Schwann cells form basal laminae (BLs) containing laminin-2 (Ln-2; heterotrimer α2β1γ1) and Ln-8 (α4β1γ1). Loss of Ln-2 in humans and mice carrying α2-chain mutations prevents developing Schwann cells from fully defasciculating axons, resulting in partial amyelination. The principal pathogenic mechanism is thought to derive from structural defects in Schwann cell BLs, which Ln-2 scaffolds. However, we found loss of Ln-8 caused partial amyelination in mice without affecting BL structure or Ln-2 levels. Combined Ln-2/Ln-8 deficiency caused nearly complete amyelination, revealing Ln-2 and -8 together have a dominant role in defasciculation, and that Ln-8 promotes myelination without BLs. Transgenic Ln-10 (α5β1γ1) expression also promoted myelination without BL formation. Rather than BL structure, we found Ln-2 and -8 were specifically required for the increased perinatal Schwann cell proliferation that attends myelination. Purified Ln-2 and -8 directly enhanced in vitro Schwann cell proliferation in collaboration with autocrine factors, suggesting Lns control the onset of myelination by modulating responses to mitogens in vivo.

During interprofessional intensive care unit (ICU) rounds each member of the interprofessional team is responsible for gathering and interpreting information from the electronic health records (EHR) to facilitate effective team decision-making. This study was conducted to determine how each professional group reviews EHR data in preparation for rounds and their ability to identify patient safety issues. Twenty-five physicians, 29 nurses, and 20 pharmacists participated. Individual participants were given verbal and written sign-out and then asked to review a simulated record in our institution's EHR, which contained 14 patient safety items. After reviewing the chart, subjects presented the patient and the number of safety items recognised was recorded. About 40%, 30%, and 26% of safety issues were recognised by physicians, nurses, and pharmacists, respectively (p = 0.0006) and no item recognised 100% of the time. There was little overlap between the three groups with only 50% of items predicted to be recognised 100% of the time by the team. Differential recognition was associated with marked differences in EHR use, with only 3/152 EHR screens utilised by all three groups and the majority of screens used exclusively only by one group. There were significant and non-overlapping differences in individual profession recognition of patient safety issues in the EHR. Preferential identification of safety issues by certain professional groups may be attributed to differences in EHR use. Future studies will be needed to determine if shared decision-making during rounds can improve recognition of safety issues.

Objective-The Electronic Health Record (EHR) is a primary source of information for all professional groups participating in ICU rounds. We previously demonstrated that, individually, all professional groups involved in rounds have significant blind spots in recognition of patient safety issues in the EHR. However, it is unclear how team dynamics impacts identification and verbalization of viewed data. Therefore, we created an ICU rounding simulation to assess how the interprofessional team recognized and reported data and its impact on decision making. Design-Each member of the ICU team reviewed a simulated ICU chart in the EHR which contained embedded patient safety issues. The team conducted simulated rounds according to the ICU's existing rounding script and was assessed for recognition of safety issues. Setting-Academic Medical Center Subjects-ICU residents, nurses and pharmacists Intervention-none Measurements and Main Results-28 teams recognized 68.6% of safety issues with only 50% teams having the primary diagnosis in their differential. Individually, interns, nurses and pharmacists recognized 30.4%, 15.6% and 19.6% of safety items respectively. However, there was For information regarding this article,

Background: Proton pump inhibitor (PPI) continuous infusions or intermittent boluses are used for the treatment of upper gastrointestinal bleeding (UGIB). Intermittent boluses are easier to give and are of lower cost without affecting clinical outcomes. Objective: To compare the rate of rebleeding between intermittent bolus and continuous infusion PPI therapy. Methods: We performed a retrospective, multicenter review of patients with UGIB receiving either continuous or intermittent PPI therapy. During the study period, due to drug and supply shortages, each institution implemented policies preferring intermittent PPI bolus therapy. We performed bivariate and multivariable comparisons of the 2 treatment strategies, with the primary outcome of interest being incidence of rebleeding. Additional variables of interest included intensive care unit (ICU) and hospital lengths of stay, discharge disposition, and in-hospital mortality. Results: Compared with intermittent bolus dosing (n = 209), patients receiving continuous infusion PPI (n = 237) were associated with a higher rate of rebleeding (33.8% vs 23.0%; P = 0.012); however, no difference was detected in multivariable analysis: adjusted odds ratio, 1.50 (95% confidence interval, 0.91-2.50). There was no difference in median hospital or ICU length of stay, discharge disposition, or in-hospital mortality. Correlatively, patients receiving continuous infusion therapy were more likely to have liver disease (29.1% vs 20.1%; P = 0.028), alcohol use disorder (28.3% vs 16.3.%; P = 0.003), history of lower gastrointestinal bleeding (6.4% vs 1.9%; P = 0.021), variceal bleeding (6.3 vs 2.4%, P = 0.045), and be admitted to the ICU (65.0% vs 32.5%, P = 0.00). Conclusions: Introduction of intermittent PPI bolus UGIB treatment via change in hospital policy was not associated with higher rates of rebleeding. However, continuous PPI therapy may have been perceived as more effective as it was used more commonly in high-risk patients.

No abstract