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Abstract Background Post-viral symptoms have long been known in the medical community but have received more public attention during the COVID-19 pandemic. Many post-viral symptoms were reported as particularly frequent after SARS-CoV-2 infection. However, there is still a lack of evidence regarding the specificity, frequency and persistence of these symptoms in comparison to other viral infectious diseases such as influenza. Methods We investigated a large population-based cohort based on German routine healthcare data. We matched 573,791 individuals with a PCR-test confirmed SARS-CoV-2 infection from the year 2020 to contemporary controls without SARS-CoV-2 infection and controls from the last influenza outbreak in 2018 and followed them up to 18 months. Results We found that post-viral symptoms as defined for COVID-19 by the WHO as well as tissue damage were more frequent among the COVID-19 cohort than the influenza or contemporary control cohort. The persistence of post-viral symptoms was similar between COVID-19 and influenza. Conclusion Post-viral symptoms following SARS-CoV-2 infection constitute a substantial disease burden as they are frequent and often persist for many months. As COVID-19 is becoming endemic, the disease must not be trivialized. Research should focus on the development of effective treatments for post-viral symptoms.

Abstract Background Certified cancer centers aim to ensure high-quality care by establishing structural and procedural standards according to evidence-based guidelines. Despite the high clinical and health policy relevance, evidence from a nation-wide study for the effectiveness of care for colorectal cancer in certified centers vs. other hospitals in Germany is still missing. Methods In a retrospective cohort study covering the years 2009–2017, we analyzed patient data using demographic information, diagnoses, and treatments from a nationwide statutory health insurance enriched with information on certification. We investigated whether patients with incident colon or rectal cancer did benefit from primary therapy in a certified cancer center. We used relative survival analysis taking into account mortality data of the German population and adjustment for patient and hospital characteristics via Cox regression with shared frailty for patients in hospitals with and without certification. Results The cohorts for colon and rectal cancer consisted of 109,518 and 51,417 patients, respectively, treated in a total of 1052 hospitals. 37.2% of patients with colon and 42.9% of patients with rectal cancer were treated in a certified center. Patient age, sex, comorbidities, secondary malignoma, and distant metastases were similar across groups (certified/non-certified) for both colon and rectal cancer. Relative survival analysis showed significantly better survival of patients treated in a certified center, with 68.3% (non-certified hospitals 65.8%) 5-year survival for treatment of colon cancer in certified (p

Abstract 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.

Abstract 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 ).

Abstract Despite the relevance of pressure ulcers (PU) in inpatient care, the predictive power and role of care-related risk factors (e.g. anesthesia) remain unclear. We investigated the predictability of PU incidence and its association with multiple care variables. We included all somatic cases between 2014 and 2018 with length of stay ≥ 2d in a German university hospital. For regression analyses and prediction we used Bayesian Additive Regression Trees (BART) as nonparametric modeling approach. To assess predictive accuracy, we compared BART, random forest, logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) using area under the curve (AUC), confusion matrices and multiple indicators of predictive performance (e.g. sensitivity, specificity, F1, positive/ negative predictive value) in the full dataset and subgroups. Analysing 149,006 cases revealed high predictive variable importance and associations between incident PU and ventilation, age, anesthesia (≥ 1 h) and number of care-involved wards. Despite high AUCs (range 0.89–0.90), many false negative predictions led to low sensitivity (range 0.04–0.10). Ventilation, age, anesthesia and number of care-involved wards were associated with incident PU. Using anesthesia as a proxy for immobility, an hourly repositioning is indicated. The low sensitivity indicates major challenges for correctly predicting PU based on routine data.

Abstract 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.

