Search

Annemarie Voss,1 Bianca Kollhorst,2 Katharina Platzbecker,1 Ute Amann,1 Ulrike Haug1,3 1Department of Clinical Epidemiology, Leibniz Institute for Prevention Research and Epidemiology – BIPS, Bremen, Germany; 2Department of Biometry and Data Management, Leibniz Institute for Prevention Research and Epidemiology – BIPS, Bremen, Germany; 3Faculty of Human and Health Sciences, University of Bremen, Bremen, GermanyCorrespondence: Ulrike Haug, Department of Clinical Epidemiology, Leibniz Institute for Prevention Research and Epidemiology – BIPS, Bremen, Germany, Tel +49 421 218 56862, Email haug@leibniz-bips.dePurpose: Over the last decade, the use of direct oral anticoagulants (DOACs) has strongly increased. We aimed to describe and compare risk profiles including potential changes over time among persons with non-valvular atrial fibrillation initiating treatment with different DOACs or phenprocoumon (vitamin K antagonist) between 2011 and 2019 in Germany.Patients and Methods: Using the German Pharmacoepidemiological Research Database (GePaRD; claims data of ~20% of the German population), we identified persons with a first dispensing of phenprocoumon or a DOAC and a diagnosis of non-valvular atrial fibrillation between August 2011 and December 2019. We described the morbidity of included patients prior to treatment initiation, stratified by year of treatment initiation.Results: Overall, we included 448,028 new users (phenprocoumon: N = 118,117, rivaroxaban: N = 130,997, apixaban: N = 130,300, edoxaban: N = 38,128, dabigatran: N = 30,486). Comparing new DOAC users in 2019, the proportion with prior ischemic stroke was highest for dabigatran (17%) and lowest for rivaroxaban (8%). The proportion with prior major bleeding was also highest for dabigatran (25%) and lowest for edoxaban (20%). New users of apixaban were oldest and, eg, showed the highest prevalence of congestive heart failure. Changes over time were most pronounced for phenprocoumon. For example, among persons initiating phenprocoumon in 2012 vs 2019, the proportion with prior major bleeding increased from 18% to 35%; the proportion with renal disease increased from 20% to 36% and the proportion with liver disease from 18% to 24%.Conclusion: This study demonstrated differences in risk profiles between new users of different oral anticoagulants and substantial changes over time among new phenprocoumon users. These differences have to be considered in head-to-head comparisons of these drugs based on observational data, especially regarding potential unmeasured confounding.Keywords: atrial fibrillation, oral anticoagulants, direct oral anticoagulants, DOACs, risk profiles

Presents a letter to the editor regarding typical manifestations of cutaneous T-cell lymphoma.

Background/Objectives : QTc prolongation can result in lethal arrhythmia. Risk scores like the Tisdale score can be used for risk stratification for targeted pharmaceutical interventions. However, the practical usability across different medical specialties has not been sufficiently investigated. The aim of this study was to compare relevant risk factors for QTc prolongation and to investigate the use of the Tisdale score in cardiology and gastroenterology patients. Methods : For patients on a cardiology and a gastroenterology ward receiving a weekly pharmaceutical electronic chart review, risk factors for QTc prolongation, QTc-prolonging drugs, and electrocardiograms (ECGs) were retrospectively collected for a four-month period (07-10/2023), and the Tisdale score and its sensitivity and specificity were calculated. Results : A total of 627 chart reviews (cases) (335 cardiology, 292 gastroenterology) were performed. The median age was 66 (range 20-94) years, and 39% (245) of patients were female. The presence of established risk factors (hypokalemia, renal impairment, age ≥ 68 years, cardiac diseases) differed significantly between the specialties. A median of 2 (range 0-5) QTc-prolonging drugs were prescribed in both groups. Baseline and follow-up ECG were recorded in 166 (50%) cardiology cases, of which prolonged QTc intervals were detected in 38 (23%) cases. In the 27 (9%) gastroenterology cases with baseline and follow-up ECG, no QTc prolongations were detected. Across both specialties, the Tisdale score achieved a sensitivity of 74% and a specificity of 30%. Conclusions : The presence of established risk factors for QTc prolongation differed significantly between cardiology and gastroenterology cases. The Tisdale score showed acceptable sensitivity for risk stratification; however, the limited availability of ECGs for gastroenterology cases was a limiting factor.

Purpose: Postoperative delirium (POD) is a common complication in older adult patients after surgery. A patient's preoperative anticholinergic (AC) burden is a potentially modifiable risk factor for POD. As the influence of the drug dose remains unknown, we aimed to compare three AC burden scores in relation to POD, two of which were dose-related., Methods: This retrospective cohort study (03/22-10/22) included orthopaedic and trauma surgery patients > 65 years. POD was assessed using the four A's test (4AT), delirium diagnosis, and chart review. The AC burden was determined using the non-dose-related German Anticholinergic Burden score (GerACB), an extension of the dose-related Muscarinic Acetylcholinergic Receptor ANTagonist Exposure scale (extMARANTE), and the dose-related German Drug Burden Index (GerDBI). Multivariable logistic regression analysis determined the association between the preoperative AC burden and POD. Scores were compared using kappa statistics, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV)., Results: POD was observed in 71 of 385 patients (18.4%). For all three scores, a high AC burden was significantly associated with POD after adjusting for age, sex, dementia, preoperative physical status, and number of prescribed drugs (p < 0.001). The overall agreement among the burden classifications was substantial (no POD: κ = 0.645, POD: κ = 0.632). The GerACB had the lowest sensitivity with 23.9% (extMARANTE: 42.3%, GerDBI: 40.8%), but the highest PPV with 48.6% (extMARANTE: 38.5%, GerDBI: 43.3%)., Conclusion: Both dose-related and non-dose-related AC burden scores have limited sensitivity and modest PPV for screening a patient's medication for POD. However, given the additional effort required for dose consideration, the non-dose-related GerACB remains sufficient in clinical practice, with the lowest sensitivity but highest PPV., Competing Interests: Declarations. Funding: Open Access funding enabled and organized by Projekt DEAL. Open access funding provided by the Stiftung Patient & Klinische Pharmazie, Munich, Germany. Conflicts of Interest: The project gertrud was partially funded by the Bavarian State Ministry of Health and Care within the Guideline for the Promotion of Innovative Medical Care Concepts (IMVR), grant notification dated 09.06.2021 (K1-2496-IMV-20-V4). A data sharing agreement without connection to the data of this manuscript was rewarded an allowance by Pipra AG, Zürich, Switzerland. T.S. received funding by the Munich Medical and Clinician Scientist Program, Faculty of Medicine, LMU Munich (MCSP ACS-11). The study sponsors were not involved in the study design, study execution, or data analysis. The authors have no other potential conflicts of interest to declare. Availability of Data and Material: The data that support the findings of this study are available from the corresponding author upon reasonable request. Ethics Approval: The study was approved by the Ethics Committee of LMU University Hospital Munich (No. 23-0041) and complied with the Declaration of Helsinki. Consent to Participate: The Ethics Committee of LMU University Hospital Munich waived the requirement to obtain any informed consent due to the retrospective design of the study. Consent for Publication: Not applicable Code Availability: Not applicable Author Contributions: The authors contributed to the paper as follows. Study conception: C.G., T.S., K.D., U.A., and D.S. Expert committee for anticholinergic dose values: C.R., V.S., and D.S. Data collection: C.G. and T.S. Data analysis: C.G., U.A., and D.S. Manuscript – original draft: C.G. All authors have read and approved the final version of the manuscript and agree to be accountable for the work., (© 2024. The Author(s).)

