A pilot intervention of using a mobile health app (ONC Roadmap) to enhance health-related quality of life in family caregivers of pediatric patients with cancer.

Background: The Roadmap mobile health (mHealth) app was developed to provide health-related quality of life (HRQOL) support for family caregivers of patients with cancer. Methods: Eligibility included: family caregivers (age ≥18 years) who self-reported as the primary caregiver of their pediatric patient with cancer; patients (age ≥5 years) who were receiving cancer care at the University of Michigan. Feasibility was calculated as the percentage of caregivers who logged into ONC Roadmap and engaged with it at least twice weekly for at least 50% of the 120-day study duration. Feasibility and acceptability was also assessed through a Feasibility and Acceptability questionnaire and the Mobile App Rating Scale to specifically assess app-quality. Exploratory analyses were also conducted to assess HRQOL self- or parent proxy assessments and physiological data capture. Results: Between September 2020-September 2021, 100 participants (or 50 caregiver-patient dyads) consented and enrolled in the ONC Roadmap study for 120-days. Feasibility of the study was met, wherein the majority of caregivers (N=32; 65%) logged into ONC Roadmap and engaged with it at least twice weekly for at least 50% of the study duration (defined a priori in the Protocol). The Feasibility and Acceptability questionnaire responses indicated that the study was feasible and acceptable with the majority (>50%) reporting Agree or Strongly Agree with positive Net Favorability [(Agree + Strongly Agree) - (Disagree + Totally Disagree)] in each of the domains (e.g., Fitbit use, ONC Roadmap use, completing longitudinal assessments, engaging in similar future study, study expectations). Improvements were seen across the majority of the mental HRQOL domains across all groups; even though underpowered, there were significant improvements in caregiver-specific aspects of HRQOL and anxiety and in depression and fatigue for children (ages 8-17 years), and a trend toward improvement in depression for children ages 8-17 years and in fatigue for adult patients. Conclusions: This study supports that mHealth technology may be a promising platform to provide HRQOL support for caregivers of pediatric patients with cancer. Importantly, the findings suggest that the study protocol was feasible, and participants were favorable to participate in future studies of this intervention alongside routine cancer care delivery.

The intersection of COVID-19 and autoimmunity.

Acute COVID-19, caused by SARS-CoV-2, is characterized by diverse clinical presentations, ranging from asymptomatic infection to fatal respiratory failure, and often associated with varied longer-term sequelae. Over the past 18 months, it has become apparent that inappropriate immune responses contribute to the pathogenesis of severe COVID-19. Researchers working at the intersection of COVID-19 and autoimmunity recently gathered at an American Autoimmune Related Diseases Association Noel R. Rose Colloquium to address the current state of knowledge regarding two important questions: Does established autoimmunity predispose to severe COVID-19? And, at the same time, can SARS-CoV-2 infection trigger de novo autoimmunity? Indeed, work to date has demonstrated that 10% to 15% of patients with critical COVID-19 pneumonia exhibit autoantibodies against type I interferons, suggesting that preexisting autoimmunity underlies severe disease in some patients. Other studies have identified functional autoantibodies following infection with SARS-CoV-2, such as those that promote thrombosis or antagonize cytokine signaling. These autoantibodies may arise from a predominantly extrafollicular B cell response that is more prone to generating autoantibody-secreting B cells. This Review highlights the current understanding, evolving concepts, and unanswered questions provided by this unique opportunity to determine mechanisms by which a viral infection can be exacerbated by, and even trigger, autoimmunity. The potential role of autoimmunity in post-acute sequelae of COVID-19 is also discussed.

Health Information Technology Utilization by Adolescent and Young Adult Aged Inpatients Undergoing Hematopoietic Cell Transplantation.

