Economic Evaluation of Positron Emission Tomography (PET) in Non Small Cell Lung Cancer (NSCLC), CHERE Working Paper 2007/6

Background: There are several perceived benefits from introducing positron emission tomography (PET) scanning into the staging of non small lung cancer (NSCLC). However, its greatest primary benefit is the role it can potential perform in reducing the number of unnecessary diagnostic examinations and futile surgeries. Objectives: To evaluate the economic impact and cost effectiveness of PET scanning in the management of potentially operable NSCLC patients using a cost-utility model. Methods: A literature review was conducted to find relevant studies and appropriate parameters to construct a decision model. Two strategies were compared. The first strategy was a conventional work up (CWU) consisting of an x-ray, a chest computer tomography (CT) scan and brochoscopy; the second strategy consisted of a CWU plus a whole body PET scan. These two strategies were applied to two sub-groups of NSCLC patients; those that had received a positive result on their CT scan and those that got a negative result on their CT scan. The cost-effectiveness of each strategy was dependent on a number of variables that were taken from a literature review. Costs were based on the Australian diagnostic related groups, a cost calculation for a chemotherapy course and values obtained from the literature. The life expectancy and utility scores were also taken from the literature and combined to create an incremental quality adjusted life year (QALY) value for PET for each of the patient groups. Results: The mean costs in CT negative and CT positive patients were lower in the CWU strategy, costing $A 20,427 and$A 23,578 per patient respectively compared to the PET strategy ($A 20,826 and$A 24,083 per patient respectively). The mean QALYs for both the CT positive and CT negative patients were higher in PET with 2.91 and 2.11 respectively compared to the CWU of 2.88 and 2.09. The incremental cost effectiveness ratio (ICER) for the CT negative strategy was $A 14,581 and$A 52,039 for the CT positive strategy. Conclusion: The PET strategy in CT negative and CT positive patients appears to be cost effective, however, there is much uncertainty surrounding this base result, particularly in CT positive patients.PET, non-small-cell lung cancer, economic evaluation

A model for best practice HTA

The aims of this paper are: to review and describe different approaches to HTA used in Australia and in other countries and to identify the features of best practice in HTA, particularly those likely to be most relevant to HTA at a local (ie state/regional) level. There are a number of well-developed models of HTA at the national and local levels. Most information about the operation of these models, particularly about the type and number of evaluations conducted, the recommendations/decisions made and the reasons for these is available for national processes, but there is much less readily available documentation about local level HTA. Most HTA processes that operate nationally and internationally can be categorised in one of three ways: guidance (provides structured information about appropriate technologies), mandatory (provides mandatory information about technologies to be implemented) and funding and implementation (provides structured evidence-based advice about which technologies should be implemented, the level of funding required to implement them and the source of these funds). The main factors which distinguish a high quality HTA process are that i) it is efficient in terms of setting priorities, the scope of the technologies to be assessed, avoidance of duplication and overall cost of the process, ii) the overall impact on utilisation and health budget is calculated as part of the HTA and iii) procedural justice occurs and is seen to occur; iv) it includes a comprehensive assessment of the impact on issues such as workforce, credentialing of providers and the ethical dimension of the technology; v) it influences decision making by being communicated appropriately and using trusted methods; vi) it influences adoption and diffusion of technology by ensuring that there is no diffusion prior to HTA, the results are incorporated into guidelines or recommendations, funding is linked to the decision, and remuneration arrangements and other characteristics of the HS facilitate the appropriate adoption and diffusion and vii) it influences health outcomes/efficiency/equity by ensuring that the methods and/or results are available and able to be used at a local level. Firm recommendations for an ideal system for HTA at the local level are not possible as much of the necessary information and evidence is not available about the strengths and weaknesses of HTA practices and processes currently in use. However, it is likely that the operation of a successful model of HTA at a local level would require the development of a central organizational unit, a process for implementing the results of HTA and, crucially, the building of capacity to support both types of activities. Additional expertise and skills will be required for both providers of HTA evaluations and for the commissioners and users of HTA.health technology assessment, Australia, review

Changing Professional Identity in the Transition from Practitioner to Lecturer in Higher Education: an Interpretive Phenomenological Analysis

