Coghill D.R.,University of Dundee |
Banaschewski T.,University of Mannheim |
Lecendreux M.,Robert Debre University Hospital |
Zuddas A.,University of Cagliari |
And 5 more authors.
European Child and Adolescent Psychiatry | Year: 2014
Lisdexamfetamine dimesylate (LDX) is a long-acting, prodrug stimulant therapy for patients with attention-deficit/hyperactivity disorder (ADHD). This randomized placebo-controlled trial of an optimized daily dose of LDX (30, 50 or 70 mg) was conducted in children and adolescents (aged 6-17 years) with ADHD. To evaluate the efficacy of LDX throughout the day, symptoms and behaviors of ADHD were evaluated using an abbreviated version of the Conners' Parent Rating Scale-Revised (CPRS-R) at 1000, 1400 and 1800 hours following early morning dosing (0700 hours). Osmotic-release oral system methylphenidate (OROS-MPH) was included as a reference treatment, but the study was not designed to support a statistical comparison between LDX and OROS-MPH. The full analysis set comprised 317 patients (LDX, n = 104; placebo, n = 106; OROS-MPH, n = 107). At baseline, CPRS-R total scores were similar across treatment groups. At endpoint, differences (active treatment - placebo) in least squares (LS) mean change from baseline CPRS-R total scores were statistically significant (P < 0.001) throughout the day for LDX (effect sizes: 1000 hours, 1.42; 1400 hours, 1.41; 1800 hours, 1.30) and OROS-MPH (effect sizes: 1000 hours, 1.04; 1400 hours, 0.98; 1800 hours, 0.92). Differences in LS mean change from baseline to endpoint were statistically significant (P < 0.001) for both active treatments in all four subscales of the CPRS-R (ADHD index, oppositional, hyperactivity and cognitive). In conclusion, improvements relative to placebo in ADHD-related symptoms and behaviors in children and adolescents receiving a single morning dose of LDX or OROS-MPH were maintained throughout the day and were ongoing at the last measurement in the evening (1800 hours). © 2013 The Author(s).
Grothey A.,Mayo Medical School |
Van Cutsem E.,University Hospitals |
Sobrero A.,San Martino Hospital |
Siena S.,Ospedale Niguarda Ca |
And 17 more authors.
The Lancet | Year: 2013
Background No treatment options are available for patients with metastatic colorectal cancer that progresses after all approved standard therapies, but many patients maintain a good performance status and could be candidates for further therapy. An international phase 3 trial was done to assess the multikinase inhibitor regorafenib in these patients. Methods We did this trial at 114 centres in 16 countries. Patients with documented metastatic colorectal cancer and progression during or within 3 months after the last standard therapy were randomised (in a 2:1 ratio; by computergenerated randomisation list and interactive voice response system; preallocated block design (block size six); stratifi ed by previous treatment with VEGF-targeting drugs, time from diagnosis of metastatic disease, and geographical region) to receive best supportive care plus oral regorafenib 160 mg or placebo once daily, for the fi rst 3 week s of each 4 week cycle. The primary endpoint was overall survival. The study sponsor, participants, and investigators were masked to treatment assignment. Effi cacy analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT01103323. Findings Between April 30, 2010, and March 22, 2011, 1052 patients were screened, 760 patients were randomised to receive regorafenib (n=505) or placebo (n=255), and 753 patients initiated treatment (regorafenib n=500; placebo n=253; population for safety analyses). The primary endpoint of overall survival was met at a preplanned interim analysis; data cutoff was on July 21, 2011. Median overall survival was 6.4 months in the regorafenib group versus 5.0 months in the placebo group (hazard ratio 0.77; 95% CI 0.64-0.94; one-sided p=0.0052). Treatment-related adverse events occurred in 465 (93%) patients assigned regorafenib and in 154 (61%) of those assigned placebo. The most common adverse events of grade three or higher related to regorafenib were hand-foot skin reaction (83 patients, 17%), fatigue (48, 10%), diarrhoea (36, 7%), hypertension (36, 7%), and rash or desquamation (29, 6%). Interpretation Regorafenib is the fi rst small-molecule multikinase inhibitor with survival benefi ts in metastatic colorectal cancer which has progressed after all standard therapies. The present study provides evidence for a continuing role of targeted treatment after disease progression, with regorafenib off ering a potential new line of therapy in this treatment-refractory population. Funding Bayer HealthCare Pharmaceuticals.
