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Sample records for registered antiepileptic drug

  1. The Australian Register of Antiepileptic Drugs in Pregnancy : The first 1002 pregnancies

    NARCIS (Netherlands)

    Vajda, Frank J. E.; Hitchcock, Alison; Graham, Janet; O'Brien, Terence; Lander, Cecilie; Eadie, Mervyn

    2007-01-01

    Prospective studies are needed to assess the maternal and fetal hazards of antiepileptic drug (AED) therapy in pregnancy. To make the Australian Register of AEDs in Pregnancy better known to the Australian obstetric community by presenting results derived from it. Analysis of data collected by the

  2. Malformation risks of antiepileptic drug monotherapies in pregnancy: updated results from the UK and Ireland Epilepsy and Pregnancy Registers.

    LENUS (Irish Health Repository)

    Campbell, E

    2014-09-01

    Antiepileptic drug (AED) exposure during pregnancy increases the risk of major congenital malformations (MCMs). The magnitude of this risk varies by AED exposure. Here we provide updated results from the UK Epilepsy and Pregnancy Register of the risk of MCMs after monotherapy exposure to valproate, carbamazepine and lamotrigine.

  3. Antiepileptic drugs and bone metabolism

    Directory of Open Access Journals (Sweden)

    Labban Barbara

    2006-09-01

    Full Text Available Abstract Anti-epileptic medications encompass a wide range of drugs including anticonvulsants, benzodiazepines, enzyme inducers or inhibitors, with a variety effects, including induction of cytochrome P450 and other enzyme, which may lead to catabolism of vitamin D and hypocalcemia and other effects that may significantly effect the risk for low bone mass and fractures. With the current estimates of 50 million people worldwide with epilepsy together with the rapid increase in utilization of these medications for other indications, bone disease associated with the use of anti-epileptic medications is emerging as a serious health threat for millions of people. Nevertheless, it usually goes unrecognized and untreated. In this review we discuss the pathophysiologic mechanisms of bone disease associated with anti-epileptic use, including effect of anti-epileptic agents on bone turnover and fracture risk, highlighting various strategies for prevention of bone loss and associated fractures a rapidly increasing vulnerable population.

  4. Intravenous Antiepileptic Drugs in Russia

    Directory of Open Access Journals (Sweden)

    P. N. Vlasov

    2014-01-01

    Full Text Available Launching four intravenous antiepileptic drugs: valproate (Depakene and Convulex, lacosamide (Vimpat, and levetiracetam (Keppra – into the Russian market has significantly broadened the possibilities of rendering care to patients in seizure emergency situations. The chemi- cal structure, mechanisms of action, indications/contraindications, clinical effectiveness and tolerability, advantages/disadvantages, and adverse events of using these drugs in urgent and elective neurology are discussed. 

  5. Neurodevelopmental Effects of Antiepileptic Drugs.

    Science.gov (United States)

    Kellogg, Marissa; Meador, Kimford J

    2017-07-01

    Increasing evidence suggests that exposure to certain antiepileptic drugs (AEDs) during critical periods of development may induce transient or long-lasting neurodevelopmental deficits across cognitive, motor and behavioral domains. The developing nervous system may endure prolonged chronic exposure to AEDs during pregnancy (in utero) or during childhood, which can lead to neurodevelopmental defects such as congenital neural tube defects, lower IQ, language deficits, autism and ADHD. To date, valproate is the most widely recognized AED to significantly negatively affect neurodevelopment, and demonstrates greater adverse effects than any other AEDs that have been assessed. Although some AEDs appear to have low risk (i.e., lamotrigine, levetiracetam), other AEDs have been implicated in a variety of studies detailed below, and many AEDs have not been adequately assessed. The purpose of this review article is to summarize our current understanding of the neurodevelopmental effects of AEDs.

  6. Psychopharmacological treatment with lithium and antiepileptic drugs

    DEFF Research Database (Denmark)

    Licht, R W; Vestergaard, P; Kessing, L V

    2003-01-01

    A subcommittee under the Danish Psychiatric Association and the Child and Adolescent Psychiatric Association in Denmark have recently developed national guidelines for the psychopharmacological treatment with lithium and antiepileptic drugs, and the present translation aims at contributing...... to the international discussion on the development of proper guidelines for the treatment of bipolar disorder. Among the antiepileptic drugs, the report deals with valproate, carbamazepine and lamotrigine and to a lesser extent with oxcarbazepine, gabapentin and topiramate. The various drugs will be reviewed......, outlining the scientific evidence for mood-stabilizing properties and discussing major side effects, the most important interactions with other drugs and practical use. Special considerations during pregnancy and lactation, during treatment of children and adolescents and during treatment of the elderly...

  7. Interactions between hormonal contraception and antiepileptic drugs

    DEFF Research Database (Denmark)

    Reimers, Arne; Brodtkorb, Eylert; Sabers, Anne

    2015-01-01

    Antiepileptic drugs (AEDs) and hormonal contraceptives may affect each other's metabolism and clinical efficacy. Loss of seizure control and unplanned pregnancy may occur when these compounds are used concomitantly. Although a large number of available preparations yield a plethora of possible drug...... combinations, most of these drug interactions are predictable and, thus, avoidable. Unfortunately, there is a substantial lack of data regarding the newer AEDs. Detailed understanding of these issues is necessary for those who prescribe AEDs and/or hormonal contraception to women with epilepsy, as well...

  8. Managing antiepileptic drugs during pregnancy and lactation

    DEFF Research Database (Denmark)

    Sabers, Anne; Tomson, Torbjörn

    2009-01-01

    PURPOSE OF REVIEW: This review discusses data on the pharmacokinetics of antiepileptic drugs (AEDs) in pregnancy and lactation, and the clinical consequences thereof, thus providing a basis for a rational management of AEDs during pregnancy and lactation. RECENT FINDINGS: Studies have confirmed...... of AEDs in pregnancy and during lactation is important to enable optimal treatment. Gestation induced alterations in pharmacokinetics vary with the AED but also between patients and are difficult to predict. Therapeutic drug monitoring is, therefore, advisable during pregnancy and the use...... of the individual patient's optimal prepregnancy drug level is recommended as reference. Breastfeeding is in general safe but needs appropriate observation of the nursing infant....

  9. Pharmacokinetic interactions between contraceptives and antiepileptic drugs

    DEFF Research Database (Denmark)

    Sabers, A.

    2008-01-01

    The occurrence of bi-directional drug interactions between antiepileptic drugs (AEDs) and combined oral contraceptives (M) pose potential risks of unintended pregnancy and as well as seizure deterioration. It is well established that several of the older AEDs (carbamazepine, phenytoin...... AEDs, which undergoes glucuronidation processes, such as valproate and oxcarbazepine, may be affected by OCs. The magnitude of the drug-drug interactions show in general wide inter-individual variability and the change in the elimination rate is often unpredictable and can be influenced by a number...... of co-variants such as co-medication of other drugs, as well as genetic and environmental factors. It is therefore recommended that change in OC use is assisted by AED monitoring whenever possible. (C) 2007 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved Udgivelsesdato: 2008/3...

  10. Interactions between antiepileptic drugs and hormones.

    Science.gov (United States)

    Svalheim, Sigrid; Sveberg, Line; Mochol, Monika; Taubøll, Erik

    2015-05-01

    Antiepileptic drugs (AEDs) are known to have endocrine side effects in both men and women. These can affect fertility, sexuality, thyroid function, and bone health, all functions of major importance for well-being and quality of life. The liver enzyme inducing antiepileptic drugs (EIAEDs), like phenobarbital, phenytoin, and carbamazepine, and also valproate (VPA), a non-EIAED, are most likely to cause such side effects. AED treatment can alter the levels of different sex hormones. EIAEDs increase sex hormone binding globulin (SHBG) concentrations in both men and women. Over time, this elevation can lead to lower levels of bioactive testosterone and estradiol, which may cause menstrual disturbances, sexual problems, and eventually reduced fertility. VPA can cause weight gain in both men and women. In women, VPA can also lead to androgenization with increased serum testosterone concentrations, menstrual disturbances, and polycystic ovaries. Lamotrigine has not been shown to result in endocrine side effects. The newer AEDs have not yet been thoroughly studied, but case reports indicate that some of these drugs could also be suspected to cause such effects if endocrine changes commence after treatment initiation. It is important to be aware of possible endocrine side effects of AEDs as they can have a major impact on quality of life, and are, at least partly, reversible after AED discontinuation. Copyright © 2015. Published by Elsevier Ltd.

  11. Rhabdomyolysis induced by antiepileptic drugs: characteristics, treatment and prognosis.

    Science.gov (United States)

    Jiang, Wei; Wang, Xuefeng; Zhou, Shengnian

    2016-01-01

    Rhabdomyolysis syndrome refers to a variety of factors that affect the striated muscle cell membrane, the membrane channels and its energy supply. Most cases of rhabdomyolysis are due to direct trauma. However, infection, toxins, drugs, muscle ischemia, electrolyte imbalance, metabolic diseases, genetic diseases and abnormal body temperature can also lead to rhabdomyolysis. Epilepsy is one of the most common chronic neurological diseases. The primary long-term treatment is antiepileptic drugs (AEDs), which may cause rhabdomyolysis. This article summarizes the characteristics, treatment methods and prognosis of patients with rhabdomyolysis that is induced by antiepileptic drugs. This review is based on PubMed, EMBASE and MEDLINE searches of the literature using the keywords "epilepsy", "antiepileptic drugs","status epilepticus","rhabdomyolysis", and "antiepileptic drugs and rhabdomyolysis syndrome" as well as extensive personal clinical experience with various antiepileptic drugs. Potential relationships between antiepileptic drugs and rhabdomyolysis are discussed. Worldwide, there are approximately 50 million epilepsy patients, most of whom are treated with drugs. Reports have indicated that the majority of antiepileptic drugs on the market can cause rhabdomyolysis. Although rhabdomyolysis induced by antiepileptic drugs is a rare condition with a low incidence, this condition has serious consequences and merits attention from clinicians.

  12. Severe overdosage with the antiepileptic drug oxcarbazepine

    Science.gov (United States)

    van Opstal, J M; Janknegt, R; Cilissen, J; L’Ortije, W H V M; Nel, J E; De Heer, F

    2004-01-01

    Few published human data are available concerning the acute toxicity of the new antiepileptic drug oxcarbazepine of which the metabolite 10- monohydroxy derivate (MHD) is the pharmacologically effective compound. Two hours after a documented overdosage of more than 100 tablets oxcarbazepine, the serum level of the parent compound was 10-fold higher than the therapeutic dosage (31.6 mg l−1). However, the concentration of MHD, which peaked 7 h after intake, was only twofold higher (59.0 mg l−1). No life-threatening situations occurred and the patient fully recovered. The fact that oxcarbazepine is a prodrug and that the formation of the active MHD metabolite is a rate-limiting process may contribute to the relative low toxicity of the drug in overdose. PMID:15327594

  13. Treatment of hypopituitarism in patients receiving antiepileptic drugs.

    Science.gov (United States)

    Paragliola, Rosa Maria; Prete, Alessandro; Kaplan, Peter W; Corsello, Salvatore Maria; Salvatori, Roberto

    2015-02-01

    Evidence suggests that there may be drug interactions between antiepileptic drugs and hormonal therapies, which can present a challenge to endocrinologists dealing with patients who have both hypopituitarism and neurological diseases. Data are scarce for this subgroup of patients; however, data for the interaction of antiepileptic drugs with the pituitary axis have shown that chronic use of many antiepileptic drugs, such as carbamazepine, oxcarbazepine, and topiramate, enhances hepatic cytochrome P450 3A4 (CYP3A4) activity, and can decrease serum concentrations of sex hormones. Other antiepileptic drugs increase sex hormone-binding globulin, which reduces the bioactivity of testosterone and estradiol. Additionally, the combined oestrogen-progestagen contraceptive pill might decrease lamotrigine concentrations, which could worsen seizure control. Moreover, sex hormones and their metabolites can directly act on neuronal excitability, acting as neurosteroids. Because carbamazepine and oxcarbazepine can enhance the sensitivity of renal tubules, a reduction in desmopressin dose might be necessary in patients with central diabetes insipidus. Although the effects of antiepileptic drugs in central hypothyroidism have not yet been studied, substantial evidence indicates that several antiepileptic drugs can increase thyroid hormone metabolism. However, although it is reasonable to expect a need for a thyroxine dose increase with some antiepileptic drugs, the effect of excessive thyroxine in lowering seizure threshold should also be considered. There are no reports of significant interactions between antiepileptic drugs and the efficacy of human growth hormone therapy, and few data are available for the effects of second-generation antiepileptic drugs on hypopituitarism treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Assessing suicidal risk with antiepileptic drugs

    Directory of Open Access Journals (Sweden)

    Marco Mula

    2010-09-01

    Full Text Available Marco Mula2, Gail S Bell1, Josemir W Sander1,31Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, and National Hospital for Neurology and Neurosurgery, UCL Hospitals NHS Foundation Trust, London, United Kingdom; 2Department of Clinical and Experimental Medicine, Division of Neurology, Amedeo Avogadro University, University Hospital Maggiore della Carità, Novara, Italy; 3SEIN – Epilepsy Institute in the Netherlands Foundation, Heemstede, The NetherlandsAbstract: Recently, the US Food and Drug Administration issued an alert about an increased risk for suicidality during treatment with antiepileptic drugs (AEDs for different indications, including epilepsy. We discuss the issue of suicide in epilepsy with special attention to AEDs and the assessment of suicide in people with epilepsy. It has been suggested that early medical treatment with AEDs might potentially reduce suicide risk of people with epilepsy, but it is of great importance that the choice of drug is tailored to the mental state of the patient. The issue of suicidality in epilepsy is likely to represent an example of how the underdiagnosis of psychiatric symptoms, the lack of input from professionals (eg, psychologists, social workers, and psychiatrists, and the delay in an optimized AED therapy may worsen the prognosis of the condition with the occurrence of severe complications such as suicide.Keywords: epilepsy, suicide, adverse effect, depression

  15. The challenges of treating epilepsy with 25 antiepileptic drugs.

    Science.gov (United States)

    Santulli, Lia; Coppola, Antonietta; Balestrini, Simona; Striano, Salvatore

    2016-05-01

    Nowadays a substantial armamentarium of antiepileptic drugs (AEDs) is available, including drugs with different mechanisms of action, pharmacokinetics, efficacy and tolerability; therefore the choice for the right treatment is often challenging. The specific characteristic of the drug, the epileptic syndrome, seizure types and the patient's features need to be taken into consideration driving the choice through available evidence-based studies, which are often lacking for older AEDs. Besides, study conditions in registered clinical trials (RCTs) are quite different from daily clinical practice, which is more complex and various. When dealing with first diagnosed epilepsy, monotherapy is widely accepted as the gold standard option. Likewise, alternative monotherapy should be considered when the first drug treatment fails. However, the association of different AEDs in polytherapy is a common practice. The choice of AEDs used in association is often based on clinical experience or anecdotal observations or small clinical studies. Polytherapy should be as "rational" as possible and consider the mechanism of action, the pharmacokinetic characteristics and the safety of each drug. When dealing with drug resistant patients, clinicians should never give up and consider the use of AEDs acting on new targets. An attempt to come back to a monotherapy or simpler therapeutic regimen should be pursued even in patients who were previously drug resistant. This review will focus on the strategies to treat epilepsy by choosing among 25 available drugs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Pharmacokinetics of Anti-Epileptic Drugs and their Clinical Significance

    Directory of Open Access Journals (Sweden)

    Svein I. Johannessen

    1990-01-01

    Full Text Available The serum concentration achieved and maintained following the administration of a fixed drug dosage is a direct consequence of the interactions of a wide variety of interrelated processes, including drug absorption, distribution, metabolism, and excretion, and the physiological status of the patient. These interrelationships are reviewed with specific reference to the major anti-epileptic drugs, phenobarbitone, phenytoin, sodium valproate, and carbamazepine, as well as a new first-line antiepileptic, oxcarbazepine. Both older drugs, such as phenobarbitone and phenytoin, and newer drugs, such as carbamazepine (CBZ and sodium valproate, have been studied extensively over the past years giving valuable information for drug treatment. An important feature of oxcarbazepine (OXC , which was developed through minimal changes in the structure of CBZ in order to improve on the tolerability of CBZ without sacrificing efficacy, is that its metabolites do not include the 11-epoxide which has been implicated in the side-effects of CBZ. In man, OXC is metabolized to a monohydroxy derivative which has independent anti-epileptic properties. OXC seems to lack several disadavantageous pharmacokinetic properties common to other major anti-epileptic drugs. OXC does not influence its own metabolism after repeated administration, in contrast to the auto-induction displayed by CBZ. The metabolism of OXC is not influenced by anti-epileptic co-medication and does not influence the kinetics of other anti-epileptic drugs – or if it does, then to a lesser extent than CBZ.

  17. Levels of Antiepileptic Drugs and the Ketogenic Diet

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    J Gordon Millichap

    2006-08-01

    Full Text Available Introduction of the ketogenic diet did not change the plasma levels of antiepileptic drugs in an open study of 51 children (mean age 6.6 years with refractory epilepsy studied at Karolinska University Hospital, Stockholm, Sweden.

  18. The effects of antiepileptic drugs on the growth of glioblastoma cell lines

    OpenAIRE

    Lee, Ching-Yi; Lai, Hung-Yi; Chiu, Angela; Chan, She-Hung; Hsiao, Ling-Ping; Lee, Shih-Tseng

    2016-01-01

    To determine the effects of antiepileptic drug compounds on glioblastoma cellular growth, we exposed glioblastoma cell lines to select antiepileptic drugs. The effects of selected antiepileptic drugs on glioblastoma cells were measured by MTT assay. For compounds showing significant inhibition, cell cycle analysis was performed. Statistical analysis was performed using SPSS. The antiepileptic compounds selected for screening included carbamazepine, ethosuximide, gabapentin, lamotrigine, levet...

  19. Basic Mechanisms of Action of the Antiepileptic Drugs

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    Kuzmanova R.

    2017-10-01

    Full Text Available Available antiepileptic drugs interact with a variety of different molecular targets. The mechanism of action of most anticonvulsants is most often complex with a number of affected regions. The combination of mechanisms of action of drugs in particular proportions can possibly determine the showcase of its antiepileptic activity. The common factor between the different supposed mechanisms for a number of drugs includes the possibility for modulating the excitatory and inhibitory neurotransmission through effects upon the voltage-gated ion channels, synaptic plasticity, heterogeneous receptors, and metabolism of neurotransmitters. There are controversial data on the extent to which a specific action can be the reason for the wholesome anticonvulsive characteristics of various medications, as well as the relation with the presence of undesired drug effects. The complexity of the action of some antiepileptic drugs creates conditions for optimal choice during therapy. In many cases, the insufficient familiarity with individual genetic differences and the disease related receptor damages can hinder defining a particular drug action. Characterizing the mechanisms of action of the present antiepileptic medications would increase the understanding for the pathophysiological mechanisms of epileptic seizures, as well as the development of new therapeutic strategies. The development of novel antiepileptic drugs and the ongoing research regarding the mechanism of action of established antiepileptic drugs, are continuously increasing the level of complexity in the spectrum of molecular targets relevant for epilepsy therapy. The current state of knowledge as well as the limitations in our understanding should guide future research aiming for a more detailed elucidation of the impact of genetics and pathophysiological mechanisms on interindividual differences in expression and function of antiepileptic drug targets.

  20. Antiepileptic drug poisoning: Three-year experience

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    Yahya Kemal Günaydın

    2015-01-01

    Conclusion: First generation antiepileptics are more toxic than SGAEs. In patients with serum carbamazepine level, particularly those over 30 mg/L, serious disorders of consciousness, cardiovascular toxicity, and metabolic disorders may occur. In VPA intoxication, there is a positive correlation between the serum VPA levels and ammonia levels. On account of this finding, one should be more careful about hyperammonemic hepatic encephalopathy as the serum VPA level rises.

  1. VNS Therapy versus the latest antiepileptic drug.

    Science.gov (United States)

    Ben-Menachem, Elinor; French, Jacqueline A

    2005-09-01

    Pro AED: The central issue in medical decision-making is risk-benefit assessment. Surgery of any type is still considered to be a major undertaking. To warrant these risks, the patient has a right to expect that they have a greater chance of a good outcome with an invasive therapy than with a non-invasive one. The main question is when, if ever, this becomes the case when comparing implantation of a VNS Therapy System versus adding an antiepileptic drug (AED)? After the first drug? The second? After all AEDs have failed? To date, no randomized trial comparing the addition of an AED against vagus nerve stimulation (VNS Therapy) has been undertaken, although several are currently being contemplated. Without this information, it is more difficult to make a case for early implementation of VNS Therapy. Unfortunately, few data are available regarding the potential for patients to become seizure-free after implantation of a VNS Therapy System. Another issue is side effects. It is important to remember that VNS Therapy also produces adverse events, albeit very different in character than those associated with AEDs, to which physicians have become accustomed. These include cough, dyspnea, pharyngitis, voice alteration and sleep apnea. A less frequently discussed, potentially negative consequence of VNS Therapy relates to the ability to obtain imaging of the patient. Patients who have undergone VNS Therapy System implantation are not candidates for imaging of the chest, breast, or abdomen. A second issue is that imaging of the brain can only be performed with MRI scanners that meet certain requirements, and as MRI technology develops, scanners meeting these requirements may become harder to find. However, to summarize, VNS Therapy is an excellent and useful treatment choice. Fortunately, the choice between AEDs and VNS Therapy is not an "either/or" decision. Each has a role in the treatment of patients with epilepsy, and the advantages and disadvantages of each should be

  2. Exposure to antiepileptic drugs and the risk of hip fracture: a case-control study

    DEFF Research Database (Denmark)

    Tsiropoulos, Ioannis; Andersen, Morten; Nymark, Tine

    2008-01-01

    PURPOSE: To investigate whether the use of antiepileptic drugs (AEDs) increases the risk of hip fracture. METHODS: We performed a case-control study using data from the Funen County (population 2004: 475,000) hip fracture register. Cases (n = 7,557) were all patients admitted to county hospitals...... with a hip fracture during the period 1996-2004. Controls (n = 27,575) were frequency matched by age and gender. Information on use of AEDs, other drugs, and hospital contacts was available from local registers. Odds ratios (ORs) with 95% confidence intervals (CI) for hip fracture were estimated...

  3. Antiepileptic drugs and risk of suicide: a nationwide study

    DEFF Research Database (Denmark)

    Olesen, J.B.; Hansen, Peter Riis; Erdal, Jesper

    2010-01-01

    Purpose Patients with epilepsy or psychiatric diseases have increased risk of suicide, but whether the risk is influenced by antiepileptic drug (AED) treatment is unclear. Studies have suggested that AEDs in general increase the risk of suicidal behaviour shortly after initiation. This study inve...

  4. The Effects of Antiepileptic Drugs on Classroom Performance

    Science.gov (United States)

    Titus, Jeffrey B.; Thio, Liu Lin

    2009-01-01

    Epilepsy is one of the most common neurological disorders in children, and it has been associated with an increased risk of cognitive, psychiatric, and learning problems. Although side effects of antiepileptic drugs (AEDs) have been long studied in adults, an understanding of how they manifest in children is only beginning to emerge. Careful…

  5. Co-prescription of antiepileptic drugs and contraceptives

    NARCIS (Netherlands)

    Wang, H.; Bos, J.H.; de Jong-van den Berg, L.T.

    Background: Enzyme-inducing antiepileptic drugs (AEDs) reduce the efficacy of oral contraceptives. Little is known of contraceptive practice among reproductive-age women who receive AEDs. Study Design: We explored the use of contraceptive methods among Dutch women aged 15 to 49 years with

  6. Pharmacodynamics and common drug-drug interactions of the third-generation antiepileptic drugs.

    Science.gov (United States)

    Stefanović, Srđan; Janković, Slobodan M; Novaković, Milan; Milosavljević, Marko; Folić, Marko

    2018-02-01

    Anticonvulsants that belong to the third generation are considered as 'newer' antiepileptic drugs, including: eslicarbazepine acetate, lacosamide, perampanel, brivaracetam, rufinamide and stiripentol. Areas covered: This article reviews pharmacodynamics (i.e. mechanisms of action) and clinically relevant drug-drug interactions of the third-generation antiepileptic drugs. Expert opinion: Newer antiepileptic drugs have mechanisms of action which are not shared with the first and the second generation anticonvulsants, like inhibition of neurotransmitters release, blocking receptors for excitatory amino acids and new ways of sodium channel inactivation. New mechanisms of action increase chances of controlling forms of epilepsy resistant to older anticonvulsants. Important advantage of the third-generation anticonvulsants could be their little propensity for interactions with both antiepileptic and other drugs observed until now, making prescribing much easier and safer. However, this may change with new studies specifically designed to discover drug-drug interactions. Although the third-generation antiepileptic drugs enlarged therapeutic palette against epilepsy, 20-30% of patients with epilepsy is still treatment-resistant and need new pharmacological approach. There is great need to explore all molecular targets that may directly or indirectly be involved in generation of seizures, so a number of candidate compounds for even newer anticonvulsants could be generated.

  7. [Therapeutic drug monitoring of three antiepileptic drugs - Back on twenty years of experience].

    Science.gov (United States)

    Serragui, Samira; Zalagh, Fatima; Tanani, Driss Soussi; Ouammi, Lahcen; Moussa, Latifa Ait; Badrane, Narjis; Bencheikh, Rachida Soulaymani

    2016-01-01

    The therapeutic drug monitoring (TDM) of antiepileptic drugs is a tool widely used in the management of epilepsy. In Morocco, this monitoring is carried out by the Centre Anti Poison et Pharmacovigilance (CAPM) since April 1995. This is a retrospective study spanning 20 years. It concerns the therapeutic drug monitoring of Phenobarbital (PB) of carbamazepine (CBZ) and valproic acid (VPA). Therapeutic drug monitoring of the 3 antiepileptic drugs represent 58.85% of all applications received by the CAPM. The dosage of PB was ranked first followed by that of CBZ and finally by the VPA. Weak demand for therapeutic drug monitoring in Morocco could be explained by the low number of neurologists in addition to social factors. With its affordable price by patients, PB is the most prescribed antiepileptic drug in our country, which explains the high demand for its dosage. As for the therapeutic drug monitoring of the antiepileptic drug, they were mainly related to age, the occurrence of adverse effects, the association antiepileptic drugs or in the case of verification of patient compliance. Efforts are required for promoting the interests of therapeutic drug monitoring of antiepileptic drug in the management of epilepsy in Morocco.

  8. Preventive Agents for Migraine: Focus on the Antiepileptic Drugs

    Directory of Open Access Journals (Sweden)

    R. Shahien

    2012-04-01

    Full Text Available Migraine is among the 10 most disabling disorders worldwide. It is characterized by episodes of moderate or severe headaches with various degree of disability, resulting in a considerable health burden upon the sufferers and their family. The objective of this article is to review the use of prophylaxis with antiepileptic drugs. Particular focus is given to their mechanism of action, metabolism, pharmacokinetics, safety profile, efficacy and to provide a summary of the most relevant clinical studies and patient preference.

  9. Pharmacokinetic aspects of the anti-epileptic drug substance vigabatrin

    DEFF Research Database (Denmark)

    Nøhr, Martha Kampp; Frølund, Sidsel; Holm, René

    2014-01-01

    are discussed in detail. Special focus is on the contribution of the proton-coupled amino acid transporter 1 (PAT1) for intestinal vigabatrin absorption. Furthermore, the review gives an overview of the pharmacokinetic parameters of vigabatrin across different species and drug-food and drug-drug interactions......Drug transporters in various tissues, such as intestine, kidney, liver and brain, are recognized as important mediators of absorption, distribution, metabolism and excretion of drug substances. This review gives a current status on the transporter(s) mediating the absorption, distribution......, metabolism and excretion properties of the anti-epileptic drug substance vigabatrin. For orally administered drugs, like vigabatrin, the absorption from the intestine is a prerequisite for the bioavailability. Therefore, transporter(s) involved in the intestinal absorption of vigabatrin in vitro and in vivo...

  10. Access to antiepileptic drug therapy in children in Camagüey Province, Cuba

    Science.gov (United States)

    Arencibia, Zeina Bárzaga; Leyva, Alberto López; Peña, Yordanka Mejías; Reyes, Alba Rosa González; Nápolez, Maurilys Acosta; Carbonell Perdomo, Demetrio; Manzano, Edita Fernández; Choonara, Imti

    2012-01-01

    Objective To describe access to antiepileptic drug therapy and estimate the prevalence of epilepsy in children in Camagüey Province, Cuba. Methods All the community pharmacies in the province were visited and information collected about the number of children receiving antiepileptic drugs in 2009. Availability and cost of each antiepileptic drug were determined. The prevalence of epilepsy was estimated by determining the number of children receiving antiepileptic drugs. Results There were 923 children who received a total of 977 antiepileptic drugs in Camagüey Province. The estimated prevalence of epilepsy was 5.18 per thousand children which is lower than previously reported rates in other low and lower-middle income countries. Most of the children (871, 94%) received a single antiepileptic drug. Carbamazepine and valproate were the two most frequently prescribed antiepileptic drugs. Antiepileptic drugs were available from the local pharmacy on 76% of occasions. If the antiepileptic drug was not available from the local pharmacy, the parent had to travel to another pharmacy to obtain the medicine. Conclusions The estimated prevalence of epilepsy in children in Cuba is lower than that estimated in other lower-middle income countries. Access to drug therapy in children with epilepsy can be achieved in lower-middle income countries. PMID:23134098

  11. The effect of antiepileptic drugs on cognitive functions

    Directory of Open Access Journals (Sweden)

    A. S. Kotov

    2013-01-01

    Full Text Available Impaired cognitive function is a common problem in epileptic patients. The exact cause of cognitive impairment in case of epilepsy has not been explored fully, but there is no doubt that a role in this is played by three factors: the disease underlying epilepsy; epileptic seizures proper; and negative side effects of antiepileptic drugs. Their cognitive effects are one of the major problems affecting the tolerance of therapy. The review considers the effects of phenobarbital, phenytoin, carbamazepine, valproates, oxcarbazepine, topiramate, lamotrigine, and levetiracetam in terms of their action on the cognitive function of healthy volunteers and epileptic patients.

  12. Antiepileptic drugs targeting sodium channels: subunit and neuron-type specific interactions

    NARCIS (Netherlands)

    Qiao, X.

    2013-01-01

    Certain antiepileptic drugs (e.g. carbamazepine and lamotrigine) block sodium channels in an use-dependent manner and this mechanism contributes to the anti-convulsant properties of these drugs. There are, however, subtle differences in sodium current blocking properties of the antiepileptic drugs

  13. Enzyme induction in neonates after fetal exposure to antiepileptic drugs

    International Nuclear Information System (INIS)

    Rating, D.; Jaeger-Roman, E.; Nau, H.; Kuhnz, W.; Helge, H.

    1983-01-01

    The 13 C-AP breath test is shown to be a convenient, noninvasive method to monitor velocity and capacity of P450-dependent AP N-demethylation in infancy and childhood. According to 13 C-AP breath tests, neonates have a very low capacity to eliminate 13 CO 2 , which is only 15 to 21% of the activity in adults. During the first year of life AP N-demethylation increases to reach its maximum at about 2 years; afterwards a slight decrease occurs. In 25 neonates exposed prenatally to different antiepileptic drugs 13 C-AP breath test was efficiently used to prove that cytochrome AP N-demethylation was considerably stimulated. After primidone/phenobarbitone, especially in combination with phenytoin, 13 C elimination reaches and even surpasses the range for older children. Valproate exposure during fetal life is not consistently followed by a significant increase in AP N-demethylation. The enzyme induction demonstrated by 13 C-AP breath test was often accompanied by accelerated metabolic clearance and shortened half-life times of transplacentally acquired antiepileptic drugs. There was good agreement between 13 C-AP breath tests and pharmacokinetic data for primidone/phenobarbitone but not for phenytoin. In contrast, in the case of phenytoin exposure during pregnancy the pharmacokinetic parameters and the 13 C breath test data will transport very different informations about enzyme induction in these neonates

  14. Challenges in the clinical development of new antiepileptic drugs.

    Science.gov (United States)

    Franco, Valentina; French, Jacqueline A; Perucca, Emilio

    2016-01-01

    Despite the current availability in the market of over two dozen antiepileptic drugs (AEDs), about one third of people with epilepsy fail to achieve complete freedom from seizures with existing medications. Moreover, currently available AEDs have significant limitations in terms of safety, tolerability and propensity to cause or be a target for clinically important adverse drug interactions. A review of the evidence shows that there are many misperceptions about the viability of investing into new therapies for epilepsy. In fact, there are clear incentives to develop newer and more efficacious medications. Developing truly innovative drugs requires a shift in the paradigms for drug discovery, which is already taking place by building on greatly expanded knowledge about the mechanisms involved in epileptogenesis, seizure generation, seizure spread and development of co-morbidities. AED development can also benefit by a review of the methodology currently applied in clinical AED development, in order to address a number of ethical and scientific concerns. As discussed in this article, many processes of clinical drug development, from proof-of-concept-studies to ambitious programs aimed at demonstrating antiepileptogenesis and disease-modification, can be facilitated by a greater integration of preclinical and clinical science, and by application of knowledge acquired during decades of controlled epilepsy trials. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Trigeminal neuralgia: successful antiepileptic drug combination therapy in three refractory cases

    Directory of Open Access Journals (Sweden)

    Prisco L

    2011-08-01

    Full Text Available Lara Prisco1, Mario Ganau2, Federica Bigotto1, Francesca Zornada11Department of Anaesthesiology, Intensive Care and Emergency Medicine, University Hospital of Cattinara, 2Graduate School of Nanotechnology, University of Trieste, ItalyAbstract: Antiepileptic drug combination therapy remains an empirical second-line treatment approach in trigeminal neuralgia, after treatment with one antiepileptic drug or other nonantiepileptic drugs have failed. The results in three patients followed in our clinic are not sufficient to draw definitive conclusions, but suggest the possibility of developing this type of therapeutic approach further.Keywords: trigeminal neuralgia, antiepileptic drugs, combination therapy

  16. The new generation of antiepileptic drugs: advantages and disadvantages.

    Science.gov (United States)

    Perucca, E

    1996-11-01

    1. After a hiatus of over 20 years, several new antiepileptic drugs (vigabatrin, lamotrigine, gabapentin, oxcarbazepine, topiramate, felbamate, zonisamide and tiagabine) have reached or approached the registration phase. 2. Compared with older agents, many new drugs exhibit simpler pharmacokinetics. This is especially true for vigabatrin and gabapentin, which are renally eliminated and have a low interaction potential. 3. Unlike most of the older agents, vigabatrin, lamotrigine, gabapentin and tiagabine are devoid of significant enzyme inducing or inhibiting properties. Topiramate, oxcarbazepine and felbamate may induce the metabolism of steroid oral contraceptives. In addition, felbamate also acts as a metabolic inhibitor. 4. To date, the efficacy of new drugs has been evaluated extensively only under add-on conditions in patients with partial seizures (with or without secondary generalization) refractory to conventional treatment. However, there is evidence that lamotrigine, zonisamide, felbamate and, possibly, topiramate may also be effective in generalized epilepsies. 5. In placebo-controlled studies, typically between 15 and 40% of patients with difficult-to-treat partial epilepsy have shown an improvement (defined as a 50% or greater decrease in seizure frequency) after addition of a new drug. Only a small minority of these patients achieved complete seizure control. 6. Compared with older agents, some of the new drugs may have a better tolerability profile. Felbamate, however, has been associated with a high risk of aplastic anaemia and hepatotoxicity. 7. At present, the main use of the new agents is in patients refractory to first-line drugs such as carbamazepine or valproate, and further studies are required to characterize their activity spectrum as well as their potential value in monotherapy. In most patients, new drugs cannot be recommended for first-line use until evidence is obtained that potential advantages in tolerability or ease of use outweigh

  17. Selected pharmacokinetic issues of the use of antiepileptic drugs and parenteral nutrition in critically ill patients

    Directory of Open Access Journals (Sweden)

    Abd Arwa Y

    2010-12-01

    Full Text Available Abstract Objectives To conduct a systematic review for the evidence supporting or disproving the reality of parenteral nutrition- antiepileptic drugs interaction, especially with respect to the plasma protein-binding of the drug. Methods The articles related to the topic were identified through Medline and PubMed search (1968-Feburary 2010 for English language on the interaction between parenteral nutrition and antiepileptic drugs; the search terms used were anti-epileptic drugs, parenteral nutrition, and/or interaction, and/or in vitro. The search looked for prospective randomized and nonrandomized controlled studies; prospective nonrandomized uncontrolled studies; retrospective studies; case reports; and in vitro studies. Full text of the articles were then traced from the Universiti Sains Malaysia (USM library subscribed databases, including Wiley-Blackwell Library, Cochrane Library, EBSCOHost, OVID, ScienceDirect, SAGE Premier, Scopus, SpringerLINK, and Wiley InterScience. The articles from journals not listed by USM library were traced through inter library loan. Results There were interactions between parenteral nutrition and drugs, including antiepileptics. Several guidelines were designed for the management of illnesses such as traumatic brain injuries or cancer patients, involving the use of parenteral nutrition and antiepileptics. Moreover, many studies demonstrated the in vitro and in vivo parenteral nutrition -drugs interactions, especially with antiepileptics. Conclusions There was no evidence supporting the existence of parenteral nutrition-antiepileptic drugs interaction. The issue has not been studied in formal researches, but several case reports and anecdotes demonstrate this drug-nutrition interaction. However, alteration in the drug-free fraction result from parenteral nutrition-drug (i.e. antiepileptics interactions may necessitate scrupulous reassessment of drug dosages in patients receiving these therapies. This

  18. Selected pharmacokinetic issues of the use of antiepileptic drugs and parenteral nutrition in critically ill patients.

    Science.gov (United States)

    Salih, Muhannad R M; Bahari, Mohd Baidi; Abd, Arwa Y

    2010-12-31

    To conduct a systematic review for the evidence supporting or disproving the reality of parenteral nutrition- antiepileptic drugs interaction, especially with respect to the plasma protein-binding of the drug. The articles related to the topic were identified through Medline and PubMed search (1968-Feburary 2010) for English language on the interaction between parenteral nutrition and antiepileptic drugs; the search terms used were anti-epileptic drugs, parenteral nutrition, and/or interaction, and/or in vitro. The search looked for prospective randomized and nonrandomized controlled studies; prospective nonrandomized uncontrolled studies; retrospective studies; case reports; and in vitro studies. Full text of the articles were then traced from the Universiti Sains Malaysia (USM) library subscribed databases, including Wiley-Blackwell Library, Cochrane Library, EBSCOHost, OVID, ScienceDirect, SAGE Premier, Scopus, SpringerLINK, and Wiley InterScience. The articles from journals not listed by USM library were traced through inter library loan. There were interactions between parenteral nutrition and drugs, including antiepileptics. Several guidelines were designed for the management of illnesses such as traumatic brain injuries or cancer patients, involving the use of parenteral nutrition and antiepileptics. Moreover, many studies demonstrated the in vitro and in vivo parenteral nutrition -drugs interactions, especially with antiepileptics. There was no evidence supporting the existence of parenteral nutrition-antiepileptic drugs interaction. The issue has not been studied in formal researches, but several case reports and anecdotes demonstrate this drug-nutrition interaction. However, alteration in the drug-free fraction result from parenteral nutrition-drug (i.e. antiepileptics) interactions may necessitate scrupulous reassessment of drug dosages in patients receiving these therapies. This reassessment may be particularly imperative in certain clinical situations

  19. Short-term use of antiepileptic drugs is neurotoxic to the immature brain

    Directory of Open Access Journals (Sweden)

    Yu Liu

    2015-01-01

    Full Text Available Previous studies have shown that the long-term use of antiepileptic drugs can cause nervous system damage. However, short-term antiepileptic drug treatment is frequently given to infants, especially neonates, to control seizure. Whether the short-term use of antiepileptic drugs is neurotoxic remains unclear. In the present study, immature rats, 3-21 days of age, were intraperitoneally injected with phenobarbital and/or topiramate for 3 consecutive days. Hematoxylin-eosin and immunohistochemical staining revealed that phenobarbital and topiramate, individually or in combination, were cytotoxic to hippocampal CA1 neurons and inhibited the expression of GluR1 and NR2B, excitatory glutamate receptor subunits. Furthermore, the combination of the two drugs caused greater damage than either drug alone. The results demonstrate that the short-term use of antiepileptic drugs damages neurons in the immature brain and that the combined use of antiepileptic drugs exacerbates damage. Our findings suggest that clinicians should consider the potential neurotoxic risk associated with the combined use of antiepileptic drugs in the treatment of seizure.

  20. Brivaracetam: a novel antiepileptic drug for focal-onset seizures.

    Science.gov (United States)

    Stephen, Linda J; Brodie, Martin J

    2018-01-01

    Brivaracetam (BRV), the n -propyl analogue of levetiracetam (LEV), is the latest antiepileptic drug (AED) to be licensed in Europe and the USA for the adjunctive treatment of focal-onset seizures with or without secondary generalization in patients aged 16 years or older. Like LEV, BRV binds to synaptic vesicle protein 2A (SV2A), but BRV has more selective binding and a 15- to 30-fold higher binding affinity than LEV. BRV is more effective than LEV in slowing synaptic vesicle mobilization and the two AEDs may act at different binding sites or interact with different conformational states of the SV2A protein. In animal models, BRV provides protection against focal and secondary generalized seizures and has significant anticonvulsant effects in genetic models of epilepsy. The drug undergoes first-order pharmacokinetics with an elimination half-life of 7-8 h. Although BRV is metabolized extensively, the main circulating compound is unchanged BRV. Around 95% of metabolites undergo renal elimination. No dose reduction is required in renal impairment, but it is recommended that the daily dose is reduced by one-third in hepatic dysfunction that may prolong half-life. BRV has a low potential for drug interactions. The efficacy and tolerability of adjunctive BRV in adults with focal-onset seizures have been explored in six randomized, placebo-controlled studies. These showed significant efficacy outcomes for doses of 50-200 mg/day. The most common adverse events reported were headache, somnolence, dizziness, fatigue and nausea. Patients who develop psychiatric symptoms with LEV appear to be at risk of similar side effects with BRV, although preliminary data suggest that these issues are likely to be less frequent and perhaps less severe. As with all AEDs, a low starting dose and slow titration schedule help to minimize side effects and optimize seizure control and thereby quality of life.

  1. Epilepsy, Antiepileptic Drugs, and Aggression: An Evidence-Based Review

    Science.gov (United States)

    Besag, Frank; Ettinger, Alan B.; Mula, Marco; Gobbi, Gabriella; Comai, Stefano; Aldenkamp, Albert P.; Steinhoff, Bernhard J.

    2016-01-01

    Antiepileptic drugs (AEDs) have many benefits but also many side effects, including aggression, agitation, and irritability, in some patients with epilepsy. This article offers a comprehensive summary of current understanding of aggressive behaviors in patients with epilepsy, including an evidence-based review of aggression during AED treatment. Aggression is seen in a minority of people with epilepsy. It is rarely seizure related but is interictal, sometimes occurring as part of complex psychiatric and behavioral comorbidities, and it is sometimes associated with AED treatment. We review the common neurotransmitter systems and brain regions implicated in both epilepsy and aggression, including the GABA, glutamate, serotonin, dopamine, and noradrenaline systems and the hippocampus, amygdala, prefrontal cortex, anterior cingulate cortex, and temporal lobes. Few controlled clinical studies have used behavioral measures to specifically examine aggression with AEDs, and most evidence comes from adverse event reporting from clinical and observational studies. A systematic approach was used to identify relevant publications, and we present a comprehensive, evidence-based summary of available data surrounding aggression-related behaviors with each of the currently available AEDs in both adults and in children/adolescents with epilepsy. A psychiatric history and history of a propensity toward aggression/anger should routinely be sought from patients, family members, and carers; its presence does not preclude the use of any specific AEDs, but those most likely to be implicated in these behaviors should be used with caution in such cases. PMID:27255267

  2. Antiepileptic drugs in pregnancy and hemorrhagic disease of the newborn: An update

    OpenAIRE

    Kazmin, Aleksey; Wong, Renee C.; Sermer, Mathew; Koren, Gideon

    2010-01-01

    QUESTION What is the current evidence regarding the association between hemorrhagic disease of the newborn and maternal use of hepatic enzyme-inducing antiepileptic drugs (eg, carbamazepine, phenobarbitone, topiramate)?

  3. Effect of Antiepileptic Drugs for Acute and Chronic Seizures in Children with Encephalitis.

    Directory of Open Access Journals (Sweden)

    Kuang-Lin Lin

    Full Text Available Encephalitis presents with seizures in the acute phase and increases the risk of late unprovoked seizures and epilepsy. This study aimed to evaluate the effect of antiepileptic drugs in pediatric patients with acute seizures due to encephalitis and epilepsy.Cases of acute pediatric encephalitis between January 2000 and December 2010 were reviewed. Clinical data, including onset at age, seizure type, seizure frequency, effects of antiepileptic drugs, and prognosis were analyzed.During the study period, 1038 patients (450 girls, 588 boys were enrolled. Among them, 44.6% (463 had seizures in the acute phase, 33% had status epilepticus, and 26% (251 developed postencephalitic epilepsy. At one year of follow-up, 205 of the 251 patients with postencephalitic epilepsy were receiving antiepileptic drugs while 18% were seizure free even after discontinuing the antiepileptic drugs. Among those with postencephalitic epilepsy, 67% had favorable outcomes and were using <2 anti-epileptic drugs while 15% had intractable seizures and were using ≥ 2 antiepileptic drugs. After benzodiazepines, intravenous phenobarbital was preferred over phenytoin as treatment of postencephalitic seizures in the acute phase. For refractory status epilepticus, high-dose topiramate combined with intravenous high-dose phenobarbital or high-dose lidocaine had less side effects.Children with encephalitis have a high rate of postencephalitic epilepsy. Phenobarbital and clonazepam are the most common drugs used, alone or in combination, for postencephalitic epilepsy.

  4. Strategies for improving adherence to antiepileptic drug treatment in people with epilepsy.

    Science.gov (United States)

    Al-Aqeel, Sinaa; Gershuni, Olga; Al-Sabhan, Jawza; Hiligsmann, Mickael

    2017-02-03

    Poor adherence to antiepileptic medication is associated with increased mortality, morbidity and healthcare costs. In this review, we focus on interventions designed and tested in randomised controlled trials and quasi-randomised controlled trials to assist people with adherence to antiepileptic medication. This is an updated version of the original Cochrane review published in the Cochrane Library, Issue 1, 2010. To determine the effectiveness of interventions aimed at improving adherence to antiepileptic medication in adults and children with epilepsy. For the latest update, on 4 February 2016 we searched the Cochrane Epilepsy Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO), MEDLINE (Ovid 1946 to 4 February 2016), CINAHL Plus (EBSCOhost 1937 to 4 February 2016), PsycINFO (EBSCOhost 1887 to 4 February 2016), ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform. We also searched the reference lists of relevant articles. Randomised and quasi-randomised controlled trials of adherence-enhancing interventions aimed at people with a clinical diagnosis of epilepsy (as defined in individual studies), of any age and treated with antiepileptic drugs in a primary care, outpatient or other community setting. All review authors independently assessed lists of potentially relevant citations and abstracts. At least two review authors independently extracted data and performed quality assessment of each study according to the Cochrane tool for assessing risk of bias. We graded the level of evidence for each outcome according to the GRADE working group scale.The studies differed widely according to the type of intervention and measures of adherence; therefore combining data was not appropriate. We included 12 studies reporting data on 1642 participants (intervention = 833, control = 809). Eight studies targeted adults with epilepsy, one study included participants

  5. Current status of the New Antiepileptic drugs in chronic pain.

    Directory of Open Access Journals (Sweden)

    Harpreet Singh Sidhu

    2016-08-01

    Full Text Available Antiepileptic drugs (AEDs are extensively used worldwide to treat a wide range of disorders other than epilepsy, such as neuropathic pain, migraine and bipolar disorder. Due to this situation more than 20 new third-generation AEDs have been introduced in the market recently. The future design of new AEDs must also have potential to help in the non-epileptic disorders. The wide acceptance of second generation AEDs for the management of various Non-epileptic disorders has caused the emergence of generics in the market. The wide use of approved AEDs outside epilepsy is based on both economic and scientific reasons. Bipolar disorders, migraine prophylaxis, fibromyalgia and neuropathic pain represent the most attractive indication expansion opportunities for anticonvulsant developers, providing blockbuster revenues. Strong growth in non-epilepsy conditions will see Pfizer’s Lyrica become the market leading brand by 2018. In this review we mainly focus on the current status of new AEDs in the treatment of chronic pain and migraine prophylaxis. AEDs have a strong analgesic potential and this is demonstrated by the wide use of carbamazepine in trigeminal neuralgia and sodium valproate in migraine prophylaxis. At present, data on the new AEDs for non-epileptic conditions are inconclusive. Not all AEDs are effective in the management of neuropathic pain and migraine. Only those AEDs whose mechanisms of action are match with pathophysiology of the disease, have potential to show efficacy in non-epileptic disorder. For this better understanding of the pathophysiology of the disease and mechanisms of action of new AEDs are essential requirement before initiating pre-clinical and clinical trials. Many new AEDs show good results in the animal model and open-label studies but fail to provide strong evidence at randomized, placebo-controlled trials. The final decision regarding the clinical efficacy of the particular AEDs in a specific non-epileptic disorder

  6. Fracture risk associated with use of antiepileptic drugs.

    Science.gov (United States)

    Vestergaard, Peter; Rejnmark, Lars; Mosekilde, Leif

    2004-11-01

    To assess fracture risk associated with different antiepileptic drugs (AEDs). An increased fracture risk has been reported in patients with epilepsy. Classical AEDs have been associated with decreased bone mineral density. The effects of newer AEDs are unknown. We undertook a population-based pharmacoepidemiologic case-control study with any fracture as outcome and use of AEDs as exposure variables (124,655 fracture cases and 373,962 controls). All AEDs were associated with an increased fracture risk in an unadjusted analysis. After adjustment for prior fracture, use (ever) of corticosteroids, comorbidity, social variables, and diagnosis of epilepsy, carbamazepine [CBZ; odds ratio (OR), 1.18; 95% confidence interval (CI), 1.10-1.26], [and oxcarbazepine (OXC; 1.14, 1.03-1.26)], clonazepam (CZP; 1.27, 1.15-1.41), phenobarbital (PB; 1.79, 1.64-1.95), and valproate (VPA; 1.15, 1.05-1.26) were statistically significantly associated with risk of any fracture. Ethosuximide (0.75, 0.37-1.52), lamotrigine (1.04, 0.91-1.19), phenytoin (1.20, 1.00-1.43), primidone (1.18, 0.95-1.48), tiagabine (0.75, 0.40-1.41), topiramate (1.39, 0.99-1.96), and vigabatrin (0.93, 0.70-1.22) were not statistically significantly associated with fracture risk after adjustment for confounders. The relative increase was modest and in the same range for the significant and nonsignificant results. CBZ, PB, OXC, and VPA displayed a dose-response relation. Fracture risk was more increased by liver-inducing AEDs (OR, 1.38; 95% CI, 1.31-1.45) than by noninducing AEDs (1.19; 95% CI, 1.11-1.27). A very limited increased fracture risk is present in users of CBZ, CZP, OXC, PB, and VPA. A limited significant increase cannot be excluded for the other AEDs because of the statistical power.

  7. Analysis of antiepileptic drugs in biological fluids by means of electrokinetic chromatography.

    Science.gov (United States)

    Pucci, Vincenzo; Raggi, Maria Augusta

    2005-02-01

    An overview of the electrokinetic chromatographic methods for the analysis of antiepileptic drug levels in biological samples is presented. In particular, micellar electrokinetic capillary chromatography is a very suitable method for the determination of these drugs, because it allows a rapid, selective, and accurate analysis. In addition to the electrokinetic chromatographic studies on the determination of antiepileptic drugs, some information regarding sample pretreatment will also be reported: this is a critical step when the analysis of biological fluids is concerned. The electrokinetic chromatographic methods for the determination of recent antiepileptic drugs (e.g., lamotrigine, levetiracetam) and classical anticonvulsants (e.g., carbamazepine, phenytoin, ethosuximide, valproic acid) will be discussed in depth, and their pharmacological profiles will be briefly described as well.

  8. Comparative study of antiepileptic drug use during pregnancy over a period of 12 years in Spain. Efficacy of the newer antiepileptic drugs lamotrigine, levetiracetam, and oxcarbazepine.

    Science.gov (United States)

    Martinez Ferri, M; Peña Mayor, P; Perez López-Fraile, I; Escartin Siquier, A; Martin Moro, M; Forcadas Berdusan, M

    2018-03-01

    The prescription pattern of antiepileptic drugs (AEDs) during pregnancy is changing but to what extent this is occurring in Spain remains unknown. The efficacy of newer drugs for controlling seizures is a key issue and may have changed over the years as doctors gained familiarity with these drugs during pregnancy. To assess these 2 topics, we report the results from the Spanish EURAP register gathered over a 12-year period. After signing informed consent forms, patients were included in the register and evaluated at onset of pregnancy, at the end of the second and third trimesters, after delivery, and one year after delivery. For the purposes of this study, we analysed AEDs, type of epilepsy, seizure frequency per trimester and throughout pregnancy, percentage of seizure-free pregnancies, and frequency of congenital malformations. We then compared data from 2 periods (June 2001-October 2007) and (January 2008-May 2015) RESULTS: We compared 304 monotherapies from the older period to 127 from the more recent one. There was a clear increase in the use of levetiracetam (LEV) with declining use of carbamazepine (CBZ), phenytoin, and phenobarbital; a slight decline in use of valproate (VPA), and a slight increase in the use of lamotrigine (LTG) and oxcarbazepine (OXC). Epilepsy types treated with CBZ and VPA remained unchanged, whereas fewer cases of generalised epilepsy were treated with LTG in the new period. This trend was not associated with significant changes in seizure frequency, but rather linked to better control over de novo seizures in the third trimester. LEV was similar to CBZ and VPA with regard to levels of seizure control, and more effective than LTG. Generalised epilepsy accounted for 64% of the cases treated with LEV. The prescription pattern of AEDs during pregnancy has changed in Spain, with diminishing use of CBZ, phenytoin, and phenobarbital. Changes also reflect the type of epilepsy, since there is less use of LTG for generalised epilepsy. LEV

  9. Antiepileptic drugs for chronic non-cancer pain in children and adolescents.

    Science.gov (United States)

    Cooper, Tess E; Wiffen, Philip J; Heathcote, Lauren C; Clinch, Jacqui; Howard, Richard; Krane, Elliot; Lord, Susan M; Sethna, Navil; Schechter, Neil; Wood, Chantal

    2017-08-05

    Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online, MEDLINE via Ovid, and Embase via Ovid from inception to 6 September 2016. We also searched the reference lists of retrieved studies and reviews as well as online clinical trial registries. Randomised controlled trials, with or without blinding, by any route, treating chronic non-cancer pain in children and adolescents, comparing any antiepileptic drug with placebo or an active comparator. Two review authors independently assessed studies for eligibility. We planned to use dichotomous data to calculate risk ratio and number needed to treat for one additional event, using standard methods if data were available. We assessed the evidence using GRADE and created two 'Summary of findings' tables. We included two studies with a total of 141 participants (aged 7 to 18 years) with chronic neuropathic pain, complex regional pain syndrome type 1 (CRPS-I), or fibromyalgia. One study investigated pregabalin versus placebo in participants with fibromyalgia (107 participants), and the other study investigated gabapentin versus amitriptyline in participants with CRPS-I or neuropathic pain (34 participants). We were unable to perform any quantitative analysis.Risk of bias for the two included studies varied, due to issues with randomisation (low to unclear risk), blinding of outcome assessors (low to unclear risk), reporting bias (low to unclear risk), the size of the study populations (high risk), and industry funding in the 'other' domain (low to unclear risk). We judged the remaining domains of sequence generation, blinding of participants and personnel, and attrition as low risk of bias. Primary outcomesOne study (gabapentin 900 mg/day versus amitriptyline 10 mg/day, 34 participants, for 6 weeks) did not report our primary outcomes (very low-quality evidence).The second study (pregabalin 75 to 450 mg/day versus placebo 75 to 450 mg/day, 107 participants, for 15 weeks) reported no

  10. Selection criteria for the clinical use of the newer antiepileptic drugs.

    NARCIS (Netherlands)

    Deckers, C.L.P.; Knoester, P.D.; Haan, G.J. de; Keyser, A.J.M.; Renier, W.O.; Hekster, Y.A.

    2003-01-01

    In recent years, several new antiepileptic drugs (AEDs) have been licensed: felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, vigabatrin and zonisamide. These drugs have proven efficacy as add-on therapy in patients with difficult-to-treat partial epilepsy, as

  11. Human placental perfusion method in the assessment of transplacental passage of antiepileptic drugs

    International Nuclear Information System (INIS)

    Myllynen, Paeivi; Pienimaeki, Paeivi; Vaehaekangas, Kirsi

    2005-01-01

    Epilepsy is one of the most common neurological diseases, affecting about 0.5 to 1% of pregnant women. It is commonly accepted that older antiepileptic drugs bear teratogenic potential. So far, no agreement has been reached about the safest antiepileptic drug during pregnancy. It is known that nearly all drugs cross the placenta at least to some extent. Nowadays, there is very little information available of the pharmacokinetics of drugs in the feto-placental unit. Detailed information about drug transport across the placenta would be valuable for the development of safe and effective treatments. For reasons of safety, human studies on placental transfer are restricted to a limited number of drugs. Interspecies differences limit the extrapolation of animal data to humans. Several in vitro methods for the study of placental transfer have been developed over the past decades. The placental perfusion method is the only experimental method that has been used to study human placental transfer of substances in organized placental tissue. The aim of this article is to review human placental perfusion data on antiepileptic drugs. According to perfusion data, it seems that most of the antiepileptic drugs are transferred across the placenta meaning significant fetal exposure

  12. Cross-National comparison of antiepileptic drug use: Catalonia, Denmark and Norway, 2007-2011

    Directory of Open Access Journals (Sweden)

    Pili Ferrer-Argeles

    2014-07-01

    Full Text Available Background: Antiepileptic drug  (AEDconsumption has increased in recent years mainly from those AEDs marketed since 1990. The purpose is to describe and compare AED consumption in Catalonia, Denmark and Norway.Methods: Population-based descriptive study set in the outpatient healthcare sector. Data were retrieved from the Norwegian Prescription Register, Danish Register of Medicinal Product Statistics and DATAMART® in Catalonia, for 2007-2011.We calculated defined daily doses/1000 inhabitants/day (DID, by age and gender. AEDs were defined according to the Anatomical Therapeutic Chemical classification (N03A. We reviewed the population covered by the databases, the drug data source and the definition of outpatient healthcare sector to compare the results across the three settings.Results: Total AED use steadily increased over the study period in the three settings. In 2011, consumption was highest in Catalonia (15.20 DID, followed by Denmark (15.06 DID and Norway (14.24 DID. The “other AEDs” (N03AX subgroup represented 60% of all AED use. The N03A pattern by gender did not differ across the three settings. Marked differences by age and gender appeared when studying lamotrigine, topiramate, gabapentin, pregabalin and levetiracetam.  Differences among the databases were mainly in the definition of outpatient healthcare setting.Conclusions: There was a rapid increase in “other AEDs” in all three settings. Although we did not have information on the indication for the use of AEDs, the drug data source, population coverage of the database and definition of the healthcare setting helped us interpret the results.

  13. Derangement of lipid profile in antiepileptic drugs treated patients in local population

    International Nuclear Information System (INIS)

    Zuberi, N.A.; Perveen, T.

    2012-01-01

    Epilepsy is the third most common neurological disorder. It is not a single entity. The abnormal electrical activity may result in a variety of events, including loss of consciousness, abnormal movements, a typical or odd behavior or distorted perceptions falls seizers. Epilepsy is a chronic disorder and often requiring years of treatment. A large number of drugs are used for the treatment of epilepsy. The choice among the antiepileptic drugs depends on its effectiveness and side effects. Our retrospective study investigated the effect of anti epileptic drugs on lipid profile. Serum lipid profile was measured in 160 patients in which 40 patients were not started any antiepileptic drug .The remaining 120 patients were receiving antiepileptic drugs (AEDs). 40 control subjects were taken from general population for comparison. The height, weight and body mass index (BMI) and lipid profile of antiepileptic drugs treated patients were compared with control and untreated group. The weight and body mass index of antiepileptic drugs treated group was significantly increased when compared to the control group. Total Cholesterol (TC), Triglyceride (TO), High density lipoprotein (HDL-C), low density lipoprotein (LDL-C), ratio TC/HDL-C and ratio LDL-C/HDL-C were investigated for each group of drugs and controls. TC, TO, LDL-C, ratio TC/HDL-C and ratio LDL-C/HDL-C were significantly increased in patients who were on AEDs when compared with control but HDL-C of all drug treated groups showed significantly decreased when compared with control group. There was significant change in lipid profile was seen in AEDs treated group when compared with control group. Ratio TC/HDL-C and ratio LDUHDL-C alteration showed the risk of atherosclerosis and cardiovascular diseases. Anti-epileptic drugs also alter the BMI and so it could potentially facilitate the development of diabetes mellitus. Our results additionally suggest that there is a need for careful monitoring of lipid profile in

  14. Antiepileptic Drug Behavioral Side Effects in Individuals with Mental Retardation and the Use of Behavioral Measurement Techniques.

