Although it is well known that water is essential for human homeostasis and survival, only recently have we begun to understand its role in the maintenance of brain function. Herein, we integrate emerging evidence regarding the effects of both dehydration and additional acute water consumption on cognition and mood. Current findings in the field suggest that particular cognitive abilities and mood states are positively influenced by water consumption. The impact of dehydration on cognition and mood is particularly relevant for those with poor fluid regulation, such as the elderly and children. We critically review the most recent advances in both behavioural and neuroimaging studies of dehydration and link the findings to the known effects of water on hormonal, neurochemical and vascular functions in an attempt to suggest plausible mechanisms of action. We identify some methodological weaknesses, including inconsistent measurements in cognitive assessment and the lack of objective hydration state measurements as well as gaps in knowledge concerning mediating factors that may influence water intervention effects. Finally, we discuss how future research can best elucidate the role of water in the optimal maintenance of brain health and function.

BackgroundSeveral therapies have recently been approved for use in the NHS for pretreated advanced or metastatic renal cell carcinoma (amRCC), but there is a lack of comparative evidence to guide decisions between them.ObjectiveTo evaluate the clinical effectiveness and cost-effectiveness of axitinib (Inlyta®, Pfizer Inc., NY, USA), cabozantinib (Cabometyx®, Ipsen, Slough, UK), everolimus (Afinitor®, Novartis, Basel, Switzerland), nivolumab (Opdivo®, Bristol-Myers Squibb, NY, USA), sunitinib (Sutent®, Pfizer, Inc., NY, USA) and best supportive care (BSC) for people with amRCC who were previously treated with vascular endothelial growth factor (VEGF)-targeted therapy.Data sourcesA systematic review and mixed-treatment comparison (MTC) of randomised controlled trials (RCTs) and non-RCTs. Primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary outcomes were objective response rates (ORRs), adverse events (AEs) and health-related quality of life (HRQoL). MEDLINE, EMBASE and The Cochrane Library were searched from inception to January and June 2016 for RCTs and non-RCTs, respectively. Two reviewers abstracted data and performed critical appraisals.Review methodsA fixed-effects MTC was conducted for OS, PFS [hazard ratios (HRs)] and ORR (odds ratios), and all were presented with 95% credible intervals (CrIs). The RCT data formed the primary analyses, with non-RCTs and studies rated as being at a high risk of bias included in sensitivity analyses (SAs). HRQoL and AE data were summarised narratively. A partitioned survival model with health states for pre progression, post progression and death was developed to perform a cost–utility analysis. Survival curves were fitted to the PFS and OS results from the MTC. A systematic review of HRQoL was undertaken to identify sources of health state utility values.ResultsFour RCTs (n = 2618) and eight non-RCTs (n = 1526) were included. The results show that cabozantinib has longer PFS than everolimus (HR 0.51, 95% CrI 0.41 to 0.63) and both treatments are better than BSC. Both cabozantinib (HR 0.66, 95% CrI 0.53 to 0.82) and nivolumab (HR 0.73, 95% CrI 0.60 to 0.89) have longer OS than everolimus. SAs were consistent with the primary analyses. The economic analysis, using drug list prices, shows that everolimus may be more cost-effective than BSC with an incremental cost-effectiveness ratio (ICER) of £45,000 per quality-adjusted life-year (QALY), as it is likely to be considered an end-of-life treatment. Cabozantinib has an ICER of £126,000 per QALY compared with everolimus and is unlikely to be cost-effective. Nivolumab was dominated by cabozantinib (i.e. more costly and less effective) and axitinib was dominated by everolimus.LimitationsTreatment comparisons were limited by the small number of RCTs. However, the key limitation of the analysis is the absence of the drug prices paid by the NHS, which was a limitation that could not be avoided owing to the confidentiality of discounts given to the NHS.ConclusionsThe RCT evidence suggests that cabozantinib is likely to be the most effective for PFS and OS, closely followed by nivolumab. All treatments appear to delay disease progression and prolong survival compared with BSC, although the results are heterogeneous. The economic analysis shows that at list price everolimus could be recommended as the other drugs are much more expensive with insufficient incremental benefit. The applicability of these findings to the NHS is somewhat limited because existing confidential patient access schemes could not be used in the analysis. Future work using the discounted prices at which these drugs are provided to the NHS would better inform estimates of their relative cost-effectiveness.Study registrationThis study is registered as PROSPERO CRD42016042384.FundingThe National Institute for Health Research Health Technology Assessment programme.

