Phase I Study of Acalabrutinib Plus Danvatirsen (AZD9150) in Relapsed/Refractory Diffuse Large B-Cell Lymphoma Including Circulating Tumor DNA Biomarker Assessment.

PURPOSE: Novel targeted and immunotherapies have improved outcomes in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), but toxicities limit widespread use. The selective Bruton tyrosine kinase (BTK) inhibitor acalabrutinib has activity in patients with R/R DLBCL but durable responses are uncommon. STAT3 inhibition has demonstrated clinical activity in DLBCL. PATIENTS AND METHODS: Final results of the phase I study of acalabrutinib plus STAT3 inhibitor (danvatirsen; AZD9150) in patients with R/R DLBCL are reported. Danvatirsen 200 mg intravenous infusion [Days 1, 3, 5 (Cycle 1); weekly infusions starting Day 8, Cycle 1] was administered in combination with oral acalabrutinib 100 mg twice daily until progressive disease (PD) or unacceptable toxicity. Primary endpoints were safety and tolerability. Secondary endpoints included efficacy, pharmacokinetics, and immunogenicity. RESULTS: Seventeen patients received combination treatment. One dose-limiting toxicity (Grade 3 liver transaminase) occurred in 1 patient. The most common reason for treatment discontinuation was PD (65%). In evaluable patients (n = 17), objective response rate was 24%; median duration of response was 1.9 months. All responders with available DLBCL cell-of-origin data were either activated B-cell or nongerminal center B-cell like subtype. Genetic subtype did not correlate with response. Baseline and longitudinal plasma cell-free DNA (cfDNA) concentrations were mostly higher in nonresponding patients. cfDNA changes were generally concordant with imaging. Pretreatment circulating B-cell levels were higher in responders versus nonresponders. CONCLUSIONS: Targeting both STAT3 and BTK in combination is safe and tolerable but efficacy is limited in R/R DLBCL. Results support evaluation of circulating tumor DNA as a biomarker for clinical response.

Development and validation of an A3 problem-solving assessment tool and self-instructional package for teachers of quality improvement in healthcare.

PURPOSE: A3 problem solving is part of the Lean management approach to quality improvement (QI). However, few tools are available to assess A3 problem-solving skills. The authors sought to develop an assessment tool for problem-solving A3s with an accompanying self-instruction package and to test agreement in assessments made by individuals who teach A3 problem solving. METHODS: After reviewing relevant literature, the authors developed an A3 assessment tool and self-instruction package over five improvement cycles. Lean experts and individuals from two institutions with QI proficiency and experience teaching QI provided iterative feedback on the materials. Tests of inter-rater agreement were conducted in cycles 3, 4 and 5. The final assessment tool was tested in a study involving 12 raters assessing 23 items on six A3s that were modified to enable testing a range of scores. RESULTS: The intraclass correlation coefficient (ICC) for overall assessment of an A3 (rater's mean on 23 items per A3 compared across 12 raters and 6 A3s) was 0.89 (95% CI 0.75 to 0.98), indicating excellent reliability. For the 20 items with appreciable variation in scores across A3s, ICCs ranged from 0.41 to 0.97, indicating fair to excellent reliability. Raters from two institutions scored items similarly (mean ratings of 2.10 and 2.13, p=0.57). Physicians provided marginally higher ratings than QI professionals (mean ratings of 2.17 and 2.00, p=0.003). Raters averaged completing the self-instruction package in 1.5 hours, then rated six A3s in 2.0 hours. CONCLUSION: This study provides evidence of the reliability of a tool to assess healthcare QI project proposals that use the A3 problem-solving approach. The tool also demonstrated evidence of measurement, content and construct validity. QI educators and practitioners can use the free online materials to assess learners' A3s, provide formative and summative feedback on QI project proposals and enhance their teaching.

Nursing students use of teach-back to improve patients' knowledge and satisfaction: A quality improvement project.

BACKGROUND: Nurses provide education on medications to hospitalized patients and this intervention is measured by patient's satisfaction on the Hospital Consumer Assessment of Healthcare Providers and Systems Survey [HCAHPS] (Center for Medicare & Medicaid Services[CMS], 2008). PURPOSE: Nursing students implement the teach-back method in a quality improvement project to improve patients' knowledge of medications and satisfaction on the HCAHPS survey. Specific aim 1: increase nursing students use of teach-back from the current state of 0% to 80% of their patient encounters; Specific aim 2: ensure that 80% of the patients approached can state the name, purpose and side effects of their current medications; Specific aim 3: have 80% of the patients satisfied with their medication teaching. METHODS: The Model for Improvement framework from the Institute for Healthcare Improvement was used (Ogrinc et al., 2012). Process and outcome measures and Plan-Do-Study-Act cycles were analyzed. RESULTS: Senior nursing students used teach back on 82.9%% of their patient encounters. Of the N = 55 patients who received the intervention, 58.2% could state the name and purpose, and 50.9% knew the side effects of their medications. HCAHPS survey responses did not achieve the benchmarks of 77.2% and 52.3% for "always" responses for medication education questions. However, patient satisfaction was measured at 96.4% with the One Minute Evaluation (Appendix A) by nursing students following the intervention. CONCLUSION: Integrating QI into the clinical environment is a method to not only increase patient outcomes but also exposes students to the methods of QI. Although the intervention did not meet the benchmark for patient satisfaction in "Communication about Medicines" category as measured by HCAHPS survey results, the teach-back method was an effective evidence-based tool for improving patient knowledge of medications.