Elevated protein concentrations in newborn blood and the risks of autism spectrum disorder, and of social impairment, at age 10 years among infants born before the 28th week of gestation

Among the 1 of 10 children who are born preterm annually in the United States, 6% are born before the third trimester. Among children who survive birth before the 28th week of gestation, the risks of autism spectrum disorder (ASD) and non-autistic social impairment are severalfold higher than in the general population. We examined the relationship between top quartile inflammation-related protein concentrations among children born extremely preterm and ASD or, separately, a high score on the Social Responsiveness Scale (SRS total score ≥65) among those who did not meet ASD criteria, using information only from the subset of children whose DAS-II verbal or non-verbal IQ was ≥70, who were assessed for ASD, and who had proteins measured in blood collected on ≥2 days (N = 763). ASD (N = 36) assessed at age 10 years is associated with recurrent top quartile concentrations of inflammation-related proteins during the first post-natal month (e.g., SAA odds ratio (OR); 95% confidence interval (CI): 2.5; 1.2–5.3) and IL-6 (OR; 95% CI: 2.6; 1.03–6.4)). Top quartile concentrations of neurotrophic proteins appear to moderate the increased risk of ASD associated with repeated top quartile concentrations of inflammation-related proteins. High (top quartile) concentrations of SAA are associated with elevated risk of ASD (2.8; 1.2–6.7) when Ang-1 concentrations are below the top quartile, but not when Ang-1 concentrations are high (1.3; 0.3–5.8). Similarly, high concentrations of TNF-α are associated with heightened risk of SRS-defined social impairment (N = 130) (2.0; 1.1–3.8) when ANG-1 concentrations are not high, but not when ANG-1 concentrations are elevated (0.5; 0.1–4.2)

Use of the Global Trigger Tool in patient safety improvement efforts : Nordic experiences

The Global Trigger Tool (GTT) developed by the Institute for Healthcare Improvement is a method for retrospective patient record review based on the use of triggers-signals of potential adverse events that have caused patient harm. The method has the purpose of patient safety measurement and monitoring among adult inpatient populations and has been increasingly popular among Nordic countries. Use of the GTT in the Nordic area has been part of broader legal and policy actions and initiatives supportive of patient safety promotion and is being used to establish also national level estimates of patient safety incidents. Limitations of the method are its dependency on quality of documentation and the varying inter-rater reliability observed in many studies. Strengths of the GTT are its ability to detect larger numbers, as well as different types of adverse events when compared to other incident detection methods, hence it is a good addition to the palette of means for organizational patient safety monitoring. Research on reliability, usefulness and implementation approaches of the GTT, including its automation, is ongoing in the Nordic countries and is expected to generate useful input for the international patient safety community

Exploring similarities and differences in hospital adverse event rates between Norway and Sweden using Global Trigger Tool

Objectives: In this paper, we explore similarities and differences in hospital adverse event (AE) rates between Norway and Sweden by reviewing medical records with the Global Trigger Tool (GTT). Design: All acute care hospitals in both countries performed medical record reviews, except one in Norway. Records were randomly selected from all eligible admissions in 2013. Eligible admissions were patients 18 years of age or older, undergoing care with an in-hospital stay of at least 24 hours, excluding psychiatric and care and rehabilitation. Reviews were done according to GTT methodology. Setting: Similar contexts for healthcare and similar socioeconomic and demographic characteristics have inspired the Nordic countries to exchange experiences from measuring and monitoring quality and patient safety in healthcare. The co-operation has promoted the use of GTT to monitor national and local rates of AEs in hospital care. Participants: 10 986 medical records were reviewed in Norway and 19 141 medical records in Sweden. Results: No significant difference between overall AE rates was found between the two countries. The rate was 13.0% (95% CI 11.7% to 14.3%) in Norway and 14.4% ( 95% CI 12.6% to 16.3%) in Sweden. There were significantly higher AE rates of surgical complications in Norwegian hospitals compared with Swedish hospitals. Swedish hospitals had significantly higher rates of pressure ulcers, falls and other AEs. Among more severe AEs, Norwegian hospitals had significantly higher rates of surgical complications than Swedish hospitals. Swedish hospitals had significantly higher rates of postpartum AEs. Conclusions: The level of patient safety in acute care hospitals, as assessed by GTT, was essentially the same in both countries. The differences between the countries in the rates of several types of AEs provide new incentives for Norwegian and Swedish governing bodies to address patient safety issues.Funding Agencies|Akershus University Hospitals Health Services Research Unit; Norwegian Computing Center; Swedish Association of Local Authorities and Regions (SALAR)</p

Arginase activity - a marker of disease status in patients with visceral leishmaniasis in ethiopia.

