Evaluation of a Rural Emergency Medical Service Project in Germany: Protocol for a Multimethod and Multiperspective Longitudinal Analysis.

BACKGROUND: German emergency medical services are a 2-tiered system with paramedic-staffed ambulances as the primary response, supported by prehospital emergency doctors for life-threatening conditions. As in all European health care systems, German medical practitioners are in short supply, whereas the demand for timely emergency medical care is constantly growing. In rural areas, this has led to critical delays in the provision of emergency medical care. In particular, in cases of cardiac arrest, time is of the essence because, with each passing minute, the chance of survival with good neurological outcome decreases. OBJECTIVE: The project has 4 main objectives: (1) reduce the therapy-free interval through widespread reinforcement of resuscitation skills and motivating the public to provide help (ie, bystander cardiopulmonary resuscitation), (2) provide faster professional first aid in addition to rescue services through alerting trained first aiders by mobile phone, (3) make more emergency physicians available more quickly through introducing the tele-emergency physician system, and (4) enhance emergency care through improving the cooperation between statutory health insurance on-call medical services (German: Kassenärztlicher Bereitschaftsdienst) and emergency medical services. METHODS: We will evaluate project implementation in a tripartite prospective and intervention study. First, in medical evaluation, we will assess the influences of various project measures on quality of care using multiple methods. Second, the economic evaluation will mainly focus on the valuation of inputs and outcomes of the different measures while considering various relevant indicators. Third, as part of the work and organizational analysis, we will assess important work- and occupational-related parameters, as well as network and regional indexes. RESULTS: We started the project in 2017 and will complete enrollment in 2020. We finished the preanalysis phase in September 2018. CONCLUSIONS: Overall, implementation of the project will entail realigning emergency medicine in rural areas and enhancing the quality of medical emergency care in the long term. We expect the project to lead to a measurable increase in medical laypersons' individual motivation to provide resuscitation, to strengthen resuscitation skills, and to result in medical laypersons providing first aid much more frequently. Furthermore, we intend the project to decrease the therapy-free interval in cases of cardiac arrest by dispatching first aiders via mobile phones. Previous projects in urban regions have shown that the tele-emergency physician system can provide a higher availability and quality of emergency call-outs in regular health care. We expect a closer interrelation of emergency practices of statutory health insurance physicians with the rescue service to lead to better coordination of rescue and on-call services. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/14358.

Surgical Aspects of Liver Transplantation and Domino Liver Transplantation in Maple Syrup Urine Disease: Analysis of 15 Donor-Recipient Pairs.

Liver transplantation (LT) has been shown to be a feasible treatment in patients with severe forms of maple syrup urine disease (MSUD). Because of a sufficient extrahepatic enzyme activity in non-MSUD individuals, the organ of MSUD patients can be used as a domino graft. We performed a retrospective data collection of all LTs for MSUD carried out at the University Medical Center Hamburg-Eppendorf (2016-2018). Moreover, data from all consecutive domino LTs of the MSUD grafts either transplanted at our institution or allocated to other transplant centers were analyzed. During the study period, 15 LTs in MSUD patients were performed (12 children, 3 adults; median age, 10.9 years; range, 0.3-26.1 years). Biliary complications occurred in 20%, and 13.3% suffered from bleeding complications. No further surgical problems occurred. At present, all MSUD patients are alive with a well-functioning liver graft and on an unrestricted diet. In total, 14 consecutive domino LTs were performed. No surgical complications requiring intervention occurred. One patient died because of HCC relapse, and all other patients are alive with good liver graft function. In conclusion, the use of MSUD livers as domino grafts is safe and allows application of LT in MSUD patients without net extraction of a liver graft from the limited donor pool.

Blind testing cross-linking/mass spectrometry under the auspices of the 11th critical assessment of methods of protein structure prediction (CASP11).

Determining the structure of a protein by any method requires various contributions from experimental and computational sides. In a recent study, high-density cross-linking/mass spectrometry (HD-CLMS) data in combination with ab initio structure prediction determined the structure of human serum albumin (HSA) domains, with an RMSD to X-ray structure of up to 2.5 Å, or 3.4 Å in the context of blood serum. This paper reports the blind test on the readiness of this technology through the help of Critical Assessment of protein Structure Prediction (CASP). We identified between 201-381 unique residue pairs at an estimated 5% FDR (at link level albeit with missing site assignment precision evaluation), for four target proteins. HD-CLMS proved reliable once crystal structures were released. However, improvements in structure prediction using cross-link data were slight. We identified two reasons for this. Spread of cross-links along the protein sequence and the tightness of the spatial constraints must be improved. However, for the selected targets even ideal contact data derived from crystal structures did not allow modellers to arrive at the observed structure. Consequently, the progress of HD-CLMS in conjunction with computational modeling methods as a structure determination method, depends on advances on both arms of this hybrid approach.

