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Christiane Eickhoff,1 Uta Müller,1 Sophie Thomas,2 Christian Schmidt,2 Lisa Sophie Hartling,3 Sebastian Michael,3,4 Martin Schulz,1,5 Thilo Bertsche2,6 1Department of Medicine, ABDA – Federal Union of German Associations of Pharmacists, Berlin, Germany; 2Clinical Pharmacy Department, Institute of Pharmacy, Medical Faculty, Leipzig University, Leipzig, Germany; 3Löwen-Apotheke Waldheim e.K, Waldheim, Germany; 4Saxon Pharmacists Association, Leipzig, Germany; 5Institute of Pharmacy, Freie Universität Berlin, Berlin, Germany; 6Drug Safety Center, Medical Faculty, Leipzig University and Leipzig University Hospital, Leipzig, GermanyCorrespondence: Christiane Eickhoff, Department of Medicine, ABDA – Federal Union of German Associations of Pharmacists, Heidestrasse 7, Berlin, 10557, Germany, Tel +49 30 40004-529, Fax +49 30 40004-513, Email C.Eickhoff@abda.dePurpose: A medication list (ML) is a document listing the patient’s entire medication, instructions for use, and indications. In Germany, a national standard was established in 2016 by law. However, data on patients’ use of this standardized ML are scarce. We investigated (i) patients’ practical use of the ML, (ii) patients’ understanding of the ML, (iii) completeness and correctness of the current ML version, and (iv) reasons why patients did not adhere to their ML.Patients and Methods: Community pharmacists recruited patients possessing a standardized ML with ≥ 5 medications. Information sources to evaluate the ML were: (a) brown bag analysis, (b) practical demonstration, (c) patient interview, and (d) patient file. Data were analyzed using qualitative and quantitative methods.Results: Two hundred and eighty-eight patients (median age: 76 years, range: 27– 95) were enrolled. (i) 38.5% of the patients used their ML regularly to prepare their medication and 73.3% to inform their physician. (ii) Overall, patients’ understanding of the ML was good, with > 80% of the patients being able to identify all relevant information. (iii) While n = 2779 medications were actually taken, n = 2539 were documented on the ML. No ML was fully correct and complete. Regarding particularly relevant items, ie, active ingredient, strength, dosage, medication missing or listed but not taken, 79.2% of ML were incorrect or incomplete. Handwritten modifications on the ML were frequent. (iv) Almost 60% of all patients did not follow their ML with “fear of adverse drug reactions” being the most frequently (n = 50) mentioned reason.Conclusion: Completeness and correctness of the current ML version was poor with handwritten modifications being frequent. Additionally, most of the patients did not adhere to their ML. This indicates that measures that lead to correct and up-to-date ML and improvements in patient counseling about their medication should be developed and implemented into routine practice.Keywords: medication list, medication schedule, medication plan, community pharmacy, medication safety, polypharmacy

Marten Schulz, Frank Tacke Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum (CVK) Und Campus Charité Mitte (CCM), Berlin, GermanyCorrespondence: Marten Schulz Email marten.schulz@charite.deAbstract: Steatosis is a condition of hepatic fat overload that is associated with overweight and the metabolic syndrome. Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease with a global impact on healthcare. A proportion of NAFLD patients develops nonalcoholic steatohepatitis (NASH), liver fibrosis, cirrhosis or hepatocellular carcinoma (HCC). Identifying patients at risk for potentially life-threatening complications is crucial in their prevention, surveillance and treatment. In addition to hepatic disease progression (cirrhosis, portal hypertension, HCC), NAFLD patients are also at risk of cardiovascular and metabolic diseases as well as extrahepatic malignancies. Liver fibrosis is related to morbidity and mortality in NASH patients, and biomarkers, imaging techniques (ultrasound, elastography, MRI) as well as liver biopsy help in diagnosing fibrosis. In this review, we discuss the tools for identifying patients at risk and their reasonable application in clinical routine in order to stratify prevention and treatment of this emerging disease.Keywords: NAFLD, fibrosis, cirrhosis, hepatocellular carcinoma, elastography, liver-stiffness measurement

