[Therapeutic utilization of stem cells in orthopedics]. / Therapeutische Anwendung von Stammzellen in der Orthopädie.

Stem cells are becoming increasingly more important in the field of regenerative medicine. Adult mesenchymal stem cells (MSCs) are harvested predominantly from bone marrow or adipose tissue, are already being used in the clinical setting and have a low potential for side effects. In orthopedics, experience has been gained in the treatment of bone defects, non-unions, cartilage defects, osteoarthritis and tendon pathologies. The current data are derived from case studies and randomized controlled trials are missing; therefore, there are many open questions concerning the optimal cell source, number of cells, administration technique (e.g. injections and matrices) or combinations with growth factors; however, it is evident from the data that MSCs have a positive effect on tissue regeneration and are safe to use.

Economic outcomes of sequences which include monoclonal antibodies against vascular endothelial growth factor and/or epidermal growth factor receptor for the treatment of unresectable metastatic colorectal cancer.

BACKGROUND: Patients with unresectable, metastatic colorectal cancer with wild type Kirsten ras mutational status are eligible for sequential treatments which include monoclonal antibodies as first line (1L), second line (2L), or third line (3L) regimens. OBJECTIVE: To compare the economic outcomes of different sequences which include monoclonal antibodies for the treatment of unresectable metastatic colorectal cancer. METHODS: Individual drug regimens for 1L, 2L, and 3L treatments were compiled according to the clinical studies in the Summary of Product Characteristics for monoclonal antibodies. They were combined into plausible treatment sequences. Health outcomes were approximated using additive median PFS benefit, and economic outcomes were calculated with a treatment sequencing costing tool. Limitations of the analysis include the clinical trial data sources, cost assumptions, and the additive PFS approach. RESULTS: Seventeen sequences were evaluated. Results of the analysis show that sequences including 1L anti-EGFRs generally have relatively low-to-medium health outcomes at the highest comparative sequence costs compared to sequences including 2L anti-EGFRs, which have lower health outcomes at the lowest cost. Sequences including 3L anti-EGFRs (sequential bevazicumab-based 1L and 2L) have the highest health outcomes, with potential cost savings of €5972-€11,676 if replacing 2L anti-EGFRs or an additional cost of €5909-€12,708 if replacing 1L anti-EGFR regimens. CONCLUSION: Clinical sequences consisting of 1L and 2L line bevacizumab followed by 3L anti-EGFR potentially yield the greatest health outcomes associated with a reasonable trade-off in additional cost when replacing 1L anti-EGFRs and are potentially cost-saving if replacing 2L anti-EGFRs, per patient per lifetime. To maximize health outcomes, optimal sequences include anti-EGFRs as 3L regimen, with an approximately equivalent trade-off in costs between the most costly (anti-EGFR 2L) and least costly (anti-EGFR 1L) sequences.

Homozygous familial hypercholesterolemia (HoFH) in Germany: an epidemiological survey.

INTRODUCTION: In Europe a disease is recognized as rare if less than 1 in 2000 people suffer from the specific disease. In patients with familial homozygous hypercholesterolemia (HoFH) the accumulation of low-density lipoprotein cholesterol (LDL-C) leads to generalized atherosclerosis due to an insufficient functioning of the LDL-C receptors. Patients die early sometimes even in the mid-30s, from myocardial infarction or stroke. For the German population, insufficient epidemiological evidence exists. METHODS: A systematic literature search in EMBASE and Medline was performed in conjunction with a targeted manual search for epidemiological HoFH studies. Additionally a nationwide survey was conducted in Germany in all identified apheresis- and lipid centers. The purpose of the survey was the validation of the systematic literature search results based on empirical (practice) data. RESULTS: In total 961 publications were found, 874 were excluded based on pre-defined exclusion criteria leaving only 87 for further review. After review of the identified abstracts (n = 87) 23 publications were identified as epidemiological studies. Only one publication was found which reported a prevalence of 1:1,000,000. The qualitative survey among 187 physicians in Germany also revealed a low prevalence: 95 HoFH patients were identified in 35 centers. CONCLUSION: The estimated frequency of homozygous familial hypercholesterolemia patients in Germany is around 95 (1:860,000) and the disease should be recognized as rare according to the definition of the European Medical Agency.

Microeconomic surplus in health care: applied economic theory in health care in four European countries.

