Brighton and Sussex Medical School Brighton UK
Dowell N.G.,Brighton and Sussex Medical School Brighton UK |
Evans S.L.,University of Sussex |
Tofts P.S.,Brighton and Sussex Medical School Brighton UK |
King S.L.,University of Sussex |
And 2 more authors.
NMR in Biomedicine | Year: 2016
The presence of the e4 allele of the apolipoprotein E (APOE) gene is the best-known genetic risk factor for Alzheimer's disease. In this study, we investigated the link between functional and behavioural differences and regional brain volume and cortical thickness differences in those who carry the e4 allele (e4+) and those who only carry the e3 allele (e3/e3). We studied these genotype populations in two age groups: a young group (average age, 21years) and a mid-age group (average age, 50years). High-resolution T1-weighted MRI scans were analysed with Freesurfer to measure regional white matter brain volume and cortical thickness differences between genotype groups at each age. These data were correlated with behavioural findings in the same cohort. Resting-state MRI was also conducted to identify differences in underlying brain functional connectivity. We found that there was a positive correlation between the thickness of the parahippocampal cortex in young e4+ individuals and performance on an episodic memory task. Young e4+ individuals also showed a positive correlation between white matter volume in the left anterior cingulate and performance on a covert attention task. At mid-age, e4+ individuals had structural differences relative to e3/e3 individuals in these areas: the parahippocampal cortex was thicker and white matter volume in the left anterior cingulate was greater than in e3/e3 individuals. We discuss the possibility that an over-engagement with these regions by e4+ individuals in youth may have a neurogenic effect that is observable later in life. The cuneus appears to be an important region for APOE-driven differences in the brain, with greater functional connectivity among young e3/e3 individuals and greater white matter volume in young e4+ individuals. © 2016 John Wiley & Sons, Ltd.
Wilkins E.,North Manchester General Hospital Manchester UK |
Fisher M.,Brighton and Sussex Medical School Brighton UK |
Brogan A.J.,RTI Health Solutions Research Triangle Park NC United States |
Talbird S.E.,RTI Health Solutions Research Triangle Park NC United States |
La E.M.,RTI Health Solutions Research Triangle Park NC United States
HIV Medicine | Year: 2015
Objectives: The aim of the study was to assess the cost-effectiveness of the four regimens studied in the AIDS Clinical Trials Group (ACTG) 5202 clinical trial, tenofovir/emtricitabine (TDF/FTC) or abacavir/lamivudine (ABC/3TC) in combination with efavirenz (EFV) or atazanavir/ritonavir (ATV/r), for treatment-naïve adults with HIV-1 infection in the UK. Methods: A Markov model with six health states based on CD4 cell count ranges was developed to predict long-term costs and health outcomes for individuals on first-line therapy. Head-to-head efficacy data comparing TDF/FTC + EFV, TDF/FTC + ATV/r, ABC/3TC + EFV, and ABC/3TC + ATV/r were obtained from ACTG 5202 for up to 192 weeks. Antiretroviral drug costs were based on current list prices. Other medical costs (2013 UK pounds sterling), utility values, and mortality rates were obtained from published sources. Base-case, sensitivity, and subgroup analyses (by baseline viral load) were conducted. Results: Individuals using TDF/FTC-based regimens were predicted to remain on first-line therapy longer and accrue more quality-adjusted life-years (QALYs) than individuals using ABC/3TC-based regimens. At a willingness-to-pay threshold of £30 000 per QALY gained, TDF/FTC-based regimens were predicted to be cost-effective compared with ABC/3TC-based regimens, with incremental cost-effectiveness ratios of £23 355 for TDF/FTC + EFV vs. ABC/3TC + EFV and £23 785 for TDF/FTC + ATV/r vs. ABC/3TC + ATV/r. Results were generally robust in subgroup, sensitivity, and scenario analyses. Conclusions: In an analysis of the regimens studied in ACTG 5202 for treatment-naïve adults with HIV-1 infection in the UK, TDF/FTC-based regimens yielded more favourable health outcomes and were generally predicted to be cost-effective compared with ABC/3TC-based regimens. These results confirm that TDF/FTC-based regimens are not only clinically effective but also cost-effective. © 2015 British HIV Association.