Alpha-1-antitrypsin-deficiency is associated with lower cardiovascular risk: an approach based on federated learning.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an inflammatory multisystemic disease caused by environmental exposures and/or genetic factors. Inherited alpha-1-antitrypsin deficiency (AATD) is one of the best recognized genetic factors increasing the risk for an early onset COPD with emphysema. The aim of this study was to gain a better understanding of the associations between comorbidities and specific biomarkers in COPD patients with and without AATD to enable future investigations aimed, for example, at identifying risk factors or improving care. METHODS: We focused on cardiovascular comorbidities, blood high sensitivity troponin (hs-troponin) and lipid profiles in COPD patients with and without AATD. We used clinical data from six German University Medical Centres of the MIRACUM (Medical Informatics Initiative in Research and Medicine) consortium. The codes for the international classification of diseases (ICD) were used for COPD as a main diagnosis and for comorbidities and blood laboratory data were obtained. Data analyses were based on the DataSHIELD framework. RESULTS: Out of 112,852 visits complete information was available for 43,057 COPD patients. According to our findings, 746 patients with AATD (1.73%) showed significantly lower total blood cholesterol levels and less cardiovascular comorbidities than non-AATD COPD patients. Moreover, after adjusting for the confounder factors, such as age, gender, and nicotine abuse, we confirmed that hs-troponin is a suitable predictor of overall mortality in COPD patients. The comorbidities associated with AATD in the current study differ from other studies, which may reflect geographic and population-based differences as well as the heterogeneous characteristics of AATD. CONCLUSION: The concept of MIRACUM is suitable for the analysis of a large healthcare database. This study provided evidence that COPD patients with AATD have a lower cardiovascular risk and revealed that hs-troponin is a predictor for hospital mortality in individuals with COPD.

Cerebral aneurysms: Germany-wide real-world outcome data of endovascular or neurosurgical treatment from 2007 to 2019.

BACKGROUND: Evidence on clinical outcome after endovascular treatment (EVT) vs neurosurgical clipping of intracranial aneurysms (IAs) is based on one randomized and one pseudo-randomized trial for ruptured aneurysms. Herein, we analyze nationwide real-world hospital outcomes after EVT vs clipping of ruptured and unruptured IAs. METHODS: This cohort study analyzed all EVT and clipping procedures for IAs in Germany between 2007 and 2019. The data basis was the billing-data of all German hospitals from the German Federal Statistical Office. EVT and clipping interventions, comorbidities, and in-hospital outcomes were identified using International Classification of Diseases (ICD) and Operation and Procedure (OPS) codes. Discharge type was used as a surrogate marker for functional independence. Poor clinical outcome at discharge was additionally defined by the dichotomous US National Inpatient Sample-Subarachnoid hemorrhage Outcome Measure score (NIH-SOM). Secondary outcomes included length of hospital stay, prolonged mechanical ventilation (>48 hour), and hospital reimbursement. RESULTS: We analyzed 90 039 procedures (62.6% EVT, 35.52% clipping, 1.8% combined) for the treatment of IAs. After adjustment in-hospital mortality was equal after EVT compared with clipping, in ruptured IAs (adjusted OR (aOR) 0.98, p=0.707) and unruptured IAs (aOR 0.92, p=0.482). Functional independence was more likely after EVT for ruptured (aOR 0.81, p<0.001) and unruptured IAs (aOR 0.4, p<0.001). Poor clinical outcome was more likely after clipping for ruptured (aOR 0.67, p<0.001) and unruptured IAs (aOR 0.56, p<0.001). CONCLUSIONS: In German clinical practice, we observed higher rates of functional independence and lower rates of poor outcomes at discharge with equal mortality for EVT.

Acute respiratory distress syndrome after SARS-CoV-2 infection on young adult population: International observational federated study based on electronic health records through the 4CE consortium.

PURPOSE: In young adults (18 to 49 years old), investigation of the acute respiratory distress syndrome (ARDS) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been limited. We evaluated the risk factors and outcomes of ARDS following infection with SARS-CoV-2 in a young adult population. METHODS: A retrospective cohort study was conducted between January 1st, 2020 and February 28th, 2021 using patient-level electronic health records (EHR), across 241 United States hospitals and 43 European hospitals participating in the Consortium for Clinical Characterization of COVID-19 by EHR (4CE). To identify the risk factors associated with ARDS, we compared young patients with and without ARDS through a federated analysis. We further compared the outcomes between young and old patients with ARDS. RESULTS: Among the 75,377 hospitalized patients with positive SARS-CoV-2 PCR, 1001 young adults presented with ARDS (7.8% of young hospitalized adults). Their mortality rate at 90 days was 16.2% and they presented with a similar complication rate for infection than older adults with ARDS. Peptic ulcer disease, paralysis, obesity, congestive heart failure, valvular disease, diabetes, chronic pulmonary disease and liver disease were associated with a higher risk of ARDS. We described a high prevalence of obesity (53%), hypertension (38%- although not significantly associated with ARDS), and diabetes (32%). CONCLUSION: Trough an innovative method, a large international cohort study of young adults developing ARDS after SARS-CoV-2 infection has been gather. It demonstrated the poor outcomes of this population and associated risk factor.

