Brief Behavioral Therapy and Bupropion for Sleep and Fatigue in Young Adults With Crohn's Disease: An Exploratory Open Trial Study.

BACKGROUND/AIMS: Sleep disturbances and fatigue are common symptoms amongst patients with Crohn's disease (CD). The aim of this study was to test the feasibility and effects of a pragmatic, stepped-care intervention for the treatment of poor sleep quality and fatigue in adolescents and young adults with CD. METHODS: This study is a two-phase open trial exploring interventions for sleep and fatigue. After the initial comprehensive assessment which included quantitative measures and an interview to evaluate sleep and physical and mental health, the 12-week intervention consisted of two sequential steps: 1) a brief behavioral therapy for sleep in inflammatory bowel disease (IBD) (BBTS-I; 4 weeks) and 2) adding the psychotropic medication, bupropion sustained release (BUP-SR; 8 weeks), for the subset of subjects continuing to experience fatigue. RESULTS: 232 CD patients (median age=24, median sex=female) were approached over 18 months, of whom 112 screened positive on the Pittsburgh Sleep Quality Index (PSQI) and multi-dimensional fatigue inventory (MFI), with 68 CD patients completing the more comprehensive baseline assessment. Of the 68 patients, 52 participated in Phase I of the BBTS-I intervention. Following 4-weeks of the BBTS-I, there were significant improvements in sleep quality (p < .001) and fatigue (p < .001). As part of Phase II, of the 52 patients who met fatigue threshold criteria, 33 patients participated in the BUP-SR+BBTS-I arm while 19 participated in the BBTS-I only intervention group. After 8 weeks of Phase II, both intervention groups saw significant further improvement in sleep, fatigue, anxiety and depressive symptoms, but without significant differences between the two intervention groups. CONCLUSIONS: A stepped-care approach shows that we can improve sleep disturbance with BBTS-I in CD patients, but fatigue only partially improves. For a subset of patients who chose to add BUP-SR to their behavioral therapy, fatigue improves further but not to a statistically significant effect compared to behavioral therapy alone.

Development and Validation of Computerized Adaptive Assessment Tools for the Measurement of Posttraumatic Stress Disorder Among US Military Veterans.

Importance: Veterans from recent and past conflicts have high rates of posttraumatic stress disorder (PTSD). Adaptive testing strategies can increase accuracy of diagnostic screening and symptom severity measurement while decreasing patient and clinician burden. Objective: To develop and validate a computerized adaptive diagnostic (CAD) screener and computerized adaptive test (CAT) for PTSD symptom severity. Design, Setting, and Participants: A diagnostic study of measure development and validation was conducted at a Veterans Health Administration facility. A total of 713 US military veterans were included. The study was conducted from April 25, 2017, to November 10, 2019. Main Outcomes and Measures: The participants completed a PTSD-symptom questionnaire from the item bank and provided responses on the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (PCL-5). A subsample of 304 participants were interviewed using the Clinician-Administered Scale for PTSD for DSM-5. Results: Of the 713 participants, 585 were men; mean (SD) age was 52.8 (15.0) years. The CAD-PTSD reproduced the Clinician-Administered Scale for PTSD for DSM-5 PTSD diagnosis with high sensitivity and specificity as evidenced by an area under the curve of 0.91 (95% CI, 0.87-0.95). The CAT-PTSD demonstrated convergent validity with the PCL-5 (r = 0.88) and also tracked PTSD diagnosis (area under the curve = 0.85; 95% CI, 0.79-0.89). The CAT-PTSD reproduced the final 203-item bank score with a correlation of r = 0.95 with a mean of only 10 adaptively administered items, a 95% reduction in patient burden. Conclusions and Relevance: Using a maximum of only 6 items, the CAD-PTSD developed in this study was shown to have excellent diagnostic screening accuracy. Similarly, using a mean of 10 items, the CAT-PTSD provided valid severity ratings with excellent convergent validity with an extant scale containing twice the number of items. The 10-item CAT-PTSD also outperformed the 20-item PCL-5 in terms of diagnostic accuracy. The results suggest that scalable, valid, and rapid PTSD diagnostic screening and severity measurement are possible.

Inter-channel phase differences during sleep spindles are altered in Veterans with PTSD.

