Ensuring accountability for consideration of sex as a biological variable in research.

The National Institute of Health (NIH) policy, Consideration of Sex as a Biological Variable (SABV) in NIH-funded Research (2015), focuses on the expectation that researchers account for the influence of SABV in vertebrate animal and human studies and provide a strong justification for single-sex investigations. When SABV is considered in the research design, data analyses, and reporting, the rigor and reproducibility of the research are elevated and inform best practices and precision health for all people. Additional recommendations include the appropriate use of terminology, integration into curricula, intersection with social determinants of health, and application of sex and gender equity guidelines when disseminating research. This paper is a "call to action" for nurse researchers to lean into and apply this policy's principles and our recommendations, from the bench to the bedside, to advance the equity and health of all people.

Effects of a yoga-based stress reduction intervention on stress, psychological outcomes and cardiometabolic biomarkers in cancer caregivers: A randomized controlled trial.

Caregiving stress is a risk factor for cardiometabolic disease. Therefore, integrating cardiometabolic biomarkers into caregiving research provides a more comprehensive assessment of an individual's health and response to an intervention. The objective of this study was to examine the effects of a yoga-based stress reduction intervention on stress, psychological outcomes, and cardiometabolic biomarkers in cancer caregivers. This prospective randomized controlled trial enrolled family caregivers of adult patients who underwent an allogeneic HSCT at the National Institutes of Health (NIH) Clinical Center. All subjects received usual care education. Participants in the intervention group received an Iyengar yoga intervention self-administered over six weeks using an audio recording file. The primary outcome was perceived stress (measured using the NIH toolbox Perceived Stress). The secondary outcomes were psychological factors (depression and anxiety measured using PROMIS® Depression and Anxiety), and cardiometabolic biomarkers measured by nuclear magnetic resonance spectroscopy. A total of 50 family caregivers (mean [SD] age, 44.9 [15.2] years; 42 [84.0%] women) were randomized, 25 to the intervention group and 25 to the control group. No group differences were noted in stress, depression, and anxiety. Significant interaction effects between group and time were found in large TRL-P (F(1,43) = 10.16, p = 0.003) and LP-IR (F(1,42) = 4.28, p = 0.045). Post-hoc analyses revealed that the levels of large TRL-P (mean difference = 1.68, CI = [0.86, 2.51], p< .001) and LP-IR (mean difference = 5.67, CI = [1.15, 10.18], p = 0.015) significantly increased over time in the control group but while remained stable in the intervention group (mean difference = -0.15, CI = [-0.96, 0.66], p = 0.718; mean difference = -0.81, CI = [-5.22, 3.61], p = 0.714, respectively). Even when perceptions of psychological distress remain unchanged, incorporating gentle yoga poses and breathing exercises may reduce the risk of cardiometabolic disease in caregivers by inhibiting the development of insulin resistance. Standard lipids of cardiometabolic risk do not appear to be robust enough to detect short-term early changes of cardiometabolic risk in caregivers. Trial registration: ClinicalTrials.gov Identifier: NCT02257853.

Caregiving stress and burden associated with cardiometabolic risk in family caregivers of individuals with cancer.

