of an International Workshop
on Comparative Effectiveness Research
Andrew I.R. Maas, David K. Menon,2 Hester F. Lingsma,3 Jose A. Pineda,4
1
M. Elizabeth Sandel,5 and Geoffrey T. Manley 6
Abstract
During the National Neurotrauma Symposium 2010, the DG Research of the European Commission and the
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS) organized
a workshop on comparative effectiveness research (CER) in traumatic brain injury (TBI). This workshop re-
viewed existing approaches to improve outcomes of TBI patients. It had two main outcomes: First, it initiated a
process of re-orientation of clinical research in TBI. Second, it provided ideas for a potential collaboration
between the European Commission and the NIH/NINDS to stimulate research in TBI. Advances in provision of
care for TBI patients have resulted from observational studies, guideline development, and meta-analyses of
individual patient data. In contrast, randomized controlled trials have not led to any identifiable major advances.
Rigorous protocols and tightly selected populations constrain generalizability. The workshop addressed addi-
tional research approaches, summarized the greatest unmet needs, and highlighted priorities for future research.
The collection of high-quality clinical databases, associated with systems biology and CER, offers substantial
opportunities. Systems biology aims to identify multiple factors contributing to a disease and addresses complex
interactions. Effectiveness research aims to measure benefits and risks of systems of care and interventions in
ordinary settings and broader populations. These approaches have great potential for TBI research. Although
not new, they still need to be introduced to and accepted by TBI researchers as instruments for clinical research.
As with therapeutic targets in individual patient management, so it is with research tools: one size does not fit all.
Key words: comparative effectiveness research; clinical research; clinical trials; methodology; systems biology;
traumatic brain injury
Introduction vehicles in low- and middle-income countries (Maas et al.,
2008). Vulnerable road users (pedestrians, cyclists, and mo-
Epidemiologic considerations
torcyclists) are at high risk. The World Health Organization
T he worldwide importance of traumatic brain injury
(TBI) requires an effective, widely applicable response.
The annual incidence of TBI is estimated at up to 500/100,000
(WHO) predicts that deaths from road traffic incidents (pri-
marily due to TBI) will double between 2000 and 2020, and
that this increase will come exclusively in low- and middle-
in the U.S. and Europe, and results in over 200 per 100,000 income countries (WHO/OMS, 2009).
individuals being admitted to hospitals each year in Europe In developed, westernized societies the occurrence of TBI is
(Langlois et al., 2006; Maas et al., 2008; Styrke et al., 2007; mainly increasing in people aged over 60 years (https:/ /
Tagliaferri et al., 2006). Epidemiological surveillance suggests webgate.ec.europa.eu/idb/documents/2009-IDB-Report_
that the nature of TBI is changing over time. Globally the screen.pdf; http:/ /www.cdc.gov/traumaticbraininjury/tbi_
incidence is increasing, due mainly to greater use of motor ed.html). In the past, a TBI in this age group was thought to
1
Department of Neurosurgery, Antwerp University Hospital, Edegem, Belgium.
2
University of Cambridge, Cambridge, United Kingdom.
3
Department of Public Health, Center for Medical Decision Making, Erasmus MC, Rotterdam, The Netherlands.
4
Departments of Pediatrics and Neurology, Division of Critical Care Medicine, Washington University School of Medicine, St Louis,
Missouri.
5
Kaiser Foundation Rehabilitation Center, Vallejo, California.
6
Department of Neurological Surgery, Brain and Spinal Injury Center, University of California–San Francisco, San Francisco, California.
32
2. TBI AND COMPARATIVE EFFECTIVENESS RESEARCH 33
lead to a uniformly bad outcome; however, current experience cal outcomes in everyday clinical practice. To quote Goethe,
is that a favorable outcome is possible and not uncommon. ‘‘Knowing is not enough; we must apply. Willing is not en-
Nevertheless, the classic age range for inclusion in many ough; we must do.’’
clinical trials excludes such people and makes trial data less These considerations provided the context for the DG
relevant to their treatment (Dhruva and Redberg, 2008). An- Research of the European Commission and NIH/NINDS
other development is that the increasing burden of TBI due to to organize a workshop during the National Neurotrauma
military conflicts, and the exposure of civilians in combat Symposium 2010 on comparative effectiveness research
zones has modified the epidemiology and clinical pattern of (CER).
TBI (Risdall and Menon, 2011). Worldwide, TBI has devas- The aims of this workshop on CER were to: (1) perform a
tating effects on patients and their relatives and results in critical re-appraisal of approaches to clinical research in TBI;
high socioeconomic costs to society. This necessitates a (2) identify the greatest unmet needs from a clinical perspec-
widespread international effort to combat TBI and improve tive; (3) discuss the potential of CER in the field of TBI; and (4)
outcomes. explore the possibility and the added value of a joint EU-U.S.
effort in this field. This article summarizes the results of this
workshop.
Discordance between experimental and clinical
success: The complexity of clinical research in TBI
Approaches to clinical research in TBI: What has
Research in basic science has disclosed that multiple
(and has not) made a difference?
mechanisms are involved in the pathophysiology of TBI
(Marklund et al., 2006). This has led to the development of Clinical trials. Traditionally, the efficacy of new treat-
many neuroprotective agents with promising potential, but ments has been investigated in randomized controlled trials
none have yielded benefits in clinical testing. The gap between (RCTs). In TBI, these trials have been conducted on a range of
bench and bedside raises the question of why benefits from neuroprotective agents and surgical and medical approaches
seemingly effective interventions have not been seen in large (Maas et al., 2010a). Whereas various single-center studies
randomized clinical trials. One explanation for this discrep- have reported benefits of a range of interventions (for example
ancy may be that the clinical situation is far more complex and hyperbaric oxygen, mannitol, hypothermia, and decom-
unpredictable than that seen with experimental models of pressive craniectomy), none of these findings were general-
TBI. Experimentally, the type and degree of injury can be izable in multicenter RCTs. Furthermore, substantial selection
standardized, while in the clinical situation wide variability bias may have existed in reporting benefits in single-center
exists, both in type (e.g., diffuse and focal injuries) and in studies (Maas et al., 2010a). For example, of the 20 multicenter
severity of injury. In the clinical situation, pretreatment is studies on neuroprotective agents, only one reported a sig-
impossible, and intervention within short therapeutic win- nificant treatment benefit: the HIT III study researchers
dows can be challenging. Adverse effects of systemic insults, (Harders et al., 1996) found a beneficial effect of the calcium
such as hypoxia and hypotension, on outcome might easily channel modulator nimodipine, but targeted only patients
overwhelm any benefit from a new therapy. The identification with traumatic subarachnoid hemorrhage. The generaliz-
of relevant covariates and the development of robust prog- ability of this relatively small study (n = 123) is therefore
nostic models by the CRASH (MRC CRASH Trial Colla- questionable, and taken in combination with negative results
borators, 2008) and IMPACT (Steyerberg et al., 2008) from three other studies on nimodipine, these findings have
collaborations are very useful for dealing with the heteroge- not changed clinical practice.