Drug information (DI) provided by hospital pharmacies aims to promote rational and safe drug therapy. While quality assessment for this task is recommended, more knowledge on the factors determining the quality is needed. We aimed to evaluate the impacts of different factors on the quality of DI provided by hospital pharmacies to healthcare professionals. Retrospectively, answers on fictitious enquiries about annual DI tests for German hospital pharmacies over five years were evaluated for content-related and structural requirements. Multivariate analysis was performed for the impact of the enquiry complexity, DI organization (specialized DI center; pharmacist responsible per day; DI on top of other routine tasks), and quality measures (second look; experience of answering pharmacist in DI/on ward; use of documentation database). In 2017-2021, 45, 71, 79, 118, and 122 hospital pharmacies participated. The enquiry complexity had a statistically significant impact on the content-related quality, with poor results for a higher complexity (years 2018/2021, OR 0.25/0.04, p < 0.01). The DI centers achieved better results regarding content-related quality than for a pharmacist responsible per day (OR 0.76/ p = 0.65) or DI on top of routine tasks (OR 0.35/ p = 0.02). The DI centers scored better in structural quality. The second look showed an overall trend of a better content-related and structural quality. In conclusion, specialized DI centers and second looks are recommended as quality-improving measures. Training for answering complex enquiries should be intensified.

Background: Postoperative delirium (POD) is the most common complication following surgery in elderly patients. During pharmacist-led medication reconciliation (PhMR), a predictive risk score considering delirium risk-increasing drugs and other available risk factors could help to identify risk patients., Methods: Orthopaedic and trauma surgery patients aged ≥ 18 years with PhMR were included in a retrospective observational single-centre study 03/2022-10/2022. The study cohort was randomly split into a development and a validation cohort (6:4 ratio). POD was assessed through the 4 A's test (4AT), delirium diagnosis, and chart review. Potential risk factors available at PhMR were tested via univariable analysis. Significant variables were added to a multivariable logistic regression model. Based on the regression coefficients, a risk score for POD including delirium risk-increasing drugs (DRD score) was established., Results: POD occurred in 42/328 (12.8%) and 30/218 (13.8%) patients in the development and validation cohorts, respectively. Of the seven evaluated risk factors, four were ultimately tested in a multivariable logistic regression model. The final DRD score included age (66-75 years, 2 points; > 75 years, 3 points), renal impairment (eGFR < 60 ml/min/1.73m 2 , 1 point), anticholinergic burden (ACB-score ≥ 3, 1 point), and delirium risk-increasing drugs (n ≥ 2; 2 points). Patients with ≥ 4 points were classified as having a high risk for POD. The areas under the receiver operating characteristic curve of the risk score model were 0.89 and 0.81 for the development and the validation cohorts, respectively., Conclusion: The DRD score is a predictive risk score assessable during PhMR and can identify patients at risk for POD. Specific preventive measures concerning drug therapy safety and non-pharmacological actions should be implemented for identified risk patients., (© 2024. The Author(s).)

Use of endothelin receptor antagonists (ERAs) and riociguat, approved for treatment of pulmonary hypertension (PH), is contraindicated during pregnancy due to reported teratogenicity in animals. We aimed to investigate prescribing of these drugs in girls/women of childbearing age and to explore - as a secondary aim - the occurrence of pregnancies exposed to these drugs. Using the German Pharmacoepidemiological Research Database (GePaRD, claims data from 20% of the German population) we conducted cross-sectional analyses to determine prescribing prevalence of ERAs and riociguat between 2004 and 2019 and to characterize users and prescribing patterns. In a cohort analysis, we assessed the occurrence of pregnancies exposed to these drugs in the critical time window. Overall, we identified 407 women with ≥ 1 dispensation of bosentan between 2004 and 2019; the respective number was 73 for ambrisentan, 182 for macitentan, 31 for sitaxentan, and 63 for riociguat. In nearly all years, more than 50% of the girls/women were ≤ 40 years. Age-standardized prevalence was highest for bosentan (0.04/1000) in 2012 and 2013, followed by macitentan (0.03/1000) in 2018 and 2019. We observed 10 exposed pregnancies: 5 to bosentan, 3 to ambrisentan, and 2 to macitentan. The increased prevalence of macitentan and riociguat from 2014 onwards might reflect changes in PH treatment. Even though PH is a rare disease and pregnancy should be avoided in women with PH, particularly if they use ERAs, we identified pregnancies exposed to ERAs. Multi-database studies will be needed to assess the risk of these drugs on the unborn child., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Aims: Observational research has indicated that proton pump inhibitors (PPIs) might increase the long-term risk of cardiovascular events. This study evaluated the evidence from observational studies for an effect of PPI monotherapy on the risk of incident cardiovascular events and cardiovascular mortality., Methods: The databases MEDLINE, EMBASE, and Scopus were systematically searched up to September 2021. The primary outcome was first cardiovascular event, i.e. first myocardial infarction or first ischaemic stroke. The secondary outcome was cardiovascular mortality. Studies were included following a detailed risk of bias assessment with the ROBINS-I tool. Sensitivity and bias analyses adjusted for potential publication bias, immortal time bias, and unmeasured confounding., Results: We included ten studies with 75,371 first cardiovascular events, as well as seven studies on cardiovascular mortality with 50,329 cardiovascular deaths in total. The pooled hazard ratios (HRs) for PPI use and cardiovascular events were 1.05 with a 95% confidence interval of (0.96; 1.15) before and 0.99 (0.93; 1.04) after adjusting for observational study design bias. The pooled HRs for PPI use and cardiovascular mortality were 1.27 (1.11; 1.44) before and 1.06 (0.96; 1.16) after adjusting for publication bias and observational study design bias., Conclusion: It is questionable, whether PPI monotherapy constitutes a cardiovascular risk factor., Competing Interests: Declaration of Competing Interest UA is member of the advisory board of Vetter Pharma-Fertigung GmbH & Co. KG, Ravensburg, Germany., (Copyright © 2022. Published by Elsevier B.V.)

