From a decentralized clinical trial to a decentralized and clinical-trial-in-a-box platform: Towards patient-centric and equitable trials.

Background/Objective: Despite the intuitive attractiveness of bringing research to participants rather than making them come to central study sites, widespread decentralized enrollment has not been common in clinical trials. Methods: The need for clinical research in the context of the COVID-19 pandemic, along with innovations in technology, led us to use a decentralized trial approach in our Phase 2 COVID-19 trial. We used real-time acquisition and transmission of health-related data using home-based monitoring devices and mobile applications to assess outcomes. This approach not only avoids spreading COVID-19 but it also can support inclusion of participants in more diverse socioeconomic circumstances and in rural settings. Results: Our team developed and deployed a decentralized trial platform to support patient engagement and adverse event reporting. Clinicians, engineers, and informaticians on our research team developed a Clinical-Trial-in-a-Box tool to optimally collect and analyze data from multiple decentralized platforms. Conclusion: Applying the decentralized model in Long COVID, using digital health technology and personal devices integrated with our telehealth platform, we share the lessons learned from our work, along with challenges and future possibilities.

The use of N-of-1 trials to generate real-world evidence for optimal treatment of individuals and populations.

Introduction: Ideally, real-world data (RWD) collected to generate real-world evidence (RWE) should lead to impact on the care and health of real-world patients. Deriving from care in which clinicians and patients try various treatments to inform therapeutic decisions, N-of-1 trials bring scientific methods to real-world practice. Methods: These single-patient crossover trials generate RWD and RWE by giving individual patients various treatments in a double-blinded way in sequential periods to determine the most effective treatment for a given patient. Results: This approach is most often used for patients with chronic, relatively stable conditions that provide the opportunity to make comparisons over multiple treatment periods, termed Type 1 N-of-1 trials. These are most helpful when there is heterogeneity of treatment effects among patients and no a priori best option. N-of-1 trials also can be done for patients with rare diseases, potentially testing only one treatment, to generate evidence for personalized treatment decisions, designated as Type 2 N-of-1 trials. With both types, in addition to informing individual's treatments, when uniform protocols are used for multiple patients with the same condition, the data collected in the individual N-of-1 trials can be aggregated to provide RWD/RWE to inform more general use of the treatments. Thereby, N-of-1 trials can provide RWE for the care of individuals and for populations. Conclusions: To fulfill this potential, we believe N-of-1 trials should be built into our current healthcare ecosystem. To this end, we are building the needed infrastructure and engaging the stakeholders who should receive value from this approach.

How Do We Reduce Burnout In Nursing?

Burnout syndrome has been defined as a state of chronic stress characterized by high levels of emotional exhaustion and depersonalization with low levels of professional efficacy. The effects of nurse burnout include poor job satisfaction and turnover. Nurses' physical and mental well-being are both essential to sustaining a healthy nursing workforce with factors such as an empowering work environment showing positive effects on reducing burnout. Formal and informal individual and organizational approaches to supporting novice nurses' transition and experienced nurses' sustained practice fulfillment are key to addressing burnout and fostering retention.

Comparison of Factors Associated with Physician and Nurse Burnout.

Burnout is a condition resulting from chronic workplace stress that has not been effectively managed, described in 3 dimensions: (a) feelings of energy depletion or exhaustion, (b) increased mental distance from one's job, and (c) reduced professional efficacy. Burnout is a widespread problem reaching concerning levels among health care professionals, with more than 50% of physicians and one-third as many as 80% of nurses reporting symptoms. The National Academy of Medicine (NAM) action collaborative on clinician well-being and resilience has prioritized exploring ways to enhance baseline understanding of clinician well-being and promotion of multidisciplinary solutions to burnout.

The Effect of Burnout on Quality of Care Using Donabedian's Framework.

Donabedian's framework offers a model to evaluate the relationship between patient outcomes, influenced by clinical care delivery structures and processes. Applying this model proposes that adequate and appropriate structures and processes within organizations are necessary to realize optimal outcomes; it is imperative that leadership focuses on those structures and processes to reduce the risk of burnout. Current research cannot determine whether burnout causes decreased quality or working in a setting with decreased quality causes burnout. The follow-up question is whether curtailing burnout will improve quality or whether improving quality of care will reduce provider burnout?

Participant and research team perspectives on the conduct of a remote therapeutic COVID-19 clinical trial: A mixed methods approach.

