M-ficolin in the neonatal period: Associations with need for mechanical ventilation and mortality in premature infants with necrotising enterocolitis

OBJECTIVE: Necrotising enterocolitis (NEC) causes significant mortality in premature infants. The involvement of the innate immune system in the pathogenesis of NEC remains unclear. M-, L- and H-ficolins recognize microorganisms and activate the complement system, but their role in host defense is largely unknown. This study investigated whether ficolin concentrations are associated with NEC. STUDY DESIGN: Case-control study including 30 premature infants with NEC and 60 controls. M-, L- and H-ficolins were measured in cord blood using time-resolved immunofluorometric assays. Multivariate logistic regression was performed. RESULTS: Of the 30 NEC cases (median gestational age, 29.5 weeks), 12 (40%) were operated and 4 (13%) died. No difference regarding ficolin concentration was found when comparing NEC cases versus controls (p>0.05). However, infants who died of NEC had significantly lower M-ficolin cord blood concentrations than NEC survivors (for M-ficolin <300ng/ml; multivariate OR 12.35, CI 1.03-148.59, p=0.048). In the entire study population, M-, L- and H-ficolins were positively correlated with gestational age (p<0.001) and birth weight (p<0.001). Infants with low M-ficolin required significantly more often mechanical ventilation after birth multivariate (OR 10.55, CI 2.01-55.34, p=0.005). CONCLUSIONS: M-, L- and H-ficolins are already present in cord blood and increase with gestational age. Low cord blood concentration of M-ficolin was associated with higher NEC-associated fatality and with increased need for mechanical ventilation. Future studies need to assess whether M-ficolin is involved in multiorgan failure and pulmonary disease.

Hierarchical modeling gave plausible estimates of associations between metabolic syndrome and components of antiretroviral therapy

OBJECTIVE: Hierarchical modeling has been proposed as a solution to the multiple exposure problem. We estimate associations between metabolic syndrome and different components of antiretroviral therapy using both conventional and hierarchical models. STUDY DESIGN AND SETTING: We use discrete time survival analysis to estimate the association between metabolic syndrome and cumulative exposure to 16 antiretrovirals from four drug classes. We fit a hierarchical model where the drug class provides a prior model of the association between metabolic syndrome and exposure to each antiretroviral. RESULTS: One thousand two hundred and eighteen patients were followed for a median of 27 months, with 242 cases of metabolic syndrome (20%) at a rate of 7.5 cases per 100 patient years. Metabolic syndrome was more likely to develop in patients exposed to stavudine, but was less likely to develop in those exposed to atazanavir. The estimate for exposure to atazanavir increased from hazard ratio of 0.06 per 6 months' use in the conventional model to 0.37 in the hierarchical model (or from 0.57 to 0.81 when using spline-based covariate adjustment). CONCLUSION: These results are consistent with trials that show the disadvantage of stavudine and advantage of atazanavir relative to other drugs in their respective classes. The hierarchical model gave more plausible results than the equivalent conventional model.

Depressive symptoms from kindergarten to early school age: longitudinal associations with social skills deficits and peer victimization

BACKGROUND: Depressive symptoms in children are associated with social skills deficits and problems with peers. We propose a model which suggests different mechanisms for the impact of deficits in self-oriented social skills (assertiveness and social participation) and other-oriented social skills (pro-social, cooperative and non-aggressive behaviors) on children's depressive symptoms. We hypothesized that deficits in self-oriented social skills have a direct impact on children's depressive symptoms because these children have non-rewarding interactions with peers, whereas the impact of deficits in other-oriented social skills on depressive symptoms is mediated through negative reactions from peers such as peer victimization. METHOD: 378 kindergarten children (163 girls) participated at two assessments (Age at T1: M = 5.8, T2: M = 7.4). Teachers completed questionnaires on children's social skills at T1. Teacher reports on peer victimization and depressive symptoms were assessed at both assessment points. RESULTS: Our study partially confirmed the suggested conceptual model. Deficits in self-oriented social skills significantly predicted depressive symptoms, whereas deficits in other-oriented social skills were more strongly associated with peer victimization. Longitudinal associations between other-oriented social skills and depressive symptoms were mediated through peer victimization. CONCLUSION: The study emphasizes the role of deficits in self-oriented social skills and peer victimization for the development of internalizing disorders.