This longitudinal study examined feasibility of "Roadmap 1.0," a modular health information application integrated with the electronic medical record, provided to 30 adolescent and young adult (AYA) inpatients 11-24 years of age undergoing hematopoietic stem cell transplantation (HSCT). Feasibility was demonstrated: 70% accessed the application. Utilization was highest the first 2 weeks of hospitalization, with the laboratory results module used most. Users' tension and fatigue were higher than nonusers' at baseline, but not hospital discharge or day 100. Results suggest AYAs utilize health information technology in ways consistent with the HSCT trajectory and Roadmap 1.0 addressed informational and psychological needs.

Promoting Health and Well-Being Through Mobile Health Technology (Roadmap 2.0) in Family Caregivers and Patients Undergoing Hematopoietic Stem Cell Transplantation: Protocol for the Development of a Mobile Randomized Controlled Trial.

BACKGROUND: Cancer patients who undergo allogeneic hematopoietic stem cell transplantation are among the most medically fragile patient populations with extreme demands for caregivers. Indeed, with earlier hospital discharges, the demands placed on caregivers continue to intensify. Moreover, an increased number of allogeneic hematopoietic stem cell transplantations are being performed worldwide, and this expensive procedure has significant economic consequences. Thus, the health and well-being of family caregivers have attracted widespread attention. Mobile health technology has been shown to deliver flexible, and time- and cost-sparing interventions to support family caregivers across the care trajectory. OBJECTIVE: This protocol aims to leverage technology to deliver a novel caregiver-facing mobile health intervention named Roadmap 2.0. We will evaluate the effectiveness of Roadmap 2.0 in family caregivers of patients undergoing hematopoietic stem cell transplantation. METHODS: The Roadmap 2.0 intervention will consist of a mobile randomized trial comparing a positive psychology intervention arm with a control arm in family caregiver-patient dyads. The primary outcome will be caregiver health-related quality of life, as assessed by the PROMIS Global Health scale at day 120 post-transplant. Secondary outcomes will include other PROMIS caregiver- and patient-reported outcomes, including companionship, self-efficacy for managing symptoms, self-efficacy for managing daily activities, positive affect and well-being, sleep disturbance, depression, and anxiety. Semistructured qualitative interviews will be conducted among participants at the completion of the study. We will also measure objective physiological markers (eg, sleep, activity, heart rate) through wearable wrist sensors and health care utilization data through electronic health records. RESULTS: We plan to enroll 166 family caregiver-patient dyads for the full data analysis. The study has received Institutional Review Board approval as well as Code Review and Information Assurance approval from our health information technology services. Owing to the COVID-19 pandemic, the study has been briefly put on hold. However, recruitment began in August 2020. We have converted all recruitment, enrollment, and onboarding processes to be conducted remotely through video telehealth. Consent will be obtained electronically through the Roadmap 2.0 app. CONCLUSIONS: This mobile randomized trial will determine if positive psychology-based activities delivered through mobile health technology can improve caregiver health-related quality of life over a 16-week study period. This study will provide additional data on the effects of wearable wrist sensors on caregiver and patient self-report outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04094844; https://www.clinicaltrials.gov/ct2/show/NCT04094844. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/19288.

Electronic Medical Record Search Engine (EMERSE): An Information Retrieval Tool for Supporting Cancer Research.

PURPOSE: The Electronic Medical Record Search Engine (EMERSE) is a software tool built to aid research spanning cohort discovery, population health, and data abstraction for clinical trials. EMERSE is now live at three academic medical centers, with additional sites currently working on implementation. In this report, we describe how EMERSE has been used to support cancer research based on a variety of metrics. METHODS: We identified peer-reviewed publications that used EMERSE through online searches as well as through direct e-mails to users based on audit logs. These logs were also used to summarize use at each of the three sites. Search terms for two of the sites were characterized using the natural language processing tool MetaMap to determine to which semantic types the terms could be mapped. RESULTS: We identified a total of 326 peer-reviewed publications that used EMERSE through August 2019, although this is likely an underestimation of the true total based on the use log analysis. Oncology-related research comprised nearly one third (n = 105; 32.2%) of all research output. The use logs showed that EMERSE had been used by multiple people at each site (nearly 3,500 across all three) who had collectively logged into the system > 100,000 times. Many user-entered search queries could not be mapped to a semantic type, but the most common semantic type for terms that did match was "disease or syndrome," followed by "pharmacologic substance." CONCLUSION: EMERSE has been shown to be a valuable tool for supporting cancer research. It has been successfully deployed at other sites, despite some implementation challenges unique to each deployment environment.

