Carbamazepine causes various forms of hypersensitivity reactions, ranging from maculopapular exanthema to severe blistering reactions. Researchers have now identified a gene, called HLA-A*3101, in Caucasian patients that increases the risk of developing a reaction to the drug from 5% to 26%.
The research undertaken, in collaboration with the Wellcome Trust Sanger Institute, screened more than a million variants in DNA across the human genome to understand why some patients are more prone to the drug's side-effects than others. Research in Taiwan has already shown that carbamazepine-induced Steven Johnson Syndrome–Toxic Epidermal Necropysis is strongly associated with the HLA-B*1502 allele gene in the south east asian population , but Liverpool scientists discovered that this gene could not be used to predict the reaction in Caucasian people.
Dr Ana Alfirevic, from the University's Wolfson Centre for Personalised Medicine, said: "This is a significant finding that highlights the importance and advancement of new genetic technologies. We aim to support the development of medicines based on a patient's unique genetic make-up to allow clinicians to prescribe the most effective and safe treatments."
Citation
McCormack M, Alfirevic A, Bourgeois S, Farrell JJ, Kasperavičiūtė D, Carrington M, et al. HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans. The New England journal of medicine. 2011 Mar ;364(12):1134-43. [pubmed]
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Researchers at Concordia University have pioneered a computer-based method to detect epileptic seizures as they occur - a new technique that may open a window on the brain's electrical activity. Their paper, "A Novel Morphology-Based Classifier for Automatic Detection of Epileptic Seizures," presented at the annual meeting of the Engineering in Medicine and Biology Society, documents the very successful application of this new seizure-detection method.
An epileptic seizure, which is caused by disruptions in the normal electrical activity of the brain, can produce a range of symptoms including convulsions and unconsciousness. To learn more about the timing and nature of seizures, the electrical activity of patients' brains is often recorded using electroencephalograms (EEGs). At the moment, however, epilepsy experts must review these recordings manually - a time-consuming process.
"EEG recordings may cover a period of several weeks," explains study co-author Rajeev Agarwal, a professor in Concordia's Department of Electrical and Computer Engineering. "That's a lot of data to review. Automating the process is difficult, because there's no exact definition for a seizure, so there's no template to look for. Every seizure is different with every patient."
However, seizures have certain recognizable characteristics. They occur when neurons fire in a synchronous or rhythmic manner. As seizures progress, the EEG signals have very strong transitions. Seen on an EEG recording, the waves of electrical activity tend to be spike-like.
The Concordia team, led by PhD candidate and lead author Rajeev Yadav, devised an algorithm to check the sharpness of the electrical signals on the EEG recordings as measured by their angle or slope. A series of sharp signals indicate a seizure.
This approach proved extremely successful. In the study of EEG recordings of seven patients, the new method detected every seizure while scoring an extremely low rate of false positives. Results are far better than those obtained with existing methods.
This method of detecting seizures may have applications beyond epilepsy. "Patterns of sharp electrical activity in the brain are generally not a good thing," says Agarwal, who is also co-founder, chief technical officer and vice-president of Leap Medical Inc.
"Think of comatose patients in the ICU for example," he continues. "Some of them may be having seizures or epileptic form like activity, but there's no way to know at the moment. Our method may allow health professionals to gain a much clearer picture of patients' brain function."
The research team continues to evaluate and refine this method of seizure detection. More patient data from several different centres is being reviewed, and further publications on the subject are planned. So far, according to Agarwal, results are promising.
Partners in research:
This research was supported by the Natural Sciences and Engineering Research Council of Canada and the Regroupement Stratégique en Microsystèmes du Québec.
Source:
Concordia University
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New data suggest that the drug Topamax (topiramate) and its generic versions increase the risk for the birth defects cleft lip and cleft palate in babies born to women who use the medication during pregnancy, the U.S. Food and Drug Administration said today.
Before prescribing topiramate, approved to treat certain types of seizures in people who have epilepsy, health care professionals should warn patients of childbearing age about the potential hazard to the fetus if a woman becomes pregnant while using the drug.
Topiramate also is approved to prevent migraine headaches, but not to relieve the pain of migraines.
“Health care professionals should carefully consider the benefits and risks of topiramate when prescribing it to women of childbearing age,” said Russell Katz, M.D., director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research. “Alternative medications that have a lower risk of birth defects should be considered.”
Cleft lip and cleft palate, collectively called oral clefts, are birth defects that occur when parts of the lip or palate do not completely fuse together early in the first trimester of pregnancy, a time when many women do not know they are pregnant. The defects range from a small notch in the lip to a groove that runs into the roof of the mouth and nose, possibly leading to problems with eating, talking, and to ear infections. Surgery often is performed to close the lip and palate and most children do well after treatment.
Data from the North American Antiepileptic Drug (AED) Pregnancy Registry indicate an increased risk of oral clefts in infants exposed to topiramate during the first trimester of pregnancy. Infants exposed to topiramate as a single therapy experienced a 1.4 percent prevalence of oral clefts, compared with a prevalence of 0.38 percent – 0.55 percent in infants exposed to other antiepileptic drugs.
