Nutritional Support for Moderate-to-Late-Preterm Infants - A Randomized Trial.

BACKGROUND: Most moderate-to-late-preterm infants need nutritional support until they are feeding exclusively on their mother's breast milk. Evidence to guide nutrition strategies for these infants is lacking. METHODS: We conducted a multicenter, factorial, randomized trial involving infants born at 32 weeks 0 days' to 35 weeks 6 days' gestation who had intravenous access and whose mothers intended to breast-feed. Each infant was assigned to three interventions or their comparators: intravenous amino acid solution (parenteral nutrition) or dextrose solution until full feeding with milk was established; milk supplement given when maternal milk was insufficient or mother's breast milk exclusively with no supplementation; and taste and smell exposure before gastric-tube feeding or no taste and smell exposure. The primary outcome for the parenteral nutrition and the milk supplement interventions was the body-fat percentage at 4 months of corrected gestational age, and the primary outcome for the taste and smell intervention was the time to full enteral feeding (150 ml per kilogram of body weight per day or exclusive breast-feeding). RESULTS: A total of 532 infants (291 boys [55%]) were included in the trial. The mean (±SD) body-fat percentage at 4 months was similar among the infants who received parenteral nutrition and those who received dextrose solution (26.0±5.4% vs. 26.2±5.2%; adjusted mean difference, -0.20; 95% confidence interval [CI], -1.32 to 0.92; P = 0.72) and among the infants who received milk supplement and those who received mother's breast milk exclusively (26.3±5.3% vs. 25.8±5.4%; adjusted mean difference, 0.65; 95% CI, -0.45 to 1.74; P = 0.25). The time to full enteral feeding was similar among the infants who were exposed to taste and smell and those who were not (5.8±1.5 vs. 5.7±1.9 days; P = 0.59). Secondary outcomes were similar across interventions. Serious adverse events occurred in one infant. CONCLUSIONS: This trial of routine nutrition interventions to support moderate-to-late-preterm infants until full nutrition with mother's breast milk was possible did not show any effects on the time to full enteral feeding or on body composition at 4 months of corrected gestational age. (Funded by the Health Research Council of New Zealand and others; DIAMOND Australian New Zealand Clinical Trials Registry number, ACTRN12616001199404.).

Peripheral Parenteral Nutrition Solutions and Bed Bath Towels as Risk Factors for Nosocomial Peripheral Venous Catheter-related Bloodstream Infection by Bacillus cereus.

In Japan, China, and Singapore, several studies have reported increased incidences of peripheral venous catheter-related bloodstream infection by Bacillus cereus during the summer. Therefore, we hypothesized that bed bathing with a B. cereus-contaminated "clean" towels increases B. cereus contact with the catheter and increases the odds of contaminating the peripheral parenteral nutrition (PPN). We found that 1) professionally laundered "clean" towels used in hospitals have B. cereus (3.3×104 colony forming units (CFUs) / 25cm2), 2) B. cereus is transferable onto the forearms of volunteers by wiping with the towels (n=9), and 3) B. cereus remain detectable (80∼660 CFUs /50cm2) on the forearms of volunteers even with subsequent efforts of disinfection using alcohol wipes. We further confirmed that B. cereus grow robustly (102 CFUs /mL to more than 106 CFUs /mL) within 24hours at 30°C in PPN. Altogether we find that bed bathing with a towel contaminated with B. cereus leads to spore attachments to the skin, and that B. cereus can proliferate at an accelerated rate at 30°C compared to 20°C in PPN. We therefore highly recommend ensuring the use of sterile bed bath towels prior to PPN administration with catheter in patients requiring bed bathing.

[Review of parenteral nutrition practices in four university hospital's pharmacies in Auvergne-Rhône-Alpes region]. / État des lieux des pratiques de nutrition parentérale dans quatre pharmacies à usage intérieur de centre hospitalier et universitaire de la région Auvergne-Rhône-Alpes.

