Handoffs and transitions in critical care-understanding scalability: study protocol for a multicenter stepped wedge type 2 hybrid effectiveness-implementation trial.

BACKGROUND: The implementation of evidence-based practices in critical care faces specific challenges, including intense time pressure and patient acuity. These challenges result in evidence-to-practice gaps that diminish the impact of proven-effective interventions for patients requiring intensive care unit support. Research is needed to understand and address implementation determinants in critical care settings. METHODS: The Handoffs and Transitions in Critical Care-Understanding Scalability (HATRICC-US) study is a Type 2 hybrid effectiveness-implementation trial of standardized operating room (OR) to intensive care unit (ICU) handoffs. This mixed methods study will use a stepped wedge design with randomized roll out to test the effectiveness of a customized protocol for structuring communication between clinicians in the OR and the ICU. The study will be conducted in twelve ICUs (10 adult, 2 pediatric) based in five United States academic health systems. Contextual inquiry incorporating implementation science, systems engineering, and human factors engineering approaches will guide both protocol customization and identification of protocol implementation determinants. Implementation mapping will be used to select appropriate implementation strategies for each setting. Human-centered design will be used to create a digital toolkit for dissemination of study findings. The primary implementation outcome will be fidelity to the customized handoff protocol (unit of analysis: handoff). The primary effectiveness outcome will be a composite measure of new-onset organ failure cases (unit of analysis: ICU). DISCUSSION: The HATRICC-US study will customize, implement, and evaluate standardized procedures for OR to ICU handoffs in a heterogenous group of United States academic medical center intensive care units. Findings from this study have the potential to improve postsurgical communication, decrease adverse clinical outcomes, and inform the implementation of other evidence-based practices in critical care settings. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04571749 . Date of registration: October 1, 2020.

Prophylactic phenylephrine for iatrogenic priapism: a pilot study with Peyronie's patients.

PURPOSE: Although penile duplex Doppler ultrasonography (PDDU) is a common and integral procedure in a Peyronie's disease workup, the intracavernosal injection of vasoactive agents can carry a serious risk of priapism. Risk factors include young age, good baseline erectile function, and no coronary artery disease. In addition, patients with Peyronie's disease undergoing PDDU in an outpatient setting are at increased risk given the inability to predict optimal dosing. The present study was conducted to provide support for a standard protocol of early administration of phenylephrine in patients with a sustained erection after diagnostic intracavernosal injection of vasoactive agents to prevent the deleterious effects of iatrogenic priapism. MATERIALS AND METHODS: This was a retrospective review of Peyronie's disease patients who received phenylephrine reversal after intracavernosal alprostadil (prostaglandin E1) administration to look at the priapism rate. Safety was determined on the basis of adverse events reported by subjects and efficacy was determined on the basis of the rate of priapism following intervention. RESULTS: Patients with Peyronie's disease only had better hemodynamic values on PDDU than did patients with Peyronie's disease and erectile dysfunction. All of the patients receiving prophylactic phenylephrine had complete detumescence of erections without adverse events, including no priapism cases. CONCLUSIONS: The reversal of erections with phenylephrine after intracavernosal injections of alprostadil to prevent iatrogenic priapism can be effective without increased adverse effects.

A genetic mouse model of adult-onset, pervasive central nervous system demyelination with robust remyelination.

Adult-onset demyelinating disorders of the central nervous system represent the most common neurological abnormalities in young adults. Nevertheless, our understanding of disease pathogenesis and recovery in demyelinating disorders remains incomplete. To facilitate investigation into these processes, we have developed a new mouse model system that allows for the induction of dipththeria toxin A subunit expression in adult oligodendrocytes, resulting in widespread oligodendrocyte loss and demyelination of the central nervous system. These mice develop severe ataxia and tremor that correlates with impaired axonal conduction in the spinal cord. Strikingly, these animals fully recover from their motor and physiological defects and display extensive oligodendrocyte replenishment and widespread remyelination. This model system demonstrates the robust reparative potential of myelin in the central nervous system and provides a promising model for the quantitative assessment of therapeutic interventions that promote remyelination.

T helper type 1 and 17 cells determine efficacy of interferon-beta in multiple sclerosis and experimental encephalomyelitis.

Interferon-beta (IFN-beta) is the major treatment for multiple sclerosis. However, this treatment is not always effective. Here we have found congruence in outcome between responses to IFN-beta in experimental autoimmune encephalomyelitis (EAE) and relapsing-remitting multiple sclerosis (RRMS). IFN-beta was effective in reducing EAE symptoms induced by T helper type 1 (T(H)1) cells but exacerbated disease induced by T(H)17 cells. Effective treatment in T(H)1-induced EAE correlated with increased interleukin-10 (IL-10) production by splenocytes. In T(H)17-induced disease, the amount of IL-10 was unaltered by treatment, although, unexpectedly, IFN-beta treatment still reduced IL-17 production without benefit. Both inhibition of IL-17 and induction of IL-10 depended on IFN-gamma. In the absence of IFN-gamma signaling, IFN-beta therapy was ineffective in EAE. In RRMS patients, IFN-beta nonresponders had higher IL-17F concentrations in serum compared to responders. Nonresponders had worse disease with more steroid usage and more relapses than did responders. Hence, IFN-beta is proinflammatory in T(H)17-induced EAE. Moreover, a high IL-17F concentration in the serum of people with RRMS is associated with nonresponsiveness to therapy with IFN-beta.

The greater fragility of females' versus males' closest same-sex friendships.

Sixty females and 60 males between 10 and 15 years of age were interviewed about difficulties in current and past close same-sex friendships. Based on prior studies, it was hypothesized that females' closest same-sex friendships would be more fragile than those of males. Analyses comparing only the closest same-sex friendship of the two sexes demonstrated that females' current friendships were of a shorter duration, that females were more distressed than males when imagining the potential termination of their friendships, that more females' than males' friends already had done something to hurt the friendship, and that females had more former friendships that had ended than males had. Possible reasons are discussed for the greater vulnerability of this type of relationship for females.