Assessment of atherosclerotic carotid plaque volume with multidetector computed tomography angiography

Purpose The amount of atherosclerotic plaque and its components (calcifications, fibrous tissue, and lipid core) could be better predictors of acute events than the now currently used degree of stenosis. Therefore, we evaluated a dedicated software tool for volume measurements of atherosclerotic carotid plaque and its components in multidetector computed tomography angiography (MDCTA) images. Materials and Methods Data acquisition was approved by the Institutional Review Board and all patients gave written informed consent. MDCTA images of 56 carotid arteries were analyzed by three observers. Plaque volumes were assessed by manual drawing of the outer vessel contour. The luminal boundary was determined based on a Hounsfield-Unit (HU) threshold. The contribution of different components was measured by the number of voxels within defined ranges of HU-values (calcification >130 HU, fibrous tissue 60–130 HU, lipid core <60 HU). Interobserver variability (IOV) was assessed. Results Plaque volume was 1,259 ± 621 mm3. The calcified, fibrous and lipid volumes were 238 ± 252 mm3, 647 ± 277 mm3 and 376 ± 283 mm3, respectively. IOV was moderate with interclass correlation coefficients (ICC) ranging from 0.76 to 0.99 and coefficients of variation (COV) ranging from 3% to 47%. Conclusion Atherosclerotic carotid plaque volume and plaque component volumes can be assessed with MDCTA with a reasonable observer variability

Follow-up of atheroma burden with sequential whole body contrast enhanced MR angiography:a feasibility study

Assess the feasibility of whole body magnetic resonance angiography (WB-MRA) for monitoring global atheroma burden in a population with peripheral arterial disease (PAD). 50 consecutive patients with symptomatic PAD referred for clinically indicated MRA were recruited. Whole body MRA (WB-MRA) was performed at baseline, 6 months and 3 years. The vasculature was split into 31 anatomical arterial segments. Each segment was scored according to degree of luminal narrowing: 0 = normal, 1 = <50 %, 2 = 50–70 %, 3 = 71–99 %, 4 = vessel occlusion. The score from all assessable segments was summed, and then normalised to the number of assessable vessels. This normalised score was divided by four (the maximum vessel score) and multiplied by 100 to give a final standardised atheroma score (SAS) with a score of 0–100. Progression was assessed with repeat measure ANOVA. 36 patients were scanned at 0 and 6 months, with 26 patients scanned at the 3 years follow up. Only those who completed all three visits were included in the final analysis. Baseline atherosclerotic burden was high with a mean SAS of 15.7 ± 10.3. No significant progression was present at 6 months (mean SAS 16.4 ± 10.5, p = 0.67), however there was significant disease progression at 3 years (mean SAS 17.7 ± 11.5, p = 0.01). Those with atheroma progression at follow-up were less likely to be on statin therapy (79 vs 100 %, p = 0.04), and had significantly higher baseline SAS (17.6 ± 11.2 vs 10.7 ± 5.1, p = 0.043). Follow up of atheroma burden is possible with WB-MRA, which can successfully quantify and monitor atherosclerosis progression at 3 years follow-up

A comparison of two methods for expert elicitation in health technology assessments.

BACKGROUND: When data needed to inform parameters in decision models are lacking, formal elicitation of expert judgement can be used to characterise parameter uncertainty. Although numerous methods for eliciting expert opinion as probability distributions exist, there is little research to suggest whether one method is more useful than any other method. This study had three objectives: (i) to obtain subjective probability distributions characterising parameter uncertainty in the context of a health technology assessment; (ii) to compare two elicitation methods by eliciting the same parameters in different ways; (iii) to collect subjective preferences of the experts for the different elicitation methods used. METHODS: Twenty-seven clinical experts were invited to participate in an elicitation exercise to inform a published model-based cost-effectiveness analysis of alternative treatments for prostate cancer. Participants were individually asked to express their judgements as probability distributions using two different methods - the histogram and hybrid elicitation methods - presented in a random order. Individual distributions were mathematically aggregated across experts with and without weighting. The resulting combined distributions were used in the probabilistic analysis of the decision model and mean incremental cost-effectiveness ratios and the expected values of perfect information (EVPI) were calculated for each method, and compared with the original cost-effectiveness analysis. Scores on the ease of use of the two methods and the extent to which the probability distributions obtained from each method accurately reflected the expert's opinion were also recorded. RESULTS: Six experts completed the task. Mean ICERs from the probabilistic analysis ranged between £162,600-£175,500 per quality-adjusted life year (QALY) depending on the elicitation and weighting methods used. Compared to having no information, use of expert opinion decreased decision uncertainty: the EVPI value at the £30,000 per QALY threshold decreased by 74-86 % from the original cost-effectiveness analysis. Experts indicated that the histogram method was easier to use, but attributed a perception of more accuracy to the hybrid method. CONCLUSIONS: Inclusion of expert elicitation can decrease decision uncertainty. Here, choice of method did not affect the overall cost-effectiveness conclusions, but researchers intending to use expert elicitation need to be aware of the impact different methods could have.This paper presents independent research funded by the National Institute of Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West Peninsula