OBJECTIVES: To carry out an assessment of parenteral nutrition (PN) practices in hospital pharmacies of the Auvergne-Rhône-Alpes region in order to explore a harmonisation of practices and a collaboration between the different centres. METHODS: Status of practices was carried out on the basis of an observational study inspired by the survey of the General Inspectorate of Social Affairs. It was carried out in Auvergne-Rhône-Alpes region in four university hospital pharmacies with a production unit of PN. It focused on the different stages of the PN process: prescription, formulation, compounding and quality control. It also covered the support processes such as the quality assurance system and the management of premises and equipment. RESULTS: Most preparations made in the region are individualized parenteral nutritional admixtures for paediatric and neonatal hospitalization departments. The production units of PN of each centre are located in premises in compliance with Good Preparation Practices. However, compounding equipment and raw materials used are heterogeneous in the four centres. All centres control the quality of their finished preparations. But, the performance of analytical control is disparate in terms of equipment and specifications. CONCLUSION: This assessment explains the similarities and differences in PN practices between various university hospitals in the Auvergne-Rhône-Alpes region and thus makes possible to provide a collective regional work to harmonise practices.

Optical Identification of Parenteral Nutrition Solutions Exploiting Refractive Index Sensing.

Parenteral artificial nutrition (PAN) is a lifesaving treatment for a large population of patients affected by different diseases, and it consists of intravenous injection of nutritive fluids by means of infusion pumps. Wrong PAN solutions are, unfortunately, often administered, thus threatening the patients' well-being. Here, we report an optofluidic label-free sensor that can distinguish PAN solutions on the basis of their volumetric refractive index (RI). In our system, a monochromatic light beam, generated by a laser diode, travels obliquely through a transparent, square-section polystyrene channel, is then back-reflected by a mirror, and finally exits the channel in a position that depends on the filling fluid RI. The displacement of the output light spot ΔXexperim is easily detected with a linear, 1-D position sensitive detector (PSD). We initially calibrated the sensor with water-glucose solutions demonstrating a sensitivity S = ΔXexperim/Δn = 13,960 µm/RIU. We then clearly distinguished six commercial PAN solutions, commonly administered to patients. To the best of our knowledge, this is the first reported healthcare sensing platform for remote contactless recognition of PAN fluids, which could be inserted into infusion pumps to improve treatment safety, by checking the compliance to the prescription of the fluid actually delivered to the patient.

Determination of Inorganic Ions in Parenteral Nutrition Solutions by Ion Chromatography.

A new, simple and sensitive ion chromatography (IC) method for the determination of sodium, potassium, magnesium, calcium and chloride in a parenteral nutrition (PN) solution was developed and validated. Before sample analysis, a sample pretreatment by calcination was applied which could totally remove interference from other constituents of the PN solution. Methanesulfonic acid (MSA) and sodium hydroxide were used as the mobile phase for the determination of cations and anions, respectively. The calibration curves showed good correlation between analyte peak area and concentration (r2 > 0.999). Detection limits ranged from 0.0001 to 0.02 mg/L and quantification limits from 0.0002 to 0.06 mg/L. Relative standard deviation (RSD) values for repeatability and inter-day precision did not exceed 1.0% and the recoveries for all analytes were between 99.1−101.1%. The robustness was verified by using an experimental design.

Editorial: Light shielding of bags and tubing used for parenteral nutrition of infants.

PURPOSE OF REVIEW: In July 2019, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) recommended light protection of all parenteral nutrition (PN) solutions containing amino acids (AA) and/or lipids, with or without admixture of vitamins or trace elements, during administration for preterm infants, term infants and children less than 2 years of age. The aim of the present paper was to review the available evidence and to provide recommendations for in hospital and home PN light protection in children. RECENT FINDINGS: Lipid emulsions and multivitamins are susceptible to photooxidation and generation of oxidation products. There is no conclusive evidence to justify recommending light protection for PN solutions without lipid emulsions and/or vitamins during administration (solutions containing e.g. AA, glucose, electrolytes, or trace elements). SUMMARY: Lipid emulsions and/or vitamins containing PN solutions should be protected from light during administration (bags and tubing) to reduce the generation of oxidation products.

Bacterial contamination of lightproof covers for high-calorie infusion solutions in wards.

