The ACCELERATE Plus (assessment and communication excellence for safe patient outcomes) Trial Protocol: a stepped-wedge cluster randomised trial, cost-benefit analysis, and process evaluation.

BACKGROUND: Nurses play an essential role in patient safety. Inadequate nursing physical assessment and communication in handover practices are associated with increased patient deterioration, falls and pressure injuries. Despite internationally implemented rapid response systems, falls and pressure injury reduction strategies, and recommendations to conduct clinical handovers at patients' bedside, adverse events persist. This trial aims to evaluate the effectiveness, implementation, and cost-benefit of an externally facilitated, nurse-led intervention delivered at the ward level for core physical assessment, structured patient-centred bedside handover and improved multidisciplinary communication. We hypothesise the trial will reduce medical emergency team calls, unplanned intensive care unit admissions, falls and pressure injuries. METHODS: A stepped-wedge cluster randomised trial will be conducted over 52 weeks. The intervention consists of a nursing core physical assessment, structured patient-centred bedside handover and improved multidisciplinary communication and will be implemented in 24 wards across eight hospitals. The intervention will use theoretically informed implementation strategies for changing clinician behaviour, consisting of: nursing executive site engagement; a train-the-trainer model for cascading facilitation; embedded site leads; nursing unit manager leadership training; nursing and medical ward-level clinical champions; ward nurses' education workshops; intervention tailoring; and reminders. The primary outcome will be a composite measure of medical emergency team calls (rapid response calls and 'Code Blue' calls), unplanned intensive care unit admissions, in-hospital falls and hospital-acquired pressure injuries; these measures individually will also form secondary outcomes. Other secondary outcomes are: i) patient-reported experience measures of receiving safe and patient-centred care, ii) nurses' perceptions of barriers to physical assessment, readiness to change, and staff engagement, and iii) nurses' and medical officers' perceptions of safety culture and interprofessional collaboration. Primary outcome data will be collected for the trial duration, and secondary outcome surveys will be collected prior to each step and at trial conclusion. A cost-benefit analysis and post-trial process evaluation will also be undertaken. DISCUSSION: If effective, this intervention has the potential to improve nursing care, reduce patient harm and improve patient outcomes. The evidence-based implementation strategy has been designed to be embedded within existing hospital workforces; if cost-effective, it will be readily translatable to other hospitals nationally. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ID: ACTRN12622000155796. Date registered: 31/01/2022.

Pregnancy and the risk of a traffic crash.

INTRODUCTION: Pregnancy causes diverse physiologic and lifestyle changes that may contribute to increased driving and driving error. We compared the risk of a serious motor vehicle crash during the second trimester to the baseline risk before pregnancy. METHODS: We conducted a population-based self-matched longitudinal cohort analysis of women who gave birth in Ontario between April 1, 2006, and March 31, 2011. We excluded women less than age 18 years, those living outside Ontario, those who lacked a valid health card identifier under universal insurance, and those under the care of a midwife. The primary outcome was a motor vehicle crash resulting in a visit to an emergency department. RESULTS: A total of 507,262 women gave birth during the study period. These women accounted for 6922 motor vehicle crashes as drivers during the 3-year baseline interval (177 per mo) and 757 motor vehicle crashes as drivers during the second trimester (252 per mo), equivalent to a 42% relative increase (95% confidence interval 32%-53%; p<0.001). The increased risk extended to diverse populations, varied obstetrical cases and different crash characteristics. The increased risk was largest in the early second trimester and compensated for by the third trimester. No similar increase was observed in crashes as passengers or pedestrians, cases of intentional injury or inadvertent falls, or self-reported risky behaviours. INTERPRETATION: Pregnancy is associated with a substantial risk of a serious motor vehicle crash during the second trimester. This risk merits attention for prenatal care.

The LXR agonist GW3965 increases apoA-I protein levels in the central nervous system independent of ABCA1.

Lipoprotein metabolism in the central nervous system (CNS) is based on high-density lipoprotein-like particles that use apoE as their predominant apolipoprotein rather than apoA-I. Although apoA-I is not expressed in astrocytes and microglia, which produce CNS apoE, apoA-I is reported to be expressed in porcine brain capillary endothelial cells and also crosses the blood-brain barrier (BBB). These mechanisms allow apoA-I to reach concentrations in cerebrospinal fluid (CSF) that are approximately 0.5% of its plasma levels. Recently, apoA-I has been shown to enhance cognitive function and reduce cerebrovascular amyloid deposition in Alzheimer's Disease (AD) mice, raising questions about the regulation and function of apoA-I in the CNS. Peripheral apoA-I metabolism is highly influenced by ABCA1, but less is known about how ABCA1 regulates CNS apoA-I. We report that ABCA1 deficiency leads to greater retention of apoA-I in the CNS than in the periphery. Additionally, treatment of symptomatic AD mice with GW3965, an LXR agonist that stimulates ABCA1 expression, increases apoA-I more dramatically in the CNS compared to the periphery. Furthermore, GW3965-mediated up-regulation of CNS apoA-I is independent of ABCA1. Our results suggest that apoA-I may be regulated by distinct mechanisms on either side of the BBB and that apoA-I may serve to integrate peripheral and CNS lipid metabolism. This article is part of a Special Issue entitled Advances in High Density Lipoprotein Formation and Metabolism: A Tribute to John F. Oram (1945-2010).

