Chapter  2:  Rehabilitation for Traumatic Brain Injury: Evidence Report/Technology Assessment Number 2

Question 1

One small, retrospective, observational study from a single rehabilitation facility supports an association between the acute institution of formalized, multidisciplinary, physiatrist-driven TBI rehabilitation and decreased length of stay (acute hospital and acute rehabilitation) and some measures of short-term physiologic (noncognitive) patient outcomes. The level of evidence is Class III. This study concerned adult patients with severe brain injury (Glasgow Coma Scale 3-8); there is no evidence from comparative studies for or against early rehabilitation in patients with mild and moderate injury.

Question 2

When measured as the hours of application of individual or grouped therapies, there is no indication that the intensity of acute, inpatient TBI rehabilitation is related to outcome. Because of methodological weaknesses, however, previous studies are likely to have missed a significant relationship if one exists (a Type II error). These studies contained insufficient information about severity of injury and baseline function to ensure the comparability of compared groups. Also, these studies did not consider the quality of individual treatments, their lack of autonomy in the cognitive realm, and the delivery milieu. One or more of these factors may affect the outcome of care more than the time spent in each modality. Therefore, future research into efficacy of acute inpatient TBI rehabilitation must more adequately measure such factors and include the factors in their predictive models. Future studies also must employ a wider spectrum of outcome measures, including measurement of outcomes across longer periods of time after discharge.

From a clinical aspect, the evidence does not support equating different TBI rehabilitation delivery systems based on equivalent times of patient exposure to various therapeutic modalities. For example, this analysis would not support predicting that patient benefit would be equal if an equal time spectrum of rehabilitation therapies were delivered at a rehabilitation center as compared with a skilled nursing facility. More detailed analysis of factors involved in predicting response to rehabilitation modalities must be considered in approaching such questions.

Additionally, mandating a minimum number of hours of applied therapy for all TBI patients is not supported by the present state of scientific knowledge. How much of which intervention(s) optimizes recovery in a given type of patient has been inadequately studied. It is certainly reasonable to avoid situations in which patients do not receive potentially beneficial treatment. Based on the above studies, however, defining a minimal rehabilitation program in terms of time of applied therapy is not likely to optimize either the therapists' time or patients' recovery. It is probable that specific basic programs will have to be related to individual patient groups. Developing such algorithms requires further research.

Many patients who suffer TBI do not enter acute inpatient rehabilitation. Only one study of the effectiveness of inpatient rehabilitation included a comparison group of patients who did not undergo inpatient rehabilitation. Future studies should compare acute, inpatient rehabilitation to commonly used alternatives to inpatient rehabilitation, such as care in a well-staffed skilled nursing facility or in less intense variations of acute rehabilitation. Very little is known about the outcomes of TBI in these settings.

Question 3

There is evidence from two small studies (Class I and Class III) that a personally adapted electronic device, a notebook, and an alarm wristwatch reduce everyday memory failures for people with TBI. There is evidence from one study (Class II[a]) that compensatory cognitive rehabilitation (CCR) reduces anxiety and improves self-concept and relationships for people with TBI. Evidence from two studies (Class I and Class II[b]) supports the use of computer-aided cognitive rehabilitation (CACR) to improve immediate recall on neuropsychological testing, but the clinical importance of this finding has not been validated.

Question 4

Class II evidence indicates that supported employment can improve the vocational outcomes of TBI survivors. Nearly all information about supported employment comes from two bodies of work, each of which used different experimental designs and different models of supported employment. The findings have not been replicated in other settings or by other centers, so the generalizability of these programs remains untested.

Question 5

There have been very few studies on the effectiveness of case management, and the results of these studies are mixed. The only outcome for which there were results in the same direction from two or more studies pertained to changes in vocational status. This was associated with the single case-manager and insurance approach, as well as with the combined nurse and vocational case-manager model. There were conflicting results about the effects of case management on disability or functional status, living status, family impact, and other aspects, and some findings were mentioned in only one study. The clinical trial resulted in no functional status changes among case-managed subjects, despite an extended period of rehabilitation. However, when two forms of case management were compared, both the single and multiple case-manager/insurance approaches showed significant functional improvements.

Incidence and Costs of TBI

TBI is the leading cause of death and disability among children and young adults in the United States (CDC, 1998). An estimated 56,000 lives are lost in the United States each year to TBI (Kraus and McArthur, 1996). Motor vehicle accidents, followed by injuries due to firearms and falls, are the leading causes of death from TBI (Sosin, Sniezek, and Waxweiler, 1995). Males are 3.4 times as likely as females to die of TBI (National Institute of Neurological Disorders and Stroke). About 50 percent of people who sustain TBI are intoxicated at the time of injury (Ruff, Marshall, Klauber, et al., 1990; Kreutzer, Doherty, Harris, et al., 1990).

Figure 1. Incidence of traumatic brain injury per 100,000 (more...)

   Figure 1. Incidence of traumatic brain injury per 100,000 U.S. population

Source: MMWR - Morbidity and Mortality Weekly Report. 46(1):8-11, 1997 Jan 10.

Figure 1

Table 1. Direct medical care and rehabilitation costs (more...)

Table 1. Direct medical care and rehabilitation costs

Type of costs	Cost definitions
Direct personal care costs	All additional costs of supported living arrangements required by the person with TBI relative to independent community living.
Direct family out-of-pocket costs	Copayments and deductibles for covered health care services, expenses for uncovered health care services, child care expenses while attending rehabilitation, child care costs due to inability of patient to care for child, transportation to/from rehabilitation, cost of home renovation to adapt to the needs of the person with TBI (e.g., wheelchair access, installing a bathroom on a main floor).
Indirect medical care and rehabilitation costs	Travel time receiving rehabilitation treatment, waiting time, time spent by caregivers, family members, or friends in providing care.
Lost productivity	Lost productivity for the person with TBI and caregiver(s) because of the person with TBI.
Friction costs	Transaction costs (e.g., hiring, training) associated with replacement of a worker.
Insurance	Loading fees (profit and claims administration costs) for health and liability insurance, increase in experience-rated health insurance premiums for people with TBI subsequent to their injuries.
Education	Costs of formal retraining of workers with TBI into former or new jobs because of their disabilities.
Social welfare	Administrative costs of social welfare system to determine eligibility and set up transfer payments for income maintenance, direct publicly financed treatment (rehabilitation and sheltered living arrangements), and health insurance.
Consumer auto modifications	Costs of modifications to automobiles driven by people with TBI to install adaptive devices to compensate for impairments.
Legal/justice system	Costs of the tort liability system for determining the compensatory damages for TBI resulting from negligence; costs of the tort system for appealing decisions from the social welfare system relating to income maintenance for people with TBI.
Pain, suffering, bereavement	Bodily pain and unobservable psychological and emotional distress for people with TBI and their families caused by the injury, its treatment, and the associated loss of functioning. Note that these costs are separate from the lost productivity effects associated with chronic pain and emotional distress. Ideally, these effects would be valued by a person's willingness to pay to avoid these TBI symptoms.

Note: Shading in the cells denotes the settings of treatment phase or application of techniques in that phase. Grid shading denotes greater correlation of phase with setting or technique.

Although it is difficult to precisely quantify costs, useful information can be gleaned by studying charge data from published studies in various settings. The total cost of traumatic brain injuries in the United States is estimated to be $48.3 billion annually. Hospitalization accounts for an estimated $31.7 billion, whereas fatal brain injuries cost the Nation approximately $16.6 billion (Lewin, 1992).

In recent years, LOS and inpatient costs for rehabilitation have decreased. In the years 1988-1992, reports of average LOS for the initial admission for inpatient rehabilitation range from 40 to 165 days (Blackerby, 1990; Carey, Seibert, and Posavac, 1988; Giacino, Kezmarsky, DeLuca, et al., 1991; Mackay, Bernstein, Chapman, et al., 1992; McMordie and Barker, 1988; Rappaport, Herrero-Backe, Rappaport, et al., 1989). In one older multicenter study (the Model Systems study), the average rehabilitation length of stay (LOS) was 61 days, and the average charge was $64,648 exclusive of physician fees. Total charges averaged $154,256 (Lehmkulh, Hall, Mann, et al., 1993). In more recent studies performed in the early 1990s, rehabilitation LOS and charges were lower, ranging from 19 days and $24,000 for patients with milder injuries to 27 days and $38,000 for those with severe injuries (Cowen, Meythaler, DeVivo, et al., 1995). In the Medicare population in 1994, mean charges for patients admitted for brain injury (excluding stroke) were $42,056 (Chan, Koepsell, Deyo, et al., 1997).

Conceptual Model of the Lifetime Burden of Illness

Figure 2. The career of a TBI survivor

   Figure 2. The career of a TBI survivor

Figure 2

Mechanisms of Brain Injury

In TBI, the disease process begins at the moment of impact and extends thereafter for a protracted period of time. In strictly biological aspects, the brain injury disease process can be divided into primary and secondary insults. The primary insult initiates with the physical trauma to the brain. The secondary insults occur thereafter and, in many cases, are the primary determinants of outcome.

Beginning at impact and continuing for a generally brief period, primary insults to the brain include formation of intracranial hematomas (subdural or epidural), intracerebral hematoma, cerebral parenchymal contusions, cerebral swelling, and/or diffuse axonal injury. Intracranial hematomas such as subdurals and epidurals occur outside of the brain parenchyma and exert much of their pathological effects via increasing pressure on the brain (elevation of intracranial pressure [ICP]). Particularly with respect to epidural hematomas, if this pressure is avoided or rapidly reversed through expedient surgery, there may be no damage to the underlying brain and no residual effects of the hematoma. When there is a period of protracted intracranial hypertension, the ICP elevation may result in herniation of the brain tissue through orifices of the skull and/or cerebral ischemia due to interference with cerebral blood flow. Depending on magnitude and duration, such insults can produce deficits that vary from subtle to mortal.

Subdural hematomas also can cause significant intracranial hypertension and have a high likelihood of damaging underlying brain. This damage is often the primary determinant of long-term recovery.

Similar concerns about ICP are also relevant to cerebral swelling. Intracranial processes such as increased extracellular or intracellular fluid or elevated intracranial blood volume can raise ICP and impair adequate blood flow to the brain. In addition, some of these processes can cause primary cellular damage or ischemia by interfering with oxygen transport between vessels and cells.

Injuries such as intracerebral hematomas and cerebral contusions result in blood intermixed with brain. In the case of contusions, the pathology includes primary damage to neuronal cells. In both instances, the presence of blood within brain tissue appears to have significant toxic effects which can produce profound secondary insults to the injured tissue.

Diffuse axonal injury is a somewhat different disease entity. In this injury type, the physical forces the brain sustains during an injury characteristically consist of linear as well as angular acceleration or deceleration. These forces disrupt axons within the cerebral white matter, and these are called shear injuries. In this injury type, there may be no herniation or intracranial hypertension and, indeed, computer tomographic (CT) studies often may be normal or remarkably benign in appearance. Unfortunately, the widespread damage to the white matter will produce a recovery that is characteristically slow and incomplete.

Primary brain injuries occur at the time of injury and, by definition, must be treated post hoc. Secondary brain injuries are initiated sometime after injury and are often due to systemic factors. Their generally delayed onset allows them to be treated when they occur and also to be forestalled. This aspect of prevention has stimulated many of our trauma protocols and drives significant ongoing pharmaceutical research efforts.

The best known and possibly most devastating secondary brain insult is that of cerebral ischemia due to systemic hypotension. Systemic hypotension is extremely common, occurring in about one-third of patients with TBI during the period of injury through the end of resuscitation. A single hypotensive episode is associated with a doubling of mortality (Chesnut, Marshall, Klauber et al., 1993). Systemic hypotension illustrates the profound influence secondary brain insults can have on recovery and strongly supports the potential benefits of optimal trauma care.

Secondary brain insults may be due to intracranial processes that are initiated by:

1. Primary brain injury.

2. Secondary systemic insults such as hypoxia or hypotension.

3. Injuries to extracranial organ systems.

4. Systemic complications directly or indirectly related to the initial traumatic incident.

Secondary brain insults arising from the initial trauma include a number of toxic cellular and subcellular biologic processes, including:

1. Cerebral edema.

2. Alterations in intracranial ionic homeostasis (e.g., calcium, chloride).

3. Free radical formation.

4. Alterations at the molecular biology level.

These processes may result in ongoing and self-perpetuating brain injury. Cerebral edema will interfere with transport of nutrients, oxygen, and waste products and cause injuries to cells surrounding the area of primary injury as well as impair the healing of the initially damaged cells. Alterations in ionic homeostasis will disrupt the transmission properties of the neuronal and neighboring cells. Free radical formation can initiate a self-perpetuating cascade of toxic elements that may damage cells initially untouched by the injury. Finally, alterations at the molecular biology level will interfere with the primary genetic cellular control processes.

