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Title of Application:Assessment of Guidelines of Management in Severe Head Injury 評估嚴重頭部外傷處理準則對病患存活情形及健康相關生活品質之衝擊 頭部外傷照護之主要目的是降低其死亡率及殘障程度,並盡可能的提高傷者之生活 品質。自 1970 年以來,許多報告指出對於嚴重之頭部外傷病患採用加護重症照顧可顯著 降低死亡率及殘障程度,美國更於 1995 年正式發表嚴重頭部外傷處理準則(Guidelines of management in severe head injury),其中主張嚴重病患應裝置顱內壓(Intracranial pressure, ICP)監測,除了強調顱內壓的控制外,更應著重於腦灌流壓(Cerebral perfusion pressure, CPP)的維持,藉此以避免腦部缺血所造的細胞壞死,這種新觀念與傳統的治療方法截然 不同,甚至背道而馳。此突破性知識已在歐美國家廣泛實施,而且經過五年之評估,認為 此一新觀念確實有其臨床效果。 然而,目前台灣對此新觀念尚未完全接受,有些神經外科醫師甚至採存疑的態度, 因此在提倡依照準則的新觀念時,常由於本土性的相關研究佐證不夠而有爭議,甚至受到 阻礙。有鑑於此,建立依全台灣人口為基礎之研究,提供有力之證據,實為刻不容緩之工 作,藉此以加速推動醫療機構接受此新觀念,進而造福病人。 本研究之目的在於藉由持續性的登錄全國頭部外傷資料,瞭解目前台灣之醫療機構, 使用 ICP 監測之新照護準則的情況,並利用 Glasgow Outcome Scale(GOS)及 CPP 療程存活 追蹤 Health-related Quality of Life(HRQL)調查以瞭解是否應用 ICP 監測及 CPP 照護之嚴重 頭部外傷病患其預後及健康相關生活品質之差異情形。另外並將針對神經外科醫師,舉辦 數場演講及研討會以宣導新的照護觀念,並於一年後重新評估其效益。 研究之進行方式可略分為以下之六步驟: 一、全國頭部外傷資料登錄,並由登錄資料中找出嚴重之頭部外傷患者。 二、重新審閱嚴重頭部外傷病患之病歷,並將之區分為如下述之三個族群以比較預後之差 異。 1.有顱內壓監測及腦灌流壓照護管理之病患; 2.有顱內壓監測,但無腦灌流壓照護管理之病患; 3.無顱內壓監測,亦無腦灌流壓照護之頭部外傷病患。 三、以 HRQL 問卷持續追蹤此三目標族群之存活結果及健康相關生活品質,以進行評估及 比較此三組間差異。 四、訪視神經外科醫師其 CPP 照護之經驗,故可藉此而評估國內神經外科醫師對此新照 護準則之瞭解程度及實際實施情形。 五、於計畫中期舉辦各講座、講習以有效協助神經外科醫師對於「嚴重頭部外傷處理準則」 之認知與瞭解。 六、藉由瞭解國內醫療機構使用顱內監測及腦灌流壓照護比率之變化,以評估「嚴重頭部 外傷處理準則」宣導之成效。 Abstract The objective of head injury management is primarily to reduce the mortality rate and disability, and to promote the quality of life (QOL) from the unfortunate. A large body of published data reports that significant reductions in mortality and morbidity can be achieved in patients with severe head injury by using intensive management protocols. Of the recent “Guideline of Management in Sever Head Injury” developed by the American Association of Neurological Surgeon and the Brain Trauma Foundation since 1995, intensive monitoring of intracranial pressure (ICP) is essential in determining the adequate cerebral perfusion pressure (CPP) and thus, salvage the swelling brain from further ischemia. This break through knowledge has been greatly implicated as the guideline in U.S. and Euro-countries. New protocols provide converse view from the earlier management of decompression. New idea suggested that poor cerebral perfusion could be harmful, and a somewhat elevated blood pressure could protect against brain ischemia in a patient with high ICP. After the assessment for 5 years, magnificent results have been observed in clinical trials. However, Taiwan is still absent in providing evidence-based research and promotion of the significance of ICP monitoring while lack of study in Taiwan has also resulted in great controversy over the issue of adequate CPP management. Thus, a population base study in Taiwan is not only mandatory in resolving the debate of the issue and further, in pushing the application of new protocols in major health institution. From the continuation of prior data registry, the purposes of our research are to understand the current status in the implication of “Guideline of Management in Severe Head Injury” involving the use of ICP monitoring among major heath institutions in Taiwan, to investigate the outcome difference (Glasgow Outcome Scale (GOS) & Health-related Quality Of Life (HRQL) ) among patients with severe head injury (Glasgow Comma Scale (GCS)≦ 8) after the application of ICP monitoring and CPP based management in Taiwan, and to re-evaluate the effectiveness after one year of promotion by providing lectures and symposium for neurosurgeons regarding the use of “Guideline of Management in Severe Head Injury”. Method of the study will be addressed in six major approaches: 1.Head injury data registration to find out severe head injury population. 2.Review the medical chart of patients with severe head injury. According to the review, patients will further be divided into three groups as followed and will be assessed and compared in the difference of their outcomes: a.Patient who were managed under both ICP monitoring and adequate CPP management. b.Patients who were managed under only the ICP monitoring without further application of CPP management. c.Patients who were never managed under the above procedures. 3.Follow up the target population with their survival outcomes and HRQL. comparison will also be carried out. Assessment and 4.Interview with neurosurgeon about their experience in CPP management and thus, current status of surgeon’s acknowledgement and actual performance (from chart review) can be evaluated. 5.In the middle of the study period, symposiums and lectures will be held to educate the neurosurgeons regarding the knowledge of “Guideline of Management in Severe Head Injury.” 6.After the promotion period, assessment of the effectiveness of promotion will be performed base on the proportion change in the institutions that practice the ICP monitoring and CPP management. The purposes of the proposal are: 1. To continue the long-term data registry of head injury in Taiwan and thus, to further identify the severe head injury population for quality-adjusted survival time assessment. 