Deterioration of drugs due to light exposure is one of the major concerns, especially regarding protection of high-calorie infusion solutions, lightproof covers are used in hospitals. In the absence of any set standards regarding their usage, they are often reused. This study aimed to investigate bacterial contamination of lightproof covers used in hospital wards. For this, lightproof covers which had been used or stored in wards were collected and bacterial cultures were carried out from them. Examination of the cultures revealed that bacteria were present in the used lightproof covers. The bacterial species detected in the used lightproof covers were Bacillus species Coagulase-negative Staphylococci (CNS) and Methicillin-resistant Staphylococcus aureus (MRSA). Bacillus species and CNS were also detected in lightproof covers stored in wards, whereas MRSA was not detected. Intestinal bacteria were detected in only one lightproof cover. However, no bacteria were detected from either inside or outside of the unused lightproof covers that were stored in the drugs department. After allowing the unused lightproof covers stored in the drugs department to stand for 24 h, Bacillus species and CNS were detected in only one of the covers, whereas no bacteria was detected in other covers. These results indicate that there is a risk of bacterial contamination in the reuse of lightproof covers and that they should either be disposed off properly after usage or hand, finger disinfectants should be used while handling them to prevent any possible contamination.

Phytosterolaemia associated with parenteral nutrition administration in adult patients.

Vegetable lipid emulsions (LE) contain non-declared phytosterols (PS). We aimed to determine PS content depending on the brand and LE batch, and in adult hospitalised patients treated with parenteral nutrition (PN), to establish the association between plasma and administered PS. Part I was the LE study: totals and fractions of PS in three to four non-consecutive batches from six LE were analysed. Part II was the patient study: patients with at least 7 previous days of PN with 0·8 g/kg per d of an olive/soyabean (O/S) LE were randomised (day 0) 1:1 to O/S or 100 % fish oil (FO) at a dose of 0·4 g/kg per d for 7 d (day 7). Plasma PS, its fractions, total cholesterol on days 0 and 7, their clearance and their association with PS administered by LE were studied. In part I, LE study: differences were found in the total PS, their fractions and cholesterol among different LE brands and batches. Exclusive soyabean LE had the highest content of PS (422·36 (sd 130·46) µg/ml). In part II, patient study: nineteen patients were included. In the O/S group, PS levels were maintained (1·11 (sd 6·98) µg/ml) from day 0 to 7, while in the FO group, significant decreases were seen in total PS (-6·21 (sd 4·73) µg/ml) and their fractions, except for campesterol and stigmasterol. Plasma PS on day 7 were significantly associated with PS administered (R2 0·443). PS content in different LE brands had great variability. PS administered during PN resulted in accumulation and could be prevented with the exclusive administration of FO LE.

Unintentional Manganese Delivery in Neonatal Parenteral Nutrition.

Iatrogenic manganese (Mn) neurotoxicity is a safety concern in neonates receiving parenteral nutrition (PN). Prior studies suggest Mn contamination of PN ingredients represents an unintended source of Mn delivery. In order to determine the relative contribution of unsourced Mn to total Mn exposure in neonatal PN, this study measured Mn concentrations in neonatal PN solutions using inductively coupled plasma mass spectrometry. Solutions prepared using a standard fixed dose neonatal multiple trace element product were compared with test solutions prepared using individual trace element ingredients not including Mn. The standard solutions (n = 6) contained a mean (SD) Mn concentration of 56.63 µg/L (0.94), compared with 6.04 µg/L (0.39) in the test solutions without added Mn (n = 6). This study suggests that neonatal PN contains significant quantities of Mn not intentionally added during PN preparation. Further studies are needed to identify individual ingredient sources of unintentional Mn, and the feasibility of Mn omission strategies.

Bactericidal and Antiproliferative Effects of Peripheral Parenteral Nutrition Solutions with Sodium Bisulfite on Pathogenic Microorganisms in Catheter Lumens.

Catheter-related bloodstream infections (CRBSIs) due to pathogenic microorganisms pose a major threat to patients requiring parenteral nutrition (PN). Additives contained in medicines and foods have antiproliferative and bacteriostatic effects on pathogenic microorganisms. Therefore, PN solutions containing additives may also have an antibacterial effect. However, so far, there have been no reports on or observations of a PN solution with bactericidal activity. In this study, we assessed several nutrition solutions with antimicrobial activities and investigated their effects on pathogenic microorganisms colonizing catheter lumens. We selected the highly acidic Plas-Amino® (PA), which contains a large amount of sodium bisulfite as a preservative and potentially has an antimicrobial effect. In this study, we used the following pathogenic bacteria as the main causatives of CRBSIs: Staphylococcus aureus, Staphylococcus epidermidis, Bacillus cereus, Serratia marcescens, Pseudomonas aeruginosa, and Candida albicans. We then created a catheter lumen microorganism contamination model and evaluated the antibacterial effect of PA; we found that all bacteria in the control group grew significantly in the catheter lumen in a time-dependent manner at 48 and 72 h. On the other hand, we demonstrated that PA has bactericidal effects on S. aureus, S. epidermidis, B. cereus, S. marcescens, and P. aeruginosa in the catheter lumen and confirmed that it has a remarkable antiproliferative effect on C. albicans. Hence, we concluded that highly acidic PN solutions that contain a preservative like sodium bisulfite have bactericidal and growth inhibition effects on microorganisms in the catheter lumens of patients with CRBSIs and patients with totally implantable central venous access devices, in whom it is difficult to remove the catheter.

