Comparative characterisation of extracellular vesicles from canine and human plasma: a necessary step in biomarker discovery.

Extracellular Vesicles (EV) have become an interesting focus as novel biomarkers of disease and are increasingly reported upon in humans and other species. The Minimal Information for Studies of Extracellular Vesicles 2018 (MISEV2018) guidelines were published to improve rigor and standardisation within the EV field and provide a framework for the reliable isolation and characterisation of EV populations. However, this rigor and standardisation has been challenging in the area of comparative medicine. Herein we present the successful isolation of EVs from human and canine plasma using Size Exclusion Chromatography and characterise these EVs according to best international practice. This study provides evidence for the reliable comparison of human and canine EVs isolated by this approach, and a baseline description of the EVs from healthy dogs to inform future biomarker studies. This work also demonstrates that the MISEV2018 guidelines can be successfully applied to EVs isolated from canine plasma.

Clinicopathological features of peripheral odontogenic fibromas in dogs and risk factors for their laboratory diagnosis.

OBJECTIVES: To explore clinicopathological features of peripheral odontogenic fibromas in dogs and risk factors for their diagnosis. MATERIALS AND METHODS: Data of cases with a histopathological diagnosis of peripheral odontogenic fibromas were obtained from a UK-based diagnostic laboratory and retrospectively reviewed. Prevalence amongst all biopsy submissions was assessed using binomial tests and Clopper-Pearson intervals. Age at diagnosis was assessed using t-test for independent samples. Lesion location, sex, and neuter status were assessed using χ2 and post hoc binomial tests. Breed odds ratios were calculated using univariable logistic regression modelling. RESULTS: The prevalence of peripheral odontogenic fibromas amongst all biopsy submissions was 2.8% (1001 of 35,328, 95% confidence interval [CI]: 2.7 to 3.0). The mean (sd) age was 8.1 (±2.7) years. The most affected quadrant was the rostral maxilla (40.1%). The ratio of maxillary to mandibular lesions was 1.3:1 (95% CI: 1.1 to 1.5), and for cases of multiple peripheral odontogenic fibromas the ratio of maxillary to mandibular lesions was 2.4:1 (95% CI: 1.1 to 5.6). Males had 1.2 times the odds of suffering of peripheral odontogenic fibromas compared to females (odds ratio [OR]: 1.2, 95% CI: 1.1 to 1.4). Neutering was associated with an increased risk of diagnosis (OR: 1.6, 95% CI: 1.3 to 1.9). Breeds with increased odds of peripheral odontogenic fibromas compared to crossbreed dogs included boxers (OR: 3.78, 95% CI: 2.80 to 5.09), border terriers (OR: 3.21, 95% CI: 2.10 to 4.91) and Basset Hounds (OR: 3.18, 95% CI: 1.58 to 6.44). Breeds with increased odds of multiple simultaneous peripheral odontogenic fibromas compared to crossbreed dogs included: Boxers (OR: 12.02, 95% CI: 7.13 to 20.24), border terriers (OR: 5.05, 95% CI: 2.32 to 11.43) and Staffordshire Bull terriers (OR: 2.42, 95% CI: 1.33 to 4.41). CLINICAL SIGNIFICANCE: Knowledge of clinicopathological features and at-risk breeds for peripheral odontogenic fibroma development can assist clinicians with making a diagnosis. The identification of risk factors provides targets for future research investigating peripheral odontogenic fibroma pathogenesis.

Rhythmicity of patient flow in an acute medical unit: relationship to hospital occupancy, 7-day working and the effect of COVID-19.

