Neonatal sepsis: a systematic review of core outcomes from randomised clinical trials.

BACKGROUND: The lack of a consensus definition of neonatal sepsis and a core outcome set (COS) proves a substantial impediment to research that influences policy and practice relevant to key stakeholders, patients and parents. METHODS: A systematic review of the literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. In the included studies, the described outcomes were extracted in accordance with the provisions of the Core Outcome Measures in Effectiveness Trials (COMET) handbook and registered. RESULTS: Among 884 abstracts identified, 90 randomised controlled trials (RCTs) were included in this review. Only 30 manuscripts explicitly stated the primary and/or secondary outcomes. A total of 88 distinct outcomes were recorded across all 90 studies included. These were then assigned to seven different domains in line with the taxonomy for classification proposed by the COMET initiative. The most frequently reported outcome was survival with 74% (n = 67) of the studies reporting an outcome within this domain. CONCLUSIONS: This systematic review constitutes one of the initial phases in the protocol for developing a COS in neonatal sepsis. The paucity of standardised outcome reporting in neonatal sepsis hinders comparison and synthesis of data. The final phase will involve a Delphi Survey to generate a COS in neonatal sepsis by consensus recommendation. IMPACT: This systematic review identified a wide variation of outcomes reported among published RCTs on the management of neonatal sepsis. The paucity of standardised outcome reporting hinders comparison and synthesis of data and future meta-analyses with conclusive recommendations on the management of neonatal sepsis are unlikely. The final phase will involve a Delphi Survey to determine a COS by consensus recommendation with input from all relevant stakeholders.

Mediators of the longitudinal relationship between childhood adversity and late adolescent psychopathology.

BACKGROUND: Childhood adversity (CA) is commonly associated with an increased risk of subsequent psychopathology. It is important to identify potential mediators of this relationship which can allow for the development of interventions. In a large population-based cohort study we investigated the relationship between CA and late adolescent psychopathology and early adolescent candidate mediators of this relationship. METHODS: We used data from three waves (n = 6039) of Cohort 98' of the Growing up in Ireland Study (age 9, 13 and 17). We used doubly robust counterfactual analyses to investigate the relationship between CA (reported at age-9) with psychopathology (internalizing and externalizing problems), measured using the Strengths and Difficulties Questionnaire at age-17. Counterfactual and traditional mediation was used to investigate the mediating effects of the parent-child relationship, peer relations, self-concept, computer usage and physical activity. RESULTS: CA was associated with an increased risk of internalizing and externalizing problems at age-17. Parent-child conflict mediated 35 and 42% of the relationship between CA and late adolescent externalizing problems and internalizing problems, respectively. Self-concept and physical activity mediated an additional proportion of the relationship between CA and internalizing problems. These results were robust to unmeasured confounding. CONCLUSIONS: Parent-child conflict explains more than a third of the relationship between CA and later psychopathology. Self-concept and physical activity explain the additional proportion of the relationship between CA and internalizing problems. This suggests that these factors may be good targets for intervention in young people who have experienced CA to prevent subsequent psychopathology.