    Science.gov (United States)

    Kalachnik, John E.; And Others

    1995-01-01

    Behavioral psychology measurement methods helped assess antiepileptic drug behavioral side effects in five individuals with mental retardation who could not verbally communicate presence of side effects. When the suspected antiepileptic drug was altered, an 81% reduction of maladaptive behaviors occurred. The measurement methods enabled systematic…

  15. Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry

    DEFF Research Database (Denmark)

    Tomson, Torbjörn; Battino, Dina; Bonizzoni, Erminio

    2011-01-01

    Prenatal exposure to antiepileptic drugs is associated with a greater risk of major congenital malformations, but there is inadequate information on the comparative teratogenicity of individual antiepileptic drugs and the association with dose. We aimed to establish the risks of major congenital ...

  16. Co-morbidity and clinically significant interactions between antiepileptic drugs and other drugs in elderly patients with newly diagnosed epilepsy.

    Science.gov (United States)

    Bruun, Emmi; Virta, Lauri J; Kälviäinen, Reetta; Keränen, Tapani

    2017-08-01

    A study was conducted to investigate the frequency of potential pharmacokinetic drug-to-drug interactions in elderly patients with newly diagnosed epilepsy. We also investigated co-morbid conditions associated with epilepsy. From the register of Kuopio University Hospital (KUH) we identified community-dwelling patients aged 65 or above with newly diagnosed epilepsy and in whom use of the first individual antiepileptic drug (AED) began in 2000-2013 (n=529). Furthermore, register data of the Social Insurance Institution of Finland were used for assessing potential interactions in a nationwide cohort of elderly subjects with newly diagnosed epilepsy. We extracted all patients aged 65 or above who had received special reimbursement for the cost of AEDs prescribed on account of epilepsy in 2012 where their first AED was recorded in 2011-2012 as monotherapy (n=1081). Clinically relevant drug interactions (of class C or D) at the time of starting of the first AED, as assessed via the SFINX-PHARAO database, were analysed. Hypertension (67%), dyslipidemia (45%), and ischaemic stroke (32%) were the most common co-morbid conditions in the hospital cohort of patients. In these patients, excessive polypharmacy (more than 10 concomitant drugs) was identified in 27% of cases. Of the patients started on carbamazepine, 52 subjects (32%) had one class-C or class-D drug interaction and 51 (31%) had two or more C- or D-class interactions. Only 2% of the subjects started on valproate exhibited a class-C interaction. None of the subjects using oxcarbazepine displayed class-C or class-D interactions. Patients with 3-5 (OR 4.22; p=0.05) or over six (OR 8.86; p=0.003) other drugs were more likely to have C- or D-class interaction. The most common drugs with potential interactions with carbamazepine were dihydropyridine calcium-blockers, statins, warfarin, and psychotropic drugs. Elderly patients with newly diagnosed epilepsy are at high risk of clinically relevant pharmacokinetic

  17. COST ANALYSIS OF LONG ESTABLISHED AND NEWER ORAL ANTIEPILEPTIC DRUGS AVAILABLE IN THE INDIAN MARKET

    Directory of Open Access Journals (Sweden)

    Phatak Abhishek M, Hotwani Jitendra H, Deshmukhkiran R, Panchal Sagar S, Naik Madhura S

    2015-10-01

    Full Text Available Background: Large number of pharmaceutical companies manufactures antiepileptic drugs in India. The price variations among the marketed drugs are wide. Aims: The present study was aimed to find the cost of different oral antiepileptic drugs available in Indian market as monotherapy, combination therapy and number of manufacturing companies for each, to evaluate difference in cost of different brands of same dosage of same active drug by calculating percentage variation of cost. Methods and Materials: Cost of a drug being manufactured by different companies, in the same strength and dosage forms was obtained from “Indian Drug Review” Vol. XXI, Issue No.4, 2014 and “Current Index of Medical Specialties” July-October 2014. The difference in the maximum and minimum price of the same drug manufactured by different pharmaceutical companies and percentage variation in price was calculated. Results: The percentage price variation noted of long-established drugs was – Phenytoin (50mg: 140%, Carbamazepine (100mg: 1033%, Phenobarbital (30mg : 730%, Valproic acid (300mg : 420%. Newer drugs –Levetiracetam (250mg: 75%, Lamotrigine (25mg: 66%, Topiramate (50mg: 108%, Zonisamide (100mg: 19%. Combination drugs – Phenobarbital + Phenytoin (30+100 mg: 354.55%. Conclusion: The percentage price variation of different brands of the same commonly used long-established oral antiepileptic drug manufactured in India is very wide. The formulation or brand of Antiepileptic drugs (AED’s should preferably not be changed since variations in bioavailability or different pharmacokinetic profiles may increase the potential for reduced effect or excessive side effects. Hence, manufacturing companies should aim to decrease the price variation while maintaining the therapeutic efficacy.

  18. Selection of Antiepileptic Drug Polytherapy Based on Mechanisms of Action: The Evidence Reviewed

    NARCIS (Netherlands)

    Deckers, C.L.P.; Czuczwar, S.J.; Hekster, Y.A.; Keyser, A.J.M.; Kubova, H.; Meinardi, H.; Patsalos, P.N.; Renier, W.O.; Rijn, C.M. van

    2000-01-01

    Purpose: When monotherapy with antiepileptic drugs (AEDs) fails, combination therapy is tried so as to improve effectiveness, by improving either efficacy, or tolerability, or both. We have reviewed the available studies (both animal and human) on AED polytherapy to determine whether AEDs can be

  19. Intelligence quotient improves after antiepileptic drug withdrawal following pediatric epilepsy surgery

    NARCIS (Netherlands)

    Boshuisen, Kim; van Schooneveld, Monique M. J.; Uiterwaal, Cuno S. P. M.; Cross, J. Helen; Harrison, Sue; Polster, Tilman; Daehn, Marion; Djimjadi, Sarina; Yalnizoglu, Dilek; Turanli, Guzide; Sassen, Robert; Hoppe, Christian; Kuczaty, Stefan; Barba, Carmen; Kahane, Philippe; Schubert-Bast, Susanne; Reuner, Gitta; Bast, Thomas; Strobl, Karl; Mayer, Hans; de Saint-Martin, Anne; Seegmuller, Caroline; Laurent, Agathe; Arzimanoglou, Alexis; Braun, Kees P. J.

    ObjectiveAntiepileptic drugs (AEDs) have cognitive side effects that, particularly in children, may affect intellectual functioning. With the TimeToStop (TTS) study, we showed that timing of AED withdrawal does not majorly influence long-term seizure outcomes. We now aimed to evaluate the effect of

  20. Chronic antiepileptic drug use and functional network efficiency : a functional magnetic resonance imaging study

    NARCIS (Netherlands)

    van Veenendaal, T.M.; IJff, D.M.; Aldenkamp, A.P.; Lazeron, R.H.C.; Hofman, P.A.M.; de Louw, A.J.A.; Backes, W.H.; Jansen, J.F.A.

    2017-01-01

    AIM: To increase our insight in the neuronal mechanisms underlying cognitive side-effects of antiepileptic drug (AED) treatment. METHODS: The relation between functional magnetic resonance-acquired brain network measures, AED use, and cognitive function was investigated. Three groups of patients

  1. Antiepileptic drug use in seven electronic health record databases in Europe: a methodological comparison.

    NARCIS (Netherlands)

    Groot, M.C.H. de; Schuerch, M.; Vries, F. de; Hesse, U.; Oliva, B.; Huerta Alvarez, C.; Gil, M.; Requena, G.; Abajo, F.; Afonso, A.; Souverein, P.C.; Alvarez, Y.; Slattery, J.; Rottenkolber, M.; Schmiedl, S.; Dijk, L. van; Schlienger, R.; Reynolds, R.; Klungel, O.

    2013-01-01

    Background: The annual prevalence of antiepileptic drug (AED) prescribing reported in the literature differs considerably among European countries; this may be due to differences in type of data sources, time periods, population distributions, and methodology. Objectives: To assess the prevalence of

  2. Antiepileptic drug use in seven electronic health record databases in europe: A methodological comparison

    NARCIS (Netherlands)

    De Groot, Mark C.H.; Schuerch, Markus; De Vries, Frank; Hesse, Ulrik; Oliva, Belén; Alvarez, Consuelo Huerta; Gil, Miguel; Requena, Gema; Abajo, Francisco; Afonso, Ana; Souverein, Patrick C.; Alvarez, Yolanda; Slattery, Jim; Rottenkolber, Marietta; Schmiedl, Sven; Van Dijk, Liset; Schlienger, Raymond G.; Reynolds, Robert; Klungel, Olaf

    2013-01-01

    Background: The annual prevalence of antiepileptic drug (AED) prescribing reported in the literature differs considerably among European countries; this may be due to differences in type of data sources, time periods, population distributions, and methodology. Objectives: To assess the prevalence of

  3. The Use of Antiepileptic Drugs (AEDs) for the Treatment of Pediatric Aggression and Mood Disorders

    OpenAIRE

    Munshi, Kaizad R.; Oken, Tanya; Guild, Danielle J.; Trivedi, Harsh K.; Wang, Betty C.; Ducharme, Peter; Gonzalez-Heydrich, Joseph

    2010-01-01

    Aggressive symptomatology presents across multiple psychiatric, developmental, neurological and behavioral disorders, complicating the diagnosis and treatment of the underlying pathology. Anti-Epileptic Drugs (AEDs) have become an appealing alternative in the treatment of aggression, mood lability and impulsivity in adult and pediatric populations, although few controlled trials have explored their efficacy in treating pediatric populations. This review of the literature synthesizes the avail...

  4. [Social aspects of epilepsy: marriage, pregnancy, driving, antiepileptic drug withdrawal and against social stigma].

    Science.gov (United States)

    Tsuji, Sadatoshi

    2004-11-01

    Persons with epilepsy need adequate advice and effective counselling about issues such as marriage, pregnancy, risks of inheriting epilepsy, driving, employment and antiepileptic drug withdrawal, because these persons are not receiving important information and education about their condition and possible adverse effects of treatment. Furthermore, women with epilepsy have increased rates of pregnancy complications and poor fetal outcomes including congenital malformations and developmental delay related to both their epilepsy and antiepileptic drugs. However, approximately 90% of all women with epilepsy undergo normal pregnancy and give birth to children free of birth defects. Pregnancy is generally safe in women with epilepsy. The study of long-term prognosis of childhood-onset epilepsy in Japan shows that the majority of these patients have lower levels of educational background as well as employment and marital status compared with the general population (Wakamoto H. et al). Of patients with epilepsy, 60% to 70% achieve control with antiepileptic medication. However, several antiepileptic drug withdrawal studies show variable rates of success, with relapse rates ranging from 12% to 63% (Britton J.W.). Driving is listed as major problem in persons with epilepsy. However, the patients with seizure-free more than two years have been able to get the driver's license since June, 2002. Social attitudes towards epilepsy cause more distress to the patient than the disease itself. We should realize that persons with epilepsy are normal or near-normal. To ameliorate the social stigma against epilepsy, continuous and repetitive educational efforts would be needed.

  5. Drug Interactions between some antiepileptic and certain hypocholesterolaemic drugs in irradiated animals

    International Nuclear Information System (INIS)

    Shaaban, D.M.L.

    2015-01-01

    Drug Interactions between antiepileptic drug such as phenytoin and certain hypercholesterolaemia drug namely rosuvastatin were investigated on several biological parameters. Phenytoin (60 mg/kg i.p) and rosuvastatin (1.25 mg/kg i.p) were given either alone and in combination to normal and irradiated animals to investigate drug interactions between the test drugs. Anticonvulsant activity was evaluated using pentylenetetrazole in a dose (80 mg/kg i.p) in normal and irradiated mice. Brain neurotransmitters (glutamate and GABA) were investigated. Lipid profile (total cholesterol (TC), Triacylglycerol (TG), High density lipoprotein-cholesterol (HDL-C) and low density lipoprotein- cholesterol (LDL-C) were determined. Liver functions such as serum Aspartate amino transferase (AST) and serum alanine amino transferase (ALT) were also estimated. Oxidative stress bio markers namely serum malondialdehyde (MDA), serum nitric oxide (NO) and blood superoxide dismutase activity (SOD) were studied. Histopathological examinations of brain and liver tissues were performed. Administration of phenytoin concurrently with rosuvastatin is not recommended in patients receiving radiotherapy as dangerous side effects on liver functions and lipid profile may occur. The interactions between the two drugs in normal rats improve liver functions and lipid peroxidation. Apart from the action of the combination on total cholesterol, it improves lipid profile pattern. Rosuvastatin administration in combination with phenytoin may have additive anticonvulsant activity.

  6. [Antiepileptic drugs in the control of the impulses disorders].

    Science.gov (United States)

    Roncero, C; Rodríguez-Urrutia, A; Grau-López, L; Casas, M

    2009-01-01

    The disorders classified as control of the impulses; explosive intermittent disorder, pathological gambling, kleptomania, pyromania, pathological gambling, hair pullers, compulsive purchases, skin picking and onychophagia are a heterogeneous set of clinical entities, most of them with little prevalence. Nevertheless, they cause important personal and social dysfunctions and present great comorbidity with other psychiatric disorders. Antipsychotics, antidepressive agents, serotoninergic agonists, naltrexone, beta blockers antiandrogen, lithium and anticonvulsants have been used in their pharmacological treatment. Currently, interest is growing on the use of the antiepileptics because their possible usefulness has been described in these disorders. However, the neurobiological effects are only partially known in some cases. We have reviewed the literature regarding the treatment of these disorders with mood stabilizers, (lithium, carbamazepine, valproate, phenitoin, oxcarbacepin, topiramate, lamotrigin, leviteracetam) and have described those studies on which the current knowledge and evidence are based. The results must be considered as provisional and must be updated in the future, since they are mostly based on case reports, case series or opened clinical trials, their being little knowledge based on double blind clinical trials.

  7. Reduced Adult Hippocampal Neurogenesis and Cognitive Impairments following Prenatal Treatment of the Antiepileptic Drug Valproic Acid

    Directory of Open Access Journals (Sweden)

    Berry Juliandi

    2015-12-01

    Full Text Available Prenatal exposure to valproic acid (VPA, an established antiepileptic drug, has been reported to impair postnatal cognitive function in children born to VPA-treated epileptic mothers. However, how these defects arise and how they can be overcome remain unknown. Using mice, we found that comparable postnatal cognitive functional impairment is very likely correlated to the untimely enhancement of embryonic neurogenesis, which led to depletion of the neural precursor cell pool and consequently a decreased level of adult neurogenesis in the hippocampus. Moreover, hippocampal neurons in the offspring of VPA-treated mice showed abnormal morphology and activity. Surprisingly, these impairments could be ameliorated by voluntary running. Our study suggests that although prenatal exposure to antiepileptic drugs such as VPA may have detrimental effects that persist until adulthood, these effects may be offset by a simple physical activity such as running.

  8. Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data.

    Science.gov (United States)

    Nevitt, Sarah J; Sudell, Maria; Weston, Jennifer; Tudur Smith, Catrin; Marson, Anthony G

    2017-12-15

    Epilepsy is a common neurological condition with a worldwide prevalence of around 1%. Approximately 60% to 70% of people with epilepsy will achieve a longer-term remission from seizures, and most achieve that remission shortly after starting antiepileptic drug treatment. Most people with epilepsy are treated with a single antiepileptic drug (monotherapy) and current guidelines from the National Institute for Health and Care Excellence (NICE) in the United Kingdom for adults and children recommend carbamazepine or lamotrigine as first-line treatment for partial onset seizures and sodium valproate for generalised onset seizures; however a range of other antiepileptic drug (AED) treatments are available, and evidence is needed regarding their comparative effectiveness in order to inform treatment choices. To compare the time to withdrawal of allocated treatment, remission and first seizure of 10 AEDs (carbamazepine, phenytoin, sodium valproate, phenobarbitone, oxcarbazepine, lamotrigine, gabapentin, topiramate, levetiracetam, zonisamide) currently used as monotherapy in children and adults with partial onset seizures (simple partial, complex partial or secondary generalised) or generalised tonic-clonic seizures with or without other generalised seizure types (absence, myoclonus). We searched the following databases: Cochrane Epilepsy's Specialised Register, CENTRAL, MEDLINE and SCOPUS, and two clinical trials registers. We handsearched relevant journals and contacted pharmaceutical companies, original trial investigators, and experts in the field. The date of the most recent search was 27 July 2016. We included randomised controlled trials of a monotherapy design in adults or children with partial onset seizures or generalised onset tonic-clonic seizures (with or without other generalised seizure types). This was an individual participant data (IPD) review and network meta-analysis. Our primary outcome was 'time to withdrawal of allocated treatment', and our secondary

  9. Epileptic seizure, as the first symptom of hypoparathyroidism in children, does not require antiepileptic drugs

    OpenAIRE

    Liu, Meng-Jia; Li, Jiu-Wei; Shi, Xiu-Yu; Hu, Lin-Yan; Zou, Li-Ping

    2016-01-01

    Objective Patients with hypoparathyroidism exhibit metabolic disorders (hypocalcemia) and brain structural abnormalities (brain calcifications). Currently, studies have determined whether antiepileptic drug (AED) treatment is required for epileptic seizures in children with hypoparathyroidism. Method This study aims to evaluate the data of two medical centers in Beijing based on the diagnosis of epileptic seizures as the first symptom of hypoparathyroidism in children. Result A total of 42 pa...

  10. Inhibition of human aromatase complex (CYP19) by antiepileptic drugs

    DEFF Research Database (Denmark)

    Jacobsen, Naja Wessel; Halling-Sørensen, Bent; Birkved, Franziska Maria A Kramer

    2008-01-01

    of 1.4-49.7 mM. Carbamazepine, gabapentin, primidone, topiramate and vigabatrin showed no inhibition. Additionally, binary drug combinations were tested to investigate if combination therapy could potentiate the aromatase inhibition. Additive inhibition was seen in combination experiments...... with valproate and phenobarbital. When adding carbamazepine to a range of valproate concentrations no additional inhibition was seen. The data for some of the AEDs show that side effects on steroid synthesis in humans due to inhibition of aromatase should be considered....

  11. The role side effects play in the choice of antiepileptic therapy in brain tumor-related epilepsy: a comparative study on traditional antiepileptic drugs versus oxcarbazepine

    Directory of Open Access Journals (Sweden)

    Carapella Maria Carmine

    2009-05-01

    Full Text Available Abstract Background Seizure control doesn't represent the only challenging goal in patients with brain tumor-related epilepsy. Side effects have often taken precedence for patients' quality of life. Methods We performed an observational retrospective study on patients with brain tumor-related epilepsy: 35 who had assumed oxcarbazepine monotherapy and 35 patients who had undergone treatment with traditional antiepileptic drugs. Primary variable of efficacy was the mean seizure frequency per month and safety variables were the drop-out for side effects and total incidence of side effects. We applied the Propensity Score technique to minimize selection bias. Results Our results showed a similar efficacy of oxcarbazepine and traditional antiepileptic drugs over time, but the difference in safety and tolerability between the two groups was significant: traditional AEDs caused more side effects, both serious and non serious. Conclusion This study highlights the importance of taking into consideration not only seizure control but also the appearance of side effects when choosing antiepileptic drugs in this patients population.

  12. The role side effects play in the choice of antiepileptic therapy in brain tumor-related epilepsy: a comparative study on traditional antiepileptic drugs versus oxcarbazepine

    Science.gov (United States)

    Maschio, Marta; Dinapoli, Loredana; Vidiri, Antonello; Pace, Andrea; Fabi, Alessandra; Pompili, Alfredo; Carapella, Maria Carmine; Jandolo, Bruno

    2009-01-01

    Background Seizure control doesn't represent the only challenging goal in patients with brain tumor-related epilepsy. Side effects have often taken precedence for patients' quality of life. Methods We performed an observational retrospective study on patients with brain tumor-related epilepsy: 35 who had assumed oxcarbazepine monotherapy and 35 patients who had undergone treatment with traditional antiepileptic drugs. Primary variable of efficacy was the mean seizure frequency per month and safety variables were the drop-out for side effects and total incidence of side effects. We applied the Propensity Score technique to minimize selection bias. Results Our results showed a similar efficacy of oxcarbazepine and traditional antiepileptic drugs over time, but the difference in safety and tolerability between the two groups was significant: traditional AEDs caused more side effects, both serious and non serious. Conclusion This study highlights the importance of taking into consideration not only seizure control but also the appearance of side effects when choosing antiepileptic drugs in this patients population. PMID:19419544

  13. Neuronal and non-neuronal GABA transporters as targets for antiepileptic drugs

    DEFF Research Database (Denmark)

    Madsen, Karsten K; White, H Steve; Schousboe, Arne

    2010-01-01

    of transmembrane transport and enzymatic degradation. The development of tiagabine selectively inhibiting the GABA transporter GAT1 constitutes a proof of concept that the GABA transporters are interesting drug targets in the context of antiepileptic drugs. The review provides a detailed analysis of the role......,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol) has been shown to possess a novel anticonvulsant profile in animal models of epilepsy, involving the ability to inhibit GABA transport mediated by GAT1 and BGT1 at the same time....

  14. Prenatal exposure to antiepileptic drugs and dental agenesis.

    Directory of Open Access Journals (Sweden)

    Pernille E Jacobsen

    Full Text Available OBJECTIVE: The aim of the study was to investigate the association between prenatal exposure to AEDs and the risk of dental agenesis and to differentiate between the possible effects of the different drugs used. METHODS: Data on 214 exposed and 255 unexposed children, aged 12-18 years, were extracted from the Prescription Database of the Central Denmark Region and North Denmark Region and the Danish Medical Birth Registry. The children's dental charts were examined for the presence of dental agenesis. RESULTS: Overall, children exposed to AED in utero had an increased risk of developing dental agenesis, but as a group, the difference was not significant (OR = 1.7; [95% CI: 0.8-3.6]. The risk of developing dental agenesis was three-fold increased (OR = 3.1; [95% CI: 1.3-7.4] in children exposed to valproate in mono- or in poly-therapy with other AEDs than carbamazepine or oxcarbazepine. The risk was further increased (OR = 11.2; [95% CI: 2.4-51.9] in children exposed to valproate and carbamazepine or oxcarbazepine in combination. CONCLUSIONS: The present study shows that dental agenesis is a potential congenital abnormality that is related to prenatal exposure to valproate, and dental agenesis may be considered a sensitive marker for the teratogenicity of valproate.

  15. Brain Graph Topology Changes Associated with Anti-Epileptic Drug Use

    Science.gov (United States)

    Levin, Harvey S.; Chiang, Sharon

    2015-01-01

    Abstract Neuroimaging studies of functional connectivity using graph theory have furthered our understanding of the network structure in temporal lobe epilepsy (TLE). Brain network effects of anti-epileptic drugs could influence such studies, but have not been systematically studied. Resting-state functional MRI was analyzed in 25 patients with TLE using graph theory analysis. Patients were divided into two groups based on anti-epileptic medication use: those taking carbamazepine/oxcarbazepine (CBZ/OXC) (n=9) and those not taking CBZ/OXC (n=16) as a part of their medication regimen. The following graph topology metrics were analyzed: global efficiency, betweenness centrality (BC), clustering coefficient, and small-world index. Multiple linear regression was used to examine the association of CBZ/OXC with graph topology. The two groups did not differ from each other based on epilepsy characteristics. Use of CBZ/OXC was associated with a lower BC. Longer epilepsy duration was also associated with a lower BC. These findings can inform graph theory-based studies in patients with TLE. The changes observed are discussed in relation to the anti-epileptic mechanism of action and adverse effects of CBZ/OXC. PMID:25492633

  16. Safety Profile of the Newest Antiepileptic Drugs: A Curated Literature Review.

    Science.gov (United States)

    Palleria, Caterina; Cozza, Giuseppe; Khengar, Rajeshree; Libri, Vincenzo; De Sarro, Giovambattista

    2017-01-01

    Despite the introduction of new antiepileptic drugs (AEDs), the quality of life and therapeutic response for patients with epilepsy remain unsatisfactory. In addition, whilst several antiepileptic drugs (AEDs) have been approved and consequently marketed in recent years, little is known about their long-term safety and tolerability. Availability of the newest AEDs, characterized by improved pharmacokinetic profiles, has positively impacted the treatment approach for patients with partial seizures in clinical practice. However, the main cause of treatment failure is still poor patient compliance due to the occurrence of adverse drug reactions (ADRs) that lead to treatment withdrawal in about 25% of cases before achieving maximal efficacy, and is associated with increasing health care costs. In this Review, we conducted an online database search using Medline, PubMed, Embase, and the Cochrane Online Library to review the available studies highlighting the clinical relevance of side effects, pharmacological interactions, safety and tolerability of the newest AEDs: Brivaracetam (BRV), Cannabidiol (CBD), Eslicarbazepine acetate (ESL), Lacosamide (LCM), and Perampanel (PER). The principal benefit of the newest AEDs, in addition to reduced frequency and seizure severity, is the low number and severity of ADRs reported compared to more historic drugs. Early detection of ADRs could lead to an improvement in patients' quality of life, therefore it is important to monitor ADRs and to adequately perform post marketing surveillance in the clinical practice setting. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Differential impact of contraceptive methods on seizures varies by antiepileptic drug category: Findings of the Epilepsy Birth Control Registry.

    Science.gov (United States)

    Herzog, Andrew G; Mandle, Hannah B; Cahill, Kaitlyn E; Fowler, Kristen M; Hauser, W Allen

    2016-07-01

    The aim of this study was to determine whether categories of contraception differ in their impact on seizures in women with epilepsy and whether the impact varies by antiepileptic drug category. Retrospective survey data came from 2712 contraceptive experiences reported by 1144 women with epilepsy. We compared risk ratios for reports of increase and decrease in seizure frequency on hormonal versus nonhormonal contraception, stratified by antiepileptic drug categories. More women with epilepsy reported a change in seizures on hormonal (28.2%) than on nonhormonal contraception (9.7%) (pcontraception (4.2%) was 4.47 (pcontraception (5.5%) was 1.71, pcontraception, the risk ratio for seizure increase was greater than for decrease (1.98, pmethod with a greater risk ratio for seizure decrease than combined pills. Seizure increase was greater for hormonal than nonhormonal contraception for each antiepileptic drug category (pcontraception, relative to the non-enzyme-inducing antiepileptic drug category which had the lowest rate, each of the other categories had significantly greater risks for seizure increase, especially the enzyme-inhibiting (valproate) category (risk ratio=2.53, p=0.0002). The findings provide community-based, epidemiological survey evidence that contraceptive methods may differ in their impact on seizures and that this impact may vary by antiepileptic drug category. Copyright © 2016. Published by Elsevier Inc.

  18. Individualized prediction of seizure relapse and outcomes following antiepileptic drug withdrawal after pediatric epilepsy surgery.

    Science.gov (United States)

    Lamberink, Herm J; Boshuisen, Kim; Otte, Willem M; Geleijns, Karin; Braun, Kees P J

    2018-03-01

    The objective of this study was to create a clinically useful tool for individualized prediction of seizure outcomes following antiepileptic drug withdrawal after pediatric epilepsy surgery. We used data from the European retrospective TimeToStop study, which included 766 children from 15 centers, to perform a proportional hazard regression analysis. The 2 outcome measures were seizure recurrence and seizure freedom in the last year of follow-up. Prognostic factors were identified through systematic review of the literature. The strongest predictors for each outcome were selected through backward selection, after which nomograms were created. The final models included 3 to 5 factors per model. Discrimination in terms of adjusted concordance statistic was 0.68 (95% confidence interval [CI] 0.67-0.69) for predicting seizure recurrence and 0.73 (95% CI 0.72-0.75) for predicting eventual seizure freedom. An online prediction tool is provided on www.epilepsypredictiontools.info/ttswithdrawal. The presented models can improve counseling of patients and parents regarding postoperative antiepileptic drug policies, by estimating individualized risks of seizure recurrence and eventual outcome. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.

  19. The Effect of Antiepileptic Drug of Lamotrigine, on the Function of Reproductive Hormones in Male Rats

    Directory of Open Access Journals (Sweden)

    R. Khezri Motlagh

    2016-08-01

    Full Text Available Introduction: Lamotrigine is one of the never anti-epileptic drug. In this study the effects of lamotrigine have been observed on serum concentration of LH (Luteinizing hormone, FSH (Follicle-stimulating hormone, testosterone ,body and testis weight in male rat. Methods: The animal used in this experiment were 40 adult male rat from wistar race which were divided in to 5 group of 8.consisting of control group which received nothings, Sham group which received 0.2 ml distilled water via oral. Experimental group which received 100, 200, 400 mg/kg lamotrigine via oral after 14th day body weight were measured in all group and then the blood sample was taken from heart and concentration of LH.FSH, testosterone was measured. In addition the testis were separated and testis weight were measured in all group. Results: The result show that concentration of LH in experimental group did not show significant difference in compared with control group but in experimental group received 400mg/kg of lamotrigine  show a significant decrease in concentration of FSH and testosterone in comparison with control group .In addition lamotrigine had effect and testis weight in middle and high dose was reduce. Conclusion: Lamotrigine, an antiepileptic drug, reduced reproductive activity by inhibiting of hypothalamic-pituitary-gonadal axis in adult male rats.

  20. The effect of depression and side effects of antiepileptic drugs on injuries in patients with epilepsy.

    Science.gov (United States)

    Gur-Ozmen, S; Mula, M; Agrawal, N; Cock, H R; Lozsadi, D; von Oertzen, T J

    2017-09-01

    People with epilepsy are at increased risk of accidents and injuries but, despite several studies on this subject, data regarding preventable causes are still contradictory. The aim of this study was to investigate the relationship between injuries, side effects of antiepileptic drugs (AEDs) and depression. Data from a consecutive sample of adult patients with epilepsy attending the outpatient clinics at St George's University Hospital in London were included. All patients were asked if they had had any injury since the last clinic appointment and completed the Liverpool Adverse Event Profile (LAEP) and Neurological Disorders Depression Inventory for Epilepsy. Among 407 patients (243 females, mean age 43.1 years), 71 (17.4%) reported injuries since the last appointment. A two-step cluster analysis revealed two clusters with the major cluster (53.5% of the injured group) showing a total score for LAEP ≥45, a positive Neurological Disorders Depression Inventory for Epilepsy screening and presence of AED polytherapy. A total score for LAEP ≥45 was the most important predictor. Antiepileptic drug treatment should be reviewed in patients reporting injuries in order to evaluate the potential contribution and burden of AED side effects. © 2017 EAN.

  1. A survey of antiepileptic drug responses identifies drugs with potential efficacy for seizure control in Wolf-Hirschhorn syndrome.

    Science.gov (United States)

    Ho, Karen S; Markham, Leah M; Twede, Hope; Lortz, Amanda; Olson, Lenora M; Sheng, Xiaoming; Weng, Cindy; Wassman, E Robert; Newcomb, Tara; Wassman, E Robert; Carey, John C; Battaglia, Agatino

    2018-04-01

    Seizures are present in over 90% of infants and children with Wolf-Hirschhorn syndrome (WHS). When present, they significantly affect quality of life. The goal of this study was to use caregiver reports to describe the comparative efficacies of commonly used antiepileptic medications in a large population of individuals with WHS. A web-based, confidential caregiver survey was developed to capture seizure semiology and a chronologic record of seizure treatments as well as responses to each treatment. Adverse events for each drug were also cataloged. We received 141 complete survey responses (47% response rate) describing the seizures of individuals ranging in age from 4months to 61years (90 females: 51 males). Using the Early Childhood Epilepsy Severity Scale (E-Chess), WHS-associated seizures are demonstrably severe regardless of deletion size. The best-performing antiepileptic drugs (AEDs) for controlling seizures in this cohort were broad spectrum drugs clobazam, levetiracetam, and lamotrigine; whereas, the three commonly used carboxamide class drugs: carbamazepine, phenytoin, and oxcarbazepine, were reported to have little effect on, or even exacerbate, seizures. The carboxamide class drugs, along with phenobarbital and topiramate, were also associated with the highest rate of intolerance due to cooccurrence of adverse events. Levetiracetam, clobazam, and clonazepam demonstrated higher tolerability and comparatively less severe adverse events (Wilcoxon rank sum comparison between performance of levetiracetam and carboxamide class drugs gives a psyndromes which may have complex seizure etiologies. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Successful Treatment of Antiepileptic Drug-Induced DRESS Syndrome with Pulse Methylprednisolone

    Directory of Open Access Journals (Sweden)

    Celebi Kocaoglu

    2013-01-01

    Full Text Available Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome is a rare but potentially life-threatening syndrome characterized by skin rash, fever, lymph node enlargement, and involvement of internal organs. It is most commonly induced by aromatic anticonvulsants and antibiotics. Nonaromatic anticonvulsants are rarely encountered as the causes of DRESS syndrome. In the present report, three discrete cases with DRESS syndrome developing due to three antiepileptic drugs, including valproic acid (nonaromatic, carbamazepine (aromatic, and lamotrigine (aromatic, and their treatment modalities were aimed to be discussed in light of the literature. To the best of our knowledge, our cases are the first children to be treated with pulse methylprednisolone in the literature.

  3. Importance of competing risks in the analysis of anti-epileptic drug failure

    Directory of Open Access Journals (Sweden)

    Sander Josemir W

    2007-03-01

    Full Text Available Abstract Background Retention time (time to treatment failure is a commonly used outcome in antiepileptic drug (AED studies. Methods Two datasets are used to demonstrate the issues in a competing risks analysis of AEDs. First, data collection and follow-up considerations are discussed with reference to information from 15 monotherapy trials. Recommendations for improved data collection and cumulative incidence analysis are then illustrated using the SANAD trial dataset. The results are compared to the more common approach using standard survival analysis methods. Results A non-significant difference in overall treatment failure time between gabapentin and topiramate (logrank test statistic = 0.01, 1 degree of freedom, p-value = 0.91 masked highly significant differences in opposite directions with gabapentin resulting in fewer withdrawals due to side effects (Gray's test statistic = 11.60, 1 degree of freedom, p = 0.0007 but more due to poor seizure control (Gray's test statistic = 14.47, 1 degree of freedom, p-value = 0.0001. The significant difference in overall treatment failure time between lamotrigine and carbamazepine (logrank test statistic = 5.6, 1 degree of freedom, p-value = 0.018 was due entirely to a significant benefit of lamotrigine in terms of side effects (Gray's test statistic = 10.27, 1 degree of freedom, p = 0.001. Conclusion Treatment failure time can be measured reliably but care is needed to collect sufficient information on reasons for drug withdrawal to allow a competing risks analysis. Important differences between the profiles of AEDs may be missed unless appropriate statistical methods are used to fully investigate treatment failure time. Cumulative incidence analysis allows comparison of the probability of failure between two AEDs and is likely to be a more powerful approach than logrank analysis for most comparisons of standard and new anti-epileptic drugs.

  4. Newer anti-epileptic drugs, vitamin status and neuropathy: A cross-sectional analysis.

    Science.gov (United States)

    Cahill, V; McCorry, D; Soryal, I; Rajabally, Y A

    Whether new antiepileptic drugs (AEDs) may result in neuropathy is unknown but possible given their effects on vitamin metabolism. This analysis aimed to determine frequency and correlates of neuropathy in subjects treated with new AEDs in relation to drug used, length of exposure and serum vitamin B12 and folate levels. We performed a cross-sectional study of 52 consecutive epileptic subjects. Presence of neuropathy was determined using the Utah Early Neuropathy Score (UENS). Exposure to anti-epileptic drugs was quantified. Serum vitamin B12 and folate levels were measured. Commonly used AEDs were levetiracetam (28/52), carbamazepine (20/52), lamotrigine (20/52), sodium valproate (10/52) and zonisamide (10/52). Eight of 52 (15.4%) patients had neuropathy. There was no association with any particular AED. Neuropathy correlated with age (P=0.038) and total exposure to AEDs (P=0.032). UENS correlated with age (P=0.001), total AED exposure (P=0.001) and serum vitamin B12L (P=0.018). Independent association of neuropathy was found with total AED exposure (P=0.032), but not age. UENS was independently associated with total exposure to AEDs (Pvitamin B12L (P=0.002), but not age. Serum vitamin B12 and folate levels were highly inter-correlated (Pvitamin B12 and folate metabolism. Although further research from controlled studies is needed and despite the presence of other possible confounding factors, monitoring for neuropathy and vitamin B12 and folate levels merits consideration in patients on long-term treatment with new AEDs. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  5. Development Enamel Defects in Children Prenatally Exposed to Anti-Epileptic Drugs

    DEFF Research Database (Denmark)

    Jacobsen, Pernille Endrup; Henriksen, Tine Brink; Haubek, Dorte

    2013-01-01

    Objective Some anti-epileptic drugs (AED) have well-known teratogenic effects. The aim of the present study was to elucidate the effect of prenatal exposure to AED and the risk of enamel defects in the primary and permanent dentition. Methods A total of 38 exposed and 129 non-exposed children, 6......–10 years of age, were recruited from the Aarhus Birth Cohort and the Department of Neurology, Viborg Regional Hospital, Denmark. Medication during pregnancy was confirmed by the Danish Prescription Database. All children had their teeth examined and outcomes in terms of enamel opacities and enamel...... hypoplasia were recorded. Results Children prenatally exposed to AED have an increased prevalence of enamel hypoplasia (11% vs. 4%, odds ratio (OR) = 3.6 [95% confidence interval (CI): 0.9 to 15.4]), diffuse opacities (18% vs. 7%, OR = 3.0; [95% CI: 1.0 to 8.7, p3) white opacities (18...

  6. The Risk of Specific Congenital Anomalies in Relation to Newer Antiepileptic Drugs

    DEFF Research Database (Denmark)

    de Jong, Josta; Garne, Ester; de Jong-van den Berg, Lolkje T.W.

    2016-01-01

    BACKGROUND: More information is needed about possible associations between the newer anti-epileptic drugs (AEDs) in the first trimester of pregnancy and specific congenital anomalies of the fetus. OBJECTIVES: We performed a literature review to find signals for potential associations between newer...... studies with pregnancies exposed to newer AEDs and detailed information on congenital anomalies. The congenital anomalies in the studies were classified according to the congenital anomaly subgroups of European Surveillance of Congenital Anomalies (EUROCAT). We compared the prevalence of specific...... and were not supported by other studies. No signals were found for the other newer AEDs, or the information was too limited to provide such a signal. CONCLUSION: In terms of associations between monotherapy with a newer AED in the first trimester of pregnancy and a specific congenital anomaly, the signals...

  7. Glucuronidation of antiepileptic drugs in women with epilepsy : on the role of age, steroid hormones and oral contraceptives

    NARCIS (Netherlands)

    Wegner, I.

    2013-01-01

    Epilepsy is a common neurological disorder with clinically important gender differences in both the expression and the impact of epilepsy. Understanding the complex interactions between sex hormones, epilepsy and antiepileptic drugs (AEDs) can greatly improve the care for women with epilepsy. This

  8. Utilization of antiepileptic drugs during pregnancy : Comparative patterns in 38 countries based on data from the EURAP registry

    NARCIS (Netherlands)

    Battino, D.; Bonizzoni, E.; Craig, J.; Lindhout, D.; Perucca, E.; Sabers, A.; Tomson, T.; Vajda, F.

    2009-01-01

    P>We assessed the utilization of antiepileptic drugs (AEDs), 1999-2005, in 4,798 prospective epilepsy pregnancies from 38 countries participating in EURAP, an international AED and pregnancy registry. Prominent differences in utilization patterns were observed across the various countries. Exposure

  9. Transient Splenial Lesion of Corpus Callosum Associated with Antiepileptic Drug: Conventional and Diffusion-weighted Magnetic Resonance Images

    Energy Technology Data Exchange (ETDEWEB)

    Hakyemez, B.; Erdogan, C.; Yildirim, N.; Gokalp, G.; Parlak, M. [Uludag Univ. Medical School, Bursa (Turkey). Dept. of Radiology

    2005-11-01

    Transient focal lesions of splenium of corpus callosum can be seen as a component of many central nervous system diseases, including antiepileptic drug toxicity. The conventional magnetic resonance (MR) findings of the disease are characteristic and include ovoid lesions with high signal intensity at T2-weighted MRI. Limited information exists about the diffusion-weighted MRI characteristics of these lesions vanishing completely after a period of time. We examined the conventional, FLAIR, and diffusion-weighted MR images of a patient complaining of depressive mood and anxiety disorder after 1 year receiving antiepileptic medication.

  10. Antiepileptic drug prescribing patterns in Iraq and Afghanistan war veterans with epilepsy.

    Science.gov (United States)

    Rohde, Natalie N; Baca, Christine B; Van Cott, Anne C; Parko, Karen L; Amuan, Megan E; Pugh, Mary Jo

    2015-05-01

    We examined patterns of antiepileptic drug (AED) use in a cohort of Iraq/Afghanistan war veterans (IAVs) who were previously identified as having epilepsy. We hypothesized that clinicians would be more likely to prescribe newer AEDs and would select specific AEDs to treat seizures based on patient characteristics including gender and comorbidities. From the cohort of IAVs previously identified with epilepsy between fiscal years 2009 and 2010, we selected those who received AEDs from the Veterans Health Administration in FY2010. Regimens were classified as monotherapy or polytherapy, and specific AED use was examine overall and by gender. Multivariable logistic regression examined associations of age; gender; race/ethnicity; medical, psychiatric, and neurological comorbidities; and receipt of neurology specialty care associated with the six most commonly used AEDs. Among 256,284 IAVs, 2123 met inclusion criteria (mean age: 33years; 89% men). Seventy-two percent (n=1526) received monotherapy, most commonly valproate (N=425) and levetiracetam (n=347). Sixty-one percent of those on monotherapy received a newer AED (levetiracetam, topiramate, lamotrigine, zonisamide, oxcarbazepine). Although fewer women than men received valproate, nearly 90% (N=45) were of reproductive age (≤45years). Antiepileptic drug prescribing patterns were associated with posttraumatic stress disorder, bipolar disorder, cerebrovascular disease, dementia/cognitive impairment, headache, and receipt of neurological specialty care (all p<0.01). In this cohort of veterans with epilepsy, most received AED monotherapy and newer AEDs. Prescribing patterns were different for men and women. The patterns observed between AEDs and neurological/psychiatric comorbidities suggest that clinicians are practicing rational prescribing. Copyright © 2015. Published by Elsevier Inc.

  11. NMDA Receptor Signaling Is Important for Neural Tube Formation and for Preventing Antiepileptic Drug-Induced Neural Tube Defects.

    Science.gov (United States)

    Sequerra, Eduardo B; Goyal, Raman; Castro, Patricio A; Levin, Jacqueline B; Borodinsky, Laura N

    2018-05-16

    Failure of neural tube closure leads to neural tube defects (NTDs), which can have serious neurological consequences or be lethal. Use of antiepileptic drugs (AEDs) during pregnancy increases the incidence of NTDs in offspring by unknown mechanisms. Here we show that during Xenopus laevis neural tube formation, neural plate cells exhibit spontaneous calcium dynamics that are partially mediated by glutamate signaling. We demonstrate that NMDA receptors are important for the formation of the neural tube and that the loss of their function induces an increase in neural plate cell proliferation and impairs neural cell migration, which result in NTDs. We present evidence that the AED valproic acid perturbs glutamate signaling, leading to NTDs that are rescued with varied efficacy by preventing DNA synthesis, activating NMDA receptors, or recruiting the NMDA receptor target ERK1/2. These findings may prompt mechanistic identification of AEDs that do not interfere with neural tube formation. SIGNIFICANCE STATEMENT Neural tube defects are one of the most common birth defects. Clinical investigations have determined that the use of antiepileptic drugs during pregnancy increases the incidence of these defects in the offspring by unknown mechanisms. This study discovers that glutamate signaling regulates neural plate cell proliferation and oriented migration and is necessary for neural tube formation. We demonstrate that the widely used antiepileptic drug valproic acid interferes with glutamate signaling and consequently induces neural tube defects, challenging the current hypotheses arguing that they are side effects of this antiepileptic drug that cause the increased incidence of these defects. Understanding the mechanisms of neurotransmitter signaling during neural tube formation may contribute to the identification and development of antiepileptic drugs that are safer during pregnancy. Copyright © 2018 the authors 0270-6474/18/384762-12$15.00/0.

  12. Simultaneous HPLC-F analysis of three recent antiepileptic drugs in human plasma.

    Science.gov (United States)

    Mercolini, Laura; Mandrioli, Roberto; Amore, Mario; Raggi, Maria Augusta

    2010-09-21

    An original high-performance liquid chromatographic method with fluorescence detection is presented for the simultaneous determination of the three antiepileptic drugs gabapentin, vigabatrin and topiramate in human plasma. After pre-column derivatisation with dansyl chloride, the analytes were separated on a Hydro-RP column with a mobile phase composed of phosphate buffer (55%) and acetonitrile (45%) and detected at lambda(em)=500 nm, exciting at 300 nm. An original pre-treatment procedure on biological samples, based on solid-phase extraction with MCX cartridges for gabapentin and vigabatrin, and with Plexa cartridges for topiramate, gave high extraction yields (>91%), satisfactory precision (RSDvigabatrin and in the 1.0-50.0 microg mL(-1) range for topiramate, with limits of detection (LODs) between 0.1 and 0.3 microg mL(-1). After validation, the method was successfully applied to some plasma samples from patients undergoing therapy with one or more of these drugs. Accuracy results were satisfactory (recovery >91%). Therefore, the method seems to be suitable for the therapeutic drug monitoring (TDM) of patients treated with gabapentin, vigabatrin and topiramate. Copyright 2010 Elsevier B.V. All rights reserved.

  13. Neuropsychological effects of antiepileptic drugs (carbamazepine versus valproate in adult males with epilepsy

    Directory of Open Access Journals (Sweden)

    Ghaydaa A Shehata

    2009-10-01

    Full Text Available Ghaydaa A Shehata,1 Abd El-aziz M Bateh,2 Sherifa A Hamed,1 Tarek A Rageh,1 Yaser B Elsorogy11Department of Neurology and Psychiatry, Faculty of Medicine, Assiut University, Egypt; 2Department of Psychology, Faculty of Arts, Banha University, EgyptPurpose: To evaluate the effect of antiepileptic drugs (AEDs on cognition and behavior in adult epileptic males controlled on treatment with conventional antiepileptic medications. Methods: Cognitive, mood, behavior and personality traits were assessed in 45 epileptic patients treated with carbamazepine and/or valproate and free of seizures for ≥1 year. Thirty-four newly diagnosed or untreated patients with epilepsy and 58 matched healthy subjects were also included for comparison. A battery of psychometric tests was utilized including Stanford-Binet (4th edition, Beck Inventory for Depression, Aggressive Scale and Eysenck Personality Questionnaire.Results: Compared to matched control subjects, treated and untreated epileptic patients had poor performance in different cognitive and behavioral functions testing. Treated patients had worse scores in memory for digits forward and backward, total short-term memory, extroversion and psychosis. The duration of AEDs intake was correlated with memory of objects (r = -0.323; P = 0.030, bead memory (r = -0.314; P = 0.036 and total nonverbal short-term memory (r = -0.346; P = 0.020. Treated and untreated epileptic patients had poor performance of similar extent in behavioral functions testing (depression, aggression and neurosis. The dose of AEDs was correlated with testing scores for neurosis (r = 0.307; P = 0.040, verbal aggression (r = 0.483; P = 0.001 and nonverbal aggression (r = 0.526; P = 0.000, and duration of drug intake was correlated with scores for depression (r = 0.384; P = 0.009, psychosis (r = 0.586; P = 0.0001 and nonverbal aggression (r = 0.300; P = 0.045.Conclusions: This study provides support for the notion that AEDs can impair performance

  14. The effect of antiepileptic drugs on the kidney function and structure.

    Science.gov (United States)

    Hamed, Sherifa Ahmed

    2017-09-01

    Long-term use of antiepileptic drugs (AEDs) is associated with number of somatic conditions. Data from experimental, cross-sectional and prospective studies have evidence for the deleterious effect of some AEDs on the kidney. Areas covered: This review summarized the current knowledge of the effect of AEDs on the kidney including evidence and mechanisms. Fanconi syndrome was reported with valproate (VPA) therapy in severely disabled children with epilepsy. Renal tubular acidosis and urolithiasis were reported with acetazolamide, topirmate and zonisamide, drugs with carbonic anhydrase inhibition properties. Increased levels of urinary N-acetyl-beta-D-glucosaminidase (NAG) to urinary creatinine (U-NAG/UCr), urinary excretion of α1-micrglobulin, β-galactosidase activity; and urinary malondialdehyde to creatinine (MDA/Cr), markers of renal glomerular and tubular injury, were reported with chronic use of some AEDs (VPA, carbamazepine and phenytoin). The mechanism(s) of kidney dysfunction/injury induced by AEDs is unknown. Experimental and clinical studies have shown that VPA induces oxidative stress, mitochondrial deficits, carnitine deficiency and inflammation and fibrosis in renal tissue in mice and in vitro studies. Expert commentary: It seems reasonable to monitor kidney function during treating patients with epilepsy at high risk of kidney injury (e.g. on combined therapy with more than one AED, severely disabled children, etc).

  15. Adverse events with use of antiepileptic drugs: a prescription and event symmetry analysis

    DEFF Research Database (Denmark)

    Tsiropoulos, Ioannis; Andersen, Morten; Hallas, Jesper

    2009-01-01

    Database (OPED) for the period of 1 August 1990-31 December 2006, and diagnoses from the County Hospital register for the period of 1994-2006 to perform sequence symmetry analysis. The method assesses the distribution of disease entities and prescription of other drugs (ODs), before and after initiation...

  16. Trends in Antiepileptic Drug Use in Children and Adolescents With Epilepsy.

    Science.gov (United States)

    Liu, Xinyue; Carney, Paul R; Bussing, Regina; Segal, Richard; Cottler, Linda B; Winterstein, Almut G

    2017-09-01

    We describe the trends in antiepileptic drug (AED) use in children and adolescents with epilepsy in the United States. We undertook a cross-sectional study based on Medicaid Analytic eXtract data set from 26 US states. Children and adolescents aged three to 18 years with at least one year continuous Medicaid fee-for-service coverage after the second outpatient or the first inpatient diagnosis of epilepsy in each calendar year during 1999 to 2009 were included in the study; therefore, 11 cohorts were established. A patient was defined as being exposed to a specific AED if he or she had at least one-day supply of the AED during the 1-year follow-up period. The annual prevalence of AEDs was reported, stratified by gender and age. The trends in AED use were evaluated through linear regression. The sample sizes of the 11 cohorts ranged between 17,304 and 22,672. The annual prevalence of valproic acid use declined from 42.4% in 1999 to 26.5% in 2009, and the prevalence of carbamazepine use declined from 37.1% to 10.2%. Meanwhile, the prevalence of levetiracetam use increased from 5.1% to about 32.0% in 2009, and the prevalence of oxcarbazepine use increased from 1.3% to 19.1%. Since 2008, levetiracetam (29.6%) has replaced valproic acid (27.8%) as the most commonly used AED in children and adolescents with epilepsy. The prevalence of diazepam use increased from 11.6% to 28.1%. Compared with first- and second-generation antiepileptic drugs, third-generation AEDs have fewer adverse side effects, resulting in increased patient treatment adherence. Equally important is the economic impact of these newer AEDs. This first-of-its-kind study underscores the need for large database studies that objectively assess the cost-effectiveness of third-generation AEDs versus first- and second-generation AEDs in the treatment of childhood epilepsy. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. The Teratogenic Effects of Antiepileptic Drug, Topiramate, on the Development of Chick Embryos

    Directory of Open Access Journals (Sweden)

    Jantima Roongruangchai

    2017-05-01

    Full Text Available Background: Anti-epileptic drugs are known to be the risk of teratogenicity. Topiramate (TPM is a new kind of such drug, for which no research has confirmed the incidence of producing congenital abnormalities. Objective: This study was conducted to study the teratogenic effects of TPM by using chick embryos as an animal model and the results can be compared to the human embryo of the same stage. Methods: Fertilized Leghorn hen eggs were injected in ovo with two concentrations of TPM, which were 10mg, and 20mg, in NSS at a volume of 0.1 ml into the yolk sac at 21 hrs of incubation and repeated injections at 72 hrs at a volume of 0.05 ml. The chick embryos on day 3, 6 and 11 of incubation were sacrificed and all living embryos were processed for total mount and serial section. Results: The mortality rate increased corresponding to the concentrations of TPM, and the embryonic stage. The total mount of day 3 showed major abnormalities of the eye and heart, such as microphthalmia and looser of heart looping. The serial section of day 3 showed opening of the anterior neuropore, ectopia viscerae and multiple malformations of the eye and heart. Day 6 chick embryos showed ectopia cordis and ectopia viscerae. Moreover, there were retardation and abnormalities of several organs such as eye, heart, liver, mesonephros and gonads. Day 11 chick embryos showed ectopia viscerae and several growth retardations, retardation of ossification of both limb bones and skull bones. Conclusion: This study showed that TPM might cause embryonic death, growth retardation and abnormalities of the eye, heart, an opening of the anterior neuropore and ectopia viscerae. This might indicate abnormalities to the baby born from mother with gestational epilepsy who was taking this drug continuously, and it might lead to spontaneous abortion or congenital anomalies of the fetus.

  18. Use of antiepileptic drugs and risk of falls in old age: A systematic review.

    Science.gov (United States)

    Haasum, Ylva; Johnell, Kristina

    2017-12-01

    The aim of this study is to systematically review the scientific literature to investigate if use of antiepileptic drugs (AEDs) is associated with falls and/or recurrent falls in old age. We searched the literature for relevant articles in PubMed and Embase published up until 3rd December 2015. Studies on people aged 60 years and over with an observational design assessing the risk of fall in people exposed to AEDs compared to people not exposed to AED were included. We found 744 studies by searching Medline and Embase and an additional 9 studies by reviewing relevant reference lists. Of these studies, 13 fulfilled our predefined criteria. The articles were of various study design, sizes and follow-up times, and presented the results in different ways. Also, confounder adjustment varied considerably between the studies. Ten studies presented results for the association between use of any AED and any fall/injurious fall. Of these studies, 6 presented adjusted estimates, of which all but one showed statistically significant associations between use of any AED and any fall/injurious fall. Six studies investigated the association between use of any AED and recurrent falls. Of these, only 3 studies presented adjusted effect estimates of which 2 reached statistical significance for the association between use of AEDs and recurrent falls in elderly people. Our results indicate an association between use of AEDs and risk of falls and recurrent falls in older people. This finding may be clinically important given that a substantial amount of older people use these drugs. However, further research is needed to increase the knowledge about the actual risk of falls when using these drugs in old age. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Women with epilepsy in childbearing age: Pregnancy-related knowledge, information sources, and antiepileptic drugs.

    Science.gov (United States)

    Friedrich, Latica; Sruk, Ana; Bielen, Ivan

    2018-03-01

    Pregnancy-related issues in epilepsy (PRIE) are essential for management of epilepsy in women. We conducted a study among women with epilepsy (WWE) aged 15-45years about their knowledge, sources, and needs for information regarding PRIE, which included their current antiepileptic drugs (AEDs) usage. Women with epilepsy, visitors of Croatian Association for Epilepsy webpage, were offered an online questionnaire, and 200 responses were analyzed. The mean number of correct answers about PRIE was 3.5 out of 5. Main predictors of knowledge on PRIE were a prior consultation with a neurologist and higher usage of books/brochures. A prior neurologist consultation on PRIE was stated by 45% of subjects. As the preferred future mode of being informed on PRIE, majority of women (61%) chooses their neurologist, 22% written materials distributed by a neurologist, and only 13% Internet. Levetiracetam was the most commonly used AED (34.5%). Valproate was used by 26%, and of those 59% stated no previous consultation on PRIE with their neurologist. In summary, we believe our study shows that knowledge of PRIE among WWE in their childbearing age is unsatisfactory, as are the neurologist consultation rates about PRIE. Our results demonstrate that, despite modern technologies, educational activities should be based on neurologist consultations and providing the patients with appropriate written materials. This is especially true for the relatively large proportion of women still taking valproate. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. The impact of the use of antiepileptic drugs on the growth of children

    Science.gov (United States)

    2013-01-01

    Background This study investigated whether long-term treatment with antiepileptic drugs (AEDs) had negative effects on statural growth and serum calcium levels in children with epilepsy in Taiwan. Methods Children with epilepsy treated with one prescription of AEDs (monotherapy) for at least 1 year were selected. The AEDs included valproic acid (VPA; Deparkin) in 27 children (11 boys and 16 girls) aged 4-18 years, oxcarbazepine (Trileptal) in 30 children (15 boys and 15 girls) aged 5-18 years, topiramate (Topamax) in 19 children (10 boys and 9 girls) aged 6-18 years, and lamotrigine (Lamicta) in eight children (5 boys and 3 girls) aged 5-13 years. Patients with a history of febrile convulsions were selected as the controls. Results One year of VPA treatment significantly impaired the statural growth of pediatric patients with epilepsy (p effect of VPA on the proliferation of growth plate chondrocytes rather than alterations of serum calcium. Conclusions These results raise serious concerns about the growth of pediatric epilepsy patients who use AEDs, and potentially the need to closely monitor growth in children with epilepsy and adolescents under AED treatment, especially VPA. PMID:24354857

  1. Impact of antiepileptic drugs on bone health: Need for monitoring, treatment, and prevention strategies

    Directory of Open Access Journals (Sweden)

    Ekta Arora

    2016-01-01

    Full Text Available Epilepsy is the most common neurological disorder affecting approximately 50 million people worldwide. In India, overall prevalence of epilepsy is reported to be 5.59/1000 population. Antiepileptic drugs (AEDs constitute the main-stay of treatment with a large number of AEDs available in the market. High incidence of adverse effects is a major limitation with AEDs. One of the major concerns is significant metabolic effects on the bone. However, little attention has been paid to this issue because most of the bone effects remain subclinical for a long time and may take years to manifest clinically. The main effects include hypocalcemia, hypophosphatemia, reduced serum levels of Vitamin D, increase in parathormone (PTH levels, and alterations in bone turnover markers. The CYP450 enzyme-inducing AEDs such as phenytoin, phenobarbital, carbamazepine, and primidone are the most common AEDs associated with bone disorders while the data regarding the effect of valproate and newer AEDs such as lamotrigine, gabapentin, vigabatrin, levetiracetam, and topiramate on bone metabolism and bone density are scanty and controversial. Deficiency of Vitamin D is commonly described as a cause for the bone loss in epileptic patients while others being decreased absorption of calcium, increased PTH levels, and inhibition of calcitonin secretion, etc. However, there are no formal practical guidelines for the management of bone disease among those taking AEDs. Evidence-based strategies regarding monitoring, prevention, and treatment of bone diseases in patients on AED therapy are needed.

  2. Antiepileptic drugs during pregnancy in primary care: a UK population based study.

    Directory of Open Access Journals (Sweden)

    Shuk-Li Man

    Full Text Available Antiepileptic drugs (AEDs are commonly prescribed for epilepsy and bipolar disorder but little is known about their use in pregnancy. We examined secular trends in AED prescribing in pregnancy and pregnancy as a determinant for stopping AED prescribing.We identified 174,055 pregnancies from The Health Improvement Network UK primary care database. Secular trends in AED prescribing during pregnancy were examined between 1994 and 2009. We used Cox's regression analyses to compare time to discontinuation of AED prescriptions between pregnant and non-pregnant women and to identify predictors of discontinuation of AEDs in pregnancy.Prescribing of carbamazepine and sodium valproate have declined since 1994 despite being the most commonly prescribed AEDs in pregnancy up to 2004. Prescribing of lamotrigine in pregnancy has steadily increased and has been the most popular AED prescribed in pregnancy since 2004. Pregnant women with epilepsy were twice as likely to stop receiving AEDs (Hazard Ratio (HR 2.00, 95% Confidence Interval (CI 1.62-2.47 when compared to non-pregnant women and for women with bipolar disorder this was even higher (HR 3.07, 95% CI 2.04-4.62. For pregnant women with epilepsy, those receiving AEDs less regularly before pregnancy were more likely to stop receiving AEDs in pregnancy.Lamotrigine has been increasingly prescribed in pregnancy over older AEDs namely carbamazepine and sodium valproate. Pregnancy is a strong determinant for the discontinuation of AED prescribing particularly for women with bipolar disorder.