An ABCA1-independent pathway for recycling a poorly lipidated 8.1 nm apolipoprotein E particle from glia.

Lipid transport in the brain is coordinated by glial-derived lipoproteins that contain apolipoprotein E (apoE) as their primary protein. Here we show that apoE is secreted from wild-type (WT) primary murine mixed glia as nascent lipoprotein subspecies ranging from 7.5 to 17 nm in diameter. Negative-staining electron microscropy (EM) revealed rouleaux, suggesting a discoidal structure. Potassium bromide (KBr) density gradient ultracentrifugation showed that all subspecies, except an 8.1 nm particle, were lipidated. Glia lacking the cholesterol transporter ABCA1 secreted only 8.1 nm particles, which were poorly lipidated and nondiscoidal but could accept lipids to form the full repertoire of WT apoE particles. Receptor-associated-protein (RAP)-mediated inhibition of apoE receptor function blocked appearance of the 8.1 nm species, suggesting that this particle may arise through apoE recycling. Selective deletion of the LDL receptor (LDLR) reduced the level of 8.1 nm particle production by approximately 90%, suggesting that apoE is preferentially recycled through the LDLR. Finally, apoA-I stimulated secretion of 8.1 nm particles in a dose-dependent manner. These results suggest that nascent glial apoE lipoproteins are secreted through multiple pathways and that a greater understanding of these mechanisms may be relevant to several neurological disorders.

ATP-binding cassette transporter A1 mediates the beneficial effects of the liver X receptor agonist GW3965 on object recognition memory and amyloid burden in amyloid precursor protein/presenilin 1 mice.

The cholesterol transporter ATP-binding cassette transporter A1 (ABCA1) moves lipids onto apolipoproteins including apolipoprotein E (apoE), which is the major cholesterol carrier in the brain and an established genetic risk factor for late-onset Alzheimer disease (AD). In amyloid mouse models of AD, ABCA1 deficiency exacerbates amyloidogenesis, whereas ABCA1 overexpression ameliorates amyloid load, suggesting a role for ABCA1 in Aß metabolism. Agonists of liver X receptors (LXR), including GW3965, induce transcription of several genes including ABCA1 and apoE, and reduce Aß levels and improve cognition in AD mice. However, the specific role of ABCA1 in mediating beneficial responses to LXR agonists in AD mice is unknown. We evaluated behavioral and neuropathogical outcomes in GW3965-treated female APP/PS1 mice with and without ABCA1. Treatment of APP/PS1 mice with GW3965 increased ABCA1 and apoE protein levels. ABCA1 was required to observe significantly elevated apoE levels in brain tissue and cerebrospinal fluid upon therapeutic (33 mg/kg/day) GW3965 treatment. At 33 mg/kg/day, GW3965 was also associated with a trend toward redistribution of Aß to the carbonate-soluble pool independent of ABCA1. APP/PS1 mice treated with either 2.5 or 33 mg/kg/day of GW3965 showed a clear trend toward reduced amyloid burden in hippocampus and whole brain, whereas APP/PS1-treated mice lacking ABCA1 failed to display reduced amyloid load in the whole brain and showed trends toward increased hippocampal amyloid. Treatment of APP/PS1 mice with either dose of GW3965 completely restored novel object recognition memory to wild-type levels, which required ABCA1. These results suggest that ABCA1 contributes to several beneficial effects of the LXR agonist GW3965 in APP/PS1 mice.

Is one head and neck immobilization system as good as another? One center's experience.

The William Buckland Radiotherapy Center has used 2 different immobilization systems for patients requiring radiotherapy to the head-and-neck region. A polycarbonate mask was manufactured for radical treatments and a thermoplastic mask for palliative treatments. This study evaluated field placement accuracy, staff opinion, and production costs of both systems. The manual matching program of Varian PortalVision Electronic Portal Imaging (EPI) System was used to assess field placement accuracy on a daily basis. Radiation therapists (RTs) were surveyed before and after the study to determine their opinions of each system. Production time and required materials were recorded to assess cost. Nineteen patients from each system had daily EPI results compiled with no statistically significant difference observed in field placement accuracy. The thermoplastic system was found to be more cost efficient due to a combination of the reduced production time and reuseability of the masks. User acceptability of the thermoplastic system has increased so that it is now the preferred system. In conclusion, the thermoplastic system is a viable alternative to the polycarbonate system in terms of treatment accuracy and cost. It is recommended that the thermoplastic system be used for all radical and palliative treatments. In addition, RTs prefer the thermoplastic system.