Cost-effectiveness of patient-matched pre- and on-treatment biomarkers in cancer therapy response prediction

BACKGROUND: The development of new biomarkers allows for the accurate prediction of breast cancer therapy response in the neoadjuvant setting. The implementation of these tools in routine NHS operations could have the potential for better clinical outcomes and a more cost-effective use of resources. AIMS: A decision-analytic modelling platform was created to evaluate the clinical effectiveness and cost-effectiveness of on-treatment biomarker-based predictive tools in a routine NHS implementation. The biomarker-based tool used in the simulation was EER4, developed at Edinburgh Institute of Genetics and Cancer. METHODS: Patient simulation models were constructed by integrating molecular biomarker data with clinical outcomes and healthcare cost data. The simulation benefits from the incorporation of NHS patient data and it features two complementary sub-models: a Discrete Event Simulation for the neoadjuvant setting and a Markov cohort model for the adjuvant setting. The results of the simulation compare the per-patient costs and health outcomes, expressed as Quality Adjusted Life Years (QALY), for each of the evaluated strategies. Moreover, this study includes a decision and budget impact analysis of OncotypeDX after its introduction in Edinburgh’s Breast Clinic. RESULTS: Treatment-decision strategies that utilize EER4 are likely to be cost-effective. Specifically, EER4 in conjunction with PREDICT shows lower costs and marginally superior QALYs, compared to PREDICT alone or OncotypeDX with PREDICT. At a threshold of 20,000£/QALY, EER4 with PREDICT has an 86% probability of being a cost-effective alternative to the current standard of care. EER4 in conjunction with neoadjuvant Letrozole increases breast-conserving surgery rates, displacing radical mastectomy by 16%. The Probabilistic One-way Sensitivity Analysis shows that results are robust to the uncertainty of EER4 per-unit costs and clinical performance. The decision and budget impact analysis of OncotypeDX indicates that while this technology might reduce the number of chemotherapies administered, the unit cost is greater than any savings produced by chemotherapy displacement. CONCLUSION: The early cost-effectiveness analysis shows that these biomarker-based technologies are likely to be cost-effective. However, further research is needed to assess the clinical effectiveness of EER4. The simulation platform developed in this study has the potential for further evaluation of decision-making tools for other subtypes of breast malignancies

Variation in hospital cost trajectories at the end of life by age, multimorbidity and cancer type

Background Approximately thirty thousand people in Scotland are diagnosed with cancer annually, of whom a third live less than one year. The timing, nature and value of hospital-based healthcare for patients with advanced cancer are not well understood. The study's aim was to describe the timing and nature of hospital-based healthcare use and associated costs in the last year of life for patients with a cancer diagnosis. Methods We undertook a Scottish population-wide administrative data linkage study of hospital-based healthcare use for individuals with a cancer diagnosis, who died aged 60 and over between 2012 and 2017. Hospital admissions and length of stay (LOS), as well as the number and nature of outpatient and day case appointments were analysed. Generalised linear models were used to adjust costs for age, gender, socioeconomic deprivation status, rural-urban (RU) status and comorbidity. Results The study included 85,732 decedents with a cancer diagnosis. For 64,553 (75.3%) of them, cancer was the primary cause of death. Mean age at death was 80.01 (SD 8.15) years. The mean number of inpatient stays in the last year of life was 5.88 (SD 5.68), with a mean LOS of 7 days. Admission rates rose sharply in the last month of life. One year adjusted and unadjusted costs decreased with increasing age. A higher comorbidity burden was associated with higher costs. Major cost differences were present between cancer types. Conclusions People in Scotland in their last year of life with cancer are high users of secondary care. Hospitalisation accounts for a high proportion of costs, particularly in the last month of life. Further research is needed to examine triggers for hospitalisations and to identify influenceable reasons for unwarranted variation in hospital use among different cancer cohorts

