Multifaceted Intervention to Improve Patient Safety Incident Reporting in Intensive Care Units.

OBJECTIVES: Patient safety incident reporting in our institution's intensive care units (ICUs) had fallen 30% below national benchmarks during the COVID-19 pandemic. Underreporting diminishes awareness of risks and precludes organizational learning from near misses. We aimed to increase the ICU number of patient safety incident reports by 30% from 27 to 35 reports/1000 patient-days without negatively impacting culture of safety as measured by patient-care staff surveys. METHODS: Single-institution prospective interventional study with 9 ICUs receiving a multifaceted intervention developed using quality improvement methodology during February-April 2022. Study intervention involved creation of patient safety peer-leadership role, feedback process, interactive dashboards for patient safety data, and education resources accessible via quick response codes. Primary outcome was patient safety incident reports/1000 patient-days. Intensive care unit patient-care staff culture of safety was assessed with surveys. RESULTS: Intensive care unit patient safety incident reporting increased by 48% after intervention (40 versus 27 reports/1000 patient-days [ P = 0.136]). Near misses were the most common incident report. Intensive care unit patient-care staff ratings of patient safety did not change; 80% rated patient safety as good or better after intervention versus 78% at baseline ( P = 0.465). However, significant improvement was observed for subcomponents related to learning culture and support for staff involved in patient safety incidents. Most reports (>80%) were submitted by nurses. CONCLUSIONS: This multifaceted quality improvement intervention increased patient safety incident reporting in the ICUs. Increases in ratings of learning culture and support for staff underline the importance of a well-functioning patient safety incident reporting system in an institutional culture of safety.

Rabbits transgenic for human IgG genes recapitulating rabbit B-cell biology to generate human antibodies of high specificity and affinity.

Transgenic animals incorporating human antibody genes are extremely attractive for drug development because they obviate subsequent antibody humanization procedures required for therapeutic translation. Transgenic platforms have previously been established using mice, but also more recently rats, chickens, and cows and are now in abundant use for drug development. However, rabbit-based antibody generation, with a strong track record for specificity and affinity, is able to include gene conversion mediated sequence diversification, thereby enhancing binder maturation and improving the variance/selection of output antibodies in a different way than in rodents. Since it additionally frequently permits good binder generation against antigens that are only weakly immunogenic in other organisms, it is a highly interesting species for therapeutic antibody generation. We report here on the generation, utilization, and analysis of the first transgenic rabbit strain for human antibody production. Through the knockout of endogenous IgM genes and the introduction of human immunoglobulin sequences, this rabbit strain has been engineered to generate a highly diverse human IgG antibody repertoire. We further incorporated human CD79a/b and Bcl2 (B-cell lymphoma 2) genes, which enhance B-cell receptor expression and B-cell survival. Following immunization against the angiogenic factor BMP9 (Bone Morphogenetic Proteins 9), we were able to isolate a set of exquisitely affine and specific neutralizing antibodies from these rabbits. Sequence analysis of these binders revealed that both somatic hypermutation and gene conversion are fully operational in this strain, without compromising the very high degree of humanness. This powerful new transgenic strategy will allow further expansion of the use of endogenous immune mechanisms in drug development.