ObjectiveTo compare the effectiveness and safety of treatments for advanced or metastatic renal cell carcinoma (amRCC) after treatment with vascular endothelial growth factor (VEGF)-targeted treatment.DesignSystematic review and network meta-analysis of randomised controlled trials (RCTs) and comparative observational studies. MEDLINE, EMBASE and Cochrane Library were searched up to January 2018.ParticipantsPeople with amRCC requiring treatment after VEGF-targeted treatment.InterventionsAxitinib, cabozantinib, everolimus, lenvatinib with everolimus, nivolumab, sorafenib and best supportive care (BSC).OutcomesPrimary outcomes were overall survival (OS) and progression-free survival (PFS); secondary outcomes were objective response rate (ORR), adverse events, and health-related quality of life (HRQoL).ResultsTwelve studies were included (n=5144): five RCTs and seven observational studies. Lenvatinib with everolimus significantly increased OS and PFS over everolimus (HR 0.61, 95% Credible Interval [95%CrI]: 0.36 to 0.96 and 0.47, 95%CrI: 0.26 to 0.77, respectively) as did cabozantinib (HR 0.66, 95%CrI: 0.53 to 0.82 and 0.51, 95%CrI: 0.41 to 0.63, respectively). This remained the case when observational evidence was included. Nivolumab also significantly improved OS versus everolimus (HR 0.74, 95%CrI: 0.57 to 0.93). OS sensitivity analysis, including observational studies, indicates everolimus being more effective than axitinib and sorafenib. However, inconsistency was identified in the OS sensitivity analysis. PFS sensitivity analysis suggests axitinib is more effective than everolimus, which may be more effective than sorafenib. The results for ORR supported the OS and PFS analyses. Nivolumab is associated with fewer grade 3 or grade 4 adverse events than lenvatinib with everolimus or cabozantinib. HRQoL could not be analysed due to differences in tools used.ConclusionsLenvatinib with everolimus, cabozantinib and nivolumab are effective in prolonging the survival for people with amRCC subsequent to VEGF-targeted treatment, but there is considerable uncertainty about how they compare to each other and how much better they are than axitinib and sorafenib.PROSPERO registrationnumberCRD42017071540.

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This study compared the vegetable intake of preschool children from three European countries [Italy, Poland, and the United Kingdom (UK)] and explored the parent, child, and environmental factors that predicted intake in each country. A total of 408 parents of preschoolers (Italy: N = 61, Poland: N = 124, and UK: N = 225; child mean age = 32.2 months, SD = 9.47) completed an online survey comprising a set of standardised questionnaires. For all three countries, the questionnaires included measures of children’s vegetable intake (VegFFQ), child eating behaviour (CEBQ-FF), parents’ mealtime goals (FMGs), and sociodemographic questions about family background and environment. In the UK and Italy, additional questionnaires were used to assess child temperament (EAS-T) and parents’ feeding practices (CFPQ). The results showed that the number of child-sized portions of vegetables consumed per day varied significantly across countries; Polish children consumed the most (∼3 portions) and Italian children the least (∼1.5 portions). Between-country differences were seen in parents’ goals for family mealtimes; compared to Italian parents, Polish and UK parents were more motivated to minimise mealtime stress, increase family involvement in meal preparation, and share the same foods with family members. British and Italian parents also adopted different feeding practices; parents in the UK reported more use of healthy modelling behaviours and more use of foods to support their child’s emotion regulation. In terms of child factors, Italian children were reported to be more emotional and more sociable than British children. Analyses of the relationships between the parent, child, and environmental factors and children’s vegetable intake revealed both similarities and differences between countries. Negative predictors of vegetable intake included child food fussiness in the UK and Poland, child temperament (especially, shyness) in Italy, and the use of food as a reward and child emotionality in the UK. Positive predictors included the parental mealtime goal of ‘family involvement’ in the UK. These results highlight differences in the extent to which European preschoolers achieve recommended levels of vegetable intake, and in the factors that influence whether they do. The results suggest a need to develop healthy eating interventions that are adopted to meet the specific needs of the countries in which they are implemented.