Factors associated with the humoral response after three doses of COVID-19 vaccination in kidney transplant recipients.

Introduction: Kidney transplant recipients showed a weak humoral response to the mRNA COVID-19 vaccine despite receiving three cumulative doses of the vaccine. New approaches are still needed to raise protective immunity conferred by the vaccine administration within this group of high-risk patients. Methods: To analyze the humoral response and identify any predictive factors within these patients, we designed a prospective monocentric longitudinal study of Kidney transplant recipients (KTR) who received three doses of mRNA-1273 COVID-19 vaccine. Specific antibody levels were measured by chemiluminescence. Parameters related to clinical status such as kidney function, immunosuppressive therapy, inflammatory status and thymic function were analyzed as potential predictors of the humoral response. Results: Seventy-four KTR and sixteen healthy controls were included. One month after the administration of the third dose of the COVID-19 vaccine, 64.8% of KTR showed a positive humoral response. As predictive factors of seroconversion and specific antibody titer, we found that immunosuppressive therapy, worse kidney function, higher inflammatory status and age were related to a lower response in KTR while immune cell counts, thymosin-a1 plasma concentration and thymic output were related to a higher humoral response. Furthermore, baseline thymosin-a1 concentration was independently associated with the seroconversion after three vaccine doses. Discussion: In addition to the immunosuppression therapy, condition of kidney function and age before vaccination, specific immune factors could also be relevant in light of optimization of the COVID-19 vaccination protocol in KTR. Therefore, thymosin-a1, an immunomodulatory hormone, deserves further research as a potential adjuvant for the next vaccine boosters.

Massed vs Intensive Outpatient Prolonged Exposure for Combat-Related Posttraumatic Stress Disorder: A Randomized Clinical Trial.

Importance: Improved, efficient, and acceptable treatments are needed for combat-related posttraumatic stress disorder (PTSD). Objective: To determine the efficacy of 2 compressed prolonged exposure (PE) therapy outpatient treatments for combat-related PTSD. Design, Setting, and Participants: This randomized clinical trial was conducted among military personnel and veterans at 4 sites in Texas from 2017 to 2019. Assessors were blinded to conditions. Data were analyzed from November 2020 to October 2022. Interventions: The interventions were massed-PE, which included 15 therapy sessions of 90 minutes each over 3 weeks, vs intensive outpatient program PE (IOP-PE), which included 15 full-day therapy sessions over 3 weeks with 8 treatment augmentations. The IOP-PE intervention was hypothesized to be superior to massed-PE. Main Outcomes and Measures: Coprimary outcomes included the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5) (CAPS-5) and the PTSD Checklist for DSM-5 (PCL-5) administered at baseline and posttreatment follow-ups. Measures ranged from 0 to 80, with higher scores indicating greater severity. Diagnostic remission and reliable change were secondary outcomes. Results: Among 319 military personnel and veterans screened, 234 were randomized (mean [SD] age, 39.20 [7.72] years; 182 [78%] male participants), with 117 participants randomized to IOP-PE and 117 participants randomized to massed-PE. A total of 61 participants (26%) were African American, 58 participants (25%) were Hispanic, and 102 participants (44%) were White; 151 participants (65%) were married. Linear mixed-effects models found that CAPS-5 scores decreased in both treatment groups at the 1-month follow-up (IOP-PE: mean difference, -13.85 [95% CI, -16.47 to -11.23]; P < .001; massed-PE: mean difference, -14.13 [95% CI, -16.63 to -11.62]; P < .001). CAPS-5 change scores differed from 1- to 6-month follow-ups (mean difference, 4.44 [95% CI, 0.89 to 8.01]; P = .02). PTSD symptoms increased in massed-PE participants during follow-up (mean difference, 3.21 [95% CI, 0.65 to 5.77]; P = .01), whereas IOP-PE participants maintained treatment gains (mean difference, 1.23 [95% CI, -3.72 to 1.27]; P = .33). PCL-5 scores decreased in both groups from baseline to 1-month follow-up (IOP-PE: mean difference, -21.81 [95% CI, -25.57 to -18.04]; P < .001; massed-PE: mean difference, -19.96 [95% CI, -23.56 to -16.35]; P < .001) and were maintained at 6 months (IOP-PE: mean change, -0.21 [95% CI, -3.47 to 3.06]; P = .90; massed-PE: mean change, 3.02 [95% CI, -0.36 to 6.40]; P = .08). Both groups had notable PTSD diagnostic remission at posttreatment (IOP-PE: 48% [95% CI, 36% to 61%] of participants; massed-PE: 62% [95% CI, 51% to 73%] of participants), which was maintained at 6 months (IOP-PE: 53% [95% CI, 40% to 66%] of participants; massed-PE: 52% [95% CI, 38% to 66%] of participants). Most participants demonstrated reliable change on the CAPS-5 (61% [95% CI, 52% to 69%] of participants) and the PCL-5 (74% [95% CI, 66% to 81%] of participants) at the 1-month follow-up. Conclusions and Relevance: These findings suggest that PE can be adapted into compressed treatment formats that effectively reduce PTSD symptoms. Trial Registration: ClinicalTrials.gov Identifier: NCT03529435.

