Empirically Derived Patterns of Posttraumatic Stress and Growth: A Systematic Review.

The relationship between posttraumatic stress (PTS) and posttraumatic growth (PTG) has been extensively studied; however, the nature of the relationship remains unclear. Inconsistencies in the literature could be, in part, due to the use of variable level approaches. Person centered methods may further our understanding of this relationship, as they enable the identification of clinically meaningful subgroups based on PTS/PTG scores. This review aimed to identify commonly found subgroups of PTS and PTG, clinically relevant factors that distinguish the subgroups and to critically appraise the utility of categorizing individuals into subgroups based on PTS/PTG scores. Five databases (Embase, Medline, Web of Science, PILOTS, and PsycINFO) were searched. Seven studies (with a total of eight study samples; n = 6,776) met the eligibility criteria. A narrative synthesis of the findings revealed that the majority of the analyses (n = 6) found three patterns of PTS/PTG. These were categorized as: (1) low PTS/PTG (representing 26.89% of the entire sample), (2) high PTS/PTG (weighted mean percentage = 20.05%), and (3) low PTS/high PTG (weighted mean percentage = 43.1%). The role of social support was examined in five studies and higher social support was consistently found to predict membership in the low PTS/high PTG class. All five studies that examined the role of trauma characteristics found that it was a significant predictor of class membership. These findings could inform the developments of tailored interventions. The utility of person-centered approaches was discussed and recommendations to improve the application and reporting of such methods were made.

Results of genetic analysis of 11 341 participants enrolled in the My Life, Our Future hemophilia genotyping initiative in the United States.

BACKGROUND: Hemophilia A (HA) and hemophilia B (HB) are rare inherited bleeding disorders. Although causative genetic variants are clinically relevant, in 2012 only 20% of US patients had been genotyped. OBJECTIVES: My Life, Our Future (MLOF) was a multisector cross-sectional US initiative to improve our understanding of hemophilia through widespread genotyping. METHODS: Subjects and potential genetic carriers were enrolled at US hemophilia treatment centers (HTCs). Bloodworks performed genotyping and returned results to providers. Clinical data were abstracted from the American Thrombosis and Hemostasis Network dataset. Community education was provided by the National Hemophilia Foundation. RESULTS: From 2013 to 2017, 107 HTCs enrolled 11 341 subjects (68.8% male, 31.2% female) for testing for HA (n = 8976), HB (n = 2358), HA/HB (n = 3), and hemophilia not otherwise specified (n = 4). Variants were detected in most male patients (98.2%% HA, 98.1% HB). 1914 unique variants were found (1482 F8, 431 F9); 744 were novel (610 F8, 134 F9). Inhibitor data were available for 6986 subjects (5583 HA; 1403 HB). In severe HA, genotypes with the highest inhibitor rates were large deletions (77/80), complex intron 22 inversions (9/17), and no variant found (7/14). In severe HB, the highest rates were large deletions (24/42). Inhibitors were reported in 27.3% of Black versus 16.2% of White patients. CONCLUSIONS: The findings of MLOF are reported, the largest hemophilia genotyping project performed to date. The results support the need for comprehensive genetic approaches in hemophilia. This effort has contributed significantly towards better understanding variation in the F8 and F9 genes in hemophilia and risks of inhibitor formation.

The Mediating Role of Distress Tolerance in the Relationship Between Childhood Maltreatment and Mental Health Outcomes Among University Students.

A wealth of empirical literature has documented that the experience of childhood maltreatment is related to an increased risk for the development of psychopathologies in adulthood. Empirical studies examining the factors that could possibly explain this relationship, however, remain sparse. The emerging literature on distress tolerance (DT) suggests that it could possibly act as an explanatory or mediating factor within this relationship. The current study, therefore, examined the mediating role of DT in the relationship between childhood maltreatment and psychopathology (posttraumatic stress disorder, depression, anxiety, and alcohol use) in adulthood in a university student population sample (N = 642). Results showed that childhood maltreatment was positively associated with caseness for all mental health outcomes under investigation. It was also found that individuals with higher levels of DT were less likely to experience adverse mental health outcomes. The results of the mediation analysis indicated that the exposure to childhood maltreatment remained associated with elevated risk for being in the symptomatic group across mental health outcomes, and that DT significantly mediated this relationship. These results provide insight into the relationship between childhood maltreatment and mental ill-health later in life, highlighting the importance of considering DT as a potential risk and resilience factor in this relationship.