neity of the TBI population. However, adjustments for base- At the other extreme, a mega-trial of steroids in TBI was
line prognostic risk ignore the contribution of aspects of care, halted early because of increased mortality at 14 days in pa-
such as the quality of intensive care and rehabilitation, on tients treated with corticosteroids (Roberts et al., 2004), but
outcome. For example, data from the NABISH-I study (Clif- did not show a significant effect on quality of outcome at
ton et al., 2001) showed that inter-center variations in clinical 6 months (Edwards et al., 2005).
care could produce substantial noise in results of clinical trials. It is not surprising that the past decade has seen a sharp
Recent findings from the IMPACT studies have shown that decline in the number of clinical trials initiated in TBI, par-
the risk of poor outcomes could differ between centers, and is ticularly in those on neuroprotective agents (Fig. 1). This may
up to three times higher than would be expected by chance be due to disappointment in the results of previous studies,
after adjustment for baseline prognostic risk (Lingsma et al., along with the perception that TBI is a high-risk and costly
2011). How much of the observed variability reflects vari- indication. Increasing overhead costs required by academic
ability in clinical management is unknown. research institutions in the EU and U.S. contribute signifi-
The impact that variability of care may have on clinical cantly to the high cost of clinical trials, in some cases
outcomes requires rigorous examination, because identifica- amounting to or even exceeding 100% overhead, which
tion of underlying causes could result in real improvements in doubles the amount of funding required to conduct the trial.
outcomes. Identification of best clinical practices and efforts to The result is that academic institutions are pricing themselves
minimize recognized variances in care (Clifton et al., 2001), out of the market, and a clear shift in research has been seen
through, for example, ‘‘Six Sigma’’ processes (Schweikhart towards the Far East and Latin America, where the potential
and Dembe, 2009), may yield benefits. These may exceed for patient recruitment is higher and study costs are lower
those provided by research addressing a single aspect in the (Maas et al., 2010a).
continuum of care. It is therefore important to undertake more However, there is uncertainty whether findings obtained
implementation-based research to ensure that current and in these settings may be extrapolated to higher-income
future effective therapies are translated into improving clini- countries, and about the importance of components of care
3. 34 MAAS ET AL.
FIG. 1. Number of clinical trials initiated over the past 30 years, differentiated by studies of neuroprotective agents versus
therapeutic strategies. Adapted from Maas et al., 2010a.
systems. As the search for effective therapies continues, there cols that are sometimes difficult to replicate in the wider
is a need for comparative studies in which differences, for clinical care spectrum. The discrepancy between clinical trial
example in access to acute and post-acute care, in trauma data and real world practice, and the need for other ap-
organization, and in treatment, may be explored and the proaches to gathering evidence as a basis for clinical man-
consequences for generalizability estimated. agement, was highlighted 15 years ago (Black, 1996).
Guideline development. Some consistency in approach to Observational studies. Although relatively small in
care has been achieved by management guidelines comparison to the number of clinical trials conducted in TBI,
(www.tbiguidelines.org; www.nice.org.uk; Maas et al., 1997). observational studies have had a substantial impact upon
Most of these guidelines are evidence-based, and follow a clinical management.
rigorous and systematic analysis of the available literature. The Glasgow group initiated prospective data collection on
Despite isolated reports that suggest otherwise (Cremer et al., severe head injury in 1968, and expanded this to an interna-
2005), most reports show that adoption of such guidelines has tional level in 1972, including centers from the U.S. and the
resulted in improvements in TBI mortality and functional Netherlands ( Jennett et al., 1976, 1977, 1980). These studies
outcome (Bulger et al., 2002; Clayton et al., 2004; Elf et al., were facilitated by the introduction of the Glasgow Coma
2002; Fakhry et al., 2004; Patel et al., 2002; Stein et al., 2010; Scale (GCS) and the Glasgow Outcome Scale (GOS), both of
Suarez et al., 2004; Varelas et al., 2006). Nevertheless, the level which are still universally accepted for classification of initial
of evidence underpinning the guidelines is, on average, only injury severity and outcome. Treatment approaches were
low. Of the 229 recommendations contained in seven guide- compared, and extensive prognostic studies revealed that
line publications, only four are based on class I evidence age, GCS score, and pupillary reactivity were the main pre-
(Table 1). dictors of outcome in severe TBI, and prognostic rules were
The limited number of recommendations that are sup- developed.
ported by high-quality evidence is not unique to TBI, but has The Traumatic Coma Data Bank (TCDB; 1984–1987) pro-
also been noted in other fields of medicine. A recent review of spectively collected data from four U.S. centers (Foulkes et al.,
practice guidelines developed by the American College of 1991). This study highlighted the importance of systemic
Cardiology and the American Heart Association found that hypoxia and hypotension as determinants of outcome
relatively few recommendations were based on high-quality (Chesnut et al., 1993).
evidence from overviews of RCTs, and many were based More recent reports suggest that physiological insults
solely on expert opinion, individual case studies, or standard continue to be an issue, both in the emergency room and in the
of care (Tricoci et al., 2009). critical care unit context (Hlatky et al., 2004; Manley et al.,
The paucity of high-quality evidence reflects the many 2001). Numerous studies in animal models have confirmed
uncertainties about the benefits and risks of multiple treat- the significance of these clinical observations, while adding to
ment approaches, and the limited funding available for TBI our understanding of the pathological mechanisms involved
clinical research. We will never be able to mount adequately (DeWitt et al., 1995; Ishige et al., 1988; Statler et al., 2001). A
powered trials to address all of these uncertainties. Further- major advance employed in the TCDB was the Marshall CT
more, traditional clinical trials do not address the effect of classification as a descriptive measure for the type of brain
different clinical practices available in the real world, and damage and the risk of increased intracranial pressure (ICP).
have limited external validity since the effect of treatment is Further studies have confirmed its importance as a prognostic
evaluated in selected populations, with management proto- parameter (Maas et al., 2007b).