Sleep disturbances are common complaints in patients with post-traumatic stress disorder (PTSD). To date, however, objective markers of PTSD during sleep remain elusive. Sleep spindles are distinctive bursts of brain oscillatory activity during non-rapid eye movement (NREM) sleep and have been implicated in sleep protection and sleep-dependent memory processes. In healthy sleep, spindles observed in electroencephalogram (EEG) data are highly synchronized across different regions of the scalp. Here, we aimed to investigate whether the spatiotemporal synchronization patterns between EEG channels during sleep spindles, as quantified by the phase-locking value (PLV) and the mean phase difference (MPD), are altered in PTSD. Using high-density (64-channel) EEG data recorded from 78 combat-exposed Veteran men (31 with PTSD and 47 without PTSD) during two consecutive nights of sleep, we examined group differences in the PLV and MPD for slow (10-13 Hz) and fast (13-16 Hz) spindles separately. To evaluate the reproducibility of our findings, we set apart the first 47 consecutive participants (18 with PTSD) for the initial discovery and reserved the remaining 31 participants (13 with PTSD) for replication analysis. In the discovery analysis, compared to the non-PTSD group, the PTSD group showed smaller MPDs during slow spindles between the frontal and centro-parietal channel pairs on both nights. We obtained reproducible results in the replication analysis in terms of statistical significance and effect size. The PLVs during slow or fast spindles did not significantly differ between groups. The reduced inter-channel phase difference during slow spindles in PTSD may reflect pathological changes in the underlying thalamocortical circuits. This novel finding, if independently validated, may prove useful in developing sleep-focused PTSD diagnostics and interventions.

Deployment Length, Inflammatory Markers, and Ambulatory Blood Pressure in Military Couples.

INTRODUCTION: Changes in the frequency, duration, and nature of military deployments over the past 14 years have spurred efforts to understand the effects of deployment on the health of military service members and their spouses. However, few studies have examined the impact of deployments on health outcomes in both veterans and their partners. This study aims to examine the association between deployment length and health, including ambulatory blood pressure (BP) and stress-related markers of inflammation, in military veterans and their spouses. MATERIALS AND METHODS: This study includes 32 male veterans and 29 female civilian partners. Veterans reported about their deployment and military experiences, including deployment length, combat exposure, and post-traumatic stress disorder (PTSD) symptoms. Plasma measures of inflammatory markers, C-reactive protein (CRP) and interleukin 6 (IL-6), were collected from veterans and spouses. Participants also completed 48 hours of BP monitoring for calculation of mean arterial pressure (MAP) during wakefulness and sleep, and sleep/wake MAP ratio, as an indicator BP nondipping. Regression models examined the association between deployment length and each outcome in the combined sample of veterans and their spouses, including tests of interactions between gender and deployment length, controlling for age, gender, waist circumference, current PTSD, and combat exposure. RESULTS: Longer deployment length was associated with higher CRP levels in veterans and their spouses, although this effect became nonsignificant when limiting analyses to individuals with CRP ≤10 mg/L. There was a significant gender by deployment length interaction effect on MAP ratio, such that longer deployments were associated with higher MAP ratios in female spouses. There was no significant effect of combat exposure in these models. CONCLUSION: Longer deployments are associated with health-related markers in military veterans as well as their spouses. These results suggest the importance of monitoring health during and postdeployment, and of finding ways to mitigate the adverse impact of deployment on health in both members of military couples.

Psychometric properties of the Brazilian version of the Pittsburgh Sleep Quality Index Addendum for PTSD (PSQI-A)

Objective: Sleep disturbances play a fundamental role in the pathophysiology posttraumatic stress disorder (PTSD), and are not only a secondary feature. The aim of this study was to validate and assess the psychometric properties of the Brazilian version of the Pittsburgh Sleep Quality Index Addendum for PTSD (PSQI-A-BR), a self-report instrument designed to assess the frequency of seven disruptive nocturnal behaviors, in a sample of participants with and without PTSD. Methods: PSQI-A was translated into Brazilian Portuguese and applied to a convenience sample of 190 volunteers, with and without PTSD, who had sought treatment for the consequences of a traumatic event. Results: The PSQI-A-BR displayed satisfactory internal consistency (Cronbach's coefficient of 0.83 between all items) and convergent validity with the Clinician Administered PTSD Scale (CAPS), even when excluding sleep-related items (r = 0.52). Test-retest yielded high agreement in the global PSQI-A-BR, with good stability over time (r = 0.88). A global PSQI-A-BR cutoff score of 7 yielded a sensitivity of 79%, specificity of 64%, and a global score of 7 yielded a positive predictive value of 93% for discriminating participants with PTSD from those without PTSD. Conclusion: The PSQI-A-BR is a valid instrument for PTSD assessment, applicable to both clinical and research settings. .

