Where’s WALY? : A proof of concept study of the ‘wellbeing adjusted life year’ using secondary analysis of cross-sectional survey data

Background The Quality-Adjusted Life Year (QALY) is a measure that combines life extension and health improvement in a single score, reflecting preferences around different types of health gain. It can therefore be used to inform decision-making around allocation of health care resources to mutually exclusive options that would produce qualitatively different health benefits. A number of quality-of-life instruments can be used to calculate QALYs. The EQ-5D is one of the most commonly used, and is the preferred option for submissions to NICE (https://www.nice.org.uk/process/pmg9/). However, it has limitations that might make it unsuitable for use in areas such as public and mental health where interventions may aim to improve well-being. One alternative to the QALY is a Wellbeing-Adjusted Life Year. In this study we explore the need for a Wellbeing-Adjusted Life Year measure by examining the extent to which a measure of wellbeing (the Warwick-Edinburgh Mental Well-being Scale) maps onto the EQ-5D-3L. Methods Secondary analyses were conducted on data from the Coventry Household Survey in which 7469 participants completed the EQ-5D-3L, Warwick-Edinburgh Mental Well-being Scale, and a measure of self-rated health. Data were analysed using descriptive statistics, Pearson’s and Spearman’s correlations, linear regression, and receiver operating characteristic curves. Results Approximately 75 % of participants scored the maximum on the EQ-5D-3L. Those with maximum EQ-5D-3L scores reported a wide range of levels of mental wellbeing. Both the Warwick-Edinburgh Mental Well-being Scale and the EQ-5D-3L were able to detect differences between those with higher and lower levels of self-reported health. Linear regression indicated that scores on the Warwick-Edinburgh Mental Well-being Scale and the EQ-5D-3L were weakly, positively correlated (with R2 being 0.104 for the index and 0.141 for the visual analogue scale). Conclusion The Warwick-Edinburgh Mental Well-being Scale maps onto the EQ-5D-3L to only a limited extent. Levels of mental wellbeing varied greatly amongst participants who had the maximum score on the EQ-5D-3L. To evaluate the relative effectiveness of interventions that impact on mental wellbeing, a new measure – a Wellbeing Adjusted Life Year – is needed

Enhanced Brain Disposition and Effects of Δ9-Tetrahydrocannabinol in P-Glycoprotein and Breast Cancer Resistance Protein Knockout Mice

The ABC transporters P-glycoprotein (P-gp, Abcb1) and breast cancer resistance protein (Bcrp, Abcg2) regulate the CNS disposition of many drugs. The main psychoactive constituent of cannabis Δ9-tetrahydrocannabinol (THC) has affinity for P-gp and Bcrp, however it is unknown whether these transporters modulate the brain accumulation of THC and its functional effects on the CNS. Here we aim to show that mice devoid of Abcb1 and Abcg2 retain higher brain THC levels and are more sensitive to cannabinoid-induced hypothermia than wild-type (WT) mice. Abcb1a/b (−/−), Abcg2 (−/−) and wild-type (WT) mice were injected with THC before brain and blood were collected and THC concentrations determined. Another cohort of mice was examined for THC-induced hypothermia by measuring rectal body temperature. Brain THC concentrations were higher in both Abcb1a/b (−/−) and Abcg2 (−/−) mice than WT mice. ABC transporter knockout mice exhibited delayed elimination of THC from the brain with the effect being more prominent in Abcg2 (−/−) mice. ABC transporter knockout mice were more sensitive to THC-induced hypothermia compared to WT mice. These results show P-gp and Bcrp prolong the brain disposition and hypothermic effects of THC and offer a novel mechanism for both genetic vulnerability to the psychoactive effects of cannabis and drug interactions between CNS therapies and cannabis

Phenological Changes of Blooming Diatoms Promoted by Compound Bottom-Up and Top-Down Controls

Understanding phytoplankton species-specific responses to multiple biotic and abiotic stressors is fundamental to assess phenological and structural shifts at the community level. Here, we present the case of Thalassiosira curviseriata, a winter-blooming diatom in the Bahía Blanca Estuary, Argentina, which displayed a noticeable decrease in the past decade along with conspicuous changes in phenology. We compiled interannual field data to assess compound effects of environmental variations and grazing by the invasive copepod Eurytemora americana. The two species displayed opposite trends over the period examined. The diatom decreased toward the last years, mainly during the winters, and remained relatively constant over the other seasons, while the copepod increased toward the last years, with an occurrence restricted to winter and early spring. A quantitative assessment by structural equation modeling unveiled that the observed long-term trend of T. curviseriata resulted from the synergistic effects of environmental changes driven by water temperature, salinity, and grazing. These results suggest that the shift in the abundance distribution of T. curviseriata toward higher annual ranges of temperature and salinity—as displayed by habitat association curves—constitutes a functional response to avoid seasonal overlapping with its predator in late winters. The observed changes in the timing and abundance of the blooming species resulted in conspicuous shifts in primary production pulses. Our results provide insights on mechanistic processes shaping the phenology and structure of phytoplankton blooms