Virtual flavor: High-fidelity simulation of real flavor experiences

Food and drink are key parts of our lives. While virtual reality has the potential to provide a high-fidelity simulation of real experiences in virtual worlds, the incorporation of flavor appreciation within these virtual experiences has largely been ignored. This article introduces a virtual flavor device to simulate real flavor experiences. The goal is to provide virtual flavor experiences, using food-safe chemicals for the three components of a flavor (taste, aroma, mouthfeel), which are perceived as “indistinguishable” from the equivalent real experience. Furthermore, because we are delivering a simulation, the same device can be used to take a user on a “flavor discovery journey” from a start flavor to a new, preferred flavor by adding or removing any amount of the components. In the first experiment, participants (N = 28) were exposed to real and virtual samples of orange juice, and the health product, rooibos tea, and asked to rate their similarity. The second experiment investigated how participants (N = 6) could move within “flavor space” from one flavor to another. The results show that it is possible to simulate, with a high degree of precision, a real flavor experience, and precisely controlled “flavor discovery journeys” can be undertaken using virtual flavors

Is the assumption of waning of treatment effect applied consistently across NICE technology appraisals? A case-study focusing on disease-modifying therapies for treatment of multiple sclerosis

Objectives Whether the effects of therapies may wane over time is a matter of debate, especially when considering their long-term cost-effectiveness. Here, we examined how the assumption of the waning of treatment effect was applied across the National Institute for Health and Care Excellence (NICE) appraisals for disease-modifying therapies (DMTs) used in multiple sclerosis. Methods We undertook a document analysis following a search of the NICE website. The inclusion criteria of the study were as follows: all publicly available documents related to completed appraisals for DMTs (period: January 2000 to July 2021). The exclusion criteria of the study were as follows: all documents that did not meet the inclusion criteria, especially pertaining to drugs used in other disease areas. We extracted information about the waning of treatment effect assumption as considered by companies, assessment groups, and appraisal committees, and we analyzed trends over time. Results We reviewed fifteen appraisals that reported guidance on sixteen DMTs. Irrespective of the drugs’ mechanism of action or their pharmaceutical nature, there was substantial variation in the modalities when the assumption of waning was implemented. We noted the recent preference to use all-cause discontinuation as a proxy. This heterogeneity did not appear to affect acceptance of the DMTs (all but one were recommended for use across the National Health System (NHS)). Conclusions Modeling the long-term effect of therapies is challenging, especially given the limited follow-up duration of related trials. This generates recurrent debates on the presence of waning of treatment efficacy and heterogeneity across appraisals. More refined recommendations obtained by consensus among stakeholders could help to achieve greater consistency in decision making

ADAMS project: a genetic Association study in individuals from Diverse Ancestral backgrounds with Multiple Sclerosis based in the UK

PURPOSE: Genetic studies of multiple sclerosis (MS) susceptibility and severity have focused on populations of European ancestry. Studying MS genetics in other ancestral groups is necessary to determine the generalisability of these findings. The genetic Association study in individuals from Diverse Ancestral backgrounds with Multiple Sclerosis (ADAMS) project aims to gather genetic and phenotypic data on a large cohort of ancestrally-diverse individuals with MS living in the UK. PARTICIPANTS: Adults with self-reported MS from diverse ancestral backgrounds. Recruitment is via clinical sites, online (https://app.mantal.co.uk/adams) or the UK MS Register. We are collecting demographic and phenotypic data using a baseline questionnaire and subsequent healthcare record linkage. We are collecting DNA from participants using saliva kits (Oragene-600) and genotyping using the Illumina Global Screening Array V.3. FINDINGS TO DATE: As of 3 January 2023, we have recruited 682 participants (n=446 online, n=55 via sites, n=181 via the UK MS Register). Of this initial cohort, 71.2% of participants are female, with a median age of 44.9 years at recruitment. Over 60% of the cohort are non-white British, with 23.5% identifying as Asian or Asian British, 16.2% as Black, African, Caribbean or Black British and 20.9% identifying as having mixed or other backgrounds. The median age at first symptom is 28 years, and median age at diagnosis is 32 years. 76.8% have relapsing-remitting MS, and 13.5% have secondary progressive MS. FUTURE PLANS: Recruitment will continue over the next 10 years. Genotyping and genetic data quality control are ongoing. Within the next 3 years, we aim to perform initial genetic analyses of susceptibility and severity with a view to replicating the findings from European-ancestry studies. In the long term, genetic data will be combined with other datasets to further cross-ancestry genetic discoveries

