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In Germany, the use of TAVR increased substantially between 2007 and 2013, whereas the use of surgical aortic-valve replacement decreased modestly. Patients undergoing TAVR were older and at higher operative risk. Mortality decreased over time in both groups. Surgical aortic-valve replacement was a major clinical advance in the 1960s 1 and offered a cure for aortic stenosis, a condition for which no disease-modifying pharmacologic therapy is available. Surgical replacement remained the only treatment option until 2007, when devices for transcatheter aortic-valve replacement (TAVR) were approved. 2 Since then, TAVR has become established not only as an effective therapy for patients for whom surgery is not an option 3 but also as an alternative for high-risk patients. 4 The introduction of TAVR has led to questions about the effect of this relatively new approach on current clinical practice and its effect on surgical . . .

BackgroundA central element in the management of cardiogenic shock (CS) comprises mechanical circulatory support (MCS) systems to maintain cardiac output (CO). This study aims to quantify incidence, outcome and influence of MCS in CS over the last decade.MethodsAll patients hospitalized with CS in a tertiary university hospital in Germany between 2007 and 2017 were identified utilizing the international coding system ICD-10 with code R57.0. Application of MCS was identified via German procedure classification codes (OPS).Results383,983 cases of cardiogenic shock were reported from 2007 to 2017. Patients had a mean age of 71 years and 38.5% were female. The incidence of CS rose by 65.6% from 26,828 cases in 2007 (33.1 per 100,000 person-years, hospital survival 39.2%) to 44,425 cases in 2017 (53.7 per 100,000 person-years, survival 41.2%). In 2007, 16.0% of patients with CS received MCS (4.6 per 100,000 person-years, survival 46.6%), dropping to 13.9% in 2017 (6.6 per 100,000 person-years, survival 38.6%). Type of MCS changed over the years, with decreasing use of the intra-aortic balloon pump (IABP), an increase in extracorporeal membrane oxygenation (VA-ECMO) and percutaneous ventricular assist device (pVAD) usage. Significant differences regarding in-hospital survival were observed between the devices (survival: overall: 40.2%; medical treatment = 39.5%; IABP = 49.5%; pVAD = 36.2%; VA-ECMO = 30.5%; p < 0.001).ConclusionsThe incidence of CS is increasing, but hospital survival remains low. MCS was used in a minority of patients, and the percentage of MCS usage in CS has decreased. The use rates of the competing devices change over time.

Background Intensive care units represent one of the largest clinical cost centers in hospitals. Mechanical ventilation accounts for a significant share of this cost. There is a relative dearth of information quantifying the impact of ventilation on daily ICU cost. We thus determine daily costs of ICU care, incremental cost of mechanical ventilation per ICU day, and further differentiate cost by underlying diseases. Methods Total ICU costs, length of ICU stay, and duration of mechanical ventilation of all 10,637 adult patients treated in ICUs at a German hospital in 2013 were analyzed for never-ventilated patients ( N  = 9181), patients ventilated at least 1 day, ( N  = 1455) and all patients ( N  = 10,637). Total ICU costs were regressed on the number of ICU days. Finally, costs were analyzed separately by ICD-10 chapter of main diagnosis. Results Daily non-ventilated costs were €999 (95%CI €924 - €1074), and ventilated costs were €1590 (95%CI €1524 - €1657), a 59% increase. Costs per non-ventilated ICU day differed substantially and were lowest for endocrine, nutritional or metabolic diseases (€844), and highest for musculoskeletal diseases (€1357). Costs per ventilated ICU day were lowest for diseases of the circulatory system (€1439) and highest for cancer patients (€1594). The relative cost increase due to ventilation was highest for diseases of the respiratory system (94%) and even non-systematic for patients with musculoskeletal diseases (13%, p  = 0.634). Conclusions Results show substantial variability of ICU costs for different underlying diseases and underline mechanical ventilation as an important driver of ICU costs.