BACKGROUND: The Acute Medical Unit (AMU) provides care for unscheduled hospital admissions. Seven-day consultant presence and morning AMU discharges have been advocated to improve hospital bed management. AIMS: To determine whether a later time of daily peak AMU occupancy correlates with measures of hospital stress; whether 7-day consultant presence, for COVID-19, abolished weekly periodicity of discharges. DESIGN: Retrospective cohort analysis. METHODS: : Anonymised AMU admission and discharge times were retrieved from the Profile Information Management System (PIMS), at a large, urban hospital from 14 April 2014 to 31 December 2018 and 20 March to 2 May 2020 (COVID-19 peak). Minute-by-minute admission and discharge times were combined to construct a running total of AMU bed occupancy. Fourier transforms were used to determine periodicity. We tested association between (i) average AMU occupancy and (ii) time of peak AMU occupancy, with measures of hospital stress (total medical bed occupancy and 'medical outliers' on non-medical wards). RESULTS: : Daily, weekly and seasonal patterns of AMU bed occupancy were evident. Timing of AMU peak occupancy was unrelated to each measure of hospital stress: total medical inpatients (Spearman's rho, rs = 0.04, P = 0.24); number of medical outliers (rs = -0.06, P = 0.05). During COVID-19, daily bed occupancy was similar, with continuation of greater Friday and Monday discharges than the weekend. CONCLUSIONS: : Timing of peak AMU occupancy did not alter with hospital stress. Efforts to increase morning AMU discharges are likely to have little effect on hospital performance. Seven-day consultant presence did not abolish weekly periodicity of discharges-other factors influence weekend discharges.

The mechanical influence of bone spicules in the osteochondral junction: A finite element modelling study.

While much has been done to study how cartilage responds to mechanical loading, as well as modelling such responses, arguably less has been accomplished around the mechanics of the cartilage-bone junction. Previously, it has been reported that the presence of bony spicules invading the zone of calcified cartilage, preceded the formation of new subchondral bone and the advancing of the cement line (Thambyah and Broom in Osteoarthr Cartil 17:456-463, 2009). In this study, the morphology and frequency of bone spicules in the cartilage-bone interface of osteochondral beams subjected to three-point bending were modelled, and the results are discussed within the context of biomechanical theories on bone formation. It was found that the stress and strain magnitudes, and their distribution were sensitive to the presence and number of spicules. Spicule numbers and shape were shown to affect the strain energy density (SED) distribution in the areas of the cement line adjacent to spicules. Stresses, strains and SED analyses thus provided evidence that the mechanical environment with the addition of spicules promotes bone formation in the cartilage-bone junction.

Canine NAPEPLD-associated models of human myelin disorders.

Canine leukoencephalomyelopathy (LEMP) is a juvenile-onset neurodegenerative disorder of the CNS white matter currently described in Rottweiler and Leonberger dogs. Genome-wide association study (GWAS) allowed us to map LEMP in a Leonberger cohort to dog chromosome 18. Subsequent whole genome re-sequencing of a Leonberger case enabled the identification of a single private homozygous non-synonymous missense variant located in the highly conserved metallo-beta-lactamase domain of the N-acyl phosphatidylethanolamine phospholipase D (NAPEPLD) gene, encoding an enzyme of the endocannabinoid system. We then sequenced this gene in LEMP-affected Rottweilers and identified a different frameshift variant, which is predicted to replace the C-terminal metallo-beta-lactamase domain of the wild type protein. Haplotype analysis of SNP array genotypes revealed that the frameshift variant was present in diverse haplotypes in Rottweilers, and also in Great Danes, indicating an old origin of this second NAPEPLD variant. The identification of different NAPEPLD variants in dog breeds affected by leukoencephalopathies with heterogeneous pathological features, implicates the NAPEPLD enzyme as important in myelin homeostasis, and suggests a novel candidate gene for myelination disorders in people.

A single unit transfusion policy reduces red cell transfusions in general medical in-patients.

BACKGROUND: The NICE guidelines for blood transfusion and the patient blood management recommendations state that a single unit of red cells should be the standard dose for patients with stable anaemia who are not bleeding. Studies have shown that changing clinical transfusion practice can be difficult and that many clinicians' order two units of blood as standard for patients needing a transfusion. AIM: A collaborative project between NHS Blood and Transplant and Kings College Hospital started in September 2014 to evaluate the impact of a single unit policy on blood usage. DESIGN METHODS: Training and education was undertaken for clinical staff on eight general medical wards and all staff working in the blood transfusion laboratory. We collected transfusion data for 12 months, (6 months before and after implementation). RESULTS: There was a decrease of 50% red cell unit usage between the two periods, equating to a unit cost saving of £28 670. The number of single unit transfusions, increased from 30 to 53% whilst the number of two units decreased from 65 to 43% (P < 0.001). DISCUSSION/CONCLUSION: This project has shown that transfusion practice can be changed and savings in blood usage can be achieved through the successful implementation of the single unit transfusions policy. Key to the implementation was engagement from key medical staff within the medical department in which the policy was implemented and support from the hospital transfusion team. Continued attention and training shall be needed to support these, and implement other, patient blood management recommendations.