Development of a National Caregiver Health Survey for Hematopoietic Stem Cell Transplant: Qualitative Study of Cognitive Interviews and Verbal Probing.

BACKGROUND: Roadmap 1.0 is a mobile health app that was previously developed for caregivers of patients who have undergone hematopoietic stem cell transplantation (HSCT). Formative research targeted toward its end users (caregivers) can help inform app design and development, allowing additional components to be incorporated into the app, which can then be tested in a future randomized controlled trial. OBJECTIVE: This study aimed to create a methodologically rigorous national survey that would help inform the development of Roadmap 2.0. METHODS: We conducted a prospective, qualitative research study that took place between November 18, 2018, and February 7, 2019, in a blood and marrow transplant unit within a large academic medical institution in the midwestern part of the United States. Cognitive interviews, including think-aloud and verbal probing techniques, were conducted in 10 adult caregivers (≥18 years) of patients who had undergone HSCT. RESULTS: Most participants were female (9/10, 90%), white (9/10, 90%), married (9/10, 90%), employed at least part time (6/10, 60%), caregivers of adult patients (7/10, 70%), and had some college education (9/10, 90%) and an annual household income of $60,000 or higher (6/10, 60%). All but one interview was audio-recorded, with permission. Overall, participants were engaged in the cognitive interview process of the draft survey, which included 7 topics. The interviews highlighted areas wherein survey items could be further refined, such as offering more response choices (eg, "NA") or clarifying the type of transplant (eg, autologous or allogeneic) or context of transplant care (eg, pre-HSCT, during HSCT, post-HSCT, inpatient, and outpatient). Apart from these findings, the items in demographics, caregiving experiences, technology, positive activities, and mood were generally interpreted as intended. On the basis of the transcript data and field notes by the interviewer, items within self-efficacy (Caregiver Self-Efficacy Scale) and coping (Brief Coping Orientation to Problems Experienced inventory) questionnaires generated more confusion among interviewer and participants, reflecting difficulties in interpreting the meaning of some survey items. CONCLUSIONS: This study incorporated the four cognitive aspects of survey methodology that describe the question-answering process-(1) comprehension, (2) information retrieval, (3) judgment and decision making, and (4) responding-by using the think-aloud and probing techniques in cognitive interviews. We conclude that this methodologically rigorous process informed revisions and improved our final questionnaire design. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/resprot.49188.

Harnessing mobile health technology to support long-term chronic illness management: exploring family caregiver support needs in the outpatient setting.

OBJECTIVE: Family caregiving is an important public health issue, particularly with the aging population. In recent years, mobile health (mHealth) technology has emerged as a potential low-cost, scalable platform to address caregiver support needs, and thereby alleviate the burden on caregivers. This study sought to examine the support needs of family caregivers in their lived experiences of outpatient care to inform the development of a future mHealth intervention. MATERAILS AND METHODS: We conducted 20 semi-structured interviews in 2 outpatient hematopoietic cell transplant (HCT) clinics at a large academic medical center in the Midwestern United States. A thematic analysis was performed to define emerging themes. RESULTS: Qualitative data analysis identified 5 primary themes that HCT caregivers faced: (I) lifestyle restrictions due to the patient's immunocompromised state; (II) Unmet needs due to limitations in the current resources, including unfamiliar medical tasks without necessary trainings; and (III) caregivers' adaptive strategies, including reformation of social relationships with family and friends. Based on these findings, we suggest 3 design considerations to guide the development of a future mHealth intervention. CONCLUSIONS: The findings herein captured the family caregiver's lived experiences during outpatient care. There was broad agreement that caregiving was challenging and stressful. Thus, effective and scalable interventions to support caregivers are needed. This study provided data to guide the content and design of a future mHealth intervention in the outpatient setting.

