Effectiveness of care models for chronic disease management: A scoping review of systematic reviews.

OBJECTIVE: To conduct a scoping review of models of care for chronic disease management to identify potentially effective components for management of chronic traumatic brain injury (TBI). METHODS: Information sources: Systematic searches of three databases (Ovid MEDLINE, Embase, and Cochrane Database of Systematic Reviews) from January 2010 to May 2021. ELIGIBILITY CRITERIA: Systematic reviews and meta-analyses reporting on the effectiveness of the Chronic Care Model (CCM), collaborative/integrated care, and other chronic disease management models. DATA: Target diseases, model components used (n = 11), and six outcomes (disease-specific, generic health-related quality of life and functioning, adherence, health knowledge, patient satisfaction, and cost/health care use). SYNTHESIS: Narrative synthesis, including proportion of reviews documenting outcome benefits. RESULTS: More than half (55%) of the 186 eligible reviews focused on collaborative/integrated care models, with 25% focusing on CCM and 20% focusing on other chronic disease management models. The most common health conditions were diabetes (n = 22), depression (n = 16), heart disease (n = 12), aging (n = 11), and kidney disease (n = 8). Other single medical conditions were the focus of 22 reviews, multiple medical conditions of 59 reviews, and other or mixed mental health/behavioral conditions of 20 reviews. Some type of quality rating for individual studies was conducted in 126 (68%) of the reviews. Of reviews that assessed particular outcomes, 80% reported disease-specific benefits, and 57% to 72% reported benefits for the other five types of outcomes. Outcomes did not differ by the model category, number or type of components, or target disease. CONCLUSIONS: Although there is a paucity of evidence for TBI per se, care model components proven effective for other chronic diseases may be adaptable for chronic TBI care.

Investigating whole-brain metabolite abnormalities in the chronic stages of moderate or severe traumatic brain injury.

BACKGROUND: Evidence suggests that neurometabolic abnormalities can persist after traumatic brain injury (TBI) and drive clinical symptoms such as fatigue and cognitive disruption. Magnetic resonance spectroscopy has been used to investigate metabolite abnormalities following TBI, but few studies have obtained data beyond the subacute stage or over large brain regions. OBJECTIVE: To measure whole-brain metabolites in chronic stages of TBI. DESIGN: Observational study. SETTING: University. PARTICIPANTS: Eleven men with a moderate or severe TBI more than 12 months prior and 10 age-matched healthy controls completed whole-brain spectroscopic imaging. MAIN MEASURES: Ratios of N-acetylaspartate (NAA), choline (CHO), and myo-inositol (MI) to creatine (CR) were measured in whole-brain gray and white matter as well as 64 brain regions of interest. Arterial spin labeling (ASL) data were also collected to investigate whether metabolite abnormalities were accompanied by differences in cerebral perfusion. RESULTS: There were no differences in metabolite ratios within whole-brain gray and white matter regions of interest (ROIs). Linear regression showed lower NAA/CR in the white matter of the left occipital lobe but higher NAA/CR in the gray matter of the left parietal lobe. Metabolite abnormalities were observed in several brain regions in the TBI group including the corpus callosum, putamen, and posterior cingulate. However, none of the findings survived correction for multiple comparison. There were no differences in cerebral blood flow between patients and controls. CONCLUSION: Higher MI/CR may indicate ongoing gliosis, and it has been suggested that low CHO/CR at chronic time points may indicate cell death or lack of healthy turnover and repair. However, with the small sample size of this study, we caution against the over interpretation of our results. None of the findings within ROIs survived correction for multiple comparison. Thus, they may be considered possible avenues for future research in this area.

Phase IIB Randomized Trial on the Use of 4-Aminopyridine in Guillain-Barré Syndrome.