Valerian and postoperative sleep: a retrospective cohort analysis of gynecological, urologic, and general surgical patients.

STUDY OBJECTIVES: Postoperative sleep disturbances appear to be a common complication after surgery being treated with sleep-promoting medication such as valerian, but robust data and evidence of medicinal approaches are lacking. METHODS: We performed a retrospective cohort analysis of all 21 168 urological, gynecological, and general surgical patients of the University Medical Center Freiburg, Germany, who underwent surgery between 2015 and 2020. Target parameters were the usage of sleep-promoting medication to estimate the occurrence of postoperative sleep disturbances as well as the kind of sleep medication with a special focus on herbal medication such as valerian. RESULTS: Drug-treated sleep disturbances occurred in 15% (n = 3083) of the patients. Valerian was the second most applied drug (n = 814, 26.4%) after classic benzodiazepines (n = 1 138, 36.9%). The majority of patients got valerian as monotherapy. Age, length of stay, and comorbidities were associated with demand for sleep medication in general (p < .001). Valerian monotherapy was more common in women (OR 1.53, 95% CI: 1.33-1.77, p < .001), elderly patients (OR 1.50, 95% CI: 1.29-1.75, p < .001), and patients with prolonged hospital stay (OR 2.23, 95% CI: 1.91-2.61, p < .001). CONCLUSIONS: Valerian plays an important role in the treatment of postoperative sleep disturbances clinically, and it appears to be a promising therapeutic approach especially in women, older and sicker patients, and those with prolonged hospital stay. Further research has to clarify the efficacy of valerian postoperatively. CLINICAL TRIAL REGISTRATION: DRKS00027903, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00027903.

Navigating hospitals safely through the COVID-19 epidemic tide: Predicting case load for adjusting bed capacity.

BACKGROUND: The pressures exerted by the coronavirus disease 2019 (COVID-19) pandemic pose an unprecedented demand on healthcare services. Hospitals become rapidly overwhelmed when patients requiring life-saving support outpace available capacities. OBJECTIVE: We describe methods used by a university hospital to forecast case loads and time to peak incidence. METHODS: We developed a set of models to forecast incidence among the hospital catchment population and to describe the COVID-19 patient hospital-care pathway. The first forecast utilized data from antecedent allopatric epidemics and parameterized the care-pathway model according to expert opinion (ie, the static model). Once sufficient local data were available, trends for the time-dependent effective reproduction number were fitted, and the care pathway was reparameterized using hazards for real patient admission, referrals, and discharge (ie, the dynamic model). RESULTS: The static model, deployed before the epidemic, exaggerated the bed occupancy for general wards (116 forecasted vs 66 observed), ICUs (47 forecasted vs 34 observed), and predicted the peak too late: general ward forecast April 9 and observed April 8 and ICU forecast April 19 and observed April 8. After April 5, the dynamic model could be run daily, and its precision improved with increasing availability of empirical local data. CONCLUSIONS: The models provided data-based guidance for the preparation and allocation of critical resources of a university hospital well in advance of the epidemic surge, despite overestimating the service demand. Overestimates should resolve when the population contact pattern before and during restrictions can be taken into account, but for now they may provide an acceptable safety margin for preparing during times of uncertainty.

Acute Stroke in Times of the COVID-19 Pandemic: A Multicenter Study.

BACKGROUND AND PURPOSE: This study aims to assess the number of patients with acute ischemic cerebrovascular events seeking in-patient medical emergency care since the implementation of social distancing measures in the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In this retrospective multicenter study, data on the number of hospital admissions due to acute ischemic stroke or transient ischemic attack and numbers of reperfusion therapies performed in weeks 1 to 15 of 2020 and 2019 were collected in 4 German academic stroke centers. Poisson regression was used to test for a change in admission rates before and after the implementation of extensive social distancing measures in week 12 of 2020. The analysis of anonymized regional mobility data allowed for correlations between changes in public mobility as measured by the number and length of trips taken and hospital admission for stroke/transient ischemic attack. RESULTS: Only little variation of admission rates was observed before and after week 11 in 2019 and between the weeks 1 and 11 of 2019 and 2020. However, reflecting the impact of the COVID-19 pandemic, a significant decrease in the number of admissions for transient ischemic attack was observed (-85%, -46%, -42%) in 3 of 4 centers, while in 2 of 4 centers, stroke admission rates decreased significantly by 40% and 46% after week 12 in 2020. A relevant effect on reperfusion therapies was found for 1 center only (thrombolysis, -60%; thrombectomy, -61%). Positive correlations between number of ischemic events and mobility measures in the corresponding cities were identified for 3 of 4 centers. CONCLUSIONS: These data demonstrate and quantify decreasing hospital admissions due to ischemic cerebrovascular events and suggest that this may be a consequence of social distancing measures, in particular because hospital resources for acute stroke care were not limited during this period. Hence, raising public awareness is necessary to avoid serious healthcare and economic consequences of undiagnosed and untreated strokes and transient ischemic attacks.

