Evaluating cost-effectiveness in the management of neuroendocrine neoplasms

The rapid evolution of novel, costly therapies for neuroendocrine neoplasia (NEN) warrants formal high-quality cost-effectiveness evaluation. Costs of individual investigations and therapies are high; and examples are presented. We aimed to review the last ten years of standalone health economic evaluations in NEN. Comparing to published standards, EMBASE, Cochrane library, Database of Abstracts of Reviews of Effects (DARE), NHS Economic Evaluation Database and the Health Technology Assessment (HTA) Database were searched for health economic evaluations (HEEs) in NEN published between 2010 and October 2019. Of 12 economic evaluations, 11 considered exclusively pharmacological treatment (3 studies of SSAs, 7 studies of sunitinib, everolimus and/or 177Lu-DOTATATE and 1 study of telotristat ethyl) and 1 compared surgery with intraarterial therapy. 7 studies of pharmacological treatment had placebo or best supportive care as the only comparator. There remains a paucity of economic evaluations in NEN with the majority industry funded. Most HEEs reviewed did not meet published health economic criteria used to assess quality. Lack of cost data collected from patient populations remains a significant factor in HEEs where clinical expert opinion is still often substituted. Further research utilizing high-quality effectiveness data and rigorous applied health economic analysis is needed

Development and Psychometric Evaluation of an Item Bank for Computerized Adaptive Testing of the EORTC Insomnia Dimension in Cancer Patients (EORTC CAT-SL)

To further advance assessment of patient-reported outcomes, the European Organisation of Research and Treatment of Cancer (EORTC) Quality of Life Group has developed computerized adaptive test (CAT) versions of all EORTC Quality of Life Core Questionnaire (QLQ-C30) scales/items. The aim of this study was to develop and evaluate an item bank for CAT measurement of insomnia (CAT-SL). In line with the EORTC guidelines, the developmental process comprised four phases: (I) defining the concept insomnia and literature search, (II) selection and formulation of new items, (III) pre-testing and (IV) field-testing, including psychometric analyses of the final item bank. In phase I, the literature search identified 155 items that were compatible with our conceptualisation of insomnia, including both quantity and quality of sleep. In phase II, following a multistep-approach, this number was reduced to 15 candidate items. Pre-testing of these items in cancer patients (phase III) resulted in an item list of 14 items, which were field-tested among 1094 patients in phase IV. Psychometric evaluations showed that eight items could be retained in a unidimensional model. The final item bank yielded greater measurement precision than the original QLQ-C30 insomnia item. It was estimated that administering two or more items from the insomnia item bank with CAT results in a saving in sample size between approximately 15–25%. The 8-item EORTC CAT-SL item bank facilitates precise and efficient measurement of insomnia as part of the EORTC CAT system of health-related quality life assessment in both clinical research and practice

Creating Creative Technologists: playing with(in) education

Since the industrial revolution, the organization of knowledge into distinct scientific, technical or creative categories has resulted in educational systems designed to produce and validate particular occupations. The methods by which students are exposed to different kinds of knowledge are critical in creating and reproducing individual, professional or cultural identities. (“I am an Engineer. You are an Artist”). The emergence of more open, creative and socialised technologies generates challenges for discipline-based education. At the same time, the term “Creative Technologies” also suggests a new occupational category (“I am a Creative Technologist”). This chapter presents a case-study of an evolving ‘anti-disciplinary’ project-based degree that challenges traditional degree structures to stimulate new forms of connective, imaginative and explorative learning, and to equip students to respond to a changing world. Learning is conceived as an emergent process; self-managed by students through critique and open peer review. We focus on ‘playfulness’ as a methodology for achieving multi-modal learning across the boundaries of art, design, computer science, engineering, games and entrepreneurship. In this new cultural moment, playfulness also re-frames the institutional identities of teacher and learner in response to new expectations for learning

Comparative Genomics and Transcriptomics of Propionibacterium acnes

The anaerobic Gram-positive bacterium Propionibacterium acnes is a human skin commensal that is occasionally associated with inflammatory diseases. Recent work has indicated that evolutionary distinct lineages of P. acnes play etiologic roles in disease while others are associated with maintenance of skin homeostasis. To shed light on the molecular basis for differential strain properties, we carried out genomic and transcriptomic analysis of distinct P. acnes strains. We sequenced the genome of the P. acnes strain 266, a type I-1a strain. Comparative genome analysis of strain 266 and four other P. acnes strains revealed that overall genome plasticity is relatively low; however, a number of island-like genomic regions, encoding a variety of putative virulence-associated and fitness traits differ between phylotypes, as judged from PCR analysis of a collection of P. acnes strains. Comparative transcriptome analysis of strains KPA171202 (type I-2) and 266 during exponential growth revealed inter-strain differences in gene expression of transport systems and metabolic pathways. In addition, transcript levels of genes encoding possible virulence factors such as dermatan-sulphate adhesin, polyunsaturated fatty acid isomerase, iron acquisition protein HtaA and lipase GehA were upregulated in strain 266. We investigated differential gene expression during exponential and stationary growth phases. Genes encoding components of the energy-conserving respiratory chain as well as secreted and virulence-associated factors were transcribed during the exponential phase, while the stationary growth phase was characterized by upregulation of genes involved in stress responses and amino acid metabolism. Our data highlight the genomic basis for strain diversity and identify, for the first time, the actively transcribed part of the genome, underlining the important role growth status plays in the inflammation-inducing activity of P. acnes. We argue that the disease-causing potential of different P. acnes strains is not only determined by the phylotype-specific genome content but also by variable gene expression