Chronic stress is a well-established risk factor for cardiometabolic disease. Caregiving for individuals with cancer is perceived as a chronic stressor yet research on the risk for cardiometabolic disease in this population, opposed to the elderly and those with Alzheimer's disease, is limited. Additionally, few studies have explored the early physiological changes that occur in family caregivers suggesting an elevated risk for illness. This cross-sectional study was designed to examine levels of cardiometabolic risk biomarkers and their correlates in caregivers of patients with colorectal cancer. Caregivers completed questionnaires that measure exposures to stress and vulnerability factors, psychological distress, and health habits as potential correlates. Traditional lipid and nontraditional lipoprotein particle biomarkers (e.g. concentration and size for all lipoprotein classes) were assayed from blood serum. Caregivers (N = 83, mean age = 49.8, 73% female) displayed levels of cardiometabolic biomarkers that suggest an elevated risk for cardiometabolic disease. Caregivers who were Hispanic, married, highly educated, employed, reported more hours spent caregiving daily, experienced higher caregiver burden associated with the lack of family support and impact on schedule, and psychological distress, demonstrated an elevated risk for cardiometabolic disease; primarily determined by nontraditional lipid biomarkers - large TRL-P, LDL-P, small HDL-P, large HDL-P, TRL-Z, LDL-Z and HDL-Z. These findings suggest that traditional lipid biomarkers may not be robust enough to detect early physiological changes associated with cardiometabolic disease risk in family caregivers. Moreover, findings reiterate the importance of assessing caregiver burden and providing evidence-based interventions to manage caregiving stress with the potential to improve caregivers' cardiometabolic health.

Factors That Influence Health-Promoting Behaviors in Cancer Caregivers.

OBJECTIVES: To describe cancer caregivers' participation in health-promoting behaviors and to identify factors influencing participation. SAMPLE & SETTING: 129 informal cancer caregivers at the National Institutes of Health Clinical Center. METHODS & VARIABLES: Cross-sectional survey methodology using Health-Promoting Lifestyle Profile-II (HPLP-II), PROMIS® Global Physical Health, NIH Toolbox Stress and Self-Efficacy, Caregiver Reaction Assessment, and Family Care Inventory Mutuality subscale. RESULTS: Caregivers reported the highest HPLP-II subscale scores for spirituality and interpersonal relationships and the lowest for physical activity. Caregivers who were older, with lower body mass indices, in better physical health, and with higher self-efficacy and mutuality participated in more health-promoting behaviors. Sixty percent of the caregivers reported that they exercised less since becoming a caregiver, and 47% reported that their diet was worse. IMPLICATIONS FOR NURSING: Future research is needed to examine novel interventions to increase health-promoting activities in cancer caregivers, and these interventions might be strengthened by including components that focus on increasing self-efficacy and/or improving the strength of the relationship between the caregiver and care recipient.

Cancer across the ages: a narrative review of caregiver burden for patients of all ages.

PROBLEM IDENTIFICATION: Approximately 2.8 million Americans care for an individual with cancer. Because the literature typically describes caregiving experiences within patient age-groups (e.g., pediatrics, geriatrics), the purpose of this narrative review was to describe common and unique burdens and distress among caregivers of cancer-patients of different ages. LITERATURE SEARCH: We identified representative peer-reviewed manuscripts related to caregivers of pediatric, adolescent, young-, middle-, and late-adult oncology patients. We combined search terms "caregiver" and "cancer" with "burden," "distress," and/or age-related terms ("pediatric" or "geriatric"). Included studies focused on factors of caregiver-burden and distress. DATA EVALUATION/SYNTHESIS: Universal cancer-caregiving experiences include negative impacts on work-productivity, finances, social-/family-dynamics, and physical/emotional health. Age-related life experiences shape outcomes; pediatric caregivers may have fewer financial resources, whereas concurrent comorbidities create challenges for geriatric caregivers. CONCLUSIONS: Caregiving for cancer patients has universal, shared, and patient age-specific burdens. IMPLICATIONS FOR PRACTICE: Supportive care based on patient-age may improve caregiver well-being.

Factors influencing loneliness in cancer caregivers: A longitudinal study.