OBJECTIVE: To determine the safety and efficacy of orally delivered 4-aminopyridine (4-AP) in persons with Guillain-Barré Syndrome (GBS) >6 months from initial diagnosis. DESIGN: A randomized, double-blind, placebo-controlled, crossover study. SETTING: Tertiary care clinical outpatient program. PARTICIPANTS: Nineteen participants enrolled (14 male, 5 female; N=19), neurologic impairment secondary to GBS and functional loss on the FIM motor score (stable for ≥12mo) and >3.0 but <5.0 on the American Spinal Injury motor scale. Twelve participants (mean age, 59y; range, 23-77y) completed the study. INTERVENTIONS: A 4-AP dose-escalation study with 8 weeks in each period with a 3-week washout period, followed by 3 months open-label follow-up. MAIN OUTCOME MEASURES: FIM motor score was the primary outcome measure; also evaluated were the American Spinal Injury motor strength score (all limbs), handheld dynamometer, 6-minute walk test, Medical Outcomes Study 12-Item Short Form, Center for Epidemiological Studies Depression scale, Positive and Negative Affect Schedule, pain, GBS disability scale, Jepsen-Taylor Hand Function Test, Minnesota Manual Dexterity Test and Minnesota Rate of Manipulation Test, Get Up and Go Test, McGill Pain Inventory, Craig Handicap Assessment and Reporting Technique, and participant self-evaluation. RESULTS: Seven participants discontinued the study prematurely: 3 because of adverse events, 3 because of travel difficulties or relocation, and 1 because of pretreatment laboratory abnormalities. After removing 3 participants with maximum FIM scores, 4-AP arm trended superior to placebo (P=.065). Patients subjectively could always tell when they were on the active agent usually by tingling sensations or a sense of wellness. No statistically significant differences were found for other outcome measures although there were strong trends. CONCLUSIONS: This study demonstrates the safety of 4-AP in the patient population with GBS as the predominate goal of the study. A trend toward improved function after treatment was noted with most patients electing to stay on the medication after the trial.

Factors Increasing Risk of Suicide after Traumatic Brain Injury: A State-of-the-Science Review of Military and Civilian Studies.

Primary Objective: Survey TBI literature to identify evidence of risk for post-injury suicide.Literature Selection: Search terms ((traumatic brain injury OR TBI) AND (suicidality OR suicidal behaviour OR suicidal ideation)) entered in PubMed, OVID Medline, PsychInfo, and Web of Science for papers published in print 01/01/1997 to 06/30/2019.Analysis of Literature: Authors screened abstracts, excluding duplicates and articles not meeting inclusion/exclusion criteria. Full papers were reviewed to make final exclusions. Data were extracted from 40 papers included co- and premorbid disorders, demographics, injury-related and psychological factors.Results: Persons with TBI have a higher risk for suicide than the general population. Reviewed articles reported comorbid depression and/or PTSD as risk factors for post-TBI suicide. Co- or premorbid substance misuse, sex, and sleep disturbance moderate risk. Quality of the literature was limited by sample size, the predominance of male participants, and inconsistency in reporting of findings.Conclusions: Comorbid depression and PTSD are significant post-TBI risk factors for suicide. Several variables combine to moderate or mediate TBI's connection with suicide. Civilian and military clinician cross-talk and consistent reporting of results from reproducible studies of post-TBI suicide risk factors could improve prevention and treatment efforts in veterans and civilians.

Effects of Statin Treatment on Outcomes after Traumatic Brain Injury.

Neuroprotective treatments that have shown promise in reducing secondary injury and improving recovery in animal models of traumatic brain injury (TBI) have not been found effective to date in humans. One reason may be the delay after injury in initiating treatment. Statin medications are among the promising neuroprotective agents in animal models, and their presence in the bloodstream of many individuals at the time of injury might optimize their clinical impact. This observational study conducted by a subset of centers participating in the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR)-funded TBI Model System program sought to examine the effects of taking statin medication at the time injury on functional outcomes. Participants >50 years of age were prospectively enrolled during patient rehabilitation. Demographic data, cardiovascular history, and brain injury history were obtained through chart abstraction and interview. Prescription medication use in the year prior to enrollment was determined from a national pharmacy search service. Propensity scoring was used to create 49 pairs of participants who were well matched on demographic and clinical attributes but discordant for statin use. The treated and untreated participants did not differ on initial Glasgow Coma Score, time until commands were followed, duration of post-traumatic amnesia, or Functional Independence Measure (FIM) scores at rehabilitation admission, discharge, or 1 year post-injury, or on acute or rehabilitation hospital lengths of stay. Evidence of greater and lesser statin compliance was not associated with outcome. This study did not provide support for a clinically important benefit of statin use at the time of moderate to severe TBI.

The effect of donepezil on the cognitive ability early in the course of recovery from traumatic brain injury.

