Lancet
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Important advances have been made in our understanding of severe sepsis. Outcome can be improved by targeted interventions, including early and appropriate antibiotic therapy and goal-directed resuscitation, and might be further improved by selective decontamination of the digestive tract, tight control of glucose, and possibly by giving corticosteroids to selected patients. Drugs that target specific steps in the septic cascade include cytokine inhibitors, anti-endotoxins, and the three naturally occurring anticoagulants. Only one of these trials, which assessed the efficacy of activated protein C, reported significant improvements in outcome. Translation of these results into practice has been hampered by high drug costs, and by apparent discrepancies between interim results and final outcomes in two of the trials with natural anticoagulants. ⋯ Recently, Steven Opal and colleagues (Crit Care Med 2004; 32: 332-41) reported a randomised trial with platelet-activating-factor acetylhydrolase to suppress the inflammatory response in septic patients. No effects on outcome were observed (mortality 24% with placebo vs 25% with the intervention). By contrast, Jose Garnacho-Montero and colleagues, in a cohort study (Crit Care Med 2003; 31: 2742-51), saw large mortality reductions with initially appropriate choice of antibiotics in septic patients (19.8% reduction overall and 43.4% in patients with septic shock). These benefits were higher than those even in the most successful trial with an antisepsis agents, underscoring the importance of basic measures in severe sepsis. WHERE NEXT? Initial management in severe sepsis should include early goal-directed fluid resuscitation, appropriate antibiotic treatment, and surgical-site control. Intensive-care units should be run by specialists, with adequate medical and nursing staffing. Tight regulation of glucose, selective decontamination of the digestive tract, and moderate-dose corticosteroids in selected cases should be considered. Expensive new drugs, such as activated protein C, might further improve outcome, but should be considered only when organisational aspects and supportive care have been optimised.
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Multicenter Study
Viral shedding patterns of coronavirus in patients with probable severe acute respiratory syndrome.
Severe acute respiratory syndrome (SARS) is thought to be caused by a novel coronavirus, SARS-associated coronavirus. We studied viral shedding of SARS coronavirus to improve diagnosis and infection control. ⋯ Overall, peak viral loads were reached at 12-14 days of illness when patients were probably in hospital care, which would explain why hospital workers were prone to infection. Low rate of viral shedding in the first few days of illness meant that early isolation measures would probably be effective.
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Randomized Controlled Trial Multicenter Study Clinical Trial
Effects of morphine analgesia in ventilated preterm neonates: primary outcomes from the NEOPAIN randomised trial.
Opioid analgesia is commonly used during neonatal intensive care. We undertook the Neurologic Outcomes and Pre-emptive Analgesia in Neonates (NEOPAIN) trial to investigate whether pre-emptive morphine analgesia decreases the rate of a composite primary outcome of neonatal death, severe intraventricular haemorrhage (IVH), and periventricular leucomalacia (PVL) in preterm neonates. ⋯ Pre-emptive morphine infusions did not reduce the frequency of severe IVH, PVL, or death in ventilated preterm neonates, but intermittent boluses of open-label morphine were associated with an increased rate of the composite outcome. The morphine doses used in this study decrease clinical signs of pain but can cause significant adverse effects in ventilated preterm neonates.