Dynamic displacement of normal and detached semicircular canal cupula

© 2009 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution Noncommercial License. The definitive version was published in JARO - Journal of the Association for Research in Otolaryngology 10 (2009): 497-509, doi:10.1007/s10162-009-0174-y.The dynamic displacement of the semicircular canal cupula and modulation of afferent nerve discharge were measured simultaneously in response to physiological stimuli in vivo. The adaptation time constant(s) of normal cupulae in response to step stimuli averaged 36 s, corresponding to a mechanical lower corner frequency for sinusoidal stimuli of 0.0044 Hz. For stimuli equivalent to 40–200 deg/s of angular head velocity, the displacement gain of the central region of the cupula averaged 53 nm per deg/s. Afferents adapted more rapidly than the cupula, demonstrating the presence of a relaxation process that contributes significantly to the neural representation of angular head motions by the discharge patterns of canal afferent neurons. We also investigated changes in time constants of the cupula and afferents following detachment of the cupula at its apex—mechanical detachment that occurs in response to excessive transcupular endolymph pressure. Detached cupulae exhibited sharply reduced adaptation time constants (300 ms–3 s, n = 3) and can be explained by endolymph flowing rapidly over the apex of the cupula. Partially detached cupulae reattached and normal afferent discharge patterns were recovered 5–7 h following detachment. This regeneration process may have relevance to the recovery of semicircular canal function following head trauma.Financial support was provided by the NIDCD R01 DC06685 (Rabbitt) and NASA GSRP 56000135 & NSF IGERT DGE- 9987616 (Breneman)

High Quality Care and Ethical Pay-for-Performance: A Society of General Internal Medicine Policy Analysis

BACKGROUND: Pay-for-performance is proliferating, yet its impact on key stakeholders remains uncertain. OBJECTIVE: The Society of General Internal Medicine systematically evaluated ethical issues raised by performance-based physician compensation. RESULTS: We conclude that current arrangements are based on fundamentally acceptable ethical principles, but are guided by an incomplete understanding of health-care quality. Furthermore, their implementation without evidence of safety and efficacy is ethically precarious because of potential risks to stakeholders, especially vulnerable patients. CONCLUSION: We propose four major strategies to transition from risky pay-for-performance systems to ethical performance-based physician compensation and high quality care. These include implementing safeguards within current pay-for-performance systems, reaching consensus regarding the obligations of key stakeholders in improving health-care quality, developing valid and comprehensive measures of health-care quality, and utilizing a cautious evaluative approach in creating the next generation of compensation systems that reward genuine quality

Towards an optimal therapy strategy for myogenous TMD, physiotherapy compared with occlusal splint therapy in an RCT with therapy-and-patient-specific treatment durations

Appendix. Threshold of signs and symptoms. Post-hoc power analysis on measures of effectiveness. Two-way ANOVA statistical analysis for pain intensity. Rules for progressing and ending splint therapy. Rules for progressing and ending physiotherapy. A stepped-care model including two possible therapies. (PDF 86 kb

Evidence gaps and biodiversity threats facing the marine environment of the United Kingdom’s Overseas Territories

