Felix Walter Friedrich

Purpose: Patients with COPD suffer from various comorbidities, seemingly leading to a collective increase in morbidity and mortality. However, comorbidities with COPD have been largely unreported. Patients and Methods: Using healthcare claims data, only the deceased among around 250,000 COPD patients diagnosed in 2011– 2018 were evaluated by cause of death (cumulative incidence without competing risk) across a period of up to eight years. Results were compared with 1:1 propensity score-matched controls. Additionally, the prevalence of comorbidities in deceased patients was compared. Results: On average, deceased COPD patients and matched controls lived to be 75.7 and 78.0 years, respectively, and COPD patients had more comorbidities prior to death (mean 4.53 and 3.65). Both respiratory and cardiovascular-related deaths were more likely in COPD patients than in their matched controls (3.3 and 1.6 percentage points higher after eight years), and this was more extreme (9.8 and 3.4 percentage points higher, respectively) in the COPD subgroup with multiple/severe exacerbations; cumulative incidence of death increased with increasing COPD severity. Comorbidity prevalence, especially cardiovascular-related, was higher in COPD patients than in matched controls; COPD patients had a 42% higher risk of heart failure (RR 1.42; 1.38– 1.47), 30% higher risk of ischemic heart disease (RR 1.30; 1.25– 1.35), and 27% increased risk of atrial fibrillation (RR 1.27; 1.21– 1.32). Conclusion: In this real-world observational retrospective cohort study, we found patients with COPD died at a younger age, and developed more comorbidities, than matched controls. Plain Language Summary: People affected by COPD have other health issues. We studied a cohort of deceased insurees, comparing the health status of those with, to those without COPD, before death. The database had data from 250,000 COPD patients, over a period of up to eight years. More people with COPD died from respiratory or heart-related causes. They also died younger and had more additional health issues, compared to the non-COPD cohort, regardless of cause of death. The COPD cohort had higher rates of asthma, pneumonia, various heart conditions, dementia, depression, cancer, and osteoporosis, compared to the non-COPD cohort; they were more likely to have these comorbidities diagnosed particularly before death. For example, the risk of pneumonia, atrial fibrillation, and heart failure was up to 83% higher in the COPD cohort. The risk of depression was also 78% higher in those with COPD than in the cohort without COPD. This information shows a clear link between COPD and other health issues, especially those related to the lungs and heart. Treatment guidelines for COPD patients should target multiple health issues at once.

Background: Pancreatic cancer is one of the most aggressive cancers, with comparatively poor outcomes despite the use of multiagent conventional chemotherapy regimens. Real-world data from clinical... Plain language summary Cancer of the pancreas is one of the most aggressive cancers, with poor survival despite the use of strong chemotherapy. Data from clinical practice are still rare but are th...

Background: Recent studies evaluating the predictive value of different variables on future exacerbations suggest exacerbation history as the strongest predictor. We examined the effect of exacerbation history on subsequent events in a large sample population with over 250,000 COPD patients using up to 8 years of longitudinal healthcare data from Germany. Methods: Patients 40 years or older with any COPD diagnosis in primary or secondary care were included from 2011 to 2017 (index period) from healthcare insurance claims (Germany; WIG2 research database), with 12 months before index date as baseline and at least 12-month follow-up. Exacerbations during baseline were defined as moderate (treatment with oral corticosteroids or antibiotics, J01AA, J01CA) or severe (emergency visit or hospitalization). Results: Patients without (category A), with one moderate (category B), or with either one severe or several baseline exacerbations (category C) experienced an average of 0.9 (CI 0.9– 0.9), 1.9 (CI 1.9– 1.9), and 6.3 (CI 6.1– 6.3) exacerbations during the first 3 years of follow-up, respectively. By 8 years, 87.0% (CI 86.6– 87.4), 70.5% (CI 69.9– 71.0) and 49.1% (CI 48.9– 49.3) of category C, B and A patients had experienced a subsequent exacerbation. Conclusion: Baseline exacerbations increased the likelihood of, and reduced time to subsequent exacerbations. Even patients without baseline exacerbations experienced exacerbations within three years, emphasizing the importance of adequate treatment in patients with less severe disease presentation as well.

