[Recommendations for the Utilization of Claims Data During a Pandemic: Lessons Learned from the Project EgePan-Unimed of the Netzwerk Universitätsmedizin (NUM)]. / Potentiale von und Empfehlungen zur Nutzung von GKV Routinedaten in einer pandemischen Versorgungslage ­ Erfahrungen aus dem Projekt egePan-Unimed des Netzwerk Universitätsmedizin (NUM).

For appropriate response to the COVID-19 pandemic, and for obtaining answers to various relevant research questions, empirical data are required. Claims data of health insurances are a valid data source in such a situation. Within the project egePan-Unimed of the Netzwerk Universitätsmedizin (NUM) we investigated five COVID-19-related research questions using German claims data of statutory health insurances. We studied the prevalence and relevance of risk factors for a severe course of COVID-19, the background incidence of cerebral venous sinus thrombosis and myocarditis, the frequency and symptoms of post-COVID as well as the care of people with a psychiatric condition during the COVID-19 pandemic. Based on these cases, context-specific recommendations regarding the use of German claims data for future pandemics or other public health emergencies were derived, namely that the utilization of established and interdisciplinary project teams enables a timely project start and furthermore, meta-analytic methods are a valuable way to pool aggregated results of claims data analyses when data protection regulations do not allow a consolidation of data sets from different statutory health insurances. Under these circumstances, claims data are a readily available and valid data source of empirical evidence base necessary for public health measures during a pandemic.

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.

Gender-related differences in health-care and economic costs for eating disorders: A comparative cost-development analysis for anorexia and bulimia nervosa based on anonymized claims data.

OBJECTIVE: Anorexia nervosa (AN) and bulimia nervosa (BN) impose a significant financial burden and immense sufferings on affected individuals. Yet little is known about the differences between how each disorder affects males and females, respectively. METHOD: We performed a retrospective cost-development analysis of anonymized claims data from the German statutory health-insurance system. Insured persons who suffered from an onset of AN (F50.0; N = 1,242 females and 71 males) or BN (F50.2; N = 1,104 females and 64 males) were analyzed for cost-of-illness over a 5-year period, beginning 2 years before the index diagnosis. RESULTS: In total, all groups incurred similar distributions of total costs over the 5-year observation period, with roughly 14,000-20,000 EUR median costs. About two-thirds of the total costs for females and males with AN are associated with mental illness, whereas for females and males with BN, this applies to approximately half the total costs. Analyses revealed differences between disorders and genders for single outcomes. AN is associated with a stronger increase in costs within a short period following onset and higher inpatient treatment costs, whereas BN entails more instances of incapacity to work before and after onset. Compared to females, males incurred lower costs in outpatient treatments. DISCUSSION: Our study adds evidence as to the disparities in health-care utilizations and costs over the course of illness, in outcome ratios, and between genders, for both AN and BN.

Deep learning for prediction of population health costs.

BACKGROUND: Accurate prediction of healthcare costs is important for optimally managing health costs. However, methods leveraging the medical richness from data such as health insurance claims or electronic health records are missing. METHODS: Here, we developed a deep neural network to predict future cost from health insurance claims records. We applied the deep network and a ridge regression model to a sample of 1.4 million German insurants to predict total one-year health care costs. Both methods were compared to existing models with various performance measures and were also used to predict patients with a change in costs and to identify relevant codes for this prediction. RESULTS: We showed that the neural network outperformed the ridge regression as well as all considered models for cost prediction. Further, the neural network was superior to ridge regression in predicting patients with cost change and identified more specific codes. CONCLUSION: In summary, we showed that our deep neural network can leverage the full complexity of the patient records and outperforms standard approaches. We suggest that the better performance is due to the ability to incorporate complex interactions in the model and that the model might also be used for predicting other health phenotypes.

Estimates of Toxoplasmosis Incidence Based on Healthcare Claims Data, Germany, 2011-2016.

