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Propensity score methods (PSMs) such as matching and weighting have become a mainstay for the estimation of treatment effects from observational data. PSMs require the choice of a treatment effect of interest given a specific target population or subpopulation. The most commonly used treatment effects in observational studies are the average treatment effect (ATE) and the average treatment effect among the treated population (ATT). While the traditional matching approach usually discards observations that cannot be matched and is therefore mainly used for estimation of the ATT, the weighting approach utilizes all observations in most cases and can be used for estimation of both, the ATE and ATT. One concern when using the weighting approach is the occurrence of large weights which may disproportionately influence the results and yield estimates with high variance. Recently several newer approaches, including matching weights and overlap weights have been proposed to overcome these limitations. However, this may complicate the interpretation of the results as the population to be inferred depends on the PS estimate itself.

Objectives: Emerging treatments for relapsed or refractory multiple myeloma (rrMM) have led to increasing options for many patients. This study aimed to assess changes in utilization of these options in Germany with a focus on modern triplet regimens including new agents, such as carfilzomib, ixazomib, elotuzumab and daratumumab, and to evaluate whether this had an impact on rrMM‐related outcomes over time. Methods: The study population consisted of 1255 rrMM patients who were assigned to one of the following 6 treatment groups: immunomodulatory drug (IMiD)‐based doublets, proteasome inhibitor (PI)‐based doublets, daratumumab monotherapy, PI‐IMiD‐based triplets, monoclonal antibodies (mAbs)‐based triplets, or other treatment. Results: Use of triplet‐based therapy regimens increased from 5.9% in 2014 to 31.4% in 2017. In parallel, use of IMiD‐based doublets decreased from 74.3% in 2014 to 37.6% in 2017. Over the same time period, the risk of death decreased by 32% and the risk of hospitalization which was reduced by 30%. The risk for serious adverse events remained unchanged. Conclusions: Between 2014 and 2017, the use of triplet‐based therapy regimens for rrMM in Germany has significantly increased and this was associated with a significant decline in deaths and hospitalizations without an increased incidence of serious adverse events. [ABSTRACT FROM AUTHOR]

Background: Patients with non-valvular atrial fibrillation (NVAF) have a five times higher stroke risk. For more than 50 years, vitamin K antagonists (VKAs) have been the primary medication for stroke prevention. Apixaban, a non-vitamin K oral anticoagulant (NOAC), has demonstrated better efficacy and safety characteristics than the VKA warfarin in the ARISTOTLE trial. This study aims to quantify the potential societal effects of using apixaban instead of VKA in the German NVAF population from 2017 to 2030.Methods: Using an existing Markov model and a dynamic population approach, we modelled the health benefits of apixaban in patients with NVAF compared to VKA therapy in the German population from 2017 to 2030.Results: The results represent the extrapolated direct long-term health benefits of apixaban over VKA therapy for the German NVAF population. From 2017 until 2030, the use of apixaban instead of a VKA could avoid 52,185 major clinical events. This includes 15,383 non-fatal strokes or SEs, 22,483 non-fatal major bleeds, and 14,319 all-cause deaths, which correspond to 109,887 life years gained.Conclusion: This study demonstrated that using apixaban instead of VKA for stroke prevention can lead to considerable reduction in cardiovascular events. [ABSTRACT FROM AUTHOR]

The German Microcensus is a rotating panel, where the units stay in the survey for four observations. Because of the very large sample size and the mandatory participation it appears to be a valuable data base for short duration analysis. However, the German Microcensus (MC) uses area sampling where participants are not followed if they leave the area. Consequently there is no information on participants after they move. We investigate how the use of the German Socio-Economic Panel (SOEP) can help to measure the non-coverage bias of the MC. Our methodology is evaluated for labour force flows. The results indicate that the SOEP is a valuable instrument for assessing the non-coverage bias in the MC. For labour force flows the non-coverage bias of the MC appears to be only of moderate size. [ABSTRACT FROM AUTHOR]

Background: Venous thromboembolism (VTE) mainly manifests as deep vein thrombosis (TVT) or pulmonary embolism (LE), and is the third most common cardiovascular disease worldwide. However, robust evidence on the incidence of VTE in Germany is lacking., Objective: Estimation and comparison of the incidence of VTE based on different routine data sources of the German healthcare system., Methods: Estimates and comparisons of the incidence of VTE, TVT and LE were made using two databases that both covered the inpatient and the outpatient setting; the DaTraV database comprising information of all persons subject to compulsory health insurance, and the Health Risk Institute (HRI) database derived from approximately 70 statutory health insurance funds. In addition, IMS Disease Analyzer, a medical record database comprising information from the outpatient setting, was used as a data source., Results: Patterns of age- and sex-specific VTE incidence estimates were comparable between all databases used. However, estimates based on the medical record database were comparatively high. Analyses of DaTraV data led to a VTE incidence of 0.14%. Use of HRI data yielded comparable results (0.17-0.20%). VTE incidence based on data of the IMS Disease Analyzer was comparatively high (0.32%)., Discussion: Results on the VTE incidence based on DaTraV or HRI date are comparable to international evidence, whereas the use of the IMS Disease Analyzer data presumably led to an overestimation due to double-counting of VTE cases. Different types of routine healthcare data sources can therefore lead to very heterogeneous results. Thus, the selection of adequate data sources strongly depends on the study question and the quality of the dataset., (Copyright © 2018. Published by Elsevier GmbH.)

Norepinephrine (NE) stimulates phospholipase D (PLD) activity and cell proliferation in vascular smooth muscle cells (VSMCs). The objective of this study was to determine the contribution of PKC-zeta to NE-induced PLD activation and cell proliferation in VSMCs. PLD activity was measured by the formation of [3H]phosphatidylethanol in VSMCs labeled with [3H]oleic acid and exposed to ethanol. A high basal PLD activity was detected, and NE increased PLD activity over basal by 70%. This increase was abolished by the broad-range PKC inhibitor Ro 31-8220 (1 micromol/L, 30 minutes) and myristoylated PKC-zeta pseudosubstrate peptide inhibitor (25 micromol/L, 1 hour). Transfection of VSMCs with PKC-zeta antisense, but not sense, oligonucleotides, which reduced PKC-zeta protein level and basal PLD activity, caused a 92% decrease in NE-induced PLD activation. NE-induced increase in PLD activity was also reduced by 61% in cells transfected with kinase-deficient FLAG-T410A-PKC-zeta plasmid but not in those transfected with wild-type PKC-zeta. NE increased immunoprecipitable PKC-zeta activity and phosphorylation, reaching a maximum at 2 and 5 minutes, respectively. NE-induced increase in PKC-zeta activity was inhibited by Ro 31-8220 and by the pseudosubstrate inhibitor. Treatment of VSMCs for 48 hours with PKC-zeta antisense, but not sense, oligonucleotides also inhibited basal and NE-stimulated cell proliferation by 54% and 57%, respectively, as measured by [3H]thymidine incorporation. The inhibitor of PLD activity n-butanol, but not its inactive analog tert-butanol, also reduced the basal and blocked NE-induced cell proliferation. These data suggest that PKC-zeta mediates PLD activation and cell proliferation elicited by NE in rabbit VSMCs.