Secondary brain insults due to hypoxia or hypotension have become very well recognized over the past two decades and are a primary target of resuscitation protocols. The magnitude of importance of these insults is illustrated by the data on hypotension. Because we now have several tools to effectively recognize and treat such insults that are so devastating, intense interest is currently focused on managing them. Secondary insults also may occur from systemic trauma to extracranial organ systems. Although much of the influence of such extracranial trauma is mediated through hypoxia or hypotension, some aspects are unique to the individual organ system. For instance, long bone fractures may produce fat emboli to cerebral vessels that interfere with cerebral circulation. Alterations in timing and techniques of managing such fractures may improve cerebral outcome by decreasing the risk of embolism.

Finally, cerebral injury can be influenced by systemic complications occurring during the acute phase of management. The most well established of these complications as determinants of outcome include hypotension, pneumonia, sepsis, and coagulopathy. The importance of such factors in determining outcome supports the necessity of excellent critical care in managing patients with TBI.

The biologic aspects of repair or recovery are of primary importance during the early postinjury period, while the cognitive, psychological, and behavioral issues become increasingly predominant over time. The primary processes involved in biologic neuronal recovery are (1) reparative and (2) adaptive or plastic processes. Scientists believe that, except under extremely unusual circumstances, new neurons are not formed in the mature human brain, and thus when a neuron dies, its contribution to brain function is irreparably lost. Since neuronal death apparently can be induced not only by direct trauma but also by traumatic activation of inherent biological processes of programmed cell death (apoptosis), the question of cessation or reversal of such processes is an active focus of research.

Neurons have somewhat limited capabilities of self-repair, but the physiologic underpinnings of this regeneration are not completely understood. Although some clinical evidence suggests that neuronal repair can be facilitated pharmacologically in the injured spinal cord, no clinical evidence suggests that we can favorably influence such processes in the brain.

Research in animals suggests that there are critical periods during recovery wherein interventions may be particularly beneficial. The existence of similar periods has been postulated for the injured human brain, both for biological and behavioral interventions. To date, however, no clinical evidence supports the existence of such critical periods in the human.

Another biologic recovery mechanism is adaptation. In a biologic sense, this involves the formation of new circuitry to replace that lost from trauma. There is a great deal of plasticity in the nervous system, some of which continues throughout the organism's life--for example, learning of new information. At the more macroscopic level of altering neuronal circuits to directly replace those lost, however, abilities seem to be significantly limited in the adult human brain. In the immature nervous system, such plasticity is commonplace. A primary example is the alteration of laterality of language function resulting from very early injury to the left cerebral hemisphere. Unfortunately, the ability to make adaptations of such magnitude is lost early in life and the degree to which plasticity of lesser magnitude persists or can be induced in a more mature brain remains unclear. The question of such plasticity is fundamental to the concept of restorative cognitive therapy as well as to the concept of critical periods.

Memory

Brain injury can cause deficits in memory that range from mild, intermittent forgetfulness to profound inability to recall anything from the past or to integrate new information. Cognitive scientists and clinicians have made distinctions in mechanisms of memory that reflect modes of memory loss. Implicit memory records information that occurs nonconsciously; explicit memory is a function of active work such as repetition. Some brain injury depletes implicit memory but not explicit or vice versa. Semantic memory allows for understanding of the meaning of words; episodic memory records time- and place-specific experiences. Procedural memory is reflected in behavioral routines; declarative memory is reflected in the ability to explicitly report.

The burden of illness with respect to memory loss depends on the scope and degree of deficit and is also context-specific. For example, loss of procedural memory may result in devastating occupational consequences to a person whose work tasks are routine. However, if that is the only affected mechanism, other intact modes of memory may substitute for the deficit, and the person may be able to learn a new skill and regain independence.

The inability to integrate new information can result in global loss of independence, especially when accompanied by intact premorbid memory. The individual clearly remembers profession, life circumstances, and family from before the injury but nothing thereafter. Because they do not remember, they do not know that they do not remember, which leads them to insist on a daily and sometimes hourly basis that they are who they used to be. A reminder of the injury may last a minute or a day but will fade with other postmorbid information. These people cannot work, and the burden of their illness is evidenced in the consequences to family and caregivers.

Mobility and Independence

Limitations in mobility and independence may result in the inability to drive or ride a bus, work and earn a living, balance a checkbook, or prepare meals. Mobility also will be affected by physical impairment and independence by degree of memory deficit. The burden is also affected by the individual's social milieu. For example, for one person the presence of family to facilitate mobility may mediate the impact of the trauma; for someone else, dependence on family may be abhorred and may compound the burden of illness.

Organization and Productivity

Many survivors of brain injury exhibit an obsession for orderliness. Some are capable of servicing the obsession to varying degrees. For example, one person's home may be cluttered and disorganized, with one room (a computer room or tool shop) in meticulous order. The burden of illness can be observed in the amount of time and energy devoted to the orderly space and the confusion and lack of productivity experienced in the disorderly environments. Often, on a daily basis, a person never disconnects from the obsessional tasks in order to engage in other productive activities.

Physical Limitations

Physical deficits include difficulty with ambulation, hearing, vision, speaking, fatigue, and use of the hands. Such deficits may result from injuries sustained at the same time as, but distinct from, the head injury, or they may result directly from brain and spinal column nerve damage.

Inappropriate Behavior

People with traumatic brain injury often lose the ability to monitor and control behavior (Lezak, 1995). They may say whatever comes to their minds, even at inappropriate times. They may misunderstand the meaning of a situation or conversation and respond according to their misunderstanding. This problem can have profound effects on a person's life, resulting in loss of work, friends, and family.

Practice Settings

The following are practice settings. Although they are presented separately here, they often overlap to varying degrees.

• (Coma) treatment centers--A small number of people with head injuries will remain in a minimally responsive state for months or longer after injury. A few centers will accept such individuals once they are medically stable and attempt to achieve improvement by the use of various stimulation techniques. Skilled nursing care and physical therapy are also important elements of these programs.

• Acute rehabilitation programs are prepared to treat patients as soon as they are medically stable and are discharged from the acute hospital. Most of these are located in rehabilitation hospitals. Their primary emphasis is to provide intensive physical and mental restorative services in the early months after injury. Many will have specialized head injury units with an interdisciplinary team composed of physicians, nurses, speech and occupational therapists, and neuropsychologists. These programs are relatively short term, but longer stays may occur.

• Long-term rehabilitation programs provide extended rehabilitation and management services. They may provide a full range of rehabilitation services for the person with brain injury who is in need of a structured environment and is making slow improvements. Such programs generally are not for permanent placements, although they may have this service available. Usually a person may remain in the program as long as there continues to be some improvement.

• Transitional living programs--The goal of a transitional program is to prepare individuals for maximum independence, teach the skills necessary for community interaction, and work on prevocational and vocational training. Specialized programs stressing cognitive, memory, speech, and behavioral therapies are usually structured to the needs of the individual. Programs of this type are being established in a variety of settings--small group homes, special educational institutions--as part of a continuum of care in rehabilitation centers.

• Behavior management programs--Severe maladaptive or aggressive behavior will limit an individual's participation in most rehabilitation settings. While these programs treat the common behavioral problems following head injury, many of them cannot handle destructive behavior to self or others (e.g., sexual aggression).

• Day treatment programs are nonresidential facilities that emphasize services to upgrade functional skills. These services are similar to those described above under transitional living programs. Some offer day-care (supervision) services for those unable to benefit from an active program.

• Extended intensive rehabilitation--the more seriously injured person may require extended therapies in a structured program that has all the elements found in the acute rehabilitation center. Emphasis will usually be on cognitive and memory retraining, speech therapy, activities of daily living (ADLs), restructuring lost social behaviors, and continuing physical therapy. Prevocational and vocational training, recreational therapy, and community reentry are usually part of each program. Patients will remain in these programs as long as progress is being made--usually 6 to 12 months.

• Late rehabilitation--After discharge from the acute rehabilitation center, many people with head injury will need extended rehabilitation either in a residential or inpatient setting or in an outpatient program. Admission requirements may vary and be defined by a specific time after head injury.

• Independent living programs (ILPs) are community-based services that assist people with severe disabilities living in their own homes to increase personal self-determination and independence. ILPs provide both direct and indirect services ranging from residential/transitional programs to resource referral.

• Life-long residential programs--For those individuals unable to live at home or independently, a residential program may be the only alternative. There are very few programs of this type specifically set up for people with head injuries. Some facilities that have had experience with other disabled populations are beginning to explore this possibility.

• The home--For some, the home environment provides the most productive setting for therapy. In addition to in-home nursing care, rehabilitation professionals may come to the client's home on a routine basis to conduct therapy sessions.

• TBI social clubs--Although not necessarily a setting for formal rehabilitation, social clubs provide an environment in which people with TBI can associate with each other, form friendships, and instruct each other in how to manage life with a disability.

Techniques

Therapies discussed here may be provided on an individual basis or in group settings.

• Physical therapy comprises treatment designed to restore normal physical function: walking, use of hands, use of arms, and so forth. A physiatrist may specify the course of treatment, integrating physical therapy with other programs.

• Therapeutic recreation focuses on resuming leisure activities, community skills, and social skills.

• Speech and language therapy--Language disruption is common with TBI and is specifically addressed in speech therapy. Speech therapy encompasses relearning appropriate methods of communication, verbal and nonverbal, as well as relearning communication of abstract thought.

• Cognitive therapy offers retraining in the ability to think, use judgment, and make decisions. The focus is on correcting deficits in memory, concentration and attention, perception, learning, planning, sequencing, and judgment. A neuropsychologist, aided by other specialists (for example, occupational therapists [OTs], speech and language pathologists [SLPs]) may be asked to evaluate the level and kind of cognitive dysfunction following TBI, and they may reassess the individual over time to measure recovery.

• Occupational therapy offers retraining to enable the person with TBI to cope with the routine demands of a work environment. Often the occupational tasks are at a level below that of preinjury status.

• Behavioral therapy involves modification of maladjusted, asocial, or socially inappropriate behaviors.

• Psychotherapy targets emotional issues, social adaptation, and self-awareness. Group psychotherapy is useful for feedback, support, and confrontation by peers. Family members may participate in therapy to help them cope with the stress of being a caregiver and to build their ability to provide appropriate in-home support.

• Social skills training may be provided as a separate program, or it may be integrated into any of the methods described above.

Pupils

The status of the pupils (an indicator of intracranial pressure or herniation) helps predict outcome (Marshall, Gautille, Klauber, et al., 1991).

Age

Age is usually (Jennett, Teasdale, Galbraith, et al., 1979; Vollmer, Torner, Jane, et al., 1991; Waxman, Sundine, and Young, 1991; Braakman, Gelpke, Habbema, et al., 1980; Choi, Narayan, Anderson, et al., 1988) but not always (Reeder, Rosenthal, Lichtenberg, et al., 1996) found to predict GOS and function (FIM) after rehabilitation. Age appears to be a primary predictor independent of age-related factors such as systemic illnesses (Vollmer, Torner, Jane, et al., 1991).

Systemic Hypotension

The presence of severe systemic injuries is also correlated with worse outcome (Bowers and Marshall, 1980; Klauber, Marshall, Luerssen, et al., 1989; Mayer, Walker, Shasha, et al., 1981). However, when systemic hypotension occurring during the period between injury and the end of resuscitation is controlled, the influence of systemic trauma drops out (Chesnut, Marshall, Klauber, et al., 1993). This suggests that the influence of injuries to extracranial organ systems on outcomes from TBI is primarily mediated by the associated hypotension.

Intracranial Computer Tomographic (CT) Diagnosis

It would seem logical that the location, extent, and severity of damage to the brain would be predictive of outcome from TBI. Although prediction studies have correlated outcome with various parameters consistent with severity of brain injury such as skull fracture, intracranial hematoma, or presence of surgical mass lesions (Bergman, Rockswold, Haines, et al., 1987; Braakman, Gelpke, Habbema, et al., 1980; Jennett, Teasdale, Galbraith, et al., 1979; Waxman, Sundine, and Young, 1991), no one has yet demonstrated the expected degree of anatomic specificity in predicting recovery or residual deficits. This may be largely a question of defining the extent of brain injury based on the rather limited technology of computed tomography and magnetic resonance imaging. To date, the Traumatic Coma Data Bank classification of the CT imaging of the brain during the acute-care course is the most promising method of incorporating the anatomical nature of the brain injury into a predictive model (Marshall, Bowers-Marshall, Klauber, et al., 1991).