  3. Chronic antiepileptic drug use and functional network efficiency: A functional magnetic resonance imaging study.

    Science.gov (United States)

    van Veenendaal, Tamar M; IJff, Dominique M; Aldenkamp, Albert P; Lazeron, Richard H C; Hofman, Paul A M; de Louw, Anton J A; Backes, Walter H; Jansen, Jacobus F A

    2017-06-28

    To increase our insight in the neuronal mechanisms underlying cognitive side-effects of antiepileptic drug (AED) treatment. The relation between functional magnetic resonance-acquired brain network measures, AED use, and cognitive function was investigated. Three groups of patients with epilepsy with a different risk profile for developing cognitive side effects were included: A "low risk" category (lamotrigine or levetiracetam, n = 16), an "intermediate risk" category (carbamazepine, oxcarbazepine, phenytoin, or valproate, n = 34) and a "high risk" category (topiramate, n = 5). Brain connectivity was assessed using resting state functional magnetic resonance imaging and graph theoretical network analysis. The Computerized Visual Searching Task was used to measure central information processing speed, a common cognitive side effect of AED treatment. Central information processing speed was lower in patients taking AEDs from the intermediate and high risk categories, compared with patients from the low risk category. The effect of risk category on global efficiency was significant ( P effect on the clustering coefficient (ANCOVA, P > 0.2). Also no significant associations between information processing speed and global efficiency or the clustering coefficient (linear regression analysis, P > 0.15) were observed. Only the four patients taking topiramate show aberrant network measures, suggesting that alterations in functional brain network organization may be only subtle and measureable in patients with more severe cognitive side effects.

  4. Metabolic and functional MR biomarkers of antiepileptic drug effectiveness: A review.

    Science.gov (United States)

    van Veenendaal, Tamar M; IJff, Dominique M; Aldenkamp, Albert P; Hofman, Paul A M; Vlooswijk, Marielle C G; Rouhl, Rob P W; de Louw, Anton J; Backes, Walter H; Jansen, Jacobus F A

    2015-12-01

    As a large number of patients with epilepsy do not respond favorably to antiepileptic drugs (AEDs), a better understanding of treatment failure and the cause of adverse side effects is required. The working mechanisms of AEDs also alter neurotransmitter concentrations and brain activity, which can be measured using MR spectroscopy and functional MR imaging, respectively. This review presents an overview of clinical research of MR spectroscopy and functional MR imaging studies to the effects of AEDs on the brain. Despite the scarcity of studies associating MR findings to the effectiveness of AEDs, the current research shows clear potential regarding this matter. Several GABAergic AEDs have been shown to increase the GABA concentration, which was related to seizure reductions, while language problems due to topiramate have been associated with altered activation patterns measured with functional MR imaging. MR spectroscopy and functional MR imaging provide biomarkers that may predict individual treatment outcomes, and enable the assessment of mechanisms of treatment failure and cognitive side effects. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Newer antiepileptic drugs in the treatment of status epilepticus: impact on prognosis.

    Science.gov (United States)

    Jaques, Léonore; Rossetti, Andrea O

    2012-05-01

    Newer antiepileptic drugs (AEDs) are increasingly prescribed and seem to have a comparable efficacy as the classical AEDs; however, their impact on status epilepticus (SE) prognosis has received little attention. In our prospective SE database (2006-2010), we assessed the use of older versus newer AEDs (levetiracetam, pregabalin, topiramate, lacosamide) over time and its relationship to outcome (return to clinical baseline conditions, new handicap, or death). Newer AEDs were used more often toward the end of the study period (42% of episodes versus 30%). After adjustment for SE etiology, SE severity score, and number of compounds needed to terminate SE, newer AEDs were independently related to a reduced likelihood of return to baseline (p<0.001) but not to increased mortality. These findings seem in line with recent findings on refractory epilepsy. Also, in view of the higher price of the newer AEDs, well-designed, prospective assessments analyzing the impact of newer AEDs on efficacy and tolerability in patients with SE appear mandatory. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Fatigue during treatment with antiepileptic drugs: A levetiracetam-specific adverse event?

    Science.gov (United States)

    Mula, Marco; von Oertzen, Tim J; Cock, Hannah R; Yogarajah, Mahinda; Lozsadi, Dora A; Agrawal, Niruj

    2017-07-01

    To examine the prevalence and clinical correlates of fatigue as an adverse event (AE) of antiepileptic drug (AED) treatment in patients with epilepsy. Data from 443 adult outpatients with epilepsy assessed with the Adverse Event Profile (AEP) and the Neurological Disorder Depression Inventory for Epilepsy (NDDIE) were analysed. Fatigue is reported by 36.6% of patients as always a problem during AED treatment. Fatigue is more likely to be reported by females (64.8% vs. 35.2%; Chi-Square=16.762; df=3; p=0.001) and during treatment with levetiracetam (42.3% vs. 33.2%; Chi-Square=11.462; df=3; p=0.009). The associations with the female gender and levetiracetam treatment were not mediated by depression, as identified with the NDDIE, and could not be simply explained by the large number of subjects on levetiracetam treatment, as analogous figures resulted from the analysis of a monotherapy subsample (41.7% vs. 30.3%; Chi-Square=11.547; df=3; p=0.009). One third of patients with epilepsy reports fatigue as a significant problem during AED treatment. Fatigue is more likely to be reported by females and seems to be specifically associated with LEV treatment. However, fatigue is not mediated by a negative effect of LEV on mood. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. The Use of Antiepileptic Drugs (AEDs for the Treatment of Pediatric Aggression and Mood Disorders

    Directory of Open Access Journals (Sweden)

    Joseph Gonzalez-Heydrich

    2010-09-01

    Full Text Available Aggressive symptomatology presents across multiple psychiatric, developmental, neurological and behavioral disorders, complicating the diagnosis and treatment of the underlying pathology. Anti-Epileptic Drugs (AEDs have become an appealing alternative in the treatment of aggression, mood lability and impulsivity in adult and pediatric populations, although few controlled trials have explored their efficacy in treating pediatric populations. This review of the literature synthesizes the available data on ten AEDs – valproate, carbamazepine, oxcarbazepine, phenytoin, lamotrigine, topiramate, levetiracetam, zonisamide, gabapentin and tiagabine – in an attempt to assess evidence for the efficacy of AEDs in the treatment of aggression in pediatric populations. Our review revealed modest evidence that some of the AEDs produced improvement in pediatric aggression, but controlled trials in pediatric bipolar disorder have not been promising. Valproate is the best supported AED for aggression and should be considered as a first line of treatment. When monotherapy is insufficient, combining an AED with either lithium or an atypical anti-psychotic can result in better efficacy. Additionally, our review indicates that medications with predominately GABA-ergic mechanisms of action are not effective in treating aggression, and medications which decrease glutaminergic transmission tended to have more cognitive adverse effects. Agents with multiple mechanisms of action may be more effective.

  8. The Use of Antiepileptic Drugs (AEDs) for the Treatment of Pediatric Aggression and Mood Disorders.

    Science.gov (United States)

    Munshi, Kaizad R; Oken, Tanya; Guild, Danielle J; Trivedi, Harsh K; Wang, Betty C; Ducharme, Peter; Gonzalez-Heydrich, Joseph

    2010-09-10

    Aggressive symptomatology presents across multiple psychiatric, developmental, neurological and behavioral disorders, complicating the diagnosis and treatment of the underlying pathology. Anti-Epileptic Drugs (AEDs) have become an appealing alternative in the treatment of aggression, mood lability and impulsivity in adult and pediatric populations, although few controlled trials have explored their efficacy in treating pediatric populations. This review of the literature synthesizes the available data on ten AEDs - valproate, carbamazepine, oxcarbazepine, phenytoin, lamotrigine, topiramate, levetiracetam, zonisamide, gabapentin and tiagabine - in an attempt to assess evidence for the efficacy of AEDs in the treatment of aggression in pediatric populations. Our review revealed modest evidence that some of the AEDs produced improvement in pediatric aggression, but controlled trials in pediatric bipolar disorder have not been promising. Valproate is the best supported AED for aggression and should be considered as a first line of treatment. When monotherapy is insufficient, combining an AED with either lithium or an atypical anti-psychotic can result in better efficacy. Additionally, our review indicates that medications with predominately GABA-ergic mechanisms of action are not effective in treating aggression, and medications which decrease glutaminergic transmission tended to have more cognitive adverse effects. Agents with multiple mechanisms of action may be more effective.

  9. Role of reflexology and antiepileptic drugs in managing intractable epilepsy--a randomized controlled trial.

    Science.gov (United States)

    Dalal, Krishna; Devarajan, Elanchezhiyan; Pandey, Ravindra Mohan; Subbiah, Vivekanandan; Tripathi, Manjari

    2013-01-01

    This report is based on the results of a randomized parallel controlled trial conducted to determine the efficacy of reflexology therapy in managing intractable epilepsy. Subjects who failed epilepsy surgery or were not candidates for epilepsy surgery or were non-responders of antiepileptic drugs (AEDs) took part in this study. The trial was completed by 77 subjects randomly assigned to 2 arms: control (AEDs) and reflexology (AEDs + reflexology therapy). The hypothesis was that hand reflexology therapy could produce results similar to those of vagus nerve stimulation, and foot reflexology therapy could maintain homeostasis in the functional status of individual body parts. Reflexology therapy was applied by family members. The follow-up period was 1.5 years. Quality of life in epilepsy patients was assessed with the QOLIE-31 instrument. In the reflexology group, the median baseline seizure frequency decreased from 9.5 (range 2-120) to 2 (range 0-110) with statistical significance (p reflexology group were 41.05 ± 7 and 43.6 ± 8, respectively. Posttherapy data were 49.07 ± 6 and 65.4 ± 9, respectively (p reflexology method allowed detection of knee pain in 85% of the reflexology group patients (p reflexology group patients reported nausea/vomiting (n = 1), change in voice (n = 2), and hoarseness (n = 1). Reflexology therapy together with AEDs may help reducing seizure frequency and improving quality of life in individuals with epilepsy. Copyright © 2013 S. Karger AG, Basel.

  10. Effects of epilepsy and selected antiepileptic drugs on risk of myocardial infarction, stroke, and death in patients with or without previous stroke: a nationwide cohort study

    DEFF Research Database (Denmark)

    Olesen, Jonas Bjerring; Abildstrøm, Steen Zabell; Erdal, Jesper

    2011-01-01

    Patients with epilepsy have increased morbidity and mortality. We evaluated the risk of myocardial infarction (MI), stroke, and death associated with epilepsy and examined if this risk was modified by treatment with antiepileptic drugs (AEDs).......Patients with epilepsy have increased morbidity and mortality. We evaluated the risk of myocardial infarction (MI), stroke, and death associated with epilepsy and examined if this risk was modified by treatment with antiepileptic drugs (AEDs)....

  11. Prevention of Fetal Congenital Malformations with Allowance for the Pharmacogenetic Features of the Metabolism of Antiepileptic Drugs and Hereditary Abnormalities in the Folate Cycle

    Directory of Open Access Journals (Sweden)

    D. V. Dmitrenko

    2014-01-01

    Full Text Available Fetal congenital malformations are among the most dangerous complications of pregnancy in women with epilepsy taking antiepileptic drugs. Valproic acid and phenobarbital have the greatest risk of teratogenic effects. Insights into the current mechanisms of teratogenic effect of antiepileptic drugs, pharmacogenetic features of the metabolism of valproates and hereditary abnormalities in the folate cycle enables prevention of fetal congenital malformations. 

  12. Common allergies do not influence the prevalence of cutaneous hypersensitivity reactions to antiepileptic drugs.

    Science.gov (United States)

    Bosak, Magdalena; Porębski, Grzegorz; Słowik, Agnieszka; Turaj, Wojciech

    2017-09-01

    The aim of the study was to establish whether the presence of common allergies increases the risk of drug-related hypersensitivity reactions among patients with epilepsy treated with antiepileptic drugs (AEDs). We studied 753 patients with epilepsy seen in tertiary outpatient epilepsy clinic. We obtained data related to epilepsy type, past and ongoing treatment with AEDs, occurrence of maculopapular exanthema or more serious cutaneous adverse reactions (Stevens-Johnson syndrome - SJS) and their characteristics. We noted an occurrence of allergic reactions unrelated to treatment with AED, including rash unrelated to AED, bronchial asthma, persistent or seasonal allergic rhinitis, atopic dermatitis, rash after specific food and other allergic reactions. There were 61 cases of AED-related cutaneous hypersensitivity reaction (including 3 cases of SJS) noted in association with 2319 exposures to AEDs (2.63%) among 55 out of 753 patients (7.3%). Cutaneous hypersensitivity reaction to AED was most commonly noted after lamotrigine (12.1%), carbamazepine (5.4%) and oxcarbazepine (4.1%). Prevalence of allergic reactions unrelated to AED was similar between patients with and without AED-related cutaneous hypersensitivity reaction (rash unrelated to AED: 16.4% vs. 10.2%; bronchial asthma: 1.8% vs. 0.1%; persistent allergic rhinitis: 7.3% vs. 10.2%; seasonal allergic rhinitis: 7.3% vs. 11.7%; atopic dermatitis: 0 vs. 0.7%; rash after specific food: 5.4% vs. 6.4%; other allergic reactions: 5.4% vs. 5.2%, respectively; P>0.1 for each difference). Presence of common allergies is not a significant risk factor for AED-related cutaneous hypersensitivity reaction among patients with epilepsy. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. [Consensus clinical practice guidelines of the Andalusian Epilepsy Society on prescribing generic antiepileptic drugs].

    Science.gov (United States)

    Cañadillas-Hidalgo, F M; Sánchez-Alvarez, J C; Serrano-Castro, P J; Mercadé-Cerdá, J M

    Pharmaceutical spending in Spain accounts for 1.2-1.4% of the gross domestic product and is increasing by 5-12% per year. One of the measures adopted by the government to cut this spending is the possible substitution of original prescribed drugs by generics. In the case of antiepileptic drugs (AED), which are characterised by a scant therapeutic margin, these steps have sparked a scientific debate about their repercussion on the control of epileptic patients. We propose to draw up a set of implicit evidence-based consensus practice guidelines concerning issues related with this topic. A selective search for quality scientific information on the subject was conducted on PubMed-Medline, Tripdatabase and the Biblioteca Cochrane Plus. The selected references were analysed and discussed by the authors, and the recommendations deriving from them were collected. A total of 21 primary documents and 16 practice guidelines, protocols or experts' recommendations were identified. Our recommendations were explicitly included at the end of the text. The Andalusian Epilepsy Society makes the following recommendations: 1) not replacing an innovative AED by its generic in a controlled patient; 2) beginning treatment with a generic AED in monotherapy or in association is acceptable; 3) not exchanging generic AED from different pharmaceutical companies; 4) explaining to the patient the rules governing the authorization of generics and the importance of avoiding exchanges between different generic AED; and 5) if there is some worsening of the clinical condition or side effects appear following the introduction of a generic, the causes must be investigated and communicated to the bodies responsible for pharmacovigilance.

  14. Comparative effectiveness of antiepileptic drugs in patients with mesial temporal lobe epilepsy with hippocampal sclerosis.

    Science.gov (United States)

    Androsova, Ganna; Krause, Roland; Borghei, Mojgansadat; Wassenaar, Merel; Auce, Pauls; Avbersek, Andreja; Becker, Felicitas; Berghuis, Bianca; Campbell, Ellen; Coppola, Antonietta; Francis, Ben; Wolking, Stefan; Cavalleri, Gianpiero L; Craig, John; Delanty, Norman; Koeleman, Bobby P C; Kunz, Wolfram S; Lerche, Holger; Marson, Anthony G; Sander, Josemir W; Sills, Graeme J; Striano, Pasquale; Zara, Federico; Sisodiya, Sanjay M; Depondt, Chantal

    2017-10-01

    Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is a common epilepsy syndrome that is often poorly controlled by antiepileptic drug (AED) treatment. Comparative AED effectiveness studies in this condition are lacking. We report retention, efficacy, and tolerability in a cohort of patients with MTLE-HS. Clinical data were collected from a European database of patients with epilepsy. We estimated retention, 12-month seizure freedom, and adverse drug reaction (ADR) rates for the 10 most commonly used AEDs in patients with MTLE-HS. Seven hundred sixty-seven patients with a total of 3,249 AED trials were included. The highest 12-month retention rates were observed with carbamazepine (85.9%), valproate (85%), and clobazam (79%). Twelve-month seizure freedom rates varied from 1.2% for gabapentin and vigabatrin to 11% for carbamazepine. Response rates were highest for AEDs that were prescribed as initial treatment and lowest for AEDs that were used in a third or higher instance. ADRs were reported in 47.6% of patients, with the highest rates observed with oxcarbazepine (35.7%), topiramate (30.9%), and pregabalin (27.4%), and the lowest rates with clobazam (6.5%), gabapentin (8.9%), and lamotrigine (16.6%). The most commonly reported ADRs were lethargy and drowsiness, dizziness, vertigo and ataxia, and blurred vision and diplopia. Our results did not demonstrate any clear advantage of newer versus older AEDs. Our results provide useful insights into AED retention, efficacy, and ADR rates in patients with MTLE-HS. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  15. Clinical outcomes and immune benefits of anti-epileptic drug therapy in HIV/AIDS

    Directory of Open Access Journals (Sweden)

    Krentz Hartmut B

    2010-06-01

    Full Text Available Abstract Background Anti-epileptic drugs (AEDs are frequently prescribed to persons with HIV/AIDS receiving combination antiretroviral therapy (cART although the extent of AED use and their interactions with cART are uncertain. Herein, AED usage, associated toxicities and immune consequences were investigated. Methods HIV replication was analysed in proliferating human T cells during AED exposure. Patients receiving AEDs in a geographically-based HIV care program were assessed using clinical and laboratory variables in addition to assessing AED indication, type, and cumulative exposures. Results Valproate suppressed proliferation in vitro of both HIV-infected and uninfected T cells (p 0.05 but AED exposures did not affect HIV production in vitro. Among 1345 HIV/AIDS persons in active care between 2001 and 2007, 169 individuals were exposed to AEDs for the following indications: peripheral neuropathy/neuropathic pain (60%, seizure/epilepsy (24%, mood disorder (13% and movement disorder (2%. The most frequently prescribed AEDs were calcium channel blockers (gabapentin/pregabalin, followed by sodium channel blockers (phenytoin, carbamazepine, lamotrigine and valproate. In a nested cohort of 55 AED-treated patients receiving cART and aviremic, chronic exposure to sodium and calcium channel blocking AEDs was associated with increased CD4+ T cell levels (p 0.05 with no change in CD8+ T cell levels over 12 months from the beginning of AED therapy. Conclusions AEDs were prescribed for multiple indications without major adverse effects in this population but immune status in patients receiving sodium or calcium channel blocking drugs was improved.

  16. Determination of Four Anti-epileptic Drugs in Plasma Using Ultra Performance Liquid Chromatography with Mass Detection Technique.

    Science.gov (United States)

    Hassib, Sonia T; Hashem, Hanaa M A; Mahrouse, Marianne A; Mostafa, Eman A

    2018-04-10

    Status epilepticus (SE) is considered the second most frequent neurologic emergency. Its therapeutic management is performed using sequential anti-epileptic drug regimens. Diazepam (DIA), midazolam (MID), phenytoin (PHT) and phenobarbital (PB) are four drugs of different classes used sequentially in the management of SE. A sensitive, selective, accurate and precise method was developed and validated for simultaneous determination of the four anti-epileptic drugs in human plasma. Their separation and quantification were achieved using ultra performance liquid chromatography (UPLC) with mass detection using carbamazepine as internal standard (IS). For the first three drugs and IS, UPLC-MS/MS with electrospray ionization working in multiple reaction monitoring mode was used at the following transitions: m/z 285→193 for DIA, m/z 326→291 for MID, m/z 253→182 for PHT and m/z 237→194, 237→192 for IS. For the fourth drug (PB), molecular ion peak of PB [M+H] + at m/z 233 was used for its quantitation. The method was linear over concentration ranges of 5-500 ng/ml for DIA and MID and 0.25-20 μg/ml for PHT and PB, respectively. Bio-analytical validation of the developed method was carried out according to European Medicines Agency guidelines. The developed method can be applied for routine drug analysis, therapeutic drug monitoring and bioequivalence studies. This article is protected by copyright. All rights reserved.

  17. Applying a perceptions and practicalities approach to understanding nonadherence to antiepileptic drugs.

    Science.gov (United States)

    Chapman, Sarah C E; Horne, Rob; Eade, Rona; Balestrini, Simona; Rush, Jennifer; Sisodiya, Sanjay M

    2015-09-01

    Nonadherence to antiepileptic drugs (AEDs) is a common cause of poor seizure control. This study examines whether reported adherence to AEDs is related to variables identified in the National Institute for Health and Clinical Excellence (NICE) Medicines Adherence Guidelines as being important to adherence: perceptual factors (AED necessity beliefs and concerns), practical factors (limitations in capability and resources), and perceptions of involvement in treatment decisions. This was a cross-sectional study of people with epilepsy receiving AEDs. Participants completed an online survey hosted by the Epilepsy Society (n = 1,010), or as an audit during inpatient admission (n = 118). Validated questionnaires, adapted for epilepsy, assessed reported adherence to AEDs (Medication Adherence Report Scale [MARS]), perceptions of AEDs (Beliefs about Medicines Questionnaire [BMQ]), and patient perceptions of involvement in treatment decisions (Treatment Empowerment Scale [TES]). Low adherence was related to AED beliefs (doubts about necessity: t(577) = 3.90, p < 0.001; and concerns: t(995) = 3.45, p = 0.001), reported limitations in capability and resources (t(589) = 7.78, p < 0.001), and to perceptions of a lack of involvement in treatment decisions (t(623) = 4.48, p < 0.001). In multiple logistic regression analyses, these factors significantly (p < 0.001) increased variance in reported adherence, above that which could be explained by age and clinical variables (seizure frequency, type, epilepsy duration, number of AEDs prescribed). Variables identified in the NICE Medicines Adherence Guidelines as potentially important factors for adherence were found to be related to adherence to AEDs. These factors are potentially modifiable. Interventions to support optimal adherence to AEDs should be tailored to address doubts about AED necessity and concerns about harm, and to overcome practical difficulties, while engaging patients in treatment decisions. Wiley Periodicals, Inc.

  18. Antiepileptic drug behavioral side effects and baseline hyperactivity in children and adolescents with new onset epilepsy.

    Science.gov (United States)

    Guilfoyle, Shanna M; Follansbee-Junger, Katherine; Smith, Aimee W; Combs, Angela; Ollier, Shannon; Hater, Brooke; Modi, Avani C

    2018-01-01

    To examine baseline psychological functioning and antiepileptic drug (AED) behavioral side effects in new onset epilepsy and determine, by age, whether baseline psychological functioning predicts AED behavioral side effects 1 month following AED initiation. A retrospective chart review was conducted between July 2011 and December 2014 that included youths with new onset epilepsy. As part of routine interdisciplinary care, caregivers completed the Behavior Assessment System for Children, 2nd Edition: Parent Rating Scale to report on baseline psychological functioning at the diagnostic visit and the Pediatric Epilepsy Side Effects Questionnaire to identify AED behavioral side effects at the 1-month follow-up clinic visit following AED initiation. Children (age = 2-11 years) and adolescents (age = 12-18 years) were examined separately. A total of 380 youths with new onset epilepsy (M age  = 8.9 ± 4.3 years; 83.4% Caucasian; 34.8% focal epilepsy, 41.1% generalized epilepsy, 23.7% unclassified epilepsy) were included. Seventy percent of youths had at-risk or clinically elevated baseline psychological symptoms. Children had significantly greater AED behavioral side effects (M = 25.08 ± 26.36) compared to adolescents (M = 12.36 ± 17.73), regardless of AED. Valproic acid demonstrated significantly greater behavioral side effects compared to all other AEDs, with the exception of levetiracetam. Higher hyperactivity/impulsivity at baseline significantly predicted higher AED behavioral side effects 1 month after AED initiation in both age groups. Younger children seem to be more prone to experience behavioral side effects, and these are likely to be higher if youths with epilepsy have baseline hyperactivity/impulsivity. Baseline psychological screening, specifically hyperactivity, can be used as a precision medicine tool for AED selection. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  19. Psychiatric and behavioral side effects of anti-epileptic drugs in adolescents and children with epilepsy.

    Science.gov (United States)

    Chen, B; Detyniecki, K; Choi, H; Hirsch, L; Katz, A; Legge, A; Wong, R; Jiang, A; Buchsbaum, R; Farooque, P

    2017-05-01

    The objective of the study was to compare the psychiatric and behavioral side effect (PBSE) profiles of both older and newer antiepileptic drugs (AEDs) in children and adolescent patients with epilepsy. We used logistic regression analysis to test the correlation between 83 non-AED/patient related potential predictor variables and the rate of PBSE. We then compared for each AED the rate of PBSEs and the rate of PBSEs that led to intolerability (IPBSE) while controlling for non-AED predictors of PBSEs. 922 patients (≤18 years old) were included in our study. PBSEs and IPBSEs occurred in 13.8% and 11.2% of patients, respectively. Overall, a history of psychiatric condition, absence seizures, intractable epilepsy, and frontal lobe epilepsy were significantly associated with increased PBSE rates. Levetiracetam (LEV) had the greatest PBSE rate (16.2%). This was significantly higher compared to other AEDs. LEV was also significantly associated with a high rate of IPBSEs (13.4%) and dose-decrease rates due to IPBSE (6.7%). Zonisamide (ZNS) was associated with significantly higher cessation rate due to IPBSE (9.1%) compared to other AEDs. Patients with a history of psychiatric condition, absence seizures, intractable epilepsy, or frontal lobe epilepsy are more likely to develop PBSE. PBSEs appear to occur more frequently in adolescent and children patients taking LEV compared to other AEDs. LEV-attributed PBSEs are more likely to be associated with intolerability and subsequent decrease in dose. The rate of ZNS-attributed IPBSEs is more likely to be associated with complete cessation of AED. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  20. Mapping the availability, price, and affordability of antiepileptic drugs in 46 countries.

    Science.gov (United States)

    Cameron, Alexandra; Bansal, Amit; Dua, Tarun; Hill, Suzanne R; Moshe, Solomon L; Mantel-Teeuwisse, Aukje K; Saxena, Shekhar

    2012-06-01

    In low- and middle-income countries (LMICs), a large proportion of people with epilepsy do not receive treatment. An analysis of the availability, price, and affordability of antiepileptic drugs (AEDs) was conducted to evaluate whether these factors contribute to the treatment gap. Data for five AEDs (phenytoin, carbamazepine, valproic acid, phenobarbital, and diazepam) were obtained from facility-based surveys conducted in 46 countries using the World Health Organization/Health Action International (WHO/HAI) methodology. Outcome measures were percentage availability, ratios of local prices to international reference prices, and number of days' wages needed by the lowest-paid unskilled government worker to purchase treatment. Prices were adjusted for inflation/deflation and purchasing power parity. The average availability of generic AEDs in the public sector was Private sector availability of generic oral AEDs ranged from 42.2% for phenytoin to 69.6% for phenobarbital. Public sector patient prices for generic carbamazepine and phenytoin were 4.95 and 17.50 times higher than international reference prices, respectively, whereas private sector patient prices were 11.27 and 24.77 times higher, respectively. For both medicines, originator brand prices were about 30 times higher. The highest prices were observed in the lowest income countries. The lowest-paid government worker would need wages from 1-2.6 days' to purchase a month's supply of phenytoin, whereas carbamazepine would cost 2.7-16.2 days' wages. Despite its widespread use in LMICs, WHO/HAI survey data for phenobarbital was only available from a small number of countries. In LMICs, availability and affordability of AEDs are poor and may be acting as a barrier to accessing treatment for epilepsy. Ensuring a consistent supply of AEDs at an affordable price should be a priority. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

  1. Designing clinical trials to assess antiepileptic drugs as monotherapy : difficulties and solutions.

    Science.gov (United States)

    Perucca, Emilio

    2008-01-01

    Designing monotherapy trials in epilepsy is fraught with many hurdles, including diagnostic and classification difficulties, sparse information regarding the natural history of the disorder, and ethical objections to the use of placebo or a suboptimal comparator in a condition where the consequences of therapeutic failure can be serious. These issues are further complicated by regulatory differences between the US and the EU.In the US, the FDA considers that evidence of efficacy requires demonstration of superiority to a comparator. Because available antiepileptic drugs possess relatively high efficacy, in most settings it is unrealistic to expect that a new treatment will be superior to a standard treatment used at optimized dosages. To circumvent this problem, trial designs have been developed whereby patients in the control group are assigned to receive a suboptimal comparator and are required to exit from the trial if seizure deterioration occurs. This allows demonstration of a between-group difference in efficacy endpoints, such as time to exit or time to first seizure. Although these trials have come under increasing criticism because of ethical concerns, extensive information is now available on the outcome of patients with chronic epilepsy randomized to suboptimal treatment in similarly designed conversion to monotherapy trials. This has allowed the construction of a dataset of historical controls against which response to a fully active treatment can be compared. A number of studies using this novel approach are now in progress.In the EU, in addition to requiring data on conversion to monotherapy in refractory patients, the European Medicines Agency stipulates that a monotherapy indication in newly diagnosed epilepsy can only be granted if a candidate drug has shown at least a similar benefit/risk balance compared with an acknowledged standard at its optimal use during an assessment period of no less than 1 year. This has led to the implementation of

  2. Role of cytochrome P450-mediated metabolism and involvement of reactive metabolite formations on antiepileptic drug-induced liver injuries.

    Science.gov (United States)

    Sasaki, Eita; Yokoi, Tsuyoshi

    2018-01-01

    Several drugs have been withdrawn from the market or restricted to avoid unexpected adverse outcomes. Drug-induced liver injury (DILI) is a serious issue for drug development. Among DILIs, idiosyncratic DILIs have been a serious problem in drug development and clinical uses. Idiosyncratic DILI is most often unrelated to pharmacological effects or the dosing amount of a drug. The number of drugs that cause idiosyncratic DILI continue to grow in part because no practical preclinical tests have emerged that can identify drug candidates with the potential for developing idiosyncratic DILIs. Nevertheless, the implications of drug metabolism-related factors and immune-related factors on idiosyncratic DILIs has not been fully clarified because this toxicity can not be reproduced in animals. Therefore, accumulated evidence for the mechanisms of the idiosyncratic toxicity has been limited to only in vitro studies. This review describes current knowledge of the effects of cytochrome P450 (CYP)-mediated metabolism and its detoxification abilities based on studies of idiosyncratic DILI animal models developed recently. This review also focused on antiepileptic drugs, phenytoin (diphenyl hydantoin, DPH) and carbamazepine (CBZ), which have rarely caused severe adverse reactions, such as fulminant hepatitis, and have been recognized as sources of idiosyncratic DILI. The studies of animal models of idiosyncratic DILIs have produced new knowledge of chronic administration, CYP inductions/inhibitions, glutathione contents, and immune-related factors for the initiation of idiosyncratic DILIs. Considering changes in the drug metabolic profile and detoxification abilities, idiosyncratic DILIs caused by antiepileptic drugs will lead to understanding the mechanisms of these DILIs.

  3. Patient emotions and perceptions of antiepileptic drug changes and titration during treatment for epilepsy.

    Science.gov (United States)

    Fishman, Jesse; Cohen, Greg; Josephson, Colin; Collier, Ann Marie; Bharatham, Srikanth; Zhang, Ying; Wild, Imane

    2017-04-01

    To investigate the impact of antiepileptic drug (AED) change and dose titration on the emotional well-being of patients with epilepsy. Members of an online epilepsy community were invited to voluntarily participate in an online survey. The cross-sectional anonymous survey consisted of 31 multiple choice questions balanced in terms of variety and positivity/negativity of emotions concerning participants' most recent AED change. To substantiate survey results, spontaneous comments from epilepsy-related online forums and social media websites that mentioned participants' experiences with AED medication changes (termed passive listening statements) were analyzed and categorized by theme. All 345 survey participants (270 [78.3%] female; 172 [49.9%] were 26-45years old) self-reported an epilepsy/seizure diagnosis and were currently taking seizure medication; 263 (76.2%) were taking ≥2 AEDs and 301 (87.2%) had ≥1 seizure in the previous 18months. All participants reported a medication change within the previous 12months (dose increased [153 participants (44.3%)], medication added [105 (30.4%)], dose decreased [49 (14.2%)], medication removed [38 (11.0%)]). Improving seizure control (247 [71.6%]) and adverse events (109 [31.6%]) were the most common reasons for medication change. Primary emotions most associated (≥10% of participants) with an AED regimen change were (before medication change; during/after medication change) hopefulness (50 [14.5%]; 43 [12.5%]), uncertainty (50 [14.5%]; 69 [20.0%]), and anxiety (35 [10.1%]; 45 [13.0%]), and were largely due to concerns whether the change would work (212/345 [61.4%]; 180/345 [52.2%]). In the text analysis segment aimed at validating the survey, 230 participants' passive listening statements about medication titration were analyzed; additional seizure activity during dose titration (93 [40.4%]), adverse events during titration (71 [30.9%]), higher medication dosages (33 [14.3%]), and drug costs (25 [10.9%]) were the

  4. Antiepileptic drug utilization in Bangladesh: experience from Dhaka Medical College Hospital.

    Science.gov (United States)

    Habib, Mansur; Khan, Sharif Uddin; Hoque, Azhahul; Mondal, Badrul Alam; Hasan, A T M Hasibul; Chowdhury, Rajib Nayan; Haque, Badrul; Rahman, Kazi Mohibur; Chowdhury, Ahmed Hossain; Ghose, Swapon Kumar; Mohammad, Quazi Deen

    2013-11-18

    Epilepsy is a common health problem which carries a huge medical social psychological and economic impact for a developing country. The aim of this hospital-based study was to get an insight into the effectiveness and tolerability of low cost antiepileptic drugs (AEDs) in Bangladeshi people with epilepsy. This retrospective chart review was done from hospital records in weekly Epilepsy outdoor clinic of Department of Neurology, Dhaka Medical College Hospital (DMCH) from October 1998 to February 2013. A total of 854 epilepsy patients met the eligibility criteria (had a complete record of two years of follow up data) from hospital database. A checklist was used to take demographics (age and gender), epilepsy treatment and adverse event related data. At least two years of follow up data were considered for analysis. Out of 854 patients selected, majority of the patients attending outdoor clinic were >11-30 years age group (55.2%) with a mean age of 20.3 ± 9 years and with a male (53%) predominance. Focal epilepsy were more common (53%), among whom secondary generalized epilepsy was the most frequent diagnosis (67%) followed by complex partial seizure (21%). Among those with Idiopathic Generalized Epilepsy (46%), generalized tonic clonic seizure was encountered in 74% and absence seizure was observed in 13%. The number of patients on monotherapy and dual AED therapy were 67% and 24% respectively and polytherapy (i.e. >3 AEDs) was used only in 9%. CBZ (67%) was the most frequently prescribed AED, followed by VPA (43%), PHB (17%), and PHT (8%). CBZ was prescribed in 37% patients as monotherapy followed by VPA in 21% and PHB in 8% patients. Newer generation drugs eg lemotrigine and topiramate were used only as add on therapy in combination with CBZ and VPA in only 2% patients. The treatment retention rates over the follow up period for the AEDs in monotherapy varied between 86 and 91% and were highest for CBZ, followed by VPA. Most of the combination regimens had a

  5. Antiepileptic drug use and the occurrence of pressure ulcers among bedridden institutionalized elderly patients: a retrospective chart review.

    Science.gov (United States)

    Arinzon, Zeev; Zeilig, Gabriel; Berner, Yitshal N; Adunsky, Abraham

    2005-09-01

    Phenytoin (PH) is indicated primarily for the control of grand mal and psychomotor seizures. However, topical PH has been used for the treatment of various types of ulcers, including pressure ulcers. The aim of this study was to investigate the possibility of a relationship between the use of oral PH and the prevalence of pressure ulcers among bedridden institutionalized elderly patients. This retrospective chart review was conducted in a state-run urban geriatric medical center in Israel and involved long-term bedridden institutionalized patients who were receiving chronic antiepileptic medication during the 7-year period between January 1996 and December 2003. The prevalence of pressure ulcers in patients who received treatment with PH alone or in combination with other antiepileptic drugs was compared with that in patients who received antiepileptic agents other than PH. The study analyzed data from the medical charts of 153 patients, 72 of whom received PH alone or in combination with other antiepileptic drugs, and 81 of whom received antiepileptic agents other than PH. Patients' mean (SD) age was 78.5 (7.2) years; 106 (69.3%) were women. All patients were totally dependent with respect to activities of daily living (mean Katz score, 2.0 [2.0]) and had severe cognitive decline (mean Mini-Mental State Examination score, 3.5 [3.3]). Pressure ulcers occurred in 9.7% of PH recipients and 27.2% of non-PH recipients (P = 0.006; chi2 = 7.55). In PH recipients, 85.7% of pressure ulcers were of mild to moderate severity (stage I or II), compared with 59.1% of ulcers in non-PH recipients; the difference between groups was not statistically significant. Four (18.2%) non-PH recipients and no PH recipients had stage IV pressure ulcers. In the PH group, 71.4% of patients had a pressure ulcer in only 1 anatomic location, compared with 22.7% of the non-PH group (P = 0.023; chi2 = 5.13); 28.6% of PH recipients and 63.6% of non-PH recipients had pressure ulcers in 2 or 3

  6. Malformation risk of antiepileptic drug exposure during pregnancy in women with epilepsy: Results from a pregnancy registry in South India.

    Science.gov (United States)

    Thomas, Sanjeev V; Jose, Manna; Divakaran, Srividya; Sankara Sarma, Prabhakaran

    2017-02-01

    Kerala Registry of Epilepsy and Pregnancy had been prospectively evaluating the reproductive issues of women with epilepsy since April 1998. This analysis aimed to estimate the relative risk of major congenital malformations (MCM) to the registrants. All pregnancies with known outcome in this register until December 2013 were included. Malformation status was evaluated by antenatal ultrasonography, physical examination at birth, echocardiography, and abdomen ultrasonography at 3 months of age and a final review at 1 year of age. There were 1,688 fetuses (singlets 1,643, twins 21, and triplet 1) resulting in 1,622 live births. All were born to women of Asian origin living in South India. The MCM rate for all live births was 6.84% (95% confidence interval [CI] 5.71-8.18) and for all pregnancy outcomes including fetal loss was 7.11% (95% CI 5.98-8.44). The MCM rates (mean with 95% CI) for exposed group were 6.4% (5.03-8.03) for monotherapy and 9.9% (7.37-13.13) for polytherapy; internal control group (women with epilepsy [WWE] not on antiepileptic drugs [AEDs] in first trimester) 5.6% (3.34-9.11), external control group (women without epilepsy or AED exposure in first trimester) 3.45% (1.94-6.07). Valproate monotherapy group had a dose-dependent relative risk for MCM of 2.6 (95% CI 1.30-5.20) compared to the external control group. The preliminary data on MCM rate for the nine total clobazam monotherapy (22.2%; 95% CI 6.2-54.7) signals increased risk that needs further validation on larger sample size. There was no association between MCM rate and maternal socioeconomic status, epilepsy syndrome, or use of folic acid in first trimester. This dataset from South India confirms the increased risk of MCM with exposure to AEDs, particularly polytherapy. A dose-dependent increased risk was observed with valproate. The increased risk associated with clobazam monotherapy is an important signal that needs to be confirmed in a larger sample. Wiley Periodicals, Inc. © 2017

  7. Antiepileptic drug prescribing before, during and after pregnancy: a study in seven European regions.

    Science.gov (United States)

    Charlton, Rachel; Garne, Ester; Wang, Hao; Klungsøyr, Kari; Jordan, Sue; Neville, Amanda; Pierini, Anna; Hansen, Anne; Engeland, Anders; Gini, Rosa; Thayer, Daniel; Bos, Jens; Puccini, Aurora; Nybo Andersen, Anne-Marie; Dolk, Helen; de Jong-van den Berg, Lolkje

    2015-11-01

    The aim of this study was to explore antiepileptic drug (AED) prescribing before, during and after pregnancy as recorded in seven population-based electronic healthcare databases. Databases in Denmark, Norway, the Netherlands, Italy (Emilia Romagna/Tuscany), Wales and the Clinical Practice Research Datalink, representing the rest of the UK, were accessed for the study. Women with a pregnancy starting and ending between 2004 and 2010, which ended in a delivery, were identified. AED prescriptions issued (UK) or dispensed (non-UK) at any time during pregnancy and the 6 months before and after pregnancy were identified in each of the databases. AED prescribing patterns were analysed, and the choice of AEDs and co-prescribing of folic acid were evaluated. In total, 978 957 women with 1 248 713 deliveries were identified. In all regions, AED prescribing declined during pregnancy and was lowest during the third trimester, before returning to pre-pregnancy levels by 6 months following delivery. For all deliveries, the prevalence of AED prescribing during pregnancy was 51 per 10 000 pregnancies (CI95 49-52%) and was lowest in the Netherlands (43/10 000; CI95 33-54%) and highest in Wales (60/10 000; CI95 54-66%). In Denmark, Norway and the two UK databases lamotrigine was the most commonly prescribed AED; whereas in the Italian and Dutch databases, carbamazepine, valproate and phenobarbital were most frequently prescribed. Few women prescribed with AEDs in the 3 months before pregnancy were co-prescribed with high-dose folic acid: ranging from 1.0% (CI95 0.3-1.8%) in Emilia Romagna to 33.5% (CI95 28.7-38.4%) in Wales. The country's differences in prescribing patterns may suggest different use, knowledge or interpretation of the scientific evidence base. The low co-prescribing of folic acid indicates that more needs to be done to better inform clinicians and women of childbearing age taking AEDs about the need to offer and receive complete preconception care

  8. Uncertainties from a worldwide survey on antiepileptic drug withdrawal after seizure remission.

    Science.gov (United States)

    Bartolini, Luca; Majidi, Shahram; Koubeissi, Mohamad Z

    2018-04-01

    We sought to determine differences in practice for discontinuation of antiepileptic drugs (AEDs) after seizure remission and stimulate the planning and conduction of withdrawal trials. We utilized a worldwide electronic survey that included questions about AED discontinuation for 3 paradigmatic cases in remission: (1) focal epilepsy of unknown etiology, (2) temporal lobe epilepsy after surgery, and (3) juvenile myoclonic epilepsy. We analyzed 466 complete questionnaires from 53 countries, including the United States. Statistical analysis included χ 2 and multivariate logistic regression. Case 1: responders in practice for <10 years were less likely to taper AEDs: odds ratio (OR) (95% confidence interval [CI]) 0.52 (0.32-0.85), p = 0.02. The likelihood of stopping AEDs was higher among doctors treating children: OR (95% CI): 11.41 (2.51-40.13), p = 0.002. Doctors treating children were also more likely to stop after 2 years or less of remission: OR (95% CI): 6.91 (2.62-19.31), p = 0.002, and the same was observed for US physicians: OR (95% CI): 1.61 (1.01-2.57), p = 0.0049. Case 2: responders treating children were more likely to taper after 1 year or less of postoperative remission, with the goal of discontinuing all medications: OR (95% CI): 1.91 (1.09-3.12), p = 0.015, and so were US-based responders: OR (95% CI): 1.73 (1.21-2.41), p = 0.003. Case 3: epileptologists were less likely to withdraw the medication: OR (95% CI): 0.56 (0.39-0.82), p = 0.003, and so were those in practice for 10 or more years: OR (95% CI): 0.54 (0.31-0.95), p = 0.025. We observed several differences in practice for AED withdrawal after seizure remission that highlight global uncertainty. Trials of AED discontinuation are needed to provide evidence-based guidance.

  9. Comparative persistence of antiepileptic drugs in patients with epilepsy: A STROBE-compliant retrospective cohort study

    Science.gov (United States)

    Lai, Edward Chia-Cheng; Hsieh, Cheng-Yang; Su, Chien-Chou; Yang, Yea-Huei Kao; Huang, Chin-Wei; Lin, Swu-Jane; Setoguchi, Soko

    2016-01-01

    Abstract We compared persistence of antiepileptic drugs (AEDs) including carbamazepine, oxcarbazepine, gabapentin, lamotrigine, topiramate, valproic acid, and phenytoin in an Asian population with epilepsy. A retrospective cohort study was conducted by analyzing Taiwan's National Health Insurance Research Database (NHIRD). Adult epilepsy patients newly prescribed with AEDs between 2005 and 2009 were included. The primary outcome was persistence, defined as the treatment duration from the date of AED initiation to the date of AED discontinuation, switching, hospitalization due to seizure or disenrollment from databases, whichever came first. Cox proportional hazard models were used to estimate the risk of non-persistence with AEDs. Among the 13,061 new users of AED monotherapy (mean age: 58 years; 60% men), the persistence ranged from 218.8 (gabapentin) to 275.9 (oxcarbazepine) days in the first treatment year. The risks of non-persistence in patients receiving oxcarbazepine (adjusted hazard ratio [HR], 0.78; 95% CI, 0.74–0.83), valproic acid (0.88; 0.85–0.92), lamotrigine (0.72; 0.65–0.81), and topiramate (0.90; 0.82–0.98) were significantly lower than in the carbamazepine group. Compared with carbamazepine users, the non-persistence risk was higher in phenytoin users (1.10; 1.06–1.13), while gabapentin users (1.03; 0.98–1.09) had similar risk. For risk of hospitalization due to seizure and in comparison with carbamazepine users, oxcarbazepine (0.66; 0.58–0.74) and lamotrigine (0.46; 0.35–0.62) users had lower risk, while phenytoin (1.35; 1.26–1.44) users had higher risk. The results remained consistent throughout series of sensitivity and stratification analyses. The persistence varied among AEDs and was better for oxcarbazepine, valproic acid, lamotrigine, and topiramate, but worse for phenytoin when compared with carbamazepine. PMID:27583857

  10. Antiepileptic Drug Titration and Related Health Care Resource Use and Costs.

    Science.gov (United States)

    Fishman, Jesse; Kalilani, Linda; Song, Yan; Swallow, Elyse; Wild, Imane

    2018-02-27

    Unexpected breakthrough seizures resulting from suboptimal antiepileptic drug (AED) dosing during the titration period, as well as adverse events resulting from rapid AED titration, may influence the titration schedule and significantly increase health care resource use (HRU) and health care costs. To assess the relationship between AEDs, HRU, and costs during AED titration and maintenance. Practicing neurologists were recruited from a nationwide panel to provide up to 3 patient records each for this retrospective medical chart review. Patients with epilepsy who were aged ≥ 18 years and had initiated an AED between January 1, 2014, and January 1, 2016, were followed for 6 months from AED initiation. Titration duration was the time from AED initiation to the beginning of treatment maintenance as determined by the physician. Outcomes were epilepsy-specific HRU (hospitalizations, emergency department visits, outpatient visits, physician referral, laboratory testing/diagnostic imaging, and phone calls) and related costs that occurred during the titration or maintenance treatment periods. Of 811 patients, 156, 128, 125, 120, 114, 107, and 61 initiated the following AEDs: levetiracetam, lamotrigine, lacosamide, valproate, topiramate, carbamazepine, and phenytoin, respectively. Most patients (619/803 [77.1%] with complete AED data) received monotherapy. Baseline characteristics were similar across AEDs (mean [SD] age, 36.6 [14.4] years; 59.0% male). Kaplan-Meier estimates of titration duration ranged from 3.3 weeks (phenytoin) to 8.1 weeks (lamotrigine). From titration to maintenance, the overall incidence of HRU per person-month decreased 54.5%-89.3% for each HRU measure except outpatient visits (24.6% decrease). Total epilepsy-related costs decreased from $80.48 to $42.77 per person-month, or 46.9% from titration to maintenance. AED titration periods had higher HRU rates and costs than AED maintenance, suggesting that use of AEDs with shorter titration requirements

  11. Quality of antiepileptic drugs in sub-Saharan Africa: A study in Gabon, Kenya, and Madagascar.

    Science.gov (United States)

    Jost, Jeremy; Ratsimbazafy, Voa; Nguyen, Thu Trang; Nguyen, Thuy Linh; Dufat, Hanh; Dugay, Annabelle; Ba, Alassane; Sivadier, Guilhem; Mafilaza, Yattussia; Jousse, Cyril; Traïkia, Mounir; Leremboure, Martin; Auditeau, Emilie; Raharivelo, Adeline; Ngoungou, Edgard; Kariuki, Symon M; Newton, Charles R; Preux, Pierre-Marie

    2018-06-12

    Epilepsy is a major public health issue in low- and middle-income countries, where the availability and accessibility of quality treatment remain important issues, the severity of which may be aggravated by poor quality antiepileptic drugs (AEDs). The primary objective of this study was to measure the quality of AEDs in rural and urban areas in 3 African countries. This cross-sectional study was carried out in Gabon, Kenya, and Madagascar. Both official and unofficial supply chains in urban and rural areas were investigated. Samples of oral AEDs were collected in areas where a patient could buy or obtain them. Pharmacological analytical procedures and Medicine Quality Assessment Reporting Guidelines were used to assess quality. In total, 102 batches, representing 3782 units of AEDs, were sampled. Overall, 32.3% of the tablets were of poor quality, but no significant difference was observed across sites: 26.5% in Gabon, 37.0% in Kenya, and 34.1% in Madagascar (P = .7). The highest proportions of substandard medications were found in the carbamazepine (38.7%; 95% confidence interval [CI] 21.8-57.8) and phenytoin (83.3%; 95% CI 35.8-99.5) batches, which were mainly flawed by their failure to dissolve. Sodium valproate was the AED with the poorest quality (32.1%; 95% CI 15.8-42.3). The phenobarbital (94.1%; 95% CI 80.3-99.2) and diazepam (100.0%) batches were of better quality. The prevalence of substandard quality medications increased in samples supplied by public facilities (odds ratio [OR] 9.9; 95% CI 1.2-84.1; P < .04) and manufacturers located in China (OR 119.8; 95% CI 8.7-1651.9; P < .001). The prevalence of AEDs of bad quality increased when they were stored improperly (OR 5.4; 95% CI 1.2-24.1; P < .03). No counterfeiting was observed. However, inadequate AED storage conditions are likely to lead to ineffective and possibly dangerous AEDs, even when good-quality AEDs are initially imported. Wiley Periodicals, Inc. © 2018 International League Against

  12. Does brain slices from pentylenetetrazole-kindled mice provide a more predictive screening model for antiepileptic drugs?

    DEFF Research Database (Denmark)

    Hansen, Suzanne L.; Sterjev, Zoran; Werngreen, Marie

    2012-01-01

    The cortical wedge is a commonly applied model for in vitro screening of new antiepileptic drugs (AEDs) and has been extensively used in characterization of well-known AEDs. However, the predictive validity of this model as a screening model has been questioned as, e.g., carbamazepine has been...... screening model for AEDs. To this end, we compared the in vitro and in vivo pharmacological profile of several selected AEDs (phenobarbital, phenytoin, tiagabine, fosphenytoin, valproate, and carbamazepine) along with citalopram using the PTZ-kindled model and brain slices from naïve, saline...

  13. An acardiac acephalic monster following in-utero anti-epileptic drug exposure.

    Science.gov (United States)

    Kutlay, B; Bayramoglu, S; Kutlar, A I; Yesildaglar, N

    1996-04-01

    Acardia, the absence of the heart, is one of the rarest medical anomalies. The exact mechanism which causes this anomaly is still unknown. The authors report the acardiac acephalic fetus of an epileptic mother who was on primidone therapy. The mother who received no antenatal care stopped taking primidone (her sole medication) in the third month of pregnancy with the fear of delivering a malformed baby and had three convulsions until delivery. This is the first reported case of acardia associated with anti-epileptic medication. The cause of the anomaly in this patient may be an unknown genetic defect, the maternal epileptic disorder, the convulsions, the anti-epileptic medication, or a combination of these factors.

  14. Psychiatric and behavioral side effects of antiepileptic drugs in adults with epilepsy.

    Science.gov (United States)

    Chen, Baibing; Choi, Hyunmi; Hirsch, Lawrence J; Katz, Austen; Legge, Alexander; Buchsbaum, Richard; Detyniecki, Kamil

    2017-11-01

    Psychiatric and behavioral side effects (PBSEs) are common, undesirable effects associated with antiepileptic drug (AED) use. The objective of the study was to compare the PBSE profiles of older and newer AEDs in a large specialty practice-based sample of patients diagnosed with epilepsy. As part of the Columbia and Yale AED Database Project, we reviewed patient records including demographics, medical history, AED use, and side effects for 4085 adult patients (age: 18 years) newly started on an AED regimen. Psychiatric and behavioral side effects were determined by patient or physician report in the medical record, which included depressive mood, psychosis, anxiety, suicidal thoughts, irritability, aggression, and tantrum. Significant non-AED predictors of PBSE rate were first determined from 83 variables using logistic regression. Predictors were then controlled for in the comparison analysis of the rate of PBSEs and intolerable PBSEs (PBSEs that led to dosage reduction or discontinuation) between 18 AEDs. Psychiatric and behavioral side effects occurred in 17.2% of patients and led to intolerability in 13.8% of patients. History of psychiatric condition(s), secondary generalized seizures, absence seizures, and intractable epilepsy were associated with increased incidence of PBSE. Levetiracetam (LEV) had the greatest PBSE rate (22.1%). This was statistically significant when compared with the aggregate of the other AEDs (P<0.001, OR=6.87). Levetiracetam was also significantly (P<0.001) associated with higher intolerability rate (17.7%), dose decreased rate (9.4%), and complete cessation rate (8.3%), when compared with the aggregate of the other AEDs. Zonisamide (ZNS) was also significantly associated with a higher rate of PBSE (9.7%) and IPBSE (7.9%, all P<0.001). On the other hand, carbamazepine (CBZ), clobazam (CLB), gabapentin (GBP), lamotrigine (LTG), oxcarbazepine (OXC), phenytoin (PHT), and valproate (VPA) were significantly associated with a decreased PBSE

  15. SAFETY AND TOLERABILITY OF ANTIEPILEPTIC DRUGS AT WOMEN WITH EPILEPSY (DATA OF SVT. LUKA’S INSTITUTE OF CHILD NEUROLOGY AND EPILEPSY

    Directory of Open Access Journals (Sweden)

    K. Yu. Мukhin

    2015-01-01

    Full Text Available Women with epilepsy are referred to the special risk group due to the development of side effects of antiepileptic drugs (АED. Women’s neuroendocrinal disorders can be caused by the disease itself-epilepsy, as well as by the undertaken therapy. We have carried out a retrospective research in order to assess the safety and the tolerance of different AED at young girls and women of reproductive age. Was analyzed the data base of patients of Svt. Luka’s Institute of Child Neurology and Epilepsy, comprising all patients, who have been monitored in the period between 2000 and 2014 inclusive at the age between 15–40 years (n = 301. The research included patients, with different diagnosed forms of focal or generalized epilepsy, who were taking AED both during mono and polytherapy. Were analyzed all cases of neuroendocrinal, especially reproductive disorders, including the considerable gain of weight, menstrual disorder, sterility at AED background. Also was analyzed the result of all registered pregnancies at women with epilepsy (at the background of the antiepileptic therapy, as well as without treatment during pregnancy. The retrospective data analysis has revealed 51 сase (17 % in the group under review of expressed neuroendocrinal, reproductive and cosmetic side effects (including the menstrual disorder: dysmenorrhea, opsomenorrhea, amenorrhea, anovulatory cycles, sterility, unfavorable pregnancy outcomes, as well as cosmetic endocrinal side effects: obesity, hirsutism, hair loss. Most patients have got such combined side effects. Our research results show, that in most cases the pregnancy at women with epilepsy ends by birth of a healthy child, the pregnancy outcome depends on many factors, it also differs according to applied AED. Valproic acid drugs show the highest teratogenic risk. Also at the back ground of the therapy with valproic acid have been registered most cases of neuroendocrinal reproductive diseases at women

  16. Utilization of antiepileptic drugs during pregnancy: Comparative patterns in 38 countries based on data from the EURAP registry

    DEFF Research Database (Denmark)

    Battino, D.; Bonizzoni, E.; Craig, J.

    2009-01-01

    We assessed the utilization of antiepileptic drugs (AEDs), 1999-2005, in 4,798 prospective epilepsy pregnancies from 38 countries participating in EURAP, an international AED and pregnancy registry. Prominent differences in utilization patterns were observed across the various countries. Exposure...... to second-generation AEDs ranged from 3.5% in India and 7.3% in Italy to 75% in Denmark. Even wider variation was recorded in exposure to individual AEDs. The utilization of second-generation AEDs increased over time (for lamotrigine, from 9.9% of all pregnancies before 2001 to 29.6% after 2003......). The differences in use of individual AEDs across countries probably reflect lack of evidence concerning the optimal treatment of epilepsy in women of childbearing age, as well as variation in country-specific traditions, medication costs, and drug promotion. Our observations underscore the need for comparative...

  17. The EULAR Study Group for Registers and Observational Drug Studies

    DEFF Research Database (Denmark)

    Kearsley-Fleet, Lianne; Závada, Jakub; Hetland, Merete Lund

    2015-01-01

    and collate information on the availability of potential confounders within these registers. METHODS: Baseline characteristics of patients starting their first bDMARD in an arbitrary year (2008) for the treatment of RA, including demographic and disease characteristics, bDMARD drug details and co...

  18. Comparative evaluation of oral hygiene status and gingival enlargement among epileptic and healthy children as related to various antiepileptic drugs

    Directory of Open Access Journals (Sweden)

    Neelam Hasmukhbhai Joshi

    2017-01-01

    Full Text Available Background: Epilepsy is a gathering of neurological disorders characterized by epileptic seizures. Epileptic children, who are on active treatment with antiepileptic drugs, have a well-recognized side effect of gingival enlargement. Therefore, all efforts should be made, particularly for the population who are diagnosed or affected by the systemic disease. This study was conducted with an aim to determine oral hygiene status and gingival enlargement among epileptic and healthy children as related to various antiepileptic drugs. Materials and Methods: The cross-sectional observational study was conducted in the department of pedodontics and attached general hospital. A sample size of 120 participants with 60 healthy and 60 epileptic children between age 2 and 14 years were included. Oral health status of participants was examined using oral hygiene simplified index and plaque index. Gingival enlargement was assessed using Miranda–Brunet index. For statistical analysis, one-way ANOVA test, independent t-test, and Pearson's Chi-square test were used. Results: From the total participants included in the study, 49% of participants had good oral hygiene from healthy group, and 28% participants had poor oral hygiene from the epileptic group. Sodium valproate was the most common drug used and was associated with increased gingival enlargement. Conclusion: Conclusion can be drawn that epileptic children under medication had poor oral hygiene and an increased risk for gingival enlargement as compared to their healthy counterparts. It must be stressed that the epileptic patients should be given dental care without conditions and provided with best possible care to restore esthetics and functions.

  19. Comparing Safety and Efficacy of "Third-Generation" Antiepileptic Drugs: Long-Term Extension and Post-marketing Treatment.

    Science.gov (United States)

    Kwok, Charlotte S; Johnson, Emily L; Krauss, Gregory L

    2017-11-01

    Four "third-generation" antiepileptic drugs (AEDs) were approved for adjunctive treatment of refractory focal onset seizures during the past 10 years. Long-term efficacy and safety of the drugs were demonstrated in large extension studies and in reports of subgroups of patients not studied in pivotal trials. Reviewing extension study and post-marketing outcome series for the four newer AEDs-lacosamide, perampanel, eslicarbazepine acetate and brivaracetam-can guide clinicians in treating and monitoring patients. AED extension studies evaluate treatment retention, drug tolerability, and drug safety during individualized treatment with flexible dosing and thus provide information not available in rigid pivotal trials. Patient retention in the studies ranged from 75 to 80% at 1 year and from 36 to 68% at 2-year treatment intervals. Safety findings were generally similar to those of pivotal trials, with no major safety risks identified and with several specific adverse drug effects, such as hyponatremia, reported. The third-generation AEDs, some through new mechanisms and others with improved tolerability compared to related AEDs, provide new options in efficacy and tolerability.

  20. A Review for the Analysis of Antidepressant, Antiepileptic and Quinolone Type Drugs in Pharmaceuticals and Environmental Samples.

    Science.gov (United States)

    Rani, Susheela; Malik, Ashok Kumar; Kaur, Ramandeep; Kaur, Ripneel

    2016-09-02

    The analysis of drugs in various biological fluids is an important criterion for the determination of the physiological performance of a drug. After sampling of the biological fluid, the next step in the analytical process is sample preparation. Sample preparation is essential for isolation of desired components from complex biological matrices and greatly influences their reliable and accurate determination. The complexity of biological fluids adds to the challenge of direct determination of the drug by chromatographic analysis, therefore demanding a sample preparation step that is often time consuming, tedious and frequently overlooked. However, direct online injection methods offer the advantage of reducing sample preparation steps and enabling effective pre-concentration and clean-up of biological fluids. These procedures can be automated and therefore reduce the requirements for handling potentially infectious biomaterial, improve reproducibility, and minimize sample manipulations and potential contamination. This review is focused on the discovery and development of high-performance liquid chromatography (HPLC) and gas chromatography (GC) with different detectors. The drugs covered in this review are antiepileptics, antidepressant (AD), and quinolones. The application of these methods for determination of these drugs in biological, environmental and pharmaceutical samples has also been discussed.