Developments in pediatric liver transplantation since implementation of the new allocation rules in Eurotransplant.

Liver allocation in the Eurotransplant (ET) region has changed from a waiting time to an urgency-based system using the model of end-stage liver disease (MELD) score in 2006. To allow timely transplantation, pediatric recipients are allocated by an assigned pediatric MELD independent of severity of illness. Consequences for children listed at our center were evaluated by retrospective analysis of all primary pediatric liver transplantation (LTX) from deceased donors between 2002 and 2010 (110 LTX before/50 LTX after new allocation). Of 50 children transplanted in the MELD era, 17 (34%) underwent LTX with a high-urgent status that was real in five patients (median lab MELD 22, waiting time five d) and assigned in 12 patients (lab MELD 7, waiting time 35 d). Thirty-three children received a liver by their assigned pediatric MELD (lab MELD 15, waiting time 255 d). Waiting time in the two periods was similar, whereas the wait-list mortality decreased (from about four children/yr to about one child/yr). One- and three-yr patient survival showed no significant difference (94.5/97.7%; p = 0.385) as did one- and three-yr graft survival (80.7/75.2%; and 86.5/82%; p = 0.436 before/after). Introduction of a MELD-based allocation system in ET with assignment of a granted score for pediatric recipients has led to a clear priorization of children resulting in a low wait-list mortality and good clinical outcome.

Cost-effectiveness analysis of antiviral treatment in liver transplant recipients with HCV infection.

Within 5-10 years, 20-40% of hepatitis C virus (HCV)-infected liver transplant recipients can be expected to develop cirrhosis. Here, cost-effectiveness of antiviral therapy was assessed. A Markov model was developed to simulate disease progression and calculate outcome and costs of treatment. In the baseline analysis, Peg-IFN/RBV treatment prevented organ loss/death, gained quality-adjusted life-years (QALYs) and undercut the limit of cost-effectiveness of €50 000/QALY with an incremental cost-effectiveness ratio of approximately €40 400/QALY and €21 000/QALY for HCV genotype 1 and 2/3 patients, respectively. Furthermore, sensitivity analysis testing modified model parameters according to extreme data described in the literature confirmed cost-effectiveness for a lower or higher rate of fibrosis progression, increased non-HCV-related mortality, lower limits of utilities, a time horizon of 30 years, and additional costs in the year of death. On the other hand, cost-effectiveness was lost for patients with genotype 1 in case of doubled antiviral or life-time costs or an increased discount rate of 7%. New treatment strategies for HCV genotype 1 infected patients remained on the same level cost-effective, if additional costs did not exceed €10 774 per 10% sustained virologic response gain. We conclude that Peg-IFN/RBV treatment is cost-effective post transplant. This may support treatment decision in individual cases.

Mental and physical quality of life in actual living liver donors versus potential living liver donors: a prospective, controlled, multicenter study.

In a quasi-experimental design, we investigated the quality of life (QOL) in actual liver donors (n = 43) and potential liver donors (n = 33) before and 3 months after liver transplantation. This is the first study in this field combining a prospective design with an adequate control group. Potential donors served as a control group because they also had a relative in need of a liver transplant and were as emotionally involved with the recipient as actual donors, but they were not subjected to the donor operation. Groups did not differ in age, gender, marital status, donor-recipient relationship, urgency of transplantation, or recipient group (adult versus child). Actual donors showed decreased physical QOL, whereas potential donors were not affected. However, for both groups, a decrease in anxiety was found. Furthermore, actual donors showed a better mental QOL postoperatively than potential donors. The recipients of these 2 groups did not differ with respect to postoperative complications. Furthermore, the groups did not report a different caregiver burden, but actual donors showed higher self-esteem. Because of the surgery, the worsening of physical symptoms in actual donors was expected. It is remarkable, however, that although actual donors still showed a limited physical QOL 3 months after the operation, in both groups, a similar reduction in anxiety could be observed, and actual donors even demonstrated a better mental QOL postoperatively than potential donors. The latter might be due to a psychological benefit that actual donors derived from the fact that they were able to help the recipients.