Monitoring of Argatroban in Critically Ill Patients: A Prospective Study Comparing Activated Partial Thromboplastin Time, Point-of-Care Viscoelastic Testing with Ecarin Clotting Time and Diluted Thrombin Time to Mass Spectrometry.

BACKGROUND: The direct thrombin inhibitor argatroban is indicated for the treatment of heparin-induced thrombocytopenia II, but it is also used off-label to treat critically ill patients presenting with heparin resistance, severe antithrombin deficiency, or hypercoagulability. Direct drug monitoring is not routinely available, and argatroban dosing is mainly based on global coagulation assays such as activated partial thromboplastin time (PTT) or diluted thrombin time (TT), both of which have limitations in patients with hypercoagulability. METHODS: Blood samples were obtained from critically ill patients treated with argatroban. Activated PTT and diluted TT were measured with a STA R Max3 analyzer (STAGO Deutschland GmbH, Germany) using an argatroban-calibrated kit. Ecarin clotting time was measured using a point-of-care viscoelastic test device. Liquid chromatography with tandem mass spectrometry was performed using a reversed-phase column, a solvent gradient, and an API4000 mass spectrometer with electrospray. Correlation was described using Pearson correlation coefficient r and Bayesian multilevel regression to estimate relationships between outcomes and covariates. RESULTS: From June 2021 to March 2022, 205 blood samples from 22 patients were analyzed, allowing for 195 activated PTT-liquid chromatography with tandem mass spectrometry comparisons, 153 ecarin clotting time-liquid chromatography with tandem mass spectrometry comparison, and 105 diluted TT-liquid chromatography with tandem mass spectrometry comparisons. Compared to liquid chromatography with tandem mass spectrometry, performance of argatroban quantification was best for diluted TT (r = 0.91), followed by ecarin clotting time (r = 0.58) and activated PTT (r = 0.48). Regression analysis revealed that patients with sepsis were more prone to argatroban overdosing (coefficient, 4.194; 95% credible interval, 2.220 to 6.792). CONCLUSIONS: Although activated PTT monitoring of argatroban is the most commonly used test, in critically ill patients, diluted TT provides more precise measurements. Alternately, point-of-care viscoelastic ecarin clotting time also provides guidance for argatroban dosing to identify overdosing if available. The data also suggested that patients with sepsis are at greater risk for argatroban overdosing.

Treatment in certified cancer centers is related to better survival in patients with colon and rectal cancer: evidence from a large German cohort study.

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 < 0.001) and 65.0% (58.8%) 5-year survival in case of rectal cancer (p < 0.001), respectively. Cox regression with adjustment for relevant covariates yielded a lower hazard of death for patients treated in certified centers for both colon (HR = 0.92, 95% CI = 0.89-0.95) and rectal cancer (HR = 0.92, 95% CI = 0.88-0.95). The results remained robust in a series of sensitivity analyses. CONCLUSIONS: This large cohort study yields new important evidence that patients with colorectal cancer have a better chance of survival if treated in a certified cancer center. Certification thus provides one powerful means to improve the quality of care for colorectal cancer. To decrease the burden of disease, more patients should thus receive cancer care in a certified center.

Early Intubation in Endovascular Therapy for Basilar Artery Occlusion: A Post Hoc Analysis of the BASICS Trial.

BACKGROUND: The optimal anesthetic management for endovascular therapy (EVT) in patients with posterior circulation stroke remains unclear. Our objective was to investigate the impact of early intubation in patients enrolled in the BASICS trial (Basilar Artery International Cooperation Study). METHODS: BASICS was a multicenter, randomized, controlled trial that compared the efficacy of EVT compared with the best medical care alone in patients with basilar artery occlusion. In this post hoc analysis, early intubation within the first 24 hours of the estimated time of basilar artery occlusion was examined as an additional covariate using regression modeling. We estimated the adjusted relative risks (RRs) for favorable outcomes, defined as modified Rankin Scale scores of 0 to 3 at 90 days. An adjusted common odds ratio was estimated for a shift in the distribution of modified Rankin Scale scores at 90 days. RESULTS: Of 300 patients in BASICS, 289 patients were eligible for analysis (151 in the EVT group and 138 in the best medical care group). compared with medical care alone, EVT was related to a higher risk of early intubation (RR, 1.29 [95% CI, 1.09-1.53]; P<0.01), and early intubation was negatively associated with favorable outcome (RR, 0.61 [95% CI, 0.45-0.84]; P=0.002). Whereas there was no overall treatment effect of EVT on favorable outcome (RR, 1.22 [95% CI, 0.95-1.55]; P=0.121), EVT was associated with favorable outcome (RR, 1.34 [95% CI, 1.05-1.71]; P=0.018) and a shift toward lower modified Rankin Scale scores (adjusted common odds ratio, 1.63 [95% CI, 1.04-2.57]; P=0.033) if adjusted for early intubation. CONCLUSIONS: In this post hoc analysis of the neutral BASICS trial, early intubation was linked to unfavorable outcomes, which might mitigate a potential benefit from EVT by indirect effects due to an increased risk of early intubation. This relationship may be considered when assessing the efficacy of EVT in patients with basilar artery occlusion in future trials.

