Heart Rate Variability and Cognitive Bias Feedback Interventions to Prevent Post-deployment PTSD: Results from a Randomized Controlled Trial.

Introduction: There is a long history of pre-deployment PTSD prevention efforts in the military and effective pre-deployment strategies to prevent post-deployment PTSD are still needed. Materials and Methods: This randomized controlled trial included three arms: heart rate variability biofeedback (HRVB), cognitive bias modification for interpretation (CBM-I), and control. The hypothesis was that pre-deployment resilience training would result in lower post-deployment PTSD symptoms compared with control. Army National Guard soldiers (n = 342) were enrolled in the Warriors Achieving Resilience (WAR) study and analyzed. The outcome was PTSD symptom severity using the PTSD Checklist - Military version (PCL) measured at pre-deployment, 3- and 12-month post-deployment. Due to the repeated measures for each participant and cluster randomization at the company level, generalized linear mixed models were used for the analysis. This study was approved by the Army Human Research Protection Office, Central Arkansas Veterans Healthcare System Institutional Review Board (IRB), and Southeast Louisiana Veterans Health Care System IRB. Results: Overall, there was no significant intervention effect. However, there were significant intervention effects for subgroups of soldiers. For example, at 3-months post-deployment, the HRVB arm had significantly lower PCL scores than the control arm for soldiers with no previous combat zone exposure who were age 30 and older and for soldiers with previous combat zone exposure who were 45 and older (unadjusted effect size -0.97 and -1.03, respectively). A significant difference between the CBM-I and control arms was found for soldiers without previous combat zone exposure between ages 23 and 42 (unadjusted effect size -0.41). Similarly, at 12-months post-deployment, the HRVB arm had significantly lower PCL scores in older soldiers. Conclusion: Pre-deployment resilience training was acceptable and feasible and resulted in lower post-deployment PTSD symptom scores in subgroups of older soldiers compared with controls. Strengths of the study included cluster randomization at the company level, use of iPod device to deliver the resilience intervention throughout the deployment cycle, and minimal disruption of pre-deployment training by using self-paced resilience training. Weaknesses included self-report app use, study personnel not able to contact soldiers during deployment, and in general a low level of PTSD symptom severity throughout the study. In future studies, it would important for the study team and/or military personnel implementing the resilience training to be in frequent contact with participants to ensure proper use of the resilience training apps.

Heart rate variability: Pre-deployment predictor of post-deployment PTSD symptoms.

Heart rate variability is a physiological measure associated with autonomic nervous system activity. This study hypothesized that lower pre-deployment HRV would be associated with higher post-deployment post-traumatic stress disorder (PTSD) symptoms. Three-hundred-forty-three Army National Guard soldiers enrolled in the Warriors Achieving Resilience (WAR) study were analyzed. The primary outcome was PTSD symptom severity using the PTSD Checklist - Military version (PCL) measured at baseline, 3- and 12-month post-deployment. Heart rate variability predictor variables included: high frequency power (HF) and standard deviation of the normal cardiac inter-beat interval (SDNN). Generalized linear mixed models revealed that the pre-deployment PCL*ln(HF) interaction term was significant (p<0.0001). Pre-deployment SDNN was not a significant predictor of post-deployment PCL. Covariates included age, pre-deployment PCL, race/ethnicity, marital status, tobacco use, childhood abuse, pre-deployment traumatic brain injury, and previous combat zone deployment. Pre-deployment heart rate variability predicts post-deployment PTSD symptoms in the context of higher pre-deployment PCL scores.

Illness apprehension, depression, anxiety, and quality of life in liver transplant candidates: implications for psychosocial interventions.

BACKGROUND: End-stage liver disease is associated with diminished quality of life (QOL). Numerous physical and psychosocial problems that affect QOL are common in those undergoing evaluation for liver transplantation. OBJECTIVE: Identifying which of these challenges are most closely associated with QOL would be helpful in developing priority targets for evidence-based interventions specific to those undergoing transplant evaluation. METHOD: A total of 108 adults undergoing psychologic assessment for liver transplant completed clinical interview, neuropsychologic testing, and self-report inventories of depression, anxiety, cognitive appraisal characteristics, support resources, and QOL. RESULTS: Multiple regression analyses revealed that while emotional symptoms (anxiety and depression) were primarily associated with mental QOL, illness apprehension was the only variable uniquely associated with physical QOL after accounting for severity of liver disease, cognitive status, emotional symptoms, and support resources. CONCLUSION: Findings suggest that psychosocial interventions prioritizing reduction of illness-related fear and symptoms of anxiety/depression would likely have the greatest effect on QOL in persons with end-stage liver disease awaiting transplantation.