Background and Purpose: Understanding the adverse effects of proton pump inhibitors (PPIs) is important due to their widespread use, but the available evidence for an increased dementia risk amongst patients taking PPIs is inconclusive. The present study aimed to estimate the causal effect of PPIs on the risk of dementia by target trial emulation and time-varying exposure modeling., Methods: Using claims data of 2,698,176 insured people of a large German statutory health insurer, a target trial was conceptualized in which individuals aged 40 years and older were classified as PPI initiators or non-initiators between 2008 and 2018, and were followed until diagnosis of dementia, death, loss to follow-up or end of study. Incidence of dementia (International Classification of Diseases 10 codes F00, F01, F03, F05.1, G30, G31.0, G31.1, G31.9 and F02.8+G31.82) was defined applying a 1-year lag window. Weighted Cox models were used to estimate the effect of PPI initiation versus non-initiation on dementia risk and weighted pooled logistic regression was used to estimate the effect of time-varying use versus non-use., Results: In all, 29,746 PPI initiators (4.4%) and 26,830 non-initiators (1.3%) were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio for dementia was 1.54 (95% confidence interval 1.51-1.58). The hazard ratio for time-dependent PPI use versus non-use was 1.56 (95% confidence interval 1.50-1.63). Differentiated subtypes, including unspecified dementia, Alzheimer's disease and vascular dementia, showed increased risk by PPI initiation and time-varying PPI use., Conclusions: This study suggests that PPI initiation and time-varying PPI use may increase overall dementia risk., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Purpose: The German annual drug prescription-report has indicated overuse of proton pump inhibitors (PPIs) for many years; however, little was known about the characteristics of people using PPIs. This study aimed to provide comprehensive utilization data and describe frequencies of potential on- and off-label PPI-indications in Bavaria, Germany., Methods: Claims data of statutorily insured people from 2010 to 2018 were used. Defined daily doses (DDDs) of PPIs by type of drug, prevalence of PPI-use and DDDs prescribed per 1000 insured people/day were analyzed. For 2018, proportions of users and DDDs per 1000 insured people were calculated by age and sex. To elucidate changes in prescribing practices due to a suspected drug-drug interaction, we examined co-prescribing of clopidogrel and PPIs between 2010 and 2018. For PPI new users, sums of DDDs and frequencies of potential indications were examined., Results: PPI prescribing increased linearly from 2010 to 2016 and gradually decreased from 2016 to 2018. In 2018, 14.7% of women and 12.2% of men received at least one prescription, and 64.8 DDDs (WHO-def.) per 1000 insured people/day were prescribed. Overall, omeprazole use decreased over the observation period and was steadily replaced by pantoprazole, especially when co-prescibed with clopidogrel. An on-label PPI-indication was not reported at first intake in 52.0% of new users., Conclusions: The utilization of prescribed PPIs has decreased since 2016. However, a large proportion of new PPI-users had no documentation of a potential indication, and the sums of DDDs prescribed often seemed not to comply with guidelines., (© 2021. The Author(s).)

Aim: This study examines epidemiological trends of acute myocardial infarction (AMI) in Germany from 2004-2015 across different age groups, using data of the population-based KORA myocardial infarction registry., Methods: Annual age-standardised, age-group- and sex-specific mortality and event rates (incident and recurrent) per 100,000 population as well as 28-day case fatality were calculated from all registered cases of AMI and coronary heart disease deaths in 25-74-year-olds from 2004-2015 and 75-84-year-olds from 2009-2015. Average annual percentage changes (AAPC) were calculated by joinpoint regression., Results: Mortality rates declined considerably among the elderly (75-84 years), in men by -6.0% annually, due to declines of case fatality by -3.0% and incidence rate by 3.4% and in women by -10.0%, driven by declines in incidence (-9.1%) and recurrence rate (-4.9%). Significant mortality declines also occurred in males, 65-74 years of age (AAPC -3.8%). Among the age groups 25-54 years and 55-64 years, there was no substantial decline in mortality, event rates or case fatality except for a decline of incidence rate in 55-64-year-old men (AAPC -1.8%)., Conclusion: Inhomogeneous AMI trends across age-groups indicate progress in prevention and treatment for the population >64 years, while among <55-year-olds, we found no significant trend in AMI morbidity and mortality.KEY MESSAGESAge standardised AMI mortality continued to decline from 2009 to 2015 in the study region.Declines in AMI mortality were driven by declines in event rates (both incidence and recurrence rates) and case fatality.AMI trends were inconsistent across different age groups with the strongest declines in mortality and event rates among the elderly population (75-84 years of age).