  1. Modulation of Antioxidant Enzymatic Activities by Certain Antiepileptic Drugs (Valproic Acid, Oxcarbazepine, and Topiramate): Evidence in Humans and Experimental Models

    Science.gov (United States)

    Cárdenas-Rodríguez, Noemí; Coballase-Urrutia, Elvia; Rivera-Espinosa, Liliana; Romero-Toledo, Arantxa; Sampieri, Aristides III; Ortega-Cuellar, Daniel; Montesinos-Correa, Hortencia; Floriano-Sánchez, Esaú; Carmona-Aparicio, Liliana

    2013-01-01

    It is estimated that at least 100 million people worldwide will suffer from epilepsy at some point in their lives. This neurological disorder induces brain death due to the excessive liberation of glutamate, which activates the postsynaptic N-methyl-D-aspartic acid (NMDA) receptors, which in turn cause the reuptake of intracellular calcium (excitotoxicity). This excitotoxicity elicits a series of events leading to nitric oxide synthase (NOS) activation and the generation of reactive oxygen species (ROS). Several studies in experimental models and in humans have demonstrated that certain antiepileptic drugs (AEDs) exhibit antioxidant effects by modulating the activity of various enzymes associated with this type of stress. Considering the above-mentioned data, we aimed to compile evidence elucidating how AEDs such as valproic acid (VPA), oxcarbazepine (OXC), and topiramate (TPM) modulate oxidative stress. PMID:24454986

  2. Modulation of Antioxidant Enzymatic Activities by Certain Antiepileptic Drugs (Valproic Acid, Oxcarbazepine, and Topiramate: Evidence in Humans and Experimental Models

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    Noemí Cárdenas-Rodríguez

    2013-01-01

    Full Text Available It is estimated that at least 100 million people worldwide will suffer from epilepsy at some point in their lives. This neurological disorder induces brain death due to the excessive liberation of glutamate, which activates the postsynaptic N-methyl-D-aspartic acid (NMDA receptors, which in turn cause the reuptake of intracellular calcium (excitotoxicity. This excitotoxicity elicits a series of events leading to nitric oxide synthase (NOS activation and the generation of reactive oxygen species (ROS. Several studies in experimental models and in humans have demonstrated that certain antiepileptic drugs (AEDs exhibit antioxidant effects by modulating the activity of various enzymes associated with this type of stress. Considering the above-mentioned data, we aimed to compile evidence elucidating how AEDs such as valproic acid (VPA, oxcarbazepine (OXC, and topiramate (TPM modulate oxidative stress.

  3. Intestinal absorption of the antiepileptic drug substance vigabatrin is altered by infant formula in vitro and in vivo

    DEFF Research Database (Denmark)

    Nielsen, Carsten Uhd

    2014-01-01

    Vigabatrin is an antiepileptic drug substance mainly used in pediatric treatment of infantile spasms. The main source of nutrition for infants is breast milk and/or infant formula. Our hypothesis was that infant formula may affect the intestinal absorption of vigabatrin. The aim was therefore...... to investigate the potential effect of coadministration of infant formula with vigabatrin on the oral absorption in vitro and in vivo. The effect of vigabatrin given with an infant formula on the oral uptake and transepithelial transport was investigated in vitro in Caco-2 cells. In vivo effects of infant...... formula and selected amino acids on the pharmacokinetic profile of vigabatrin was investigated after oral coadministration to male Sprague–Dawley rats using acetaminophen as a marker for gastric emptying. The presence of infant formula significantly reduced the uptake rate and permeability of vigabatrin...

  4. Zebrafish embryotoxicity test for developmental (neuro)toxicity : Demo case of an integrated screening approach system using anti-epileptic drugs

    NARCIS (Netherlands)

    Beker van Woudenberg, Anna; Snel, Cor; Rijkmans, Eke; De Groot, Didima; Bouma, Marga; Hermsen, Sanne; Piersma, Aldert; Menke, Aswin; Wolterbeek, André

    2014-01-01

    To improve the predictability of the zebrafish embryotoxicity test (ZET) for developmental (neuro)toxicity screening, we used a multiple-endpoints strategy, including morphology, motor activity (MA), histopathology and kinetics. The model compounds used were antiepileptic drugs (AEDs): valproic acid

  5. Zebrafish embryotoxicity test for developmental (neuro)toxicity: Demo case of an integrated screening approach system using anti-epileptic drugs

    NARCIS (Netherlands)

    Beker van Woudenberg, A.; Snel, C.; Rijkmans, E.; Groot, D. de; Bouma, M.; Hermsen, S.; Piersma, A.; Menke, A.; Wolterbeek, A.

    2014-01-01

    To improve the predictability of the zebrafish embryotoxicity test (ZET) for developmental (neuro)toxicity screening, we used a multiple-endpoints strategy, including morphology, motor activity (MA), histopathology and kinetics. The model compounds used were antiepileptic drugs (AEDs): valproic acid

  6. An Australian nationwide survey on medicinal cannabis use for epilepsy: History of antiepileptic drug treatment predicts medicinal cannabis use.

    Science.gov (United States)

    Suraev, Anastasia S; Todd, Lisa; Bowen, Michael T; Allsop, David J; McGregor, Iain S; Ireland, Carol; Lintzeris, Nicholas

    2017-05-01

    Epilepsy Action Australia conducted an Australian nationwide online survey seeking opinions on and experiences with the use of cannabis-based products for the treatment of epilepsy. The survey was promoted via the Epilepsy Action Australia's main website, on their Facebook page, and by word of mouth. The survey consisted of 39 questions assessing demographics, clinical factors, including diagnosis and seizure types, and experiences with and opinions towards cannabis use in epilepsy. A total of 976 responses met the inclusion criteria. Results show that 15% of adults with epilepsy and 13% of parents/guardians of children with epilepsy were currently using, or had previously used, cannabis products to treat epilepsy. Of those with a history of cannabis product use, 90% of adults and 71% of parents reported success in reducing seizure frequency after commencing cannabis products. The main reasons for medicinal cannabis use were to manage treatment-resistant epilepsy and to obtain a more favorable side-effect profile compared to standard antiepileptic drugs. The number of past antiepileptic drugs tried was a significant predictor of medicinal cannabis use in both adults and children with epilepsy. Fifty-six percent of adults with epilepsy and 62% of parents/guardians of children with epilepsy expressed willingness to participate in clinical trials of cannabinoids. This survey provides insight into the use of cannabis products for epilepsy, in particular some of the likely factors influencing use, as well as novel insights into the experiences of and attitudes towards medicinal cannabis in people with epilepsy in the Australian community. This article is part of a Special Issue entitled "Cannabinoids and Epilepsy". Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Vinpocetine inhibits glutamate release induced by the convulsive agent 4-aminopyridine more potently than several antiepileptic drugs.

    Science.gov (United States)

    Sitges, M; Sanchez-Tafolla, B M; Chiu, L M; Aldana, B I; Guarneros, A

    2011-10-01

    4-Aminopyridine (4-AP) is a convulsing agent that in vivo preferentially releases Glu, the most important excitatory amino acid neurotransmitter in the brain. Here the ionic dependence of 4-AP-induced Glu release and the effects of several of the most common antiepileptic drugs (AEDs) and of the new potential AED, vinpocetine on 4-AP-induced Glu release were characterized in hippocampus isolated nerve endings pre-loaded with labelled Glu ([3H]Glu). 4-AP-induced [3H]Glu release was composed by a tetrodotoxin (TTX) sensitive and external Ca2+ dependent fraction and a TTX insensitive fraction that was sensitive to the excitatory amino acid transporter inhibitor, TBOA. The AEDs: carbamazepine, phenytoin, lamotrigine and oxcarbazepine at the highest dose tested only reduced [3H]Glu release to 4-AP between 50-60%, and topiramate was ineffective. Vinpocetine at a much lower concentration than the above AEDs, abolished [3H]Glu release to 4-AP. We conclude that the decrease in [3H]Glu release linked to the direct blockade of presynaptic Na+ channels, may importantly contribute to the anticonvulsant actions of all the drugs tested here (except topiramate); and that the significantly greater vinpocetine effect in magnitude and potency on [3H]Glu release when excitability is exacerbated like during seizures, may involve the increase additionally exerted by vinpocetine in some K+ channels permeability. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. The Effect of High and Low Antiepileptic Drug Dosage on Simulated Driving Performance in Person's with Seizures: A Pilot Study

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    Alexander M. Crizzle

    2015-10-01

    Full Text Available Background: Prior studies examining driving performance have not examined the effects of antiepileptic drugs (AED’s or their dosages in persons with epilepsy. AED’s are the primary form of treatment to control seizures, but they are shown to affect cognition, attention, and vision, all which may impair driving. The purpose of this study was to describe the characteristics of high and low AED dosages on simulated driving performance in persons with seizures. Method: Patients (N = 11; mean age 42.1 ± 6.3; 55% female; 100% Caucasian were recruited from the Epilepsy Monitoring Unit and had their driving assessed on a simulator. Results: No differences emerged in total or specific types of driving errors between high and low AED dosages. However, high AED drug dosage was significantly associated with errors of lane maintenance (r = .67, p < .05 and gap acceptance (r = .66, p < .05. The findings suggest that higher AED dosages may adversely affect driving performance, irrespective of having a diagnosis of epilepsy, conversion disorder, or other medical conditions. Conclusion: Future studies with larger samples are required to examine whether AED dosage or seizure focus alone can impair driving performance in persons with and without seizures.

  9. Prevalence of Different Combinations of Antiepileptic Drugs and CNS Drugs in Elderly Home Care Service and Nursing Home Patients in Norway.

    Science.gov (United States)

    Halvorsen, Kjell H; Johannessen Landmark, Cecilie; Granas, Anne Gerd

    2016-01-01

    Introduction. Antiepileptic drugs (AEDs) are used to treat different conditions in elderly patients and are among the drug classes most susceptible to be involved in drug-drug interactions (DDI). The aim of the study was to describe and compare use of AEDs between home care service and nursing home patients, as these patients are not included in nationwide databases of drug utilization. In the combined population, we investigate DDI of AEDs with other central nervous system- (CNS-) active drugs and DDIs involving AEDs in general. Materials and Methods. Point-prevalence study of Norwegian patients in home care services and nursing homes in 2009. At the patient level, we screened for different DDIs involving AEDs. Results. In total, 882 patients (7.8%) of 11,254 patients used AEDs and number of users did not differ between home care services and nursing homes (8.2% versus 7.7%). In the combined population, we identified 436 potential DDIs in 45% of the patients. Conclusions. In a large population of elderly, home care service and nursing home patients do not differ with respect to exposure of AEDs but use more AEDs as compared to the general population of similar age. The risk of DDIs with AEDs and other CNS-active drugs should be taken into consideration and individual clinical evaluations are assessed in this population.

  10. Quantitative EEG and Current Source Density Analysis of Combined Antiepileptic Drugs and Dopaminergic Agents in Genetic Epilepsy: Two Case Studies.

    Science.gov (United States)

    Emory, Hamlin; Wells, Christopher; Mizrahi, Neptune

    2015-07-01

    Two adolescent females with absence epilepsy were classified, one as attention deficit and the other as bipolar disorder. Physical and cognitive exams identified hypotension, bradycardia, and cognitive dysfunction. Their initial electroencephalograms (EEGs) were considered slightly slow, but within normal limits. Quantitative EEG (QEEG) data included relative theta excess and low alpha mean frequencies. A combined treatment of antiepileptic drugs with a catecholamine agonist/reuptake inhibitor was sequentially used. Both patients' physical and cognitive functions improved and they have remained seizure free. The clinical outcomes were correlated with statistically significant changes in QEEG measures toward normal Z-scores in both anterior and posterior regions. In addition, low resolution electromagnetic tomography (LORETA) Z-scored source correlation analyses of the initial and treated QEEG data showed normalized patterns, supporting a neuroanatomic resolution. This study presents preliminary evidence for a neurophysiologic approach to patients with absence epilepsy and comorbid disorders and may provide a method for further research. © EEG and Clinical Neuroscience Society (ECNS) 2014.

  11. Brain tumors in eloquent areas: A European multicenter survey of intraoperative mapping techniques, intraoperative seizures occurrence, and antiepileptic drug prophylaxis.

    Science.gov (United States)

    Spena, Giannantonio; Schucht, Philippe; Seidel, Kathleen; Rutten, Geert-Jan; Freyschlag, Christian Franz; D'Agata, Federico; Costi, Emanule; Zappa, Francesca; Fontanella, Marco; Fontaine, Denys; Almairac, Fabien; Cavallo, Michele; De Bonis, Pasquale; Conesa, Gerardo; Foroglou, Nicholas; Gil-Robles, Santiago; Mandonnet, Emanuel; Martino, Juan; Picht, Thomas; Viegas, Catarina; Wager, Michel; Pallud, Johan

    2017-04-01

    Intraoperative mapping and monitoring techniques for eloquent area tumors are routinely used world wide. Very few data are available regarding mapping and monitoring methods and preferences, intraoperative seizures occurrence and perioperative antiepileptic drug management. A questionnaire was sent to 20 European centers with experience in intraoperative mapping or neurophysiological monitoring for the treatment of eloquent area tumors. Fifteen centers returned the completed questionnaires. Data was available on 2098 patients. 863 patients (41.1%) were operated on through awake surgery and intraoperative mapping, while 1235 patients (58.8%) received asleep surgery and intraoperative electrophysiological monitoring or mapping. There was great heterogeneity between centers with some totally AW oriented (up to 100%) and other almost totally ASL oriented (up to 92%) (31% SD). For awake surgery, 79.9% centers preferred an asleep-awake-asleep anesthesia protocol. Only 53.3% of the centers used ECoG or transcutaneous EEG. The incidence of intraoperative seizures varied significantly between centers, ranging from 2.5% to 54% (p mapping technique and the risk of intraoperative seizures. Moreover, history of preoperative seizures can significantly increase the risk of intraoperative seizures (p mapping and monitoring protocols and the management of peri- and intraoperative seizures. This data can help identify specific aspects that need to be investigated in prospective and controlled studies.

  12. Behavioral effects of antiepileptic drugs in rats: Are the effects on mood and behavior detectable in open-field test?

    Science.gov (United States)

    Zimcikova, Eva; Simko, Julius; Karesova, Iva; Kremlacek, Jan; Malakova, Jana

    2017-11-01

    Behavioral side effects of antiepileptic drugs (AEDs) are common including both positive and negative effects on mood, anxiety, depression, and psychosis. We aimed to evaluate behavioral patterns in rats after administration of lamotrigine, levetiracetam, phenytoin, topiramate, carbamazepine, gabapentin, pregabalin, and zonisamide. The open-field test was performed and locomotion, rearing, grooming, central latency and defecation were recorded over a 5min interval for each rat (8 rats in each group receiving AED and 16 controls). Kruskal-Wallis nonparametric test or ANOVA were used to assess differences among the groups. The experimental groups did not differ in latency to enter the center compartment, neither in the decline of locomotor activity in the 1st and the 5th minute of the observation, nor in number of rears. Significant differences among groups were observed in the total number of lines crossed, grooming, as well in the number of fecal pellets. Locomotor activity was significantly increased in lamotrigine, if compared with gabapentin and pregabalin (ANOVA; p <0.05). Rats exposed to topiramate displayed a significantly increased number of grooming (when compared to pregabalin: p<0.01). Defecation (the number of fecal pellets) significantly increased in the gabapentin and carbamazepine group. There are significant differences between AEDs in terms of their behavioral profile. It is of great importance to evaluate these effects in clinical practice to bring more clear insight into these positive or negative side effects of AEDs. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  13. Possible roles for frequent salivary antiepileptic drug monitoring in the management of epilepsy.

    Science.gov (United States)

    Herkes, G K; Eadie, M J

    1990-07-01

    Salivary levels of phenytoin, phenobarbitone, carbamazepine and carbamazepine-epoxide correlate with the simultaneous plasma water levels of these substances, after correcting for the effects of pH differences between saliva and plasma in the case of phenobarbitone. Saliva is easy and painless to collect, and salivary levels of the drugs are conveniently measured. Frequent (often daily) monitoring of pre-dose morning anticonvulsant drug concentrations in saliva over periods of weeks or months in 3 groups of epileptic subjects showed that (i) in some but not all poorly controlled epileptic patients seizures tended to occur on days when salivary anticonvulsant levels were lower than on non-seizure days, (ii) in such subjects it was possible to estimate an anticipated optimal drug concentration and dose to minimize seizure activity from the plot of seizure frequency against drug concentrations, (iii) in women with 'catamenial' epilepsy, salivary anticonvulsant levels were lower on perimenstrual days than at mid-cycle in half of the subjects studied, and (iv) in pregnant epileptic women the time course of the change in drug levels relative to dose could be followed more closely throughout pregnancy and the post-natal period than was practicable when using blood level measurements. Frequent measurement of salivary anticonvulsant concentrations appears a promising and inexpensive adjunct to the investigation and management of certain problem areas in epilepsy.

  14. Food intake and antiepileptic drugs: evidence for a role of GABA in circadian time keeping.

    Science.gov (United States)

    Rietveld, W J; van Schravendijk, K

    1987-01-01

    Long-term application of sodium-valproate was studied while recording food intake of rats. It was found that sodium valproate was able to decrease the period length of free-running circadian rhythmicity. After withdrawal of the drug, the period length returned to the predrug values.

  15. Comparison of phenobarbital with bromide as a first-choice antiepileptic drug for treatment of epilepsy in dogs.

    Science.gov (United States)

    Boothe, Dawn Merton; Dewey, Curtis; Carpenter, David Mark

    2012-05-01

    To compare efficacy and safety of treatment with phenobarbital or bromide as the first-choice antiepileptic drug (AED) in dogs. Double-blinded, randomized, parallel, clinical trial. 46 AED-naïve dogs with naturally occurring epilepsy. Study inclusion was based on age, history, findings on physical and neurologic examinations, and clinicopathologic test results. For either phenobarbital treatment (21 dogs) or bromide treatment (25), a 7-day loading dose period was initiated along with a maintenance dose, which was adjusted on the basis of monthly monitoring. Efficacy and safety outcomes were compared between times (baseline and study end [generally 6 months]) and between drugs. Phenobarbital treatment resulted in eradication of seizures (17/20 [85%]) significantly more often than did bromide (12/23 [52%]); phenobarbital treatment also resulted in a greater percentage decrease in seizure duration (88 ± 34%), compared with bromide (49 ± 75%). Seizure activity worsened in 3 bromide-treated dogs only. In dogs with seizure eradication, mean ± SD serum phenobarbital concentration was 25 ± 6 μg/mL (phenobarbital dosage, 4.1 ± 1.1 mg/kg [1.9 ± 0.5 mg/lb], p.o., q 12 h) and mean serum bromide concentration was 1.8 ± 0.6 mg/mL (bromide dosage, 31 ± 11 mg/kg [14 ± 5 mg/lb], p.o., q 12 h). Ataxia, lethargy, and polydipsia were greater at 1 month for phenobarbital-treated dogs; vomiting was greater for bromide-treated dogs at 1 month and study end. Both phenobarbital and bromide were reasonable first-choice AEDs for dogs, but phenobarbital was more effective and better tolerated during the first 6 months of treatment.

  16. Suicide-related behaviors in older patients with new anti-epileptic drug use: data from the VA hospital system

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    Dersh Jeffrey J

    2010-01-01

    Full Text Available Abstract Background The U.S. Food and Drug Administration (FDA recently linked antiepileptic drug (AED exposure to suicide-related behaviors based on meta-analysis of randomized clinical trials. We examined the relationship between suicide-related behaviors and different AEDs in older veterans receiving new AED monotherapy from the Veterans Health Administration (VA, controlling for potential confounders. Methods VA and Medicare databases were used to identify veterans 66 years and older, who received a care from the VA between 1999 and 2004, and b an incident AED (monotherapy prescription. Previously validated ICD-9-CM codes were used to identify suicidal ideation or behavior (suicide-related behaviors cases, epilepsy, and other conditions previously associated with suicide-related behaviors. Each case was matched to controls based on prior history of suicide-related behaviors, year of AED prescription, and epilepsy status. Results The strongest predictor of suicide-related behaviors (N = 64; Controls N = 768 based on conditional logistic regression analysis was affective disorder (depression, anxiety, or post-traumatic stress disorder (PTSD; Odds Ratio 4.42, 95% CI 2.30 to 8.49 diagnosed before AED treatment. Increased suicide-related behaviors were not associated with individual AEDs, including the most commonly prescribed AED in the US - phenytoin. Conclusion Our extensive diagnostic and treatment data demonstrated that the strongest predictor of suicide-related behaviors for older patients newly treated with AED monotherapy was a previous diagnosis of affective disorder. Additional, research using a larger sample is needed to clearly determine the risk of suicide-related behaviors among less commonly used AEDs.

  17. Comparison of brand versus generic antiepileptic drug adverse event reporting rates in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).

    Science.gov (United States)

    Rahman, Md Motiur; Alatawi, Yasser; Cheng, Ning; Qian, Jingjing; Plotkina, Annya V; Peissig, Peggy L; Berg, Richard L; Page, David; Hansen, Richard A

    2017-09-01

    Despite the cost saving role of generic anti-epileptic drugs (AEDs), debate exists as to whether generic substitution of branded AEDs may lead to therapeutic failure and increased toxicity. This study compared adverse event (AE) reporting rates for brand vs. authorized generic (AG) vs. generic AEDs. Since AGs are pharmaceutically identical to brand but perceived as generics, the generic vs. AG comparison minimized potential bias against generics. Events reported to the U.S. Food and Drug Administration Adverse Event Reporting System between January 2004 to March 2015 with lamotrigine, carbamazepine, and oxcarbazepine listed as primary or secondary suspect were classified as brand, generic, or AG based on the manufacturer. Disproportionality analyses using the reporting odds ratio (ROR) assessed the relative rate of reporting of labeled AEs compared to reporting these events with all other drugs. The Breslow-Day statistic compared RORs across brand, AG, and other generics using a Bonferroni-corrected Pbrand and generics for all three drugs of interest (Breslow-Day Pbrands and generics have similar reporting rates after accounting for generic perception biases. Disproportional suicide reporting was observed for generics compared with AGs and brand, although this finding needs further study. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Effect of the new antiepileptic drug retigabine in a rodent model of mania

    DEFF Research Database (Denmark)

    Dencker, Ditte; Dias, Rebecca; Pedersen, Mette Lund

    2008-01-01

    Bipolar spectrum disorders are severe chronic mood disorders that are characterized by episodes of mania or hypomania and depression. Because patients with manic symptoms often experience clinical benefit from treatment with anticonvulsant drugs, it was hypothesized that retigabine, a novel...... compound with anticonvulsant efficacy, may also possess antimanic activity. The amphetamine (AMPH)+chlordiazepoxide (CDP)-induced hyperactivity model has been proposed as a suitable model for studying antimanic-like activity of novel compounds in mice and rats. The aims of the present study in rats were...

  19. Czech Teratology Information Service: comparison of treatments by psychotropic and antiepileptic drugs.

    Science.gov (United States)

    Manáková, Eva; Hubicková-Heringová, Lucie; Jelínek, Richard

    2006-12-01

    Care, treatment and follow-up in psychiatric and epileptic pregnant women were compared with women inquiring Czech Teratology Information Service (CZTIS) due to other exposure to drugs during pregnancy. Data were collected by CZTIS, member of European Network of Teratology Information Services from 1996. Exposed groups were compared with pregnant women exposed to drugs which were not classified as major teratogens or hyperthermia. Groups do not vary in age, reproductive history and other parameters. We observed higher frequency of miscarriage and voluntary termination of pregnancy in the group of psychiatric patients. The number of malformation in prospective follow-up cases was lower than in control group. Chronic diseases as epilepsy or psychiatric disorders have to be treated during pregnancy. Women should obtain accurate information about possible risk before pregnancy. Co-operation is needed in these cases. Physicians should keep in mind that appropriate information is to be given to the patient according to her disease, education and comprehension of the problem. If there is any doubt they should organize help for their patients.

  20. Orientações ao pediatra sobre o manejo das drogas psicoativas e antiepilépticas Use of psychoactive and antiepileptic drugs: guidelines for pediatricians

    Directory of Open Access Journals (Sweden)

    Gibsi P. Rocha

    2004-04-01

    Full Text Available OBJETIVO: Revisar as indicações e o manejo clínico das drogas psicoativas e antiepilépticas na infância e adolescência. FONTES DE DADOS: Estudo baseado em revisão de literatura. Os autores organizam, de acordo com os quadros patológicos, uma rotina para o manejo dos psicofármacos e das drogas antiepilépticas na infância e na adolescência. SÍNTESE DOS DADOS: Indicação clínica, dosagem terapêutica e efeitos colaterais dos psicofármacos e drogas antiepilépticas são descritos. O uso de psicofármacos na infância e adolescência está se tornando mais freqüente, com a disponibilidade de novos medicamentos e com o crescimento do conhecimento sobre diagnóstico de transtornos emocionais nessa faixa etária. CONCLUSÕES: O manejo dos psicofármacos e drogas antiepilépticas na faixa etária pediátrica requer amplo conhecimento da farmacocinética dos mesmos, assim como de seus efeitos colaterais deletérios. A escolha do fármaco adequado é determinante no sucesso terapêutico.OBJECTIVE: To review the guidelines for the use of psychoactive and antiepileptic drugs in childhood and adolescence. SOURCES OF DATA: Literature review. SUMMARY OF THE FINDINGS: The clinical indications, dosage and side effects of psychoactive and antiepileptic drugs are presented. The use of psychoactive drugs is increasing due to the release of new drugs and to the better understanding of emotional disorders in children and adolescents. CONCLUSIONS: The use of antiepileptic and psychoactive drugs in childhood requires extensive knowledge concerning pharmacokinetics and deleterious side effects. An adequate choice of drugs is essential to ensure a successful treatment.

  1. Off-label use analysis of novel antiepileptic drugs in Sichuan area: a multicenter survey in pediatric patients

    Directory of Open Access Journals (Sweden)

    CAI Qian-yun

    2012-10-01

    Full Text Available Objective To investigate current status and safety about off-label use of levetiracetam, topiramate, oxcarbazepine, lamotrigine among pediatric patients in Sichuan area, so as to provide baseline data for formulating guidelines of off-label drug use. Methods Medical records of pediatric epileptic patients receiving antiepileptic drugs (AEDs from July 2010 to November 2011 were collected at the following hospitals: West China Second University Hospital of Sichuan University, Chengdu Women's and Children's Central Hospital and Sichuan Provincial People's Hospital. The numbers of patients receiving AEDs and novel AEDs were calculated. Off-label drug use and the category of off-label drug use were judged according to the indications listed in drug instructions. The incidence of off-label drug use was calculated. The patients receiving novel AEDs were devided into on-label and off-label use groups; the clinical characteristics of these two groups were summarized and adverse reactions of two groups were compared by using χ2 test. Results During the study period, there were totally 854 patients receiving AEDs including 670 patients receiving novel AEDs. Among 670 patients 406 patients off-label use group received off-label use of novel AEDs, accounting for 47.54% (406/854 of the total patients receiving AEDs and 60.60% (406/670 of patients receiving novel AEDs. When compared with on-label use group, off-label use group had more younger patients, more patients with single-drug use and more patients with generalized epilepsy or epileptic syndrome. The rates of off-label using drug were levetiracetam 78.50% (157/200, topiramate 79.81% (253/317, oxcarbazepine 21.32% (42/197 and lamotrigine 33.33% (21/63. The off-label use of levetiracetam and topiramate occured in all three aspects: age, single-drug use and seizure type. The adverse reaction rates of off-label use were oxcarbazepine 16.67% (7/42, topiramate 14.81% (36/243, levetiracetam 10.60% (16

  2. POSSIBILITIES FOR ANTIEPILEPTIC DRUGS USE IN THE TREATMENT OF TIC HYPERKINESIS AND TOURETTE SYNDROME IN CHILDREN

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    V. P. Zykov

    2016-01-01

    Full Text Available Objective: to evaluate the efficacy of topiramate at a dose of 1–2 mg/kg in 34 patients aged 7–17 with tic hyperkinesis and Tourette syndrome (TS.Materials and methods. We performed clinical evaluation of hyperkinesis severity along with the assessment of somatosensory evoked potentials (SSEP and the analysis of surface electromyography (EMG data prior to treatment initiation and after 6 weeks of therapy. SSEP investigation was carried out in accordance with a standard protocol. Interpeak latencies on the tracks Cp–Fpz (D, S, Cerv6–Fpz (D, S, Erb’i–Erb’c (D, S were evaluated in order to determine the afferentation between relevant brain structures: N9–N13, N13–N20, N9–N20. N20–P23 potentials reflected primary activity of somatosensory cortex. The investigation of tic hyperkinesis was conducted using surface EMG of facial muscles (m. orbicularis oculi, the muscles of the shoulder girdle (m. supraspinatus, and the muscles of the upper extremities (m. flexor digitorum superficialis according to the standard protocol. Interference curve was recorded at rest and after hyperkinesis stimulation with the use of provocative tests. High-amplitude (more than 500 mkV oscillations were considered as burst activity. The severity of clinical manifestations was evaluated using the Yale Global Tic Severity Scale (1989 and the method of tics counting during 20 minutes (V.P. Zykov, 2009. The control group comprised 15 healthy children matched for sex and age.Results. The use of topiramate in patients with chronic motor/vocal tics and TS has significantly decreased the severity of hyperkinesis manifestations, evaluated both by the Yale Global Tic Severity Scale (p < 0,05 and by the method of tics counting during 20 minutes (p < 0,05. It also helped to decrease the prevalence of burst activity in EMG while registering hyperkinesis in different muscle groups. SSEP data showed the normalization of interpeak latency values and the decrease of N20

  3. The Influence of Solid Microneedles on the Transdermal Delivery of Selected Antiepileptic Drugs

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    Julia Nguyen

    2016-11-01

    Full Text Available The aim of this project was to examine the effect of microneedle rollers on the percutaneous penetration of tiagabine hydrochloride and carbamazepine across porcine skin in vitro. Liquid chromatography-mass spectrometric analysis was carried out using an Agilent 1200 Series HPLC system coupled to an Agilent G1969A TOF-MS system. Transdermal flux values of the drugs were determined from the steady-state portion of the cumulative amount versus time curves. Following twelve hours of microneedle roller application, there was a 6.74-fold increase in the percutaneous penetration of tiagabine hydrochloride (86.42 ± 25.66 µg/cm2/h compared to passive delivery (12.83 ± 6.30 µg/cm2/h. For carbamazepine in 20% ethanol, passive transdermal flux of 7.85 ± 0.60 µg/cm2/h was observed compared to 10.85 ± 0.11 µg/cm2/h after microneedle treatment. Carbamazepine reconstituted in 30% ethanol resulted in only a 1.19-fold increase in drug permeation across porcine skin (36.73 ± 1.83 µg/cm2/h versus 30.74 ± 1.32 µg/cm2/h. Differences in flux values of untreated and microneedle-treated porcine skin using solid microneedles for the transdermal delivery of tiagabine were statistically significant. Although there were 1.38- and 1.19-fold increases in transdermal flux values of carbamazepine when applied as 20% and 30% ethanol solutions across microneedle-treated porcine skin, respectively, the increases were not statistically significant.

  4. Comparative Long-Term Effectiveness of a Monotherapy with Five Antiepileptic Drugs for Focal Epilepsy in Adult Patients: A Prospective Cohort Study

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    Zhu, Pan; He, Ru-Qian; Bao, Yi-Xin; Zheng, Rong-Yuan; Xu, Hui-Qin

    2015-01-01

    Objective To evaluate and compare long-term effectiveness of five antiepileptic drugs (AEDs) for monotherapy of adult patients with focal epilepsy in routine clinical practice. Methods Adult patients with focal epilepsy, who were prescribed with carbamazepine (CBZ), valproate (VPA), lamotrigine (LTG), topiramate (TPM), or oxcarbazepine (OXC) as monotherapy, during the period from January 2004 to June 2012 registered in Wenzhou Epilepsy Follow Up Registry Database (WEFURD), were included in the study. Prospective long-term follow-up was conducted until June 2013. The endpoints were time to treatment failure, time to seizure remission, and time to first seizure. Results This study included 654 patients: CBZ (n=125), VPA (n=151), LTG (n=135), TPM (n=76), and OXC (n=167). The retention rates of CBZ, VPA, LTG, TPM, and OXC at the third year were 36.1%, 32.4%, 57.6%, 37.9%, and 41.8%, respectively. For time to treatment failure, LTG was significantly better than CBZ and VPA (LTG vs. CBZ, hazard ratio, [HR] 0.80 [95% confidence interval: 0.67-0.96], LTG vs. VPA, 0.53 [0.37-0.74]); TPM was worse than LTG (TPM vs. LTG, 1.77 [1.15-2.74]), and OXC was better than VPA (0.86 [0.78-0.96]). After initial target doses, the seizure remission rates of CBZ, VPA, LTG, TPM, and OXC were 63.0%, 77.0%, 83.6%, 67.9%, and 75.3%, respectively. LTG was significantly better than CBZ (1.44 [1.15-1.82]) and OXC (LTG vs. OXC, 0.76 [0.63-0.93]); OXC was less effective than LTG in preventing the first seizure (1.20 [1.02-1.40]). Conclusion LTG was the best, OXC was better than VPA only, while VPA was the worst. The others were equivalent for comparisons between five AEDs regarding the long-term treatment outcomes of monotherapy for adult patients with focal epilepsy in a clinical practice. For selecting AEDs for these patients among the first-line drugs, LTG is an appropriate first choice; others are reservation in the first-line but VPA is not. PMID:26147937

  5. Comparative Long-Term Effectiveness of a Monotherapy with Five Antiepileptic Drugs for Focal Epilepsy in Adult Patients: A Prospective Cohort Study.

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    Qing-Yi Zeng

    Full Text Available To evaluate and compare long-term effectiveness of five antiepileptic drugs (AEDs for monotherapy of adult patients with focal epilepsy in routine clinical practice.Adult patients with focal epilepsy, who were prescribed with carbamazepine (CBZ, valproate (VPA, lamotrigine (LTG, topiramate (TPM, or oxcarbazepine (OXC as monotherapy, during the period from January 2004 to June 2012 registered in Wenzhou Epilepsy Follow Up Registry Database (WEFURD, were included in the study. Prospective long-term follow-up was conducted until June 2013. The endpoints were time to treatment failure, time to seizure remission, and time to first seizure.This study included 654 patients: CBZ (n=125, VPA (n=151, LTG (n=135, TPM (n=76, and OXC (n=167. The retention rates of CBZ, VPA, LTG, TPM, and OXC at the third year were 36.1%, 32.4%, 57.6%, 37.9%, and 41.8%, respectively. For time to treatment failure, LTG was significantly better than CBZ and VPA (LTG vs. CBZ, hazard ratio, [HR] 0.80 [95% confidence interval: 0.67-0.96], LTG vs. VPA, 0.53 [0.37-0.74]; TPM was worse than LTG (TPM vs. LTG, 1.77 [1.15-2.74], and OXC was better than VPA (0.86 [0.78-0.96]. After initial target doses, the seizure remission rates of CBZ, VPA, LTG, TPM, and OXC were 63.0%, 77.0%, 83.6%, 67.9%, and 75.3%, respectively. LTG was significantly better than CBZ (1.44 [1.15-1.82] and OXC (LTG vs. OXC, 0.76 [0.63-0.93]; OXC was less effective than LTG in preventing the first seizure (1.20 [1.02-1.40].LTG was the best, OXC was better than VPA only, while VPA was the worst. The others were equivalent for comparisons between five AEDs regarding the long-term treatment outcomes of monotherapy for adult patients with focal epilepsy in a clinical practice. For selecting AEDs for these patients among the first-line drugs, LTG is an appropriate first choice; others are reservation in the first-line but VPA is not.

  6. Vitamin D Levels in Children and Adolescents with Antiepileptic Drug Treatment

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    Baek, Jung-Hyun; Seo, Young-Ho; Kim, Gun-Ha; Kim, Mi-Kyung

    2014-01-01

    Purpose This study was to evaluate the relationship of 25(OH)D3 levels with anticonvulsant use and other possible factors in epileptic children and adolescents. Materials and Methods We studied 143 patients with epilepsy (90 boys, 53 girls; 11.21±4.49 years), who had been treated with anticonvulsants for more than 1 year. Patients who had taken multiple vitamins before the blood test and those who have the limitation of physical activity (wheelchair-bound) were excluded from the study. We evaluated the difference in vitamin D status according to the type and number of anticonvulsants taken and other factors such as gender, age, intelligence and seizure variables. Results For patients with mental retardation or developmental delay, 25(OH)D3 levels were lower than the levels in patients with normal intelligence quotient levels (p=0.03). 25(OH)D3 levels were lower in patients who had taken anticonvulsants for more than 2 years as compared to those who had taken them for less than 2 years (p=0.03). Those taking oxcarbazepine had significantly lower vitamin D levels than patients taking valproic acid (p=0.01). However, no effects of number of anticonvulsants taken were detectable. More than two-thirds of the patients were diagnosed with osteopenia or osteoporosis in patients showing either vitamin D insufficiency or deficiency. Conclusion The possibility of vitamin D deficiency can be considered in pediatric patients taking anticonvulsants if they have mental retardation or developmental delay or if they have been taking anticonvulsants for more than 2 years or taking hepatic enzyme inducing drugs. PMID:24532512

  7. Age-Related Inducibility of Carboxylesterases by the Antiepileptic Agent Phenobarbital and Implications in Drug Metabolism and Lipid Accumulation 1, 2

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    Xiao, Da; Chen, Yi-Tzai; Yang, Dongfang; Yan, Bingfang

    2014-01-01

    Carboxylesterases (CES) constitute a class of hydrolytic enzymes that play critical roles in drug metabolism and lipid mobilization. Previous studies with a large number of human liver samples have suggested that the inducibility of carboxylesterases is inversely related with age. To directly test this possibility, neonatal (10 days of age) and adult mice were treated with the antiepileptic agent phenobarbital. The expression and hydrolytic activity were determined on six major carboxylesterases including ces1d, the ortholog of human CES1. Without exception, all carboxylesterases tested were induced to a greater extent in neonatal than adult mice. The induction was detected at mRNA, protein and catalytic levels. Ces1d was greatly induced and found to rapidly hydrolyze the antiplatelet agent clopidogrel and support the accumulation of neutral lipids. Phenobarbital represents a large number of therapeutic agents that induce drug metabolizing enzymes and transporters in a species-conserved manner. The higher inducibility of carboxylesterases in the developmental age likely represents a general phenomenon cross species including human. Consequently, individuals in the developmental age may experience greater drug-drug interactions. The greater induction of ces1d also provides a molecular explanation to the clinical observation that children on antiepileptic drugs increase plasma lipids. PMID:22513142

  8. Physical growth and psychomotor development of infants exposed to antiepileptic drugs in utero.

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    Arulmozhi, T; Dhanaraj, M; Rangaraj, R; Vengatesan, A

    2006-03-01

    To evaluates the physical growth and psychomotor development of infants born to women with epilepsy on regular Anti Epileptic Drugs (AEDs). Govt. Stanley Medical College and Hospital, Tertiary care referral centre, Chennai. Open prospective cohort study with a control group. Consecutive women with epilepsy who were on regular anticonvulsants were followed up from their first trimester. Their babies were examined at birth and anthropometric measurements including anterior fontanelle size were noted. They were followed up till one year and periodically evaluated at 1st, 6th and 12th month of age. Development testing using Griffith scale was done at 2nd, 6th and 12th month. An equal number of control babies were also studied using the same scale for one year at the specified intervals. The results in both the groups were compared. 30 babies were enrolled in the case and control group. The AEDs received by the mothers with epilepsy were Phenytoin, Carbamazepine, and Sodium valproate. At birth and 1st month the weight, head circumference and length of case and control babies were equal. At 6th and 12th month reduction in the above 3 parameters were noted in the case babies ( P < 0.01). Area of anterior fontanelle (AF) was larger in the study group particularly in those exposed to phenytoin in utero (P < 0.001). In the case babies reduction in the sitting, prone and erect progression of the locomotor scores was observed at 2nd month (P < 0.001). Prone progression alone improved by 12th month and other two remained less than the control (P < 0.001). No difference was observed in reaching behaviour and personal/social scores in both groups. Infants exposed to Phenytoin monotherapy had a negative impact on sitting progression. Among infants exposed to AEDs in utero physical growth was equal to that of control at birth but reduced at 6th and 12th month probably due to extraneous factors. The Locomotor scores showed reduction in all areas in 2nd, 6th and 12th month except

  9. The Brain Activity in Brodmann Area 17: A Potential Bio-Marker to Predict Patient Responses to Antiepileptic Drugs.

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    Yida Hu

    Full Text Available In this study, we aimed to predict newly diagnosed patient responses to antiepileptic drugs (AEDs using resting-state functional magnetic resonance imaging tools to explore changes in spontaneous brain activity. We recruited 21 newly diagnosed epileptic patients, 8 drug-resistant (DR patients, 11 well-healed (WH patients, and 13 healthy controls. After a 12-month follow-up, 11 newly diagnosed epileptic patients who showed a poor response to AEDs were placed into the seizures uncontrolled (SUC group, while 10 patients were enrolled in the seizure-controlled (SC group. By calculating the amplitude of fractional low-frequency fluctuations (fALFF of blood oxygen level-dependent signals to measure brain activity during rest, we found that the SUC patients showed increased activity in the bilateral occipital lobe, particularly in the cuneus and lingual gyrus compared with the SC group and healthy controls. Interestingly, DR patients also showed increased activity in the identical cuneus and lingual gyrus regions, which comprise Brodmann's area 17 (BA17, compared with the SUC patients; however, these abnormalities were not observed in SC and WH patients. The receiver operating characteristic (ROC curves indicated that the fALFF value of BA17 could differentiate SUC patients from SC patients and healthy controls with sufficient sensitivity and specificity prior to the administration of medication. Functional connectivity analysis was subsequently performed to evaluate the difference in connectivity between BA17 and other brain regions in the SUC, SC and control groups. Regions nearby the cuneus and lingual gyrus were found positive connectivity increased changes or positive connectivity changes with BA17 in the SUC patients, while remarkably negative connectivity increased changes or positive connectivity decreased changes were found in the SC patients. Additionally, default mode network (DMN regions showed negative connectivity increased changes or

  10. Comparative safety of antiepileptic drugs for neurological development in children exposed during pregnancy and breast feeding: a systematic review and network meta-analysis

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    Veroniki, Areti Angeliki; Rios, Patricia; Cogo, Elise; Straus, Sharon E; Finkelstein, Yaron; Kealey, Ryan; Reynen, Emily; Soobiah, Charlene; Thavorn, Kednapa; Hutton, Brian; Hemmelgarn, Brenda R; Yazdi, Fatemeh; D'Souza, Jennifer; MacDonald, Heather; Tricco, Andrea C

    2017-01-01

    Objectives Compare the safety of antiepileptic drugs (AEDs) on neurodevelopment of infants/children exposed in utero or during breast feeding. Design and setting Systematic review and Bayesian random-effects network meta-analysis (NMA). MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched until 27 April 2017. Screening, data abstraction and quality appraisal were completed in duplicate by independent reviewers. Participants 29 cohort studies including 5100 infants/children. Interventions Monotherapy and polytherapy AEDs including first-generation (carbamazepine, clobazam, clonazepam, ethosuximide, phenobarbital, phenytoin, primidone, valproate) and newer-generation (gabapentin, lamotrigine, levetiracetam, oxcarbazepine, topiramate, vigabatrin) AEDs. Epileptic women who did not receive AEDs during pregnancy or breast feeding served as the control group. Primary and secondary outcome measures Cognitive developmental delay and autism/dyspraxia were primary outcomes. Attention-deficit hyperactivity disorder, language delay, neonatal seizures, psychomotor developmental delay and social impairment were secondary outcomes. Results The NMA on cognitive developmental delay (11 cohort studies, 933 children, 18 treatments) suggested that among all AEDs only valproate was statistically significantly associated with more children experiencing cognitive developmental delay compared with control (OR=7.40, 95% credible interval (CrI) 3.00 to 18.46). The NMA on autism (5 cohort studies, 2551 children, 12 treatments) suggested that oxcarbazepine (OR 13.51, CrI 1.28 to 221.40), valproate (OR 17.29, 95% CrI 2.40 to 217.60), lamotrigine (OR 8.88, CrI 1.28 to 112.00) and lamotrigine+valproate (OR 132.70, CrI 7.41 to 3851.00) were associated with significantly greater odds of developing autism compared with control. The NMA on psychomotor developmental delay (11 cohort studies, 1145 children, 18 treatments) found that valproate (OR 4.16, CrI 2.04 to 8

  11. Effect of impaired ambulation and anti-epileptic drug intake on vitamin D status of children with cerebral palsy.

    Science.gov (United States)

    Seth, Anju; Aneja, Satinder; Singh, Ritu; Majumdar, Ritu; Sharma, Neera; Gopinath, Muthuselvan

    2017-08-01

    Children with cerebral palsy (CP) are vulnerable to developing vitamin D deficiency. There is little information on the prevalence and severity of vitamin D deficiency in these patients. To study vitamin D status in children with CP with special reference to their intake of anti-epileptic drugs (AED) and ambulatory status. The relative effects of AED use and ambulatory status on the vitamin D status of 120 children with CP aged 2-10 years were examined in this observational study. The patients were classified into four groups (30 in each) on the basis of AED use and ambulatory status: ambulatory (CPA), ambulatory receiving AED (CPAD), non-ambulatory (CPNA) and non-ambulatory receiving AED (CPNAD). A control group of 30 age-matched healthy children was also included. Parameters assessed included dietary calcium intake, sun exposure, serum total and ionised calcium (tCa, iCa), inorganic phosphate (iP), alkaline phosphatase (ALP), parathormone (PTH), 25 hydroxy vitamin D [25(OH)D] levels and a wrist radiograph to detect rickets. Vitamin D status was defined on the basis of serum 25(OH)D levels as normal (>50 nmol/L), mild deficiency (25-50 nmol/L), moderate deficiency (12.5-25 nmol/L), severe deficiency (D levels in patients with CP were 35.6 (26.75-64) nmol/L compared with 60 (37-69.25) nmol/L in controls (p = 0.04). Sixty per cent of children with CP and 36.7% of controls were vitamin D-deficient [25(OH)D D-deficient with median (IQR) 25(OH)D levels of 33.5 (12.5-45.25) nmol/L. Also, 53.3% of them had raised ALP and 17.2% raised PTH levels. Children with CP are highly vulnerable to vitamin D deficiency. In these patients, AED use and lack of sun exposure contribute towards poor vitamin D status, the effect being more pronounced when they co-exist.

  12. The reasons for the epilepsy treatment gap in Kilifi, Kenya: using formative research to identify interventions to improve adherence to antiepileptic drugs.

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    Carter, Julie A; Molyneux, Catherine S; Mbuba, Caroline K; Jenkins, Jo; Newton, Charles R J C; Hartley, Sally D

    2012-12-01

    Many people with epilepsy (PWE) in resource-poor countries do not receive appropriate treatment, a phenomenon referred to as the epilepsy treatment gap (ETG). We conducted a qualitative study to explore the reasons for this gap and to identify possible interventions in Kilifi, Kenya. Focus group discussions (FGDs) were carried out of PWE and their caregivers. Individual interviews were conducted of PWE, their caregivers, traditional healers, community health workers and leaders, nurses and doctors. In addition, a series of workshops was conducted, and four factors contributing to the ETG were identified: 1) lack of knowledge about the causes, treatment and prognosis of epilepsy; 2) inaccessibility to antiepileptic drugs; 3) misconceptions about epilepsy derived from superstitions about its origin; 4) and dissatisfaction with the communication skills of health providers. These data indicated possible interventions: 1) education and support for PWE and their caregivers; 2) communication skills training for health providers; 3) and improved drug provision. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Comparative effectiveness of eight antiepileptic drugs in adults with focal refractory epilepsy: the influence of age, gender, and the sequence in which drugs were introduced onto the market.

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    Mäkinen, Jussi; Peltola, Jukka; Raitanen, Jani; Alapirtti, Tiina; Rainesalo, Sirpa

    2017-07-01

    The first objective was to determine the long-term retention rate of eight antiepileptic drugs (AEDs) commonly used as adjunctive therapy in adults with focal refractory epilepsy. Second, we assessed the effects of age and gender on retention rates. Third, we examined if the retention rate could be influenced by the sequence in which the AEDs had entered the market. Patients with focal refractory epilepsy treated with any of the eight AEDs in Tampere University Hospital were identified retrospectively (N = 507). Retention rates were evaluated with the Kaplan-Meier method. Follow-up started at the first date of treatment and each individual was followed a maximum of 36 months. We calculated the following 3-year retention rates: lacosamide 77.1% (N = 137), lamotrigine 68.3% (N = 177), levetiracetam 66.7% (N = 319), clobazam 65.6% (N = 130), topiramate 61.6% (N = 178), zonisamide 60.4% (N = 103), pregabalin 54.6% (N = 127), and gabapentin 40.2% (N = 66). Lacosamide, levetiracetam, and clobazam were the most effective AEDs in the elderly. The retention rate for pregabalin was higher in males (65%) than females (51%) whereas females had higher retention rates for both topiramate (72 vs. 58%) and zonisamide (67 vs. 57%). The retention rate was influenced by the sequence in which these AEDs entered the market. We provide important information about practical aspects of these eight AEDs, revealing that there are differences in their effectiveness as adjunctive treatment for focal refractory epilepsy. Most importantly, the retention rate appears to be influenced by the sequence in which these AEDs were introduced onto the market.

  14. Phenobarbital or potassium bromide as an add-on antiepileptic drug for the management of canine idiopathic epilepsy refractory to imepitoin.

    Science.gov (United States)

    Royaux, E; Van Ham, L; Broeckx, B J G; Van Soens, I; Gielen, I; Deforce, D; Bhatti, S F M

    2017-02-01

    Imepitoin has recently been approved in Europe for the management of dogs with idiopathic epilepsy. Currently, there is no evidence-based information available on the efficacy of antiepileptic drugs used as additions to the therapeutic regimen in dogs with idiopathic epilepsy that are not well controlled with imepitoin. The goal of this study was to evaluate the efficacy of phenobarbital or potassium bromide (KBr) as add-on antiepileptic drugs for controlling dogs refractory to a maximum dose of imepitoin (30 mg/kg twice daily). The study was performed as a prospective, randomised, controlled clinical trial. The efficacy of phenobarbital and KBr was evaluated by comparing monthly seizure frequency (MSF), monthly seizure day frequency (MSDF), the presence of cluster seizures during a retrospective 2-month period with a prospective follow-up of 6 months, and the overall responder rate. Twenty-seven dogs were included in the study, 14 dogs in the phenobarbital group and 13 dogs in the KBr group. Both median MSF and MSDF decreased in the phenobarbital group (both P = 0.001) and in the KBr group (P = 0.004 and P = 0.003, respectively). Overall, the number of dogs with cluster seizures decreased (P = 0.0005). The responder rate was 79% vs. 69% in the phenobarbital and KBr groups, respectively. We conclude that phenobarbital or KBr add-on treatment decreases median MSF and MSDF in epileptic dogs refractory to a maximum dose of imepitoin. Combination therapy was generally well tolerated and resulted in an improvement in seizure management in the majority of the dogs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. [Adult patients treated for focal epilepsy with antiepileptic drugs (AEDs) in combination in France: description according to the 2009 ILAE definition of AED resistance (ESPERA study)].

    Science.gov (United States)

    Vespignani, H; de Zélicourt, M; Laurendeau, C; Fagnani, F; Levy-Bachelot, L; Murat, C; Kahane, P; de Toffol, B

    2014-02-01

    To describe the adult population treated with antiepileptic drugs (AEDs) in combination for focal epilepsy according to the definition of AED resistance proposed by the International League Against Epilepsy (ILAE) in 2009 and to evaluate its implementation in current practice. ESPERA was a multicenter, observational, cross-sectional study with a clinical data collection covering the past 12 months conducted by neurologists. Classifications according to AED responsiveness established by investigators for each enrolled patient were revised by two experts. Seventy-one neurologists enrolled 405 patients. Their mean age was 42.7 years (sex-ratioM/F 0.98). According to the investigators, 60% of epilepsies were drug-resistant, 37% drug-responsive and 3% had an undefined drug-responsiveness. After revision of experts, 71% of epilepsies were classified as drug resistant, 22% as responsive and 7% as undefined. Among the participating neurologists, 76% have made at least one error in classifying their patients according to the 2009 ILAE definition of AED resistance. Because of epilepsy, 24% of patients (age≤65) were inactive and 42% could not drive (respectively 29 and 49% of patients with AED resistant epilepsy). Half of patients had at least one other chronic condition. Number of prescribed drugs in combination and health care resource utilisation were significantly higher in patients with drug-resistant epilepsies than in patients with drug responsive epilepsies. ESPERA study shows that the use of new definition of drug-resistance in everyday practice seems difficult without any additional training and that the social and professional disability is frequent in adults with focal epilepsies treated with polytherapy. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  16. Availability and cost of major and first-line antiepileptic drugs: a comprehensive evaluation in the capital of Madagascar.

    Science.gov (United States)

    Jost, Jeremy; Raharivelo, Adeline; Ratsimbazafy, Voa; Nizard, Mandy; Auditeau, Emilie; Newton, Charles R; Preux, Pierre-Marie

    2016-01-01

    The prevalence of epilepsy is high in Madagascar (23.5/1000), as is the treatment gap (estimated at 92 %). The health system of the country is underfunded; some AEDs are used, and the national drug policy does not encourage price regulation or the administration of generic agents. We conducted a cross-sectional study to assess the availability and cost of solid oral AED formulations in Antananarivo, capital of Madagascar. Data were gathered from all officially registered pharmacies (according to the drug agency list, updated in 2015) by means of telephone interviews lasting no more than 10 min and conducted by a native Malagasy speaker. With regard to other sources (hospitals, illicit sales) data were obtained at specific visits. The study received ethical approval from the Madagascar Ministry of Health. A total of 91 of 100 pharmacies (the nine not included were because of an inoperative phone number), two of three public hospitals, and two illegal outlets were investigated. Sodium valproate was available in 84.6 % of the pharmacies, while carbamazepine and phenobarbital were available in 68.1 % and 36.3 % of the pharmacies, respectively, but phenytoin was not available in any supply chain. There were more originator brands than generic formulations, with a higher cost (range 20.3-81.1 %, median 40.7 %) compared to the equivalent generic. The public system had only a very limited choice of AED, but offered the lowest costs. Illicit sources were more expensive by 54.3 % for carbamazepine and 62.5 % for phenobarbital. Concerning the annual cost of treatment, the average percentage of the gross national income per capita based on the purchasing power parity was 29.8 %/19.0 % (brand/generic) for sodium valproate, 16.4 %/7.3 % (brand/generic) for carbamazepine, 8.9 %/5.1 % (brand/generic) for phenobarbital. The main sources of AEDs were private pharmacies, but the stocks held were low. The financial burden was still important in the capital of Madagascar

  17. Retrospective evaluation of low long-term efficacy of antiepileptic drugs and ketogenic diet in 39 patients with CDKL5-related epilepsy.

    Science.gov (United States)

    Müller, A; Helbig, I; Jansen, C; Bast, T; Guerrini, R; Jähn, J; Muhle, H; Auvin, S; Korenke, G C; Philip, S; Keimer, R; Striano, P; Wolf, N I; Püst, B; Thiels, Ch; Fogarasi, A; Waltz, S; Kurlemann, G; Kovacevic-Preradovic, T; Ceulemans, B; Schmitt, B; Philippi, H; Tarquinio, D; Buerki, S; von Stülpnagel, C; Kluger, G

    2016-01-01

    Mutations in the CDKL5 gene cause an early-onset epileptic encephalopathy. To date, little is known about effective antiepileptic treatment in this disorder. Accordingly, the aim of this retrospective study was to explore the role of different antiepileptic drugs (AEDs) and the ketogenic diet (KD) in the treatment of this rare genetic disorder. We evaluated the efficacy in 39 patients with CDKL5 mutations at 3, 6 and 12 months after the introduction of each treatment. One patient was lost to follow-up after 6 and 12 months. The responder rate (>50% reduction in seizure frequency) to at least one AED or KD was 69% (27/39) after 3 months, 45% (17/38) after 6 months and 24% (9/38) after 12 months. The highest rate of seizure reduction after 3 months was reported for FBM (3/3), VGB (8/25), CLB (4/17), VPA (7/34), steroids (5/26), LTG (5/23) and ZNS (2/11). Twelve patients (31%) experienced a seizure aggravation to at least one AED. Most patients showed some but only initial response to various AEDs with different modes of actions. Considering both age-related and spontaneous fluctuation in seizure frequency and the unknown impact of many AEDs or KD on cognition, our data may help defining realistic treatment goals and avoiding overtreatment in patients with CDKL5 mutations. There is a strong need to develop new treatment strategies for patients with this rare mutation. Copyright © 2015. Published by Elsevier Ltd.

  18. Opioids, antiepileptic and anticholinergic drugs and the risk of fractures in patients 65 years of age and older: a prospective population-based study.

    Science.gov (United States)

    Nurminen, Janne; Puustinen, Juha; Piirtola, Maarit; Vahlberg, Tero; Lyles, Alan; Kivelä, Sirkka-Liisa

    2013-05-01

    in men, the concomitant use of two or more benzodiazepines or two or more antipsychotics is associated with an increased risk of fracture(s). Potential associations between the concomitant use of drugs with central nervous system effects and fracture risk have not been studied. the purpose was to describe the gender-specific risk of fractures in a population aged 65 years or over associated with the use of an opioid, antiepileptic or anticholinergic drug individually; or, their concomitant use with each other; or the concomitant use of one of these with a psychotropic drug. this study was part of a prospective, population-based study performed in Lieto, Finland. Information about fractures in 1,177 subjects (482 men and 695 women) was confirmed with radiology reports. at 3 years of follow-up, the concomitant use of an opioid with an antipsychotic was associated with an increased risk of fractures in men. During the 6-year follow-up, the concomitant use of an opioid with a benzodiazepine was also related to the risk of fractures for males. No significant associations were found for females. the concomitant use of an opioid with an antipsychotic, or with a benzodiazepine may increase the risk of fractures in men aged 65 years and older.

  19. Patient safety: numerical skills and drug calculation abilities of nursing students and registered nurses.

    Science.gov (United States)

    McMullan, Miriam; Jones, Ray; Lea, Susan

    2010-04-01

    This paper is a report of a correlational study of the relations of age, status, experience and drug calculation ability to numerical ability of nursing students and Registered Nurses. Competent numerical and drug calculation skills are essential for nurses as mistakes can put patients' lives at risk. A cross-sectional study was carried out in 2006 in one United Kingdom university. Validated numerical and drug calculation tests were given to 229 second year nursing students and 44 Registered Nurses attending a non-medical prescribing programme. The numeracy test was failed by 55% of students and 45% of Registered Nurses, while 92% of students and 89% of nurses failed the drug calculation test. Independent of status or experience, older participants (> or = 35 years) were statistically significantly more able to perform numerical calculations. There was no statistically significant difference between nursing students and Registered Nurses in their overall drug calculation ability, but nurses were statistically significantly more able than students to perform basic numerical calculations and calculations for solids, oral liquids and injections. Both nursing students and Registered Nurses were statistically significantly more able to perform calculations for solids, liquid oral and injections than calculations for drug percentages, drip and infusion rates. To prevent deskilling, Registered Nurses should continue to practise and refresh all the different types of drug calculations as often as possible with regular (self)-testing of their ability. Time should be set aside in curricula for nursing students to learn how to perform basic numerical and drug calculations. This learning should be reinforced through regular practice and assessment.

  20. Modulation of Cytokine Production by Drugs with Antiepileptic or Mood Stabilizer Properties in Anti-CD3- and Anti-CD40-Stimulated Blood In Vitro

    Directory of Open Access Journals (Sweden)

    Hubertus Himmerich

    2014-01-01

    Full Text Available Increased cytokine production possibly due to oxidative stress has repeatedly been shown to play a pivotal role in the pathophysiology of epilepsy and bipolar disorder. Recent in vitro and animal studies of valproic acid (VPA report antioxidative and anti-inflammatory properties, and suppression of interleukin (IL-6 and tumor necrosis factor (TNF-α. We tested the effect of drugs with antiepileptic or mood stabilizer properties, namely, primidone (PRM, carbamazepine (CBZ, levetiracetam (LEV, lamotrigine (LTG, VPA, oxcarbazepine (OXC, topiramate (TPM, phenobarbital (PB, and lithium on the production of the following cytokines in vitro: interleukin (IL-1β, IL-2, IL-4, IL-6, IL-17, IL-22, and TNF-α. We performed a whole blood assay with stimulated blood of 14 healthy female subjects. Anti-human CD3 monoclonal antibody OKT3, combined with 5C3 antibody against CD40, was used as stimulant. We found a significant reduction of IL-1 and IL-2 levels with all tested drugs other than lithium in the CD3/5C3-stimulated blood; VPA led to a decrease in IL-1β, IL-2, IL-4, IL-6, IL-17, and TNF-α production, which substantiates and adds knowledge to current hypotheses on VPA’s anti-inflammatory properties.

