QUIRIS Healthcare

Background/Objectives: The term “nutraceuticals” refers to food and dietary supplements promoted for their health benefits in addition to their nutritional value. These products contain plant- or animal-derived nutrients, vitamins, minerals, trace elements, and similar compounds aimed at enhancing skin health and influencing visible skin quality. This review provides an overview of the current research on nutraceuticals and the scientific evidence supporting their effects on skin health. Methods: The literature on more than 50 selected nutraceuticals was examined to assess any clinically substantiated, beneficial effects on skin health. The assessment was based on scientific evidence, including the quality and quantity of empirically gathered and evaluated findings. Results: A total of 17 common dietary supplements, either as individual compounds or categorized into groups, along with some combination products, were identified as nutraceuticals with well-supported effects on skin health. These include, among others, vitamins A, B7, C, and E; collagen peptides; carotenoids; and various plant extracts. For many other nutraceuticals, clinical evidence for their effects on skin health is limited or insufficient. Conclusions: The literature indicates that many nutraceuticals marketed for skin health are more or less suitable for this application based on the evidence assessment.

BackgroundOver the last century infectious diseases have been kept under control in industrialized countries thanks to advances in hygiene, prevention and antimicrobial treatments. However, the emergence of HIV, the COVID-19 pandemic, and the rise of resistant bacteria exemplify that infectious diseases continue to pose a global threat. A comprehensive understanding of the caseload, spectrum of infectious diseases and the economic impact they pose is required to develop strategies for managing infectious diseases in a resilient healthcare system.Objectives(i) to determine the proportion of adult patients discharged from German hospitals with primary diagnoses classified as an infectious disease, (ii) to describe the clinical spectrum of these diagnoses, case characteristics, and hospital settings, and (iii) to estimate the total economic burden that these cases contribute to the in-patient sector of the healthcare system.MethodsA retrospective case-control study was performed using publicly available data on ICD10 codes assigned as primary diagnoses, case characteristics, treatment settings, and cost weights from all patients discharged from German hospitals in 2022.Results1,728,824 adult patients (12% of all adult patients) were discharged with a primary diagnosis classified as an infectious disease. They were assigned 912 individual ICD10 codes. The 15 and 79 most frequently used codes comprised 40% (top 40% ID population) and 80% (top 80% ID population) of all infectious disease cases, respectively. In the top 80% ID population, patients were older, were more likely to be male, and had higher complexity and comorbidity levels than the reference population, which consisted of all adult patients minus the patients in the top 80% ID population. The mean length of stay of patients forming the top 80% ID population was 8.0 days vs. 6.1 days in the reference population. The median (IQR) cost weight was 0.663 (0.544–1.030) translating into €2,541 per case.ConclusionsIn Germany, patients with infectious diseases constitute a significant proportion of all inpatients, with a broad spectrum of conditions. These patients are generally older, more severely ill, and require longer hospital stays than those without a primary infectious disease diagnosis, contributing substantially to the overall economic burden on the healthcare system.Supplementary InformationThe online version contains supplementary material available at 10.1007/s15010-025-02507-x.

PurposeNext-generation sequencing (NGS) tools have clinical advantages over blood culture but are more expensive. This study assesses the budget impact and break-even point of NGS testing costs from a healthcare provider’s perspective in Germany.MethodsThe budget impact was calculated based on aggregated data of German post-operative surgery cases. Simulated cost savings were calculated based on a simulated reduction in hospital length of stay (LOS) of four or eight days with a positivity rate of 71% and compared to the costs of one (scenario A) or two tests (scenario B) per case. Furthermore, the break-even point of the cost of two tests compared to saved costs through shortened LOS was conducted.ResultsFor 9,450 cases, an average budget impact for scenario A and scenario B of €1,290.41 [95% CI €1,119.64 – €1,461.19] and - €208.59 [95% CI - €379.36 – - €37.81] was identified for gastrointestinal and kidney surgery cases, and €1,355.58 [95% CI €1,049.62 – €1,661.55] and €18.72 [95% CI - €324.69 – €287.24] for vascular artery surgery cases, respectively. The break-even analysis showed that using two tests per case could achieve a minimum positive contribution margin with an average of 1.9 tests per case across the study population.ConclusionThe results revealed a positive budget impact for one NGS test and a slightly negative budget impact for two NGS tests per case. Findings suggest that largest cost savings are generated for more severe cases and are highly dependent on the patient population.

