WHAT'S KNOWN ON THIS SUBJECT: Preterm infants dependent on parenteral nutrition are vulnerable to deficits in early postnatal nutritional intake. This coincides with a period of suboptimal head growth. Observational studies indicate that poor nutritional intake is associated with suboptimal head growth and neurodevelopmental outcome. WHAT THIS STUDY ADDS:This study provides randomized controlled trial evidence that head growth failure in the first 4 weeks of life can be ameliorated with early nutritional intervention. Early macronutrient intake can be enhanced by optimizing a standardized, concentrated neonatal parenteral nutrition regimen. abstract BACKGROUND: Early postnatal head growth failure is well recognized in very preterm infants (VPIs). This coincides with the characteristic nutritional deficits that occur in these parenteral nutrition (PN) dependent infants in the first month of life. Head circumference (HC) is correlated with brain volume and later neurodevelopmental outcome. We hypothesized that a Standardized, Concentrated With Added Macronutrients Parenteral (SCAMP) nutrition regimen would improve early head growth. The aim was to compare the change in HC (DHC) and HC SD score (DSDS) achieved at day 28 in VPIs randomly assigned to receive SCAMP nutrition or a control standardized, concentrated PN regimen. METHODS:Control PN (10% glucose, 2.8 g/kg per day protein/lipid) was started within 6 hours of birth. VPIs (birth weight ,1200 g; gestation ,29 weeks) were randomly assigned to either start SCAMP (12% glucose, 3.8 g/kg per day protein/lipid) or remain on the control regimen. HC was measured weekly. Actual daily nutritional intake data were collected for days 1 to 28.RESULTS: There were no differences in demographic data between SCAMP (n = 74) and control (n = 76) groups. Comparing cumulative 28-day intakes, the SCAMP group received 11% more protein and 7% more energy. The SCAMP group had a greater DHC at 28 days (P , .001). The difference between the means (95% confidence interval) for DHC was 5 mm (2 to 8), and DSDS was 0.37 (0.17 to 0.58). HC differences are still apparent at 36 weeks' corrected gestational age. Dr Morgan developed the original concept and designed the study, ensured regulatory approvals, performed some study measurements, data collection and collation, coordinated data analysis, and drafted the initial manuscript; Mr McGowan performed most of the study measurements, data collection, and collation, contributed to data analysis and made study design modifications; Mr Herwitker was involved with study design and regulatory approval, overseeing study PN manufacture, and some data collation; Ms Hart provided the medical statistical support at the design, monitoring, and analytical stages of the study; Dr Turner was involved in study design and data analysis; and all authors approved the final manuscript as submitted. CONCLUSIONS:This trial has been registered with the ISRCTN Register (http:// isrctn.org) (identifier ISRCTN76597892 Improved survival of very preterm infants (VPIs) ha...

BackgroundInfants born <29 weeks gestation are at high risk of neurocognitive disability. Early postnatal growth failure, particularly head growth, is an important and potentially reversible risk factor for impaired neurodevelopmental outcome. Inadequate nutrition is a major factor in this postnatal growth failure, optimal protein and calorie (macronutrient) intakes are rarely achieved, especially in the first week. Infants <29 weeks are dependent on parenteral nutrition for the bulk of their nutrient needs for the first 2-3 weeks of life to allow gut adaptation to milk digestion. The prescription, formulation and administration of neonatal parenteral nutrition is critical to achieving optimal protein and calorie intake but has received little scientific evaluation. Current neonatal parenteral nutrition regimens often rely on individualised prescription to manage the labile, unpredictable biochemical and metabolic control characteristic of the early neonatal period. Individualised prescription frequently fails to translate into optimal macronutrient delivery. We have previously shown that a standardised, concentrated neonatal parenteral nutrition regimen can optimise macronutrient intake.MethodsWe propose a single centre, randomised controlled exploratory trial of two standardised, concentrated neonatal parenteral nutrition regimens comparing a standard macronutrient content (maximum protein 2.8 g/kg/day; lipid 2.8 g/kg/day, dextrose 10%) with a higher macronutrient content (maximum protein 3.8 g/kg/day; lipid 3.8 g/kg/day, dextrose 12%) over the first 28 days of life. 150 infants 24-28 completed weeks gestation and birthweight <1200 g will be recruited. The primary outcome will be head growth velocity in the first 28 days of life. Secondary outcomes will include a) auxological data between birth and 36 weeks corrected gestational age b) actual macronutrient intake in first 28 days c) biomarkers of biochemical and metabolic tolerance d) infection biomarkers and other intravascular line complications e) incidence of major complications of prematurity including mortality f) neurodevelopmental outcome at 2 years corrected gestational ageTrial registrationCurrent controlled trials: ISRCTN76597892; EudraCT Number: 2008-008899-14

