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Aim We aimed to develop a risk score to calculate a person’s individual risk for a severe COVID-19 course (POINTED score) to support prioritization of especially vulnerable patients for a (booster) vaccination. Subject and methods This cohort study was based on German claims data and included 623,363 individuals with a COVID-19 diagnosis in 2020. The outcome was COVID-19 related treatment in an intensive care unit, mechanical ventilation, or death after a COVID-19 infection. Data were split into a training and a test sample. Poisson regression models with robust standard errors including 35 predefined risk factors were calculated. Coefficients were rescaled with a min–max normalization to derive numeric score values between 0 and 20 for each risk factor. The scores’ discriminatory ability was evaluated by calculating the area under the curve (AUC). Results Besides age, down syndrome and hematologic cancer with therapy, immunosuppressive therapy, and other neurological conditions were the risk factors with the highest risk for a severe COVID-19 course. The AUC of the POINTED score was 0.889, indicating very good predictive validity. Conclusion The POINTED score is a valid tool to calculate a person’s risk for a severe COVID-19 course.

ObjectivesTo investigate whether the risk of developing an incident autoimmune disease is increased in patients with previous COVID-19 disease compared to people without COVID-19.MethodA cohort was selected from German routine health care data covering 38.9 million individuals. Based on documented diagnoses, we identified individuals with polymerase chain reaction (PCR)-confirmed COVID-19 through December 31, 2020. Patients were matched 1:3 to control patients without COVID-19. Both groups were followed up until June 30, 2021. We used the four quarters preceding the index date until the end of follow-up to analyze the onset of autoimmune diseases during the post-acute period. Incidence rates (IR) per 1000 person-years were calculated for each outcome and patient group. Poisson models were deployed to estimate the incidence rate ratios (IRRs) of developing an autoimmune disease conditional on a preceding diagnosis of COVID-19.ResultsIn total, 641,704 patients with COVID-19 were included. Comparing the incidence rates in the COVID-19 (IR=15.05, 95% CI: 14.69-15.42) and matched control groups (IR=10.55, 95% CI: 10.25-10.86), we found a 42.63% higher likelihood of acquiring autoimmunity for patients who had suffered from COVID-19. This estimate was similar for common autoimmune diseases, such as Hashimoto thyroiditis, rheumatoid arthritis, or Sjögren syndrome. The highest IRR was observed for autoimmune disease of the vasculitis group. Patients with a more severe course of COVID-19 were at a greater risk for incident autoimmune diseases.ConclusionsSARS-CoV-2 infection is associated with an increased risk of developing new-onset autoimmune diseases after the acute phase of infection.

The connection between Pediatric Inflammatory Multisystem Syndrome (PIMS) and Kawasaki Disease (KD) is not yet fully understood. Using the same national registry, clinical features and outcome of children hospitalized in Germany, and Innsbruck (Austria) were compared. Reported to the registry were 395 PIMS and 69 KD hospitalized patients. Patient age in PIMS cases was higher than in KD cases (median 7 [IQR 4–11] vs. 3 [IQR 1–4] years). A majority of both PIMS and KD patients were male and without comorbidities. PIMS patients more frequently presented with organ dysfunction, with the gastrointestinal (80%), cardiovascular (74%), and respiratory (52%) systems being most commonly affected. By contrast, KD patients more often displayed dermatological (99% vs. 68%) and mucosal changes (94% vs. 64%), plus cervical lymph node swelling (51% vs. 34%). Intensive care admission (48% vs. 19%), pulmonary support (32% vs. 10%), and use of inotropes/vasodilators (28% vs. 3%) were higher among PIMS cases. No patients died. Upon patient discharge, potentially irreversible sequelae – mainly cardiovascular – were reported (7% PIMS vs. 12% KD). Despite differences in age distribution and disease severity, PIMS and KD cases shared many common clinical and prognostic characteristics. This supports the hypothesis that the two entities represent a syndrome continuum.