IntroductionThis pilot study investigated the effects of a 12-week administration of a nutritional supplement containing special collagen peptides on the structural and molecular properties of the collagen fiber network in the human skin. For the assessments, the suction blister method and electron microscopical comparisons were used.MethodsThree suction blisters were generated on the inner forearm of each test subject before and after the 12-week administration of the nutritional supplement. High-resolution scanning electron microscopy (SEM) was employed to meticulously investigate the structural characteristics of the skin’s collagen network, including the length and diameter of collagen fibers within the suction blister roof. Furthermore, the analysis included immunohistochemistry and fluorescence light microscopy to study hyaluronic acid within the extracellular matrix. Additional assessments encompassed changes in various epidermal parameters. Nine female participants within the age range of 43.7–61.8 years (mean: 52.5 ± 5.9 years) completed the study in accordance with the study protocol.ResultsCompared with baseline, the 12-week supplementation regimen led to a statistically significant average increase in the collagen fiber network size of 34.56% (p < 0.0001). Additionally, collagen fiber cross-linking and fiber length were substantially increased. The ingestion of the supplement also resulted in an 18.08% elevation in epidermal hyaluronic acid concentration (p < 0.0001). No adverse events were recorded during the study.ConclusionUsing an innovative approach, this study demonstrated the ability of a targeted nutritional supplement to effectively restore the ultrastructural integrity of the dermal collagen network, which is typically disrupted by the natural aging process of the skin. These findings not only corroborate existing data regarding the positive effects of oral collagen peptides on skin structure and function but also contribute to our understanding of ultrastructural morphological aspects of changes in the skin’s collagen network. Supplementation can induce regeneration of the collagen fiber network in the human skin.Trial Registration NumberGerman Clinical Trials Register, DRKS-ID DRKS00034161- Date of registration: 06.05.2024, retrospectively registered.

Background: There is a variety of treatment options for patients with transplant-ineligible relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). One established option is the chemotherapy-based regimen of rituximab, gemcitabine, and oxaliplatin (R-GemOx). Since 2018, the European Medicines Agency has approved several novel targeted therapies for this indication, including CAR T therapies axicabtagene ciloleucel (axi-cel), lisocabtagene maraleucel (liso-cel), and tisagenlecleucel (tisa-cel), as well as the antibody-drug conjugate polatuzumab vedotin alongside bendamustine and rituximab (pola-BR) and the anti-CD19 monoclonal antibody tafasitamab in combination with lenalidomide (Tafa-L). Despite promising impacts on clinical outcomes, these interventions are associated with high treatment costs. The resulting economic burden necessitates the performance of cost-effectiveness analyses (CEAs). In Germany, efficiency frontiers (EF) are the recommended approach to conduct CEAs within one indication area. Aims: The objective was to conduct a health economic evaluation of costs and benefits of third-line and beyond (3+L) interventions for transplant-ineligible R/R DLBCL from a healthcare payer´s perspective in Germany. Methods: A systematic literature review was conducted in PubMed to determine the clinical benefit in terms of median overall survival (OS) of the 3+L interventions R-GemOx, axi-cel, liso-cel, tisa-cel, pola-R, and Tafa-L. Where applicable, the most probable mean value of the varying median OS was estimated via bootstrapping. Following the methods of early benefit assessment of medicinal products in Germany, the annual costs of the first year of treatment were determined. Based on the reference year 2022, drug costs and costs for outpatient medical services were calculated. For CAR T treatment, costs for its inpatient administration were added. Results of clinical benefit and treatment costs were graphically summarized in an EF. Results: The systematic literature review resulted in 11 studies. After applying the bootstrap method for interventions with more than one result for median OS (axi-cel, liso-cel, tisa-cel) clinical benefit estimations were 18.69 (months, standard deviation (SD) 3.1), 18.08 (3.2), and 10.02 (1.32), respectively. Results of median OS (months) for interventions with only one result were: 12.0, 9.5, and 15.5 for R-GemOx, pola-BR, and Tafa-L, respectively. Annual treatment costs were calculated for axi-cel, liso-cel, tisa-cel, R-GemOx, pola-BR, and Tafa-L with € 308,393, € 371,393, € 291,393, € 29,080, € 96,200, € 104,541. Drug costs represented the main cost driver, ranging from € 345,000 (liso-cel) to € 26,510 (R-GemOx). Outpatient medical services consisted of physician fees, fees for medication administration, laboratory, and imaging; highest for Tafa-L (€ 3,861), lowest for CAR T treatment (€ 1,330). Inpatient CAR T administration equaled € 25,063. Thus, the EF is formed by R-GemOx, Tafa-L, and axi-cel. Pola-BR and tisa-cel are dominated by R-GemOx respectively Tafa-L. High uncertainty was found for point estimates of liso-cel and axi-cel.Summary/Conclusion: Although the EF approach is currently under discussion, it provides interesting insights into the cost-effectiveness of interventions to guide decision-making for the pricing of new interventions. We found R-GemOx, Tafa-L and axi-cel to be cost-effective, but uncertainty shows that liso-cel could also be part of the EF. For Tafa-L, the highest increase in benefit per euro is obtained, expressed by the steepest slope compared to the previous intervention (R-GemOx). Keywords: DLBCL, CAR-T, Cost effectiveness, Diffuse large B cell lymphoma

