IntroductionAcute kidney injury is a frequent complication in critically ill patients with and without COVID-19. The aim of this study was to evaluate the incidence of, and risk factors for, acute kidney injury and its effect on clinical outcomes of critically ill COVID-19 patients in Tyrol, Austria.MethodsThis multicenter prospective registry study included adult patients with a SARS-CoV-2 infection confirmed by polymerase chain reaction, who were treated in one of the 12 dedicated intensive care units during the COVID-19 pandemic from February 2020 until May 2022.ResultsIn total, 1042 patients were included during the study period. The median age of the overall cohort was 66 years. Of the included patients, 267 (26%) developed acute kidney injury during their intensive care unit stay. In total, 12.3% (n = 126) required renal replacement therapy with a median duration of 9 (IQR 3–18) days. In patients with acute kidney injury the rate of invasive mechanical ventilation was significantly higher with 85% (n = 227) compared to 41% (n = 312) in the no acute kidney injury group (p < 0.001). The most important risk factors for acute kidney injury were invasive mechanical ventilation (OR = 4.19, p < 0.001), vasopressor use (OR = 3.17, p < 0.001) and chronic kidney disease (OR = 2.30, p < 0.001) in a multivariable logistic regression analysis. Hospital and intensive care unit mortality were significantly higher in patients with acute kidney injury compared to patients without acute kidney injury (Hospital mortality: 52.1% vs. 17.2%, p < 0.001, ICU-mortality: 47.2% vs. 14.7%, p < 0.001).ConclusionAs in non-COVID-19 patients, acute kidney injury is clearly associated with increased mortality in critically ill COVID-19 patients. Among known risk factors, invasive mechanical ventilation has been identified as an independent and strong predictor of acute kidney injury.Graphical abstract

6588 Background: Antiresorptive therapy with bisphosphonates or denosumab is standard care for patients with primary or secondary osseous metastasized breast cancer. The most important toxicity of this class of drugs is medication-related osteonecrosis of the jaw (MRONJ). MRONJ represents a major medical burden and impairs quality of life. Based on recent studies, the risk of MRONJ occurrence ranges from 1% to 3%. The objective of this study was to assess the population-based incidence of MRONJ in breast cancer patients with bone metastases in Tyrol, Austria. Methods: This retrospective multicenter study was conducted between 2000 and 2020 at nine centers across Tyrol, Austria, including 8,860 patients with breast cancer. Depending on whether patients with bone metastases received denosumab, bisphosphonates or denosumab following bisphosphonates they were allocated to one of three groups. Data was collected using an electronic case report form (e-CRF) and managed via the web-based database AskiMed. MRONJ incidences with 95% confidence intervals and the differences between the median of cumulative incidences were calculated in patients treated with bisphosphonates and/or denosumab. Results: A total of 639 patients had bone metastasis and received antiresorptive therapy. MRONJ was diagnosed in 56 (8.8%) patients. Regarding the 292 (45.7%) patients treated with denosumab alone, the MRONJ incidence was 11.6% (95%CI 8.2%-15.9%). The group of patients treated with only bisphosphonates included 255 (39.9%) patients; their MRONJ incidence was 2.7% (95%CI 1.1%-5.6%). Of the 92 (14.4%) patients receiving both antiresorptive therapies consecutively, the MRONJ incidence was 16.3% (95%CI 9.4%-25.5%). Thus, a total of 49 (12.8%) MRONJ cases were detected in patients using denosumab alone as well as using the combination of denosumab following bisphosphonates. Patients treated with denosumab developed a MRONJ in median 60 months earlier than with bisphosphonates alone or followed by denosumab. The hazard ratio for MRONJ from start of therapy of denosumab compared to bisphosphonates alone or followed by denosumab was 7.9 (3.8-16.2; p-value &lt; 0.0001). Conclusions: This study showed a substantially higher MRONJ incidence for denosumab alone or bisphosphonates followed by denosumab in the tyrolean cohort when compared to other recent studies. Future comparative real-world-evidence research provide explicit benefit-harm tradeoffs to inform treatment decision making.

ObjectivesThis open comparative study aimed to analyze the effects of a one-week vacation with various activity programs on well-being, heart rate variability (HRV) and sleep quality in healthy vacationers.MethodsFifty-two healthy untrained vacationers spent a one-week vacation with regular exercise in East Tyrol. Exercise was performed on six of seven days. The study participants were divided into a) Group 1, playing golf (G), and b) Group 2 performing Nordic walking or e-biking (NW&EB). Well-being was measured with the WHO-5 well-being-index; stress and recovery status was obtained with the EBF-24-questionnaire (recovery-stress questionnaire). HRV parameters in the time and frequency domain (SDNN, pNN50, r-MSSD, log LF/HF and total power) were measured with a 24-h-ECG (electrocardiogram). Sleep quality was derived from the EBF-24 questionnaire and sleep architecture from HRV-analysis. Examinations were performed one day before and after the vacation.ResultsWell-being significantly improved in the G group (+ 40%, p < 0.001) and NW&EB group (+ 19%, p = 0.019). The stress and recovery profile also improved significantly in both groups (stress-decrease: -43.7% G group; -44.7% NW&EB group; recovery-increase: + 23.6% G group; + 21.5% NW&EB group). Except for the SDNN (standard deviation of the NN interval), no significant change was noted in HRV-parameters. SDNN improved significantly only in the NW&EB group (+ 9%, p < 0.05). Sleep quality (+ 21% G group, p = 0.029; + 19% NW&EB group, p = 0.007) and architecture (-10% G group, p = 0.034; -23% NW&EB group, p = 0.012) significantly improved in both groups.ConclusionA short-term vacation with regular exercise was well tolerated by the study participants and improved well-being, sleep quality, HRV and autonomic regulation.Trial registrationRegistry and the registration no. of the study/trial: Approval was received from the ethics committee of the Leopold Franzens University of Innsbruck (AN2013-0059 332/4.8).