Reduced Rate of Inpatient Hospital Admissions in 18 German University Hospitals During the COVID-19 Lockdown.

The COVID-19 pandemic has caused strains on health systems worldwide disrupting routine hospital services for all non-COVID patients. Within this retrospective study, we analyzed inpatient hospital admissions across 18 German university hospitals during the 2020 lockdown period compared to 2018. Patients admitted to hospital between January 1 and May 31, 2020 and the corresponding periods in 2018 and 2019 were included in this study. Data derived from electronic health records were collected and analyzed using the data integration center infrastructure implemented in the university hospitals that are part of the four consortia funded by the German Medical Informatics Initiative. Admissions were grouped and counted by ICD 10 chapters and specific reasons for treatment at each site. Pooled aggregated data were centrally analyzed with descriptive statistics to compare absolute and relative differences between time periods of different years. The results illustrate how care process adoptions depended on the COVID-19 epidemiological situation and the criticality of the disease. Overall inpatient hospital admissions decreased by 35% in weeks 1 to 4 and by 30.3% in weeks 5 to 8 after the lockdown announcement compared to 2018. Even hospital admissions for critical care conditions such as malignant cancer treatments were reduced. We also noted a high reduction of emergency admissions such as myocardial infarction (38.7%), whereas the reduction in stroke admissions was smaller (19.6%). In contrast, we observed a considerable reduction in admissions for non-critical clinical situations, such as hysterectomies for benign tumors (78.8%) and hip replacements due to arthrosis (82.4%). In summary, our study shows that the university hospital admission rates in Germany were substantially reduced following the national COVID-19 lockdown. These included critical care or emergency conditions in which deferral is expected to impair clinical outcomes. Future studies are needed to delineate how appropriate medical care of critically ill patients can be maintained during a pandemic.

Finding the Needle in the Hay Stack: An Open Architecture to Support Diagnosis of Undiagnosed Patients.

Clinical Decision Support Systems (CDSS) are promising to support physicians in finding the right diagnosis of patients with rare diseases (RD). The MIRACUM consortium, which includes ten university hospitals in Germany, will establish a diagnosis support system for RD. This system conducts a similarity analysis on distributed clinical data with the aim to identify similar patient cases at each MIRACUM site to offer the physician a hint to a possible diagnosis.

Influence of Postoperative Intraocular Pressure on Graft Detachment After Descemet Membrane Endothelial Keratoplasty.

PURPOSE: Descemet membrane endothelial keratoplasty (DMEK) seems to be the most promising technique for treating endothelium-related disorders of the cornea. However, graft detachment is a frequent complication. It often can be treated by rebubbling procedures. Unfortunately, this increases the risk of subsequent graft failure. It is therefore essential to define risk factors for graft detachment in DMEK. In this study, postoperative intraocular pressure (IOP) is investigated in this regard. METHODS: In total, 1047 DMEK procedures in patients with Fuchs endothelial dystrophy or bullous keratopathy were reviewed. All rebubbling procedures were recorded as well as postoperative IOP values (first measure 2 hours postoperatively and highest and lowest value within 3 days after surgery), donor factors (donor age, organ culture time, and endothelial cell count), and whether DMEK surgery had been combined with cataract surgery (triple-DMEK). Incidence rates were estimated with the Kaplan-Meier method. Cox regression was used to assess statistical significance. RESULTS: The overall rebubbling rate was 24% after 8 weeks. Relative dips in IOP may be associated with a higher risk for graft detachment (hazards ratio = 0.41; P < 0.001). Graft detachment was neither significantly influenced by donor factors, first or maximum IOP, nor by simultaneous cataract surgery (triple-DMEK). CONCLUSIONS: Avoiding dips in IOP may reduce the risk for graft detachment after DMEK. To prevent lowering of IOP values in the early postsurgical period, it may be advisable to achieve tight surgical wounds at the end of DMEK surgery and optimal filling of the anterior chamber with air and optionally with gas.