Background The clinical progress of patients hospitalized due to COVID-19 is often associated with severe pneumonia which may require intensive care, invasive ventilation, or extracorporeal membrane oxygenation (ECMO). The length of intensive care and the duration of these supportive therapies are clinically relevant outcomes. From the statistical perspective, these quantities are challenging to estimate due to episodes being time-dependent and potentially multiple, as well as being determined by the competing, terminal events of discharge alive and death. Methods We used multistate models to study COVID-19 patients’ time-dependent progress and provide a statistical framework to estimate hazard rates and transition probabilities. These estimates can then be used to quantify average sojourn times of clinically important states such as intensive care and invasive ventilation. We have made two real data sets of COVID-19 patients ( n  = 24* and n  = 53**) and the corresponding statistical code publically available. Results The expected lengths of intensive care unit (ICU) stay at day 28 for the two cohorts were 15.05* and 19.62** days, while expected durations of mechanical ventilation were 7.97* and 9.85** days. Predicted mortality stood at 51%* and 15%**. Patients mechanically ventilated at the start of the example studies had a longer expected duration of ventilation (12.25*, 14.57** days) compared to patients non-ventilated (4.34*, 1.41** days) after 28 days. Furthermore, initially ventilated patients had a higher risk of death (54%* and 20%** vs. 48%* and 6%**) after 4 weeks. These results are further illustrated in stacked probability plots for the two groups from time zero, as well as for the entire cohort which depicts the predicted proportions of the patients in each state over follow-up. Conclusions The multistate approach gives important insights into the progress of COVID-19 patients in terms of ventilation duration, length of ICU stay, and mortality. In addition to avoiding frequent pitfalls in survival analysis, the methodology enables active cases to be analyzed by allowing for censoring. The stacked probability plots provide extensive information in a concise manner that can be easily conveyed to decision makers regarding healthcare capacities. Furthermore, clear comparisons can be made among different baseline characteristics.

Background The aim of the present study is to investigate the impact of the Covid-19 pandemic on the effectiveness of psychosomatic rehabilitation. Methods Between April 2019 and March 2022, a total of 18,388 patients from 7 rehabilitation centres could be included in the study. For each patient, score values from the HEALTH-49 and ICF AT-50 Psych questionnaires were calculated at the beginning and at the end of rehabilitation and the effectiveness of the rehabilitation program was determined by comparing the scores at the beginning and at the end of the rehabilitation programme. Using risk adjusted linear mixed models, three time intervals were compared: a pre-pandemic episode (April 2019 to March 2020), the first year of the pandemic (April 2020 to March 2021) and the second year of the pandemic (April 2021 to March 2022). Results Overall, it can be stated that the pandemic has substantially impaired the effectiveness of psychosomatic rehabilitation measures. This phenomenon can be observed across a wide range of psychosocial markers and even two years after the start of the pandemic there is no end to the limited effectiveness. With regard to ‘psychological and somatoform disorders’, for example, there was a relative decrease in the effectiveness of the rehabilitation measure by 11.29% in the first year of the pandemic compared to the pre-pandemic episode, p  < 0.001. In the second year of the pandemic, the effectiveness of the rehabilitation measure was still decreased by 8.8% compared to the pre-pandemic episode, p  < 0.001. In addition, the evaluations show that a division of the pandemic effect into direct effects (on the individual) and indirect effects (via further complication of the occupational problem environment) can be made and that the pandemic-related complication of the occupational problem environment are still prevalent more than two years after the start of the pandemic. Discussion The Covid-19 pandemic has had a significant impact on the psychosomatic rehabilitation programs reducing the effectiveness of treatment not only for a short period of time but constantly until March 2022. Trial Registration Number DRKS00029669; Date of registration: 02/08/2022.

