Enzyme replacement therapy for infantile-onset Pompe disease.

BACKGROUND: Infantile-onset Pompe disease is a rare and progressive autosomal-recessive disorder caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). Current treatment involves enzyme replacement therapy (with recombinant human alglucosidase alfa) and symptomatic therapies (e.g. to control secretions). Children who are cross-reactive immunological material (CRIM)-negative require immunomodulation prior to commencing enzyme replacement therapy.Enzyme replacement therapy was developed as the most promising therapeutic approach for Pompe disease; however, the evidence is lacking, especially regarding the optimal dose and dose frequency. OBJECTIVES: To assess the effectiveness, safety and appropriate dose regimen of enzyme replacement therapy for treating infantile-onset Pompe disease. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register, which is compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the Cochrane Central Register of Controlled Trials (CENTRAL), Embase (Ovid), PubMed and LILACS, and CBM, CNKI, VIP, and WANFANG for literature published in Chinese. In addition, we searched three online registers: WHO International Clinical Trials Registry Platform ClinicalTrials.gov, and www.genzymeclinicalresearch.com. We also searched the reference lists of relevant articles and reviews.Date of last search of the Group's Inborn Errors of Metabolism Trials Register: 24 November 2016. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials of enzyme replacement therapy in children with infantile-onset Pompe disease. DATA COLLECTION AND ANALYSIS: Two authors independently selected relevant trials, assessed the risk of bias and extracted data. We contacted investigators to obtain important missing information. MAIN RESULTS: We found no trials comparing the effectiveness and safety of enzyme replacement therapy to another intervention, no intervention or placebo.We found one trial (18 participants) that fulfilled the selection criteria, comparing different doses of alglucosidase alfa. The trial provided low-quality evidence (this was a small trial, there were no numerical results available by dose group, random sequence generation and allocation concealment were unclear, and there was a lack of blinding). The duration of alglucosidase alfa treatment ranged from 52 weeks (the length of the original study) to up to three years (including the extended phase of the trial), with a median duration of treatment being 2.3 years.The trial only reported that clinical responses including cardiac function and motor development, as well as the proportion of children that were free of invasive ventilation, were similar in the 20 mg/kg every two weeks and the 40 mg/kg every two weeks groups (low-quality evidence). Long-term alglucosidase alfa treatment markedly extended survival as well as ventilation-free survival and improved cardiomyopathy (low-quality evidence). In relation to the number of children experiencing one or more infusion-related events, there was no significant difference between dose groups, risk ratio 0.83 (95% confidence interval 0.40 to 1.76) (low-quality of evidence). However, of note, at 52 weeks, five children in the 20 mg/kg every two weeks dose group experienced a total of 41 mild or moderate (none severe) infusion-related events and the six children in the 40 mg/kg every two weeks dose group experienced a total of 123 infusion-related events. By the end of the extended phase of the trial, five children in the 20 mg/kg every two weeks dose group experienced a total of 47 infusion-related events and the six children in the 40 mg/kg every two weeks dose group experienced a total of 177 infusion-related events. The trial was supported by the Genzyme Corporation. AUTHORS' CONCLUSIONS: The search found no trials comparing the effectiveness and safety of enzyme replacement therapy to another intervention, no intervention or placebo. One small randomized controlled trial provided no robust evidence for which dosing schedule of alglucosidase alfa was more effective to treat infantile-onset Pompe disease. It is not deemed ethical to proceed with new placebo-controlled trials, therefore a randomized controlled trial with a large sample size comparing different dosing schedules of enzyme replacement therapy is needed. The main clinical outcomes (i.e. cardiac function, invasive ventilation, survival, motor development, adverse events (e.g. the development of antibodies)) should be standardized when evaluated and reported.

A prospective study of the use of antibiotics in the Emergency Department of a Chinese University Hospital.

BACKGROUND: Antibiotics are one of the most widely misused group of medicines. The aim of this study was to investigate the use of antibiotics in one of the paediatric emergency departments in China. METHODS: We performed a prospective, cross-sectional study of antibiotic use in the paediatric emergency room of West China Second University Hospital. A total of 500 consecutive patients from March 25 to April 3 2013 were included. Clinical details of the patients were also collected in order to analyse antibiotic use. KEY FINDINGS: The median age of patients was 2 years 2 months. The five most common conditions seen in the emergency department were wheezy bronchitis, upper respiratory tract infections, tonsillitis, pneumonia and diarrhoea. A total of 311 children (62%) received antibiotics. The antibiotics prescribed were predominantly cephalosporins and penicillins. More than one antibiotic was used in 51 patients. In total, 75% of the antibiotics prescribed were cephalosporins. More than three-quarters of the young children with wheezy bronchitis received antibiotics. Antibiotic use for children with an upper respiratory tract infections or tonsillitis was greater than the 20% maximum recommended by the European Surveillance of Antimicrobial Consumption. CONCLUSIONS: The majority of children attending the emergency department received antibiotics. For many of the conditions, the use of antibiotics was inappropriate.

20% subcutaneous immunoglobulin for patients with primary immunodeficiency diseases: A systematic review.

BACKGROUND: Primary immunodeficiency diseases (PID) are a group of rare disorders that patients do not have normal function of the immune system. Subcutaneous immunoglobulin 20% (SCIG-20%) was a candidate when considering replacement therapy with immunoglobulin in PID, but the evidence was not clear. To understand and interpret the available evidence, we conducted a systematic review to assess the efficacy and safety of SCIG-20% for patients with PID. METHOD: Literature searches were conducted in PUBMED, EMBASE, Cochrane Library, CBM, VIP, CNKI, WanFang, LILACS and U.S. ClinicalTrials.gov. Clinical studies published in full text that met predefined inclusion criteria were eligible irrespective of language. Reviewers independently assessed all potential studies and extracted data. The fixed-effect model was used in meta-analysis. RESULTS: 4 studies involving 100 patients were included. The pooled rate of infection was 0.80 with the annual rate of 3.74. 38% patients missed days from work/school and annual rate was 4.54days in one year per patient. Only 4% patients were hospitalized due to infection and it costs 1.57days in one year per patient. 70% patients used antibiotics during 58.4days in one year per patient. 80 patients (80.0%) who experienced 1630 AEs were considered related to SCIG-20%. Only 7 related AEs were severe, of which, 4 were local reactions and 3 were headaches. Studies on health related quality of life and satisfaction suggested that patients with SCIG-20% had a good life quality and satisfied with SCIG treatment. CONCLUSIONS: SCIG-20% treatment was not recommended for patients with primary immunodeficiency. Low quality of each outcome suggested that the evidence on effect of SCIG-20% for patients with PID is inadequate. Further comparative studies are urgently needed, especially in comparison with IVIG or SCIG of other concentrations.