Managing Critical Patient-Reported Outcome Measures in Oncology Settings: System Development and Retrospective Study.

BACKGROUND: Remote monitoring programs based on the collection of patient-reported outcome (PRO) data are being increasingly adopted in oncology practices. Although PROs are a great source of patient data, the management of critical PRO data is not discussed in detail in the literature. OBJECTIVE: This first-of-its-kind study aimed to design, describe, and evaluate a closed-loop alerting and communication system focused on managing PRO-related alerts in cancer care. METHODS: We designed and developed a novel solution using an agile software development methodology by incrementally building new capabilities. We evaluated these new features using participatory design and the Fit between Individuals, Task, and Technology framework. RESULTS: A total of 8 questionnaires were implemented using alerting features, resulting in an alert rate of 7.82% (36,838/470,841) with 13.28% (10,965/82,544) of the patients triggering at least one alert. Alerts were reviewed by 501 staff members spanning across 191 care teams. All the alerts were reviewed with a median response time of 1 hour (SD 185 hours) during standard business hours. The most severe (red) alerts were documented 56.83% (2592/4561) of the time, whereas unlabeled alerts were documented 27.68% (1298/4689) of the time, signaling clinician concordance with the alert thresholds. CONCLUSIONS: A PRO-based alert and communication system has some initial benefits in reviewing clinically meaningful PRO data in a reasonable amount of time. We have discussed key system design considerations, workflow integration, and the mitigation of potential impact on the burden of care teams. The introduction of a PRO-based alert and communication system provides a reliable mechanism for care teams to review and respond to patient symptoms quickly. The system was standardized across many different oncology settings, demonstrating system flexibility. Future studies should focus on formally evaluating system usability through qualitative methods.

Impact of Health Perception and Knowledge on Genetic Testing Decisions Using the Health Belief Model.

PURPOSE: Early detection of cancer risk is essential as it is associated with a higher chance of survival, more successful treatment, and improved quality of life. Genetic testing helps at-risk patients estimate the likelihood of developing cancer in a lifetime. This study aims to indentify the factors (perceived susceptibility, severity, benefits, and self-efficacy) that impact one's decision to take the genetic test. METHODS: We examined the impacts of different factors of the health belief model on the engagement of patients in genetic testing using data from the National Cancer Institute's 2020 cross-sectional nationally representative data published in 2021. Complete surveys were answered by 3,865 participants (weighted population size = 253,815,197). All estimates were weighted to be nationally representative of the US population using the jackknife weighting method for parameter estimation. We used multivariable logistic regression to test our hypotheses for patients who have taken the genetic test for cancer risk detection. We adjusted the multivariate model for age, education, income, race, sex, cancer history, familial cancer history, and education. RESULTS: We tested five hypotheses using the health belief model. Respondents who had genetic testing were more likely to rely on their health care providers and genetic counselors to make their decisions. Respondents who had genetic tests also reported less reliability on other sources than doctors: for the internet and social media (odds ratio = 0.33; P < .001) and for journals and magazines (odds ratio = 0.48; P = .007). CONCLUSION: The findings show that patients generally rely on suggestions from their health care providers and counselors in genetic testing decisions. These findings also indicate that health care providers play a critical role in helping patients decide whether to use genetic testing to detect cancer risk in the early stages.

Oncology Patients' Perspectives on Remote Patient Monitoring for COVID-19.

PURPOSE: Oncology patients are vulnerable to adverse outcomes associated with COVID-19, and clinical deterioration must be identified early. Several institutions launched remote patient monitoring programs (RPMPs) to care for patients with COVID-19. We describe patients' perspectives on a COVID-19 RPMP at a National Comprehensive Cancer Center. METHODS: Patients who tested positive for COVID-19 were eligible. Enrolled patients received a daily electronic COVID-19 symptom assessment, and a subset of high-risk patients also received a pulse oximeter. Monitoring was provided by a centralized team and was discontinued 14 days after a patient's positive test result and following 3 days without worsening symptoms. Patients who completed at least one assessment and exited the program were sent a patient engagement survey to evaluate the patient's experience with digital monitoring for COVID-19. RESULTS: The survey was distributed to 491 patients, and 257 responded (52% completion rate). The net promoter score was 85%. Most patients agreed that the RPMP was worthwhile, enabled better management of their COVID-19 symptoms, made them feel more connected to their healthcare team, and helped prevent emergency room visits. Identified themes regarding patient-perceived value of a RPMP included (1) security: a clinical safety net; (2) connection: a link to their clinical team during a period of isolation; and (3) empowerment: an education on the virus and symptom management. CONCLUSION: RPMPs are perceived to be of value to oncology patients with COVID-19. Policymakers should consider how these programs can be reimbursed to keep vulnerable patients at home and out of the acute care setting.