Shirish Gadgeel,1 Alice T Shaw,2 Fabrice Barlesi,3 Lucio Crino,4 James CH Yang,5 Anne-Marie Dingemans,6 Dong-Wan Kim,7 Filippo de Marinis,8 Mathias Schulz,8 Shiyao Liu,9 Ravindra Gupta,9 Vlatka Smoljanovic,10 Sai-Hong Ignatius Ou11 1Department of Internal Medicine, Division of Hematology and Oncology, The University of Michigan, Ann Arbor, MI 48109, USA; 2Center for Thoracic Cancers, Massachusetts General Hospital, Boston, MA, USA; 3Multidisciplinary Oncology and Therapeutic Innovations Department, Aix-Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille 13005, France; 4Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) Srl I.R.C.C.S., Meldola, FC 47014, Italy; 5National Taiwan University Hospital and National Taiwan University Cancer Centre, Taipei City, Taiwan; 6Department of Pulmonology, Maastricht University Medical Centre, Maastricht 6229 HX, The Netherlands; 7Department of Internal Medicine, Seoul National University Hospital, Jongno-Gu, Seoul 03080, South Korea; 8Division of Thoracic Oncology, European Institute of Oncology IRCCS, Milan 20146, Italy; 9Genentech Inc., South San Francisco, CA, USA; 10F. Hoffmann-La Roche Ltd., Basel CH-4070, Switzerland; 11Division of Hematology-Medical Oncology, Department of Internal Medicine, University of California, Irvine School of Medicine, Orange, CA 92617, USACorrespondence: Sai-Hong Ignatius OuUniversity of California, Irvine School of Medicine, 1001 Health Sciences Road, Irvine, Orange, CA 92617, USATel +1 714 456 8104Email siou@uci.eduIntroduction: Alectinib is a highly selective and potent ALK inhibitor, approved for the treatment of patients with metastatic ALK+ NSCLC based on results from the Phase II global NP28673 (NCT01801111) and North American NP28761 (NCT01871805) studies.Methods: This exploratory analysis of two Phase II studies of alectinib (NP28673/NP28761) investigated time to systemic response (TTR) and time to central nervous system (CNS) response (TTCR) in patients with previously treated advanced anaplastic lymphoma kinase fusion gene-positive (ALK+) non-small-cell lung cancer. Patients (n=225) received 600 mg oral alectinib twice daily and had scans every 6/8 weeks (NP28673/NP28761).Results: For NP28673 and NP28761, respectively: median follow-up was 21.3 months/17.0 months; most responders (72.6%/82.9%) responded by the first disease assessment; median TTR was 8 weeks (95% confidence interval [CI]: 8.00–8.14)/6 weeks (95% CI: 5.86–6.14); median TTCR in responders with measurable baseline CNS disease was 8 weeks (95% CI: 7.86–10.29)/6 weeks (95% CI: 5.71–not evaluable). Similar results were observed regardless of measurable/non-measurable disease.Discussion: These data suggest that alectinib achieves a rapid response in patients, both systemically and in the CNS.Keywords: alectinib, non-small-cell lung cancer, NP28673, NP28761, time to response

