In this study, we found no evidence of any association between micronutrient/antioxidant intake or plasma/serum levels of micronutrients/antioxidants and asthma. Reduction of platelet GSH-Px activity in the most severe patients suggests that these patients have a diminished capacity to restore part of the antioxidant defences.

Background: Observational studies have suggested that accelerated surgery is associated with improved outcomes in patients with a hip fracture. The HIP ATTACK trial assessed whether accelerated surgery could reduce mortality and major complications. Methods:We randomised 2970 patients from 69 hospitals in 17 countries. Patients with a hip fracture that required surgery and were ≥45 years of age were eligible. Patients were randomly assigned to accelerated surgery (goal of surgery within 6 hours of diagnosis; 1487 patients) or standard care (1483 patients). The co-primary outcomes were 1.) mortality, and 2.) a composite of major complications (i.e., mortality and non-fatal myocardial infarction, stroke, venous thromboembolism, sepsis, pneumonia, life-threatening bleeding, and major bleeding) at 90 days after randomisation. Outcome adjudicators were masked to treatment allocation, and patients were analysed according to the intention-to-treat principle; ClinicalTrials.gov, NCT02027896. Findings:The median time from hip fracture diagnosis to surgery was 6 hours (interquartile range [IQR] 4-9) in the accelerated-surgery group and 24 hours (IQR 10-42) in the standard-care group, p<0.0001. Death occurred in 140 patients (9%) assigned to accelerated surgery and 154 patients (10%) assigned to standard care; hazard ratio (HR) 0.91, 95% CI 0.72-1.14; absolute risk reduction (ARR) 1%, 95% CI -1-3%; p=0.40. The primary composite outcome occurred in 321 patients (22%) randomised to accelerated surgery and 331 patients (22%) randomised to standard care; HR 0.97, 95% CI 0.83-1.13; ARR 1%, 95% CI -2-3%; p=0.71.Interpretation: Among patients with a hip fracture, accelerated surgery did not significantly lower the risk of mortality or a composite of major complications compared to standard care.

There is little known about pharmacogenetic of fluoxetine in children and adolescents. In this study, we evaluate, for the first time, the influence of CYP2D6, CYP2C9 and ABCB1 genotypes on the steady-state plasma concentrations of fluoxetine and its active metabolite (S)-norfluoxetine, and on the clinical improvement in children and adolescent patients receiving fluoxetine treatment. The assessment was performed in 83 patients after 8 and 12 weeks of treatment. Fluoxetine/(S)-norfluoxetine ratio was negatively correlated with the number of active CYP2D6 alleles (r: -0.450; P<0.001). Regarding the G2677T ABCB1 polymorphism, T allele carriers showed significantly higher improvements on the majority of scales including the Clinical Global Impression-Improvement scale (P<0.001). Our results confirm the influence of CYP2D6 genetic variants in fluoxetine pharmacokinetics and provide evidence for the potential effect of the ABCB1 genotype on the clinical improvement in children and adolescent patients treated with fluoxetine.

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Background: There is substantial evidence that postpartum prophylaxis with lithium lowers the rate of relapse in bipolar disorder. However, it is contraindicated during breastfeeding due to the high variability of the transfer into breast milk.Aims: We conducted a systematic review of the current evidence of studies assessing the transfer of lithium to lactating infants and short-term infant outcomes.Methods: An a priori protocol was designed based on PRISMA guidelines. Searches in PubMed and LactMed were conducted until September 2018. Studies assessing lithium pharmacokinetic parameters and short-term infant outcomes were included. Quality was assessed using a checklist based on international guidelines (i.e., FDA).Results: From 344 initial studies, 13 case reports/series with 39 mother–child dyads were included. Only 15% of studies complied with ≥50% of the items on the quality assessment checklist. Infants breastfeed a mean (SD) of 58.9 (83.3) days. Mean maternal lithium dose was 904 (293) mg/day, corresponding lithium plasma/serum concentration was 0.73(0.26) mEq/L, and breast milk concentration was 0.84(0.14) mEq/L. Mean infant lithium plasma/serum concentration was 0.23(0.26) mEq/L. Twenty-six (80%) infants had concentrations ≤0.30 mEq/L without adverse effects. Eight (20%) showed a transient adverse event (i.e., acute toxicity or thyroid alterations). All of them were also prenatally exposed to lithium monotherapy or polytherapy.Conclusion: The current evidence comes from studies with a degree of heterogeneity and of low-moderate quality. However, it identifies areas of improvement for future clinical lactation studies of lithium and provides support for some clinical recommendations.