Other Variables

Other variables that have been suggested as predictive of outcome, as measured by GOS, include mechanism of injury (Waxman, Sundine, and Young, 1991), brainstem reflexes (Born, Albert, Hans, et al., 1985), evoked potentials (Anderson, Bundlie, and Rockswold, 1984), cerebrospinal fluid (CSF) catecholamines (Woolf, Hamill, Lee, et al., 1987), degree and severity of intracranial hypertension (Alberico, Ward, Choi, et al., 1987; Jones, Andrews, Midgley, et al., 1994; Marmarou, Anderson, Ward, et al., 1991), jugular venous desaturation (Gopinath, Robertson, Contant, et al., 1994; Jones, Andrews, Midgley, et al., 1994; Robertson, Contant, Gokaslan, et al., 1992), cerebral perfusion pressure (Gopinath, Robertson, Contant, et al., 1994; Jones, Andrews, Midgley, et al., 1994; Robertson, Contant, Gokaslan, et al., 1992), fever (Jones, Andrews, Midgley, et al., 1994), and in-hospital hypotension (Chesnut, Marshall, Piek, et al., 1993; Jones, Andrews, Midgley, et al., 1994). The statistical independence of these various factors remains to be clearly delineated. It cannot be suggested at this time that they be included as potential injury severity confounding variables in rehabilitation studies. When planning such investigations, however, the present state of the literature must be assessed since some of these indexes, or variations thereof, may develop as mandated covariables.

Two other indexes, duration of PTA and coma, are frequently used in quasiexperimental studies to adjust for severity of injury. Both of these are determined at some time following the injury.

The use of PTA originated with Russell and colleagues in the 1930s (Russell, 1932; Russell, 1935; Russell, 1971; Russell and Nathan, 1946; Russell and Smith, 1961). Russell classified injuries with PTA < 5 minutes as very mild; 5 to 60 minutes as mild; 1 to 14 hours as moderate; > 24 hours as severe; > 1 week as very severe; and > 4 weeks as extremely severe. In a study of 1,766 patients, Russell and Smith (1961) found the duration of PTA to be the single best predictor of neurological outcome.

In many studies, PTA is measured retrospectively by reviewing patient charts. Unfortunately, retrospective PTA is unreliable (Gronwall and Wrightson, 1980). PTA is best determined prospectively using as an index the attainment of a criterion score (e.g., 85 percent) on the Galveston Orientation and Amnesia Test (GOAT) (Levin, O'Donnell, and Grossman, 1979).

It is difficult to reconcile PTA with the more commonly used GCS score as an index of TBI severity. Using a PTA of > 24 hours as their criterion for the diagnosis of severe TBI, Bishara and colleagues found that 81 percent of such patients attained a good outcome (GOS 4-5) at 1 year (Bishara, Partridge, Godfrey, et al., 1992). This contrasts with only 43 percent of patients achieving such an outcome in the Traumatic Coma Data Bank (TCDB), where severe head injury was defined as a postresuscitation GCS = 8 (Marshall, Gautille, Klauber, et al., 1991). Such a discrepancy suggests that these two indexes cannot be used interchangeably as they will be predictive of markedly different courses of recovery.

Duration of coma has been used to quantify the severity of brain injury and to predict outcome. Patients in coma for < 20 days frequently regain independence in functional activities, whereas those who remain in coma > 20 days are usually profoundly disabled (Jones, 1981; Pazzaglia, Frank, Frank, et al., 1975). Like the PTA, duration of coma is unreliable when determined retrospectively, and it is not interchangeable with the GCS score. In addition, its determination can be confounded by the use of medications which are commonly administered during treatment of TBI patients.

Average LOS in acute care after TBI has been used as a gross indicator of the "sickness" of the patient during the immediate, posttraumatic period. More recent studies have reported acute care stays ranging from 20 to 60 days (Lehmkulh, Hall, Mann, et al., 1993; Mackay, Bernstein, Chapman, et al., 1992; Sakata, Ostby, and Leung, 1991; Sparadeo and Gill, 1989). Unfortunately, this variable is sensitive to socioeconomic issues, which may be difficult to control when using it as an indicator of trauma severity.

The above considerations reveal that the prediction of outcome based on physiologic indicators of TBI remains in a state of active development. At present, a credible attempt to control for (or match on) severity of illness should include the five best physiologic indicators described above. Older studies frequently do not use these indicators, the importance of which was not clearly established until recently.

Even today, retrospective analyses are hampered by the lack of reliability and absence of the necessary data in patient charts. Properly approaching this problem in the future will require a coordinated effort in data collection beginning at admission and continuing through rehabilitation wherein common definitions are used throughout.

Data Abstraction

We designed an instrument to record data abstracted from each eligible article (Appendix 4). The instrument includes items for patient characteristics, interventions, cointerventions, outcomes, study methods, relevance to the specific research questions, and results of the study. The instrument has two components: the first three pages of the instrument apply to all articles specified for inclusion in the study. The remaining pages are individual instruments that apply to one of the five questions. To abstract an article, a reader used the initial abstraction instrument plus one or more of the five question-specific instruments.

Figure 3

Managing the Database of Articles

Retrieved articles were kept in an electronic database (EndNotes Plus^TM). User-defined fields were used to record results of the eligibility screen, review for inclusion, and number of reviews performed. Paper copies of the articles were maintained in a master file. Throughout the literature review process, any articles identified from sources such as bibliographies or reference lists, manual searches of journals not contained in electronic databases, or references recommended by outside parties were added to the electronic databases.

Specification of Level of Evidence

We used a three-level system to rate individual studies:

• Class I

• Properly designed randomized controlled trials.

• Class II

• Class II(a): Randomized controlled trials that contain design flaws preventing a specification of Class I. An example of a design flaw is failure to blind raters or lack of followup data.Class II(a): Multicenter or population-based longitudinal (cohort) studies.Class II(b): Controlled trials that were not randomized.Class II(b): Case control studies.Class II(b): Case series with adequate description of the patient population, interventions, and outcomes measured.

• Class III

• Descriptive studies (uncontrolled case series).Expert opinion.Case reports.Clinical experience.

A well-done, prospective, multicenter or population-based cohort study can provide valuable information that, in some ways, is more representative of results in actual practice than are data from a randomized trial done in a highly selected sample. However, an uncontrolled case series is generally classified as Class III, indicating a low level of confidence for inferences about effectiveness.

Why is a control group needed to make inferences about effectiveness? Information about the long-term natural history of TBI provides too little certainty about the outcome to forgo the use of a control group. If the consequences of brain injury in the absence of rehabilitation could be predicted accurately, a control group would not be needed. Some evidence suggests a natural course of recovery from TBI in both basic and complex functions (Dikmen, Reitan, and Temkin, 1983), especially in the first 6 months after injury (Bond, 1979; Levin, Benton, and Grossman, 1982; Levin, Gary, Eisenberg, et al., 1990). After 6 months, survivors of TBI recognize their disabilities as they stabilize and often maximize their functional status, but major deficits in social and leisure activities tend to persist (Oddy and Humphrey, 1980).

A "gray zone" exists between Class II and definite Class III articles. Much of the research in rehabilitation uses quasiexperimental designs. In these observational study designs, control groups are sometimes identified from a separate population of people with TBI. One study compared patients undergoing inpatient rehabilitation with a sample of people with TBI who had been treated in a region of the country where formal inpatient TBI rehabilitation was not available (Aronow, 1987). This was an entirely separate patient group, and all the data except outcome measures came from an independent database.

The main difficulty with the quasi-experimental design is lack of control over the constitution of the compared groups. Since there is no randomization and generally no control over the details of the selection process through which the study participants received their separate therapies, the groups are likely to differ in the frequency of characteristics that are associated with the outcomes of interest. Even when significant efforts are made to match the experimental and the quasicontrol groups, groups still are likely to differ significantly.

Quasiexperimental designs rely heavily on multivariate statistical analysis and matching to counter this problem. While this is common practice, making inferences about effectiveness from statistically controlled data is controversial because these methods do not necessarily guarantee that the results are reliable or that serious bias and confounding have been eliminated. There are at least three major barriers to accuracy in the practice of statistical adjustment for risks. First, all of the confounding variables must be recognized and be associated with accurate and reliable measurement instruments. Second, data on all of these confounding variables must be available in comparable formats in the compared groups. For example, in the study mentioned earlier, baseline data, such as admission functional status scores, may be available for patients who entered inpatient rehabilitation but missing for patients who did not. Third, statistical methods must be selected and applied properly.

Since the first two barriers are virtually never overcome and the third remains somewhat controversial, the execution of a statistically valid quasiexperimental study is a daunting and generally unrealized task. Most studies using retrospective data suffer from the absence of well-measured data on a number of important confounding variables. The few prospective studies generally suffer from a lack of consensus on the proper measurement instruments for many of these variables. Finally, while the standard of practice for use of statistical methods to remove confounding is not completely defined, many studies do not use, or fail to report, available methods to improve the reliability and robustness of these methods.

Much of the literature relevant to the five questions addressed in this report falls into the "gray zone" between Class II and Class III. For this reason, critical appraisal of key studies plays a particularly important role in this review. A number of characteristics of these studies were considered relevant to all rehabilitation questions and were recorded in the data abstraction form. Evaluation of the following factors played a major role in critically appraising these articles:

• Prospective collection of data.

• Complete description of parent patient population.

• Large study population size (driven by hypothesis, power, type I error threshold).

• Study setting--a single center, many centers, or population-based.

• Descriptions of reasons for referral to service being studied.

• Methods described completely enough to allow study replication.

• Complete description of rehabilitation technique in question (independent variable).

• Complete and adequate description of differences between "control" and "experimental" groups.

• Conditions determining whether study subjects did or did not receive the rehabilitation technique in question.

• Information about potential confounders, including types and severity of injury; age; and others (including, in some cases, economic status, educational level, lack of family support).

• Measurement of confounding variables using instruments validated as accurate, sensitive, and reliable.

• Payer group.

• Choice of outcome variables that are meaningful to survivors as well as caregivers.

• Use of functional status and other health outcomes rather than surrogate intermediate outcomes.

• Measurement of outcome variables using instruments validated as accurate, sensitive, and reliable.

• Timing of outcome measurements.

• Assessment of survivor characteristics and outcomes by blinded observer.

• Use of multivariate statistical analysis: Were interactions sought and controlled for? Were risk estimates calibrated? Were all relevant confounders included as candidate variables?

The criteria used to classify articles and the features to be considered in critically appraising them were discussed at the subcommittee, committee, national expert panel, and Aspen Neurobehavioral Conference levels with the goal of maintaining consensus on at least the relative stratification of individual articles.

Direct Evidence

There is no direct evidence from randomized trials about the effect of early neurological rehabilitation on health outcomes.

Indirect Evidence

Conclusions for Question 1

One small, retrospective, observational study from a single rehabilitation facility supports an association between the acute institution of formalized, multidisciplinary, physiatrist-driven TBI rehabilitation and decreased length of stay (acute hospital and acute rehabilitation) and some measures of short-term physiologic (noncognitive) patient outcomes (MacKay, Bernstein, Chapman, et al., 1992). The level of evidence is Class III. This study concerned patients with severe brain injury (GCS 3-8); there is no evidence from comparative studies for or against early rehabilitation in patients with mild or moderate injury.

Some indirect evidence also confirms that early rehabilitation is associated with a shorter inpatient rehabilitation LOS, but this association rests on important assumptions that have not been examined in prospective studies. Most important, the association of acute LOS with rehabilitation LOS and greater rehabilitation costs does not directly imply that shortening acute LOS will result in favorable changes in these outcomes. A common confounding variable in the studies reviewed in this section is the inability to control for the possible correlation between the velocity of recovery and the acute hospital LOS. Patients with TBI who have similar GCS scores on admission may recover at markedly different rates. If a patient evidencing rapid recovery reaches threshold for rehabilitation admission and continues to recover quickly thereafter, his or her acute rehabilitation LOS and total LOS days will be fewer than someone who reaches the same landmark at a slower rate. Because present indicators of TBI severity do not measure rate of recovery, this oversight might explain why the relation between acute LOS and rehabilitation LOS persists even after statistical control for severity of illness on admission.

Another finding in the studies reviewed in this section is that rehabilitation admission FIM and acute care LOS are strongly associated with rehabilitation LOS and outcome. This finding suggests that acute hospitalization LOS is not simply a proxy for injury severity or level of recovery on transfer to rehabilitation.

Future Research on Question 1

In essence, this question addresses the efficacy of starting formal rehabilitation efforts very early during the acute-care stay at the trauma center as opposed to "filling in" until the patient is transferred to a rehabilitation program. Certain therapeutic modalities such as physical therapy are generally felt to be properly started soon after admission because of the known rapidity with which complications such as contractures begin. Although the details of the proper techniques, timing, and intensity of such treatment remain to be determined, it is unlikely that a control group of patients that would receive no acute physical therapy could be ethically formed. Although the indications for early application of other rehabilitation-oriented therapeutic modalities are less clear, similar ethical constraints will likely prevent the development of pure control groups for any specific discipline.

