Randomised controlled trial of tyrosine supplementation on neuropsychological performance in phenylketonuria. Effect of high-dose tyrosine supplementation on brain function in adults with phenylketonuria. Parenteral glutamine supplementation does not reduce the risk of mortality or late-onset sepsis in extremely low birth weight infants. A randomised controlled trial of glutamine-enriched neonatal parenteral nutrition in Malaysia. Effect of oral supplementation with iron(III)-hydroxide polymaltose complex on the immunological profile of adolescents with varying iron status. Iron supplementation improves iron status and reduces morbidity in children with or without upper respiratory tract infections: a randomized controlled study in Colombo, Sri Lanka. A randomized, masked study of triiodothyronine plus thyroxine administration in preterm infants less than 28 weeks of gestational age: hormonal and clinical effects. Failure of twice-weekly iron supplementation to increase blood haemoglobin and serum ferritin concentrations: results of a randomized controlled trial. A group randomized trial to improve safe use of nonsteroidal anti-inflammatory drugs.
To test the efficacy of tyrosine supplementation, as an adjunct to dietary treatment, on neuropsychological test performance in individuals with phenylketonuria.
                A randomised controlled trial of tyrosine supplementation using a double blind crossover procedure with three four week phases.
                The Hospital for Sick Children, Toronto.
                21 individuals with phenylketonuria (ages 6 to 28 years, mean 11.3).
                Participants were given 100 mg/kg body weight/d of L-tyrosine or L-alanine (placebo).
                At baseline, performance on several of the neuropsychological test measures was correlated with tyrosine levels. Dietary supplements of tyrosine increased plasma tyrosine concentrations; however, no change in test performance was found across the tyrosine and placebo phases of the study.
                Tyrosine supplementation of this type does not appear to alter neuropsychological performance in individuals with phenylketonuria. To characterize abnormalities of brain function in patients with phenylketonuria (PKU) who had relaxed or stopped the dietary regimen and to test whether oral high-dose tyrosine (Tyr) supplementation has a beneficial effect.
                Comparison with a control group; double-blind, placebo-controlled study comprising six test times; crossover treatment groups; oral high-dose Tyr therapy (100 mg/kg body weight per day) or placebo administration for 4 weeks.
                Twenty-four early-treated patients with PKU aged 20.8 (16 to 25) years; 24 control subjects.
                Plasma concentrations of phenylalanine and Tyr were monitored. Neuropsychologic tasks, visual evoked potentials, and spectral analysis of electroencephalographic activity were used to evaluate brain function.
                When patients with PKU were compared with control subjects, deficits in certain aspects of brain function were confirmed (i.e., a decreased ability to sustain attention, prolonged latencies of visual evoked potential peaks N1 and P2, and a reduced amount of fast-wave activity on the electroencephalogram). Baseline plasma phenylalanine and Tyr concentrations were in the typical range of adult patients with PKU. The plasma Tyr concentration increased approximately 200% during Tyr supplementation, but no beneficial effects were observed.
                High-dose Tyr supplementation cannot be recommended as an "alternative" treatment for patients with PKU after relaxation or termination of strict dietary adherence. Glutamine is one of the most abundant amino acids in both plasma and human milk, yet it is not included in standard intravenous amino acid solutions. Previous studies have suggested that parenteral nutrition (PN) supplemented with glutamine may reduce sepsis and mortality in critically ill adults. Whether glutamine supplementation would provide a similar benefit to extremely low birth weight (ELBW) infants is not known.
                We performed a multicenter, randomized, double-masked, clinical trial to assess the safety and efficacy of early PN supplemented with glutamine in decreasing the risk of death or late-onset sepsis in ELBW infants. Infants 401 to 1000 g were randomized within 72 hours of birth to receive either TrophAmine (control) or an isonitrogenous study amino acid solution with 20% glutamine whenever they received PN up to 120 days of age, death, or discharge from the hospital. The primary outcome was death or late-onset sepsis.
                Of the 721 infants who were assigned to glutamine supplementation, 370 (51%) died or developed late-onset sepsis, as compared with 343 of the 712 infants (48%) assigned to control (relative risk: 1.07; 95% confidence interval: 0.97-1.17). Glutamine had no effect on tolerance of enteral feeds, necrotizing enterocolitis, or growth. No significant adverse events were observed with glutamine supplementation.