Toxoplasmosis is a zoonotic infection contracted through Toxoplasma gondii-contaminated food, soil, or water. Seroprevalence in Germany is high, but estimates of disease incidence are scarce. We investigated incidences for various toxoplasmosis manifestations using anonymized healthcare claims data from Germany for 2011-2016. Patients with a toxoplasmosis diagnosis during the annual observational period were considered incident. The estimated incidence was adjusted to the general population age/sex distribution. We estimated an annual average of 8,047 toxoplasmosis patients in Germany. The average incidence of non-pregnancy-associated toxoplasmosis patients was 9.6/100,000 population. The incidence was highest in 2011, at 10.6 (95% CI 9.4-12.6)/100,000 population, and lowest in 2016, at 8.0 (95% CI 7.0-9.4)/100,000 population. The average incidence of toxoplasmosis during pregnancy was 40.3/100,000 pregnancies. We demonstrate a substantial toxoplasmosis disease burden in Germany. Public health and food safety authorities should implement toxoplasmosis-specific prevention programs.

Health Care Analysis on Myocardial Revascularization in Patients with Chronic Coronary Artery Disease: The Multicenter REVASK Study: Design and Protocol.

Coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) are available for revascularization of coronary artery disease (CAD) with the aims to reduce cardiovascular morbidity and mortality and to improve disease-related quality of life in particular. The German National Care Guideline (NVL-cKHK) on chronic CAD recommends the establishment of so-called heart teams for decision making in myocardial revascularization to improve the quality of care. Preferred recommendations for PCI or CABG are given for different patient subgroups depending on patient characteristics, concomitant diseases, and coronary morphology. The myocardial revascularization study (REVASK) is a noninterventional cohort study on care of patients undergoing PCI or CABG based on retrospective statutory health insurance (SHI) routine data, registry data from the German Cardiac Society (DGK) resp., the German Society for Thoracic and Cardiovascular Surgery (DGTHG), combined with prospective primary data collection from health care providers and patients. The primary goal is to investigate whether and to which extent heart teams, consisting of cardiologists and cardiac surgeons, increase guideline adherence in decision making for myocardial revascularization. Ultimately the study project aims to improve patient care in terms of decision making for appropriate myocardial revascularization. Through the consistent implementation of the German National Care Guideline on chronic Coronary Artery Disease (NVL-cKHK) and the European Guidelines on myocardial revascularization, the reduction of morbidity, mortality and the reduced need for subsequent revascularization procedures are also desirable from a health economics perspective.

[Patient safety in the treatment of rheumatic diseases : Laboratory monitoring in methotrexate treatment]. / Patientensicherheit in der Rheumatherapie : Labormonitoring bei Methotrexat.

BACKGROUND: Methotrexate (MTX) is the most commonly prescribed disease-modifying drug in the treatment of rheumatic diseases. Regular laboratory testing is recommended to recognize side effects, such as hepatotoxicity and myelotoxicity as well as decreases in renal function that may cause toxic MTX accumulation. Additionally, folic acid is recommended as prophylaxis against specific side effects. In this study we investigated whether laboratory monitoring and prescription of folic acid took place according to published recommendations. MATERIAL AND METHODS: Claims data from the statutory health insurance from 1 January 2009 to 31 December 2013 were retrospectively analyzed. A total of 40,087 adults with a rheumatic diagnosis (ICD10 codes M05-M18), no malignant disease and no previous MTX prescription within 12 months were extracted from the InGef (Institute for Applied Health Research in Berlin, formerly Health Risk Institute) research database. The frequency of recommended laboratory testing, appointments with rheumatologists and the prescription of folic acid prophylaxis were investigated. RESULTS: Of the patients 12,451 began treatment with MTX in the observation period. Between 42% and 46% of recommended blood counts, liver values and kidney function tests and 14% of urinalyses were performed according to recommendations. Of the patients 84% were seen regularly by a rheumatologist and 74% received a prescription for prophylactic folic acid. Serious conditions potentially resulting from MTX treatment were observed in 0.7-3.5 cases/1000 person years. DISCUSSION: Laboratory monitoring in the context of MTX treatment is carried out less frequently than recommended in the literature. Potential MTX-associated serious complications are rare from a practice perspective. On the one hand solutions are needed for a better coordination of laboratory monitoring. On the other hand more empirical evidence is needed regarding the benefits of laboratory monitoring and the appropriate intervals thereof.

Dual renin-angiotensin-aldosterone blockade: Implementation of published research and Dear Doctor letters in ambulatory care: A retrospective observational study using prescription data.

