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Martin R. Späth Malte P. Bartram Nicolàs Palacio-Escat K. Johanna R. Hoyer Cedric Debes Fatih Demir Christina B. Schroeter Amrei M. Mandel Franziska Grundmann Giuliano Ciarimboli Andreas Beyer Jayachandran N. Kizhakkedathu Susanne Brodesser Heike Göbel Jan U. Becker Thomas Benzing Bernhard Schermer Martin Höhne Markus M. Rinschen 《Kidney international》2019,95(2):333-349
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The retroviral protease of human immunodeficiency virus (HIV) is an excellent target for antiviral inhibitors for treating HIV/AIDS. Despite the efficacy of therapy, current efforts to control the disease are undermined by the growing threat posed by drug resistance. This review covers the historical background of studies on the structure and function of HIV protease, the subsequent development of antiviral inhibitors, and recent studies on drug-resistant protease variants. We highlight the important contributions of Dr. Stephen Oroszlan to fundamental knowledge about the function of the HIV protease and other retroviral proteases. These studies, along with those of his colleagues, laid the foundations for the design of clinical inhibitors of HIV protease. The drug-resistant protease variants also provide an excellent model for investigating the molecular mechanisms and evolution of resistance. 相似文献
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Stefan Scholz Florian Koerber Kinga Meszaros Rosa Maya Fassbender Bernhard Ultsch Robert R. Welte Wolfgang Greiner 《Vaccine》2019,37(12):1692-1701
Introduction
Invasive meningococcal disease (IMD) is a severe disease mainly affecting infants and young children. The most common serogroup causing IMD in Germany is the serogroup type B Neisseria meningitidis (MenB). The aim of the present study is to estimate the economic burden of MenB-related IMD in Germany.Method
A bottom-up, model-based costing approach has been used to calculate the diagnose- and age-specific yearly lifetime costs of a hypothetical cohort of MenB-related IMD cases. Direct costs contain the treatment cost for the acute phase of the disease, long-term sequelae, costs for rehabilitation, and public health response. Indirect costs are calculated for the human-capital approach and the friction-cost approach considering productivity losses of patients or parents for the acute phase and long-term sequelae. Publicly available databases from the Federal Statistical Office, the SOEP panel data set, literature, and expert opinion were used as data sources. All future costs beyond the reference year of 2015 were discounted at 3%.Results
The total costs for the hypothetical cohort (343 patients) from a societal perspective are €19.6 million (€57,100/IMD case) using the friction-cost approach and €58.8 million (€171,000/IMD case) using the human-capital approach. Direct costs amount to €18.6 million or €54,300 €/case. Sequelae are responsible for 81% of the direct costs/case.Discussion
The elevated costs/MenB-related IMD case reflect the severity of the disease. The total costs are sensitive to the productivity-loss estimation approach applied. MenB is an uncommon but severe disease; The costs/case reflect the severity of the disease and is within the same magnitude as for human papilloma virus infections. The available literature on sequelae is due to the uncommonness limited and heterogeneous. 相似文献6.
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Anna C. Rienmüller Sandro M. Krieg Franziska A. Schmidt Elias L. Meyer Bernhard Meyer 《The spine journal》2019,19(1):113-120
Background Context
The concept of dynamic stabilization (DS) of the lumbar spine for treatment of degenerative instability has been introduced almost two decades ago. Dynamic stabilization follows the principle of controlling movement in the coronal plane by providing load transfer of the spinal segment without fusion and, at the same time, reducing side effects such as adjacent segment disease (ASD). So far, only little is known about revision rates after DS due to ASD and screw loosening (SL).Purpose
The present study aimed to evaluate the longitudinal revision rates following dynamic pedicle screw stabilization in the lumbar spine and to determine specific risk factors predictive for ASD, SL, and overall reoperation in a large cohort with considerable follow-up.Design
We carried out a post hoc analysis of a prospectively collected database in a level I spine center.Patients Example
The patient sample comprised 283 (151 female/132 male) consecutive patients suffering from painful degenerative lumbar segmental instability with or without spinal stenosis who underwent DS of the lumbar spine (Ulrich Cosmic, Ulrich Medical, Ulm, Germany) between January 2008 and December 2011.Outcome Measures
Longitudinal reoperation rate and risk factors predictive for revision surgery were evaluated.Methods
We analyzed the longitudinal reoperation rate due to ASD and SL and overall reoperation. Risk factors such as age, gender, body mass index, lumbar lordosis (LL), number of segments, and number of previous surgeries were taken into account. Regular and mixed model logistic regressions were performed to determine risk factors for revision surgery on a patient and on a screw level.Results
The mean age was 65.7±10.2 years (range 31–88). One hundred thirty-two patients were stabilized in 1 segment, 134 in 2 segments, 15 in 3 segments, and 2 patients in 4 segments. Reoperation rate for ASD and SL after 1 year was 7.4 %, after 2 years was 15.0%, and after a mean follow-up of 51.4±15 months was 22.6%. Reasons for revision were SL in 19 cases (6.6%), ASD in 39 cases (13.7%), SL and ASD in 6 cases, hematoma in 2 cases (0.7%), cerebrospinal fluid fistulae in 3 cases (1.1%), infection in 6 cases (2.1%), and implant failure in 1 case (0.4%). The patients' age, the number of stabilized segments, and the number of previous surgeries and postoperative LL had a significant influence on the probability for revision surgery.Conclusions
Reoperation rates after DS of the lumbar spine are comparable with rigid fixations. The younger the patient and the more segments are involved, the lower the LL and the more previous surgeries were found, the higher was the risk of revision. Risk of revision was almost twice as high in men compared with women. We therefore conclude that for clear clinical indication and careful evaluation of preoperative imaging data, DS using the Cosmic system seems to be a possible option. The presented data will help to further tailor indication and patient selection. 相似文献8.
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