Implementation of coverage with evidence development schemes for medical devices : a decision tool for late technology adopter countries

Experiences with coverage with evidence development (CED) schemes are fairly limited in Central and Eastern European (CEE) countries, which are usually late adopters of new health technologies. Our aim was to put forward recommendations on how CEE health technology assessment bodies and payer organizations can apply CED to reduce decision uncertainty on reimbursement of medical devices, with a particular focus on transferring the structure and data from CED schemes in early technology adopter countries in Western Europe. Structured interviews on the practices and feasibility of transferring CED schemes were conducted and subsequently, a draft tool for the systematic classification of decision alternatives and recommendations was developed. The decision tool was reviewed in a focus group discussion and validated within a wider group of CEE experts in a virtual workshop. Transferability assessment is needed in case of (1) joint implementation of a CED scheme; (2) transferring the structure of an existing CED scheme to a CEE country; (3) reimbursement decisions that are linked to outcomes of an ongoing CED scheme in another country and (4) real-world evidence transferred from completed CED schemes. Efficient use of available resources may be improved by adequately transferring evidence and policy tools from early technology adopter countries

Neustonic versus epiphytic bacteria of eutrophic lake and their biodegradation ability on deltamethrin

This study evaluated biodegradation of the insecticide deltamethrin (1 μg l−1) by pure cultures of neustonic (n = 25) and epiphytic (n = 25) bacteria and by mixed cultures (n = 1), which consisted of a mixture of 25 bacterial strains isolated from the surface microlayer (SM ≈ 250 μm) and epidermis of the Common Reed (Phragmites australis, (Cav.) Trin. ex Steud.) growing in the littoral zone of eutrophic lake Chełmżyńskie. Results indicate that neustonic and epiphytic bacteria are characterized by a similar average capacity to degrade deltamethrin. After a 15-day incubation, bacteria isolated from the surface microlayer reduced the initial concentration of deltamethrin by 60%, while the average effectiveness of the bacteria found on the Common Reed equaled 47%

Yellow light emission of Vibrio fischeri strain Y-1: purification and characterization of the energy-accepting yellow fluorescent protein.

A strain of luminous bacteria, Vibrio fischeri Y-1, emits yellow light rather than the blue-green emission typical of other luminous bacteria. The yellow emission has been postulated previously to result from energy transfer from an electronically excited species formed in the bacterial luciferase-catalyzed reaction to a secondary emitter protein, termed the yellow fluorescent protein (YFP). We report here the purification of YFP to homogeneity without loss of the chromophore. The protein was found to be a homodimer of Mr 22,000 subunits with one weakly bound FMN per subunit. The FMN-protein complex was stabilized by 10% (vol/vol) glycerol in the buffers, allowing purification of the active holo-YFP. The protein migrated as a single spot with an isoelectric point of approximately 6.5 on two-dimensional polyacrylamide gel electrophoresis and gave an N-terminal sequence of Met-Phe-Lys-Gly-Ile-Val-Glu-Gly-Ile-Gly-Ile-Ile-Glu-Lys-Ile. Addition of purified YFP to a reaction in which luciferase was supplied with FMNH2 (reduced FMN) by a NADH:FMN oxidoreductase resulted in a dramatic enhancement in the intensity of bioluminescence and an additional peak in the emission spectrum at about 534 nm. The resulting bimodal bioluminescence emission spectrum had peaks at 484 nm, apparently due to emission from the luciferase-flavin complex, and at 534 nm, corresponding to the fluorescence emission maximum of YFP. This bimodal spectrum closely matched the emission spectrum in vivo

T-Typ-Ca2+-Kanalblocker und Alzheimer-Demenz – neue präklinische Befunde, translationale pharmakotherapeutische Aspekte und potenzielle pharmakovigilatorische Implikationen

