Does the Implementation of the PRO-IMPLANT Foundation Treatment Algorithm Improve the Outcome of Chronic Periprosthetic Knee Infections? Mid-Term Results of a Prospective Study. / Verbessert die Implementierung des PRO-IMPLANT Foundation Behandlungsalgorithmus die Therapie chronischer periprothetischer Knieprotheseninfektionen? Ergebnisse einer prospektiven Studie.

BACKGROUND: Several treatment options for chronic periprosthetic joint infections have been published in the current literature, with an on-going discussion to determine effective management algorithms. OBJECTIVES: To compare outcomes of the two-stage exchange procedure in revision TKA prior to and after implementation of the PRO-IMPLANT Foundation treatment algorithm. The primary endpoints were defined as (i) revisions during the interval time, (ii) duration of the interval time and (iii) successful PJI eradication. MATERIAL AND METHODS: Between 02/2013 and 09/2016, 122 patients were included in a single-centre cohort analysis. 55 patients were treated according to the previously used algorithm (K1) and 67 according to the PRO-IMPLANT Foundation algorithm (K2). A minimum follow-up period of 3 years was set as the inclusion criterion. Successful eradication of infection was defined in accordance with the consensus criteria by Diaz-Ledezma et al. RESULTS: Successful eradication was achieved in 42 (67%) patients in K1 and 47 (85.5%) in K2 (p ≤ 0.005). The mean interval time was 88 days (range 51 - 353) in K1 and 52 days (range 42 - 126) in K2 (p ≤ 0.005). In K1, a mean of 0.8 (range 0 - 6) revisions were necessary during the interval period compared with 0.5 (range 0 - 4) in K2 (p = 0.066). CONCLUSION: Implementation of the PRO-IMPLANT treatment algorithm led to significant improvement in the outcome of periprosthetic joint infections. During mid-term follow-up, infection eradication was highly successful, with decreases in the interval time as well as the number of revisions.

Cost-effectiveness of anticoagulation in patients with nonvalvular atrial fibrillation with edoxaban compared to warfarin in Germany.

We compared the cost-utility analysis for edoxaban at both doses with that of dabigatran at both doses, rivaroxaban, and apixaban (non vitamin K antagonist oral anticoagulants, NOAC) in a German population. Data of clinical outcome events were taken from edoxaban's ENGAGE-AF, dabigatran's RE-LY, rivaroxaban's ROCKET, and apixaban's ARISTOTLE trials. The base-case analyses of a 65-year-old person with a CHADS2 score >1 gained 0.17 and 0.21 quality-adjusted life years over warfarin for 30 mg od and 60 mg od edoxaban, respectively. The incremental cost-effectiveness ratio was 50.000 and 68.000 euro per quality-adjusted life years for the higher and lower dose of edoxaban (Monte Carlo simulation). These findings were also similar to those for apixaban and more cost-effective than the other NOAC regimens. The current market costs for direct oral anticoagulants are high in relation to the quality of life gained from a German public health care insurance perspective. The willingness-to-pay threshold was lowest for 60 mg edoxaban compared to all direct oral anticoagulants and for 30 mg edoxaban compared to dabigatran and rivaroxaban.

Comparison of cost-effectiveness of anticoagulation with dabigatran, rivaroxaban and apixaban in patients with non-valvular atrial fibrillation across countries.

We did a cost-utility analysis for the new oral anticoagulants (NOACs) in the German population based on the quality-adjusted life years (QALY), total costs, and incremental cost-effectiveness ratios (ICER). The aim of our investigation was to examine cost-utility for current German drug market costs and compared to other countries. Outcome data were taken from dabigatran's RE-LY, rivaroxaban's ROCKET AF, and apixaban's ARISTOTLE trials. A Markov decision model, the Monte Carlo simulation (MCS), and further sensitivity analyses were used to simulate comparisons between NOACs over a follow up period of 20 years. The main perspective used for the analyses is from a German public health care insurance perspective. The base-case analyses of a 65 years old person with a CHADS2 score >1 resulted in 7.56-7.64 QALYs gained for warfarin. NOACs added 0.04-0.19 QALYs. Total costs for warfarin ranged from 7622 to 9069 and for NOACs from 19537 to 20048. The sensitivity analysis indicated that current German market costs for the NOACs exceed a willingness-to-pay threshold of (hypothetical) 50000/QALY in all treatment regimen. The MCS showed willingness-to-pay thresholds from 60500/QALY for apixaban to 278000/QALY for dabigatran 110 mg bid, with values for dabigatran 150 mg bid and rivaroxaban in between. In conclusion, from a German public health care insurance perspective current market costs are high in relation to the quality of life gained. These results from clinical studies (efficacy) remain to be confirmed under real life conditions (effectiveness).

New anticoagulants - promising and failed developments.

New direct and indirect acting factor Xa (FXa) and thrombin inhibitors are being developed to overcome the downsides of the conventional anticoagulants - unfractionated and low molecular weight heparins and vitamin K antagonists. Ximelagatran and idraparinux failed to demonstrate an acceptable safety profile. Rivaroxaban and dabigatran are approved for the post-operative prevention of thromboembolic complications after elective hip or knee replacement surgery; dabigatran is approved for the prevention of embolism in patients with atrial fibrillation in an increasing number of countries. Several novel indirect antithrombin-dependent anticoagulants as well as antithrombin-independent oral direct FXa and thrombin inhibitors are investigated in multiple indications for the prophylaxis and treatment of venous thromboembolism and the prophylaxis of arterial thrombotic disorders. Quality-adjusted life years costs and incremental cost-effectiveness ratios are relatively high at present, but may decrease after approval of more new anticoagulants for additional indications.