Background: Proton pump inhibitors (PPIs) are well tolerated in the short term but have recently been associated with increased long-term cardiovascular risk in observational studies., Aims: To evaluate long-term risks of myocardial infarction (MI) and ischaemic stroke (IS) associated with PPI vs H 2 -receptor antagonist (H 2 RA) therapy in adults without pre-existing cardiovascular or cerebrovascular disease METHODS: Using administrative claims data (2008-2018), we emulated a target trial comparing MI and IS risks in new users of PPIs vs H 2 RAs. Treatment was identified using dispensed prescriptions. MI and IS were defined using hospital discharge codes. Inverse probability weighting was used to adjust for confounding, and Cox models to estimate hazard ratios (HRs). Survival curves were estimated using weighted Kaplan-Meier estimators., Results: We identified 1 143 948 new users of PPIs and 36 229 new users of H 2 RAs who were free of prevalent cardiovascular or cerebrovascular disease. The mean follow-up time was 6.2 years for PPI initiators and 5.3 years for H 2 RA initiators. After 10 years, the HRs for MI and IS were 0.96 (95% confidence interval (CI): 0.80-1.16) and 0.98 (95% CI: 0.89-1.08), respectively., Conclusions: This analysis of claims data of a large German health insurer did not provide evidence that PPI therapy increased the risk of MI or IS in the first decade after treatment initiation., (© 2021 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Limited data on prehospital and early in-hospital coronary heart disease (CHD) deaths is available. Aims of this study were to provide a comprehensive description on CHD cases and to analyse determinants of prehospital death. From a population-based myocardial infarction (MI) registry in Augsburg, Germany we included 12,572 CHD cases aged 25-74 years between 2003-2017 and 4754 CHD cases aged 75-84 years between 2009-2017. Multivariable logistic regression models were conducted to identify patient characteristics associated with prehospital death compared to 28-day survival. In patients aged 25-74 years, 1713 (13.6%) died prehospital, 941 (7.5%) died within the first 24 h in-hospital and 560 (4.5%) died within the 2nd and 28th day after the acute event; in patients aged 75-84 years the numbers were 1263 (26.6%), 749 (15.8%) and 329 (6.9%), respectively. In both age groups increasing age, actual smoking or nicotine abuse, previous MI, angina pectoris and previous stroke were more likely and hypertension was less likely in cases, who died prehospital compared to 28-day survivors. For example, in the 25-74 years old we revealed an adjusted odds ratio (OR) of 4.53 (95% CI 3.84-5.34) for angina pectoris and an OR of 0.69 (95% CI 0.57-0.85) for hypertension. In cases aged 25-74 years, an association of living alone (OR 1.26, 95% CI 1.06-1.49) and diabetes (OR 1.20, 95% CI 1.03-1.41) with prehospital death was found. Whereas in cases aged 75-84 years, chronic obstructive pulmonary disease (OR 2.20, 95%CI 1.69-0.2.85) was associated with prehospital death. In summary, we observed high prehospital and early in-hospital case fatality. Besides classical cardiac risk factors, the impact of living alone on prehospital death was more important in patients aged 25-74 years than in older patients., (© 2021. The Author(s).)

Purpose: Due to conflicting scientific evidence for an increased risk of dementia by intake of proton pump inhibitors (PPIs), this study investigates associations between PPI use and brain volumes, estimated brain age, and cognitive function in the general population., Methods: Two surveys of the population-based Study of Health in Pomerania (SHIP) conducted in Northeast Germany were used. In total, 2653 participants underwent brain magnetic resonance imaging (MRI) and were included in the primary analysis. They were divided into two groups according to their PPI intake and compared with regard to their brain volumes (gray matter, white matter, total brain, and hippocampus) and estimated brain age. Multiple regression was used to adjust for confounding factors. Cognitive function was evaluated by the Verbal Learning and Memory Test (VLMT) and the Nuremberg Age Inventory (NAI) and put in relation to PPI use., Results: No association was found between PPI use and brain volumes or the estimated brain age. The VLMT score was 1.11 lower (95% confidence interval: - 2.06 to - 0.16) in immediate recall, and 0.72 lower (95% CI: - 1.22 to - 0.22) in delayed recall in PPI users than in non-users. PPI use was unrelated to the NAI score., Conclusions: The present study does not support a relationship between PPI use and brain aging.

Study Objectives: To investigate the association between admission blood glucose levels and 28-day mortality as well as in-hospital complications in older patients with incident acute myocardial infarction (AMI) undergoing modern treatment., Methods: From a German population-based regional MI registry, 5530 patients (2016 women), aged 65-84 years, hospitalised with an incident AMI between 1 January 2009 and 31 December 2016 were included in the study. Multivariable logistic regression models were used to assess the associations between admission blood glucose and 28-day mortality as well as in-hospital complications after AMI. Analyses stratified according to age, diabetes and type of infarction (ST-elevation MI (STEMI)/non-STEMI) were conducted., Results: The adjusted ORs for the association between admission blood glucose and 28-day mortality in young-old (65-74 years) and old (75-84 years) patients with AMI were 1.40 (95% CI: 1.21 to 1.62) and 1.21 (95% CI: 0.98 to 1.50) per 1 SD increase in admission blood glucose, respectively. Furthermore, higher admission blood glucose was related to case fatality irrespective of the diabetes status and type of infarction only in the under-75 group. For the patients aged 75-84 years, it was only true for those without diabetes and STEMI. Admission blood glucose was also associated with major cardiac complications in both age groups., Conclusion: Admission blood glucose was significantly associated with 28-day case fatality in patients with AMI aged 65-74 years but not 75-84 years; furthermore, in both age groups there was an increased risk of major complications. It seems that admission glucose may play a rather minor role in terms of case fatality in higher aged patients with AMI., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The aim of this study was to evaluate the impact of the COVID-19 pandemic lockdown on acute myocardial infarction (AMI) care, and to identify underlying stressors in the German model region for complete AMI registration. The analysis was based on data from the population-based KORA Myocardial Infarction Registry located in the region of Augsburg, Germany. All cases of AMI (n = 210) admitted to one of four hospitals in the city of Augsburg or the county of Augsburg from February 10th, 2020, to May 19, 2020, were included. Patients were divided into three groups, namely pre-lockdown, strict lockdown, and attenuated lockdown period. An additional survey was conducted asking the patients for stress and fears in the 4 weeks prior to their AMI. The AMI rate declined by 44% in the strict lockdown period; in the attenuated lockdown period the rate was 17% lower compared to the pre-lockdown period. The downward trend in AMI rates during lockdown was seen in STEMI and NSTEMI patients, and independent of sex and age. The door-to-device time decreased by 70-80% in the lockdown-periods. In the time prior to the infarction, patients felt stressed mainly due to fear of infection with Sars-CoV-2 and less because of the restrictions and consequences of the lockdown. A strict lockdown due to the Covid-19 pandemic had a marked impact on AMI care even in a non-hot-spot region with relatively few cases of COVID-19. Fear of infection with the virus is presumably the main reason for the drop in hospitalizations due to AMI., (© 2021. The Author(s).)

