Estimated Annual Healthcare Costs After Acute Pulmonary Embolism: Results From a Prospective Multicentre Cohort Study.

OBJECTIVE: Patients surviving acute pulmonary embolism (PE) necessitate long-term treatment and follow-up. However, the chronic economic impact of PE on European healthcare systems remains to be determined. METHODS AND RESULTS: We calculated the direct cost of illness during the first year after discharge for the index PE, analyzing data from a multicentre prospective cohort study in Germany. Main and accompanying readmission diagnoses were used to calculate DRG-based hospital reimbursements; anticoagulation costs were estimated from the exact treatment duration and each drug's unique national identifier; and outpatient post-PE care costs from guidelines-recommended algorithms and national reimbursement catalogues. Of 1017 patients enrolled at 17 centres, 958 (94%) completed ≥ 3-month follow-up; of those, 24% were rehospitalized (0.34 [95% CI 0.30-0.39] readmissions per PE survivor). Age, coronary artery, pulmonary and kidney disease, diabetes, and (in the sensitivity analysis of 837 patients with complete 12-month follow-up) cancer, but not recurrent PE, were independent cost predictors by hurdle gamma regression accounting for zero readmissions. Estimated rehospitalization cost was €1138 (95% CI 896-1420) per patient. Anticoagulation duration was 329 (IQR 142-365) days, with estimated average per-patient costs of €1050 (median 972; IQR 458-1197); costs of scheduled ambulatory follow-up visits amounted to €181. Total estimated direct per-patient costs during the first year after PE ranged from €2369 (primary analysis) to €2542 (sensitivity analysis). CONCLUSIONS: By estimating per-patient costs and identifying cost drivers of post-PE care, our study may inform decisions concerning implementation and reimbursement of follow-up programmes aiming at improved cardiovascular prevention. (Trial registration number: DRKS00005939).

Informing pandemic management in Germany with trustworthy living evidence syntheses and guideline development: lessons learned from the COVID-19 evidence ecosystem.

OBJECTIVES: We present the 'COVID-19 evidence ecosystem' (CEOsys) as a German network to inform pandemic management and to support clinical and public health decision-making. We discuss challenges faced when organizing the ecosystem and derive lessons learned for similar networks acting during pandemics or health-related crises. STUDY DESIGN AND SETTING: Bringing together 18 university hospitals and additional institutions, CEOsys key activities included research prioritization, conducting living systematic reviews (LSRs), supporting evidence-based (living) guidelines, knowledge translation (KT), detecting research gaps, and deriving recommendations, backed by technical infrastructure and capacity building. RESULTS: CEOsys rapidly produced 31 high-quality evidence syntheses and supported three living guidelines on COVID-19-related topics, while also developing methodological procedures. Challenges included CEOsys' late initiation in relation to the pandemic outbreak, the delayed prioritization of research questions, the continuously evolving COVID-19-related evidence, and establishing a technical infrastructure. Methodological-clinical tandems, the cooperation with national guideline groups and international collaborations were key for efficiency. CONCLUSION: CEOsys provided a proof-of-concept for a functioning evidence ecosystem at the national level. Lessons learned include that similar networks should, among others, involve methodological and clinical key stakeholders early on, aim for (inter)national collaborations, and systematically evaluate their value. We particularly call for a sustainable network.

Burst versus continuous delivery design in digital mental health interventions: Evidence from a randomized clinical trial.

Objective: Digital mental health interventions delivered via smartphone-based apps effectively treat various conditions; however, optimizing their efficacy while minimizing participant burden remains a key challenge. In this study, we investigated the potential benefits of a burst delivery design (i.e. interventions delivered only in pre-defined time intervals) in comparison to the continuous delivery of interventions. Methods: We randomly assigned 93 participants to the continuous delivery (CD) or burst delivery (BD) group. The CD group engaged in ReApp, a mobile app that increases positive cognitive reappraisal with a consistent delivery schedule that provides five prompts per day throughout the 3-week-long study, while the BD group received five daily prompts only in the first and third weeks of the study. Results: No significant differences were found between the groups in terms of adherence, mental health outcomes (specifically depressive and anxiety symptoms), level of perceived stress, and perceived helpfulness of intervention. The BD group showed a significantly decreased perceived difficulty of intervention over time. Conclusions: The results suggest that the burst delivery may be as suitable for digital mental health interventions as the continuous delivery. The perceived difficulty of the intervention declined more steeply for the BD group, indicating that it improved the feasibility of the positive cognitive reappraisal intervention without hurting its efficacy. This outcome may inform the design of less burdensome interventions with improved outcomes in future research.

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.

Intraindividual time-varying dynamic network of affects: linear autoregressive mixed-effects models for ecological momentary assessment.

