Use of in vitro ADME methods to identify suitable analogs of homosalate and octisalate for use in a read-across safety assessment.

Case studies are needed to demonstrate the use of human-relevant New Approach Methodologies in cosmetics ingredient safety assessments. For read-across assessments, it is crucial to compare the target chemical with the most appropriate analog; therefore, reliable analog selection should consider physicochemical properties, bioavailability, metabolism, as well as the bioactivity of potential analogs. To complement in vitro bioactivity assays, we evaluated the suitability of three potential analogs for the UV filters, homosalate and octisalate, according to their in vitro ADME properties. We describe how technical aspects of conducting assays for these highly lipophilic chemicals were addressed and interpreted. There were several properties that were common to all five chemicals: they all had similar stability in gastrointestinal fluids (in which no hydrolysis to salicylic occurred); were not substrates of the P-glycoprotein efflux transporter; were highly protein bound; and were hydrolyzed to salicylic acid (which was also a major metabolite). The main properties differentiating the chemicals were their permeability in Caco-2 cells, plasma stability, clearance in hepatic models, and the extent of hydrolysis to salicylic acid. Cyclohexyl salicylate, octisalate, and homosalate were identified suitable analogs for each other, whereas butyloctyl salicylate exhibited ADME properties that were markedly different, indicating it is unsuitable. Isoamyl salicylate can be a suitable analog with interpretation for octisalate. In conclusion, in vitro ADME properties of five chemicals were measured and used to pair target and potential analogs. This study demonstrates the importance of robust ADME data for the selection of analogs in a read-across safety assessment.

Specific Elements of Team-Based Learning Used in Nursing Education: A Scoping Review.

BACKGROUND: Team-based learning (TBL) is an evidence-based, highly structured teaching strategy. PURPOSE: The purpose of this review was to explore the specific TBL structure and process design elements reported in nursing education studies. METHODS: A scoping review was undertaken according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. Databases were searched on February 15, 2021, using search terms related to nursing, education, and TBL. RESULTS: Of 226 potentially relevant citations, 45 studies were included. The specific TBL design elements reported were team size (n = 41), team formation (n = 24), readiness assurance process (n = 45), immediate feedback (n = 42), activity sequencing (n = 42), 4S application design (n = 13), incentive structure(s) (n = 22), and peer evaluation (n = 13). CONCLUSIONS: There was variability in the reporting of TBL design elements. Preclass preparation and individual and team Readiness Assurance Tests were well reported. Application exercise design and approach to peer evaluation were gaps in the included studies.

Effective exposure of chemicals in in vitro cell systems: A review of chemical distribution models.

Nominal effect concentrations from in vitro toxicity assays may lead to inaccurate estimations of in vivo toxic doses because the nominal concentration poorly reflects the concentration at the molecular target in cells in vitro, which is responsible for initiating effects and can be referred to as the biologically effective dose. Chemicals can differentially distribute between in vitro assay compartments, including serum constituents in exposure medium, microtitre plate plastic, headspace and extracellular matrices. The partitioning of test chemicals to these extracellular compartments reduces the concentration at the molecular target. Free concentrations in medium and cell-associated concentrations are considered better proxies of the biologically effective dose. This paper reviews the mechanisms by which test chemicals distribute between in vitro assay compartments, and also lists the physicochemical properties driving the extent of this distribution. The mechanisms and physicochemical properties driving the distribution of test chemical in vitro help explain the makeup of mass balance models that estimate free concentrations and cell-associated concentrations in in vitro toxicity assays. A thorough understanding of the distribution processes and assumptions underlying these mass balance models helps define chemical and biological applicability domains of individual models, as well as provide a perspective on how to improve model predictivity and quantitative in vitro-in vivo extrapolations.

Team-based learning in nursing education: A scoping review.