OBJECTIVE: To investigate the effect of donepezil on cognitive ability in patients who have sustained a traumatic brain injury (TBI). We hypothesized that donepezil, an acetylcholinesterase inhibitor, would enhance cognitive recovery beyond that of usual care in an acute rehabilitation facility. METHODS: This retrospective, longitudinal analysis included 55 patients who were non-randomly prescribed donepezil during acute care and compared them to 74 patients who received usual rehabilitation treatment. All 129 patients completed neuropsychological assessment at two time points. Donepezil was increased from 5 to 10 mg 7-10 days after initiation and maintained until follow-up cognitive assessment. MAIN OUTCOMES: Primary cognitive abilities of interest included processing speed, attention and memory. Cognitive and functional abilities were assessed by a standard neuropsychological battery for TBI. RESULTS: Propensity scores were used to adjust for differences between groups. Mixed effect model analysis showed no significant differences between treatment and control groups on all neuropsychological subtests over time. CONCLUSIONS: Acute administration of donepezil did not significantly improve measures of cognitive or functional ability beyond that of treatment as usual in patients with moderate-to-severe TBI.

Do rehospitalization rates differ among injury severity levels in the NIDRR Traumatic Brain Injury Model Systems program?

OBJECTIVE: To compare the rate and nature of rehospitalization in a cohort of patients enrolled in the National Institute on Disability and Rehabilitation Research Traumatic Brain Injury Model Systems (TBIMS) who have disorders of consciousness (DOC) at the time of rehabilitation admission with those in persons with moderate or severe traumatic brain injury (TBI) but without DOC at rehabilitation admission. DESIGN: Prospective observational study. SETTING: Inpatient rehabilitation within TBIMS with annual follow-up. PARTICIPANTS: Of 9028 persons enrolled from 1988 to 2009 (N=9028), 366 from 20 centers met criteria for DOC at rehabilitation admission and follow-up data, and another 5132 individuals met criteria for moderate (n=769) or severe TBI (n=4363). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Participants and/or their family members completed follow-up data collection including questions about frequency and nature of rehospitalizations at 1 year postinjury. For the subset of participants with DOC, additional follow-up was conducted at 2 and 5 years postinjury. RESULTS: The DOC group demonstrated an overall 2-fold increase in rehospitalization in the first year postinjury relative to those with moderate or severe TBI without DOC. Persons with DOC at rehabilitation admission have a higher rate of rehospitalization across several categories than persons with moderate or severe TBI. CONCLUSIONS: Although the specific details of rehospitalization are unknown, greater injury severity resulting in DOC status on rehabilitation admission has long-term implications. Data highlight the need for a longitudinal approach to patient management.

A preliminary assessment of the benefits of the addition of botulinum toxin a to a conventional therapy program on the function of people with longstanding stroke.

OBJECTIVE: To determine if botulinum toxin type A (BTX-A) combined with therapy can facilitate improved upper-extremity (UE) functional status versus therapy alone. DESIGN: Double-blind randomized crossover trial. SETTING: Tertiary care outpatient rehabilitation center. PARTICIPANTS: Convenience sample of 21 men and women (ages 19-80 y) with stroke more than 6 months after insult who had tone greater than 3 on the Ashworth Scale for 2 joints in the involved UE. INTERVENTION: Subjects were consecutively recruited and randomized to a double-blind crossover trial. Subjects received either BTX-A combined with a defined therapy program or placebo injection combined with a therapy program in two 12-week sessions. MAIN OUTCOME MEASURES: The primary functional outcome measure was the Motor Activity Log (MAL). Subjects were also assessed on physiologic measures including tone (Ashworth Scale), range of motion, and motor strength. RESULTS: Improvements were noted in the functional status of the subjects in both arms of the study as measured by the MAL. All subjects had a significant change in functional status on MAL with therapy (P<.05). The use of BTX-A combined with therapy as compared with therapy only improved the functional status of the subjects on the MAL Quality of Movement subscale (P=.0180, t test) and showed a trend toward significance in the Amount of Use subscale (P=.0605, analysis of variance). Six weeks after treatment, the BTX-A combined with therapy decreased the Ashworth score statistically (P=.0271), but the therapy alone group decreased a similar amount at 6 weeks (P=.0117), indicating that most of the physiologic tone change could be attributed to therapy. After each 12-week period, tone had largely returned to baseline (P>.05). CONCLUSION: A focused therapy program showed the most improvement in function in this defined stroke population. BTX-A combined with a focused traditional therapy program slightly enhanced the functional status of stroke subjects beyond that obtained with therapy alone 12 weeks after injection.

Orally delivered baclofen to control spastic hypertonia in acquired brain injury.