Background: COPD exacerbations may result in increased morbidity and mortality. Recent studies using models to evaluate the predictive value of different variables on future exacerbations, suggest that exacerbation history is the strongest predictor. We examined the effect of exacerbation history on subsequent exacerbations in a large sample population with over 250,000 real-world COPD patients, using up to 8 years of longitudinal healthcare data from Germany. Methods and Results: Healthcare insurance claims (Germany; WIG2 research database) were obtained 2011 – 2017 as the index period with 12 months before and after for baseline assessment and follow-up. Patients 40 years or older with any COPD diagnosis in primary or secondary care within the study time frame (January 1st, 2011 to December 31st, 2017) were included. Baseline exacerbations 12 months pre-index were defined as moderate (treatment with oral corticosteroids or antibiotics, J01AA, J01CA) or severe (emergency visit or hospitalization). Exacerbation risk by baseline exacerbation number and severity was estimated as cumulative incidence with 95% CIs adjusted for death. A total of 250,723 COPD patients (mean age 63.0 years, 43% women) were included. On average, patients with one moderate baseline exacerbation experienced 1.9 (1.9 – 1.9) exacerbations during the first 3 years of follow-up, whereas patients with either one severe baseline exacerbation, or 2 or more moderate and/or severe baseline exacerbations experienced 6.3 (6.1 – 6.3) exacerbations. More than half of patients with a moderate baseline exacerbation developed another event within 3 years, more than a third of patients without baseline exacerbations experienced at least one exacerbation during the same time frame. Conclusion: Patients with a severe or multiple baseline exacerbation history had a markedly higher risk for and shorter time to a subsequent exacerbation. Having had one moderate baseline exacerbation increased the risk of a subsequent exacerbation throughout follow-up. The present data highlights a need for strategies regarding management and treatment of COPD patients to prevent subsequent exacerbations. Article published online: 30 April 2021 © 2021. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

The purpose of the present study was to assess whether 6-week ranolazine application on top of guideline-based treatment impacts on the arginine/NO pathway and urinary isoprostane 8-iso-PGF_2α as marker of oxidative stress in patients directly after a myocardial infarction. 20 patients with unstable angina pectoris and proof of acute cardiac ischemia entered the study. 10 subjects received the study drug ranolazine in addition to standard treatment, the others received only standard treatment. Urine and venous blood were collected before and after treatment. At the end of the study and compared to baseline, homoarginine levels had increased in the control group. This was not the case in ranolazine-patients. Interestingly, in ranolazine-treated-patients arginine plasma levels were significantly higher at the end of the study than at baseline (difference +26 µmol/L, 95% CI 8.6 to 44 µmol/L). ADMA and SDMA levels were not different. Urine levels of the oxidative stress marker 8-iso-PGF_2α tended to be lower in ranolazine-treated patients (−144 pmol/mg creatinine). Findings of this hypothesis-driven study give evidence that ranolazine treatment enhances arginine plasma levels and lowers oxidative stress.

Background: Many forms of hypertrophic cardiomyopathy (HCM) show an increased myofilament Ca²⁺ sensitivity. This observation has been mainly made in HCM mouse models, myofilament systems, and cardiomyocytes. Studies of multicellular tissues from patients with different HCM-associated gene mutations are scarce. We investigated Ca²⁺ sensitivity in multicellular cardiac muscle strips of HCM patients. We furthermore evaluated the use of epigallocatechin-3-gallate (EGCg), a Ca²⁺ desensitizer. Methods: After strip isolation from cardiac tissues with single (MYBPC3, MYH7) or double heterozygous mutations (MYBPC3/FLNC, MYH7/LAMP2, MYBPC3/MYH7) and permeabilization, we performed contractility measurements ±EGCg. We furthermore evaluated gene expression with a customized heart failure gene panel using the NanoString technology. Results: F_max tended to be higher in HCM than in non-failing (NF) control strips and in single than in double heterozygous strips. Ca²⁺ sensitivity was higher by trend in most HCM vs. NF strips and by trend in tissues with double vs. single heterozygous mutations. EGCg desensitized myofilaments to Ca²⁺ in most of the strips and tended to induce a more pronounced shift in strips with truncating than missense or single than double heterozygous mutations. Gene expression analysis revealed lower ATP2A2, PPP1R1A, and FHL2 and higher NPPA, NPPB, COL1A1, CTGF, and POSTN marker levels in HCM than in NF tissues. NPPA, NPPB, ACTA1, CTGF, COL1A1, and POSTN levels were higher in tissues with missense than truncating mutations. Conclusion: We report an increased myofilament Ca²⁺ sensitivity in native multicellular cardiac HCM strips, which by trend was more pronounced in samples with double heterozygous mutations. EGCg could have differential effects depending on the underlying genetic status (single vs. double heterozygous) and type (missense vs. truncating).