PURPOSE: This study aims to assess the implementation of published research, contraindications, and warnings on the prescription of dual renin-angiotensin-hormone system (RAS) blockade in ambulatory care in Germany. METHODS: Cohort study based on health claims data of 6.7 million subjects from 2008 to 2015. Yearly prevalence and incidence for dual RAS blockade with (a) angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers (ACEI + ARB) and (b) aliskiren and ACEI or ARB (aliskiren + ACEI/ARB) were calculated. We assessed prescriber specialty and associations between discontinuing dual RAS blockade with specialist (internal medicine, cardiology, nephrology) visits and hospital discharge in the previous year. RESULTS: A total of 2 984 517 patients were included (age 51.4 ± SD 18.4 y, 48.5% male). Prescription rates for ACEI + ARB decreased from 0.6% (n = 17 907) to 0.4% (n = 12 237) and for aliskiren + ACEI/ARB from 0.23% (n = 6634) to 0.03% (n = 818). Incident prescriptions decreased from 0.23% (n = 6705) to 0.19% (n = 5055) (ACE + ARB) and from 0.1% (n = 2796) to 0.005% (n = 142) (aliskiren + ACE/ARB); 59% of ACEI + ARB and 48% of aliskiren + ACE/ARB combinations were prescribed only by one physician. Of those, 73% (ACEI + ARB) and 58% (aliskiren + ACE/ARB) were primary care providers (PCPs). Discontinuing dual RAS blockade was associated with specialist care and hospital discharge in the previous year (specialist care: RR 1.4, 95% CI, 1.3-1.6; hospital visit: RR 1.5, 95% CI, 1.3-1.6). CONCLUSIONS: Our results suggest a delayed uptake of treatment recommendation for ACEI + ARB and a higher impact of Dear Doctor letters addressing PCPs directly compared with published research, contraindications, and warnings. Targeted continuous medical education, practice software alerts, and stronger involvement of pharmacists might improve the implementation of medication safety recommendations in ambulatory care.

Comparison of Approaches to Select a Propensity Score Matched Control Group in the Absence of an Obvious Start of Follow Up for this Group: An Example Study on the Economic Impact of the DMP Bronchial Asthma.

BACKGROUND: Claims data are a valuable data source to investigate the economic impact of new health care services. While the date of enrollment into the new service is an obvious start of follow-up for participants, the strategy to select potential controls is not straightforward due to a missing start of follow-up to ascertain possible confounders. The aim of this study was to compare different approaches to select controls via Propensity Score Matching (PSM) using the disease management program (DMP) bronchial asthma (BA) as an example. METHODS: We conducted a retrospective cohort study of BA patients between 2013 and 2016 to examine total one-year health care costs and all-cause mortality. We implemented different scenarios regarding the selection of potential controls: I) allotment of a random index date with subsequent PSM, II) calendar year-based PSM (landmark analysis) and III) calendar quarter-based PSM. In scenario I, we applied 2 approaches to assign a random index date: a) assign random index date among all quarters with a BA diagnosis and b) assign random index date and thereafter examine if a BA diagnosis was documented in that quarter. RESULTS: No significant differences in total one-year health care costs between DMP BA participants and non-participants were observed in any of the scenarios. This could to some extent be explained by the higher mortality in the control groups in all scenarios. CONCLUSION: If the loss of potential controls can be compensated, scenario Ib is a pragmatic option to select a control group. If that is not the case, scenario III is the more sophisticated approach, with the limitation that baseline characteristics prior PSM cannot be depicted and computational time or memory size needed to conduct the analysis need to be sufficient.

Sodium-glucose co-transporter-2 inhibitors and the risk of fractures of the upper or lower limbs in patients with type 2 diabetes: A nested case-control study.