Enhanced contractility of intraparenchymal arterioles after global cerebral ischaemia in rat - new insights into the development of delayed cerebral hypoperfusion.

AIM: Delayed cerebral hypoperfusion is a secondary complication found in the days after transient global cerebral ischaemia that worsens the ischaemic damage inflicted by the initial transient episode of global cerebral ischaemia. A recent study demonstrated increased cerebral vasoconstriction in the large arteries on the brain surface (pial arteries) after global cerebral ischaemia. However, smaller arterioles inside the brain (parenchymal arterioles) are equally important in the regulation of cerebral blood flow and yet their pathophysiology after global cerebral ischaemia is largely unknown. Therefore, we investigated whether increased contractility occurs in the intraparenchymal arterioles. METHODS: Global cerebral ischaemia was induced in male Wistar rats by bilateral common carotid occlusion for 15 min combined with hypovolaemia. Regional cerebral blood flow was determined by quantitative autoradiography. Intraparenchymal arterioles were isolated and pressurized, and concentration-response curves to endothelin-1 with and without the endothelin B receptor-selective antagonist BQ788 was generated. Endothelin B receptor expression was investigated by quantitative flow cytometry and immunohistochemistry. RESULTS: We observed increased endothelin-1-mediated contractility of parenchymal arterioles correlating with reduced cerebral blood flow of the cortex, hippocampus and caudate nucleus 48 h after global cerebral ischaemia. The increased endothelin-1-mediated contractility was abolished by BQ788, and the vascular smooth muscle cell-specific expression of endothelin B receptors was significantly increased after global cerebral ischaemia. CONCLUSION: Increased endothelin-1-mediated contractility and expression of endothelin B receptors in the intraparenchymal vasculature contributes to the development of delayed cerebral hypoperfusion after global cerebral ischaemia in combination with vascular changes of the pial vasculature.

Early detection of cryptic memory and glucose uptake deficits in pre-pathological APP mice.

Earlier diagnosis and treatment of Alzheimer's disease would greatly benefit from the identification of biomarkers at the prodromal stage. Using a prominent animal model of aspects of the disease, we here show using clinically relevant methodologies that very young, pre-pathological PDAPP mice, which overexpress mutant human amyloid precursor protein in the brain, exhibit two cryptic deficits that are normally undetected using standard methods of assessment. Despite learning a spatial memory task normally and displaying normal brain glucose uptake, they display faster forgetting after a long delay following performance to a criterion, together with a strong impairment of brain glucose uptake at the time of attempted memory retrieval. Preliminary observations suggest that these deficits, likely caused by an impairment in systems consolidation, could be rescued by immunotherapy with an anti-ß-amyloid antibody. Our data suggest a biomarker strategy for the early detection of ß-amyloid-related abnormalities.

Impact of proctoring on success rates for percutaneous revascularisation of coronary chronic total occlusions.

OBJECTIVE: To assess the impact of proctoring for chronic total occlusion (CTO) percutaneous coronary intervention (PCI) in six UK centres. METHODS: We retrospectively analysed 587 CTO procedures from six UK centres and compared success rates of operators who had received proctorship with success rates of the same operators before proctorship (pre-proctored) and operators in the same institutions who had not been proctored (non-proctored). There were 232 patients in the pre-proctored/non-proctored group and 355 patients in the post-proctored group. Complexity was assessed by calculating the Japanese CTO (JCTO) score for each case. RESULTS: CTO PCI success was greater in the post-proctored compared with the pre-proctored/non-proctored group (77.5% vs 62.1%, p<0.0001). In more complex cases where JCTO≥2, the difference in success was greater (70.7% vs 49.5%, p=0.0003). After proctoring, there was an increase in CTO PCI activity in centres from 2.5% to 3.5%, p<0.0001 (as a proportion of total PCI), and the proportion of very difficult cases with JCTO score ≥3 increased from 15.3% (35/229) to 29.7% (105/354), p<0.0001. CONCLUSIONS: Proctoring resulted in an increase in procedural success for CTO PCI, an increase in complex CTO PCI and an increase in total CTO PCI activity. Proctoring may be a valuable way to improve access to CTO PCI and the likelihood of procedural success.

Intestinal adenocarcinoma in a herd of farmed Sika deer (Cervus nippon): a novel syndrome.