The underlying mechanisms resulting in the profound immune suppression characteristic of human visceral leishmaniasis (VL) are not fully understood. Here, we tested the hypothesis that arginase, an enzyme associated with immunosuppression, is higher in patients with VL and contributes to impaired T cell responses. We recruited patients with VL before and after treatment and healthy controls and measured the arginase metabolism in the blood of these individuals. Our results show that arginase activity is significantly higher in the blood of patients with active VL as compared to controls. These high levels of arginase decline considerably once the patients are successfully treated. We identified the phenotype of arginase-expressing cells among PBMCs as neutrophils and show that their frequency was increased in PBMCs of patients before treatment; this coincides with reduced levels of L-arginine in the plasma and decreased expression levels of CD3ζ in T cells

Cortisol awakening response and developmental outcomes at 6–7 years in children born extremely preterm

BackgroundExtremely preterm (EPT) birth has been related to dysregulation of stress responses and behavioral/learning problems at school age. Early adverse experiences can blunt HPA axis reactivity. We hypothesized that an attenuated cortisol awakening response would be associated with developmental and behavioral problems at school age in EPT children.MethodsThis secondary analysis of a sub-cohort of the SUPPORT study included children born between 24 and 27 weeks, evaluated at 6-7 years with a neurodevelopmental battery and cortisol measures. Differences were tested between EPT and a term-born group. Relationships of cortisol awakening response to test scores were analyzed.ResultsCortisol was measured in 110 EPT and 29 term-born 6-7 year olds. Unadjusted WISC-IV and NEPSY-II scores were significantly worse among EPT children only. Conners Parent Rating Scale behavior scores were significantly worse among EPT children. After adjusting for covariates, blunted cortisol awakening responses were found to be associated with poorer scores on memory tests and greater problems with inattention for the EPT group (p &lt; 0.05) only.ConclusionsAmong children born EPT, we identified an association of blunted cortisol awakening response with memory and inattention problems. This may have implications related to stress reactivity and its relationship to learning problems in children born EPT.ClinicaltrialsGov idExtended Follow-up at School Age for the SUPPORT Neuroimaging and Neurodevelopmental Outcomes (NEURO) Cohort: NCT00233324.ImpactIn children born EPT, stress reactivity may have a relationship to learning problems. Cortisol awakening response should be a component for follow-up in EPT born children. Components of executive function, such as memory and attention, are related to stress reactivity

Behavioral Deficits at 18-22 Months of Age Are Associated with Early Cerebellar Injury and Cognitive and Language Performance in Children Born Extremely Preterm

To investigate associations in toddlers born extremely preterm (<28 weeks) between neonatal neuroimaging and 18- to 22-month developmental and behavioral outcomes. Cohort analysis from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network Surfactant Positive Airway Pressure and Pulse Oximetry Trial Neuroimaging and Neurodevelopmental Outcomes Study of infants born extremely preterm. Subjects underwent cranial ultrasonography and near-term magnetic resonance imaging (MRI). At 18-22 months of corrected age, the assessment included the Brief Infant Toddler Social Emotional Assessment (BITSEA) Problem and Competence Scale scores and the Bayley Scales of Infant Development, Third Edition (Bayley-III). The BITSEA Problem Scale assesses dysregulation; the Competence Scale assesses social-emotional competence. We examined associations of Problem and Competence scores and positive screen rates with cranial ultrasonography and near-term MRI. Mean BITSEA and Bayley-III scores were compared using ANOVA and positive screen rates with the χ2 test. We computed correlations between BITSEA and Bayley-III scores. Of the 397 children, positive BITSEA screens were found in 34% for the Problem score and 26% for the Competence score. Presence of lesions on near-term MRI that included cerebellar lesions were significantly associated with lower BITSEA Competence but not with Problem scores; Competence scores were inversely related to the presence/significance of lesions. Positive screens on Competence scores and on both Competence and Problem scores were significantly associated with Bayley-III cognitive and language scores <85 (P < .001). Social–emotional competence contributes to deficits in cognitive and language development. Presence of injury on near-term MRI that includes cerebellar lesions is associated with later social–emotional competence and may be a useful predictor to guide early assessment and intervention. ClinicalTrials.gov: NCT00063063 and NCT00233324