A Mobile Health App (Roadmap 2.0) for Patients Undergoing Hematopoietic Stem Cell Transplant: Qualitative Study on Family Caregivers' Perspectives and Design Considerations.

BACKGROUND: Hematopoietic stem cell transplantation (HCT), also referred to as blood and marrow transplantation (BMT), is a high-risk, but potentially curative therapy for a number of cancer and noncancer conditions. BMT Roadmap (Roadmap 1.0) is a mobile health app that was developed as a family caregiver-facing tool to provide informational needs about the health status of patients undergoing inpatient HCT. OBJECTIVE: This study explored the views and perceptions of family caregivers of patients undergoing HCT and their input regarding further technology development and expansion of BMT Roadmap into the outpatient setting (referred to as Roadmap 2.0). METHODS: Semistructured qualitative interviews were conducted among 24 family caregivers. Questions were developed from existing literature coupled with prior in-depth observations and interviews in hospital-based settings to explore the study objectives. Participants were recruited during routine outpatient clinic appointments of HCT patients, and all interviews were conducted in the participants' homes, the setting in which Roadmap 2.0 is intended for use. A thematic analysis was performed using a consistent set of codes derived from our prior research. New emerging codes were also included, and the coding structure was refined with iterative cycles of coding and data collection. RESULTS: Four major themes emerged through our qualitative analysis: (1) stress related to balancing caregiving duties; (2) learning and adapting to new routines (resilience); (3) balancing one's own needs with the patient's needs (insight); and (4) benefits of caregiving. When caregivers were further probed about their views on engagement with positive activity interventions (ie, pleasant activities that promote positive emotions and well-being such as expressing gratitude or engaging in activities that promote positive thoughts, emotions, and behaviors), they preferred a "menu" of positive activities to help support caregiver health and well-being. CONCLUSIONS: This study involved family caregivers as participants in the development of new components for Roadmap 2.0. Our research provided a further understanding of the many priorities that hematopoietic stem cell transplant family caregivers face while maintaining balance in their lives. Their schedules can often be unpredictable, even more so once the patient is discharged from the hospital. Our findings suggest that expanding Roadmap 2.0 into the outpatient setting may provide critical caregiver support and that HCT caregivers are interested in and willing to engage in positive activities that may enhance well-being and attenuate the stress associated with caregiving. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/resprot.4918.

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.

A data-driven concept schema for defining clinical research data needs.

OBJECTIVES: The Patient, Intervention, Control/Comparison, and Outcome (PICO) framework is an effective technique for framing a clinical question. We aim to develop the counterpart of PICO to structure clinical research data needs. METHODS: We use a data-driven approach to abstracting key concepts representing clinical research data needs by adapting and extending an expert-derived framework originally developed for defining cancer research data needs. We annotated clinical trial eligibility criteria, EHR data request logs, and data queries to electronic health records (EHR), to extract and harmonize concept classes representing clinical research data needs. We evaluated the class coverage, class preservation from the original framework, schema generalizability, schema understandability, and schema structural correctness through a semi-structured interview with eight multidisciplinary domain experts. We iteratively refined the schema based on the evaluations. RESULTS: Our data-driven schema preserved 68% of the 63 classes from the original framework and covered 88% (73/82) of the classes proposed by evaluators. Class coverage for participants of different backgrounds ranged from 60% to 100% with a median value of 95% agreement among the individual evaluators. The schema was found understandable and structurally sound. CONCLUSIONS: Our proposed schema may serve as the counterpart to PICO for improving the research data needs communication between researchers and informaticians.

FLT3 mutational status is an independent risk factor for adverse outcomes after allogeneic transplantation in AML.