Study Objective: Long-term intake of proton pump inhibitors (PPIs) might increase the risk of cardiovascular events. One suggested mechanism is that PPIs inhibit the enzyme dimethylarginine dimethylaminohydrolase (DDAH) and thereby block the degradation of endothelial asymmetrical dimethylarginine (ADMA). Excess ADMA in turn leads to impaired endothelial nitric oxide (NO) generation. So far, this mechanism has only been established in human cell cultures. Previous studies that examined this pathway in human populations measured circulating ADMA and found no association with PPI use and excess plasma ADMA. But in a recent study, plasma ADMA was not correlated with intracellular ADMA. We therefore focused on changes in plasma citrulline as an indicator for potential DDAH inhibition., Design: We analyzed the association between regular daily PPI intake and flow-mediated dilation (FMD) of the brachial artery as well as plasma concentrations of citrulline, arginine, ADMA, and symmetric dimethylarginine using inverse probability weighting to adjust for confounding and censoring., Data Source: Data of 1298 participants from two independent cohorts of the population-based Study of Health in Pomerania were used., Patients: Participants of the population-based Study of Health in Pomerania are a stratified random sample of the study region., Intervention: Regular daily intake of PPIs., Measurements: FMD of the brachial artery and plasma concentrations of citrulline, arginine, ADMA, and symmetric dimethylarginine., Main Results: Eighty-seven participants (57.5% female) were regular daily users of PPIs. In the fully adjusted models, associations were identified for FMD and plasma citrulline concentrations. PPI users revealed a 0.99% (95% CI: -1.96 to -0.02) lower FMD and 3.03 µmol/L (95% CI: -4.96 to -1.10) lower plasma citrulline levels as compared to non-users., Conclusion: Our data provide evidence that long-term intake of PPIs might inhibit human DDAH activity, resulting in impaired endothelial NO production and reduced vascular function. In the long run, this might explain an increased risk for cardiovascular diseases associated with long-term PPI use., (© 2021 The Authors. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy published by Wiley Periodicals LLC on behalf of Pharmacotherapy Publications, Inc.)

Background: Hypertension remains a significant modifiable risk factor for cardiovascular diseases and a major determinant of morbidity and mortality. We aimed to describe sex-stratified age-standardized estimates of prevalence, awareness, treatment and control of hypertension, and their associated factors in older adults., Methods: The KORA-Age1 is a population-based cross-sectional survey carried out in 2008/2009 on individuals aged 65-94 years in Augsburg region, Germany. Blood pressure measurements were available for 1052 out of 1079 persons who participated in the physical examination. Factors associated with prevalence, awareness and control of hypertension were investigated by multivariable logistic regression., Results: The overall prevalence of hypertension (≥140/90 mmHg) was 73.8% [95% confidence interval (CI), 69.3-77.9], representing 74.8% (95% CI, 68.4-80.2) in men and 73.5% (95% CI, 66.8-79.3) in women. Among those with hypertension, 80.2% (95% CI, 75.3-84.4) were aware of their hypertensive condition and 74.4% (95% CI, 69.2-79.1) were on treatment for hypertension. Among those aware of their hypertension status, 92.8% (95% CI, 88.8-95.6) were on treatment and 53.7% (95% CI, 47.0-60.1) had their blood pressure controlled. Hypertension was more frequent in individuals who were older, obese, or had diabetes. Higher education attainment or presence of comorbidities was associated with higher level of hypertension awareness. Individuals taking three antihypertensive drug classes were more likely to have controlled hypertension compared with those taking one antihypertensive drug class, odds ratio (OR), 1.85 (95% CI, 1.14-2.99)., Conclusion: Our findings identified high prevalence of hypertension and relevant health gaps on awareness, treatment and suboptimal control of hypertension in older adults in Germany. Screening for hypertension should especially target older adults with low educational attainment and 'healthy' elderly with less contact to physicians.

The present study evaluated the ability of the visceral adiposity index (VAI), the lipid accumulation product (LAP), and product of triglycerides and glucose (TyG), three novel, insulin resistance-related markers, to discriminate prediabetes/diabetes in the general German population. Altogether 2,045 Germans (31-72 years, 53.3% women) without known diabetes and a history of Myocardial Infarction (MI)/stroke from the Cooperative Health Research in the Region of Augsburg (KORA) F4 Study were eligible. The discriminatory accuracy of the markers for oral glucose tolerance test (OGTT)-defined prediabetes/diabetes according to the American Diabetes Association (ADA) criteria was assessed by the area under the receiver operating characteristic (ROC) curve (AUC). The Youden Index (YI) was used to determine optimal cut-off values, and a non-parametric ROC regression was used to examine whether the discriminatory accuracy varied by sex and age. 365 men (38.2%) and 257 women (23.6%) were newly diagnosed with prediabetes/diabetes. AUCs for TyG, LAP and VAI were 0.762 (95% CI 0.740-0.784), 0.743 (95% CI 0.720-0.765), and 0.687 (95% CI 0.662-0.712), respectively. The optimal cut-off values for the LAP and TyG were 56.70 and 8.75 in men, and 30.40 and 8.53 in women. In conclusion, TyG and LAP provide good discrimination of persons with prediabetes/diabetes.