Early versus late parenteral nutrition for critically ill term and late preterm infants.

BACKGROUND: Recently conducted randomised controlled trials (RCTs) suggest that late commencement of parenteral nutrition (PN) may have clinical benefits in critically ill adults and children. However, there is currently limited evidence regarding the optimal timing of commencement of PN in critically ill term and late preterm infants. OBJECTIVES: To evaluate the benefits and safety of early versus late PN in critically ill term and late preterm infants. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (5 April 2019), MEDLINE Ovid (1966 to 5 April 2019), Embase Ovid (1980 to 5 April 2019), EMCare (1995 to 5 April 2019) and MEDLINE via PubMed (1966 to 5 April 2019). We searched for ongoing or recently completed clinical trials, and also searched the grey literature and reference lists of relevant publications. SELECTION CRITERIA: We included RCTs comparing early versus late initiation of PN in term and late preterm infants. We defined early PN as commencing within 72 hours of admission, and late PN as commencing after 72 hours of admission. Infants born at 37 weeks' gestation or more were defined as term, and infants born between 34 and 36+6 weeks' gestation were defined as late preterm. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the trials, extracted the data and assessed the risk of bias. Treatment effects were expressed using risk ratio (RR) and risk difference (RD) for dichotomous outcomes and mean difference (MD) for continuous data. The quality of the evidence was assessed using the GRADE approach. MAIN RESULTS: Two RCTs were eligible for inclusion. Data were only available from a subgroup (including 209 term infants) from one RCT in children (aged from birth to 17 years) conducted in Belgium, the Netherlands and Canada. In that RCT, children with medium to high risk of malnutrition were included if a stay of 24 hours or more in the paediatric intensive care unit (PICU) was expected. Early PN and late PN were defined as initiation of PN within 24 hours and after day 7 of admission to PICU, respectively. The risk of bias for the study was considered to be low for five domains and high for two domains. The subgroup of term infants that received late PN had significantly lower risk of in-hospital all-cause mortality (RR 0.35, 95% confidence interval (CI) 0.14 to 0.87; RD -0.10, 95% CI -0.18 to -0.02; number needed to treat for an additional beneficial outcome (NNTB) = 10; 1 trial, 209 participants) and neonatal mortality (death from any cause in the first 28 days since birth) (RR 0.29, 95% CI 0.10 to 0.88; RD -0.09, 95% CI -0.16 to -0.01; NNTB = 11; 1 trial, 209 participants). There were no significant differences in rates of healthcare-associated blood stream infections, growth parameters and duration of hospital stay between the two groups. Neurodevelopmental outcomes were not reported. The quality of evidence was considered to be low for all outcomes, due to imprecision (owing to the small sample size and wide confidence intervals) and high risk of bias in the included studies. AUTHORS' CONCLUSIONS: Whilst late commencement of PN in term and late preterm infants may have some benefits, the quality of the evidence was low and hence our confidence in the results is limited. Adequately powered RCTs, which evaluate short-term as well as long-term neurodevelopmental outcomes, are needed.

Standardised neonatal parenteral nutrition formulations - Australasian neonatal parenteral nutrition consensus update 2017.