Patterns of acute stress disorder in a sample of blast-injured military service members: A latent profile analysis.

OBJECTIVE: The primary aims of this study were to identify latent profiles of acute stress disorder (ASD) symptoms and to evaluate postconcussive symptom differences across the identified profiles as measured by the Acute Stress Disorder Scale and the Military Acute Concussion Evaluation, respectively. METHOD: Participants (N = 315) in the current study were predominantly active-duty (75.0%), enlisted (97.8%) males (97.4%) serving in the U.S. Army (87.8%). Approximately, half of the sample reported being married or engaged (51.1%) and was on average 25.94 (SD = 6.31) years old. Participants were referred to the Air Force Theater Hospital, 332nd Air Expeditionary Wing, Joint Base Balad, Iraq, to be evaluated as part of routine clinical assessment for neurocognitive and psychological symptoms following exposure to a blast. RESULTS: A 3-profile solution was identified as the most parsimonious and best-fitting model based on statistical model fit indices. Blast injured service members in Profile 3 had greater ASD total and subscale severity compared to the other 2 subgroups, with effect size estimates largely differing by hyperarousal and reexperiencing symptoms. Furthermore, Profiles 2 and 3 were more likely to demonstrate postconcussive symptoms compared to Profile 1. CONCLUSIONS: Findings provide novel information on heterogenous ASD symptom profiles during the acute phase following a blast injury and highlight the relationship between psychological and physical symptoms. Classification of blast-injured service members may help identify at-risk individuals who would benefit from further clinical care and mitigate long-term psychological and neurocognitive issues. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Combining a stellate ganglion block with prolonged exposure therapy for posttraumatic stress disorder: A nonrandomized clinical trial.

Prolonged exposure therapy (PE) is an efficacious treatment for active duty service members and veterans with posttraumatic stress disorder (PTSD). However, PE is sometimes associated with high dropout rates, limited tolerability, and temporary symptom exacerbation during treatment. Stellate ganglion blocks (SGBs) are an emerging treatment that has the potential to enhance outcomes for PTSD when combined with trauma-focused psychotherapy. To date, no study of which we are aware has examined the potential additive benefits of SGB injections when administered in conjunction with trauma-focused behavioral treatment for PTSD. Thus, we conducted a nonrandomized clinical trial to evaluate the use of an SGB combined with massed PE therapy for combat-related PTSD. Participants (N = 12) were treated with 10 daily 90-min PE sessions delivered over 2 weeks and received a single SGB injection between Sessions 1 and 2. PE sessions lasted 90 min each. Participants reported a mean posttreatment PTSD symptom reduction of 32 points on the PTSD Checklist for DSM-5 (PCL-5), Hedges' gs = 1.28-2.80. Most participants (90.9%) demonstrated clinically significant change on the PCL-5 (i.e., ≥10 points) by the final treatment session and 50.0% no longer met the diagnostic criteria for PTSD per the Clinician-Administered PTSD Scale for DSM-5 at 1-month follow-up. Adverse events for the combined treatment were consistent with those previously reported for standalone SGB and PE. This combined treatment approach provides promising results for improving the tolerability of trauma-focused therapies, reducing symptom severity, and increasing PTSD remission rates.

Post-9/11 service members: Associations between gender, marital status, and psychiatric aeromedical evacuations from combat zones.

Psychiatric aeromedical evacuations are one of the leading causes of medical related evacuations of US military personnel from combat. Currently, no studies have examined gender and marital status of individuals who were evacuated from combat for a psychiatric diagnosis. Psychiatric aeromedical evacuation data from 5,957 United States military personnel deployed to Iraq or Afghanistan between 2001 and 2013 were analyzed using chi-square tests of independence, odds ratios (OR), and standardized residuals. Analyses showed that female service members were evacuated at higher rates (178 per 100,000) than males (115 per 100,000). When compared to nonmarried females, married females did not present with increased risk of psychiatric aeromedical evacuation on any diagnosis. Married males, however, were more likely to be evacuated than married females for PTSD (OR = 1.98) and TBI (OR = 1.14). Likewise, married males, compared to nonmarried males, were more likely to be evacuated for PTSD (OR = 1.66) and anxiety (OR = 1.38). Although deployments can be extremely stressful experiences for some military service members, they may be especially so among unmarried females and married males. This study provides a unique contribution to enhancing the understanding of risk factors related to psychiatric aeromedical evacuation for deployed service members.