2. To understand the current status of the implication of “Guidelines of Management in Severe Head Injury” involving the management with adequate cerebral perfusion pressure (CPP) among major heath institutions in Taiwan. 3. To investigate the outcome difference [Glasgow Outcome Scale (GOS), survival analysis and Health-related Quality Of Life (HRQL)] among patients with severe head injury (Glasgow Comma Scale (GCS)≦ 8) after the application of intracranial pressure (ICP) monitoring and adequate CPP-based management in Taiwan. 4. To improve the outcomes of severe head injured patients in national health via the promotion of “Guidelines of Management in Severe Head Injury” and re-education of neurosurgeons. 5. To re-evaluate the effectiveness of education after providing lectures and symposium for neurosurgeons regarding the use of “Guidelines of Management in Severe Head Injury.” Specific Aims 1. Continuously monitoring secular trends of head injury while focused on aims to construct a first population base study in Taiwan to understand status of current implication and to access the difference of outcomes in relating to management of adequate CPP. 2. Resolve the controversy over the issue of CPP management between the “right wing” and “left wing” parties of neurosurgeons in Taiwan. Like Western Countries, our research will hopefully bring the revolution into neurosurgical field, especially in intensive care procedure of head injured patients. 3. Through the promotion and education of neurosurgeons the use of “Guidelines of Management in Severe Head Injury,” we wish to obtain similar mortality rate (34%) as demonstrated by Western scholars among patients with severe head injury (GCS≦8). 4. Base on literature reviews from Medline, our research may be the first population base study globally on how the ICP monitoring and adequate CPP management can help to preserve the HRQL of patients with severe head injury. Background and Significance Ever since 1970’s1, a large body of publications has reported that significant reduction in mortality and morbidity can be achieved by using intensive management protocols.2.3.4 The protocols emphasized early intubation, rapid transportation to an appropriate trauma care facility, accurate diagnosis, prompt resuscitation, immediate evacuation of mass lesion if necessary, and followed by meticulous management in an intensive care unit (ICU) setting. Of the recent protocol “Guideline of management in severe head injury” developed by both the American Association of Neurological Surgeons and The Brain Trauma Foundation since 1995, intensive monitoring of intracranial pressure (ICP)5.6.7 is essential in determining the adequate cerebral perfusion pressure (CPP)8 and thus, salvage the swelling brain from further ischemia. In the U.S. a Traumatic Coma Data Bank was purposely set up for the assessment of outcomes of these neurosurgical protocols. Compared to early studies of 50% mortality,9 the results of efforts in investigating the proper procedures among each stages, from the incidence of impact to the moment of discharge, reveals a reduction of mortality rate to average of 36% among severe head injured patients.10 Among these major discussions, a controversial issue proposed by Rosner in the late 1980’s in determining the protocol of management of severe head injury patients by adequate CPP management was not only the revolutionary break through in the filed of neurosurgery but more, ever since then the idea has been challenged by many right wing neurosurgeon and sustained. The idea of management has specifically emphasized the importance of ICP monitoring in sustaining adequate CPP and thus, avoid secondary brain damage. In converse, not until the 1995 while more outstanding results have supported the idea, previous management emphasized the importance in all measures to reduce the ICP regardless of the ICP monitoring, blood pressure and CPP. These treatments included large dose of mannitol without proper maintenance of body fluid, the use of hyperventilation in activating the auto-regulation of vessel constricture, the use of barbiturate to sedate the patients, and the induction of hypothermia. Controversy has arisen ever since the left wing party lead by Dr. Rosner suggested that CPP management directs proper therapy to the pressure gradient across the brain rather than to the isolated ICP. It requires constant assessment of systemic arterial blood pressure (SABP) – ICP – CPP interactions corresponds to the view that ICP measurement integrates brain swelling, brain edema, and tissue perfusion. Demonstrated in the series by Muzelaar and his co-workers, decreases in ICP were frequently observed when CPP was increased while cerebral flow (CBF) also increased about 46% after induced hypertension.11 Cerebral perfusion pressure therapy is not isolated from that of ICP: however the effect of many conventional ICP therapies are transient, potentially toxic, and better used sparingly if not under proper ICP monitoring.12 Conversely, concern