OBJECTIVE: To describe levels of loneliness in cancer caregivers over a 6 month time period, and to examine factors that influence changes in loneliness in caregivers over time. METHODS: Prospective, repeated measures design was utilized to examine levels of loneliness and factors that influence loneliness in 129 family caregivers of individuals undergoing cancer treatment at three time points over a 6 month period. Measures included: PROMIS global health and sleep disturbance; NIH Toolbox loneliness, self-efficacy and perceived stress; Family Care Inventory mutuality scale; and Caregiver Reaction Assessment. RESULTS: Approximately one third (30.2%, n = 39) of the caregivers had high levels of loneliness, and levels of loneliness did not change over the three time points (P = .985). For any given time point, caregivers who were not married (P = .008), not working (P = .027), with worse mental health (P = .015), more perceived-stress (P < .0001), and more caregiver burden (P = .003) reported higher levels of loneliness. CONCLUSION: This study provides guidance for clinicians attempting to identify at-risk caregivers by confirming the findings of previous research that caregivers with higher burden, stress and in poor mental health are at increased risk for loneliness. This study provides preliminary evidence that continuing to work during the caregiving trajectory may be beneficial to caregivers by reducing levels of loneliness. Future research is needed to confirm these findings and to examine novel interventions to reduce loneliness in cancer caregivers.

Family Caregiver Strain and Burden: A Systematic Review of Evidence-Based Interventions When Caring for Patients With Cancer.

BACKGROUND: Caregivers of patients with cancer experience high levels of caregiver-related strain and burden (CGSB). Cancer caregiving is complex and can change dramatically depending on the cancer trajectory. Often, this experience leads to poor health outcomes for the caregiver. OBJECTIVES: This review appraises the evidence on CGSB published from 2007 to October 2017. METHODS: 128 interventional studies found in PubMed® and CINAHL® were appraised and categorized based on the Oncology Nursing Society's Putting Evidence Into Practice schema. FINDINGS: Psychoeducation, supportive care/support interventions, and cognitive behavioral interventions are recommended to decrease CGSB. Caregiver skill training, couples therapy, decision support, mindfulness-based stress reduction, multicomponent interventions, and palliative care are likely to be effective. The evidence is not established for 13 interventions. Despite the proliferation of studies focusing on CGSB, studies with stronger designs and larger samples are needed.

Enhancing the cancer caregiving experience: Building resilience through role adjustment and mutuality.

PURPOSE: The purpose of this study was to explore the dyadic experience of caring for a family member with cancer. Particular attention was given to examine the relationship between dyadic perceptions of role adjustment and mutuality as facilitators in resilience for posttreatment cancer patients and family caregivers. METHOD: For this convergent parallel, mixed-methods study using grounded theory methodologies, 12 dyads were recruited from the National Institutes of Health Clinical Center in Bethesda, Maryland, USA. Qualitative data collection focused on social interactions between cancer patients and their family caregivers to better understand and describe how post-treatment patients and caregivers create mutuality in their relationships, how they describe the processes of role-adjustment, and how these processes facilitate dyadic resiliency. Quantitative data collected through electronic survey included the Family Caregiving Inventory (FCI) for Mutuality Scale, Neuro QoL Ability to Participate in Social Roles and Activities, and Satisfaction with Social Roles and Activities-Short Forms, and Mental Health Continuum-Short Form (MHC). RESULTS: Eleven participants were spouses. Twenty-two self-reported as Caucasian. The sample ranged from 35 to 71 years of age (Caregiver M = 53.7, Patient M = 54.3). Most of the caregivers were female (n = 8; 66.7%) and most of the patients were male (n = 9; 75%). Qualitative interview data illuminated two primary psychosocial processes relating to resilience, role adjustment and mutuality, as key facilitators for transformation and growth within dyadic partnerships coping with the challenges of cancer treatment and cancer caregiving. The FCI-mutuality score for patients (M = 3.65 ±â€¯0.47) and caregivers (M = 3.45 ±â€¯0.42) reflected an average level of relationship quality. Relative to participation in, and satisfaction with social roles and activities, patients (M = 50.66 ±â€¯7.70, M = 48.81 ±â€¯6.64, respectively) and caregivers (M = 50.69 ±â€¯8.6, M = 51.9 ±â€¯8.75, respectively) reported scores that were similar to the US General Population (M = 50 ±â€¯10). CONCLUSIONS: New patterns of role adjustment and mutuality can assist with making meaning and finding benefit, and these patterns contribute to dyadic resilience when moving through a cancer experience. There are few interventions that target the function of the dyad, yet the emergent model identified in this paper provides a direction for future dyadic research. By developing interventions at a dyadic level, providers have the potential to encourage dyadic resilience and sustain partnerships from cancer treatment into survivorship.

