Tyrosine supplementation for phenylketonuria.

BACKGROUND: Phenylketonuria is an inherited disease for which the main treatment is the dietary restriction of the amino acid phenylalanine. The diet has to be initiated in the neonatal period to prevent or reduce mental handicap. However, the diet is very restrictive and unpalatable and can be difficult to follow. A deficiency of the amino acid tyrosine has been suggested as a cause of some of the neuropsychological problems exhibited in phenylketonuria. Therefore, this review aims to assess the efficacy of tyrosine supplementation for phenylketonuria. This is an update of previously published versions of this review. OBJECTIVES: To assess the effects of tyrosine supplementation alongside or instead of a phenylalanine-restricted diet for people with phenylketonuria, who commenced on diet at diagnosis and either continued on the diet or relaxed the diet later in life. To assess the evidence that tyrosine supplementation alongside, or instead of a phenylalanine-restricted diet improves intelligence, neuropsychological performance, growth and nutritional status, mortality rate and quality of life. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register which is comprised of references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. Additional studies were identified from handsearches of the Journal of Inherited Metabolic Disease (from inception in 1978 to 1998). The manufacturers of prescribable dietary products used in the treatment of phenylketonuria were also contacted for further references. Date of the most recent search of the Group's Inborn Errors of Metabolism Trials Register: 07 December 2020. SELECTION CRITERIA: All randomised or quasi-randomised trials investigating the use of tyrosine supplementation versus placebo in people with phenylketonuria in addition to, or instead of, a phenylalanine-restricted diet. People treated for maternal phenylketonuria were excluded. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the trial eligibility, methodological quality and extracted the data. MAIN RESULTS: Six trials were found, of which three trials reporting the results of a total of 56 participants, were suitable for inclusion in the review. The blood tyrosine concentrations were significantly higher in the participants receiving tyrosine supplements than those in the placebo group, mean difference 23.46 (95% confidence interval 12.87 to 34.05). No significant differences were found between any of the other outcomes measured. The trials were assessed as having a low to moderate risk of bias across several domains. AUTHORS' CONCLUSIONS: 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. However, given this is not an active area of research, we have no plans to update this review in the future.

Combination antimicrobial susceptibility testing for acute exacerbations in chronic infection of Pseudomonas aeruginosa in cystic fibrosis.

BACKGROUND: Antibiotic therapy for acute pulmonary exacerbations in people with cystic fibrosis is usually chosen based on the results of antimicrobial susceptibility testing of individual drugs. Combination antimicrobial susceptibility testing assesses the efficacy of drug combinations including two or three antibiotics in vitro and can often demonstrate antimicrobial efficacy against bacterial isolates even when individual antibiotics have little or no effect. Therefore, choosing antibiotics based on combination antimicrobial susceptibility testing could potentially improve response to treatment in people with cystic fibrosis with acute exacerbations. This is an updated version of a previously published review. OBJECTIVES: To compare antibiotic therapy based on conventional antimicrobial susceptibility testing to antibiotic therapy based on combination antimicrobial susceptibility testing in the treatment of acute pulmonary exacerbations in people with cystic fibrosis and chronic infection with Pseudomonas aeruginosa. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Cystic Fibrosis Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of latest search: 19 March 2020. We also searched ongoing trials registries. Date of latest search: 07 April 2020. SELECTION CRITERIA: Randomised and quasi-randomised controlled studies of antibiotic therapy based on conventional antimicrobial susceptibility testing compared to antibiotic therapy based on combination antimicrobial susceptibility testing in the treatment of acute pulmonary exacerbations in cystic fibrosis due to chronic infection with Pseudomonas aeruginosa. DATA COLLECTION AND ANALYSIS: Both authors independently selected studies, assessed their quality and extracted data from eligible studies. Additionally, the authors contacted the study investigators to obtain further information. MAIN RESULTS: The search identified one multicentre study eligible for inclusion in the review. This study prospectively assessed whether the use of multiple combination bactericidal antibiotic testing improved clinical outcomes in participants with acute pulmonary exacerbations of cystic fibrosis who were infected with multiresistant bacteria. A total of 132 participants were randomised in the study. The study investigators provided data specific to the 82 participants who were only infected with Pseudomonas aeruginosa for their primary outcome of time until next pulmonary exacerbation. For participants specifically infected with only Pseudomonas aeruginosa, the hazard ratio of a subsequent exacerbation was 0.82, favouring the control group (95% confidence interval 0.44 to 1.51) (P = 0.52). No further data for any of this review's outcomes specific to participants infected with Pseudomonas aeruginosa were available. The risk of bias for the included study was deemed to be low. The quality of the evidence was moderate for the only outcome providing data solely for individuals with infection due to Pseudomonas aeruginosa. For other outcomes, we were unable to judge the quality of the evidence as no data were available for the relevant subset of participants. AUTHORS' CONCLUSIONS: The current evidence, limited to one study, shows that there is insufficient evidence to determine effect of choosing antibiotics based on combination antimicrobial susceptibility testing compared to choosing antibiotics based on conventional antimicrobial susceptibility testing in the treatment of acute pulmonary exacerbations in people with cystic fibrosis with chronic Pseudomonas aeruginosa infection. A large international and multicentre study is needed to further investigate this issue. The only study included in the review was published in 2005, and we have not identified any further relevant studies up to March 2017. We therefore do not plan to update this review until new studies are published.