Background: Responding to the need to investigate potential treatments of COVID-19, a research team employed a telehealth platform to determine whether niclosamide, an oral anthelmintic drug that had shown antiviral activity, reduced SARS-CoV-2 shedding and duration of symptoms in patients with mild-to-moderate symptoms of COVID-19. To encourage compliance with patient self-quarantine, this randomized placebo-controlled clinical trial was conducted utilizing a remote telehealth design to complete all study visits, monitor symptoms, and coordinate participant self-collected specimens. Methods: A mixed methods approach employing surveys and interviews of trial participants and interviews of research team members was used to collect their experiences with and perspectives on the acceptability of the remote clinical trial design and delivery. Results: Of the 67 eligible trial participants invited to take part in a study to evaluate the telehealth platform, 46% (n = 31) completed a post-participation survey. While 97% (n = 30) of respondents had not previously participated in a clinical trial, 77% (n = 24) reported they would consider taking part in a future remote research study. The majority of respondents were moderately or very comfortable (93%) with using the technology. Conclusions: The COVID-19 crisis was a call to action to expand understanding of the conduct of remote clinical trials, including the experiences of research participants. Our findings showed that this approach can be both effective for the conduct of research and positive for participants. Further research on the use of telehealth research platforms seems warranted in rural, underserved populations, and remote trials of prevention, screening, and treatment.

Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19: A Phase 2 Randomized Clinical Trial.

Importance: Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective: To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants: This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions: In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures: Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase-polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results: Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 (P = .37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, -2.6 [95% CI, -7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P = .31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P = .82). Conclusions and Relevance: In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT04399356.

Systematic Review of Burnout in US Nurses.

Nurses experience high levels of burnout, and this has become a major factor in recruitment and retention of nurses. Several factors have been associated with burnout, but it is not clear which factors are the most significant predictors. Understanding the most prevalent factors that are associated with burnout will allow for the development and implementation of interventions to ameliorate and/or reduce burnout in the nursing workforce.

Effect of an audit and feedback intervention on hospitalized oncology patients' perception of nurse practitioner care.

Although patient satisfaction has been used traditionally as a measure of excellence, research has suggested that the perception of being well cared for is likely a more promising indicator of quality than satisfaction alone. Expectations, physical environment, communication, participation and involvement, technical competence, and the influence of healthcare organizations are factors that may impair patients' ability to distinguish nursing care from their overall healthcare experience. This study evaluated the effect of a nurse practitioner audit and feedback intervention on hospitalized patients' perception of care.

Patient online self-reporting of toxicity symptoms during chemotherapy.

PURPOSE: Tracking symptoms related to treatment toxicity is standard practice in routine care and during clinical trials. Currently, clinicians collect symptom information via complex and often inefficient mechanisms, but there is growing interest in collecting outcome information directly from patients. PATIENTS AND METHODS: The National Cancer Institute Common Terminology Criteria for Adverse Events schema for seven common symptoms was adapted into a Web-based patient-reporting system, accessible from desktop computers in outpatient clinics and from home computers. Eighty patients with gynecologic malignancies beginning standard chemotherapy regimens were enrolled between April and September 2004. During an 8-week observation period, participants were encouraged to log in and report symptoms at each follow-up visit, or alternatively, to access the system from home. RESULTS: All patients completed an initial log in. At each subsequent appointment, most enrollees (80% to 85%) reported symptoms using the online system, with a mean of three follow-up visits per patient during the observation period (range, one to six). Sixty of 80 patients (75%) logged in at least once from home. Use was significantly associated with prior Internet experience. Forty-two severe toxicities (grade 3 to 4) entered from home prompted seven clinician interventions. Most patients (96%) found the system useful and would recommend it to others. CONCLUSION: Patients are capable of reporting symptoms experienced during chemotherapy using a Web-based interface. Assessment in the clinical trial setting and comparison of direct patient- versus clinician-based approaches for reporting symptoms and their severity are warranted.

Symptom Monitoring With Patient-Reported Outcomes During Routine Cancer Treatment: A Randomized Controlled Trial.