Caregiver availability and patient access to hematopoietic cell transplantation: social worker perspectives inform practice.

PURPOSE: Hematopoietic cell transplantation (HCT) often involves a long hospitalization and recovery period, with patients generally required to have a caregiver. This study aimed to identify transplant center (TC) requirements for a caregiver, describe challenges that impact caregiver availability, and identify potential solutions. METHODS: An exploratory sequential mixed-methods approach was used. Qualitative data was obtained from focus groups of TC social workers in the United States (US) (three focus groups; n = 15 total participants). Results informed the development of a national, web-based survey that was administered to the primary social worker contact at TCs in the National Marrow Donor Program (NMDP)/Be The Match Network (n = 133). RESULTS: Respondents included social workers from adult (n = 47) and pediatric (n = 19) TCs (response rate = 49%). The majority (89%) of both adult and pediatric TCs required a caregiver for a patient to proceed to transplant, but requirements varied in length of time, formality, transplant type, and HCT setting. Regardless of transplant type or patient population, social workers identified loss of caregiver income as the greatest challenge to caregiver availability, with the most common solution being allowing patients to have multiple caregivers throughout the transplant course. DISCUSSION: Caregiver availability is an important concern for patients considering and receiving HCT, and may be a barrier proceeding to HCT when a caregiver is unavailable. Results from this study highlight caregiver availability barriers and solutions of TCs across the US. These results can inform TCs about other center experiences with caregiver availability and identify potential practice changes for individual TCs.

A Conceptual Framework and Key Research Questions in Educational Needs of Blood and Marrow Transplantation Patients, Caregivers, and Families.

Patient, caregiver, and family education and support was 1 of 6 key areas of interest identified by the National Marrow Donor Program/Be The Match 2-year project to prioritize patient-centered outcomes research (PCOR) goals for the blood and marrow transplantation (BMT) community. PCOR focuses on research to help patients and their caregivers make informed decisions about health care. Therefore, each area of interest was assigned to a working group with broad representation, including patients, caregivers, and clinicians. Each working group was charged with identifying gaps in knowledge and making priority recommendations for critical research to fill those gaps. The report from this working group presents a conceptual framework to address gaps in knowledge regarding patient and caregiver education in BMT and recommendations for priority research questions on this topic.

Fatigue predicts impaired social adjustment in survivors of allogeneic hematopoietic cell transplantation (HCT).

PURPOSE: The aim of this study is to examine social adjustment to illness and to identify factors related to social adjustment in allogeneic hematopoietic cell transplantation (HCT) survivors. METHODS: Cross-sectional data were drawn from a longitudinal study of patients ≥ 3 years after their first HCT. The five subscales of the Psychosocial Adjustment to Illness Scale (PAIS) that reflect social adjustment, specifically vocational environment (VE); domestic environment (DE); sexual relationships (SEX); extended family relationships (ER); and social environment (SE) were examined in this analysis. Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) measured cancer-related fatigue. RESULTS: Subjects (N = 171) were a median of 5.19 years from HCT (range 3-16). The most impaired dimension of social adjustment was ER with 38% of participants reaching clinically relevant (score ≥ 62) levels of social maladjustment. Unmarried and unemployed participants had lower levels of social adjustment in VE (p < .001 and p < .001, respectively) and DE (p = .004 and p = .006, respectively). Survivors with some college had poorer SEX adjustment than those with less or more education (p < .005). Hispanics reported lower adjustment with respect to ER adjustment (p = .002). Participants with higher fatigue had poorer adjustment in all five dimensions (p < .001). CONCLUSIONS: Although the majority of survivors are well adjusted, subgroups may experience significant poor social adjustment. Specifically, survivors with fatigue are at risk to experience lower levels of social adjustment. Development of effective rehabilitation strategies to improve affected areas of social health is warranted, and all HCT survivors should be screened periodically for social maladjustment and provided with resources and referrals.