BackgroundLong-term health sequelae of the Coronavirus Disease 2019 (COVID-19) are a major public health concern. However, evidence on post-acute COVID-19 syndrome (post-COVID-19) is still limited, particularly for children and adolescents. Utilizing comprehensive healthcare data on approximately 46% of the German population, we investigated post-COVID-19-associated morbidity in children/adolescents and adults.Methods and findingsWe used routine data from German statutory health insurance organizations covering the period between January 1, 2019 and December 31, 2020. The base population included all individuals insured for at least 1 day in 2020. Based on documented diagnoses, we identified individuals with polymerase chain reaction (PCR)-confirmed COVID-19 through June 30, 2020. A control cohort was assigned using 1:5 exact matching on age and sex, and propensity score matching on preexisting medical conditions. The date of COVID-19 diagnosis was used as index date for both cohorts, which were followed for incident morbidity outcomes documented in the second quarter after index date or later.Overall, 96 prespecified outcomes were aggregated into 13 diagnosis/symptom complexes and 3 domains (physical health, mental health, and physical/mental overlap domain). We used Poisson regression to estimate incidence rate ratios (IRRs) with 95% confidence intervals (95% CIs). The study population included 11,950 children/adolescents (48.1% female, 67.2% aged between 0 and 11 years) and 145,184 adults (60.2% female, 51.1% aged between 18 and 49 years). The mean follow-up time was 236 days (standard deviation (SD) = 44 days, range = 121 to 339 days) in children/adolescents and 254 days (SD = 36 days, range = 93 to 340 days) in adults. COVID-19 and control cohort were well balanced regarding covariates. The specific outcomes with the highest IRR and an incidence rate (IR) of at least 1/100 person-years in the COVID-19 cohort in children and adolescents were malaise/fatigue/exhaustion (IRR: 2.28, 95% CI: 1.71 to 3.06, p < 0.01, IR COVID-19: 12.58, IR Control: 5.51), cough (IRR: 1.74, 95% CI: 1.48 to 2.04, p < 0.01, IR COVID-19: 36.56, IR Control: 21.06), and throat/chest pain (IRR: 1.72, 95% CI: 1.39 to 2.12, p < 0.01, IR COVID-19: 20.01, IR Control: 11.66). In adults, these included disturbances of smell and taste (IRR: 6.69, 95% CI: 5.88 to 7.60, p < 0.01, IR COVID-19: 12.42, IR Control: 1.86), fever (IRR: 3.33, 95% CI: 3.01 to 3.68, p < 0.01, IR COVID-19: 11.53, IR Control: 3.46), and dyspnea (IRR: 2.88, 95% CI: 2.74 to 3.02, p < 0.01, IR COVID-19: 43.91, IR Control: 15.27). For all health outcomes combined, IRs per 1,000 person-years in the COVID-19 cohort were significantly higher than those in the control cohort in both children/adolescents (IRR: 1.30, 95% CI: 1.25 to 1.35, p < 0.01, IR COVID-19: 436.91, IR Control: 335.98) and adults (IRR: 1.33, 95% CI: 1.31 to 1.34, p < 0.01, IR COVID-19: 615.82, IR Control: 464.15). The relative magnitude of increased documented morbidity was similar for the physical, mental, and physical/mental overlap domain. In the COVID-19 cohort, IRs were significantly higher in all 13 diagnosis/symptom complexes in adults and in 10 diagnosis/symptom complexes in children/adolescents. IRR estimates were similar for age groups 0 to 11 and 12 to 17. IRs in children/adolescents were consistently lower than those in adults. Limitations of our study include potentially unmeasured confounding and detection bias.ConclusionsIn this retrospective matched cohort study, we observed significant new onset morbidity in children, adolescents, and adults across 13 prespecified diagnosis/symptom complexes, following COVID-19 infection. These findings expand the existing available evidence on post-COVID-19 conditions in younger age groups and confirm previous findings in adults.Trial registrationClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT05074953.

Abstract Background Total knee replacement (TKR) is one of the most commonly performed routine procedures in the world. Prognostic studies indicate that the number of TKR will further increase constituting growing burden on healthcare systems. There is also substantial regional heterogeneity in TKR rates within and between countries. Despite the known therapeutic effects, a subset of patients undergoing TKR does not benefit from the procedure as intended. To improve the appropriateness of TKR indication, the EKIT initiative (“evidence and consensus based indication critera for total arthroplasty”) developed a clinical guideline for Germany on the indication of TKR. This guideline is the basis for a digital medical decision aid (EKIT tool) to facilitate shared decision making (SDM) in order to improve decision quality for elective surgery. The aim of this cluster randomized trial is to investigate the effectiveness of the EKIT tool on decision quality. Methods The Value-based TKR study is a prospective pragmatic multi-center, stepped wedge, cluster randomized controlled trial (SW-RCT). The EKIT tool provides (1) a systematic presentation of individual patient and disease-specific information (symptoms, expectations), (2) the fulfillment of the indication criteria and (3) health information about safety and effectiveness of TKR. All study sites will follow routine care as control clusters until the start of the intervention. In total, there will be 10 clusters (study sites) and 6 sequential steps over 16 month, with clusters receiving the intervention with a minimum 2 months of standard routine care. The primary outcome is patients’ decision quality measured with the Decision Quality Instrument (DQI)-Knee Osteoarthritis questionnaire. Furthermore, we will collect information on global patient satisfaction, patient reported outcome measures and the fulfilment of the individual expectations 12 months after SDM. The power calculation yielded an estimated power of 89% using robust Poisson regression under the following assumptions: 10 study sites with a total of N=1,080 patients (including a dropout rate of 11%), a 10% increase in decision quality due to the use of the EKIT tool, and a significance level of 5%. Discussion There is a high potential for transferring the intervention into routine practice if the evaluation is positive. Trial registration ClinicalTrials.gov: NCT04837053 . Registered on 08/04/2021.

