DESIGN: Secondary analysis of a cross-sectional point prevalence study.
SETTING: A total of 128 PICUs in 26 countries.
PATIENTS: Less than 18 years with severe sepsis on 5 separate days (2013-2014).
INTERVENTIONS: None.
MEASUREMENTS AND MAIN RESULTS: Patients were categorized as having either no neurologic dysfunction or neurologic dysfunction (i.e., present at or after sepsis recognition), which was defined as Glasgow Coma Scale score less than 5 and/or fixed dilated pupils. Our primary outcome was death or new moderate disability (i.e., Pediatric Overall [or Cerebral] Performance Category score ≥3 and change ≥1 from baseline) at hospital discharge, and 87 of 567 severe sepsis patients (15%) had neurologic dysfunction within 7 days of sepsis recognition (61 at sepsis recognition and 26 after sepsis recognition). Primary site of infection varied based on presence of neurologic dysfunction. Death or new moderate disability occurred in 161 of 480 (34%) without neurologic dysfunction, 45 of 61 (74%) with neurologic dysfunction at sepsis recognition, and 21 of 26 (81%) with neurologic dysfunction after sepsis recognition (p < 0.001 across all groups). On multivariable analysis, in comparison with those without neurologic dysfunction, neurologic dysfunction whether at sepsis recognition or after was associated with increased odds of death or new moderate disability (adjusted odds ratio, 4.9 [95% CI, 2.3-10.1] and 10.7 [95% CI, 3.8-30.5], respectively). We failed to identify a difference between these adjusted odds ratios of death or new moderate disability that would indicate a differential risk of outcome based on timing of neurologic dysfunction (p = 0.20).
CONCLUSIONS: In this severe sepsis international cohort, the presence of neurologic dysfunction during sepsis is associated with worse outcomes at hospital discharge. The impact of early versus late onset of neurologic dysfunction in sepsis on outcome remains unknown, and further work is needed to better understand timing of neurologic dysfunction onset in pediatric sepsis.
OBJECTIVES: To present the protocol and analysis plan of a large randomised clinical trial investigating the effect of a sedation strategy, in critically ill patients who are mechanically ventilated, based on a protocol targeting light sedation using dexmedetomidine as the primary sedative, termed "early goal-directed sedation", compared with usual practice.
METHODS: This is a multinational randomised clinical trial in adult intensive care patients expected to require mechanical ventilation for longer than 24 hours. The main exclusion criteria include suspected or proven primary brain pathology or having already been intubated or sedated in an intensive care unit for longer than 12 hours. Randomisation occurs via a secured website with baseline stratification by site and suspected or proven sepsis. The primary outcome is 90-day all-cause mortality. Secondary outcomes include death, institutional dependency, cognitive function and health-related quality of life 180 days after randomisation, as well as deliriumfree, coma-free and ventilation-free days at 28 days after randomisation. A predefined subgroup analysis will also be conducted. Analyses will be on an intention-to-treat basis and in accordance with this pre-specified analysis plan.
CONCLUSION: SPICE III is an ongoing large scale clinical trial. Once completed, it will inform sedation practice in critically ill patients who are ventilated.
DESIGN: Multi-national, multi-center collaborative network.
METHODS: The Research Standing Committee of the Asia-Pacific Academy of Ophthalmology and the Asia-Pacific Society of Eye Genetics fostered this research collaboration, which brings together renowned institutions and experts for inherited eye diseases in the Asia-Pacific region. The immediate priority of the network will be inherited retinal diseases (IRDs), where there is a lack of detailed characterization of these conditions and in the number of established registries.
RESULTS: The network comprises 55 members from 35 centers, spanning 12 countries and regions, including Australia, China, India, Indonesia, Japan, South Korea, Malaysia, Nepal, Philippines, Singapore, Taiwan, and Thailand. The steering committee comprises ophthalmologists with experience in consortia for eye diseases in the Asia-Pacific region, leading ophthalmologists and vision scientists in the field of IRDs internationally, and ophthalmic geneticists.
CONCLUSIONS: The Asia Pacific Inherited Eye Disease (APIED) network aims to (1) improve genotyping capabilities and expertise to increase early and accurate genetic diagnosis of IRDs, (2) harmonise deep phenotyping practices and utilization of ontological terms, and (3) establish high-quality, multi-user, federated disease registries that will facilitate patient care, genetic counseling, and research of IRDs regionally and internationally.