over induced systemic hypertension by the right wing neurosurgeons has been based on fear of worsening cerebral blood volume and “vasogenic” edema. The party claimed that there was no correlation between cerebral oxygen consumption and CPP, instead cerebral oxygen consumption manifests linear relationship corresponding to level of consciousness (measured by comma scale.)10 In the study of Cruz 1996, he demonstrated that low CBF values were nonischemic, and thereby associated with normal cerebral oxygen extraction while he also suggested that in Rosner statements, he did not take into account that measuring of CBF and metabolism were totally independent of those measuring CPP.10 However, as time would tell, eventually more studies have proposed strong evidence links systemic hypotension with poorer outcomes in head injured patients and the basis of this association appears to be the absence of adequate CPP.13.14.15.16 While many studies other than CPP specific research also demonstrated results to support the idea of adequate CPP management. In the series by Jones, he had pointed out that in early hydrocephalus (one of the causes that result in elevated ICP), there was a reduction in membrane synthesis (as ilustrated by the significant decrease in PME). In the progression of hydrocephalus (sustained high ICP), there were also significant reduction in ATP and PCr, indicating a reduced capacity in energy metabolism while finally, there were reduction in great number of components such as NAA, Asp, Glu, Gln, etc. Especially that low concentration of NAA as discussed by Harris,17 indicates the presence of impaired neuronal development or cortical atrophy. Thus, changes in metabolite concentration with hydrocephalus could be confounded unless allowance is made for the water content.18 Meantime, a biochemical study by Higashi et al. (1986) on hydrocephalus adult animals, also showed modest decreases in ATP and PCr in several brain regions, especially together with substantial decreases in blood flow. Decrease blood flow was further demonstrated by the study of Hadani in 1997, he proposed the finding that a significant number of patients develop increased flow velocities compatible with vasospasm in the basilar artery after severe head injury. This phenomenon may present an additional factor contributing to the poor outcome of severely head injured patients.19 While earlier studies of severe head injury focused on the importance of intracranial pressure elevations,20.21 current evidence emphasizes the importance of the CPP.16 Although the “Guidelines of Management in Severe Head Injury” has been proposed regarding the importance of ICP monitoring in maintenance of adequate CPP in Western countries, controversy has been persisted (even now, still a large body of conservative neurosurgeons who continuously challenge this new trend of management), the striking results reported from 1970 to the present with ICP-based techniques is how little impact, if any. Their application seems to have made on outcome to conclude that ICP monitoring is not useful while their main focus is on all possible procedures to prevent ICP elevation without intensive ICP monitoring and management of adequate CPP. In comparison, CPP management also has permissive role in determining the effect one expected from conventional management such as use of mannitol,11.22.23 barbiturate24 and other therapeutic modalitite. The main difference is not changing the management procedure but modifying with intensive ICP monitoring. For example, barbiturate therapy is still most effective when CPP is high and requires immediate pressure reduction, although it may lower the CPP threshold.25 Mannitol application is a routine procedure in the “Guidelines of Management in Severe Head Injury” knowing that under adequate CPP, mannitol can reach maximum effect on ICP reduction as well as through increasing effects on oxygen delivery.11.22.23.26.27.28 To prove that any therapy or intervention (such as ICP monitoring) reduces mortality rate of severe head injured patients from 35% to 25% with α of 5% and β of 20% requires sample size of 349 in each treatment group. In other words, to prove that ICP monitoring reduces mortality rate would require a prospective randomized study with (698 + 10%) = 768 patients (10% is to compensate the missing and loss of follow up patients). In Western countries, the study of this nature has not been fully carried out for the following reasons: 1) ICP monitoring has become an integral part of the management of severe head injury in virtually all head injury research centers. Thus, the constructing of control group may be questionable due to the ethical and moral issues. 