Nicholas A.K.,University of Cambridge |
Khurshid M.,University of Cambridge |
Desir J.,Free University of Colombia |
Carvalho O.P.,University of Cambridge |
And 14 more authors.
Nature Genetics | Year: 2010
Autosomal recessive primary microcephaly (MCPH) is a disorder of neurodevelopment resulting in a small brain. We identified WDR62 as the second most common cause of MCPH after finding homozygous missense and frame-shifting mutations in seven MCPH families. In human cell lines, we found that WDR62 is a spindle pole protein, as are ASPM and STIL, the MCPH7 and MCHP7 proteins. Mutant WDR62 proteins failed to localize to the mitotic spindle pole. In human and mouse embryonic brain, we found that WDR62 expression was restricted to neural precursors undergoing mitosis. These data lend support to the hypothesis that the exquisite control of the cleavage furrow orientation in mammalian neural precursor cell mitosis, controlled in great part by the centrosomes and spindle poles, is critical both in causing MCPH when perturbed and, when modulated, generating the evolutionarily enlarged human brain. © 2010 Nature America, Inc. All rights reserved.
Dahmani S.,Robert Debre University Hospital |
Dahmani S.,University Paris Diderot |
Dahmani S.,French Institute of Health and Medical Research |
Delivet H.,Robert Debre University |
And 3 more authors.
Current Opinion in Anaesthesiology | Year: 2014
Purpose of Review: Emergence delirium in children is still considered as a mysterious complication occurring after pediatric anesthesia. Although the pharmacology of fast-acting volatile agent is highly suspected in the genesis of this complication, no strong evidence has been published to support this hypothesis. This review summarizes the recent findings concerning this complication. RECENT FINDINGS: Emergence delirium occurs typically in preschool children, with a high intensity of anxiety, after sevoflurane or desflurane anesthesia. In addition, although pain has been suspected in the genesis of this complication, emergence delirium has also been described after nonpainful procedure (imaging). Prevention of this complication relies on preventing preoperative anxiety (using premedication and psychological approaches), providing a sufficient analgesia (either systemically or by regional analgesia) and administering intraoperative sedative agents such as ketamine, clonidine, dexmedetomidine, gabapentine, midazolam, magnesium, hydroxyzine, midazolam and dexamethasone. Treatment of emergence delirium should be pharmacological when facing intense agitation with self-injury risks. This could be achieved using propofol, opioid agents or dexmedetomidine. As a result of the delayed discharge from a postoperative care unit associated with these agents, dexmedetomidine should be favored because of its analgesic and postoperative nausea and vomiting preventive effects. As emergence delirium shares many risk factors with long-lasting cognitive complications such as postoperative maladaptative behavioral changes, letting parents know about these complications is requested. SUMMARY: Emergence delirium in children is a frequent but preventable complication. Strategies for prevention and therapy include particularly pain management and medication with alpha-2 agonists. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.
De Mestier L.,Robert Debre University Hospital |
Brixi H.,Robert Debre University Hospital |
Gincul R.,Hospital Edouard Herriot |
Ponchon T.,Hospital Edouard Herriot |
Cadiot G.,Robert Debre University Hospital
Endoscopy | Year: 2013
Rectal neuroendocrine tumors (NETs) account for approximately one-third of all digestive NETs, with an increasing incidence and good overall prognosis. Although recent guidelines have been published, endoscopic techniques have expanded substantially and the most recent reports should be taken into account for clinical practice. The objectives of this report were to review the latest advances on prognosis, pre-interventional explorations, treatment - with particular focus on endoscopy - and surveillance of well-differentiated rectal NETs, excluding poorly differentiated and metastatic tumors. © 2013 Georg Thieme Verlag KG Stuttgart New York.
