Romiplostim for Treatment of Children and Young Adults With Severe Aplastic Anemia and Myelodysplastic Syndrome.

Thrombopoietin receptor agonists (TPO-RAs) induce trilineage hematopoiesis under conditions with acquired hematopoietic failure. We evaluated safety, tolerability, and preliminary efficacy of a TPO-RA, romiplostim (Nplate), with or without standard-of-care immunosuppressive therapy (±IST) for children (ages < 21 y) with newly diagnosed and relapsed/refractory severe aplastic anemia (SAA) and myelodysplastic syndrome (MDS). Data were collected from an observational study and a single arm interventional pilot study. The safety outcome was treatment-related adverse events (AEs). Efficacy was evaluated by complete hematopoietic response (CHR) at week 24. Romiplostim was commenced at 5 µg/kg/week, with dose escalation of 2.5 µg/kg/week (maximum, 20 µg/kg/dose) based on platelet response. Romiplostim was continued until CHR was observed. Ten subjects (SAA, 9 [IST, 4; without IST, 5]; MDS, 1) completed the study (median age: 9.2 y). Median romiplostim dose was 10 µg/kg/week (range: 5 to 17.5 µg/kg/week). The cumulative incidence of CHR was 70.4% (95% CI, 20.2%-92.6%). Among 21 AEs (Grade 1 to 3), 3 were attributed to romiplostim. At a median posttherapy follow-up of 10.9 months (range: 0.7 to 77.5), no clonal evolution, bone marrow fibrosis or mortality was reported. This proof-of-concept study provides data about short-term safety, tolerability, and preliminary efficacy of romiplostim (±IST) for treatment of pediatric SAA/MDS.

Experiences of cultural stress among U.S. citizen migrants: A mixed method approach.

On September 20, 2017, Hurricane Maria made landfall in Puerto Rico, devastating the archipelago and forcing thousands of Puerto Ricans to migrate to the U.S. mainland. Guided by a cultural stress theory framework, the present mixed method study examined how various cultural stressors impact participants' daily interactions and mental health outcomes. A total of 319 adult Hurricane Maria survivors residing on the U.S. mainland participated in the study. A mixed method sequential explanatory design was used. First, we used latent profile analysis (LPA) and multinomial logistic regression to identify the varied cultural stress experiences that participants had. Then we used data from semistructured interviews to better understand the experiences of participants classified into the different LPA profiles. Four profiles were identified: "moderate cultural stress" (35%), "overall low" (29%), "high cultural stress" (26%), and "low language stress" (10%). Multinomial regression indicated that members of the moderate cultural stress, high cultural stress, and low language stress profiles all reported significantly higher depressive and anxiety symptoms compared to members of the overall low profile. Qualitative data exemplified the daily experiences of participants placed into each profile, demonstrating that participants have rich and varied experiences that can contribute to their mental health symptoms. The present study documents the contributions of hurricane trauma and cultural stress vis-à-vis current mental health symptoms. Clinicians working with Hurricane Maria survivors should be cognizant of and inquire about migration-related cultural stressors including discrimination, feelings of being unwelcomed, and difficulty communicating in the destination community's dominant language. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Interplay of premigration crisis exposure and postmigration cultural stress on depressive symptoms among Venezuelan crisis migrants in Colombia.

OBJECTIVES: A growing body of research points to a relationship between exposure to migration-related cultural stress and mental health problems. However, such research is often conducted with the tacit assumption that postmigration experiences are the primary-if not singular-driver of psychological distress. In the present study, we aim to extend the cultural-stress paradigm by examining the influences of both premigration crisis exposure and postmigration cultural stress on depression in a sample of Venezuelan crisis migrants in Colombia. METHOD: Survey data for the present study were collected from Venezuelan youth (N = 429, ages 12-17, Mage = 14.0 years, 49% female) and adults (N = 566, ages 18+, Mage = 35.1 years, 82% female) in Bogota and Medellin, Colombia between April and June 2023. RESULTS: Both crisis exposure and discrimination were independently related to depressive symptoms. However, when examined in a multivariate model along with discrimination, crisis exposure was not a significant predictor of depressive symptoms among youth, and its influence weakened considerably among adults. Among both youth and adults, a Crisis Exposure × Discrimination interaction term significantly predicted depressive symptoms, indicating that discrimination was a more robust predictor of depressive symptoms among those endorsing lower levels of crisis exposure than among those reporting high levels of crisis exposure. CONCLUSION: Our research provides new insights into the experiences of Venezuelan migrant youth and adults in Colombia. It provides further support for the importance of drawing from a crisis-informed cultural-stress framework when working with crisis migrant populations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The impact of cultural stress on family functioning among Puerto Rican displaced families and the effect on mental health.