Infants of mothers who did not have epilepsy and were not being treated with other antiepileptic drugs had a prevalence of 0.07 percent. Similar data from the United Kingdom Epilepsy and Pregnancy Register supported the North American AED Pregnancy Registry data.
Based on the data, topiramate will have a stronger warning in its prescribing information (labeling). The pregnancy category will be changed to Pregnancy Category D. This means that there is positive evidence of human fetal risk based on human data, but the potential benefits of the drug in pregnant women may outweigh the risks in certain situations. The FDA previously designated the drug as Pregnancy Category C because of the lack of human data. More information about the Pregnancy Categories can be found in the FDA’s Drug Safety Communication.
The patient medication guide and prescribing information for Topamax and generic topiramate will be updated with the new information.
Before starting topiramate, pregnant women and women of childbearing potential should discuss other treatment options with their health care professional. Women taking topiramate should tell their health care professional immediately if they are planning to or become pregnant. Patients taking topiramate should not stop taking it unless told to do so by their health care professional.
Women who become pregnant while taking topiramate should talk to their health care professional about registering with theNorth American Antiepileptic Drug Pregnancy Registry, a group that collects information about outcomes in infants born to women treated with antiepileptic drugs during pregnancy.
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The results of the landmark major multi-center randomized clinical trial "Management of Myelomeningocele Study (MOMS)" report on fetal surgery for spina bifida has been published in the 9 February issue of the New England Journal of Medicine, NEJM. The results indicate that prenatal surgery for spina bifida has greatly improved benefits over postnatal repair, by reducing the need for shunting and improving motor outcomes.
The randomized clinical trial is the first that systematically evaluated the best treatment for myelomeningocele. The eight-year trial was stopped early since the results suggested that fetal surgery greatly reduced the need for postnatal intervention. The early intervention in utero also resulted in improved motor development.The early success of the trial has been cause for celebration at UCSF, who carried out the first human fetal surgery some thirty years ago.The surgical procedures evaluated in this trial, known as the Management of Myelomeningocele Study (MOMS), were developed at UCSF's Fetal Treatment Center, under the direction of Michael Harrison, UCSF professor emeritus of clinical surgery, pediatrics, obstetrics and gynecology.Harrison, often referred to as the "Father of Fetal Surgery", performed the world's first open fetal surgery 30 years ago at UCSF, and the institution has also trained most of the current leaders in the field.
The study originally planned to enroll 200 pregnant women carrying a child with myelomeningocele, but was stopped early, with only 183 participants enrolled, because of the significant benefits shown in the children who underwent fetal surgery. The pregnant women were randomly assigned to one of two groups: a prenatal surgery group and a postnatal surgery group. The prenatal group underwent surgery to close the spinal defect in the fetus before the 26th week of pregnancy. The babies born in the postnatal group had the standard surgery in the usual time frame. The children underwent independent evaluation at 12 months and 30 months. At 12 months of age only 39.7% of children in the prenatal surgery group needed csf shunt surgery compared to 82.5% in the postnatal surgery group. Standardized motor and cognitive outcome assessments performed at 30 months saw the prenatal surgery group scoring significantly higher than the postnatal surgery group. 41.9% of the children in the fetal surgery group were able to walk unaided compared to only 20.9% in the postnatal group.
It should however be noted that there are risks to the mother and fetus associated with early intervention and this option might not be suitable in all cases.
A Randomized Trial of Prenatal versus Postnatal Repair of Myelomeningocele. N. Scott Adzick, Elizabeth A. Thom, Catherine Y. Spong, John W. Brock, Pamela K. Burrows, Mark P. Johnson, Lori J. Howell, Jody A. Farrell, Mary E. Dabrowiak, Leslie N. Sutton, Nalin Gupta, Noel B. Tulipan, Mary E. D'Alton, Diana L. Farmer (2011)
New England Journal of Medicine p. 110209140307019
http://www.nejm.org/doi/abs/10.1056/NEJMoa1014379
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American Academy of Pediatrics (AAP) publishes updated practice guidelines on simple febrile seizures, in the January 31 issue of Pediatrics. Following a comprehensive review of the evidence based literature from 1996 to February 2009, the AAP have published updated guidelines on simple febrile seizures which replaces the 1996 practice statndards.
The recommendations stresses the importance of identifying the etiology in children presenting with fever. A lumbar puncutre should be performed if there are any signs or symptoms concerning meningitis. In infants between 6 and 12 months, who are unimmunized or in whose vaccination status is unclear, a lumbar puncture should be considered. The guidelines also suggest that a lumbar puncture should be considered where the child had already received antibiotics. Simple febrile seizures do not normally require any further investigations particularly EEG or neuroimaging.
Subcommittee on Febrile Seizures. Neurodiagnostic evaluation of the child with a simple febrile seizure. Pediatrics. 2011 Feb;127(2):389-94. PubMed PMID:
21285335. [ Free Full Text]
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