Predictors of PTSD Treatment Response Trajectories in a Sample of Childhood Sexual Abuse Survivors: The Roles of Social Support, Coping, and PTSD Symptom Clusters.

This study aimed to (a) identify posttraumatic stress disorder (PTSD) trajectories in a sample of Danish treatment-seeking childhood sexual abuse (CSA) survivors and (b) examine the roles of social support, coping style, and individual PTSD symptom clusters (avoidance, reexperiencing, and hyperarousal) as predictors of the identified trajectories. We utilized a convenience sample of 439 CSA survivors attending personalized psychotherapy treatment in Denmark. Four assessments were conducted on a six monthly basis over a period of 18 months. We used latent class growth analysis (LCGA) to test solutions with one to six classes. Following this, a logistic regression was conducted to examine predictors of the identified trajectories. Results revealed four distinct trajectories which were labeled high PTSD gradual response, high PTSD treatment resistant, moderate PTSD rapid response, and moderate PTSD gradual response. Emotional and detached coping and more severe pretreatment avoidance and reexperiencing symptoms were associated with more severe and treatment resistant PTSD. High social support and a longer length of time since the abuse were associated with less severe PTSD which improved over time. The findings suggested that treatment response of PTSD in CSA survivors is characterized by distinct patterns with varying levels and rates of PTSD symptom improvement. Results revealed that social support is protective and that emotional and detached coping and high pretreatment levels of avoidance and reexperiencing symptoms are risk factors in relation to PTSD severity and course. These factors could potentially identify patients who are at risk of not responding to treatment. Furthermore, these factors could be specifically addressed to increase positive outcomes for treatment-seeking CSA survivors.

The odds and implications of coinheritance of hemophilia A and B.

We report 2 patients with coinheritance of the X-linked bleeding disorders hemophilia A and hemophilia B. We describe the family pedigrees, clinical features, and genotyping. The case report addresses the key clinical questions of how to manage patients with both hemophilia A and B and how to counsel families regarding recurrence risk. The patients with coinherited hemophilia A and B require a combination of factor VIII and factor IX replacement to achieve hemostasis. We calculated the estimated genomic meiotic recombination frequency between F8 and F9 to be 38%. The findings in these cases are consistent with this calculation. These findings provide critical information for management of families with coinherited hemophilia A and B.

Genomic characterization of the RH locus detects complex and novel structural variation in multi-ethnic cohorts.

PURPOSE: Rh antigens can provoke severe alloimmune reactions, particularly in high-risk transfusion contexts, such as sickle cell disease. Rh antigens are encoded by the paralogs, RHD and RHCE, located in one of the most complex genetic loci. Our goal was to characterize RH genetic variation in multi-ethnic cohorts, with the focus on detecting RH structural variation (SV). METHODS: We customized analytical methods to estimate paralog-specific copy number from next-generation sequencing (NGS) data. We applied these methods to clinically characterized samples, including four World Health Organization (WHO) genotyping references and 1135 Asian and Native American blood donors. Subsequently, we surveyed 1715 African American samples from the Jackson Heart Study. RESULTS: Most samples in each dataset exhibited SV. SV detection enabled prediction of the immunogenic RhD and RhC antigens in concordance (>99%) with serological phenotyping. RhC antigen expression was associated with exon 2 hybrid alleles (RHCE*CE-D(2)-CE). Clinically relevant exon 4-7 hybrid alleles (RHD*D-CE(4-7)-D) and exon 9 hybrid alleles (RHCE*CE-D(9)-CE) were prevalent in African Americans. CONCLUSION: This study shows custom NGS methods can accurately detect RH SV, and that SV is important to inform prediction of relevant RH alleles. Additionally, this study provides the first large NGS survey of RH alleles in African Americans.

Empirically derived lifespan polytraumatization typologies: A systematic review.