An interesting recent development in emotion research and clinical psychology is the discovery that affective states can be modeled as a network of temporally interacting moods or emotions. Additionally, external factors like stressors or treatments can influence the mood network by amplifying or dampening the activation of specific moods. Researchers have turned to multilevel autoregressive models to fit these affective networks using intensive longitudinal data gathered through ecological momentary assessment. Nonetheless, a more comprehensive examination of the performance of such models is warranted. In our study, we focus on simple directed intraindividual networks consisting of two interconnected mood nodes that mutually enhance or dampen each other. We also introduce a node representing external factors that affect both mood nodes unidirectionally. Importantly, we disregard the potential effects of a current mood/emotion on the perception of external factors. We then formalize the mathematical representation of such networks by exogenous linear autoregressive mixed-effects models. In this representation, the autoregressive coefficients signify the interactions between moods, while external factors are incorporated as exogenous covariates. We let the autoregressive and exogenous coefficients in the model have fixed and random components. Depending on the analysis, this leads to networks with variable structures over reasonable time units, such as days or weeks, which are captured by the variability of random effects. Furthermore, the fixed-effects parameters encapsulate a subject-specific network structure. Leveraging the well-established theoretical and computational foundation of linear mixed-effects models, we transform the autoregressive formulation to a classical one and utilize the existing methods and tools. To validate our approach, we perform simulations assuming our model as the true data-generating process. By manipulating a predefined set of parameters, we investigate the reliability and feasibility of our approach across varying numbers of observations, levels of noise intensity, compliance rates, and scalability to higher dimensions. Our findings underscore the challenges associated with estimating individualized parameters in the context of common longitudinal designs, where the required number of observations may often be unattainable. Moreover, our study highlights the sensitivity of autoregressive mixed-effect models to noise levels and the difficulty of scaling due to the substantial number of parameters.

Modelling costs of interventional pulmonary embolism treatment: implications of US trends for a European healthcare system.

AIMS: Catheter-directed treatment (CDT) of acute pulmonary embolism (PE) is entering a growth phase in Europe following a steady increase in the USA 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 USA. The conservative model was based on admission data from the National Inpatient Sample (NIS) 2016-20 and the model reflecting increasing access to advanced treatment from the PERT™ national quality assurance database registry 2018-21. 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 2025-30. The NIS-based model yielded a slow increase, reaching 3.1% (95% confidence interval 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.

Surgical site infection after trochanteric and subtrochanteric fractures: a single centre retrospective analysis.

Surgical site infection (SSI) following osteosynthesis of trochanteric or subtrochanteric fractures is a rare but serious complication with incidence rate ranging from 1 to 3%. SSIs are associated with higher mortality and increased length of hospital stay resulting in higher healthcare costs and loss of life quality. In this retrospective analysis all patients with SSI following osteosynthesis of trochanteric or subtrochanteric fractures at the Department of Trauma Surgery were identified. We included all surgical procedures performed from 1992 to 2018, using data from electronic health records and SSI-Trauma-Registry. The aim was to describe epidemiological data, as well as to identify parameters correlating with the occurrence of SSI and mortality. Of 2753 patients, 53 (1.9%) developed SSI. Longer operative time was demonstrated among patients with SSI (P = 0.008). Mortality during the first postoperative year was significantly higher in the SSI group (32.1% vs. 19.1%; P = 0.018), with detection of methicillin-sensitive (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA; HR 4.13, CI 95% 1.24-13.80; P = 0.021) or Enterococcus spp. (HR 5.58, CI 95% 1.67-18.65; P = 0.005) being independent risk factors. Male sex (HR 2.25, 95% CI 1.86-2.73; P < 0.001) and higher mean age (HR 1.05, 95% CI 1.04-1.06; P < 0.001) were found to be predictors for 1-year mortality in non-infected patients. SSI rate was low with 1.9% and longer duration of surgery was associated with infection. Patients with SSI had a higher 1-year mortality, with detection of MSSA, MRSA and enterococci significantly increasing the risk of dying. Male sex and higher age were risk factors for one-year mortality in patients without SSI.

Alpha-1-antitrypsin-deficiency is associated with lower cardiovascular risk: an approach based on federated learning.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an inflammatory multisystemic disease caused by environmental exposures and/or genetic factors. Inherited alpha-1-antitrypsin deficiency (AATD) is one of the best recognized genetic factors increasing the risk for an early onset COPD with emphysema. The aim of this study was to gain a better understanding of the associations between comorbidities and specific biomarkers in COPD patients with and without AATD to enable future investigations aimed, for example, at identifying risk factors or improving care. METHODS: We focused on cardiovascular comorbidities, blood high sensitivity troponin (hs-troponin) and lipid profiles in COPD patients with and without AATD. We used clinical data from six German University Medical Centres of the MIRACUM (Medical Informatics Initiative in Research and Medicine) consortium. The codes for the international classification of diseases (ICD) were used for COPD as a main diagnosis and for comorbidities and blood laboratory data were obtained. Data analyses were based on the DataSHIELD framework. RESULTS: Out of 112,852 visits complete information was available for 43,057 COPD patients. According to our findings, 746 patients with AATD (1.73%) showed significantly lower total blood cholesterol levels and less cardiovascular comorbidities than non-AATD COPD patients. Moreover, after adjusting for the confounder factors, such as age, gender, and nicotine abuse, we confirmed that hs-troponin is a suitable predictor of overall mortality in COPD patients. The comorbidities associated with AATD in the current study differ from other studies, which may reflect geographic and population-based differences as well as the heterogeneous characteristics of AATD. CONCLUSION: The concept of MIRACUM is suitable for the analysis of a large healthcare database. This study provided evidence that COPD patients with AATD have a lower cardiovascular risk and revealed that hs-troponin is a predictor for hospital mortality in individuals with COPD.