Up to 7% of term and late-preterm neonates in high-income countries receive antibiotics during the first 3 days of life because of suspected early-onset sepsis. The prevalence of culture-proven ...early-onset sepsis is 0·1% or less in high-income countries, suggesting substantial overtreatment. We assess whether procalcitonin-guided decision making for suspected early-onset sepsis can safely reduce the duration of antibiotic treatment.
We did this randomised controlled intervention trial in Dutch (n=11), Swiss (n=4), Canadian (n=2), and Czech (n=1) hospitals. Neonates of gestational age 34 weeks or older, with suspected early-onset sepsis requiring antibiotic treatment were stratified into four risk categories by their treating physicians and randomly assigned 1:1 using a computer-generated list stratified per centre to procalcitonin-guided decision making or standard care-based antibiotic treatment. Neonates who underwent surgery within the first week of life or had major congenital malformations that would have required hospital admission were excluded. Only principal investigators were masked for group assignment. Co-primary outcomes were non-inferiority for re-infection or death in the first month of life (margin 2·0%) and superiority for duration of antibiotic therapy. Intention-to-treat and per-protocol analyses were done. This trial was registered with ClinicalTrials.gov, number NCT00854932.
Between May 21, 2009, and Feb 14, 2015, we screened 2440 neonates with suspected early-onset sepsis. 622 infants were excluded due to lack of parental consent, 93 were ineligible for reasons unknown (68), congenital malformation (22), or surgery in the first week of life (3). 14 neonates were excluded as 100% data monitoring or retrieval was not feasible, and one neonate was excluded because their procalcitonin measurements could not be taken. 1710 neonates were enrolled and randomly assigned to either procalcitonin-guided therapy (n=866) or standard therapy (n=844). 1408 neonates underwent per-protocol analysis (745 in the procalcitonin group and 663 standard group). For the procalcitonin group, the duration of antibiotic therapy was reduced (intention to treat: 55·1 vs 65·0 h, p<0·0001; per protocol: 51·8 vs 64·0 h; p<0·0001). No sepsis-related deaths occurred, and 9 (<1%) of 1710 neonates had possible re-infection. The risk difference for non-inferiority was 0·1% (95% CI −4·6 to 4·8) in the intention-to-treat analysis (5 0·6% of 866 neonates in the procalcitonin group vs 4 0·5% of 844 neonates in the standard group) and 0·1% (−5·2 to 5·3) in the per-protocol analysis (5 0·7% of 745 neonates in the procalcitonin group vs 4 0·6% of 663 neonates in the standard group).
Procalcitonin-guided decision making was superior to standard care in reducing antibiotic therapy in neonates with suspected early-onset sepsis. Non-inferiority for re-infection or death could not be shown due to the low occurrence of re-infections and absence of study-related death.
The Thrasher Foundation, the NutsOhra Foundation, the Sophia Foundation for Scientific research.
The purpose of this study is to demonstrate that within the United States health care system, a number of institutions have evolved which have given rise to a perverse set of incentives that direct ...technological change. As a result of these incentives, the diffusion and utilization of new and existing technologies is carried out in a random and indiscrete fashion, subsequently placing upward pressure on the costs of health care. This analysis relies on the empirical work, observations, and writings of a large number of physicians, social scientists, hospital administrators, and federal bureaucrats.
Bone fragility increases with age as the result of the concurrent decline of bone mass, quality, and mechanosensitivity. While the coordinated decline of these behaviors remains unexplained, the role ...of osteocytes in each of these processes, and the age‐related degeneration of the lacunocanalicular network (LCN) in which they reside, implicate osteocytes in bone aging. Using a combination of imaging and computational modeling, we identify canalicular pruning as a driver behind declining bone functionality with age. Furthermore, these analyses predict novel opportunities to restore function to aged osteocyte networks through expansion of the pericellular space.
The ability of bone to resist fracture is determined by the combination of bone mass and bone quality. Like bone mass, bone quality is carefully regulated. Of the many aspects of bone quality, this ...review focuses on biological mechanisms that control the material quality of the bone extracellular matrix (ECM). Bone ECM quality depends upon ECM composition and organization. Proteins and signaling pathways that affect the mineral or organic constituents of bone ECM impact bone ECM material properties, such as elastic modulus and hardness. These properties are also sensitive to pathways that regulate bone remodeling by osteoblasts, osteoclasts, and osteocytes. Several extracellular proteins, signaling pathways, intracellular effectors, and transcription regulatory networks have been implicated in the control of bone ECM quality. A molecular understanding of these mechanisms will elucidate the biological control of bone quality and suggest new targets for the development of therapies to prevent bone fragility.
To be so imprinted and inscribed, to have a "penetrated subjectivity," was to be a quixotic reader and also "to be feminized, but feminized in a way that shifted from the mid-to late eighteenth ...century" (10). Beginning with Charlotte Lennox's 1752 The Female Quixote (whose eponymous heroine counterintuitively turns out to be the least restrictively "female" of all, and rather the most "potentially universal model of subjectivity" 148), Dale ranges easily among different genres of fiction, from the obscure to the classic, and from the middle to the end of the eighteenth century. The political threat represented by the quixotic reader figure by the end of the eighteenth century, according to Dale, involves "enthusiastic, materialist misreading" (this is indeed where it seems that more attention to Austen might have complicated the conclusion 120).
The climate emergency is a source of anxiety for many young people. Images of drought, heat waves, wildfires, storms and flooding are increasingly appearing in the media. Today's children stand to be ...the recipients of our legacy of climate change, while not feeling empowered to do anything about it, so perhaps it is no wonder they are anxious. Teachers should be helping children to understand what causes climate change, its effects and what can be done to prevent further damage (as well as to mitigate the effects of the damage already done). Alongside this, educators need to give children the tools and confidence to help them make a difference where they can. In this article, professional engineer and STEM educator Caroline Alliston presents her ideas to help primary teachers deliver a comprehensive curriculum-linked programme on climate change and sustainability without the need to have a detailed knowledge of the subject.
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