Vitali Gorenoi

Age-related changes of serum sex hormones, insulin-like growth factor-1 and sex-hormone binding globulin levels in men: cross-sectional data from a healthy male cohort.

The age‐dependent decline of the gonadal and somatotopic axis has been causally linked to frailty in the elderly by their effects on muscle mass and bone mineral density. However, for healthy men data on serum oestrogens and androgens, as well as IGF‐1, as a common outcome measure covering the whole adult age range are scarce. We therefore studied healthy, nonobese male subjects between 20 and 80 years of age to asses their morning concentrations of total (T), free (FT), bioavailable testosterone (bT), oestradiol (E2), bioavailable oestradiol (bE2), oestrone (E1), sex‐hormone binding globulin (SHBG), and insulin‐like growth factor 1 (IGF‐1).

Bone graft substitutes for the treatment of traumatic fractures of the extremities.

Health political and scientific background Bone graft substitutes are increasingly being used as supplements to standard care or as alternative to bone grafts in the treatment of traumatic fractures. Research questions The efficacy and cost-effectiveness of bone graft substitutes for the treatment of traumatic fractures as well as the ethical, social and legal implications of their use are the main research questions addressed. Methods A systematic literature search was conducted in electronic medical databases (MEDLINE, EMBASE etc.) in December 2009. Randomised controlled trials (RCT), where applicable also containing relevant health economic evaluations and publications addressing the ethical, social and legal aspects of using bone graft substitutes for fracture treatment were included in the analysis. After assessment of study quality the information synthesis of the medical data was performed using metaanalysis, the synthesis of the health economic data was performed descriptively. Results 14 RCT were included in the medical analysis, and two in the heath economic evaluation. No relevant publications on the ethical, social and legal implications of the bone graft substitute use were found. In the RCT on fracture treatment with bone morphogenetic protein-2 (BMP-2) versus standard care without bone grafting (RCT with an elevated high risk of bias) there was a significant difference in favour of BMP-2 for several outcome measures. The RCT of calcium phosphate (CaP) cement and bone marrow-based composite materials versus autogenous bone grafts (RCT with a high risk of bias) revealed significant differences in favour of bone graft substitutes for some outcome measures. Regarding the other bone graft substitutes, almost all comparisons demonstrated no significant difference. The use of BMP-2 in addition to standard care without bone grafting led in the study to increased treatment costs considering all patients with traumatic open fractures. However, cost savings through the additional use of BMP-2 were calculated in a patient subgroup with high-grade open fractures (Gustilo-Anderson grade IIIB). Cost-effectiveness for BMP-2 versus standard care with autologous bone grafts as well as for other bone graft substitutes in fracture treatment has not been determined yet. Discussion Although there were some significant differences in favour of BMP-2, due to the overall poor quality of the studies the evidence can only be interpreted as suggestive for efficacy. In the case of CaP cements and bone marrow-based bone substitute materials, the evidence is only weakly suggestive for efficacy. From an overall economic perspective, the transferability of the results of the health economic evaluations to the current situation in Germany is limited. Conclusions The current evidence is insufficient to evaluate entirely the use of different bone graft substitutes for fracture treatment. From a medical point of view, BMP-2 is a viable alternative for treatment of open fractures of the tibia, especially in cases where bone grafting is not possible. Autologous bone grafting is preferable comparing to the use of OP-1. Possible advantages of CaP cements and composites containing bone marrow over autogenous bone grafting should be taken into account in clinical decision making. The use of the hydroxyapatite material and allograft bone chips compared to autologous bone grafts cannot be recommended. From a health economic perspective, the use of BMP-2 in addition to standard care without bone grafting is recommended as cost-saving in patients with high-grade open fractures (Gustilo-Anderson grade IIIB). Based on the current evidence no further recommendations can be made regarding the use of bone graft substitutes for the treatment of fractures. To avoid legal implications, use of bone graft substitutes outside their approved indications should be avoided.