Allogeneic hematopoietic cell transplantation (HCT) has been increasingly used in the setting of FMS-like tyrosine kinase-3 (FLT3)-mutated AML. However, its role in conferring durable relapse-free intervals remains in question. Herein we sought to investigate FLT3 mutational status on transplant outcomes. We conducted a retrospective cohort study of 262 consecutive AML patients who underwent first-time allogeneic HCT (2008-2014), of whom 171 had undergone FLT3-ITD (internal tandem duplication) mutational testing. FLT3-mutated AML was associated with nearly twice the relapse risk (RR) compared with those without FLT3 mutation 3 years post-HCT (63% vs 37%, P<0.001) and with a shorter median time to relapse (100 vs 121 days). FLT3 mutational status remained significantly associated with this outcome after controlling for patient, disease and transplant-related risk factors (P<0.05). Multivariate analysis showed a significant association of FLT3 mutation with increased 3-year RR (hazard ratio (HR) 3.63, 95% confidence interval (CI): 2.13, 6.19, P<0.001) and inferior disease-free survival (HR 2.05, 95% CI: 1.29, 3.27, P<0.01) and overall survival (HR 1.92, 95% CI: 1.14, 3.24, P<0.05). These data demonstrate high risk of early relapse after allogeneic HCT for FLT3-mutated AML that translates into adverse disease-free and overall survival outcomes. Additional targeted and coordinated interventions are needed to maintain durable remission after allogeneic HCT in this high-risk population.

User-Centered Design Groups to Engage Patients and Caregivers with a Personalized Health Information Technology Tool.

Health information technology (IT) has opened exciting avenues for capturing, delivering and sharing data, and offers the potential to develop cost-effective, patient-focused applications. In recent years, there has been a proliferation of health IT applications such as outpatient portals. Rigorous evaluation is fundamental to ensure effectiveness and sustainability, as resistance to more widespread adoption of outpatient portals may be due to lack of user friendliness. Health IT applications that integrate with the existing electronic health record and present information in a condensed, user-friendly format could improve coordination of care and communication. Importantly, these applications should be developed systematically with appropriate methodological design and testing to ensure usefulness, adoption, and sustainability. Based on our prior work that identified numerous information needs and challenges of HCT, we developed an experimental prototype of a health IT tool, the BMT Roadmap. Our goal was to develop a tool that could be used in the real-world, daily practice of HCT patients and caregivers (users) in the inpatient setting. Herein, we examined the views, needs, and wants of users in the design and development process of the BMT Roadmap through user-centered Design Groups. Three important themes emerged: 1) perception of core features as beneficial (views), 2) alerting the design team to potential issues with the user interface (needs); and 3) providing a deeper understanding of the user experience in terms of wider psychosocial requirements (wants). These findings resulted in changes that led to an improved, functional BMT Roadmap product, which will be tested as an intervention in the pediatric HCT population in the fall of 2015 (ClinicalTrials.govNCT02409121).

Identifying unmet informational needs in the inpatient setting to increase patient and caregiver engagement in the context of pediatric hematopoietic stem cell transplantation.

BACKGROUND: Patient-centered care has been shown to improve patient outcomes, satisfaction, and engagement. However, there is a paucity of research on patient-centered care in the inpatient setting, including an understanding of unmet informational needs that may be limiting patient engagement. Pediatric hematopoietic stem cell transplantation (HSCT) represents an ideal patient population for elucidating unmet informational needs, due to the procedure's complexity and its requirement for caregiver involvement. METHODS: We conducted field observations and semi-structured interviews of pediatric HSCT caregivers and patients to identify informational challenges in the inpatient hospital setting. Data were analyzed using a thematic grounded theory approach. RESULTS: Three stages of the caregiving experience that could potentially be supported by a health information technology system, with the goal of enhancing patient/caregiver engagement, were identified: (1) navigating the health system and learning to communicate effectively with the healthcare team, (2) managing daily challenges of caregiving, and (3) transitioning from inpatient care to long-term outpatient management. DISCUSSION: We provide four practical recommendations to meet the informational needs of pediatric HSCT patients and caregivers: (1) provide patients/caregivers with real-time access to electronic health record data, (2) provide information about the clinical trials in which the patient is enrolled, (3) provide information about the patient's care team, and (4) properly prepare patients and caregivers for hospital discharge. CONCLUSION: Pediatric HSCT caregivers and patients have multiple informational needs that could be met with a health information technology system that integrates data from several sources, including electronic health records. Meeting these needs could reduce patients' and caregivers' anxiety surrounding the care process; reduce information asymmetry between caregivers/patients and providers; empower patients/caregivers to participate in the care process; and, ultimately, increase patient/caregiver engagement in the care process.