Julius L Katzmann,1 Felix Mahfoud,2 Michael Böhm,2 Martin Schulz,3,4 Ulrich Laufs1 1Department of Cardiology, Universitätsklinikum Leipzig, Leipzig, Germany; 2Medical Clinic III, Cardiology, Angiology, Intensive Care, Universitätsklinikum des Saarlandes, Homburg, Germany; 3Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universität Berlin, Berlin, Germany; 4Department of Medicine, ABDA – Federal Union of German Associations of Pharmacists, Berlin, Germany Background: Many patients at high cardiovascular risk do not reach targets for low-density lipoprotein cholesterol (LDL-C) and blood pressure (BP). Depression is a frequent comorbidity in these patients and contributes to poor medication adherence.Objective: The aim of this study was to elucidate the associations between adherence to lipid- and BP-lowering drugs, the diagnosis of depression, and the control of LDL-C and BP.Patients and methods: This study was conducted as multicenter, single-visit cross-sectional study in Germany. Adherence was assessed by the Morisky Medication Adherence Scale-8 (MMAS-8), and depression was assessed as documented in the patient chart.Results: A total of 3,188 ambulatory patients with hypercholesterolemia (39.8%), stable coronary artery disease (CAD; 7.4%), or both (52.9%) were included. Patients had a history of myocardial infarction (30.8%), diabetes (42.0%), were smokers (19.7%), and 16.1% had the investigator-reported diagnosis of depression. High or moderate adherence to lipid-lowering medication compared to low adherence was associated with lower LDL-C levels (105.5±38.3 vs 120.8±42.4 mg/dL) and lower BP (systolic BP 133.4±14.5 vs 137.9±13.9 mmHg, diastolic BP 78.3±9.6 vs 81.8±9.6 mmHg) and with a higher proportion of patients achieving the guideline-recommended LDL-C (16.9% vs 10.1%) and BP target (52.2% vs 40.8%, all comparisons P

Florian Custodis,1 Franziska Rohlehr,1 Angelika Wachter,1 Michael Böhm,1 Martin Schulz,2 Ulrich Laufs1 1Department of Internal Medicine III, Cardiology, Angiology and Intensive Care Medicine, Saarland University Medical Center, Homburg/Saar, 2Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, Berlin, Germany Background: A substantial aspect of health literacy is the knowledge of prescribed medication. In chronic heart failure, incomplete intake of prescribed drugs (medication non-adherence) is inversely associated with clinical prognosis. Therefore, we assessed medication knowledge in a cohort of patients with decompensated heart failure at hospital admission and after discharge in a prospective, cross-sectional study.Methods: One hundred and eleven patients presenting at the emergency department with acute decompensated heart failure were included (mean age 78.4±9.2, 59% men) in the study. Patients’ medication knowledge was assessed during individual interviews at baseline, course of hospitalization, and 3 months after discharge. Individual responses were compared with the medical records of the referring general practitioner.Results: Median N-terminal prohormone of brain natriuretic peptide plasma concentration in the overall population at baseline was 4,208 pg/mL (2,023–7,101 pg/mL [interquartile range]), 20 patients died between the second and third interview. The number of prescribed drugs increased from 8±3 at baseline to 9±3 after 3 months. The majority of patients did not know the correct number of their drugs. Medication knowledge decreased continuously from baseline to the third interview. At baseline, 37% (n=41) of patients stated the correct number of drugs to be taken, whereas only 18% (n=16) knew the correct number 3 months after discharge (P=0.008). Knowledge was inversely related to N-terminal prohormone of brain natriuretic peptide levels.Conclusion: Medication knowledge of patients with acute decompensated heart failure is poor. Despite care in a university hospital, patients’ individual medication knowledge decreased after discharge. The study reveals an urgent need for better strategies to improve and promote the knowledge of prescribed medication in these very high-risk patients. Keywords: medication knowledge, hospitalization, chronic heart failure, health literacy