BACKGROUND: The first consensus standardised neonatal parenteral nutrition formulations were implemented in many neonatal units in Australia in 2012. The current update involving 49 units from Australia, New Zealand, Singapore, Malaysia and India was conducted between September 2015 and December 2017 with the aim to review and update the 2012 formulations and guidelines. METHODS: A systematic review of available evidence for each parenteral nutrient was undertaken and new standardised formulations and guidelines were developed. RESULTS: Five existing preterm Amino acid-Dextrose formulations have been modified and two new concentrated Amino acid-Dextrose formulations added to optimise amino acid and nutrient intake according to gestation. Organic phosphate has replaced inorganic phosphate allowing for an increase in calcium and phosphate content, and acetate reduced. Lipid emulsions are unchanged, with both SMOFlipid (Fresenius Kabi, Australia) and ClinOleic (Baxter Healthcare, Australia) preparations included. The physicochemical compatibility and stability of all formulations have been tested and confirmed. Guidelines to standardise the parenteral nutrition clinical practice across facilities have also been developed. CONCLUSIONS: The 2017 PN formulations and guidelines developed by the 2017 Neonatal Parenteral Nutrition Consensus Group offer concise and practical instructions to clinicians on how to implement current and up-to-date evidence based PN to the NICU population.

A triple-chamber parenteral nutrition solution was associated with improved protein intake in very low birthweight infants.

AIM: We evaluated the nutrient intakes of very low birthweight (VLBW) infants weighing less than 1500 g and tested the hypothesis that using a triple-chamber parenteral nutrition (PN) solution, containing lipids, glucose and amino acids, would improve protein intake. METHODS: This retrospective cohort study comprised 953 VLBW infants born in 2005-2013 at a gestational age of less than 32 + 0/7 weeks and admitted to the neonatal care unit at Helsinki Children's Hospital, Finland. The infants were divided into four groups according their birth year and PN regime. Nutrient intakes were obtained from computerised medication administration records. RESULTS: In 2012-2013, when a triple-chamber PN solution was used, infants were more likely to reach the target parenteral protein intake of 3.5 g/kg/d, and reach it 3-7 days earlier, compared with infants who received individual PN or standard two-in-one PN solutions in 2005-2011. In addition, infants in the triple-chamber group had the highest median energy intake (90 kcal/kg/d) during the first week. They also had higher median protein intakes in weeks one, two and three (3.1, 3.4 and 3.7 g/kg/d) than infants born in 2005-2011 (P < .05). CONCLUSION: Using a triple-chamber PN solution was associated with improved protein intake, and the protein target was more likely to be achieved.

Safety of a Triple-chamber Bag Parenteral Nutrition in Children Ages up to 24 Months: An Observational Study.

OBJECTIVES: Hypermagnesemia has been reported in preterm neonates treated with commercial pediatric triple-chamber bag (3CB) parenteral nutrition (PN). This postmarketing study was requested by the European Medicines Agency to assess the safety of a 3CB PN product in full-term neonates and children up to 24 months of age. METHODS: This prospective, multicenter, observational study enrolled hospitalized, full-term, newborn infants and children up to 24 months of age receiving >70% of nutrition as PN and requiring ≥50% of nutrition as PN for ≥5 days. All patients received 3CB PN during the study for ≤15 days. The primary outcome was serum magnesium, summarized by age group (0-1, >1-12, and >12-24 months). Secondary outcomes were nutritional intake and adverse events (AEs), including clinically significant abnormal laboratory results and vital signs. RESULTS: A total of 102 eligible patients were included. Median (interquartile range) parenteral magnesium intake was 0.23 (0.18-0.30) mmol ·â€Škg ·â€Šday. Mean serum magnesium showed no consistent changes during treatment in any age group. One moderate and 3 mild AEs of hypermagnesemia were reported in 4 patients (3.9%), all ages 0 to 1 month. Other AEs in >2 patients were hypertriglyceridemia (6.9%), laryngitis (3.9%), hyperkalemia, hypokalemia, hyponatremia, hypophosphatemia, and neonatal hypotension (each 2.9%). Other serum electrolytes were stable, and revealed no safety concerns. CONCLUSIONS: Mean serum magnesium levels were not affected by 3CB PN in full-term neonates and children up to 24 months of age. The risk of hypermagnesemia AEs was low when providing median parenteral magnesium of 0.2 to 0.3 mmol ·â€Škg ·â€Šday in this population.

Optimizing Vitamin and Trace Element Profiles in Blood after Gastrointestinal Tract Surgery by a New Parenteral Nutrition Formula.

