Povlsenslater0967

The current standard of care for paroxysmal nocturnal hemoglobinuria (PNH) are the C5 inhibitors eculizumab and ravulizumab, both monoclonal antibodies designed to target the complement protein C5, thereby preventing its cleavage and the formation of the terminal attack complex. C5 inhibitors have yielded substantial improvements in the treatment of PNH and changed the mortality and morbidity, as well as health-related quality of life of patients with the disease. These treatments target underlying intravascular hemolysis; however, they do not address extravascular hemolysis, resulting in incomplete response and remaining symptoms in some patients. Therefore, despite treatment with a C5 inhibitor, some patients still experience anemia with associated fatigue, transfusion needs, and impaired health-related quality of life. DISCLOSURES This research was developed under a research contract between RTI Health Solutions and Apellis Pharmaceuticals and was funded by Apellis Pharmaceuticals. Bektas, Copley-Merriman, and Khan are employees of RTI Health Solutions. Sarda is an employee of Apellis Pharmaceuticals. Shammo consults for Apellis Pharmaceuticals.The complement system is part of the innate immune response system, which comprises more than 50 distinct plasma and serum proteins that interact to opsonize pathogens (i.e., mark pathogens for destruction) and induce inflammatory responses to fight infection. The role of the complement system is 2-fold immune surveillance and host defense. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, chronic, acquired, hematologic disease caused by somatic mutations in the gene PIGA in the hematopoietic stem cells. CHR2797 concentration These stem cells produce abnormal clone blood cells that lack the complement regulatory proteins CD55 and CD59, causing the body to recognize these otherwise healthy red blood cells as damaged. The complement system destroys cells without these protective proteins, resulting in general hemolysis. PNH is characterized by fatigue; hemolytic anemia that can be severe and debilitating; increased lactic dehydrogenase level, reticulocyte count, and bilirubin level; propensity for thrombotic events; and renal dysfunction. Epidemiologic data, while sparse, suggest that an estimated 5,000-6,000 individuals in the United States are affected by PNH. If left untreated, PNH has a 10-year mortality rate of 29%, although the natural history of this disease has been recently altered by the introduction of complement inhibitors for the treatment of PNH. DISCLOSURES This research was developed under a research contract between RTI Health Solutions and Apellis Pharmaceuticals and was funded by Apellis Pharmaceuticals. Bektas, Copley-Merriman, and Khan are employees of RTI Health Solutions. Sarda is an employee of Apellis Pharmaceuticals. Shammo consults for Apellis Pharmaceuticals.Patients with paroxysmal nocturnal hemoglobinuria (PNH) often experience a lengthy path to diagnosis. Fewer than 40% of patients with PNH receive a diagnosis within 12 months of symptom onset, and 24% of all PNH diagnoses can take 5 years or longer. Diagnostic delay is a source of distress and can affect emotional well-being for patients with PNH. In PNH disease management, patients and care providers focus on risk of organ failure and mortality related to disease progression; nonetheless, patients' health-related quality of life (HRQOL) is largely affected by extensive treatment requirements and nonfatal complications of disease, such as fatigue. In particular, thrombosis is associated with significant impairments in physical and social functioning and global health status and significant fatigue. Among patients with anemia who are transfusion dependent, the burden of transfusion is considerable. Transfusion dependence has a negative effect on HRQOL; is associated with risks and complications, including iron overload; and results in lost productivity due to travel times to and time spent at infusion centers. DISCLOSURES This research was developed under a research contract between RTI Health Solutions and Apellis Pharmaceuticals and was funded by Apellis Pharmaceuticals. Bektas, Copley-Merriman, and Khan are employees of RTI Health Solutions. Sarda is an employee of Apellis Pharmaceuticals. Shammo consults for Apellis Pharmaceuticals.Childhood maltreatment (CM) is thought to be linked to adult narcissistic traits. However, it remains unclear how CM is associated with each type of narcissism, vulnerable and grandiose, and what mechanism mediates these links. One potential candidate is dissociation. This study examines the relations among CM, dissociation, vulnerable narcissism, and grandiose narcissism. A total of 322 women completed self-reported questionnaires assessing CM, dissociation, vulnerable narcissism, and grandiose narcissism. To examine the relations among CM, dissociation, and each type of narcissism, we performed Pearson's correlations and mediation analyses. In secondary analyses, we conducted latent class analyses to classify different types of CM and to assess their relations with the study variables. We found small to moderate correlations between CM and vulnerable narcissism, (r = .35, p less then .001) and CM and grandiose narcissism (r = .2, p less then .001), with the former association being greater than the latter (z = -3.25, p less then .001). Dissociation was found to mediate the link between CM and each type of narcissism (p less then .001). Results suggest that CM may play a role in the etiology of vulnerable and grandiose narcissism, and that dissociation links CM to each type of narcissism. Findings highlight that CM may lead to different responses in terms of narcissism-through the same mediation process.Violent injury is a leading cause of death and disability among young Black men, with the highest rates occurring in low-income urban populations. Hospital-based violence intervention programs (HVIPs) offer a promising opportunity to address the biopsychosocial factors that adversely affect this population. However, there are major gaps between the needs of young Black male survivors of violent injury and the forms of care provided by HVIPs. Patient-centered outcomes research provides a useful mode of inquiry to develop strategies to decrease these differences. Care for survivors, including treatment for traumatic stress disorders, must be reconceptualized to center the lived experiences of young Black men. This paper qualitatively explores how these survivors of gun violence express symptoms of traumatic stress and the ways in which their narratives can inform the implementation of the biopsychosocial model in HVIPs. A phenomenological variant ecological systems theory framework was used to analyze participant narratives to aid in understanding their symptoms of traumatic stress and post-injury affective changes as both psychologically and socially important experiences.