Servizi ICT al MIUR

Le attività istituzionali del CASPUR si rivolgono alle Università consorziate ed al Ministero dell’Istruzione, dell’Università e della Ricerca (MIUR). Il CASPUR è presente presso la sede del MIUR di Piazza Kennedy 20 da oltre quattordici anni, garantendo, con adeguate professionalità e competenze, la continuità dei servizi informatici di base e lo sviluppo dell’infrastruttura ICT. Il supporto del CASPUR presso il MIUR è organizzato in due aree funzionali: l’area Sistemi e quella Sviluppo Software. La prima si occupa delle attività di gestione, manutenzione e presidio della sala macchina e provvede alla connettività ed alla sicurezza dell’infrastruttura di rete locale. Mentre l’area funzionale Sviluppo Software si occupa delle attività di redazione tecnica dei siti web del MIUR, della realizzazione di applicazioni software ed offre consulenza e formazione agli utenti del Ministero sull’uso dei prodotti in dotazione

More than a Sonic Wave: Sound as/and Cultural Communication

Der von Anna Symanczyk, Daniela Wagner und Miriam Wendling in der Schriftenreihe der Isa-Lohmann-Siems-Stiftung herausgegebene multidisziplinäre Sammelband Klang – Kontakte. Kommunikation, Konstruktion und Kultur von Klängen untersucht in 13 inhaltlich, methodisch und historisch sehr unterschiedlich verorteten Beiträgen besonders den vermittelnden Aspekt von Klängen in kulturellen Kommunikationsprozessen. Hierbei steht vornehmlich Transmedialität, d.h. die Transformation und Darstellung von Klängen in Sprache, Text und (Ab-)Bild im Zentrum des Forschungsinteresses. Als mehrheitlich geisteswissenschaftlich geprägt ergänzt dieser Band das im Vergleich zur Musikpsychologie und (Psycho-) Akustik bisher noch verhältnismäßig junge Forschungsfeld der Klang- bzw. Sound Studies und bietet disziplinspezifische Anregungen.Klang – Kontakte. Kommunikation, Konstruktion und Kultur von Klängen (Isa-Lohmann-Siems publication series, Vol. 9) is a multidisciplinary publication edited by Anna Symanczyk, Daniela Wagner, und Miriam Wendling. 13 contributions differing in methodological, historical, and content-related perspectives aim at understanding and exploring mediating aspects of sound in cultural communication processes. Within this context, it is especially transformation into and representation of sounds in language, text, and images that are key subjects of research in this volume. As a humanities-based anthology, this volume supplements the research field of sound studies, which is relatively young compared to the fields of the psychology of music and psycho-acoustics, and offers discipline-specific impulses

Evidence for a role of gamma delta T cells in demyelinating diseases as determined by activation states and responses to lipid antigens

In this report we review current information on the phenotypic and functional properties of gamma delta T cells in demyelinating disorders. The results support the conclusion that although gamma delta T cells show evidence of activation in patients with either multiple sclerosis (MS) or Guillain Barre syndrome (GBS), differences exist in the phenotypic and functional properties of these cells between the two diseases. In particular. our data indicate that in patients with MS the V delta 2 subset is activated and that these cells can be induced to secrete high levels of proinflammatory cytokines. in contrast, in patients with GBS, the V delta 2 subset is expanded and can be induced to secrete cytokines more associated with a humoral response

T cell response to N-formylated peptides in humans

We present the first evidence of a T lymphocyte response to N-formylated peptides in humans. N-formylated peptide sequences from self (mitochondrial) and foreign (microbial) antigens were used to isolate antigen-specific T cell clones from healthy individuals, including a set of monozygotic twins. The observed response differed from that previously described in mouse (CD4(+) phenotype and MHC class II restriction in humans vs. CD8(+) phenotype and class I restriction in mice). These lymphocytes produce substantial amounts of IFN-gamma. They were isolated in only one of the monozygotic twins, which suggests that their expansion in the healthy immune repertoire is independent of the genetic background. Our result will help in assessing the relevance of N-formylated peptide-specific T cells in protection against infections within the human immune system