Hurricane María caused significant devastation on the island of Puerto Rico, impacting thousands of lives. Puerto Rican crisis migrant families faced stress related to displacement and relocation (cultural stress), often exhibited mental health symptoms, and experienced distress at the family level. Although cultural stress has been examined as an individual experience, little work has focused on the experience as a family. To address this gap, we conducted a mixed-methods study designed to examine the predictive effects of cultural stress on family conflict and its mental health implications among Puerto Rican Hurricane María parent and child dyads living on the U.S. mainland. In the quantitative phase of the study, 110 parent-child dyads completed an online survey assessing cultural stress, family dynamics, and mental health. As part of our primary analysis, we estimated a structural equation path model. Findings from the quantitative phase showed a significant positive relationship between family cultural stress and family conflict, as well as individual parent and child mental health symptoms. In the qualitative phase of the study, 35 parent-child dyads participated in individual interviews. Findings from the interviews revealed variations in difficulties related to language, discrimination, and financial burdens, with some participants adapting more quickly and experiencing fewer stressors. Findings also highlight the impact on mental health for both parents and youth, emphasizing the family-level nature of cultural stress, while noting a potential discrepancy between qualitative and quantitative findings in the discussion of family conflict.

Importance of survey demographic questions to foster inclusion in medicine and research and reduce health inequities for LGBTQIA2S+ individuals.

A clear, inclusive, and accurate approach to the collection of demographic information in clinical research and medical practice is critical to understanding the healthcare needs of the specific population. Inclusive demography constitutes appropriate and accurate characterization of an individual's sexual orientation and gender identity (SOGI) data. Appropriate demography fosters sense of inclusion and belonging for those belonging to medically marginalized communities such as the lesbian, gay, bisexual, transgender, queer, intersex, asexual, and Indigenous Two-Spirit (LGBTQIA2S+) communities and improves health outcomes. Acquiring inclusive demographics in healthcare research is needed for the following critical reasons. First, LGBTQIA2S+ individuals experience undue psychological harm when their identities are not appropriately captured in survey data, promoting further alienation of the LGBTQIA2S+ community in medicine and research. Second, LGBTQIA2S+ populations are disproportionately burdened by several major cardiovascular and cardiovascular-associated diseases, including hypertension and diabetes. Failure to include these populations, and accurately characterize their participation, in research leads to failure to identify associations between identities and disease, resulting in worse health outcomes. Furthermore, this lack of precision in current data for sex, gender, and sexual orientation may lead to inaccurate data for all populations, not just the LGBTQIA2S+ community. Finally, there are currently major political and social threats and attacks on the LGBTQIA2S+ community and, in particular, on transgender and gender-diverse individuals. Proper medical inclusion and advocacy for the LGBTQIA2S+ community by the medical community may help protect the community from further undue harm through creating sense of belonging and reductions in marginalization-related health inequities.

Sex differences in cardiovascular disease and dysregulation in Down syndrome.

This meta-analysis, which consisted of a scoping review and retrospective medical record review, is focused on potential sex differences in cardiovascular diseases in patients with Down syndrome. We limited our review to peer-reviewed, primary articles in the English language, in the PubMed and Web of Science databases from 1965 to 2021. Guidelines for scoping reviews were followed throughout the process. Four categorical domains were identified and searched using additional keywords: 1) congenital heart disease, 2) baseline physiology and risk factors, 3) heart disease and hypertension, and 4) stroke and cerebrovascular disease. Articles were included if they reported male and female distinct data, participants with Down syndrome, and one of our keywords. The retrospective medical record review was completed using 75 participating health care organizations to identify the incidence of congenital and cardiovascular diseases and to quantify cardiovascular risk factors in male and female patients. Female patients with Down syndrome are at higher risk of hypertension, ischemic heart disease, and cerebrovascular disease. The risk of congenital heart disease is higher in males with Down syndrome at all ages included in our analyses. Some of the male-to-female sex differences in cardiovascular disease risk in the general patient population are not present, or reversed in the Down syndrome population. This information should be considered for future investigations and ongoing patient care.NEW & NOTEWORTHY In patients with Down syndrome (DS), CHD is the leading cause of death <20 yr old and cardiovascular disease is a leading cause of death in individuals >20 yr old. Men with DS live longer than women. It is unknown if sex differences are present in cardiovascular disease and dysregulation in DS across the lifespan. We observed higher risk of hypertension, ischemic heart disease, and cerebrovascular disease in females and a higher risk of CHD in males with DS.