Lea Botermann,1,2 Katrin Krueger,1 Christiane Eickhoff,1 Charlotte Kloft,2 Martin Schulz1–31Department of Medicine, ABDA – Federal Union of German Associations of Pharmacists, Berlin, 2Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, Berlin, 3Department of Pharmacology, Goethe-University Frankfurt, Frankfurt am Main, GermanyPurpose: The Action Plan for Medication Safety by the German Federal Ministry of Health introduced a standardized medication plan (MP), a printable document for the patient. The practical handling needs to be tested before the nationwide implementation in Germany. Therefore, the aims of our study were 1) to develop an instrument to evaluate the usage of the standardized MP, 2) to assess if patients can locate, and 3) understand important information. Moreover, we explored patients’ opinion and suggestions regarding the standardized MP template.Patients and methods: We conducted a cross-sectional study to evaluate the practical handling of the standardized MP. We interviewed 40 adult patients in seven community pharmacies in Germany, who took at least five medicines regularly and gave their written informed consent. The interview consisted of questions regarding finding and understanding information provided on a mock-up MP, patients’ opinion and the execution of the information on the MP by filling pill boxes. We eventually developed a new evaluation method to quantify the practical handling of the MP by rating the pill boxes filled by the patients.Results: Overall, the participants rated the MP positively. Thirty-nine (98%) participants found important information on a mock-up standardized MP. Patients were questioned to identify if they understood information on medical intake as it relates to meals. In particular, they were questioned about medicine intake “1 hour before a meal”, which 98% (n=39) interpreted correctly, and “during a meal”, which 100% (n=40) interpreted correctly. The less precise advice of “before a meal” was interpreted correctly by 73% (n=29), and only 15% (n=6) correctly interpreted the term “after the meal”. The evaluation of the filled pill boxes resulted in the “Evaluation Tool to test the handling of the Medication Plan” (ET-MP) – a weighted scoring system.Conclusion: The standardized MP is clearly arranged, and patients are able to find important information. The findings of this study resulted in minor but important revisions of the standardized MP template. The developed evaluation tool ET-MP may serve as an objective instrument to assess patients’ ability to transfer written information on the MP into practical handling of medicines.Keywords: medication plan, medication schedule, ET-MP, Action Plan for Medication Safety, Germany, patient safety, pharmacotherapy

La criopreservación de espermatozoides y su utilización en inseminación artificial ha causado gran impacto sobre la reproducción de especies comerciales y en humanos. Sin embargo, a pesar del gran avance en el tema, constantemente se modifican los procedimientos de congelamiento, a fin de obtener mejores resultados de viabilidad y movilidad espermática, para lograr de esta forma mayores porcentajes de fecundaciones exitosas. No obstante, el proceso de criopreservación induce perdida de la función espermática que se refleja en alteraciones de la membrana plasmática, daño a nivel mitocondrial, deterioro en la integridad del ADN, aumento en la producción de las especies reactivas de oxígeno (ROS) y alteraciones del citoesqueleto, lo que finalmente tiene efectos negativos en la viabilidad y motilidad espermática, elementos esenciales para la fecundación. En la búsqueda de métodos que induzcan el menor daño celular, es que ha desarrollado en los últimos años los métodos de vitrificación espermática. Estos han permitido no solo superar en cuanto a la mantención de la función espermática a los métodos convencionales de congelación, sino también que lo hace más rápido, seguro y de menor costo. Esto último al eliminar los equipos necesarios para la congelación lenta y también en algunos casos la no utilización de nitrógeno líquido para el almacenamiento, bastando un congelador de - 80°C. Su aplicación en mamíferos, ha sido reportada exitosamente en humanos con nacimientos de niños sanos, tanto en técnicas de fecundación in vitro como inseminación intrauterina y recientemente con el nacimiento de los primeros felinos (gatos) con técnicas de inseminación intrauterina.

HL-LHC will confront the WLCG community with enormous data storage, management and access challenges. These are as much technical as economical. In the WLCG-DOMA Access working group, members of the experiments and site managers have explored different models for data access and storage strategies to reduce cost and complexity, taking into account the boundary conditions given by our community.Several of these scenarios have been evaluated quantitatively, such as the Data Lake model and incremental improvements of the current computing model with respect to resource needs, costs and operational complexity.To better understand these models in depth, analysis of traces of current data accesses and simulations of the impact of new concepts have been carried out. In parallel, evaluations of the required technologies took place. These were done in testbed and production environments at small and large scale.We will give an overview of the activities and results of the working group, describe the models and summarise the results of the technology evaluation focusing on the impact of storage consolidation in the form of Data Lakes, where the use of streaming caches has emerged as a successful approach to reduce the impact of latency and bandwidth limitation.We will describe the experience and evaluation of these approaches in different environments and usage scenarios. In addition we will present the results of the analysis and modelling efforts based on data access traces of the experiments.