Demographic and Occupational Risk Factors Associated With Suicide-Related Aeromedical Evacuation Among Deployed U.S. Military Service Members.

INTRODUCTION: Suicide is a significant problem in the U.S. military, with rates surpassing the U.S. general population as of 2008. Although there have been significant advances regarding suicide risk factors among U.S. military service members and veterans, there is little research about risk factors associated with suicide that could be potentially identified in theater. One salient study group consists of service members who receive a psychiatric aeromedical evacuation out of theater. The primary aims of this study were as follows: (1) determine the incidence of suicide-related aeromedical evacuation in deployed service members, (2) identify demographic and military characteristics associated with suicide-related aeromedical evacuation, and (3) evaluate the relationship between suicide-related aeromedical evacuation from a deployed setting and military separation. MATERIALS AND METHODS: This was an archival analysis of U.S. Transportation Command Regulating and Command and Control Evacuation System and Defense Manpower Data Center electronic records of U.S. military service members (N = 7023) who were deployed to Iraq or Afghanistan and received a psychiatric aeromedical evacuation out of theater between 2001 and 2013. χ2 tests of independence and standardized residuals were used to identify cells with observed frequencies and proportions, respectively, that significantly differed from what would be expected by chance. In addition, odds ratios were calculated to provide context about the nature of any significant relationships. RESULTS: For every 1000 psychiatric aeromedical evacuations that occurred between 2001 and 2013, 34.4 were suicide related. Gender, ethnicity, branch of service, occupation classification, and deployment theater were associated with suicide-related aeromedical evacuation (odds ratios ranged from 1.37 to 3.02). Overall, 53% of all service members who received an aeromedical evacuation for any psychiatric condition had been separated from the military for a variety of reasons (both voluntary and involuntary) upon record review in 2015. Suicide-related aeromedical evacuation was associated with a 37% increased risk of military separation compared to evacuation for another psychiatric condition (P < 0.02). CONCLUSIONS: Findings provide novel information on risk factors associated with suicide-related aeromedical evacuation as well as military separation following a suicide-related aeromedical evacuation. In many cases, the psychiatric aeromedical evacuation of a service member for suicidal ideations and their subsequent separation from active duty is in the best interest of the individual and the military. However, the evacuation and eventual military separation can be costly for the military and the service member. Consequently, the military should focus on indicated prevention interventions for individuals who show sufficient early signs of crisis and functional problems so that specialized interventions can be used in theater to prevent evacuation. Indicated prevention interventions should start with leaders' awareness and mitigation of risk and, when feasible, evidence-based interventions for suicide risk provided by behavioral health (eg, brief cognitive behavioral therapy for suicide). Future research should evaluate the feasibility, safety, and efficacy of delivering suicide-related interventions in theater.

The Trauma and Suicide Potential Index-5: Psychometric Evaluation in College Samples.

We provide a brief description of the development of the Trauma and Suicide Potential Index-5 (TSPI-5) and report on the psychometric properties of scores from the new instrument. The TSPI-5 is designed to assess an individual's desire to attempt suicide due to experiencing a trauma. We examined the structure of the instrument in two independent undergraduate samples. Study 1 (N = 415) examined the structure of the TSPI-5 using exploratory structural equation modeling. Study 2 (N = 538) reexamined the instrument structure using the same modeling strategy and also examined other validity estimates. Study 1 demonstrated an adequate fit to the sample data (χ2 [1, N = 415] = 215.99, p < .001, comparative fit index (CFI ) = .969, Tucker-Lewis non-normed fit index (TLI) = .939, root mean squared error of approximation (RMSEA) = .319 [90% confidence interval (CI) = .283, .356], p < .001) and suggested evidence for unidimensionality. Study 2 confirmed the unidimensionality of the TSPI-5 as shown by acceptable fit estimates to the sample data, χ2 (5, N = 538) = 80.45, p < .001, CFI = .996, TLI = .99, RMSEA = .17 (90% CI = .140, .200), p < .001. Scale reliability estimates for the TSPI-5 were good in Study 1 (omega = .94) and Study 2 (omega = .96). The TSPI-5 is a brief unidimensional instrument and its scores demonstrated good reliability and validity for assessing suicide-related behaviors due to experiencing a trauma in undergraduate samples.

The Functional Ability of MCI and Alzheimer's Patients Predicts Caregiver Burden.

