Phase I/II study to evaluate consolidative hypofractionated radiation therapy for boosting the residual primary disease in combination with durvalumab after definitive chemoradiation therapy for stage III non-small cell lung cancer (NSCLC): study protocol for a prospective trial.

Background: Recent advancements in the management of non-small cell lung cancer (NSCLC) have confirmed the utility of adding adjuvant immunotherapy to concurrent chemoradiotherapy in stage III disease but intrathoracic progression remains at high rate. Additional studies have sought to investigate the synergistic relationship of immunotherapy and radiation therapy (RT). The goal of this study is to evaluate the safety and efficacy of combining consolidative hypofractionated radiation therapy (hfRT) using stereotactic body radiotherapy (SBRT) technique for boosting the residual primary lung cancer with adjuvant anti-programmed death-ligand 1 (PD-L1) therapy concurrently after completion of definitive chemoradiation therapy (dCRT) in the rates of tumor control locoregionally and distantly. Methods: Eligible subjects with stage III NSCLC must have gross residual tumor that is smaller than 5.0 cm in maximal dimension following dCRT. Consolidative hfRT will be delivered 1 to 2 months after finishing dCRT and concurrently with adjuvant anti-PD-L1 therapy using durvalumab. Consolidative hfRT will start from 6.5 Gy ×2 fractions and dose escalate to 10 Gy ×2 fractions in a 3+3 design. At the final determined consolidative hfRT dose level, a total of 32 subjects with pathologically documented stage III NSCLC treated with two or more cycles of platinum-based doublet chemotherapy concurrently with RT will be enrolled for data analyses. Discussion: We hypothesize that the use of consolidative hfRT directed to the residual primary lung tumor in combination with adjuvant anti-PD-L1 therapy will provide additional immunostimulation and therefore improved locoregional and distant control when compared to either modality used independently. Registration: Clinicaltrials.gov: NCT04748419.

Nurse practitioner-led, virtually delivered, motivational enhancement and device support intervention to improve CPAP adherence: A feasibility randomized control trial.

BACKGROUND: Evidence indicates continuous positive airway pressure (CPAP) therapy improves several important patient-centered outcomes. However, adherence to this safe and effective intervention remains poor. OBJECTIVES: Assess nine feasibility outcomes of a nurse practitioner-led, virtually delivered motivational enhancement and device support (MENDS) intervention to improve CPAP adherence in adults with Obstructive Sleep Apnea (OSA). Secondary aims compared the changes in CPAP adherence to patient-reported outcomes, patient activation, and perceived self-efficacy. METHODS: This two-group feasibility randomized controlled trial included 29 patients newly diagnosed with OSA and prescribed CPAP therapy. The study was conducted from July 2020 through December 2021 at a midwestern sleep/pulmonary clinic. Participants were randomized to the MENDS intervention group (n=14) (30-45 minute interactive tele-discussions on weeks 2, 4, 6, and 8) or to the usual care (n=15) group. Feasibility, patient-reported outcomes, and behavioral constructs were measured at baseline and 12 weeks. CPAP adherence was measured weekly. RESULTS: Feasibility of the MENDS sessions was demonstrated (56 sessions offered, 52 completed remotely without technical difficulties) with minimal participant attrition and no missing CPAP data. Generalized linear mixed models showed no statistically significant time-by-group interactions on adherence or patient-reported outcomes. Higher adherence and lower CPAP apnea-hypopnea index (AHI) scores were associated with declines in pre- to post-changes in fatigue and sleep disturbance. Lower CPAP AHI scores were associated with pre- to post-decreases in PROMIS Anxiety scores (r=.532, p=.005). CONCLUSION: The virtual MENDS intervention was feasible. Higher CPAP adherence and lower AHI levels led to positive improvements in fatigue, sleep disturbance, and anxiety.

Fatty Acids, Amphiregulin Production, and Lung Function in a Cohort of Midwestern Veterans.

Rationale: The relationship between many fatty acids and respiratory outcomes remains unclear, especially with regard to mechanistic actions. Altered regulation of the process of lung repair is a key feature of chronic lung disease and may impact the potential for pulmonary rehabilitation, but underlying mechanisms of lung repair following injury or inflammation are not well-studied. The epidermal growth factor receptor agonist amphiregulin (AREG) has been demonstrated to promote lung repair following occupational dust exposure in animals. Studies suggest the polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) may enhance the production of AREG. The objective of this study was to determine the relationship between fatty acids and lung function in a population of veterans and determine if fatty acid status is associated with concentrations of AREG. Materials and Methods: Data were collected from a cross-sectional study of veterans within the Nebraska-Western Iowa Health Care System. Whole blood assays were performed to quantify AREG concentrations via a commercially available ELISA kit. Fatty acids from plasma samples from the same patients were measured using gas-liquid chromatography. Intakes of fatty acids were quantified with a validated food frequency questionnaire. Linear regression models were used to determine whether plasma fatty acids or intakes of fatty acids predicted lung function or AREG concentrations. A p < 0.05 was considered statistically significant. Results: Ninety participants were included in this analysis. In fully adjusted models, plasma fatty acids were associated with AREG production, including the PUFA eicosapentaenoic acid (EPA) (ß = 0.33, p = 0.03) and the monounsaturated fatty acid octadecenoic acid: (ß = -0.56, p = 0.02). The omega-3 PUFA docosapentaenoic acid (DPA) was positively associated with lung function (ß = 0.28, p = 0.01; ß = 26.5, p = 0.05 for FEV1/FVC ratio and FEV1 % predicted, respectively), as were the omega-6 PUFAs eicosadienoic acid (ß = 1.13, p < 0.001; ß = 91.2, p = 0.005 for FEV1/FVC ratio and FEV1 % predicted, respectively) and docosadienoic acid (ß = 0.29, p = 0.01 for FEV1/FVC ratio). Plasma monounsaturated and saturated fatty acids were inversely associated with lung function. Conclusion: Opposing anti- and pro-inflammatory properties of different fatty acids may be associated with lung function in this population, in part by regulating AREG induction.