Self-monitoring of blood glucose (SMBG) is clearly correlated with increased life expectancy and quality of life in type 2 diabetic patients. Objective: The objective of our study was to record and assess the errors patients make in preparing, performing, and processing self-monitoring of blood glucose (SMBG). Furthermore, the study aimed to determine to what extent a single standardized SMBG instruction session in a community pharmacy might reduce the number of patients making errors or the number of errors per patient. Methods: Between May and October 2005, SMBG of 462 randomly selected patients with type 2 diabetes was monitored in 32 pharmacies specialized in diabetes care. The patients performed blood glucose self-tests using their own blood glucose meters. Self-testing was monitored using a standardized documentation sheet on which any error made during the performance of the test was recorded. If necessary, patients were instructed in the accurate operation of their meter and the use of the necessary equipment. Additionally, patients obtained written instructions. Six weeks later, assessment of the quality of patient’s SMBG was repeated.Results: During the first observation, 383 patients (83%) made at least one mistake performing SMBG. By the time of the second observation, this frequency had fallen to 189 (41%) (p

Background: Generic substitution can have unintended consequences. In Germany, brand name to generic or generic to generic switching is mainly driven by rebate contracts. Frequent switching may raise concerns about bio- and therapeutic equivalence. Expected patient confusion may result in compromised medication adherence or new onset of other drug-related problems. Since 2008, pharmacists are allowed to deviate from rebate contracts by denying substitution due to pharmaceutical concerns on an individual basis. Objectives: To explore the frequency of documented pharmaceutical concerns in Germany between July 2011 and December 2013 and to identify the medicines most frequently related to pharmaceutical concerns in 2013. Methods: We analyzed documented pharmaceutical concerns in all prescribed drugs at the expense of any statutory health insurance company requiring pharmacies’ generic substitution according to rebate contracts. Results: Since July 2011, the frequency of documented pharmaceutical concerns in relation to prescribed drug products with rebate contracts requiring substitution increased consistently and doubled between July 2011 and July 2013. Overall in 2013, the trend of the two previous years continued and reached approximately 1.5%. The most affected drugs/drug classes were thyroid hormones (in particular combinations with iodide; 15.9%) followed by ondansetron (12.5%), and levothyroxine (11.3%). For all drugs/drug classes under investigation, product-, patient- or disease-related aspects could be identified which are potential reasons to deny substitution and to document pharmaceutical concerns. Conclusions: Although there is no electronic recording of the specific reasons for pharmaceutical concerns in claims data, our analyses support the assumption that pharmacists make use of this instrument based on individual clinical decisions and as required by contract. Pharmaceutical concerns are, therefore, an important instrument for pharmacies to refuse generic substitution. They are considered to prevent compromised medication safety and to assure pharmacotherapy effectiveness in a generic substitution environment driven by low drug prizes above all.

