A Component of Retinal Light Adaptation Mediated by the Thyroid Hormone Cascade

Analysis with DNA-microrrays and real time PCR show that several genes involved in the thyroid hormone cascade, such as deiodinase 2 and 3 (Dio2 and Dio3) are differentially regulated by the circadian clock and by changes of the ambient light. The expression level of Dio2 in adult rats (2–3 months of age) kept continuously in darkness is modulated by the circadian clock and is up-regulated by 2 fold at midday. When the diurnal ambient light was on, the expression level of Dio2 increased by 4–8 fold and a consequent increase of the related protein was detected around the nuclei of retinal photoreceptors and of neurons in inner and outer nuclear layers. The expression level of Dio3 had a different temporal pattern and was down-regulated by diurnal light. Our results suggest that DIO2 and DIO3 have a role not only in the developing retina but also in the adult retina and are powerfully regulated by light. As the thyroid hormone is a ligand-inducible transcription factor controlling the expression of several target genes, the transcriptional activation of Dio2 could be a novel genomic component of light adaptation

Is individualized medicine more cost-effective? A systematic review.

Background: Individualized medicine (IM) is a rapidly evolving field that is associated with both visions of more effective care at lower costs and fears of highly priced, low-value interventions. It is unclear which view is supported by the current evidence. Objective: Our objective was to systematically review the health economic evidence related to IM and to derive general statements on its cost-effectiveness. Data sources: A literature search of MEDLINE database for English- and German-language studies was conducted. Study appraisal and synthesis method: Cost-effectiveness and cost-utility studies for technologies meeting the MEDLINE medical subject headings (MeSH) definition of IM (genetically targeted interventions) were reviewed. This was followed by a standardized extraction of general study characteristics and cost-effectiveness results. Results: Most of the 84 studies included in the synthesis were from the USA (n = 43, 51 %), cost-utility studies (n = 66, 79 %), and published since 2005 (n = 60, 71 %). The results ranged from dominant to dominated. The median value (cost-utility studies) was calculated to be rounded $US22,000 per quality-adjusted life year (QALY) gained (adjusted to$US, year 2008 values), which is equal to the rounded median cost-effectiveness in the peer-reviewed English-language literature according to a recent review. Many studies reported more than one strategy of IM with highly varying cost-effectiveness ratios. Generally, results differed according to test type, and tests for disease prognosis or screening appeared to be more favorable than tests to stratify patients by response or by risk of adverse effects. However, these results were not significant. Limitations: Different definitions of IM could have been used. Quality assessment of the studies was restricted to analyzing transparency. Conclusions: IM neither seems to display superior cost-effectiveness than other types of medical interventions nor to be economically inferior. Instead, rather than 'whether' healthcare was individualized, the question of 'how' it was individualized was of economic relevance

Managed Entry Agreements in Deutschland: Konzepte, rechtliche Grundlagen und systematischer Review.

Zielsetzung: Ziel dieser Arbeit ist es, den Stand der Evidenz bezüglich der Nutzung von Managed Entry Agreements (MEAs) in Deutschland in der Literatur zu ermitteln. Einführend soll zudem ein Überblick über die gesundheitsökonomische Literatur zu MEAs sowie zu den relevanten rechtlichen Grundlagen auf der Basis ergänzender, explorativer Reviews gegeben werden. Methodik: Es wurde eine umfangreiche Literaturrecherche zu publizierten Fallstudien und Übersichtsarbeiten in PubMed, Google, auf fachspezifischen Internetseiten von 53 Stakeholdern (Krankenkassen, Pharmaunternehmen, weitere gesundheitspolitisch relevante Institutionen) sowie auf ausgewählten deutschsprachigen Fachzeitschriften durchgeführt. Ergebnisse: Es konnten insgesamt 23 potenzielle MEAs identifiziert werden (10 gesundheitsorientierte, 13 kostenorientierte MEAs). Zu zehn dieser potenziellen MEAs lagen jedoch nur unzureichende Informationen zur Abgrenzung von anderen Vertragsmodellen vor. Schlussfolgerung: Aufgrund des eingeschränkten Zugangs der Öffentlichkeit zu Vertragsinformationen sind die Möglichkeiten einer umfassenden Darstellung begrenzt. Es besteht weiterer ökonomischer, juristischer und ethischer Forschungsbedarf, um das Potenzial von MEAs für den Kontext des deutschen Gesundheitswesens voll nutzbar zu machen