Kosteneffektivitätsbewertung Prädiktiver Molekulardiagnostik am Beispiel des Hereditären Nichtpolypösen Kolorektalkarzinoms (HNPCC)

STUDY OBJECTIVE Four different diagnostic strategies, with and without various molecular diagnostic tests, are compared and contrasted not only by years gained and the cost of therapy and diagnosis, but also by the cost-effectiveness of the diagnostic strategies. METHODOLOGY A fictitious cohort of 100,000 people, whose genetic pre-disposition leading to the development of colorectal cancer corresponds to a representative average amongst the current population, will be studied from their 1st to their 85th year. This data will be then put through Markov models specifically developed for the study. At the end of the Markov process, it will then be possible to compile a cost-effectiveness report in regard to the various diagnostic and treatment strategies. RESULTS A tiered diagnosis (with family case history, micro-satellite instability, molecular diagnostic diagnosis of an index person and subsequent genetic analysis of all people at risk) represents the most cost-effective method at a rate of euro 3,867 per year gained. The cost-effectiveness of a purely clinical diagnosis has a rate of euro 4,397 per year gained and is followed by the cost of direct gene testing of people at risk from families at risk at a rate of euro 6,208. The worst level of cost-effectiveness, with a rate of euro 15,705, was shown by nationwide gene screening. The incremental cost-effectiveness of Strategy IV and Strategy II is euro 124,168 per gained year. CONCLUSIONS With the scenarios put forward we can show that a 65% reduction in gene test costs is necessary in order for a cost-effective nationwide gene screening for HNPCC to take place. The break-even level, however, depends only on a few cost-effectiveness drivers such as screening and therapy costs, proportion of HNPCC of all colorectal cancer and discounting rate. Should these changes (e.g., through a restructured medical environment), then we would see such a change in the break-even cost of a gene test and that a cost-effective nationwide gene screening could be made plausible. In a final evaluation of the use of predictive molecular diagnostics, other dimensions (such as possible psychological problems and discriminatory risks) apart from cost-effectiveness should also be included.

Perkutane Koronarintervention zusätzlich zu optimaler medikamentöser Therapie bei stabiler koronarer Herzkrankheit

OBJECTIVE We evaluated the effect of percutaneous coronary interventions (PCI) in addition to optimal medical therapy in stable coronary artery disease (CAD). METHODS A systematic literature search was conducted in the online databases MEDLINE, EMBASE etc. in June 2010, updated in February 2013 in MEDLINE and completed by a hand search. Randomized controlled trials (RCT) and systematic reviews of RCT comparing PCI vs. no PCI in stable CAD  were identified and evaluated. Results for death, myocardial infarction and angina pectoris of the RCTs using optimal medical therapy were combined with meta-analysis for relative risk (RR). The strength of the evidence was appraised based on GRADE. RESULTS After evaluation of 7 systematic reviews and 23 RCT 4 RCTs using optimal medical therapy (Betablockers, ASS, Statins in more than 80% and ACE-Inhibitors in more than 50% of patients the study) were identified. No significant difference was found for the risks of death and of myocardial infarction between the alternatives up to 5 years after beginning the therapy. The PCI reduced the proportion of patients with angina pectoris attacks up to 3 years after beginning the therapy, RR = 0,81 (95 % CI: 0,71 to 0,92). The strength of the evidence was appraised as moderate. CONCLUSION The use of PCI in addition to optimal medical therapy in stable CAD  may reduce the proportion of patients with angina pectoris attacks up to 3 years after beginning the therapy.

Gesundheitsökonomische Modellierung zum Einsatz von Medikamente freisetzenden Stents im Vergleich zu Bypassoperationen bei koronarer Herzkrankheit