Multilevel Quality Indicators: Methodology and Monte Carlo Evidence.

BACKGROUND: Quality indicators are frequently used to assess the performance of health care providers, in particular hospitals. Established approaches to the design of such indicators are subject to distortions due to indirect standardization and high variance of estimators. Indicators for geographical regions are rarely considered. OBJECTIVES: To develop and evaluate a methodology of multilevel quality indicators (MQIs) for both health care providers and geographical regions. RESEARCH DESIGN: We formally derived MQIs from a statistical multilevel model, which may include characteristics of patients, providers, and regions. We used Monte Carlo simulation to assess the performance of MQIs relative to established approaches based on the standardized mortality/morbidity ratio (SMR) and the risk-standardized mortality rate (RSMR). MEASURES: Rank correlation between true provider/region effects and quality indicator estimates; shares of the 10% best and 10% worst providers identified by the quality indicators. RESULTS: The proposed MQIs are (1) standardized hospital outcome rate (SHOR), (2) regional SHOR, and (3) regional standardized patient outcome rate. Monte Carlo simulations indicated that the SHOR provides substantially better estimates of provider performance than the SMR and risk-standardized mortality rate in almost all scenarios. The regional standardized patient outcome rate was slightly more stable than the regional SMR. We also found that modeling of regional characteristics generally improves the adequacy of provider-level estimates. CONCLUSIONS: MQIs methodology facilitates adequate and efficient estimation of quality indicators for both health care providers and geographical regions.

Post-COVID-19-associated morbidity in children, adolescents, and adults: A matched cohort study including more than 157,000 individuals with COVID-19 in Germany.

BACKGROUND: Long-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 FINDINGS: We 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. CONCLUSIONS: In 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 REGISTRATION: ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT05074953.

Is treatment in certified cancer centers related to better survival in patients with pancreatic cancer? Evidence from a large German cohort study.

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 ).

Exploring relationships between in-hospital mortality and hospital case volume using random forest: results of a cohort study based on a nationwide sample of German hospitals, 2016-2018.

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.

Patient-Level and Hospital-Level Risk Factors for In-Hospital Mortality in Patients Ventilated for More Than 24 Hours: Results of a Nationwide Cohort Study.

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 <100 beds = 1.412, 95% CI = 1.095-1.820) and negatively related to cumulated ventilation patient time (per 1000 days RR = 0.995, 95% CI = 0.993-0.996). University hospital status was identified as an effect modifier, particularly with regard to the patients' admission reasons. The RR of in-hospital death in patients admitted after transfer from another hospital was higher in university hospitals (RR = 1.456, 95% CI = 1.298-1.634) compared to nonuniversity hospitals (RR = 1.077, 95% CI = 1.019-1.139). Likewise, patients admitted as emergency case had a higher relative risk in university hospitals (RR = 1.619, 95% CI = 1.359-1.929) than in nonuniversity hospitals (RR = 1.141, 95% CI = 1.080-1.205). 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.

Health-related quality of life in elderly, multimorbid individuals with and without depression and/or mild cognitive impairment using a telemonitoring application.

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.

An individualized decision aid for physicians and patients for total knee replacement in osteoarthritis (Value-based TKR study): study protocol for a multi-center, stepped wedge, cluster randomized controlled trial.

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.

Hospital admissions following emergency medical services in Germany: analysis of 2 million hospital cases in 2022.

BACKGROUND: The use of emergency medical services (EMS) in Germany has increased substantially over the last few decades. While current reform efforts aim to increase effectiveness and efficiency of the German hospital and EMS systems, there is lack of data on characteristics of hospital cases using EMS. OBJECTIVES: To analyze and compare the characteristics of cases hospitalized with and without the use of EMS. MATERIALS AND METHODS: The BARMER health insurance data on more than 2 million hospital cases admitted in 2022 were analyzed. The distributions of age, clinical complexity (measured by patient clinical complexity levels, PCCL), main diagnoses, costs for EMS and hospital treatment, and multiple severity indicators were described. The overall severity of hospital cases was classified as "low or moderate" or "high" based on a combined severity indicator. All analyses were stratified by use of EMS and EMS type. RESULTS: A total of 28% of all included hospital cases used EMS. Relative to hospital cases without use of EMS, hospital cases with use of EMS were older (physician-staffed ambulance: 75 years, interquartile range [IQR] 59-84, double-crewed ambulance: 78 years, IQR 64-85) and had a higher clinical complexity. The severity of more than 30% of the cases using EMS (except for patient transport service ambulance) was classified as "low or moderate". The distributions of main diagnoses differed by severity and use of EMS. CONCLUSIONS: The high proportion of cases with low or moderate severity using EMS may indicate a substantial potential to avoid the use of EMS in the context of hospital admissions in Germany. Further investigation is required to explore whether the proportion of cases using EMS could be reduced by optimizing preclinical service.