Die systemische und zelluläre Ca2+-Homöostase markiert einen Grundpfeiler regelhafter exzitabler Prozesse im ZNS. Störungen der Ca2+-Homöostase können zu Veränderungen neuronaler Aktivitätsmuster und/oder neuronalem Zelluntergang führen. Bei der Alzheimer- Demenz, aber auch anderen demenziellen Erkrankungen spielen diese Prozesse pathogenetisch eine wichtige Rolle. Sowohl präklinische wie auch klinische Studien haben hier gezeigt, dass die Wiederherstellung der zellulären Ca2+-Homöostase einen vielversprechenden therapeutischen Ansatz darstellen kann. Insbesondere die „Ca2+-Überladung“ der Zellen scheint pathogenetisch ein Kernproblem zu sein und so fokussierte sich die Aufmerksamkeit schnell auf Ca2+-Kanalblocker und deren Wirksamkeit bei neurodegenerativen Erkrankungen. Die vielfach in klinischen Studien eingesetzten L-Typ-Ca2+-Kanalblocker scheinen hier durchaus ihre Wirksamkeit unter Beweis gestellt zu haben, auch wenn die Datenlage nicht immer eindeutig ist. Basierend auf diesen Befunden wurden die potenziell positiven Erwartungen auch auf die T-Typ-Ca2+-Kanalblocker ausgeweitet. Inwiefern dies gerechtfertigt ist und ob Arzneimittel mit T-Typ blockierenden Eigenschaften, insbesondere bei älteren Menschen und Demenz-Patienten, eine genauere pharmakovigilatorische Beobachtung erfordern, wird im Folgenden erläutert

Validity of Surrogate Endpoints and Their Impact on Coverage Recommendations: A Retrospective Analysis across International Health Technology Assessment Agencies

Background: Surrogate endpoints (i.e., intermediate endpoints intended to predict for patient-centered outcomes) are increasingly common. However, little is known about how surrogate evidence is handled in the context of health technology assessment (HTA). Objectives: 1) To map methodologies for the validation of surrogate endpoints and 2) to determine their impact on acceptability of surrogates and coverage decisions made by HTA agencies. Methods: We sought HTA reports where evaluation relied on a surrogate from 8 HTA agencies. We extracted data on the methods applied for surrogate validation. We assessed the level of agreement between agencies and fitted mixed-effects logistic regression models to test the impact of validation approaches on the agency’s acceptability of the surrogate endpoint and their coverage recommendation. Results: Of the 124 included reports, 61 (49%) discussed the level of evidence to support the relationship between the surrogate and the patient-centered endpoint, 27 (22%) reported a correlation coefficient/association measure, and 40 (32%) quantified the expected effect on the patient-centered outcome. Overall, the surrogate endpoint was deemed acceptable in 49 (40%) reports (k-coefficient 0.10, P = 0.004). Any consideration of the level of evidence was associated with accepting the surrogate endpoint as valid (odds ratio [OR], 4.60; 95% confidence interval [CI], 1.60–13.18, P = 0.005). However, we did not find strong evidence of an association between accepting the surrogate endpoint and agency coverage recommendation (OR, 0.71; 95% CI, 0.23–2.20; P = 0.55). Conclusions: Handling of surrogate endpoint evidence in reports varied greatly across HTA agencies, with inconsistent consideration of the level of evidence and statistical validation. Our findings call for careful reconsideration of the issue of surrogacy and the need for harmonization of practices across international HTA agencies

Whole genome transcriptome data from the WT cortex and hippocampus of female and male control and APP/PS1 Alzheimer's disease mice

A variety of Alzheimer disease (AD) mouse models has been established and characterized within the last decades. These models are generated to meet the principal criteria of AD isomorphism, homology and predictability to a max- imum extent. To get an integrative view of the sophisti- cated etiopathogenesis of AD, whole genome transcriptome data analysis turns out to be indispensable. Here, we present a microarray-based transcriptome data collection based on RNA extracted from the retrosplenial (RS) cortex and the hippocampus of APP/PS1 AD mice and control animals. Experimental animals were age matched and importantly, both sexes were considered separately. Isolated RNA was purified, quantified und quality controlled prior to the hybridization procedure with SurePrint G3 Mouse Gene Expression v2 8 ×60K microarrays. Following immunofluo- rescent measurement und preprocessing/extraction of image data, raw transcriptome data were uploaded including differ- entially expressed gene candidates and related fold changes in APP/PS1 AD mice and controls. Our data allow further insight into alterations in gene transcript levels in APP/PS1 AD mice compared to controls and enable the reader/user to carry out complex transcriptome analysis to characterize potential age-, sex- and brain-region-specific alterations in e.g., neuroinflammatory, immunological, neurodegenerative and ion channel pathways