  1. Time Course of the Changes in Novel Trioxane Antimalarial 99/411 Pharmacokinetics upon Antiepileptic Drugs Co-Administration in SD Rats

    Directory of Open Access Journals (Sweden)

    Yeshwant Singh

    2014-01-01

    Full Text Available Objective. The study aimed to evaluate the influences of coadministration of antiepileptic drugs (AEDs on an antimalarial candidate 99/411 pharmacokinetic (PK profile. Method. For this, single oral dose PK drug interaction studies were conducted between 99/411 and FDA approved AEDs, namely, Phenytoin (PHT, Carbamazepine (CBZ, and Gabapentin (GB in both male and female SD rats, to assess the coadministered and intersexual influences on 99/411 PK profile. Results. Studies revealed that there were no significant alterations in the PK profile of 99/411 upon PHT and CBZ coadministration in both male and female rats, while systemic exposure of 99/411 was significantly increased by about 80% in female rats upon GB coadministration. In terms of AUC, there was an increase from 2471 ± 586 to 4560 ± 1396 ng·h/mL. Overall, it was concluded that simultaneous administration of AEDs with 99/411 excludes the requirements for dose adjustment, additional therapeutic monitoring, contraindication to concomitant use, and/or other measures to mitigate risk, except for GB coadministration in females. These findings are further helpful to predict such interactions in humans, when potentially applied through proper allometric scaling to extrapolate the data.

  2. Management of Antiepileptic Treatment After Epilepsy Surgery

    DEFF Research Database (Denmark)

    Rubboli, Guido; Sabers, Anne; Uldall, Peter

    2017-01-01

    BACKGROUND: Although epilepsy surgery is a recognized treatment option for drug-resistant epilepsies since several decades, the management of antiepileptic drugs (AEDs) after successful surgery still remains one of the most difficult and unsolved therapeutic challenges. Indeed, no systematic cont...

  3. IS IT POSSIBLE TO USE BEVACIZUMAB BIOSIMILAR IN ALL INDICATIONS REGISTERED FOR ORIGINAL DRUG?

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    S. V. Orlov

    2016-01-01

    Full Text Available The possibility of extrapolation of indications for biosimilars is one of the issues widely discussed in modern literature. Currently, the European Medicines Agency (EMA and the Food and Drug Administration (FDA have identified specific conditions under which for biosimilars extrapolation of indications is possible. In2015, athe first bioanalogue bevacizumab, (produced by JSC "BIOCAD", has been registered. The article provides summary of the pivotal clinical study of Bevacizumab bioanalogue conducted in patients with non-small cell lung cancer. The article includes detailed scientific justification for the extrapolation of data on the efficacy, safety and immunogenicity obtained in the pivotal study to other indications, registered for the original bevacizumab drug.

  4. Introducing rapid diagnostic tests for malaria into registered drug shops in Uganda

    DEFF Research Database (Denmark)

    Mbonye, Anthony K; Clarke, Sîan E; Lal, Sham

    2015-01-01

    BACKGROUND: Malaria is a major public health problem in Uganda and the current policy recommends introduction of rapid diagnostic tests for malaria (RDTs) to facilitate effective case management. However, provision of RDTs in drug shops potentially raises a new set of issues, such as adherence...... to RDTs results, management of severe illnesses, referral of patients, and relationship with caretakers. The main objective of the study was to examine the impact of introducing RDTs in registered drug shops in Uganda and document lessons and policy implications for future scale-up of malaria control...... in the private health sector. METHODS: A cluster-randomized trial introducing RDTs into registered drug shops was implemented in central Uganda from October 2010 to July 2012. An evaluation was undertaken to assess the impact and the processes involved with the introduction of RDTs into drug shops, the lessons...

  5. The roles of variants in human multidrug resistance (MDR1 gene and their haplotypes on antiepileptic drugs response: a meta-analysis of 57 studies.

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    Hui Li

    Full Text Available Previous studies reported the associations between the ATP-binding cassette sub-family B member 1 (ABCB1, also known as MDR1 polymorphisms and their haplotypes with risk of response to antiepileptic drugs in epilepsy, however, the results were inconclusive.The Pubmed, Embase, Web of Science, CNKI and Chinese Biomedicine databases were searched up to July 15, 2014. Pooled odds ratios (ORs and 95% confidence intervals (CIs were calculated using a fixed-effects or random-effects model based on heterogeneity tests. Meta-regression and Galbraith plot analysis were carried out to explore the possible heterogeneity.A total of 57 studies involving 12407 patients (6083 drug-resistant and 6324 drug-responsive patients with epilepsy were included in the pooled-analysis. For all three polymorphisms (C3435T, G2677T/A, and C1236T, we observed a wide spectrum of minor allele frequencies across different ethnicities. A significantly decreased risk of AEDs resistance was observed in Caucasian patients with T allele of C3435T variant, which was still significant after adjusted by multiple testing corrections (T vs C: OR=0.83, 95%CI=0.71-0.96, p=0.01. However, no significant association was observed between the other two variants and AEDs resistance. Of their haplotypes in ABCB1 gene (all studies were in Indians and Asians, no significant association was observed with AEDs resistance. Moreover, sensitivity and Cumulative analysis showed that the results of this meta-analysis were stable.In summary, this meta-analysis demonstrated that effect of C3435T variant on risk of AEDs resistance was ethnicity-dependent, which was significant in Caucasians. Additionally, further studies in different ethnic groups are warranted to clarify possible roles of haplotypes in ABCB1 gene in AEDs resistance, especially in Caucasians.

  6. Aspectos farmacológicos relevantes de los antiepilépticos nuevos Relevant pharmacological aspects of the new antiepileptic drugs

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    Alicia Zapata Martínez

    2005-12-01

    Full Text Available Dada la importancia de la epilepsia como enfermedad crónica no transmisible, se decidió realizar una revisión de los fármacos nuevos que en los últimos años han sido comercializados para su tratamiento en el mundo. Se enfatizó en la necesidad de establecer una correcta relación beneficio/riesgo/costo a partir del conocimiento de la eficacia, seguridad, conveniencia y costo de los fármacos empleados en el tratamiento de cualquier enfermedad, y por supuesto, de la epilepsia. Los nuevos medicamentos antiepilépticos todavía no han demostrado de forma convincente ser superiores a los ya conocidos, y de los cuales también se exponen sus principales características farmacológicas. Aunque en la mayoría de las ocasiones no son mejores, sí no hay dudas que son más caros e incrementan el precio de los tratamientos.Due to the importance of epilepsy as a non-communicable chronic disease, it was decided to make a review of the new drugs that in the last years have been commercialized for its treatement in the world. Emphasis was given to the need of establishing a correct benefit/risk/cost relation, starting from the knowledge of efficiency, safety, convenience and cost of the drugs used in the treatment of any disease and, of course, of epilepsy. The new antiepileptic drugs have not proved yet to be superior than the already known, whose main pharmacological characteristics are also exposed. Though in most of the ocassions they are not better, they are undoubtedly more expensive and increase the prices of the treatments.

  7. Effects of derivatization reagents consisting of n-alkyl chloroformate/n-alcohol combinations in LC-ESI-MS/MS analysis of zwitterionic antiepileptic drugs.

    Science.gov (United States)

    Kostić, Nađa; Dotsikas, Yannis; Malenović, Anđelija; Medenica, Mirjana

    2013-11-15

    In the current study, three antiepileptic drugs with zwitterionic properties, namely vigabatrin, pregabalin and gabapentin, were chosen as model analytes to undergo derivatization by applying various n-alkyl chloroformate/n-alcohol combinations, followed by LC-ESI-MS/MS analysis. The employment of 16 combinations per drug using methyl, ethyl, propyl or butyl chloroformate coupled with methanol, ethanol, propanol or butanol, greatly affected a series of parameters of the derivatives, such as retention time on C8 column, signal expressed via areas, limit of detection values, as well as the yields of the main and side reactions. Practically, even slight modification of n-alkyl group of either chloroformate or alcohol resulted in significant changes in the chromatographic and mass spectrometric behavior of the novel derivative. It was clearly demonstrated that all the estimated parameters were highly correlated with the length of n-alkyl groups of the involved chloroformate and alcohol. The most significant influence was monitored in peak area values, indicating that the length of the n-alkyl chain plays an important role in electrospray ionization efficiency. For this parameter, increasing the n-alkyl chain from methyl to butyl led to increment up to 2089%, 508.7% and 1075% for area values of derivatized vigabatrin, pregabalin and gabapentin, respectively. These changes affected also the corresponding values of limits of detection, with the estimated improvements up to 1553%, 397.7% and 875.0% for the aforementioned derivatized drugs, respectively. Besides the obvious utilization of these conclusions in the development of bioanalytical methods for these analytes with the current protocol, this study offers valuable data which can be useful in more general approaches, giving insights into the effects of this derivatization reaction and its performances. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. FT-Raman, FT-IR and UV-visible spectral investigations and ab initio computations of anti-epileptic drug: Vigabatrin

    Science.gov (United States)

    Edwin, Bismi; Joe, I. Hubert

    2013-10-01

    Vibrational analysis of anti-epileptic drug vigabatrin, a structural GABA analog was carried out using NIR FT-Raman and FTIR spectroscopic techniques. The equilibrium geometry, various bonding features and harmonic vibrational wavenumbers were studied using density functional theory method. The detailed interpretation of the vibrational spectra has been carried out with the aid of VEDA.4 program. Vibrational spectra, natural bond orbital analysis and optimized molecular structure show clear evidence for the effect of electron charge transfer on the activity of the molecule. Predicted electronic absorption spectrum from TD-DFT calculation has been compared with the UV-vis spectrum. The Mulliken population analysis on atomic charges and the HOMO-LUMO energy were also calculated. Good consistency is found between the calculated results and experimental data for the electronic absorption as well as IR and Raman spectra. The blue-shifting of the Csbnd C stretching wavenumber reveals that the vinyl group is actively involved in the conjugation path. The NBO analysis confirms the occurrence of intramolecular hyperconjugative interactions resulting in ICT causing stabilization of the system.

  9. FT-Raman, FT-IR and UV-visible spectral investigations and ab initio computations of anti-epileptic drug: vigabatrin.

    Science.gov (United States)

    Edwin, Bismi; Joe, I Hubert

    2013-10-01

    Vibrational analysis of anti-epileptic drug vigabatrin, a structural GABA analog was carried out using NIR FT-Raman and FTIR spectroscopic techniques. The equilibrium geometry, various bonding features and harmonic vibrational wavenumbers were studied using density functional theory method. The detailed interpretation of the vibrational spectra has been carried out with the aid of VEDA.4 program. Vibrational spectra, natural bond orbital analysis and optimized molecular structure show clear evidence for the effect of electron charge transfer on the activity of the molecule. Predicted electronic absorption spectrum from TD-DFT calculation has been compared with the UV-vis spectrum. The Mulliken population analysis on atomic charges and the HOMO-LUMO energy were also calculated. Good consistency is found between the calculated results and experimental data for the electronic absorption as well as IR and Raman spectra. The blue-shifting of the C-C stretching wavenumber reveals that the vinyl group is actively involved in the conjugation path. The NBO analysis confirms the occurrence of intramolecular hyperconjugative interactions resulting in ICT causing stabilization of the system. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. The influence of folate serum levels on depressive mood and mental processing in patients with epilepsy treated with enzyme-inducing anti-epileptic drugs.

    Science.gov (United States)

    Rösche, J; Uhlmann, C; Weber, R; Fröscher, W

    2003-04-01

    Folate deficiency is common in patients with epilepsy and also occurs in patients with depression or cognitive deficits. This study investigates whether low serum folate levels may contribute to depressive mood and difficulties in mental processing in patients with epilepsy treated with anti-epileptic drugs inducing the cytochrome P450. We analysed the serum folate levels, the score in the Self Rating Depression Scale (SDS) and the results of a bedside test in mental processing in 54 patients with epilepsy. There was a significant negative correlation between the serum folate levels and the score in SDS and significant positive correlations between the score in SDS and the time needed to process an interference task or a letter-reading task. Low serum folate levels may contribute to depressive mood and therefore to difficulties in mental processing. Further studies utilizing total plasma homocysteine as a sensitive measure of functional folate deficiency and more elaborate tests of mental processing are required to elucidate the impact of folate metabolism on depressive mood and cognitive function in patients with epilepsy.

  11. Simultaneous determination of ten antiepileptic drugs in human plasma by liquid chromatography and tandem mass spectrometry with positive/negative ion-switching electrospray ionization and its application in therapeutic drug monitoring.

    Science.gov (United States)

    Yin, Lei; Wang, Tingting; Shi, Meiyun; Zhang, Ying; Zhao, Xiaojun; Yang, Yan; Gu, Jingkai

    2016-03-01

    A simple, rapid, and high-throughput liquid chromatography with tandem mass spectrometry method for the simultaneous quantitation of ten antiepileptic drugs in human plasma has been developed and validated. The method required only 10 μL of plasma. After simple protein precipitation using acetonitrile, the analytes and internal standard diphenhydramine were separated on a Zorbax SB-C18 column (50 × 4.6 mm, 2.7 μm) using acetonitrile/water as the mobile phase at a flow rate of 0.9 mL/min. The total run time was 6 min for each sample. The validation results of specificity, matrix effects, recovery, linearity, precision, and accuracy were satisfactory. The lower limit of quantification was 0.04 μg/mL for carbamazepine, 0.02 μg/mL for lamotrigine, 0.01 μg/mL for oxcarbazepine, 0.4 μg/mL for 10-hydroxycarbazepine, 0.1 μg/mL for carbamazepine-10,11-epoxide, 0.15 μg/mL for levetiracetam, 0.06 μg/mL for phenytoin, 0.3 μg/mL for valproic acid, 0.03 μg/mL for topiramate, and 0.15 μg/mL for phenobarbital. The intraday precision and interday precision were less than 7.6%, with the accuracy ranging between -8.1 and 7.9%. The method was successfully applied to therapeutic drug monitoring of 1237 patients with epilepsy after administration of standard antiepileptic drugs. The method has been proved to meet the high-throughput requirements in therapeutic drug monitoring. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. An RNAi-mediated screen identifies novel targets for next-generation antiepileptic drugs based on increased expression of the homeostatic regulator pumilio.

    Science.gov (United States)

    Lin, Wei-Hsiang; He, Miaomiao; Fan, Yuen Ngan; Baines, Richard A

    2018-05-02

    Despite availability of a diverse range of anti-epileptic drugs (AEDs), only about two-thirds of epilepsy patients respond well to drug treatment. Thus, novel targets are required to catalyse the design of next-generation AEDs. Manipulation of neuron firing-rate homoeostasis, through enhancing Pumilio (Pum) activity, has been shown to be potently anticonvulsant in Drosophila. In this study, we performed a genome-wide RNAi screen in S2R + cells, using a luciferase-based dPum activity reporter and identified 1166 genes involved in dPum regulation. Of these genes, we focused on 699 genes that, on knock-down, potentiate dPum activity/expression. Of this subgroup, 101 genes are activity-dependent based on comparison with genes previously identified as activity-dependent by RNA-sequencing. Functional cluster analysis shows these genes are enriched in pathways involved in DNA damage, regulation of cell cycle and proteasomal protein catabolism. To test for anticonvulsant activity, we utilised an RNA-interference approach in vivo. RNAi-mediated knockdown showed that 57/101 genes (61%) are sufficient to significantly reduce seizure duration in the characterized seizure mutant, para bss . We further show that chemical inhibitors of protein products of some of the genes targeted are similarly anticonvulsant. Finally, to establish whether the anticonvulsant activity of identified compounds results from increased dpum transcription, we performed a luciferase-based assay to monitor dpum promoter activity. Third instar larvae exposed to sodium fluoride, gemcitabine, metformin, bestatin, WP1066 or valproic acid all showed increased dpum promoter activity. Thus, this study validates Pum as a favourable target for AED design and, moreover, identifies a number of lead compounds capable of increasing the expression of this homeostatic regulator.

  13. Depressive and anxiety disorders in epilepsy: do they differ in their potential to worsen common antiepileptic drug-related adverse events?

    Science.gov (United States)

    Kanner, Andres M; Barry, John J; Gilliam, Frank; Hermann, Bruce; Meador, Kimford J

    2012-06-01

    To compare the effect of anxiety disorders, major depressive episodes (MDEs), and subsyndromic depressive episodes (SSDEs) on antiepileptic drug (AED)-related adverse events (AEs) in persons with epilepsy (PWE). The study included 188 consecutive PWE from five U.S. outpatient epilepsy clinics, all of whom underwent structured interviews (SCID) to identify current and past mood disorders and other current Axis I psychiatric diagnoses according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria. A diagnosis of SSDE was made in patients with total Beck Depression Inventory-II (BDI-II) scores >12 or the Centers of Epidemiologic Studies-Depression (CES-D) > 16 (in the absence of any DSM diagnosis of mood disorder. The presence and severity of AEs was measured with the Adverse Event Profile (AEP). Compared to asymptomatic patients (n = 103), the AEP scores of patients with SSDE (n = 26), MDE only (n = 10), anxiety disorders only (n = 21), or mixed MDE/anxiety disorders (n = 28) were significantly higher, suggesting more severe AED-related AEs. Univariate analyses revealed that having persistent seizures in the last 6 months and taking antidepressants was associated with more severe AEs. Post hoc analyses, however, showed that these differences were accounted for by the presence of a depressive and/or anxiety disorders. Depressive and anxiety disorders worsen AED-related AEs even when presenting as a subsyndromic type. These data suggest that the presence of psychiatric comorbidities must be considered in their interpretation, both in clinical practice and AED drug trials. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

  14. Neurological adverse events of new generation sodium blocker antiepileptic drugs. Meta-analysis of randomized, double-blinded studies with eslicarbazepine acetate, lacosamide and oxcarbazepine.

    Science.gov (United States)

    Zaccara, Gaetano; Giovannelli, Fabio; Maratea, Dario; Fadda, Valeria; Verrotti, Alberto

    2013-09-01

    Analysis of overall tolerability and neurological adverse effects (AEs) of eslicarbazepine acetate (ESL), lacosamide (LCM) and oxcarbazepine (OXC) from double-blind, placebo-controlled trials. Indirect comparisons of patients withdrawing because of AEs, and the incidence of some vestibulocerebellar AEs between these three antiepileptic dugs (AEDs). We searched MEDLINE for all randomized, double-blind, placebo-controlled trials investigating therapeutic effects of fixed oral doses of ESL, LCM and OXC in patients with drug resistant epilepsy. Withdrawal rate due to AEs, percentages of patients with serious AEs, and the proportion of patients experiencing any neurological AE, nausea and vomiting were assessed for their association with the experimental drug. Analyses were performed between recommended daily doses of each AED according to the approved summary of product characteristics (SPC). Risk differences were used to evaluate the association of any AE [99% confidence intervals (CIs)] or study withdrawals because of AEs (95% CIs) with the experimental drug. Indirect comparisons between withdrawal rate and AEs dizziness, coordination abnormal/ataxia and diplopia were estimated according to network meta-analysis (Net-MA). Eight randomized, placebo-controlled, double-blind trials (4 with ESL, 3 with LCM, and 1 with OXC) were included in our analysis. At high doses (OXC 1200mg, ESL 1200mg and LCM 400mg) there was an increased risk of AE-related study withdrawals compared to placebo for all drugs. Several AEs were associated with the experimental drug. Both number and frequency of AEs were dose-related. At high recommended doses, patients treated with OXC withdrew from the experimental treatment significantly more frequently than patients treated with ESL and LCM. Furthermore, the AEs coordination abnormal/ataxia and diplopia were significantly more frequently observed in patients treated with OXC compared to patients treated with LCM and ESL. The overall tolerability

  15. Interaction of an antiepileptic drug, lamotrigine with human serum albumin (HSA): Application of spectroscopic techniques and molecular modeling methods.

    Science.gov (United States)

    Poureshghi, Fatemeh; Ghandforoushan, Parisa; Safarnejad, Azam; Soltani, Somaieh

    2017-01-01

    Lamotrigine (an epileptic drug) interaction with human serum albumin (HSA) was investigated by fluorescence, UV-Vis, FTIR, CD spectroscopic techniques, and molecular modeling methods. Binding constant (K b ) of 5.74×10 3 and number of binding site of 0.97 showed that there is a slight interaction between lamotrigine and HSA. Thermodynamic studies was constructed using the flourimetric titrations in three different temperatures and the resulted data used to calculate the parameters using Vant Hoff equation. Decreased Stern Volmer quenching constant by enhanced temperature revealed the static quenching mechanism. Negative standard enthalpy (ΔH) and standard entropy (ΔS) changes indicated that van der Waals interactions and hydrogen bonds were dominant forces which facilitate the binding of Lamotrigine to HSA, the results were confirmed by molecular docking studies which showed no hydrogen binding. The FRET studies showed that there is a possibility of energy transfer between Trp214 and lamotrigine. Also the binding of lamotrigine to HSA in the studied concentrations was not as much as many other drugs, but the secondary structure of the HSA was significantly changed following the interaction in a way that α-helix percentage was reduced from 67% to 57% after the addition of lamotrigine in the molar ratio of 4:1 to HSA. According to the docking studies, lamotrigine binds to IB site preferably. Copyright © 2016. Published by Elsevier B.V.

  16. Anti-Epileptic Drugs Delay Age-Related Loss of Spiral Ganglion Neurons via T-type Calcium Channel

    Science.gov (United States)

    Lei, Debin; Gao, Xia; Perez, Philip; Ohlemiller, Kevin K; Chen, Chien-Chang; Campbell, Kevin P.; Hood, Aizhen Yang; Bao, Jianxin

    2011-01-01

    Loss of spiral ganglion neurons is a major cause of age-related hearing loss (presbycusis). Despite being the third most prevalent condition afflicting elderly persons, there are no known medications to prevent presbycusis. Because calcium signaling has long been implicated in age-related neuronal death, we investigated T-type calcium channels. This family is comprised of three members (Cav3.1, Cav3.2, and Cav3.3), based on their respective main pore-forming alpha subunits: α1G, α1H, and α1I. In the present study, we report a significant delay of age-related loss of cochlear function and preservation of spiral ganglion neurons in α1H null and heterozygous mice, clearly demonstrating an important role for Cav3.2 in age-related neuronal loss. Furthermore, we show that anticonvulsant drugs from a family of T-type calcium channel blockers can significantly preserve spiral ganglion neurons during aging. To our knowledge, this is the first report of drugs capable of diminishing age-related loss of spiral ganglion neurons. PMID:21640179

  17. Are adverse effects of antiepileptic drugs different in symptomatic partial and idiopathic generalized epilepsies? The Portuguese-Brazilian validation of the Liverpool Adverse Events Profile.

    Science.gov (United States)

    Martins, H H; Alonso, N B; Vidal-Dourado, M; Carbonel, T D; de Araújo Filho, G M; Caboclo, L O; Yacubian, E M; Guilhoto, L M

    2011-11-01

    We report the results of administration of the Portuguese-Brazilian translation of the Liverpool Adverse Events Profile (LAEP) to 100 patients (mean age=34.5, SD=12.12; 56 females), 61 with symptomatic partial epilepsy (SPE) and 39 with idiopathic generalized epilepsy (IGE) (ILAE, 1989) who were on a stable antiepileptic drug (AED) regimen and being treated in a Brazilian tertiary epilepsy center. Carbamazepine was the most commonly used AED (43.0%), followed by valproic acid (32.0%). Two or more AEDs were used by 69.0% of patients. The mean LAEP score (19 questions) was 37.6 (SD=13.35). The most common adverse effects were sleepiness (35.0%), memory problems (35.0%), and difficulty in concentrating (25.0%). Higher LAEP scores were associated with polytherapy with three or more AEDs (P=0.005), female gender (P0.001) and Hospital Anxiety and Depression Scale (Depression: r=0.637, P<0.001; Anxiety: r=0.621, P<0.001) dimensions. LAEP overall scores were similar in people with SPE and IGE and were not helpful in differentiating adverse effects in these two groups. Clinical variables that influenced global LAEP were seizure frequency (P=0.050) and generalized tonic-clonic seizures in the last month (P=0.031) in the IGE group, and polytherapy with three or more AEDs (P=0.003 and P=0.003) in both IGE and SPE groups. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Etiologic features and utilization of antiepileptic drugs in people with chronic epilepsy in China: Report from the Epilepsy Cohort of Huashan Hospital (ECoH).

    Science.gov (United States)

    Ge, Yan; Yu, Peimin; Ding, Ding; Wang, Ping; Shi, Yunbo; Zhao, Ting; Tang, Xinghua; Hong, Zhen

    2015-10-01

    Chronic epilepsy is estimated to affect more than 2 million people in China. However, data of its clinical characteristics was rarely reported in China. In the present study, we summarized the etiologic features and utilization patterns of antiepileptic drugs (AEDs) in people with chronic epilepsy in a tertiary medical center in China. We prospectively recruited people with chronic epilepsy treated at the Epilepsy Outpatient Clinic of Huashan Hospital during October 2009 to August 2013. Demographic data, clinical characteristics, AED treatment, epilepsy-associated risk factors and medical history, and results of supplementary examinations of each participant were collected retrospectively via an interviewer-administered questionnaire and confirmed by the medical records. Among 554 people with chronic epilepsy, 58.0% of them were male, 66.8% had focal seizure, and 29.2% had symptomatic cause. Developmental anomalies of cerebral structure (16.7%) and cerebral trauma (16.7%) shared the leading cause of symptomatic epilepsy among children with epilepsy. While cerebral trauma (29.1%) and cerebrovascular disorder (36.4%) were the most common causes in groups of adults and elderly. Fifty percent of participants were taking AED monotherapy. Proportions of people with idiopathic, cryptogenic and symptomatic epilepsy treated by multitherapy were 35%, 46% and 45.6%, respectively. Valproic acid (VPA) was the most frequently utilized AED as monotherapy (32.7%) and within multitherapy (62.5%). This hospital-based study reported that etiologic features were diverse in different age groups of people with chronic epilepsy. VPA was widely utilized to treat chronic epilepsy in mainland China. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Use of peri-operative anti-epileptic drugs in patients with newly diagnosed high grade malignant glioma: a single center experience.

    Science.gov (United States)

    Lwu, Shelly; Hamilton, Mark G; Forsyth, Peter A; Cairncross, J Gregory; Parney, Ian F

    2010-02-01

    An American Academy of Neurology practice parameter recommends that long-term prophylactic anti-epileptic drugs (AED) should not be routine in patients with newly diagnosed brain tumors. However, prospective multi-center North American data shows that most newly diagnosed glioma patients receive prophylactic AED. We examined our own peri-operative AED practice patterns in newly-diagnosed patients with malignant glioma to determine if we deviate from published guidelines. A retrospective chart review was performed in adult patients with newly diagnosed malignant gliomas undergoing surgery in southern Alberta between January 2003 and December 2005. Demographic information, AED use, seizure incidence, adverse effects, tumor size, and tumor location were recorded. Of 164 eligible patients, 54 (33%) presented with seizures and all received AED. Prophylactic AED were given to 44 patients (27%). Peri-operative seizures (within 1 week) occurred in two patients without (3%) and no patients with seizure prophylaxis. Adverse AED reactions and adverse effects attributable to seizures were both rare. Prophylactic AED were continued >1 week post-op in 30 patients (18%). Patients receiving prophylactic AED were more likely to have had tumors involving the temporal lobe than those who did not (50 vs. 20%; P < 0.01). Patients receiving peri-operative AED prophylaxis were common, had a trend to reduced peri-operative seizures, and had few adverse effects. However, most of these patients were maintained on prophylactic AED continued beyond the first peri-operative week, contradicting published guidelines. Increased awareness of practice guidelines may help modify AED prescription patterns in malignant glioma patients.

  20. Seizure characteristics and the use of anti-epileptic drugs in children and young people with brain tumours and epileptic seizures: Analysis of regional paediatric cancer service population.

    Science.gov (United States)

    Pilotto, Chiara; Liu, Jo-Fen; Walker, David A; Whitehouse, William P

    2018-03-21

    Epileptic seizures complicate the management of childhood brain tumours. There are no published standards for clinical practice concerning risk factors, treatment selection or strategies to withdraw treatment with antiepileptic drugs (AED). we undertook a case note review of 120 patients with newly diagnosed brain tumours, referred to a regional paediatric cancer service. data was available on 117/120 (98%) children seizures. A cortical tumour location was associated with the highest risk of seizures (OR: 7.1; CI 95% 2.9-17.3). At a median follow up of 24 months (IQR 25°-75° : 15-48), 22/35 (63%) with seizures, had a single seizure episode, 15/35 (43%) were seizure free (SF) on AEDs, 13/35 (37%) were SF off AEDs, and 7/35 (20%) experienced continuing epileptic seizures. Overall 34/35 (97%) were treated with AEDs after a seizure, of whom 12/35 (35%) withdrew from AED medication, and although 4/35 (12%) had seizure relapse, all were after further acute events. The median duration of AED before withdrawal was 11 months (IQR 25°-75° 5-14 months), and the median follow up after withdrawal was 15 months (IQR 25°-75° 5-34 months). Seizures affect about 1/3rd of children and young people presenting with and being treated for brain tumours particularly when the tumour is in the cerebral cortex. The low risk of recurrent seizures after AED treatment justifies consideration of early withdrawal of AED after seizure control. Copyright © 2018. Published by Elsevier Ltd.

  1. Brand name to generic substitution of antiepileptic drugs does not lead to seizure-related hospitalization: a population-based case-crossover study.

    Science.gov (United States)

    Polard, Elisabeth; Nowak, Emmanuel; Happe, André; Biraben, Arnaud; Oger, Emmanuel

    2015-11-01

    There is still controversy on brand-to-generic (B-G) antiepileptic drugs (AEDs) substitution. To assess association between B-G AED substitution and seizure-related hospitalization, we designed a case crossover using the French National Health Insurance Database. We identified a cohort of adult patients who filled a prescription in 2009-2011 for AEDs with at least one brand name and one generic form. The outcome date was defined as the date of hospitalization, coded G40.x or G41.x, with a G40/G41 hospitalization-free period of at least 1 year. Patients with a medical history of cancer and women who gave birth in 2009-2011 were excluded. We required individuals to have regular dispensations of AEDs within the year preceding the outcome date. Free patients were defined as patients who had only brand name dispensations before the control period. Eight thousand three hundred seventy nine patients (mean age ± standard deviation, 52.7 ± 18.8 years; sex ratio male/female, 1.27) were analyzed. Discordant pairs were 491 with B-G substitution in the control period only and 478 with B-G substitution in the case period only; odds ratio (95% confidence interval) 0.97 (0.86-1.10). No statistically significant interaction was detected among the four prespecified subgroup analyses (gender, age strata, free or non-free, and strict AED monotherapy or not). Controlling for non-seizure-related hospitalizations made no material difference. Sensitivity analyses yielded similar results. Brand-to-generic AED substitution was not associated with an elevated risk of seizure-related hospitalization. Copyright © 2015 John Wiley & Sons, Ltd.

  2. Mortality rates and causes of death in children with epilepsy prescribed antiepileptic drugs: a retrospective cohort study using the UK General Practice Research Database.

    Science.gov (United States)

    Ackers, Ruth; Besag, Frank M C; Hughes, Elaine; Squier, Waney; Murray, Macey L; Wong, Ian C K

    2011-05-01

    Patients with epilepsy, including children, have an increased risk of mortality compared with the general population. Antiepileptic drugs (AEDs) were the most frequent class of drugs reported in a study looking at fatal suspected adverse drug reactions in children in the UK. The objective of the study was to identify cases and causes of death in a paediatric patient cohort prescribed AEDs with an associated epilepsy diagnosis. This was a retrospective cohort study supplemented with general practitioner-completed questionnaires, post-mortem reports and death certificates. The setting was UK primary care practices contributing to the General Practice Research Database. Participants were children and adolescents aged 0-18 years prescribed AEDs between 1993 and 2005. Causality assessment was undertaken by a consensus panel comprising paediatric specialists in neuropathology, neurology, neuropsychiatry, paediatric epilepsy, pharmacoepidemiology and pharmacy to determine crude mortality rate (CMR) and standardized mortality ratios (SMRs), and the likelihood of an association between AED(s) and the event of death. There were 6190 subjects in the cohort (contributing 26,890 person-years of data), of whom 151 died. Median age at death was 8.0 years. CMR was 56.2 per 10,000 person-years and the SMR was 22.4 (95% CI 18.9, 26.2). The majority of deceased subjects had severe underlying disorders. Death was attributable to epilepsy in 18 subjects; in 9 the cause of death was sudden unexpected death in epilepsy (SUDEP) [3.3 per 10 000 person-years (95% CI 1.5, 6.4)]. AEDs were probably (n = 2) or possibly (n = 3) associated causally with death in five subjects. Two status epilepticus deaths were associated causally with AED withdrawal. Children prescribed AEDs have an increased risk of mortality relative to the general population. Most of the deaths were in children with serious underlying disorders. A small number of SUDEP cases were identified. AEDs are not a major

  3. Algunas consideraciones en relación con los medicamentos antiepilépticos de nueva generación en los niños Some considerations in relation to the new generation antiepileptic drugs in children

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    Desiderio Pozo Lauzán

    2005-06-01

    Full Text Available El objetivo de este trabajo es revisar las principales drogas antiepilépticas de segunda generación y su administración en los niños: vigabatrina, felbamato, lamotrigina, topiramato, tiagabina, oxcarbazepina, zonisamida, levetiracetam y stiripentol. Al inicio se recomendaron en pacientes adultos con epilepsias focales refractarias, sin embargo desde hace varios años, se ha demostrado su eficacia en diferentes tipos de crisis en los niños. La lamotrigina y el topiramato se consideran medicamentos de amplio espectro. Se enfatiza en el metabolismo, vías de eliminación, indicaciones, dosis en los niños, interacciones medicamentosas y efectos colaterales de los medicamentos antiepilépticos de segunda generación. Se mencionan algunos de los nuevos medicamentos que actualmente están en investigación como antiepilépticos y que constituyen una tercera generaciónThe objective of this paper is to review the main second generation antiepileptic drugs and their administration in children: vigatrine, felbamate, lamotrigine, topiramate, tiagabine, oxcarbazepine, zonisamide, leventiracetam and stiripentol. At the beginning, they were recommended in adult patients with focal refractory epilepsies; however, their efficacy in different types of seizures in children has been proved for some years. Lamotrigine and topiramate are considered drugs of wide spectrum. Emphasis is made on metabolism, routes of elimination, indications, doses in children, drug interactions and side effects of the second generation antiepileptic drugs. Some of the new drugs that are currently under study as antiepileptic and that constitute a third generation, are mentioned.

  4. Determination of a selection of anti-epileptic drugs and two active metabolites in whole blood by reversed phase UPLC-MS/MS and some examples of application of the method in forensic toxicology cases.

    Science.gov (United States)

    Karinen, Ritva; Vindenes, Vigdis; Hasvold, Inger; Olsen, Kirsten Midtbøen; Christophersen, Asbjørg S; Øiestad, Elisabeth

    2015-07-01

    Quantitative determination of anti-epileptic drug concentrations is of great importance in forensic toxicology cases. Although the drugs are not usually abused, they are important post-mortem cases where the question of both lack of compliance and accidental or deliberate poisoning might be raised. In addition these drugs can be relevant for driving under the influence cases. A reversed phase ultra-performance liquid chromatography-tandem mass spectrometry method has been developed for the quantitative analysis of the anti-epileptic compounds carbamazepine, carbamazepine-10,11-epoxide, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, 10-OH-carbazepine, phenobarbital, phenytoin, pregabalin, and topiramate in whole blood, using 0.1 mL sample volume with methaqualone as internal standard. Sample preparation was a simple protein precipitation with acetonitrile and methanol. The diluted supernatant was directly injected into the chromatographic system. Separation was performed on an Acquity UPLC® BEH Phenyl column with gradient elution and a mildly alkaline mobile phase. The mass spectrometric detection was performed in positive ion mode, except for phenobarbital, and multiple reaction monitoring was used for drug quantification. The limits of quantification for the different anti-epileptic drugs varied from 0.064 to 1.26 mg/L in blood, within-day and day-to-day relative standard deviations from 2.2 to 14.7% except for phenobarbital. Between-day variation for phenobarbital was 20.4% at the concentration level of 3.5 mg/L. The biases for all compounds were within ±17.5%. The recoveries ranged between 85 and 120%. The corrected matrix effects were 88-106% and 84-110% in ante-mortem and post-mortem whole blood samples, respectively. Copyright © 2014 John Wiley & Sons, Ltd.

  5. Stability-indicating liquid chromatographic method for quantification of new anti-epileptic drug lacosamide in bulk and pharmaceutical formulation

    Directory of Open Access Journals (Sweden)

    Chhalotiya Usmangani K.

    2012-01-01

    Full Text Available An isocratic stability indicating reversed-phase liquid chromatographic determination was developed for the quantitative determination of lacosamide in the pharmaceutical dosage form. A Hypersil C-18, 4.5μm column with mobile phase containing acetonitrile-water (20:80, v/v was used. The flow rate was 1.0 mL min-1 and effluents were monitored at 258 nm. The retention time of lacosamide was 8.9 min. The method was found to be linear in the concentration range of 5-100 μg/ml and the recovery was found to be in the range of 99.15 - 100.09 %. The limit of detection and limit of quantification were found to be 2 μg/ml and 5 μg/ml, respectively. Lacosamide stock solutions were subjected to acid and alkali hydrolysis, chemical oxidation and dry heat degradation. The drug was found to be stable to the dry heat and acidic condition attempted. The proposed method was validated and successfully applied to the estimation of lacosamide in tablet dosage forms.

  6. Long-term Effectiveness of Antiepileptic Drug Monotherapy in Partial Epileptic Patients: A 7-year Study in an Epilepsy Center in China

    Science.gov (United States)

    Zhu, Fei; Lang, Sen-Yang; Wang, Xiang-Qing; Shi, Xiao-Bing; Ma, Yun-Feng; Zhang, Xu; Chen, Ya-Nan; Zhang, Jia-Tang

    2015-01-01

    Background: It is important to choose an appropriate antiepileptic drug (AED) to manage partial epilepsy. Traditional AEDs, such as carbamazepine (CBZ) and valproate (VPA), have been proven to have good therapeutic effects. However, in recent years, a variety of new AEDs have increasingly been used as first-line treatments for partial epilepsy. As the studies regarding the effectiveness of new drugs and comparisons between new AEDs and traditional AEDs are few, it is determined that these are areas in need of further research. Accordingly, this study investigated the long-term effectiveness of six AEDs used as monotherapy in patients with partial epilepsy. Methods: This is a retrospective, long-term observational study. Patients with partial epilepsy who received monotherapy with one of six AEDs, namely, CBZ, VPA, topiramate (TPM), oxcarbazepine (OXC), lamotrigine (LTG), or levetiracetam (LEV), were identified and followed up from May 2007 to October 2014, and time to first seizure after treatment, 12-month remission rate, retention rate, reasons for treatment discontinuation, and adverse effects were evaluated. Results: A total of 789 patients were enrolled. The median time of follow-up was 56.95 months. CBZ exhibited the best time to first seizure, with a median time to first seizure of 36.06 months (95% confidential interval: 30.64–44.07). CBZ exhibited the highest 12-month remission rate (85.55%), which was significantly higher than those of TPM (69.38%, P = 0.006), LTG (70.79%, P = 0.001), LEV (72.54%, P = 0.005), and VPA (73.33%, P = 0.002). CBZ, OXC, and LEV had the best retention rate, followed by LTG, TPM, and VPA. Overall, adverse effects occurred in 45.87% of patients, and the most common adverse effects were memory problems (8.09%), rashes (7.76%), abnormal hepatic function (6.24%), and drowsiness (6.24%). Conclusion: This study demonstrated that CBZ, OXC, and LEV are relatively effective in managing focal epilepsy as measured by time to first seizure

  7. Long-term Effectiveness of Antiepileptic Drug Monotherapy in Partial Epileptic Patients: A 7-year Study in an Epilepsy Center in China

    Directory of Open Access Journals (Sweden)

    Fei Zhu

    2015-01-01

    Full Text Available Background: It is important to choose an appropriate antiepileptic drug (AED to manage partial epilepsy. Traditional AEDs, such as carbamazepine (CBZ and valproate (VPA, have been proven to have good therapeutic effects. However, in recent years, a variety of new AEDs have increasingly been used as first-line treatments for partial epilepsy. As the studies regarding the effectiveness of new drugs and comparisons between new AEDs and traditional AEDs are few, it is determined that these are areas in need of further research. Accordingly, this study investigated the long-term effectiveness of six AEDs used as monotherapy in patients with partial epilepsy. Methods: This is a retrospective, long-term observational study. Patients with partial epilepsy who received monotherapy with one of six AEDs, namely, CBZ, VPA, topiramate (TPM, oxcarbazepine (OXC, lamotrigine (LTG, or levetiracetam (LEV, were identified and followed up from May 2007 to October 2014, and time to first seizure after treatment, 12-month remission rate, retention rate, reasons for treatment discontinuation, and adverse effects were evaluated. Results: A total of 789 patients were enrolled. The median time of follow-up was 56.95 months. CBZ exhibited the best time to first seizure, with a median time to first seizure of 36.06 months (95% confidential interval: 30.64-44.07. CBZ exhibited the highest 12-month remission rate (85.55%, which was significantly higher than those of TPM (69.38%, P = 0.006, LTG (70.79%, P = 0.001, LEV (72.54%, P = 0.005, and VPA (73.33%, P = 0.002. CBZ, OXC, and LEV had the best retention rate, followed by LTG, TPM, and VPA. Overall, adverse effects occurred in 45.87% of patients, and the most common adverse effects were memory problems (8.09%, rashes (7.76%, abnormal hepatic function (6.24%, and drowsiness (6.24%. Conclusion: This study demonstrated that CBZ, OXC, and LEV are relatively effective in managing focal epilepsy as measured by time to first

  8. Danish register-based study on the association between specific cardiovascular drugs and fragility fractures

    DEFF Research Database (Denmark)

    Torstensson, Maia; Hansen, Annette Højmann; Leth-Møller, Katja

    2015-01-01

    OBJECTIVE: To determine whether drugs used in treatment of cardiovascular diseases (CVD-drugs), including hypertension, increase the risk of fragility fractures in individuals above the age of 65 years. DESIGN: Retrospective nationwide cohort study. SETTING: Danish nationwide national registers...... and statins) was determined by prescription claims from pharmacies. The association between use of specific CVD-drugs and fragility fractures was assessed using multivariable Poisson regression models, and adjusted incidence rate ratios (IRRs) were calculated. RESULTS: Overall, 1 586 554 persons were included......, of these 16.1% experienced a fall-related fracture. The multivariable Poisson regression analysis showed positive associations between fracture and treatment with furosemide, thiazide and digoxin. IRRs during the first 14 days of treatment were for furosemide IRR 1.74 (95% CI 1.61 to 1.89) and for thiazides...

  9. Antiepileptic drugs and intrauterine death

    DEFF Research Database (Denmark)

    Tomson, Torbjörn; Battino, Dina; Bonizzoni, Erminio

    2015-01-01

    ) after prenatal AED exposure. Using EURAP data, we prospectively monitored pregnancies exposed to the 6 most common AED monotherapies and to polytherapy. Intrauterine death (spontaneous abortion and stillbirth combined) was the primary endpoint. RESULTS: Of 7,055 pregnancies exposed to monotherapy...... with lamotrigine (n = 1,910), carbamazepine (n = 1,713), valproic acid (n = 1,171), levetiracetam (n = 324), oxcarbazepine (n = 262), or phenobarbital (n = 260), and to polytherapy (n = 1,415), 632 ended in intrauterine deaths (592 spontaneous abortions and 40 stillbirths). Rates of intrauterine death were similar...... that the risk was greater with polytherapy vs monotherapy (risk ratio [RR] 1.38; 95% CI 1.14-1.66), parental history of MCMs (RR 1.92; 1.20-3.07), maternal age (RR 1.06; 1.04-1.07), and number of previous intrauterine deaths (RR 1.09; 1.00-1.19). The risk was greater with early enrollment and decreased...

  10. Prognostic analysis of patients with epilepsy according to time of relapse after withdrawal of antiepileptic drugs following four seizure-free years.

    Science.gov (United States)

    Park, Soochul; Lee, Dong Hyun; Kim, Seung Woo; Roh, Yun Ho

    2017-01-01

    We performed a retrospective, prognostic analysis of a cohort of patients with epilepsy according to time of relapse after four seizure-free years. Planned withdrawal of antiepileptic drugs (AEDs) and at least 3 years of follow-up after AED discontinuation were performed. The following two groups were assessed: (1) an early relapse (ER) group of patients who experienced recurrence during AED withdrawal and (2) a late relapse (LR) group of patients who experienced recurrence after completion of the AED discontinuation process. After dichotomization, the relapse rate, prognostic factors, and their impacts for each group were compared with those of a group of patients who continued to be seizure-free after AED withdrawal (SF group) using multiple logistic regression analysis. The AED intake mode was also analyzed. Two hundred seventeen (64.6%) of the 336 total patients experienced relapse. One hundred thirty-nine patients (41.4%) and 78 patients (23.2%) were included in the LR and ER groups, respectively. Symptom duration >120 months showed the strongest negative prognostic impact as demonstrated by the 4.7-fold higher risk of recurrence in the ER group compared with the SF group. Additional factors with a negative prognostic impact included an age at epilepsy onset of ≤20 years and the presence of localization-related epilepsy. No reliable predictor between the SF and LR groups was revealed. After exclusion of the SF group, post hoc analysis according to age at epilepsy onset and symptom duration showed that the above-mentioned negative prognostic factors significantly affected the relapse patterns of the LR and ER groups. The results suggest that longer symptom duration, which could be associated with intrinsic reactivation of epilepsy, is the strongest negative prognostic factor for relapse. Relapse after AED withdrawal in prolonged follow-up of seizure-free patients is one aspect of the natural history of epilepsy. © 2016 The Authors. Epilepsia published by

  11. Effects of adjunctive eslicarbazepine acetate on serum lipids in patients with partial-onset seizures: Impact of concomitant statins and enzyme-inducing antiepileptic drugs.

    Science.gov (United States)

    Mintzer, Scott; Wechsler, Robert T; Rogin, Joanne B; Gidal, Barry E; Schwab, Matthias; Ben-Menachem, Elinor; Carreño, Mar; da Silva, Patrício Soares; Moreira, Joana; Li, Yan; Blum, David; Grinnell, Todd

    2018-03-01

    To evaluate the effects of eslicarbazepine acetate (ESL) on lipid metabolism and to determine whether reduced statin exposure during ESL therapy has clinical consequences. We conducted a post-hoc analysis of pooled data for serum lipids (laboratory values) from three phase III, multicenter, randomized, double-blind, placebo-controlled trials of adjunctive ESL therapy (400, 800, or 1200 mg once daily) in patients with treatment-refractory partial-onset seizures. Changes from baseline in serum lipid levels were analyzed according to use of statins and/or enzyme-inducing antiepileptic drugs (EIAEDs) during the baseline period. In total, 426 and 1021 placebo- and ESL-treated patients, respectively, were included in the analysis. With regard to the changes from baseline in serum concentrations, there were statistically significant differences between the placebo and ESL 1200 mg QD groups, for both total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), but the effect sizes were small (+4.1 mg/dL and +1.8 mg/dL, respectively). A small but significant difference in low-density lipoprotein cholesterol (LDL-C; -5.0 mg/dL) was observed between the ESL 400 mg QD group and the placebo group. In patients not taking a concomitant EIAED, there were no changes with ESL 400 mg QD, but modest and statistically significant increases in cholesterol fractions (TC, LDL-C and HDL-C) with ESL 800 mg QD (ESL 1200 mg QD (ESL had no consistent effect on lipids in patients taking a concomitant EIAED. In patients taking statins during baseline, there were no clinically relevant changes in serum lipids during use of ESL, although the subgroups were small. These results suggest that ESL does not appear to have clinically significant effects on serum lipids, nor does the pharmacokinetic interaction between ESL and statins have an impact on serum lipid concentrations. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Congenital Anomalies in Children of Mothers Taking Antiepileptic Drugs with and without Periconceptional High Dose Folic Acid Use: A Population-Based Cohort Study.

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    Lu Ban

    Full Text Available Antenatal antiepileptic drug (AED use has been found to be associated with increased major congenital anomaly (CA risks. However whether such AED-associated risks were different according to periconceptional high dose (5mg daily folic acid supplementation is still unclear.We included 258,591 singleton live-born children of mothers aged 15-44 years in 1990-2013 from The Health Improvement Network, a large UK primary care database. We identified all major CAs according to the European Surveillance of Congenital Anomalies classification. Absolute risks and adjusted odds ratios (aOR were calculated comparing children of mothers prescribed AEDs to those without such prescriptions, stratified by folic acid prescriptions around the time of conception (one month before conception to two months post-conception.CA risk was 476/10,000 in children of mothers with first trimester AEDs compared with 269/10,000 in those without AEDs equating to an aOR of 1.82, 95% confidence interval 1.30-2.56. The highest system-specific risks were for heart anomalies (198/10,000 and 79/10,000 respectively, aOR 2.49,1.47-4.21. Sodium valproate and lamotrigine were both associated with increased risks of any CA (aOR 2.63,1.46-4.74 and aOR 2.01,1.12-3.59 respectively and system-specific risks. Stratification by folic acid supplementation did not show marked reductions in AED-associated risks (e.g. for CAs overall aOR 1.75, 1.01-3.03 in the high dose folic acid group and 1.94, 95%CI 1.21-3.13 in the low dose or no folic acid group; however, the majority of mothers taking AEDs only initiated high dose folic acid from the second month of pregnancy.Children of mothers with AEDs in the first trimester of pregnancy have a 2-fold increased risk of major CA compared to those unexposed. We found no evidence that prescribed high dose folic acid supplementation reduced such AED-associated risks. Although statistical power was limited, prescribing of folic acid too late for it to be

  13. What does the U.S. Medicare administrative claims database tell us about initial antiepileptic drug treatment for older adults with new-onset epilepsy?

    Science.gov (United States)

    Martin, Roy C; Faught, Edward; Szaflarski, Jerzy P; Richman, Joshua; Funkhouser, Ellen; Piper, Kendra; Juarez, Lucia; Dai, Chen; Pisu, Maria

    2017-04-01

    Disparities in epilepsy treatment are not uncommon; therefore, we examined population-based estimates of initial antiepileptic drugs (AEDs) in new-onset epilepsy among racial/ethnic minority groups of older US Medicare beneficiaries. We conducted retrospective analyses of 2008-2010 Medicare administrative claims for a 5% random sample of beneficiaries augmented for minority representation. New-onset epilepsy cases in 2009 had ≥1 International Classification of Diseases, Ninth Revision (ICD-9) 345.x or ≥2 ICD-9 780.3x, and ≥1 AED, AND no seizure/epilepsy claim codes or AEDs in preceding 365 days. We examined AED use and concordance with Quality Indicators of Epilepsy Treatment (QUIET) 6 (monotherapy as initial treatment = ≥30 day first prescription with no other concomitant AEDs), and prompt AED treatment (first AED within 30 days of diagnosis). Logistic regression examined likelihood of prompt treatment by demographic (race/ethnicity, gender, age), clinical (number of comorbid conditions, neurology care, index event occurring in the emergency room (ER)), and economic (Part D coverage phase, eligibility for Part D Low Income Subsidy [LIS], and ZIP code level poverty) factors. Over 1 year of follow-up, 79.6% of 3,706 new epilepsy cases had one AED only (77.89% of whites vs. 89% of American Indian/Alaska Native [AI/AN]). Levetiracetam was the most commonly prescribed AED (45.5%: from 24.6% AI/AN to 55.0% whites). The second most common was phenytoin (30.6%: from 18.8% Asians to 43.1% AI/AN). QUIET 6 concordance was 94.7% (93.9% for whites to 97.3% of AI/AN). Only 50% received prompt AED therapy (49.6% whites to 53.9% AI/AN). Race/ethnicity was not significantly associated with AED patterns, monotherapy use, or prompt treatment. Monotherapy is common across all racial/ethnic groups of older adults with new-onset epilepsy, older AEDs are commonly prescribed, and treatment is frequently delayed. Further studies on reasons for treatment delays are warranted

  14. Drug induced mortality: a multiple cause approach on Italian causes of death Register

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    Francesco Grippo

    2015-04-01

    Full Text Available Background: Drug-related mortality is a complex phenomenon that has several health, social and economic effects. In this paper trends of drug-induced mortality in Italy are analysed. Two approaches have been followed: the traditional analysis of the underlying cause of death (UC (data refers to the Istat mortality database from 1980 to 2011, and the multiple cause (MCanalysis, that is the analysis of all conditions reported on the death certificate (data for 2003-2011 period.Methods: Data presented in this paper are based on the Italian mortality register. The selection of Icd codes used for the analysis follows the definition of the European Monitoring Centre for Drugs and Drug Addiction. Using different indicators (crude and standardized rates, ratio multiple to underlying, the results obtained from the two approaches (UC and MC have been compared. Moreover, as a measure of association between drug-related causes and specific conditions on the death certificate, an estimation of the age-standardized relative risk (RR has been used.Results: In the years 2009-2011, the total number of certificates whit mention of drug use was 1,293, 60% higher than the number UC based. The groups of conditions more strongly associated with drug-related causes are the mental and behavioral disorders (especially alcohol consumption, viral hepatitis, cirrhosis and fibrosis of liver, AIDS and endocarditis.Conclusions : The analysis based on multiple cause approach shows, for the first time, a more detailed picture of the drug related death; it allows to better describe the mortality profiles and to re-evaluate  the contribution of a specific cause to death.

  15. A staged screening of registered drugs highlights remyelinating drug candidates for clinical trials

    Science.gov (United States)

    Eleuteri, C.; Olla, S.; Veroni, C.; Umeton, R.; Mechelli, R.; Romano, S.; Buscarinu, Mc.; Ferrari, F.; Calò, G.; Ristori, G.; Salvetti, M.; Agresti, C.

    2017-04-01

    There is no treatment for the myelin loss in multiple sclerosis, ultimately resulting in the axonal degeneration that leads to the progressive phase of the disease. We established a multi-tiered platform for the sequential screening of drugs that could be repurposed as remyelinating agents. We screened a library of 2,000 compounds (mainly Food and Drug Administration (FDA)-approved compounds and natural products) for cellular metabolic activity on mouse oligodendrocyte precursors (OPC), identifying 42 molecules with significant stimulating effects. We then characterized the effects of these compounds on OPC proliferation and differentiation in mouse glial cultures, and on myelination and remyelination in organotypic cultures. Three molecules, edaravone, 5-methyl-7-methoxyisoflavone and lovastatin, gave positive results in all screening tiers. We validated the results by retesting independent stocks of the compounds, analyzing their purity, and performing dose-response curves. To identify the chemical features that may be modified to enhance the compounds’ activity, we tested chemical analogs and identified, for edaravone, the functional groups that may be essential for its activity. Among the selected remyelinating candidates, edaravone appears to be of strong interest, also considering that this drug has been approved as a neuroprotective agent for acute ischemic stroke and amyotrophic lateral sclerosis in Japan.

  16. Does the number of siblings affect health in midlife? Evidence from the Swedish Prescribed Drug Register

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    Anna Baranowska-Rataj

    2016-11-01

    Full Text Available Background: In many societies, growing up in a large family is associated with receiving less parental time, attention, and financial support. As a result, children with a large number of siblings may have worse physical and mental health outcomes than children with fewer siblings. Objective: Our objective is to examine the long-term causal effects of sibship size on physical and mental health in modern Sweden. Methods: We employ longitudinal data covering the entire Swedish population from the Multigenerational Register and the Medical Birth Register. This data includes information on family size and on potential confounders such as parental background. We use the Prescribed Drug Register to identify the medicines that have been prescribed and dispensed. We use instrumental variable models with multiple births as instruments to examine the causal effects of family size on the health outcomes of children, as measured by receiving medicines at age 45. Results: Our results indicate that in Sweden, growing up in a large family does not have a detrimental effect on physical and mental health in midlife. Contribution: We provide a systematic overview of the health-related implications of growing up in a large family. We adopt a research design that gives us the opportunity to make causal inferences about the long-term effects of family size. Moreover, our paper provides evidence on the links between family size and health outcomes in the context of a developed country that implements policies oriented towards reducing social inequalities in health and other living conditions.

  17. Agreement between PRE2DUP register data modeling method and comprehensive drug use interview among older persons

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    Taipale, Heidi; Tanskanen, Antti; Koponen, Marjaana; Tolppanen, Anna-Maija; Tiihonen, Jari; Hartikainen, Sirpa

    2016-01-01

    Background PRE2DUP is a modeling method that generates drug use periods (ie, when drug use started and ended) from drug purchases recorded in dispensing-based register data. It is based on the evaluation of personal drug purchasing patterns and considers hospital stays, possible stockpiling of drugs, and package information. Objective The objective of this study was to investigate person-level agreement between self-reported drug use in the interview and drug use modeled from dispensing data with PRE2DUP method for various drug classes used by older persons. Methods Self-reported drug use was assessed from the GeMS Study including a random sample of persons aged ≥75 years from the city of Kuopio, Finland, in 2006. Drug purchases recorded in the Prescription register data of these persons were modeled to determine drug use periods with PRE2DUP modeling method. Agreement between self-reported drug use on the interview date and drug use calculated from register-based data was compared in order to find the frequently used drugs and drug classes, which was evaluated by Cohen’s kappa. Kappa values 0.61–0.80 were considered to represent good and 0.81–1.00 as very good agreement. Results Among 569 participants with mean age of 82 years, the agreement between interview and register data was very good for 75% and very good or good for 93% of the studied drugs or drug classes. Good or very good agreement was observed for drugs that are typically used on regular bases, whereas “as needed” drugs represented poorer results. Conclusion PRE2DUP modeling method validly describes regular drug use among older persons. For most of drug classes investigated, PRE2DUP-modeled register data described drug use as well as interview-based data which are more time-consuming to collect. Further studies should be conducted by comparing it with other methods and in different drug user populations. PMID:27785101

  18. Association of Folic Acid Supplementation During Pregnancy With the Risk of Autistic Traits in Children Exposed to Antiepileptic Drugs In Utero.

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    Bjørk, Marte; Riedel, Bettina; Spigset, Olav; Veiby, Gyri; Kolstad, Eivind; Daltveit, Anne Kjersti; Gilhus, Nils Erik

    2018-02-01

    Strategies to prevent autism in children exposed to antiepileptic drugs (AEDs) during pregnancy are important. To explore whether folic acid supplementation and folate status in pregnancy are associated with reduced risk of autistic traits owing to in utero AED exposure. The population-based, prospective Norwegian Mother and Child Cohort Study approached Norwegian-speaking women attending routine ultrasonographic examinations from June 1999 through December 31, 2008 (163 844 of 277 702 women refused). No exclusion criteria were applied beyond language. Questionnaires during and after pregnancy, analysis of blood samples, and linkage to the Medical Birth Registry of Norway were performed. Children aged 18 to 36 months of women with available information on use of AEDs and of folic acid supplementation (n = 104 946) were included in the analysis from March 1, 2016, through June 13, 2017. Maternal folic acid supplementation 4 weeks before to 12 weeks after conception. Plasma folate concentration was analyzed at gestational weeks 17 to 19. Autistic traits were evaluated using the Modified Checklist for Autism in Toddlers and Social Communication Questionnaire. Odds ratios (ORs) for autistic traits in children by maternal use vs nonuse of folic acid supplements were adjusted for maternal health and socioeconomic factors. Folate concentrations and folic acid doses were associated with the degree of autistic traits. The overall mean (SD) age of the 104 946 mothers of participating children was 29.8 (4.6) years, with complete information available for analysis in 103 868. Mean (SD) age of women with epilepsy who received AED treatment was 29.4 (4.9); women with epilepsy who did not receive AED treatment, 29.1 (4.9); and without epilepsy, 29.8 (4.6) years. In the 335 children exposed to AEDs, the risk for autistic traits was significantly higher at 18 months of age (adjusted OR [AOR], 5.9; 95% CI, 2.2-15.8) and 36 months of age (AOR, 7.9; 95% CI, 2.5-24.9) when

  19. Seizure Recurrence in Children after Stopping Antiepileptic Medication: 5-Year Follow-Up

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    Inn-Chi Lee

    2017-08-01

    Conclusion: We found that a history of status epilepticus, symptomatic partial epilepsy, treatment duration before stopping antiepileptic drugs, and an abnormal EEG when the medication was stopped are important predictors of SR. The risk factors of SR after discontinuing antiepileptic drugs have been investigated in several studies. However, a history of status epilepticus as a predictive factor is rarely mentioned.

  20. Influence of genetic variants of CYP2D6, CYP2C9, CYP2C19 and CYP3A4 on antiepileptic drug metabolism in pediatric patients with refractory epilepsy.