Cost-effectiveness of an individualized first-line treatment strategy offering erlotinib based on <em>EGFR</em> mutation testing in advanced lung adenocarcinoma patients in Germany.

BACKGROUND: Lung cancer is among the top causes of cancer-related deaths. Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors can increase progression-free survival compared with standard chemotherapy in patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC). OBJECTIVE: The aim of the study was to evaluate the cost-effectiveness of EGFR mutation analysis and first-line therapy with erlotinib for mutation-positive patients compared with non-individualized standard chemotherapy from the perspective of German statutory health insurance. METHODS: A state transition model was developed for a time horizon of 10&nbsp;years (reference year 2014). Data sources were published data from the European Tarceva versus Chemotherapy (EURTAC) randomized trial for drug efficacy and safety and German cost data. We additionally performed deterministic, probabilistic and structural sensitivity analyses. RESULTS: The individualized strategy incurred 0.013 additional quality-adjusted life-years (QALYs) and additional costs of 200, yielding an incremental cost-effectiveness ratio (ICER) of 15,577/QALY. Results were most sensitive to uncertainty in survival curves and changes in utility values. Cross-validating health utility estimates with recent German data increased the ICER to about 58,000/QALY. The probabilistic sensitivity analysis indicated that the individualized strategy is cost-effective, with a probability exceeding 50&nbsp;% for a range of possible willingness-to-pay thresholds. LIMITATIONS: The uncertainty of the predicted survival curves is substantial, particularly for overall survival, which was not a primary endpoint in the EURTAC study. Also, there is limited data on quality of life in metastatic lung cancer patients. CONCLUSIONS: Individualized therapy based on EGFR mutation status has the potential to provide a cost-effective alternative to non-individualized care for patients with advanced adenocarcinoma. Further clinical research is needed to confirm these results

Il Costo Degli Eventi Avversi Associati ad Afatinib, Erlotinib e Gefitinib Nel Trattamento del Tumore del Polmone non a Piccole Cellule con Mutazione EGFR

Costs of adverse events associated with afatinib, erlotinib, and gefitinib first-line therapies in advanced non-small-cell lung cancer harboring EGFR-activating mutationsIntroductionEpidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) afatinib, erlotinib, and gefitinib are an established treatment for advanced non-small cell lung cancer (NSCLC) with EGFR mutation.ObjectivesConsistent with published meta-analyses, this study compares the cost of management of the adverse events (AEs) associated with these three drugs from the perspective of the Italian National Health System (NHS).MethodsThe frequency of AEs was established based on a recently published meta-analysis. Only the costs of management of the AEs were considered. Resource utilization in the management of the AEs was estimated by a panel of Italian oncologists and based on previously published studies.ResultsThe mean cost per patient treated with afatinib, erlotinib, and gefitinib was €141.03, €90.74 and 121.87, respectively. With afatinib, the cost per patient and per AE of grades ≤2 and ≥3 was €36.70 and €104.33. With erlotinib, the cost per patient and per AE of grades ≤2 and ≥3 was €46.99 and €40.75, whereas the cost with gefitinib was €34.76 and €87.11, respectively.ConclusionIn advanced EGFR mutation-positive NSCLC patients, first-line treatment with erlotinib could reduce the cost of management of the AEs for the NHS

P23H opsin knock-in mice reveal a novel step in retinal rod disc morphogenesis

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