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.

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).

Online xenophobia and mental health among Venezuelan migrant youth in Colombia: The interplay with "in-person" discrimination.

Emerging research provides insights into migration-related cultural stress experiences and mental health among Venezuelan migrants; however, prior studies have not considered the critical distinction between online xenophobia and in-person discrimination. To address this gap, we assess the psychometric properties of an abbreviated version of the Perceived Online Racism Scale (PORS) with Venezuelan migrant youth and examine the interplay between online xenophobia, in-person discrimination, and mental health. Survey data were collected from Venezuelan migrant youth (N = 319; ages 13-17, 49.5% female) in Colombia in April-July 2023. Confirmatory factor analysis (CFA) was used to examine the PORS, and multiple regression was conducted to examine key associations. The CFA showed excellent model fit: χ²(7) = 13.498, p = .061; comparative fit index = .989; Tucker-Lewis index = .977; root-mean-square error of approximation = .055; standardized root-mean-square residual = .026. Controlling for demographic factors, online xenophobia was associated with depressive symptoms (ß = .253, p < .001) and anxiety (ß = .200, p = .001). The online xenophobia-mental health association weakened when controlling for in-person discrimination but remained nevertheless significant (depression: ß = .181, p = .002, anxiety: ß = .135, p = .026). Interaction effects (Online × In-Person) revealed a pattern in which greater exposure to online xenophobia was associated with greater distress, but only at relatively low levels of in-person discrimination. Findings provide new insights regarding (a) the properties of an increasingly relevant measure of cultural stress, (b) how online xenophobia relates to mental health, and (c) the interplay of online and in-person cultural stressors vis-à-vis mental health among Venezuelan migrant youth. (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.

The Crisis Migration Experience Scale: Developing and validating a tool for Venezuelan youth and adults residing in Colombia.

OBJECTIVE: Although prior research has shown that an array of distinct experiences related to crisis migration are associated with mental health, there is a pressing need for a theory-driven, multidimensional measure to assess the broad spectrum of crisis migration experiences. As such, the present study focused on developing and validating the Crisis Migration Experience Scale (CMES) with a sample of Venezuelan migrants in Colombia. METHOD: Participants were adolescent (ages 12-17; n = 430) and adult migrants from Venezuela (ages 18+; n = 569). Randomly splitting the adolescent and adult samples in half, exploratory factor analysis and confirmatory factor analyses were conducted with 26 original items. After identifying a satisfactory factor structure to generate a 16-item CMES (CMES-16), we examined the associations of the CMES-16 with mental health outcomes. RESULTS: We provide evidence for reliability, factorial validity, and concurrent validity of scores generated by the CMES-16 in a sample of Venezuelan crisis migrants in Colombia. Whereas our a priori conceptualization included seven domains, the exploratory and confirmatory factor analyses indicated that four are especially salient: material hardship, desperation, danger, and unplanned departure. CONCLUSIONS: Crisis migration is an increasingly important construct frequently referenced in the literature on migrant health and by international humanitarian organizations. The number of crisis migrant groups worldwide is increasing, with Ukrainians and Afghans recently added to the list of such groups, along with Venezuelans, Syrians, South Sudanese, Iraqis, and Central Americans. Developing and validating the CMES-16 with Venezuelan crisis migrants opens up important avenues of research, including work that incorporates other crisis migrant populations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

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).

Measuring Anxiety Among Latino Immigrant Populations: Within-Country and Between-Country Comparisons.

Anxiety is the most prevalent mental health disorder among adults worldwide. Given its increased prevalence among migrants due to their marginalized position in the societies where they reside, psychometric evaluations of anxiety measures such as the Generalized Anxiety Disorder-7 (GAD-7) are needed for use with migrants. The present study is the first attempt to compare the structure of GAD-7 scores for (a) different Latino groups in the same country and (b) the same Latino group in two different countries. Using three samples of Mexican and Venezuelan migrants (total N = 933), we provide reliability and validity evidence of the GAD-7 for use with adult Latino migrants. Utilizing confirmatory factor analysis and item response theory, we demonstrate that the GAD-7 is internally consistent, possesses a strong single-factor structure, and generates scores with equivalent psychometric properties. GAD-7 is appropriate for use with Mexican and Venezuelan migrants across differing gender groups and education levels.

A machine learning approach using migration-related cultural stress to classify depression and post-traumatic stress disorder among hurricane survivors.