A Novel Health Information Technology Communication System to Increase Caregiver Activation in the Context of Hospital-Based Pediatric Hematopoietic Cell Transplantation: A Pilot Study.

BACKGROUND: Pediatric hematopoietic cell transplantation (HCT), commonly referred to as blood and marrow transplantation (BMT), is an intense treatment modality that requires the involvement of engaged caregivers during the patient's (child's) prolonged hospitalization. The ubiquity of electronic health records (EHRs) and a trend toward patient-centered care could allow a novel health information technology (IT) system to increase parental engagement. The paucity of research on acute care, hospital-based (inpatient) health IT applications for patients or caregivers provides an opportunity for testing the feasibility of such applications. The pediatric BMT population represents an ideal patient group to conduct an evaluation due to the lengthy inpatient stays and a heightened need for patient activation. OBJECTIVE: The primary objective of this study is to assess the feasibility of implementing the BMT Roadmap in caregivers as an intervention during their child's inpatient hospitalization. The BMT Roadmap is an inpatient portal prototype optimized for tablet with a user-centered design. It integrates patient-specific laboratory and medication data from the EHR in real-time and provides support in terms of discharge goals, home care education, and other components. Feasibility will be proven if (1) the BMT Roadmap functions and can be managed by the study team without unexpected effort, (2) the system is accessed by users at a defined minimum threshold, and (3) the qualitative and quantitative research conducted provides quality data that address the perceived usefulness of the BMT Roadmap and could inform a study in a larger sample size. METHODS: This will be a single-arm, nonrandomized feasibility study. We aim to enroll 10 adult caregivers (age ≥ 18 years) of pediatric patients (aged 0-25 years) undergoing autologous (self-donor) or allogeneic (alternative donor) BMT. Assenting minors (aged 10-18) will also be invited to participate. Recruitment of study participants will take place in the outpatient pediatric BMT clinic. After signing an informed consent, the research study team will provide participants with the BMT Roadmap, available on an Apple iPad, which will used throughout the inpatient hospitalization. To measure the study outcomes, approximately 6-8 semistructured qualitative interviews will be conducted periodically from pre-BMT to 100 days post-BMT and an additional 15-20 semistructured interviews will be conducted among BMT health care providers to assess perceived usefulness and usability of the system, as well as any associated workflow impacts. Quantitative survey instruments will only be administered to adult participants (age ≥ 18 years). RESULTS: Recruitment will begin in September 2015, and preliminary findings are expected in 2016. CONCLUSIONS: This protocol offers a framework for the design and analysis of a personalized health IT system that has the potential to increase patient and caregiver engagement in acute care, hospital-based contexts.

Retrospective Study of Sirolimus and Cyclophosphamide in Patients with Advanced Differentiated Thyroid Cancers.

