Long-Term Safety of Roflumilast in Patients with Chronic Obstructive Pulmonary Disease, a Multinational Observational Database Cohort Study.

Purpose: This study evaluated the long-term safety of roflumilast in patients with chronic obstructive pulmonary disease or chronic bronchitis using electronic healthcare databases from Germany, Norway, Sweden, and the United States (US).

Patients And Methods: The study population consisted of patients aged ≥40 years who had been exposed to roflumilast and a matched cohort unexposed to roflumilast. The matching was based on sex, age, calendar year of cohort entry date (2010-2011, 2012, or 2013), and a propensity score that included variables such as demographics, markers of chronic obstructive pulmonary disease (COPD) severity and morbidity, and comorbidities.

Elucidating the risk of cardiopulmonary consequences of an exacerbation of COPD: results of the EXACOS-CV study in Germany.

Background: Exacerbations of chronic obstructive pulmonary disease (COPD) represent a period of vulnerability. This study explored the association between time periods following an exacerbation and the risk of severe cardiovascular (CV) events or death in Germany.

Methods: A longitudinal cohort study was conducted using routinely collected healthcare data.

Risk of cardiovascular events after an exacerbation of chronic obstructive pulmonary disease: results from the EXACOS-CV cohort study using the PHARMO Data Network in the Netherlands.

Background: People living with chronic obstructive pulmonary disease (COPD) have an increased risk of experiencing cardiovascular (CV) events, particularly after an exacerbation. Such CV burden is not yet known for incident COPD patients. We examined the risk of severe CV events in incident COPD patients in periods following either moderate and/or severe exacerbations.

EXAcerbations of COPD and their OutcomeS on CardioVascular diseases (EXACOS-CV) Programme: protocol of multicountry observational cohort studies.

Introduction: In patients with chronic obstructive pulmonary disease (COPD), the risk of certain cardiovascular (CV) events is increased by threefold to fivefold in the year following acute exacerbation of COPD (AECOPD), compared with a non-exacerbation period. While the effect of severe AECOPD is well established, the relationship of moderate exacerbation or prior exacerbation to elevated risk of CV events is less clear. We will conduct cohort studies in multiple countries to further characterise the association between AECOPD and CV events.

Rare Variation in Drug Metabolism and Long QT Genes and the Genetic Susceptibility to Acquired Long QT Syndrome.

Background: Acquired long QT syndrome (aLQTS) is a serious unpredictable adverse drug reaction. Pharmacogenomic markers may predict risk.

Methods: Among 153 aLQTS patients (mean age 58 years [range, 14-88], 98.

Use of intravenous iron and risk of anaphylaxis: A multinational observational post-authorisation safety study in Europe.

Purpose: This post-authorisation safety study estimated the risk of anaphylaxis in patients receiving intravenous (IV) iron in Europe, with interest in iron dextran and iron non-dextrans. Studies conducted in the United States have reported risk of anaphylaxis to IV iron ranging from 2.0 to 6.

Sodium-Glucose Co-Transporter 2 Inhibitors and the Risk of Venous Thromboembolism in Patients with Type 2 Diabetes: A Cohort Study.

Purpose: We assessed whether sodium-glucose co-transporter type 2 (SGLT2) inhibitors are associated with a higher incidence rate of venous thromboembolism in patients with type 2 diabetes.

Methods: We conducted a population-based cohort study using the InGef database including patients with type 2 diabetes newly treated with noninsulin antidiabetic drugs between 2012 and 2018. Cases of venous thromboembolism identified during follow-up were matched to 40 controls on age, sex, cohort entry date, and duration of follow-up.

Incidence of second primary malignancies in metastatic castration-resistant prostate cancer: results from observational studies in three countries.

This reports some of the first incidence rate (IR) estimates of second primary malignancies (SPMs) in men with metastatic castration-resistant prostate cancer (mCRPC) in three countries. Claims data from the German Pharmacoepidemiological Research Database; registry data from the Prostate Cancer Data Base Sweden; and combined registry-claims data from the US Surveillance, Epidemiology and End Results-Medicare database were analyzed to obtain overall survival and incidence of SPMs in men with mCRPC. SPMs occurred in 308 German (n = 2360), 273 Swedish (n = 2849) and 172 US (n = 2234) men with mCRPC.