To determine if oral/systemic delivery of baclofen can effectively decrease spastic hypertonia due to acquired brain injury (traumatic brain injury, stroke, anoxia, or encephalopathy). Tertiary care outpatient rehabilitation center directly attached to a university hospital. Patients were a convenience sample recruited consecutively who had been referred for treatment of their spastic hypertonia to our spasticity clinic over a 5-year period. The spastic hypertonia was due to an acquired brain injury by either traumatic brain injury (TBI), stroke, or anoxic brain injury. All patients were more than 6 months postinjury or illness. Retrospective review of patients before and after initiation of treatment with oral baclofen, per standardized clinical data sheets. Thirty-five patients (22 TBI patients) were started on oral baclofen and were reevaluated between 1 to 3 months after initiation of treatment. Data for motor tone (Ashworth scores), spasm scores (Penn spasm frequency score), and deep tendon reflex scores were collected on the affected upper extremity (UE) and lower extremity (LE) side(s). Normal extremities were not assessed. Differences over time were assessed via descriptive statistics and Wilcoxon signed-rank. After 1 to 3 months of treatment when subjects had reached their maximal tolerated dosage, the average LE Ashworth score in the affected lower extremities (LEs) decreased from 3.5 to 3.2 (P =.0003), the reflex score decreased from 2.5 to 2.2 (P =.0274), and there was no statistical difference in the spasm score (P >.05). When the 22 TBI patients are analyzed separately, the average LE Ashworth score decreased from 3.5 to 3.2 (P =.0044) and the reflex score decreased from 2.7 to 2.0 (P =.0003). There was no statistically significant change in UE tone, spasm frequency, or reflexes after 1 to 3 months of treatment (P >.05). The average dosage at follow-up was 57 mg/day of baclofen (range 15-120 mg/day). There was a 17% incidence of somnolence that limited the maximum daily dosage of the medication. The oral delivery of baclofen is capable of reducing LE spastic hypertonia resulting from acquired brain injury. The lack of effect upon the upper extremities may be due to receptor specificity issues. GABA-B receptors may be less involved in the modulation of UE spastic hypertonia.

Cyproheptadine for intrathecal baclofen withdrawal.

OBJECTIVE: To evaluate the efficacy of cyproheptadine in the management of acute intrathecal baclofen (ITB) withdrawal. DESIGN: Descriptive case series. SETTING: University hospital with a comprehensive in- and outpatient rehabilitation center. PARTICIPANTS: Four patients (3 with spinal cord injury, 1 with cerebral palsy) with implanted ITB infusion pumps for treatment of severe spasticity, who had ITB withdrawal syndrome because of interruption of ITB infusion. INTERVENTIONS: Patients were treated with 4 to 8mg of cyproheptadine by mouth every 6 to 8 hours, 5 to 10mg of diazepam by mouth every 6 to 12 hours, 10 to 20mg of baclofen by mouth every 6 hours, and ITB boluses in some cases. MAIN OUTCOME MEASURES: Clinical signs and symptoms of ITB withdrawal of varying severity were assessed by vital signs (temperature, heart rate), physical examination (reflexes, tone, clonus), and patient report of symptoms (itching, nausea, headache, malaise). RESULTS: The patients in our series improved significantly when the serotonin antagonist cyproheptadine was added to their regimens. Fever dropped at least 1.5 degrees C, and heart rate dropped from rates of 120 to 140 to less than 100bpm. Reflexes, tone, and myoclonus also decreased. Patients reported dramatic reduction in itching after cyproheptadine. These changes were associated temporally with cyproheptadine dosing. DISCUSSION: Acute ITB withdrawal syndrome occurs frequently in cases of malfunctioning intrathecal infusion pumps or catheters. The syndrome commonly presents with pruritus and increased muscle tone. It can progress rapidly to high fever, altered mental status, seizures, profound muscle rigidity, rhabdomyolysis, brain injury, and death. Current therapy with oral baclofen and benzodiazepines is useful but has variable success, particularly in severe cases. We note that ITB withdrawal is similar to serotonergic syndromes, such as in overdoses of selective serotonin reuptake inhibitors or the popular drug of abuse 3,4-methylenedioxymethamphetamine (Ecstasy). We postulate that ITB withdrawal may be a form of serotonergic syndrome that occurs from loss of gamma-aminobutyric acid B receptor-mediated presynaptic inhibition of serotonin. CONCLUSION: Cyproheptadine may be a useful adjunct to baclofen and benzodiazepines in the management of acute ITB withdrawal syndrome.

Screening for venous thromboembolism in traumatic brain injury: limitations of D-dimer assay.