Case study of the integration of electronic patient-reported outcomes as standard of care in a head and neck oncology practice: Obstacles and opportunities.

BACKGROUND: Patient-reported outcomes (PROs) allow for the direct measurement of functional and psychosocial effects related to treatment. However, technological barriers, survey fatigue, and clinician adoption have hindered the meaningful integration of PROs into clinical care. The objective of the authors was to develop an electronic PROs (ePROs) program that meets a range of clinical needs across a head and neck multidisciplinary disease management team. METHODS: The authors developed the ePROs module using literature review and stakeholder input in collaboration with health informatics. They designed an ePROs platform that was integrated as the standard of care for personalized survey delivery by diagnosis across the disease management team. Tableau software was used to create dashboards for data visualization and monitoring at the clinical enterprise, disease subsite, and patient levels. All patients who were treated for head and neck cancer were eligible for ePROs assessment as part of the standard of care. A descriptive analysis of ePROs program implementation is presented herein. RESULTS: The Head and Neck Service at Memorial Sloan Kettering Cancer Center has integrated ePROs into clinical care. Surveys are delivered via the patient portal at the time of diagnosis and longitudinally through care. From August 1, 2018, to February 1, 2020, a total of 4154 patients completed ePROs surveys. The average patient participation rate was 69%, with a median time for completion of 5 minutes. CONCLUSIONS: Integration of the head and neck ePROs program as part of clinical care is feasible and could be used to assess value and counsel patients in the future. Continued qualitative assessments of stakeholders and workflow will refine content and enhance the health informatics platform. LAY SUMMARY: Patients with head and neck cancer experience significant changes in their quality of life after treatment. Measuring and integrating patient-reported outcomes as a part of clinical care have been challenging given the multimodal treatment options, vast subsites, and unique domains affected. The authors present a case study of the successful integration of electronic patient-reported outcomes into a high-volume head and neck cancer practice.

Molecular imaging of expression of vascular endothelial growth factor a (VEGF a) in femoral bone grafts transplanted into living mice.

The biology of cells transplanted with bone grafts is incompletely understood. Focusing on the early angiogenic response postgrafting, we report a mouse femur graft model in which grafts were derived from mice transgenic for a firefly luciferase (FLuc) bioluminescence reporter gene driven by a promoter for the angiogenic signaling molecule vascular endothelial growth factor (VEGF). Upon transplantation into wild-type (wt) mice, in vivo bioluminescence imaging (BLI) permitted longitudinal visualization and measurements of VEGF promoter activity in the transplanted graft cells and demonstrated a lag period of 7 days posttransplantation prior to robust induction of the promoter. To determine cellular mediators of VEGF induction in graft bone, primary graft-derived osteoblastic cells (GDOsts) were characterized. In vitro BLI on GDOsts showed hypoxia-induced VEGF expression and that this induction depended on PI3K signaling and, to a lesser degree, on the MEK pathway. This transcriptional regulation correlated with VEGF protein production and was validated in GDOsts seeded on demineralized bone matrix (DBM), a bone graft substitute material. Together, combined imaging of VEGF expression in living animals and in live cells provided clues about the regulation of VEGF in cells post-bone grafting. These data are particularly significant toward the development of future smart bone graft substitutes.

Loss of transcription factor early growth response gene 1 results in impaired endochondral bone repair.

