Period of hospitalization and mortality in transferred versus non-transferred COVID-19 patients: results from Germany.

COVID-19 was a challenge for health-care systems worldwide, causing large numbers of hospitalizations and inter-hospital transfers. We studied whether transfer, as well as its reason, was associated with the duration of hospitalization in non-ICU and ICU patients. For this purpose, all patients hospitalized due to COVID-19 between August 1st and December 31st, 2021, in a network of hospitals in Southern Germany were comprehensively characterized regarding their clinical course, therapy, complications, transfers, reasons for transfer, involved levels of care, total period of hospitalization and in-hospital mortality, using univariate and multiple regression analyses. While mortality was not significantly associated with transfer, the period of hospitalization was. In non-ICU patients (n = 545), median (quartiles) time was 7.0 (4.0-11.0) in non-transferred (n = 458) and 18.0 (11.0-29.0) days in transferred (n = 87) patients (p < 0.001). In ICU patients (n = 100 transferred, n = 115 non-transferred) it was 12.0 (8.3-18.0) and 22.0 (15.0-34.0) days (p < 0.001). Beyond ECMO therapy (4.5%), reasons for transfer were medical (33.2%) or capacity (61.9%) reasons, with medical/capacity reasons in 32/49 of non-ICU and 21/74 of ICU patients. Thus, the transfer of COVID-19 patients between hospitals was associated with longer periods of hospitalization, corresponding to greater health care utilization, for which specific patient characteristics and clinical decisions played a role.

[Retrospective clinical-causal evaluation of a positive PCR for SARS-CoV-2 in hospitalised patients across the age spectrum in a primary care hospital]. / Retrospektive klinisch-kausale Bewertung einer positiven PCR für SARS-CoV-2 bei hospitalisierten Patienten des gesamten Altersspektrums in einem Krankenhaus der Schwerpunktversorgung.

INTRODUCTION: It is often discussed that a positive PCR for SARS-CoV-2 in hospitalized patients may not be causally linked to the hospital stay, but no scientific data are available from Germany. Therefore, we analyzed to what extent a positive PCR test could be assessed as causal or secondary to admission according to clinical criteria in a tertiary care hospital of the first 4 months of 2022. METHODS: SARS-CoV-2-positive patients of RoMed-Klinikum Rosenheim/Bavaria from 01/01/2022 to 30/04/2022 were included. Patients were divided into a group with COVID-19 as direct reason for admission (CAW), and a group, in which this did not apply according to a comprehensive clinical assessment (nCAW). Patients with no clear allocation to these groups were counted separately. Categorization was based on a multilevel procedure and performed by an internist experienced in COVD-19 (M.H.). It included all available clinical, radiological, and laboratory findings as well as treatment decisions. RESULTS: 647 cases were included (age 10 days to 101 years, median 68 years; 49.5% women), including 13 patients in two admissions with positive PCR. 45.3% (n=293) were attributable to the group with COVID as the reason for admission, 48.8% (n=316) were not, no clear decision could be made in 35 patients, 3 patients were transferred from other clinics for isolation. In infants (up to 1 year), a positive PCR test was more frequently categorized as causative than in older patients. Leading symptoms of classification were found to be fatigue/fatigue, fever/chills, and cough on admission. Febrile convulsions accounted for the reason for admission in 10 cases of children (age 1.1-7.6 years). Length of stay did not differ significantly between groups (median (quartiles) 5 (2; 10) days for CAW, 5 (2; 12) for nCAW), nor did in-hospital mortality and median age of deceased or survivors. DISCUSSION: A retrospective analysis of all clinical data revealed that positive SARS-CoV-2 PCR played a major and - according to clinical criteria - causative role for admission and hospitalization in nearly 50% of cases, whereas it was an incidental finding in just under 50%. These results confirm data from other countries and demonstrate that the role of a positive SARS-CoV-2 PCR test for hospitalization can only be answered by a comprehensive and elaborate analysis of individual data.

First-line nab-paclitaxel plus carboplatin for patients with advanced non-small cell lung cancer: Final results of the NEPTUN study.

