Effect of Thalidomide on Clinical Remission in Children and Adolescents with Ulcerative Colitis Refractory to Other Immunosuppressives: Pilot Randomized Clinical Trial.

BACKGROUND: In a randomized controlled trial, thalidomide has shown to be effective in refractory Crohn's disease in children. This pilot study aimed at evaluating thalidomide in refractory pediatric ulcerative colitis (UC). METHODS: Double-blind, placebo-controlled randomized clinical trial on thalidomide 1.5 to 2.5 mg/kg/day in children with active UC despite multiple immunosuppressive treatments. In an open-label extension, nonresponders to placebo received thalidomide for an additional 8 weeks; all responders were followed up for a minimum of 52 weeks. RESULTS: Twenty-six children with refractory UC were randomized to thalidomide or placebo. Clinical remission at week 8 was achieved by significantly more children treated with thalidomide {10/12 (83.3%) versus 2/11 (18.8%); risk ratio, 4.5 (95% confidence interval [CI], 1.2-16.4); P = 0.005; number needed to treat, 1.5}. Of the nonresponders to placebo who were switched to thalidomide, 8 of 11 (72.7%) subsequently reached remission at week 8 (risk ratio, 4.0 [95% CI, 1.1-14.7]; number needed to treat, 2.45; P = 0.01). Clinical remission in the thalidomide group was 135.0 weeks (95% CI, 32-238), compared with 8.0 weeks (95% CI, 2.4-13.6) in the placebo group (P < 0.0001). Cumulative incidence of severe adverse events was 3.1 per 1000 patient-weeks. Peripheral neuropathy and amenorrhea were the most frequent adverse events. CONCLUSIONS: In this pilot randomized controlled trial on cases of UC refractory to immunosuppressive therapy, thalidomide compared with placebo resulted in improved clinical remission at 8 weeks of treatment and in longer term maintenance of remission. These findings require replication in larger clinical studies evaluating both thalidomide efficacy and safety.

Effect of thalidomide on clinical remission in children and adolescents with refractory Crohn disease: a randomized clinical trial.

IMPORTANCE: Pediatric-onset Crohn disease is more aggressive than adult-onset disease, has high rates of resistance to existing drugs, and can lead to permanent impairments. Few trials have evaluated new drugs for refractory Crohn disease in children. OBJECTIVE: To determine whether thalidomide is effective in inducing remission in refractory pediatric Crohn disease. DESIGN, SETTING, AND PATIENTS: Multicenter, double-blind, placebo-controlled, randomized clinical trial of 56 children with active Crohn disease despite immunosuppressive treatment, conducted August 2008-September 2012 in 6 pediatric tertiary care centers in Italy. INTERVENTIONS: Thalidomide, 1.5 to 2.5 mg/kg per day, or placebo once daily for 8 weeks. In an open-label extension, nonresponders to placebo received thalidomide for an additional 8 weeks. All responders continued to receive thalidomide for an additional minimum 52 weeks. MAIN OUTCOMES AND MEASURES: Primary outcomes were clinical remission at week 8, measured by Pediatric Crohn Disease Activity Index (PCDAI) score and reduction in PCDAI by ≥25% or ≥75% at weeks 4 and 8. Primary outcomes during the open-label follow-up were clinical remission and 75% response. RESULTS: Twenty-eight children were randomized to thalidomide and 26 to placebo. Clinical remission was achieved by significantly more children treated with thalidomide (13/28 [46.4%] vs 3/26 [11.5%]; risk ratio [RR], 4.0 [95% CI, 1.2-12.5]; P = .01; number needed to treat [NNT], 2.86). Responses were not different at 4 weeks, but greater improvement was observed at 8 weeks in the thalidomide group (75% response, 13/28 [46.4%] vs 3/26 [11.5%]; RR, 4.0 [95% CI, 1.2-12.5]; NNT = 2.86; P = .01; and 25% response, 18/28 [64.2%] vs 8/26 [30.8%]; RR, 2.1 [95% CI, 1.1-3.9]; NNT = 2.99; P = .01). Of the nonresponders to placebo who began receiving thalidomide, 11 of 21 (52.4%) subsequently reached remission at week 8 (RR, 4.5 [95% CI, 1.4-14.1]; NNT = 2.45; P = .01). Overall, 31 of 49 children treated with thalidomide (63.3%) achieved clinical remission, and 32 of 49 (65.3%) achieved 75% response. Mean duration of clinical remission in the thalidomide group was 181.1 weeks (95% CI, 144.53-217.76) vs 6.3 weeks (95% CI, 3.51-9.15) in the placebo group (P < .001). Cumulative incidence of severe adverse events was 2.1 per 1000 patient-weeks, with peripheral neuropathy the most frequent severe adverse event. CONCLUSIONS AND RELEVANCE: In children and adolescents with refractory Crohn disease, thalidomide compared with placebo resulted in improved clinical remission at 8 weeks of treatment and longer-term maintenance of remission in an open-label follow-up. These findings require replication to definitively determine clinical utility of this treatment. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00720538.