Enteral tube feeding for cystic fibrosis.

BACKGROUND: Enteral tube feeding is routinely used in many cystic fibrosis centres when oral dietary and supplement intake has failed to achieve an adequate nutritional status. The use of this method of feeding is assessed on an individual basis taking into consideration the patients age and clinical status. This is a final update of a previously published review. OBJECTIVES: To examine the evidence that in people with cystic fibrosis, supplemental enteral tube feeding improves nutritional status, respiratory function, and quality of life without significant adverse effects. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also contacted the companies that market enteral feeds and reviewed their databases.Date of the most recent search of the Group's Cystic Fibrosis Trials Register: 10 July 2019.Date of the most recent hand search of PubMed: 26 October 2018. SELECTION CRITERIA: All randomised controlled trials comparing supplemental enteral tube feeding for one month or longer with no specific intervention in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: The searches identified 44 trials; however, none were eligible for inclusion in this review. MAIN RESULTS: There are no trials included in this review. AUTHORS' CONCLUSIONS: Supplemental enteral tube feeding is widely used throughout the world to improve nutritional status in people with cystic fibrosis. The methods mostly used, nasogastric or gastrostomy feeding, are expensive and may have a negative effect on self-esteem and body image. Reported use of enteral tube feeding suggests that it results in nutritional and respiratory improvement; but, efficacy has not been fully assessed by randomised controlled trials. It is acknowledged, however, that performing a randomised controlled trial would be difficult due to the ethics of withholding an intervention in a group of people whose nutritional status necessitates it.

Early additional food and fluids for healthy breastfed full-term infants.