AIMS: To investigate whether the use of SGLT-2 inhibitors is associated with an increased risk of fractures. MATERIAL AND METHODS: We conducted a cohort study with nested case-control analysis based on the InGef database between November 2011 and December 2016 among patients with type 2 diabetes who were initiating treatment with, switching to, or adding a new class of non-insulin antidiabetic drug. Patients with a hospital or ambulatory diagnosis of fractures of the upper or lower limbs were included and were matched to up to 40 randomly sampled control subjects. Conditional logistic regression was used to estimate confounder adjusted odds ratios (ORs) of fractures, comparing current use of metformin plus SGLT-2 inhibitor or metformin plus another antidiabetic drug class to metformin plus DPP-4 inhibitor as reference. RESULTS: The cohort comprised 210 042 new users of non-insulin antidiabetic drugs. For the nested case-control analysis, 7522 patients with fractures were matched to 296 845 control subjects. In the crude and confounder adjusted analyses, current use of metformin plus SGLT-2 inhibitor compared to current use of metformin plus DPP-4 inhibitor was not associated with fractures (OR: 1.00; 95% CI: 0.72-1.39 and OR: 0.99; 95% CI: 0.71-1.37, respectively). Similarly, no statistically significant association was found for current use of metformin plus another antidiabetic drug class. No treatment effect modification was observed after stratification by number of documented risk factors for falls and fractures (< 4 vs ≥ 4) and age (< 75 vs ≥ 75 years). CONCLUSION: Our study suggests that use of SGLT-2 inhibitors and other antidiabetic drug classes are not associated with an increased risk of fractures of the upper or lower limbs compared to use of DPP-4 inhibitors in patients with type 2 diabetes.

How can we define and analyse drug exposure more precisely to improve the prediction of hospitalizations in longitudinal (claims) data?

BACKGROUND: Risk prediction models can be powerful tools to support clinical decision-making, to help targeting interventions, and, thus, to improve clinical and economic outcomes, provided that model performance is good and sensitivity and specificity are well balanced. Drug utilization as a potential risk factor for unplanned hospitalizations has recently emerged as a meaningful predictor variable in such models. Drug treatment is a rather unstable (i.e. time-dependent) phenomenon and most drug-induced events are concentration-dependent and therefore individual drug exposure will likely modulate the risk. This especially applies to longitudinal monitoring of appropriate drug treatment within claims data as another promising application for prediction models. METHODS AND RESULTS: To guide future research towards this direction, we firstly reviewed current risk prediction models for unplanned hospitalizations that explicitly included information on drug utilization and were surprised to find that these models rarely attempted to consider dose and frequent modulators of drug clearance such as interactions with co-medication or co-morbidities. As another example, they often presumed class effects where in fact, differences between active moieties were well established. In addition, the study designs and statistical risk analysis disregarded the fact that medication and risk modulators and, thus, adverse events can vary over time. In a simulation study, we therefore evaluated the potential benefit of time-dependent Cox models over standard binary regression approaches with a fixed follow-up period. CONCLUSIONS: Longitudinal drug information could be utilized much more efficiently both by precisely estimating individual drug exposure and by applying more refined statistical methodology to account for time-dependent drug utilization patterns.

Characteristics and external validity of the German Health Risk Institute (HRI) Database.

PURPOSE: The aim of this study was to describe characteristics and external validity of the German Health Risk Institute (HRI) Database. METHODS: The HRI Database is an anonymized healthcare database with longitudinal data from approximately six Mio Germans. In addition to demographic information (gender, age, region of residence), data on persistence of insurants over time, hospitalization rates, mortality rates and drug prescription rates were extracted from the HRI database for 2013. Corresponding national reference data were obtained from official sources. RESULTS: The proportion of men and women was similar in the HRI Database and Germany, but the database population was slightly younger (mean 40.4 vs 43.7 years). The proportion of insurants living in the eastern part of Germany was lower in the HRI Database (10.1% vs 19.7%). There was good accordance to German reference data with respect to hospitalization rates, overall mortality rate and prescription rates for the 20 most often reimbursed drug classes, with the overall burden of morbidity being slightly lower in the HRI database. From insurants insured on 1 January 2009 (N = 6.2 Mio), a total of 70.6% survived and remained continuously insured with the same statutory health insurance until 31 December 2013. This proportion increased to 77.5% if only insurants ≥40 years were considered. CONCLUSIONS: There was good overall accordance of the HRI database and the German population in terms of measures of morbidity, mortality and drug usage. Persistence of insurants with the database over time was high, indicating suitability of the data source for longitudinal epidemiological analyses.

Routine practice data of three cancer entities: Comparison among cancer registry and health insurance data.