2) In the U.S., most trauma centers can enter only about 50 severe head injury patients into such studies, this would require a multi-center design and take 4-5 years to complete. An estimate of over US$5 million dollars for such project was based on past experience.29 On the contrary, in Taiwan, the nature of high rate of traumatic head injury and the lag of advanced knowledge provide our research group the study environment without such limitation and problems related to ethical basis issue in the U.S. However, one of the aims of this research proposal is to catch up with the Modern Western neurosurgical improvements through education of neurosurgeons in Taiwan. We have also found significant difference in outcomes (base on GOS) between Rosner data and our previous databank of head injury in Taiwan (Table 1). Further, for the research purpose, we believe that through CPP management protocols, the “Guidelines of Management in Severe Head Injury” would reduce not only the mortality rate but also improve HRQL of the patients, which from our understanding has not been studied elsewhere. Table 1. Comparison of patients’ outcome according to admission GCS score GOS Score GCS Score & No of Patients (% of Group) 3 4 5 6 7 N % N % N % N % N % Dr. Rosner Death 12 (52) 12 Vegetative 1 (4) 1 Severe 2 (9) 3 Moderate 5 (22) 7 Good 3 (13) 7 Databank in Taiwan (1994-1998) Death 697 (69) 243 Vegetative 63 (6) 26 Severe 55 (5) 34 Moderate 57 (6) 35 Good 140 (14) 88 (40) (3) (10) (23) (23) 12 1 5 10 7 (35) (3) (15) (29) (21) 7 1 1 8 28 (16) (2) (2) (18) (62) 3 0 3 2 16 (12) (0) (12) (8) (67) (57) (6) (8) (8) (21) 186 25 69 51 150 (39) (5) (14) (11) (31) 160 31 107 96 265 (24) (5) (16) (15) (40) 108 35 114 109 433 (14) (4) (14) (14) (54) There are reasons supporting our belief that of patients who are treated under adequate CPP management has better HRQL. These are also factors that withheld the belief of adequate CPP management against arguments from neurosurgeons of conventional treatments. CPP is the stimulus to which the autoregulatory response of the vasculature occurs.30.31.32 While also been demonstrated by Fortune, et al., increase in CPP should always result in some degree of increase in CBF.33 The series by Shalmon and his colleagues reported intact coupling of flow and metabolism in a series of severe TBI patients (mean GCS score 6.4) in whom CPP was 85 to 90 mm Hg. As the result, CPP therapy can minimize ICP by reducing intracranial blood volume through autoregulation of vasoconstriction without deficit in oxygenation extraction and through prevention of cerebral ischemia. Schrader and associates provided evidence to demonstrate that systemic hypertension is protective in the face of elevated ICP and mass lesion.34.35 Meanwhile, Dr. Drummond and his co-workers also indirectly rendered the support of the idea that adequate blood flow may preserve neuronal function by demonstrating that infarct size after permanent middle cerebral artery occlusion and subsequent edema is mitigated by systemic hypertension. If the neuronal function could be preserved and secondary brain damage be minimized, we believe that the benefit would show in functional improvements at discharge and better HRQL later. Although outcome evaluation has long been proposed and implemented as a necessary procedure for health service evaluation, it usually focused on mortality or case fatality.36 If the quality of medical care increases under CPP management, many patients will survive head injury that previously would have proved to be fatal and thus, it is important to determine the effect of CPP management on their quality of life because survivors may leave with permanent physical, emotional, and psychological sequelae requiring intensive and long term rehabilitation.37 Quality of life refers to the qualitative aspects of recovery and therefore represents the more subjective, “sociopersonal” aspects of existence.38 Base on WHOQOL-BREF, measures of quality of life actually conceptualized in multi-dimensional terms and include four domains: physical, psychological, environmental, and social well-being. However, while death as the common end point is the same and relatively easy to measure for all kinds of illness, end point of morbidity or QOL are relatively difficult to define, measure or compare. In this study, we intend to assess the result of CPP management base on quality adjusted survival time39.40, rather than to provide only the index of quality of life or only the timing of death. QAST is an estimator by multiplying the QOL into the survival function, which can be used in outcome evaluation. Research Designs and Methods This proposal is designed for the study, which will include the period from January 1, 2002 to December 31, 2006. Our research proposal has its intention to collect data of head injury casualty cascade from four quadrants of Taiwan such as North, South, East and West. Data from four major areas will be collected to represent each quadrant of Taiwan geographically. Taipei City was selected to represent urban northern part of Taiwan. Hualien County represents rural eastern part of Taiwan. Taichung City and Taichung County represent central western part of Taiwan and finally, Kaoshong City and Kaoshong County represents southern part of Taiwan. Study Area Taipei, the center of economy, politics and cultural