Real-world data on the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) are still limited. The NEPTUN study evaluated effectiveness and safety of first-line nab-paclitaxel (Abraxane) plus carboplatin (nab-P/C) in patients with advanced NSCLC in routine clinical practice in Germany. Patients included in our study were aged ≥18 years, diagnosed with locally advanced or metastatic NSCLC and with decision for first-line nab-P/C in routine clinical practice. Primary objective was 6-month progression-free survival rate (PFS6), secondary objectives included overall survival (OS), overall response rate (ORR) and safety. From 2016 to 2019, 408 patients from 75 sites were enrolled. PFS6 was 39.5% (95% CI: 34.2-44.8), median PFS was 5.1 months (95% CI: 4.6-5.6), ORR was 42.9% (95% CI: 37.7-48.2). Median OS was 10.5 months (95% CI: 9.2-11.6). In subgroup analyses, median OS for squamous vs non-squamous histology was 11.5 months (95% CI: 9.2-13.8) vs 9.8 months (95% CI: 8.1-11.3) and for patients aged ≥70 vs <70 years median OS was 12.4 months (95% CI: 9.8-15.1) vs 9.6 months (95% CI: 7.7-11.1). Adverse events (AEs) related to nab-paclitaxel were reported in 247 (66.4%) patients, while carboplatin-related AEs were documented in 224 (60.2%) patients. Most frequently related AEs were leukopenia (22.3%) for nab-paclitaxel and anemia (20.2%) for carboplatin. Nab-P/C-related deaths were reported in 2 (0.5%) patients (sepsis and neutropenic sepsis). No new or unexpected safety signals emerged. These results support the effectiveness and safety of first-line nab-P/C in patients with advanced NSCLC reported in the pivotal trial and highlight the clinical value of this regimen in the real-world setting.

A simple risk score for mortality including the PCR Ct value upon admission in patients hospitalized due to COVID-19.

PURPOSE: To develop a simple score for the outcomes from COVID-19 that integrates information obtained at the time of admission including the Ct value (cycle threshold) for SARS-CoV-2. METHODS: Patients with COVID-19 hospitalized from February 1st to May 31st 2021 in RoMed hospitals, Germany, were included. Clinical and laboratory parameters upon admission were recorded and patients followed until discharge or death. Logistic regression analysis was used to determine predictors of outcomes. Regression coefficients were used to develop a risk score for death. RESULTS: Of 289 patients (46% female, median age 66 years), 29% underwent high-flow nasal oxygen (HFNO) therapy, 28% were admitted to the Intensive Care Unit (ICU, 51% put on invasive ventilation, IV), and 15% died. Age > 70 years, oxygen saturation ≤ 90%, oxygen supply upon admission, eGFR ≤ 60 ml/min and Ct value ≤ 26 were significant (p < 0.05 each) predictors for death, to which 2, 2, 1, 1 and 2 score points, respectively, could be attributed. Sum scores of ≥ 4 or ≥ 5 points were associated with a sensitivity of 95.0% or 82.5%, and a specificity of 72.5% or 81.7% regarding death. The high predictive value of the score was confirmed using data obtained between December 15th 2020 and January 31st 2021 (n = 215). CONCLUSION: In COVID-19 patients, a simple scoring system based on data available shortly after hospital admission including the Ct value had a high predictive value for death. The score may also be useful to estimate the likelihood for required interventions at an early stage.

Associations of Post-Acute COVID syndrome with physiological and clinical measures 10 months after hospitalization in patients of the first wave.

BACKGROUND: For a better understanding of the factors underlying the Post-Acute COVID Syndrome, we studied the relationship between symptoms and functional alterations in COVID-19 patients 10 months after hospitalization. METHODS: One-hundred-one patients hospitalized between March 1st and June 30th 2020 participated in a follow-up visit for an assessment of clinical history, comorbidities, lung function, physical capacity and symptoms, including the SGRQ for health-related quality of life, PHQ-9-D for depression, and SOMS-2 J for somatoform disorders. Data were analyzed by univariate comparisons and multiple logistic regression analyses. RESULTS: Median age was 60 years, 42% were female, 76% had at least one comorbidity, the median length of the hospital stay was 8 days, 19% had been on the ICU. The most prevalent symptoms included shortness of breath (49%), fatigue (49%) and cognitive impairment (39%). Signs of major depression (PHQ-9-D ≥ 10) occurred in 28%/2% (p < 0.05) of patients with/without self-reported cognitive impairment, with median total SGRQ score being 25.4/5.3 (p < 0.05). There were associations between shortness of breath and BMI, SGRQ and hemoglobin levels; between fatigue, SGRQ and PHQ-9-D; and between cognitive impairment and PHQ-9-D (p < 0.05 each) but not with lung function or physical capacity. Characteristics of the acute disease were not related to symptoms. CONCLUSIONS: The findings demonstrate that 10 months after discharge from a hospital stay due to COVID-19, the percentages of patients with symptoms were high. Symptoms showed a consistent pattern but could not be attributed to altered lung function or physical capacity. Our results suggest a role for alternative etiologies including psychosocial factors.