AIMS AND OBJECTIVES: To explore the use and student outcomes of Team-Based Learning in nursing education. BACKGROUND: Team-Based Learning is a highly structured, evidence-based, student-centred learning strategy that enhances student engagement and facilitates deep learning in a variety of disciplines including nursing. However, the breadth of Team-Based Learning application in nursing education and relevant outcomes are not currently well understood. DESIGN: A scoping review of international, peer-reviewed research studies was undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. METHODS: The following databases were searched on 7 May 2020: Cumulative Index of Nursing and Allied Health Literature, MEDLINE Complete, PsycINFO and Education Resources Information Center. Search terms related to nursing, education and Team-Based Learning. Original research studies, published in English, and reporting on student outcomes from Team-Based Learning in nursing education programmes were included. RESULTS: Of the 1081 potentially relevant citations, 41 studies from undergraduate (n = 29), postgraduate (n = 4) and hospital (n = 8) settings were included. The most commonly reported student outcomes were knowledge or academic performance (n = 21); student experience, satisfaction or perceptions of Team-Based Learning (n = 20); student engagement with behaviours or attitudes towards Team-Based Learning (n = 12); and effect of Team-Based Learning on teamwork, team performance or collective efficacy (n = 6). Only three studies reported clinical outcomes. CONCLUSIONS: Over the last decade, there has been a growing body of knowledge related to the use of Team-Based Learning in nursing education. The major gaps identified in this scoping review were the lack of randomised controlled trials and the dearth of studies of Team-Based Learning in postgraduate and hospital contexts. RELEVANCE TO CLINICAL PRACTICE: This scoping review provides a comprehensive understanding of the use and student outcomes of Team-Based Learning in nursing education and highlights the breadth of application of Team-Based Learning and variability in the outcomes reported.

Engaging patients and families in communication across transitions of care: An integrative review.

OBJECTIVE: To determine the current evidence about patient and family engagement in communication with health professionals during transitions of care to, within and from acute care settings. METHODS: An integrative review using seven international databases was conducted for 2003-2017. Forty eligible studies were analysed and synthesised using framework synthesis. RESULTS: Four themes: 1) Partnering in care: patients and families should be partners in decision-making and care; 2) Augmenting communication during transitions: intrinsic and extrinsic factors supported transition communication between patients, families and health professionals; 3) Impeding information exchange: the difficulties faced by patients and families taking an active role in transition; and 4) Outcomes of communication during transitions: reported experiences for patients, families and health professionals. CONCLUSION: While attitudes towards engaging patients and family in transition communication in acute settings are generally positive, current practices are variable. Structural supports for practice are not always present. PRACTICE IMPLICATIONS: Organisational strategies to improve communication must incorporate an understanding of patient needs. A structured approach which considers timing, privacy, location and appropriateness for patients and families is needed. Communication training is required for patients, families and health professionals. Health professionals must respect a patient's right to be informed by regularly communicating.

Dermal absorption study OECD TG 428 mass balance recommendations based on the EFSA database.

The European Food Safety Authority (EFSA) guidance (EFSA, 2017) for dermal absorption (DA) studies recommends stringent mass balance (MB) limits of 95-105%. EFSA suggested that test material can be lost after penetration and requires that for chemicals with <5% absorption the non-recovered material must be added to the absorbed dose if MB is <95%. This has huge consequences for low absorption pesticides. Indeed, one third of the MBs in the EFSA DA database are outside the refined criteria. This is also true for DA data generated by Cosmetics Europe (Gregoire et al., 2019), indicating that this criterion is often not achieved even when using highly standardized protocols. While EFSA hypothesizes that modern analytical and pipetting techniques would enable to achieve this criterion, no scientific basis was provided. We describe how protocol procedures impact MB and evaluate the EFSA DA database to demonstrate that MB is subject to random variation. Generic application of "the addition rule" skews the measured data and increases the DA estimate, which results in unnecessary risk assessment failure. In conclusion, "missing material" is just a random negative deviation to the nominal dose. We propose a data-driven MB criterion of 90-110%, fully in line with OECD recommendations.

An analysis of nursing students' decision-making in teams during simulations of acute patient deterioration.

