Order Substitutions and Education for Balanced Crystalloid Solution Use in an Integrated Health Care System and Association With Major Adverse Kidney Events.

Importance: Trials comparing balanced crystalloids with normal saline have yielded mixed results regarding reductions in kidney complications and mortality for hospitalized patients receiving intravenous fluids. Objective: To evaluate the association of a multifaceted implementation program encouraging the preferential use of lactated Ringer solution with patient outcomes and intravenous fluid-prescribing practices in a large, multilevel health care system. Design, Setting, and Participants: This type 2 hybrid implementation and comparative effectiveness study enrolled all patients 18 years or older who received 1 L or more of intravenous fluids while admitted to an emergency department and/or inpatient unit at 1 of 22 hospitals in Idaho and Utah between November 1, 2018, and February 29, 2020. An interrupted time series analysis was used to assess study outcomes before and after interventions to encourage use of lactated Ringer solution. Exposures: Implementation program combining order set modification, electronic order entry alerts, and sequential clinician-targeted education to encourage prescribing of lactated Ringer solution instead of normal saline. Main Outcomes and Measures: The primary implementation outcome was the patient-level proportion of intravenous fluids that was balanced crystalloids. The primary effectiveness outcome was the incidence of major adverse kidney events (MAKE30)-a composite of new persistent kidney dysfunction, new initiation of dialysis, and death-at 30 days. Results: Among 148 423 patients (median [IQR] age, 47 [30-67] years; 91 302 women [61%]), the proportion of total fluids received that was lactated Ringer solution increased from 28% to 75% in the first week vs the last week of the study (immediate implementation effect odds ratio [OR], 3.44; 95% CI, 2.79-4.24). The estimated MAKE30 absolute risk reduction was 2.2% (95% CI, 1.3%-3.3%) based on interrupted time series analysis showing a decrease in the week-on-week trend for MAKE30 (OR difference, 0.03; 95% CI, 0.03-0.03, P < .001). The immediate postimplementation OR for MAKE30 was 0.88 (95% CI, 0.76-1.01), with a decrease in persistent kidney dysfunction (OR, 0.80; 95% CI, 0.69-0.93) and mortality (OR, 0.78; 95% CI, 0.65-0.93) but not dialysis (OR, 1.00; 95% CI, 0.76-1.32). Conclusions and Relevance: In this comparative effectiveness study, an implementation program was associated with an increase in the proportion of fluids administered as lactated Ringer solution compared with normal saline and was associated with a reduction in MAKE30 events among patients treated in a large integrated health care system.

The salutary effect of an integrated system on the rate of repeat CT scanning in transferred trauma patients: Improved costs and efficiencies.

BACKGROUND: Duplication of Computed Tomography (CT) scanning in trauma patients has been a source of quality waste in healthcare and potential harm for patients. Integrated and regional health systems have been shown to promote opportunities for efficiencies, cost savings and increased safety. METHODS: This study evaluated traumatically injured patients who required transfer to a Level One Trauma Center (TC) from either within a vertically integrated healthcare system (IN) or from an out-of-network (OON) hospital. RESULTS: We found the rate of repeat CT scanning, radiology costs and total costs for day one of hospitalization to be significantly lower for trauma patients transferred from an IN hospital as compared to those patients transferred from OON hospitals. CONCLUSION: The inefficiencies and waste often associated with transferred patients can be mitigated and strategies to do so are necessary to reduce costs in the current healthcare environment.

Inhibition of HIV transmission in human cervicovaginal explants and humanized mice using CD4 aptamer-siRNA chimeras.

The continued spread of the HIV epidemic underscores the need to interrupt transmission. One attractive strategy is a topical vaginal microbicide. Sexual transmission of herpes simplex virus type 2 (HSV-2) in mice can be inhibited by intravaginal siRNA application. To overcome the challenges of knocking down gene expression in immune cells susceptible to HIV infection, we used chimeric RNAs composed of an aptamer fused to an siRNA for targeted gene knockdown in cells bearing an aptamer-binding receptor. Here, we showed that CD4 aptamer-siRNA chimeras (CD4-AsiCs) specifically suppress gene expression in CD4⁺ T cells and macrophages in vitro, in polarized cervicovaginal tissue explants, and in the female genital tract of humanized mice. CD4-AsiCs do not activate lymphocytes or stimulate innate immunity. CD4-AsiCs that knock down HIV genes and/or CCR5 inhibited HIV infection in vitro and in tissue explants. When applied intravaginally to humanized mice, CD4-AsiCs protected against HIV vaginal transmission. Thus, CD4-AsiCs could be used as the active ingredient of a microbicide to prevent HIV sexual transmission.