First-line nab-paclitaxel plus carboplatin for patients with advanced non-small cell lung cancer: Results of the NEPTUN study.

BACKGROUND: Platinum-based chemotherapy remains a first-line standard of care for approximately 30% of patients with non-small cell lung cancer (NSCLC) not harboring a druggable alteration. Favorable efficacy and safety of the nab-paclitaxel/carboplatin (nab-P/C) combination was shown in the pivotal phase 3 trial. However, information on effectiveness of nab-P/C in a real-world setting in Germany is missing. The NEPTUN study prospectively investigated the effectiveness and safety of nab-P/C in patients with advanced NSCLC in a real-world setting. METHODS: Patients with advanced or metastatic NSCLC received first-line nab-P/C according to clinical routine. The primary endpoint was 6-month progression-free survival rate (PFS6). Other endpoints included further effectiveness parameters, safety and quality of life. Data were analyzed descriptively. RESULTS: 408 patients were enrolled. PFS6 was 40.8% (95% confidence interval [CI], 35.3-46.2); median PFS was 5.2 months (95% CI, 4.5-5.7). overall response rate was 41.5% (95% CI, 36.3-46.8). Median overall survival (OS) was 10.5 months (95% CI, 9.2-11.6). Subgroup analyses revealed median OS for squamous versus non-squamous histology (11.8 months [95% CI, 9.2-13.8] vs. 9.6 months [95% CI, 7.7-11.2]) and age ≥70 versus <70 years (11.7 months [95% CI, 9.4-14.3] vs. 9.6 months [95% CI, 7.5-11.2]). Most common treatment-emergent adverse events (TEAEs) were anemia (26.5%), leukopenia (25.7%), and thrombocytopenia (16.6%). Mostly reported grade 3/4 TEAEs were leukopenia (10.2%), anemia (8.6%), and pneumonia (5.1%). nab-paclitaxel-related deaths as reported by the investigator occurred in 0.8% of patients. CONCLUSION: These real-world data support the effectiveness and safety of nab-P/C as first-line treatment for patients with advanced NSCLC independent of tumor histology. The results are comparable with the pivotal phase 3 trial. No new safety signals emerged.

Patients' treatment limitations as predictive factor for mortality in COVID-19: results from hospitalized patients of a hotspot region for SARS-CoV-2 infections.

BACKGROUND: In hospitalized patients with SARS-CoV-2 infection, outcomes markedly differ between locations, regions and countries. One possible cause for these variations in outcomes could be differences in patient treatment limitations (PTL) in different locations. We thus studied their role as predictor for mortality in a population of hospitalized patients with COVID-19. METHODS: In a region with high incidence of SARS-CoV-2 infection, adult hospitalized patients with PCR-confirmed SARS-CoV-2 infection were prospectively registered and characterized regarding sex, age, vital signs, symptoms, comorbidities (including Charlson comorbidity index (CCI)), transcutaneous pulse oximetry (SpO2) and laboratory values upon admission, as well as ICU-stay including respiratory support, discharge, transfer to another hospital and death. PTL assessed by routine clinical procedures comprised the acceptance of ICU-therapy, orotracheal intubation and/or cardiopulmonary resuscitation. RESULTS: Among 526 patients included (median [quartiles] age 73 [57; 82] years, 47% female), 226 (43%) had at least one treatment limitation. Each limitation was associated with age, dementia and eGFR (p < 0.05 each), that regarding resuscitation additionally with Charlson comorbidity index (CCI) and cardiac disease. Overall mortality was 27% and lower (p < 0.001) in patients without treatment limitation (12%) compared to those with any limitation (47%). In univariate analyses, age and comorbidities (diabetes, cardiac, cerebrovascular, renal, hepatic, malignant disease, dementia), SpO2, hemoglobin, leucocyte numbers, estimated glomerular filtration rate (eGFR), C-reactive protein (CRP), Interleukin-6 and LDH were predictive for death (p < 0.05 each). In multivariate analyses, the presence of any treatment limitation was an independent predictor of death (OR 4.34, 95%-CI 2.10-12.30; p = 0.001), in addition to CCI, eGFR < 55 ml/min, neutrophil number > 5 G/l, CRP > 7 mg/l and SpO2 < 93% (p < 0.05 each). CONCLUSION: In hospitalized patients with SARS-CoV-2, the percentage of patients with treatment limitations was high. PTL were linked to age, comorbidities and eGFR assessed upon admission and strong, independent risk factors for mortality. These findings might be useful for further understanding of COVID-19 mortality and its regional variations. Clinical trial registration ClinicalTrials.gov Identifier: NCT04344171.