INTRODUCTION: Though micronutrient formulations for parenteral nutrition (PN) have been revised, the impacts of these changes on nutritional parameters, blood micronutrient levels, and safety have yet to be clarified. We examined the efficacy and safety of a new PN formulation with a micronutrient composition based on the Food and Drug Administration 2000 recommendation in surgical patients. METHODS: This phase III clinical trial (JapicCTI-No. 142610) was a prospective, randomized, controlled, parallel-group, open-label, multicenter study. Two types of PN, OPF-108 (revised formula, n = 51) and ELN (previous formula mainly based on American Medical Association 1975 guidelines, n = 59), were given to patients from POD1 or 2 to POD7 after surgery. OPF-108 contains more vitamin B1, B6, C, and folic acid, a much lower dose of vitamin K, and less iron than ELN. Nutritional parameters and micronutrient profiles in blood and safety were evaluated. RESULTS: Nutritional parameters on POD5 and 8 were similar between the 2 groups. Blood vitamin B1, B6, and folic acid levels on POD 5 and 8 were higher in the OPF-108 group than in the ELN group. Only OPF-108 restored vitamin C levels to within the normal range on POD5 and 8. Vitamin K levels far exceeded the upper limit of the standard range on POD5 and 8 in the ELN group, whereas OPF-108 essentially maintained these levels within the standard ranges. Serum iron levels on POD8 were nearly normal in both the OPF-108 and ELN groups. CONCLUSION: Beneficial effects of the new micronutrient formulation were demonstrated in surgical patients.

[Quality control of mixtures for pediatric parenteral nutrition: Validation of sodium and potassium assay method]. / Contrôle qualité des mélanges pour nutrition parentérale pédiatriques : validation de la méthode de dosage du sodium et du potassium.

OBJECTIVES: Control of electrolyte concentration in mixtures for parenteral nutrition (MPN) for newborns is crucial before the release of the final product. We aimed to assess the validation of the electrolytes assay in MPN. METHODS: Electrolytes assay was performed with Ilyte Analyzer®. Validation of method was realized in accordance with ICH (International Conference on Harmonization) guideline Q2(R1) and the commission report of the French society of pharmaceutical science and technology. Linearity test solutions were prepared in triplicate using five levels of concentrations for sodium and potassium (60-140% of theoretical concentrations). Accuracy of the method was deducted from the same results of linearity. The intermediate precision was ensured by dosing the main electrolyte in six MPN, during three successive days. RESULTS: Linearity was assessed with correlation coefficients greater than 0.996 for both electrolytes. A non-significant result of comparison test of the intercept with zero (Student test) was obtained. A highly significant result of the test of existence of slopes (Fisher test) proved a linear regression for the 2 electrolytes (P<0.1%). Inter-day precision values were 2.68% and 2.65% respectively for sodium and potassium. CONCLUSION: The validation of sodium and potassium assay method was successfully performed with Ilyte Analyzer® allowing routine quality control in MPN.

Enteral nutritional therapy for induction of remission in Crohn's disease.