This paper examines the transnational dimensions of low-level conflict and state repression. In this regard, special emphasis is placed on the role of political regimes. Drawing on a simple model, we argue that democracy has opposing effects on conflict intensity. On one hand, democracy satisfies demand for political participation and thus reduces conflict potential, while, on the other hand, we highlight that domestic democracy may spur dissatisfaction and conflict abroad, which, in turn, may induce conflict spillovers. As a result, the net effect of democracy on low-level conflict and state repression is ambiguous and depends on the level of democracy in the neighborhood: We predict that democracy is more pacifying in democratic environments and may spur conflict in autocratic environments. By the symmetry of the model, we also predict that democratic environments are more pacifying for democratic countries and may spur conflict in autocracies. Empirical evidence using panel data on different types of low-level conflict and state repression for 160 countries in the period from 1950 to 2011 supports these hypotheses. Additionally, two case studies illustrate the mechanisms of our model.

Purpose Multimorbidity leads to decreasing health-related quality of life (HRQoL). Telemedicine may help to improve HRQoL. The present study was conducted to show (I) differences in HRQoL and changes in HRQoL over time in elderly, multimorbid individuals with and without depression and/or mild cognitive impairment (MCI) using a telemonitoring application (TMA) and (II) associations between engagement with measurements by study participants using a TMA and changes in their HRQoL. Methods The present feasibility study was part of a longitudinal intervention study. Recruited general practitioners (GPs) enrolled individuals and assigned them to risk groups according to absence/presence of depression and/or MCI. Depression was assessed using the Geriatric Depression Scale (GDS-15), MCI using the Mini-Mental State Examination (MMSE), and HRQoL using the SF-12. The TMA consisted of tablets, software, and measuring devices. Measured vital data were transferred to a care and case manager for monitoring and possible intervention. Results Nine GPs recruited 177 individuals, 97 of whom were included in the HRQoL analysis. Significantly lower physical and mental component summary (PCS/MCS) scores were revealed in study participants with depression, and with both depression and MCI, compared to participants with no mental disorders. PCS scores did not differ between study dates, but MCS scores had significantly increased over time. Participants’ engagement with measurements was significantly associated with an increased MCS score, but not with the PCS score. Discussion Depression and/or MCI are negatively associated with the HRQoL of elderly, multimorbid people using a TMA. Engagement of individuals with vital data measurements via a TMA may increase their mental HRQoL. Mentally impaired people should be closely involved as co-designers and experts in development processes of TMAs to benefit from tailored solutions. An individual’s increased mental HRQoL can be a decisive factor in their engagement with a GP treatment regimen and telemonitoring processes.

Introduction: Medical care of soft-tissue sarcoma (STS) and bone sarcoma (BS) patients in Germany has rarely been investigated. The objectives of this article were (1) to investigate medical care and survival in STS and BS patients, and (2) to examine methodological aspects of corresponding analyses based on administrative healthcare data. Methods: We analyzed data from a statutory health insurance located in Saxony, Germany, covering approximately 2 million individuals. We identified incident STS and BS patients in the period 2012–2016 using 4 different case definitions. We examined treatment rates and visits to medical oncologists and medical practices descriptively, and then compared results between case definitions. We investigated survival prospects using a relative survival analysis and estimated hazard ratios (HRs) for risk factors for mortality using Cox regression. Results: Across case definitions, the number of included sarcoma patients (STS: n = 871–1,757; BS: n = 216–689) and applied treatments (STS: 42.2–83.1%; BS: 28.3–77.8%) varied substantially. Irrespective of the case definition, the minority of patients visited medical oncologists (STS: 9.8–10.8% BS: 4.4–7.9%) and “experienced” medical practices (STS: 27.7–38.4%; BS: 18.3–23.6%). Survival prospects were better for patients who visited “experienced” medical practices (STS: HR = 0.55; BS: HR = 0.42). Conclusion: Treatment rates clearly

