Kosten und Lebensqualität bei ambulanter vs. stationärer kardiologischer Rehabilitation – ein gesundheitsökonomischer Ansatz

Hintergrund: Die ischämischen Herzerkrankungen wie der Myokardinfarkt gewinnen in Deutschland, unter anderem auf Grund des demographischen Wandels, zunehmend auch ökonomisch an Bedeutung. Die sich an die Phase der Akutversorgung anschließende kardiologische Rehabilitation wurde bisher in Deutschland überwiegend stationär durchgeführt. Ziel: Das Ziel der SARAH-Studie war es, basierend auf einem klinischen Versuch, die Kosten für die unterschiedlichen Rehabilitationsmaßnahmen sowie die erzielten Effekte hinsichtlich der Lebensqualität zu ermitteln und die Ergebnisse von ambulanter und stationärer Rehabilitation miteinander zu vergleichen. Methoden: Es wurde eine kontrollierte Beobachtungsstudie mit 163 Patienten durchgeführt, die einem comprehensive cohort design folgte. Die Beobachtung erstreckte sich über einen Zeitraum von 12 Monaten nach der Rehabilitation. Die Kosten wurden anhand der Kostenrechnung der Rehazentren und anhand der Patientenangaben zu einer retrospektiven Kostenbefragung ermittelt. Die gesundheitsbezogene Lebensqualität wurde mit dem EuroQol (EQ-5D) gemessen und bewertet. Ergebnisse: Über den gesamten Beobachtungszeitraum konnten die Daten von 140 Patienten ausgewertet werden, d.h. es wurde eine Rücklaufquote von 86% erreicht. Die Studie ergab einen deutlichen Lebensqualitätsgewinn, sowohl bei der stationären, als auch bei der ambulanten Rehabilitationsmaßnahme; diese Verbesserung der Lebensqualität bleibt bei beiden Settings größtenteils über den gesamten Nachbeobachtungszeitraum erhalten. Zwischen den Settings gab es allerdings keinen statistisch signifikanten Unterschied. Bei den direkten Kosten war das ambulante Setting auf Grund der niedrigeren tagesgleichen Kosten um 760€ günstiger als die stationäre Rehabilitation. Diskussion: Einschränkungen der Studie ergeben sich durch die geringe Bereitschaft der Patienten, sich wie vorgesehen randomisieren zu lassen, was eine entsprechende Analyse verhinderte und zu einer geringen Besetzung des ambulanten Arms führte; ferner konnten nur Kosten jeweils einer Angebotseinheit untersucht werden. Stärken sind im Einsatz vorab getesteter Messinstrumente, im hohen Rücklauf und in der Plausibilität der Angaben zu finden. Schlussfolgerung: Auch nach Betrachtung der indirekten Kosten und der statistischen Anpassung der Daten kann ein Kostenvorteil einer ambulanten Rehabilitationsmaßnahme gegenüber einer stationären Maßnahme nicht ausgeschlossen werden

Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection

Identification of full-length transmitted HIV-1 genomes could be instrumental in HIV-1 pathogenesis, microbicide, and vaccine research by enabling the direct analysis of those viruses actually responsible for productive clinical infection. We show in 12 acutely infected subjects (9 clade B and 3 clade C) that complete HIV-1 genomes of transmitted/founder viruses can be inferred by single genome amplification and sequencing of plasma virion RNA. This allowed for the molecular cloning and biological analysis of transmitted/founder viruses and a comprehensive genome-wide assessment of the genetic imprint left on the evolving virus quasispecies by a composite of host selection pressures. Transmitted viruses encoded intact canonical genes (gag-pol-vif-vpr-tat-rev-vpu-env-nef) and replicated efficiently in primary human CD4+ T lymphocytes but much less so in monocyte-derived macrophages. Transmitted viruses were CD4 and CCR5 tropic and demonstrated concealment of coreceptor binding surfaces of the envelope bridging sheet and variable loop 3. 2 mo after infection, transmitted/founder viruses in three subjects were nearly completely replaced by viruses differing at two to five highly selected genomic loci; by 12–20 mo, viruses exhibited concentrated mutations at 17–34 discrete locations. These findings reveal viral properties associated with mucosal HIV-1 transmission and a limited set of rapidly evolving adaptive mutations driven primarily, but not exclusively, by early cytotoxic T cell responses

Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection

Identification of full-length transmitted HIV-1 genomes could be instrumental in HIV-1 pathogenesis, microbicide, and vaccine research by enabling the direct analysis of those viruses actually responsible for productive clinical infection. We show in 12 acutely infected subjects (9 clade B and 3 clade C) that complete HIV-1 genomes of transmitted/founder viruses can be inferred by single genome amplification and sequencing of plasma virion RNA. This allowed for the molecular cloning and biological analysis of transmitted/founder viruses and a comprehensive genome-wide assessment of the genetic imprint left on the evolving virus quasispecies by a composite of host selection pressures. Transmitted viruses encoded intact canonical genes (gag-pol-vif-vpr-tat-rev-vpu-env-nef) and replicated efficiently in primary human CD4+ T lymphocytes but much less so in monocyte-derived macrophages. Transmitted viruses were CD4 and CCR5 tropic and demonstrated concealment of coreceptor binding surfaces of the envelope bridging sheet and variable loop 3. 2 mo after infection, transmitted/founder viruses in three subjects were nearly completely replaced by viruses differing at two to five highly selected genomic loci; by 12–20 mo, viruses exhibited concentrated mutations at 17–34 discrete locations. These findings reveal viral properties associated with mucosal HIV-1 transmission and a limited set of rapidly evolving adaptive mutations driven primarily, but not exclusively, by early cytotoxic T cell responses

Slow glycosylation:Activation of trichloroacetimidates under mild conditions using lithium salts and the role of counterions

Glycosylations were carried out with the two glycosyl donors 4-O-acetyl-2,3-O-isopropylidene-1-O-trichloroacetimidoyl-alpha-L-rhamnopyranose and 2,3,4-tri-O-benzyl-1-O-trichloro-acetimidoyl-alpha-L-rhamnopyranose in combination with the two alcohols 1-adamantanol and L-menthol as model glycosyl acceptors. As catalysts, the five lithium salts LiNTf2, LiI, LiClO4, LiPF6 and LiOTf were investigated. We demonstrated that both lithium and the respective counterions are playing a role in the activation of trichloroacetimidate glycosyl donors at rt. Under these very mild conditions, the glycosylations are slow and completed in two to eight days. Depending on the counterion, the rate and yield of the reaction differs; however, the selectivity of all investigated lithium salts is deficient

Dynamics of humoral and cellular immune responses after homologous and heterologous SARS-CoV-2 vaccination with ChAdOx1 nCoV-19 and BNT162b2

Background Vaccines are an important means to overcome the SARS-CoV-2 pandemic. They induce specific anti-body and T-cell responses but it remains open how well vaccine-induced immunity is preserved over time following homologous and heterologous immunization regimens. Here, we compared the dynamics of humoral and cellular immune responses up to 180 days after homologous or heterologous vaccination with either ChAdOx1-nCoV-19 (ChAd) or BNT162b2 (BNT) or both.Methods Various tests were used to determine the humoral and cellular immune response. To quantify the antibody levels, we used the surrogate neutralization (sVNT) assay from YHLO, which we augmented with pseudo-and real virus neutralization tests (pVNT and rVNT). Antibody avidity was measured by a modified ELISA. To determine cel-lular reactivity, we used an IFN-g Elispot, IFN-g/IL Flurospot, and intracellular cytokine staining.Findings Antibody responses significantly waned after vaccination, irrespective of the regimen. The capacity to neu-tralize SARS-CoV-2 -including variants of concern such as Delta or Omicron -was superior after heterologous compared to homologous BNT vaccination, both of which resulted in longer-lasting humoral immunity than homol-ogous ChAd immunization. All vaccination regimens induced stable, polyfunctional T-cell responses. Interpretation These findings demonstrate that heterologous vaccination with ChAd and BNT is a potent alternative to induce humoral and cellular immune protection in comparison to the homologous vaccination regimens.Copyright (c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/