Risk Factors for COVID-19 in College Students Identified by Physical, Mental, and Social Health Reported During the Fall 2020 Semester: Observational Study Using the Roadmap App and Fitbit Wearable Sensors.

BACKGROUND: The COVID-19 pandemic triggered a seismic shift in education to web-based learning. With nearly 20 million students enrolled in colleges across the United States, the long-simmering mental health crisis in college students was likely further exacerbated by the pandemic. OBJECTIVE: This study leveraged mobile health (mHealth) technology and sought to (1) characterize self-reported outcomes of physical, mental, and social health by COVID-19 status; (2) assess physical activity through consumer-grade wearable sensors (Fitbit); and (3) identify risk factors associated with COVID-19 positivity in a population of college students prior to release of the vaccine. METHODS: After completing a baseline assessment (ie, at Time 0 [T0]) of demographics, mental, and social health constructs through the Roadmap 2.0 app, participants were instructed to use the app freely, wear the Fitbit, and complete subsequent assessments at T1, T2, and T3, followed by a COVID-19 assessment of history and timing of COVID-19 testing and diagnosis (T4: ~14 days after T3). Continuous measures were described using mean (SD) values, while categorical measures were summarized as n (%) values. Formal comparisons were made on the basis of COVID-19 status. The multivariate model was determined by entering all statistically significant variables (P<.05) in univariable associations at once and then removing one variable at a time through backward selection until the optimal model was obtained. RESULTS: During the fall 2020 semester, 1997 participants consented, enrolled, and met criteria for data analyses. There was a high prevalence of anxiety, as assessed by the State Trait Anxiety Index, with moderate and severe levels in 465 (24%) and 970 (49%) students, respectively. Approximately one-third of students reported having a mental health disorder (n=656, 33%). The average daily steps recorded in this student population was approximately 6500 (mean 6474, SD 3371). Neither reported mental health nor step count were significant based on COVID-19 status (P=.52). Our analyses revealed significant associations of COVID-19 positivity with the use of marijuana and alcohol (P=.02 and P=.046, respectively) and with lower belief in public health measures (P=.003). In addition, graduate students were less likely and those with ≥20 roommates were more likely to report a COVID-19 diagnosis (P=.009). CONCLUSIONS: Mental health problems were common in this student population. Several factors, including substance use, were associated with the risk of COVID-19. These data highlight important areas for further attention, such as prioritizing innovative strategies that address health and well-being, considering the potential long-term effects of COVID-19 on college students. TRIAL REGISTRATION: ClinicalTrials.gov NCT04766788; https://clinicaltrials.gov/ct2/show/NCT04766788. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/29561.

Assessment of Individual versus Composite Endpoints of Acute Graft-versus-Host Disease in Determining Long-Term Survival after Allogeneic Transplantation.

The overall composite of graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS), defined as survival free of grade III-IV acute GVHD (aGVHD), chronic GVHD (cGVHD) requiring systemic immunosuppressive therapy (IST), or relapse, has emerged as a useful composite in clinical trials and to capture clinically meaningful events that impact quantity and quality of survival after allogeneic hematopoietic cell transplantation (HCT). We reviewed 565 consecutive patients aged ≥18 years undergoing HCT for hematologic malignancy to analyze how baseline incidence, specifics of clinical definitions, and proposed reductions in any one individual event may dynamically alter the overall performance of the composite To determine the relative impact of each GRFS event (excluding death), we accounted for competing risks using Fine and Gray methods, and correlated each event with overall survival (OS) using Kaplan-Meier methods. The consequences of modulating individual or composite endpoints on OS, such as hypothesized reductions of events of an HCT interventional trial, were examined using Monte Carlo simulations. The median age of the cohort was 54 years (range, 18 to 73 years). The majority of patients received HLA-matched unrelated donor HCT (53%), consisting of peripheral blood stem cell grafts (90%) after myeloablative conditioning (68%). Relapse conferred the greatest risk for death (hazard ratio [HR], 7.89; 95% confidence interval [CI], 5.83 to 10.69), followed by grade III-IV aGVHD (HR, 6.16; 95% CI, 4.42 to 8.56) and cGVHD requiring IST (HR, 1.69; 95% CI, 1.16 to 2.46). The overall GRFS composite correlated with an HR of 4.81 (95% CI, 3.61 to 6.41), which was lower compared with either relapse or grade III-IV aGVHD. Statistical simulations found that modulating the combined risk of both relapse and grade III-IV aGVHD predicted the greatest change in 5-year OS. These simulations suggest that GRFS as currently defined may be less optimal for correlating with OS, and further refinement of composite endpoints is needed. Nonetheless, composite endpoints may be particularly helpful in mitigating potential difficulties in interpretation when competing risks are present, most commonly seen in HCT studies.

