A Theory-Driven, Longitudinal Evaluation of the Impact of Team Training on Safety Culture in 24 Hospitals

Effective teamwork facilitates collective learning, which is integral to safety culture. There are no rigorous evaluations of the impact of team training on the four components of safety culture—reporting, just, flexible and learning cultures. We evaluated the impact of a year-long team training programme on safety culture in 24 hospitals using two theoretical frameworks

The impact of post-fall huddles on repeat fall rates and perceptions of safety culture: a quasi-experimental evaluation of a patient safety demonstration project

Background: Conducting post-fall huddles is considered an integral component of a fall-risk-reduction program. However, there is no evidence linking post-fall huddles to patient outcomes or perceptions of teamwork and safety culture. The purpose of this study is to determine associations between conducting post-fall huddles and repeat fall rates and between post-fall huddle participation and perceptions of teamwork and safety culture. Methods: During a two-year demonstration project, we developed a system for 16 small rural hospitals to report, benchmark, and learn from fall events, and we trained them to conduct post-fall huddles. To calculate a hospital’s repeat fall rate, we divided the total number of falls reported by the hospital by the number of unique medical record numbers associated with each fall. We used Spearman correlations with exact P values to determine the association between the proportion of falls followed by a huddle and the repeat fall rate. At study end, we used the TeamSTEPPS® Teamwork Perceptions Questionnaire (T-TPQ) to assess perceptions of teamwork support for fall-risk reduction and the Hospital Survey on Patient Safety Culture (HSOPS) to assess perceptions of safety culture. We added an item to the T-TPQ for respondents to indicate the number of post-fall huddles in which they had participated. We used a binary logistic regression with a logit link to examine the effect of participation in post-fall huddles on respondent-level percent positive T-TPQ and HSOPS scores. We accounted for clustering of respondents within hospitals with random effects using the GLIMMIX procedure in SAS/STAT. Result: Repeat fall rates were negatively associated with the proportion of falls followed by a huddle. As compared to hospital staff who did not participate in huddles, those who participated in huddles had more positive perceptions of four domains of safety culture and how team structure, team leadership, and situation monitoring supported fall-risk reduction. Conclusions: Post-fall huddles may reduce the risk of repeat falls. Staff who participate in post-fall huddles are likely to have positive perceptions of teamwork support for fall-risk reduction and safety culture because huddles are a team-based approach to reporting, adapting, and learnin

Evaluating the use of multiteam systems to manage the complexity of inpatient falls in rural hospitals

Objective To evaluate the implementation and outcomes of evidence-based fall-risk-reduction processes when those processes are implemented using a multiteam system (MTS) structure. Data Sources/Study Setting Fall-risk-reduction process and outcome measures from 16 small rural hospitals participating in a research demonstration and dissemination study from August 2012 to July 2014. Previously, these hospitals lacked a fall-event reporting system to drive improvement. Study Design A one-group pretest-posttest embedded in a participatory research framework. We required hospitals to implement MTSs, which we supported by conducting education, developing an online toolkit, and establishing a fall-event reporting system. Data Collection Hospitals used gap analyses to assess the presence of fall-risk-reduction processes at study beginning and their frequency and effectiveness at study end; they reported fall-event data throughout the study. Principal Findings The extent to which hospitals implemented 21 processes to coordinate the fall-risk-reduction program and trained staff specifically about the program predicted unassisted and injurious fall rates during the end-of-study period (January 2014-July 2014). Bedside fall-risk-reduction processes were not significant predictors of these outcomes. Conclusions Multiteam systems that effectively coordinate fall-risk-reduction processes may improve the capacity of hospitals to manage the complex patient, environmental, and system factors that result in falls

Cardiac Gene Transfer of Short Hairpin RNA Directed Against Phospholamban Effectively Knocks Down Gene Expression but Causes Cellular Toxicity in Canines

