Testing predictions from the Memory and Identity Theory of ICD-11 Complex Posttraumatic Stress Disorder: Measurement development and initial findings

Background: The ‘Memory and Identity Theory’ of ICD-11 Complex Posttraumatic Stress Disorder (CPTSD) was recently published but has not yet been subjected to empirical testing. The objective of this study was to evaluate newly developed measures of memory and identity disturbances and test hypothesized structural relations between these constructs and CPTSD symptoms. Methods: Self-report data were collected from a nationwide sample of adults living in Ukraine (N = 2050) in September 2023. Exploratory factor analysis was used to assess the latent structure of the newly developed measures, and structural equation modeling was used to test the associations between memory and identity disturbances and CPTSD symptoms. Results: 90 % of participants experienced a lifetime trauma, and 9.2 % screened positive for ICD-11 CPTSD. Results indicated that the newly developed measures of memory and identity problems possessed satisfactory psychometric properties, and all but one of the model-implied structural associations were observed. Conclusion: This study provides initial empirical support for the Memory and Identity theory of ICD-11 CPTSD, indicating that the basis of this disorder lies in distinct memory and identity processes. Several effects not predicted by the theory were observed, and these can provide the basis for further model testing and refinement.</p

Does requiring trauma exposure affect rates of ICD-11 PTSD and complex PTSD? Implications for DSM-5

Objective: There is little evidence that posttraumatic stress disorder (PTSD) is more likely to follow traumatic events defined by Criterion A than non-Criterion A stressors. Criterion A events might have greater predictive validity for ICD-11 PTSD which is a condition more narrowly defined by core features. We evaluated the impact of using Criterion A, an ‘expanded’ trauma definition in line with ICD-11 guidelines, and no exposure criterion on rates of ICD-11 PTSD and Complex PTSD (CPTSD). We also assessed if five psychologically threatening events included in the expanded definition were as strongly associated with PTSD and CPTSD as ‘standard’ Criterion A events. Method: A nationally representative sample from Ireland (N = 1,020) completed self-report measures. Results: Most participants were trauma-exposed based on Criterion A (82%) and the ‘expanded’ (88%) criterion. When no exposure criterion was used, 13.7% met diagnostic requirements for PTSD or CPTSD; 13.2% when the expanded criterion was used, and 13.2% when Criterion A was used. The five psychologically threatening events were as strongly associated with PTSD and CPTSD as the Criterion A events. In a multivariate analysis, only the psychologically threatening events were significantly associated with PTSD (stalking) and CPTSD (bullying, emotional abuse, and neglect). Conclusions: Certain non-Criterion A events involving extreme fear and horror should be considered traumatic. The ICD-11 approach of providing clinical guidance rather than a formal definition offers a viable solution to some of the problems associated with the current and previous attempts to define traumatic exposure

Haplotype structure and selection of the MDM2 oncogene in humans

The MDM2 protein is an ubiquitin ligase that plays a critical role in regulating the levels and activity of the p53 protein, which is a central tumor suppressor. A SNP in the human MDM2 gene (SNP309 T/G) occurs at frequencies dependent on demographic history and has been shown to have important differential effects on the activity of the MDM2 and p53 proteins and to associate with altered risk for the development of several cancers. In this report, the haplotype structure of the MDM2 gene is determined by using 14 different SNPs across the gene from three different population samples: Caucasians, African Americans, and the Ashkenazi Jewish ethnic group. The results presented in this report indicate that there is a substantially reduced variability of the deleterious SNP309 G allele haplotype in all three populations studied, whereas multiple common T allele haplotypes were found in all three populations. This observation, coupled with the relatively high frequency of the G allele haplotype in both and Caucasian and Ashkenazi Jewish population data sets, suggests that this haplotype could have undergone a recent positive selection sweep. An entropy-based selection test is presented that explicitly takes into account the correlations between different SNPs, and the analysis of MDM2 reveals a significant departure from the standard assumptions of selective neutrality

Relationship between resident workload and self-perceived learning on inpatient medicine wards: a longitudinal study

BACKGROUND: Despite recent residency workload and hour limitations, little research on the relationship between workload and learning has been done. We sought to define residents' perceptions of the optimal patient workload for learning, and to determine how certain variables contribute to those perceptions. Our hypothesis was that the relationship between perceived workload and learning has a maximum point (forming a parabolic curve): that either too many or too few patients results in sub-optimal learning. METHODS: Residents on inpatient services at two academic teaching hospitals reported their team and individual patient censuses, and rated their perception of their learning; the patient acuity; case variety; and how challenged they felt. To estimate maximum learning scores, linear regression models with quadratic terms were fit on learning score. RESULTS: Resident self-perceived learning correlated with higher acuity and greater heterogeneity of case variety. The equation of census versus learning score, adjusted for perception of acuity and case mix scores, showed a parabolic curve in some cases but not in others. CONCLUSION: These data suggest that perceived resident workload is complex, and impacted by additional variables including patient acuity and heterogeneity of case variety. Parabolic curves exist for interns with regard to overall census and for senior residents with regard to new admissions on long call days

Posttraumatic stress disorder (PTSD) and complex PTSD (CPTSD) as per ICD-11 proposals: A population study in Israel