ZusammenfassungHintergrund und Fragestellung:Wichtige Behandlungsmethoden bei koronarer Herzkrankheit (KHK) sind Bypassoperationen (CABG) und perkutane Revaskularisationen mit Implantation eines Medikamente freisetzenden Stent (DES). Es stellt sich die Frage nach der Kostenwirksamkeit beim Einsatz von DES versus CABG bei KHK-Patienten.Methodik:Eine gesundheitsökonomische Modellierung wurde aus einer eingeschränkten gesellschaftlichen Perspektive mit einem Zeithorizont von 1 bzw. 3 Jahren durchgeführt. Klinische Wahrscheinlichkeitsannahmen wurden für CABG der ARTS-I- und für DES der ARTS-II-Studie entnommen. Für die Kostenannahmen wurden die Bewertungsrelationen aus den deutschen Fallpauschalen (G-DRG-2007) herangezogen. Als Basisfallwert wurden 2 800 Euro angenommen. Der Preis für einen DES wurde mit 1 200 Euro, die Anzahl der angewendeten Stents pro Patient mit 3,7 und die Tagestherapiekosten für Clopidogrel mit 2,57 Euro pro Patient angesetzt, die angenommene Therapiedauer mit Clopidogrel betrug 12 Monate.Ergebnisse:Die Gesamtkosten pro Patient 1 Jahr bzw. 3 Jahre nach CABG betrugen 13 373 bzw. 13 630 Euro und nach DES 10 443 bzw. 10 905 Euro, d.h., es ergab sich ein Kostenunterschied von 2 930 bzw. 2 725 Euro zugunsten der DES-Implantation. Bei den durchgeführten Sensitivitätsanalysen kam es zu keiner Umkehr des Kostenunterschieds.Schlussfolgerung:Der vorliegende Hinweis auf einen möglichen ökonomischen Vorteil von DES-Implantationen im Vergleich zu CABG sollte im langfristigen Follow-up und in randomisiert-kontrollierten Studien überprüft werden.AbstractBackground and Purpose:The therapy of coronary heart disease (CHD) leads to an enormous economic burden on health-care systems. Coronary artery bypass grafting (CABG) and percutaneous revascularizations with implantation of drug-eluting stents (DES) are important treatment methods in CHD. The presented evaluation addresses cost efficacy of the use of DES versus CABG in CHD patients.Methods:A health-economic model considering linear resource use was performed from a restricted societal perspective for time periods of 1 and 3 years. Because of the short time horizon discounting was not applied. The clinical assumptions for event rates at 1 and 3 years were derived from the ARTS-I study for CABG, and from the ARTS-II study for DES (sirolimus-eluting stents). Cost assumptions for the resources used were based on the German Diagnosis Related Groups 2007 (G-DRG-2007). The base case value was assumed to be 2,800 Euros, the average DES price 1,200 Euros, and the average DES use per patient 3.7. The average per-patient daily clopidogrel costs were assumed to be 2.57 Euros, and the duration of the clopidogrel therapy 12 months. Within the scope of sensitivity analyses, different model parameters were varied and the evaluation was tested for its robustness.Results:The average costs for percutaneous coronary intervention (PCI) without DES were found to be 4,420 Euros, for CABG 12,840 Euros, and for DES intervention 8,860 Euros (Table 4). 1-year clopidogrel intake resulted in 938 Euros, the treatment of patients with myocardial infarction during follow-up in 3,989 Euros.The 1-year per-patient total costs after CABG were calculated to be 13,373 Euros and after DES 10,443 Euros, leading to a difference of 2,930 Euros in favor of DES implantation (Table 6). The 3-year per-patient total costs after CABG were estimated to be 13,630 Euros and after DES 10,905 Euros, showing a Rehabilitationsmaßcost difference of 2,725 Euros in favor of DES implantation (Table 6). Changes in cost-weights of G-DRG-2007 for CABG and PCI, DES price and DES use per patient as well as in the duration of the clopidogrel therapy influenced the cost differences considerably; however, they did not reach a break-even point (Figures 2 and 3).Changes in the clinical follow-up assumptions showed a lower effect on the difference in total costs (Figures 2 and 3).Conclusion:The presented data, indicating a possible economic middle-term advantage of DES versus CABG, should be proven with clinical assumptions derived from randomized clinical trials.BACKGROUND AND PURPOSE The therapy of coronary heart disease (CHD) leads to an enormous economic burden on health-care systems. Coronary artery bypass grafting (CABG) and percutaneous revascularizations with implantation of drug-eluting stents (DES) are important treatment methods in CHD. The presented evaluation addresses cost efficacy of the use of DES versus CABG in CHD patients. METHODS A health-economic model considering linear resource use was performed from a restricted societal perspective for time periods of 1 and 3 years. Because of the short time horizon discounting was not applied. The clinical assumptions for event rates at 1 and 3 years were derived from the ARTS-I study for CABG, and from the ARTS-II study for DES (sirolimus-eluting stents). Cost assumptions for the resources used were based on the German Diagnosis Related Groups 2007 (G-DRG-2007). The base case value was assumed to be 2,800 Euros, the average DES price 1,200 Euros, and the average DES use per patient 3.7. The average per-patient daily clopidogrel costs were assumed to be 2.57 Euros, and the duration of the clopidogrel therapy 12 months. Within the scope of sensitivity analyses, different model parameters were varied and the evaluation was tested for its robustness. RESULTS The average costs for percutaneous coronary intervention (PCI) without DES were found to be 4,420 Euros, for CABG 12,840 Euros, and for DES intervention 8,860 Euros (Table 4). 1-year clopidogrel intake resulted in 938 Euros, the treatment of patients with myocardial infarction during follow-up in 3,989 Euros. The 1-year per-patient total costs after CABG were calculated to be 13,373 Euros and after DES 10,443 Euros, leading to a difference of 2,930 Euros in favor of DES implantation (Table 6). The 3-year per-patient total costs after CABG were estimated to be 13,630 Euros and after DES 10,905 Euros, showing a Rehabilitationsmasscost difference of 2,725 Euros in favor of DES implantation (Table 6). Changes in cost-weights of G-DRG-2007 for CABG and PCI, DES price and DES use per patient as well as in the duration of the clopidogrel therapy influenced the cost differences considerably; however, they did not reach a break-even point (Figures 2 and 3). Changes in the clinical follow-up assumptions showed a lower effect on the difference in total costs (Figures 2 and 3). CONCLUSION The presented data, indicating a possible economic middle-term advantage of DES versus CABG, should be proven with clinical assumptions derived from randomized clinical trials.