PURPOSE: There is growing interest to enhance symptom monitoring during routine cancer care using patient-reported outcomes, but evidence of impact on clinical outcomes is limited. METHODS: We randomly assigned patients receiving routine outpatient chemotherapy for advanced solid tumors at Memorial Sloan Kettering Cancer Center to report 12 common symptoms via tablet computers or to receive usual care consisting of symptom monitoring at the discretion of clinicians. Those with home computers received weekly e-mail prompts to report between visits. Treating physicians received symptom printouts at visits, and nurses received e-mail alerts when participants reported severe or worsening symptoms. The primary outcome was change in health-related quality of life (HRQL) at 6 months compared with baseline, measured by the EuroQol EQ-5D Index. Secondary endpoints included emergency room (ER) visits, hospitalizations, and survival. RESULTS: Among 766 patients allocated, HRQL improved among more participants in the intervention group than usual care (34% v 18%) and worsened among fewer (38% v 53%; P < .001). Overall, mean HRQL declined by less in the intervention group than usual care (1.4- v 7.1-point drop; P < .001). Patients receiving intervention were less frequently admitted to the ER (34% v 41%; P = .02) or hospitalized (45% v 49%; P = .08) and remained on chemotherapy longer (mean, 8.2 v 6.3 months; P = .002). Although 75% of the intervention group was alive at 1 year, 69% with usual care survived the year (P = .05), with differences also seen in quality-adjusted survival (mean of 8.7 v. 8.0 months; P = .004). Benefits were greater for participants lacking prior computer experience. Most patients receiving intervention (63%) reported severe symptoms during the study. Nurses frequently initiated clinical actions in response to e-mail alerts. CONCLUSION: Clinical benefits were associated with symptom self-reporting during cancer care.

Primary Care Provider Evaluation of Cancer Survivorship Care Plans Developed for Patients in their Practice.

OBJECTIVE: Survivorship care plans (SCP), which describe a cancer survivor's diagnosis, treatment and follow-up, are recommended. The study objective was to evaluate primary care providers' (PCP) responses to SCPs developed for breast and colorectal cancer survivors in their practice and to determine whether PCP response to the SCPs varied according to characteristics of the practitioner and their practice. METHOD: SCPs were created using the Journey Forward® Care Plan for breast and colorectal cancer patients in rural and urban settings. The SCP and a survey were sent to PCPs. PARTICIPANTS: Primary care physicians. MAIN MEASURES: Attitudes regarding survivorship care plans. RESULTS: Thirty-nine (70.9% response rate) surveys were completed. Most felt the SCP was useful (90%), that it enhanced understanding (75%) and that detail was sufficient (>80%). However, 15% disagreed that the care plan helped them understand their role, a perception especially prevalent among PCPs in the rural setting. Among PCPs with ≤ 18 years in practice, 95% agreed that the SCP would improve communication with patients, contrasted with 60% of those with >21 years in practice. The most common barrier to providing follow-up care was limited access to survivors. CONCLUSIONS: While SCPs appear to improve PCPs understanding of a cancer diagnosis and treatment, clear delineation of each provider's role in follow-up care is needed. Additional detail on which tests are needed and education on late and long term effects of cancer may improve coordination of care.

Patient satisfaction with breast and colorectal cancer survivorship care plans.

Cancer survivors face several challenges following the completion of active treatment, including uncertainty about late effects of treatment and confusion about coordination of follow-up care. The authors evaluated patient satisfaction with personalized survivorship care plans designed to clarify those issues. The authors enrolled 48 patients with breast cancer and 10 patients with colorectal cancer who had completed treatment in the previous two months from an urban academic medical center and a rural community hospital. Patient satisfaction with the care plan was assessed by telephone interview. Overall, about 80% of patients were very or completely satisfied with the care plan, and 90% or more agreed that it was useful, it was easy to understand, and the length was appropriate. Most patients reported that the care plan was very or critically important to understanding an array of survivorship issues. However, only about half felt that it helped them better understand the roles of primary care providers and oncologists in survivorship care. The results provide evidence that patients with cancer find high value in personalized survivorship care plans, but the plans do not eliminate confusion regarding the coordination of follow-up care. Future efforts to improve care plans should focus on better descriptions of how survivorship care will be coordinated.

Barriers and facilitators to implementing cancer survivorship care plans.