The ability to study the efficacy of a formalized program, however, is not subject to such constraints at the present time. The concept of the acute initiation of formal rehabilitation should be defined as an attempt to begin rehabilitation independently of the patient's location or other extraneous constraints such as medical complications, bed availability, and so forth. Such a formalized system is an attempt to "blur the line" between the stay at the trauma center and the time at a rehabilitation center. It would attempt to divorce the treatment from the milieu so that the patient's needs would drive the treatment.

As such, the integration of such a formalized program into an acute care center's operating procedures could be effected in a prospectively randomized fashion without ethical constraints. Since such rehabilitation efforts properly come under the aegis of a physiatrist, the primary independent variable would be the involvement of a physiatrist overseeing explicit formalized application of rehabilitation techniques to the "experimental" group as compared with continuation of the status quo in the "control group." The dependent variables would be acute care and rehabilitation LOS, outcome at time of discharge from acute care (admission to inpatient rehabilitation), outcome at discharge from rehabilitation, and cost-effectiveness of resource utilization.

For such an investigation to work, patients would have to be classified into working categories at a very early stage so that formalized and standardized rehabilitation protocols designed to meet their needs could be applied. If every patient were to be treated differently, it would not be possible to control for the resulting confounding of treatment variables with the independent variable. On the other hand, since different patients need a different array of therapeutic modalities (differing in terms of treatments, timing, and intensity), managing all patients in the same fashion would not be proper. Therefore, if the research is to be useful, such issues must be addressed prior to onset of the investigation.

It also would be necessary to strictly define the applied therapies, since these would be confounding variables in the analysis. Issues such as timing, intensity, modalities, therapist training, milieu, and so forth would have to be standardized within and between treatment groups. This will be especially critical if multiple centers are to be included in the study and combined in the data analysis.

Such a study would not address which modalities should be applied at what point during the acute care stage. These are separate questions addressing the efficacy of rehabilitation modalities in general. The suggested investigation would, however, address the present, seemingly artificial dependence of the initiation of formal rehabilitation on extraneous variables which commonly occur during the early postinjury period.

Challenges in Assessing the Effectiveness of Inpatient Rehabilitation

A precise knowledge of the natural, untreated prognosis of brain injury could reduce uncertainty about the effectiveness of inpatient rehabilitation, but such knowledge is lacking. Because experimental trials of inpatient rehabilitation are unlikely to be performed, investigators have relied on statistical methods to adjust for differences in the baseline characteristics between the groups of patients compared in studies. These groups might be patients who received different intensities of rehabilitation services, received rehabilitation services relatively early or late, or did not receive rehabilitation in the usual course of care. The validity of these methods depends in large part on the predictive ability of the risk factors measured in these studies.

As discussed below, the likelihood of a good outcome depends on many patient characteristics. For this reason, it is impossible to interpret studies that fail to describe the baseline characteristics of the sample under study. In such studies, it is not clear whether the results were due to the interventions under study or to unreported selection factors. Two extremes characterize these studies with respect to the description of populations and samples. On one hand, it is common to have a sample described as "patients who were considered ready for (the intervention) by their occupational therapists" or "consecutive referrals to a vocational rehabilitation program who were considered employable under the right circumstances." On the other hand, the inclusion criteria for the sample may be a lengthy list of narrow parameters, including scores falling within a specific range on a series of neuropsychological tests. In one case, there may be no description of the patients. In the other, the description may be so specific that the results do not apply to the greater proportion of patients.

The nature of rehabilitation makes it difficult to evaluate its effectiveness. Multidisciplinary rehabilitation is a complex intervention. Even in studies that provide evidence that patients undergoing rehabilitation improved, it usually is not possible to determine which specific components of rehabilitation are effective. In general, little description of the precise components of multidisciplinary rehabilitation programs is available. Some studies use the number of hours of performance of individual treatment modalities (e.g., physical therapy, occupational therapy, speech therapy, etc.) as a measure of the intensity of rehabilitation. However, additional hours of specific treatments may be provided to patients who enter rehabilitation with more severe deficits. In addition, their control for the confounding variables that they collected would have been considerably strengthened by the use of multivariate statistical methods such as regression analysis. Even without this confounding, an aggregate measure like time spent with the patient cannot capture the social factors and relationships that can be important components of the therapeutic process.

At present there is no reliable method to measure the effect of exposure to the milieu of the rehabilitation program--the interactions between patients and other patients, nurses, therapists, and physiatrists during the course of an inpatient TBI rehabilitation stay--or to separate their effects from the content of the actual therapy provided. Such information may be critical when attempting to determine whether an inpatient rehabilitation unit or a skilled nursing facility may be interchangeable for a given patient.

Most studies do not provide even descriptive information about the components of rehabilitation and the content of specific interventions. In these studies, rehabilitation is somewhat of a black box--it is defined, by default, as whatever happens between admission to and discharge from a rehabilitation unit. The lack of detail about what constitutes rehabilitation reduces the generalizability of each study's findings and makes it difficult to compare the results of different studies attempting to assess the effectiveness of rehabilitation.

In formulating a strategy for reviewing the literature, we focused on whether information was available to examine the actual mechanisms by which inpatient TBI rehabilitation affects outcomes. Specifically, we sought to examine whether the results of rehabilitation vary according to (1) whether the intervention was directed and managed by a physiatrist and (2) the number, kinds, and frequency of methods applied. Secondarily, we sought to examine which factors predict a good outcome and how these factors may be used in decisions about how and when patients might benefit from inpatient rehabilitation.

The population for this question consists of people who sustained TBI between the ages of 18 and 65 years whose injury severity warranted a trip to a hospital emergency department, transfer to acute care, and subsequent transfer to inpatient rehabilitation. We also intended to focus predominantly on studies that included or measured the following patient characteristics:

• Age.

• Glasgow Coma Scale score.

• Severity of injury.

• Multiple injuries.

• Premorbid data.

• Mechanism of injury (kind of trauma).

• Intracranial diagnosis.

• Functional status.

Finally, studies had to report one or more of the following outcome measures:

• Length of stay in a rehabilitation facility.

• Immediate care costs and long-term financial burden.

• Health status at discharge from inpatient rehabilitation.

• Long-term measure of impairment.

• Long-term measure of disability.

• Independence, relationships, family life, satisfaction.

Figure 3

How effective is acute inpatient TBI rehabilitation in general?

Before addressing whether the intensity of inpatient TBI rehabilitation is associated with improved outcome, we examined the more general question of the effectiveness of TBI rehabilitation itself. A large number of uncontrolled case series show that people with brain injuries generally improve by the time of discharge from the acute inpatient rehabilitation facility (Ashley, Persel, and Krych, 1993; Basso, Capitani, and Vignolo, 1979; Ben-Yishay, Silver, Piasetsky, et al., 1987; Cope, Cole, Hall, et al., 1991; Cope and Hall, 1982; David, Enderby, and Bainton, 1982; Dresser, Meirwosky, Weiss, et al., 1973; Eames and Wood, 1985; Evans and Ruff, 1992; Johnston, 1991; Jones and Evans, 1992; Lomas and Kertesz, 1978; Malec, Smigielski, DePompolo, et al., 1993; 1Mills, Nesbeda, Katz, et al., 1992; Panikoff, 1983; Pazzaglia, Frank, Frank, et al., 1975; Prigatano, Fordyce, Zeiner, et al., 1984; Sarno, 1976; Scherzer, 1986; Tuel, Presty, Meythaler, et al., 1992). Because of imperfect knowledge about the natural history of TBI and the nearly complete absence of data about the results of alternative methods of rehabilitation after discharge from the acute care hospital, these Class III studies provide only weak evidence that inpatient rehabilitation is effective. Comparing these studies and aggregating their results into a systematic examination of results was not possible because data were too incomplete to discern the relationship between types of populations or interventions and outcomes.

One quasiexperimental study used an unmatched control group to assess the effectiveness of acute inpatient TBI rehabilitation (Aronow, 1987). Sixty-eight patients were selected from 107 consecutively discharged patients treated at a single inpatient brain injury rehabilitation center. Their long-term outcomes were compared with those of 61 patients selected from 1,400 cases consecutively entered into an epidemiologic database of TBI inpatients at a neurosurgical unit in an area of the country with no comprehensive rehabilitation available for severe TBI. These two groups were termed "rehabilitation" and "nonrehabilitation," respectively. The selection criteria were TBI (> 1 hour of unconsciousness and > 24 hours of altered consciousness), age at injury between 5 and 80, acute hospital LOS > 15 days, and not comatose at the time of acute hospital discharge.

Measures of TBI severity in the Aronow (1987) study were PTA, acute hospital LOS, presence or absence of open brain injury, and number of skull fractures. Age, sex, race, and years postinjury were measured as confounding variables. TBI severity and the other potentially confounding variables were controlled for by using regression analysis, entering the confounding factors into the model prior to adding the rehabilitation versus no rehabilitation variable. The outcome measure was a 13-variable measure that included vocational status; living arrangement; number of recent inpatient treatment episodes; number of recent outpatient episodes; hours of daytime care required; functional status in self-care, mobility, and residential skills; number of home and outside social contacts; and number of physical, cognitive, and emotional symptoms. This standardized outcome measurement was developed unique to this study and has not been otherwise tested. Outcome data were obtained via telephone interview with the person with TBI or a caregiver/relative during a set study period not indexed to time after injury or rehabilitation. Chi square analysis was used to examine differences in PTA between groups, and linear multiple regression modeling was used to control for confounding variables in determining the relationship between rehabilitation and outcome.

At baseline, the rehabilitation and nonrehabilitation groups differed significantly in PTA, the major index of TBI severity used in the study (Aronow, 1987). Seventy percent of the rehabilitation group had PTAs > 4 months, while 74 percent of the nonrehabilitation group had PTAs 1 month. The nonrehabilitation group also was less impaired in self-care activities and memory.

In a multiple regression model adjusting for age, sex, race, injury severity (PTA, acute hospital LOS, open brain injury, number of skull fractures), and years postinjury, rehabilitation was associated with a better long-term outcome (Aronow, 1987). The overall R2 value was 0.551, suggesting that about one-half of the variance in this group was accounted for by the nine predictors plus rehabilitation. Days in acute hospital, duration of posttraumatic amnesia, age at onset, sex, and whether rehabilitation was performed were statistically significant predictors of outcome. However, the correlation coefficient (Pearson r) for rehabilitation was only 0.159, suggesting that only about 3 percent of the variance was related to whether or not rehabilitation was done.

This study (Aronow, 1987) mildly supports the hypothesis that acute inpatient TBI rehabilitation improves outcome. The finding of a benefit despite worse initial severity in the rehabilitation group lends some credence to the results. The study has important weaknesses that have been enumerated by others (High, Boake, and Lehmkuhl, 1995). The obvious baseline differences between the two groups means that the attempt to identify a suitably comparable control population failed. While the statistical analysis was well done, this method of control works best when there is good reason to believe that the two groups being compared are similar. The differences also reflect the underlying problem that the subset of patients admitted to a rehabilitation unit are not representative of the population thought to benefit from it.

Because this was a retrospective study (Aronow, 1987), the authors were limited to information that had been recorded in the patients' charts or (in the case of the control group) data recorded in an epidemiologic study, although all records were abstracted using the same protocol and all followup interviews were conducted using an identical instrument and process. Data on the timing of followup (how long after injury, acute hospital discharge, and rehabilitation discharge the outcome data were collected) were not available. GCS data also were unavailable. Finally, the use of a proprietary outcome instrument prevents comparison of their data to other studies.

Is the intensity of acute inpatient TBI rehabilitation services related to outcome?

A retrospective multicenter study of 140 patients admitted between 1990 and 1991 to one of eight rehabilitation hospitals was the best of these studies (Heinemann, Hamilton, Linacre, et al., 1995). Although the study was retrospective, all of the participating hospitals were prospectively collecting data using the Uniform Data Set for Medical Rehabilitation (Granger, Hamilton, and Sherwin, 1986). Intensity of therapy was defined either by the number of billed hours of individual therapeutic modalities (physical therapy, occupational therapy, speech and language services, and psychological services) or by all services combined. The authors examined whether a higher level of services was associated with better motor and cognitive FIM scores, achievement of motor or cognitive potential ([D/C FIM-admit FIM]/[100-admit FIM]), and efficiency of change ([D/C FIM-admit FIM]) at the time of discharge.

An analysis of the interrelationships between intensity and severity of injury or other descriptors revealed that they were not independent. Intensity of treatment covaried with functional status at admission, patient demographics, and medical characteristics. This suggests that the functional status on admission is actually related to the therapy intensity the patient receives. It appears that the patients received more therapy if they were admitted with less cognitive function, had uninterrupted stays, had a longer delay to admission, were younger, and so forth.