AIM: The aim of this study was to examine the decision-making of nursing students during team based simulations on patient deterioration to determine the sources of information, the types of decisions made and the influences underpinning their decisions. BACKGROUND: Missed, misinterpreted or mismanaged physiological signs of deterioration in hospitalized patients lead to costly serious adverse events. Not surprisingly, an increased focus on clinical education and graduate nurse work readiness has resulted. DESIGN: A descriptive exploratory design. METHODS: Clinical simulation laboratories in three Australian universities were used to run team based simulations with a patient actor. A convenience sample of 97 final-year nursing students completed simulations, with three students forming a team. Four teams from each university were randomly selected for detailed analysis. Cued recall during video review of team based simulation exercises to elicit descriptions of individual and team based decision-making and reflections on performance were audio-recorded post simulation (2012) and transcribed. RESULTS: Students recalled 11 types of decisions, including: information seeking; patient assessment; diagnostic; intervention/treatment; evaluation; escalation; prediction; planning; collaboration; communication and reflective. Patient distress, uncertainty and a lack of knowledge were frequently recalled influences on decisions. CONCLUSIONS: Incomplete information, premature diagnosis and a failure to consider alternatives when caring for patients is likely to lead to poor quality decisions. All health professionals have a responsibility in recognizing and responding to clinical deterioration within their scope of practice. A typology of nursing students' decision-making in teams, in this context, highlights the importance of individual knowledge, leadership and communication.

Lateral positioning for critically ill adult patients.

BACKGROUND: Critically ill patients require regular body position changes to minimize the adverse effects of bed rest, inactivity and immobilization. However, uncertainty surrounds the effectiveness of lateral positioning for improving pulmonary gas exchange, aiding drainage of tracheobronchial secretions and preventing morbidity. In addition, it is unclear whether the perceived risk levied by respiratory and haemodynamic instability upon turning critically ill patients outweighs the respiratory benefits of side-to-side rotation. Thus, lack of certainty may contribute to variation in positioning practice and equivocal patient outcomes. OBJECTIVES: To evaluate effects of the lateral position compared with other body positions on patient outcomes (mortality, morbidity and clinical adverse events) in critically ill adult patients. (Clinical adverse events include hypoxaemia, hypotension, low oxygen delivery and global indicators of impaired tissue oxygenation.) We examined single use of the lateral position (i.e. on the right or left side) and repeat use of the lateral position (i.e. lateral positioning) within a positioning schedule. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 5), MEDLINE (1950 to 23 May 2015), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1937 to 23 May 2015), the Allied and Complementary Medicine Database (AMED) (1984 to 23 May 2015), Latin American Caribbean Health Sciences Literature (LILACS) (1901 to 23 May 2015), Web of Science (1945 to 23 May 2015), Index to Theses in Great Britain and Ireland (1950 to 23 May 2015), Trove (2009 to 23 May 2015; previously Australasian Digital Theses Program (1997 to December 2008)) and Proquest Dissertations and Theses (2009 to 23 May 2015; previously Proquest Digital Dissertations (1980 to 23 May 2015)). We handsearched the reference lists of potentially relevant reports and two nursing journals. SELECTION CRITERIA: We included randomized and quasi-randomized trials examining effects of lateral positioning in critically ill adults. We included manual or automated turns but limited eligibility to studies that included duration of body position of 10 minutes or longer. We examined each lateral position versus at least one comparator (opposite lateral position and/or another body position) for single therapy effects, and the lateral positioning schedule (repeated lateral turning) versus other positioning schedules for repetitive therapy effects. DATA COLLECTION AND ANALYSIS: We pre-specified methods to be used for data collection, risk of bias assessment and analysis. Two independent review authors carried out each stage of selection and data extraction and settled differences in opinion by consensus, or by third party adjudication when disagreements remained unresolved. We planned analysis of pair-wise comparisons under composite time intervals with the aim of considering recommendations based on meta-analyses of studies with low risk of bias. MAIN RESULTS: We included 24 studies of critically ill adults. No study reported mortality as an outcome of interest. Two randomized controlled trials (RCTs) examined lateral positioning for pulmonary morbidity outcomes but provided insufficient information for meta-analysis. A total of 22 randomized trials examined effects of lateral positioning (four parallel-group and 18 cross-over designs) by measuring various continuous data outcomes commonly used to detect adverse cardiopulmonary events within critical care areas. However, parallel-group studies were not comparable, and cross-over studies provided limited data as the result of unit of analysis errors. Eight studies provided some data; most of these were single studies with small effects that were imprecise. We pooled partial pressure of arterial oxygen (PaO2) as a measure to detect hypoxaemia from two small studies of participants with unilateral lung disease (n = 19). The mean difference (MD) between lateral positions (bad lung down versus good lung down) was approximately 50 mmHg (MD -49.26 mmHg, 95% confidence interval (CI) -67.33 to -31.18; P value < 0.00001). Despite a lower mean PaO2 for bad lung down, hypoxaemia (mean PaO2 < 60 mmHg) was not consistently reported. Furthermore, pooled data had methodological shortcomings with unclear risk of bias. We had similar doubts regarding internal validity for other studies included in the review. AUTHORS' CONCLUSIONS: Review authors could provide no clinical practice recommendations based on the findings of included studies. Available research could not eliminate the uncertainty surrounding benefits and/or risks associated with lateral positioning of critically ill adult patients. Research gaps include the effectiveness of lateral positioning compared with semi recumbent positioning for mechanically ventilated patients, lateral positioning compared with prone positioning for acute respiratory distress syndrome (ARDS) and less frequent changes in body position. We recommend that future research be undertaken to address whether the routine practice of repositioning patients on their side benefits all, some or few critically ill patients.