activities of Taiwan, faces a serious mass-transportation system problem. The government is already on the process of solving this dilemma. The mass rapid transit system, touted as the solution to this problem, has been completed in the turn of century. But the system only covers few major sites recently. A substantial number of people still rely on motorcycles, buses and cars, particularly the former, as their means of transportation. The total population in Taipei in 1999 was 2,641,312, males numbering 1,309,434 and females numbering 1,331,878. Most of head injury cases end up in the emergency rooms of large-sized teaching hospitals in Taipei. Some cases are referred from medium- or small-sized hospitals, where very few operations are performed. All cases of head injuries from 19 medium and large-sized hospitals in Taipei City will be collected. Taichung county and its heart, Taichung City, a newly developed metropolitan area with well-organized city plan, represent the central geographical quadrant of Taiwan. Because of its excellent city construction, Taichung does not face the mass-transportation issues like Taipei, however, its medical facilities are not as abundant as Taipei. The total population in 1999 was 2,421,996, males 1,226,514, and females 1,195,482. Motorcycles are the primary choice of transportation in this area and head injury cases will be collected from 13 major hospitals in Taichung. In 1999, Kaoshong City and Kaoshong County have total population of 2,705,857 which is also the largest city in the east coast, geographically. Out of its total population, there are 1,386,376 males and 1,319,481 females. Head injury cases will be collected from 13 major hospitals in the area. Hualien County, the largest administrative unit in the eastern Taiwan, includes as many as fifteen cities and towns. The total population in 1999 is 355,686, males 188,587, females 167,099. Four large-scale hospitals provide emergency care to head-injured patients in Hualien County. Tsu-Chi Hospital is the tertiary referral hospital in the area; another 3 hospitals were also equipped to perform emergency craniotomy on head-injured patients, and all head injury cases. Subjects Medical centers were selected according to two criterias: having 100 beds inpatient facility and neurosurgery department. Head injuries were often treated in the medical centers though sometimes small and middle-sized hospitals also had head injured patients, who were often transferred to medical centers for treatment. The ICD-9 Classification Code was used to determine the clinical cases. Head-injured patient was defined as one who, after having received direct or indirect injury of head, exhibits obvious brain concussion, contusion, skull fracture or any of the clinical manifestations of skull fractures and ICH. GCS was first determined regarding the severity of patients during admission in emergency department. Followed up clinical manifestations may persist or deteriorate, which included loss of consciousness, amnesia, neurological deficit, and seizures. Since only hospital inpatients and death during hospitalization are registered; therefore, the recordings do not include non-hospital death such as death on-arrival at the hospital. In general, a patient with one or more of the fore-mentioned symptoms or diagnoses was registered as a head-injured patient, and their treatment and recovery outcomes were also recorded. Definition The classification by Kraus et al. was adopted to grade the degree of head injuries, such as brain concussion, skull bone fracture, brain damage with clear neurological deficit and clinically observable cognitive deficit, post traumatic amnesia, neurological sequelae and any evidence of intracerebral hemorrhage. Presence of any one of the above conditions confirmed the diagnosis of head injury in the registry. A. Glasgow Coma Scale (GCS) was used to categorize the severity of head injury. a). Severe: GCS score below 8. b). Moderate: GCS score between 9 and 12. Patient underwent neurological operations. or had abnormal computerized tomographic findings of the brain. c). Mild: Conditions not described above. B. Glasgow Outcome Scale (GOS) - extension version was used to categorize the outcome of patients after hospital discharge. a). Death. b). Vegetative state. c). Severe disability – conscious but requiring 24-hour care. d). Moderate disability – disabled but having the ability of self-care. e). Good clinical recovery. Data Registry Procedures Data will be collected form the 49 health institutions within four major geographical domains of Taiwan. Through the assistance of Taiwan Neurosurgery Association and Injury Prevention Association,R.O.C., we may reach a common consensus with these health institutions and most of the neurosurgeons. With the assistance of physicians and nurses in the Neurosurgery Department, new admission cases of head injury can be followed up weekly by either hand-written questionnaire or disk-contained file. While they will also be well informed and trained through lectures regarding the important items of the questionnaire (or file) and selection of the cases. From the review of medical charts, head injury cases were selected and non-resident patients were excluded from the present study. Data registry involved the following procedures: 1. For non-fatal cases, admission records and hospital charts of all the studied hospitals were reviewed. 