BACKGROUND: Widespread recommendations from health organisations encourage exclusive breastfeeding for six months. However, the addition of other fluids or foods before six months is common in many countries and communities. This practice suggests perceived benefits of early supplementation or lack of awareness of the possible risks. OBJECTIVES: To assess the benefits and harms of supplementation for full-term healthy breastfed infants and to examine the timing and type of supplementation. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (21 March 2014) and reference lists of all relevant retrieved papers. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials in infants under six months of age comparing exclusive breastfeeding versus breastfeeding with any additional food or fluids. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the trials, extracted data and assessed risk of bias. MAIN RESULTS: We included eight trials (984 randomised infants/mothers). Six trials (n = 613 analysed) provided data on outcomes of interest to this review. The variation in outcome measures and time points made it difficult to pool results from trials. Data could only be combined in a meta-analysis for one secondary outcome (weight change). The trials that provided outcome data compared exclusively breastfed infants with breastfed infants who were allowed additional nutrients in the form of artificial milk, glucose, water or solid foods.In relation to the majority of the older trials, the description of study methods was inadequate to assess the risk of bias. The two more recent trials, were found to be at low risk of bias for selection and detection bias. The overall quality of the evidence for the main comparison was low.In one trial (170 infants) comparing exclusively breastfeeding infants with infants who were allowed additional glucose water, there was a significant difference favouring exclusive breastfeeding up to and including week 20 (risk ratio (RR) 1.45, 95% confidence interval (CI) 1.05 to 1.99), with more infants in the exclusive breastfed group still exclusively breastfeeding. Conversely in one small trial (39 infants) comparing exclusive breastfed infants with non-exclusive breastfed infants who were provided with artificial milk, fewer infants in the exclusive breastfed group were exclusively breastfeeding at one week (RR 0.58, 95% CI 0.37 to 0.92) and at three months (RR 0.44, 95% CI 0.26 to 0.76) and there was no significant difference in the proportion of infants continuing any breastfeeding at three months between groups (RR 0.76, 95% CI 0.56 to 1.03).For infant morbidity (six trials), one newborn trial (170 infants) found a statistically, but not clinically, significant difference in temperature at 72 hours (mean difference (MD) 0.10 degrees, 95% CI 0.01 to 0.19), and that serum glucose levels were higher in glucose supplemented infants in the first 24 hours, though not at 48 hours (MD -0.24 mmol/L, 95% CI -0.51 to 0.03). Weight loss was also higher (grams) in infants at six, 12, 24 and 48 hours of life in the exclusively breastfed infants compared to those who received additional glucose water (MD 7.00 g, 95% CI 0.76 to 13.24; MD 11.50 g, 95% CI 1.71 to 21.29; MD 13.40 g, 95% CI 0.43 to 26.37; MD 32.50 g, 95% CI 12.91 to 52.09), but no difference between groups was observed at 72 hours of life. In another trial (47 infants analysed), we found no significant difference in weight loss between the exclusively breastfeeding group and the group allowed either water or glucose water on either day three or day five (MD 1.03%, 95% CI -0.18 to 2.24) and (MD 0.20%, 95% CI -1.18 to 1.58).Three trials with four- to six-month-old infants provided no evidence to support any benefit from the addition of complementary foods at four months versus exclusive breastfeeding to six months nor any risks related either morbidity or weight change (or both).None of the trials reported on the remaining primary outcomes, infant mortality or physiological jaundice. AUTHORS' CONCLUSIONS: We were unable to fully assess the benefits or harms of supplementation or to determine the impact from timing and type of supplementation. We found no evidence of benefit to newborn infants and possible negative effects on the duration of breastfeeding from the brief use of additional water or glucose water, and the quality of the evidence from a small pilot study on formula supplementation was insufficient to suggest a change in practice away from exclusive breastfeeding. For infants at four to six months, we found no evidence of benefit from additional foods nor any risks related to morbidity or weight change. Future studies should examine the longer-term effects on infants and mothers, though randomising infants to receive supplements without medical need may be problematic.We found no evidence for disagreement with the recommendation of international health associations that exclusive breastfeeding should be recommended for healthy infants for the first six months.

Early additional food and fluids for healthy breastfed full-term infants.

BACKGROUND: Widespread recommendations from health organisations encourage exclusive breastfeeding for six months. However the addition of other fluids or foods before six months is common practice in many countries and communities. This practice suggests perceived benefits of early supplementation or lack of awareness of the possible risks. OBJECTIVES: To assess the benefits and harms of supplementation for full-term healthy breastfed infants and to examine the timing and type of supplementation. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (1 March 2011) and reference lists of all relevant retrieved papers. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials in infants under six months of age comparing exclusive breastfeeding versus breastfeeding with any additional food or fluids. DATA COLLECTION AND ANALYSIS: Two authors independently selected the trials; three extracted data and assessed risk of bias. MAIN RESULTS: We included six trials (814 infants). Two trials in the early days after birth that reported data did not indicate that giving additional fluids was beneficial. For duration of breastfeeding, there was a significant difference favouring exclusive breastfeeding up to and including week 20 (risk ratio (RR) 1.45, 95% confidence interval (CI) 1.05 to 1.99), indicating that supplements may contribute to reducing the duration.For infant morbidity (three trials), one newborn trial found a statistically, but not clinically, significant difference in temperature at 72 hours (MD 0.10 degrees, 95% CI 0.01 to 0.19), and that serum glucose levels were higher in glucose supplemented infants in the first 24 hours, though not at 48 hours (MD -0.24mmol/l, 95% CI -0.51 to 0.03). Two trials with four- to six-month-old infants did not indicate any benefit to supplemented infants to 26 weeks nor any risks related to morbidity or weight change.None of the trials reported on the remaining primary outcomes, infant mortality or physiological jaundice. AUTHORS' CONCLUSIONS: We were unable to fully assess the benefits or harms of supplementation or to determine the impact from timing and type of supplementation .We found no benefit to newborn infants and possible negative effects on the duration of breastfeeding from the brief use of additional water or glucose water. For infants at four to six months, we found no benefit from additional foods nor any risks related to morbidity or weight change. Future studies should examine the longer term effects on infants and mothers, though randomising infants to receive supplements without medical need may be considered unethical.We found no evidence for disagreement with the recommendation of international health associations that exclusive breastfeeding should be recommended for healthy infants for the first six months.