Introduction: Helicobacter pylori ( H. pylori ) is a common infection and known risk factor for gastric cancer. We assessed cross-sectional and longitudinal associations to study the impact of H. pylori seropositivity on metabolic diseases. Methods: Helicobacter pylori seropositivity in serum samples of the KORA study was analyzed by multiplex serology. We calculated sex-specific prevalence of H. pylori seropositivity for the year 2007 based on the first follow-up survey (termed F4) of the KORA study S4. We identified factors associated with H. pylori seropositivity in the F4 survey. Further, we assessed relative risks of incident metabolic diseases/risk factors at the time of the second follow-up survey of S4 (termed FF4) and H. pylori seropositivity at the F4 survey as a determinant. Models were adjusted for age, sex, overweight status, physical activity, smoking status, education level, alcohol intake, and other metabolic diseases. Results: Based on 3,037 persons aged 32 to 82 years, the H. pylori prevalence for 2007 was 30.2% in men ( n = 1,465) and 28.1% in women ( n = 1,572). Increasing age, current smoking, low education and no alcohol intake were significantly associated with H. pylori seropositivity in the F4 survey. However, no association between H. pylori seropositivity and BMI, metabolic diseases (type 2 diabetes, hypertension and dyslipidemia, gout or increased uric acid) and gastrointestinal diseases (gastritis, inflammatory bowel disease, and gastric or duodenal ulcer) was observed. No significant associations between H. pylori seropositivity and one of the five investigated incident metabolic diseases/risk factors were detected in the longitudinal analysis. Conclusion: We identified associations between age, smoking, education and alcohol intake and H. pylori seropositivity but no impact of H. pylori seropositivity on incident metabolic diseases/risk factors.

Background: Sleep-related investigations in acute myocardial infarction (AMI) patients are rare. The aim of this study was to examine sex-specific associations of patient-reported sleep disturbances within 4 weeks before AMI and long-term survival., Methods: From a German population-based, regional AMI registry, 2511 men and 828 women, aged 28-74 years, hospitalized with a first-time AMI between 2000 and 2008 and still alive after 28 days, were included in the study (end of follow-up: 12/2011). Frequency of any sleep disturbances within 4 weeks before AMI was inquired by a 6-categorical item summarized to 'never', 'sometimes' and 'nightly'. Cox regression models were calculated., Results: Over the median follow-up time of 6.1 years (IQR: 4.1) sleep disturbances were reported by 32.3% of male and 48.4% of female patients. During the observation period, 318 men (12.7%) and 131 women (15.8%) died. Men who 'sometimes' had sleep disturbances showed a 56% increased mortality risk compared to those without complaints in an age-adjusted model (HR 1.56; 95%-CI 1.21-2.00). Additional adjustment for confounding variables attenuated the effect to 1.40 (95%-CI 1.08-1.81). Corresponding HRs among women were 0.97 (95%-CI 0.65-1.44) and 0.99 (95%-CI 0.66-1.49). HRs for patients with nightly sleep disturbances did not suggest any association for both sexes., Conclusions: Our study found that nightly sleep disturbances have no influence on long-term survival in male and female AMI patients. Contrary to women, men who reported sometimes sleep disturbances had a higher mortality. Further investigations on this topic taking into account the role of obstructive sleep apnoea are needed.

Purpose: We evaluated the pharmacological treatment of distal sensorimotor polyneuropathy (DSPN) among older subjects from the general population., Methods: The study included subjects aged 61 to 82 years from the KORA F4 survey (2006-2008). DSPN was defined as the presence of bilaterally impaired foot-vibration perception and/or bilaterally impaired foot-pressure sensation. Pain intensity was assessed with the painDETECT questionnaire., Results: From the included 1076 older persons, 172 (16%) persons reported pain in the lower extremities and DSPN was present in 150 (14%) subjects. Forty-eight people with pain in the lower extremities reported DSPN. Only 38% of the subjects with DSPN reporting an average pain level of ≥4 during the past 4 weeks received medical treatment, predominantly nonsteroidal anti-inflammatory drugs (NSAIDs 20% and opioids 12%). The medication of choice for neuropathic pain, antidepressants, anticonvulsants, and opioids was relatively being underused. However, opioids and neuropathy preparations were prescribed preferably for subjects with painful DSPN., Conclusions: In the older general population, only a small proportion of subjects with painful DSPN receive analgesic pharmacotherapy. Although not recommended by guidelines for the treatment of neuropathic pain, NSAIDs were the most frequently used class of analgesic drugs., (Copyright © 2018 John Wiley & Sons, Ltd.)

Background: Adherence to recommendations and medication is deemed to be important for effectiveness of case management interventions. Thus, reasons for non-adherence and effects on health-related quality of life (HRQoL) should be fully understood. The objective of this research was to identify determinants of non-adherence to medication and recommendations, and to test whether increased adherence improved HRQoL in patients after myocardial infarction (MI) in a case management intervention., Methods: Data were obtained from the intervention group of the KORINNA study, a randomized controlled trail of a nurse-led case management intervention with targeted recommendations in the elderly after MI in Germany. Reasons for non-adherence were described. Logistic mixed effects models and OLS (ordinary least squares) were used to analyze the effect of recommendations on the probability of adherence and the association between adherence and HRQoL., Results: One hundred and twenty-seven patients with 965 contacts were included. Frequent reasons for non-adherence to medication and recommendations were "forgotten" (22%; 11%), "reluctant" (18%; 18%), "side effects" (38%; 7%), "the problem disappeared" (6%; 13%), and "barriers" (0%; 13%). The probability of adherence was lowest for disease and self-management (38%) and highest for visits to the doctor (61%). Only if patients diverging from prescribed medication because of side effects were also considered as adherent, 3-year medication adherence was associated with a significant gain of 0.34 quality-adjusted life years (QALYs)., Conclusions: Most important determinants of non-adherence to medication were side effects, and to recommendations reluctance. Recommended improvements in disease and self-management were least likely adhered. Medication adherence was associated with HRQoL., Trial Registration: Current Controlled Trials ISRCTN02893746 , retrospectively registered, date assigned 27/03/2009.