Tick-borne encephalitis (TBE) is the most important tick-borne viral disease in Eurasia and causes disease in humans and in a number of animals, among them dogs and horses. There is still no good correlation between tick numbers, weather conditions and human cases. There is the hypothesis that co-feeding due to simultaneous occurrence of larvae and nymphs may be a factor for the increased transmission of the virus in nature and for human disease. Based on long-term data from a natural TBEV focus, phylogenetic results and meteorological data we sought to challenge this hypothesis. Ticks from an identified TBE natural focus were sampled monthly from 04/2009 to 12/2018. Ticks were identified and pooled. Pools were tested by RT-qPCR. Positive pools were confirmed by virus isolation and/or sequencing of additional genes (E gene, NS2 gene). Temperature data such as the decadal (10-day) mean daily maximum air temperature (DMDMAT) were obtained from a nearby weather station and statistical correlations between tick occurrence and minimal infection rates (MIR) were calculated. In the study period from 04/2009 to 12/2018 a total of 15,530 ticks (2,226 females, 2,268 males, 11,036 nymphs) were collected. The overall MIR in nymphs over the whole period was 77/15,530 (0.49%), ranging from 0.09% (2009) to 1.36% (2015). The overall MIR of female ticks was 0.76% (17/2,226 ticks), range 0.14% (2013) to 3.59% (2016). The overall MIR of males was 0.57% (13/2,268 ticks), range from 0.26% (2009) to 0.97% (2015). The number of nymphs was statistically associated with a later start of spring/vegetation period, indicated by the onset of forsythia flowering. There was no particular correlation between DMDMAT dynamics in spring and/or autumn and the MIR of nymphs or adult ticks detected. However, there was a positive correlation between the number of nymphs and the number of reported human TBE cases in the following months, but not in the following year. The hypothesis of the importance of co-feeding of larvae and nymphs for the maintenance of transmission cycle of TBEV in nature is not supported by our findings.

Background Prone positioning (PP) has shown to improve survival in patients with severe acute respiratory distress syndrome (ARDS). To this point, it is unclear if PP is also beneficial for ARDS patients treated with veno-venous extracorporeal membrane oxygenation (VV ECMO) support. Methods We report retrospective data of a single-centre registry of patients with severe ARDS requiring VV ECMO support between October 2010 and May 2018. Patients were allocated to the PP group if PP was performed during VV ECMO treatment or the supine positioning group. VV ECMO weaning success and hospital survival were analysed before and after propensity score matching. Results A total of 158 patients could be analysed, and 38 patients (24.1%) received PP. There were no significant differences in VV ECMO weaning rate (47.4% vs. 46.7%, p  = 0.94) and hospital survival (36.8% vs. 36.7%, p  = 0.98) between the prone and supine groups, respectively. The analysis of 38 propensity score matched pairs also showed no difference in hospital survival (36.8% vs. 36.8%, p  = 1.0) or VV ECMO weaning rate (47.4% vs. 44.7%, p  = 0.82). Hospital survival was superior in the subgroup of patients treated with early PP (cutoff < 17 h via Youden’s Index) as compared to late or no PP (81.8% vs. 33.3%, p  = 0.02). Conclusion In this propensity score matched cohort of severe ARDS patients requiring VV ECMO support, prone positioning at any time was not associated with improved weaning or survival. However, early initiation of prone positioning was linked to a significant reduction of hospital mortality.

ABSTRACT BACKGROUND Delayed cerebral ischemia (DCI) has a strong impact on outcome of patients with aneurysmal subarachnoid hemorrhage (SAH). Positive effect of antiplatelet therapy on DCI rates has been supposed upon smaller SAH series. OBJECTIVE To analyze the benefit/risk profile of antiplatelet use in SAH patients. METHODS This retrospective case–control study was based on institutional observational cohort with 994 SAH patients treated between January 2003 and June 2016. The individuals with postcoiling antiplatelet therapy (aspirin with/without clopidogrel) were compared to a control group without antiplatelet therapy. Occurrence of DCI, major/minor bleeding events in the follow-up computed tomography scans, and favorable outcome at 6 mo after SAH (modified Rankin scale < 3) were compared in both groups. RESULTS Of 580 patients in the final analysis, 329 patients received post-treatment antiplatelet medication. There were no significant differences between the compared groups with regard to basic outcome confounders. Aspirin use was independently associated with reduced DCI risk (P < .001, adjusted odds ratio = 0.41, 95% confidence interval 0.24-0.65) and favorable outcome (P = .02, adjusted odds ratio = 1.78, 95% confidence interval 1.06-2.98). Regarding bleeding complications, aspirin was associated only with minor bleeding events (P = .02 vs P = .51 for major bleeding events). CONCLUSION Regular administration of aspirin might have a positive impact on DCI risk and outcome of SAH patients, without increasing the risk for clinically relevant bleeding events. In our SAH cohort, dual antiplatelet therapy showed no additional benefit on DCI risk, but increased the likelihood of major bleeding events.