Gesundheitsökonomische Modellierung zum Einsatz von Medikamente freisetzenden Stents im Vergleich zu Bypassoperationen bei koronarer Herzkrankheit@@@Health-Economic Modeling on the Use of Drug-Eluting Stents versus Coronary Artery Bypass Graft Surgery in Coronary Heart Disease

ZusammenfassungHintergrund und Fragestellung:Wichtige Behandlungsmethoden bei koronarer Herzkrankheit (KHK) sind Bypassoperationen (CABG) und perkutane Revaskularisationen mit Implantation eines Medikamente freisetzenden Stent (DES). Es stellt sich die Frage nach der Kostenwirksamkeit beim Einsatz von DES versus CABG bei KHK-Patienten.Methodik:Eine gesundheitsökonomische Modellierung wurde aus einer eingeschränkten gesellschaftlichen Perspektive mit einem Zeithorizont von 1 bzw. 3 Jahren durchgeführt. Klinische Wahrscheinlichkeitsannahmen wurden für CABG der ARTS-I- und für DES der ARTS-II-Studie entnommen. Für die Kostenannahmen wurden die Bewertungsrelationen aus den deutschen Fallpauschalen (G-DRG-2007) herangezogen. Als Basisfallwert wurden 2 800 Euro angenommen. Der Preis für einen DES wurde mit 1 200 Euro, die Anzahl der angewendeten Stents pro Patient mit 3,7 und die Tagestherapiekosten für Clopidogrel mit 2,57 Euro pro Patient angesetzt, die angenommene Therapiedauer mit Clopidogrel betrug 12 Monate.Ergebnisse:Die Gesamtkosten pro Patient 1 Jahr bzw. 3 Jahre nach CABG betrugen 13 373 bzw. 13 630 Euro und nach DES 10 443 bzw. 10 905 Euro, d.h., es ergab sich ein Kostenunterschied von 2 930 bzw. 2 725 Euro zugunsten der DES-Implantation. Bei den durchgeführten Sensitivitätsanalysen kam es zu keiner Umkehr des Kostenunterschieds.Schlussfolgerung:Der vorliegende Hinweis auf einen möglichen ökonomischen Vorteil von DES-Implantationen im Vergleich zu CABG sollte im langfristigen Follow-up und in randomisiert-kontrollierten Studien überprüft werden.AbstractBackground and Purpose:The therapy of coronary heart disease (CHD) leads to an enormous economic burden on health-care systems. Coronary artery bypass grafting (CABG) and percutaneous revascularizations with implantation of drug-eluting stents (DES) are important treatment methods in CHD. The presented evaluation addresses cost efficacy of the use of DES versus CABG in CHD patients.Methods:A health-economic model considering linear resource use was performed from a restricted societal perspective for time periods of 1 and 3 years. Because of the short time horizon discounting was not applied. The clinical assumptions for event rates at 1 and 3 years were derived from the ARTS-I study for CABG, and from the ARTS-II study for DES (sirolimus-eluting stents). Cost assumptions for the resources used were based on the German Diagnosis Related Groups 2007 (G-DRG-2007). The base case value was assumed to be 2,800 Euros, the average DES price 1,200 Euros, and the average DES use per patient 3.7. The average per-patient daily clopidogrel costs were assumed to be 2.57 Euros, and the duration of the clopidogrel therapy 12 months. Within the scope of sensitivity analyses, different model parameters were varied and the evaluation was tested for its robustness.Results:The average costs for percutaneous coronary intervention (PCI) without DES were found to be 4,420 Euros, for CABG 12,840 Euros, and for DES intervention 8,860 Euros (Table 4). 