Nurses and health-promoting self-care: Do we practice what we preach?

AIMS: To examine the health-promoting behaviours performed by registered nurses (RNs), as well as workplace factors that influence participation in those behaviours. BACKGROUND: Nurses have high levels of overweight/obesity and may not be engaging in health-promoting self-care. METHODS: A cross-sectional Web-based survey collected information from 335 RNs regarding their physical activity, sedentariness and fruit/vegetable consumption. RESULTS: More than half were overweight (34.1%) or obese (23.4%), and 80.1% were "sedentary" (≥3 hr sitting/day), particularly those working outside of direct patient care in management, research and education. Only 47.2% consumed 5+ servings of fruits/vegetables daily. Nurses who enjoyed their jobs (higher levels of compassion satisfaction) reported higher levels of physical activity (p = 0.03) and fruit/vegetable consumption (p = 0.02). CONCLUSION: RNs who work outside of direct patient care might be at increased risk for sedentariness and obesity. RNs who enjoy their jobs may experience less stress and have more energy to exercise and to prepare/consume healthy meals. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers should practice self-care by engaging in exercise, proper nutrition and demonstrating work-life balance, both to protect their own health and to serve as role models for RNs in direct patient care.

Results of a national survey of certified nurse coaches with implications for advanced practice nurses.

BACKGROUND AND PURPOSE: Evidence suggests that nurse-coaching can improve health outcomes, but application of this skill is not well understood. The purpose of this study is to describe the practices of nurse coaches including their work settings, clients/health conditions, motivations behind becoming certified as coaches, and the personal benefits experienced by nurse coaches. METHODS: A cross-sectional online survey was emailed to certified nurse coaches (n = 315); 164 completed the survey, including 68 (41.5%) advanced practice nurses. CONCLUSIONS: The most frequent conditions seen by coaches included the following: anxiety/stress (n = 39, 27.1%), cardiometabolic conditions (n = 24, 16.7%), and pain (n = 20, 13.9%). Coaching varied in frequency, method (individual versus group), and mode (in-person, by phone, or electronically). Participants became coaches to gain skills for enhancing their practice, deliver care that fits with their values and philosophy, meet personal needs (starting a private practice and improve their own self-care), attain credentials/validation, and empower others. The majority agreed/strongly agreed that since becoming a nurse coach, their own interpersonal relationships (80.3%), health/health behaviors (84.8%), and job satisfaction (70.7%) improved. IMPLICATIONS FOR PRACTICE: Nurse practitioners may be strategically situated to provide coaching and have the knowledge and skills needed to intervene with medically complex, at-risk populations.

The Role of Biomarkers in Research on Caregivers for Cancer Patients: A Scoping Review.

BACKGROUND: Biomarkers can be used as prognostic, predictive, or monitoring indicators of an associated outcome. The purpose of this review was to provide a comprehensive summary of the research examining the use of biomarkers as surrogate end points for clinical outcomes in family caregivers for cancer patients, identify gaps, and make recommendations for future research. METHODS: A scoping review, a process of mapping the existing literature, was conducted. Studies comparing biomarkers across caregivers and controls and/or examining relationships between biomarkers and psychological health were reviewed. RESULTS: The studies ( N = 18) of caregivers for cancer patients who were identified used biomarkers to predict outcomes ( n = 13) and to monitor the efficacy of interventions ( n = 6). Biomarkers were divided into two categories based on physiological systems involved: (1) neuroendocrine function (sympathetic-adrenal-medullary axis activity, hypothalamic-pituitary-adrenal axis activity) and (2) immune function. Predictive biomarkers were sensitive to differences between caregivers and controls. The biomarkers were used to evaluate outcomes frequently associated with stress, depression, and anxiety. Cortisol was the biomarker most commonly measured to monitor the efficacy of interventions. DISCUSSION: Biomarkers are most commonly incorporated into caregiver studies to predict group membership and psychological health. Neuroendocrine biomarkers, specifically cortisol, are most frequently assessed. Future research should include biomarkers of other physiologic functions (e.g., cardiovascular function, cognitive dysfunction, and cell aging) and those that serve as multisystem indicators. Expanding the scientific study of biomarkers will contribute to our understanding of the mechanisms through which stress may influence caregiver health.