This research explores the experiences of five professional practitioners from disciplines including teaching, youth work, sport and health who had become lecturers in Higher Education. Their experiences are considered using Interpretative Phenomenological Analysis and tentative conclusions are reached on the meaning of such experiences for the individuals. The work extends previous studies (Shreeve 2010, 2011; Gourlay 2011a, 2011b; Boyd & Harris 2010) to consider the relationship between knowledge and influence and how institutional preference for knowledge gained from research impacts on the validity of knowledge derived from professional experience. The research finds shared feelings associated with inauthenticity and loss arising from concerns that the contribution of the professional in Higher Education is undervalued. The research challenges the assumption that professional practitioners adopt the professional identity of a lecturer in Higher Education instead finding that they create their own professional identities in the liminal space between the professional and academic domains, but points to difficulties associated with constructed nature of such professional identities within the institutional structure of a Higher Education institution

The accuracy of pulse oximetry in measuring oxygen saturation by levels of skin pigmentation: a systematic review and meta-analysis

Background During the COVID-19 pandemic, there have been concerns regarding potential bias in pulse oximetry measurements for people with high levels of skin pigmentation. We systematically reviewed the effects of skin pigmentation on the accuracy of oxygen saturation measurement by pulse oximetry (SpO2) compared with the gold standard SaO2 measured by CO-oximetry. Methods We searched Ovid MEDLINE, Ovid Embase, EBSCO CINAHL, ClinicalTrials.gov, and WHO International Clinical Trials Registry Platform (up to December 2021) for studies with SpO2–SaO2 comparisons and measuring the impact of skin pigmentation or ethnicity on pulse oximetry accuracy. We performed meta-analyses for mean bias (the primary outcome in this review) and its standard deviations (SDs) across studies included for each subgroup of skin pigmentation and ethnicity and used these pooled mean biases and SDs to calculate accuracy root-mean-square (Arms) and 95% limits of agreement. The review was registered with the Open Science Framework (https://osf.io/gm7ty). Results We included 32 studies (6505 participants): 15 measured skin pigmentation and 22 referred to ethnicity. Compared with standard SaO2 measurement, pulse oximetry probably overestimates oxygen saturation in people with the high level of skin pigmentation (pooled mean bias 1.11%; 95% confidence interval 0.29 to 1.93%) and people described as Black/African American (1.52%; 0.95 to 2.09%) (moderate- and low-certainty evidence). The bias of pulse oximetry measurements for people with other levels of skin pigmentation or those from other ethnic groups is either more uncertain or suggests no overestimation. Whilst the extent of mean bias is small or negligible for all subgroups evaluated, the associated imprecision is unacceptably large (pooled SDs > 1%). When the extent of measurement bias and precision is considered jointly, pulse oximetry measurements for all the subgroups appear acceptably accurate (with Arms < 4%). Conclusions Pulse oximetry may overestimate oxygen saturation in people with high levels of skin pigmentation and people whose ethnicity is reported as Black/African American, compared with SaO2. The extent of overestimation may be small in hospital settings but unknown in community settings

Decoding the neural mechanisms of human tool use.

Sophisticated tool use is a defining characteristic of the primate species but how is it supported by the brain, particularly the human brain? Here we show, using functional MRI and pattern classification methods, that tool use is subserved by multiple distributed action-centred neural representations that are both shared with and distinct from those of the hand. In areas of frontoparietal cortex we found a common representation for planned hand- and tool-related actions. In contrast, in parietal and occipitotemporal regions implicated in hand actions and body perception we found that coding remained selectively linked to upcoming actions of the hand whereas in parietal and occipitotemporal regions implicated in tool-related processing the coding remained selectively linked to upcoming actions of the tool. The highly specialized and hierarchical nature of this coding suggests that hand- and tool-related actions are represented separately at earlier levels of sensorimotor processing before becoming integrated in frontoparietal cortex. DOI:http://dx.doi.org/10.7554/eLife.00425.001

Large-scale gene-centric analysis identifies novel variants for coronary artery disease

Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility, including analysis of many uncommon and functional variants. We examined 49,094 genetic variants in ~2,100 genes of cardiovascular relevance, using a customised gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin). We attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. Potential mechanisms through which the novel variants could affect CAD risk were explored through association tests with vascular risk factors and gene expression. We confirmed associations of several previously known CAD susceptibility loci (eg, 9p21.3:p&lt;10-33; LPA:p&lt;10-19; 1p13.3:p&lt;10-17) as well as three recently discovered loci (COL4A1/COL4A2, ZC3HC1, CYP17A1:p&lt;5×10-7). However, we found essentially null results for most previously suggested CAD candidate genes. In our replication study of 24 promising common variants, we identified novel associations of variants in or near LIPA, IL5, TRIB1, and ABCG5/ABCG8, with per-allele odds ratios for CAD risk with each of the novel variants ranging from 1.06-1.09. Associations with variants at LIPA, TRIB1, and ABCG5/ABCG8 were supported by gene expression data or effects on lipid levels. Apart from the previously reported variants in LPA, none of the other ~4,500 low frequency and functional variants showed a strong effect. Associations in South Asians did not differ appreciably from those in Europeans, except for 9p21.3 (per-allele odds ratio: 1.14 versus 1.27 respectively; P for heterogeneity = 0.003). This large-scale gene-centric analysis has identified several novel genes for CAD that relate to diverse biochemical and cellular functions and clarified the literature with regard to many previously suggested genes.</p

Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci

Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available genome-wide association studies (GWAS). Methods and Results: Through a meta-analysis of 6 GWAS datasets and a validation study totalling 10,204 cases and 107,766 controls we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches we observed no new associations between the lead AAA SNPs and coronary artery disease, blood pressure, lipids or diabetes. Network analyses identified ERG, IL6R and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions: The 4 new risk loci for AAA appear to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease

Genomic correlates of glatiramer acetate adverse cardiovascular effects lead to a novel locus mediating coronary risk

Glatiramer acetate is used therapeutically in multiple sclerosis but also known for adverse effects including elevated coronary artery disease (CAD) risk. The mechanisms underlying the cardiovascular side effects of the medication are unclear. Here, we made use of the chromosomal variation in the genes that are known to be affected by glatiramer treatment. Focusing on genes and gene products reported by drug-gene interaction database to interact with glatiramer acetate we explored a large meta-analysis on CAD genome-wide association studies aiming firstly, to investigate whether variants in these genes also affect cardiovascular risk and secondly, to identify new CAD risk genes. We traced association signals in a 200-kb region around genomic positions of genes interacting with glatiramer in up to 60 801 CAD cases and 123 504 controls. We validated the identified association in additional 21 934 CAD cases and 76 087 controls. We identified three new CAD risk alleles within the TGFB1 region on chromosome 19 that independently affect CAD risk. The lead SNP rs12459996 was genome-wide significantly associated with CAD in the extended meta-analysis (odds ratio 1.09, p = 1.58×10-12). The other two SNPs at the locus were not in linkage disequilibrium with the lead SNP and by a conditional analysis showed p-values of 4.05 × 10-10 and 2.21 × 10-6. Thus, studying genes reported to interact with glatiramer acetate we identified genetic variants that concordantly with the drug increase the risk of CAD. Of these, TGFB1 displayed signal for association. Indeed, the gene has been associated with CAD previously in both in vivo and in vitro studies. Here we establish genome-wide significant association with CAD in large human samples.This work was supported by grants from the Fondation Leducq (CADgenomics: Understanding CAD Genes, 12CVD02), the German Federal Ministry of Education and Research (BMBF) within the framework of the e:Med research and funding concept (e:AtheroSysMed, grant 01ZX1313A-2014 and SysInflame, grant 01ZX1306A), and the European Union Seventh Framework Programme FP7/2007-2013 under grant agreement no HEALTH-F2-2013-601456 (CVgenes-at-target). Further grants were received from the DFG as part of the Sonderforschungsbereich CRC 1123 (B2). T.K. was supported by a DZHK Rotation Grant. I.B. was supported by the Deutsche Forschungsgemeinschaft (DFG) cluster of excellence ‘Inflammation at Interfaces’. F.W.A. is supported by a Dekker scholarship-Junior Staff Member 2014T001 - Netherlands Heart Foundation and UCL Hospitals NIHR Biomedical Research Centre