BACKGROUND: Data science approaches have increasingly been used in behavioral health research and may be useful for addressing social factors contributing to disparities in health status. This study evaluated the importance of cultural stress-related factors in classifying depression and post-traumatic stress disorder (PTSD) among adult survivors (N = 319) of Hurricane Maria who migrated from Puerto Rico to the United States mainland. METHODS: We evaluated the performance of random forests (RF) and logistic regression (LR) for classifying PTSD and depression. Models included demographic, hurricane exposure, and migration-related cultural stress variables. We inspected area under the receiver operating characteristic curve (AUC), accuracy, balanced accuracy, F1 score, precision, recall, and specificity. RESULTS: Negative context of reception and language-related stressors were moderately important for accurately classifying depression and PTSD. For classifying depression, RF showed higher accuracy, balanced accuracy, specificity, precision, and F1. For classifying PTSD, RF showed higher accuracy, specificity, precision, and F1. LIMITATIONS: A more thorough classification model would also include biomarkers (e.g., of allostatic load), family, community, or neighborhood-level attributes. Findings may not generalize to other groups who have experienced crisis-related migration. CONCLUSIONS: Findings underscore the importance of culturally and linguistically appropriate and trauma-informed clinical services for recent migrants. Use of assessments to identify pre-migration and post-migration stressors could inform clinical practice with migrants presenting with behavioral health-related difficulties.

Breathing and Oxygen Carrying Capacity in Ts65Dn and Down Syndrome.

Individuals with Down syndrome (Ds) are at increased risk of respiratory infection, aspiration pneumonia, and apnea. The Ts65Dn mouse is a commonly used model of Ds, but there have been no formal investigations of awake breathing and respiratory muscle function in these mice. We hypothesized that breathing would be impaired in Ts65Dn vs. wild-type (WT), and would be mediated by both neural and muscular inputs. Baseline minute ventilation was not different at 3, 6, or 12 mo of age. However, VT/Ti, a marker of the neural drive to breathe, was lower in Ts65Dn vs. WT and central apneas were more prevalent. The response to breathing hypoxia was not different, but the response to hypercapnia was attenuated, revealing a difference in carbon dioxide sensing, and/or motor output in Ts65Dn. Oxygen desaturations were present in room air, demonstrating that ventilation may not be sufficient to maintain adequate oxygen saturation in Ts65Dn. We observed no differences in arterial PO2 or PCO2, but Ts65Dn had lower hemoglobin and hematocrit. A retrospective medical record review of 52,346 Ds and 52,346 controls confirmed an elevated relative risk of anemia in Ds. We also performed eupneic in-vivo electromyography and in-vitro muscle function and histological fiber typing of the diaphragm, and found no difference between strains. Overall, conscious respiration is impaired in Ts65Dn, is mediated by neural mechanisms, and results in reduced hemoglobin saturation. Oxygen carrying capacity is reduced in Ts65Dn vs. WT, and we demonstrate that individuals with Ds are also at increased risk of anemia.

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).

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.

Consequences of Preterm Birth: Knowns, Unknowns, and Barriers to Advancing Cardiopulmonary Health.

Preterm birth occurs in 10% of all live births and creates challenges to neonatal life, which persist into adulthood. Significant previous work has been undertaken to characterize and understand the respiratory and cardiovascular sequelae of preterm birth, which are present in adulthood, i.e., "late" outcomes. However, many gaps in knowledge are still present and there are several challenges that will make filling these gaps difficult. In this perspective we discuss the obstacles of studying adults born preterm, including (1) the need for invasive (direct) measures of physiologic function; (2) the need for multistate, multinational, and diverse cohorts; (3) lack of socialized medicine in the United States; (4) need for detailed and better-organized birth records; and (5) transfer of neonatal and pediatric knowledge to adult care physicians. We conclude with a discussion on the "future" of studying preterm birth in regards to what may happen to these individuals as they approach middle and older age and how the improvements in perinatal and postnatal care may be changing the phenotypes observed in adults born preterm on or after the year 2000.

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.

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.

CORP: Sources and degrees of variability in whole animal intermittent hypoxia experiments.

Chamber exposures are commonly used to evaluate the physiological and pathophysiological consequences of intermittent hypoxia in animal models. Researchers in this field use both commercial and custom-built chambers in their experiments. The purpose of this Cores of Reproducibility in Physiology paper is to demonstrate potential sources of variability in these systems that researchers should consider. Evaluating the relationship between arterial oxygen saturation and inspired oxygen concentration, we found that there are important sex-dependent differences in the commonly used C57BL6/J mouse model. The time delay of the oxygen sensor that provides feedback to the system during the ramp-down and ramp-up phases was different, limiting the number of cycles per hour that can be conducted and the overall stability of the oxygen concentration. The time to reach the hypoxic and normoxic hold stages, and the overall oxygen concentration, were impacted by the cycle number. These variables were further impacted by whether there are animals present in the chamber, highlighting the importance of verifying the cycling frequency with animals in the chamber. At ≤14 cycles/h, instability in the chamber oxygen concentration did not impact arterial oxygen saturation but may be important at higher cycle numbers. Taken together, these data demonstrate the important sources of variability that justify reporting and verifying the target oxygen concentration, cycling frequency, and arterial oxygen concentration, particularly when comparing different animal models and chamber configurations.NEW & NOTEWORTHY Intermittent hypoxia exposures are commonly used in physiology and many investigators use chamber systems to perform these studies. Because of the variety of chamber systems and protocols used, it is important to understand the sources of variability in intermittent hypoxia experiments that can impact reproducibility. We demonstrate sources of variability that come from the animal model, the intermittent hypoxia protocol, and the chamber system that can impact reproducibility.