Investigation of the relationship between intensity of therapy and their (Heinemann, Hamilton, Linacre, et al., 1995) various outcome measures (discharge motor and cognitive FIM scores, achievement of motor or cognitive potential, and efficiency of change) did not reveal any significant relationship for occupational, physical, or speech therapy intensities. There was also no significant intensity:outcome relationship for intensity of all therapies combined. Only the number of hours of psychologic work per day, usually delivered as cognitive therapy, were associated with any alterations in outcome. These alterations were improvements in discharge cognitive, FIM score, achieved potential gains in cognitive FIM score, and efficiency of cognitive recovery.

The major weaknesses of this paper (Heinemann, Hamilton, Linacre, et al., 1995) are the absence of a specific definition of TBI and lack of control for severity of injury as a confounding, predictive variable. It is unlikely that the admission FIM will cover all of the variance otherwise subsumed by GCS, PTA, and/or duration of unconsciousness (coma). There was no control over or description of differences in treatment between the involved hospitals. Also, the use of billing hours as the index of therapeutic intensity probably included time not spent directly in patient care. Finally, the authors only used one outcome measure (FIM), and there is no long-term followup. Despite these weaknesses, however, the use of prospective data collection and credible analytic techniques make this the most important paper to address the issue of the relationship between intensity of therapy and outcome. It is the only Class II study in this category.

A retrospective study (Spivack, Spettel, Ellis, et al., 1992) examined the influence on outcome measured at rehabilitation discharge of therapeutic intensity during the first treatment month and over the entire stay on 95 patients with TBI. The cohort consisted of patients with a complete set of records who had been admitted to a single inpatient rehabilitation unit between 1988 and 1990. A definition of TBI was not given. It was noted that not all patients were comatose on admission. LOS ranged from 20 to 412 days with a median of 58 days.

Intensity of treatment was calculated as hours of actual treatment performance measured in 15-minute intervals for PT, OT, ST, cognitive remediation, vocational services, neurophysiology, respiratory therapy, therapeutic recreation, and medical services. Intensity of treatment during the first month was the total hours of treatment during that month. Subjects were separated into high- and low-intensity groups based on the median split of treatment hours during the first month. The median was 76 hours with a range of 18 to 196 hours. Average daily intensity of treatment over the entire stay was calculated, and subjects were again classified into high- and low-intensity groups based on the median split. The median was 4 hours per day with a range of 1.4-12.25 hours. The authors (Spivack, Spettel, Ellis, et al., 1992) felt that the true time spent per weekday was probably about one-third higher, since these estimates did not take account of days when therapy could not be administered (passes, holidays, weekends, etc.).

GCS was measured within 24 hours of admission to the trauma hospital. Head AIS score, duration of coma, severity of extracranial injuries (highest non-head AIS), and time since TBI were also measured. The statistical method used to control for these confounding variables was unclear.

The independent variables were intensity of treatment during the first month of rehabilitation, average daily intensity of treatment over the entire LOS, and LOS. All of these independent variables were made binary using the median split method as described above.

The dependent variables were outcome measures. RLA scores were measured on admission and discharge. In addition, therapy-specific outcomes on admission and at discharge were assessed using a seven-point functional status scale developed by clinicians within each rehabilitation discipline. A principal components analysis was used with a varimax rotation conducted on the matrix of correlations among functional scale scores at admission to group the scores on various axes. This resulted in grouping along axes of physical performance, higher-level cognitive skills, and cognitively mediated physical skills. In addition, patients were rated on their RLA scores on admission and discharge.

The statistical methods for assessing the relationships between the independent and dependent variables were analyses of variance and covariance controlling for multiple comparisons.

Analysis of covariants (ANCOVA) with repeated measures analysis was used to investigate treatment intensity and LOS on the dependent variables of admission and discharge scores on physical performance, higher level cognitive skills, cognitively mediated physical skills, and RLA level. In this analysis, LOS and intensity of treatment during the first month of rehabilitation and LOS and average daily intensity of treatment over the entire LOS were separately analyzed.

LOS significantly influenced outcome across all outcome groups. With respect to either intensity of treatment during the first month of rehabilitation or average daily intensity of treatment over the entire LOS, the only statistically significant relationship was between discharge RLA and 1-month treatment intensity. Spivak, Spettel, Ellis, and colleagues (1992) found a borderline nonsignificant relationship (p=0.06) between higher level cognitive skills and average daily treatment intensity. They also found a borderline nonsignificant relationship (p=0.07) for the triple interaction of RLA, LOS, and average daily treatment intensity. Based on this borderline relationship, the authors performed univariate ANOVA analysis on this interaction. This revealed a significant effect of high-intensity treatment during the entire stay on RLA scores on patients with longer stays. This relationship did not hold for patients with short lengths of stay. ANOVA analyses of age and LOS as confounding variables suggested that these variables could not explain the correlation.

There are a number of weaknesses in the paper by Spivak, Spettel, Ellis, and colleagues (1992). Because a precise definition of TBI was not provided, it is difficult to determine the parent population. Additionally, the focus of the analyses was on outcome measures that were derived in the unit and were, therefore, of unestablished validity and reliability. The major weaknesses in this study, however, are the use of the median split method to dichotomize the independent variables and the lack of powerful multivariate statistical methods.

In this case, the median split method is a dichotomizing method of convenience and does not necessarily reflect any underlying physiologic basis. The distribution of intensity times may be influenced by confounding influences of various origins, including brain and extracranial injury characteristics, patient personality, payer characteristics, and so forth. One method to force independent variables into binary distributions would be to determine split thresholds recursively in terms of their influence on outcome. Alternatively, intensity of treatment could have been analyzed during the first month of rehabilitation and average daily intensity of treatment over the entire LOS as continuous variables. The use of the median split method in dividing independent variables might have increased the likelihood of a type II error.

The other major weakness in the paper by Spivak, Spettel, Ellis, and colleagues (1992) is the lack of powerful, multivariate control for confounding variables. As was demonstrated (Heinemann, Hamilton, Linacre, et al., 1995), it is not proper to assume independence between intensity of therapy and severity of injury or other patient descriptors. The analysis would have been considerably strengthened by using regression-type analysis.

In the analysis of results, several inferences were made from the nonsignificant but borderline interactions between higher level cognitive skills and average daily treatment intensity (p=0.06) and the triple interaction of RLA, LOS, and average daily treatment intensity (p=0.07). Based on the latter borderline relationship, a significant effect was found of intensity of treatment during the entire stay on RLA scores on patients with long LOSs. Based on this interaction, suggestions were made on managing the intensity of treatment for patients with more severe injuries. However, the original interaction that inspired these suggestions was not significant (p=.07); consequently, the value of the suggestions is not substantial.

In one retrospective study (Blackerby, 1990), the influence on brain injury outcome of a change in mean daily therapeutic intensity that accompanied a major programmatic change at the study institution was investigated. The study took place at two commercial inpatient head injury rehabilitation provider units run by Rebound, Inc., a commercial provider of head injury rehabilitation services. The charts of all 149 patients with brain injury in the program between 1986 and 1988 were evaluated; 97 percent of the patients were admitted with a diagnosis of TBI. There was no description of TBI provided. Patients were either in a coma treatment program or an acute treatment program. For the prechange group, 55 percent were in the coma treatment program (54 of 98 patients), whereas only 27 percent of patients in the postchange group were in the coma treatment program (14 of 51 patients).

There was no precise measure of TBI severity. Confounding variables quoted in this study included age, level of function on admission, and length of time postinjury as measured on admission. The measure of function on admission was not specified. It was reported that the two groups did not differ with respect to these variables, although the method of handling them as confounding variables is not stated and the raw data are not provided.

The independent variable was intensity of therapy measured as mean number of daily therapy hours for all types of therapy combined. The two groups were formed in 1986 when the rehabilitation provider units altered the structure of their rehabilitation service delivery system. At this time, the intensity of inpatient rehabilitation was increased from an average of 5.5 hours per day to an average of 8 hours per day.

The dependent variable was inpatient rehabilitation LOS. The relationship between the independent and dependent variables was analyzed using t statistics, separately analyzing the coma treatment and acute treatment groups.

The results demonstrated a large change in average length of stay in both the coma and acute treatment programs following the programmatic changes. The variability in the LOS also decreased after the programmatic change. The only statistical examination was a t-test between pre- and postchange LOS for both the coma treatment program and the acute treatment program. Both of these changes were statistically significant as tested.

The differences between these groups in terms of cost was evaluated. The average daily cost for the rehabilitation programs was $785 per day with $350 representing the fixed costs. For the patients in the coma treatment program, the average savings would be $16,950 per patient. For the patients in the acute treatment program, the average savings would be $18,504. It was noted that such cost savings, as well as the decreased variability in LOS that appeared to accompany the change in mean daily therapeutic intensity, would be of use to insurance carriers in predicting and controlling costs.

There are a number of weaknesses in the paper by Blackerby (1990). A strict definition of TBI was not provided, making it difficult to determine the parent population. In addition, there was a lack of control for severity of TBI or other confounding variables. No data on these variables were provided.

The major weakness, however, was the lack of statistical controls for a number of potentially significant confounding variables that are intrinsic to this experimental design. It appears there were major changes in this rehabilitation delivery system that accompanied the increase in mean daily therapy intensity. The paradigm change was described as a change to a "naturalistic activity, total therapeutic day model" that apparently involved adaptations of those activities of interest to the individual before head injury. It was suggested that implementation of internal case management was part of the new system and that "senior clinical staff were added to the programs in the roles of clinical consultants and case managers, which increased staff experience and personnel." The occurrence of programmatic changes of such magnitude will, almost by definition, alter patient management in ways outside of those resulting from the increase in mean daily therapy intensity. If all of these changes could be described and quantified, their confounding influences could be addressed using multivariate statistics. In the absence of these data and such statistical analyses, it is difficult to interpret the results of this report.

Conclusions for Question 2

Based on the current literature, there appears to be little evidence that therapeutic intensity, measured as hours of treatment, is related to the beneficial effects of acute, inpatient TBI rehabilitation when the analysis controls for confounding variables. The only Class II study (Heinemann, Hamilton, Linacre, et al., 1995) found no correlation between intensity of individual or grouped therapeutic interventions and outcome. The second study found statistically significant correlations only for discharge RLA and 1-month treatment intensity (Spivack, Spettell, Ellis, et al., 1992). Nonsignificant trends were reported toward associations between higher level cognitive skills and average daily treatment intensity and for a triple interaction of RLA, LOS, and average daily treatment intensity, but the interpretation of these trends is unclear in the absence of statistical significance or other supporting evidence. The third report (Blackerby, 1990) appears to have been so highly confounded by uncontrolled variables as to render questionable any comparative interpretation of findings.

There are a number of possible reasons why various intensities of rehabilitation do not appear to correlate with functional improvements. First, the effect of specific comorbidities was underinvestigated in these papers. Second, there is a lack of long-term followup in all three studies. Third, these studies did not examine the quality of treatments or the reasons the various therapies were applied.

Another potential explanation for the demonstrated lack of correlation between therapeutic intensity and outcome is that all patients were receiving enough therapy and that added hours did not make a difference. Similarly, the ranges of intensities of treatment (lack of treatment variability) may have been too limited to show differential effect. As Heinemann, Hamilton, Linacre, and others (1995) noted, the Health Care Financing Administration (HCFA) mandated 3 hours per day of therapy for each patient starting in 1983. The legislation may have decreased practice variation that, prior to the regulations, might have been wide enough to affect patient outcomes. Future studies should either consider suspending such constraints or including the influence of such mandated decreases in variation in therapeutic effort into the power calculations used to determine the minimal size of their patient populations.

Overall, however, it also is debatable whether hours of applied therapy is the proper index for therapeutic intensity. The impact of individual therapeutic disciplines may not be independent or even separable, and the time spent in each might not be the best index of their intensity.

The use of hours of applied therapy as the index for therapeutic intensity also raises the question of how to measure the "milieu effect" of comprehensive rehabilitation. The potential contributions to recovery that might arise from formal and/or informal patient-patient, patient-nurse, patient-therapist, and patient-TBI rehabilitation environments have not been addressed in any study to date. Particularly in units devoted to TBI, such a milieu effect should be taken into account in attempting to determine the mechanism of efficacy of the present rehabilitation efforts. This is particularly relevant to such questions as whether delivery of rehabilitation services to a similar group in a setting outside of a formal inpatient rehabilitation unit (i.e., a less expensive setting) is an equally efficacious and, therefore, acceptable alternative method of care delivery.

Future Research on Question 2

Future research into the question of intensity of inpatient rehabilitation must deal specifically with the limitations highlighted in the present body of literature. These deal specifically with the way the question has been asked and generally with the details of describing the patient population and the therapies applied.

