Psychiatric Care of the Post-September 11 Combat Veteran: A Review.

BACKGROUND: Post-September 11, 2001 combat veterans represent a growing cohort of patients with unique mental health needs, particularly around post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI). The United States (US) remains engaged in conflicts around the globe, so this patient cohort will continue to grow in number. With around 40% of American combat veterans from Iraq and Afghanistan seeking mental health care outside of the Veterans Affairs, understanding the psychiatric needs of the post-September 11 combat veteran is an important goal for all psychiatrists. These patients are relevant to consultation-liaison (C-L) psychiatrists because of their high comorbidity of conditions such as TBI, obstructive sleep apnea, insomnia, and chronic pain. This article reviews the current literature on mental health care for the post-September 11 combat veteran, emphasizing PTSD and TBI treatment, and culling evidence-based recommendations from randomized controlled trials of combat veterans. Emphasis is also placed on the Veterans Affairs/Department of Defense Clinical Practice Guidelines. The authors also bring unique clinical expertise of having served on active duty as psychiatrists for the US Army, including in a combat zone, and both currently work in a Veterans Affairs Iraq and Afghanistan combat veteran mental health clinic. OBJECTIVE: This review outlines useful treatment approaches for PTSD and TBI and briefly covers the comorbid conditions of major depression, chronic pain, and substance use disorders. This review will prepare C-L psychiatrists to care for this challenging patient cohort.

Aripiprazole for Post-traumatic Stress Disorder: A Systematic Review.

OBJECTIVE: The aim of this study was to review the safety and efficacy of aripiprazole as monotherapy and adjunct therapy for the treatment of post-traumatic stress disorder (PTSD). METHODS: A search of both MEDLINE (1956 to May 2017) and EMBASE (1957 to May 2017) was conducted using the terms "aripiprazole" and "post-traumatic stress disorder," "posttraumatic stress disorder," or "PTSD." Studies evaluating the primary endpoint of PTSD in patients taking aripiprazole as monotherapy or adjunct therapy were analyzed for relevance. Those that met the objective of this study were included for evaluation: 1 placebo-controlled trial; 4 open-label trials; and 1 retrospective chart review. RESULTS: In patients with a history of PTSD, aripiprazole resulted in significant improvements in the primary outcome, including Clinician-Administered PTSD Symptom Scale or PTSD Checklist-Military scores, in all but 1 study analyzed. Study durations ranged from 10 to 16 weeks. Initial doses of aripiprazole ranged from 2 to 15 mg daily that could be titrated up or down in the range of 2 to 30 mg daily based on efficacy and tolerability. Overall, aripiprazole was well tolerated with the most common treatment-related study discontinuations attributed to the adverse events of anxiety, insomnia, akathisia, asthenia, restlessness, and somnolence. CONCLUSIONS: Based on the reviewed literature, aripiprazole is a reasonable therapy option as monotherapy or adjunct therapy in patients with PTSD. Larger randomized controlled trials are needed to better understand the role of this atypical antipsychotic in patients with PTSD.

An RCT of Effects of Telephone Care Management on Treatment Adherence and Clinical Outcomes Among Veterans With PTSD.

OBJECTIVE: This study assessed whether adding telephone care management to usual outpatient mental health care improved treatment attendance, medication compliance, and clinical outcomes of veterans with posttraumatic stress disorder (PTSD). METHODS: In a multisite randomized controlled trial, 358 veterans were assigned to either usual outpatient mental health treatment (N=165) or usual care plus twice-a-month telephone care management (TCM) and support in the first three months of treatment (N=193). Treatment utilization and medication refills were determined from U.S. Department of Veterans Affairs administrative data. PTSD, depression, quality of life, aggressive behavior, and substance use were assessed with self-report questionnaires at intake, four months, and 12 months. RESULTS: Telephone care managers reached 95% of TCM participants (N=182), completing an average 5.1 of 6.0 planned telephone calls. During the three-month intervention period, TCM participants completed 43% more mental health visits (M±SD=5.9±6.8) than did those in usual care (4.1±4.2) (incident rate ratio=1.36, χ2=6.56, df=1, p<.01). Treatment visits in the nine-month follow-up period and medication refills did not differ by condition. Only 9% of participants were scheduled to receive evidence-based psychotherapy. Slopes of improvement in PTSD, depression, alcohol misuse, drug problems, aggressive behavior, and quality of life did not differ by condition or treatment attendance. CONCLUSIONS: TCM improved PTSD patients' treatment attendance but not their outcomes. TCM can enhance treatment engagement, but outcomes depend on the effectiveness of the treatments that patients receive.