Effect of clinical peer review on mortality in patients ventilated for more than 24 hours: a cluster randomised controlled trial.

BACKGROUND: Although clinical peer review is a well-established instrument for improving quality of care, clinical effectiveness is unclear. METHODS: In 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. RESULTS: We 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. CONCLUSIONS: This 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.

Identification of patients at high risk for brain death using an automated digital screening tool: a prospective diagnostic accuracy study.

BACKGROUND: An automated digital screening tool (DETECT) has been developed to aid in the early identification of patients who are at risk of developing brain death during critical care. METHODS: This prospective diagnostic accuracy study included consecutive patients ≥ 18 years admitted to neurocritical care for primary or secondary acute brain injury. The DETECT screening tool searched routinely monitored patient data in the electronic medical records every 12 h for a combination of coma and absence of bilateral pupillary light reflexes. In parallel, daily neurological assessment was performed by expert neurointensivists in all patients blinded to the index test results. The primary target condition was the eventual diagnosis of brain death. Estimates of diagnostic accuracy along with their 95%-confidence intervals were calculated to assess the screening performance of DETECT. RESULTS: During the 12-month study period, 414 patients underwent neurological assessment, with 8 (1.9%) confirmed cases of brain death. DETECT identified 54 positive patients and sent 281 notifications including 227 repeat notifications. The screening tool had a sensitivity of 100% (95% CI 63.1-100%) in identifying patients who eventually developed brain death, with no false negatives. The mean time from notification to confirmed diagnosis of brain death was 3.6 ± 3.2 days. Specificity was 88.7% (95% CI 85.2-91.6%), with 46 false positives. The overall accuracy of DETECT for confirmed brain death was 88.9% (95% CI 85.5-91.8%). CONCLUSIONS: Our findings suggest that an automated digital screening tool that utilizes routinely monitored clinical data may aid in the early identification of patients at risk of developing brain death.

A comparison of pediatric inflammatory multisystem syndrome temporarily-associated with SARS-CoV-2 and Kawasaki disease.

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.

Incident autoimmune diseases in association with SARS-CoV-2 infection: a matched cohort study.

OBJECTIVES: To investigate whether the risk of developing an incident autoimmune disease is increased in patients with prior COVID-19 disease compared to those without COVID-19, a large cohort study was conducted. METHOD: A cohort was selected from German routine health care data. 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. RESULTS: In 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 diseases of the vasculitis group. Patients with a more severe course of COVID-19 were at a greater risk for incident autoimmune disease. CONCLUSIONS: SARS-CoV-2 infection is associated with an increased risk of developing new-onset autoimmune diseases after the acute phase of infection. Key Points • In the 3 to 15 months after acute infection, patients who had suffered from COVID-19 had a 43% (95% CI: 37-48%) higher likelihood of developing a first-onset autoimmune disease, meaning an absolute increase in incidence of 4.50 per 1000 person-years over the control group. • COVID-19 showed the strongest association with vascular autoimmune diseases.

Treatment of Colorectal Cancer in Certified Centers: Results of a Large German Registry Study Focusing on Long-Term Survival.

(1) Background: The WiZen study is the largest study so far to analyze the effect of the certification of designated cancer centers on survival in Germany. This certification program is provided by the German Cancer Society (GCS) and represents one of the largest oncologic certification programs worldwide. Currently, about 50% of colorectal cancer patients in Germany are treated in certified centers. (2) Methods: All analyses are based on population-based clinical cancer registry data of 47.440 colorectal cancer (ICD-10-GM C18/C20) patients treated between 2009 and 2017. The primary outcome was 5-year overall survival (OAS) after treatment at certified cancer centers compared to treatment at other hospitals; the secondary endpoint was recurrence-free survival. Statistical methods included Kaplan-Meier analysis and multivariable Cox regression. (3) Results: Treatment at certified hospitals was associated with significant advantages concerning 5-year overall survival (HR 0.92, 95% CI 0.89, 0.96, adjusted for a broad range of confounders) for colon cancer patients. Concentrating on UICC stage I-III patients, for whom curative treatment is possible, the survival benefit was even larger (colon cancer: HR 0.89, 95% CI 0.84, 0.94; rectum cancer: HR 0.91, 95% CI 0.84, 0.97). (4) Conclusions: These results encourage future efforts for further implementation of the certification program. Patients with colorectal cancer should preferably be directed to certified centers.

Development of a risk score to identify patients at high risk for a severe course of COVID-19.

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. Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-023-01884-7.

Prediction of inpatient pressure ulcers based on routine healthcare data using machine learning methodology.

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.

Relationships between multiple patient safety outcomes and healthcare and hospital-related risk factors in colorectal resection cases: cross-sectional evidence from a nationwide sample of 232 German hospitals.

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.