Utilizing digital pathology and immunohistochemistry of p53 as an adjunct to molecular testing in myeloid disorders.

TP53 mutation status guides early therapeutic decisions in the treatment of clonal myeloid disorders and serves as a simple means of monitoring response to treatment. We aim here to develop a standardized protocol for evaluating TP53 mutation status in myeloid disorders using immunohistochemistry assisted by digital image analysis and further compare this approach to manual interpretation alone. To accomplish this, we obtained 118 bone marrow biopsies from patients with hematologic malignancy and molecular testing for mutations associated with acute myeloid leukemia was performed. Clot or core biopsy slides were stained for p53 and digitally scanned. Overall mutation burden was assessed digitally using two different metrics to determine positivity, compared to the results of manual review, and correlated with molecular results. Using this approach, we found that digital analysis of immunohistochemistry stained slides performed worse than manual categorization alone in predicting TP53 mutation status in our cohort (PPV 91%, NPV 100% vs. PPV 100%, NPV 98%). While digital analysis reduced inter- and intraobserver variability when assessing mutation burden, there was poor correlation between the quantity and intensity of p53 staining and molecular analysis (R2 = 0.204). Therefore, digital image analysis of p53 immunohistochemistry accurately predicts TP53 mutation status as confirmed by molecular testing but does not offer a significant advantage over manual categorization alone. However, this approach offers a highly standardized methodology for monitoring disease status or response to treatment once a diagnosis has been made.

Management of two circulations in a COVID-19 patient with secondary superinfection.

Optimal oxygenation in the intensive care unit requires adequate pulmonary gas exchange, oxygen-carrying capacity in the form of hemoglobin, sufficient delivery of oxygenated hemoglobin to the tissue, and an appropriate tissue oxygen demand. In this Case Study in Physiology, we describe a patient with COVID-19 whose pulmonary gas exchange and oxygen delivery were severely compromised by COVID-19 pneumonia requiring extracorporeal membrane oxygenation (ECMO) support. His clinical course was complicated by a secondary superinfection with staphylococcus aureus and sepsis. This case study is provided with two goals in mind (1) We outline how basic physiology was used to address life-threatening consequences of a novel infection-COVID-19. (2) We describe a strategy of whole-body cooling to lower the cardiac output and oxygen consumption, use of the shunt equation to optimize flow to the ECMO circuit, and transfusion to improve oxygen-carrying capacity when ECMO alone failed to provide sufficient oxygenation.

Hurricane stress, cultural stress, and mental health among hurricane Maria migrants in the U.S. mainland.

Hurricane Maria (2017) caused great damage to Puerto Rico, undermining people's quality of life and forcing thousands to migrate to the U.S. mainland. Identifying individuals at elevated risk of suffering mental health problems as a function of being exposed to hurricane and cultural stress is crucial to reducing the burden of such health outcomes. The present study was conducted in 2020-2021 (3-4 years postdisaster) with 319 adult Hurricane Maria survivors on the U.S. mainland. We aimed to (a) identify latent stress subgroups, as defined by hurricane stress and cultural stress, and (b) map these latent stress subgroups or classes onto sociodemographic characteristics and mental health indicators (i.e., symptoms of posttraumatic stress disorder, depression, and anxiety). We used latent profile analysis and multinomial regression modeling to accomplish the study aims. We extracted four latent classes: (a) low hurricane stress/low cultural stress (44.7%), (b) low hurricane stress/moderate cultural stress (38.7%), (c) high hurricane stress/moderate cultural stress (6.3%), and (d) moderate hurricane stress/high cultural stress (10.4%). Individuals in the low hurricane stress/low cultural stress class reported the highest household incomes and levels of English-language proficiency. The moderate hurricane stress/high cultural stress class reported the worst mental health outcomes. While postmigration cultural stress, as a chronic stressor, emerged as the most important predictor of poor mental health, hurricane stress, as an acute stressor that occurred several years earlier, emerged as less influential. Our findings might be used to inform mental health prevention experts who work with natural disaster survivors forced to migrate. (PsycInfo Database Record (c) 2023 APA, all rights reserved).