INTRODUCTION: In economic theory economic surplus refers to two related quantities: Consumer and producer surplus. Applying this theory to health care "convenience" could be one way how consumer benefits might manifest itself. METHODS: Various areas of economic surplus were identified and subsequently screened and analyzed in Germany, Spain, The Netherlands, and the UK: Cesarean births, emergency room visits (nights or weekends), drug availability after test results, and response surplus. A targeted literature search was being conducted to identify the associated costs. Finally the economic surplus (convenience value) was calculated. RESULTS: The economic surplus for different health care areas was being calculated. The highest economic surplus was obtained for the example of response surplus IVF-treatments in The Netherlands. CONCLUSION: The analyzed examples in this article support the underlying hypothesis for this research: "Value of convenience defined as the consumer surplus in health care can be shown in different health care settings." Again, this hypothesis should be accepted as a starting point in this research area and hence further primary research is strongly recommended in order to fully proof this concept.

Costs of managing adverse events in the treatment of first-line metastatic renal cell carcinoma: bevacizumab in combination with interferon-alpha2a compared with sunitinib.

BACKGROUND: Bevacizumab plus interferon-alpha2a (IFN) prolongs progression-free survival to >10 months, which is comparable with sunitinib as first-line treatment of metastatic renal cell carcinoma (RCC). The two regimens have different tolerability profiles; therefore, costs for managing adverse events may be an important factor in selecting therapy. METHODS: Costs of managing adverse events affecting patients with metastatic RCC eligible for treatment with bevacizumab plus IFN or sunitinib were evaluated using a linear decision analytical model. Management costs were calculated from the published incidence of adverse events and health-care costs for treating adverse events in the United Kingdom, Germany, France and Italy. RESULTS: Adverse event management costs were higher for sunitinib than for bevacizumab plus IFN. The average cost per patient for the management of grade 3-4 adverse events was markedly lower with bevacizumab plus IFN compared with sunitinib in the United Kingdom (euro1475 vs euro804), Germany (euro1785 vs euro1367), France (euro2590 vs euro1618) and Italy (euro891 vs euro402). The main cost drivers were lymphopaenia, neutropaenia, thrombocytopaenia, leucopaenia and fatigue/asthaenia for sunitinib; and proteinuria, fatigue/asthaenia, bleeding, anaemia and gastrointestinal perforation for bevacizumab plus IFN. CONCLUSION: The costs of managing adverse events are lower for bevacizumab plus IFN than for sunitinib. The potential for cost savings should be considered when selecting treatments for RCC.

Insulin glargine added to therapy with oral antidiabetic agents improves glycemic control and reduces long-term complications in patients with type 2 diabetes - a simulation with the Diabetes Mellitus Model (DMM).

OBJECTIVE: The purpose of this study was to compare the effect of two insulin therapies with respect to long-term complications in type 2 diabetes patients using the Diabetes Mellitus Model (DMM). The therapies under investigation were insulin glargine combined with the oral antidiabetic agents, glimepiride and metformin, (BOT = basal supported oral treatment) and premixed insulin (CT = conventional therapy). METHODS: The DMM predicts complications over a 10-year period using data from published studies. Particular interest is placed on the influence of HbA1c levels related to time. The simulations are based on 10,000 virtual patients taking BOT and CT and the clinical data are based on the results of the LAPTOP study (Lantus + Amaryl + metformin versus premixed insulin in patients with type 2 diabetes mellitus after failing oral treatment pathways) comparing BOT and CT for 24 weeks. The simulations were performed in patients aged 60 A+/- 9 years with type 2 diabetes in which the duration of disease had a baseline of 9 A+/- 7 years. Sensitivity analyses were carried out by changing the response rate of those on BOT, the age of patients and duration of diabetes. RESULTS: The overall relative risk reductions obtained with BOT versus CT for the base case are, 11% for the nervous and vascular systems, 7% for the renal system, 5% for ophthalmic disorders, 3% for the cardiovascular system and mortality and 6% for any kind of event after 10 years. The advantages of BOT were robust to all the changes in the sensitivity analyses. When compared with the base case, the best therapeutic effects were obtained in younger patients who had been diabetic for a shorter period. CONCLUSIONS: Using the DMM data from the LAPTOP study, simulations based on both therapies showed that the BOT regimen provides better glycemic control and reduction in HbA1c thereby leading to a reduction in the long-term complications of diabetes and mortality.

Oligodendroglioma pontocerebeloso en la infancia / Cerecellopontine oligodendroglioma in childhood

Los oligodendrogliomas constituyen el 4.2% de los tumores cerebrales primarios y el 1-2% de los tumores intracraneanos en ninos. Se presenta un caso de oligodendroglioma del angulo pontocerebeloso derecho, que consulto por ataxia aguda y que posteriormente presento hipertension endocraneana. La poca frecuencia de estas lesiones y la localizacion inusual en la fosa posterior, motivo la revision de la bibliografia nacional e internacional referente al tema