Intestinal adenocarcinomas were identified in 76 adult deer from a closed herd of 193 breeding animals grazing pasture heavily infested with bracken fern (Pteridium aquilinum). Tumors were observed postmortem in 32 animals with rapid weight loss, and similar neoplasms were detected in a further 44 clinically normal deer at "cull." Tumors were located in distal ileum, cecum, and proximal colon and presented as single (26%) or multiple (74%), variably sized, pale-gray, firm, poorly circumscribed neoplasms with associated intestinal strictures. Histopathologically tumors were well-differentiated, locally infiltrative, low-grade adenocarcinomas of tubular (51%), mucinous (33.5%), or mixed (15.5%) types. Extraintestinal metastases were not observed. The high incidence of intestinal adenocarcinoma within this herd suggests a specific and novel syndrome, and genetic and/or environmental factors may be involved in the pathogenesis.

Balancing the risks and benefits of genomic data sharing: genome research participants' perspectives.

BACKGROUND: Technological advancements are rapidly propelling the field of genome research forward, while lawmakers attempt to keep apace with the risks these advances bear. Balancing normative concerns of maximizing data utility and protecting human subjects, whose privacy is at risk due to the identifiability of DNA data, are central to policy decisions. Research on genome research participants making real-time data sharing decisions is limited; yet, these perspectives could provide critical information to ongoing deliberations. METHODS: We conducted a randomized trial of 3 consent types affording varying levels of control over data release decisions. After debriefing participants about the randomization process, we invited them to a follow-up interview to assess their attitudes toward genetic research, privacy and data sharing. RESULTS: Participants were more restrictive in their reported data sharing preferences than in their actual data sharing decisions. They saw both benefits and risks associated with sharing their genomic data, but risks were seen as less concrete or happening in the future, and were largely outweighed by purported benefits. CONCLUSION: Policymakers must respect that participants' assessment of the risks and benefits of data sharing and their privacy-utility determinations, which are associated with their final data release decisions, vary. In order to advance the ethical conduct of genome research, proposed policy changes should carefully consider these stakeholder perspectives.

Urocortin 3 transgenic mice exhibit a metabolically favourable phenotype resisting obesity and hyperglycaemia on a high-fat diet.

AIMS/HYPOTHESIS: Urocortins are the endogenous ligands for the corticotropin-releasing factor receptor type 2 (CRFR2), which is implicated in regulating energy balance and/or glucose metabolism. We determined the effects of chronic CRFR2 activation on metabolism in vivo, by generating and phenotyping transgenic mice overproducing the specific CRFR2 ligand urocortin 3. METHODS: Body composition, glucose metabolism, insulin sensitivity, energy efficiency and expression of key metabolic genes were assessed in adult male urocortin 3 transgenic mice (Ucn3(+)) under control conditions and following an obesogenic high-fat diet (HFD) challenge. RESULTS: Ucn3(+) mice had increased skeletal muscle mass with myocyte hypertrophy. Accelerated peripheral glucose disposal, increased respiratory exchange ratio and hypoglycaemia on fasting demonstrated increased carbohydrate metabolism. Insulin tolerance and indices of insulin-stimulated signalling were unchanged, indicating these effects were not mediated by increased insulin sensitivity. Expression of the transgene in Crfr2 (also known as Crhr2)-null mice negated key aspects of the Ucn3(+) phenotype. Ucn3(+) mice were protected from the HFD-induced hyperglycaemia and increased adiposity seen in control mice despite consuming more energy. Expression of uncoupling proteins 2 and 3 was higher in Ucn3(+) muscle, suggesting increased catabolic processes. IGF-1 abundance was upregulated in Ucn3(+) muscle, providing a potential paracrine mechanism in which urocortin 3 acts upon CRFR2 to link the altered metabolism and muscular hypertrophy observed. CONCLUSIONS/INTERPRETATION: Urocortin 3 acting on CRFR2 in skeletal muscle of Ucn3(+) mice results in a novel metabolically favourable phenotype, with lean body composition and protection against diet-induced obesity and hyperglycaemia. Urocortins and CRFR2 may be of interest as potential therapeutic targets for obesity.

Mechanism of acute tryptophan depletion: is it only serotonin?