Patient reported outcomes in GNE myopathy: incorporating a valid assessment of physical function in a rare disease.

BACKGROUND: The aim of this analysis was to evaluate the psychometric properties of three patient reported outcome (PRO) measures characterizing physical function in GNE myopathy: the Human Activity Profile, the Inclusion Body Myositis Functional Rating Scale, and the Activities-specific Balance Confidence scale. METHODS: This analysis used data from 35 GNE myopathy subjects participating in a natural history study. For construct validity, correlational and known-group analyses were between the PROs and physical assessments. Reliability of the PROs between baseline and 6 months was evaluated using the intra-class correlation coefficient model; internal consistency was tested with Cronbach's alpha. RESULTS: The hypothesized moderate positive correlations for construct validity were supported; the strongest correlation was between the human activity profile adjusted activity score and the adult myopathy assessment endurance subscale score (r = 0.81; p < 0.0001). The PROs were able to discriminate between known high and low functioning groups for the adult myopathy assessment tool. Internal consistency of the PROs was high (α > 0.8) and there was strong reliability (ICC >0.62). CONCLUSION: The PROs are valid and reliable measures of physical function in GNE myopathy and should be incorporated in investigations to better understand the impact of progressive muscle weakness on physical function in this rare disease population. Implications for Rehabilitation GNE myopathy is a rare muscle disease that results in slow progressive muscle atrophy and weakness, ultimately leading to wheelchair use and dependence on a caregiver. There is limited knowledge on the impact of this disease on the health-related quality of life, specifically physical function, of this rare disease population. Three patient reported outcomes have been shown to be valid and reliable in GNE myopathy subjects and should be incorporated in future investigations to better understand how progressive muscle weakness impacts physical functions in this rare disease population. The patient reported outcome scores of GNE myopathy patients indicate a high risk for falls and impaired physical functioning, so it is important clinicians assess and provide interventions for these subjects to maintain their functional capacity.

Hematopoietic Stem Cell Transplantation Recipient and Caregiver Factors Affecting Length of Stay and Readmission.

PURPOSE/OBJECTIVES: To evaluate the contributions of patient and caregiver factors to length of stay (LOS) and 30-day readmission status for recipients of allogeneic hematopoietic stem cell transplantation (HSCT).
. DESIGN: Secondary data analysis from a phase 2 clinical trial.
. SETTING: National Institutes of Health Clinical Center in Bethesda, Maryland.
. SAMPLE: 68 dyads (N = 136) comprised of patients receiving HSCT and their caregivers. 
. METHODS: Multiple linear regression and logistic regression analyses were used to investigate associations between caregiver and patient factors and outcomes.
. MAIN RESEARCH VARIABLES: Patients' initial LOS, 30-day readmission, and demographic and disease characteristics; caregiver demographic factors, health problems, psychological distress, burden, and self-efficacy. 
. FINDINGS: Twenty-five patients were readmitted within 30 days after hospital discharge following their initial hospitalization for HSCT. LOS was 34% longer for patients with infection than patients without infection. Patients with grade 2 or greater acute graft-versus-host disease (GVHD) stayed longer compared to patients with no or mild acute GVHD. Patients who had nonspousal caregivers stayed longer than patients with spousal caregivers. Infection was significantly related to readmission.
. CONCLUSIONS: Knowledge regarding factors associated with increased LOS and 30-day readmission can help nurses and transplantation team members anticipate the healthcare needs of patients receiving HSCT, improve outcomes, and decrease the use of expensive health services. 
. IMPLICATIONS FOR NURSING: Educating patients and caregivers on infection prevention is critically important to reduce LOS and 30-day readmission after HSCT.