                Parenteral glutamine supplementation as studied did not decrease mortality or the incidence of late-onset sepsis in ELBW infants. Consequently, although no harm was demonstrated, routine use of parenteral glutamine supplementation cannot be recommended in this population. The addition of glutamine to parenteral nutrition (PN) in neonates has not shown significant benefits as compared to adults thus far. This study aimed to determine the potential benefits of the addition of glutamine to neonatal PN in a tertiary hospital in a middle-income country.
                This was a double-blinded randomised controlled trial. Babies who were admitted to the neonatal intensive care unit (NICU) and who required PN were eligible for inclusion in the study. The subjects were randomised to receive either glutamine-added PN (intervention) or standard PN (control). The most important outcomes included time to full enteral nutrition, incidence of sepsis and necrotising enterocolitis (NEC), clinical or culture-proven sepsis.
                Out of 270 subjects, 132 were randomised to the intervention group and 138, to the control group. Baseline data were comparable in both groups. The median time taken to reach full enteral nutrition was similar for both intervention and control groups (six days in each group, p-value is 0.52). The incidences of NEC, clinical sepsis and culture-proven sepsis did not differ significantly in the intervention and control groups (5.8 vs. 7.1 percent, p-value is 0.68; 15.7 percent vs. 10.2 percent, p-value is 0.21 and 16.5 percent vs. 15.7 percent, p-value is 0.38, respectively). Other outcomes such as duration of ventilation, duration of NICU stay and a subgroup analysis for preterm and term babies also showed no statistically significant differences.
                Addition of glutamine to neonatal PN was not shown to improve outcome. To assess the effects of iron supplementation on immunological parameters of adolescents with varying iron status.
                Adolescents of both sexes with varying iron status were allocated to four treatment groups by using inclusion criteria. Three of the four groups received iron(III)-hydroxide polymaltose complex (IPC, Maltofer) containing 100 mg of iron 6 days a week for 8 months. The fourth group was given a placebo. Immunological parameters were assessed at baseline and after 4 and 8 months of supplementation.
                Increases from baseline to 4 months and from 4 to 8 months of supplementation were observed for Bactericidal Capacity of Neutrophils (BCA), NitroBlue Tetrazolium Reduction Test (NBT), and phytohaemagglutinin (PHA) in all three supplemented groups. No increase was found in the control placebo group except for PHA. No side effects were noted in any participants.
                IPC supplementation for eight months led to significant improvements of immunological parameters in iron deficient adolescents with and without anemia. Iron deficiency anemia and recurrent infections are common among children of low socioeconomic status.
                The objective was to evaluate the effects of iron supplementation on iron status and morbidity in children with or without infection.
                Children aged 5-10 y were recruited for a randomized, controlled, double-blind study from outpatients attending the Children's Hospital, Colombo, Sri Lanka. Clinical, inflammatory, nutritional, and iron statuses were determined at baseline and after the intervention. Children with a history of recurrent upper respiratory tract infections (URTIs) and with laboratory and clinical evidence of a current URTI constituted the infection group (n = 179), and children without infection constituted the control group (n = 184). Subjects in both groups were supplemented with ferrous sulfate (60 mg Fe) or placebo once daily for 8 wk. Morbidity from URTIs, the number of gastrointestinal infections, and compliance were recorded every 2 wk.
                The overall prevalence of anemia was 52.6%. Iron supplementation significantly improved iron status by increasing hemoglobin (P < 0.001) and serum ferritin (P < 0.001) concentrations from baseline values in the children with or without infection. There was no significant improvement in iron status in the children who received placebo. In both the infection group and the control group, the mean number of URTI episodes and the total number of days sick with an URTI during the period of intervention were significantly lower (P < 0.005 and P < 0.001, respectively) in the children who received iron supplements than in those who received placebo.