Achieving a Diverse, Equitable and Inclusive Environment Using the Pathway to Excellence® Framework as a Model.

Diversity, equity, inclusion, and belonging (DEIB) are essential in building effective healthcare teams to provide quality patient care. Striving to achieve a DEIB culture in the healthcare setting presents challenges and opportunities, and using a framework facilitates this important work. This article details how 2 Pathway to Excellence® (Pathway) designated organizations used the Pathway framework foundations around leadership, shared decision-making, professional development, safety, quality, and well-being to build and support their DEIB structures.

The impact of hurricane trauma and cultural stress on posttraumatic stress among hurricane Maria survivors relocated to the U.S. mainland.

OBJECTIVES: Following Hurricane Maria, scores of Puerto Rican "Maria migrants" fled the island with thousands permanently resettling on the United States (U.S.) mainland. Emerging evidence suggests that many Maria migrants are exposed to migration-related cultural stressors, including discrimination, negative context of reception, and language stress. The present study examines the associations of premigration hurricane trauma and postmigration cultural stress with posttraumatic stress disorder (PTSD) symptom severity and positive PTSD screens. METHOD: Participants were 319 adult (age 18+, 71% female) Puerto Rican Hurricane Maria survivors on the U.S. mainland. Data were collected virtually between August 2020 and October 2021. Participants completed Spanish-language measures of hurricane-related trauma, postmigration cultural stress exposure, PTSD symptoms, and positive screens. RESULTS: One in five (20.5%) Maria migrants reported PTSD scores in the range indicating a likely PTSD diagnosis (i.e., positive screen of 50+). Both hurricane trauma and migration-related cultural stressors independently predicted posttraumatic stress and positive PTSD screens. Additionally, controlling for the effect of hurricane trauma, discrimination and language stress were strongly linked with PTSD. Further, hurricane trauma and cultural stressors interact such that cultural stress predicts PTSD-positive screens at low-to-moderate levels of hurricane trauma exposure but not at high-to-very-high levels. CONCLUSION: Findings underscore the importance of providing mental health and other psychosocial supports to hurricane survivors and evacuees beyond the immediate aftermath of the disaster, and the need to consider both premigration trauma and postmigration experiences in terms of the mental health of crisis migrant populations. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The importance of acculturation orientation in understanding the impact of pre- and post-migration stressors on behavioral health: Evidence from a crisis migrant sample.

OBJECTIVE: We examine the interplay of acculturation orientation, cultural stress, and hurricane trauma exposure with behavioral health among Puerto Rican crisis migrants who relocated to the US mainland after Hurricane Maria. METHOD: Participants were 319 adult (Mage = 39 years; 71% female; 90% arriving in 2017-2018) Hurricane Maria survivors surveyed on the US mainland. Latent profile analysis was used to model acculturation subtypes. In turn, ordinary least squares regression was executed to examine the associations of cultural stress and hurricane trauma exposure with behavioral health while stratifying by acculturation subtype. RESULTS: Five acculturation orientation subtypes were modeled, three of which-Separated (24%), Marginalized (13%), and Full Bicultural (14%)-align closely with prior theorizing. We also identified Partially Bicultural (21%) and Moderate (28%) subtypes. Stratifying by acculturation subtype, with behavioral health (depression/anxiety symptoms) specified as the dependent variable, hurricane trauma and cultural stress accounted for only 4% of explained variance in the Moderate class, a somewhat greater percentage in the Partial Bicultural (12%) and Separated (15%) classes, and substantially greater amounts of variance in the Marginalized (25%) and Full Bicultural (56%) classes. CONCLUSION: Findings underscore the importance of accounting for acculturation in understanding the relationship between stress and behavioral health among climate migrants.

Wearable Monitors Facilitate Exercise in Adult and Pediatric Stem Cell Transplant.

Hematopoietic stem cell transplant (HSCT) is a potentially curative treatment for hematopoietic malignancies, complicated by decreased performance status and quality of life. Exercise therapy improves outcomes in HSCT, but several barriers have prevented exercise from becoming routine clinical practice. Based on existing data that wearable technologies facilitate exercise participation in other sedentary and chronic illness populations, we propose the novel hypothesis that wearable technologies are a valuable tool in transcending barriers and developing exercise therapy programs for HSCT patients.

Diversity, Equity, and Inclusion in Nursing: The Pathway to Excellence Framework Alignment.