Background Psychiatric comorbidities are relevant for the diagnostic and therapeutic regimes in somatic hospital care. The main aim of this study was to analyse the association between psychiatric comorbidities and hospital costs per inpatient episode. A further aim was to discuss and address the methodological challenges in the estimation of these outcomes based on retrospective data. Methods The study included 338,162 inpatient episodes consecutively discharged between 2011 and 2014 at a German university hospital. We used detailed resource use data to calculate day-specific hospital costs. We adjusted analyses for sex, age, somatic comorbidities and main diagnoses. We addressed potential time-related bias in retrospective diagnosis data with sensitivity analyses. Results Psychiatric comorbidities were associated with an increase in hospital costs per episode of 40% and an increase of reimbursement per episode of 28%, representing marginal effects of 1344 € and 1004 €, respectively. After controlling for length of stay, sensitivity analyses provided a lower bound increase in daily costs and reimbursement of 207 € and 151 €, respectively. Conclusion If differences in hospital costs between patient groups are not adequately accounted for in DRG-systems, perverse incentives are created that can reduce the efficiency of care. Therefore, we suggest intensifying the inclusion of psychiatric comorbidities in the German DRG system. Future research should investigate the appropriate inclusion of psychiatric comorbidities in other health care systems’ payment schemes.

The aim of this study was to describe the number and type of drugs used to treat depressive disorders in inpatient psychiatry and to analyse the determinants of potential drug-drug interactions (pDDI) and potentially inappropriate medication (PIM). Our study was part of a larger pharmacovigilance project funded by the German Innovation Funds. It included all inpatients with a main diagnosis in the group of depressive episodes (F32, ICD-10) or recurrent depressive disorders (F33) discharged from eight psychiatric hospitals in Germany between 1 October 2017 and 30 September 2018 or between 1 January and 31 December 2019. The study included 14,418 inpatient cases. The mean number of drugs per day was 3.7 (psychotropic drugs = 1.7; others = 2.0). Thirty-one percent of cases received at least five drugs simultaneously (polypharmacy). Almost one half of all cases received a combination of multiple antidepressant drugs (24.8%, 95% CI 24.1%-25.5%) or a treatment with antidepressant drugs augmented by antipsychotic drugs (21.9%, 95% CI 21.3%-22.6%). The most frequently used antidepressants were selective serotonin reuptake inhibitors, followed by serotonin and norepinephrine reuptake inhibitors and tetracyclic antidepressants. In multivariate analyses, cases with recurrent depressive disorders and cases with severe depression were more likely to receive a combination of multiple antidepressant drugs (Odds ratio recurrent depressive disorder: 1.56, 95% CI 1.41-1.70, severe depression 1.33, 95% CI 1.18-1.48). The risk of any pDDI and PIM in elderly patients increased substantially with each additional drug (Odds Ratio: pDDI 1.32, 95% CI: 1.27-1.38, PIM 1.18, 95% CI: 1.14-1.22) and severity of disease (Odds Ratio per point on CGI-Scale: pDDI 1.29, 95% CI: 1.11-1.46, PIM 1.27, 95% CI: 1.11-1.44), respectively. This study identified potential sources and determinants of safety risks in pharmacotherapy of depressive disorders and provided additional data which were previously unavailable. Most inpatients with depressive disorders receive multiple psychotropic and non-psychotropic drugs and pDDI and PIM are relatively frequent. Patients with a high number of different drugs must be intensively monitored in the management of their individual drug-related risk-benefit profiles.