2. Medical charts were reviewed for identification of fatal cases and ICD-9 codes were also employed to identify cases. A final list of 9 ICD rubrics of diagnoses was adopted (Table 5). The hospital chart of each potential case as obtained from the ICD rubrics was examined to determine if evidence of head injury was noted and if the above criteria were met. Table 5. ICD-9 Coding Description Rubric NO. 800 801 803 804 850 851 852 853 854 Description Fractured vault of skull Fractured base of skull Other unqualified skull fracture Multiple fracture skull/face Cerebral concussion Cerebral laceration and contusion Subdural, subarachnoid, extradural hemorrhage Other and unspecified intracranial hemorrhage Intracranial injury: other unspecified 3. Additional information from the medical chart review regarding the ICP monitoring and adequate CPP management such as ICP measurement, volume of cerebrospinal fluid drainage, volume of intakes, volume of outputs, measurement of blood pressure, daily dose of mannitol treatment, daily dose of barbiturate treatment, presence of hyperventilation treatment, and presence of vasopressor treatment will also be specifically noted. The interviewers are only responsible for recording data but not to categorize the cases. The criteria for the categorization will only be determined by our research team and all the cases can be then categorized into the following three groups when data analysis is processing: a. Patient who were managed under both ICP monitoring and adequate CPP management. b. Patients who were managed under only the ICP monitoring without further application of CPP management. c. Patients who were never managed under the above procedures. 4. Through the data collection from these 49 health institutions, comparison of the effect of the protocol would be made within and between hospitals. Severe cases who admitted to institutions and have not been carried out of ICP monitoring nor CPP management will be our control group. 5. To develop the WHOQOL-BREF of Head Injury – Taiwan version, a HRQoL committee will then be organized to review trauma-related references, test the internal and external validity and reliability by experts and focus groups. 6. After receiving the weekly registry from data collectors, research personnel will select the cases of severe ones (GCS≦8) and follow up with surveillance of their HRQL and survival status. The measurement of HRQL is base on the WHOQOL-BREF – Taiwan Version.59.60.61 Follow up will be carried out for every 3, 6, and 12 months according to patients’ admission date. 7. In the third, fourth, and fifth year, the objective will focus on the promotion of the new protocol and re-education of neurosurgeons. Workshop will be held in the beginning of the third year to discuss the result from previous years and symposiums will be held throughout the year nationwide. We wish to broadcast the information to nationwide health institutions under the assistance of Neurosurgery Association and Injury Prevention and Control Association. 8. The purposes of interviewing with neurosurgeons are to evaluate the difference of their perception and practice when taking care of TBI patients, and to obtain the percentage of adherence to the CPP management in our country. To reach these two purposes, a questionnaire must be developed and tested for its validity before it is adopted. Time-Table As previously addressed, to prove that any therapy or intervention (such as ICP monitoring) improves mortality of severe head injured patients from 35% to 25% with an alpha of 5% and beta of 20% requires sample size of 349 in each treatment group. From the traumatic head injury databank in 1999, we have obtained about 600 severe cases and among them, an estimation of 40% of patients assume to be treated under the ICP monitoring. However, of the 240 ICP monitoring cases, less than 60% of patients were actually treated with the “Guideline of Management in Severe Head Injury” involving adequate CPP management. Thus, data registry for minimum of two-years is necessary to obtain substantial number of population for statistical significance. The details of proposed time schedule among the 5 years of study period is as followed: The First Year In the first year, data will be coded and basic analysis will be done on a weekly basis. Evaluations of the project will be made periodically. GOS will be extracted from the discharge note. Follow up interview with severe head injured patients about their HRQL will be carried out independently at 3, 6, 12 months after the admission date. Meanwhile, we will do additional evaluation on information related to head injury