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    López-García, Miguel A; Feria-Romero, Iris A; Serrano, Héctor; Rayo-Mares, Darío; Fagiolino, Pietro; Vázquez, Marta; Escamilla-Núñez, Consuelo; Grijalva, Israel; Escalante-Santiago, David; Orozco-Suarez, Sandra

    2017-06-01

    Identified the polymorphisms of CYP2D6, CYP2C9, CYP2C19 and CYP3A4, within a rigorously selected population of pediatric patients with drug-resistant epilepsy. The genomic DNA of 23 drug-resistant epilepsy patients and 7 patients with good responses were analyzed. Ten exons in these four genes were genotyped, and the drug concentrations in saliva and plasma were determined. The relevant SNPs with pharmacogenomics relations were CYP2D6*2 (rs16947) decreased your activity and CYP2D6*4 (rs1065852), CYP2C19*2 (rs4244285) and CYP3A4*1B (rs2740574) by association with poor metabolizer. The strongest risk factors were found in the AA genotype and allele of SNP rs3892097 from the CYP2D6 gene, followed by the alleles A and T of SNPs rs2740574 and rs2687116, respectively from CYP3A4. The most important concomitance was between homozygous genotype AA of rs3892097 and genotype AA of rs2740574 with 78.3% in drug-resistant epilepsy patients as compared to 14.3% in control patients. The results demonstrated the important role of the CYP 3A4*1B allelic variant as risk factor for developing drug resistance and CYP2D6, CYP2C19 SNPs and haplotypes may affect the response to antiepileptic drugs. Copyright © 2017. Published by Elsevier Urban & Partner Sp. z o.o.

  1. Modification of polydopamine-coated Fe3O4 nanoparticles with multi-walled carbon nanotubes for magnetic-μ-dispersive solid-phase extraction of antiepileptic drugs in biological matrices.

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    Zhang, Ruiqi; Wang, Siming; Yang, Ye; Deng, Yulan; Li, Di; Su, Ping; Yang, Yi

    2018-06-01

    In this study, multi-walled carbon nanotubes were coated on the surface of magnetic nanoparticles modified by polydopamine. The synthesized composite was characterized and applied to magnetic-μ-dispersive solid-phase extraction of oxcarbazepine (OXC), phenytoin (PHT), and carbamazepine (CBZ) from human plasma, urine, and cerebrospinal fluid samples prior to analysis by a high-performance liquid chromatography-photodiode array detector. The extraction parameters were investigated and the optimum condition was obtained when the variables were set to the following: sorbent type, Fe 3 O 4 @polyDA-MWCNTs (length Graphical abstract Magnetic multi-walled carbon nanotube core-shell composites were applied as magnetic-μ-dispersive solid-phase extraction adsorbents for determination of antiepileptic drugs in biological matrices.

  2. Definition of rational antiepileptic polypharmacy.

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    Wilder, B J; Homan, R W

    1996-01-01

    Rational polypharmacy is in its earliest stages of development and will require substantial additional development to realize its full potential. Indeed, despite the powerful appeal of the concept, clinical proof is not yet available that RP is superior to monotherapy. Important questions need to be addressed: 1. Will RP control seizures more effectively than monotherapy? 2. What data are needed to develop RP for a specific patient? 3. Will RP be cost effective? 4. Can RP be developed which will treat or prevent epilepsy while controlling seizures? Possible approaches to these questions could include: 1. The development of a data base for prospective use to monitor patients being treated at Epilepsy Centers using RP principles. 2. Use the data obtained from the above to construct more specific studies to compare identified combination therapies with monotherapy. 3. Prospectively compare in a placebo controlled, blinded study, the effect of the combination of an anti-ictal medication and a laboratory proven antiepileptic drug for prevention of the development of epilepsy in an at risk population such as head trauma or stroke.

  3. High risk behaviors of injection drug users registered with harm reduction programme in Karachi, Pakistan

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    Memon Ashraf

    2007-02-01

    Full Text Available Abstract Background Surveillance data of Sindh AIDS Control Programme, Pakistan suggest that HIV infection is rapidly increasing among IDUs in Karachi and has reached 9% in 2004–5 indicating that the country has progressed from nascent to concentrated level of HIV epidemic. Findings of 2nd generation surveillance in 2004–5 also indicate 104/395 (26.3% IDUs HIV positive in the city. Methods We conducted a cross sectional study among registered IDUs of a needle exchange and harm reduction programme in Karachi, Pakistan. A total of 161 IDUs were included in the study between October–November 2003. A detailed questionnaire was implemented and blood samples were collected for HIV, hepatitis B & C and syphilis. HIV, hepatitis B and C antibody tests were performed using Enzyme Linked Immunosorbent Assay (ELISA method. Syphilis tests (RPR & TPHA were performed on Randox kit. Besides calculating frequencies univariate analysis was performed using t tests for continuous variables as age, age at first intercourse and average age of initiation of addiction and chi square for categorical variables like paid for sex or not to identify risk factors for hepatitis B and C and syphilis. Results Average age of IDU was 35.9 years and average age of initiation of drugs was 15.9 years. Number of drug injections per day was 2.3. Shooting drugs in group sharing syringes was reported by 128 (79.5% IDUs. Over half 94 (58.3% reported paying for sex and 64% reported never using a condom. Commercial selling of blood was reported by 44 (28%. 1 of 161 was HIV positive (0.6%. The prevalence of hepatitis B was 12 (7.5%, hepatitis C 151 (94.3% and syphilis 21 (13.1%. IDUs who were hepatitis C positive were more likely to start sexual activity at an earlier age and had never used condoms. Similarly IDUs who were hepatitis B positive were more likely to belong to a younger age group. Syphilis positive IDUs were more likely to have paid for sex and had never used a condom

  4. Papel de los fármacos antiepilépticos genéricos en el tratamiento de la epilepsia infantil Role of generic antiepileptic drugs in the treatment of childhood epilepsy

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    Jaime Campos-Castelló

    2009-01-01

    Full Text Available La aparición de fármacos genéricos en el mercado, en sustitución de marcas registradas®, y las adecuadas regulaciones de las autoridades sanitarias en los distintos países ha condicionado hasta la actualidad una polémica sobre el riesgo costo/beneficio de tal sustitución en el paciente afecto de epilepsia. El binomio costo/beneficio debe dar por demostrado de manera clara que el paciente puede beneficiarse de tal sustitución sin correr riesgo alguno significativo. Por ello se valoran los distintos aportes en la literatura médica al respecto, que analizan estos riesgos y beneficios y en especial el hecho esencial de la bioequivalencia de ambas formulaciones, en especial en las situaciones de aquellos fármacos antiepilépticos de margen o índice terapéutico estrecho que hagan inviable la equivalencia de la biodisponibilidad del fármaco, la ausencia de repercusión clínica real en el paciente así como la evidencia que existe un beneficio económico claro al valorar el citado binomio riesgo/beneficio. La revisión efectuada señala la clara existencia de desventajas potenciales del cambio de un fármaco antiepiléptico (FAE original de marca a un genérico como: distinta biodisponibilidad, bioequivalencia no demostrada, riesgo de reaparición de crisis en pacientes controlados y variabilidad de la respuesta de los FAE en el paciente epiléptico, imposible de predecir. Por ello se aconseja valorar la importancia de un fracaso terapéutico tras un cambio a genérico, en especial en casos de margen terapéutico estrecho, la biodisponibilidad permisible con valoración de la variabilidad individual del paciente, situación médico-legal de tal cambio y la realidad de los ahorros y costos potenciales derivados.The use of generic instead of trade mark antiepileptic drugs raises the question of cost/benefit risks. The efficacy and side effects of the generic AED should be similar to the trade mark drugs. Otherwise, the substitution is not

  5. Drug use in patients with dementia: a register-based study in the health region of Girona (Catalonia/Spain).

    Science.gov (United States)

    Avila-Castells, Pilar; Garre-Olmo, Josep; Calvó-Perxas, Laia; Turró-Garriga, Oriol; Alsina, Elisabet; Carmona, Olga; Perkal, Héctor; Roig, Anna Maria; Cuy, Josep Ma; Lozano, Manuela; Molins, Albert; Vallmajó, Natàlia; López-Pousa, Secundino

    2013-05-01

    To describe the pattern of drug consumption among patients with dementia in a geographically defined general population in Catalonia (Spain), and to determine its association with age, gender, type of dementia and severity indicators. Cross-sectional study that included 1,894 cases of dementia registered by the Registry of Dementias of Girona from 2007 to 2009. Prescribed drugs were categorized according to the Anatomical Therapeutic Chemical (ATC) classification. A descriptive analysis of drug consumption was stratified according to age, gender, dementia subtypes and dementia severity. Binary logistic regression models were adjusted to detect the association of these variables with drug consumption according to the ATC groups. The most commonly prescribed drugs were for the central nervous system (CNS) (96.4 %), cardiovascular system (79.4 %) and digestive and metabolic system categories (77.7 %). No significant differences were found between the use of nervous system drugs and age, gender, dementia subtypes or dementia severity. The use of alimentary tract and metabolism related drugs, as well as cardiovascular and blood system drugs, were positively correlated with age and secondary dementia. The prevalence of use of cardiovascular and musculoskeletal drugs was higher in women than in men (OR: 1.34; OR: 1.26 respectively). A negative association was found between the severity of dementia and the use of musculoskeletal drugs (OR: 0.71), while its use was significantly higher in the youngest patients (OR: 1.71). Almost all patients with dementia received a CNS drug, being at risk of inappropriate treatment. Treatment for comorbidities in patients with dementia should not be withheld on the basis of age or dementia severity, but rather on the benefit/risk ratio of its prescription. Further studies are needed to evaluate potentially inappropriate drug use and possible untreated conditions in this population.

  6. Pharmacogenetic evaluation of ABCB1, Cyp2C9, Cyp2C19 and methylene tetrahydrofolate reductase polymorphisms in teratogenicity of anti-epileptic drugs in women with epilepsy

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    Manna Jose

    2014-01-01

    Full Text Available Aim: Pregnancy in women with epilepsy (WWE who are on anti-epileptic drugs (AEDs has two- to three-fold increased risk of fetal malformations. AEDs are mostly metabolized by Cyp2C9, Cyp2C19 and Cyp3A4 and transported by ABCB1. Patients on AED therapy can have folate deficiency. We hypothesize that the polymorphisms in ABCB1, Cyp2C9, Cyp2C19 and methylene tetrahydrofolate reductase (MTHFR might result in differential expression resulting in differential drug transport, drug metabolism and folate metabolism, which in turn may contribute to the teratogenic impact of AEDs. Materials and Methods: The ABCB1, Cyp2C9, Cyp2C19 and MTHFR polymorphisms were genotyped for their role in teratogenic potential and the nature of teratogenecity in response to AED treatment in WWE. The allelic, genotypic associations were tested in 266 WWE comprising of 143 WWE who had given birth to babies with WWE-malformation (WWE-M and 123 WWE who had normal offsprings (WWE-N. Results: In WWE-M, CC genotype of Ex07 + 139C/T was overrepresented (P = 0.0032 whereas the poor metabolizer allele FNx012 and FNx012 FNx012 genotype of CYP2C219 was significantly higher in comparison to WWE-N group (P = 0.007 and P = 0.005, respectively. All these observations were independent of the nature of malformation (cardiac vs. non cardiac malformations. Conclusion: Our study indicates the possibility that ABCB1 and Cyp2C19 may play a pivotal role in the AED induced teratogenesis, which is independent of nature of malformation. This is one of the first reports indicating the pharmacogenetic role of Cyp2C19 and ABCB1 in teratogenesis of AED in pregnant WWE.

  7. Rufinamide, an antiepileptic drug, improves cognition and increases neurogenesis in the aged gerbil hippocampal dentate gyrus via increasing expressions of IGF-1, IGF-1R and p-CREB.

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    Chen, Bai Hui; Ahn, Ji Hyeon; Park, Joon Ha; Song, Minah; Kim, Hyunjung; Lee, Tae-Kyeong; Lee, Jae Chul; Kim, Young-Myeong; Hwang, In Koo; Kim, Dae Won; Lee, Choong-Hyun; Yan, Bing Chun; Kang, Il Jun; Won, Moo-Ho

    2018-04-25

    Rufinamide is a novel antiepileptic drug and commonly used in the treatment of Lennox-Gastaut syndrome. In the present study, we investigated effects of rufinamide on cognitive function using passive avoidance test and neurogenesis in the hippocampal dentate gyrus using Ki-67 (a marker for cell proliferation), doublecortin (DCX, a marker for neuroblast) and BrdU/NeuN (markers for newly generated mature neurons) immunohistochemistry in aged gerbils. Aged gerbils (24-month old) were treated with 1 mg/kg and 3 mg/kg rufinamide for 4 weeks. Treatment with 3 mg/kg rufinamide, not 1 mg/kg rufinamide, significantly improved cognitive function and increased neurogenesis, showing that proliferating cells (Ki-67-immunoreactive cells), differentiating neuroblasts (DCX-immunoreactive neuroblasts) and mature neurons (BrdU/NeuN-immunoreactive cells) in the aged dentate gyrus compared with those in the control group. When we examined its mechanisms, rufinamide significantly increased immunoreactivities of insulin-like growth factor-1 (IGF-1), its receptor (IGF-1R), and phosphorylated cAMP response element binding protein (p-CREB). However, rufinamide did not show any increase in immunoreactivities of brain-derived neurotrophic factor and its receptor. Therefore, our results indicate that rufinamide can improve cognitive function and increase neurogenesis in the hippocampus of the aged gerbil via increasing expressions of IGF-1, IGF-1R and p-CREB. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Evolução sócio-profissional de 140 pacientes epilépticos submetidos a tratamento medicamentoso The socio-professional evolution of 140 epileptic patients submitted to antiepileptic drug therapy

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    Luís Marques-Assis

    1968-09-01

    Full Text Available É estudada a evolução sócio-profissional de 140 doentes epilépticos, submetidos apenas a tratamento medicamentoso. Foram empregadas drogas de fácil aquisição em nosso meio (barbitúricos, hidantoinatos, primidona e trimetadiona, utilizadas isolada ou combinadamente. No estudo foram consideradas basicamente as atividades escolares, domésticas e profissionais. A evolução sócio-profissional foi estudada em relação às manifestações clínicas, ao tempo de doença, à freqüência das crises e ao padrão eletrencefalográfico. Os resultados, expressos em índices percentuais, permitiram ao autor concluir que na maioria dos pacientes epilépticos, convenientemente tratados do ponto de vista clínico, os problemas sociais e profissionais podem ser corrigidos ou evitados, independentemente de outras medidas especializadas que possam ser postas em prática.The socio-professional evolution of 140 epileptic patients submitted to antiepileptic drug therapy is studied. Only barbiturates, hydantoin, primidone and trimethadione were administered to the patients, isolated or in association. The school, house keeper and professional activities were considered in the investigation. The socio-professional follow-up was investigated regarding to clinic manifestations, time of disease, frequency of seizures and electroencephalographic pattern. The results, analysed in percentage, led the author to the conclusion that in most epileptic patients, adequately controlled with drugs, the social and the professional problems can be avoided.

  9. Russian Register of Pregnancy and Epilepsy

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    D. V. Dmitrenko

    2017-01-01

    Full Text Available The use of antiepileptic drugs (AEDs during pregnancy is associated with an increased risk of congenital malformations (CMF. Information on the teratogenicity of AEDs is contradictory. The potential negative effects of new-generation AEDs are less well known. Many physicians and patients face difficulties in establishing a balance between the risk of seizures during pregnancy and that of teratogenicity in the use of AEDs. In most foreign countries, there are national and international pregnancy and epilepsy registries that make possible to centralize and systematize information on the safety of AEDs and to also give a true picture of the state of the problem.The Russian pregnancy and epilepsy register (RPER has been launched since 2017. RPER is a Russian national prospective and retrospective observational study, without interfering with the antiepileptic therapy prescribed by an attending physician to childbearing-aged patients living in the subjects of the Russian Federation. RPER is an independent research initiative and is implemented by neurologists and psychiatrists who provide assistance to women with epilepsy. The main goal of the RPER is to compare the risk of serious CMFs following the maternal intake of various AEDs and their combinations in different regions of the Russian Federation and to develop strategies for preventing CMFs. 

  10. A Cluster Randomised Trial Introducing Rapid Diagnostic Tests into Registered Drug Shops in Uganda: Impact on Appropriate Treatment of Malaria

    Science.gov (United States)

    Mbonye, Anthony K.; Magnussen, Pascal; Lal, Sham; Hansen, Kristian S.; Cundill, Bonnie; Chandler, Clare; Clarke, Siân E.

    2015-01-01

    Background Inappropriate treatment of malaria is widely reported particularly in areas where there is poor access to health facilities and self-treatment of fevers with anti-malarial drugs bought in shops is the most common form of care-seeking. The main objective of the study was to examine the impact of introducing rapid diagnostic tests for malaria (mRDTs) in registered drug shops in Uganda, with the aim to increase appropriate treatment of malaria with artemisinin-based combination therapy (ACT) in patients seeking treatment for fever in drug shops. Methods A cluster-randomized trial of introducing mRDTs in registered drug shops was implemented in 20 geographical clusters of drug shops in Mukono district, central Uganda. Ten clusters were randomly allocated to the intervention (diagnostic confirmation of malaria by mRDT followed by ACT) and ten clusters to the control arm (presumptive treatment of fevers with ACT). Treatment decisions by providers were validated by microscopy on a reference blood slide collected at the time of consultation. The primary outcome was the proportion of febrile patients receiving appropriate treatment with ACT defined as: malaria patients with microscopically-confirmed presence of parasites in a peripheral blood smear receiving ACT or rectal artesunate, and patients with no malaria parasites not given ACT. Findings A total of 15,517 eligible patients (8672 intervention and 6845 control) received treatment for fever between January-December 2011. The proportion of febrile patients who received appropriate ACT treatment was 72·9% versus 33·7% in the control arm; a difference of 36·1% (95% CI: 21·3 – 50·9), pshop vendors adhered to the mRDT results, reducing over-treatment of malaria by 72·6% (95% CI: 46·7– 98·4), pshop vendors using presumptive diagnosis (control arm). Conclusion Diagnostic testing with mRDTs compared to presumptive treatment of fevers implemented in registered drug shops substantially improved appropriate

  11. Use of Fall-Risk Inducing Drugs in Patients Using Anti-Parkinson Drugs (APD: A Swedish Register-Based Study.

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    Ylva Haasum

    Full Text Available Many drugs increase the risk of falls in old age. Although persons with Parkinson's disease (PD are at increased risk of experiencing falls and fractures, the use of fall-risk inducing drugs (FRIDs in this population has not previously been investigated. The objective of this study was to investigate the burden of use of FRIDs in older persons treated with anti-Parkinson drugs (APD; used as a proxy for PD, compared to persons without APD.We analyzed individual data on age, sex, type of housing and drug use in 1 346 709 persons aged ≥ 65 years in the Swedish Prescribed Drug Register on the date of 30 September 2008. Main outcome measure was the use of FRIDs.FRIDs were used by 79% of persons with APD and 75% of persons without APD. Persons with APD were more likely to use ≥ 1 FRIDs compared to persons without APD (adjusted OR: 1.09; 95% CI: 1.06-1-12. The association was stronger for concomitant use of ≥ 5 FRIDS (adjusted OR: 1.49; 95% CI: 1.44-1.55.The high use of FRIDs among persons with APD indicates that these patients may be at increased risk of drug-induced falls. Further studies are needed to investigate how these drugs affect the risk of falling in persons with PD.

  12. Health-related quality of life in epilepsy patients receiving anti-epileptic drugs at National Referral Hospitals in Uganda: a cross-sectional study.

    Science.gov (United States)

    Nabukenya, Anne M; Matovu, Joseph K B; Wabwire-Mangen, Fred; Wanyenze, Rhoda K; Makumbi, Fredrick

    2014-04-12

    Epilepsy is a devastating disorder that impacts on patients' quality of life, irrespective of use of anti epileptic drugs (AEDs). This study estimates the health-related quality of life (HRQOL) and its associated predictors among epilepsy patients receiving AEDs. A total of 175 epilepsy patients already receiving AED for at least 3 months were randomly selected and interviewed from mental clinics at Mulago and Butabika national referral hospitals in Uganda between May - July 2011. A HRQOL index, the primary outcome, was constructed using items from Quality Of Life in Epilepsy Inventory (QOLIE-31) and the Hospital Anxiety and Depression Scale (HADS) questionnaires. The internal consistency and adequacy of these items was also computed using Cronbach's alpha and Kaiser-Meyer-Olkin tests. Partial correlations were used to evaluate the contribution of the health dimensions (mental, psychological, social, physical functioning and emotional well being) and, multiple linear regressions to determine factors independently associated with HRQOL. Just about half of the respondents (54%) were males, and nearly two thirds (62%) had received AEDs for at least 12 months. The average age was 26.6 years (SD = 11.1). The overall HRQOL mean score was 58 (SD = 13) on a scale of 0-100. The average scores of different dimensions or subscales ranged from 41 (physical) to 65 (psychological). At least three quarters (75%) of all subscales had good internal consistency and adequacy. The largest variations in the overall HRQOL were explained by social and mental functioning; each accounting for about 30% of the difference in the HRQOL but seizure control features explained a little (6%) variation. Factors negatively associated with HRQOL were poly-therapy (-1.16, p = 0.01) and frequency of seizures (-2.29, p = 0.00). Other factors associated with overall HRQOL included drug side effects, sex, marital status and education. Duration on AEDs was not a significant predictor of HRQOL. The HRQOL

  13. Papel de la monoterapia con nuevos fármacos antiepilépticos en el tratamiento de la epilepsia infantil Role of monotherapy with new antiepileptic drugs in the treatment of childhood epilepsy

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    Ignacio Valencia

    2009-01-01

    Full Text Available En este trabajo se revisa la información actual sobre el uso de los nuevos fármacos antiepilépticos (FAEs en monoterapia en niños, resaltando nuestra experiencia personal. Específicamente, se incluyen los siguientes FAEs: lamotrigina (Lamictal®, topiramato (Topamax®, zonisamida (Zonegran®, levetiracetam (Keppra®, y oxcarbacepina (Trileptal®. Todos estos FAEs tienen un amplio espectro de acción en el tratamiento de crisis epilépticas parciales y generalizadas, excepto la oxcarbacepina, que es eficaz exclusivamente en crisis parciales. No está claro si la monoterapia con estos FAEs, en comparación con los FAEs clásicos (fenobarbital, fenitoína, carbamacepina, valproato sódico, proporciona una mayor eficacia y/o causa menos efectos secundarios y, si por lo tanto, mejora significativamente la calidad de vida de los niños con epilepsia. Se necesitan más estudios para poder contestar estas preguntas.In this paper we review the current information regarding the use of new antiepileptic drugs (AEDs used as monotherapy in children. We specifically include the following AEDs: lamotrigine (Lamictal®, topiramate (Topamax®, zonisamide (Zonegran®, levetiracetam (Keppra®, and oxcarbazepine (Trileptal®. All of these AEDs have a broad spectrum of action in the treatment of partial and generalized seizures, except Oxcarbazepine, which is effective only in partial seizures. It is unclear whether or not monotherapy with the new AEDs offers higher efficacy and/or lower side effects compared to classic AEDs (phenobarbital, phenytoin, carbamazepine, or valproate thereby significantly improving the quality of life in children with epilepsy. More studies are needed to answer these questions.

  14. Recent Advances in Antiepileptic Herbal Medicine.

    Science.gov (United States)

    Manchishi, Stephen M

    2018-01-01

    Epilepsy is one of the most common neurological disorders worldwide, with about 80 percent of cases thought to be in developing nations where it is mostly linked to superstition. The limited supply, high cost as well as low efficacy and adverse side effects of antiepileptic drugs (AEDs) is a matter of major concern. Herbal medicine has always been traditionally part of treatment of epilepsy. Herbal medicines are generally well tolerated, with fewer side effects. To highlight some herbal extracts that have been studied for their anticonvulsant activity in animal models, literature search from PubMed and Science Direct, was performed. The keywords for the search consisted of combinations of the following terms: Herbal antiepileptic and/or anticonvulsant, botanicals + epilepsy. Literature published in the last five years was considered. Eighteen (18) anticonvulsant herbal agents are reported and discussed. Experiments mostly consisted of phenotypic screens in rodents, with little diversity in screening methods. In most experiments, the tested extracts prolonged the time to onset of seizures and decreased their duration. Most experimenters implicate potentiation of GABAergic activity as the mode of action of the extracts, even though some experimenters did not fully characterise the bioactive chemical composition of their extracts. Potential herbal remedies have shown positive results in animal models. It remains unclear how many make it into clinical trials and eventually making part of the AED list. More rigorous research, applying strict research methodology with uniform herbal combinations, as well as clinical studies are urgently needed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Adherence to drug label recommendations for avoiding drug interactions causing statin-induced myopathy--a nationwide register study.

    Directory of Open Access Journals (Sweden)

    Jennifer Settergren

    Full Text Available To investigate the extent to which clinicians avoid well-established drug-drug interactions that cause statin-induced myopathy. We hypothesised that clinicians would avoid combining erythromycin or verapamil/diltiazem respectively with atorvastatin or simvastatin. In patients with statin-fibrate combination therapy, we hypothesised that gemfibrozil was avoided to the preference of bezafibrate or fenofibrate. When combined with verapamil/diltiazem or fibrates, we hypothesized that the dispensed doses of atorvastatin/simvastatin would be decreased.Cross-sectional analysis of nationwide dispensing data. Odds ratios of interacting erythromycin, verapamil/diltiazem versus respective prevalence of comparator drugs doxycycline, amlodipine/felodipine in patients co-dispensed interacting statins simvastatin/atorvastatin versus patients unexposed (pravastatin/fluvastatin/rosuvastatin was calculated. For fibrates, OR of gemfibrozil versus fenofibrate/bezafibrate in patients co-dispensed any statin was assessed.OR of interacting erythromycin versus comparator doxycycline did not differ between patients on interacting and comparator statins either in patients dispensed high or low statin doses (adjusted OR 0.87; 95% CI 0.60-1.25 and 0.92; 95% CI 0.69-1.23. Interacting statins were less common among patients dispensed verapamil/diltiazem as compared to patients on amlodipine/felodipine (OR high dose 0.62; CI 0.56-0.68 and low dose 0.63; CI 0.58-0.68. Patients on any statin were to a lesser extent dispensed gemfibrozil compared to patients not dispensed a statin (OR high dose 0.65; CI 0.55-0.76 and low dose 0.70; CI 0.63-0.78. Mean DDD (SD for any statin was substantially higher in patients co-dispensed gemfibrozil 178 (149 compared to patients on statin monotherapy 127 (93, (p<0.001.Prescribers may to some extent avoid co-prescription of statins with calcium blockers and fibrates with an increased risk of myopathy. We found no evidence for avoiding co

  16. Risk assessment of antiepileptic drugs in pregnancy

    NARCIS (Netherlands)

    Boersma-Jentink, Janneke

    2011-01-01

    Vrouwen die anti-epileptica nodig hebben en zwanger willen worden moeten ruim voor de conceptie de neuroloog consulteren en hun kinderwens kenbaar maken, zodat de medicatie, het handhaven of veranderen van de therapie, hierop afgestemd kan worden. Want uiteindelijk kan de beste therapie alleen

  17. Anticataleptic and antiepileptic activity of ethanolic extract of leaves of Mucuna pruriens: A study on role of dopaminergic system in epilepsy in albino rats.

    Science.gov (United States)

    Champatisingh, D; Sahu, P K; Pal, A; Nanda, G S

    2011-04-01

    To assess the anticataleptic and antiepileptic activity of leaves of Mucuna pruriens in albino rats. Haloperidol-induced catalepsy (HIC), maximum electro-shock (MES) method, pilocarpine-induced Status epilepticus (PISE) and single-dose effect of M. pruriens were employed. M. pruriens (100 mg/kg) had significant anticataleptic and antiepileptic activity in HIC, MES, and PISE. M. pruriens extract has the potential to be an anticataleptic and antiepileptic drug. Dopamine and 5-HT may have a role in such activity.

  18. Antiepileptic and Antidepressive Polypharmacy in Patients with Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Georg Anton Giæver Beiske

    2015-01-01

    Full Text Available Objective. Patients with multiple sclerosis (MS are often suffering from neuropathic pain. Antiepileptic drugs (AEDs and tricyclic antidepressants (TCAs are commonly used and are susceptible to be involved in drug interactions. The aim of this retrospective study was to investigate the prevalence of use of antiepileptic and antidepressive drugs in MS patients and to discuss the theoretical potential for interactions. Methods. Review of the medical records from all patients treated at a dedicated MS rehabilitation centre in Norway between 2009 and 2012. Results. In total 1090 patients attended a rehabilitation stay during the study period. Of these, 342 (31%; 249 females with mean age of 53 (±10 years and EDSS 4.8 (±1.7 used at least one AED (gabapentin 12.7%, pregabalin 7.7%, clonazepam 7.8%, and carbamazepine 2.6% or amitriptyline (9.7%. Polypharmacy was widespread (mean 5.4 drugs with 60% using additional CNS-active drugs with a propensity to be involved in interactions. Age, gender, and EDSS scores did not differ significantly between those using and not using AED/amitriptyline. Conclusion. One-third of MS patients attending a rehabilitation stay receive AED/amitriptyline treatment. The high prevalence of polypharmacy and use of CNS-active drugs calls for awareness of especially pharmacodynamic interactions and possible excessive adverse effects.

  19. [Enlightenment of drug application and evaluation procedures of medicines registered (listed) in Australia on studies of new traditional Chinese medicines].

    Science.gov (United States)

    Ren, Jian-Xun; Liu, Jian-Xun

    2014-11-01

    Modern and international studies on new traditional Chinese medicines are the main trend of the development of traditional Chinese medicines at present. In Australia, new traditional Chinese medicines refer to complementary medicines, which are mainly registered and launched as listed medicines. The application documents of registered (listed) medicines in Australia mainly cover detailed description of active pharmaceutical ingredients, pharmacological and toxicological studies, dosage form and adverse effects. Each part has detailed specifications and instructions, which helps ensure that applicants could accurately understand the requirements in application for registering (listing) medicines, and provides very important reference to the studies and development of new traditional Chinese medicines in China.

  20. Anti-epileptic drug intake adherence: the value of the blood drug level measurement and the clinical approach Aderência à ingestão de medicamentos antiepilépticos: o valor da avaliação dos níveis sanguíneos e a abordagem clínica

    Directory of Open Access Journals (Sweden)

    MARLEIDE DA MOTA GOMES

    1998-12-01

    Full Text Available It was evaluated the patient antiepileptic drug (AED intake adherence in a pilot cross-sectional study carried out at a neurologic out-patient clinic of a university hospital. Ninety-three AED blood concentration (phenobarbital, phenytoin, carbamazepine were analyzed from 24 patients. The variability of the AED blood level was measured (in the steady state period by means of the variation coefficient and compared with the self-reported antiepileptic medication non-adherence, AED blood level according to the range (therapeutic or not, and the seizure control. It was not observed any strong correlation between the higher value of variability and the other three parameters of no adherence. The highest correlation was with the blood drug level (therapeutic or not. The evaluation of blood drug measurement alone, except in cases of extreme low adherence and variability of drug intake, is not enough for the recognition of incorrect drug intake, but the clinical markers and the self-reported adherence have to be also considered for this sort of evaluation.Avaliou-se a aderência à ingesta de drogas antiepilépticas (DAE em estudo piloto transversal conduzido em ambulatório de hospital neurológico universitário. Noventa e três amostras sanguíneas com concentraç��o de DAE (fenobarbital, fenitoína, carbamazepina foram analisadas de 24 pacientes. A variabilidade dos níveis sanguíneos das DAE (em estado estável - steady state period, analizada por meio do coeficiente de variação foi comparada com a auto-referida não aderência à ingesta da DAE, níveis sanguíneos das DAE de acordo com a faixa (terapêutica ou não e o controle das crises epilépticas. Não foi observada correlação forte entre o maior valor da variabilidade e os outros três parâmetros de aderência, apesar da maior correlação com o nível sanguíneo (terapêutico ou não. A avaliação do nível sérico isolado, exceto em caso de extrema baixa aderência e

  1. Extent and quality of drug use in community-dwelling people aged ≥75 years: A Swedish nationwide register-based study.

    Science.gov (United States)

    Lagerin, Annica; Törnkvist, Lena; Nilsson, Gunnar; Johnell, Kristina; Fastbom, Johan

    2017-12-01

    It is important for district nurses and other health professionals in primary care to gain more insight into the patterns and quality of drug use in community-dwelling older people, particularly in 75-year-olds, who have been the target of preventive home visits. This study aimed to examine the extent and quality of drug use in community-dwelling older people and to compare drug use in 75-year-olds with that of older age groups. Data from 2013 on people aged ≥75 years were obtained from the Swedish Prescribed Drug Register. Those living in the community (671,940/739,734 people aged ≥75 years) were included in the study. Quality of drug use was assessed by using a selection of indicators issued by the Swedish National Board of Health and Welfare. The prevalence of polypharmacy and of many drug groups increased with age, as did several indicators of inappropriate drug use. However some drug groups, as well as inappropriate drugs, were prevalent in 75-year-olds and declined with age, for example diabetes drugs, drugs with major anticholinergic effects and nonsteroidal anti-inflammatory drugs. The substantial use of some drugs as early as 75 years of age confirms the value of including drug use as a topic in preventive home visits to 75-year-olds. The finding that polypharmacy and many measures of inappropriate drug use increased with age in community-dwelling older people also underscores the importance of district nurses' role in continuing to promote safe medication management at higher ages.

  2. Treatment of fevers prior to introducing rapid diagnostic tests for malaria in registered drug shops in Uganda

    DEFF Research Database (Denmark)

    Mbonye, Anthony K.; Lal, Sham; Cundill, Bonnie

    2013-01-01

    questionnaire to capture data on drug shops (n=65) including provider characteristics, knowledge on treatment of malaria, previous training received, type of drugs stocked, reported drug sales, and record keeping practices; and a patient questionnaire to capture data from febrile patients (n=540) exiting drug...

  3. Antiepileptic Medications in Autism Spectrum Disorder: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Hirota, Tomoya; Veenstra-VanderWeele, Jeremy; Hollander, Eric; Kishi, Taro

    2014-01-01

    Electroencephalogram-recorded epileptiform activity is common in children with autism spectrum disorder (ASD), even without clinical seizures. A systematic literature search identified 7 randomized, placebo-controlled trials of antiepileptic drugs (AEDs) in ASD (total n = 171), including three of valproate, and one each of lamotrigine,…

  4. Spontaneous abortions and malformations in the offspring of nurses exposed to anaesthetic gases, cytostatic drugs, and other potential hazards in hospitals, based on registered information of outcome

    Energy Technology Data Exchange (ETDEWEB)

    Hemminki, K; Kyyroenen, P L; Lindbohm, M L

    1985-06-01

    Nurses working in selected departments of general hospitals in Finland were collected from a central register on health personnel in Finland. Using the Hospital Discharge Register and the Register of Congenital Malformations, case nurses were selected who had had a spontaneous abortion (N = 217) or a malformed child (N = 46) between the years 1973 and 1979. Controls consisted of three nurses who had had a normal birth; the control nurses were matched for age and hospital of employment. Information on exposure in the first trimester of pregnancy was sought through the head nurses of the hospitals. No significant increase in risk of spontaneous abortion or of malformation was observed after exposure to anaesthetic gases (odds ratio for spontaneous abortion 1.2), sterilizing gases and soaps, or x-rays. Handling of cytostatic drugs did not affect the frequency of spontaneous abortion but was associated with malformations in the offspring. The odds ratio, based on eight cases, was 4.7 (p = 0.02) when the logistic model was adopted. The results suggest that the exposures investigated, other than cytostatic drugs, do not cause a strong reproductive risk. Further studies are needed, particularly on cytostatic drugs.

  5. Distribution of blood derivatives by registered blood establishments that qualify as health care entities; Prescription Drug Marketing Act of 1987; Prescription Drug Amendments of 1992; delay of applicability date. Final rule; delay of applicability date.

    Science.gov (United States)

    2006-11-13

    The Food and Drug Administration (FDA) is further delaying, until December 1, 2008, the applicability date of a certain requirement of a final rule published in the Federal Register of December 3, 1999 (64 FR 67720) (the final rule). The final rule implements the Prescription Drug Marketing Act of 1987 (PDMA), as modified by the Prescription Drug Amendments of 1992 (PDA), and the Food and Drug Administration Modernization Act of 1997 (the Modernization Act). The provisions of the final rule became effective on December 4, 2000, except for certain provisions whose effective or applicability dates were delayed in five subsequent Federal Register notices, until December 1, 2006. The provision with the delayed applicability date would prohibit wholesale distribution of blood derivatives by registered blood establishments that meet the definition of a "health care entity." In the Federal Register of February 1, 2006 (71 FR 5200), FDA published a proposed rule specific to the distribution of blood derivatives by registered blood establishments that qualify as health care entities (the proposed rule). The proposed rule would amend certain limited provisions of the final rule to allow certain registered blood establishments that qualify as health care entities to distribute blood derivatives. In response to the proposed rule, FDA received substantive comments. As explained in the SUPPLEMENTARY INFORMATION section of this document, further delaying the applicability of Sec. 203.3(q) (21 CFR 203.3(q)) to the wholesale distribution of blood derivatives by health care entities is necessary to give the agency additional time to address comments on the proposed rule, consider whether regulatory changes are appropriate, and, if so, to initiate such changes.

  6. The potential of the European network of congenital anomaly registers (EUROCAT) for drug safety surveillance: a descriptive study.

    Science.gov (United States)

    Meijer, Willemijn M; Cornel, Martina C; Dolk, Helen; de Walle, Hermien E K; Armstrong, Nicola C; de Jong-van den Berg, Lolkje T W

    2006-09-01

    European Surveillance of Congenital Anomalies (EUROCAT) is a network of population-based congenital anomaly registries in Europe surveying more than 1 million births per year, or 25% of the births in the European Union. This paper describes the potential of the EUROCAT collaboration for pharmacoepidemiology and drug safety surveillance. The 34 full members and 6 associate members of the EUROCAT network were sent a questionnaire about their data sources on drug exposure and on drug coding. Available data on drug exposure during the first trimester available in the central EUROCAT database for the years 1996-2000 was summarised for 15 out of 25 responding full members. Of the 40 registries, 29 returned questionnaires (25 full and 4 associate members). Four of these registries do not collect data on maternal drug use. Of the full members, 15 registries use the EUROCAT drug code, 4 use the international ATC drug code, 3 registries use another coding system and 7 use a combination of these coding systems. Obstetric records are the most frequently used sources of drug information for the registries, followed by interviews with the mother. Only one registry uses pharmacy data. Percentages of cases with drug exposure (excluding vitamins/minerals) varied from 4.4% to 26.0% among different registries. The categories of drugs recorded varied widely between registries. Practices vary widely between registries regarding recording drug exposure information. EUROCAT has the potential to be an effective collaborative framework to contribute to post-marketing drug surveillance in relation to teratogenic effects, but work is needed to implement ATC drug coding more widely, and to diversify the sources of information used to determine drug exposure in each registry.

  7. Das sprachliche Register (Speech Registers)

    Science.gov (United States)

    Hess-Luttich, Ernest W. B.

    1974-01-01

    The linguistic behavior of a given individual varies; he will on different occasions speak (or write) differently according to what may be roughly described as different social situations: he will use a number of different registers. The application of such registers both in the field of text analysis and in the preparation of teaching materials…

  8. Duration of residence and psychotropic drug use in recently settled refugees in Sweden - a register-based study

    DEFF Research Database (Denmark)

    Brendler-Lindqvist, Maria; Nørredam, Marie Louise; Hjern, Anders

    2014-01-01

    INTRODUCTION: Recently settled refugee populations have consistently been reported to have high rates of mental health problems, particularly Post-traumatic stress disorder, depression, and anxiety disorders. The aim of this study was to investigate psychotropic drug use among young adult refugee...

  9. How participation in a Drug Company-Managed Clinical Trial Influenced GPs’ Guideline Adherence and Drug Preference: A Register-Based study

    DEFF Research Database (Denmark)

    Andersen, Morten; Kragstrup, Jakob; Søndergaard, Jens

    2005-01-01

    21 st International Con ference on Pharmacoepidemiology and Therapeytic Risk Management, Nashville, Tennessee, USA, Abstract 187 i Pharmacoepidemiology and drug safety 2004;14:494......21 st International Con ference on Pharmacoepidemiology and Therapeytic Risk Management, Nashville, Tennessee, USA, Abstract 187 i Pharmacoepidemiology and drug safety 2004;14:494...

  10. Alteration of the threshold stimulus for intraoperative brain mapping via use of antiepileptic medications

    Directory of Open Access Journals (Sweden)

    John W. Amburgy, MD

    2015-03-01

    Full Text Available Intraoperative seizures during awake craniotomy with cortical and subcortical mapping are a common occurrence. Patients are routinely treated preoperatively with anti-convulsive medications to reduce seizure occurrence. Historically these drugs have not been believed to significantly affect awake craniotomy procedures. We report a patient undergoing intraoperative mapping with differential response and seizure occurrence based upon antiepileptic drug usage. A 43 year old female presented with history of seizures, right sided hemiparesis, electrical sensations, and difficulty with language function. She was determined to have a mass lesion involving the left frontal and temporal lobes and subsequently elected to undergo resection by awake craniotomy with intraoperative mapping. A first attempt at lesion resection was performed after a missed dose of anti-convulsant medication (levetiracetam and was subsequently aborted because of repeated seizure activity. The threshold for seizure generation (1.75 mA was observed to be significantly lower than expected. Therapy was begun with both levetiracetam and phenytoin prior to a second attempted resection one week later. Thresholds for cortical motor response in the second operation were significantly higher than expected (> 9.0 mA, and no intraoperative seizure activity was observed. To our knowledge this is the first quantitative example of antiepileptic drugs affecting the current required for intraoperative mapping. This case highlights the potential for higher current requirements in patients preoperatively treated with high doses of antiepileptic drugs, as well as the importance of confirming adequate dosage of antiepileptic drugs in patients at an increased risk of seizure generation.

  11. [The register GiViTI about the use of the drug Xigris® in the Italian intensive care units].

    Science.gov (United States)

    Rossi, Carlotta; Giardino, Michele; Crespi, Daniele; Anghileri, Abramo; Poole, Daniele; Bertolini, Guido

    2013-06-01

    The Register was aimed at monitoring the use, possible side effects, and clinical effectiveness of Xigris® - drotrecogin alfa (activated) - for the treatment of severe sepsis in Italian intensive care units (ICUs). Data collection was performed using an online web form or a specific electronic module of the software Margherita, available only for the ICUs adhering to the GiViTI. Drug purchase information available for each center was used to identify and stimulate collaboration of non-compliant centers. Several countermeasures were taken to have the largest participation. We analyzed data from 1001 patients treated in 161 ICUs between July 2003 and September 2007, corresponding to 70% of all the patients who received the drug in that period. The off-label use of the drug was frequent: 15.6% of cases before and 27.3% after the label change with the introduction of timing restrictions. Treatment was temporarily interrupted in 10%, and definitely stopped in 25% of cases, after the occurrence of adverse events, the most frequent being bleeding. Severe bleeding occurred in 3.8% of patients. Multivariable analysis, which allowed an adjusted comparison with a control group, showed that treatment increased mortality among elective-surgery patients (OR 2.79, 95%CI 1.31-5.97). The results of this study and other evidences led the European Medicines Agency (EMA) to require a confirmatory trial in 2007. In October 2011 Ely-Lilly, the producer of the drug, announced the worldwide withdrawal from the market of Xigris®, on the basis of the negative results of the confirmatory trial. The availability of purchase information is essential to carry out post-marketing drug surveillance studies, since it allows to identify and contact non-compliant centers. Actually, a representative sample of treated patients provides reliable information on the use, efficacy, and safety of the drug in daily clinical practice that could positively influence healthcare policies.

  12. Antiepileptic popular ketogenic diet: emerging twists in an ancient story.

    Science.gov (United States)

    Vamecq, Joseph; Vallée, Louis; Lesage, Florian; Gressens, Pierre; Stables, James P

    2005-01-01

    The antiepileptic activity associated with ketogenic diets (KD) have been known for some time. First reports date back to the Middle Ages and even Biblical times where KD was achieved by fasting (i.e. "water diet") [see Swink, T.D., Vining, E.P.G., Freeman, J.M., 1997. The ketogenic diet: 1997. Adv. Pediatr. 44, 297-329, and references therein]. In the early 20th century, changes in the design of the KD were introduced, shifting the so-called "water diet" to a high-fat diet. Initial clinical evaluations undertaken between the 1920s and 1940s were enthusiastic, but the popularity of the KD was retrograded upon clinical introduction of phenytoin and subsequently other antiepileptic drugs. Today, despite a pharmacological arsenal targeting cerebral receptors and specific events in seizure initiation and development, about 30-40% patients are still refractory to available medications. Thus, the KD has been re-introduced in recent years as an alternative therapy, averring to be efficacious against some instances of resistant or intractable epilepsy. Despite a long historical background and enlarged clinical use, identification of the underlying anticonvulsant mechanisms associated with this nonpharmacological approach is still in stagnation. The present review is an attempt to encourage current research orientation through well-based and directed proposals for putative emerging candidates mediating KD anticonvulsant mechanisms. The reader is provided with a special emphasis on ATP-sensitive and recently cloned two-pore (or tandem) domain potassium channels, as well as several emerging conceptual views and advances such as nuclear receptors, uncoupling proteins and gap junctions that the authors speculate may contribute to understanding the basic mechanisms linked to the KD.

  13. Using probability of drug use as independent variable in a register-based pharmacoepidemiological cause-effect study-An application of the reverse waiting time distribution

    DEFF Research Database (Denmark)

    Hallas, Jesper; Pottegård, Anton; Støvring, Henrik

    2017-01-01

    generated adjusted ORs in the upper range (4.37-4.75) while at the same time having the most narrow confidence intervals (ratio between upper and lower confidence limit, 1.46-1.50). Some ORs generated by conventional measures were higher than the probabilistic ORs, but only when the assumed period of intake......BACKGROUND: In register-based pharmacoepidemiological studies, each day of follow-up is usually categorized either as exposed or unexposed. However, there is an underlying continuous probability of exposure, and by insisting on a dichotomy, researchers unwillingly force a nondifferential...... misclassification into their analyses. We have recently developed a model whereby probability of exposure can be modeled, and we tested this on an empirical case of nonsteroidal anti-inflammatory drug (NSAID)-induced upper gastrointestinal bleeding (UGIB). METHODS: We used a case-controls data set, consisting...

  14. The antiepileptic Materia Medica of Pediacus Dioscorides.

    Science.gov (United States)

    Eadie, M J

    2004-09-01

    Since it was written about the middle of the 1st Century AD, and up to comparatively recent times, the great Herbal, or Materia Medica, of Dioscorides provided medicine with its chief source of information about what were then considered therapeutic substances. The work contained data on various materials of botanical, biological and mineral origin which were claimed to provide benefit to sufferers from epilepsy, though often with no clear underlying rationale for their use. Some of these materials continued to be used as antiepileptic remedies over many centuries till they were finally recognised to be without useful effect in the disorder. The longest survivor amongst the Dioscoridean antiepileptic remedies was a rather esoteric one, viz. two stones taken from the belly of a young swallow during the rising phase of the moon and also whilst the swallow's parent birds were absent from the nest. The stones, or one of them, were worn against the skin of the seizure sufferer. The use of the swallow stones for epilepsy was recommended as late as in the writings of Thomas Willis (1675).

  15. Classical neurotransmitters and neuropeptides involved in generalized epilepsy in a multi-neurotransmitter system: How to improve the antiepileptic effect?

    Science.gov (United States)

    Werner, Felix-Martin; Coveñas, Rafael

    2017-06-01

    Here, we describe in generalized epilepsies the alterations of classical neurotransmitters and neuropeptides acting at specific subreceptors. In order to consider a network context rather than one based on focal substrates and in order to make the interaction between neurotransmitters and neuropeptides and their specific subreceptors comprehensible, neural networks in the hippocampus, thalamus, and cerebral cortex are described. In this disease, a neurotransmitter imbalance between dopaminergic and serotonergic neurons and between presynaptic GABAergic neurons (hypoactivity) and glutaminergic neurons (hyperactivity) occurs. Consequently, combined GABA A agonists and NMDA antagonists could furthermore stabilize the neural networks in a multimodal pharmacotherapy. The antiepileptic effect and the mechanisms of action of conventional and recently developed antiepileptic drugs are reviewed. The GASH:Sal animal model can contribute to examine the efficacy of antiepileptic drugs. The issues of whether the interaction of classical neurotransmitters with other subreceptors (5-HT 7 , metabotropic 5 glutaminergic, A 2A adenosine, and alpha nicotinic 7 cholinergic receptors) or whether the administration of agonists/antagonists of neuropeptides might improve the therapeutic effect of antiepileptic drugs should be addressed. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic". Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Registered partnerships

    CERN Multimedia

    Staff Association

    2015-01-01

    In recent decades, family patterns have changed significantly. National laws have taken these changes into account, recognizing new forms of unions, different to heterosexual marriage. Indeed, recently some countries have given the possibility to same-sex couples to enter into various forms of unions. Staff regulations of international organizations are not directly affected by national laws, but in the context of diversity policies, the lack of recognition of these new forms of unions, may appear to discriminate based on sexual orientation and to limit the freedom of choosing marital status. A study by the International Service for Remunerations and Pensions (iSRP) of the OECD in January 2015 (PROS Report (1015) 04) shows that in comparison with other international organizations, CERN offers the least favorable social conditions for its Staff with in a registered partnership. As part of the Five-year review in 2015, it is important that CERN aligns itself with the practice of these other organizations...

  17. Identification and preclinical testing of novel antiepileptic compounds.

    Science.gov (United States)

    Meldrum, B S

    1997-01-01

    Procedures for identifying novel antiepileptic drugs (AEDs) are changing and need to change more. Widespread reliance on two primary screens has led to the identification of novel compounds that resemble either phenytoin (suppressing high-frequency repetitive firing in cultured neurons and prolonging inactivation of voltage-dependent sodium channels identified by the maximal electroshock test) or benzodiazepines (potentiating the inhibitory effect of gamma-aminobutyric acid (GABA), identified by the threshold pentylenetetrazol test). Advances in molecular neurobiology have identified specific molecular targets (subunits of ion channels, neurotransmitter receptors, and transporters) and have made them available in a form permitting high-throughput screening. AEDs can be designed to interact with specific sites on the target molecules. Alternatively, the molecular screens can be used to identify active components in natural products, including folk remedies. Preclinical in vivo screens can be improved by using animals with genetic or acquired epilepsies that have similar modifications in the properties of the target molecules as do human epilepsy syndromes. Future work is likely to define molecular targets for AEDs that will block or reverse chronic epileptogenesis.

  18. Drug: D05817 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D05817 Drug Seletracetam (USAN/INN) ... C10H14F2N2O2 D05817.gif ... Neuropsychiatric agent ... DG02038 ... Piracetam... antiepileptics Chemical group: DG02506 ... Piracetam derivative Treatment of epilepsy

  19. Comparative effectiveness of generic versus brand-name antiepileptic medications.

    Science.gov (United States)

    Gagne, Joshua J; Kesselheim, Aaron S; Choudhry, Niteesh K; Polinski, Jennifer M; Hutchins, David; Matlin, Olga S; Brennan, Troyen A; Avorn, Jerry; Shrank, William H

    2015-11-01

    The objective of this study was to compare treatment persistence and rates of seizure-related events in patients who initiate antiepileptic drug (AED) therapy with a generic versus a brand-name product. We used linked electronic medical and pharmacy claims data to identify Medicare beneficiaries who initiated one of five AEDs (clonazepam, gabapentin, oxcarbazepine, phenytoin, zonisamide). We matched initiators of generic versus brand-name versions of these drugs using a propensity score that accounted for demographic, clinical, and health service utilization variables. We used a Cox proportional hazards model to compare rates of seizure-related emergency room (ER) visit or hospitalization (primary outcome) and ER visit for bone fracture or head injury (secondary outcome) between the matched generic and brand-name initiators. We also compared treatment persistence, measured as time to first 14-day treatment gap, between generic and brand-name initiators. We identified 19,760 AED initiators who met study eligibility criteria; 18,306 (93%) initiated a generic AED. In the matched cohort, we observed 47 seizure-related hospitalizations and ER visits among brand-name initiators and 31 events among generic initiators, corresponding to a hazard ratio of 0.53 (95% confidence interval, 0.30 to 0.96). Similar results were observed for the secondary clinical endpoint and across sensitivity analyses. Mean time to first treatment gap was 124.2 days (standard deviation [sd], 125.8) for brand-name initiators and 137.9 (sd, 148.6) for generic initiators. Patients who initiated generic AEDs had fewer adverse seizure-related clinical outcomes and longer continuous treatment periods before experiencing a gap than those who initiated brand-name versions. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Adult epileptic patients’ perception of social support during rational antiepileptic therapy

    Directory of Open Access Journals (Sweden)

    P. N. Vlasov

    2012-01-01

    Full Text Available The problem of stigmatization of a patient with epilepsy is frequently essential in restricting the capacities of his social performance. Society is often unready to recognize an epileptic patient as its equal member. The authors consider the main sources of social support (SS to patients with epilepsy: the patient’s family takes first place; friends and other important persons also play a major role. The perception of SS has been found to be related to the number of used antiepileptic drugs and the hemispheric lateralization of a leading epileptic focus.

  1. Practitioner Review: Use of Antiepileptic Drugs in Children

    Science.gov (United States)

    Guerrini, Renzo; Parmeggiani, Lucio

    2006-01-01

    Background: The aim in treating epilepsy is to minimise or control seizures with full respect of quality-of-life issues, especially of cognitive functions. Optimal treatment first demands a correct recognition of the major type of seizures, followed by a correct diagnosis of the type of epilepsy or of the specific syndrome. Methods: Review of data…

  2. Antiepileptic drugs and risk of suicide: a nationwide study

    DEFF Research Database (Denmark)

    Olesen, Jonas Bjerring; Hansen, Peter Riis; Erdal, Jesper

    2010-01-01

    . The case-crossover analysis estimated AED treatment initiation to increase the risk of suicide (odds ratio (OR): 1.84, 95% confidence interval (CI): 1.36-2.49). Clonazepam (OR: 2.01, CI: 1.25-3.25), valproate (OR: 2.08, CI: 1.01-4.16), lamotrigine (OR: 3.15, CI: 1.35-7.34) and phenobarbital (OR: 1.96, CI...... that clonazepam, valproate, lamotrigine and phenobarbital relatively shortly after treatment initiation may increase the risk of suicide. The increased risk of suicide associated with these AEDs appears to be a consistent finding. Copyright (C) 2010 John Wiley & Sons, Ltd...

  3. Patterns of antiepileptic drug use and seizure control among people ...

    African Journals Online (AJOL)

    Background Epilepsy is characterized by episodic and unpredictable seizure recurrences which are often amenable to medical treatment. Simple and readily available medications can be used to control seizures in epilepsy. However, in many communities in developing countries seizure control among people living with ...

  4. Antiepileptic drug prescribing before, during and after pregnancy

    DEFF Research Database (Denmark)

    Charlton, Rachel; Garne, Ester; Wang, Hao

    2015-01-01

    and after pregnancy were identified in each of the databases. AED prescribing patterns were analysed, and the choice of AEDs and co-prescribing of folic acid were evaluated. Results In total, 978 957 women with 1 248 713 deliveries were identified. In all regions, AED prescribing declined during pregnancy...... co-prescribed with high-dose folic acid: ranging from 1.0% (CI950.3–1.8%) in Emilia Romagna to 33.5% (CI9528.7–38.4%) in Wales. Conclusion The country's differences in prescribing patterns may suggest different use, knowledge or interpretation of the scientific evidence base. The low co......-prescribing of folic acid indicates that more needs to be done to better inform clinicians and women of childbearing age taking AEDs about the need to offer and receive complete preconception care....

  5. PPAR-alpha agonists as novel antiepileptic drugs: preclinical findings.

    Directory of Open Access Journals (Sweden)

    Monica Puligheddu

    Full Text Available Nicotinic acetylcholine receptors (nAChRs are involved in seizure mechanisms. Hence, nocturnal frontal lobe epilepsy was the first idiopathic epilepsy linked with specific mutations in α4 or β2 nAChR subunit genes. These mutations confer gain of function to nAChRs by increasing sensitivity toward acetylcholine. Consistently, nicotine elicits seizures through nAChRs and mimics the excessive nAChR activation observed in animal models of the disease. Treatments aimed at reducing nicotinic inputs are sought as therapies for epilepsies where these receptors contribute to neuronal excitation and synchronization. Previous studies demonstrated that peroxisome proliferator-activated receptors-α (PPARα, nuclear receptor transcription factors, suppress nicotine-induced behavioral and electrophysiological effects by modulating nAChRs containing β2 subunits. On these bases, we tested whether PPARα agonists were protective against nicotine-induced seizures. To this aim we utilized behavioral and electroencephalographic (EEG experiments in C57BL/J6 mice and in vitro patch clamp recordings from mice and rats. Convulsive doses of nicotine evoked severe seizures and bursts of spike-waves discharges in ∼100% of mice. A single dose of the synthetic PPARα agonist WY14643 (WY, 80 mg/kg, i.p. or chronic administration of fenofibrate, clinically available for lipid metabolism disorders, in the diet (0.2% for 14 days significantly reduced or abolished behavioral and EEG expressions of nicotine-induced seizures. Acute WY effects were reverted by the PPARα antagonist MK886 (3 mg/kg, i.p.. Since neocortical networks are crucial in the generation of ictal activity and synchrony, we performed patch clamp recordings of spontaneous inhibitory postsynaptic currents (sIPSCs from frontal cortex layer II/III pyramidal neurons. We found that both acute and chronic treatment with PPARα agonists abolished nicotine-induced sIPSC increases. PPARα within the CNS are key regulators of neuronal activity through modulation of nAChRs. These effects might be therapeutically exploited for idiopathic or genetically determined forms of epilepsy where nAChRs play a major role.

  6. Patients' perspectives on antiepileptic medication: relationships between beliefs about medicines and adherence among patients with epilepsy in UK primary care.

    OpenAIRE

    Chapman, S. C.; Horne, R.; Chater, A.; Hukins, D.; Smithson, W. H.

    2014-01-01

    BACKGROUND: Nonadherence to antiepileptic drugs (AEDs) can result in suboptimal outcomes for patients. AIM: This study aimed to assess the utility of a theory-based approach to understanding patient perspectives on AEDs and adherence. METHOD: Patients with epilepsy, identified by a GP case note review, were mailed validated questionnaires assessing their perceptions of AEDs and their adherence to them. RESULTS: Most (84.9%) of the 398 AED-treated respondents accepted the necessity of AEDs, bu...

  7. Bone mineral density and serum levels of 25 OH vitamin D in chronic users of antiepileptic drugs Densidade mineral óssea e níveis séricos de 25 OH vitamina D em usuários crônicos de drogas antiepilépticas

    Directory of Open Access Journals (Sweden)

    Carolina A.M. Kulak

    2004-12-01

    Full Text Available The aim of this cross sectional study was to evaluate bone mineral density (BMD and serum levels of 25-hydroxy vitamin D (25OHD in a group of patients taking antiepileptic drugs (AED for a seizure disorder. Between May-2001 and January-2003, we evaluated 58 patients (40 women/18 men, 34.4±6 years old living in Curitiba or in its metropolitan area, on antiepileptic therapy for 2 to 38 years (10 on monotherapy /48 on multiple drugs regime. The group was matched by age, gender, and bone mass index to 29 healthy subjects (20 women/ 9 men; 34.2±5.9 years old. Medical history and physical exam were performed on all subjects with particular information sought about fractures and risks factors for osteoporosis. Blood samples were collected for total serum calcium, albumin, phosphorus, creatinine, total alkaline phosphatase, and liver function tests. BMD of the lumbar spine, femur and forearm was determined by dual energy X-ray absorptiometry (DXA, Hologic QDR 1000. Between February and April-2003, other blood samples were collected to measure 25OHD, intact paratohormone (PTH and calcium. Unemployment and smoking history were more frequent among patients than among controls (pO objetivo deste estudo transversal foi avaliar a densidade mineral óssea (DMO e os níveis de 25hidroxi vitamina D (25OHD em um grupo de pacientes com epilepsia e usuários crônicos de drogas antiepilépticas (DAE. Entre maio-2001 e janeiro-2003 avaliamos 58 pacientes (40 mulheres/18 homens residentes em Curitiba ou região metropolitana da cidade, com média de idade 34,4±6 anos e tempo de tratamento entre 2 e 38 anos (10 em monoterapia/48 em politerapia. O grupo de pacientes foi emparelhado por idade, sexo e índice de massa corpórea com 29 indivíduos aparentemente sadios (20 mulheres/9 homens; 34,2±5,9 anos. Pacientes e controles foram submetidos a anamnese e exame clínico, com ênfase na história de fraturas e fatores de risco para osteoporose. Nas visitas foram

  8. The evaluation of 25-hydroxy vitamin D, calcium, phosphate and alkaline phosphatase levels in epileptic children under antiepileptic medication

    Directory of Open Access Journals (Sweden)

    Keyhani doost Z

    2011-01-01

    Full Text Available "n 800x600 Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 st1":*{behavior:url(#ieooui } /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman","serif";} Background: Epilepsy is a common disease in the pediatric neurology. There are frequent anti-epileptic drugs which are used in management of epilepsy. Anti-epileptic drugs may have some complications on bone and vitamin-D metabolism. In this study we aimed to evaluate vitamin-D metabolism in epileptic children."n"nMethods: The study was a prospective and cross sectional one. A total 89 epileptic children who were taking anti-epileptic drugs for longer than six months with no underlying disorder in Imam Khomeini and Bahrami Hospitals in Tehran, Iran were enrolled in our study"n"nResults: Forty nine boys and 40 girls were enrolled in this study; mean age of the patients was 7.8±2.1 years. Mean duration of anti-epileptic drug therapy was 2.3 years (SD=0.4, 70 of patients were under monotherapy and 19 were under polytherapy. None of the patients had signs of rickets. Serum calcium and phosphor levels were within normal ranges. Serum alkaline phosphates levels were increased more than two times in 43%. 42% had vitamin-D deficiency (25-OH Vit D<10 ng/ml and another 33% had vitamin-D insufficiency (10<25-oh Vit D<20 ng/ml. 29 patients (32% were taking prophylactic supplemental Vit D (200-400 IU/day. There was significant difference between patients taking supplemental vitamin-D as prophylaxis and patients who did not (p=0.04. There was no significant difference in vitamin-D levels between patients according to age, gender or different drugs."n"nConclusion: Periodic

  9. Epilepsy, anti-epileptic medication use and risk of cancer

    DEFF Research Database (Denmark)

    Kaae, Jeanette; Carstensen, Lisbeth; Wohlfahrt, Jan

    2014-01-01

    Whether the powerful medications used to treat epilepsy increase the risk of cancer has been debated for decades, but until now no study could disentangle the contributions of anti-epileptic medications and epilepsy itself to cancer risk. Using a cohort comprising all Danish residents ≥ 16 years ...