BACKGROUND: We hypothesize that the combination of an mTOR inhibitor, sirolimus, with a well-known cytotoxic agent, cyclophosphamide, provides a well-tolerated and promising alternative treatment for advanced, differentiated thyroid cancers (DTC). METHODS: This retrospective review extracted data from patients treated for advanced DTC at the University of Michigan Comprehensive Cancer Center from 1995 through 2013. Fifteen patients treated with combination sirolimus and cyclophosphamide were identified as the sirolimus+cyp group. Seventeen patients treated with standard of care and enrolled in clinical trials were identified as the comparison group. RESULTS: The one-year progression free survival rate (PFS) was 0.45, 95% CI [0.26, 0.80] in the sirolimus+cyp population and 0.30, 95% CI [0.13, 0.67] in the comparison population. The hazard ratio for PFS from initiation of treatment was 1.47, 95% CI [0.57, and 3.78]. In patients treated as first line, one-year PFS rate was 0.57, 95% CI [0.30, 1.00] in the sirolimus+cyp group and relatively unchanged at 0.29, 95% CI [0.11, 0.74] in the comparison group. The hazard ratio for PFS for first line patients was 1.10, 95% CI[ 0.4, and 3.5]. In patients with 3 or fewer sites of metastases, the one year PFS was 0.58, 95% CI [0.33, 1.00] in the sirolimus+cyp group, and 0.37, 95% CI [0.17, 0.80] in the comparison group. The average number of toxicities was 0.87 in the sirolimus+cyp patients and 1.71 in the comparison group. CONCLUSIONS: The combination of sirolimus and cyclophosphamide was generally well tolerated with similar progression free survival, highlighting its applicability in patients with limited options.

Engraftment syndrome after allogeneic hematopoietic cell transplantation predicts poor outcomes.

Engraftment syndrome (ES), characterized by fever, rash, pulmonary edema, weight gain, liver and renal dysfunction, and/or encephalopathy, occurs at the time of neutrophil recovery after hematopoietic cell transplantation (HCT). In this study, we evaluated the incidence, clinical features, risk factors, and outcomes of ES in children and adults undergoing first-time allogeneic HCT. Among 927 patients, 119 (13%) developed ES at a median of 10 days (interquartile range 9 to 12) after HCT. ES patients experienced significantly higher cumulative incidence of grade 2 to 4 acute GVHD at day 100 (75% versus 34%, P < .001) and higher nonrelapse mortality at 2 years (38% versus 19%, P < .001) compared with non-ES patients, resulting in lower overall survival at 2 years (38% versus 54%, P < .001). There was no significant difference in relapse at 2 years (26% versus 31%, P = .772). Suppression of tumorigenicity 2, interleukin 2 receptor alpha, and tumor necrosis factor receptor 1 plasma biomarker levels were significantly elevated in ES patients. Our results illustrate the clinical significance and prognostic impact of ES on allogeneic HCT outcomes. Despite early recognition of the syndrome and prompt institution of corticosteroid therapy, outcomes in ES patients were uniformly poor. This study suggests the need for a prospective approach of collecting clinical features combined with correlative laboratory analyses to better characterize ES.

Osteochondromas after radiation for pediatric malignancies: a role for expanded counseling for skeletal side effects.

BACKGROUND: A relationship has been reported between total body irradiation (TBI) and later development of osteochondromas in children who receive radiation therapy as conditioning before hematopoietic stem cell transplantation (HSCT). The goal of this study was to better characterize osteochondromas occurring in these children. METHODS: We identified all children (0 to 18 y) who received an allogeneic HSCT and TBI from 2000 to 2012 from a blood and marrow transplant (BMT) database. Thereafter, we identified those who developed osteochondromas through a chart review. In addition, we searched for diagnosis and operative codes from 1996 to 2012 in our pediatric orthopaedic clinical records, isolating osteochondroma patients with a history of radiation exposure. RESULTS: Four patients who underwent allogeneic HSCT and were later diagnosed with osteochondromas were identified from the BMT database (N=233 children); all 4 were among a group of 72 patients who received TBI. Three patients were identified from orthopaedic records. The cohort included 5 boys and 2 girls with acute lymphoblastic leukemia (N=5) or neuroblastoma (N=2), diagnosed at a median age of 2.0 years. Therapy for all patients included chemotherapy, radiation therapy (TBI, N=5; abdominal, N=2), and HSCT. A diagnosis of osteochondroma was made at a median age of 11.7 years (range, 5 to 16 y), on average 8.6 years after radiation therapy. Diagnosis was incidental in 2 patients and secondary to symptoms (pain or genu valgum) in 5. Locations of osteochondromas were the proximal tibia (N=3), distal tibia, distal femur, distal ulna, and the distal phalanx (N=1 each). Three patients underwent surgical resection. CONCLUSIONS: Children may be more likely to develop osteochondromas after early exposure to radiation therapy, which may cause pain and require surgical resection. To the best of our knowledge, this is the first reported case of a radiation-induced osteochondroma causing lower extremity malalignment. Patients typically present to the pediatric orthopaedist's attention when symptomatic, but there may be an expanded role for counseling for potential for long-term skeletal effects in this group. LEVEL OF EVIDENCE: Level IV, case series.

