Convalescent plasma associates with reduced mortality and improved clinical trajectory in patients hospitalized with COVID-19.

BACKGROUNDEvidence supporting convalescent plasma (CP), one of the first investigational treatments for coronavirus disease 2019 (COVID-19), has been inconclusive, leading to conflicting recommendations. The primary objective was to perform a comparative effectiveness study of CP for all-cause, in-hospital mortality in patients with COVID-19.METHODSThe multicenter, electronic health records-based, retrospective study included 44,770 patients hospitalized with COVID-19 in one of 176 HCA Healthcare-affiliated community hospitals. Coarsened exact matching (1:k) was employed, resulting in a sample of 3774 CP and 10,687 comparison patients.RESULTSExamination of mortality using a shared frailty model, controlling for concomitant medications, date of admission, and days from admission to transfusion, demonstrated a significant association of CP with lower mortality risk relative to the comparison group (adjusted hazard ratio [aHR] = 0.71; 95% CI, 0.59-0.86; P < 0.001). Examination of patient risk trajectories, represented by 400 clinico-demographic features from our real-time risk model (RTRM), indicated that patients who received CP recovered more quickly. The stratification of days to transfusion revealed that CP within 3 days after admission, but not within 4 to 7 days, was associated with a significantly lower mortality risk (aHR = 0.53; 95% CI, 0.47-0.60; P < 0.001). CP serology level was inversely associated with mortality when controlling for its interaction with days to transfusion (HR = 0.998; 95% CI, 0.997-0.999; P = 0.013), yet it did not reach univariable significance.CONCLUSIONSThis large, diverse, multicenter cohort study demonstrated that CP, compared with matched controls, is significantly associated with reduced risk of in-hospital mortality. These observations highlight the utility of real-world evidence and suggest the need for further evaluation prior to abandoning CP as a viable therapy for COVID-19.FUNDINGThis research was supported in whole by HCA Healthcare and/or an HCA Healthcare-affiliated entity, including Sarah Cannon and Genospace.

The mediating impact of PTSD symptoms on cortisol awakening response in the context of intimate partner violence.

Multi-level modeling examined the association between cortisol awakening responses (CAR) and different PTSD symptom clusters in a sample of 158 female participants presenting with intimate partner violence-related PTSD. Results revealed that arousal over the past week and month, respectively ([ß = -0.124, z = -2.33, p = .028; ß = -.147, z = -2.19, p = .028]) significantly moderated the trajectory of cortisol levels, and emotional numbing symptom severity (over the past week [ß = -0.122, z = -2.07, p = .076]) was found to be trending toward significance. In each case higher symptom severity was associated with flatter CAR slopes compared to those with lower symptom severity. Assessing PTSD symptom clusters in relation to cortisol may better inform future interventions compared to studies that assess PTSD globally. Our findings suggest a subtype of PTSD patients displaying higher levels of arousal may be more likely to experience alterations in HPA axis functioning.

Genomic influences on self-reported childhood maltreatment.