management and prevention such as assessment of risk factors among minor head injury, of trend of head injury among the bicycle riders, and of relative increase in associated injuries of motorcyclist. During the last 2 months of the year, we will re-examine the whole study and calculate the quality-adjusted survival time. Following formula will be inquired for obtaining the quality-adjusted survival time in the time interval (ti, ti+1): QSi = [ S(ti) – S(ti+1) ] / 2 * [ qol(ti) – qol(ti+1) ] / 2 + S(ti+1) * [ qol(ti) + qol(ti+1) ]/2 Details will be further addressed in analysis section. Eventually, we will write a report on the difficulties and task limits found during the course of the study and on the completeness of the registry. The Second Year In the second year, continuation of data registry will be collected while we will also modify the study according to the recommendations of the report written at the end of the previous year in order to reduce labor and increase the usefulness of the collected data. Base on the information related to ICP monitoring and CPP management, the ratio of institutions who has currently practiced the “Guidelines of Management in Severe Head Injury” (the Guidelines) will be estimated from the data obtained (current status of implication). Meanwhile interviews with neurosurgeons will base on the designed questionnaire used to identify the acknowledgement of the Guidelines among neurosurgeons (ideal status of implication). Questionnaire will be designed under the assistance from Dr. Sheng-Jean Huang, Shin-Yuan Chen, and Jia-Wei Lin. From the assessment of the status and ratio of institutions performing management base on the Guidelines, it will provide essential information for adjustment of the collecting period to obtained statistical significant number of population. Constant periodic evaluation of the project will also be made. At last two months of the second year, preparation of symposium related to management under the Guidelines will be promoted through the help from major governmental division or private sectors. Our project result, summary of international study, and protocols practiced in western countries will be demonstrated in the Symposium. Scholars from abroad will also be invited in addition to the domestic speakers. The Symposium will be carried over to the third year. The Third Year The major focus during this year will be pushing the implication of the Guidelines through the proper channel or promotion. Major expense will be the preparation of Conference and Symposium. Meantime under the condition of inadequate amount of statistical significant population, we will continue the data registry and assessment of HRQL of the severe injured patients. Additional study on the possible risk factors and complications associated with the ICP monitoring will also be done during the year. The Fourth Year In this year, procedure will be carried out similar to the first year. Evaluation of the effectiveness of the promotion will be constructed based on the assessment of records associated with ICP monitoring and CPP management which are collected from the same health institutions. Investigation of the surgical outcomes and quality adjusted survival time will also be routinely carried out to demonstrate possible improvements in patients’ outcomes. Base on the promotion of the Guidelines involving adequate CPP management, we expect a shorter duration of collecting period because of the increasing use of CPP management, and the adjustments of collecting period will be done. The Fifth Year Similar procedures as the second year will be done in the beginning of the year. The analysis of effectiveness of promotion (base on both interviews with neurosurgeons and data assessment) is expected for completeness by the middle of the year. Under permitted time and funding, we intend to design a research relating to cost-utility analysis, and propose a proper set of guidelines that is suitable for medical environment in Taiwan. The First Year Time-Table for Study Tasks 1-2Mon 3-4Mon 5-6Mon 7-8Mon 9-10Mon 11-12Mon Data Registry Survival & HRQL Follow Up Coding Data Analysis Project Re-examination Periodic Evaluation Report The Second Year Time-Table for Study Tasks 1-2Mon 3-4Mon 5-6Mon 7-8Mon 9-10Mon 11-12Mon Data Registry Survival & HRQL Follow Up Preparation for Symposiums Interview w/ Neurosurgeons Basic Analysis Implication Status Analysis Project Re-examination Periodic Evaluation Report The Third Year Time-Table for Study Tasks Data Registry HRQL Follow Up Promotion & Education Basic Analysis Periodic Evaluation Report 1-2Mon 3-4Mon 5-6Mon 7-8Mon 9-10Mon 11-12Mon The Fourth Year Time-Table for Study Tasks 1-2Mon 3-4Mon 5-6Mon 7-8Mon 9-10Mon 11-12Mon Modify Research Method Data Registry HRQL Follow Up Data Analysis Advanced Analysis Project Re-examination Periodic Evaluation Report The Fifth Year Time-Table for Study Tasks Data Registry HRQL Follow Up Interview w/ Neurosurgeons Data Analysis Outcome Analysis Cost-Utility Analysis Project