Abstract PRS-344/S095012 is a bispecific antibody-Anticalin® fusion protein targeting PD-L1 and 4-1BB. It is designed to block the PD-1/PD-L1 axis and localize 4-1BB co-stimulation to PD-L1-positive tumor microenvironment (TME) or tumor draining lymph nodes with the aim of maximizing antitumor immunity and increasing the therapeutic window of 4-1BB monoclonal antibodies (mAbs). Multiple in vitro assays have shown that PRS-344/S095012 inhibits PD-1/PD-L1 signaling while simultaneously activating 4-1BB signaling on T cells. This resulted in a synergistic effect on both pathways leading to anti-tumor immune responses. PRS-344/S095012 presents mAb-like pharmacokinetics in vivo and non-clinical mouse models demonstrated dose-dependent efficacy in anti-PD-L1 refractory tumors. In the higher dose range, complete tumor regression was achieved in PD-L1 high and PD-L1 low expressing xenograft mouse models. This first-in-human (FIH), phase 1/2, open-label, multi center, dose escalation and cohort expansion study is designed to determine the safety and tolerability of intravenously administered PRS-344/S095012 in patients with advanced and/or metastatic solid tumors (NCT05159388). Patients with histologically confirmed diagnosis of unresectable, locally advanced, or metastatic solid tumors for which standard treatment options are not available, no longer effective, or not tolerated are eligible. Patients must have Eastern Cooperative Oncology Group (ECOG) status 0 or 1, RECIST 1.1 measurable disease and should have documented progression on prior therapy. Prior therapy with 4-1BB agonists is prohibited. Phase 1 is a dose escalation guided by a Bayesian Logistic Regression Model and a 28-day dose limiting toxicities (DLT) period. Primary objectives are safety and tolerability of PRS-344/S095012; secondary objectives include exploration of antitumor activity and evaluation of pharmacokinetics. Pharmacodynamics and comprehensive biomarker program will be explored. Additional patients may be enrolled to backfill cohort(s)to further explore pharmacokinetic/pharmacodynamic signals. Phase 2 is an expansion with primary objective of anti-tumor activity. First patient was dosed in November 2021 and the study is planned to enroll at sites in Belgium, Spain and Australia. Citation Format: Christiane Jungels, Nuria Kotecki, Emiliano Calvo, Elena Garralda, Timothy Price, Xiaojiang Zahn, Atif Abbas, Lisa Mahnke, Winrich Rauschning, Aizea Morales-Kastresana, Lucia Pattarini, Birgit Bossenmaier, Alix Scholer-Dahirel, Tim Demuth, Julie Legrande. Study of PRS-344/S095012 a PD-L1/4-1BB bispecific antibody-Anticalin®-fusion in patients with solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT255.

PurposeFirst detected in China in 2019, the novel coronavirus disease (COVID-19) has rapidly spread globally. Since then, healthcare systems are exposed to major challenges due to scarce personnel and financial resources. Therefore, this analysis intended to examine treatment costs of COVID-19 inpatients in a German single centre during the first pandemic wave in 2020 from a healthcare payer perspective. Potential cost savings were assessed considering the administration of remdesivir according to the European Medicines Agency label.MethodsA retrospective medical-chart review was conducted on COVID-19 patients treated at University Hospital Cologne, Germany. Patients were clustered according to an eight-category ordinal scale reflecting different levels of supplemental oxygen. Potential cost savings due to the administration of remdesivir were retrospectively modelled based on a reduced length of stay, as shown in the Adaptive COVID-19 Treatment Trial.Results105 COVID-19 patients were identified. There was wide variability in the service data with median treatment costs from EUR 900 to EUR 53,000 per patient, depending on major diagnosis categories and clinical severity. No supplemental oxygen was needed in 40 patients (38.1%). Forty-three (41.0%) patients were treated in intensive-care units, and 30 (69.8%) received invasive ventilation. In our model, in-label administration of remdesivir would have resulted in costs savings of EUR 2100 per COVID-19 inpatient (excluding acquisition costs).ConclusionWe found that COVID-19 inpatients suffer from heterogeneous disease patterns with a variety of incurred G-DRG tariffs and treatment costs. Theoretically shown in the model, financial resources can be saved by the administration of remdesivir in eligible inpatients.

Fresh leaf artichoke extracts contain high amounts of cynarin and related caffeoylquinic acids which possess high antioxidant activity. We have investigated mitochondrial stimulation and confirmed radical scavenging activity of cynarin, the lead compound of the special extract [15 – 30:1] from fresh leafs instead of dried material from Cynara cardunculus var. scolymus (L.) Benth., and its main bioactive metabolites caffeic acid, ferulic acid, dihydroferulic acid and their amide derivatives formed after administration of the fresh leaf artichoke extract to humans.