Lardiere-Deguelte S.,Robert Debre University Hospital
Neuroendocrinology | Year: 2015
Introduction: In patients with small intestinal neuroendocrine tumours (siNET), the surgical resection of the primary tumour and associated mesenteric lymph nodes (LN) is recommended but is not well standardized and can be risky in patients with superior mesenteric vessels involvement. We aimed to evaluate the correlation between the length of resected small bowel and the number of removed LN, and to propose a preoperative morphological classification of siNET-associated LN. Methods: Records of patients operated on for siNET at two expert centers between August 2005 and November 2013 were analyzed. Two specialist radiologists reviewed the preoperative imaging and classified mesenteric LN into 5 stages according to their proximity to the truck and/or branches of the superior mesenteric artery. Results: Seventy-two patients were included. The mean number of removed LN was 12 ± 15 and the length of removed small intestine 53 ± 43 cm. No correlation existed between the length of small bowel resection and the number of removed LN. Overall, 9 (12%), 13 (18%), 36 (50%), 14 (19%) and 0 patients were classified into LN-stage 0, I, II, III and IV. The correlation rate between the two observers was 0.98. Patients with LN-stage III (hardly resectable) had more removed LN than those with LN-stages 0, I or II (easily removable). Conclusion: An optimal lymphadenectomy is not always associated to an extended small bowel resection. In the era of small bowel-sparing surgery, the preoperative classification of mesenteric LN could help standardizing the surgical management of patients with siNET. © 2015 S. Karger AG, Basel Copyright © 2015, S. Karger AG. All rights reserved.
Lecendreux M.,Robert Debre University Hospital
Pediatric Drugs | Year: 2014
Narcolepsy is a neurological disorder frequently occurring from childhood and persisting through adolescence and adulthood. Individuals suffering from narcolepsy exhibit excessive daytime somnolence, sleep attacks, cataplexy, dysomnia, metabolic perturbations including weight gain, and problems in social interaction and academic performance. The prevalence of narcolepsy in childhood is not known but can be estimated from adult studies to be greater than 20–60 per 100,000 in Western countries. The 2009 (A) H1N1 vaccination campaign led to an increase of narcoleptic cases both in children and in adults, supporting the autoimmune hypothesis of the disease. This article focuses on the epidemiology, etiology, and particularities of treatment in pediatric narcolepsy and details the effects of the drugs used to treat this condition, including recent trends in the field. Future therapeutic directions are also discussed. At present, medications used to treat children or adolescents have shown efficacy mostly based on clinical experience, given the lack of level 1 evidence-based studies in the pediatric population. Therefore, most compounds used in adult narcolepsy to target clinical symptoms such as wake-promoting or anticataplectic agents are prescribed off-label in pediatric patients. Published research shows the benefit of drug therapy for narcoleptic children, but these must be dispensed with caution in the absence of well conducted clinical trials. © 2014, Springer International Publishing Switzerland.
Dahmani S.,Robert Debre University Hospital |
Stany I.,Robert Debre University Hospital |
Brasher C.,Robert Debre University Hospital |
Lejeune C.,Robert Debre University Hospital |
And 5 more authors.
British Journal of Anaesthesia | Year: 2010
Background. Emergence agitation (EA) in children is increased after sevoflurane anaesthesia. The efficacy of prophylactic treatment is controversial. The aim of this study was to provide a meta-analysis of the studies of the pharmacological prevention of EA in children.MethodsA comprehensive literature search was conducted to identify clinical trials that focused on the prevention of EA in children anaesthetized with sevoflurane, desflurane, or both. The data from each trial were combined using the Mantel-Haenszel model to calculate the pooled odds ratio (OR) and 95 confidence interval. I2 statistics were used to assess statistics heterogeneity and the funnel plot and the Begg-Mazumdar test to assess bias.ResultsThirty- seven articles were found which included a total of 1695 patients in the intervention groups and 1477 in the control ones. Midazolam and 5HT3 inhibitors were not found to have a protective effect against EA [OR=0.88 (0.44, 1.76); OR=0.39 (0.12, 1.31), respectively], whereas propofol [OR=0.21 (0.16, 0.28)], ketamine [OR=0.28 (0.13, 0.60)], 2-adrenoceptors [OR=0.23 (0.17, 0.33)], fentanyl [OR=0.31 (0.18, 0.56)], and peroperative analgesia [OR=0.15 (0.07, 0.34)] were all found to have a preventive effect. Subgroup analysis according to the peroperative analgesia given does not affect the results.ConclusionsThis meta-analysis found that propofol, ketamine, fentanyl, and preoperative analgesia had a prophylactic effect in preventing EA. The analgesic properties of these drugs do not seem to have a role in this effect.