PURPOSE/OBJECTIVES: To evaluate the process of survivorship care plan (SCP) completion and to survey oncology staff and primary care physicians (PCPs) regarding challenges of implementing SCPs. DESIGN: Descriptive pilot study. SETTING: Two facilities in Vermont, an urban academic medical center and a rural community academic cancer center. SAMPLE: 17 oncology clinical staff created SCPs, 39 PCPs completed surveys, and 58 patients (breast or colorectal cancer) participated in a telephone survey. METHODS: Using Journey Forward tools, SCPs were created and presented to patients. PCPs received the SCP with a survey assessing its usefulness and barriers to delivery. Oncology staff were interviewed to assess perceived challenges and benefits of SCPs. Qualitative and quantitative data were used to identify challenges to the development and implementation process as well as patient perceptions of the SCP visit. MAIN RESEARCH VARIABLES: SCP, healthcare provider perception of barriers to completion and implementation, and patient perception of SCP visit. FINDINGS: Oncology staff cited the time required to obtain information for SCPs as a challenge. Completing SCPs 3-6 months after treatment ended was optimal. All participants felt advanced practice professionals should complete and review SCPs with patients. The most common challenge for PCPs to implement SCP recommendations was insufficient knowledge of cancer survivor issues. Most patients found the care plan visit very useful, particularly within six months of diagnosis. CONCLUSIONS: Creation time may be a barrier to widespread SCP implementation. Cancer survivors find SCPs useful, but PCPs feel insufficient knowledge of cancer survivor issues is a barrier to providing best follow-up care. Incorporating SCPs in electronic medical records may facilitate patient identification, appropriate staff scheduling, and timely SCP creation. IMPLICATIONS FOR NURSING: Oncology nurse practitioners are well positioned to create and deliver SCPs, transitioning patients from oncology care to a PCP in a shared-care model of optimal wellness. Institution support for the time needed for SCP creation and review is imperative for sustaining this initiative. KNOWLEDGE TRANSLATION: Accessing complete medical records is an obstacle for completing SCPs. A 3-6 month window to develop and deliver SCPs may be ideal. PCPs perceive insufficient knowledge of cancer survivor issues as a barrier to providing appropriate follow-up care.

Implementation of cancer pain guidelines by acute care nurse practitioners using an audit and feedback strategy.

PURPOSE: Despite the availability of clinical practice guidelines (CPGs) for cancer pain, consistent integration of these principles into practice has not been achieved. The optimal method for implementing CPGs and the impact of guidelines on healthcare outcomes remain uncertain. This study evaluated the effect of an audit and feedback (A/F) intervention on nurse practitioner (NP) implementation of cancer pain CPGs and on hospitalized patients' self-report of pain and satisfaction with pain relief. DATA SOURCES: Eight NPs and two groups of 96 patients were the sources of data. Eligible patients in both groups completed the Brief Pain Inventory-Short Form (BPI-SF) within 24 h of admission and every 48 h until discharge. During A/F, NPs received weekly feedback on pain scores and guideline adherence. CONCLUSIONS: Nurse practitioner adherence to CPGs increased during A/F. Pain intensity did not significantly differ between groups. Intervention group patients reported significantly less overall pain interference (p < .0001), interference with general activity (p = .0003), and sleep (p = .006). Satisfaction with pain relief increased from 68.4% to 95.1% during A/F (p < .0001). IMPLICATIONS FOR PRACTICE: A/F is an effective strategy to promote CPG use. Improved functional status in the absence of decreased pain severity underscores the need to consider symptom clusters when studying pain.

Audit and feedback as a clinical practice guideline implementation strategy: a model for acute care nurse practitioners.

BACKGROUND: The transfer of research evidence into practice and changing provider behavior is challenging, even when the advantages are strong. Despite the availability of supportive care clinical practice guidelines (CPG), consistent integration of these principles into practice has not been achieved. The failure of dissemination strategies has been identified as a key barrier to successful implementation. A potentially effective approach to facilitating the transfer of research evidence into practice is audit and feedback. Audit and feedback is a summary of provider performance over a specified period of time, with or without recommendations to improve practice. RATIONALE: Cancer pain is an optimal symptom to examine when studying the effect of an audit and feedback intervention. It is a common condition with important consequences, established CPG are available, measurable outcomes are defined, and there is potential for improvement in current practice. Acute care nurse practitioners (NPs) are often responsible for overseeing and directly managing symptoms such as pain and are well positioned to implement CPG and study the effects of adherence to guidelines on patients' pain outcomes. METHODOLOGY: A systematic review of published articles, MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library computerized databases was performed to evaluate the state of the science on audit and feedback as a professional practice change strategy. A behavior change model is proposed for its application to advanced practice nursing. IMPLICATIONS FOR PRACTICE: Recognized in medicine as a valuable intervention to improve healthcare quality, audit and feedback is a strategy that has not been widely studied in nursing. Although cancer pain cannot always be entirely eliminated, appropriate use of available therapies can effectively relieve pain in a majority of patients. This article is a review of the literature on audit and feedback as a professional practice change strategy and indicates a model for operationalizing the intervention.