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Topical fluoroquinolones (FQs) are an established treatment for suspected microbial keratitis. An increased FQ resistance in some classes of bacterial pathogens is a concern. Some recently developed FQs have an extended spectrum of activity, making them a suitable alternative for topical ophthalmic use. For example, the new generation FQs, avarofloxacin, delafloxacin, finafloxacin, lascufloxacin, nadifloxacin, levonadifloxacin, nemonoxacin and zabofloxacin have good activity against the common ophthalmic pathogens such asStaphylococcus aureus,Pseudomonas aeruginosa,Streptococcus pneumoniaeand several of theEnterobacteriaceae. However, because there are no published ophthalmic break-point concentrations, the susceptibility of an isolated micro-organism to a topical FQ is extrapolated from systemic break-point data and wild type susceptibility. The purpose of this review is to compare the pharmacokinetics and pharmacodynamics of the FQs licensed for topical ophthalmic use with the same parameters for new generation FQs. We performed a literature review of the FQs approved for topical treatment and the new generation FQs licensed to treat systemic infections. We then compared the minimum inhibitory concentrations (MIC) of bacterial isolates and the published concentrations that FQs achieved in the cornea and aqueous. We also considered the potential suitability of new generation FQs for topical use based on their medicinal properties. Notably, we found significant variation in the reported corneal and aqueous FQ concentrations so that reliance on the reported mean concentration may not be appropriate, and the first quartile concentration may be more clinically relevant. The provision of the MIC for the microorganism together with the achieved lower (first) quartile concentration of a FQ in the cornea could inform management decisions such as whether to continue with the prescribed antimicrobial, increase the frequency of application, use a combination of antimicrobials or change treatment.

Background Postnatal head growth failure is well recognised in very preterm infants (VPI), the largest deficit occurs at 3–4 weeks followed by some catch-up growth until 36weeks corrected gestational age (36wCGA). Head circumference (HC) is correlated with brain volume and later neurodevelopmental outcome. Early nutritional deficits commonly occur in parenteral nutrition (PN) dependent VPI. We hypothesised that a Standardised, Concentrated with Added Macronutrients Parenteral (SCAMP) nutrition regimen would improve early head growth. Aim To compare the change in HC (ΔHC) and standard deviation score (ΔSDS) achieved at day 28 in VPI randomised to receive SCAMP nutrition (12% glucose, 3.8g/kg/day protein/lipid) or a control standardised, concentrated PN regimen (10% glucose, 2.8g/kg/day protein/lipid). Methods The double-blind study (ISRCTN: 76597892) received ethical approval. Control PN was started within 6 hours of birth. Following parental consent, VPI (<1200g; <29 weeks) were randomised (day 2–5) to either start SCAMP or remain on the control regimen. HC was measured at randomisation, day 7 and then weekly until 36wCGA. Actual daily nutritional intake, biochemical and metabolic data were collected for day 1–28. Weekly growth data and major preterm complications were collected until 36wCGA. Results 150/196 eligible infants were randomised at mean age 73.5 hours. Mean (SD) birthweight (g) and gestation (weeks) was: 900(158) versus 884(183) and 26.8(1.3) versus 26.6(1.4) in SCAMP (n = 74) and control (n = 76) groups respectively. SCAMP achieved higher mean actual protein/energy intakes (calculated weekly) with largest difference occurring in week 2: 25.5g/kg versus 20.9g/kg and; 762kcal/kg versus 664kcal/kg. Abstract G169 Table 1Primary outcome (mean/SD; 28-day survivors) Age SCAMP HC (n = 66) SCAMP SDS (n = 66) Control HC (n = 69) Control SDS (n = 69) P value Randomisation 240mm (12) -1.55 (0.73) 240mm (13) -1.48 (0.68) ΔHC/ΔSDS Day 28 31mm (9) +0.05 (0.66) 26mm (8) -0.32(0.65) <0.001 Differences in ΔHC are already apparent at day 7 (p < 0.05) with the greatest difference at 3–4 weeks (28-day-ΔHC difference equates to 6% difference head/brain volume). Group HC differences are still apparent at 36wCGA (p < 0.05). Conclusion Early postnatal head growth failure in VPI can be prevented by optimising PN.