Objectives Studies 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.Design Cross-sectional study.Setting German inpatient routine care data of colorectal resections between 2016 and 2018.Participants We 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 measures Additionally 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.Results Weekend 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).Conclusions Transfer 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 number ISRCTN10188560.

BackgroundThe standardized mortality ratio (SMR) is often used to assess and compare hospital performance. While it has been recognized that hospitals may differ in their SMRs due to differences in patient composition, there is a lack of rigorous analysis of this and other-largely unrecognized-properties of the SMR.MethodsThis paper proposes five axiomatic requirements for adequate standardized mortality measures: strict monotonicity (monotone relation to actual mortality rates), case-mix insensitivity (independence of patient composition), scale insensitivity (independence of hospital size), equivalence principle (equal rating of hospitals with equal actual mortality rates in all patient groups), and dominance principle (better rating of unambiguously better performing hospitals). Given these axiomatic requirements, effects of variations in patient composition, hospital size, and actual and expected mortality rates on the SMR were examined using basic algebra and calculus. In this regard, we distinguished between standardization using expected mortality rates derived from a different dataset (external standardization) and standardization based on a dataset including the considered hospitals (internal standardization). The results were illustrated by hypothetical examples.ResultsUnder external standardization, the SMR fulfills the axiomatic requirements of strict monotonicity and scale insensitivity but violates the requirement of case-mix insensitivity, the equivalence principle, and the dominance principle. All axiomatic requirements not fulfilled under external standardization are also not fulfilled under internal standardization. In addition, the SMR under internal standardization is scale sensitive and violates the axiomatic requirement of strict monotonicity.ConclusionsThe SMR fulfills only two (none) out of the five proposed axiomatic requirements under external (internal) standardization. Generally, the SMRs of hospitals are differently affected by variations in case mix and actual and expected mortality rates unless the hospitals are identical in these characteristics. These properties hamper valid assessment and comparison of hospital performance based on the SMR.

Due to increasing demand and scarce financial resources for healthcare, health system efficiency has become a major topic in political and scientific debates. While previous studies investigating determinants of health system efficiency focused primarily on economic and social influence factors, the role of the political regime has been neglected. In addition, there is a lack of formal theoretical work on this specific topic, which ensures transparency and logical consistency of arguments and implications. Using a public choice approach, this paper provides a rigorous theoretical and empirical investigation of the relationships between health system efficiency and political institutions. We develop a simple principal-agent model describing the behavior of a government with respect to investments in population health under different political regimes. The main implication of the theoretical model is that governments under more democratic regimes put more effort in reducing embezzlement of health expenditure than non-democratic regimes. Accordingly, democratic countries are predicted to have more efficient health systems than non-democratic countries. We test this hypothesis based on a broad dataset including 158 countries over the period 1995-2015. The empirical results clearly support the implications of the theoretical model and withstand several robustness checks, including the use of alternative indicators for population health and democracy and estimations accounting for endogeneity. The empirical results also indicate that the effect of democracy on health system efficiency is more pronounced in countries with higher income levels. From a policy perspective, we discuss the implications of our findings in the context of health development assistance.

BACKGROUND:The conceptualization of hospital quality indicators usually includes some form of risk adjustment to account for hospital differences in case mix. For binary outcome variables like in-hospital mortality, frequently utilized risk adjusted measures include the standardized mortality ratio (SMR), the risk standardized mortality rate (RSMR), and excess risk (ER). All of these measures require the estimation of expected hospital mortality, which is often based on logistic regression models. In this context, an issue that is often neglected is correlation between hospital performance (e.g. care quality) and patient-specific risk factors. The objective of this study was to investigate the impact of such correlation on the adequacy of hospital rankings based on different measures and methods. METHODS:Using Monte Carlo simulation, the impact of correlation between hospital care quality and patient-specific risk factors on the adequacy of hospital rankings was assessed for SMR/RSMR, and ER based on logistic regression and random effects logistic regression. As an alternative method, fixed effects logistic regression with Firth correction was considered. The adequacies of the resulting hospital rankings were assessed by the shares of hospitals correctly classified into quintiles according to their true (unobserved) care qualities. RESULTS:The performance of risk adjustment approaches based on logistic regression and random effects logistic regression declined when correlation between care quality and a risk factor was induced. In contrast, fixed-effects-based estimations proved to be more robust. This was particularly true for fixed-effects-logistic-regression-based ER. In the absence of correlation between risk factors and care quality, all approaches showed similar performance. CONCLUSIONS:Correlation between risk factors and hospital performance may severely bias hospital rankings based on logistic regression and random effects logistic regression. ER based on fixed effects logistic regression with Firth correction should be considered as an alternative approach to assess hospital performance.