BACKGROUND: Corticosteroids are often preferred over enteral nutrition (EN) as induction therapy for Crohn's disease (CD). Prior meta-analyses suggest that corticosteroids are superior to EN for induction of remission in CD. Treatment failures in EN trials are often due to poor compliance, with dropouts frequently due to poor acceptance of a nasogastric tube and unpalatable formulations. This systematic review is an update of a previously published Cochrane review. OBJECTIVES: To evaluate the effectiveness and safety of exclusive EN as primary therapy to induce remission in CD and to examine the importance of formula composition on effectiveness. SEARCH METHODS: We searched MEDLINE, Embase and CENTRAL from inception to 5 July 2017. We also searched references of retrieved articles and conference abstracts. SELECTION CRITERIA: Randomized controlled trials involving patients with active CD were considered for inclusion. Studies comparing one type of EN to another type of EN or conventional corticosteroids were selected for review. DATA COLLECTION AND ANALYSIS: Data were extracted independently by at least two authors. The primary outcome was clinical remission. Secondary outcomes included adverse events, serious adverse events and withdrawal due to adverse events. For dichotomous outcomes, we calculated the risk ratio (RR) and 95% confidence interval (CI). A random-effects model was used to pool data. We performed intention-to-treat and per-protocol analyses for the primary outcome. Heterogeneity was explored using the Chi2 and I2 statistics. The studies were separated into two comparisons: one EN formulation compared to another EN formulation and EN compared to corticosteroids. Subgroup analyses were based on formula composition and age. Sensitivity analyses included abstract publications and poor quality studies. We used the Cochrane risk of bias tool to assess study quality. We used the GRADE criteria to assess the overall quality of the evidence supporting the primary outcome and selected secondary outcomes. MAIN RESULTS: Twenty-seven studies (1,011 participants) were included. Three studies were rated as low risk of bias. Seven studies were rated as high risk of bias and 17 were rated as unclear risk of bias due to insufficient information. Seventeen trials compared different formulations of EN, 13 studies compared one or more elemental formulas to a non-elemental formula, three studies compared EN diets of similar protein composition but different fat composition, and one study compared non-elemental diets differing in glutamine enrichment. Meta-analysis of 11 trials (378 participants) demonstrated no difference in remission rates. Sixty-four per cent (134/210) of patients in the elemental group achieved remission compared to 62% (105/168) of patients in the non-elemental group (RR 1.02, 95% CI 0.88 to 1.18; GRADE very low quality). A per-protocol analysis (346 participants) produced similar results (RR 1.04, 95% CI 0.91 to 1.18). Subgroup analyses performed to evaluate the different types of elemental and non-elemental diets (elemental, semi-elemental and polymeric) showed no differences in remission rates. An analysis of 7 trials including 209 patients treated with EN formulas of differing fat content (low fat: < 20 g/1000 kCal versus high fat: > 20 g/1000 kCal) demonstrated no difference in remission rates (RR 1.03; 95% CI 0.85 to 1.26). Very low fat content (< 3 g/1000 kCal) and very low long chain triglycerides demonstrated higher remission rates than higher content EN formulas. There was no difference between elemental and non-elemental diets in adverse event rates (RR 1.00, 95% CI 0.63 to 1.60; GRADE very low quality), or withdrawals due to adverse events (RR 1.29, 95% CI 0.80 to 2.09; GRADE very low quality). Common adverse events included nausea, vomiting, diarrhea and bloating.Ten trials compared EN to steroid therapy. Meta-analysis of eight trials (223 participants) demonstrated no difference in remission rates between EN and steroids. Fifty per cent (111/223) of patients in the EN group achieved remission compared to 72% (133/186) of patients in the steroid group (RR 0.77, 95% CI 0.58 to 1.03; GRADE very low quality). Subgroup analysis by age showed a difference in remission rates for adults but not for children. In adults 45% (87/194) of EN patients achieved remission compared to 73% (116/158) of steroid patients (RR 0.65, 95% CI 0.52 to 0.82; GRADE very low quality). In children, 83% (24/29) of EN patients achieved remission compared to 61% (17/28) of steroid patients (RR 1.35, 95% CI 0.92 to 1.97; GRADE very low quality). A per-protocol analysis produced similar results (RR 0.93, 95% CI 0.75 to 1.14). The per-protocol subgroup analysis showed a difference in remission rates for both adults (RR 0.82, 95% CI 0.70 to 0.95) and children (RR 1.43, 95% CI 1.03 to 1.97). There was no difference in adverse event rates (RR 1.39, 95% CI 0.62 to 3.11; GRADE very low quality). However, patients on EN were more likely to withdraw due to adverse events than those on steroid therapy (RR 2.95, 95% CI 1.02 to 8.48; GRADE very low quality). Common adverse events reported in the EN group included heartburn, flatulence, diarrhea and vomiting, and for steroid therapy acne, moon facies, hyperglycemia, muscle weakness and hypoglycemia. The most common reason for withdrawal was inability to tolerate the EN diet. AUTHORS' CONCLUSIONS: Very low quality evidence suggests that corticosteroid therapy may be more effective than EN for induction of clinical remission in adults with active CD. Very low quality evidence also suggests that EN may be more effective than steroids for induction of remission in children with active CD. Protein composition does not appear to influence the effectiveness of EN for the treatment of active CD. EN should be considered in pediatric CD patients or in adult patients who can comply with nasogastric tube feeding or perceive the formulations to be palatable, or when steroid side effects are not tolerated or better avoided. Further research is required to confirm the superiority of corticosteroids over EN in adults. Further research is required to confirm the benefit of EN in children. More effort from industry should be taken to develop palatable polymeric formulations that can be delivered without use of a nasogastric tube as this may lead to increased patient adherence with this therapy.

