Drivers and recent trends of hospitalisation costs related to acute pulmonary embolism.

BACKGROUND AND AIMS: The socio-economic burden imposed by acute pulmonary embolism (PE) on European healthcare systems is largely unknown. We sought to determine temporal trends and identify cost drivers of hospitalisation for PE in Germany. METHODS AND RESULTS: We analysed the totality of reimbursed hospitalisation costs in Germany (G-DRG system) in the years 2016-2020. Overall, 484 884 PE hospitalisations were coded in this period. Direct hospital costs amounted to a median of 3572 (IQR, 2804 to 5869) euros, resulting in average total reimbursements of 710 million euros annually. Age, PE severity, comorbidities and in-hospital (particularly bleeding) complications were identified by multivariable logistic regression as significant cost drivers. Use of catheter-directed therapy (CDT) constantly increased (annual change in the absolute proportion of hospitalisations with CDT + 0.40% [95% CI + 0.32% to + 0.47%]; P < 0.001), and it more than doubled in the group of patients with severe PE (28% of the entire population) over time. Although CDT use was overall associated with increased hospitalisation costs, this association was no longer present (adjusted OR 1.02 [0.80-1.31]) in patients with severe PE and shock; this was related, at least in part, to a reduction in the median length of hospital stay (for 14.0 to 8.0 days). CONCLUSIONS: We identified current and emerging cost drivers of hospitalisation for PE, focusing on severe disease and intermediate/high risk of an adverse early outcome. The present study may inform reimbursement decisions by policymakers and help to guide future health economic analysis of advanced treatment options for patients with PE.

Modelling Costs of Interventional Pulmonary Embolism Treatment: Implications of US Trends for a European Healthcare System.

BACKGROUND: Catheter-directed treatment (CDT) of acute pulmonary embolism (PE) is entering a growth phase in Europe following a steady increase in the United States (US) in the past decade, but the potential economic impact on European healthcare systems remains unknown. METHODS AND RESULTS: We built two statistical models for the monthly trend of proportion of CDT among patients with severe (intermediate- or high-risk) PE in the US. The conservative model was based on admission data from the National Inpatient Sample (NIS) 2016-2020, and the model reflecting increasing access to advanced treatment from the PERTTM national quality assurance database registry 2018-2021. By applying these models to the forecast of annual PE-related hospitalizations in Germany, we calculated the annual number of severe PE cases and the expected increase in CDT use for the period 2025-2030. The NIS-based model yielded a slow increase, reaching 3.1% (95% CI 3.0-3.2%) among all hospitalizations with PE in 2030; in the PERT-based model, increase would be steeper, reaching 8.7% (8.3-9.2%). Based on current reimbursement rates, we estimated an increase of annual costs for PE-related hospitalizations in Germany ranging from 15.3 to 49.8 million euros by 2030. This calculation does not account for potential cost savings, including those from reduced length of hospital stay. CONCLUSION: Our approach and results, which may be adapted to other European healthcare systems, provide a benchmark for healthcare costs expected to result from CDT. Data from ongoing trials on clinical benefits and cost savings are needed to determine cost-effectiveness and inform reimbursement decisions.

Healthcare resource utilisation and associated costs after low-risk pulmonary embolism: pre-specified analysis of the Home Treatment of Pulmonary Embolism (HoT-PE) study.

BACKGROUND: Pulmonary embolism (PE) and its sequelae impact healthcare systems globally. Low-risk PE patients can be managed with early discharge strategies leading to cost savings, but post-discharge costs are undetermined. PURPOSE: To define healthcare resource utilisation and overall costs during follow-up of low-risk PE. METHODS: We used an incidence-based, bottom-up approach and calculated direct and indirect costs over 3-month follow-up after low-risk PE, with data from the Home Treatment of Patients with Low-Risk Pulmonary Embolism (HoT-PE) cohort study. RESULTS: Average 3-month costs per patient having suffered low-risk PE were 7029.62 €; of this amount, 4872.93 € were associated with PE, accounting to 69.3% of total costs. Specifically, direct costs totalled 3019.33 €, and of those, 862.64 € (28.6%) were associated with PE. Anticoagulation (279.00 €), rehospitalisations (296.83 €), and ambulatory visits (194.95 €) comprised the majority of the 3-month direct costs. The remaining costs amounting to 4010.29 € were indirect costs due to loss of productivity. CONCLUSION: In a patient cohort with acute low-risk PE followed over 3 months, the majority of costs were indirect costs related to productivity loss, whereas direct, PE-specific post-discharge costs were low. Effective interventions are needed to reduce the burden of PE and associated costs, especially those related to productivity loss.