Background: Emergency hormonal contraceptives (EHC) are contraceptives used to prevent unintended pregnancy following unprotected sexual intercourse (USI) or contraceptive failure. The EHCs available without a prescription include medicines containing levonorgestrel (LNG) in more than 80 countries and, recently, based on an EU-switch ellaOne®, which contains ulipristal acetate (UPA). EHCs work by stopping or delaying ovulation. Those containing LNG can be used up to 72 hours after USI or contraceptive failure, while UPA can be used up to 120 hours. In the context of the UPA implementation process, Germany switched LNG to non-prescription status as well. Objectives: To develop recommendations, a protocol, and a continuing education program for pharmacists to assure quality when giving advice and dispensing EHCs in community pharmacies without a medical prescription. Methods: The recommendations were developed by an iterative process of drafting, recognizing, and discussing comments and proposals for amendments as well a seeking agreement with a number of stakeholders such as the Federal Ministry of Health (BMG), Federal Institute for Drugs and Medical Devices (BfArM), Federal Chamber of Physicians (BÄK), Drug Commission of German Physicians (AkdÄ), professional organizations/associations of gynaecologists, pharmaceutical OTC-industry as well as government-controlled, private, and church-based organizations and centres providing advice on sex education and family planning. Results: The recommendations were eventually endorsed by the BMG in consultation with the BfArM. Conclusions: The recommendations were made public, published in the professional journal and used in an uncounted number of continuing education programs based on the curriculum and provided by the State Chambers of Pharmacists.

This paper reports on a mixed-methods study with high school students. The study focused on the reasons they give with regard to "what they find interesting about their physics lesson" and "what makes them want to study their physics lesson" during a school year. The sample consisted of 219 students, who attended public high schools, located in various geographical regions of Greece. Journal entries made by all students--that is, students from junior high and senior high schools--were content-analyzed through a grounded theory approach. A total of eight categories were identified. Quantitative differences between these categories, and between the two groups of students, were also identified. Even though some of the identified categories are well-known motivators in science education, three specific categories deserve particular attention: "connection to one's own self", "purpose", and "utility". Notwithstanding the limitations of the present research design (i.e., volunteer sample, lack of standardization in students' and especially in teachers' activities), these categories, along with two quantitative indicators--that is, number of journal entries and student percentages--challenge us to rethink what makes the ideas of science, especially those of physics, meaningful or simply relevant to the life of the students.

Over the past few decades, the geographical distribution of emissions of substances that alter the atmospheric energy balance has changed due to economic growth and air pollution regulations. Here, we show the resulting changes to aerosol and ozone abundances and their radiative forcing using recently updated emission data for the period 1990-2015, as simulated by seven global atmospheric composition models. The models broadly reproduce large-scale changes in surface aerosol and ozone based on observations (e.g.-1 to-3%yr-1 in aerosols over the USA and Europe). The global mean radiative forcing due to ozone and aerosol changes over the 1990-2015 period increased by +0.17±0.08Wm-2, with approximately one-third due to ozone. This increase is more strongly positive than that reported in IPCC AR5. The main reasons for the increased positive radiative forcing of aerosols over this period are the substantial reduction of global mean SO2 emissions, which is stronger in the new emission inventory compared to that used in the IPCC analysis, and higher black carbon emissions.

The Aerosol Chemistry Model Intercomparison Project (AerChemMIP) is endorsed by the Coupled-Model Intercomparison Project 6 (CMIP6) and is designed to quantify the climate and air quality impacts of aerosols and chemically reactive gases. These are specifically near-term climate forcers (NTCFs: methane, tropospheric ozone and aerosols, and their precursors), nitrous oxide and ozone-depleting halocarbons. The aim of AerChemMIP is to answer four scientific questions. 1. How have anthropogenic emissions contributed to global radiative forcing and affected regional climate over the historical period? 2. How might future policies (on climate, air quality and land use) affect the abundances of NTCFs and their climate impacts? 3.How do uncertainties in historical NTCF emissions affect radiative forcing estimates? 4. How important are climate feedbacks to natural NTCF emissions, atmospheric composition, and radiative effects? These questions will be addressed through targeted simulations with CMIP6 climate models that include an interactive representation of tropospheric aerosols and atmospheric chemistry. These simulations build on the CMIP6 Diagnostic, Evaluation and Characterization of Klima (DECK) experiments, the CMIP6 historical simulations, and future projections performed elsewhere in CMIP6, allowing the contributions from aerosols and/or chemistry to be quantified. Specific diagnostics are requested as part of the CMIP6 data request to highlight the chemical composition of the atmosphere, to evaluate the performance of the models, and to understand differences in behaviour between them.