                Iron supplementation significantly improves iron status and reduces morbidity from URTIs in children with or without infection. A randomized, placebo-controlled, masked study was conducted of the responses of thyroid parameters, cortisol, and the cardiovascular system to a single dose of triiodothyronine (T(3)) 24 h after birth, followed by a daily dose of thyroxine (T(4)) during 6 wk to infants <28 wk gestational age. Thirty-one infants were assigned to three groups: 1) group A: T(3) 24 h after birth plus daily T(4) during 6 wk; 2) group B: placebo T(3) and T(4) during 6 wk; and 3) group C: placebo T(3) and placebo T(4). T(4), free T(4), T(3), free T(3), reverse T(3), thyroid-stimulating hormone, and cortisol were measured in cord blood and on days 1, 3, 7, 14, 21, 42, and 56. Data on pulse rate, blood pressure, and cumulative dose of inotropic agents were collected. T(3) (0.5 microg/kg) resulted in a plasma increase until day 3. Thereafter, plasma T(3) levels were comparable between the groups. T(4), free T(4), and reverse T(3) were increased in groups A and B during the period of T(4) administration. Thyroid-stimulating hormone suppression was of shorter duration in group A. T(3) and T(4) administration did not have any effect on cortisol levels. We did not find any effects of T(3) or of T(4) administration on the cardiovascular system. A single injection of T(3) (0.5 microg/kg) given 22-26 h after birth only leads to a 2-d increase of T(3) levels and does not have effects on the cardiovascular system. This study does not support the use of T(3) according to our regimen in preterm infants. In order to increase the intestinal absorption of iron whilst simultaneously minimising the side-effects and thus increasing compliance, once- or twice-weekly, instead of daily, iron supplementation has been widely recommended. In a randomized, placebo-controlled, double-blind study in western Kenya, a tablet of ferrous dextran (containing 60 mg elemental iron) or an identical-looking placebo tablet was provided twice-weekly for 12 months to each child or adult investigated. At baseline each subject had a moderately low blood concentration of haemoglobin (Hb). Initial Hb and serum ferritin (SF) concentrations were determined and each subject was tested for malarial and helminth infection and treated, if necessary, with the appropriate anthelminthic drug(s). Overall, 200 children (aged 4-15 years) and 129 adults (aged 16-63 years) completed the 12-month study. At baseline, 47.5% of the children and 58.1% of the adults were anaemic, hookworm (detected in 60.0% of the children and 69.9% of the adults) was the most common helminth infection, and malaria was endemic. The results of bivariate analyses indicated that twice-weekly iron supplementation had no significant effect on blood Hb or SF concentrations, either in the children or the adults investigated. The results were confirmed in multiple linear-regression analyses, which revealed that the predictors of the final Hb concentration in the children investigated were age and infection, after enrollment, with Ascaris lumbricoides. Gender and the serum concentration of alpha-1-antichymotrypsin (ACT) at final follow-up were predictors of the final SF concentration in the children. In adults, the predictors of the final Hb concentration were gender and HIV infection, and the predictors of the final SF concentration were age and the serum concentration of ACT at the final follow-up. Twice-weekly iron supplementation did not increase Hb or iron stores in children or adults. Since compliance appeared to be high, this lack of effect may be the result of an inadequate dose of iron or of subjects who have deficiencies in micronutrients other than iron. To determine whether audit/feedback and educational materials improve adherence to recommendations for laboratory monitoring and cytoprotective agents to detect and prevent adverse events caused by nonsteroidal anti-inflammatory agents (NSAIDs).
                Controlled, cluster-randomized trial.
                Physicians commonly prescribing NSAIDs were identified within a large managed care organization and randomized to a control or an intervention group (audit/feedback with peer-derived benchmarks and continuing medical education). Medical records were examined 10 months before and after the intervention for clinical data and receipt of complete blood count (CBC), creatinine testing, and cytoprotective agents (process measures). Primary analysis compared intervention versus control physicians among those who initially performed below a peer-derived benchmark. General estimating equations accounted for patient clustering.
                Of 101 physicians initially randomized, 85 remained eligible (38 internists, 36 family physicians, 11 rheumatologists) postintervention. Mean percent change in performance between intervention and control physicians for CBC monitoring was 16% versus 10%; for creatinine monitoring, 0% versus 17%; and use of cytoprotective agents, -3% versus -1%. None of these changes were significant. Rheumatology specialty, number of NSAID prescriptions and physician visits, and patient risk factors for NSAID-related toxicity were more strongly associated with improved safety practices than the intervention.
                Audit/feedback and educational materials had no observed effect on improving NSAID-related safety practices. Potentially contributing factors include high baseline performance (ceiling effect), dilution of the intervention effect by case mix and provider factors, nonreceipt of intervention materials, and diverse indications for lab tests.
From the available evidence no recommendations can be made about whether tyrosine supplementation should be introduced into routine clinical practice. Further randomised controlled studies are required to provide more evidence.