Risk factors of hepatic function alterations in hospitalized adult patients treated with short-term parenteral nutrition receiving the same lipid composition at the same dose.

BACKGROUND: High doses and vegetable origin of lipid emulsions (LE) are prominent factors for liver test (LT) alterations in patients treated with parenteral nutrition (PN). This study aims to determine incidence of LT alterations, and risk factors related to these alterations in patients with short term PN with homogenous LE. METHODS: Adult non-critically ill hospitalized patients, with normal LTs at the beginning of PN, receiving 0.8 g/kg/day of an olive/soybean LE were included. A paired Student t-test was applied to compare final with initial LT values. LT variation (end vs start of PN) according to type of surgery and infection was studied by means of an analysis of the variance. Univariate and multivariate analyses were constructed to relate the variations of each of the 4 LTs with the adjustment variables. RESULTS: One hundred eighty one patients (66.57 ± 12.89 years; 72.4% men), 66.8% suffered from cancer. Final LT values increased from initial values for gamma-glutamyltransferase (GGT) 2.69 ± 2.49 µkat/L vs 0.55 ± 0.36 µkat/L, alkaline phosphatase (AP) 1.97 ± 1.49 µkat/L vs 1.04 ± 0.33 µkat/L, and alanine aminotransferase (ALT) 0.57 ± 0.92 µkat/L vs 0.32 ± 0.26 µkat/L. GGT and AP variations were associated with days of PN; GGT, AP and total bilirubin with surgical patients, AP variations with infection, and GGT with cancer. Multivariate analysis: elevation of GGT, AP and ALT was related to infection, days of PN and surgery. CONCLUSIONS: Factors that increased the risk of LTs elevation during short term PN treatment were duration of PN, surgery, cancer, and infection associated with oxidative stress.

In vitro detection of Candida and Aspergillus antigen in parenteral nutrition and fixed combinations of piperacillin-tazobactam.

BACKGROUND: Screening for Aspergillus (Asp-AG) and Candida antigen (Ca-AG) with immunoassays is established for stem cell recipients at high risk for invasive fungal infections (IFI). While parenteral nutrition (PN) will be applied in case of complications leading to insufficient alimentation, piperacillin-tazobactam (TZP) is started at the onset of febrile neutropenia. OBJECTIVES: The aim of this study was to investigate drug-laboratory interactions between PN and TZP and both immunoassays which could affect the specificity of the assays and lead to the false assumption of an IFI. METHODS: Batches of TZP and PN were tested with both assays in vitro. In total, 380 samples of 83 batches were analysed. RESULTS: None of the examined preparations were tested positive with Asp-AG assay. Measurable amounts of Ca-AG were detected in a lipid emulsion, two different trace element supplements, a fat-soluble vitamin preparation and all tested brands of TZP. CONCLUSIONS: We conclude that false positivity of Asp-AG assay due to TZP and PN does not occur. Cross reactions with Ca-AG assay have been detected in some preparations. The in vivo relevance of Ca-AG positivity has to be reviewed in further studies considering an effect of dilution. Physicians should be aware of a possible cross reaction with Ca-AG assays which could lead to false-positive results.

A Review of the Parenteral Nutrition Supply Service in an Irish Neonatal Unit

Background Neonatal Intensive Care (NICU) patients have individual nutritional requirements often requiring Patient Specific Parenteral Nutrition (PSPN). From October 2015, the national PSPN compounding service availability changed from 7 days per week service to 5 days per week (i.e. no weekend and limited bank holiday ordering available). The aim of this study was to examine the introduction of a 5 day only PSPN supply on neonatal patient parenteral nutrition availability in a tertiary NICU. Methods We performed a prospective assessment of the provision of a 5 day rather than 7 day ordering of PSPN over a one month period (June 2017). Results Fifteen neonatal patients received a cumulative 89 days of PN during June 2017. 10 (66%) patients received PSPN during this time period. There was same day availability of PSPN in 62 of 89 days of PN (69%). Conclusion Thorough education and training will help prescribers to make appropriate PSPN ordering decisions. Improvements to available stock bags may reduce the amount of PSPN that is required but a 7 day PSPN ordering service would improve efficient provision of clinically indicated PSPN to premature infants in NICU in Ireland.