INTRODUCTION: Claims data and cancer registry data are valuable secondary data sources for addressing health service research questions. This study provides a thorough insight into the comparability of data from health insurance companies and cancer registries in Germany regarding breast, prostate, and lung cancer patients and their treatment. METHODS: For this study claims data of the InGef database and data of the Cancer Registry of Rhineland-Palatinate were used to identify patients living in Rhineland-Palatinate with an incident breast, prostate, or lung cancer diagnosis between Jan. 1, 2018 and Dec. 31, 2019. Both datasets were compared for patient and tumour characteristics as well as treatment strategy. For the descriptive analysis of tumour localisation and treatment all patients were followed up for a maximum of two years. RESULTS: A total of 1,470 incident cancer cases were identified in the InGef database and 1,694 in the Cancer Registry. Data on sex, age, and tumour localisation matched well for all cancer entities in the cohorts. Data for early UICC stages I+II varied between the cohorts for prostate cancer (84% InGef, 66% Cancer Registry) and lung cancer (29% InGef, 20% Cancer Registry). Larger deviations were found for antihormonal treatment (breast 54% vs. 44%, prostate 32% vs. 18%). Significant differences were found for surgery (breast and lung) and radiation (breast and prostate), respectively. DISCUSSION: Age at diagnosis, tumour localisation, and treatment for breast cancer was well documented in both databases. Tumour-specific deviations were observed for tumour localisations (lung cancer), UICC stage (prostate and lung cancer) and treatment options. CONCLUSION: Both databases show very good completeness across cancer entities, but at the same time have minor limitations where they could readily complement each other. Individual linkage of claims and registry data could be an important step to improve oncological studies with routine practice data and to overcome the limitations identified.

Effectiveness and Safety of Direct Oral Anticoagulants Among Octogenarians with Venous Thromboembolism: An International Multidatabase Cohort Study.

BACKGROUND: The effects of direct oral anticoagulants (DOACs) among octogenarian patients with venous thromboembolism remains poorly understood. To address this knowledge gap, our study aimed to assess the effectiveness and safety of DOACs compared to vitamin K antagonists (VKAs) among octogenarians with venous thromboembolism. METHODS: We conducted an international cohort study using administrative health care databases from Québec, Canada, and Germany. We assembled 2 population-based cohorts of octogenarians with incident venous thromboembolism initiating treatment with DOACs or VKAs. The study period spanned from January 2012 to the most recent date of data availability (Québec: December 2016; Germany: December 2019). Using an as-treated exposure definition, we compared use of DOACs to use of VKAs, applying inverse probability of treatment weighting based on high-dimensional propensity scores to balance exposure groups. Cox proportional hazards models estimated site-specific hazard ratios (HRs) and 95% confidence intervals (CIs) of recurrent venous thromboembolism, major bleeding, and all-cause mortality. The results were meta-analyzed using random-effects models. RESULTS: Overall, our study included 6737 octogenarians with venous thromboembolism (Québec: n = 2556; Germany: n = 4181) who initiated use of DOACs (n = 3778) or VKAs (n = 2959). When compared to VKAs, DOACs were associated with similar risks of recurrent venous thromboembolism (weighted HR, 0.80; 95% CI, 0.43-1.46; I2 = 0.00), major bleeding (weighted HR, 0.96; 95% CI, 0.57-1.63; I2 = 0.59), and all-cause mortality (weighted HR, 1.04; 95% CI, 0.81-1.34; I2 = 0.00). CONCLUSIONS: Among octogenarians with venous thromboembolism, DOACs showed a comparable effectiveness and safety compared to VKAs. Our results support the use of DOACs in this high-risk group.

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.

Real-world anticoagulatory treatment after percutaneous mitral valve repair using MitraClip: a retrospective, observational study on 1300 patients.