4. TBI AND COMPARATIVE EFFECTIVENESS RESEARCH 35
Table 1. Evidence-Based Guidelines for Management of Traumatic Brain Injury (TBI):
Strength of Recommendations
Recommendations (n)
Guideline Reference Topics (n) Class I Class II Class III
Prehospital management Brain Trauma Foundation, 2000 7 0 5 12
Penetrating brain injury Aarabi et al., 2001 7 0 0 12
Pediatric guidelines Adelson et al., 2003 17 0 6 40
U.K. guidelines for triage, U.K. National Institute for Health 27 3 16 107
assessment, investigation, and Clinical Excellence, 2003
and management of TBI
Field management of Brain Trauma Foundation, 2005 5 0 3 15
combat-related head trauma
Surgical management of TBI Bullock et al., 2006 5 0 0 26
Revised guidelines for management Brain Trauma Foundation, 2007 15 1 14 17
of severe TBI
Total 83 4 44 229
a
Classification of evidence on therapeutic effectiveness
Class I lack sufficient patient numbers, or suffer from other methodological inadequacies that render them
class II or III.
Class II that were based on reliable data. Comparison of two or more groups must be clearly distinguished. Types
of studies include observational, cohort, prevalence, and case-control. Class II evidence may also be derived
from flawed RCTs.
Class III Types of studies include case series, databases or registries, case reports, and expert opinions. Class III
evidence may also be derived from flawed RCTs, cohort, or case-control studies.
a
From Guidelines for the Management of Severe Traumatic Brain Injury, 3rd ed., Brain Trauma Foundation, www.tbiguidelines.org.
In the NICE guidelines (http://www.nice.org/), the grading scheme for level of recommendations was adapted from the Oxford Centre for
Evidence Based Medicine levels of evidence as level A–D; for consistency, we considered grade A class I, grade B as class II, and grades C and
D as class III.
The core data survey conducted by the European Brain predictive value of many known predictors, has yielded new
Injury Consortium (EBIC) concerned a 3-month data collec- predictors, and has resulted in the presentation of validated
tion period in moderate and severe TBI across 67 centers prognostic models for use in moderate and severe TBI
(Murray et al., 1999). This study resulted in four publications (Steyerberg et al., 2008). These models have much wider ap-
and demonstrated the evolution of CT lesions over time plications than only in the context of trial design (Lingsma
(Servadei et al., 2000), as well as the importance of traumatic et al., 2010). Simulation studies demonstrated that broad in-
subarachnoid hemorrhage (Servadei et al., 2002). Wide vari- clusion criteria, pre-specified covariate adjustment, and an
ations in intensive care management were reported across ordinal analysis all promote an efficient trial, yielding gains in
participating centers, without evidence of an association with statistical efficiency of over 40%. This means that smaller but
improved outcomes (Stocchetti et al., 2001). clinically relevant treatment effects can now be detected
In an analysis of patients with head injury from the registry without increasing trial size or duration, and these findings
of the Trauma Audit and Research Network (TARN) in the have the potential to revolutionize the design and analysis of
U.K., Patel and associates (2005) found that improvements clinical trials in TBI (Maas et al., 2010b).
over time in outcomes of patients with head injuries were less In summary, major advances in understanding and im-
than those observed in other trauma patients. Patients with proving TBI care have come not from clinical trials, but from
severe head injuries treated in a hospital without a neuro- observational studies, guideline development, and meta-
surgeon had a 2.15-fold increase in the odds of death after analysis of individual patient data. Rigorously conducted
adjustment for case mix, compared to those treated in a unit observational studies in large and diverse populations have
with neurosurgical facilities. the potential to identify better clinical practices and to reshape
care for patients with TBI in the future.
Meta-analysis of individual patient data. The IMPACT A critical re-appraisal of the experience within and across
studies (Maas et al., 2007a) brought together individual pa- clinical trials in TBI illustrates the inadequacies of approaches
tient data from eight RCTs and three observational studies to study design and analysis, clinical assessments, classifica-
(n = 9205; Marmarou et al., 2007). Relevant parameters from tion, and management.
the individual studies were merged into a large dataset,
forming a ‘‘culture medium’’ for exploring concepts for im-
Bridging the gap between bench and beside
proving the design of clinical trials in TBI (Maas et al., 2007a).
The IMPACT studies have yielded important contributions to The possible causes for translational failures in clinical
advance the field of clinical research in TBI. Extensive prog- neuroprotection in TBI have been addressed in many previ-
nostic analysis has defined and quantified more precisely the ous publications (Green, 2002; Ikonomidou and Turski, 2002;
5. 36 MAAS ET AL.