Off-label prescribing patterns of antiemetics in children: a multicenter study in Italy.

UNLABELLED: Acute gastroenteritis (AG) represents both the main cause of acute vomiting in children under 3 years old and a major cause of access to the emergency department. Even if several drugs may be able to reduce the emesis, the pharmacological treatment of vomiting in children remains a controversial issue, and several drugs are prescribed outside their authorized drug label with respect dosage, age, indication, or route of administration and are named as off-label. The aim of present study was to assess the off-label use of antiemetic drugs in patients less than 18 years with vomiting related to AG. This study was carried out in eight pediatric emergency departments in Italy. The following data were obtained crossing the pharmacy distribution records with emergency departments' patient data: sex and age of the patients and detailed information for each drug used (indication, dose, frequency, and route of administration). We recorded that antiemetic drugs were prescribed in every year, particularly in children up to 2 years old, and compared with both literature data and data sheet; 30 % of the administered antiemetics were used off-label. In particular, domperidone was the only antiemetic used labeled for AG treatment in pediatric patients, while metoclopramide and ondansetron have been off-label for both age and indications (i.e., AG treatment). CONCLUSIONS: In conclusion, we documented an off-label use of antiemetics in children, and this could represents a problem of safety for the patient and a legal risk for the prescribing physician if patients have an unwanted or bad outcome from treatment.

A web-based system for total parenteral nutrition prescription in a pediatric hospital - biomed 2010.

otal Parenteral Nutrition (TPN) is defined as feeding a patient by infusing nutrients intravenously, bypassing the usual process of eating and digestion. There are two kinds of TPN: short-term TPN may be used when a patient's digestive system is temporarily nonfunctional because of an interruption in its continuity; long-term TPN is used to treat patients with an impairment or a lack in nutrient absorption. TPN has extended the life of children born with nonexistent or severely deformed digestive organs and is a vital support for these patients. In Burlos Pediatric Department, pediatricians fill in a pharmacy request form in which nutritional needs are included for each patient. Subsequently, clinical pharmacists evaluate the patients individual data and decide which TPN formula to prepare. To enhance the TPN prescription process, an intranet web-based system has been developed to replicate the original paper-based forms. The software, developed in PHP and based on open source tools and services, has been constructed according to pharmacists requirements. These professionals, together with the Hospital Information System technicians, thanks to the availability of affordable instruments, perceive the advantages that such a system would have in improving clinical practice and quality of care. The system was devised with the goal to avoid common reading errors, to improve the correct text comprehension, to ensure prescription preparation, administration and tracking. According to a process of total quality control, the system reduces clinical risks regarding issues such as the correct and rapid availability of medical prescriptions and the incorrect identification of the patients. In comparison with paper-based TPN prescriptions, electronic-based forms have reduced the incidence of errors, the possible lack of patient data and reading misunderstandings. Regarding future improvements, IT technicians are defining the procedures to implement digital signature and medical aspects of the electronic TPN medical prescriptions.