Drug-induced liver injury (DILI) continues to be a major source of clinical attrition, precautionary warnings, and post-market withdrawal of drugs. Accordingly, there is a need for more predictive tools to assess hepatotoxicity risk in drug discovery. Three-dimensional (3D) spheroid hepatic cultures have emerged as promising tools to assess mechanisms of hepatotoxicity, as they demonstrate enhanced liver phenotype, metabolic activity, and stability in culture not attainable with conventional two-dimensional hepatic models. Increased sensitivity of these models to drug-induced cytotoxicity has been demonstrated with relatively small panels of hepatotoxicants. However, a comprehensive evaluation of these models is lacking. Here, the predictive value of 3D human liver microtissues (hLiMT) to identify known hepatotoxicants using a panel of 110 drugs with and without clinical DILI has been assessed in comparison to plated two-dimensional primary human hepatocytes (PHH). Compounds were treated long-term (14 days) in hLiMT and acutely (2 days) in PHH to assess drug-induced cytotoxicity over an 8-point concentration range to generate IC₅₀ values. Regardless of comparing IC₅₀ values or exposure-corrected margin of safety values, hLiMT demonstrated increased sensitivity in identifying known hepatotoxicants than PHH, while specificity was consistent across both assays. In addition, hLiMT out performed PHH in correctly classifying hepatotoxicants from different pharmacological classes of molecules. The hLiMT demonstrated sufficient capability to warrant exploratory liver injury biomarker investigation (miR-122, HMGB1, α-GST) in the cell-culture media. Taken together, this study represents the most comprehensive evaluation of 3D spheroid hepatic cultures up to now and supports their utility for hepatotoxicity risk assessment in drug discovery.

Shifting people in higher income countries toward more plant-based diets would protect the natural environment and improve population health. Research in other domains suggests altering the physical environments in which people make decisions (“nudging”) holds promise for achieving socially desirable behavior change. Here, we examine the impact of attempting to nudge meal selection by increasing the proportion of vegetarian meals offered in a year-long large-scale series of observational and experimental field studies. Anonymized individual-level data from 94,644 meals purchased in 2017 were collected from 3 cafeterias at an English university. Doubling the proportion of vegetarian meals available from 25 to 50% (e.g., from 1 in 4 to 2 in 4 options) increased vegetarian meal sales (and decreased meat meal sales) by 14.9 and 14.5 percentage points in the observational study (2 cafeterias) and by 7.8 percentage points in the experimental study (1 cafeteria), equivalent to proportional increases in vegetarian meal sales of 61.8%, 78.8%, and 40.8%, respectively. Linking sales data to participants’ previous meal purchases revealed that the largest effects were found in the quartile of diners with the lowest prior levels of vegetarian meal selection. Moreover, serving more vegetarian options had little impact on overall sales and did not lead to detectable rebound effects: Vegetarian sales were not lower at other mealtimes. These results provide robust evidence to support the potential for simple changes to catering practices to make an important contribution to achieving more sustainable diets at the population level.

Objective: The aims of the study were to report on the development and evaluation of a staff training intervention in dementia care designed for use in the general hospital setting: the ‘Getting to Know Me’ training programme. The study also aimed to undertake initial psychometric analysis on two new outcome scales designed to measure knowledge and confidence in dementia care.Methods: The study comprised two phases. The first phase comprised the design of two questionnaires which are shared within this paper: Confidence in Dementia (CODE) Scale and Knowledge in Dementia (KIDE) Scale. In phase two, staff undertook the ‘Getting to Know Me’ training programme (n = 71). The impact of the programme was evaluated using a pre–post design which explored: (1) changes in confidence in dementia; (2) changes in knowledge in dementia; and (3) changes in beliefs about challenging behaviour.Results: The psychometric properties of the CODE and KIDE scales are reported. Statistically significant change was identified pre–post training on all outcome measures. Clinically meaningful change was demonstrated on the CODE scale.Conclusions: The ‘Getting to Know Me’ programme was well received and had a significant impact on staff knowledge and confidence. Our findings add to a growing evidence base which will be strengthened by further robust studies, the exploration of the impact of staff training on direct patient outcomes, and further identification of ways in which to transfer principles of care from specialist dementia environments into general hospital settings.

Background: Family members provide vital care at end of life, enabling patients to remain at home. Such informal care contributes significantly to the economy while supporting patients’ preferences and government policy. However, the value of care-givers’ contributions is often underestimated or overlooked in evaluations. Without information on the activities and expenditures involved in informal care-giving, it is impossible to provide an accurate assessment of carers’ contribution to end-of-life care. Aim: The aim of this study was to investigate the contributions and expenditure of informal, family care-giving in end-of-life cancer care. Design: A national census survey of English cancer carers was conducted. Survey packs were mailed to 5271 people who registered the death of a relative to cancer during 1–16 May 2015. Data were collected on decedents’ health and situation, care support given, financial expenditure resulting from care, carer well-being and general background information. Results: In all, 1504 completed surveys were returned (28.5%). Over 90% of respondents reported spending time on care-giving in the last 3 months of the decedent’s life, contributing a median 69 h 30 min of care-giving each week. Those who reported details of expenditure (72.5%) spent a median £370 in the last 3 months of the decedent’s life. Conclusion: Carers contribute a great deal of time and money for day-to-day support and care of patients. This study has yielded a unique, population-level data set of end-of-life care-giving and future analyses will provide estimates of the economic value of family care-givers’ contributions.

There is growing evidence for the effectiveness of choice architecture or 'nudge' interventions to change a range of behaviours including the consumption of alcohol, tobacco and food. Public acceptability is key to implementing these and other interventions. However, few studies have assessed public acceptability of these interventions, including the extent to which acceptability varies with the type of intervention, the target behaviour and with evidence of intervention effectiveness. These were assessed in an online study using a between-participants full factorial design with three factors: Policy (availability vs size vs labelling vs tax) x Behaviour (alcohol consumption vs tobacco use vs high-calorie snack food consumption) x Evidence communication (no message vs assertion of policy effectiveness vs assertion and quantification of policy effectiveness [e.g., a 10% change in behaviour]). Participants (N = 7058) were randomly allocated to one of the 36 groups. The primary outcome was acceptability of the policy. Acceptability differed across policy, behaviour and evidence communication (all ps < .001). Labelling was the most acceptable policy (supported by 78%) and Availability the least (47%). Tobacco use was the most acceptable behaviour to be targeted by policies (73%) compared with policies targeting Alcohol (55%) and Food (54%). Relative to the control group (60%), asserting evidence of effectiveness increased acceptability (63%); adding a quantification to this assertion did not significantly increase this further (65%). Public acceptability for nudges and taxes to improve population health varies with the behaviour targeted and the type of intervention but is generally favourable. Communicating that these policies are effective can increase support by a small but significant amount, suggesting that highlighting effectiveness could contribute to mobilising public demand for policies. While uncertainty remains about the strength of public support needed, this may help overcome political inertia and enable action on behaviours that damage population and planetary health.