The ADAMS project - a genetic Association study in individuals from Diverse Ancestral backgrounds with Multiple Sclerosis based in the United Kingdom

Purpose Genetic studies of multiple sclerosis (MS) susceptibility and severity have focused on populations of European ancestry. Studying MS genetics in other ancestral groups is necessary to determine the generalisability of these findings. The genetic Association study in individuals from Diverse Ancestral backgrounds with Multiple Sclerosis (ADAMS) project aims to gather genetic and phenotypic data on a large cohort of ancestrally-diverse individuals with MS living in the UK. Participants Adults with self-reported MS from diverse ancestral backgrounds. Recruitment is via clinical sites, online (https://app.mantal.co.uk/adams) or the UK MS Register. We are collecting demographic and phenotypic data using a baseline questionnaire and subsequent healthcare record linkage. We are collecting DNA from participants using saliva kits (Oragene-600) and genotyping using the Illumina Global Screening Array V.3. Findings to date As of 3 January 2023, we have recruited 682 participants (n=446 online, n=55 via sites, n=181 via the UK MS Register). Of this initial cohort, 71.2% of participants are female, with a median age of 44.9 years at recruitment. Over 60% of the cohort are non-white British, with 23.5% identifying as Asian or Asian British, 16.2% as Black, African, Caribbean or Black British and 20.9% identifying as having mixed or other backgrounds. The median age at first symptom is 28 years, and median age at diagnosis is 32 years. 76.8% have relapsing–remitting MS, and 13.5% have secondary progressive MS. Future plans Recruitment will continue over the next 10 years. Genotyping and genetic data quality control are ongoing. Within the next 3 years, we aim to perform initial genetic analyses of susceptibility and severity with a view to replicating the findings from European-ancestry studies. In the long term, genetic data will be combined with other datasets to further cross-ancestry genetic discoveries

A longitudinal study of biomarkers in primary progressive multiple sclerosis

This thesis describes the work performed using conventional (whole and regional brain volume) and non-conventional magnetic resonance imaging (MRI) which measures diffusion tensor imaging, magnetization transfer imaging and magnetic resonance spectroscopy, to arrive at the most sensitive way of detecting neurodegenerative change in patients with primary progressive multiple sclerosis (PPMS). The experiments described aim to identify the most useful surrogate marker or combination of such markers that could be used to power trials of neuroprotective agents in PPMS. First, we compared within-patient variability using the same primary progressive MS cohort and a small number of healthy controls of a number of different MR outcome measures. We outlined efforts made to reduce this measurement related variability. We then demonstrated significant longitudinal change over one year in most MR measures in our PPMS cohort compared to healthy controls. We also compared these values to the measured change over time and the across group standard deviation which are necessary values required to power studies. Next we explored the value of non-conventional MRI metrics at baseline and time to get to a baseline value (disease duration) to predict brain atrophy longitudinally over one year. We demonstrated that baseline corpus callosum volume predicted percentage brain volume change over the 6 subsequent year and this correlation between the two became stronger when the annual baseline loss in corpus callosum volume (CCV) was considered. Finally, we showed that the grey matter volume when incorporated into the power calculation for a longitudinal study was the single measure that reduced the sample size required by the most. The combination of volumetric measures (Thalamic Volume+GM Volume) was the most powerful combination, interestingly more powerful than combinations involving PBVC which is the current gold standard. Sample sizes were halved by combining two measures and reduced even futhur by using three measures in combination compared to using a single MR measure.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