Sixty patients and their caregivers participated in this study. Patients completed activities of daily living tasks and several neuropsychological tests assessing memory, abstract reasoning, and language. Caregivers completed self-report measures assessing caregiver burden and psychological distress. Results revealed that the mAD caregivers endorsed greater physical burden and feelings of missing out on life compared to MCI caregivers. The mAD caregivers indicated greater depression and anxiety relative to MCI caregivers. Stepwise regression found that fewer patient neuropsychological scores predicted caregiver burden, as compared to patients' daily functioning. Overall, mAD displayed more severe types of burden and psychological distress relative to MCI caregivers and patients' daily functional abilities better predicated caregivers' burden and psychological distress than patients' neuropsychological functioning.

Intensive prolonged exposure therapy for combat-related posttraumatic stress disorder: Design and methodology of a randomized clinical trial.

Combat-related posttraumatic stress disorder (PTSD) is the most common psychological health condition in military service members and veterans who have deployed to the combat theater since September 11, 2001. One of the highest research priorities for the Department of Defense and the Department of Veterans Affairs is to develop and evaluate the most efficient and efficacious treatments possible for combat-related PTSD. However, the treatment of combat-related PTSD in military service members and veterans has been significantly more challenging than the treatment of PTSD in civilians. Randomized clinical trials have demonstrated large posttreatment effect sizes for PTSD in civilian populations. However, recent randomized clinical trials of service members and veterans have achieved lesser reductions in PTSD symptoms. These results suggest that combat-related PTSD is unique. Innovative approaches are needed to augment established evidence-based treatments with targeted interventions that address the distinctive elements of combat-related traumas. This paper describes the design, methodology, and protocol of a randomized clinical trial to compare two intensive prolonged exposure therapy treatments for combat-related PTSD in active duty military service members and veterans and that can be administered in an acceptable, efficient manner in this population. Both interventions include intensive daily treatment over a 3-week period and a number of treatment enhancements hypothesized to result in greater reductions in combat-related PTSD symptoms. The study is designed to advance the delivery of care for combat-related PTSD by developing and evaluating the most potent treatments possible to reduce PTSD symptomatology and improve psychological, social, and occupational functioning.

Acute Assessment of Traumatic Brain Injury and Post-Traumatic Stress After Exposure to a Deployment-Related Explosive Blast.

Introduction: Traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are two of the signature injuries in military service members who have been exposed to explosive blasts during deployments to Iraq and Afghanistan. Acute stress disorder (ASD), which occurs within 2-30 d after trauma exposure, is a more immediate psychological reaction predictive of the later development of PTSD. Most previous studies have evaluated service members after their return from deployment, which is often months or years after the initial blast exposure. The current study is the first large study to collect psychological and neuropsychological data from active duty service members within a few days after blast exposure. Materials and Methods: Recruitment for blast-injured TBI patients occurred at the Air Force Theater Hospital, 332nd Air Expeditionary Wing, Joint Base Balad, Iraq. Patients were referred from across the combat theater and evaluated as part of routine clinical assessment of psychiatric and neuropsychological symptoms after exposure to an explosive blast. Four measures of neuropsychological functioning were used: the Military Acute Concussion Evaluation (MACE); the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS); the Headminder Cognitive Stability Index (CSI); and the Automated Neuropsychological Assessment Metrics, Version 4.0 (ANAM4). Three measures of combat exposure and psychological functioning were used: the Combat Experiences Scale (CES); the PTSD Checklist-Military Version (PCL-M); and the Acute Stress Disorder Scale (ASDS). Assessments were completed by a deployed clinical psychologist, clinical social worker, or mental health technician. Results: A total of 894 patients were evaluated. Data from 93 patients were removed from the data set for analysis because they experienced a head injury due to an event that was not an explosive blast (n = 84) or they were only assessed for psychiatric symptoms (n = 9). This resulted in a total of 801 blast-exposed patients for data analysis. Because data were collected in-theater for the initial purpose of clinical evaluation, sample size varied widely between measures, from 565 patients who completed the MACE to 154 who completed the CES. Bivariate correlations revealed that the majority of psychological measures were significantly correlated with each other (ps ≤ 0.01), neuropsychological measures were correlated with each other (ps ≤ 0.05), and psychological and neuropsychological measures were also correlated with each other (ps ≤ 0.05). Conclusions: This paper provides one of the first descriptions of psychological and neuropsychological functioning (and their inter-correlation) within days after blast exposure in a large sample of military personnel. Furthermore, this report describes the methodology used to gather data for the acute assessment of TBI, PTSD, and ASD after exposure to an explosive blast in the combat theater. Future analyses will examine the common and unique symptoms of TBI and PTSD, which will be instrumental in developing new assessment approaches and intervention strategies.