Maas et al., 1999; Narayan et al., 2002; Tolias and Bullock, Classification
2004). One of the aspects highlighted during the panel dis-
General approaches to classification of TBI are by cause
cussions of the workshop was the uncertain relevance of re-
(mechanistic) and severity. In clinical practice the conven-
sults obtained from experimental studies in rodents to human
tional categorization of the severity of brain injury is primarily
subjects, reflecting differences in brain development, brain
based on the GCS score. While the GCS represented a sig-
anatomy, and physiology. While studies in lissencephalic
nificant advance in the characterization of TBI, more recent
species may continue to be useful in elucidating and antago-
studies suggest that its accuracy and prognostic power in
nizing disease mechanisms, a strong plea was heard to im-
more severely injured patients may be reduced due to effects
plement more intermediate studies in larger gyrencephalic
of early sedation, neuromuscular blockade, and ventilation
mammals, such as pigs and sheep, before clinical translation is
(Czosnyka et al., 2005; Stocchetti et al., 2004). Further, it
attempted. An alternative or adjunctive approach to such
should be realized that the commonly employed differentia-
large animal studies may be more preparatory clinical re-
tion into mild (GCS score 13–15), moderate (GCS score 9–12),
search, including the use of strategies to optimize candidate
and severe (GCS score 8 or less) injury is artificial, and that
therapies before initiation of formal Phase II trials in patients
clinical severity lies on a continuum. Pathoanatomical and
( Janowitz and Menon, 2010). In TBI, perhaps uniquely among
pathophysiological processes may occur across the spectrum
acute CNS diseases, conventional protocols for clinical care
of clinical severity, but may vary in frequency and severity.
provide unparalleled access to key biological compartments
Moreover, patients with similar clinical severity as assessed
through techniques such as microdialysis, ventriculostomy,
by the GCS may have widely differing types of injury (Fig. 2).
and jugular bulb catheterization. This access, and the common
Additional major issues are the physiological vulnerability of
use of serial imaging (universally with computed tomography
patients with TBI, particularly of those with moderate or se-
[CT], but increasingly with magnetic resonance imaging
vere injury and extracranial injuries. Thus the classification of
[MRI], and sometimes with positron emission tomography
TBI is multidimensional and complex. A recent authoritative
[PET]), provides opportunities to examine disease mecha-
workshop has made a strong case for a new and more com-
nisms, drug pharmacokinetics, and proof of principle of
prehensive categorization of TBI in clinical trials (Saatman
therapy in small, well-designed studies. We suggest that those
et al., 2008). The workshop also recommended the develop-
monitoring and investigation tools that are commonly used in
ment of a common data set of TBI data elements, and the
patients with TBI may provide a route to facilitate a more
establishment of a large prospective patient database across
rational approach to translational research. This suggestion is
the spectrum of injury severity. Common data elements have
underpinned by existing research data on disease biology,
been proposed (Maas et al., 2011), but a large prospective data
drug delivery, and treatment response obtained with these
set is still required.
methods ( Janowitz and Menon, 2010).
Mechanistic targeting
Genetic make-up and response to injury
Different pathophysiological processes may occur simul-
A major gap in knowledge concerns different responses to taneously or sequentially, and to varying degrees. The con-
similar injuries. Such patient-specific differences could in part cept of mechanistic targeting—the ideal for clinical trials—
be genetically determined, and much research will be needed will require reliable identification of occurrence and time
in the areas of genomics and metabolomics to elucidate the course of pathophysiological mechanisms in individual
wide variability in the response to brain injury. The relevance patients. There is the emerging hope that multimodality
of genetics may be seen by the observation that recovery is monitoring may allow us to differentiate between patho-
poorer in patients with stroke or TBI who have the APOE e4 physiologies that appear superficially similar, but require
allele than in those who do not have this allele (Alexander different treatment. For example, the combination of con-
et al., 2007). Other genes for which evidence exists for asso- ventional monitoring with brain tissue oximetry and micro-
ciations with outcomes are the TP53, COMT, DRD2, CAC- dialysis may allow us to differentiate between classical
NA1A, and BCL2 genotypes ( Jordan, 2007; Zangrilli Hoh ischemia (which may respond to cerebral perfusion pressure
et al., 2010). [CPP] elevation), and diffusion hypoxia (Menon et al., 2004),
or mitochondrial dysfunction (Vespa et al., 2005), which may
Premorbid factors and comorbidity respond to normobaric hyperoxia (Nortje et al., 2008). The
emerging fields of advanced MRI imaging and of proteomic
The importance of premorbid factors and comorbidity biomarkers offer opportunities for detection and tracking of
has often been neglected in TBI, on the assumption that pri- pathophysiological processes.
marily young and otherwise healthy subjects are afflicted.
Awareness of the increase of TBI in older people and in
Individualizing clinical management
those with prior problems has changed this. A recent analysis
revealed that one in four U.S. citizens now lives with at least Protocol-driven approaches are currently the standard in
two chronic comorbidities (Parekh and Barton, 2010). These the treatment of TBI. These approaches are often poorly
comorbidities imply impaired physiological reserve and a focused, utilizing a stepwise approach, with an escalating
range of pre-existing medications (including anticoagulant intensity of therapy, regardless of the underlying patho-
therapy and platelet aggregation inhibitors). These factors physiology. They adhere to the concept of a ‘‘one pill for ev-
will influence both disease course (e.g., via more hemorrhagic erybody’’ approach. The introduction of novel monitoring
expansion), and the pharmacokinetic interactions and phar- technology, and advances in neuroimaging techniques, now
macodynamic safety of new therapies in TBI. offer opportunities for advancing care from a one-size-fits-all
6. TBI AND COMPARATIVE EFFECTIVENESS RESEARCH 37
FIG. 2. Types of brain injury may differ greatly in patients with similar initial clinical severity as assessed by the Glasgow
Coma Scale. Adapted from Saatman et al., 2008 (EDH, extradural hematoma; DAI, diffuse axonal injury; SDH, subdural
hematoma; SAH, subarachnoid hemorrhage; IVH, intraventricular hemorrhage).
approach, to a more focused approach, targeted to the needs more relevant than the actual values of ICP. Second, the use of
of an individual patient. The concept of individualized man- ICP as a surrogate outcome marker neglects the side effects of
agement is closely related to the possibilities for mechanistic therapies (Coles et al., 2002, 2007). The importance of com-
targeting. There are clear benefits to be gained from the em- plications following, for example decompressive cra-
ployment of personalized approaches. For example, the curve niectomy, was recently demonstrated in the DECRA trial
of the relationship between CPP and outcome shows an in- (Cooper et al. 2011).
