Incidence and costs of cardiac device infections: retrospective analysis using German health claims data.

AIM: Estimate incidence and costs of cardiac device infections (CDIs) in Germany. MATERIALS & METHODS: Patients had an implantable cardioverter defibrillator implanted over 2010-2013 and were followed to December 2014 using German health insurance claims data. A case-controlled analysis was performed using propensity score matching methods. RESULTS: Risk of CDI 12 months post-implant was 3.4% overall, either 2.9% for de novo procedures versus 4.4% for replacement procedures. Mean 3-year incremental expenditure per patient for patients with CDI compared with controls was €31,493 for de novo implant patients and €33,777 for replacement patients. Mean incremental expenditure was €59,419 per patient with a major infection. CONCLUSION: CDIs are highly expensive to manage, reinforcing the need for strategies to reduce their occurrence.

Prevalence of comorbidities in COPD patients by disease severity in a German population.

Chronic obstructive pulmonary disease (COPD) is commonly associated with multiple comorbidities. Our objective was to assess the prevalence of comorbidities in patients with COPD and to relate their prevalence to the severity of the disease by using a large German health care database. Based on the retrospective analysis of a two-year (2013-2014) database from the German Statutory Health Insurance system, we obtained a representative sample of 4,075,493 german insurants. This sample included 146,141 patients with COPD (age: ≥35 years). To these patients, we matched 1:1 by age and gender randomly selected non-COPD controls. We assessed the comorbidities and the use of cardiovascular drugs, and examined COPD subgroups according to lung function (ICD-10-coded FEV1) and the treatment with long-acting inhaled bronchodilators. Compared to non-COPD, patients with COPD had a higher prevalence of hypertension, congestive heart failure, diabetes, gastroesophageal reflux disease, chronic kidney disease, osteoporosis, psychiatric disease and lung cancer, and used more cardiovascular-related drugs. However, the prevalence of comorbidities did not correlate to the severity of airflow limitation. The results of this sizeable nationwide survey support the concept that individuals with COPD need careful evaluation regarding comorbidities. This can already be of relevance in patients with mild to moderate airflow limitation. TAKE HOME MESSAGE: Comorbidities in COPD have a complex relationship with disease severity, requiring a comprehensive therapy approach.

The Burden of Severely Drug-Refractory Epilepsy: A Comparative Longitudinal Evaluation of Mortality, Morbidity, Resource Use, and Cost Using German Health Insurance Data.

PURPOSE: To evaluate long-term outcome of three years and treatment patterns of patients suffering from severely drug-refractory epilepsy (SDRE). METHODS: This analysis was population-based and retrospective, with data collected from four million individuals insured by statutory German health insurance. ICD-10 codes for epilepsy (G40*) and intake of anticonvulsants were used to identify prevalent cases, which were then compared with a matched cohort drawn from the population at large. Insurance data were available from 2008 to 2013. Any patient who had been prescribed with at least four different antiepileptic drugs (AEDs) in an 18-month period was defined as an SDRE case. RESULTS: A total of 769 patients with SDRE were identified. Of these, 19% were children and adolescents; the overall mean age was 42.3 years, 45.4% were female and 54.6% male. An average of 2.7 AEDs per patient was prescribed during the first follow-up year. The AEDs most commonly prescribed were: levetiracetam (53.5%), lamotrigine (41.4%), valproate (41.3%), lacosamide (20.4%), and topiramate (17.8%). During 3-year follow-up, there was an annual rate of hospitalization in the range 42.7 to 55%, which was significantly higher than the 11.6-12.8% (p < 0.001) for the matched controls. Admissions to hospital because of epilepsy ranged between 1.7 and 1.9 per year, with an average duration for each epilepsy-caused hospitalization of 10-11.1 days. The number of comorbidities for SDRE patients was significantly increased compared with the matched controls: depression (28% against 10%), vascular disorders (22% against 5%), and injury rates were also higher (head 16% against 3%, trunk and limbs 16% against 8%). The 3-year mortality rate for SDRE patients was 14% against 2.1% in the matched cohort. CONCLUSION: SDRE patients are treated with AED polytherapy for all of the 3-year follow-up period. They are hospitalized more frequently than the general population and show increased morbidity levels and a sevenfold increase in mortality rate over 3 years. Further examination is required of ways in which new approaches to treatment could lead to better outcomes in severely affected patients.

Two conserved regions within the tissue-type plasminogen activator gene promoter mediate regulation by brain-derived neurotrophic factor.

Tissue-type plasminogen activator (t-PA) has recently been identified as a modulator of neuronal plasticity and can initiate conversion of the pro-form of brain-derived neurotrophic factor (BDNF) into its mature form. BDNF also increases t-PA gene expression implicating t-PA as a downstream effector of BDNF function. Here we demonstrate that BDNF-mediated induction of t-PA mRNA requires an increase in t-PA gene transcription. Reporter constructs harboring 9.5 kb of the human t-PA promoter conferred BDNF-responsiveness in transfected mouse primary cortical neurons. This regulation was recapitulated in HEK 293 cells coexpressing the TrkB neurotrophin receptor. t-PA promoter-deletion analysis revealed the presence of two BDNF-responsive domains, one located between -3.07 and -2.5 kb and the other within the proximal promoter. The upstream region was shown to confer BDNF responsiveness in a TrkB-dependent manner when attached to a heterologous promoter. We also identify homologous regions within the murine and bovine t-PA gene promoters and demonstrate that the equivalent upstream murine sequence functions as a BDNF-responsive enhancer when inserted 5' of the human proximal t-PA promoter. Hence, BDNF-mediated induction of t-PA transcription relies on conserved modular promoter elements including a novel upstream BDNF-responsive domain and the proximal t-PA gene promoter.