Background: Treatment of acute traumatic pain is a core task for mountain rescue services. Intravenous access, however, is often difficult, and the vast majority of missions are carried out without a physician at the scene. The spectrum of analgesics available for use by non-physician personnel is limited. Inhaled analgesics, such as methoxyflurane, might prove useful, but currently no data exist on their application by non-physicians in the alpine setting. Methods: This prospective observational alpine field study was conducted over a period of 15 months. Patients suffering traumatic injuries with moderate to severe pain (pain score ≥ 5) after downhill bike accidents in the Tyrol mountains (1,362 m to 2,666 m above sea level) were enrolled. Teams of four mountain rescue service members, one of them a trained EMT, treated the patients with 3 ml of methoxyflurane by inhaler. We measured efficacy as reduction in pain from baseline to 15 minutes after treatment on a numerical rating scale. Safety was assessed by change in vital signs or occurrence of side-effects. Sample-size calculations were based on the efficacy outcome and yielded a need for 20 patients at a power of 0.8. Results: From June 29, 2020 to September 30, 2021, a total of 20 patients (two females; mean age 37 years) were included. The mean initial pain score was 7.2 (SD 1.0) points. After 15 minutes, pain was significantly reduced by a mean of 2.9 (SD 1.4) points. No major adverse events or relevant changes in vital signs were observed. Conclusion: The use of methoxyflurane by EMTs during alpine rescue operations in our study proved to be safe and efficient. We observed no reduction in the efficacy of the inhaler device at moderate altitude.

Objective: The German/Austrian Diabetes Patient Follow-up Registry (Diabetes-Patienten-Verlaufsdokumentation or DPV), England/Wales National Pediatric Diabetes Audit (NPDA), and Type 1 Diabetes Exchange (T1DX) in the United States investigated changes in hemoglobin A1c (HbA1c) and diabetes technology use from 2010 to 2018. Methods: Registry/audit data from 2010 to 2018 were analyzed in annual cohorts using linear regression for those <18 years of age with type 1 diabetes diagnosed at age >6 months. Time trends in HbA1c, pump, and continuous glucose monitoring (CGM) use were studied using repeated measurements linear and logistic regression models with an autoregressive covariance structure and with year and data source as independent variables. Results: A total of 1,172,980 visits among 114,264 (54,119 DPV, 43,550 NPDA, 16,595 T1DX) patients were identified. HbA1c remained clinically stable in DPV (7.7% [61 mmol/mol] to 7.6% [60 mmol/mol]), decreased in the NPDA (8.7% [72 mmol/mol] to 7.9% [63 mmol/mol]), and increased in T1DX (8.0% [64 mmol/mol] to 8.5% [69 mmol/mol] from 2010 to 2018). In all registries/audits, insulin pump and CGM use increased over time with greatest pump use in T1DX and lowest uptake reported in NPDA. Conclusions: These data reveal three different longitudinal patterns of change in registry/audit HbA1c from 2010 to 2018. Diabetes technology use increased throughout, at different rates. Quality improvement (QI) programs in DPV have been ongoing for 25 years, began in NPDA in 2009 and T1DX in 2016. We speculate that in England/Wales, development of networks, peer review, and implementation of QI measures contributed to reductions in population HbA1c. Many of these interventions had been implemented in DPV before 2010. Further efforts to understand this improvement, including the role of QI, and continued success within standardized documentation and benchmarking could inform T1DX programs to reduce HbA1c.

The complexity of systems continues to increase rapidly, especially due to the multi-level integration of subsystems from different domains into cyber-physical systems. This results in special challenges for the efficient verification and validation (V&V) of these systems with regard to their requirements and properties. In order to tackle the new challenges and improve the quality assurance processes, the V&V workflows have to be documented and analyzed. In this paper, a novel approach for the workflow modelling of V&V activities is presented. The generic approach is tailorable to different industrial domains and their specific constraints, V&V methods, and toolchains. The outcomes comprise a dedicated modelling notation (VVML) and tool-support using the modelling framework Enterprise Architect for the efficient documentation and implementation of workflows in the use cases. The solution enables the design of re-usable workflow assets such as V&V activities and artifacts that are exchanged between workflows. This work is part of the large scale European research project VALU3S that deals with the improvement and evaluation of V&V processes in different technical domains, focusing on safety, cybersecurity, and privacy properties.