AIMS: This study sought to investigate current anticoagulatory treatment patterns and clinical outcome in patients undergoing transcatheter mitral valve repair (MitraClip). METHODS AND RESULTS: In a retrospective study of a German claims database (InGef research database), anticoagulatory treatment regimens were assessed using any drug prescription post discharge within the first 90 days after MitraClip procedure. Clinical events between 30 days and 6 months were examined by treatment regime. The study population comprised 1342 patients undergoing MitraClip procedure between 2014 and 2018. 22.4% received antiplatelet monotherapy, 20.8% oral anticoagulation (OAC) plus antiplatelet therapy, 19.4% OAC monotherapy, 11.7% dual antiplatelet therapy, 2.8% triple therapy and 21.0% did not receive any anticoagulatory drugs. 63% of patients with OAC received non-vitamin-K antagonist oral anticoagulants (NOAC). A total of 168 patients were newly prescribed OAC after MitraClip, of whom 12 patients (7.1%) had no diagnosis of atrial fibrillation or venous thromboembolism. 40% of patients with OAC prior to MitraClip did not have any OAC after MitraClip. The adjusted risk of all-cause mortality was significantly increased in patients with no anticoagulatory treatment (HR 3.84, 95% CI 2.33-6.33, p < 0.0001) when compared to antiplatelet monotherapy whereas the other regimes were not significantly different. CONCLUSIONS: This large real-world data analysis demonstrates a heterogeneous spectrum of prescriptions for anticoagulant therapies after MitraClip. Considering relevant differences in clinical outcome across treatment groups, major effort is warranted for controlled trials in order to establish evidence-based recommendations on anticoagulatory treatment after percutaneous mitral valve repair.

Effectiveness and safety of direct oral anticoagulants with antiplatelet agents in patients with venous thromboembolism: A multi-database cohort study.

BACKGROUND: Patients with venous thromboembolism (VTE) often have comorbidities that require use of antiplatelets. However, evidence on the effects of concomitant use of direct oral anticoagulants (DOACs) and antiplatelets in this high-risk population is scarce. Our international, multi-database cohort study assessed the real-world effectiveness and safety of concomitant use of DOACs and antiplatelets among patients with VTE. METHODS: We assembled two population-based cohorts using administrative health care databases from Québec and Germany. We included patients with incident VTE who initiated treatment with a DOAC or a vitamin K antagonist (VKA), while being exposed to antiplatelets (acetylsalicylic acid, clopidogrel, ticagrelor, prasugrel, dipyridamole). The study period spanned from 2012 to 2016 (Québec) or 2019 (Germany). Concomitant use of DOACs and antiplatelets was compared with concomitant use of VKAs and antiplatelets, using inverse probability of treatment weighting to balance exposure groups. Cox proportional hazards models estimated site-specific hazard ratios (HRs) and 95% confidence intervals (CIs) of major bleeding, all-cause mortality (primary outcomes), and recurrent VTE (secondary outcome). Site-specific estimates were meta-analyzed using random-effects models. RESULTS: Overall, 4971 patients with VTE initiated concomitant use of a DOAC (n = 2289) or a VKA (n = 2682) and antiplatelets. Compared with concomitant use of VKAs and antiplatelets, concomitant use of DOACs and antiplatelets was associated with similar risks of major bleeding (HR, 0.81; 95% CI, 0.46-1.45), all-cause mortality (HR, 1.25; 95% CI, 0.87-1.79), and recurrent VTE (HR, 0.96; 95% CI, 0.40-2.27). CONCLUSIONS: Among patients with VTE using antiplatelets, there were no major differences in effectiveness and safety between DOACs and VKAs.

Machine learning-based identification of risk-factor signatures for undiagnosed atrial fibrillation in primary prevention and post-stroke in clinical practice.

AIMS: Atrial fibrillation (AF) carries a substantial risk of ischemic stroke and other complications, and estimates suggest that over a third of cases remain undiagnosed. AF detection is particularly pressing in stroke survivors. To tailor AF screening efforts, we explored German health claims data for routinely available predictors of incident AF in primary care and post-stroke using machine learning methods. METHODS AND RESULTS: We combined AF predictors in patients over 45 years of age using claims data in the InGef database (n = 1 476 391) for (i) incident AF and (ii) AF post-stroke, using machine learning techniques. Between 2013-2016, new-onset AF was diagnosed in 98 958 patients (6.7%). Published risk factors for AF including male sex, hypertension, heart failure, valvular heart disease, and chronic kidney disease were confirmed. Component-wise gradient boosting identified additional predictors for AF from ICD-codes available in ambulatory care. The area under the curve (AUC) of the final, condensed model consisting of 13 predictors, was 0.829 (95% confidence interval (CI) 0.826-0.833) in the internal validation, and 0.755 (95% CI 0.603-0.890) in a prospective validation cohort (n = 661). The AUC for post-stroke AF was of 0.67 (95% CI 0.651-0.689) in the internal validation data set, and 0.766 (95% CI 0.731-0.800) in the prospective clinical cohort. CONCLUSION: ICD-coded clinical variables selected by machine learning can improve the identification of patients at risk of newly diagnosed AF. Using this readily available, automatically coded information can target AF screening efforts to identify high-risk populations in primary care and stroke survivors.