Selective inhibition of the human tie-1 promoter with triplex-forming oligonucleotides targeted to ets binding sites

The Tie receptors (Tie-1 and Tie-2/Tek) are essential for angiogenesis and vascular remodeling/integrity. Tie receptors are up-regulated in tumor-associated endothelium, and their inhibition disrupts angiogenesis and can prevent tumor growth as a consequence. To investigate the potential of anti-gene approaches to inhibit tie gene expression for anti-angiogenic therapy, we have examined triple-helical (triplex) DNA formation at 2 tandem Ets transcription factor binding motifs (designated E-1 and E-2) in the human tie-1 promoter. Various tie-1 promoter deletion/mutation luciferase reporter constructs were generated and transfected into endothelial cells to examine the relative activities of E-1 and E-2. The binding of antiparallel and parallel (control) purine motif oligonucleotides (21-22 bp) targeted to E-1 and E-2 was assessed by plasmid DNA fragment binding and electrophoretic mobility shift assays. Triplex-forming oligonucleotides were incubated with tie-1 reporter constructs and transfected into endothelial cells to determine their activity. The Ets binding motifs in the E-1 sequence were essential for human tie-1 promoter activity in endothelial cells, whereas the deletion of E-2 had no effect. Antiparallel purine motif oligonucleotides targeted at E-1 or E-2 selectively formed strong triplex DNA (K(d) approximately 10(-7) M) at 37 degrees C. Transfection of tie-1 reporter constructs with triplex DNA at E-1, but not E-2, specifically inhibited tie-1 promoter activity by up to 75% compared with control oligonucleotides in endothelial cells. As similar multiple Ets binding sites are important for the regulation of several endothelial-restricted genes, this approach may have broad therapeutic potential for cancer and other pathologies involving endothelial proliferation/dysfunction

Critical appraisal of health-state utility values used in breast cancer-related cost–utility analyses

© 2017, Springer Science+Business Media New York. Purpose: To review the data sources of health-state utility values (HSUVs), as well as their elicitation and use, in 140 breast cancer-related cost–utility analyses (CUAs), and to provide a critical appraisal of these. Methods: A checklist was developed to guide the process of the critical appraisal. It is divided into three parts: the data source (three questions), elicitation method (four questions), and use (ten questions) of HSUVs in CUAs. Two independent reviewers performed the data extraction. A consensus was reached in case of disagreements. Data sources were categorized as “original study,” “derived from the literature,” or “other.” Results: The data source of HSUVs was always specified. When HSUVs were derived from the literature (90% of cases), the authors referred to a median number of two references as data sources. The critical appraisal of the elicitation of HSUVs in CUAs revealed considerable variability in terms of the quality of the reporting of the data source selection of HSUV. More details were provided by authors when HSUVs were elicited from an original study rather than derived from the literature. The use of HSUVs elicited from an original study was generally better described in terms of the checklist than were those derived from the literature. Conclusions: Based on the developed checklist, we were able to highlight the challenges that authors are facing when trying to adequately report HSUV used in CUAs. Our proposed checklist offers a good starting point for encouraging more explicit and comprehensive reporting of HSUVs in CUAs

The EORTC Quality of Life Questionnaire for cancer patients (QLQ‐C30): Australian general population reference values

Objectives To generate Australian general population reference values for the EORTC Quality of Life Questionnaire for cancer patients (QLQ‐C30); to compare Australian values with published EORTC general population reference values, and to explore associations between socio‐demographic and health characteristics and QLQ‐C30 subscale scores. Design Analysis of responses to cross‐sectional, online survey (QLQ‐C30), March 2015 – February 2016, and supplementary health‐related and socio‐demographic questions. Setting, participants 1979 people quota‐sampled from a national online survey panel to be representative of the Australian general population by age and sex. Main outcome measures Mean QLQ‐C30 subscale scores, adjusted for socio‐demographic characteristics and comorbid conditions, by sex and age group. Results Data for 1821 participants were analysed (92% completion rate); 924 (50.7%) were women. Higher psychological distress was associated with worse outcomes on all QLQ‐C30 subscales. Better self‐reported general health was associated with better global quality of life and better functioning (except cognitive functioning), and less fatigue, pain, dyspnoea and insomnia. Having arthritis or rheumatism was associated with poorer global quality of life, and poorer physical, role and social functioning, and with more fatigue, pain, insomnia, diarrhoea, and financial difficulties. Although differences between Australian QLQ‐C30 subscale scores and EORTC general population values were clinically trivial, the Australian values are more accurate benchmarks for QLQ‐C30 results from Australians with cancer. Conclusions Our Australian QLQ‐C30 reference values provide normative benchmarks that facilitate interpretation of data for Australians with cancer in terms of burden of disease and its treatment. In survivorship studies and studies without pre‐disease baseline data, comparisons with reference values can indicate the extent to which people have returned to better levels of health