CONTEXT: Polytraumatization classes based on trauma endorsement patterns relate to distinct clinical outcomes. Person-centered approaches robustly evaluate the nature, and construct validity of polytraumatization classes. OBJECTIVE: Our review examined evidence for the nature and construct validity of lifespan polytraumatization typologies. DATA SOURCES: In September 2016, we searched Pubmed, PSYCINFO, PSYC ARTICLES, Academic Search Complete, PILPTS, Web of Science, CINAHL, Medline, PsycEXTRA, and PBSC. Search terms included "latent profile," "latent class," "latent analysis," "person-centered," "polytrauma," "polyvictimization," "traumatization," "lifetime," "cooccurring," "complex," "typology," "multidimensional," "sequential," "multiple," "subtype," "(re)victimization," "cumulative," "maltreatment," "abuse," and "stressor." Inclusionary criteria included: peer-reviewed; latent class/latent profile analyses (LCA/LPA) of lifespan polytrauma classes; adult samples of size greater than 200; only trauma types as LCA/LPA indicators; mental health correlates of typologies; and individual-level trauma assessment. Of 1,397 articles, nine met inclusion criteria. DATA EXTRACTION: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, research assistants completed a secondary reference search, and independently extracted data with standardized coding forms. RESULTS: Three-class (n = 5) or four-class (n = 4) solutions were found. Seven studies found a class characterized by higher trauma endorsement (high-trauma). All studies found a class characterized by lower trauma endorsement (low-trauma), and predominance of specific traumas (specific-trauma; e.g., childhood maltreatment). High-trauma versus low-trauma classes and specific-trauma versus low-trauma classes differed on mental health correlates. CONCLUSION: Evidence supports the prevalence of a high-trauma class experiencing poorer mental health, and the detrimental impact of aggregated interpersonal and other traumas. We highlight the clinical importance of addressing polytraumatization classes, and comprehensively assessing the impact of all traumas.

Predicting Time Spent in Treatment in a Sample of Danish Survivors of Child Sexual Abuse.

The aim of this study was to identify significant predictors of length of time spent in treatment. In a convenience sample of 439 Danish survivors of child sexual abuse, predictors of time spent in treatment were examined. Assessments were conducted on a 6-month basis over a period of 18 months. A multinomial logistic regression analysis revealed that the experience of neglect in childhood and having experienced rape at any life stage were associated with less time in treatment. Higher educational attainment and being male were associated with staying in treatment for longer periods of time. These factors may be important for identifying those at risk of terminating treatment prematurely. It is hoped that a better understanding of the factors that predict time spent in treatment will help to improve treatment outcomes for individuals who are at risk of dropping out of treatment at an early stage.

Novel approach to genetic analysis and results in 3000 hemophilia patients enrolled in the My Life, Our Future initiative.

Hemophilia A and B are rare, X-linked bleeding disorders. My Life, Our Future (MLOF) is a collaborative project established to genotype and study hemophilia. Patients were enrolled at US hemophilia treatment centers (HTCs). Genotyping was performed centrally using next-generation sequencing (NGS) with an approach that detected common F8 gene inversions simultaneously with F8 and F9 gene sequencing followed by confirmation using standard genotyping methods. Sixty-nine HTCs enrolled the first 3000 patients in under 3 years. Clinically reportable DNA variants were detected in 98.1% (2357/2401) of hemophilia A and 99.3% (595/599) of hemophilia B patients. Of the 924 unique variants found, 285 were novel. Predicted gene-disrupting variants were common in severe disease; missense variants predominated in mild-moderate disease. Novel DNA variants accounted for ∼30% of variants found and were detected continuously throughout the project, indicating that additional variation likely remains undiscovered. The NGS approach detected >1 reportable variants in 36 patients (10 females), a finding with potential clinical implications. NGS also detected incidental variants unlikely to cause disease, including 11 variants previously reported in hemophilia. Although these genes are thought to be conserved, our findings support caution in interpretation of new variants. In summary, MLOF has contributed significantly toward variant annotation in the F8 and F9 genes. In the near future, investigators will be able to access MLOF data and repository samples for research to advance our understanding of hemophilia.

Assessing childhood maltreatment and mental health correlates of disordered eating profiles in a nationally representative sample of English females.