  10. EFFICACY OF RUFINAMIDE IN THE TREATMENT OF DRUG-RESISTANT FOCAL EPILEPSIES IN PAEDIATRIC PRACTICE

    Directory of Open Access Journals (Sweden)

    I. O. Shchederkina

    2016-01-01

    Full Text Available Among drug-resistant epilepsies, epileptic syndromes, characterized by combination of several types of seizures, are considered to be the most difficult in terms of treatment. Lennox–Gastaut syndrome is one of them. It manifests with polymorphic seizures (tonic axial, myatonic, atypical absence seizures, status epilepticus of minor motor seizures, myoclonic, generalized convulsive, and focal seizures. This is a heterogeneous disease, represented by a complex of clinical and electroencephalographic manifestations with various etiology. Current review is devoted to a novel antiepileptic drug rufinamide, which has a new mechanism of action. The drug has been registered in Russia in 2015. The authors also describe their own experience of rufinamide usage in the treatment of drug-resistant focal epilepsy as a part of multicomponent therapy for polymorphic seizures. One patient achieved clinical remission for 16 months; the second one had more than 50 % decrease in seizures frequency with a remission of drop-attacks.

  11. The Effects of Fall-Risk-Increasing Drugs on Postural Control : A Literature Review

    NARCIS (Netherlands)

    de Groot, Maartje H.; van Campen, Jos P. C. M.; Moek, Marije A.; Tulner, Linda R.; Beijnen, Jos H.; Lamoth, Claudine J. C.

    Meta-analyses showed that psychotropic drugs (antidepressants, neuroleptics, benzodiazepines, antiepileptic drugs) and some cardiac drugs (digoxin, type IA anti-arrhythmics, diuretics) are associated with increased fall risk. Because balance and gait disorders are the most consistent predictors of

  12. National Register Historic Districts

    Data.gov (United States)

    Iowa State University GIS Support and Research Facility — The National Register Historic District layer is a shape file showing the boundaries of Historic Districts that are listed on the National Register of Historic Places.

  13. Socioeconomic correlates of drug use based on prescription data: a population-based cross-sectional register study in Denmark 1999

    DEFF Research Database (Denmark)

    Mortensen, Jens T; Olesen, Anne V; Bøggild, Henrik

    2007-01-01

    with slightly more male top managers using cardiovascular drugs. People in the upper half of the socioeconomic scale were somewhat less likely to redeem prescriptions for treating muscle, joints and bone, and central nervous system. CONCLUSION: Social or economic barriers in buying medicine are generally small......INTRODUCTION: In the public health system we study medical treatment which is ideally provided according to need and independently of economic means. We report use of prescription drugs according to socioeconomic classifications in North Jutland County in Denmark in 1999. METHOD: We conducted...

  14. THE WAY OF ASSESSING THE ADHERENCE TO MODERN DRUG THERAPY CLINICAL GUIDELINES AIMED AT REDUCING THE RISK OF RECURRENT STROKE (ACCORDING TO THE LIS-2 REGISTER

    Directory of Open Access Journals (Sweden)

    A. Yu. Suvorov

    2015-09-01

    Full Text Available Aim. To develop a method for the assessment of quality of medical prevention of recurrent stroke and its’ testing using the results of the LIS-2 register (Lyubertsy study of mortality in patients after stroke.Material and methods. The scale evaluation of the quality of therapy for the prevention of recurrent stroke developed in accordance with the modern clinical practice guidelines, as well as the recurrent stroke prevention index (RSPI for this assessment were elaborated. The analysis of the therapy was performed in patients after stroke in LIS-2 registers (n=219. The assessment of the quality of treatment was performed using RSPI, the influence of the index results on the in-hospital mortality was studied.Results. Two groups of patients [with RSPI=0 (n=137 and RSPI>0 (n=82] were formed on the basis of the results evaluation via RSPI. Significant differences between groups were not found. At the same time higher in-hospital mortality (p=0.014; χ2 Pearson was detected in patients with RSPI=0; relative risk of in-hospital death (after adjustment for sex and age was 2.04 [1.07-3.91] (p=0.031. Analysis of the length of survival and duration of hospital stay was performed in both groups using the Kaplan-Meier method. In-hospital mortality was significantly higher in patients with RSPI=0, which was confirmed by the log-rank test (p=0.032.Conclusion. The results of the quality of medical care assessment in accordance with the developed method are significantly related to the outcomes during the stay in a hospital. The developed method, based on current clinical recommendations, can serve as an example of the implementation of evidence-based medicine in actual practice.

  15. Antiepileptic activity of total triterpenes isolated from Poria cocos is mediated by suppression of aspartic and glutamic acids in the brain.

    Science.gov (United States)

    Gao, Yanqiong; Yan, Hua; Jin, Ruirui; Lei, Peng

    2016-11-01

    Triterpenes from Poria cocos Wolf (Polyporaceae) have been used to treat various diseases in traditional Chinese medicine. However, the antiepileptic effects and mechanism are not fully understood. The objective of this study is to investigate the antiepileptic properties of total triterpenes (TTP) from the whole P. cocos. The ethanol extract TTP was identified by HPLC fingerprint analysis. Male ICR mice were gavaged (i.g.) with TTP (5, 20, 80 or 160 mg/kg) or reference drugs twice a day for 7 d. Antiepileptic activities of TTP were evaluated by maximal electroshock (MES)- and pentylenetetrazole (PTZ)-induced seizures in mice for 30 and 60 min, respectively. Locomotor activity and Rota-rod tests were performed for 60 min and 5 min, respectively. The levels of glutamic acid (Glu), aspartic acid (Asp), γ-aminobutyric acid (GABA) and glycine (Gly) in convulsive mice were estimated. The chronic epileptic model of Wistar rats was built to measure expressions of glutamate decarboxylase 65 (GAD65) and GABA A in rat brain after TTP treatment. The LC 50 of TTP (i.g.) was above 6 g/kg. TTP (5-160 mg/kg) protected mice against MES- and PTZ-induced convulsions at 65.0% and 62.5%, respectively, but have no effect on rota-rod treadmill; TTP (20-160 mg/kg) significantly reduced the locomotor activities, shortened the onset of pentobarbital sodium-induced sleep; TTP decreased Glu and Asp levels in convulsive mice, but increased the GAD65 and GABA A expressions in chronic epileptic rats at doses usage. TTP extracted from P. cocos possessed potential antiepileptic properties and is a candidate for further antiepileptic drug development.

  16. Prophylactic drug management for febrile seizures in children

    Directory of Open Access Journals (Sweden)

    Martin Offringa

    Full Text Available BACKGROUND Febrile seizures occurring in a child older than one month during an episode of fever affect 2% to 4% of children in Great Britain and the United States and recur in 30%. Rapid-acting antiepileptics and antipyretics given during subsequent fever episodes have been used to avoid the adverse effects of continuous antiepileptic drugs. OBJECTIVE To evaluate the effectiveness and safety of antiepileptic and antipyretic drugs used prophylactically to treat children with febrile seizures. METHODS Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL (The Cochrane Library 2011. Issue 3; MEDLINE (1966 to May 2011; EMBASE (1966 to May 2011; Database of Abstracts of Reviews of Effectiveness (DARE (May 2011. No language restrictions were imposed. We also contacted researchers in the field to identify continuing or unpublished studies. Selection criteria: Trials using randomized or quasi-randomized patient allocation that compared the use of antiepileptic or antipyretic agents with each other, placebo or no treatment. Data collection and analysis: Two review authors (RN and MO independently applied pre-defined criteria to select trials for inclusion and extracted the pre-defined relevant data, recording methods for randomization, blinding and exclusions. Outcomes assessed were seizure recurrence at 6, 12, 18, 24, 36 months and at age 5 to 6 years in the intervention and non-intervention groups, and adverse medication effects. The presence of publication bias was assessed using funnel plots. MAIN RESULTS Thirty-six articles describing 26 randomized trials with 2740 randomized participants were included. Thirteen interventions of continuous or intermittent prophylaxis and their control treatments were analyzed. Methodological quality was moderate to poor in most studies. We could not do a meta-analysis for 8 of the 13 comparisons due to insufficient numbers of trials. No significant benefit for valproate, pyridoxine

  17. Use of psychotropic drugs before pregnancy and the risk for induced abortion: population-based register-data from Finland 1996-2006

    OpenAIRE

    Ritvanen Annukka; Artama Miia; Gissler Mika; Wahlbeck Kristian

    2010-01-01

    Abstract Background Some, though not all studies have reported an increased risk for mental health problems after an induced abortion. Problems with design and data have compromised these studies and the generalisation of their results. Methods The Finnish Medication and Pregnancy database (N = 622 671 births and 114 518 induced abortions for other than fetal reasons) in 1996-2006 was utilised to study the use of psychotropic drugs in the three months before a pregnancy ending in a birth or a...

  18. Registers of multiple sclerosis in Denmark

    DEFF Research Database (Denmark)

    Koch-Henriksen, N; Magyari, M; Laursen, B

    2015-01-01

    between a number of different environmental exposures in the past and the subsequent risk of MS. Some of these studies have been able to exonerate suspected risk factors. The other register, the nationwide Danish Multiple Sclerosis Treatment Register, is a follow-up register for all patients who have......There are two nationwide population-based registers for multiple sclerosis (MS) in Denmark. The oldest register is The Danish Multiple Sclerosis Registry (DMSR), which is an epidemiological register for estimation of prevalence and incidence of MS and survival, and for identifying exposures earlier...... received disease-modifying treatments since 1996. It has, in particular, contributed to the knowledge of the role of antibodies against the biological drugs used for the treatment of MS....

  19. Drug utilization profile in adult patients with refractory epilepsy at a tertiary referral center

    Directory of Open Access Journals (Sweden)

    Priscila de Freitas-Lima

    2013-11-01

    Full Text Available Objective To evaluate the utilization profile of antiepileptic drugs in a population of adult patients with refractory epilepsy attending a tertiary center. Method Descriptive analyses of data were obtained from the medical records of 112 patients. Other clinical and demographic characteristics were also registered. Results Polytherapies with ≥3 antiepileptic drugs were prescribed to 60.7% of patients. Of the old agents, carbamazepine and clobazam were the most commonly prescribed (72.3% and 58.9% of the patients, respectively. Among the new agents, lamotrigine was the most commonly prescribed (36.6% of the patients. At least one old agent was identified in 103 out of the 104 polytherapies, while at least one new agent was prescribed to 70.5% of the population. The most prevalent combination was carbamazepine + clobazam + lamotrigine. The mean AED load found was 3.3 (range 0.4–7.7. Conclusion The pattern of use of individual drugs, although consistent with current treatment guidelines, is strongly influenced by the public health system.

  20. Treatment results of patients with multiple and extensive drug resistance registered in 2012 in the Russian Federation and in the world

    Directory of Open Access Journals (Sweden)

    S. A. Sterlikov

    2016-01-01

    Full Text Available The chemotherapy results have been analyzed in tuberculosis patients suffering from multiple drug resistance registered for treatment in the Russian Federation in 2011-2012 compared with the treatment outcomes of MDR patients registered for treatment in the world, BRICS and countries of the former Soviet Union in 2011. Treatment outcomes of XDR TB patients have been analyzed for the first time. Chemotherapy efficiency in MDR TB patients in the Russian Federation in the cohort of 2011 made 37.1%, and in the cohort of 2012 made 39.1%, which significantly lower than in the world in general (47.5%, in BRICS and countries of the former Soviet Union; this low treatment efficiency is mostly due to treatment failures (18.3% and those died (19.1%. The treatment efficiency of XDR TB patients registered for treatment in the Russian Federation in 2012 made 26.2% versus 22.0% in the cohort of 2011. Considering the significant financial costs spent on the treatment, the chemotherapy efficiency of M/XDR TB patients in the Russian Federation is too low to improve the epidemic situation and some additional measures are to be taken for its improvement.

  1. Use of psychotropic drugs before pregnancy and the risk for induced abortion: population-based register-data from Finland 1996-2006.

    Science.gov (United States)

    Gissler, Mika; Artama, Miia; Ritvanen, Annukka; Wahlbeck, Kristian

    2010-06-30

    Some, though not all studies have reported an increased risk for mental health problems after an induced abortion. Problems with design and data have compromised these studies and the generalisation of their results. The Finnish Medication and Pregnancy database (N = 622 671 births and 114 518 induced abortions for other than fetal reasons) in 1996-2006 was utilised to study the use of psychotropic drugs in the three months before a pregnancy ending in a birth or an induced abortion. In total 2.1% of women with a birth and 5.1% of women with an induced abortion had used a psychotropic medicine 0-3 months before pregnancy. Psychotropic drug users terminated their pregnancies (30.9%) more often than other pregnant women (15.5%). Adjustment for background characteristics explained one third of this elevated risk, but the risk remained significantly increased among users of psychotropic medicine (OR 1.94, 95% confidence intervals 1.87-2.02). A similar risk was found for first pregnancies (30.1% vs. 18.9%; adjusted OR 1.53, 95% confidence intervals 1.42-1.65). The rate for terminating pregnancy was the highest for women using hypnotics and sedatives (35.6% for all pregnancies and 29.1% for first pregnancies), followed by antipsychotics (33.9% and 36.0%) and antidepressants (32.0% and 32.1%). The observed increased risk for induced abortion among women with psychotropic medication highlights the importance to acknowledge the mental health needs of women seeking an induced abortion. Further studies are needed to establish the impact of pre-existing differences in mental health on mental health outcomes of induced abortions compared to outcomes of pregnancies ending in a birth.

  2. Use of psychotropic drugs before pregnancy and the risk for induced abortion: population-based register-data from Finland 1996-2006

    Directory of Open Access Journals (Sweden)

    Ritvanen Annukka

    2010-06-01

    Full Text Available Abstract Background Some, though not all studies have reported an increased risk for mental health problems after an induced abortion. Problems with design and data have compromised these studies and the generalisation of their results. Methods The Finnish Medication and Pregnancy database (N = 622 671 births and 114 518 induced abortions for other than fetal reasons in 1996-2006 was utilised to study the use of psychotropic drugs in the three months before a pregnancy ending in a birth or an induced abortion. Results In total 2.1% of women with a birth and 5.1% of women with an induced abortion had used a psychotropic medicine 0-3 months before pregnancy. Psychotropic drug users terminated their pregnancies (30.9% more often than other pregnant women (15.5%. Adjustment for background characteristics explained one third of this elevated risk, but the risk remained significantly increased among users of psychotropic medicine (OR 1.94, 95% confidence intervals 1.87-2.02. A similar risk was found for first pregnancies (30.1% vs. 18.9%; adjusted OR 1.53, 95% confidence intervals 1.42-1.65. The rate for terminating pregnancy was the highest for women using hypnotics and sedatives (35.6% for all pregnancies and 29.1% for first pregnancies, followed by antipsychotics (33.9% and 36.0% and antidepressants (32.0% and 32.1%. Conclusions The observed increased risk for induced abortion among women with psychotropic medication highlighs the importance to acknowledge the mental health needs of women seeking an induced abortion. Further studies are needed to establish the impact of pre-existing differences in mental health on mental health outcomes of induced abortions compared to outcomes of pregnancies ending in a birth.

  3. Arthroplasty register for Germany

    Directory of Open Access Journals (Sweden)

    Hagen, Anja

    2009-10-01

    Full Text Available Scientific background: The annual number of joint replacement operations in Germany is high. The introduction of an arthroplasty register promises an important contribution to the improvement of the quality of patient’s care. Research questions: The presented report addresses the questions on organization and functioning, benefits and cost-benefits as well as on legal, ethical and social aspects of the arthroplasty registers. Methods: A systematic literature search was conducted in September 2008 in the medical databases MEDLINE, EMBASE etc. and was complemented with a hand search. Documents describing arthroplasty registers and/or their relevance as well as papers on legal, ethical and social aspects of such registers were included in the evaluation. The most important information was extracted and analysed. Results: Data concerning 30 arthroplasty registers in 19 countries as well as one international arthroplasty register were identified. Most of the arthroplasty registers are maintained by national orthopedic societies, others by health authorities or by their cooperation. Mostly, registries are financially supported by governments and rarely by other sources.The participation of the orthopedists in the data collection process of the arthroplasty registry is voluntary in most countries. The consent of the patients is usually required. The unique patient identification is ensured in nearly all registers.Each data set consists of patient and clinic identification numbers, data on diagnosis, the performed intervention, the operation date and implanted prostheses. The use of clinical scores, patient-reported questionnaires and radiological documentation is rare. Methods for data documentation and transfer are paper form, electronic entry as well as scanning of the data using bar codes. The data are mostly being checked for their completeness and validity. Most registers offer results of the data evaluation to the treating orthopedists and

  4. The Danish Pathology Register

    DEFF Research Database (Denmark)

    Bjerregaard, Beth; Larsen, Ole B

    2011-01-01

    The National Board of Health, Denmark in 1997 published guidelines for reporting of pathology data and the Danish Pathology Register (DPR) was established.......The National Board of Health, Denmark in 1997 published guidelines for reporting of pathology data and the Danish Pathology Register (DPR) was established....

  5. Registered Nurse (Associate Degree).

    Science.gov (United States)

    Ohio State Univ., Columbus. Center on Education and Training for Employment.

    This document, which is designed for use in developing a tech prep competency profile for the occupation of registered nurse (with an associate degree), lists technical competencies and competency builders for 19 units pertinent to the health technologies cluster in general and 5 units specific to the occupation of registered nurse. The following…

  6. The Danish Adoption Register

    DEFF Research Database (Denmark)

    Petersen, Liselotte; Sørensen, Thorkild I A

    2011-01-01

    The Danish Adoption Register was established in 1963-1964 to explore the genetic and environmental contribution to familial aggregation of schizophrenia.......The Danish Adoption Register was established in 1963-1964 to explore the genetic and environmental contribution to familial aggregation of schizophrenia....

  7. Josephson shift registers

    International Nuclear Information System (INIS)

    Przybysz, J.X.

    1989-01-01

    This paper gives a review of Josephson shift register circuits that were designed, fabricated, or tested, with emphasis on work in the 1980s. Operating speed is most important, since it often limits system performance. Older designs used square-wave clocks, but most modern designs use offset sine waves, with either two or three phases. Operating margins and gate bias uniformity are key concerns. The fastest measured Josephson shift register operated at 2.3 GHz, which compares well with a GaAs shift register that consumes 250 times more power. The difficulties of high-speed testing have prevented many Josephson shift registers from being operated at their highest speeds. Computer simulations suggest that 30-GHz operation is possible with current Nb/Al 2 O 3 /Nb technology. Junctions with critical current densities near 10 kA/cm 2 would make 100-GHz shift registers feasible

  8. Federal Register in XML

    Data.gov (United States)

    National Archives and Records Administration — The Federal Register is the official daily publication for rules, proposed rules, and notices of Federal agencies and organizations, as well as executive orders and...

  9. The Danish Adoption Register.

    Science.gov (United States)

    Petersen, Liselotte; Sørensen, Thorkild I A

    2011-07-01

    The Danish Adoption Register was established in 1963-1964 to explore the genetic and environmental contribution to familial aggregation of schizophrenia. The register encompass information on all 14,425 non-familial adoptions of Danish children legally granted in Denmark 1924-1947. It includes name and date of birth of each adoptee and his or her biological and adoptive parents, date of transfer to adoptive parents and date of formal adoption. The linkage to biological and adoptive parents is close to complete, even biological fathers are registered for 91.4% of the adoptees. Adoption registers are a unique source allowing disentangling of genetic and familial environmental influences on traits, risk of diseases, and mortality.

  10. Molecular Electronic Shift Registers

    Science.gov (United States)

    Beratan, David N.; Onuchic, Jose N.

    1990-01-01

    Molecular-scale shift registers eventually constructed as parts of high-density integrated memory circuits. In principle, variety of organic molecules makes possible large number of different configurations and modes of operation for such shift-register devices. Several classes of devices and implementations in some specific types of molecules proposed. All based on transfer of electrons or holes along chains of repeating molecular units.

  11. IT Risk register

    OpenAIRE

    Kohout, Karel

    2011-01-01

    The theoretical part of the thesis analyzes several selected methodologies and best-practices related to information technology risks management, with focus on documents and guidance developed by ISACA. It builds a set of ideas and basic requirements for effective model of an IT risk register. Strong emphasis is placed on mapping CobiT 4.1 based Risk IT to COBIT 5. The practical part describes implementation of an exploratory web-based IT risk register in Python programming language utilizing...

  12. National Drug Code Directory

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Drug Listing Act of 1972 requires registered drug establishments to provide the Food and Drug Administration (FDA) with a current list of all drugs manufactured,...

  13. Register-based studies of cardiovascular disease

    DEFF Research Database (Denmark)

    Abildstrøm, Steen Z; Torp-Pedersen, Christian; Madsen, Mette

    2011-01-01

    Introduction: The use of the unique personal identification number in the Nordic database systems enables the researchers to link the registers at the individual level. The registers can be used for both defining specific patient populations and to identify later events during follow-up. This rev...... the hospitalisation rate and treatment of cardiovascular disease. The risk of unmeasured factors affecting the results calls for cautious interpretation of the results.......-up. This review gives three examples within cardiovascular epidemiology to illustrate the use of the national administrative registers available to all researchers upon request. Research topics: The hospitalisation rate of acute myocardial infarction (AMI) was expected to be increased and case-fatality rate......-based treatment increased significantly over time and adherence to treatment was high. Finally, use of specific nonsteroidal antiinflammatory drugs by healthy subjects was associated with a dose-dependent increase in cardiovascular risk. CONCLUSION: The nationwide registers have proven very useful in monitoring...

  14. Validation of the danish national diabetes register

    DEFF Research Database (Denmark)

    Green, Anders; Sortsø, Camilla; Jensen, Peter Bjødstrup

    2015-01-01

    The Danish National Diabetes Register (NDR) was established in 2006 and builds on data from Danish health registers. We validated the content of NDR, using full information from the Danish National Patient Register and data from the literature. Our study indicates that the completeness in NDR...... is ≥95% concerning ascertainment from data sources specific for diabetes, ie, prescriptions with antidiabetic drugs and diagnoses of diabetes in the National Patient Register. Since the NDR algorithm ignores diabetes-related hospital contacts terminated before 1990, the establishment of the date...... of encounter, has been taken as the date of inclusion in NDR. We also find that some 20% of the registrations in NDR may represent false positive inclusions of persons with frequent measurements of blood glucose without having diabetes. We conclude that NDR is a novel initiative to support research...

  15. Hello! Are You Registered?

    Science.gov (United States)

    Institute for Political/Legal Education, Sewell, NJ.

    Organizational procedures and appropriate forms for high school students to conduct a community survey of non-registered voters are provided. Duties for student coordinator, field staff, and clerical staff are described and a flow chart depicts the relationship of personnel to one another and to the community. Students are instructed to notify…

  16. EU Transparency Register

    NARCIS (Netherlands)

    Mańko, R.; Thiel, M.; Bauer, E.

    2014-01-01

    Widespread lobbying in the EU institutions has led to criticism regarding the transparency and accountability of the EU's decision-making process. In response to these concerns, the Parliament set up its transparency register in 1995, followed by the Commission in 2008. The two institutions merged

  17. The Danish heart register

    DEFF Research Database (Denmark)

    Abildstrøm, Steen Z; Madsen, Mette

    2011-01-01

    Introduction: The Danish Heart Register (DHR) is a clinical database of invasive procedures within cardiology. Content: All providers of these procedures have been obliged to report to DHR since 2000. DHR is used to monitor the activity and quality of the procedures and serves as a data source...

  18. Register for Suicide Attempts

    DEFF Research Database (Denmark)

    Christiansen, Erik; Jensen, Børge Frank

    2004-01-01

    The Register for Suicide Attempts (RSA) is a product of the WHO research project "WHO/Euro Multicentre Study on Parasuicide", which, among other things, had the purpose of collecting data on suicide attempts from 13 European countries. Data is collected in order to calculate trends and identify...

  19. Oxcabazepine (®Trileptal in Anti-Epileptic Polytherapy

    Directory of Open Access Journals (Sweden)

    Peder Klosterskov Jensen

    1990-01-01

    Full Text Available The anti-epileptic activity of oxcarbazepine (OXC was compared with that of carbamazepine (CBZ and the primary active metabolite of OXC, a monohydroxy derivative (MHD. Altogether 255 patients receiving either OXC or MHD (192 and 63 patients respectively were included in the analysis of efficacy. Out of these 255 patients a total of 40 were children. The duration of treatment varied between 8 and 24weeks. The daily dose of OXC or MHD varied between 600 and 5400 mg (in children 600–2400 mg. Out of five studies two were double-blind controlled studies (including a total of 105 patients whereas the remaining three were open studies. The results of these studies indicate that, in adults with epilepsy, there is no statistically significant difference in overall seizure frequency between CBZ and OXC. In one double-blind study the number of generalized tonic-clonic seizures was significantly less frequent during treatment with OXC than with CBZ. No statistically significant difference with regard to side-effects was observed between OXC and CBZ. The results in children with epilepsy show a statistically significant difference in seizure frequency in favour of OXC, in comparison with CBZ. Overall, the polytherapy studies in adults and children support the effectiveness and safety of oxcarbazepine.

  20. Register / Andri Ksenofontov

    Index Scriptorium Estoniae

    Ksenofontov, Andri, 1962-

    2007-01-01

    Näitused: Eesti Kujundusgraafikute Liidu aastanäitus "Register 2007" Kunstihoone galeriis, Signe Kivi "Võimuvaibad ja vaimukleidid" Arhitektuuri- ja Disainigaleriis, "Kehaturg / Sex market" (Dagmar Kase, Eveli Variku tööd) Tallinna Kunstihoones, Andrei Maksimjuki "Surematu klassika" Ühispanga galeriis, Katrin Veegeni "Varsti" A-galeriis, Eda Lõhmuse "Ülespoole" ja Rein Kelpmani "Grosso modo" ArtDepoo Galeriis, Jaan Elkeni "Valge valgus" Galeriis 008, Paul Rodgersi "Transplants" Hobusepea galeriis, Masayo Ave "Haptic Interface Design" Arhitektuuri- ja Disainigaleriis ja workshop Eesti Kunstiakadeemias

  1. Registered Replication Report

    DEFF Research Database (Denmark)

    Bouwmeester, S.; Verkoeijen, P. P.J.L.; Aczel, B.

    2017-01-01

    and colleagues. The results of studies using time pressure have been mixed, with some replication attempts observing similar patterns (e.g., Rand et al., 2014) and others observing null effects (e.g., Tinghög et al., 2013; Verkoeijen & Bouwmeester, 2014). This Registered Replication Report (RRR) assessed...... the size and variability of the effect of time pressure on cooperative decisions by combining 21 separate, preregistered replications of the critical conditions from Study 7 of the original article (Rand et al., 2012). The primary planned analysis used data from all participants who were randomly assigned...

  2. The Danish Education Registers

    DEFF Research Database (Denmark)

    Jensen, Vibeke Myrup; Rasmussen, Astrid Würtz

    to adults continuing education and training stem from administrative education reports. Therefore, for cohorts born 1945-1990, 97 percent of the Danish population has a valid education identifier. For the immigrant population born in the same cohorts the coverage is 85-90 percent. Despite a higher level......Collection of systematic information on education is a long established practice in Denmark. Since 1910, the Danish Ministry of Education's annual reports collects information about individual-level test scores in e.g. compulsory schooling. Today, several registers from compulsory schooling...

  3. The Danish Education Registers

    DEFF Research Database (Denmark)

    Jensen, Vibeke Myrup; Würtz Rasmussen, Astrid

    to adults continuing education and training stem from administrative education reports. Therefore, for cohorts born 1945-1990, 97 percent of the Danish population has a valid education identifier. For the immigrant population born in the same cohorts the coverage is 85-90 percent. Despite a higher level......Collection of systematic information on education is a long established practice in Denmark. Since 1910, the Danish Ministry of Education’s annual reports collects information about individual-level test scores in e.g. compulsory schooling. Today, several registers from compulsory schooling...

  4. The Danish Education Registers

    DEFF Research Database (Denmark)

    Jensen, Vibeke Myrup; Rasmussen, Astrid Würtz

    2011-01-01

    Collection of systematic information on education is a long established practice in Denmark. Since 1910, the Danish Ministry of Education’s annual reports collects information about individual-level test scores in e.g. compulsory schooling. Today, several registers from compulsory schooling...... to adults continuing education and training stem from administrative education reports. Therefore, for cohorts born 1945-1990, 97 percent of the Danish population has a valid education identifier. For the immigrant population born in the same cohorts the coverage is 85-90 percent. Despite a higher level...

  5. The Danish multiple sclerosis treatment register

    DEFF Research Database (Denmark)

    Magyari, Melinda; Koch-Henriksen, Nils; Sørensen, Per Soelberg

    2016-01-01

    Aim of the database: The Danish Multiple Sclerosis Treatment Register (DMSTR) serves as a clinical quality register, enabling the health authorities to monitor the quality of the diseasemodifying treatment, and it is an important data source for epidemiological research. Study population: The DMSTR...... includes all patients with multiple sclerosis who had been treated with disease-modifying drugs since 1996. At present, more than 8,400 patients have been registered in this database. Data are continuously entered online into a central database from all sites in Denmark at start and at regular visits. Main...... variables: Include age, sex, onset year and year of the diagnosis, basic clinical information, and information about treatment, side effects, and relapses. Descriptive data: Notification is done at treatment start, and thereafter at every scheduled clinical visit 3 months after treatment start...

  6. Improving clinical drug development regulatory procedures for anticonvulsants

    Directory of Open Access Journals (Sweden)

    Janković Slobodan

    2015-01-01

    Full Text Available Background: Clinical development of antiepileptic drugs is demanding due to complex character of the disorder and to diversity of its forms and etiologies. Objective: The aim of this review was to suggest improvements in regulatory procedures for clinical development of antiepileptic drugs. Methods: The following databases of scientific articles were searched: MEDLINE, SCOPUS and SCINDEKS. In total 558 publications were retrieved. The types of articles selected were reviews, reports on clinical trials and letters to the Editor. Results: There are several changes of regulatory documents necessary for improving process of clinical development of antiepileptic drugs: preference of parallel groups design for add-on trials should be explicit; the noninferiority design for monotherapy clinical trials should be acceptable; restrictive formulations when trials of antiepileptic drugs in children are in question should be avoided; requirements in regard to the efficacy measures should be harmonized among the regulatory bodies; proactive attitude towards discovery of adverse events; and precise requirements for clinical trials specifically designed to prove anti-epileptogenic effects should be made clear. Conclusion: Current regulatory documents are incomplete in many aspects; an international effort to improve and harmonize guidelines for clinical development of antiepileptic drugs is necessary for improvement of this process.

  7. Homeostasis or channelopathy? Acquired cell type-specific ion channel changes in temporal lobe epilepsy and their antiepileptic potential

    Science.gov (United States)

    Wolfart, Jakob; Laker, Debora

    2015-01-01

    Neurons continuously adapt the expression and functionality of their ion channels. For example, exposed to chronic excitotoxicity, neurons homeostatically downscale their intrinsic excitability. In contrast, the “acquired channelopathy” hypothesis suggests that proepileptic channel characteristics develop during epilepsy. We review cell type-specific channel alterations under different epileptic conditions and discuss the potential of channels that undergo homeostatic adaptations, as targets for antiepileptic drugs (AEDs). Most of the relevant studies have been performed on temporal lobe epilepsy (TLE), a widespread AED-refractory, focal epilepsy. The TLE patients, who undergo epilepsy surgery, frequently display hippocampal sclerosis (HS), which is associated with degeneration of cornu ammonis subfield 1 pyramidal cells (CA1 PCs). Although the resected human tissue offers insights, controlled data largely stem from animal models simulating different aspects of TLE and other epilepsies. Most of the cell type-specific information is available for CA1 PCs and dentate gyrus granule cells (DG GCs). Between these two cell types, a dichotomy can be observed: while DG GCs acquire properties decreasing the intrinsic excitability (in TLE models and patients with HS), CA1 PCs develop channel characteristics increasing intrinsic excitability (in TLE models without HS only). However, thorough examination of data on these and other cell types reveals the coexistence of protective and permissive intrinsic plasticity within neurons. These mechanisms appear differentially regulated, depending on the cell type and seizure condition. Interestingly, the same channel molecules that are upregulated in DG GCs during HS-related TLE, appear as promising targets for future AEDs and gene therapies. Hence, GCs provide an example of homeostatic ion channel adaptation which can serve as a primer when designing novel anti-epileptic strategies. PMID:26124723

  8. The effects of antiepileptic inducers in neuropsychopharmacology, a neglected issue. Part II: Pharmacological issues and further understanding.

    Science.gov (United States)

    de Leon, Jose

    2015-01-01

    The literature on inducers in epilepsy and bipolar disorder is seriously contaminated by false negative findings. Part II of this comprehensive review on antiepileptic drug (AED) inducers provides clinicians with further educational material about the complexity of interpreting AED drug-drug interactions. The basic pharmacology of induction is reviewed including the cytochrome P450 (CYP) isoenzymes, the Uridine Diphosphate Glucuronosyltransferases (UGTs), and P-glycoprotein (P-gp). CYP2B6 and CYP3A4 are very sensitive to induction. CYP1A2 is moderately sensitive while CYP2C9 and CYP2C19 are only mildly sensitive. CYP2D6 cannot be induced by medications. Induction of UGT and P-gp are poorly understood. The induction of metabolic enzymes such as CYPs and UGTs, and transporters such as P-gp, implies that the amount of these proteins increases when they are induced; this is almost always explained by increasing synthesis mediated by the so-called nuclear receptors (constitutive androstane, estrogen, glucocorticoid receptors and pregnaneX receptors). Although parti provides correction factors for AEDs, extrapolation from an average to an individual patient may be influenced by administration route, absence of metabolic enzyme for genetic reasons, and presence of inhibitors or other inducers. AED pharmacodynamic DDIs may also be important. Six patients with extreme sensitivity to AED inductive effects are described. Copyright © 2014 SEP y SEPB. Published by Elsevier España. All rights reserved.

  9. The effects of antiepileptic inducers in neuropsychopharmacology, a neglected issue. Part I: A summary of the current state for clinicians.

    Science.gov (United States)

    de Leon, Jose

    2015-01-01

    The literature on inducers in epilepsy and bipolar disorder is seriously contaminated by false negative findings. This is part i of a comprehensive review on antiepileptic drug (AED) inducers using both mechanistic pharmacological and evidence-based medicine to provide practical recommendations to neurologists and psychiatrists concerning how to control for them. Carbamazepine, phenobarbital and phenytoin, are clinically relevant AED inducers; correction factors were calculated for studied induced drugs. These correction factors are rough simplifications for orienting clinicians, since there is great variability in the population regarding inductive effects. As new information is published, the correction factors may need to be modified. Some of the correction factors are so high that the drugs (e.g., bupropion, quetiapine or lurasidone) should not co-prescribed with potent inducers. Clobazam, eslicarbazepine, felbamate, lamotrigine, oxcarbazepine, rufinamide, topiramate, vigabatrin and valproic acid are grouped as mild inducers which may (i)be inducers only in high doses; (ii)frequently combine with inhibitory properties; and (iii)take months to reach maximum effects or de-induction, definitively longer than the potent inducers. Potent inducers, definitively, and mild inducers, possibly, have relevant effects in the endogenous metabolism of (i)sexual hormones, (ii) vitamin D, (iii)thyroid hormones, (iv)lipid metabolism, and (v)folic acid. Copyright © 2014 SEP y SEPB. Published by Elsevier España. All rights reserved.

  10. Evaluation of antiepileptic activity of the methanol extract of Trachyspermum ammi (L.

    Directory of Open Access Journals (Sweden)

    Rajput Muhammad Ali

    2013-01-01

    Full Text Available This study aims to investigate the effect of a methanol extract of Trachyspermum ammi (L. as an antiepileptic agent. Tests were conducted with a single- and multiple-dosing schedule of Trachyspermum ammi (L., using a strychnine-induced seizure model for epilepsy. Twenty-one animals were divided into three groups; control (vehicle, standard (diazepam and test (Trachyspermum ammi (L. extract. Trachyspermum ammi (L. demonstrated antiepileptic effects, since there was a highly significant delay in the onset of convulsions as compared to the control, whereas the percentage of animals that survived or ignored seizure was also greater compared to the control. However, the duration of convulsions was significantly increased with both Trachyspermum ammi (L. and diazepam as compared to the control. The methanol extract of Trachyspermum ammi (L. showed antiepileptic activity, which may be due to the presence of thymol.

  11. [Psychoactive drugs and costs in the Madrid III (Valdemoro) prison].

    Science.gov (United States)

    Algora-Donoso, I; Varela-González, O

    2008-01-01

    Annual pharmaceutical expenditures in prisons increases dramatically and the rising costs of psychoactive drugs have especially contributed to this. These drugs are often prescribed in order to find therapeutic uses in the field of personality disorders, addictions, and dysfunctional behaviours that are not included in the authorized indications (compassionate use). This study has enabled a detailed description of the use of psychoactive drugs at the Madrid III prison, a centre with one of the lowest levels of pharmaceutical expenditure in this autonomous community. During a two-week period, all prescriptions of psychoactive drugs were collected and registered along with data of several possible conditioning factors. 20.5% of the population was receiving some kind of psychoactive drug; 76% of those inmates undergoing treatment were receiving one or two substances; 65% were taking anxiolytics, 38% antidepressants and 27% antipsychotics. The total amount of psychoactive drugs consumed was 9,840 defined daily doses, 46% of which were anxiolytics, 17% antidepressants and 14% antipsychotics. The total cost of the fortnight's treatment was euros 5,379 with a saving of euro 611 due to requesting and selecting offers carried out by the pharmacist. 72% of the costs were spent on anti-psychotics and the newer psychoactive drugs, representing 66% of the prescriptions, accounted for 98% of expenditure. The prescriber was one of the key influential factors over the amount, type and cost of the treatments. There are signs that compassionate use of current antipsychotics and antiepileptics, and newer antidepressants are a main cause of the dramatic increase in the costs, with cost-efficiency not always clearly demonstrated. These results are not an isolated fact restricted only to prisons, as demonstrated by consumption data published by the National Health System in the same year.

  12. Catalog of 199 register-based definitions of chronic conditions

    DEFF Research Database (Denmark)

    Hvidberg, Michael F; Johnsen, Søren P; Glümer, Charlotte

    2016-01-01

    INTRODUCTION: The aim of the current study was to present and discuss a broad range of register-based definitions of chronic conditions for use in register research, as well as the challenges and pitfalls when defining chronic conditions by the use of registers. MATERIALS AND METHODS: The definit......INTRODUCTION: The aim of the current study was to present and discuss a broad range of register-based definitions of chronic conditions for use in register research, as well as the challenges and pitfalls when defining chronic conditions by the use of registers. MATERIALS AND METHODS......: The definitions were defined based on information from nationwide Danish public healthcare registers. Medical and epidemiological specialists identified and grouped relevant diagnosis codes that covered chronic conditions, using the International Classification System version 10 (ICD-10). Where relevant...... definitions were proposed based on record linkage between multiple registers, including registers of prescribed drugs and use of general practitioners' services. CONCLUSIONS THIS STUDY PROVIDED A CATALOG OF REGISTER-BASED DEFINITIONS FOR CHRONIC CONDITIONS FOR USE IN HEALTHCARE PLANNING AND RESEARCH, WHICH IS...

  13. Portable shift register

    International Nuclear Information System (INIS)

    Halbig, J.K.; Bourret, S.C.; Hansen, W.J.; Hicks, D.V.; Klosterbuer, S.F.; Krick, M.S.

    1994-01-01

    An electronics package for a small, battery-operated, self-contained, neutron coincidence counter based on a portable shift-register (PSR) has been developed. The counter was developed for applications not adequately addressed by commercial packages, including in-plant measurements to demonstrate compliance with regulations (domestic and international), in-plant process control, and in-field measurements (environmental monitoring or safeguards). Our package's features, which address these applications, include the following: Small size for portability and ease of installation;battery or mains operation; a built-in battery to power the unit and a typical detector such as a small sample counter, for over 6 h if power lines are bad or noisy, if there is a temporary absence of power, or if portability is desired; complete support, including bias, for standard neutron detectors; a powerful communications package to easily facilitate robust external control over a serial port; and a C-library to simplify creating external control programs in computers or other controllers. Whereas the PSR specifically addresses the applications mentioned above, it also performs all the measurements made by previous electronics packages for neutron coincidence counters developed at Los Alamos and commercialized. The PSR electronics package, exclusive of carrying handle, is 8 by 10 by 20 cm; it contains the circuit boards, battery, and bias supply and weighs less than 2 kg. This instrument package is the second in an emerging family of portable measurement instruments being developed; the first was the Miniature and Modular Multichannel Analyzer (M 3 CA). The PSR makes extensive use of hardware and software developed for the M 3 CA; like the M 3 CA, it is intended primarily for use with an external controller interfaced over a serial channel

  14. The Danish Hip Arthroplasty Register

    DEFF Research Database (Denmark)

    Gundtoft, Per Hviid; Varnum, Claus; Pedersen, Alma Becic

    2016-01-01

    AIM OF DATABASE: The aim of the Danish Hip Arthroplasty Register (DHR) is to continuously monitor and improve the quality of treatment of primary and revision total hip arthroplasty (THA) in Denmark. STUDY POPULATION: The DHR is a Danish nationwide arthroplasty register established in January 1995...

  15. Possible drug-drug interaction between pregabalin and clozapine in patients with schizophrenia

    DEFF Research Database (Denmark)

    Schjerning, O; Lykkegaard, S; Damkier, P

    2015-01-01

    INTRODUCTION: Pregabalin is an antiepileptic drug with anti-anxiety properties and is approved for treatment of generalized anxiety disorder. Anxiety is common in patients with schizophrenia and pregabalin has been suggested as an off-label add-on treatment. METHODS: Pregabalin was added...... patient was less clear. DISCUSSION: This short report discusses the possible mechanism of a pregabalin-clozapine interaction....

  16. New avenue in the treatment of temporal lobe epilepsy by classical anti-epileptics: A hypothetical establishment of executioner Caspase 3 inactivation by molecular modeling

    Directory of Open Access Journals (Sweden)

    M Vijey Aanandhi

    2015-01-01

    Full Text Available Patients with temporal lobe epilepsy (TLE are prescribed first-line antiepileptic drugs and surgery to the management of this disorder. Unfortunately, the surgical treatment has been shown to be beneficial for the selected patients but fails to provide a seizure-free outcome in 20-30% of TLE patients. In our present study, we investigate the possibilities of marketed antiepileptic drugs in a different manner to improve the present situation in TLE. Molecular docking simulation study and various open source computational tools were used to perform the study. AutoDock 4.2 MGL tools, Pymol visualize tools, Patch dock server, and Swarm Dock servers (protein-protein docking were used to perform the molecular modeling. FTsite and computed atlas of surface topography of protein open source server were used to understand the pocket and ligand binding information respectively. Toxtree application was used to determine the toxicity profile of the drug by Cramers rule. The obtained molecular docking models (Caspase 3, Procaspase 8, and Fas-associated death domain [FADD] with selected compounds (Clonazepam, Clobazepam, and Retigabine showed promising trio blocking event of FADD, Caspase 3, and Procaspase 8 (−6.66 kcal, −8.1 kcal, 6.46 kcal by Clonazepam respectively. Protein-protein interaction study (Swarm Dock, Patch Dock server indicated promising results that helped to establish our hypothesis. Toxtree showed a quantitative structure toxicity relationship report that helps to clarify the toxicity of the selected compounds. Clonazepam showed a trio inhibition property that may lead to develop a new era of the new generation benzodiazepine prototype drugs in the future. Filtered compounds will further process for higher in vitro, in vivo models for better understanding of the mechanism.

  17. Is primary prevention with antiepileptic drugs effective in brain tumors or brain metastases?

    Directory of Open Access Journals (Sweden)

    Diego Lobos-Urbina

    2017-03-01

    Full Text Available Resumen Los pacientes con tumores cerebrales, primarios o metastásicos, presentan riego de desarrollar convulsiones durante la evolución de su enfermedad, por lo que se ha propuesto el uso profiláctico de anticonvulsivantes. Sin embargo, el efecto de esta intervención no está claro. Para responder esta pregunta utilizamos la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en múltiples bases de datos. Identificamos 12 revisiones sistemáticas que en conjunto incluyen ochenta estudios primarios. Doce corresponden a estudios aleatorizados, pero sólo dos responden la pregunta de interés. Extrajimos los datos, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. Concluimos que la prevención primaria con anticonvulsivantes podría no disminuir el riesgo de convulsiones en tumores o metástasis cerebrales, y se asocia a efectos adversos frecuentes.

  18. Antiepileptic drugs-induced hyponatremia: Review and analysis of 560 hospitalized patients.

    Science.gov (United States)

    Intravooth, Tassanai; Staack, Anke M; Juerges, Katharina; Stockinger, Jakob; Steinhoff, Bernhard J

    2018-07-01

    Recent evidence suggests that eslicarbazepine acetate (ESL) might be an appropriate alternative to carbamazepine (CBZ) and oxcarbazepine (OXC) due to its better safety profile. Hyponatremia may be one of the limiting safety problems in CBZ and OXC whereas it has been indicated that ESL is less sensitive for the adverse event. Since our clinical experience is different we investigated the incidence of hyponatremia in 560 consecutive adult inpatients treated at our center in 2015 by reviewing their medical records. Only CBZ, OXC and ESL were associated with hyponatremia. The incidence of hyponatremia induced by ESL was not statistically different from that induced by OXC (43% of patients with OXC and 33% with ESL, p > 0.05). Both were associated with hyponatremia more often than CBZ (16%). OXC-induced hyponatremia was dose-related, ESL-induced hyponatremia was not. Furthermore, both OXC- and ESL-induced hyponatremia occurred particularly often in elderly epilepsy patients. Thus, for elderly patients, both OXC and ESL should be considered with caution. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Bone mineral density in adult patients treated with various antiepileptic drugs

    DEFF Research Database (Denmark)

    Beniczky, Simona Alexandra; Viken, Janina; Jensen, Lars Thorbjørn

    2012-01-01

    adult consecutive outpatients treated with AEDs for more than 2 years, and who underwent measurement of the BMD. We compared the incidence of decreased BMD among the patients treated with 6 different AEDs: carbamazepine (CBZ), oxcarbazepine (OXC), valproic acid (VPA), lamotrigine (LTG), topiramate (TPM...

  20. A Drosophila systems model of pentylenetetrazole induced locomotor plasticity responsive to antiepileptic drugs

    Directory of Open Access Journals (Sweden)

    Singh Priyanka

    2009-01-01

    Full Text Available Abstract Background Rodent kindling induced by PTZ is a widely used model of epileptogenesis and AED testing. Overlapping pathophysiological mechanisms may underlie epileptogenesis and other neuropsychiatric conditions. Besides epilepsy, AEDs are widely used in treating various neuropsychiatric disorders. Mechanisms of AEDs' long term action in these disorders are poorly understood. We describe here a Drosophila systems model of PTZ induced locomotor plasticity that is responsive to AEDs. Results We empirically determined a regime in which seven days of PTZ treatment and seven days of subsequent PTZ discontinuation respectively cause a decrease and an increase in climbing speed of Drosophila adults. Concomitant treatment with NaVP and LEV, not ETH, GBP and VGB, suppressed the development of locomotor deficit at the end of chronic PTZ phase. Concomitant LEV also ameliorated locomotor alteration that develops after PTZ withdrawal. Time series of microarray expression profiles of heads of flies treated with PTZ for 12 hrs (beginning phase, two days (latent phase and seven days (behaviorally expressive phase showed only down-, not up-, regulation of genes; expression of 23, 2439 and 265 genes were downregulated, in that order. GO biological process enrichment analysis showed downregulation of transcription, neuron morphogenesis during differentiation, synaptic transmission, regulation of neurotransmitter levels, neurogenesis, axonogenesis, protein modification, axon guidance, actin filament organization etc. in the latent phase and of glutamate metabolism, cell communication etc. in the expressive phase. Proteomic interactome based analysis provided further directionality to these events. Pathway overrepresentation analysis showed enrichment of Wnt signaling and other associated pathways in genes downregulated by PTZ. Mining of available transcriptomic and proteomic data pertaining to established rodent models of epilepsy and human epileptic patients showed overrepresentation of epilepsy associated genes in our PTZ regulated set. Conclusion Systems biology ultimately aims at delineating and comprehending the functioning of complex biological systems in such details that predictive models of human diseases could be developed. Due to immense complexity of higher organisms, systems biology approaches are however currently focused on simpler organisms. Amenable to modeling, our model offers a unique opportunity to further dissect epileptogenesis-like plasticity and to unravel mechanisms of long-term action of AEDs relevant in neuropsychiatric disorders.

  1. Huperzine A as a neuroprotective and antiepileptic drug: a review of preclinical research.

    Science.gov (United States)

    Damar, U; Gersner, R; Johnstone, J T; Schachter, S; Rotenberg, A

    2016-06-01

    Huperzine A (HupA) is an acetylcholinesterase (AChE) inhibitor extracted from Huperzia Serrata, a firmoss, which has been used for various diseases in traditional Chinese medicine for fever and inflammation. More recently, it has been used in Alzheimer's disease and other forms of dementia with a presumed mechanism of action via central nicotinic and muscarinic receptors. HupA is marketed as a dietary supplement in the U.S. This article reviews newly proposed neuroprotective and anticonvulsant HupA properties based on animal studies. HupA exerts its effects mainly via α7nAChRs and α4β2nAChRs, thereby producing a potent anti-inflammatory response by decreasing IL-1β, TNF-α protein expression, and suppressing transcriptional activation of NF-κB signaling. Thus, it provides protection from excitotoxicity and neuronal death as well as increase in GABAergic transmission associated with anticonvulsant activity.

  2. Use of antiepileptic drugs during pregnancy and risk of spontaneous abortion and stillbirth

    DEFF Research Database (Denmark)

    Bech, Bodil Hammer; Kjaersgaard, Maiken Ina Siegismund; Pedersen, Henrik Søndergaard

    2014-01-01

    Dette studie undersøger, om brugen af antiepileptika under graviditeten kan øge risikoen for spontan abort eller dødfødsel. Resultaterne viser, at 16 ud af 100 gravide kvinder, som brugte antiepileptika, mistede fostret ved en spontan abort, mens det kun var 13 ud af 100 gravide kvinder, som ikke...

  3. Registering Researchers in Authority Files

    NARCIS (Netherlands)

    Altman, M.; Conlon, M.; Cristan, A.L.; Dawson, L.; Dunham, J.; Hickey, T.; Hook, D.; Horstmann, W.; MacEwan, A.; Schreur, P.; Smart, L.; Smith-Yoshimura, K.; Wacker, M.; Woutersen, S.

    2014-01-01

    Registering researchers in some type of authority file or identifier system has become more compelling as both institutions and researchers recognize the need to compile their scholarly output. The report presents functional requirements and recommendations for six stakeholders: researchers,

  4. Relating timed and register automata

    Directory of Open Access Journals (Sweden)

    Diego Figueira

    2010-11-01

    Full Text Available Timed automata and register automata are well-known models of computation over timed and data words respectively. The former has clocks that allow to test the lapse of time between two events, whilst the latter includes registers that can store data values for later comparison. Although these two models behave in appearance differently, several decision problems have the same (undecidability and complexity results for both models. As a prominent example, emptiness is decidable for alternating automata with one clock or register, both with non-primitive recursive complexity. This is not by chance. This work confirms that there is indeed a tight relationship between the two models. We show that a run of a timed automaton can be simulated by a register automaton, and conversely that a run of a register automaton can be simulated by a timed automaton. Our results allow to transfer complexity and decidability results back and forth between these two kinds of models. We justify the usefulness of these reductions by obtaining new results on register automata.

  5. Patients' perspectives on antiepileptic medication: relationships between beliefs about medicines and adherence among patients with epilepsy in UK primary care.

    Science.gov (United States)

    Chapman, S C E; Horne, R; Chater, A; Hukins, D; Smithson, W H

    2014-02-01

    Nonadherence to antiepileptic drugs (AEDs) can result in suboptimal outcomes for patients. This study aimed to assess the utility of a theory-based approach to understanding patient perspectives on AEDs and adherence. Patients with epilepsy, identified by a GP case note review, were mailed validated questionnaires assessing their perceptions of AEDs and their adherence to them. Most (84.9%) of the 398 AED-treated respondents accepted the necessity of AEDs, but over half expressed doubts, with 55% disagreeing or uncertain about the statement 'I would prefer to take epilepsy medication than risk a seizure'. Over a third (36.4%) expressed strong concerns about the potential negative effects of AEDs. We used self-report and medication possession ratio to classify 36.4% of patients as nonadherent. Nonadherence was related to beliefs about medicines and implicit attitudes toward AEDs (pbeliefs about pharmaceuticals (BMQ General: General Harm, General Overuse, and General Benefit scales) and perceptions of personal sensitivity to medicines (PSM scale). We identified salient, adherence-related beliefs about AEDs. Patient-centered interventions to support medicine optimization for people with epilepsy should take account of these beliefs. © 2013.

  6. Register

    African Journals Online (AJOL)

    Denotes required field. Privacy Statement. The names and email addresses entered here will be used exclusively for the stated purposes of AJOL. We take your privacy seriously and we protect your personal information, which will not be made available for any other purpose or to any other party. AJOL African Journals ...

  7. Register

    African Journals Online (AJOL)

    Form Language. English, Français. To enter the information below in additional languages, first select the language. Username *. The username must contain only lowercase letters, numbers, and hyphens/underscores. Password *. The password must be at least 6 characters. Repeat password *. Salutation. First Name *.

  8. The Danish Medical Birth Register

    DEFF Research Database (Denmark)

    Bliddal, Mette; Broe, Anne; Pottegård, Anton

    2018-01-01

    The Danish Medical Birth Register was established in 1973. It is a key component of the Danish health information system. The register enables monitoring of the health of pregnant women and their offspring, it provides data for quality assessment of the perinatal care in Denmark, and it is used...... on all births in Denmark and comprises primarily of data from the Danish National Patient Registry supplemented with forms on home deliveries and stillbirths. It contains information on maternal age provided by the Civil Registration System. Information on pre-pregnancy body mass index and smoking...

  9. Danish registers on aspects of reproduction

    DEFF Research Database (Denmark)

    Blenstrup, Lene Tølbøll; Knudsen, Lisbeth B.

    2011-01-01

    Introduction: The establishing of three Danish population based registers, namely the Fertility Database, the Register of Legally Induced Abortions and the In Vitro Fertilisation register aimed at providing data for surveying of reproductive outcome. Content: The registers include information...... on births, abortions and assisted reproduction as well as selected characteristics of the women (and men) involved. Validity and Coverage: Both the validity and coverage of each register is considered of high quality. Conclusions: These registers provide, both individually and in combination, unique...

  10. Drug taper during long-term video-EEG monitoring

    DEFF Research Database (Denmark)

    Guld, A. T.; Sabers, A.; Kjaer, T. W.

    2017-01-01

    Objectives: Anti-epileptic drugs (AED) are often tapered to reduce the time needed to record a sufficient number of seizure during long-term video-EEG monitoring (LTM). Fast AED reduction is considered less safe, but few studies have examined this. Our goal is to examine whether the rate of AED r...

  11. The Pediatric Cataract Register (PECARE)

    DEFF Research Database (Denmark)

    Haargaard, Birgitte; Nyström, Alf; Rosensvärd, Annika

    2015-01-01

    examination with a pencil light at age 5 weeks, whereas newborn red reflex examination using a handheld ophthalmoscope is routine protocol in Swedish maternity wards. Data regarding age of referral were derived from the Pediatric Cataract Register (PECARE). All children operated on before 1 year of age...

  12. Are Local Registers the Solution?

    NARCIS (Netherlands)

    Baldwin, R.; English, C.; Lemmen, C.H.J.; Rose, I.; Smith, A.; Solovov, A.; Sullivan, T.

    2018-01-01

    This paper explores the possibility of using local registers to manage and update land rights. Secure land rights are largely taken for granted in the developed world. Yet for many people in developing nations, clear and enforceable land rights are not a reality. In the developed world, land rights

  13. Signaling to P-glycoprotein-A new therapeutic target to treat drug-resistant epilepsy?

    NARCIS (Netherlands)

    Hartz, A.M.; Notenboom, S.; Bauer, B.

    2009-01-01

    Epilepsy affects more than 60 million people worldwide. While most patients can be treated with antiepileptic drugs, up to 40% of patients respond poorly to pharmacotherapy. This drug resistance is not well understood and presents a major clinical problem. In this short review we provide background

  14. The Danish Multiple Sclerosis Treatment Register

    Directory of Open Access Journals (Sweden)

    Magyari M

    2016-10-01

    Full Text Available Melinda Magyari,1,3 Nils Koch-Henriksen,1,2 Per Soelberg Sørensen3 1Danish Multiple Sclerosis Registry, Department of Neurology, Rigshospitalet, Copenhagen, 2Department of Clinical Epidemiology, Clinical Institute, University of Aarhus, Aarhus, 3Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Aim of the database: The Danish Multiple Sclerosis Treatment Register (DMSTR serves as a clinical quality register, enabling the health authorities to monitor the quality of the disease-modifying treatment, and it is an important data source for epidemiological research. Study population: The DMSTR includes all patients with multiple sclerosis who had been treated with disease-modifying drugs since 1996. At present, more than 8,400 patients have been registered in this database. Data are continuously entered online into a central database from all sites in Denmark at start and at regular visits. Main variables: Include age, sex, onset year and year of the diagnosis, basic clinical information, and information about treatment, side effects, and relapses. Descriptive data: Notification is done at treatment start, and thereafter at every scheduled clinical visit 3 months after treatment start, and thereafter every 6 months. The longitudinally collected information about the disease activity and side effects made it possible to investigate the clinical efficacy and adverse events of different disease-modifying therapies. Conclusion: The database contributed to a certain harmonization of treatment procedures in Denmark and will continue to be a major factor in terms of quality in clinical praxis, research and monitoring of adverse events, and plays an important role in research. Keywords: multiple sclerosis, epidemiology, immunomodulatory treatment, neutralizing antibodies, observational studies, registry research, disease modifying therapy

  15. The Copenhagen School Health Records Register

    DEFF Research Database (Denmark)

    Baker, Jennifer L; Sørensen, Thorkild I A

    2011-01-01

    The Copenhagen School Health Records Register is an electronic register of health examination information on 372,636 children who attended school in Copenhagen, Denmark from 1936 to 2005.......The Copenhagen School Health Records Register is an electronic register of health examination information on 372,636 children who attended school in Copenhagen, Denmark from 1936 to 2005....

  16. ANTICONVULSANT AND ANTIEPILEPTIC ACTIONS OF 2-DEOXY-DGLUCOSE IN EPILEPSY MODELS

    Science.gov (United States)

    Stafstrom, Carl E.; Ockuly, Jeffrey C.; Murphree, Lauren; Valley, Matthew T.; Roopra, Avtar; Sutula, Thomas P.