The present unidimensional definition of intensity as hours of application appears to be neither an appropriate definition of intensity nor an adequate descriptor of the therapies. In order to examine the importance of hours of application, there must be a description of and control for the other aspects that make up each therapy. These include modalities used, therapist training, interactions between therapeutic disciplines, and so forth, as well as the milieu in which the therapies are delivered. For instance, it is questionable if it is valid to compare two separate physical therapy sessions solely in terms of time spent without addressing what is done within those sessions, who performs the therapies, which aspects of other treatment modalities (for example, cognitive therapy) might be imbedded, etc. Such confounding variables either need to be standardized (preferable) or described in a fashion amenable to subsequent statistical control.

It also is necessary to better describe the patient population being treated. It is highly unlikely that all people with TBI will receive optimal benefit from the same general therapeutic approach. It is critical that the types and magnitudes of impairments resulting from the TBI be described for the patient population, including both the severity of injury and the resultant degrees of physical and cognitive dysfunction. If adequate descriptions are provided, it will be possible to determine the interaction of the various facets of the individual treatment modalities with the types of impairment demonstrated by the people being studied. In addition, it will facilitate subsequent focused studies addressing matching treatment protocols to patient subtypes.

If treatments can be standardized and the patient population can be adequately described, it is possible that RCTs could be performed addressing hours of therapy as the independent variable and outcome as the dependent variable. With the proper standardization, the influence of general milieu also could be addressed by adding it as a second independent variable. Such investigations, if performed in fashions that are replicable and comparable between studies, should prove extremely valuable in furthering our understanding of optimizing types and intensities of treatments for people with specific, defined levels of TBI-induced impairments.

Direct Evidence

Indirect Evidence

Observational Research

Although research designs without control groups are limited, they can be a source of hypotheses which could be tested in controlled trial settings. This section highlights insights from studies with uncontrolled research designs identified in our literature search.

The other eight studies either compared clients' performance from baseline phase to treatment phase, provided the same or similar treatments to different matched groups, or combined group and individual methods of measurement. In general, results indicate that for the selected clients treated in these clinical studies, one-on-one interaction with therapists in a rehabilitation environment is likely to improve individual performance on targeted laboratory tasks. Because the studies are not comparative, the improvement observed does not contribute to the body of evidence about the intervention being provided. However, the fact that clients do in fact improve gives rise to innovations in rehabilitation technology that may be useful to people with TBI and thus warrant further evaluation.

All participants had significant decreases in EMFs during treatment. During return-to-baseline, EMFs increased for 11 of the 15 participants; five increases were statistically significant. The results of this study suggest that the use of an electronic cueing device decreases EMFs for some people with TBI. These findings also contribute to the evidence for the link represented by Arc 1 of the causal pathway. The observational design of this study weakens its value as evidence of effectiveness. However, in considering that the nature of most of the interventions reviewed here are not individually adapted and on face value do not appear to be as pragmatic as an effective reminder device, this study is useful in that it generates a hypothesis about an intervention that may have the potential to prosthetically improve memory for a person with TBI.

Conclusions for Question 3

Very few controlled studies of cognitive rehabilitation have examined health outcomes or employment. Two small randomized controlled trials (Class I) and one observational study provide evidence of the direct effect of compensatory cognitive devices (notebooks, wristwatch alarms, programmed reminder devices) on the reduction of EMFs for people with TBI. A second randomized controlled trial provides evidence that compensatory cognitive rehabilitation reduces anxiety and improves self-concept and interpersonal relationships for people with TBI.

In the absence of strong and sufficient evidence for a direct effect of cognitive interventions on health and employment, we examined a causal pathway linking cognitive rehabilitation to intermediate measures of cognition and subsequent associations between those measures and health or employment. Two small randomized controlled trials (Class I) provide limited evidence that practice and CACR improve performance on laboratory-based measures of immediate recall. However, no studies evaluated the link between cognitive tests and health outcomes, and associations between performance on cognitive tests and posttrauma employment and productivity were inconsistent.

Future Research on Question 3

Identifying and evaluating outcomes that are relevant to people with TBI and their families is the first priority of a research agenda. Among the studies we reviewed, perhaps the most pragmatic outcome measure used was that of everyday memory failures. It is possible that the absence of treatment effect in these studies could be a function of the study's lack of relevance in the lives of the people being evaluated, represented in outcome measures and interventions that have little meaning to those people.

It is also important to identify the laboratory tests that are strongest and most reliable in their ability to measure cognitive function in relevant contexts, and to standardize their use across research projects and hospital and clinical settings.

Two other questions for future research on topics not specifically addressed in this review are: (1) When is the client ready for the intervention? and (2) What are the markers of that readiness? Large, multicenter comparisons may provide initial information for a research design to investigate these questions.

In general, the studies in this review that did not produce a treatment effect compared one form of cognitive rehabilitation with another form, CACR to non-CACR practice, and were specific to unstructured rehabilitation methods. Treatment effects were not observed when one kind of remediation was compared with another when there were equal levels of stimulation for both treatment and comparison groups. What are the differential effects of general stimulation and technology? As TBI rehabilitation technology grows, costs escalate. Consequently, certain subsets of the total population of survivors--those with liberal insurance policies and/or private money--will receive the intervention. It is important for clients as well as payers to know if the new technology leads to improvement or whether the increased level of stimulation used to deliver the technology results in the improvement.

Definitions

• Job placement. This includes (a) matching job needs to client abilities and potential, (b) facilitating employer and client communications, (c) facilitating caretaker communications, (d) arranging travel arrangements or training, and (e) analyzing the job environment to detect potential problems.

• Job site training and advocacy. This emphasizes the active role of the employment specialist, job coordinator, or job coach, who is often cited as the key professional in supported employment programs (Wehman, West, Fry, et al., 1989; Ellerd and Moore, 1992). The job coach serves functions usually left to the employer in conventional vocational rehabilitation (e.g., training). The job coach also is proactive in identifying problems and designing solutions in cooperation with all the parties involved.

• Ongoing assessment. This involves continuous monitoring of key aspects of the client's work performance. There is an intense intervention by the job coach at the beginning, but this is expected to diminish, or "fade," as the client settles into a successful work adjustment (Ellerd and Moore, 1992; Wehman, Sherron, Kregel, et al., 1993). This process is well illustrated in Figure 1 of the article by Wehman, Kreutzer, West, et al., 1990.

• Job retention and follow-along. A continuing, proactive process in which the job coach tries to anticipate problems and intervene early to prevent crises from disrupting the client's adapted job placement. This assistance to the client is of indefinite duration, although it is expected to diminish over time (Wehman, Sherron, Kregel, et al., 1993).

The hallmark of supported employment methods is that they are applied on the job, in the actual work environment, to help the client succeed. Off-job training and practice to prepare the client for work may be an important prelude to supported employment in some programs, but the job coach always accompanies the client to the job site to work out on-the-spot solutions to problems as they arise and to mediate between employer and client. This problem-solving-in-situ is a defining principle of the method of supported employment (Kreutzer, Wehman, Morton, et al., 1988). Finally, these programs usually aim at competitive employment, usually defined as employment in a setting about 95 percent occupied by workers without disabilities and paying at least the official minimum wage (Wehman, Kreutzer, West, et al., 1990; Ellerd and Moore, 1992). They do not aim at placement in sheltered workshops or other settings designed primarily to accommodate the needs of disabled workers. There is a strong commitment to placing the client in the highest job position possible and to approach or exceed the preinjury level of work.

Supported employment is necessary only in cases where standard vocational rehabilitation is not sufficient to secure the desired level of employment for a survivor of TBI. In this respect, supported employment could be considered an extension of vocational rehabilitation into the actual job site as the final stage of helping a particular survivor resume a productive life. Studies of postinjury employment in which survivors are sorted by severity of injury show that not all survivors of TBI require this extra step. People suffering mild injury (GCS = 13) are usually reemployed at high rates: from about 60 to 85 percent within 1 year postinjury, and this high rate is maintained up to 15 years later (Dikman, Temkin, Machamer, et al., 1994; Schwab, Grafman, Salazar, et al., 1993; Edna and Cappelen, 1987; Fraser, Dikman, McLean, et al., 1988). In those same studies, people suffering from moderate or severe injury do not fare as well. The reemployment rates for moderate injury (GCS = 9 to 12) for the same periods are 50 to 60 percent, and for severe injury (GCS = 8), reemployment ranges from 20 to 30 percent.

The GCS alone may not always be the best predictor of employment success in multivariate analyses including other severity measures (Abrams and Toms Barker, 1991). It seems evident, however, that supported employment is most necessary for severe injury because regular vocational rehabilitation programs are insufficient. Even a variety of other interventions before job placement--such as cognitive training, with and without occupational trials, and behavior modification--show only limited success (Wehman, Kreutzer, West, et al., 1990). In addition, about one-half of survivors with moderate TBI and at least 15 to 20 percent of survivors with mild cases also might benefit from supported employment programs.

Ideally, as an extension of vocational rehabilitation, supported employment would address the problems that lead to lost jobs. Devany and colleagues at the Medical College of Virginia (Devany, Kreutzer, Halberstadt, et al., 1991) found that survivors of TBI who had trouble with reemployment suffered from four kinds of difficulties:

• Somatic problems, like debility, loss of balance, and motor deficiencies.

• Cognitive problems, like loss of memory, inability to focus attention, obsessions, and indecisiveness.

• Behavioral problems, like inertia, restlessness, depression, and impatience.

• Communication and social problems, like contentiousness and various disorders of speech and writing.

They also found that the survivors' scores on the Minnesota Multiphasic Personality Inventory (MMPI) showed peaks on scales 8 (schizophrenia), 4 (psychopathic deviate), and 2 (depression), in that order of magnitude. Valid MMPI scores might be problematic with this population, but the pattern found seems to match the common clinical impression. A configuration of 8-4-2 on the MMPI indicates a depressed person with severe interpersonal and social deficits who could easily alarm or offend others. Add this to the various motor and cognitive deficits already noted, and we have a formidable set of obstacles to placing and maintaining a person with a severe TBI in a job setting. The underlying assumption of the supported employment model is that all people referred to the program are employable under suitable conditions (Wehman, Sherron, Kregel, et al., 1993). Successful programs focus on finding or making those conditions in support of client success at work.

Of the 93 articles retrieved for review, 42 were excluded based on initial exclusion criteria, reducing the total number of articles to 51. Two investigators read all articles retrieved through the database search, as well as five additional articles acquired from reference lists and recommendations from peers, for a total of 56 articles.

Direct Evidence

There is no direct evidence from randomized trials about the efficacy of supported employment.

Indirect Evidence

No Class I or IIa studies of supported employment were found in the literature. In one prospective, controlled, observational study, Haffey and Abrams (1991) measured job placement and retention rates of 130 participants in a program of supported employment, the "Work Reentry Program" or WRP. These results were compared with those of 35 clients in a day-treatment program and 76 individuals who had received no postacute rehabilitation (the "comparison group"). Participants in the WRP program were recontacted every 6 months for up to 3 years. Other subjects were followed for varying amounts of time over 3 years, depending on when they entered the study. A total of 87 (67 percent) of the 130 participants entering the program were placed in employment. Followup for the 87 placements was as follows:

• 1 to 6 months of followup: 18 participants.

• 7 to 12 months of followup: 23 participants.

• 13 to 18 months of followup: 17 participants.

• 19 to 24 months of followup: 15 participants.

• > 24 months of followup: 14 participants.

The second series has been reported in a number of publications (Wehman, West, Fry, et al., 1989; Wehman, Kreutzer, West, et al., 1989; Wehman, Kreutzer, West, et al., 1990; Wehman, Sherron, Kregel, et al., 1993). These studies evaluated the outcomes of supported employment in a prospective registry study. In the first article cited, the sample included five survivors followed for 75 weeks (1.4 years); by the last article in the series the sample had increased to 115 consecutive referrals followed for up to 60 months (5 years). These individuals passed through two consecutive phases of vocational rehabilitation: first, the standard postrehabilitation services, then a supported employment program.

For convenience in the remainder of this report, we will refer to the first study as Haffey and Abrams and to the second series of studies, taken as a group, as the Virginia series, after the home of the researchers in the Medical College of Virginia.

Posttrauma vocational success in the Virginia series was compared with the rates of preinjury employment success of each client, who served as his or her own control in the study. Preinjury employment is thus taken as a baseline control for results in the two subsequent phases of intervention--the last of which was supported employment--as each client passed through the following history: Preinjury employment (baseline) => posttrauma employment (1st phase intervention) => supported employment (2nd phase intervention).

Measures of employment success in the Virginia series were (1) number of jobs held per client, (2) mean hourly wage, (3) mean monthly wage, (4) mean annual wage, (5) monthly employment ratio (MER). The last is an index of vocational success developed by the Virginia group. It is the ratio (with specific definitions of the two variables): number of months client employed/number of months client could have been employed (Wehman, Sherron, Kregel, et al., 1993).