Derangements in calcium cycling have been described in failing hearts, and preclinical studies have suggested that therapies aimed at correcting this defect can lead to improvements in cardiac function and survival. One strategy to improve calcium cycling would be to inhibit phospholamban (PLB), the negative regulator of SERCA2a that is upregulated in failing hearts. The goal of this study was to evaluate the safety and efficacy of using adeno-associated virus (AAV)-mediated cardiac gene transfer of short hairpin RNA (shRNA) to knock down expression of PLB. Six dogs were treated with self-complementary AAV serotype 6 (scAAV6) expressing shRNA against PLB. Three control dogs were treated with empty AAV6 capsid, and two control dogs were treated with scAAV6 expressing dominant negative PLB. Vector was delivered via a percutaneously inserted cardiac injection catheter. PLB mRNA and protein expression were analyzed in three of six shRNA dogs between days 16 and 26. The other three shRNA dogs and five control dogs were monitored long-term to assess cardiac safety. PLB mRNA was reduced 16-fold, and PLB protein was reduced 5-fold, with treatment. Serum troponin elevation and depressed cardiac function were observed in the shRNA group only at 4 weeks. An enzyme-linked immunospot assay failed to detect any T cells reactive to AAV6 capsid in peripheral blood mononuclear cells, heart, or spleen. Microarray analysis revealed alterations in cardiac expression of several microRNAs with shRNA treatment. AAV6-mediated cardiac gene transfer of shRNA effectively knocks down PLB expression but is associated with severe cardiac toxicity. Toxicity may result from dysregulation of endogenous microRNA pathways

Experimental variables that affect human hepatocyte MV transduction in liver chimeric mice

Adeno-associated virus (AAV) vector serotypes vary in their ability to transduce hepatocytes from different species. Chimeric mouse models harboring human hepatocytes have shown translational promise for liver-directed gene therapies. However, many variables that influence human hepatocyte transduction and transgene expression in such models remain poorly defined. Here, we aimed to test whether three experimental conditions influence AAV transgene expression in immunodeficient, fumaryl-acetoactetate-hydrolase-deficient (Fah(-/-)) chimeric mice repopulated with primary human hepatocytes. We examined the effects of the murine liver injury cycle, human donor variability, and vector doses on hepatocyte transduction with various AAV serotypes expressing a green fluorescent protein (GFP). We determined that the timing of AAV vector challenge in the liver injury cycle resulted in up to 7-fold differences in the percentage of GFP expressing human hepatocytes. The GFP+ hepatocyte frequency varied 7-fold between human donors without, however, changing the relative transduction efficiency between serotypes for an individual donor. There was also a clear relationship between AAV vector doses and human hepatocyte transduction and transgene expression. We conclude that several experimental variables substantially affect human hepatocyte transduction in the Fah(-/-) chimera model, attention to which may improve reproducibility between findings from different laboratories

Translational Data from Adeno-Associated Virus-Mediated Gene Therapy of Hemophilia B in Dogs

Preclinical testing of new therapeutic strategies in relevant animal models is an essential part of drug development. The choice of animal models of disease that are used in these studies is driven by the strength of the translational data for informing about safety, efficacy, and success or failure of human clinical trials. Hemophilia B is a monogenic, X-linked, inherited bleeding disorder that results from absent or dysfunctional coagulation factor IX (FIX). Regarding preclinical studies of adeno-associated virus (AAV)-mediated gene therapy for hemophilia B, dogs with severe hemophilia B (<1% FIX) provide well-characterized phenotypes and genotypes in which a species-specific transgene can be expressed in a mixed genetic background. Correction of the hemophilic coagulopathy by sustained expression of FIX, reduction of bleeding events, and a comprehensive assessment of the humoral and cell-mediated immune responses to the expressed transgene and recombinant AAV vector are all feasible end points in these dogs. This review compares the preclinical studies of AAV vectors used to treat dogs with hemophilia B with the results obtained in subsequent human clinical trials using muscle- and liver-based approaches