verted ‘‘U’’ shape, suggesting that there is an optimum level of A more rational option would be to use definitive markers
CPP, and that higher or lower levels are disadvantageous of tissue fate in the brain. Biomarkers may have great poten-
(Balestreri et al., 2006). Indeed, the use of management tial in TBI (Table 2). Advances in this emerging field offer
schemes that incorporate vigorous CPP augmentation can hope for the identification of biochemical and other markers
result in significant cardiorespiratory complications (Ro- that are clinically relevant for quantifying and tracking dis-
bertson et al., 1999). Further, there is accumulating evidence ease processes. Further, if we could use patients as their own
that the optimum level of CPP varies between patients, and controls in determining if an intervention altered the trajec-
the optimum level in a given patient may be identifiable using tory of neuronal loss, we could at least determine whether a
autoregulatory indices (Howells et al., 2005; Steiner et al., neuroprotective intervention was initially effective, in that it
2002), or brain oximetry (Spiotta et al., 2010). reduced incremental tissue injury. Serial MRI with diffusion
tensor imaging (DTI; Niogi et al., 2008), and MR spectroscopy
Early end-points and mechanistic targets (Ashwal et al., 2006; Govind et al., 2010), may provide clini-
cally viable methods of assessing such incremental neuronal
Major advances in the fields of cardiovascular medicine, losses, but this approach needs to be tested in large
oncology, and AIDS research have resulted from the use of
early (mechanistic) end-points, for example troponin in
myocardial infarction and CD4 counts in HIV. In TBI, how-
ever, early end-points that reliably predict quality of recovery
Table 2. Potential Uses for Biomarkers
are not yet available. In the past, ICP has been used, either in Traumatic Brain Injury (TBI)
explicitly or implicitly, as a surrogate end-point, especially in
early-stage trials in clinical TBI. While this approach has some Establishing a diagnosis of TBI (relevant to mild cases)
merit, it is important to recognize two important confounders. Assessing the severity and nature of TBI
First, modern neuro-ICU practices have substantially Monitoring the evolution of injury and recovery in individ-
blunted our ability to use ICP as a surrogate marker in this ual patients or groups of patients
way. It is possible to control ICP by intensifying ICP/CPP Defining treatments needed
therapies until the system terminally decompensates and in- Monitoring of treatment effects
Mechanistic target for clinical trials
tracranial hypertension becomes refractory to therapy. In this
Prediction of outcome
context, the intensity of ICP/CPP-targeted therapy may be
7. 38 MAAS ET AL.
prospective studies that map the temporal trajectories of le- consistent with post-traumatic stress disorder (PTSD) are re-
sion evolution with conventional treatment. ported in up to 40% of military personnel returning from
deployment following mild blast TBI (Hoge et al., 2008), al-
Post-acute assessments and care though the study is controversial because it may have un-
derestimated the percentage of patients with mild TBI who
Consistent standardized methods are largely lacking to experienced PTSD (Correspondence NEJM, 2009). Questions
track service utilization and changes in functional status fol- persist concerning the best methods for the determination of
lowing acute care discharge. Where they do exist, general use the neurological and/or psychological aspects and etiologies
is often inhibited by the copyright protection imposed by of these interrelated disorders (Bryant, 2008). In one study
developers. In comparison to acute care studies, post-acute using survey techniques for military personnel injured in Iraq
studies are often small in size and research is fragmented. In and Afghanistan, researchers found that 12% of respondents
particular, there is little continuity in research between acute reported a history consistent with mild TBI, and 11% screened
and post-acute care studies. Nevertheless, disparities in access positive for PTSD (Schneiderman et al., 2008). Advanced
to post-acute care may influence the recovery process and neuroimaging techniques such as MRI spectroscopy offer
confound interpretation of outcomes. A major challenge in the opportunities for the diagnosis of brain abnormalities in this
post-acute care phase is posed by the highly variable time population (Hoge et al., 2009). Civilian TBI studies have rarely
periods at which data are recorded, confounding compara- included measures of PTSD, and consequently the incidence
bility of studies and interpretation of their results. Thus a of this combined diagnosis is unknown in civilian popula-
great need exists for more prospective longitudinal studies tions. There is clearly a great need for further research in this
bridging the gap between acute and post-acute research in area, including studies that allow us to differentiate more
TBI. accurately between PTSD and the sequelae of TBI in all
populations.
Outcome
The GOS is currently accepted by investigators and regu- Pediatric considerations
latory authorities alike as the standard end-point for judging
efficacy in a cohort of patients with TBI. Outcome after TBI, Despite past and current prevention efforts, TBI continues
however, is by definition multidimensional, including neu- to kill and disable more children and adolescents than any
rophysical disabilities, disturbances in mental functioning other cause (Forsyth et al., 2008; Langlois et al., 2005). There is
(e.g., cognitive and executive functioning), and consequent a paucity of widely-applied, effective therapies, and results
problems in social reintegration. Moreover, even the Ex- from adult studies may not be applicable to children. While
tended GOS is relatively insensitive in its upper ranges, and conducting research in pediatric TBI, researchers need to
may therefore be less suited for patients with milder injuries. carefully balance the need for better therapies and delivery of
Recently, the Neurological Outcome Scale for TBI (NOS-TBI) care with the consideration that children with TBI are a vul-
has been proposed as an effective and simple tool to quantify nerable population in whom to conduct research. There is
neurological deficits after TBI (Wilde et al., 2010). This ap- only fragmented understanding of disease biology, and the
proach already takes some multidimensional aspects of out- frequency and geographical distribution of pediatric TBI
come assessment into consideration. create unique challenges for researchers (Natale et al., 2006).
Relatively few TBI studies have utilized Health-Related Translation of knowledge and effective therapies from the
Quality of Life (HRQoL) measures. There is a need for com- bench to the bedside are of particular significance in pediatric
prehensive disease-specific instruments for HRQoL assess- TBI. While a body of research has provided important pre-
ment in persons after TBI, such as the novel disease-specific clinical data, TBI models in immature animals have unique
scale Quality of Life in Brain Injury (QOLIBRI; Truelle et al., limitations, including differences in brain development be-
2010; von Steinbuechel et al., 2005, 2010a, 2010b). There is a tween humans and the species used in the laboratory, injury
need to develop a multidimensional approach to outcome mechanics, and evaluation of recovery (Prins and Hovda,
assessment and classification, including the patient’s quality 2003). Pre-clinical studies have and will continue to make
of life. contributions to the field, but more work needs to be done to
improve our understanding of the biology of TBI in children.