A pilot randomized placebo-controlled trial of adjunctive aripiprazole for chronic PTSD in US military Veterans resistant to antidepressant treatment.

Many individuals with post-traumatic stress disorder (PTSD) experience persistent symptoms despite pharmacological treatment with antidepressants. Several open-label monotherapy and adjunctive studies have suggested that aripiprazole (a second-generation antipsychotic) may have clinical utility in PTSD. However, there have been no randomized placebo-controlled trials of aripiprazole use for PTSD. We thus conducted a pilot randomized controlled trial of adjunctive aripiprazole versus placebo among Veterans with chronic PTSD serving in the US military since 11 September 2001 to assess the feasibility, safety, tolerability, and therapeutic potential of aripiprazole. Sixteen Veterans were randomized, and 14 completed at least 4 weeks of the study; 12 completed the entire 8-week trial. Outcome measures included the Clinician-Administered PTSD Scale (CAPS), PTSD Checklist, Beck Depression Inventory, Second Edition, and Positive and Negative Syndrome Scale scores. Aripiprazole was well-tolerated in this cohort, and improvements in CAPS, PTSD Checklist, Beck Depression Inventory, Second Edition, and Positive and Negative Syndrome Scale scores were as hypothesized. Although CAPS change scores did not reach statistical significance, aripiprazole outperformed placebo by 9 points on the CAPS in the last observation carried forward analysis compared with the placebo group (n = 7 per group), and by 20 points in the group randomized to aripiprazole that completed the entire study (n = 5) compared with the placebo group (n = 7). Results suggest promise for aripiprazole as an adjunctive strategy for the treatment of PTSD.

Rehabilitation of Combat-Related Injuries in the Veterans Administration: A Web of Support.

The Department of Veterans Affairs provides acute, subacute, and continuing rehabilitation for veterans using a hub-and-spoke system of hospitals and outpatient facilities. Using traumatic brain injury as an example, this commentary illustrates how this system provides interdisciplinary rehabilitative care to veterans throughout North Carolina.

An open-source toolbox for automated phenotyping of mice in behavioral tasks.

Classifying behavior patterns in mouse models of neurological, psychiatric and neurodevelopmental disorders is critical for understanding disease causality and treatment. However, complete characterization of behavior is time-intensive, prone to subjective scoring, and often requires specialized equipment. Although several reports describe automated home-cage monitoring and individual task scoring methods, we report the first open source, comprehensive toolbox for automating the scoring of several common behavior tasks used by the neuroscience community. We show this new toolbox is robust and achieves equal or better consistency when compared to manual scoring methods. We use this toolbox to study the alterations in behavior that occur following blast-induced traumatic brain injury (bTBI), and study if these behavior patterns are altered following genetic deletion of the transcription factor Ets-like kinase 1 (Elk-1). Due to the role of Elk-1 in neuronal survival and proposed role in synaptic plasticity, we hypothesized that Elk-1 deletion would improve some neurobehavioral deficits, while impairing others, following blast exposure. In Elk-1 knockout (KO) animals, deficits in open field, spatial object recognition (SOR) and elevated zero maze performance after blast exposure disappeared, while new significant deficits appeared in spatial and associative memory. These are the first data suggesting a molecular mediator of anxiety deficits following bTBI, and represent the utility of the broad screening tool we developed. More broadly, we envision this open-source toolbox will provide a more consistent and rapid analysis of behavior across many neurological diseases, promoting the rapid discovery of novel pathways mediating disease progression and treatment.

Attenuation of blast pressure behind ballistic protective vests.