Simple Summary Novel therapies have become available in the routine care of metastatic melanoma in recent years. We conducted a retrospective cohort study based on SHI data from Germany (2010–2020) to investigate overall mortality between patients that received different substance classes. We included 463 patients with distant metastases in the main analysis. Classical chemotherapeutics (CTx) as well as targeted therapeutics (TT) and immune checkpoint inhibitors (ICI) showed protective effects after treatment initiation, which decreased over time. Predicted survival of an average patient over five years since first metastasis was best by sequential treatment with ICI and TT. The worst survival was seen in patients treated with TT alone. However, it is conceivable that the observed high survival differences were overestimated due to bias, such as confounding by indication. It is likely that patients treated exclusively with TT were in an extremely serious condition and died before they could have received an ICI. Abstract (1) Background: Targeted (TT) and immune checkpoint inhibitor (ICI) therapies have become available in the routine care of metastatic melanoma in recent years. (2) Objective: We compared mortality in patients with metastatic melanoma and different systemic therapies. (3) Methods: A retrospective cohort study, based on pseudonymized health insurance data of about two million individuals from Saxony, Germany, was conducted for the years 2010 to 2020. Only patients with an advanced stage, i.e., distant metastases were considered for the main analysis. Relative survival since metastasis and predicted survivor curves derived from a Cox model were used to assess potential differences in mortality. (4) Results: Relative survival was highest in the subgroup with sequential use of ICI and TT. All treatments except interferon had significant hazard ratios (HR) in the Cox model with time-dependent effects indicating a protective effect after treatment initiation (HR 0.01–0.146) but decreasing over time (HR 1.351–2.310). The predicted survivor curves revealed best survival under ICI-TT treatment and worst survival under TT treatment alone. (5) Conclusions: We found real-world evidence for survival benefits of patients with metastatic melanoma who received sequential ICI and TT treatment. It is conceivable that the observed high survival differences were overestimated due to bias, such as confounding by indication.

Background Treatment of cancer patients in certified cancer centers, that meet specific quality standards in term of structures and procedures of medical care, is a national treatment goal in Germany. However, convincing evidence that treatment in certified cancer centers is associated with better outcomes in patients with pancreatic cancer is still missing. Methods We used patient-specific information (demographic characteristics, diagnoses, treatments) from German statutory health insurance data covering the period 2009–2017 and hospital characteristics from the German Standardized Quality Reports. We investigated differences in survival between patients treated in hospitals with and without pancreatic cancer center certification by the German Cancer Society (GCS) using the Kaplan–Meier estimator and Cox regression with shared frailty. Results The final sample included 45,318 patients with pancreatic cancer treated in 1,051 hospitals (96 GCS-certified, 955 not GCS-certified). 5,426 (12.0%) of the patients were treated in GCS-certified pancreatic cancer centers. Patients treated in certified and non-certified hospitals had similar distributions of age, sex, and comorbidities. Median survival was 8.0 months in GCS-certified pancreatic cancer centers and 4.4 months in non-certified hospitals. Cox regression adjusting for multiple patient and hospital characteristics yielded a significantly lower hazard of long-term, all-cause mortality in patients treated in GCS-certified pancreatic centers (Hazard ratio = 0.89; 95%-CI = 0.85–0.93). This result remained robust in multiple sensitivity analyses, including stratified estimations for subgroups of patients and hospitals. Conclusion This robust observational evidence suggests that patients with pancreatic cancer benefit from treatment in a certified cancer center in terms of survival. Therefore, the certification of hospitals appears to be a powerful strategy to improve patient outcomes in pancreatic cancer care. Trial registration ClinicalTrials.gov (NCT04334239).