Driving simulation can improve insight into impaired driving skills in cirrhosis.

BACKGROUND: Minimal hepatic encephalopathy (MHE) is associated with poor driving skills and insight. Increasing insight may improve receptiveness for therapy or driving restrictions. AIM: To evaluate the change in the self-assessment of driving skills (SADS) using a driving simulator. METHODS: Cirrhotic patients and age/education-matched controls underwent MHE testing with inhibitory control (ICT) and the psychometric hepatic encephalopathy score (PHES). SADS, a Likert scale from 0 to 10, was administered just before and after a standardized driving simulation comprising testing and navigation tasks. The percentage SADS change from baseline was compared within/between groups. RESULTS: A total of 84 patients (60% men, age 55 years) and 12 controls were included. Controls were significantly better than cirrhotics on cognitive/simulator testing. The baseline SADS was similar between the groups. The baseline patient SADS was only correlated with ICT lures (r = -0.4, P = 0.001). Post-simulation, 60% of patients improved their insight, i.e., reduced SADS (from 8 to 6.5, P = 0.0001) compared to 25% of controls (P = 0.02). The mean percentage SADS reduction was also higher in cirrhotics (18% vs. 8%, P = 0.03). MHE on ICT patients had a significantly higher SADS improvement (P = 0.004) compared to the other patients; no difference was seen in those with/without MHE due to the PHES. The percentage SADS reduction in patients was correlated with getting lost (r = 0.468, P < 0.0001), crashes (P = 0.002), and centerline/road-edge excursions (P = 0.01). There was a significantly higher percentage SADS reduction in cirrhotics who got lost (25%) compared to those who did not get lost (12%) and controls (8%, P = 0.014). CONCLUSIONS: Insight into driving skills in cirrhosis improves after driving simulation and is highest in those with navigation errors and MHE on ICT. Driving simulator-associated insight improvement may be the first step towards the cognitive rehabilitation of driving skills in cirrhosis.

The multi-dimensional burden of cirrhosis and hepatic encephalopathy on patients and caregivers.

OBJECTIVES: Cirrhosis and hepatic encephalopathy (HE) can adversely affect survival, but their effect on socioeconomic and emotional burden on the family is not clear. The aim was to study the emotional and socioeconomic burden of cirrhosis and HE on patients and informal caregivers. METHODS: A cross-sectional study in two transplant centers (Veterans and University) of cirrhotic patients and their informal caregivers was performed. Demographics for patient/caregivers, model-for-end-stage liver disease (MELD) score, and cirrhosis complications were recorded. Patients underwent a cognitive battery, sociodemographic, and financial questionnaires. Caregivers were given the perceived caregiver burden (PCB; maximum=155) and Zarit Burden Interview (ZBI)-Short Form (maximum=48) and questionnaires for depression, anxiety, and social support. RESULTS: A total of 104 cirrhotics (70% men, 44% previous HE, median MELD 12, 49% veterans) and their caregivers (66% women, 77% married, relationship duration 32±14 years) were included. Cirrhosis severely impacted the family unit with respect to work (only 56% employed), finances, and adherence. Those with previous HE had worse unemployment (87.5 vs. 19%, P=0.0001) and financial status (85 vs. 61%, P=0.019) and posed a higher caregiver burden; PCB (75 vs. 65, P=0.019) and ZBI (16 vs. 11, P=0.015) compared with others. Cognitive performance and MELD score were significantly correlated with employment and caregiver burden. Veterans and non-veterans were equally affected. On regression, depression score, MELD, and cognitive tests predicted both PCB and ZBI score. CONCLUSIONS: Previous HE and cognitive dysfunction are associated with worse employment, financial status, and caregiver burden. Cirrhosis-related expenses impact the family unit's daily functioning and medical adherence. A multidisciplinary approach to address this burden is required.

Rifaximin improves driving simulator performance in a randomized trial of patients with minimal hepatic encephalopathy.