Results were measured over 5 years of operation with measures of outcome taken weekly (Wehman, Kreutzer, West, et al., 1989). During that time, 80 of the 115 entering clients were placed in jobs, but it is not clear how many of the 115 were followed for all 5 years. In the whole series of studies, we have reports on 5 clients in 1989 (Wehman, West, Fry, et al., 1989) and 20 clients later in the same year (Wehman, Kreutzer, West, et al., 1989). In 1990, there is a report of 53 clients (Wehman, Kreutzer, West, et al., 1990) and in 1993 the total is 115 (Wehman, Sherron, Kregel, et al., 1993). From this pattern in the reports, we may infer that about five clients were followed for a full 5 years, 15 clients for between 4 and 5 years, 33 clients for at least 3 years, and 62 for less than 3 years.

Outcomes

Table 7. Postinjury employment outcomes of TBI clients (more...)

Table 7. Postinjury employment outcomes of TBI clients in a supported employment program

	Preinjury	No SE1	SE
Employment outcome	(n = 62)	(n = 37)	(n = 80)
Mean number of jobs/client	2.04	1.24	1.49
Mean hourly wage earned	$4.19	$1.55	$4.90
Mean monthly wage earned	$508	$107	$658
Mean annual wage earned	$6,101	$1,290	$7,899
Monthly employment ratio	0.40	0.13	0.67

1

SE = supported employment.

Source: Adapted from table 3 , Wehman, Sherron, Kregel, et al., 1993.

Outcomes are summarized in the evidence tables. In the Haffey and Abrams study, 68 percent of the WRP clients secured competitive employment, and only 18 percent were considered chronically unemployed. Only 39 percent of the day-treatment group and 34 percent of the comparison group reported any employment after discharge. At the last followup period reported, 71 percent of the WRP clients placed were still working, but no retention rates for the day-treatment and comparison groups were reported. See Table 7 for a summary of the results from the Virginia studies (Wehman, Sherron, Kregel, et al., 1993).

Conclusions for Question 4

There is Class IIb evidence that supported employment can improve the vocational outcomes of TBI survivors. Almost all information about supported employment comes from two bodies of work, each of which use different experimental designs and different models of supported employment. The findings have not been replicated in other settings or by other centers, so the generalizability of these programs remains untested.

In the Virginia studies, the clients all had severe cases of TBI as rated by the GCS. In the Haffey and Abrams experiment, no GCS scores are given, but the data provided on severity of injury show median length of coma in the three groups ranging from 6 to 7 days, with the median value for the entire sample of 199 cases at 7 days and the overall range from 0 to > 30 days. In the 80 job-placed survivors of the Virginia series (Wehman, Sherron, Kregel, et al., 1993), the average length of coma was 48 days, and the range was from 0 to 182 days. Clearly, the Haffey and Abrams sample contained many people with moderate or even mild injuries, while the Virginia sample consisted entirely of people with severe injuries. We have already noted, in the Introduction to this report, that severity of injury has an important effect on vocational success.

The problems with the Virginia series are of another sort. They arise from the inherent limitations of the design itself, since case-control studies without separate control groups and unbiased allocation of participants are unable to untangle confounded variables. Repeated measures on a single group are bound to be confounded with variables for which there are no controls. An observation made by Wehman, Sherron, Kregel, et al. (1993) will illustrate the problem. They note that during the economic recession of 1990 to 1992--the worst in the United States since the 1970s--nearly 20 percent of their program participants lost their jobs due to layoffs. The design of the Virginia studies compares baseline levels of employment preinjury with subsequent performance under two levels of vocational rehabilitation, including supported employment as the final stage.

In the Virginia sample, the average age at injury was 24.8 years, and the average age at referral to the program was 30.9 years, making the average interval from injury to entry in the program 6.1 years. The average time to job placement after program entry is about 1 year more, and the subsequent followup in the series of studies under review ranges up to 5 years, with a substantial proportion of the clients at least 3 years into followup. Simple arithmetic discloses that the average time from preinjury employment to postinjury followup is on the order of 10 to 12 years, and for about half the clients the interval will be even longer. This is the time elapsed between baseline measures of preinjury vocational success and postinjury outcome measures under supported employment. It is a significant possibility that economic changes over a 10- to 12-year period (or more, for half of the sample) would have significant effects on employment. Those economic effects will be confounded with the effects of supported employment programs running at the same time, and there is no way to separate the two kinds of effects unless a control group of clients, without supported employment, is measured over the same interval. Likely, there are many other confounded variables at play in the same way, including unknown ones.

In spite of the problems mentioned, it remains true that all the programs of supported employment reviewed showed better rates of vocational success than the baseline expectations of survivors of TBI who received only standard postacute rehabilitation or even with special kinds of preemployment vocational counseling and training (see "Problems Addressed" section in the Introduction to this report). The success documented by the Virginia series with survivors with severe injuries is especially convincing in this respect. Supported employment appears to be a promising way to increase the vocational success of survivors of TBI, but the present literature does not give definitive proof of its effectiveness and does not provide enough clarity on why it works or guidance to the best applications of the method.

Future Research on Question 4

Definitions

Case management has emerged as a possible solution because it systematically monitors client needs over time and facilitates access to services in various institutions and programs across communities. Case managers usually serve people with long-term or chronic conditions because they have complex needs and find it difficult to navigate the health and/or social care systems.

According to the Commission for Case Manager Certification (1996), case management is: A means for achieving client wellness and autonomy through advocacy, communication, education, identification of service resources and service facilitation while ensuring that available resources are being used in a timely and cost-effective manner in order to obtain optimum value for both the client and the reimbursement source (p. 2).

The role typically includes admission or intake assessment, care-plan development, service referral, coordination of service details, and collaboration with care providers, informal caregivers, and the client (Goering, Farkas, Lancee, et al., 1988; Goodwin, 1994) and may also include authorization of service payments (Ashley, Krych, Persel, et al., 1994; Evans and Watke, 1995). The domain is to determine service needs and to access service elements with a sequence and timing that will result in desired outcomes for the client and family as well as desired outcomes such as cost control for the service organization.

Case Management Characteristics and Desired Outcomes

One characteristic of case management is the adopted mission of the employing organization. Since case managers are found in hospitals, rehabilitation programs, health departments, aging services departments, mental health services, insurance companies, and managed care organizations (Gerber, 1994), the focus can vary from acute-care disposition planning to long-term patient advocacy to service cost control. As the orientation and purpose of case management programs vary, outcomes may reflect the differences. In order for case management interventions to be compared and tested for effectiveness, it is important to define the specific purposes and aspects of case management that are provided.

Case managers also focus on helping clients move across institutional or organizational systems and across provider disciplines. Managing these boundary issues calls for a collaborative approach around a common focus--the client and family. Understanding case management role specifications and the extent of boundary work is also critical for comparing programs and interpreting research that tests case management effects.

Within this context of TBI incidence and long-term effects, problems experienced by clients and their families, and the definition and role of case management, our study was conducted to identify evidence of case management effectiveness. The purpose was to review the literature for controlled clinical studies of the influence of care coordination on targeted outcomes among TBI rehabilitation populations of clients and their families.

Of the 69 articles retrieved for review, 27 were excluded based on the initial exclusion criteria, reducing the total number of articles reviewed to 42. Two investigators read all retrieved articles from the database search, as well as relevant articles found on reference lists of the retrieved articles and those obtained from colleagues, for a total of 73 articles. The only criterion for study selection in this phase was that case management was an independent variable. By mutual agreement three studies were critically analyzed and entered into Tables 1 and 2 to report evidence of case management effectiveness in TBI rehabilitation.

Results

Does the provision of long-term care coordination enhance the general functional status of people with TBI? The search strategies yielded three controlled studies of case management effectiveness in TBI rehabilitation. Two studies compared case management with non-case management, and one study compared two types of case management. Two studies were completed trials (Ashley, Krych, Persel, et al., 1994; Greenwood and Brooks, 1994), and one article (Malec, Buffington, Moessner, et al., 1995) presented preliminary results after 1 year of data collection.

Each selected study focused on a different subpopulation. In two studies, the subjects were homogeneous for level of disability: either moderate disability (mean Disability Rating Scale [DRS] scores of 4.95 and 5.17) (Ashley, Krych, Persel, et al., 1994); or severe disability (mean DRS scores of 16.2 and 18.3, and mean Glasgow Coma Scale [GCS] scores of 6.6 and 5.5) (Greenwood and Brooks, 1994). In the third study, the sample at 1 year consisted of clients with mild injuries (79 percent), as rated with the GCS and moderate or severe injuries (21 percent) Malec, Buffington, Moessner, et al., 1995). Comparison group differences made it necessary to control for aspects that may have affected the outcomes, but no controls were mentioned in the preliminary report by Malec, Buffington, Moessner, et al., 1995.

The studies also tested different models of case management intervention. Ashley, Krych, Persel, et al. (1994) evaluated two insurance-coverage models in which the key aspects were the authority to approve disability payment and rehabilitation service claims, although this was not defined, and differences between the two groups for this characteristic were not reported. Also, the report did not include any other behavioral or role descriptors to compare and contrast the two intervention models. In fact, although a key independent variable was same versus different case managers, it is not clear from the description whether all subjects in one group had the same case manager or whether each subject in the group had one case manager for the entire post-TBI period. Greenwood and Brooks (1994) tested a medical model of case management, defined as clinical needs assessment during acute hospital care, formulation of a proactive rehabilitation plan, and facilitation of rehabilitation cooperation and involvement among patients, family, and professionals.

Malec, Buffington, Moessner, et al. (1995) evaluated a medical-plus-vocational model of case management. They defined it as assessment and rehabilitation planning during acute hospital care for the provision of medical outpatient rehabilitation services and for vocational counseling and planning related to employment services available in the community. Although there were presumably common role behaviors in these two models, there were not enough details offered in the Greenwood and Brooks (1994) report to determine whether the case manager referrals had led to subsequent care coordination by vocational counselors and others. If so, the Greenwood model would have been similar to the Malec model. Only one study identified the discipline or training that the case managers had received (Malec, Buffington, Moessner, et al., 1995). Also, the intervention periods varied by study and by client need, which no doubt influenced the results.

In addition, other design aspects differed among the studies. The data collection points ranged from 1 month to 24 months, with only two studies measuring outcomes at 12 months. In two projects, the research spanned 2 years, but subjects were followed for less than 2 years if they had not entered the study at the beginning. Also, due to the team-oriented nature of case management and the close institutional quarters of the subjects, blind assessments of the subjects were not possible. Therefore, care delivered by the case managers and other team members could have differed among groups and influenced the outcomes. Additionally, there was almost no information about possible cointerventions--such as other service providers--who may have offered care coordination and continuity, and there was very limited information about the other types of rehabilitation services that may have influenced client outcomes.

There are very few studies of the effectiveness of case management. The results of these studies are mixed (Evidence Table for case management, 2). There is evidence from Class III studies that case management improved vocational status. This was associated with the single case manager and insurance approach (Ashley, Krych, Persel, et al., 1994), as well as with the combined nurse and vocational case manager model (Malec, Buffington, Moessner, et al., 1995).

There were conflicting results about the effects of case management on disability or functional status, living status, family impact, and other aspects, and some findings were mentioned in only one study. The clinical trial resulted in no functional status changes among case managed subjects, despite an extended period of rehabilitation (Greenwood and Brooks, 1994). However, when two forms of case management were compared, both the single and multiple case manager/insurance approaches showed significant functional improvements (Ashley, Krych, Persel, et al., 1994).

Findings also conflicted on the effect of case management on subjects' living arrangements. Greater independence was demonstrated with the single case manager and insurance approach (Ashley, Krych, Persel, et al., 1993), while greater dependence was found with the general case manager model (Greenwood and Brooks, 1994). In the only study that measured the effect of case management on families, the result was that families sought more medical care, and they changed their amount of leisure time (although the direction was not identified) (Greenwood and Brooks, 1994). A modest majority of respondents in the Malec, Buffington, Moessner, et al. (1995) study found the case manager helpful, but the report did not mention whether this rating referred to the nurse case manager and/or the vocational case manager. Single-study findings included lower rehabilitation costs and higher disability payments for the single case manager model (Ashley, Krych, Persel, et al., 1993) and identification of unmet case management needs among adolescents, seniors, and alcoholic clients (Malec, Buffington, Moessner, et al., 1995).