Background: Little data is available on short- and long-term survival in patients with peripheral arterial disease (PAD) after acute myocardial infarction (AMI). We aimed to examine the association of PAD and 28-day case fatality as well as long-term mortality in a population-based sample of patients with incident AMI., Methods: In this secondary analysis of data from the German MONICA/KORA Myocardial Infarction Registry 4307 patients aged 28-74years with incident AMI with and without history of PAD (information derived from medical chart) were included. Data were collected between 2000 and 2008. Patients were followed-up until December 2011. Associations between PAD and 28-day case fatality were examined via multivariable logistic regression models, between PAD and long-term mortality with Cox proportional hazards regression models, respectively., Results: From 303 (8.9%) patients with PAD, 22 (7.3%) died within 28-days post-AMI in contrast to 96 (2.9%) of patients without PAD. However, the fully adjusted model (OR 1.55, 95% CI 0.89-2.70) revealed no significant association. Long-term follow-up (median 5.7years) yielded 100 (32.4%) versus 483 (14.4%) cases of deaths among patients with and without PAD, respectively. This association was significant (fully adjusted model: HR 1.70, 95% CI 1.35-2.13), persisted up to 11years after AMI and was present in all subgroups according to age, sex and history of diabetes. The highest long-term mortality risk was found for patients younger than 63years with PAD (HR 2.19; 95% CI 1.41-3.39)., Conclusion: AMI patients with PAD differ considerably from their counterparts without PAD in terms of long-term survival., (Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background Challenging clinical practice guidelines that recommend serum potassium concentration between 4.0-5.0 mEq/L or ≥4.5 mEq/L in patients with acute myocardial infarction, recent studies found increased mortality risks in patients with a serum potassium concentration of ≥4.5 mEq/L. Studies investigating consequences of hypokalemia after acute myocardial infarction revealed conflicting results. Therefore, the aim of this systematic review and meta-analysis was to combine evidence from previous studies on the association of serum potassium concentration with both short and long-term mortality as well as the occurrence of ventricular arrhythmias. Design Systematic review and meta-analysis. Methods A structured search of MEDLINE and EMBASE databases yielded 23 articles published between 1990 and January 2017 that met the inclusion criteria. Study selection, data extraction and quality assessment were carried out by three reviewers. Random effects models were used to pool estimates across the included studies and sensitivity analyses were performed when possible. Results Twelve studies were included in the meta-analysis. Both pooled results from six studies investigating short-term mortality and from five studies examining long-term mortality revealed significantly increased risks in patients with serum potassium concentrations of <3.5 mEq/L, 4.5-<5.0 mEq/L and ≥5.0 mEq/L after acute myocardial infarction. In addition, a serum potassium concentration of <3.5 mEq/L was significantly associated with the occurrence of ventricular arrhythmias. Conclusions Mortality, both short and long term, and the occurrence of ventricular arrhythmias in patients with acute myocardial infarction seem to be negatively associated with hypokalemic serum potassium concentration. There is evidence for adverse consequences of serum potassium concentrations of ≥4.5 mEq/L. Due to the heterogeneity among existing studies, further research is necessary to confirm the need to change clinical practice guidelines.

Background: Previous studies have shown that the presence of anemia is associated with increased short- and long-term outcomes in patients with acute myocardial infarction (AMI). This study aims at examining the impact of admission anemia on long-term, all-cause mortality following AMI in patients recruited from a population-based registry. Contrary to most prior studies, we distinguished between patients with mild and moderate to severe anemia., Methods: This prospective study was conducted in 2011 patients consecutively hospitalized for AMI that occurred between January 2005 and December 2008. Patients who survived more than 28 days after AMI were followed up until December 2011. Hemoglobin (Hb) concentration was measured at hospital admission and classified according to the World Health Organization (WHO). Mild anemia was defined as Hb concentration of 11 to < 12 g/dL in women and 11 to < 13 g/dL in men; moderate to severe anemia as Hb concentration of < 11 g/dL. Adjusted Cox regression models were calculated to compare survival in patients with and without anemia., Results: Mild anemia and moderate to severe anemia was found in 183 (9.1%) and 100 (5%) patients, respectively. All-cause mortality after a median follow-up time of 4.2 years was 11.9%. The Cox regression analysis showed significantly increased mortality risks in both patients with mild (HR 1.74, 95% CI 1.23-2.45) and moderate to severe anemia (HR 2.05, 95% CI 1.37-3.05) compared to patients without anemia., Conclusion: This study shows that anemia adversely affects long-term survival following AMI. However, further studies are needed to confirm that anemia can solely explain worse long-term outcomes after AMI.