The method of acute tryptophan depletion (ATD), which reduces the availability of the essential amino acid tryptophan (TRP), the dietary serotonin (5-hydroxytryptamine (5-HT)) precursor, has been applied in many experimental studies. ATD application leads to decreased availability of TRP in the brain and its synthesis into 5-HT. It is therefore assumed that a decrease in 5-HT release and subsequent blunted neurotransmission is the underlying mechanism for the behavioural effects of ATD. However, direct evidence that ATD decreases extracellular 5-HT concentrations is lacking. Furthermore, several studies provide support for alternative underlying mechanisms of ATD. This may question the utility of the method as a selective serotonergic challenge tool. As ATD is extensively used for investigating the role of 5-HT in cognitive functions and psychiatric disorders, the potential of alternative mechanisms and possible confounding factors should be taken into account. It is suggested that caution is required when interpreting ATD effects in terms of a selective serotonergic effect.

Acute tryptophan depletion in rats alters the relationship between cerebral blood flow and glucose metabolism independent of central serotonin.

Acute tryptophan depletion (ATD) decreases the 5-HT precursor tryptophan (TRP) in blood and is used both clinically and preclinically to investigate the involvement of 5-HT in the development of depressive symptomatology. Depression is associated with both central 5-HT dysfunction and abnormalities in the normal relationship between regional cerebral blood flow (CBF) and glucose metabolism (CMRG). In this study, ATD was applied in Wistar rats to investigate the cerebrovascular effects of acute changes in peripheral TRP. Rats were orally fed with a protein-carbohydrate mixture, either containing or lacking TRP. Four hours later, CBF or CMRG was measured by quantitative autoradiographic imaging in 43 brain regions of interest (ROI). In plasma, ATD resulted in a 40% reduction in the ratio of TRP to the sum of other large neutral amino acids, but had no measurable effect upon TRP or 5-HT levels in hippocampus or prefrontal cortex. Nevertheless, ATD significantly reduced local CBF in 11 of the 43 brain ROIs, while local CMRG remained unchanged. Global analysis of all 43 ROIs revealed a close correlation between CBF and CMRG within both treatment groups. However, the overall ratio (=slope) after ATD (m=1.07) was significantly decreased compared to the control group (m=1.27), indicating a state of relative cerebral oligaemia. Since ATD induced a significant lowering of peripheral TRP, without affecting central TRP or 5-HT concentrations, the decrease in CBF and global change in the flow-metabolism relationship cannot be directly attributed to decreases in brain TRP availability. This could be explained if the raphe were selectively vulnerable to ATD, but the exact mechanism remains unknown. Nevertheless, these data suggest that cerebrovascular disturbances should be considered as a potential contributory factor in studies of serotonergic dysfunction, including depression, with important implications for imaging studies that use CBF alone as a measure of neuronal function.

The role of endothelin in the cerebrovascular response following intracerebral haemorrhage: experimental studies using the endothelin antagonist SB209670.

Primary intracerebral haemorrhage (ICH) is associated with considerable morbidity and mortality. Local endothelin release following ICH may contribute to the pathophysiology of perilesional ischaemia. In diabetics, endothelin release can be enhanced by hyperglycaemia and cerebrovascular dilation may be inhibited by vascular endothelial dysfunction. To examine the effects of endothelin-mediated vasoconstriction after spontaneous ICH in the normal and diabetic brain, regional cerebral blood flow (rCBF) was examined in insulin dependent BB-rats and non-diabetic BB control rats. These experiments were performed 24 h following experimental ICH in both groups of animals that were either given the endothelin antagonist SB209670 or saline. Perilesional oligaemia was similar in control and SB209670 treated diabetic rats, but SB209670 reduced perilesional oligaemia in normal rats. In brain contralateral to the experimental ICH, rCBF was increased by SB209670 in diabetic rats, but not in non-diabetic rats. These studies show that there are differences in the cerebrovascular effects of endothelin in perilesional and contralateral brain in non-diabetic and diabetic rats following ICH.

A combined-method psychometric analysis recommended modification of the multidimensional health locus of control scales.