Radoi C.,Robert Debre University Hospital |
Garcia T.,Robert Debre University Hospital |
Brugniart C.,Robert Debre University Hospital |
Ducasse A.,Robert Debre University Hospital |
Arndt C.,Robert Debre University Hospital
Graefe's Archive for Clinical and Experimental Ophthalmology | Year: 2014
Background: In non-arteritic anterior ischemic optic neuropathy (NA-AION), no treatments have demonstrated to be effective in recovering visual loss in randomized clinical trials. Oral steroids have been evaluated, and small series of intravitreal triamcinolone acetonide (IVTA) injection in NA-AION have been reported. The purpose of our study was to report the visual outcome and morphological changes in response to a single IVTA injection as a treatment for patients with NA-AION. Patients and methods: The charts of 36 patients with visual symptoms and optic disc swelling caused by NA-AION were evaluated. Twenty-one patients had received 4 mg IVTA and were compared with 15 non-treated patients. Visual acuity (VA), retinal nerve fiber layer thickness and static visual field were evaluated after 6 months. Results: VA improvement at 6 months is statistically better in the treated group than in the non-treated group (p = 0.0035). In the treated group, there was a significant inverse correlation between the delay of the injection and the visual acuity achieved at 6 months (p < 0.0083**, r = -0.56). A significant improvement of the visual field was noted in the injected group when compared with the non-treated group at 6 months (p < 0.0028). Discussion: In this retrospective study, patients receiving IVTA in the acute phase of NA-AION have better improvement of VA and visual field during the follow-up period of 6 months. However, only a large randomized controlled trial may enable to evaluate the benefits of IVTA Injections on visual outcome in NA-AION. © 2013 Springer-Verlag Berlin Heidelberg.
Langagne T.,Robert Debre University Hospital |
Leveque M.,Robert Debre University Hospital |
Schmidt P.,Robert Debre University Hospital |
Chays A.,Robert Debre University Hospital
International Journal of Pediatric Otorhinolaryngology | Year: 2010
Introduction: Permanent congenital hearing loss is one of the most frequent congenital anomaly at birth. Universal newborn hearing screening (UNHS) was introduced in numerous countries in order to allow an early diagnosis and intervention for congenital hearing impairment. Objective: First aim of this study is to evaluate the accuracy of early diagnosis of hearing impairment after UNHS. Second aim is to discuss the auditory intervention proposed after this diagnosis. Last aim is to evaluate the relevance of UNHS for early diagnosis and intervention. Materials and methods: Prospective study. UNHS program was introduced in the entire French region of Champagne-Ardenne in January 2004. Forty-one children have benefited of an early diagnosis of hearing impairment until June 2007. They were included in an intervention program consisting of an audiometric follow-up and an auditory intervention. This program was conducted until June 2008. Results: There were 28 males patients and 13 females patients. The diagnosis of hearing aid impairment was carried at an average age of 3.2-month. The auditory follow-up allowed confirming the initial diagnosis of deafness for the majority of the children as for their degree of hearing loss. Auditory intervention was heterogeneous depending on degree of hearing loss of the children. Conclusion: This UNHS program demonstrates its validity and feasibility for early diagnosis and intervention of congenital hearing impairment. It brought a major impact on the management of congenital hearing impairment in Champagne-Ardenne. © 2010 Elsevier Ireland Ltd.