Competitive tenders on analogue hospital pharmaceuticals in Denmark 2017-2020

BACKGROUND: Competitive tenders on pharmaceuticals are one of the most effective cost-containment instruments in healthcare systems. Its effectiveness has been demonstrated, among other things, in markets for generic medicine and biosimilars. In Denmark, an internationally unique model for competitive tenders on analogue substitutable pharmaceuticals has been developed and implemented for all public hospitals. METHODS: We obtained data on all analogue competitive tenders carried out by the Danish Medicines Council from its foundation on January 1, 2017, to October 9, 2020. We calculated univariate descriptive statistics, pairwise correlations and made a multiple regression analysis on tender savings. RESULTS: Average annual saving on hospital pharmaceutical purchase prices was 44.1% ranging from 0.4% to 92.8% between therapeutic areas and areas of indication. There was a significant positive correlation between tender savings and the number of competitors participating in the tender, and a significant negative correlation between tender savings and the number of days since market authorization. CONCLUSIONS: This study finds analogue tenders to be similar in effect and mechanism to competitive tenders in markets for generic medicine and biosimilars. It supports the increasing number of empirical findings that competitive tendering has a high potential to generate substantial savings on healthcare budgets

The vascular conducted response in cerebral blood flow regulation

Despite recent advances in our understanding of the molecular and cellular mechanisms behind vascular conducted responses (VCRs) in systemic arterioles, we still know very little about their potential physiological and pathophysiological role in brain penetrating arterioles controlling blood flow to the deeper areas of the brain. The scope of the present review is to present an overview of the conceptual, mechanistic, and physiological role of VCRs in resistance vessels, and to discuss in detail the recent advances in our knowledge of VCRs in brain arterioles controlling cerebral blood flow. We provide a schematic view of the ion channels and intercellular communication pathways necessary for conduction of an electrical and mechanical response in the arteriolar wall, and discuss the local signaling mechanisms and cellular pathway involved in the responses to different local stimuli and in different vascular beds. Physiological modulation of VCRs, which is a rather new finding in this field, is discussed in the light of changes in plasma membrane ion channel conductance as a function of health status or disease. Finally, we discuss the possible role of VCRs in cerebrovascular function and disease as well as suggest future directions for studying VCRs in the cerebral circulation

An update on immune checkpoint therapy for the treatment of lynch syndrome

During the recent years, immune checkpoint-based therapy has proven highly effective in microsatellite instable (MSI) solid tumors irrespective of organ site. MSI tumors are associated with a defective mismatch repair (MMR) system and a highly immune-infiltrative tumor microenvironment—both characteristics of Lynch syndrome. Lynch syndrome is a multi-tumor syndrome that not only confers a high risk of colorectal and endometrial cancer but also cancer in, eg the upper urinary tract, ovaries, and small bowel. Since the genetic predisposition for Lynch syndrome are pathogenic variants in one of the four MMR genes, MLH1, MSH2, MSH6 or PMS2, most of the Lynch syndrome cancers show MMR deficiency, MSI, and activation of the immune response system. Hence, Lynch syndrome cancer patients may be optimal candidates for immune checkpoint-based therapies. However, molecular differences have been described between sporadic MSI tumors (developed due to MLH1 promoter hypermethylation) and Lynch syndrome tumors, which may result in different treatment responses. Furthermore, the response profile of the rare Lynch syndrome cases may be masked by the more frequent cases of sporadic MSI tumors in large clinical trials. With this review, we systematically collected response data on Lynch syndrome patients treated with FDA- and EMA-approved immune checkpoint-based drugs (pembrolizumab, atezolizumab, durvalumab, avelumab, ipilimumab, and nivolumab) to elucidate the objective response rate and progression-free survival of cancer in Lynch syndrome patients. Herein, we report Lynch syndrome-related objective response rates between 46 and 71% for colorectal cancer and 14–100% for noncolorectal cancer in unselected cohorts as well as an overview of the Lynch syndrome case reports. To date, no difference in the response rates has been reported between Lynch syndrome and sporadic MSI cancer patients

Rapport fra den 12. internationale Euralex-kongres, Torino, 6.–9. september 2006

[Der findes ikke resumé til denne artikel

Kommentarer til Henning Bergenholtz og Vibeke Vrang: Ny dansk ordbog i seks bind for sekretærer og forskere

[Der findes ikke resumé til denne artikel

Nødvendigt, tilstrækkeligt, typisk? – nogle tanker om definitionspraksis

This paper deals with the general issue of writing good definitions,taking a specific starting point in the principles formulated in thestyle guide of The Danish Dictionary. After a brief historical surveyof definitional practice in selected Danish dictionaries, the paperconcentrates partly on the principles and problems of the classicaldictionary definition, partly on descriptions of the function and useof words and phrases. Giving their personal view on good and baddefinitions based on ideas of prototypicality rather than exhaustivenessand completeness, the authors end by raising the issue of differentdefinitions for different users, drawing on results from a usersurvey of the online version of The Danish Dictionary

Den Danske Ordbog: en ordbog for eksperter, godtfolk og almindeligt interesserede. Svar til Henning Bergenholtz/Vibeke Vrang

Det er næsten overvældende så stor opmærksomhed der er blevet DENDANSKE ORDBOG til del, og ikke mindst LexicoNordica har velvilligt stilletspalteplads til rådighed. Formen med kritiske bemærkninger fra anmelderneog ordbogsredaktionens svar på kritikken finder vi principielt nyttigog fair, og vi håber at den vil bidrage til en større samlet forståelse hos deninteresserede læser.Den aktuelle anmeldelse af Bergenholtz/Vrang adskiller sig fra de øvrigeved at der ikke inddrages aspekter eller oplysninger som anmelderne ikkehar været inde på før. Præmisserne er dermed uforandrede, men alligevelfælder anmelderne denne gang en betydelig mere negativ dom: Hvor detidligere anmeldelser var moderat positive i deres vurdering, fyger detdenne gang med bemærkninger som ”lige til en ommer”, ”katastrofe” og”yderst upræcis”, og hvor der tidligere burde være 100.000 lemmaer, børder nu være 200.000. Både vi og læserne må spørge os selv hvorfor denændrede vurdering ikke begrundes.Eftersom anmeldelsen altså ikke behandler nye aspekter, kan det ikkeundgås at vi kommer til at bryde princippet om ikke at gentage svar påtidligere kritik. I stedet vil vi gøre en dyd af nødvendigheden og ud over atkommentere Bergenholtz/Vrangs aktuelle kritik også gøre en slags samletstatus over de kritikpunkter der har været fremført