Engaging patients and families in communication across transitions of care: an integrative review protocol.

AIM: To describe an integrative review protocol to analyse and synthesize peer-reviewed research evidence in relation to engagement of patients and their families in communication during transitions of care to, in and from acute care settings. BACKGROUND: Communication at transitions of care in acute care settings can be complex and challenging, with important information about patients not always clearly transferred between responsible healthcare providers. Involving patients and their families in communication during transitions of care may improve the transfer of clinical information and patient outcomes and prevent adverse events during hospitalization and following discharge. Recently, optimizing patient and family participation during care transitions has been acknowledged as central to the implementation of patient-centred care. DESIGN: Integrative review with potential for meta-analysis and application of framework synthesis. REVIEW METHOD: The review will evaluate and synthesize qualitative and quantitative research evidence identified through a systematic search. Primary studies will be selected according to inclusion criteria. Data collection, quality appraisal and analysis of the evidence will be conducted by at least two authors. Nine electronic databases (including CINAHL and Medline) will be searched. The search will be restricted to 10 years up to December 2013. Data analysis will include content and thematic analysis. DISCUSSION: The review will seek to identify all types of patient engagement activities employed during transitions of care communication. The review will identify enablers for and barriers to engagement for patients, families and health professionals. Key strategies and tools for improving patient engagement, clinical communication and promoting patient-centred care will be recommended based on findings.

The clinical application of pulse contour cardiac output and intrathoracic volume measurements in critically ill patients.

Cardiac output (CO) determination by pulmonary artery (PA) catheter has increasingly been criticised within the literature due to its invasive nature and poor correlation between the pressure measurements and intravascular volume status in mechanically ventilated patients. Consequently, alternative less invasive technologies to PA catheterisation are emerging within intensive care. One such novel technology are pulse contour CO (PCCO) systems. They establish comprehensive and continuous haemodynamic monitoring utilising a central venous catheter (CVC) and an arterial line. Furthermore, a key feature of this technology is its ability to produce intrathoracic volume measurements which may provide a better estimation of cardiac preload as well as indicate the presence and severity of pulmonary oedema. This article aims to discuss the theoretical basis and clinical application of PCCO systems, how PCCO systems differ from PA catheters and how the intrathoracic volume measurements are derived. Understanding these advanced concepts will ensure that clinicians are able to employ this innovative monitoring technology more effectively.