BACKGROUND & AIMS: Patients with cirrhosis and minimal hepatic encephalopathy (MHE) have driving difficulties but the effects of therapy on driving performance is unclear. We evaluated whether performance on a driving simulator improves in patients with MHE after treatment with rifaximin. METHODS: Patients with MHE who were current drivers were randomly assigned to placebo or rifaximin groups and followed up for 8 weeks (n = 42). Patients underwent driving simulation (driving and navigation tasks) at the start (baseline) and end of the study. We evaluated patients' cognitive abilities, quality of life (using the Sickness Impact Profile), serum levels of ammonia, levels of inflammatory cytokines, and model for end-stage-liver disease scores. The primary outcome was the percentage of patients who improved in driving performance, calculated as follows: total driving errors = speeding + illegal turns + collisions. RESULTS: Over the 8-week study period, patients given rifaximin made significantly greater improvements than those given placebo in avoiding total driving errors (76% vs 31%; P = .013), speeding (81% vs 33%; P = .005), and illegal turns (62% vs 19%; P = .01). Of patients given rifaximin, 91% improved their cognitive performance, compared with 61% of patients given placebo (P = .01); they also made improvements in the psychosocial dimension of the Sickness Impact Profile compared with the placebo group (P = .04). Adherence to the assigned drug averaged 92%. Neither group had changes in ammonia levels or model for end-stage-liver disease scores, but patients in the rifaximin group had increased levels of the anti-inflammatory cytokine interleukin-10. CONCLUSIONS: Patients with MHE significantly improve driving simulator performance after treatment with rifaximin, compared with placebo.

Persistence of cognitive impairment after resolution of overt hepatic encephalopathy.

BACKGROUND & AIMS: In patients with cirrhosis, hepatic encephalopathy (HE) has acute but reversible as well as chronic components. We investigated the extent of residual cognitive impairment following clinical resolution of overt HE (OHE). METHODS: Cognitive function of cirrhotic patients was evaluated using psychometric tests (digit symbol, block design, and number connection [NCT-A and B]) and the inhibitory control test (ICT). Improvement (reduction) in ICT lures and first minus second halves (DeltaL(1-2)) were used to determine learning of response inhibition. Two cross-sectional studies (A and B) compared data from stable cirrhotic patients with or without prior OHE. We then prospectively assessed cognitive performance, before and after the first episode of OHE. RESULTS: In study A (226 cirrhotic patients), 54 had experienced OHE, 120 had minimal HE, and 52 with no minimal HE. Despite normal mental status on lactulose after OHE, cirrhotic patients were cognitively impaired, based on results from all tests. Learning of response inhibition (DeltaL(1-2) > or =1) was evident in patients with minimal HE and no minimal HE but was lost after OHE. In study B (50 additional patients who developed > or =1 documented OHE episode during follow-up), the number of OHE hospitalizations correlated with severity of residual impairment, indicated by ICT lures (r = 0.5, P = .0001), digit symbol test (r = -0.39, P = .002), and number connection test-B (r = 0.33, P = .04). In the prospective study (59 cirrhotic patients without OHE), 15 developed OHE; ICT lure response worsened significantly after OHE (12 before vs 18 after, P = .0003), and learning of response inhibition was lost. The 44 patients who did not experience OHE did not have deteriorations in cognitive function in serial testing. CONCLUSIONS: In cirrhosis, episodes of OHE are associated with persistent and cumulative deficits in working memory, response inhibition, and learning.

General intellectual decline and daily living skills.

A total of 64 elderly individuals presenting with cognitive decline were administered a test of general intelligence and a measure of adaptive knowledge and daily living skills. Premorbid ability was estimated using a demographic formula and a reading test. After controlling for age and depression, general intellectual ability accounted for a large amount of the variance in a broad range of adaptive knowledge and behavioral skills, reflecting the influence of premorbid ability and especially estimated decline. Different patterns of adaptive knowledge and skills were identified as a function of measured IQ and of estimated decline in IQ. Results suggest a threshold of intellectual decline for deterioration in daily living skills. Studies purporting to demonstrate that impairments in particular neuropsychological domains predict specific functional deficits need to control for general intellectual ability and/or the extent of intellectual decline.

Minimal hepatic encephalopathy is associated with motor vehicle crashes: the reality beyond the driving test.