The purpose of this study was to investigate if there is a link between muscular strength (MS) and markers of chronic kidney disease (CKD) among older adults. The cross-sectional analysis based on 1041 men and women, aged 65-94 years, who participated in the KORA-Age study. Participants underwent an interview and extensive examinations including anthropometric measurements, diseases and drug intake registration, determination of health-related behaviors, collection of blood samples for measurements of cystatin C and maximal muscle strength evaluation. One-Way ANOVA revealed significant differences in both mean cystatin C (1.16±0.37 vs. 1.03±0.29 vs. 0.93±0.24 mg/L, p<0.001) and mean eGFRcysC (63.61±18.61 vs. 72.14±18.92 vs. 79.87±18.19 ml/min/1.73 m 2 , p<0.05) across thirds of maximal muscular strength (from lowest to highest). MS in the lowest third was significantly associated with increased odds of having elevated cystatin C (OR: 1.70, 95% CI: 1.01-2.85, p=0.043) after controlling for age, gender, fat mass, fat-free mass, alcohol intake, smoking status, number of regularly used medications, multimorbidity status, hs-CRP, telomere length and levels of physical activity. Lower levels of MS are independently associated with higher concentrations of cystatin C and lower eGFRcysC in older individuals. Increasing the levels of muscular strength may be useful to prevent the age-related CKD disease of older adults., Competing Interests: On behalf of all authors, the corresponding author states that there is no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Prior studies reported high guideline adherence for secondary prevention medications (SPM) at hospital discharge in patients with acute myocardial infarction (AMI). Less is known about medication use in long-term AMI survivors., Methods: Of the 2077 registered persons with an AMI between 2000 and 2008 who responded to a postal follow-up survey in 2011, 1311 men and 356 women, aged between 34.4 and 84.9years, reported medication intake 7days prior to the survey. These study participants also had their current health condition and comorbidities assessed. Information regarding index AMI was selected from the population-based MONICA/KORA MI registry. Multivariable logistic regression models were conducted to identify factors associated with SPM use (all 4 drug classes)., Results: The median time between index AMI and the follow-up survey was 6.1years (IQR: 3.9). At follow-up, a total of 10,422 medications were reported and polypharmacy was observed in 73.8%. Regarding SPM, the proportion of patients taking antiplatelet agents, beta-blockers, statins, and renin-angiotensin-aldosteron system blockers were 90.9%, 86.7%, 85.4%, and 79.3% respectively. Factors associated with SPM use were hypertension (odds ratio [OR] 1.48, p=0.006), SPM prescription at hospital discharge (OR 2.68, p<0.0001), revascularization therapy at index AMI (OR 2.46, p>0.0001), number of medications taken at follow-up (OR 1.48, p<0.0001), and several comorbidities such as lung disorders (OR 0.17; p<0.0001), depression (OR 0.53, p=0.001), neurological disorders (without stroke) (OR 0.34, p=0.002), and cancer (OR 0.45, p=0.005)., Conclusion: SPM use several years after AMI was high and associated with treatment at index AMI and patients' comorbidities., (Copyright © 2017 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: Conflicting with clinical practice guidelines, recent studies demonstrated that serum potassium concentrations (SPC) of ≥4.5 mEq/l were associated with increased mortality in patients with acute myocardial infarction (AMI). This study examined the association between SPC and long-term mortality following AMI in patients recruited from a population-based registry., Methods: Included in the study were 3347 patients with AMI aged 28-74 years consecutively hospitalized between 1 January 2000 and 31 December 2008 and followed up until 31 December 2011. Patients were categorized into five SPC groups (<3.5, 3.5 to <4.0, 4.0 to <4.5, 4.5 to <5.0, and ≥5.0 mEq/l). The outcome of the study was all-cause mortality. Cox regression models adjusted for risk factors, co-morbidities and in-hospital treatment were constructed., Results: In our study population, 249 patients (7.4%) had a low SPC (<3.5 mEq/l) and 134 (4.0%) patients had a high SPC (≥5.0 mEq/l). Patients with SPC of ≥5.0 mEq/l had the highest long-term mortality (29.9%) and in the adjusted model, their risk of dying was significantly increased (HR 1.46, 95% CI 1.03 to 2.07) compared to patients with SPC between 4.0 and <4.5 mEq/l. Analyses of increasing observation periods showed a trend towards a higher risk of dying in patients with SPC between 4.5 and <5.0 mEq/l., Conclusion: An admission SPC of ≥5.0 mEq/l might be associated with an increased mortality risk in patients with AMI. Patients with an admission SPC between 4.5 and <5.0 mEq/l might have an increased mortality risk in the first few years following AMI.

Background: Although emergency medical services (EMS) use is the recommended mode of transport in case of acute coronary symptoms, many people fail to use this service., Objective: The objective of this study was to determine factors associated with EMS use in a population-based sample of German patients with recurrent acute myocardial infarction (AMI)., Methods: The sample consisted of 998 persons with a first and recurrent AMI, recruited from 1985 to 2011. Logistic regression modeling adjusted for sociodemographic, situational, and clinical variables, previous diseases, and presenting AMI symptoms was applied., Results: Emergency medical services was used by 48.8% of the patients at first, and 62.6% at recurrent AMI. In first AMI, higher age, history of hyperlipidemia, ST-segment elevation AMI, more than 4 presenting symptoms, symptom onset in daytime, and later year of AMI were significantly related with EMS use. Pain in the upper abdomen and pain between the shoulder blades were significantly less common in EMS users. In recurrent AMI, EMS use at first AMI, presence of any other symptom except chest pain, ST-segment elevation myocardial infarction, and later year of AMI were significantly related with EMS use. Significant predictors of EMS use in recurrent AMI in patients who failed to use EMS at first AMI were unmarried, experience of any symptom except chest symptoms at reinfarction, bundle branch block (first AMI), any in-hospital complication (first AMI), longer duration between first and recurrent AMI, and later year of reinfarction., Conclusions: Patients with AMI and their significant others may profit by education about the benefits of EMS use.

Background Previous studies have indicated that patients with acute myocardial infarction (AMI) who have a history of peripheral arterial disease (PAD) have different characteristics and poorer outcomes than patients without PAD. However, data on short-term mortality are conflicting and it is unclear whether patients with PAD have a different scope of AMI symptoms or differences in pre-hospital delay time (PHDT) compared with patients without PAD. The objective of this study was to determine the associations between a history of PAD and presenting AMI symptoms, PHDT and 28-day case fatality in a population-based sample of patients with AMI. Design This was an observational study. Methods Information on history of PAD was obtained from the patients' medical records and their AMI symptoms were assessed by interviews with patients. Multivariable logistic regression models were used to determine the association of PAD with AMI symptoms and 28-day case fatality. A multivariable linear regression model was developed to examine the relations between PAD and PHDT. Results From the 5848 patients with AMI included in this study, 9.8% had a history of PAD. Patients with PAD were significantly less likely to report chest symptoms (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.41-0.66) or pain in the upper left extremity (OR 0.67, 95% CI 0.54-0.84) than patients without PAD. PAD was significantly related with longer PHDT in patients <69 years of age ( p = 0.0117) and men ( p = 0.0104). A significantly higher 28-day case fatality (OR 2.09, 95% CI 1.47-2.96) was found in patients with PAD compared with patients without PAD. Conclusions Patients with PAD should receive comprehensive education on the possibility of atypical AMI symptoms and the need to call emergency medical services immediately.