The Hsp90 machinery facilitates the transport of diphtheria toxin into human cells.

Diphtheria toxin kills human cells because it delivers its enzyme domain DTA into their cytosol where it inhibits protein synthesis. After receptor-mediated uptake of the toxin, DTA translocates from acidic endosomes into the cytosol, which might be assisted by host cell factors. Here we investigated the role of Hsp90 and its co-chaperones during the uptake of native diphtheria toxin into human cells and identified the components of the Hsp90 machinery including Hsp90, Hsp70, Cyp40 and the FK506 binding proteins FKBP51 and FKBP52 as DTA binding partners. Moreover, pharmacological inhibition of the chaperone activity of Hsp90 and Hsp70 and of the peptidyl-prolyl cis/trans isomerase (PPIase) activity of Cyps and FKBPs protected cells from intoxication with diphtheria toxin and inhibited the pH-dependent trans-membrane transport of DTA into the cytosol. In conclusion, these host cell factors facilitate toxin uptake into human cells, which might lead to development of novel therapeutic strategies against diphtheria.

Benefit on motor and non-motor behavior in a specialized unit for Parkinson's disease.

Treatment of patients with Parkinson's disease in specialized units is quite common in Germany. Data on the benefit of this hospitalization of patients with Parkinson's disease on motor and non-motor symptoms in conjunction with standardized tests are rare. Objective was to determine the efficacy of this therapeutic setting. We scored disease severity and performed clinical tests, respectively, instrumental procedures under standardized conditions in consecutively referred in-patients initially and at the end of their hospital stay. There was a decrease of motor and non-motor symptoms. The extent of improvement of non-motor and motor symptoms correlated to each other. Performance of complex movement sequences became better, whereas execution of simple movement series did not ameliorate. The interval for the timed up and go test went down. We demonstrate the effectiveness of an in-patient stay in a specialized unit for Parkinson's disease. Objective standardized testing supplements subjective clinical scoring with established rating scales.

Discovery and characterization of an endogenous CXCR4 antagonist.

CXCL12-CXCR4 signaling controls multiple physiological processes and its dysregulation is associated with cancers and inflammatory diseases. To discover as-yet-unknown endogenous ligands of CXCR4, we screened a blood-derived peptide library for inhibitors of CXCR4-tropic HIV-1 strains. This approach identified a 16 amino acid fragment of serum albumin as an effective and highly specific CXCR4 antagonist. The endogenous peptide, termed EPI-X4, is evolutionarily conserved and generated from the highly abundant albumin precursor by pH-regulated proteases. EPI-X4 forms an unusual lasso-like structure and antagonizes CXCL12-induced tumor cell migration, mobilizes stem cells, and suppresses inflammatory responses in mice. Furthermore, the peptide is abundant in the urine of patients with inflammatory kidney diseases and may serve as a biomarker. Our results identify EPI-X4 as a key regulator of CXCR4 signaling and introduce proteolysis of an abundant precursor protein as an alternative concept for chemokine receptor regulation.

Sandwich enzyme-linked immunosorbent assay for the quantification of human serum albumin fragment 408-423 in bodily fluids.

Urinary levels of human serum albumin (hSA) fragment 408-423 have been proposed to represent an early marker for graft-versus-host disease (GvHD) and chronic kidney diseases. Here, we developed an enzyme-linked immunosorbent assay (ELISA) for the quantification of hSA(408-423). The sandwich ELISA has a detection limit of 0.5ng/ml and is highly specific for hSA(408-423) because it does not cross-react with other albumin fragments or the full-length precursor. This ELISA allows rapid and convenient quantification of hSA(408-423) in bodily fluids, further clarifying the prognostic and diagnostic value of this peptide in GvHD, kidney disease, and other disorders.