Background: The current study sought to advance the existing literature by providing the first assessment of the factorial and discriminant validity of the ICD-11 proposals for PTSD and CPTSD in a nation-wide level.Methods: A nationally representative sample from Israel (n = 1003) using a disorder-specific measure (ITQ; International Trauma Questionnaire) in order to assess PTSD and Complex PTSD along with the Life Events Checklist and the World Health Organization Well-Being Index.Results: Estimated prevalence rates of PTSD and CPTSD were 9.0% and 2.6% respectively. The structural analyses indicated that PTSD and disturbances in self-organization symptom clusters were multidimensional, but not necessarily hierarchical, in nature and there were distinct classes that were consistent with PTSD and CPTSD. Conclusions: These results partially support the factorial validity and strongly support the discriminant validity of the ICD-11 proposals for PTSD and CPTSD in a nationally representative sample using a disorder-specific measure, findings also supported the international applicability of these diagnoses.Further research is required to determine the prevalence rates of PTSD and CPTSD in national representative samples across different countries and explore the predictive utility of different types of traumatic life events on PTSD and CPTSD

Clinical profile and treatment of infantile spasms using vigabatrin and ACTH - a developing country perspective

Background: Infantile spasms represent a serious epileptic syndrome that occurs in the early infantile age. ACTH and Vigabatrin are actively investigated drugs in its treatment. This study describes the comparison of their efficacy in a large series of Patients with infantile spasms from Pakistan. Methods: All Patients with infantile spasms who presented to Aga Khan University Hospital, Karachi, Pakistan from January, 2006 to April, 2008 were included in this study. Inclusion criteria were clinical symptoms of infantile spasms, hypsarrythmia or modified hyparrythmia on electroencephalography, at least six months of follow-up period and receipt of any of the two drugs mentioned above. The type of drug distribution was random according to the availability, cost and ease of administration. Results: Fifty six cases fulfilled the inclusion criteria. 62.5% were males. Mean age at onset of seizures was 5 +/- 1.4 months. Fifty two (92.8%) Patients demonstrated hypsarrythmia on electroencephalography. 64.3% cases were identified as symptomatic while 19.6% were cryptogenic and 16.1% were idiopathic. Eighteen Patients received ACTH while 38 Patients received Vigabatrin as first line therapy. Initial response to first line therapy was similar (50% for ACTH and 55.3% for Vigabatrin). Overall, the symptomatic and idiopathic groups responded better to Vigabatrin. The relapse rate was higher for ACTH as compared to Vigabatrin (55.5% vs. 33.3%) when considering the first line therapy. Four Patients evolved to Lennox-Gastaut variant, all of these Patients had initially received Vigabatrin and then ACTH. Conclusion: Vigabatrin and ACTH showed no significant difference in the initial treatment of infantile spasms. However, Patients receiving ACTH were 1.2 times more likely to relapse as compared to the Patients receiving Vigabatrin when considering monotherapy. We suggest that Vigabatrin should be the initial drug of choice in Patients presenting with infantile spasms. However, larger studies from developing countries are required to validate the therapeutic trends observed in this study

International Veterinary Epilepsy Task Force Consensus Proposal: Outcome of therapeutic interventions in canine and feline epilepsy

Common criteria for the diagnosis of drug resistance and the assessment of outcome are needed urgently as a prerequisite for standardized evaluation and reporting of individual therapeutic responses in canine epilepsy. Thus, we provide a proposal for the definition of drug resistance and partial therapeutic success in canine patients with epilepsy. This consensus statement also suggests a list of factors and aspects of outcome, which should be considered in addition to the impact on seizures. Moreover, these expert recommendations discuss criteria which determine the validity and informative value of a therapeutic trial in an individual patient and also suggest the application of individual outcome criteria. Agreement on common guidelines does not only render a basis for future optimization of individual patient management, but is also a presupposition for the design and implementation of clinical studies with highly standardized inclusion and exclusion criteria. Respective standardization will improve the comparability of findings from different studies and renders an improved basis for multicenter studies. Therefore, this proposal provides an in-depth discussion of the implications of outcome criteria for clinical studies. In particular ethical aspects and the different options for study design and application of individual patient-centered outcome criteria are considered

Human Complement Regulators C4b-Binding Protein and C1 Esterase Inhibitor Interact with a Novel Outer Surface Protein of Borrelia recurrentis

The spirochete Borrelia recurrentis is the causal agent of louse-borne relapsing fever and is transmitted to humans by the infected body louse Pediculus humanus. We have recently demonstrated that the B. recurrentis surface receptor, HcpA, specifically binds factor H, the regulator of the alternative pathway of complement activation, thereby inhibiting complement mediated bacteriolysis. Here, we show that B. recurrentis spirochetes express another potential outer membrane lipoprotein, termed CihC, and acquire C4b-binding protein (C4bp) and human C1 esterase inhibitor (C1-Inh), the major inhibitors of the classical and lectin pathway of complement activation. A highly homologous receptor for C4bp was also found in the African tick-borne relapsing fever spirochete B. duttonii. Upon its binding to B. recurrentis or recombinant CihC, C4bp retains its functional potential, i.e. facilitating the factor I-mediated degradation of C4b. The additional finding that ectopic expression of CihC in serum sensitive B. burgdorferi significantly increased spirochetal resistance against human complement suggests this receptor to substantially contribute, together with other known strategies, to immune evasion of B. recurrentis