Impact of a health information technology tool addressing information needs of caregivers of adult and pediatric hematopoietic stem cell transplantation patients.

PURPOSE: We developed BMT Roadmap, a health information technology (HIT) application on a tablet, to address caregivers' unmet needs with patient-specific information from the electronic health record. We conducted a preliminary feasibility study of BMT Roadmap in caregivers of adult and pediatric HSCT patients. The study was registered on ClinicalTrials.gov (NCT03161665; NCT02409121). METHODS: BMT Roadmap was delivered to 39 caregivers of adult and pediatric patients undergoing first-time HSCT at a single study site. We assessed person-reported outcome measures (PROMs) at baseline (hospital admission), discharge, and day 100: usefulness of BMT Roadmap (Perceived Usefulness); activation (Patient Activation Measure-Caregiver version [PAM-C]); mental health ([POMS-2®]: depression, distress, vigor, and fatigue); anxiety (State-Trait Anxiety Inventory); and quality of life (Caregiver Quality of Life Index-Cancer [CQOLC]). To identify determinants of caregiver activation and quality of life, we used linear mixed models. RESULTS: BMT Roadmap was perceived useful and activation increased from baseline to discharge (p = 0.001). Further, burden decreased through discharge (p = 0.007). Overall, a pattern of increasing vigor and decreasing depression, distress, fatigue, and anxiety was apparent from baseline to discharge. However, overall quality of life lowered at discharge after accounting for BMT Roadmap use, depression, anxiety, and fatigue (p = 0.04). CONCLUSIONS: BMT Roadmap was a feasible HIT intervention to implement in HSCT caregivers. BMT Roadmap was associated with increased activation and decreased burden, but quality of life lowered across hospitalization. Findings support the need to further develop caregiver-specific self-directed resources and provide them both inpatient and outpatient across the HSCT trajectory.

Novel Health Information Technology Tool Use by Adult Patients Undergoing Allogeneic Hematopoietic Cell Transplantation: Longitudinal Quantitative and Qualitative Patient-Reported Outcomes.

PURPOSE: Health information technology (IT) is an ideal medium to improve the delivery of patient-centered care and increase patient engagement. Health IT interventions should be designed with the end user in mind and be specific to the needs of a given population. Hematopoietic cell transplantation (HCT), commonly referred to as blood and marrow transplantation (BMT), is a prime example of a complex medical procedure where patient-caregiver-provider engagement is central to a safe and successful outcome. We have previously reported on the design and development of an HCT-specific health IT tool, BMT Roadmap. METHODS: This study highlights longitudinal quantitative and qualitative patient-reported outcomes (PROs) in 20 adult patients undergoing allogeneic HCT. Patients completed PROs at three time points (baseline, day 30 post-HTC, and day 100 post-HCT) and provided weekly qualitative data through semistructured interviews while using BMT Roadmap. RESULTS: The mean hospital stay was 23.3 days (range, 17 to 37 days), and patients had access to BMT Roadmap for a mean of 21.3 days (range, 15 to 37 days). The total time spent on BMT Roadmap ranged from 0 to 139 minutes per patient, with a mean of 55 minutes (standard deviation, 47.6 minutes). We found that patients readily engaged with the tool and completed qualitative interviews and quantitative PROs. The Patient Activation Measure, a validated measure of patient engagement, increased for patients from baseline to discharge and day 100. Activation was significantly and negatively correlated with depression and anxiety PROs at discharge, suggesting that this may be an important time point for intervention. CONCLUSION: Given the feasibility and promising results reported in this study, next steps include expanding our current health IT platform and implementing a randomized trial to assess the impact of BMT Roadmap on critical PROs.