The primary objective of the IMPRESS study is to assess the causal effects of the IQM peer review on mortality in patients ventilated > 24 h. Secondary analyses are conducted for mortality in patients with myocardial infarction, stroke, COPD, pneumonia, and the procedural provision of a colorectal resection. This article provides a description of the study design and presents baseline results. Descriptive statistics for 231 included hospitals and patient characteristics. Due to randomization, the treatment/control group hospitals were similar with respect to the mortality in patients ventilated > 24 h and other patient and hospital characteristics at baseline. Mortality was highest (lowest) in patients ventilated > 24 h (with colorectal resection). The IMPRESS study provides a unique opportunity to assess the impact of the IQM peer review on the mortality in patients ventilated > 24 h. The secondary, exploratory, and qualitative analyses are expected to provide insights on determinants of in-hospital mortality, structure and process quality, and the robustness of different approaches to risk adjustment of quality indicators.

Despite extensive research, there is no agreement on the value of the elasticity of substitution between capital and labour at the aggregate or the industrial level. Utilizing 2,419 estimates from 77 studies published between 1961 and 2017, this paper provides the first meta‐regression analysis for the US economy. We show that the heterogeneity in previously reported estimates is driven primarily by modelling decisions for technological dynamics. Throughout the analysis, the hypothesis of a Cobb–Douglas production function is rejected. Based on our meta‐regression sample, we estimate a long‐run meta‐elasticity for the aggregate economy in the range of 0.45–0.87. Most industrial estimates do not deviate significantly from the estimate for the aggregate economy.

While most of the theoretical literature suggests that democracy promotes the provision of public goods, the findings of empirical studies are inconclusive. Drawing on a simple model, this paper aims at reconciling theory and evidence. We argue that the stronger dependence of more democratic governments upon public support has two opposing effects: on the one hand, it encourages these governments to increase goods provision in order to generate more loyalty. On the other hand, it raises the leaders’ incentives for kleptocratic behavior. The model predicts that the latter effect may dominate in poor countries. In countries with higher income levels, democracy is expected to increase public goods provision. Utilizing 11 indicators of education, health, infrastructure and governance both hypotheses are confirmed by panel regressions including 154 countries over the period from 1960 to 2014. We also show that the omission of per capita income as a moderator variable of democracy may result in small and insignificant empirical estimates.

ObjectivesStudies analysing colorectal resections usually focus on a specific outcome (eg, mortality) and/or specific risk factors at the individual (eg, comorbidities) or hospital (eg, volume) level. Comprehensive evidence across different patient safety outcomes, risk factors and patient groups is still scarce. Therefore the aim of this analysis was to investigate consistent relationships between multiple patient safety outcomes, healthcare and hospital risk factors in colorectal resection cases.DesignCross-sectional study.SettingGerman inpatient routine care data of colorectal resections between 2016 and 2018.ParticipantsWe analysed 54 168 colon resection and 20 395 rectum resection cases treated in German hospitals. The German Inpatient Quality Indicators were used to define colon resections and rectum resections transparently.Primary outcome measuresAdditionally to in-hospital death, postoperative respiratory failure, renal failure and postoperative wound infections we included multiple patient safety outcomes as primary outcomes/dependent variables for our analysis. Healthcare (eg, weekend surgery), hospital (eg, volume) and case (eg, age) characteristics served as independent covariates in a multilevel logistic regression model. The estimated regression coefficients were transferred into ORs.ResultsWeekend surgery, emergency admissions and transfers from other hospitals were significantly associated (ORs ranged from 1.1 to 2.6) with poor patient safety outcome (ie, death, renal failure, postoperative respiratory failure) in colon resections and rectum resections. Hospital characteristics showed heterogeneous effects. In colon resections hospital volume was associated with insignificant or adverse associations (postoperative wound infections: OR 1.168 (95% CI 1.030 to 1.325)) to multiple patient safety outcomes. In rectum resections hospital volume was protectively associated with death, renal failure and postoperative respiratory failure (ORs ranged from 0.7 to 0.8).ConclusionsTransfer from other hospital and emergency admission are constantly associated with poor patient safety outcome. Hospital variables like volume, ownership or localisation did not show consistent relationships to patient safety outcomes.Trial registration numberISRCTN10188560.