OBJECTIVE: The Multidimensional Health Locus of Control (MHLC) scales are widely used to measure beliefs about determinants of persons' health. We evaluated the scales over the largest-ever disease-specific sample of subjects using a combined-method psychometric approach. STUDY DESIGN AND SETTING: We performed a secondary analysis of data from 1,206 subjects from three osteoarthritis studies, using Rasch analysis and confirmatory factor analysis simultaneously. Differential item functioning (DIF) by gender and data source, scale dimensionality, and item fit were examined. The Rasch model fit the data if Rasch residual principal components analysis (PCA) corroborated three distinct dimensions and item fit statistics fell between 0.80 and 1.20. The confirmatory factor (CFA) model fit the data if factor loadings exceeded 0.50 for all items. RESULTS: DIF by gender or data source was not materially evident for any items. PCA supported existence of three dimensions in the data. Both Rasch and CFA models fit the data for 16 items; two items were detected as misperforming. When these items were removed, fit of both models improved. CONCLUSION: Results of this large-sample evaluation of the MHLC scales corroborated earlier findings that removal of certain items improves the scales. The combined Rasch-CFA approach provided better insight to scale performance problems than either method alone provided.

The utility of the Kohlman Evaluation of Living Skills test is associated with substantiated cases of elder self-neglect.

PURPOSE: Self-neglect is the most prevalent finding among cases reported to Adult Protective Services (APS) and is characterized by an inability to meet one's own basic needs. The Kohlman evaluation of living skills (KELS) has been validated in geriatric populations to assess performance with both instrumental and basic activities of daily living and as an assessment tool for the capacity to live independently; therefore, the purpose of this analysis was to compare the scores of the KELS between substantiated cases of self-neglect and matched community-dwelling elders. DATA SOURCES: This is a cross-sectional pilot study of 50 adults aged 65 years and older who were recruited from APS as documented cases of self-neglect and 50 control participants recruited from Harris County Hospital District outpatient clinics. Control participants were matched for age, race, gender, and ZIP code. A geriatric nurse practitioner (NP)-led team administered a comprehensive geriatric assessment in homes of all study participants. The assessment included the KELS and mini-mental state examination (MMSE) tests. Chi-square analyses were used to determine if cases of self-neglect were significantly more likely to fail the KELS test than matched controls. CONCLUSIONS: The analyses revealed that self-neglectors were significantly more likely to fail the KELS than non-self-neglectors (50% vs. 30%, p = .025). When stratified by MMSE scores, self-neglectors with intact cognitive function remained significantly more likely to fail the KELS compared to matched, cognitively intact controls (45% vs. 17%, p = .013). Abnormal results using an in-home KELS test were significantly associated with substantiated cases of self-neglect. IMPLICATIONS FOR PRACTICE: There is currently no gold-standard measure for identifying capacity with self-care behaviors among cases of self-neglect. As a result, self-neglect may remain unidentified in many clinical settings. The KELS provides clinicians with an objective measure of an individual's capacity and performance with everyday life-supporting tasks and thus, provides information that can help NPs identify elders at risk for self-neglect. These findings suggest that the KELS test has significant utility as part of a comprehensive geriatric assessment to aid clinicians in suspected cases of self-neglect.

Valuation of arthritis health states across ethnic groups and between patients and community members.

OBJECTIVE: We sought to examine differences in valuation of health by individuals from different ethnic backgrounds and between patients and community members. RESEARCH DESIGN: We surveyed 193 community members identified by random-digit dialing (ie, 64 white, 65 black, and 64 Hispanic) and 198 patients with osteoarthritis (OA), 66 per ethnic group, drawn sequentially from clinic lists of an outpatient institution. MEASURES: Participants were interviewed and asked to rate 2 scenarios describing arthritis (mild and severe) using visual analog scale (VAS), standard gamble (SG), and time trade-off (TTO). Differences were adjusted for cohort, age, gender, and education. RESULTS: Members of the public had higher preference scores for the 2 health states than patients (SG severe state: 0.77 public, 0.66 patients; SG mild state: 0.90 public, 0.84 patients). The difference score between the mild and severe states was smaller for black than white subjects (P < 0.001) by SG and TTO. Scores for Hispanics and whites did not differ. Preference scores increased with age (SG, TTO). CONCLUSIONS: Significant differences were observed in the valuation of health between members of the public and patients, among ethnic groups, and in relation to educational status and age, with the difference between utilities of health states being a more efficient measure of preference than the utility of a single state. Utilities elicited through valuation of hypothetical health scenarios are dependent on sociodemographic traits, experience of disease, and method used. These findings suggest that utilities cannot be used interchangeably across populations, with implications for economic analyses.