Childhood maltreatment is highly prevalent and serves as a risk factor for mental and physical disorders. Self-reported childhood maltreatment appears heritable, but the specific genetic influences on this phenotype are largely unknown. The aims of this study were to (1) identify genetic variation associated with self-reported childhood maltreatment, (2) estimate SNP-based heritability (h2snp), (3) assess predictive value of polygenic risk scores (PRS) for childhood maltreatment, and (4) quantify genetic overlap of childhood maltreatment with mental and physical health-related phenotypes, and condition the top hits from our analyses when such overlap is present. Genome-wide association analysis for childhood maltreatment was undertaken, using a discovery sample from the UK Biobank (UKBB) (n = 124,000) and a replication sample from the Psychiatric Genomics Consortium-posttraumatic stress disorder group (PGC-PTSD) (n = 26,290). h2snp for childhood maltreatment and genetic correlations with mental/physical health traits were calculated using linkage disequilibrium score regression. PRS was calculated using PRSice and mtCOJO was used to perform conditional analysis. Two genome-wide significant loci associated with childhood maltreatment (rs142346759, p = 4.35 × 10-8, FOXP1; rs10262462, p = 3.24 × 10-8, FOXP2) were identified in the discovery dataset but were not replicated in PGC-PTSD. h2snp for childhood maltreatment was ~6% and the PRS derived from the UKBB was significantly predictive of childhood maltreatment in PGC-PTSD (r2 = 0.0025; p = 1.8 × 10-15). The most significant genetic correlation of childhood maltreatment was with depressive symptoms (rg = 0.70, p = 4.65 × 10-40), although we show evidence that our top hits may be specific to childhood maltreatment. This is the first large-scale genetic study to identify specific variants associated with self-reported childhood maltreatment. Speculatively, FOXP genes might influence externalizing traits and so be relevant to childhood maltreatment. Alternatively, these variants may be associated with a greater likelihood of reporting maltreatment. A clearer understanding of the genetic relationships of childhood maltreatment, including particular abuse subtypes, with a range of phenotypes, may ultimately be useful in in developing targeted treatment and prevention strategies.

Improving our understanding of the relationship between emotional abuse and substance use disorders: the mediating roles of negative urgency and posttraumatic stress disorder.

Background: Emotional abuse is associated with an increased risk for substance use disorders (SUDs) as well as with negative urgency and posttraumatic stress disorder (PTSD) following a subsequent trauma. Both negative urgency and PTSD are key contributors to the relationship between emotional abuse and SUDs when examined separately. A comprehensive model including both factors can inform models of PTSD-SUD comorbidity. Furthermore, the comparison of these mechanistic roles in emotional versus other types of abuse can shed light on the specificity of these effects. Objectives: The present study tested whether negative urgency and PTSD symptom severity serially mediated the relationship between emotional abuse and substance use across two separate samples. Method: Participants were recruited from a detoxification center and completed a battery of surveys examining abuse history, PTSD symptom severity, and impulsivity measures including negative urgency and substance use history during the last 3 months. The samples consisted of predominantly (59% and 62%) males with an average age of 35 (age range: 18-65). The majority of participants (90% and 93%) were Caucasian. Results: Study 1 (N = 368) and Study 2 (N = 274) both found that negative urgency and PTSD symptom severity serially mediated the relationship between emotional abuse and substance use. When comparing indirect effects, both contributed equally. Conclusion: These findings suggest that negative urgency and PTSD symptom severity together account more for the link between emotional abuse and SUDs than either alone and argue for the inclusion of negative urgency in models of PTSD-SUD comorbidity.

A multi-level modeling approach examining PTSD symptom reduction during prolonged exposure therapy: moderating effects of number of trauma types experienced, having an HIV-related index trauma, and years since HIV diagnosis among HIV-positive adults.

People living with HIV (PLWH) have extensive interpersonal trauma histories and higher rates of posttraumatic stress disorder (PTSD) than the general population. Prolonged exposure (PE) therapy is efficacious in reducing PTSD across a variety of trauma samples; however, research has not examined factors that influence how PTSD symptoms change during PE for PLWH. Using multi-level modeling, we examined the potential moderating effect of number of previous trauma types experienced, whether the index trauma was HIV-related or not, and years since HIV diagnosis on PTSD symptom reduction during a 10-session PE protocol in a sample of 51 PLWH. In general, PTSD symptoms decreased linearly throughout the PE sessions. Experiencing more previous types of traumatic events was associated with a slower rate of PTSD symptom change. In addition, LOCF analyses found that participants with a non-HIV-related versus HIV-related index trauma had a slower rate of change for PTSD symptoms over the course of PE. However, analyses of raw data decreased this finding to marginal. Years since HIV diagnosis did not impact PTSD symptom change. These results provide a better understanding of how to tailor PE to individual clients and aid clinicians in approximating the rate of symptom alleviation. Specifically, these findings underscore the importance of accounting for trauma history and index trauma type when implementing a treatment plan for PTSD in PLWH.