Risk Factors and Outcomes of Invasive Fungal Infections in Allogeneic Hematopoietic Cell Transplant Recipients.

Allogeneic hematopoietic cell transplant (HCT) recipients are at increased risk of invasive fungal infections (IFI), which are associated with a high mortality rate. We evaluated the impact of IFI in allogeneic HCT patients. In total, 541 consecutive allogeneic HCT recipients were included. The cumulative incidence of any IFI and mold infections at 1-year post-HCT was 10 and 7%, respectively. Median times to IFI and mold infection were 200 and 210 days, respectively. There was a trend toward fewer IFI and mold infections in the last several years. Both acute graft-versus-host disease (GVHD) (OR 1.83, p = 0.05) and corticosteroid duration (OR 1.0, p = 0.026) were significantly associated with increased risk of IFI, acute GVHD (OR 2.3, p = 0.027) emerged as the most important association with mold infections. Any IFI [HR 4.1 (2.79-6.07), p < 0.0001] and mold infections [HR 3.34 (2.1-5.1), p < 0.0001] were independently associated with non-relapse mortality (NRM). This association persisted in the setting of both acute and chronic GVHD. Corticosteroid treatment for >90 days was also significantly associated with higher NRM [HR 1.9 (1.3-2.6), p < 0.0001]. This study highlights the impact of IFI on NRM among HCT patients. The decrease in number of IFI and mold infections over the last several years may reflect the benefit of prophylaxis with mold-active antifungal agents.

Allogeneic transplantation with myeloablative FluBu4 conditioning improves survival compared to reduced intensity FluBu2 conditioning for acute myeloid leukemia in remission.

The optimal intensity of conditioning for allogeneic hematopoietic stem cell transplantation (HCT) in acute myeloid leukemia (AML) remains undefined. Traditionally, myeloablative conditioning regimens improve disease control, but at the risk of greater nonrelapse mortality. Because fludarabine with myeloablative doses of intravenous busulfan using pharmacokinetic monitoring has excellent tolerability, we reasoned that this regimen would limit relapse without substantially elevating toxicity when compared to reduced intensity conditioning. We retrospectively analyzed 148 consecutive AML patients in remission receiving T cell replete HCT conditioned with fludarabine and intravenous busulfan at doses defined as reduced (6.4 mg/kg; FluBu2, n = 63) or myeloablative (12.8 mg/kg; FluBu4, n = 85). Early and late nonrelapse mortality (NRM) was similar among FluBu4 and FluBu2 recipients, respectively (day + 100: 4 vs 0 %; 5 years: 19 vs 22 %; p = 0.54). NRM did not differ between FluBu4 and FluBu2 in patients >50 years of age (24 vs 22 %, p = 0.75). Relapse was lower in recipients of FluBu4 (5 years: 30 vs 49 %; p = 0.04), especially in patients with poor risk cytogenetics (22 vs 59 %; p = 0.02) and those >50 years of age (28 vs 51 %; p = 0.02). Overall survival favored FluBu4 recipients at 5 years (53 vs 34 %, p = 0.02), a finding confirmed in multivariate analysis (HR: 0.57; 95 % CI: 0.34-0.95; p = 0.03). These data suggest that myeloablative FluBu4 may provide equivalent NRM, reduced relapse, and improved survival compared to FluBu2, emphasizing the importance of busulfan dose in conditioning for AML.