It is through this understanding that the suitability of a given
Psychological health and TBI
mechanism as a target for therapy can best be defined. On-
The workshop on ‘‘An Integrated Approach to Research in going efforts to understand the pathobiology of pediatric TBI
Psychological Health and TBI,’’ organized by NIH/NINDS, will build on previous single-center studies with limited
the Department of Defense, the Department of Veteran Af- sample sizes, and the consequent need to use pooled samples
fairs, and the National Institute on Disability and Re- (Kochanek et al., 2000). Such an approach has value, but
habilitation Research in October 2008, revealed the previously results in fragmented descriptions of the time course of
unrecognized relationship between these two seemingly un- the pathological cascades under study, and limits external
related disciplines (Thurmond et al., 2010). First, substance validity.
abuse is common in victims of TBI and may often be a con- Variability in aspects of clinical care can affect the appli-
tributing factor in injury mechanism. Second, depression and cability of controlled studies to the general population. For
anxiety disorders are relatively frequent in survivors, and this example, children with severe TBI can be admitted to adult
may adversely affect social reintegration and confound out- hospitals, adult trauma centers (with or without pediatric
come assessments. Mental health and chronic pain are con- qualifications), pediatric hospitals, or pediatric trauma cen-
sidered key areas, both pre- and post-injury. Third, symptoms ters. Furthermore, it is estimated that 17,000,000 children in
8. TBI AND COMPARATIVE EFFECTIVENESS RESEARCH 39
the United States do not have timely access to high-level pe- Table 3. Summary of Unmet Needs and Priorities
diatric trauma care (Carr and Nance, 2010). Transport deci- for Clinical Research
sions are influenced by geographic factors and emergency
Bridge the gap between bench and bedside
medical service practices. Variability of clinical care within
- Promote interaction between basic scientists and clinical
and between pediatric centers adds to these challenges. Many researchers in order to better scale experimental models
of the challenges described in the adult TBI population are to reflect human pathology both physically and patho-
magnified when it comes to pediatric TBI. Specific consider- logically
ations concern injury classification, the transition from acute - Experimental work-up should include testing in larger
to sub-acute care, and the selection of optimal outcome animals
measures that include measurements of quality of life and - Better optimization of candidate drug molecules in clinical
evaluations of psychological health (Winthrop, 2010). As re- disease through experimental medicine approaches
searchers address these challenges, the dynamic nature of - Develop mechanistic end-points in human traumatic
human development needs to be taken into account when brain injury (TBI), such as biomarkers and advanced
neuro-imaging
evaluating injury type, physiological values (such as CPP and
Integrate acute and post-acute care research
cerebral blood flow [CBF]), and cell injury mechanisms and Develop a novel approach to the classification of TBI, also
recovery (e.g., language, executive function, and measures of considering extracranial injuries
independence; Kapapa et al., 2010; Kochanek, 2006; Walker Develop a multidimensional approach to outcome assess-
et al., 2009). ment, including the patient perspective (quality of life)
During the workshop, a review of the international net- Explore the influence of gender and genetic makeup on
works available to conduct research in pediatric TBI revealed disease course and outcome
numerous opportunities and highlighted challenges. Identi- Develop tools to better capture clinical variability
fication and understanding of best clinical practices through Use information on clinical variability to develop and test
CER may help optimize and homogenize care delivery, fa- strategies for individualized management
Prediction research
cilitating mechanistic targeting and the implementation of
- Outcome: update/validate prognostic models
future effective therapies. Whether via RCTs, rigorously - Prediction of treatment response
conducted observational studies, or other forms of CER, un- - Prediction of the expected trend using monitored
derstanding pediatric TBI requires strong collaboration parameters
among multiple centers and across countries and continents. - Prediction of the risk of hemorrhagic expansion
Involve information technology personnel and other experts
Alternative Approaches and Priorities for Clinical from unrelated fields in explorations of novel approaches to
Research in Traumatic Brain Injury classification (pattern recognition), and prediction research
(machine learning techniques)
The issues summarized above highlight the complexity of ‘‘Open source’’ research: data sharing and data standard-
the challenges facing clinical TBI research. Priorities for clin- ization
ical research are summarized in Table 3. A strong collabora- A particular focus on pediatric and elderly subpopulations
tive international effort will be required to address these. Collaborate with psychological health and pain experts
In the absence of possibilities for mechanistic targeting, the Ensure that improvements in therapy are applicable to
traditional approach to clinical trials in TBI has been to de- settings where they are needed most (developing economies)
crease heterogeneity in patient populations by employing Explore whether findings obtained in a particular setting
(e.g., developing economies) may be extrapolated to other
restrictive enrollment criteria. The disadvantage of this ap-
settings
proach is that it is statistically inefficient and decreases ex-
ternal validity. The question is if attempts to limit
heterogeneity are appropriate, or alternatively, that the ex-
organisms or cell types are responsible for the pathology,
isting heterogeneity in patient populations, management ap-
there has been only limited success using this approach for
proaches, and outcomes, may be used to advantage by
more heterogeneous complex diseases, such as inflammatory
exploring these differences and analyzing the underlying
disease, diabetes, and cardiovascular disease. In these com-
causes for a given outcome or individual patient response to a
plex disorders there is likely no single factor that is respon-
selected therapy or intervention. Classical clinical trials, with
sible for the disease. This is particularly true for disorders of
large numbers and substantial costs, may not be suitable ve-
the central nervous system, such as traumatic brain injury, for
hicles for providing answers to all of the questions that we
which there is significant heterogeneity in the etiology, pa-
have. We need alternative approaches to address these
thology, mechanisms, and outcome.
questions. One direction to in which to proceed is the pro-
In contrast to the reductionistic, hypothesis-driven ap-
spective collection of large, multi-scalar (demographics,
proach that seeks to target a single variable responsible for the
physiology, proteomics, genomics, and outcome), longitudi-
disease, a systems biology approach aims to identify multiple
nal, high-quality clinical databases, associated with systems
factors that contribute to the disease. Systems biology also
biology and CER methods.