PURPOSE: Previous research suggests that childhood maltreatment is associated with the onset of eating disorders (ED). In turn, EDs are associated with alternative psychopathologies such as depression and posttraumatic stress disorder (PTSD), and with suicidality. Moreover, it has been reported that various ED profiles may exist. The aim of the current study was to examine the profiles of disordered eating and the associations of these with childhood maltreatment and with mental health psychopathology. METHODS: The current study utilised a representative sample of English females (N = 4206) and assessed for the presence of disordered eating profiles using Latent Class Analysis. Multinomial logistic regression was implemented to examine the associations of childhood sexual and physical abuse with the disordered eating profiles and the associations of these with PTSD, depression and suicidality. RESULTS: Results supported those of previous findings in that we found five latent classes of which three were regarded as disordered eating classes. Significant relationships were found between these and measures of childhood trauma and mental health outcomes. CONCLUSIONS: Childhood sexual and physical abuse increased the likelihood of membership in disordered eating classes and these in turn increased the likelihood of adverse mental health and suicidal outcomes.

Factor VIII gene variants and inhibitor risk in African American hemophilia A patients.

African American hemophilia A (HA) patients experience a higher incidence of neutralizing anti-factor VIII (FVIII) antibodies ("inhibitors") vis-à-vis white patients. Nonsynonymous single-nucleotide polymorphisms (ns-SNPs) in the F8 gene encoding FVIII-H484, FVIII-E1241, and FVIII-V2238 are more prevalent in African Americans. This study tested the hypothesis that immune responses to these sites provoke inhibitors. Blood samples were obtained from 174 African American and 198 white HA subjects and their F8 gene sequences determined. Major histocompatibility complex class II binding and T-cell recognition of polymorphic sequences were evaluated using quantitative binding assays and HLA-DRB1 tetramers. Peptides corresponding to 4 common ns-SNPs showed limited binding to 11 HLA-DRB1 proteins. CD4 T cells from 22 subjects treated with FVIII products having sequences at residues FVIII-484, 1241, and 2238 differing from those of putative proteins encoded by their F8 genes did not show high-avidity tetramer binding, whereas positive-control staining of tetanus-specific CD4 T cells was routinely successful. African Americans with an intron-22 inversion mutation showed a 2-3 times-higher inhibitor incidence than whites with the same mutation (odds ratio = 2.3 [1.1-5.0, P = .04]), but this did not correlate with any of the ns-SNPs. We conclude that immune responses to "sequence-mismatched" FVIII products are unlikely to contribute appreciably to the inhibitor incidence in African Americans.

Six amino acid residues in a 1200 Å2 interface mediate binding of factor VIII to an IgG4κ inhibitory antibody.

The development of neutralizing anti-factor VIII (FVIII) antibodies complicates the treatment of many hemophilia A patients. The C-terminal C2 domain is a particularly antigenic FVIII region. A crystal structure of recombinant FVIII-C2 bound to an Fab fragment of the patient-derived monoclonal antibody BO2C11, which recognizes an immunodominant inhibitor epitope on FVIII and blocks its ability to bind von Willebrand factor (VWF) and phospholipids, revealed that 15 amino acids in FVIII contact this antibody. Forty-three recombinant FVIII-C2 proteins, each with a surface-exposed side chain mutated to alanine or another residue, were generated, and surface plasmon resonance studies were carried out to evaluate effects of these substitutions on BO2C11/FVIII-C2 binding affinity. Thermodynamic analysis of experiments carried out at three temperatures indicated that one beta hairpin turn at the antigen-antibody interface (FVIII-F2196, N2198, M2199 and F2200) plus two non-contiguous arginines (FVIII-R2215 and R2220), contributed appreciably to the affinity. B-domain-deleted (BDD) FVIII-F2196A, FVIII-F2196K and FVIII-M2199A were generated and characterized. Their pro-coagulant activities and binding to VWF were similar to those of WT-BDD-FVIII, and FVIII-F2196K avoided neutralization by BO2C11 and murine inhibitory mAb 1B5. This study suggests specific sites for amino acid substitutions to rationally design FVIII variants capable of evading immunodominant neutralizing anti-FVIII antibodies.