Sodium-Glucose Co-Transporter 2 Inhibitors and the Risk of Venous Thromboembolism in Patients with Type 2 Diabetes: A Cohort Study.

PURPOSE: We assessed whether sodium-glucose co-transporter type 2 (SGLT2) inhibitors are associated with a higher incidence rate of venous thromboembolism in patients with type 2 diabetes. METHODS: We conducted a population-based cohort study using the InGef database including patients with type 2 diabetes newly treated with noninsulin antidiabetic drugs between 2012 and 2018. Cases of venous thromboembolism identified during follow-up were matched to 40 controls on age, sex, cohort entry date, and duration of follow-up. Using a nested case-control approach, conditional logistic regression estimated incidence rate ratios (RRs) with 95% confidence intervals (CIs) of venous thromboembolism adjusted for sociodemographic and clinical variables, comparing current use of SGLT2 inhibitors with current use of dipeptidyl peptidase-4 (DPP-4) inhibitors. RESULTS: In a cohort of 219,538 patients, we identified 2152 cases of venous thromboembolism and matched them to 85,104 controls. Compared with DPP-4 inhibitors, current use of SGLT2 inhibitors was associated with a lower rate of venous thromboembolism (RR, 0.75; 95% CI, 0.59-0.94). Effect estimates were similar for dapagliflozin (RR, 0.77; 95% CI, 0.57-1.03) and empagliflozin (RR, 0.71; 95% CI, 0.52-0.98). CONCLUSIONS: Compared with DPP-4 inhibitors, SGLT2 inhibitors were not associated with a higher rate of venous thromboembolism, providing reassurance regarding their thromboembolic safety.

Clinical outcomes and characteristics of patients hospitalized for Influenza or COVID-19 in Germany.

OBJECTIVES: Since the beginning of the severe acute respiratory syndrome coronavirus 2 pandemic, there is a discussion about the severity of coronavirus disease-2019 (COVID-19) in comparison to infections with seasonal Influenza. The objective of this study was to compare clinical and demographic characteristics of German patients hospitalized for infection with either SARS-CoV-2 or Influenza. METHODS: This study used anonymized German healthcare claims data. Patients with a confirmed COVID-19 or Influenza diagnosis, for whom a complete hospital course was available (i.e., the patient was discharged or died in hospital) were included. The data set included detailed information on patient characteristics and hospital treatment. Patients were grouped according to whether they were transferred to the intensive care unit (ICU), received mechanical ventilation (MV), or had a severe course of the disease (SD). Charlson Comorbidity Index in the eight quarters prior to hospitalization and secondary diagnoses during hospitalization were analyzed. RESULTS: A total of 2343 hospitalized patients with COVID-19 and 6762 hospitalized patients with Influenza were included. Fifty-four percent of the patients were male patients, with men being twice as frequent in the COVID-19 severe groups. For both diseases, patients >49 years accounted for almost three-quarters of hospital cases and hypertension, diabetes mellitus, chronic kidney disease, and chronic obstructive pulmonary disease were the most common comorbidities. The proportion of cases with ICU, MV, and SD was substantially higher for patients with COVID-19 (ICU+: 21 vs. 13 %; MV+: 15 vs. 9%; and SD+: 28 vs. 16%). Overall inhospital mortality was more than two-fold higher in COVID-19 vs. Influenza (14 vs. 6%).). The length of ventilation and hospitalization, and the proportion of patients diagnosed with acute respiratory distress syndrome, systemic inflammatory response syndrome, or acute kidney injury were considerably higher in patients with COVID-19. CONCLUSIONS: COVID-19 resulted in higher inhospital mortality and worse clinical outcomes than Influenza. This was not attributable to demographic characteristics, preexisting comorbidities, or patient triage, because the German healthcare system had not reached its limits in the pandemic. Discussions suggesting that COVID-19 and seasonal Influenza have similar severity cannot be based on clinical evidence.