Abstract:Objectives:To develop a Glucocorticoid Toxicity Index (GTI) to assess glucocorticoid (GC)-related morbidity and the GC-sparing ability of other therapies. Methods:Nineteen experts on glucocorticoid use and outcome measures from 11 subspecialties participated. Ten experts were from the United States; 9 from Canada, Europe, or Australia.Group consensus methods and multi-criteria decision analysis (MCDA) were utilized.A Composite GTI and Specific List comprise the overall GTI. The Composite GTI reflects toxicity likely to change during a clinical trial. The Composite GTI toxicities occur commonly, vary with GC exposure, and are weighted and scored. Relative weights for items in the Composite GTI were derived by group consensus and MCDA. The Specific List is designed to capture GC toxicity not included in the Composite GTI. The Composite GTI was evaluated by application to paper cases by the investigators and an external group of 17 subspecialists. Results:Thirty-one toxicity items were included in the Composite GTI and 23 in the Specific List.Composite GTI evaluation showed high inter-rater agreement (investigators kappa 0.88, external raters kappa 0.90). To assess the degree to which the Composite GTI corresponds to expert clinical judgment, participants ranked 15 cases by clinical judgment in order of highest to lowest GC toxicity. Expert rankings were then compared to case ranking by the Composite GTI,

ObjectiveTo compare rates of necrotising enterocolitis (NEC), late-onset sepsis, and mortality in 5-year epochs before and after implementation of routine daily multistrain probiotics administration in high-risk neonates.DesignSingle-centre retrospective observational study over the 10-year period from 1 January 2008 to 31 December 2017.SettingLevel 3 neonatal intensive care unit (NICU) of the Norfolk and Norwich University Hospital, UK.PatientsPreterm neonates at high risk of NEC: admitted to NICU within 3 days of birth at <32 weeks’ gestation or at 32–36 weeks’ gestation and of birth weight <1500 g.InterventionPrior to 1 January 2013 probiotics were not used. Thereafter, dual-species Lactobacillus acidophilus and Bifidobacterium bifidum combination probiotics were routinely administered daily to high-risk neonates; from April 2016 triple-species probiotics (L. acidophilus, B. bifidum, and B. longum subspecies infantis) were used.Main outcome measuresIncidence of NEC (modified Bell’s stage 2a or greater), late-onset sepsis, and mortality.ResultsRates of NEC fell from 7.5% (35/469 neonates) in the pre-implementation epoch to 3.1% (16/513 neonates) in the routine probiotics epoch (adjusted sub-hazard ratio=0.44, 95% CI 0.23 to 0.85, p=0.014). The more than halving of NEC rates after probiotics introduction was independent of any measured covariates, including breast milk feeding rates. Cases of late-onset sepsis fell from 106/469 (22.6%) to 59/513 (11.5%) (p<0.0001), and there was no episode of sepsis due to Lactobacillus or Bifidobacterium. All-cause mortality also fell in the routine probiotics epoch, from 67/469 (14.3%) to 47/513 (9.2%), although this was not statistically significant after multivariable adjustment (adjusted sub-hazard ratio=0.74, 95% CI 0.49 to 1.12, p=0.155).ConclusionsAdministration of multispecies Lactobacillus and Bifidobacterium probiotics has been associated with a significantly decreased risk of NEC and late-onset sepsis in our neonatal unit, and no safety issues. Our data are consistent with routine use of Lactobacillus and Bifidobacterium combination probiotics having a beneficial effect on NEC prevention in very preterm neonates.

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In a nationwide survey we found 72 PKU (phenylketonuria) patients who had terminated diet but later returned to diet. Sixty-one patients resumed diet due to clinical problems. Age at initial diet discontinuation ranged from three to 20 years. The most prevalent problems reported were poor school performance, and mood and/or behavior changes. Following diet reinstitution, only positive changes were noted for 42 patients, no changes for 19 patients, and 11 had one or more negative changes. Improvements

Background-Despite the high co-occurrence between depression and asthma, few studies have addressed methods assessing the severity of depressive symptoms among patients with asthma.