Factors associated with noninvasive coronary flow reserve in severe aortic stenosis.

BACKGROUND: Coronary flow reserve (CFR) is progressively impaired with aortic stenosis (AS) severity. However, there is a broad range of CFR in patients with severe AS, and the factors responsible for this variability are weakly characterized. The aim of this study was to assess the correlates of noninvasive CFR in patients with severe AS (≤1 cm(2) or ≤0.6 cm(2)/m(2)) and preserved left ventricular (LV) ejection fractions (LVEFs) (>50%). METHODS: Sixty-six consecutive patients (mean age, 74 ± 11 years; 31 women; mean LVEF, 69 ± 10%) with isolated severe AS (mean, 0.75 ± 0.2 cm(2) and 0.42 ± 0.1 cm(2)/m(2)), without coronary artery disease, underwent prospectively Doppler transthoracic echocardiography including CFR measurement in the distal part of the left anterior descending coronary artery (LAD) with intravenous adenosine infusion (140 µg/kg/min over 2 min). CFR was defined as hyperemic peak LAD flow velocity divided by baseline flow velocity. Twenty controls matched for age and gender served as a comparative group. Plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) was also assessed. RESULTS: Compared with controls, patients with AS had higher baseline LAD flow velocities (36 ± 11 vs 27 ± 6 cm/sec, P < 0.01), lower hyperemic LAD flow velocities (80 ± 20 vs 89 ± 18 cm/sec, P = .09), and consequently lower CFR (2.3 ± 0.7 vs 3.3 ± 0.7, P < .01). In patients with AS, there were significant inverse correlations between CFR and age, E/e', indexed LV mass, NT-proBNP, pulmonary artery systolic pressure (PASP), baseline LV rate-pressure product, heart rate, and indexed left atrial volume and a significant positive correlation between CFR and LVEF (all P values < .05). Furthermore, compared with patients with asymptomatic AS (n = 22), those with symptomatic AS had more severely impaired CFR (2.15 ± 0.6 vs 2.7 ± 0.65), and higher NT-proBNP values (all P values < .05). In multivariate analysis, NT-proBNP, PASP, and LV rate-pressure product were the main independent correlates of CFR (all P values ≤ .01), and PASP was independently predicted by E/e' and indexed left atrial volume (all P values < .01). CONCLUSIONS: In patients with severe AS and preserved LVEFs, there is a relatively broad range of CFR values. CFR is more severely impaired in patients with symptomatic AS and is mainly linked with NT-proBNP, a surrogate of increased LV wall stress, workload as measured by LV rate-pressure product, and PASP.

Predictors of acute posttraumatic stress disorder symptoms following civilian trauma: highest incidence and severity of symptoms after assault.

BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with significant morbidity following injury. The incidence and risk factors for PTSD are not well described in the civilian trauma population. We proposed to screen all trauma patients in the outpatient trauma clinic for acute PTSD symptoms and identify risk factors for PTSD. METHODS: We prospectively screened 1,386 injured patients who presented for follow-up in trauma clinic (January 2009 to September 2010) using an established PTSD screening test (PTSD Checklist-Civilian, PCL-C). A PCL-C score of ≥35, with a known sensitivity of >85% for PTSD, was considered screen-positive (PCL-C-POS). Backward stepwise logistic regression was used to determine independent risk factors for PCL-C-POS. RESULTS: Over 25% of trauma clinic patients met the threshold for positive PTSD screen (PCL-C-POS). The highest incidence (43%) was in patients who sustained assault (blunt or penetrating). Regression analysis revealed that age <55 years, female gender, motor vehicle collision, and assaultive mechanism (blunt or penetrating, excluding self-inflicted or accidental injury) were independent predictors of PCL-C-POS status. As the severity of symptoms increased (higher PCL-C scores), the risk associated with assaultive mechanism significantly increased in a dose-response fashion (p < 0.05). CONCLUSIONS: This study confirms the high incidence of acute PTSD symptoms in trauma patients and supports the feasibility of PTSD screening in the outpatient trauma clinic. Among all mechanisms of injury, patients who sustain interpersonal violence are at the highest risk of developing acute PTSD symptoms. These results suggest that PTSD screening in outpatient trauma clinic may allow early detection and referral of patients with PTSD. LEVEL OF EVIDENCE: II.