Understanding the evidence base and identifying threats to the marine environment is critical to ensure cost-effective management and to identify priorities for future research. The United Kingdom (UK) government is responsible for approximately 2% of the world’s oceans, most of which belongs to its 14 Overseas Territories (UKOTs). Containing biodiversity of global significance, and far in excess of the UK mainland’s domestic species, there has recently been a strong desire from many of the UKOTs, the UK Government, and NGOs to improve marine management in these places. Implementing evidence-based marine policy is, however, challenged by the disparate nature of scientific research in the UKOTs and knowledge gaps about the threats they face. Here, we address these issues by systematically searching for scientific literature which has examined UKOT marine biodiversity and by exploring publicly available spatial threat data. We find that UKOT marine biodiversity has received consistent, but largely low, levels of scientific interest, and there is considerable geographical and subject bias in research effort. Of particular concern is the lack of research focus on management or threats to biodiversity. The extent and intensity of threats vary amongst and within the UKOTs but unsurprisingly, climate change associated threats affect them all and direct human stressors are more prevalent in those with higher human populations. To meet global goals for effective conservation and management, there is an urgent need for additional and continued investment in research and management in the Overseas Territories, particularly those that have been of lesser focus

Breast epithelial cell proliferation is markedly increased with short-term high levels of endogenous estrogen secondary to controlled ovarian hyperstimulation

Oocyte donors have high serum estradiol (E2) levels similar to the serum levels seen in the first trimester of pregnancy. We report in this article our studies comparing cell proliferation, Ki67 (MIB1), and estrogen and progesterone receptor levels (ERα, PRA, and PRB) in the breast terminal duct lobular units of oocyte donors, women in early pregnancy, and in normally cycling women. Breast tissue and blood samples were obtained from 10 oocyte donors, and 30 pregnant women at 5–18 weeks of gestation. Breast tissue samples were also obtained from 26 normally cycling women. In the oocyte donors: peak E2 (mean ~15,300 pmol/l) was reached on the day before oocyte (and tissue) donation; peak progesterone (P4; mean 36.3 nmol/l) was reached on the day of donation; Ki67 was positively associated with level of E2, and the mean Ki67 was 7.0% significantly greater than the mean 1.8% of cycling women. In the pregnant women: mean E2 rose from ~2,000 pmol/l at 5 weeks of gestation to ~27,000 pmol/l at 18 weeks; mean P4 did not change from ~40 nmol/l until around gestational week 11 when it increased to ~80 nmol/l; mean Ki67 was 15.4% and did not vary with gestational age or E2. Oocyte donors have greatly increased levels of E2 and of breast-cell proliferation, both comparable in the majority of donors to the levels seen in the first trimester of pregnancy. Whether their short durations of greatly increased E2 levels are associated with any long-term beneficial effects on the breast, as occurring in rodent models, is not known

A Cost-Utility Analysis of Prostate Cancer Screening in Australia

Background and Objectives: The Göteborg randomised population-based prostate cancer screening trial demonstrated that Prostate Specific Antigen (PSA) based screening reduces prostate cancer deaths compared with an age matched control group. Utilising the prostate cancer detection rates from this study we have investigated the clinical and cost-effectiveness of a similar PSA-based screening strategy for an Australian population of men aged 50-69 years. Methods: A decision model that incorporated Markov processes was developed from a health system perspective.The base case scenario compared a population-based screening programme with current opportunistic screening practices. Costs, utility values, treatment patterns and background mortality rates were derived from Australian data. All costs were adjusted to reflect July 2015 Australian dollars. An alternative scenario compared systematic with opportunistic screening but with optimisation of active surveillance (AS) uptake in both groups. A discount rate of 5% for costs and benefits was utilised. Univariate and probabilistic sensitivity analyses were performed to assess the effect of variable uncertainty on model outcomes. Results: Our model very closely replicated the number of deaths from both prostate cancer and background mortality in the Göteborg study. The incremental cost per quality-adjusted life-year (QALY) for PSA screening was $AU147,528. However, for years of life gained (LYGs) PSA based screening ($AU45,890/LYG) appeared more favourable. Our alternative scenario with optimised AS improved cost-utility to $AU45,881/QALY, with screening becoming cost-effective at a 92$AU50,000/QALY. It appears more cost-effective if LYGs are used as the relevant outcome, and is more cost effective than the established Australian breast cancer screening programme on this basis. Optimised utilisation of AS increases the cost-effectiveness of prostate cancer screening dramatically