Recent data indicate that the combination of a low cholesterol diet and simvastatin following heart transplantation is associated with significant reduction of serum cholesterol levels, lower ...incidence of graft vessel disease (GVD) and significantly superior 4-year survival rates than dietary treatment alone. On the basis of this first randomised long term study evaluating survival as the clinical end-point, we investigated the cost effectiveness of the above regimens as well as the long term consequences for the patient and for heart transplantation as a high-tech procedure.
The perspective of the economic analysis was that of the German health insurance fund. Life-years gained were calculated on the basis of the Kaplan-Meier survival curves from the 4-year clinical trial and from the International Society for Heart and Lung Transplantation (ISHLT) overall survival statistics. Incremental costs and incremental cost-effectiveness ratios were determined using various sources of data, and both costs and consequences were discounted by 3% per year. Sensitivity analyses using alternative assumptions were conducted in addition to the base-case analysis.
As in the original clinical trial, the target population of the economic evaluation comprised all heart transplant recipients on standard triple immunosuppression consisting of cyclosporin, azathioprine and prednisolone, regardless of the postoperative serum lipid profile.
The therapeutic regimens investigated in the analysis were the American Heart Association (AHA) step II diet plus simvastatin (titrated to a maximum dosage of 20 mg/day) and AHA step II diet alone.
Four years of treatment with simvastatin (mean dosage 8.11 mg/day) translated into an undiscounted survival benefit per patient of 2.27 life-years; 0.64 life-years within the trial period and 1.63 life-years thereafter. Discounted costs per year of life gained were $US1050 (sensitivity analyses $US800 to $US15,400) for simvastatin plus diet versus diet alone and $US18,010 (sensitivity analyses $US17,130 to $US21,090) for heart transplantation plus simvastatin versus no transplantation (all costs reflect 1997 values; $US1 = 1.747 Deutschmarks).
Prevention of GVD with simvastatin after heart transplantation was cost effective in all the scenarios examined with impressive prolongation of life expectancy for the heart recipient. Simvastatin also achieved an internationally robust 21% improvement in the cost effectiveness of heart transplantation compared with historical cost-effectiveness data.
The effect of coil position on the head surface along the interaural line on motor-evoked potentials (MEPs) of the frontalis muscle due to cortical transcranial magnetic stimulation was investigated ...in 16 healthy subjects. Bilateral reproducible responses could be observed in all subjects investigated at coil positions varying from 2 to 12 cm lateral to the vertex. MEP amplitudes of the frontalis muscle offered no significant side differences neither in amplitude nor in onset latency. Despite a considerable overlap, a statistically significant separation (p < 0.0001) of the two areas from which reproducible MEPs of upper and lower mimetic muscles could be elicited was evident for the calculated mediolateral center with the frontalis muscle area being placed more medially. Our findings are in accordance with anatomical studies indicating a predominance of corticonuclear descending fibers to lower but not to upper facial motoneurons.
Toxoplasmosis may cause serious problems after organ transplantation. For treatment of active infection, pyrimethamine combined with a sulfonamide is recommended. During oral sulfadiazine therapy, a ...significant decrease in cyclosporine concentrations was observed in three heart transplant recipients. This interaction has not been reported previously.
Aggregating transcriptomics data across hospitals can increase sensitivity and robustness of differential expression analyses, yielding deeper clinical insights. As data exchange is often restricted ...by privacy legislation, meta-analyses are frequently employed to pool local results. However, if class labels are inhomogeneously distributed between cohorts, their accuracy may drop. Flimma (https://exbio.wzw.tum.de/flimma/) addresses this issue by implementing the state-of-the-art workflow limma voom in a privacy-preserving manner, i.e. patient data never leaves its source site. Flimma results are identical to those generated by limma voom on combined datasets even in imbalanced scenarios where meta-analysis approaches fail.
Reliability of atrial screw-in leads Markewitz, A; Wenke, K; Weinhold, C
Pacing and clinical electrophysiology,
November 1988, Letnik:
11, Številka:
11 Pt 2
Journal Article
Recenzirano
The aim of this study was to investigate long-term performance of a carbon coated atrial screw-in lead. During implantation of 247 leads of this type we measured an average stimulation threshold of ...0.74 (range: 0.2-1.6 V) at 1 ms pulse width. Mean lead impedance came to 446 ohms (range: 263-1000 ohms) resulting in an arithmetical energy consumption of 1.51 microJ (range: 0.1-7.21 microJ). Average P wave amplitude was 3.9 mV (range: 1.3-11 mV). After a mean follow-up of 16.4 months (range: 3-60 months) we found excellent threshold results in 76% of the patients permitting a safety programming at half of nominal value. An additional 14% nominal settings could be retained. With regard to chronic lead impedance of 488 ohms (range: 315-1327 ohms) we calculated an average chronic energy consumption of 10.83 microJ (range: 1.62-22.78 microJ) during safety programming. This made up 34.6% of the corresponding energy consumption during nominal programming. Eighty percent of the patients showed chronic P waves above 2 mV; nearly half of them (n = 94 = 38%) showed a proper sensing function even when programmed to minimal sensitivity settings or above 4 mV. In 19 leads (8%) we observed unsatisfying threshold results requiring high output programmings. All threshold increases occurred within the first year, 84% (n = 16/19) within the first 3 postoperative months. An additional five leads (2%) were found to have a loss of capture, and one (0.5%) a loss of sensing.
Coronavirus Disease-2019 (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus. It was first identified in Wuhan, China, and has since spread causing a global pandemic. Various studies ...have been performed to understand the molecular mechanisms of viral infection for predicting drug repurposing candidates. However, such information is spread across many publications and it is very time-consuming to access, integrate, explore, and exploit. We developed CoVex, the first interactive online platform for SARS-CoV-2 and SARS-CoV-1 host interactome exploration and drug (target) identification. CoVex integrates 1) experimentally validated virus-human protein interactions, 2) human protein-protein interactions and 3) drug-target interactions. The web interface allows user-friendly visual exploration of the virus-host interactome and implements systems medicine algorithms for network-based prediction of drugs. Thus, CoVex is an important resource, not only to understand the molecular mechanisms involved in SARS-CoV-2 and SARS-CoV-1 pathogenicity, but also in clinical research for the identification and prioritization of candidate therapeutics. We apply CoVex to investigate recent hypotheses on a systems biology level and to systematically explore the molecular mechanisms driving the virus life cycle. Furthermore, we extract and discuss drug repurposing candidates involved in these mechanisms. CoVex renders COVID-19 drug research systems-medicine-ready by giving the scientific community direct access to network medicine algorithms integrating virus-host-drug interactions. It is available at https://exbio.wzw.tum.de/covex/.