BackgroundWidely varying mortality rates of critically ill Coronavirus disease 19 (COVID-19) patients in the world highlighted the need for local surveillance of baseline characteristics, treatment strategies and outcome. We compared two periods of the COVID-19 pandemic to identify important differences in characteristics and therapeutic measures and their influence on the outcome of critically ill COVID-19 patients.MethodsThis multicenter prospective register study included all patients with a SARS-CoV‑2 infection confirmed by polymerase chain reaction, who were treated in 1 of the 12 intensive care units (ICU) from 8 hospitals in Tyrol, Austria during 2 defined periods (1 February 2020 until 17 July: first wave and 18 July 2020 until 22 February 2021: second wave) of the COVID-19 pandemic.ResultsOverall, 508 patients were analyzed. The majority (n = 401) presented during the second wave, where the median age was significantly higher (64 years, IQR 54–74 years vs. 72 years, IQR 62–78 years, p < 0.001). Invasive mechanical ventilation was less frequent during the second period (50.5% vs 67.3%, p = 0.003), as was the use of vasopressors (50.3% vs. 69.2%, p = 0.001) and renal replacement therapy (12.0% vs. 19.6%, p = 0.061), which resulted in shorter ICU length of stay (10 days, IQR 5–18 days vs. 18 days, IQR 5–31 days, p < 0.001). Nonetheless, ICU mortality did not change (28.9% vs. 21.5%, p = 0.159) and hospital mortality even increased (22.4% vs. 33.4%, p = 0.039) in the second period. Age, frailty and the number of comorbidities were significant predictors of hospital mortality in a multivariate logistic regression analysis of the overall cohort.ConclusionAdvanced treatment strategies and learning effects over time resulted in reduced rates of mechanical ventilation and vasopressor use in the second wave associated with shorter ICU length of stay. Despite these improvements, age appears to be a dominant factor for hospital mortality in critically ill COVID-19 patients.Supplementary InformationThe online version of this article (10.1007/s00508-021-01945-5) contains supplementary material, which is available to authorized users.

Heavy-duty mobile machines (HDMMs) are a wide range of machinery used in diverse and critical application areas which are currently facing several issues like skilled labor shortage, poor safety records, and harsh work environments. Consequently, efforts are underway to increase automation in HDMMs for increased productivity and safety, eventually transitioning to operator-less autonomous HDMMs to address skilled labor shortages. However, HDMM are complex machines requiring continuous physical and cognitive inputs from human-operators. Thus, developing autonomous HDMM is a huge challenge, with current research and developments being performed in several independent research domains. Through this study, we use the bounded rationality concept to propose multidisciplinary collaborations for new autonomous HDMMs and apply the transaction cost economics framework to suggest future implications in the HDMM industry. Furthermore, we introduce a conceptual understanding of collaborations in the autonomous HDMM as a unified approach, while highlighting the practical implications and challenges of the complex nature of such multidisciplinary collaborations. The collaborative challenges and potentials are mapped out between the following topics: mechanical systems, AI methods, software systems, sensors, connectivity, simulations and process optimization, business cases, organization theories, and finally, regulatory frameworks.

Hydropower is an important source of renewable energy. Due to ageing infrastructure, more and more existing hydropower plants have to be refurbished and modernised. This includes a complete review of the design parameters as well as the change of specific parts. Investments should be targeted to improve the overall performance of hydropower plants and ensure a long lasting life extension. This paper presents the concept of the submerged wall as a local high point in the headrace tunnel, which can—in combination with the intake gates—replace existing penstock shutoff valves. Such a replacement was conducted for the hydropower plant Schneiderau in Austria, which also allowed us to prove the concept based on measurements including a simulated break of the penstock. The presented solution can help to reduce investment costs and also minimise maintenance efforts and therefore is an attractive option for classic penstock shutoff valves for comparable projects.

Backgroundand purpose. COVID-19 is a novel viral disease causing worldwide pandemia. The aim of this study was to describe the effect of adjunctive individualized homeopathic treatment delivered to hospitalized patients with confirmed symptomatic SARS-CoV-2 infection. Patient presentationThirteen patients with COVID-19 were admitted. Mean age was 73.4 ± 15.0 (SD) years. Twelve (92.3%) were speedily discharged without relevant sequelae after 14.4 ± 8.9 days. A single patient admitted in an advanced stage of septic disease died in hospital. A time-dependent improvement of relevant clinical symptoms was observed in the 12 surviving patients. Six (46.2%) were critically ill and treated in the intensive care unit (ICU). Mean stay at the ICU of the 5 surviving patients was 18.8 ± 6.8 days. In six patients (46.2%) gastrointestinal disorders accompanied COVID-19. ConclusionThe observations suggest that adjunctive homeopathic treatment may be helpful to treat patients with confirmed COVID-19 even in high – risk patients especially since there is no conventional treatment of COVID-19 available at present.