Safety and effectiveness of acellular pertussis vaccination during pregnancy: a systematic review.

Background: Infants < 3 months of age are at highest risk for developing severe complications after pertussis. The majority of pregnant women has low concentrations of pertussis-specific antibodies and thus newborns are insufficiently protected by maternally transferred antibodies. Acellular pertussis vaccination during pregnancy was recently implemented in various countries.

Antidepressants and the risk of death in older patients with depression: A population-based cohort study.

Background: Antidepressants are frequently used in older patients with depression, but little is known about the comparative safety of individual agents. The objective of the study was to determine the comparative risk of death of antidepressants in older patients with depression.

Methods And Findings: We carried out a cohort study from 2004 to 2015 utilizing the German Pharmacoepidemiological Research Database, a population-based database supplied by statutory health insurance providers covering approximately 17% of the general population and all geographical regions.

Risk of acute myocardial infarction during use of individual NSAIDs: A nested case-control study from the SOS project.

Background: Use of selective COX-2 non-steroidal anti-inflammatory drugs (NSAIDs) (coxibs) has been associated with an increased risk of acute myocardial infarction (AMI). However, the risk of AMI has only been studied for very few NSAIDs that are frequently used.

Objectives: To estimate the risk of AMI for individual NSAIDs.

Risk of ischemic stroke and the use of individual non-steroidal anti-inflammatory drugs: A multi-country European database study within the SOS Project.

Background And Purpose: A multi-country European study using data from six healthcare databases from four countries was performed to evaluate in a large study population (>32 million) the risk of ischemic stroke (IS) associated with individual NSAIDs and to assess the impact of risk factors of IS and co-medication.

Methods: Case-control study nested in a cohort of new NSAID users. For each case, up to 100 sex- and age-matched controls were selected and confounder-adjusted odds ratios for current use of individual NSAIDs compared to past use calculated.

Sodium-glucose co-transporter-2 inhibitors and the risk of fractures of the upper or lower limbs in patients with type 2 diabetes: A nested case-control study.

Aims: To investigate whether the use of SGLT-2 inhibitors is associated with an increased risk of fractures.

Material And Methods: We conducted a cohort study with nested case-control analysis based on the InGef database between November 2011 and December 2016 among patients with type 2 diabetes who were initiating treatment with, switching to, or adding a new class of non-insulin antidiabetic drug. Patients with a hospital or ambulatory diagnosis of fractures of the upper or lower limbs were included and were matched to up to 40 randomly sampled control subjects.

Targeted resequencing of a locus for heparin-induced thrombocytopenia on chromosome 5 identified in a genome-wide association study.

Immune-mediated heparin-induced thrombocytopenia (HIT) is the clinically most important adverse drug reaction (ADR) in response to heparin therapy characterized by a prothrombotic state despite a decrease in platelet count. We conducted a genome-wide association study in 96 suspected HIT cases and 96 controls to explore the genetic predisposition for HIT within a case-control pharmacovigilance study followed by replication in additional 86 cases and 86 controls from the same study. One single nucleotide polymorphism (SNP, rs1433265, P = 6.

Over-The-Counter (OTC) Drug Consumption among Adults Living in Germany: Results from the German Health Interview and Examination Survey for Adults 2008⁻2011 (DEGS1).

In order to assess the effects of prescription-only (Rx) to over-the-counter (OTC) drug switches and related policies, it is imperative to distinguish self-medication from OTC drug use. The objective of this study was to estimate the OTC drug use in the adult population in Germany, to identify its predictors and to highlight methodological differences when compared to the study of a self-medication prevalence. Seven-day prevalence of OTC drug use was calculated on the basis of information provided by 7091 participants of the German Health Interview and Examination Survey for Adults (DEGS1) conducted between 2008 to 2011.

Use and Characteristics of Antipsychotic/Methylphenidate Combination Therapy in Children and Adolescents with a Diagnosis of Attention-Deficit/Hyperactivity Disorder.

Objective: Children and adolescents with attention-deficit/hyperactivity disorder (ADHD) frequently have comorbidities that are potential indications for antipsychotics (APs). Some studies have suggested that the combined use of methylphenidate (MPH) and APs is increasing in this population group. Longitudinal analyses and in-depth investigations on the substance level are lacking.