Regional Differences in Thrombectomy Rates : Secondary use of Billing Codes in the MIRACUM (Medical Informatics for Research and Care in University Medicine) Consortium.

BACKGROUND AND PURPOSE: Mechanical thrombectomy, in addition to intravenous (i.v.) thrombolysis is recommended for treatment of acute stroke in patients with large vessel occlusions (LVO) in the anterior circulation up to 6 h after symptom onset. We compared thrombectomy rates of eight university hospitals of the MIRACUM consortium to analyze the implementation of this guideline in clinical routine. METHODS: Anonymized billing data in a standardized format were loaded into a local i2b2 data warehouse by applying already existing extract, transform and load (ETL) routines. A locally executed uniform SQL (structured query language) query delivered aggregated site data for all inpatients with a discharge diagnosis of ischemic stroke (ICD-10 I63) containing counts for type of acute treatment, type of admission and age groups, which were centrally analyzed with R. RESULTS: From 2014 to 2016, the thrombectomy rate almost doubled from a mean of 4.7% to 9.6%, although significant differences between centers exist (range in 2016: 5.8-17%). The number of drip-and-ship procedures increased in 3 out of 8 centers. There was no evidence for a decrease in thrombectomy rates during weekends/holiday or among patients older than 80 years, but this age group is more likely to receive i.v. recombinant tissue plasminogen activator (rtPA). CONCLUSION: The observed increase of thrombectomy rates and drip-and-ship procedures without a significant difference between weekdays and weekends or patients of different ages is substantiating a rapid implementation of stroke guidelines within the analyzed neurovascular centers. The prototype of the MIRACUM Data Integration Center already contributes to health services research in Germany.

Diabetes and beta-adrenergic blockage are risk factors for metastatic prostate cancer.

BACKGROUND: We evaluated the influence of comorbidity inferred risks for lymph node metastasis (pN1) and positive surgical margins (R1) after radical prostatectomy in order to optimize pretherapeutic risk classification. We analyzed 454 patients after radical prostatectomy (RP) between 2009 and 2014. Comorbidities were defined by patients' medication from our electronic patient chart and stratified according to the ATC WHO code. Endpoints were lymph node metastasis (pN1) and positive surgical margins (R1). RESULTS: Rates for pN1 and R1 were 21.4% (97/454) and 29.3% (133/454), respectively. In addition to CAPRA and Gleason score, we identified diabetes as a significant medication inferred risk factor for pN1 (OR 2.9, p = 0.004/OR 3.2, p = 0.001/OR 3.5, p = 0.001) and beta-blockers for R1 (OR 1.9, p = 0.020/OR 2.9, p = 0.004). Patients with diabetes showed no statistically significant difference in Gleason score, CAPRA Score, PSA, and age compared to non-diabetic patients. CONCLUSIONS: We identified diabetes and beta1 adrenergic blockage as significant risk factors for lymph node metastasis and positive surgical margins in prostate cancer (PCa). Patients at risk will need intensive pretherapeutic staging for optimal therapeutic stratification.

Recurrent stroke after cervical artery dissection.

OBJECTIVE: Cervical artery dissection (CAD) accounts for 10-20% of all strokes in young adults, but no randomised controlled trial has investigated the best secondary prevention after ischaemic stroke or transient ischaemic attack (TIA). Because only small numbers of patient with CAD have been prospectively documented and followed up, the authors aimed to investigate the prognosis under various prevention regimens. METHODS: 30 German departments of neurology with acute stroke units prospectively documented 250 patients with acute ischaemic stroke or TIA due to CAD. A central follow-up (median 31 months) assessed recurrent stroke, recurrent CAD and death in 198 patients. RESULTS: CAD was found more often in the carotid arteries (52.0%) than in the vertebral arteries (46.8%). Thirteen patients (5.2%, CI 3.1% to 8.6%) suffered a recurrent stroke during the acute hospital stay. The rate of recurrent CAD during the first year was 1.7% (95% CI 0.3% to 3.6%). The cumulative recurrent stroke rate during the first year was 10.7% (95% CI 6.5% to 14.9%) and 14.0% (95% CI 8.9% to 19.1%) over 3 years. After discharge, the rate of recurrent stroke up to 6 months in patients treated with anticoagulants was 2.0% (95% CI 0.6% to 7.1%) and in those treated with antiplatelets 16.7% (95% CI 5.8% to 39.2%), which was statistically significant (HR 0.11; CI 0.02 to 0.69, p=0.02). CONCLUSIONS: This observational study confirms a high risk of early recurrent stroke following acute IS or TIA due to CAD. Whether anticoagulation provides any benefit over antiplatelets needs to be investigated in a randomised controlled trial.