addresses the complex interactions of these multiple variables
in a multivariate, multidimensional manner, over time. Sys-
A Systems Biology Approach
tems biology is a rapidly growing interdisciplinary field that
Traditional clinical trials and studies have relied upon a combines biology, mathematics, statistics, and computer sci-
hypothesis-driven, model-based approach. While this reduc- ence, to better understand complex biological processes.
tionistic approach has been very successful in developing In this regard systems biology may be better considered an
treatments for infectious diseases and cancer, where single ‘‘informational science’’ approach, in which hypotheses are
9. 40 MAAS ET AL.
data driven and seek to describe the behavior of the entire Table 5. Common Characteristics of Comparative
system. In lay terms, it is the description of the forest instead Effectiveness Research
of the trees. There are now numerous examples of the appli-
The objective of directly informing a specific clinical
cation of the systems approach to complex biological prob-
decision from the patient perspective, or a health policy
lems, particularly in microorganisms (Bischofs et al., 2009; decision from the population perspective
Spiro et al., 1997), and more recently complex human disease Comparison of at least two alternative interventions, each
(Chen et al., 2009; Sears et al., 2009). These studies demon- with the potential to be a best practice
strate how a systematic, integrative analysis that includes Description of results at the population and subgroup
genes, proteins, and behavior over time, can solve complex levels
problems that are insufficiently addressed by the conven- The use of outcomes—both benefits and harms—that are
tional, reductionistic approach. important to patients
Employment of methods and data sources appropriate for
Comparative effectiveness research the decision of interest
Interventions conducted in settings that are similar to
RCTs—generally considered to be the gold standard— those in which the intervention will be used in practice
address efficacy rather than effectiveness. Efficacy reflects the
degree to which an intervention produces the expected result
under carefully controlled conditions chosen to maximize the
was used in 43% of the Rotterdam cases and in 14% of the
likelihood of observing an effect if it exists. The study popu-
Groningen cases. The authors concluded that the results of
lation and setting of efficacy studies may differ in important
their study did not support the concept that an aggressive
ways from those settings in which the interventions are likely
management regimen would improve outcome. However,
to be used. By contrast, CER intends to measure differences in
the efficacy with which aggressive management was im-
outcome and to relate these to the package of care and its
plemented and the impact on target pathophysiological var-
constituent components in ordinary settings and broader
iables (such as cerebral perfusion pressure and carbon dioxide
populations. It can therefore be more relevant to policy eval-
control) was not analyzed.
uation and the health care decisions of providers and patients
This study can be considered a CER study, although per-
(Table 4; IOM, 2009).
formed long before this type of research was recognized as a
Many different official definitions of CER exist. Common
separate and important entity or even had a name. It used
characteristics are presented in Table 5.
observational data from a setting that represents clinical
The call for CER does not mean that all research must have
practice. It measured a patient-relevant outcome, and the
these characteristics. Early studies of an intervention should
study aimed to inform medical decision making.
also compare it to a placebo, standard care, or no intervention.
Similarly, the comparative analysis of treatment results
During early development of a new intervention, it is critical
between Charlottesville (U.S.) and New Delhi (India) reported
to determine safety and efficacy under a defined set of cir-
by Colohan and colleagues in 1989 qualifies as CER. An al-
cumstances (IOM, 2009).
most 8% higher mortality was found in patients with a lo-
calizing motor response in New Delhi (12.5% versus 4.8%).
Examples of comparative effectiveness research
The relative absence of pre-hospital emergency care and the
in TBI
delay in admission after head injury were considered as two
The concept of CER in TBI is not new. In 1983 Gelpke and possible causes for these differences (Colohan et al., 1989).
associates analyzed differences in outcome between two A more recent example of CER comes from the IMPACT
centers from the Netherlands (Rotterdam and Groningen) studies. Here, differences in outcome between centers were
participating in the International Data Bank of severe head quantified across 10 RCTs and three observational studies,
injury. The 1-year survival rate in Rotterdam was 45% versus containing data on 9578 patients with moderate and severe
63% in Groningen. The research question was whether the TBI (Lingsma et al., 2011). The between-center differences in
difference in survival rate was due to differences in the initial unfavorable outcome (dead, vegetative state, or severe dis-
severity of the injury or to a difference in management effi- ability as measured with the Glasgow Outcome Scale) at 6
cacy. Of the 18% difference in survival rate, 10.5% was due to months were estimated with a random effects logistic re-
differences in severity of injury on admission. The remaining gression model. An odds ratio (OR) was estimated for each
7.5% difference in survival rate was not explained, but may center by comparing the number of patients with unfavorable
have been caused by unmeasured variations in the initial outcome to the average, set at an OR of 1. The authors found
determination of severity of injury or by differences in man- that the 95% range of ORs among centers was 0.55–1.83,
agement. Groningen had a more conservative management meaning that there are centers in which the odds of unfa-
approach than Rotterdam. For example, artificial ventilation vorable outcome are almost half the average, and centers
where the odds of unfavorable outcome approach twice the
average. There is thus a more than threefold difference in the
Table 4. The Different Intents of Randomized probability over and above chance effects to have an unfa-
Controlled Trials (RCTs) and Comparative vorable outcome between the centers, which could not be
Effectiveness Studies (CERs) explained by adjustment for the most important predictors of
outcome in TBI: age, GCS motor score, and pupil reactivity.
Efficacy Can it work? RCT
Effectiveness Does it work? CER Limitations resulting from the nature of the IMPACT da-
tabase (inconsistent recording of relevant variables across
Adapted from Drummond et al., 2008. multiple studies) unfortunately precluded a detailed
10. TBI AND COMPARATIVE EFFECTIVENESS RESEARCH 41
comparative analysis aimed at exploring possible underlying versus home or outpatient care? Management issues in the
causes in depth. The observed center differences clearly acute care of more severely injured patients include which
demonstrate the potential for CER in TBI and the importance treatment modalities for treating ICP should be used and in
of rigorously conducted, comprehensive, consistent, pro- what sequence. Uncertainty exists about the optimal timing
spective data collection across multiple centers. One key step for extracranial surgery, and for the indications and timing of
in such efforts will be the development of common data ele- surgery for contusions and for treatment of raised ICP.
ments for TBI (CDEs), and the implementation of web-based, There are four unique features of TBI that make CER a
efficient data collection tools (Maas, 2009; Maas et al., 2010c, feasible approach to address these uncertainties.