OBJECTIVES: To assess whether 2 different D-dimer fibrin degradation assays-a second-generation latex immunosorbent agglutination (LIA) and an enzyme-linked immunosorbent assay (ELISA)-are predictive for the development of deep venous thrombosis (DVT) at the currently accepted level of 500 microg/L of D-dimer assay during the first weeks after traumatic brain injury (TBI) and to correlate over 8 weeks the second-generation LIA assay with the ELISA assay after acute TBI. DESIGN: A case series of persons with TBI were screened for DVT at 2 weeks (+/-3d) using real-time, spectral Doppler ultrasound, as well as D-dimer fibrin split products. All persons were rescreened at 4, 6, and 8 weeks (+/-3d) after injury using D-dimer LIA and ELISA assays. SETTING: A university hospital with a directly connected comprehensive in- and outpatient rehabilitation center that are part of the Traumatic Brain Injury Model Systems. PARTICIPANTS: Over 3 years, 35 TBI subjects with a mean Glasgow Coma Scale score of 6.5 were consecutively enrolled into the trial while on acute care. Persons were at least 16 years of age with no history of treatment for DVT. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Data were analyzed for the levels of D-dimer and risk as established by a predictive value of 500 microg/L. Changes in D-dimer values over time and within subjects were assessed by analysis of variance (ANOVA) with repeated measures, and the methods were correlated. RESULTS: The mean LIA level at 2 weeks was 4.3mg/L and averaged 1.6 mg/L at 8 weeks from injury (P=.012, ANOVA), and the ELISA dropped from 4,748 microg/L to 1.695 microg/L (P=.0022, ANOVA). Except for 1 ELISA value in 1 patient, D-dimer levels were elevated beyond 500 microg/L at 2 weeks. There was a very good correlation between the LIA and the ELISA at 2, 4, 6, and 8 weeks after TBI (P<.0001). In individual cases, there were only occasional discrepancies between the LIA and ELISA methods. There were no positive DVTs at 2 weeks using ultrasound, so prediction of the sensitivity and the specificity of D-dimer with DVT was not possible. CONCLUSION: Using the currently recommended levels of D-dimer to predict DVT is not clinically useful in the acute TBI population.

Amantadine to improve neurorecovery in traumatic brain injury-associated diffuse axonal injury: a pilot double-blind randomized trial.

BACKGROUND: Traumatic brain injury (TBI) caused by a high-speed transportation accident results in a mechanism of injury commonly described as diffuse axonal injury (DAI), which is associated with a reduction in dopamine turnover in the brain. Because of its affect on both dopamine and N-methyl-D-aspartate (NMDA) channels, amantadine has been the subject of considerable interest and clinical use in acute TBI. PARTICIPANTS: In this study, 35 subjects, who had a TBI in a transportation accident and were initially seen with a Glasgow Coma Scale score of 10 or less within the first 24 hours after admission, were randomly assigned to a double-blind, placebo-controlled, crossover design trial. MAIN OUTCOME MEASURES: Amantadine, 200 mg, or placebo was each administered for 6 weeks (12 weeks total) to patients who were recruited consecutively. RESULTS: There was an improvement in the Mini-Mental Status (MMSE) scores of 14.3 points (P =.0185), Disability Rating Scale (DRS) score of 9.8 points (P =.0022), Glasgow Outcome Scale (GOS) score of 0.8 points (P =.0077), and in the FIM Cognitive score (FIM-cog) of 15.1 points (P =.0033) in the group that received amantadine during the first 6 weeks (group 1), but there was no improvement in the second 6 weeks on placebo (P >.05). In group 2 (active drug second 6 weeks), there was an improvement in the MMSE of 10.5 points, in the DRS of 9.4 points (P =.0006), in the GOS of 0.5 points (P =.0231), and in the FIM-cog of 11.3 points (P =.0030, Wilcoxon signed rank) spontaneously in the first 6 weeks on placebo (P =.0015). However, group 2 gained a statistically significant additional 6.3 points of recovery in the MMSE (P =.0409), 3.8 points in the DRS (P =.0099), 0.5 points in the GOS (P =.4008), and 5.2 points in the FIM-cog (P =.0173, Wilcoxon signed rank) between the sixth week and the twelfth week of treatment on the active drug. CONCLUSIONS: There was a consistent trend toward a more rapid functional improvement regardless of when a patient with DAI-associated TBI was started on amantadine in the first 3 months after injury.