Computerized prescriber order entry implementation in a physician assistant-managed hematology and oncology inpatient service: effects on workflow and task switching.

PURPOSE: Little is known about the impact of computerized prescriber order entry (CPOE) systems on inpatient hematology/oncology services. The objective of this study was to quantify the impact of an inpatient CPOE implementation on workflow, with an emphasis on ordering and direct patient care time. METHODS: We conducted a direct-observation time-and-motion study of the provider team of a hematology/oncology inpatient service both before and after CPOE implementation, characterizing workflow into 60 distinct activity categories. The provider team comprised physician assistants supervised by attending physicians. Results were adjusted to account for variations in the census. We also conducted an analysis of computer logs to assess CPOE system usage. RESULTS: Study participants were observed for 228.0 hours over 53 observation sessions. There was little change in the proportion of census-adjusted time spent on ordering (10.2% before v 11.4% after) and on direct patient care (50.7% before v 47.8% after). Workflow fragmentation decreased, with providers spending an average of 131.2 seconds on a continuous task before implementation and 218.3 seconds after (P < .01). An eight-fold decrease in the number of pages was observed during the course of the study. CONCLUSION: CPOE implementation did not negatively affect time available for direct patient care. Workflow fragmentation decreased, which is likely beneficial.

Rapid reduction of central line infections in hospitalized pediatric oncology patients through simple quality improvement methods.

BACKGROUND: Pediatric hematology-oncology (PHO) patients are at significant risk for developing central line-associated bloodstream infections (CLA-BSIs) due to their prolonged dependence on such catheters. Effective strategies to eliminate these preventable infections are urgently needed. In this study, we investigated the implementation of bundled central line maintenance practices and their effect on hospital-acquired CLA-BSIs. MATERIALS AND METHODS: CLA-BSI rates were analyzed within a single-institution's PHO unit between January 2005 and June 2011. In May 2008, a multidisciplinary quality improvement team developed techniques to improve the PHO unit's safety culture and implemented the use of catheter maintenance practices tailored to PHO patients. Data analysis was performed using time-series methods to evaluate the pre- and post-intervention effect of the practice changes. RESULTS: The pre-intervention CLA-BSI incidence was 2.92 per 1,000-patient days (PD) and coagulase-negative Staphylococcus was the most prevalent pathogen (29%). In the post-intervention period, the CLA-BSI rate decreased substantially (45%) to 1.61 per 1,000-PD (P < 0.004). Early on, blood and marrow transplant (BMT) patients had a threefold higher CLA-BSI rate compared to non-BMT patients (P < 0.033). With additional infection control countermeasures added to the bundled practices, BMT patients experienced a larger CLA-BSI rate reduction such that BMT and non-BMT CLA-BSI rates were not significantly different post-intervention. CONCLUSIONS: By adopting and effectively implementing uniform maintenance catheter care practices, learning multidisciplinary teamwork, and promoting a culture of patient safety, the CLA-BSI incidence in our study population was significantly reduced and maintained.