The promotion of diversity, equity, and inclusion (DEI) in nursing is a topic of renewed importance, given the civil unrest following the death of George Floyd and identified disparities in health and health outcomes during the COVID-19 pandemic. Despite its progress, the nursing profession continues to struggle with recruiting and retaining a workforce that represents the cultural diversity of the patient population. The authors completed a review of the literature on DEI in nursing and found a scarcity of studies, and that a limitation exists due to the strength of the evidence examined. This article aims to provide a review of the literature on DEI in nursing, outcomes and strategies associated with organizational DEI efforts, and knowledge on how the American Nurses Credentialing Center Pathway to Excellence® Designation Program framework supports DEI initiatives. The authors further provided recommendations for nurse leaders and a checklist of proposed questions for assessing commitment, culture, and structural empowerment initiatives toward a more diverse, equitable, and inclusive organization.

Chronic intermittent hypoxia enhances disease progression in myeloma-resistant mice.

Obesity is the only known modifiable risk factor for multiple myeloma (MM), an incurable cancer of bone marrow plasma cells. The mechanism linking the two is unknown. Obesity is associated with an increased risk of sleep apnea, which results in chronic intermittent hypoxia (CIH), and drives solid tumor aggressiveness. Given the link between CIH and solid tumor progression, we tested the hypothesis that CIH drives the proliferation of MM cells in culture and their engraftment and progression in vivo. Malignant mouse 5TGM1 cells were cultured in CIH, static hypoxia, or normoxia as a control in custom, gas-permeable plates. Typically MM-resistant C57BL/6J mice were exposed to 10 h/day CIH (AHI = 12/h), static hypoxia, or normoxia for 7 days, followed by injection with 5TGM1 cells and an additional 28 days of exposure. CIH and static hypoxia slowed the growth of 5TGM1 cells in culture. CIH-exposed mice developed significantly more MM than controls (67 vs. 12%, P = 0.005), evidenced by hindlimb paralysis, gammopathy, bone lesions, and bone tumor formation. Static hypoxia was not a significant driver of MM progression and did not reduce survival (P = 0.117). Interestingly, 5TGM1 cells preferentially engrafted in the bone marrow and promoted terminal disease in CIH mice, despite a lower tumor burden, compared with the positive controls. These first experiments in the context of hematological cancer demonstrate that CIH promotes MM through mechanisms distinct from solid tumors and that sleep apnea may be a targetable risk factor in patients with or at risk for blood cancer.

Consequences of an early catheter-based intervention on pulmonary artery growth and right ventricular myocardial function in a pig model of pulmonary artery stenosis.

OBJECTIVE: To determine the consequences of an early catheter-based intervention on pulmonary artery (PA) growth and right ventricular (RV) myocardial function in an animal model of branch PA stenosis. BACKGROUND: Acute results and safety profiles of deliberate stent fracture within the pulmonary vasculature have been demonstrated. The long-term impact of early stent intervention and deliberate stent fracture on PA growth and myocardial function is not understood. METHODS: Implantation of small diameter stents was performed in a pig model of left PA stenosis at 6 weeks (10 kg) followed by dilations at 10 (35 kg) and 18 weeks (65 kg) with intent to fracture and implant large diameter stents. Hemodynamics, RV contractility, and 2D/3D angiography were performed with each intervention. The heart and pulmonary vasculature were histologically assessed. RESULTS: Stent fracture occurred in 9/12 and implantation of large diameter stents was successful in 10/12 animals with no PA aneurysms or dissections. The final stented PA segment and distal left PA branch origins equaled the corresponding PA diameters of sham controls. Growth of left PA immediately beyond the stent was limited and there was diffuse fibro-intimal proliferation within the distal left and right PA. RV contractility was diminished in the intervention group and the response to dobutamine occurred uniquely via increases in heart rate. CONCLUSIONS: Early stent intervention in this surgically created PA stenosis model was associated with improved growth of the distal PA vasculature but additional investigation of PA vessel physiology and impact on the developing heart are needed.

Prevention Is the Best Treatment: The Case for Understanding the Transition from Monoclonal Gammopathy of Undetermined Significance to Myeloma.

Multiple myeloma is an invariably fatal cancer of plasma cells. Despite tremendous advances in treatment, this malignancy remains incurable in most individuals. We postulate that strategies aimed at prevention have the potential to be more effective in preventing myeloma-related death than additional pharmaceutical strategies aimed at treating advanced disease. Here, we present a rationale for the development of prevention therapy and highlight potential target areas of study.