Mobile Health Self-management Interventions for Patients With Heart Failure: A Pilot Study.

BACKGROUND: Heart failure (HF) is a multifaceted syndrome that requires self-management for adherence to treatment to control symptoms. Symptoms need to be monitored to prevent impending HF exacerbations. Few HF study authors have assessed efficacy of mobile health (mHealth) interventions particularly with virtual visits to evaluate outcomes such as symptoms and healthcare utilization. OBJECTIVE: The aim of this pilot study was to evaluate the potential effect of mHealth self-management interventions on symptom status and health-related quality of life and describe health care utilization in patients with HF. METHODS: This 3-month pilot study included 74 patients with HF and used a randomized 3-group repeated-measures design (enhanced usual care, mHealth, and mHealth plus [+] virtual visits). Surveys included the Heart Failure Symptom Survey, EuroQol, and a specialized phone application for patients to report weights and medications. RESULTS: The mHealth groups had an overall decrease in most symptom severity and frequency, particularly shortness of breath. Compared to enhanced usual care, both the mHealth+ and mHealth groups showed promise with medium effect sizes (range .55-.60) in relation to shortness of breath and a medium effect (.51) for lower extremity edema for the mHealth+ group. There was a trend toward improvement in health-related quality of life in both intervention groups at month 3. The mHealth+ group had fewer rehospitalizations. CONCLUSIONS: In general, both mHealth groups fared better on symptoms and health care utilization. Small to medium effect sizes on selected symptom outcomes warrant this study to be conducted in a fully powered study. Virtual visits may assist in symptom recognition and self-management.

A pilot study of core body temperatures in healthcare workers wearing personal protective equipment in a high-level isolation unit.

Personal protective equipment used by healthcare workers to mitigate disease transmission risks while caring for patients with high-consequence infectious diseases can impair normal body cooling mechanisms and exacerbate physiological strain. Symptoms of heat strain (e.g., cognitive impairment, confusion, muscle cramping) are especially harmful in the high-risk environment of high-consequence infectious disease care. In this pilot study, the core body temperatures of healthcare workers were assessed using an ingestible, wireless-transmission thermometer while performing patient care tasks common to a high-level isolation unit setting in powered air purifying respirator (PAPR)-level. The objective was to determine the potential for occupational health hazard due to heat stress in an environmentally controlled unit. Maximum core temperatures of the six participants ranged from 37.4 °C (99.3 °F) to 39.9 °C (103.8°F) during the 4-hr shift; core temperatures of half (n = 3) of the participants exceeded 38.5 °C (101.3 °F), the upper core temperature limit. Future investigations are needed to identify other heat stress risks both in and outside of controlled units. The ongoing COVID-19 pandemic offers unique opportunities for field-based research on risks of heat stress related to personal protective equipment in healthcare workers that can lead to both short- and long-term innovations in this field.

Quadriceps Strength Influences Patient Function More Than Single Leg Forward Hop During Late-Stage ACL Rehabilitation.