BackgroundAlthough clinical peer review is a well-established instrument for improving quality of care, clinical effectiveness is unclear.MethodsIn a pragmatic cluster randomised controlled trial, we randomly assigned 60 German Initiative Qualitätsmedizin member hospitals with the highest mortality rates in ventilated patients in 2016 to intervention and control groups. The primary outcome was hospital mortality rate in patients ventilated fore more than 24 hours. Clinical peer review was conducted in intervention group hospitals only. We assessed the impact of clinical peer review on mortality using a difference-in-difference approach by applying weighted least squares (WLS) regression to changes in age-adjusted and sex-adjusted standardised mortality ratios (SMRs) 1 year before and 1 year after treatment. Recommendations for improvement from clinical peer review and hospital survey data were used for impact and process analysis.ResultsWe analysed 12 058 and 13 016 patients ventilated fore more than 24 hours in the intervention and control hospitals within the 1-year observation period. In-hospital mortality rates and SMRs were 40.6% and 1.23 in intervention group and 41.9% and 1.28 in control group hospitals in the preintervention period, respectively. The groups showed similar hospital (bed size, ownership) and patient (age, sex, mortality, main indications) characteristics. WLS regression did not yield a significant difference between intervention and control groups regarding changes in SMRs (estimate=0.04, 95% CI= −0.05 to 0.13, p=0.38). Mortality remained high in both groups (intervention: 41.8%, control: 42.1%). Impact and process analysis indicated few perceived outcome improvements or implemented process improvements following the introduction of clinical peer review.ConclusionsThis study did not provide evidence for reductions in mortality in patients ventilated for more than 24 hours due to clinical peer review. A stronger focus on identification of structures and care processes related to mortality is required to improve the effectiveness of clinical peer review.

ObjectiveTo characterize the clinical features of children and adolescents hospitalized with SARS-CoV-2 infections and to explore predictors for disease severity.DesignNationwide prospective observational cohort study.SettingData collected from 169 out of 351 children’s hospitals in Germany between March 18, 2020 and April 30, 2021 and comparison with the Statutory Notification System.Participants1,501 children and adolescents up to 19 years of age with laboratory confirmed SARS-CoV-2 infections who were admitted to children’s hospitals and subsequently reported to the COVID-19 registry of the German Pediatric Infectious Disease Society (DGPI).Main outcome measuresAdmission to intensive care, in-hospital.ResultsAs compared to the information in the statutory notification system, up to 30% of all children and adolescents hospitalized in Germany during the study period were reported to the DGPI registry. Median age was three years (IQR, 0-12), with 36% of reported cases being infants. Although roughly half of patients in the registry were not admitted to the hospital due to their SARS-CoV-2 infection, 72% showed infection-related symptoms during hospitalization. Preexisting comorbidities were present in 28%, most commonly respiratory disorders, followed by neurological, neuromuscular, and cardiovascular diseases. Median length of hospitalization was five days (IQR 3-10). Only 20% of patients received a SARS-CoV-2-related therapy. Infants were less likely to require therapy as compared to older children. Overall, 111 children and adolescents were admitted to intensive care units (ICU). In a fully adjusted model, patient age, trisomy 21, coinfections and primary immunodeficiencies (PID) were significantly associated with intensive care treatment. In a bivariate analysis, pulmonary hypertension, cyanotic heart disease, status post (s/p) cardiac surgery, fatty liver disease, epilepsy and neuromuscular impairment were statistically significant risk factors for ICU admission.ConclusionOverall, a small proportion of children and adolescents was hospitalized in Germany during the first year of the pandemic. The majority of patients within our registry was not admitted due to COVID-19 suggesting an overestimation of the disease burden even in hospitalized children. Nevertheless, a large proportion of children and adolescents with confirmed COVID-19 reported in Germany could be captured. This allowed for detailed assessment of overall disease severity and underlying risk factors in our cohort. The main risk factors for COVID-19 disease associated intensive care treatment were older patient age, trisomy 21, PIDs and coinfection at the time of hospitalization.Trial registrationRegistry of hospitalized pediatric patients with SARS-CoV-2 infection (COVID-19), DRKS00021506

