Plos One
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Shorter, more effective treatments for tuberculosis (TB) are urgently needed. While many TB drugs are available, identification of the best regimens is challenging because of the large number of possible drug-dose combinations. We have found consistently that responses of cells or whole animals to drug-dose stimulations fit a parabolic response surface (PRS), allowing us to identify and optimize the best drug combinations by testing only a small fraction of the total search space. Previously, we used PRS methodology to identify three regimens (PRS Regimens I-III) that in murine models are much more effective than the standard regimen used to treat TB. However, PRS Regimens I and II are unsuitable for treating drug-resistant TB and PRS Regimen III includes an experimental drug. Here, we use PRS methodology to identify from an expanded pool of drugs new highly effective near-universal drug regimens comprising only approved drugs. ⋯ We have identified three new regimens that rapidly sterilize the lungs of mice and dramatically shorten the time required to achieve relapse-free cure. All mouse drug doses in these regimens extrapolate to doses that are readily achievable in humans. Because PRS Regimens IV and V contain only one first line drug (PZA) and exclude fluoroquinolones and aminoglycosides, they should be effective against most TB cases that are multidrug resistant (MDR-TB) and many that are extensively drug-resistant (XDR-TB). Hence, these regimens have potential to shorten dramatically the time required for treatment of both drug-sensitive and drug-resistant TB. If clinical trials confirm that these regimens dramatically shorten the time required to achieve relapse-free cure in humans, then this radically shortened treatment has the potential to improve treatment compliance, decrease the emergence of drug resistance, and decrease the healthcare burden of treating both drug-sensitive and drug-resistant TB.
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Trauma and hemorrhagic shock can lead to acute traumatic coagulopathy (ATC) that is not fully reversed by prehospital resuscitation as simulated with a limited volume of fresh whole blood (FWB) in a rat model. Tranexamic Acid (TXA) is used as an anti-fibrinolytic agent to reduce surgical bleeding if administered prior to or during surgery, and to improve survival in trauma if given early after trauma. It is not clear from the existing clinical literature whether TXA has the same mechanism of action in both settings. ⋯ In conclusion: Limited prehospital trauma resuscitation that includes FWB and TXA may not correct established systemic ATC, but rather may improve overall outcomes of resuscitation by attenuation of acute lung injury. By contrast, TXA given prior to trauma reduced levels of fibrinolysis at the site of tissue injury and circulatory d-dimer, and delayed development of coagulopathy independent of reduction of fibrinogen levels following trauma. These findings highlight the importance of early administration of TXA in trauma, and suggest that further optimization of dosing protocols in trauma to exploit TXA's various sites and modes of action may further improve patient outcomes.
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Workload and demands on hospital staff have been growing over recent years. To ensure patient and occupational safety, hospitals increasingly survey staff about perceived working conditions and safety culture. At the same time, routine data are used to manage resources and performance. This study aims to understand the relation between survey-derived measures of how staff perceive their work-related stress and strain and patient safety on the one hand, and routine data measures of workload and quality of care (patient safety) on the other. ⋯ Perceptions of hospital personnel regarding sub-optimal workplace safety and teamwork issues correlated with worse patient outcome measures. Furthermore, objective measures of overtime work as well as objective measures of workload correlated clearly with subjective work-related stress and strain. This suggests that objective workload measures (such as overtime worked) could be used to indirectly monitor job-related psychosocial strain on employees and, thus, improve not only staff wellbeing but also patient outcomes. On the other hand, listening to their personnel could help hospitals to improve patient (and employee) safety.
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Research in applied ecology provides scientific evidence to guide conservation policy and management. Applied ecology is becoming increasingly quantitative and model selection via information criteria has become a common statistical modeling approach. Unfortunately, parameters that contain little to no useful information are commonly presented and interpreted as important in applied ecology. ⋯ Given the prevalence of studies likely to have uninformative parameters or with insufficient information to assess parameter status (71.5%), I surmise that much of the policy recommendations based on applied ecology research may not be supported by the data analysis. I provide four warning signals and a decision tree to assist authors, reviewers, and editors to screen for uninformative parameters in studies applying model selection with information criteria. In the end, careful thinking at every step of the scientific process and greater reporting standards are required to detect uninformative parameters in studies adopting an information criteria approach.
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The evidence supporting the benefit of femoral nerve block (FNB) for positioning before spinal anesthesia (SA) in patients suffering from a femur fracture remains inconclusive. In the present study, the authors intended to determine the efficacy and safety of FNB versus an intravenous analgesic (IVA) for positioning before SA in patients with a femur fracture. ⋯ Compared to IVA, FNB was an effective and safe strategy for the positioning of femur fracture patients for a spinal block, particularly patients who received SA in the sitting position.