Afatinib as first-line treatment in patients with EGFR-mutated non-small cell lung cancer in routine clinical practice.

BACKGROUND: Lung cancer is a leading cause of cancer-related death in Germany and worldwide. Non-small cell lung cancer (NSCLC) comprises ~80% of lung cancer diagnoses; in White patients, around 10% of NSCLC cases are epidermal growth factor receptor mutation-positive (EGFRm+). Head-to-head clinical trials have demonstrated superior efficacy with second-/third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) versus first-generation EGFR TKIs in EGFRm+ NSCLC. Data from routine clinical practice are necessary to confirm that clinical trial findings are transferable to real-world populations. METHODS: In NCT02047903, a prospective non-interventional study in Germany, patients with EGFRm+ NSCLC received first-line afatinib until disease progression or intolerable adverse events. Key objectives were progression-free survival (PFS) rate at 12 months, objective response rate (ORR) and overall survival (OS). Safety/tolerability was also assessed. RESULTS: Of 152 patients, 106 (69.7%) were female, 20 (13.1%) patients had an uncommon EGFR mutation and 51 patients (33.6%) had brain metastases. A starting dose of <40 mg was received by 39 (25.7%) patients. Overall, the 12-month PFS rate was 50.2% while the median PFS was 12.2 months. The ORR was 74.6% and the median OS was 30.4 months. In patients with brain metastases and uncommon mutations, the median PFS was 10.5 and 10.7 months, and the ORR was 77.3% and 83.3%, respectively. Treatment effectiveness was similar in patients with a starting dose of <40 mg (median PFS: 16.4 months; ORR, 81.3%) and a starting dose of 40 mg (median PFS: 10.8 months; ORR, 72.1%). Adverse drug reactions were manageable and consistent with the known afatinib safety profile. CONCLUSION: The results support clinical trial data for afatinib in routine clinical practice, including in patients generally excluded from clinical trials. Outcomes were positive in patients with uncommon EGFR mutations and in those with brain metastases. Treatment benefit was also seen in patients receiving a <40 mg afatinib starting dose, supporting patient-tailored dosing.

Prognostic Value of Oxygenated Hemoglobin Assessed during Acute Exacerbations of Chronic Pulmonary Disease.

BACKGROUND: Oxygenated hemoglobin(OxyHem) is a simple-to-measure marker of oxygen content capable of predicting all-cause mortality in stable chronic obstructive pulmonary disease (COPD). OBJECTIVES: We aimed to analyze its predictive value during acute exacerbations of COPD (AECOPD). METHODS: In this retrospective study, data from 227 patients discharged after severe AECOPD at RoMed Clinical Center Rosenheim, Germany, between January 2012 and March 2018, was analyzed. OxyHem (hemoglobin concentration [Hb] × fractional SpO2, g/dL) was calculated from oxygen saturation measured by pulse oximetry and hemoglobin assessed within 24 h after admission. The follow-up (1.7 ± 1.5 years) covered all-cause mortality, including readmissions for severe AECOPD. RESULTS: During the follow-up period, 127 patients died, 56 due to AECOPD and 71 due to other reasons. Survivors and non-survivors showed differences in age, FVC % predicted, C-reactive protein, hemoglobin, Cr, Charlson Comorbidity Index (CCI), and OxyHem (p < 0.05 each). Significant independent predictors of survival were BMI, Cr or CCI, FEV1 % predicted or FVC % predicted, Hb, or OxyHem. The predictive value of OxyHem (p = 0.006) was superior to that of Hb or SpO2 and independent of oxygen supply during blood gas analysis. OxyHem was also predictive when using a cutoff value of 12.1 g/dL identified via receiver operating characteristic curves in analyses including either the CCI (hazard ratio 1.85; 95% CI 1.20, 2.84; p = 0.005) or Cr (2.04; 95% CI 1.35, 3.10; p = 0.001) as covariates. CONCLUSION: The concentration of OxyHem provides independent, easy-to-assess information on long-term mortality risk in COPD, even if measured during acute exacerbations. It therefore seems worth to be considered for broader clinical use.