Background Relationships between in-hospital mortality and case volume were investigated for various patient groups in many empirical studies with mixed results. Typically, those studies relied on (semi-)parametric statistical models like logistic regression. Those models impose strong assumptions on the functional form of the relationship between outcome and case volume. The aim of this study was to determine associations between in-hospital mortality and hospital case volume using random forest as a flexible, nonparametric machine learning method. Methods We analyzed a sample of 753,895 hospital cases with stroke, myocardial infarction, ventilation > 24 h, COPD, pneumonia, and colorectal cancer undergoing colorectal resection treated in 233 German hospitals over the period 2016–2018. We derived partial dependence functions from random forest estimates capturing the relationship between the patient-specific probability of in-hospital death and hospital case volume for each of the six considered patient groups. Results Across all patient groups, the smallest hospital volumes were consistently related to the highest predicted probabilities of in-hospital death. We found strong relationships between in-hospital mortality and hospital case volume for hospitals treating a (very) small number of cases. Slightly higher case volumes were associated with substantially lower mortality. The estimated relationships between in-hospital mortality and case volume were nonlinear and nonmonotonic. Conclusion Our analysis revealed strong relationships between in-hospital mortality and hospital case volume in hospitals treating a small number of cases. The nonlinearity and nonmonotonicity of the estimated relationships indicate that studies applying conventional statistical approaches like logistic regression should consider these relationships adequately.

Background: Prolonged ventilation is associated with a high risk of death. This study investigated both patient-level and hospital-level risk factors for in-hospital mortality in patients ventilated for more than 24 hours. Methods: The analyses were conducted in the framework of a German national multicenter retrospective cohort study. Patient and hospital characteristics were examined using descriptive statistics. Risk factors of in-hospital mortality were analyzed using multilevel robust Poisson regressions for binary outcomes. Potential effect modifications were examined by stratified analyses. Results: The sample includes 95 672 cases of patients ventilated >24 hours in 163 hospitals covering the period 2016 to 2017. According to the results of multilevel Poisson regressions, main patient-level risk factors for in-hospital mortality were age (per year relative risk [RR] = 1.021, 95% CI = 1.020-1.023), stroke (RR = 1.459; 95% CI = 1.361-1.563), emergency case admission (RR = 1.273, 95% CI = 1.156-1.403), and transfer from another hospital (RR = 1.169, 95% CI = 1.084-1.261). The individual risk of in-hospital death was positively associated with hospital size (RR of hospitals with 600-799 beds vs Conclusion: By providing evidence on multiple patient-level and hospital-level risk factors for in-hospital mortality in patients ventilated for more than 24 hours, this large multicenter study has main implications for quality assessment of clinical care and the adequate specification of risk adjustment models. The revealed effect modifications indicate the relevance of stratified analyses.

Three bottom habitats in Biscayne Bay were sampled by 120 trawl samples taken during both day and night from April to August 1963. Daylight samples contained 1,391 fishes representing 41 species. Night samples contained 1,440 fishes and 49 species. The number of species per sample followed a Poisson distribution, the number of individuals per sample followed a negative binomial distribution, and the number of individuals per species followed Fisher's logarithmic series. The following generalizations apply to both number of species and number of individuals. More fishes were taken in the Thalassia area than in the Thalassia-sand area, which in turn had more than the mud-sand area. More were taken at night than during the day. Tidal direction had no significant effect. Analysis of data on the sample variance for paired 2-minute samples showed that seven to eight replicates are needed to detect a difference of five species and 10 samples are needed to detect a 10% change in the number of individuals...