BACKGROUND: A comprehensive battery of tests are used to inform return to play decisions following anterior cruciate ligament (ACL) reconstruction. Performance measures contribute to patient function, but it is not clear if achieving symmetrical performance on strength and hop tests is sufficient or if a patient also needs to meet minimum unilateral thresholds. HYPOTHESIS/PURPOSE: To determine the association of quadriceps strength and single-leg forward hop performance with patient-reported function, as measured by the IKDC Subjective Knee Form (IKDC), during late-stage ACL rehabilitation. A secondary purpose was to determine which clinical tests were the most difficult for participants to pass. STUDY DESIGN: Descriptive Laboratory Study. METHODS: Forty-eight individuals with a history of ACL-R (32 female, 16 male; mean±SD age=18.0±2.7 y; height=172.4±7.6 cm; mass=69.6±11.4 kg; time since surgery=7.7±1.8 months; IKDC=86.8±10.6) completed the IKDC survey, quadriceps isometric strength, and single-leg forward hop performance. The relationship between IKDC scores and performance measures (LSI and involved limb) was determined using stepwise linear regression. Frequency counts were used to determine whether participants met clinical thresholds (IKDC ≥ 90%, quadriceps and single-leg forward hop LSI ≥ 90%, quadriceps peak torque ≥ 3.0 Nm/kg, and single-leg forward hop ≥ 80% height for females and ≥ 90% height for males). RESULTS: Quadriceps LSI and involved limb peak torque explained 39% of the variance in IKDC scores while measures of single-leg forward hop performance did not add to the predictive model. Nearly 90% of participants could not meet established clinical thresholds on all five tests and quadriceps strength (LSI and peak torque) was the most common unmet criteria (71% of participants). CONCLUSIONS: During late-stage ACL rehabilitation deficits in quadriceps strength contribute more to patient function and are greater in magnitude compared to hop test performance. LEVEL OF EVIDENCE: Cross-Sectional Study, Level 3.

A framework for clinical and translational research in the era of rigor and reproducibility.

INTRODUCTION: Rigor and reproducibility are two important cornerstones of medical and scientific advancement. Clinical and translational research (CTR) contains four phases (T1-T4), involving the translation of basic research to humans, then to clinical settings, practice, and the population, with the ultimate goal of improving public health. Here we provide a framework for rigorous and reproducible CTR. METHODS: In this paper we define CTR, provide general and phase-specific recommendations for improving quality and reproducibility of CTR with emphases on study design, data collection and management, analyses and reporting. We present and discuss aspects of rigor and reproducibility following published examples of CTR from the literature, including one example that shows the development path of different treatments that address anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC). RESULTS: It is particularly important to consider robust and unbiased experimental design and methodology for analysis and interpretation for clinical translation studies to ensure reproducibility before taking the next translational step. There are both commonality and differences along the clinical translation research phases in terms of research focuses and considerations regarding study design, implementation, and data analysis approaches. CONCLUSIONS: Sound scientific practices, starting with rigorous study design, transparency, and team efforts can greatly enhance CTR. Investigators from multidisciplinary teams should work along the spectrum of CTR phases, and identify optimal practices for study design, data collection, data analysis, and results reporting to allow timely advances in the relevant field of research.

Measuring the Impact of the Home Health Nursing Shortage on Family Caregivers of Children Receiving Palliative Care.

The national nursing shortage translates into a gap in home nursing care available to children with complex, chronic medical conditions and their family caregivers receiving palliative care consultations. A total of 38 home health nursing surveys were completed by families receiving pediatric palliative care consultation services at a freestanding children's hospital in the Midwest. The gap in the average number of nursing hours allotted versus received was 40 h/wk per family, primarily during evening hours. Parents missed an average of 23 hours of employment per week to provide hands-on nursing care at home, ranking stress regarding personal employment due to nursing shortage at 6.2/10. Families invested an average of 10 h/mo searching for additional nursing coverage and often resorted to utilizing more than 6 different home nurse coverage personnel per month. Families reported multiple delays to hospital discharges (mean, 15 days per delay) due to inability to find home nursing coverage. Respiratory technology and lack of Medicaid coverage (P < .02) correlated with the gap in home nursing access. This study examines how the pediatric home nursing shortage translates into a lived experience for families with children with complex medical conditions receiving palliative care.

The development of an instrument to evaluate interprofessional student team competency.

Healthcare institutions, accreditation agencies for higher learning, and organizations such as the National Academy of Medicine in the United States, support interprofessional education (IPE) opportunities. However, incorporating IPE opportunities into academic settings remains difficult. One challenge is assessing IPE learning and practice outcomes, especially at the level of student performance to ensure graduates are "collaboration-ready". The Creighton-Interprofessional Collaborative Evaluation (C-ICE) instrument was developed to address the need for a measurement tool for interprofessional student team performance. Four interprofessional competency domains provide the framework for the C-ICE instrument. Twenty-six items were identified as essential to include in the C-ICE instrument. This instrument was found to be both a reliable and a valid instrument to measure interprofessional interactions of student teams. Inter-rater reliability as measured by Krippendorff's nominal alpha (nKALPHA) ranged from .558 to .887; with four of the five independent assessments achieving nKALPHA greater than or equal to 0.796. The findings indicated that the instrument is understandable (Gwet's alpha coefficient (gAC) 0.63), comprehensive (gAC = 0.62), useful and applicable (gAC = 0.54) in a variety of educational settings. The C-ICE instrument provides educators a comprehensive evaluation tool for assessing student team behaviors, skills, and performance.

Implementing Collaborative Learning in Prelicensure Nursing Curricula: Student Perceptions and Learning Outcomes.

This study evaluated learning outcomes and student perceptions of collaborative learning in an undergraduate nursing program. Participants in this 3-phase action research study included students enrolled in a traditional and an accelerated nursing program. The number of students who passed the unit examination was not significantly different between the 3 phases. Students had positive and negative perceptions about the use of collaborative learning.