2011). First, there are large between-center differences and be-
A further example of the application of CER to TBI—and tween-country differences in both outcome and management.
now in the setting of post-acute care—is based upon stan- On one hand these differences might be considered worri-
dardized data collection performed by the Kaiser Permanente some. On the other hand they provide a major opportunity to
health system in the U.S. Kaiser Permanente (KP) serves the compare alternative interventions/management strategies/
health care needs of 8.2 million members in nine states and the care organization that all are possible best practices, in ev-
District of Columbia, including California, Colorado, Georgia, eryday clinical practice.
Hawaii, Maryland, Ohio, Oregon, Virginia, and Washington. Second, robust covariates and validated prognostic models
The KP system offers a unique opportunity to compare vari- have been developed specifically for TBI by the CRASH and
ation of care and outcomes. Much of the data concerning an IMPACT collaborations (MRC CRASH Trial Collaborators,
encounter or episode of care is standardized, and permits 2008; Steyerberg et al., 2008). These models provide the pos-
comparison of populations based on demographic charac- sibility to adjust for patient characteristics that affect outcome.
teristics, care settings and trajectories, service delivery, and Third, advanced statistical models, including random ef-
also outcomes by mining and analyzing data. In the KP fects models, are available to analyze differences between
Northern California Region (KP-NCAL), where membership centers.
currently stands at 3.2 million members, the annual incidence Fourth, recommendations have been developed for stan-
of acute brain injury is approximately 2500, and a large-scale dardization of data collection and coding of variables.
genetics database is being created that will be available for TBI However, what is currently still lacking in TBI is the exis-
studies. In 2002, The Division of Research in Oakland (KP- tence of a contemporary observational dataset with high-
NCAL) created a large mild TBI registry that is also available quality, uniformly-collected highly granular, prospective
for research studies. KP has internally funded a study of TBI to data. This is crucial to performing high-quality CER studies. It
determine the risk of development of Alzheimer’s disease that has been argued that data for CER research might be drawn
was to be completed at the end of 2010. from ongoing clinical trials. This approach would, however,
With the availability of large databases and variability in violate a main principle of CER studies, namely that they
utilization of services, an opportunity exists to study the should be conducted in settings similar to those in which the
variation in outcomes of care delivery. For KP-NCAL neuro- intervention will be used in practice. Moreover, the experience
trauma patients, care may be initially provided outside the from the IMPACT studies illustrates that in-depth CER anal-
system, in a non-KP trauma center or an emergency room. For ysis of such data is not possible if specific research interests,
example, KP-NCAL patients may receive acute trauma care at such as treatment-specific effects, have not been pre-
San Francisco General Hospital, a Level 1 trauma center, or determined and data collection targeted accordingly. We ar-
Kaiser South Sacramento, a Level 2 trauma center, or in a KP gue that contemporary prospective data collection is essential
emergency department. Patients with mild TBI are often seen and should be carried out through a coordinated effort in-
in emergency departments, within or outside the KP inte- volving a large number of clinical centers in several countries.
grated health care system, and released to home with a re- This initiative would require a significant investment in terms
ferral to their primary care physicians. Others are referred of time and money. However, such an investment would be
to specialists, for example at the regional rehabilitation certainly repaid by the results that would stem from the CER
center or elsewhere, by local trauma centers. Physiatric co- analysis of the collected data. CER research has the potential
management with a primary care provider, or evaluation by a to answer the many open questions in TBI, and further offers
neuropsychologist, may also be an important model to study. opportunities for cost utility studies in the context of health
Studies of inpatient hospital versus skilled nursing facility technology assessment in TBI.
versus home or outpatient care may be further developed
using this approach.
Conclusions
In many ways this workshop points to a paradigm shift in
The future potential of comparative
clinical research in TBI. First, the joint organization by Euro-
effectiveness research in TBI
pean and U.S. funding agencies reflects the need for interna-
There are many unanswered questions in TBI, that relate to tional collaboration. Second, we have come to realize that
the process of care, trauma organization, and specific ap- approaches other than the reductionistic methods of strictly
proaches. Many uncertainties concerning best clinical practice controlled trials should be considered in clinical TBI research.
exist in TBI. Improved clinical care of TBI patients will likely depend on
How should acute trauma care and post-acute care be or- a range of research approaches, including systems biology
ganized? Does time to referral to a specialist for post-acute and CER. These approaches are not yet widely used in clinical
care matter? Can any preference in the post-acute care setting TBI research, first because of unfamiliarity, second because of
be found for inpatient hospital versus skilled nursing facility the lack of a rich and comprehensive human dataset that
11. 42 MAAS ET AL.
includes demographic, clinical, genomic, proteomic, imaging, sions. Their input was essential in making this workshop a
and detailed outcome data across multiple time points. It is success. A particular word of thanks is due to Dr. Toril
essential that CER studies comply with published guidelines Skandsen (Trondheim, Norway), for providing her notes of
for such studies (Sox et al., 2010). The lower costs of this type the discussions, to Dr. Kenneth Curley for input in drafting
of approach make it particularly attractive for studies that the manuscript, to Eno Lavrysen for administrative support in
otherwise would be cost-prohibitive. Well conducted studies preparing the manuscript, and to Sir Graham Teasdale for
will translate into clinically meaningful results, which will advice in editing the final version.
directly inform decision making in clinical practice, and thus
improve care for TBI patients. An important barrier to sys- Author Disclosure Statement
tems biology approaches is cultural, in which this new data-
driven systems approach challenges the current reductionistic All of the authors conduct research in TBI and receive
approach to clinical research, and requires a new way of funding for this research from various sources. None of the
thinking about human biology and disease. It also requires authors received any honorarium or other compensation for
multidisciplinary teams of investigators from disciplines that their participation at the workshop or for their contributions
have not previously worked together to apply and refine in writing this manuscript.
these promising mathematical and computational tools.
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