BACKGROUND: Clinical studies increasingly report brain injury and not pulmonary injury following blast exposures, despite the increased frequency of exposure to explosive devices. The goal of this study was to determine the effect of personal body armour use on the potential for primary blast injury and to determine the risk of brain and pulmonary injury following a blast and its impact on the clinical care of patients with a history of blast exposure. METHODS: A shock tube was used to generate blast overpressures on soft ballistic protective vests (NIJ Level-2) and hard protective vests (NIJ Level-4) while overpressure was recorded behind the vest. RESULTS: Both types of vest were found to significantly decrease pulmonary injury risk following a blast for a wide range of conditions. At the highest tested blast overpressure, the soft vest decreased the behind armour overpressure by a factor of 14.2, and the hard vest decreased behind armour overpressure by a factor of 56.8. Addition of body armour increased the 50th percentile pulmonary death tolerance of both vests to higher levels than the 50th percentile for brain injury. CONCLUSIONS: These results suggest that ballistic protective body armour vests, especially hard body armour plates, provide substantial chest protection in primary blasts and explain the increased frequency of head injuries, without the presence of pulmonary injuries, in protected subjects reporting a history of blast exposure. These results suggest increased clinical suspicion for mild to severe brain injury is warranted in persons wearing body armour exposed to a blast with or without pulmonary injury.

Brain injury risk from primary blast.

BACKGROUND: Military service members are often exposed to at least one explosive event, and many blast-exposed veterans present with symptoms of traumatic brain injury. However, there is little information on the intensity and duration of blast necessary to cause brain injury. METHODS: Varying intensity shock tube blasts were focused on the head of anesthetized ferrets, whose thorax and abdomen were protected. Injury evaluations included physiologic consequences, gross necropsy, and histologic diagnosis. The resulting apnea, meningeal bleeding, and fatality were analyzed using logistic regressions to determine injury risk functions. RESULTS: Increasing severity of blast exposure demonstrated increasing apnea immediately after the blast. Gross necropsy revealed hemorrhages, frequently near the brain stem, at the highest blast intensities. Apnea, bleeding, and fatality risk functions from blast exposure to the head were determined for peak overpressure and positive-phase duration. The 50% risk of apnea and moderate hemorrhage were similar, whereas the 50% risk of mild hemorrhage was independent of duration and required lower overpressures (144 kPa). Another fatality risk function was determined with existing data for scaled positive-phase durations from 1 millisecond to 20 milliseconds. CONCLUSION: The first primary blast brain injury risk assessments for mild and moderate/severe injuries in a gyrencephalic animal model were determined. The blast level needed to cause a mild/moderate brain injury may be similar to or less than that needed for pulmonary injury. The risk functions can be used in future research for blast brain injury by providing realistic injury risks to guide the design of protection or evaluate injury.

Porcine head response to blast.

Recent studies have shown an increase in the frequency of traumatic brain injuries related to blast exposure. However, the mechanisms that cause blast neurotrauma are unknown. Blast neurotrauma research using computational models has been one method to elucidate that response of the brain in blast, and to identify possible mechanical correlates of injury. However, model validation against experimental data is required to ensure that the model output is representative of in vivo biomechanical response. This study exposes porcine subjects to primary blast overpressures generated using a compressed-gas shock tube. Shock tube blasts were directed to the unprotected head of each animal while the lungs and thorax were protected using ballistic protective vests similar to those employed in theater. The test conditions ranged from 110 to 740 kPa peak incident overpressure with scaled durations from 1.3 to 6.9 ms and correspond approximately with a 50% injury risk for brain bleeding and apnea in a ferret model scaled to porcine exposure. Instrumentation was placed on the porcine head to measure bulk acceleration, pressure at the surface of the head, and pressure inside the cranial cavity. Immediately after the blast, 5 of the 20 animals tested were apneic. Three subjects recovered without intervention within 30 s and the remaining two recovered within 8 min following respiratory assistance and administration of the respiratory stimulant doxapram. Gross examination of the brain revealed no indication of bleeding. Intracranial pressures ranged from 80 to 390 kPa as a result of the blast and were notably lower than the shock tube reflected pressures of 300-2830 kPa, indicating pressure attenuation by the skull up to a factor of 8.4. Peak head accelerations were measured from 385 to 3845 G's and were well correlated with peak incident overpressure (R(2) = 0.90). One SD corridors for the surface pressure, intracranial pressure (ICP), and head acceleration are presented to provide experimental data for computer model validation.