UNLABELLED: Patients with minimal hepatic encephalopathy (MHE) have impaired driving skills, but association of MHE with motor vehicle crashes is unclear. Standard psychometric tests (SPT) or inhibitory control test (ICT) can be used to diagnose MHE. The aim was to determine the association of MHE with crashes and traffic violations over the preceding year and on 1-year follow-up. Patients with cirrhosis were diagnosed with MHE by ICT (MHEICT) and SPT (MHESPT). Self and department-of-transportation (DOT)-reports were used to determine crashes and violations over the preceding year. Agreement between self and DOT-reports was analyzed. Patients then underwent 1-year follow-up for crash/violation occurrence. Crashes in those with/without MHEICT and MHESPT were compared. 167 patients with cirrhosis had DOT-reports, of which 120 also had self-reports. A significantly higher proportion of MHEICT patients with cirrhosis experienced crashes in the preceding year compared to those without MHE by self-report (17% vs 0.0%, P = 0.0004) and DOT-reports (17% vs 3%, P = 0.004, relative risk: 5.77). SPT did not differentiate between those with/without crashes. A significantly higher proportion of patients with crashes had MHEICT compared to MHESPT, both self-reported (100% vs 50%, P = 0.03) and DOT-reported (89% vs 44%, P = 0.01). There was excellent agreement between self and DOT-reports for crashes and violations (Kappa 0.90 and 0.80). 109 patients were followed prospectively. MHEICT patients had a significantly higher future crashes/violations compared to those without (22% vs 7%, P = 0.03) but MHESPT did not. MHEICT (Odds ratio: 4.51) and prior year crash/violation (Odds ratio: 2.96) were significantly associated with future crash/violation occurrence. CONCLUSION: Patients with cirrhosis and MHEICT have a significantly higher crash rate over the preceding year and on prospective follow-up compared to patients without MHE. ICT, but not SPT performance is significantly associated with prior and future crashes and violations. There was an excellent agreement between self- and DOT-reports.

The effect of fatigue on driving skills in patients with hepatic encephalopathy.

OBJECTIVES: Hepatic encephalopathy, both overt (OHE) and minimal (MHE), is associated with poor quality of life and fatigue. The aim of this study was to define the effect of fatigue on driving skills in MHE and OHE patients. METHODS: Cirrhotics and age/education-matched controls were administered a psychometric battery of tests to diagnose MHE. Cirrhotics with recent OHE on lactulose were also included. All subjects underwent a driving simulation; to assess fatigue, the second half performance was compared with the first half of the simulation. The outcomes were collisions, speeding, road excursions, and center crossings. Actual driving-associated fatigue was assessed by the American Medical Association (AMA) driver survey. RESULTS: A total of 100 cirrhotics (51 MHE, 27 no MHE, and 22 OHE) and 67 controls were included. A significantly higher proportion of OHE and MHE patients admitted to fatigue after actual driving on the AMA survey compared with no MHE patients (P=0.02). All patients who admitted to fatigue and none who denied fatigue on the AMA survey had simulator collisions. Psychometric and simulator performance in treated OHE patients was similarly impaired to MHE patients despite therapy. Within groups, a significant increase in collisions, speeding, and center crossings in the second half (P=0.01) was seen only in MHE patients. CONCLUSIONS: Psychometric and simulator performance in patients with recent OHE on treatment is similarly impaired as that of untreated MHE patients. Simulator performance in MHE worsens over time with fatigue. OHE and MHE patients had a higher rate of actual driving-associated fatigue on the AMA survey, which was significantly predictive of simulator collisions.

Decision-making, emotional distress, and quality of life in patients affected by the recall of their implantable cardioverter defibrillator.

AIMS: We sought to investigate whether patients with implantable cardioverter defibrillators (ICDs) were suffering from emotional distress related to the recent United States Food and Drug Administration (FDA) recalls, to better understand their decision process related to device replacement, and to assess any impact of recall on quality of life (QOL). METHODS AND RESULTS: Thirty-one patients experiencing device recalls answered questions regarding their knowledge about the recall and their decision whether to replace the device. Fifty patients whose devices were not recalled reported demographic data. In both groups, psychological factors were assessed. No significant differences were found for psychological factors. Most patients reported being informed of their recall by their physician. Most estimated the risk of device failure to be low or very low, but they overestimated the fail rate. Thirty-six per cent of patients reported feeling anxious about the recall. CONCLUSION: No significant differences existed in psychological factors and QOL between patients whose ICDs were recalled compared with those whose devices were not. The majority of patients whose ICDs are the subject of an FDA advisory/recall have a realistic understanding of the risks of device failure. Prompt information, support, and reassurance provided by healthcare professionals may allay patient distress.