1-year clopidogrel intake resulted in 938 Euros, the treatment of patients with myocardial infarction during follow-up in 3,989 Euros.The 1-year per-patient total costs after CABG were calculated to be 13,373 Euros and after DES 10,443 Euros, leading to a difference of 2,930 Euros in favor of DES implantation (Table 6). The 3-year per-patient total costs after CABG were estimated to be 13,630 Euros and after DES 10,905 Euros, showing a Rehabilitationsmaßcost difference of 2,725 Euros in favor of DES implantation (Table 6). Changes in cost-weights of G-DRG-2007 for CABG and PCI, DES price and DES use per patient as well as in the duration of the clopidogrel therapy influenced the cost differences considerably; however, they did not reach a break-even point (Figures 2 and 3).Changes in the clinical follow-up assumptions showed a lower effect on the difference in total costs (Figures 2 and 3).Conclusion:The presented data, indicating a possible economic middle-term advantage of DES versus CABG, should be proven with clinical assumptions derived from randomized clinical trials.BACKGROUND AND PURPOSE The therapy of coronary heart disease (CHD) leads to an enormous economic burden on health-care systems. Coronary artery bypass grafting (CABG) and percutaneous revascularizations with implantation of drug-eluting stents (DES) are important treatment methods in CHD. The presented evaluation addresses cost efficacy of the use of DES versus CABG in CHD patients. METHODS A health-economic model considering linear resource use was performed from a restricted societal perspective for time periods of 1 and 3 years. Because of the short time horizon discounting was not applied. The clinical assumptions for event rates at 1 and 3 years were derived from the ARTS-I study for CABG, and from the ARTS-II study for DES (sirolimus-eluting stents). Cost assumptions for the resources used were based on the German Diagnosis Related Groups 2007 (G-DRG-2007). The base case value was assumed to be 2,800 Euros, the average DES price 1,200 Euros, and the average DES use per patient 3.7. The average per-patient daily clopidogrel costs were assumed to be 2.57 Euros, and the duration of the clopidogrel therapy 12 months. Within the scope of sensitivity analyses, different model parameters were varied and the evaluation was tested for its robustness. RESULTS The average costs for percutaneous coronary intervention (PCI) without DES were found to be 4,420 Euros, for CABG 12,840 Euros, and for DES intervention 8,860 Euros (Table 4). 1-year clopidogrel intake resulted in 938 Euros, the treatment of patients with myocardial infarction during follow-up in 3,989 Euros. The 1-year per-patient total costs after CABG were calculated to be 13,373 Euros and after DES 10,443 Euros, leading to a difference of 2,930 Euros in favor of DES implantation (Table 6). The 3-year per-patient total costs after CABG were estimated to be 13,630 Euros and after DES 10,905 Euros, showing a Rehabilitationsmasscost difference of 2,725 Euros in favor of DES implantation (Table 6). Changes in cost-weights of G-DRG-2007 for CABG and PCI, DES price and DES use per patient as well as in the duration of the clopidogrel therapy influenced the cost differences considerably; however, they did not reach a break-even point (Figures 2 and 3). Changes in the clinical follow-up assumptions showed a lower effect on the difference in total costs (Figures 2 and 3). CONCLUSION The presented data, indicating a possible economic middle-term advantage of DES versus CABG, should be proven with clinical assumptions derived from randomized clinical trials.