Primary blast survival and injury risk assessment for repeated blast exposures.

BACKGROUND: The widespread use of explosives by modern insurgents and terrorists has increased the potential frequency of blast exposure in soldiers and civilians. This growing threat highlights the importance of understanding and evaluating blast injury risk and the increase of injury risk from exposure to repeated blast effects. METHODS: Data from more than 3,250 large animal experiments were collected from studies focusing on the effects of blast exposure. The current study uses 2,349 experiments from the data collection for analysis of the primary blast injury and survival risk for both long- and short-duration blasts, including the effects from repeated exposures. A piecewise linear logistic regression was performed on the data to develop survival and injury risk assessment curves. RESULTS: New injury risk assessment curves uniting long- and short-duration blasts were developed for incident and reflected pressure measures and were used to evaluate the risk of injury based on blast over pressure, positive-phase duration, and the number of repeated exposures. The risk assessments were derived for three levels of injury severity: nonauditory, pulmonary, and fatality. The analysis showed a marked initial decrease in injury tolerance with each subsequent blast exposure. This effect decreases with increasing number of blast exposures. CONCLUSIONS: The new injury risk functions showed good agreement with the existing experimental data and provided a simplified model for primary blast injury risk. This model can be used to predict blast injury or fatality risk for single exposure and repeated exposure cases and has application in modern combat scenarios or in setting occupational health limits.

Development of a finite element model for blast brain injury and the effects of CSF cavitation.

Blast-related traumatic brain injury is the most prevalent injury for combat personnel seen in the current conflicts in Iraq and Afghanistan, yet as a research community,we still do not fully understand the detailed etiology and pathology of this injury. Finite element (FE) modeling is well suited for studying the mechanical response of the head and brain to blast loading. This paper details the development of a FE head and brain model for blast simulation by examining both the dilatational and deviatoric response of the brain as potential injury mechanisms. The levels of blast exposure simulated ranged from 50 to 1000 kPa peak incident overpressure and 1­8 ms in positive-phase duration, and were comparable to real-world blast events. The frontal portion of the brain had the highest pressures corresponding to the location of initial impact, and peak pressure attenuated by 40­60% as the wave propagated from the frontal to the occipital lobe. Predicted brain pressures were primarily dependent on the peak overpressure of the impinging blast wave, and the highest predicted brain pressures were 30%less than the reflected pressure at the surface of blast impact. Predicted shear strain was highest at the interface between the brain and the CSF. Strain magnitude was largely dependent on the impulse of the blast, and primarily caused by the radial coupling between the brain and deforming skull.The largest predicted strains were generally less than 10%,and occurred after the shock wave passed through the head.For blasts with high impulses, CSF cavitation had a large role in increasing strain levels in the cerebral cortex and periventricular tissues by decoupling the brain from the skull. Relating the results of this study with recent experimental blast testing suggest that a rate-dependent strain-based tissue injury mechanism is the source primary blast TBI.

Economic analysis of an intraoperative cell salvage service.

UNLABELLED: In the United States, the cost of erythrocyte transfusion exceeds 1.3 billion dollars annually. The fear of viral disease transmission popularized intraoperative salvage to reduce the use of banked blood. Although the economics of this technique have been questioned, the financial variables in providing an intraoperative autotransfusion service have not been analyzed. We designed mathematical models to determine the most cost-effective strategy based on hospital caseload. Four models were analyzed with a spreadsheet to project costs of an intraoperative autotransfusion service when fully or partially outsourced, performed by a full-time technician employee, or performed by a cross-trained employee. The Partially Outsourced model was more economical than the Fully Outsourced model when the annual caseload exceeded 185 cases. The New Employee model became more economical than the Fully Outsourced model when the annual caseload exceeded 110 cases. The Cross-Trained model was the most economical when annual caseload exceeded 55 cases. IMPLICATIONS: Cross-training an employee as a cell salvage technician is more economical than outsourcing when caseload exceeds 55 per year.