Conclusions for Question 5

From our review we conclude that there is no clear evidence that case management is effective with survivors of TBI and their families, but neither is there clear evidence that it is ineffective. Further research is warranted to resolve this question. It is not possible to directly compare the three studies reviewed because there were almost no similarities in design, sampling, or outcome measures that would provide a basis for comparison. Although all 312 subjects had been diagnosed with brain injury and had evidence of impairment, the samples represent different subpopulations based on injury severity level: moderate, severe, and mixed. For the latter sample, results were not reported by level of injury. Similarly, although there was a controlled intervention of case management provided in each study, there were key differences in the definitions and case management model characteristics. In addition, there were few, if any, specifications about the case managers' training, discipline, experience, and roles. Only one report (Greenwood and Brooks, 1994) mentioned the number of case managers who had provided the intervention (three), and it also was the only report that mentioned the number of clients that were managed by each case manager at one time (20). In no case was there any evidence of reliability or validity testing of the case management approach.

In addition, there are other weaknesses that contribute to the inability to draw conclusions from this small group of studies. One potential source of bias is the lack of control for cointerventions that may have provided service referrals, care continuity, and client and/or family support that simulated case management. This might have occurred, for example, when a study case manager referred the client to another program or service, and it also may have occurred within the family support system. Without controlling for such an effect, it is not possible to attribute any results to formal case management. Another problem is that the studies each provided case management for different amounts of time and at different stages of recovery. Moreover, they utilized different periods of time to measure the outcomes, and the measures did not continue longitudinally for all subjects. This had the statistical effect of reducing the number of subjects who were likely to benefit from the intervention. That is, even if the intervention did have a positive effect, the difference may not have been apparent. Also, because of the team-oriented nature of case management coordination, none of the researchers were able to arrange blind assessments of the subjects. For this reason, it is not possible to know whether there are provider biases associated with care provided for particular subjects or subject groups.

Finally, nothing is known about the quality of the rehabilitation programs associated with the case management models demonstrated in the reviewed studies. Greenwood and Brooks (1994) point out that since the experimental subjects did not progress despite greater rehabilitation service contact time, the cause may have been that the case manager did not have the authority to improve the quality of rehabilitation. Since client and family outcomes may be related only to rehabilitation program benefit, it would be useful to know how to control for rehabilitation program quality to identify confounding factors. Another consideration for possible effect on the targeted outcomes is the ability to access the rehabilitation programs. Since rehabilitation access depends on program availability in the community, economic feasibility for the patient, and the knowledge of others--such as family physicians and emergency care teams--it would be useful to have measures of those environmental conditions as additional outcome analysis controls.

Despite these methodological weaknesses and the incompatible findings, however, there are some observations that can be made from the collective findings of these three studies. First, two of the three studies found significant improvements associated with case management in at least one type of functional outcome (Ashley, Krych, Persel, et al., 1994; Malec, Buffington, Moessner, et al., 1995). This suggests that perhaps the model of case management that was employed in the Greenwood and Brooks (1995) study was simply the wrong model. Second, in the Greenwood and Brooks (1995) study, the dropout rate among subjects without a case manager was higher, which suggests that subjects may have found the service useful in a subjective way. These glimmers of evidence from three controlled studies provide substantive implications for continued research that can improve upon the methods described above.

Future Research on Question 5

Research studies in the future need to test for possible effects of case management that have not yet been identified. We believe it is important to conduct clinical trials that specify and test the extent of contact with the client and family, role training and competence, service-approval authority, screening/rescreening frequency, and influence within the rehabilitation community network. Reliability and validity testing also are recommended for measuring case management. In addition, controls should be in place for isolating possible cointerventions that simulate care coordination. The control variables should include postinjury rehabilitation elements such as settings, types of therapies, amount of contact times, goal achievement records, and other aspects that may directly affect client outcomes.

We suggest that there be improved outcome measures used in case management clinical trial studies for TBI subjects. In addition to outcomes of changed client functionality, there should be outcomes of changed family functionality. Since much of case management communication is directed toward helping family members learn what to expect and where to obtain services, relevant outcomes would include family use of community and rehabilitation services and indicators of family assertiveness regarding care expectations. While case management may only indirectly affect a client's functional outcomes such as level of disability, vocational status, and living status, it is possible that case management can directly affect family knowledge of TBI rehabilitation needs and services, level of psychosocial anxiety, and family competency in coping with TBI.

We also recommend separate measures and analyses for subjects with mild, moderate, and severe disability. Greenwood and Brooks (1994) interpreted their findings that more case-managed-group relatives reported a major TBI effect on the family and had more use of prescribed drugs and medical services by attributing the differences to a more severely ill sample in the case-managed group. However, this could not be verified because they had not controlled for severity of illness. Third, if family members were measured at pre- and postintervention points, the case management intervention effects should become more apparent. Finally, for purposes of study comparability, outcomes could be measured at 12-month postinjury intervals.

Question 1: Should interdisciplinary rehabilitation begin during the acute hospitalization for traumatic brain injury?

One small, retrospective, observational study from a single rehabilitation facility supports an association between the acute institution of formalized, multidisciplinary, physiatrist-driven TBI rehabilitation and decreased LOS (acute hospital and acute rehabilitation) and some measures of short-term physiologic (non-cognitive) patient outcome. The level of evidence is Class III. This study concerned patients with severe brain injury (GCS 3-8). There is no evidence from comparative studies for or against early rehabilitation in patients with mild and moderate injury.

Deriving clinical implications from the single Class III study that directly addresses this question must be done with trepidation. It is generally felt that the application of modalities such as physical therapy as early as possible following TBI is beneficial. In addition, the transition from acute stay at the trauma hospital to a rehabilitation facility for severe TBI patients is almost always driven by issues that are peripheral to the proper timing of rehabilitation efforts (e.g., systemic complications, bed availability, etc.). Since the one study did suggest that the institution of formalized, multidisciplinary, physiatrist-driven TBI rehabilitation efforts early in the posttraumatic period was favorably associated with short-term outcome and logistics, it would seem reasonable, based on the present body of literature, to include a physiatrist in the acute care team in as expedient a fashion as possible.

Question 2: Does the intensity of inpatient interdisciplinary rehabilitation affect long-term outcomes?

When measured as the hours of application of individual or group therapies, there is no indication that the intensity of acute-inpatient TBI rehabilitation is related to outcome. Because of methodological weaknesses, however, previous studies are likely to have missed a significant relationship if one exists (a Type II error). These studies contained insufficient information about severity of injury and baseline function to ensure the comparability of the compared groups. These studies also did not consider the quality of individual treatments, their lack of autonomy in the cognitive realm, and the delivery milieu. One or more of these factors might affect the outcome of care more than the time spent in each modality. Therefore, future research into efficacy of acute inpatient TBI rehabilitation must more adequately measure such factors and include them in their predictive models. Future studies also must employ a wider spectrum of outcome measures including measurement of outcomes for a longer period after discharge. Such an analysis would be an ideal application of a universal uniform data set.

With regard to the clinical aspect, the evidence does not support equating different systems of TBI rehabilitation delivery based on equivalent times of patient exposure to various therapeutic modalities. For example, this analysis would not support the assumption that patient benefit would be equal if an equal time spectrum of rehabilitation therapies were delivered at a rehabilitation center as compared with a skilled nursing facility. More detailed analysis of factors involved in predicting response to rehabilitation modalities must be considered in approaching such questions.

Additionally, mandating a minimum number of hours of applied therapy for all TBI patients is not supported by the present state of scientific knowledge. The issues of how much intervention optimizes recovery in a given type of patient remains inadequately studied. It is certainly reasonable to avoid situations in which patients do not receive potentially beneficial treatment. Based on the above studies, however, defining a minimum rehabilitation program in terms of time of applied therapy is not likely to optimize either therapist time or patient recovery. It is probable that a specific basic program will have to be related to individual patient groups. Developing such algorithms requires future research.

Many people who suffer TBI do not enter acute inpatient rehabilitation. Only one study of the effectiveness of inpatient rehabilitation included a comparison group of patients who did not undergo inpatient rehabilitation. Future studies should compare acute, inpatient rehabilitation with commonly used alternatives to inpatient rehabilitation, such as care in a well-staffed, skilled nursing facility or in less intense variations of acute rehabilitation. Very little is known about the outcomes of TBI in these settings.

Question 3: Does the application of compensatory cognitive rehabilitation enhance outcomes for people who sustain TBI?

One small randomized controlled trial (Class I) and one observational study (Class III) provide evidence of the direct effects of compensatory cognitive devices (notebooks, wristwatch alarms, programmed reminder devices) on the reduction of everyday memory failures for people with TBI. A second randomized controlled trial provides evidence that compensatory cognitive rehabilitation reduces anxiety and improves self-concept and interpersonal relationships for people with TBI. The level of evidence is Class II[a].

Two small randomized controlled trials (Class I) provide limited evidence that practice and computer-aided cognitive rehabilitation improve performance on laboratory-based measures of immediate recall. No studies evaluated the link between such cognitive tests and health outcomes, and the associations between performance on cognitive tests and employment in the literature were inconsistent.

Current practice in cognitive rehabilitation lacks a firm basis in experimental clinical studies. It is unlikely that the studies we reviewed, designed to address effectiveness, accurately describe the totality of techniques, stimulation, and human effort and ingenuity that constitute cognitive rehabilitation programs, particularly if the programs are multi- or transdisciplinary. Therapists observe that their patients improve; what is causing the improvements is not understood. In making decisions about the course of treatment, clinicians are compelled to follow their experiences and observations until strong research designs provide evidence from which guidelines and standards can be derived.

Question 4: Does the application of supported employment enhance outcomes for people with TBI?

There is some Class II evidence that supported employment can improve the vocational outcomes of survivors of TBI. Most of the evidence on the effects of supported employment comes from two programs of research, each of which used different experimental designs and different models of supported employment. Both designs used prospective data collection, but one compared the treatment group with an independent control, while the other was a case control study comparing preinjury employment with postinjury employment without and then with supported employment. The findings have not been replicated at other centers, so the results cannot be generalized to the general population of survivors of TBI. Most studies of supported employment in TBI research are of the individual placement model, but some evidence also supports the use of the apprenticeship model.

The evidence for improvement of vocational outcomes with supported employment is sufficient to warrant its use in practice while further research continues. However, much remains unknown about the amount of improvement that is actually gained by these programs and which components of the programs contribute most to the improved outcomes. It also may be important to explore other models of supported employment, like the apprenticeship model or some variations of the work enclave model.

Question 5: Does the provision of long-term care coordination enhance the general functional status of people with TBI?

Very few studies of the effectiveness of case management have been done, and results have been mixed. The clearest demonstration of improvement due to case management is in vocational status, where at least two studies, using different models of case management, showed similar improvements. One of these two programs showed superior results when a single case manager administered all the insurance benefits of each patient; the other showed results in the same direction using a combination of nurse and vocational case manager to select and time the interventions. There were conflicting results on other effects of case management, including disability or functional status, living status, and effects on the family, and some outcomes were mentioned in only one study. The clinical trial, using separate hospital systems randomly assigned to a case management condition, showed that there were no functional status changes among case management participants, despite an extended period of rehabilitation and followup. But, when two forms of case management were compared, both the single and multiple case manager/insurance models showed significant functional improvements.

Although the present evidence is mixed, it seems warranted to continue the use of several case management models to select and time interventions in cases of TBI, and it also may be of benefit to survivors to have the advocacy by the case manager in finding and obtaining treatments. There is a certain face validity to the basic idea of case management, which is simply a matter of careful planning of the choice, sequence, and timing of interventions, and some variation of it is really a standard component of most clinical practice. Also, there probably is some value to the person with TBI of an advocate able to obtain benefits that otherwise would be missed by an unaided survivor. The extent of the benefit of case management, however, remains undemonstrated, and more studies using control groups would be very beneficial in clarifying the actual improvement in outcomes due to case management. It also is unclear whether some models of case management are better than others and for what kinds of clients they might be best suited. These questions contribute to the agenda for future research.

Due to the methods through which the above five topics have been approached in the literature and the relative absence of powerful studies in these areas, the conclusions reached by this evidence-based approach and the clinical implications drawn therefrom are extremely limited. As a direct result, the utility of this document in driving profound alterations in TBI rehabilitation based on the scientific literature is very restricted. Because this report is the product of an exhaustive review of the literature in these five areas, however, we are in an ideal position to be able to summarize the shortcomings of the studies in these fields and to make generalizable recommendations regarding how future efforts could be improved. Since the five topics addressed in this work run the temporal gamut from acute care through long-term survival, this document also serves as an ideal conduit for suggesting the means for optimizing continuity and consistency of research efforts across the spectrum of recovery from TBI. Because the ability to suggest improvements in research efforts in a knowledgeable fashion is probably the most valuable result of this work, special attention was directed to this area. For further information, readers are directed to the analyses of research shortcomings and sets of recommendations presented in the Aspen Consensus Conference proceedings (Chesnut, Alexander, Antoinette, et al., forthcoming).