Transcription factors that play a role in ossification during development are expected to participate in postnatal fracture repair since the endochondral bone formation that occurs in embryos is recapitulated during fracture repair. However, inherent differences exist between bone development and fracture repair, including a sudden disruption of tissue integrity followed by an inflammatory response. This raises the possibility that repair-specific transcription factors participate in bone healing. Here, we assessed the consequence of loss of early growth response gene 1 (EGR-1) on endochondral bone healing because this transcription factor has been shown to modulate repair in vascularized tissues. Model fractures were created in ribs of wild type (wt) and EGR-1(-/-) mice. Differences in tissue morphology and composition between these two animal groups were followed over 28 post fracture days (PFDs). In wt mice, bone healing occurred in healing phases characteristic of endochondral bone repair. A similar healing sequence was observed in EGR-1(-/-) mice but was impaired by alterations. A persistent accumulation of fibrin between the disconnected bones was observed on PFD7 and remained pronounced in the callus on PFD14. Additionally, the PFD14 callus was abnormally enlarged and showed increased deposition of mineralized tissue. Cartilage ossification in the callus was associated with hyper-vascularity and -proliferation. Moreover, cell deposits located in proximity to the callus within skeletal muscle were detected on PFD14. Despite these impairments, repair in EGR-1(-/-) callus advanced on PFD28, suggesting EGR-1 is not essential for healing. Together, this study provides genetic evidence that EGR-1 is a pleiotropic regulator of endochondral fracture repair.

Early growth response gene 1 regulates bone properties in mice.

Transcriptional regulation of the postnatal skeleton is incompletely understood. Here, we determined the consequence of loss of early growth response gene 1 (EGR-1) on bone properties. Analyses were performed on both the microscopic and molecular levels utilizing micro-computed tomography (micro-CT) and Fourier transform infrared imaging (FTIRI), respectively. Mice deficient in EGR-1 (Egr-1 (-/-)) were studied and compared to sex- and age-matched wild-type (wt) control animals. Femoral trabecular bone in male Egr-1 (-/-) mice demonstrated osteopenic characteristics marked by reductions in both bone volume fraction (BV/TV) and bone mineral density (BMD). Morphological analysis revealed fewer trabeculae in these animals. In contrast, female Egr-1 (-/-) animals had thinner trabeculae, but BV/TV and BMD were not significantly reduced. Analysis of femoral cortical bone at the mid-diaphysis did not show significant osteopenic characteristics but detected changes in cross-sectional geometry in both male and female Egr-1 (-/-) animals. Functionally, this resulted in decreased resistance to three-point bending as indicated by a reduction in maximum load, failure load, and stiffness. Assessment of compositional bone properties, including mineral-to-matrix ratio, carbonate-to-phosphate ratio, crystallinity, and cross-linking, in femurs by FTIRI did not show any significant differences or an appreciable trend between Egr-1 (-/-) and wt mice of either sex. Unexpectedly, rib bone from Egr-1 (-/-) animals displayed distinct osteopenic traits that were particularly pronounced in female mice. This study provides genetic evidence that both sex and skeletal site are critical determinants of EGR-1 activity in vivo and that its site-specific action may contribute to the mechanical properties of bone.

Production of VEGF receptor 1 and 2 mRNA and protein during endochondral bone repair is differential and healing phase specific.

Physiological disturbances, including temporary hypoxia, are expected to drive angiogenesis during bone repair. Evidence suggests that the angiogenic ligand vascular endothelial growth factor (VEGF)-A plays an important role in this process. We characterized the expression of two receptors that are essential for mediating VEGF signaling, VEGFR1/Flt-1 and VEGFR2/Flk-1/KDR, in a mouse rib fracture model. Their mRNA and protein levels were assessed in four healing phases, which were characterized histologically as hemorrhage formation on postfracture day (PFD) 1, inflammatory response on PFD 3, initiation of callus development on PFD 7, and the presence of a mature callus on PFD 14. Transcript was detected for VEGFR1 and VEGFR2, as well as VEGF. While mRNA expression of VEGFR1 was monophasic throughout all healing phases, VEGFR2 showed a biphasic profile with significantly increased mRNA expression during callus formation and maturation. Expression of VEGF mRNA was characterized by a more gradual increase during callus formation. The protein level for VEGFR1 was below detection sensitivity during the initial healing phase. It was then restored to a stable level, detectable through the subsequent healing phases. Hence, the VEGFR1 protein levels partially mirrored the transcript expression profile. In comparison, the protein level of VEGFR2 increased gradually during the healing phases and peaked at callus maturation. This correlated well with the transcriptional expression of VEGFR2. Intact bone from age-matched male mice had considerable protein levels of VEGFR1 and VEGF, but no detectable VEGFR2. Together, these findings uncovered expression signatures of the VEGF-VEGFR axis in endochondral bone repair.