Introduction of Heated Cow's Milk Protein in Challenge-Proven Cow's Milk Allergic Children: The iAGE Study.

The introduction of baked milk products in cow's milk (CM) allergic children has previously been shown to accelerate induction tolerance in a selected group of children. However, there is no standardized baked milk product on the market. Recently, a new standardized, heated and glycated cow's milk protein (HP) product was developed. The aim of this study was to measure safety and tolerability of a new, well characterized heated CM protein (HP) product in cow's milk allergic (CMA) children between the age of 3 and 36 months. The children were recruited from seven clinics throughout The Netherlands. The HP product was introduced in six incremental doses under clinical supervision. Symptoms were registered after introduction of the HP product. Several questionnaires were filled out by parents of the children. Skin prick tests were performed with CM and HP product, sIgE to CM and α-lactalbumin (Bos d4), ß-lactoglobulin (Bos d5), serum albumin (Bos d 6), lactoferrin (Bos d7) and casein (Bos d8). Whereas 72% percent (18 out of 25) of the children tolerated the HP product, seven children experienced adverse events. Risk factors for intolerance to the HP product were higher skin prick test (SPT) histamine equivalent index (HEP) results with CM and the HP product, higher specific IgE levels against Bos d4 and Bos d8 levels and Bos d5 levels. In conclusion, the HP product was tolerated by 72% of the CM allergic children. Outcomes of SPT with CM and the HP product, as well as values of sIgE against caseins, α-lactalbumin, and ß-lactoglobulin may predict the tolerability of the HP product. Larger studies are needed to confirm these conclusions.

Acetylcysteine and carbocysteine for acute upper and lower respiratory tract infections in paediatric patients without chronic broncho-pulmonary disease.

BACKGROUND: Acetylcysteine and carbocysteine are the most commonly prescribed mucolytic drugs in Brazil and many European and African countries. To our knowledge, no systematic review has been published on their efficacy and safety for acute upper and lower respiratory tract infections (RTIs) in children without chronic broncho-pulmonary disease. OBJECTIVES: The objective was to assess the efficacy and safety and to establish a benefit-risk ratio of acetylcysteine and carbocysteine as symptomatic treatments for acute upper and lower RTIs in paediatric patients without chronic broncho-pulmonary disease. SEARCH METHODS: We searched CENTRAL (2013, Issue 2), MEDLINE (1966 to February week 3, 2013), EMBASE (1980 to March 2013), Micromedex (2010), Pascal (1987 to 2004) and Science Citation Index (1974 to March 2013). SELECTION CRITERIA: To study efficacy, we used randomised controlled trials (RCTs) comparing the use of acetylcysteine or carbocysteine versus placebo, either alone or as an add-on therapy. To study safety, we used trials comparing acetylcysteine or carbocysteine versus active treatment or no treatment and case reports. DATA COLLECTION AND ANALYSIS: In this review update two review authors (YD, MC), with help from a colleague, extracted data and assessed trial quality. We performed a subgroup analysis of children younger than two years of age. MAIN RESULTS: We included six trials involving 497 participants to study efficacy. They showed some benefit (e.g. reduction of cough at day seven) from mucolytic agents, although differences were of little clinical relevance. No conclusion was drawn about the subgroup of infants younger than two years because data were unavailable. Thirty-four studies, including the previous six trials involving 2064 children, were eligible to study safety. Overall safety was good but very few data were available to evaluate safety in infants younger than two years. However, 59 cases of paradoxically increased bronchorrhoea observed in infants were reported to the French pharmacovigilance system. AUTHORS' CONCLUSIONS: The results have to be interpreted with caution because they are based on a limited number of participants included in studies whose methodological quality is questionable. Acetylcysteine and carbocysteine seem to have a limited efficacy and appear to be safe in children older than two years. These results should take into consideration the fact that acetylcysteine and carbocysteine are prescribed for self limiting diseases (for example, acute cough, bronchitis). Given strong concerns about safety, these drugs should only be used for acute upper and lower RTIs in the context of a RCT with regards to children younger than two years.

Acetylcysteine and carbocysteine for acute upper and lower respiratory tract infections in paediatric patients without chronic broncho-pulmonary disease.

BACKGROUND: Acetylcysteine and carbocysteine are the most commonly prescribed mucolytic drugs in many European countries. To our knowledge, no systematic review has been published on their efficacy and safety for acute upper and lower respiratory tract infections (ARTIs) in children without chronic broncho-pulmonary disease. OBJECTIVES: The objective was to assess the efficacy and safety and to establish a benefit-risk ratio of acetylcysteine and carbocysteine as symptomatic treatments for ARTIs in children without chronic broncho-pulmonary disease. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, issue 4) which contains the Acute Respiratory Infections (ARI) Group's Specialized Register, MEDLINE (1966 to 2008), EMBASE (1980 to 2008); Micromedex (2008), Pascal (1987 to 2004), and Science Citation Index (1974 to 2008). SELECTION CRITERIA: To study efficacy, we used randomised controlled trials (RCTs) comparing the use of acetylcysteine or carbocysteine versus placebo either alone or as an add-on therapy.To study safety, we also used trials comparing the use of acetylcysteine or carbocysteine versus active treatment or no treatment and case reports. DATA COLLECTION AND ANALYSIS: At least two review authors extracted data and assessed trial quality. We performed a subgroup analysis of children younger than two years of age. MAIN RESULTS: Six trials involving 497 participants were included to study efficacy. They showed some benefit from mucolytic agents, although differences were of little clinical relevance. No conclusion was drawn about the subgroup of infants younger than two years because the data were unavailable. Thirty-four studies including the previous six trials involving 2064 children were eligible to study safety. Overall safety was good but very few data were available to evaluate safety in infants younger than two years. However, 48 cases of paradoxically increased bronchorrhoea observed in infants were reported to the French pharmacovigilance system. AUTHORS' CONCLUSIONS: The results of this review have to be interpreted with caution because it was based on a limited number of participants included in studies whose methodological quality is questionable. Acetylcysteine and carbocysteine seem to have a limited efficacy and appear to be safe in children older than two years. These results should take into consideration the fact that acetylcysteine and carbocysteine are prescribed for self-limiting diseases (for example, acute cough, bronchitis). Regarding children younger than two years, given concerns about safety, these drugs should only be used for ARTIs in the context of an RCT.

Neonatal intraventricular haemorrhage associated with maternal use of paroxetine.

Selective serotonin reuptake inhibitors (SSRIs) have been reported to inhibit serotonin uptake into platelets, resulting in decreased platelet function. We report a case of a large intraventricular haemorrhage in a 6-h-old boy, whose mother used paroxetine during pregnancy.