A longitudinal study of biomarkers in primary progressive multiple sclerosis

This thesis describes the work performed using conventional (whole and regional brain volume) and non-conventional magnetic resonance imaging (MRI) which measures diffusion tensor imaging, magnetization transfer imaging and magnetic resonance spectroscopy, to arrive at the most sensitive way of detecting neurodegenerative change in patients with primary progressive multiple sclerosis (PPMS). The experiments described aim to identify the most useful surrogate marker or combination of such markers that could be used to power trials of neuroprotective agents in PPMS. First, we compared within-patient variability using the same primary progressive MS cohort and a small number of healthy controls of a number of different MR outcome measures. We outlined efforts made to reduce this measurement related variability. We then demonstrated significant longitudinal change over one year in most MR measures in our PPMS cohort compared to healthy controls. We also compared these values to the measured change over time and the across group standard deviation which are necessary values required to power studies. Next we explored the value of non-conventional MRI metrics at baseline and time to get to a baseline value (disease duration) to predict brain atrophy longitudinally over one year. We demonstrated that baseline corpus callosum volume predicted percentage brain volume change over the 6 subsequent year and this correlation between the two became stronger when the annual baseline loss in corpus callosum volume (CCV) was considered. Finally, we showed that the grey matter volume when incorporated into the power calculation for a longitudinal study was the single measure that reduced the sample size required by the most. The combination of volumetric measures (Thalamic Volume+GM Volume) was the most powerful combination, interestingly more powerful than combinations involving PBVC which is the current gold standard. Sample sizes were halved by combining two measures and reduced even futhur by using three measures in combination compared to using a single MR measure.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Is the assumption of waning of treatment effect applied consistently across NICE technology appraisals? : A case-study focusing on disease-modifying therapies for treatment of multiple sclerosis

Peer reviewedPublisher PD

Influence of physicians’ risk perception on switching treatments between high- efficacy and non–high-efficacy disease‑modifying therapies in multiple sclerosis

Background: The decision of initiating treatment for multiple sclerosis (MS) with a high-efficacy DMT (HE DMT) or non-high-efficacy DMT (non-HE DMT) is influenced by several factors, including risk perception of patients and physicians. Objective: Investigate the influence of physicians' risk perception on decision-making when switching treatments for MS and the reasons for switching. Methods: Data were drawn from the Adelphi Real-World MS Disease-Specific Program (a retrospective survey) and analysis included people with RMS identified between 2017- 2021. Results: Of 4129 patients with reasons for switch available, 3538 switched from non-HE DMT and 591 from HE DMT. Overall, 4.7% of patients were switched treatment by their physicians due to the risk of malignancies and infections including PML risk. The proportion of switches that were made due to the risk of PML were 23.9% in the HE DMT and 0.5% in the non-HE DMT groups. The top reasons for switching were relapse frequency (non-HE DMT vs HE-DMT: 26.8% vs 15.2%), lack of efficacy (20.9 vs 11.7) and increased number of MRI lesions (20.3% vs 12.4%). Conclusions: Physicians' risk perception of malignancies and infection excluding PML was not a leading factor when switching treatment. The risk of PML was a key factor, especially for switching patients from HE DMTs. In both groups, lack of efficacy was the key contributing factor for switching. Initiating the treatment with HE DMTs may potentially reduce the number of switches due to sub-optimal efficacy. These findings might help physicians to engage more in discussions with patients about the benefit/risk profile of DMTs

Real world annualized relapse rates from contemporary multiple sclerosis clinics in the UK: A retrospective multicentre cohort study

Abstract Background: Annualized Relapse Rate (ARR) is used as an outcome measure in multiple sclerosis (MS) clinical trials. Previous studies demonstrated that ARR has reduced in placebo groups between 1990 and 2012. This study aimed to estimate real world ARRs from contemporary MS clinics in the UK, in order to improve the feasibility estimations for clinical trials and facilitate MS service planning. Methods: A multicentre observational, retrospective study of patients with MS from 5 tertiary neuroscience centres in the UK. We included all adult patients with a diagnosis of MS that had a relapse between 01/04/2020-30/06/2020. Results: 113 out of 8783 patients had a relapse during the 3-month study period. 79% of the patients with a relapse were female, the mean age was 39 years, and the median disease duration was 4.5 years; 36% of the patients that had a relapse were on disease modifying treatment. The ARR from all study sites was estimated at 0.05. The ARR for relapsing remitting MS (RRMS) was estimated at 0.08, while the ARR for secondary progressive MS (SPMS) was 0.01. Conclusions: We report a lower ARR compared to previously reported rates in MS