Cardiometabolic risk factors and health behaviors in family caregivers.

The purpose of this study was to compare components of cardiometabolic risk and health behaviors of 20 family caregivers of allogeneic hematopoietic stem cell transplant patients to those of age, gender, and race/ethnicity-matched controls. A prospective, repeated measures design was used to compare cardiometabolic risk and health behaviors in caregivers and controls at three time-points: pre-transplantation, discharge, and six weeks post-discharge. Measures included components of metabolic syndrome, Reynolds Risk Score, NMR serum lipoprotein particle analyses, and the Health-Promoting Lifestyle Profile II (HPLP-II). Mixed-model repeated measure analyses were used. There were no between or within group differences in LDL cholesterol, HDL cholesterol, and triglycerides. There was a significant interaction effect between time and role in large VLDL concentration (VLDL-P) (F (2, 76) = 4.36, p = .016), with the trajectory of large VLDL-P increasing over time in caregivers while remaining stable in controls. Within caregivers, VLDL particle size (VLDL-Z) was significantly larger at time-point three compared to time-points one (p = .015) and two (p = .048), and VLDL-Z was significantly larger in caregivers than in controls at time point three (p = .012). HPLP-II scores were lower in caregivers than controls at all time-points (p < .01). These findings suggest that caregiving may have a bigger impact on triglycerides than on other lipids, and it is through this pathway that caregivers may be at increased cardiometabolic risk. More sensitive measurement methods, such as NMR lipoprotein particle analyses, may be able to detect early changes in cardiometabolic risk.

Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia.

BACKGROUND: Acquired aplastic anemia results from immune-mediated destruction of bone marrow. Immunosuppressive therapies are effective, but reduced numbers of residual stem cells may limit their efficacy. In patients with aplastic anemia that was refractory to immunosuppression, eltrombopag, a synthetic thrombopoietin-receptor agonist, led to clinically significant increases in blood counts in almost half the patients. We combined standard immunosuppressive therapy with eltrombopag in previously untreated patients with severe aplastic anemia. METHODS: We enrolled 92 consecutive patients in a prospective phase 1-2 study of immunosuppressive therapy plus eltrombopag. The three consecutively enrolled cohorts differed with regard to the timing of initiation and the duration of the eltrombopag regimen (cohort 1 received eltrombopag from day 14 to 6 months, cohort 2 from day 14 to 3 months, and cohort 3 from day 1 to 6 months). The cohorts were analyzed separately. The primary outcome was complete hematologic response at 6 months. Secondary end points included overall response, survival, relapse, and clonal evolution to myeloid cancer. RESULTS: The rate of complete response at 6 months was 33% in cohort 1, 26% in cohort 2, and 58% in cohort 3. The overall response rates at 6 months were 80%, 87%, and 94%, respectively. The complete and overall response rates in the combined cohorts were higher than in our historical cohort, in which the rate of complete response was 10% and the overall response rate was 66%. At a median follow-up of 2 years, the survival rate was 97%; one patient died during the study from a nonhematologic cause. Marked increases in bone marrow cellularity, CD34+ cell number, and frequency of early hematopoietic progenitors were noted. Rates of relapse and clonal evolution were similar to our historical experience. Severe rashes occurred in two patients, resulting in the early discontinuation of eltrombopag. CONCLUSIONS: The addition of eltrombopag to immunosuppressive therapy was associated with markedly higher rates of hematologic response among patients with severe aplastic anemia than in a historical cohort. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT01623167 .).