Re-examination Periodic Evaluation Report 1-2Mon 3-4Mon 5-6Mon 7-8Mon 9-10Mon 11-12Mon Analysis Current methods of estimating quality adjusted life year include the follows: quality adjusted life-year (QALY) approach by Torrance, the disability adjusted life-year (DALY) approach by Murray, quality adjusted survival estimation with partitioned survival approach by Glasziou, and the quality adjusted survival time (QAST) approach by Hwang38. After careful review, the recent method of QAST by Hwang is the choice of approaches by our research team in obtaining quality-adjusted life year among patients who suffered severe head injury. QSi = [ S(ti) – S(ti+1) ] / 2 * [ qol(ti) – qol(ti+1) ] / 2 + S(ti+1) * [ qol(ti) + qol(ti+1) ]/2 QAS =Sum [qasc(tk│x)(tk+1 - tk) ] = Sum { [ S(ti) – S(ti+1) ] / 2 * [ qol(ti) – qol(ti+1) ] / 2}(tk+1-tk) In the above formula demonstrated by Hwang (quality adjusted survival time, second paper), where, S(ti) equal survival probability at time ti and qol(ti) equal mean health-related quality of life at time ti. The first term, “[ S(ti) – S(ti+1) ] / 2 * [ qol(ti) – qol(ti+1) ] / 2” corresponds to the quality adjusted survival portion contributed by patients who died in the period of (ti, ti+1) and second term derived from patients who still survive at ti+1. The expected QAST can be calculated by multiplying the HRQL into the survival function at the point of time when the HRQL is measured (3,6 and 12 months after admission). Current status of application of management involving adequate CPP will be determined by the proportion of health institutions whom information of ICP and CPP related records shows adequate measurement: presence of ICP measurement, intake is averaged 6000 cc per day, output is averaged 6000 cc per day, and mannitol is averaged 160 g per day. However the standard are not absolute, the measurements are confounding by many other factors such as underlying disease. The ideal status will be determined by the proportion of surgeons who demonstrate sufficient knowledge related to “Guidelines of Management in Severe Head Injury.” Questionnaire will be scored base on the consultation from our co-investigators who has proficient knowledge in either the neurosurgical fields or CPP management. DBASE, SPSS 10.1 and S plus software will be used as the data management system. The demographic data, cases of injury, neurological manifestation, severity, imagine diagnosis, treatment and outcome will first be analyzed in addition to our purpose of proposal. The severe head injured patients of the 3 non-overlapping groups, which was categorized base on the presence of ICP monitoring and CPP management will be further assessed on the likelihood ratio 2 test and ANOVA to evaluate the difference of the outcomes (GOS). Meanwhile, survival analysis will also be used to assess the HRQL and thus, compare the differences between each subgroup. Regression model is to identify possible risk factors associated with the new management. The differences are considered statistically significant if the p value is less then 0.05, and having significant trend if the p value is between 0.05 and 0.01.. After collection of data, database will be sent to School of Public Health, Taipei Medical University, and Department of Physical Therapy, National Taiwan University for data analysis. Prof. Hung Yi, Chiou, Jau-Yih Tsauo, and Maou-Rong Lin, investigators who have outstanding reputation in both fields of epidemiology and biostatistics, and survival analysis will assist our research team for further assessment. Anticipated Results From this study, we hope to obtained the following results: 1. Evidence to prove the outstanding result in improvements of outcome among the institutions whom severe head injured patients were managed under close ICP monitoring and maintenance of adequate CPP. 2. Through further education and promotion, we hope to bring the new concept into the neurosurgical field of Taiwan to reduce mortality rate in head injury cases. 3. Provide first assessment relating to the improvements in quality-adjusted survival time among patients who were treated with the “Guidelines of Management in Severe Head Injury.” 4. Provide information needed for future research in constructing an appropriate new neurosurgical guidelines base on cost-utility analysis suitable to National Health Insurance System in Taiwan. Also, a disease specific RQL quotes related to head injury can be designed in the future base on the information obtained and more precise assessment can be performed in quality of life among head injured patients. 5. Like the traumatic center databank (TCDB) in U.S, most of our studies will serve as references for the implementation of the prevention strategies by the government, and for the research among scholars. 6. There is difficulty in obtaining sufficient number of prospective cases for most accurate statistical assessment. Unlike U.S., our problem is to find cases under this modern management. Thus, uncertainty in collection period is our major concern.