Economic impact of disease prevention in a morbidity-based financing system: does prevention pay off for a statutory health insurance fund in Germany?

Preventable chronic diseases account for the greatest burden in the German health system and statutory health insurance (SHI) funds play a crucial role in implementing and financing prevention strategies. On the contrary, the morbidity-based scheme to distribute financial resources from the Central Reallocation Pool among the different sickness funds may counteract efforts of effective prevention from an economic perspective. We assessed financial impacts of prevention from a sickness funds perspective in a retrospective controlled study. Claims data of 6,247,275 persons were analyzed and outcomes between two propensity-matched groups (n = 852,048) of prevention users and non-users were compared in a 4-year follow-up. Using a difference-in-differences approach, we analyzed healthcare expenditures, the development of morbidity, financial transfers from the Central Reallocation Pool, and contribution margins. The group of prevention users develops less morbidity (incidences and disease aggravations) compared to the control group. Healthcare expenditures increase in both groups within 4 years, whereas the increase is lower for prevention users compared to non-users (€568.04 vs. €640.60, p < 0.0001). Taking morbidity-based financial transfers into account, the decrease in contribution margins is stronger for prevention users (- €188.44 vs. - €138.73, p < 0.0001). This study demonstrates an economic disincentive from a sickness funds' perspective. In the semi-competitive SHI market, sickness funds will be discouraged from effective prevention strategies if investments are not worth it financially. Their efforts and knowledge are, however, crucial for joint action to foster prevention over cure in the health system.

Fusion of CCL21 non-migratory active breast epithelial and breast cancer cells give rise to CCL21 migratory active tumor hybrid cell lines.

The biological phenomenon of cell fusion has been linked to tumor progression because several data provided evidence that fusion of tumor cells and normal cells gave rise to hybrid cell lines exhibiting novel properties, such as increased metastatogenic capacity and an enhanced drug resistance. Here we investigated M13HS hybrid cell lines, derived from spontaneous fusion events between M13SV1-EGFP-Neo breast epithelial cells exhibiting stem cell characteristics and HS578T-Hyg breast cancer cells, concerning CCL21/CCR7 signaling. Western Blot analysis showed that all cell lines varied in their CCR7 expression levels as well as differed in the induction and kinetics of CCR7 specific signal transduction cascades. Flow cytometry-based calcium measurements revealed that a CCL21 induced calcium influx was solely detected in M13HS hybrid cell lines. Cell migration demonstrated that only M13HS hybrid cell lines, but not parental derivatives, responded to CCL21 stimulation with an increased migratory activity. Knockdown of CCR7 expression by siRNA completely abrogated the CCL21 induced migration of hybrid cell lines indicating the necessity of CCL21/CCR7 signaling. Because the CCL21/CCR7 axis has been linked to metastatic spreading of breast cancer to lymph nodes we conclude from our data that cell fusion could be a mechanism explaining the origin of metastatic cancer (hybrid) cells.

Cell fusion is a potent inducer of aneuploidy and drug resistance in tumor cell/ normal cell hybrids.

The biological phenomenon of cell fusion is involved in several physiological (fertilization, tissue regeneration) and pathophysiological (viral infection, cancer) processes. Particularly in the tumor context, cell fusion has been associated with a progression of this disease since hybrid cells derived from fusion events between tumor cells and normal cells, such as macrophages and adult stem cells, exhibited novel properties. These included an enhanced metastatogenic capacity, an increased proliferation, an increased resistance to undergo apoptosis or an increased drug resistance. But how the high phenotypic diversity of tumor hybrid cells is achieved? Cell fusion is a strong inducer of aneuploidy and genomic instability in tumor hybrid cells. Heterokaryon-to-synkaryon transition, representing the mechanism of nuclear fusion, is associated with a loss and re-sorting of chromosomes in a random manner, resulting in unique hybrid cells, whereby the degree of the aneuploidy/ genomic instability is further enhanced during ongoing rounds of cell divisions. The random nature of cell fusion tumor hybrid cells may originate already exhibiting an increased drug resistance, e.g., due to up-regulation of drug resistance related proteins. However, due to the aneuploidy/ genomic instability the hybrid cells may originate exhibiting an enhanced adaptation capacity, enabling these cells to withstand cellular stresses.