The Risk of Hospitalizations with Injury Diagnoses in a Matched Cohort of Children and Adolescents with and without Attention Deficit/Hyperactivity Disorder in Germany: A Database Study.

Background: Attention deficit/hyperactivity disorder (ADHD) is a common neuropsychiatric disorder in children and adolescents worldwide, and children with ADHD have elevated risk of injuries. Our aim was to assess the risk of hospitalizations with injury diagnoses and their various subtypes in children and adolescents with newly diagnosed ADHD compared to those without ADHD, as well as to study sex effects on this risk in the setting of the German health care system.

Methods: The German Pharmacoepidemiological Research Database, in which 20 million insured from four statutory health insurances in Germany are included, was used to set up a matched cohort study of 3- to 17-year-old children and adolescents with and without ADHD.

Drug-induced kidney injury: A large case series from the Berlin Case-Control Surveillance Study .

Objectives: Drug-induced kidney injury (DIKI) may affect patients regardless of their baseline kidney function. Therefore, this study evaluated DIKI in patients with or without previous chronic kidney disease (CKD).

Materials And Methods: Potential DIKI cases were ascertained using the network of the Berlin Case-Control Surveillance Study in all 51 Berlin hospitals from April 2010 until December 2011.

Extent and risks of antidepressant off-label use in children and adolescents in Germany between 2004 and 2011.

Purpose: So far, only little is known about antidepressant off-label use in pediatric patients. This is the first study examining the prevalence and the risks of off-label antidepressant prescriptions in minors over time in Germany and analyzing patterns regarding age, sex, drug class, and type of off-label use.

Methods: We used claims data of about two million individuals (<18 y) to calculate the share of off-label antidepressant prescriptions for the years 2004 to 2011, stratified by age, sex, and drug class.

Extent and Risks of Antipsychotic Off-Label Use in Children and Adolescents in Germany Between 2004 and 2011.

Objective: Only little is known about antipsychotic (AP) off-label use (OLU) in pediatric populations. It was the aim of this study to examine the frequency as well as the risks of off-label AP use in underaged patients.

Methods: To calculate the frequency of off-label AP prescriptions for the years 2004-2011, we used claims data of more than two million minors aged 0-17 years.

Immobilization and high platelet count are associated with thromboembolic complications in heparin-induced thrombocytopenia.

Purpose: Immune-mediated heparin-induced thrombocytopenia (HIT type II, HIT) is a potentially serious adverse drug reaction characterized by an increased risk of venous and arterial thrombosis. This study aimed to identify risk factors associated with the development of these complications.

Methods: Our study cohort included patients with HIT assembled in our pharmacovigilance center by reports from 51 collaborating hospitals in Berlin, Germany.

Risk of acute myocardial infarction with NSAIDs in real world use: bayesian meta-analysis of individual patient data.

 To characterise the determinants, time course, and risks of acute myocardial infarction associated with use of oral non-steroidal anti-inflammatory drugs (NSAIDs). Systematic review followed by a one stage bayesian individual patient data meta-analysis. Studies from Canadian and European healthcare databases.

Use of azithromycin and risk of ventricular arrhythmia.

Background: There are conflicting findings from observational studies of the arrhythrogenic potential of azithromycin. Our aim was to quantify the association between azithromycin use and the risk of ventricular arrhythmia.

Methods: We conducted a nested case-control study within a cohort of new antibiotic users identified from a network of 7 population-based health care databases in Denmark, Germany, Italy, the Netherlands and the United Kingdom for the period 1997-2010.

From prescription-only (Rx) to over-the-counter (OTC) status in Germany 2006-2015: pharmacological perspectives on regulatory decisions.

Purpose: Little is known about the extent of switches from prescription-only (Rx) to over-the-counter (OTC) status in Europe and about the pharmacological properties of the switched substances. The objectives of this study were to provide an overview of the substances that were switched from Rx to OTC status in Germany between 2006 and 2015 and to assess their pharmacological properties.

Methods: Session minutes of the German Expert Advisory Committee for Prescription-Only Issues, changes to the German Ordinance on Prescription-Only Medicines and the Summary of Product Characteristics of the switched substances were analysed.