    2009-01-01

    Objective Conventional anticonvulsants reduce neuronal excitability through effects on ion channels and synaptic function. Anticonvulsant mechanisms of the ketogenic diet remain incompletely understood. Since carbohydrates are restricted in patients on the ketogenic diet, we evaluated the effects of limiting carbohydrate availability by reducing glycolysis using the glycolytic inhibitor 2-deoxy-D-glucose (2DG) in experimental models of seizures and epilepsy. Methods Acute anticonvulsant actions of 2DG were assessed in vitro in rat hippocampal slices perfused with 7.5mM [K+]o, 4-aminopyridine (4-AP), or bicuculline and in vivo against seizures evoked by 6 Hz stimulation in mice, audiogenic stimulation in Fring’s mice, and maximal electroshock and subcutaneous Metrazol in rats. Chronic antiepileptic effects of 2DG were evaluated in rats kindled from olfactory bulb or perforant path. Results 2DG (10mM) reduced interictal epileptiform bursts induced by high [K+]o, 4-AP and bicuculline, and electrographic seizures induced by high [K+]o in CA3 of hippocampus. 2DG reduced seizures evoked by 6 Hz stimulation in mice (ED50 = 79.7 mg/kg) and audiogenic stimulation in Fring’s mice (ED50 = 206.4 mg/kg). 2DG exerted chronic antiepileptic action by increasing afterdischarge thresholds in perforant path (but not olfactory bulb) kindling and caused a 2-fold slowing in progression of kindled seizures at both stimulation sites. 2DG did not protect against maximal electroshock or Metrazol seizures. Interpretation The glycolytic inhibitor 2DG exerts acute anticonvulsant and chronic antiepileptic actions and has a novel pattern of effectiveness in preclinical screening models. These results identify metabolic regulation as a potential therapeutic target for seizure suppression and modification of epileptogenesis. PMID:19399874

  17. National register of research projects

    Energy Technology Data Exchange (ETDEWEB)

    1985-03-01

    This Register is intended to serve as a source of information on research which is being conducted in all fields (both natural and human sciences) in the Republic of South Africa. New research projects commenced during 1983 or 1984, and significantly changed research projects, as well as project that were completed or terminated during this period, on which information was received by the compilers before December 1984, are included, with the exception of confidential projects.

  18. VISUALIZATION OF REGISTERED SUBSURFACE ANATOMY

    DEFF Research Database (Denmark)

    2010-01-01

    A system and method for visualization of subsurface anatomy includes obtaining a first image from a first camera and a second image from a second camera or a second channel of the first camera, where the first and second images contain shared anatomical structures. The second camera and the secon....... A visual interface displays the registered visualization of the first and second images. The system and method are particularly useful for imaging during minimally invasive surgery, such as robotic surgery....

  19. Use of opium as antiepileptic in patient with frontal lobe epilepsy: A case report

    Directory of Open Access Journals (Sweden)

    Naresh Nebhinani

    2015-01-01

    Full Text Available Frontal lobe epilepsy (FLE manifests with brief, nocturnal seizures arising in the frontal lobe along with unusual behavioral symptoms or postures, frequently misdiagnosed as a psychogenic nonepileptic seizure (PNES or a sleep disorder. Ancient literature has rarely mentioned the antiepileptic effect of opium or different opioids. Here we are presenting a case with FLE, though initially diagnosed PNES, who had significant relief in his symptoms on using opium, and this led to opium dependence. Index case further emphasizes concern and caution as misdiagnosis of FLE may lead to substance dependenc.

  20. Drug Establishments Current Registration Site

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Drug Establishments Current Registration Site (DECRS) is a database of current information submitted by drug firms to register establishments (facilities) which...

  1. CNS Depressant and Antiepileptic Activities of the Methanol Extract of the Leaves of Ipomoea Aquatica Forsk

    Directory of Open Access Journals (Sweden)

    Dhanasekaran Sivaraman

    2010-01-01

    Full Text Available The central nervous system (CNS depressant and antiepileptic activities of the methanol extract of the leaves of Ipomoea aquatica Forsk (IAF were investigated on various animal models including pentobarbitone sleeping time and hole-board exploratory behavior for sedation tests and strychnine, picrotoxin and pentylenetetrazole-induced convulsions in mice. IAF (200 and 400 mg/kg, p.o., like chlorpromazine HCl (1 mg/kg, i.m., produced a dose-dependent prolongation of pentobarbitone sleeping time and suppression of exploratory behavior. IAF (200 and 400 mg/kg produced dose-dependent and significant increases in onset to clonic and tonic convulsions and at 400 mg/kg, showed complete protection against seizures induced by strychnine and picrotoxin but not with pentylenetetrazole. Acute oral toxicity test, up to 14 days, did not produce any visible signs of toxicity. These results suggest that potentially antiepileptic compounds are present in leaf extract of IAF that deserve the study of their identity and mechanism of action.

  2. Effects of Various Antiepileptics Used to Alleviate Neuropathic Pain on Compound Action Potential in Frog Sciatic Nerves: Comparison with Those of Local Anesthetics

    Directory of Open Access Journals (Sweden)

    Yuhei Uemura

    2014-01-01

    Full Text Available Antiepileptics used for treating neuropathic pain have various actions including voltage-gated Na+ and Ca2+ channels, glutamate-receptor inhibition, and GABAA-receptor activation, while local anesthetics are also used to alleviate the pain. It has not been fully examined yet how nerve conduction inhibitions by local anesthetics differ in extent from those by antiepileptics. Fast-conducting compound action potentials (CAPs were recorded from frog sciatic nerve fibers by using the air-gap method. Antiepileptics (lamotrigine and carbamazepine concentration dependently reduced the peak amplitude of the CAP (IC50=0.44 and 0.50 mM, resp.. Carbamazepine analog oxcarbazepine exhibited an inhibition smaller than that of carbamazepine. Antiepileptic phenytoin (0.1 mM reduced CAP amplitude by 15%. On the other hand, other antiepileptics (gabapentin, sodium valproate, and topiramate at 10 mM had no effect on CAPs. The CAPs were inhibited by local anesthetic levobupivacaine (IC50=0.23 mM. These results indicate that there is a difference in the extent of nerve conduction inhibition among antiepileptics and that some antiepileptics inhibit nerve conduction with an efficacy similar to that of levobupivacaine or to those of other local anesthetics (lidocaine, ropivacaine, and cocaine as reported previously. This may serve to know a contribution of nerve conduction inhibition in the antinociception by antiepileptics.

  3. Association between C3435T polymorphism of MDR1 gene and the incidence of drug-resistant epilepsy in the population of Polish children.

    Science.gov (United States)

    Stasiołek, Mariusz; Romanowicz, Hanna; Połatyńska, Katarzyna; Chamielec, Maciej; Skalski, Dominik; Makowska, Marianna; Smolarz, Beata

    2016-07-08

    Epilepsy is a disease of neurological character. Approximately one third of epileptic patients demonstrate a drug-resistant phenotype, which is associated with the development of drug-resistant epilepsy. The multidrug resistance protein 1 and glycoprotein P, encoded by MDR1, play a significant role in the transmembrane transport of anti-epileptic agents. Single nucleotide polymorphism C3435T (rs1045642) within MDR1 gene may be associated with an increased expression of P-gp which affects the levels of antiepileptic drugs in plasma. The presented studies analysed the association between C3435T polymorphism of MDR1 gene and the incidence of drug-resistant epilepsy in the population of Polish children. C3435T polymorphism of MDR1 gene was analysed by the high resolution melting technique in a group of patients with drug-resistant (n = 106) and drug-responsive epilepsy (n = 67), as well as in non-epileptic children (n = 98) hospitalised at the Department of Neurology, Polish Mother's Memorial Hospital in Lodz. Genotype and allele distributions were evaluated and their compatibility with the Hardy-Weinberg distribution was assessed by means of the χ(2) test. Genotype and allele evaluation, regarding their relationship with a given feature, was supported by an analysis of odds ratio and 95 % confidence interval, calculated according to the logistic regression model. An association was observed between the incidence rate of DRE and the presence of C allele in C3435T polymorphism of MDR1 gene, which may enhance the risk of the disease. The T allele may then play a protective role. No differences were found in the studied groups, regarding either genotype or allele distribution in reference to patient's gender or concomitant diseases. Following the obtained results, C3435T polymorphism of MDR1 gene may be connected with the incidence of drug-resistant epilepsy in the population of Polish children. ISRCTN ISRCTN73824458. Registered 28th September 2014.

  4. Effect and Safety of Shihogyejitang for Drug Resistant Childhood Epilepsy

    Directory of Open Access Journals (Sweden)

    Jinsoo Lee

    2016-01-01

    Full Text Available Objective. Herbal medicine has been widely used to treat drug resistant epilepsy. Shihogyejitang (SGT has been commonly used to treat epilepsy. We investigated the effect and safety of SGT in children with drug resistant epilepsy. Design. We reviewed medical records of 54 patients with epilepsy, who failed to respond to at least two antiepileptic drugs and have been treated with SGT between April 2006 and June 2014 at the Department of Pediatric Neurology, I-Tomato Hospital, Korea. Effect was measured by the response rate, seizure-free rate, and retention rate at six months. We also checked adverse events, change in antiepileptic drugs use, and the variables related to the outcome. Results. Intent-to-treat analysis showed that, after six months, 44.4% showed a >50% seizure reduction, 24.1% including seizure-free, respectively, and 53.7% remained on SGT. Two adverse events were reported, mild skin rash and fever. Focal seizure type presented significantly more positive responses when compared with other seizure types at six months (p=0.0284, Fisher’s exact test. Conclusion. SGT is an effective treatment with excellent tolerability for drug resistant epilepsy patients. Our data provide evidence that SGT may be used as alternative treatment option when antiepileptic drug does not work in epilepsy children.

  5. Wavefunctions for topological quantum registers

    International Nuclear Information System (INIS)

    Ardonne, E.; Schoutens, K.

    2007-01-01

    We present explicit wavefunctions for quasi-hole excitations over a variety of non-abelian quantum Hall states: the Read-Rezayi states with k ≥ 3 clustering properties and a paired spin-singlet quantum Hall state. Quasi-holes over these states constitute a topological quantum register, which can be addressed by braiding quasi-holes. We obtain the braid properties by direct inspection of the quasi-hole wavefunctions. We establish that the braid properties for the paired spin-singlet state are those of 'Fibonacci anyons', and thus suitable for universal quantum computation. Our derivations in this paper rely on explicit computations in the parafermionic conformal field theories that underly these particular quantum Hall states

  6. Molecular Docking Study, Green Synthesis and Pharmacological Evaluation of 1,3,4-thiadiazole Derivatives as Potential Antiepileptic Agents

    Czech Academy of Sciences Publication Activity Database

    Sahoo, B. M.; Dinda, S. C.; Kumar, B. V. V. R.; Panda, J. R.; Brahmkshatriya, Pathik

    2013-01-01

    Roč. 13, č. 14 (2013), s. 2076-2081 ISSN 1389-5575 Institutional support: RVO:61388963 Keywords : antiepileptic activity * docking study * epilepsy * green synthesis * neurotoxicity * thiadiazole Subject RIV: CC - Organic Chemistry Impact factor: 3.186, year: 2013

  7. New Treatments for Drug-Resistant Epilepsy that Target Presynaptic Transmitter Release

    Science.gov (United States)

    2015-07-01

    may become a key piece in the arsenal of antiepileptic drugs in mesial temporal lobe epilepsy . Thereby, screening for a presynaptic action site may be...neuronal damage, mesial temporal lobe epilepsy (MTLE) in ~30% of patients, and resistance to available anticonvulsant drugs. Therefore, it is of... temporal lobe epilepsy (MTLE) (months 1-12). Working hypothesis: Drugs acting on presynaptic Ca 2+ channels, autoreceptors, and SV2a will be more

  8. Building a population-based diabetes register: an Italian experience.

    Science.gov (United States)

    Ballotari, Paola; Chiatamone Ranieri, Sofia; Vicentini, Massimo; Caroli, Stefania; Gardini, Andrea; Rodolfi, Rossella; Crucco, Roberto; Greci, Marina; Manicardi, Valeria; Giorgi Rossi, Paolo

    2014-01-01

    To describe the methodology used to set up the Reggio Emilia (northern Italy) Diabetes Register. The prevalence estimates on December 31st, 2009 are also provided. The Diabetes Register covers all residents in the Reggio Emilia province. The register was created by deterministic linkage of six routinely collected data sources through a definite algorithm able to ascertain cases and to distinguish type of diabetes and model of care: Hospital Discharge, Drug Dispensation, Biochemistry Laboratory, Disease-specific Exemption, Diabetes Outpatient Clinics, and Mortality databases. Using these data, we estimated crude prevalence on December 31st, 2009 by sex, age groups, and type of diabetes. There were 25,425 ascertained prevalent cases on December 31st, 2009. Drug Dispensation and Exemption databases made the greatest contribution to prevalence. Analyzing overlapping sources, more than 80% of cases were reported by at least two sources. Crude prevalence was 4.8% and 5.9% for the whole population and for people aged 18 years and over, respectively. Males accounted for 53.6%. Type 1 diabetes accounted for 3.8% of cases, while people with Type 2 diabetes were the overriding majority (91.2%), and Diabetes Outpatient Clinics treated 75.4% of people with Type 2 diabetes. The Register is able to quantify the burden of disease, the first step in planning, implementing, and monitoring appropriate interventions. All data sources contributed to completeness and/or accuracy of the Register. Although all cases are identified by deterministic record linkage, manual revision and General Practitioner involvement are still necessary when information is insufficient or conflicting. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  9. Pollutant Release and Transfer Register

    International Nuclear Information System (INIS)

    2008-01-01

    Since 1974 a number of organisations have been working closely together in this pollutant register (PRTR) project to collect and formally establish the yearly releases of pollutants to air, water and soil in the Netherlands. Results of this project serve to underpin the national environmental policy. Data is in this way also provided for the many environmental reports to international organisations such as the European Union and the United Nations, e.g. the National Inventory Report for the Kyoto Protocol. This website shows the yearly releases (emissions) of the most important pollutants in the Netherlands. You can explore the emission data through various channels, such as maps, graphs and tables. But you can also download all the details into your own database. The data shown in this website is updated 2 to 3 times a year. The current release shows emissions for 1990, 1995, 2000, 2004, 2005 and 2006 The 2006 emissions are preliminary data and not yet shown in the maps. We expect to add an extra year in August 2008 [nl

  10. Evaluating subjective cognitive impairment in the adult epilepsy clinic: Effects of depression, number of antiepileptic medications, and seizure frequency.

    Science.gov (United States)

    Feldman, Lauren; Lapin, Brittany; Busch, Robyn M; Bautista, Jocelyn F

    2018-04-01

    Subjective cognitive complaints are a frequent concern of patients with epilepsy. The Aldenkamp-Baker Neuropsychological Assessment Schedule (ABNAS) is a patient-reported scale validated to measure adverse cognitive effects of antiepileptic drugs (AEDs). The goals of this study were to identify predictors of patient-reported cognitive dysfunction and to assess the relationship between subjective and objective cognitive impairment. The Cleveland Clinic Knowledge Program Data Registry was used to identify adult patients seen in outpatient epilepsy clinic from January to May 2015 and who completed the following scales: ABNAS for subjective cognitive impairment, Patient Health Questionnaire (PHQ-9) for depression, Generalized Anxiety Disorder 7-item (GAD-7) scale, Quality of Life in Epilepsy (QOLIE-10), and EuroQOL five dimensions questionnaire (EQ-5D) for health-related quality of life. Topiramate (TPM) was considered a high-risk medication for cognitive impairment. Patients were categorized into groups based on total ABNAS score: subjective cognitive impairment (ABNAS>15; N=270) and no subjective cognitive impairment (ABNAS≤15; N=400). Multivariable logistic regression models were constructed to identify independent predictors of subjective cognitive impairment. In a subset of patients who had neuropsychological testing within 6months of completing the ABNAS (N=60), Pearson correlations and multivariable logistic regression models, controlling for number of AEDs, depression, and anxiety, assessed the relationship between subjective cognitive impairment and objective cognitive performance on measures of intelligence, attention/working memory, verbal fluency, naming, processing speed, manual dexterity, visuomotor processing, and verbal memory. Forty percent of patients in the overall sample (N=270/670) reported cognitive impairment. The variables most strongly associated with subjective cognitive impairment were PHQ-9 score, number of AEDs, and seizure frequency. In

  11. Drug hypersensitivity syndrome

    Directory of Open Access Journals (Sweden)

    Rashmi Kumari

    2011-01-01

    Full Text Available Drug hypersensitivity syndrome (DHS is an adverse drug reaction commonly associated with the aromatic antiepileptic drugs (AEDs, viz., phenytoin (PHT, carbamazepine (CBZ, phenobarbital (PB, lamotrigine, primidone, etc. It can also be caused by other drugs, such as sulfonamides, dapsone, minocycline, gold derivatives, cyclosporine, captopril, diltiazem, terbinafine, azathioprine and allopurinol. Diagnosis of DHS may be difficult because of the variety of clinical and laboratory abnormalities and manifestations and because the syndrome may mimic infectious, neoplastic or collagen vascular disorders. The risk for developing hypersensitivity within 60 days of the first or second prescription in new users of PHT or CBZ was estimated to be 2.3-4.5 per 10,000 and 1-4.1 per 10,000, respectively. The syndrome is defined by the fever, skin rash, lymphadenopathy and internal organ involvement within the first 2-8 weeks after initiation of therapy. Internal manifestations include, among others, agranulocytosis, hepatitis, nephritis and myositis. Insufficient detoxification may lead to cell death or contribute to the formation of antigen that triggers an immune reaction. Cross-reactivity among PHT, CBZ and PB is as high as 70%-80%. Management mainly includes immediate withdrawal of the culprit drug, symptomatic treatment and systemic steroids or immunoglobulins.

  12. Psychomotor developmental effects of prenatal exposure to psychotropic drugs: a study in EFEMERIS database.

    Science.gov (United States)

    Hurault-Delarue, Caroline; Damase-Michel, Christine; Finotto, Laurent; Guitard, Claudine; Vayssière, Christophe; Montastruc, Jean-Louis; Montastruc, François; Lacroix, Isabelle

    2016-10-01

    Little is known about neurodevelopment of children exposed to psychotropic drugs during pregnancy. The purpose of this study was to evaluate the effects of prenatal exposure to psychotropic drugs on psychomotor development in children. This observational study used the EFEMERIS database. The database records the drugs prescribed and delivered during pregnancy and the resulting outcomes. Neurodevelopment at nine and 24 months of children born to women exposed to psychotropic drugs (anxiolytics, antidepressants, neuroleptics and anti-epileptics) during the second and/or third trimesters of pregnancy was compared to children who were not exposed to these drugs. Psychomotor development of 493 children (1.5%) exposed to psychotropic drugs during pregnancy was compared to 32 303 unexposed children. Exposure to psychotropic drugs during pregnancy was associated with an increased risk of abnormal motor development at 9 months (OR = 1.3 [1.1-2.2]) and abnormal motor and mental development at 24 months (OR = 4.8 [2.1-11.0] and OR = 2.3 [1.05-4.9]). Increased risk was observed in children born to women exposed to anti-epileptic drugs, neuroleptics or antidepressants during pregnancy. This study found a higher rate of deviation from the normal developmental milestones in children born to women exposed to psychotropic drugs during pregnancy and more particularly antidepressants, neuroleptics and anti-epileptics. © 2016 Société Française de Pharmacologie et de Thérapeutique.

  13. Reuma.pt - the rheumatic diseases portuguese register.

    Science.gov (United States)

    Canhão, H; Faustino, A; Martins, F; Fonseca, J E

    2011-01-01

    Since June 2008, Portuguese rheumatologists have been collecting on a routine basis, data into the nationwide Reuma.pt, the Rheumatic Diseases Portuguese Register from the Portuguese Society of Rheumatology (SPR), which includes rheumatic patients (rheumatoid arthritis - RA, ankylosing spondylitis - AS, psoriatic arthritis - PsA and juvenile idiopathic arthritis - JIA) receiving biological therapies or patients receiving synthetic disease modifying anti-rheumatic drugs (DMARDs). The aim of this publication is to describe the structure of Reuma.pt and the population registered since June 2008. Demographic and anthropometric data, life style habits, work status, co-morbidities, disease activity and functional assessment scores, previous and current therapies, adverse events codified by the Medical Dictionary for Regulatory Activities (MedDRA), reasons for discontinuation and laboratory measurements are registered at each visit. The platform is based on a structured electronic medical record linked to a SQL Server database. All Rheumatology Departments assigned to the Portuguese National Health Service (n=21), 2 Military Hospitals (Lisboa and Porto), 1 public-private Institution and 6 private centers adhered to the Register. Until now, 18 centers have entered data into Reuma.pt. By January 2011, 3438 patients and 16130 visits had been registered. 2162 (63%) were RA patients, 700 of them treated with biological agents and 1462 with synthetic DMARDs. From the 515 (15%) AS patients, 297 were medicated with biological and 218 with non-biological therapies. 293 (8%) were PsA patients, 151 treated with biological drugs and 142 with other treatment strategies. 368 (11%) had the diagnosis of JIA, 68 were under biological treatment and 300 were managed with other treatment options. The register also includes 100 (3%) patients with other rheumatic diseases, submitted to treatments that required hospital day care infusions including 18 exposed to biological therapies. Registers

  14. Validation of a Cerebral Palsy Register

    DEFF Research Database (Denmark)

    Topp, Monica; Langhoff-Roos, Jens; Uldall, P.

    1997-01-01

    OBJECTIVES: To analyse completeness and validity of data in the Cerebral Palsy Register in Denmark, 1979-1982. METHODS: Completeness has been assessed by comparing data from The Danish National Patient Register (DNPR) with the cases included in the Cerebral Palsy Register (CPR). Agreement between......, but gestational age was subject to a systematic error, and urinary infections in pregnancy (kappa = 0.43) and placental abruption (kappa = 0.52) were seriously under-reported in the CPR. CONCLUSIONS: Completeness of the Cerebral Palsy Register in Denmark, 1979-1982, has been assessed to maximal 85%, emphasizing...

  15. Register-based studies of healthcare costs

    DEFF Research Database (Denmark)

    Kruse, Marie; Christiansen, Terkel

    2011-01-01

    Introduction: The aim of this paper is to provide an overview and a few examples of how national registers are used in analyses of healthcare costs in Denmark. Research topics: The paper focuses on health economic analyses based on register data. For the sake of simplicity, the studies are divided...... into three main categories: economic evaluations of healthcare interventions, cost-of-illness analyses, and other analyses such as assessments of healthcare productivity. Conclusion: We examined a number of studies using register-based data on healthcare costs. Use of register-based data renders...

  16. Drug-induced liver injury due to antimicrobials, central nervous system agents, and nonsteroidal anti-inflammatory drugs.

    Science.gov (United States)

    Devarbhavi, Harshad; Andrade, Raúl J

    2014-05-01

    Antimicrobial agents including antituberculosis (anti-TB) agents are the most common cause of idiosyncratic drug-induced liver injury (DILI) and drug-induced liver failure across the world. Better molecular and genetic biomarkers are acutely needed to help identify those at risk of liver injury particularly for those needing antituberculosis therapy. Some antibiotics such as amoxicillin-clavulanate and isoniazid consistently top the lists of agents in retrospective and prospective DILI databases. Central nervous system agents, particularly antiepileptics, account for the second most common class of agents implicated in DILI registries. Hepatotoxicity from older antiepileptics such as carbamazepine, phenytoin, and phenobarbital are often associated with hypersensitivity features, whereas newer antiepileptic drugs have a more favorable safety profile. Antidepressants and nonsteroidal anti-inflammatory drugs carry very low risk of significant liver injury, but their prolific use make them important causes of DILI. Early diagnosis and withdrawal of the offending agent remain the mainstays of minimizing hepatotoxicity. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  17. WITHDRAWN: Oxcarbazepine add-on for drug-resistant partial epilepsy.

    Science.gov (United States)

    Castillo, Sergio M; Schmidt, Dieter B; White, Sarah; Shukralla, Arif

    2016-11-15

    Most people with epilepsy have a good prognosis and their seizures can be well controlled with the use of a single antiepileptic drug, but up to 30% develop refractory epilepsy, especially those with partial seizures. In this review we summarize the current evidence regarding oxcarbazepine when used as an add-on treatment for drug-resistant partial epilepsy. To evaluate the effects of oxcarbazepine when used as an add-on treatment for drug-resistant partial epilepsy. We searched the Cochrane Epilepsy Group's Specialized Register (28 March 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2006), MEDLINE (1966 to March 2006). No language restrictions were imposed. We checked the reference lists of retrieved studies for additional reports of relevant studies. We also contacted Novartis (manufacturers of oxcarbazepine) and experts in the field. Randomized, placebo-controlled, double-blinded, add-on trials of oxcarbazepine in patients with drug-resistant partial epilepsy. Two review authors independently assessed trials for inclusion and extracted the relevant data. The following outcomes were assessed : (a) 50% or greater reduction in seizure frequency; (b) treatment withdrawal (any reason); (c) side effects. Primary analyses were intention-to-treat. Summary odds ratios were estimated for each outcome. Two trials were included representing 961 randomized patients.Overall Odds Ratio (OR) (95% Confidence Interval (CIs)) for 50% or greater reduction in seizure frequency compared to placebo 2.96 (2.20, 4.00).Treatment withdrawal OR (95% CIs) compared to placebo 2.17 (1.59, 2.97).Side effects: OR (99% CIs) compared to placebo, ataxia 2.93 (1.72, 4.99); dizziness 3.05 (1.99, 4.67); fatigue 1.80 (1.02, 3.19); nausea 2.88 (1.77, 4.69); somnolence 2.55 (1.84, 3.55); diplopia 4.32 (2.65, 7.04), were significantly associated with oxcarbazepine. Oxcarbazepine has efficacy as an add-on treatment in patients with drug

  18. Assessment of Human Pharmaceutical Products Registered in ...

    African Journals Online (AJOL)

    ... in order to determine the most common routes of administration and type of dosage forms that are used. Registered pharmaceutical products were categorized by route of administration and then sub-categorized by the dosage form. Oral dosage forms were the most common accounting for 73% of all registered products.

  19. In-memory interconnect protocol configuration registers

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Kevin Y.; Roberts, David A.

    2017-09-19

    Systems, apparatuses, and methods for moving the interconnect protocol configuration registers into the main memory space of a node. The region of memory used for storing the interconnect protocol configuration registers may also be made cacheable to reduce the latency of accesses to the interconnect protocol configuration registers. Interconnect protocol configuration registers which are used during a startup routine may be prefetched into the host's cache to make the startup routine more efficient. The interconnect protocol configuration registers for various interconnect protocols may include one or more of device capability tables, memory-side statistics (e.g., to support two-level memory data mapping decisions), advanced memory and interconnect features such as repair resources and routing tables, prefetching hints, error correcting code (ECC) bits, lists of device capabilities, set and store base address, capability, device ID, status, configuration, capabilities, and other settings.

  20. Registered Nurses' views on their professional role.

    Science.gov (United States)

    Furåker, Carina

    2008-11-01

    The aim is to study Registered Nurses' opinions and reflections about their work tasks, competence and organization in acute hospital care. The definition of the role of nurses has changed over time and it is often discussed whether Registered Nurses have a professional status or not. A qualitative research design was used. Data were derived from written reflections on diaries and from focus group interviews. All respondents had difficulties in identifying the essence of their work. It can be argued that being 'a spider in the web' is an important aspect of the nursing profession. Registered Nurses tend to regard their professional role as vague. Managers must be considered key persons in defining the professional role of Registered Nurses. This study contributes to an understanding of the managers' and the importance of nursing education in Registered Nurses professional development.

  1. In-memory interconnect protocol configuration registers

    Science.gov (United States)

    Cheng, Kevin Y.; Roberts, David A.

    2017-09-19

    Systems, apparatuses, and methods for moving the interconnect protocol configuration registers into the main memory space of a node. The region of memory used for storing the interconnect protocol configuration registers may also be made cacheable to reduce the latency of accesses to the interconnect protocol configuration registers. Interconnect protocol configuration registers which are used during a startup routine may be prefetched into the host's cache to make the startup routine more efficient. The interconnect protocol configuration registers for various interconnect protocols may include one or more of device capability tables, memory-side statistics (e.g., to support two-level memory data mapping decisions), advanced memory and interconnect features such as repair resources and routing tables, prefetching hints, error correcting code (ECC) bits, lists of device capabilities, set and store base address, capability, device ID, status, configuration, capabilities, and other settings.

  2. Debug register rootkits : A study of malicious use of the IA-32 debug registers

    OpenAIRE

    Persson, Emil; Mattsson, Joel

    2012-01-01

    The debug register rootkit is a special type of rootkit that has existed for over a decade, and is told to be undetectable by any scanning tools. It exploits the debug registers in Intel’s IA-32 processor architecture. This paper investigates the debug register rootkit to find out why it is considered a threat, and which malware removal tools have implemented detection algorithms against this threat. By implementing and running a debug register rootkit against the most popular Linux tools, ne...

  3. A Scandinavian Experience of Register Collaboration: The Nordic Arthroplasty Register Association (NARA)

    DEFF Research Database (Denmark)

    Havelin, Leif I; Robertsson, Otto; Fenstad, Anne M

    2011-01-01

    The Nordic (Scandinavian) countries have had working arthroplasty registers for several years. However, the small numbers of inhabitants and the conformity within each country with respect to preferred prosthesis brands and techniques have limited register research.......The Nordic (Scandinavian) countries have had working arthroplasty registers for several years. However, the small numbers of inhabitants and the conformity within each country with respect to preferred prosthesis brands and techniques have limited register research....

  4. The antiepileptic activity of Vitex agnus castus extract on amygdala kindled seizures in male rats.

    Science.gov (United States)

    Saberi, Mehdi; Rezvanizadeh, Alireza; Bakhtiarian, Azam

    2008-08-22

    The antiepileptic activity of hydrophilic extract of Vitex agnus castus fruit (Vitex) was evaluated by the kindling model of epilepsy. Intact male rats (250-300 g) were stereotaxically implanted with a tripolar and two monopolar electrodes in amygdala and dura, respectively. The afterdischarge (AD) threshold was determined in each animal and stimulated daily until fully kindled. The animals were administered different doses (60, 120 or 180 mg/kg) of Vitex or 0.1 ml of hydro alcoholic solvent intra-peritoneally (i.p.) and kindling parameters including AD threshold, seizure stages (SS), afterdischarge duration (ADD), stage 4 latency (S4L) and stage 5 duration (S5D) were recorded 30 min post-injection. The obtained data showed that even low dose (60 mg/kg) of Vitex could significantly increase the AD threshold and decrease the ADD and S5D (PVitex at the dose of 120 mg/kg, induced significant increment in S4L (PVitex can reduce or prevent epileptic activity as demonstrated by reduction of ADD and S5D (length of convulsion) in a dose dependent manner. In conclusion, Vitex at appropriate dose can probably reduce or control epileptic activities.

  5. A register-based study of the antimicrobial usage in Danish veal calves and young bulls

    DEFF Research Database (Denmark)

    Fertner, Mette Ely; Toft, Nils; Martin, Henrik Læssøe

    2016-01-01

    High antimicrobial usage and multidrug resistance have been reported in veal calves in Europe. This may be attributed to a high risk of disease as veal calves are often purchased from numerous dairy herds, exposed to stress related to the transport and commingling of new animals, and fed a new...... ration. In this study, we used national register data to characterize the use of antimicrobials registered for large Danish veal calf and young bull producing herds in 2014. A total of 325 herds with veal calf and potentially young bull production were identified from the Danish Cattle database....... According to the national Danish database on drugs for veterinary use (VetStat), a total of 537,399 Animal Daily Doses (ADD200) were registered for these 325 herds during 2014. The amount of antimicrobials registered in 2014 varied throughout the year, with the highest amounts registered in autumn...

  6. Procedure entry in the register of yachts

    Directory of Open Access Journals (Sweden)

    Zorana Kostović

    2011-01-01

    Full Text Available The procedure of ship registration is regulated in the Maritime Code of Croatia (2004. This procedure, in comparison with the recently suspended Maritime Code of Croatia (1994, includes substantial changes, especially in the domain of yacht registration. New Maritime Code has founded special yacht-register for yachts and yachts under construction. A yacht which is registered as a Croatian yacht is entitled to the benefits conffered by the Maritime Code of Croatia (right to fly a Croatian flag, etc.. There are two modes proscribed under the provisions of Maritime Code of Croatia (2004 for yacht-registration: 1 mandatory and 2 facultative. Yachts whose owners are Croatian citizens with residence i Republic Croatia or companies which are registered in the Republic of Croatia are obligated to register under the provisions of Maritime Code of Croatia (2004. On the other hand, yacht whose owners are not Croatian citizens or whose owners are Croatian citizens but without the residence in the Republic of Croatia, can be registered in the Republic of Croatia, depending on the will of the owner. Yachts under construction can be registered in special registers for such kind of vessels if they are built in Croatian shipyards (owners can be either Croatian citizens or foreigners. Jurisdiction in this matter belongs to port authorities and all procedure is carried out in accordance with the rules of administrative procedure.

  7. DILI (drug induced liver injury in a 9-month-old infant: a rare case of phenobarbital-induced hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Anna Paola Pinna

    2013-04-01

    Full Text Available Phenobarbital is one of the most commonly prescribed antiepileptic drugs in childhood, but it can rarely cause serious adverse effects, such as hepatotoxicity that includes a broad clinical spectrum (from isolate hypertransaminasemia to acute liver failure. We describe a case of DILI in a 9-month-old infant caused by chronic therapy with phenobarbital.

  8. Data register and processor for multiwire chambers

    International Nuclear Information System (INIS)

    Karpukhin, V.V.

    1985-01-01

    A data register and a processor for data receiving and processing from drift chambers of a device for investigating relativistic positroniums are described. The data are delivered to the register input in the form of the Grey 8 bit code, memorized and transformed to a position code. The register information is delivered to the KAMAK trunk and to the front panel plug. The processor selects particle tracks in a horizontal plane of the facility. ΔY maximum coordinate divergence and minimum point quantity on the track are set from the processor front panel. Processor solution time is 16 μs maximum quantity of simultaneously analyzed coordinates is 16

  9. The absorptive flux of the anti-epileptic drug substance vigabatrin is carrier-mediated across Caco-2 cell monolayers

    DEFF Research Database (Denmark)

    Nøhr, Martha Kampp; Hansen, Steen Honoré; Brodin, Birger

    2014-01-01

    of vigabatrin in Caco-2 cells, a cell culture model of the small intestinal epithelium. The uptake and transepithelial flux of vigabatrin was measured using an LC-MS method for quantification. Transepithelial transport of vigabatrin was shown to be proton-dependent and polarized in the apical-to-basolateral (A...... of the human proton-coupled amino acid transporter (hPAT1) to the apical solution. The present study indicates that the transepithelial A-B flux of vigabatrin is mainly mediated by hPAT1 in Caco-2 cells at dose-relevant concentrations....

  10. The anti-epileptic drug substance vigabatrin inhibits taurine transport in intestinal and renal cell culture models

    DEFF Research Database (Denmark)

    Plum, Jakob Munk; Nøhr, Martha Kampp; Hansen, Steen H

    2014-01-01

    , such evidence does not preclude the involvement of other transporters. The aim of the present study was, therefore, to investigate if vigabatrin interacts with taurine transport. The uptake of taurine was measured in intestinal human Caco-2 and canine MDCK cell monolayers in the absence or presence of amino...... acids such as GABA and vigabatrin. Vigabatrin inhibits the uptake of taurine in Caco-2 and MDCK cells to 34±3 and 53±2%, respectively, at a concentration of 30mM. In Caco-2 cells the uptake of vigabatrin under neutral pH conditions is concentration-dependent and saturable with a Km-value of 27mM (log......Km is 1.43±0.09). In conclusion, the present study shows that vigabatrin was able to inhibit the uptake of taurine in intestinal and renal cell culture models. Furthermore, uptake of vigabatrin in Caco-2 cells under neutral pH conditions was concentration-dependent and saturable and suggesting...

  11. The anti-epileptic drug valproic acid (VPA inhibits steroidogenesis in bovine theca and granulosa cells in vitro.

    Directory of Open Access Journals (Sweden)

    Claire Glister

    Full Text Available Valproic acid (VPA is used widely to treat epilepsy and bipolar disorder. Women undergoing VPA treatment reportedly have an increased incidence of polycystic ovarian syndrome (PCOS-like symptoms including hyperandrogenism and oligo- or amenorrhoea. To investigate potential direct effects of VPA on ovarian steroidogenesis we used primary bovine theca (TC and granulosa (GC cells maintained under conditions that preserve their 'follicular' phenotype. Effects of VPA (7.8-500 µg/ml on TC were tested with/without LH. Effects of VPA on GC were tested with/without FSH or IGF analogue. VPA reduced (P99% decrease; P<0.0001 with lesser effects on LHR, STAR, CYP11A1 and HSD3B1 mRNA (<90% decrease; P<0.05. VPA only reduced TC progesterone secretion induced by the highest (luteinizing LH dose tested; TC number was unaffected by VPA. At higher concentrations (125-500 µg/ml VPA inhibited basal, FSH- and IGF-stimulated estradiol secretion (P<0.0001 by GC without affecting progesterone secretion or cell number. VPA reversed FSH-induced upregulation of CYP19A1 and HSD17B1 mRNA abundance (P<0.001. The potent histone deacetylase (HDAC inhibitors trichostatin A and scriptaid also suppressed TC androstenedione secretion and granulosal cell oestrogen secretion suggesting that the action of VPA reflects its HDAC inhibitory properties. In conclusion, these findings refute the hypothesis that VPA has a direct stimulatory action on TC androgen output. On the contrary, VPA inhibits both LH-dependent androgen production and FSH/IGF-dependent estradiol production in this in vitro bovine model, likely by inhibition of HDAC.

  12. The synthesis of some 11C-labelled antiepileptic drugs with potential utility as radiopharmaceuticals: hydantoins and barbiturates

    International Nuclear Information System (INIS)

    Roeda, D.; Westera, G.

    1981-01-01

    11 C-labelled phenytoin and 5-ethyl-5-phenyl hydantoin were prepared using 11 COCl 2 as the starting material. 11 C-urea was used to produce 11 C-phenobarbital and 11 C-barbital. The methods developed are suitable for automation in a lead shielded cell. (author)

  13. Are the Cochrane group registers comprehensive? A case study of Japanese psychiatry trials

    Directory of Open Access Journals (Sweden)

    McGuire Hugh

    2002-04-01

    Full Text Available Abstract Background Language bias is a form of publication bias and constitutes a serious threat to meta-analyses. The Cochrane Controlled Trials Register is one attempt to remedy this and now contains more than 300,000 citations. However we are still unsure if it provides comprehensive coverage, particularly for non-English trials. Methods We have recently established a comprehensive register of Japanese trials of psychotropic drugs through extensive personal contacts, electronic searches and handsearches. We examined two Cochrane psychiatry group registers against this Japanese database. Results The Japanese register contained 56 reports of randomized controlled trials (RCTs of antidepressants for depression but the Cochrane Depression, Anxiety and Neurosis group register contained 18, with an overlap of only nine. The Japanese register contained 61 reports of RCTs of neuroleptics for schizophrenia and the Cochrane Schizophrenia group register contained 36, with an overlap of only six. Taking account of some duplicate publications, only a quarter to a third of all relevant Japanese RCTs were retrievable from the Cochrane group registers. Conclusions Similar, or worse, yields may be expected with RCTs conducted in other East Asian countries, and in other fields of medicine. What evidence there is suggests that this situation may lead to a systematic over estimate of treatment effect.

  14. Australian Mining's product register 1992-93

    Energy Technology Data Exchange (ETDEWEB)

    1993-01-01

    This annual product register contains an assessment of resources in Australia; statistical information on mine production of principal minerals; mineral industry statistics; directory of exploration and mining companies; buyers' guide; directory of consultants; list of services and a company index.

  15. Australian Mining's product register 1990-91

    Energy Technology Data Exchange (ETDEWEB)

    1990-01-01

    The Australian Minings' Product Register 1990-91 contains an industry review, resource assessment, mineral industry statistics, directory of exploration and mining companies, buyers guide and directory of consultants.

  16. Job satisfaction of South African registered dietitians

    African Journals Online (AJOL)

    2012-01-25

    Jan 25, 2012 ... career growth,5,6,9 lack of respect from healthcare professionals,39 competition from ... a reminder was posted in the ADSA monthly newsletter, six weeks ..... research and conduct open interviews with registered dietitians or.

  17. Register-based research on twins

    DEFF Research Database (Denmark)

    Christensen, Kaare; Ohm Kyvik, Kirsten; Holm, Niels V

    2011-01-01

    Introduction: The Danish Twin Registry (DTR) has for more than 50 years been based on surveys and clinical investigations and over the two last decades also on register linkage. Currently these two approaches are merged within Statistics Denmark. Research topics: Here we report on three major...... groups of register-based research in the DTR that used the uniqueness of twinning. First, we focus on the ''long-term prognosis'' of being a twin compared with being a singleton and show that Danish twins have health trajectories in adulthood similar to singletons, which is a result of interest for twins...... illustrate how the co-twin control method in a register setting can be used to control for the effect of rearing environment and genetic factors in studies of the association between exposures and health. CONCLUSION: The spectrum of register-based twin studies is very wide and have changed in accordance...

  18. National Sample Survey of Registered Nurses

    Data.gov (United States)

    U.S. Department of Health & Human Services — The National Sample Survey of Registered Nurses (NSSRN) Download makes data from the survey readily available to users in a one-stop download. The Survey has been...

  19. Register as the Situational Variety of Language

    Directory of Open Access Journals (Sweden)

    Natalya B. Boyeva-Omelechko

    2016-12-01

    Full Text Available The problem discussed in the article is topical due to the interest of scientists to different types of language variations and especially registers or situational dialects treated by M.A.K. Halliday as use-related varieties of language or varieties used in a particular social setting. As discourse categorization is a very complex problem scholarly consensus has not been reached for the definitions of the term «register». The universal criteria for defining and discriminating registers have not been worked out either. The authors of the article give the review of scientific works devoted to the problem in question especially works by M.A.K. Halliday, R. Quirk, M. Joos, D. Hymes P. Trudgill, E.I. Belyaeva and others and analyze different definitions of the term «register», spectrums of registers and criteria for their discriminating. It enables the authors to come to the conclusion that only registers with the same field (religious, political, business etc. and mode (oral/written, dialogue/monologue can be compared. The difference lies in the sphere of tenor which depends on the degree of formality, distance of power and socio-psychological distance between speakers. The authors believe that it is also necessary to take into account the cooperative/ uncooperative character of conversation and para-verbal and non-verbal components of the speech situation. With this in mind they offer their definition of the register and describe main characteristics of registers in the sphere of oral communication.

  20. Investigation of PON1 activity and MDA levels in patients with epilepsy not receiving antiepileptic treatment

    Directory of Open Access Journals (Sweden)

    Dönmezdil N

    2016-04-01

    Full Text Available Nilüfer Dönmezdil, Mehmet Uğur Çevik, Hasan Hüseyin Özdemir, Muhterem Taşin Department of Neurology, Dicle University, Diyarbakır, Turkey Purpose: There are many studies dedicated to researching the etiopathogenesis of epilepsy. In such research, oxidative and antioxidant indicators of etiopathogenesis have also been examined under the scope. Drawing on a group of patients with epilepsy who were receiving no treatment, we have tried to evaluate whether or not an increase in oxidative indicators is linked directly with the disorder, independent of epileptic medicaments.Methods: Thirty people in good health and 30 newly diagnosed with epilepsy and who received ambulatory treatment in the polyclinic of the Neurology Department took part in the study. The tests relating to serum malondialdehyde (MDA levels and paraoxonase 1 (PON1 activity were carried out in the biochemistry laboratory.Results: Even though the levels of MDA in the patient group (14.34±3.59 nmol/mL were found to be high compared to those of the control group, which consisted of people in good health (13.53±3.56 nmol/mL, there was no statistically significant difference. PON1 activity in the serum taken from people in the patient group (0.65±0.17 was lower in comparison to that observed in the serum of the control group (0.71±0.17 U/L. Nonetheless, it was not so low as to have significance from a statistical point of view.Conclusion: We conclude that such a high level of oxidative parameters should have been related to the disease and that statistically significant findings that emerged in some other studies could have been related to an antiepileptic treatment. Keywords: epilepsy, paraoxonase 1, malondialdehyde, oxidative stress, epilepsy, biochemical marker

  1. Comparative analysis of cost and efficacy for mono and dual therapy of antiepileptics among children

    Directory of Open Access Journals (Sweden)

    Easwaran Vigneshwaran

    2017-01-01

    Full Text Available Introduction: Developing countries contribute to major number of patients living with epilepsy, around five million people are living with epilepsy in India alone. Most of the epileptic children may require multiple antiepileptic therapy due to the failure of monotherapy. Basic research evidence suggest that sodium valproate and carbamazepine (CBZ may have synergistic anticonvulsant effects when they are used together. In addition to that, chronic disorders make the patients economically weak and produce more burden. Aim and Objective: Therefore, this study was designed to compare the efficacy of valproate monotherapy with valproate and CBZ dual therapy. Methodology: It is a prospective, comparative study conducted at a secondary care referral hospital and private clinic. A nonprobabilistic convenient sampling was done to recruit the study subjects. A total of fifty subjects were recruited into the present study, and they were divided into two groups, i.e., monotherapy group (CBZ and dual therapy group (CBZ and valproate. After providing appropriate counseling, subjects were interviewed to estimate the quality of life (QOL using child version of TNO-AZL Children's Quality of Life questionnaire. Hospital patient records, prescription data from the pharmacy were also used to obtain the direct and indirect cost of treatment. Results: Our study results showed that monotherapy has a potential to produce a higher level of QOL than dual therapy. It also involved with decreased seizure frequency. Although there was no statistically significant difference in terms of cost for both the treatment groups, still dual therapy is associated with higher cost burden. The average costs per QOL and changes in the frequency of seizure are also identified to produce higher economic burden to the patients.Conclusion: Thus, the present study has concluded that monotherapy may be considered as better cost-effective treatment in partial seizures than dual therapy

  2. Antiepileptic effect of fisetin in iron-induced experimental model of traumatic epilepsy in rats in the light of electrophysiological, biochemical, and behavioral observations.

    Science.gov (United States)

    Das, Jharana; Singh, Rameshwar; Sharma, Deepak

    2017-05-01

    Traumatic epilepsy is defined by episodes of recurring seizures secondary to severe brain injury. Though drugs are found effective to control seizures, their long-term use have been observed to increase reactive oxygen species in animals. Flavonoid fisetin, a natural bioactive phytonutrient reported to exert anticonvulsive effect in experimental seizure models. But, trauma-induced seizures could not be prevented by anticonvulsants was reported in some clinical studies. To study the effect of fisetin on epileptiform electrographic activity in iron-induced traumatic epilepsy and also the probable reason behind the effect in rats. Fisetin pretreatment (20 mg/kg body wt., p.o.) of rats for 12 weeks were chosen followed by injecting iron (5 µl, 100 mM) stereotaxically to generate iron-induced epilepsy. Experimental design include electrophysiological study (electroencephalograph in correlation with multiple unit activity (MUA) in the cortex and CA1 subfield of the hippocampus; spectral analysis of seizure and seizure-associated behavioral study (Morris water maze for spatial learning, open-field test for anxiety) and biochemical study (lipid peroxidation, Na + ,K + -ATPase activity) in both the cortex and the hippocampus. Fisetin pretreatment was found to prevent the development of iron-induced electrical seizure and decrease the corresponding MUA in the cortex (*P˂0.05) as well as in the hippocampus (***P˂0.001). Fisetin pretreatment decreased the lipid peroxides (*P˂0.05) and retained the Na + ,K + -ATPase activity (*P˂0.05) which was found altered in the epileptic animals and also found to attenuate the seizure-associated cognitive dysfunctions. This study demonstrated the antiepileptic action of fisetin in iron-induced model of epileptic rats by inhibiting oxidative stress.

  3. The Danish registers of causes of death

    DEFF Research Database (Denmark)

    Juel, K; Helweg-Larsen, K

    1999-01-01

    In 1875 registration of causes of death in Denmark was established by the National Board of Health, and annual statistics of death have since been published. Until 1970 the national statistics were based upon punched cards with data collected from the death certificates. Since then the register has...... been fully computerized and includes individual based data of all deaths occurring among all residents in Denmark dying in Denmark. Furthermore, a microfilm of all death certificates from 1943 and onward is kept in the National Board of Health. The Danish Institute for Clinical Epidemiology (DICE) has...... established a computerized register of individual records of deaths in Denmark from 1943 and onwards. No other country covers computerized individual based data of death registration for such a long period, now 54 years. This paper describes the history of the registers, the data sources and access to data...

  4. NUHOMS registered - MP197 transport cask

    International Nuclear Information System (INIS)

    Shih, P.; Sicard, D.; Michels, L.

    2004-01-01

    The NUHOMS registered -MP197 cask is an optimized transport design which can be loaded in the spent fuel pool (wet loading) or loaded the canister from the NUHOMS concrete modules at the ISFSI site. With impact limiters attached, the package can be transported within the states or world-wide. The NUHOMS registered -MP197 packaging can be used to transport either BWR or PWR canisters. The NUHOMS registered -MP197 cask is designed to the ASME B and PV Code and meets the requirements of Section III, Division 3 for Transport Packaging. The cask with impact limiters has undergone drop testing to verify the calculated g loadings during the 9m drops. The test showed good correlation with analytical results and demonstrate that the impact limiters stay in place and protect the package and fuel during the hypothetical accidents

  5. Very wide register : an asymmetric register file organization for low power embedded processors.

    NARCIS (Netherlands)

    Raghavan, P.; Lambrechts, A.; Jayapala, M.; Catthoor, F.; Verkest, D.T.M.L.; Corporaal, H.

    2007-01-01

    In current embedded systems processors, multi-ported register files are one of the most power hungry parts of the processor, even when they are clustered. This paper presents a novel register file architecture, which has single ported cells and asymmetric interfaces to the memory and to the

  6. Australian lobbyist registers are not serving the purposes they were designed for.

    Science.gov (United States)

    Robertson, Narelle; Kypri, Kypros; Stafford, Julia; Daube, Mike; Avery, Michelle; Miller, Peter

    2017-07-11

    There is widespread concern about the nature, extent and impacts of lobbying by industries selling unhealthy commodities, which threatens public health and undermines important democratic processes. In the last decade, all Australian jurisdictions (except the Northern Territory) have established lobbyist registers with the stated objective of increasing the capacity of government and the public to scrutinise lobbying. Our aim was to assess whether the registers are fulfilling this objective. We conducted web searches of registers in Australian jurisdictions in 2014 and 2015 to determine what type of information they collected and whether data were accessible. We supplemented searches with e-mails and phone calls to registrars to clarify policies and seek additional information. We found that the data were lacking in critical details and historical information was difficult or impossible to obtain. None of the registers required in-house lobbyists to register or to be bound by the Lobbying Codes of Conduct. None required that informal lobbying (e.g. by government relations staff within a company) be recorded, and none provided detailed information about the nature and extent of lobbying activities. The registers do not meet the stated objective of making lobbying activity transparent to the Australian public. Timely access to comprehensive information is essential to help promote the rational development of policy concerning tobacco, alcohol and gambling problems. There is an urgent need to reform lobbyist registers to ensure that they are comprehensive and transparent. [Robertson N, Kypri K, Stafford J, Daube M, Avery M, Miller P. Australian lobbyist registers are not serving the purposes they were designed for. Drug Alcohol Rev 2017;00:000-000]. © 2017 Australasian Professional Society on Alcohol and other Drugs.

  7. 78 FR 59974 - Publication Procedures for Federal Register Documents During a Funding Hiatus

    Science.gov (United States)

    2013-09-30

    ... Public Law 101-508, 104 Stat. 1388 (31 U.S.C. 1341), the Office of the Federal Register (OFR) announces... hiatus affecting one or more Federal agencies, the OFR will remain open to accept and process documents... activities such as those related to the constitutional duties of the President, food and drug inspection, air...

  8. 76 FR 12135 - Publication Procedures for Federal Register Documents During a Funding Hiatus

    Science.gov (United States)

    2011-03-04

    ... Public Law 101-508, 104 Stat. 1388 (31 U.S.C. 1341), the Office of the Federal Register (OFR) announces... more Federal agencies, the OFR will remain open to accept and process documents authorized to be... as those related to the constitutional duties of the President, food and drug inspection, air traffic...

  9. Assessment of Veterinary Pharmaceutical Products Registered in ...

    African Journals Online (AJOL)

    Topical, intramammary, intrauterine and ophthalmic routes accounted for 4.7%, 3.3%, 1.0% and 0.1% of the registered products respectively. ... Dosage forms for oral administration included solids (53.4%) namely powders, tablets, boluses, freeze dried products, granules; liquids (46.3%) namely suspensions, solutions, ...

  10. Danish Register of chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Lange, Peter; Tøttenborg, Sandra Søgaard; Sorknæs, Anne Dichmann

    2016-01-01

    AIM OF DATABASE: The Danish Register of Chronic Obstructive Pulmonary Disease (DrCOPD) is a nationwide database aiming to describe the quality of treatment of all patients with chronic obstructive pulmonary disease (COPD) in Denmark. STUDY POPULATION: DrCOPD comprises data on all patients...

  11. Registered manufacturers of renewable energy devices

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    Registered manufacturers of renewable energy devices in India are listed. The list is arranged under the headings : solar water heating system, solar cooker, solar still and water pumping wind mill. In all 38 manufacturers are listed. The list gives the postal address, name of the contact person and phone number of each manufacturer. (M.G.B.)

  12. Ca teos report in register N 13377

    International Nuclear Information System (INIS)

    Pena, S; Arrighetti, R.

    2011-01-01

    This work is about a report about ca teos carried out in register N 13377 in the department of Canelones to know the depth of the field. The drilling done allowed to identify granite and clay. This granite outcrops are developed in the east of the middle course of the stream Pando

  13. Josephson shift register design and layout

    International Nuclear Information System (INIS)

    Przybysz, J.X.; Buttyan, J.; Blaugher, R.D.

    1989-01-01

    Integrated circuit chips were designed and fabricated, based on Josephson shift register circuit that simulated operation at 25 GHz using the SPICE program. The 6.25 mm square chip featured a twelve-gate, four-stage shift register fabricated with Nb/AlO/sub x//Nb Josephson junctions with a design value of 2000 A/cm/sup 2/ critical current density. SUPERCOMPACT, a general program for the design of monolithic microwave integrated circuits, was used to model the effects of layout geometry on the uniformity and phase coherence of logic gate bias currents. Gate bias resistors were treated as resistive transmission lines. A layout geometry for the superconductive transmission lines and thin film bias resistors was developed. The original SPICE-designed circuit was modified as a result of these calculations. Modeling indicated that bias current variations could be limited to 3% for all possible logic states of the shift register, and phase coherence of the gates could be maintained to within 2 degrees of 10 Ghz. The fundamental soundness of the circuit design was demonstrated by the proper operation of fabricated shift registers

  14. Registering Names and Addresses for Information Technology.

    Science.gov (United States)

    Knapp, Arthur A.

    The identification of administrative authorities and the development of associated procedures for registering and accessing names and addresses of communications data systems are considered in this paper. It is noted that, for data communications systems using standards based on the Open Systems Interconnection (OSI) Reference Model specified by…

  15. The Austrian Toxoplasmosis Register, 1992-2008.

    Science.gov (United States)

    Prusa, Andrea-Romana; Kasper, David C; Pollak, Arnold; Gleiss, Andreas; Waldhoer, Thomas; Hayde, Michael

    2015-01-15

    We aimed to determine the incidence of primary gestational infections with Toxoplasma gondii and congenital toxoplasmosis in Austria, a country with a nationwide prenatal serological screening program since 1974. We analyzed retrospective data from the Austrian Toxoplasmosis Register of pregnant women with Toxoplasma infection and their offspring with births between 1992 and 2008, identified by the prenatal mandatory screening program. Treatment was administered to women from diagnosis of a Toxoplasma infection until delivery. Infected infants were treated up to 1 year of life routinely. Clinical manifestations in infected infants were monitored at least for 1 year and documented in the register. The Austrian Toxoplasmosis Register included 2147 pregnant women with suspected Toxoplasma infection. Annually, 8.5 per 10 000 women acquired Toxoplasma infection during pregnancy, and 1.0 per 10 000 infants had congenital toxoplasmosis (13% mean transmission rate). Our data showed that women treated according to the Austrian scheme had a 6-fold decrease in the maternofetal transmission rate compared to women without treatment. Results from the Austrian Toxoplasmosis Register show the efficiency of the prenatal screening program. Our results are of clinical relevance for infants, healthcare systems, and policy makers to consider preventive Toxoplasma screening as a potential tool to reduce the incidence of congenital toxoplasmosis. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. Single memory with multiple shift register functionality

    NARCIS (Netherlands)

    2010-01-01

    The present invention relates to a memory device comprising a memory (EM) having at least two predetermined register memory sections addressable by respective address ranges AS1-ASz) and at least one access port (P1-PZ) for providing access to said memory (EM). Furthermore, access control means (A)

  17. 21 CFR 1.241 - What are the consequences of failing to register, update, or cancel your registration?

    Science.gov (United States)

    2010-04-01

    ..., update, or cancel your registration? 1.241 Section 1.241 Food and Drugs FOOD AND DRUG ADMINISTRATION... Facilities Additional Provisions § 1.241 What are the consequences of failing to register, update, or cancel... to cancel its registration in accordance with the requirements of this subpart is a prohibited act...

  18. Drug Facts

    Medline Plus

    Full Text Available ... Why Is It So Hard to Quit Drugs? Effects of Drugs Drug Use and Other People Drug ... Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug ...

  19. 46 CFR 401.510 - Operation without Registered Pilots.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false Operation without Registered Pilots. 401.510 Section 401... REGULATIONS Penalties; Operations Without Registered Pilots § 401.510 Operation without Registered Pilots. (a... Registered Pilot when the vessel or its cargo is in distress or jeopardy. (b) A vessel may be navigated in...

  20. 1 CFR 11.7 - Federal Register Index.

    Science.gov (United States)

    2010-01-01

    ... 1 General Provisions 1 2010-01-01 2010-01-01 false Federal Register Index. 11.7 Section 11.7... REGISTER PUBLICATIONS SUBSCRIPTIONS § 11.7 Federal Register Index. The annual subscription price for the monthly Federal Register Index, purchased separately, in paper form, is $29. The price excludes postage...

  1. Enhancing resilience in registered aged care nurses.

    Science.gov (United States)

    Cameron, Fiona; Brownie, Sonya

    2010-06-01

    To identify the factors that impact the resilience of registered aged care nurses, that is their capacity to adapt to the physical, mental and emotional demands of working in aged care facilities. This study explored the lived experience of nine registered nurses working in residential aged care facilities on the Sunshine Coast, Queensland, who were asked to reflect on the phenomenon of resilience in the workplace. This study found that clinical expertise, a sense of purpose in a holistic care environment, a positive attitude and work-life balance are important determinants of resilience in aged care nurses. Resilience in nurses in residential aged care facilities is enhanced when they are able to maintain long-term, meaningful relationships with residents. Collegial support that provides opportunities to debrief and validate experiences as well as the use of humour to defuse stress promotes well-being and builds resilience in the workplace.

  2. Registered criminality and sanctioning of schizophrenia patients

    DEFF Research Database (Denmark)

    Munkner, Runa; Haastrup, Soeren; Joergensen, Torben

    2009-01-01

    BACKGROUND: Patients with schizophrenia have been shown to have an increased risk of criminality, especially violent crimes. AIMS: The aim of the current study was to describe the pattern of crimes committed by Danish patients with schizophrenia and examine the sanctions given for crimes...... in relation to the different periods in the patients' lives: not yet known to the psychiatric hospital system, known to the system but not yet diagnosed with schizophrenia, and after being diagnosed with schizophrenia. METHODS: Information from the Danish Psychiatric Central Research Register was correlated...... with data from the Danish National Crime Register. RESULTS: One of the more prominent findings was that 16% of patients diagnosed with schizophrenia receive a prison sentence or a suspended prison sentence, despite the fact that Denmark is a co-signatory of the European Prison Rules and should treat, rather...

  3. Spiritual care perspectives of Danish Registered Nurses

    DEFF Research Database (Denmark)

    Christensen, Kirsten Haugaard; Turner, de Sales

    2008-01-01

    Spiritual care perspectives of Danish Nurses The purpose of this study was to explore how Danish registered nurses understand the phenomenon of spiritual care and how their understanding impacts on their interventions with their patients. Nurses are responsible for the provision of care which...... approach rooted in the philosophy of Gadamer was chosen as methodology. In-depth interviews were used as data collection tool, and six registered nurses who worked within hospital settings in Denmark were interviewed. The findings revealed that deep knowing of the patients were essential before nurses...... would engage in provision of spiritual care. The participants acknowledged that their understanding of spirituality influenced their provision of spiritual care, which was recognized as a challenge requiring the nurse’s initiative and courage. Spirituality was primarily understood as a patient’s private...

  4. National Register of Historic Places - National Geospatial Data Asset (NGDA) NPS National Register Dataset

    Data.gov (United States)

    Federal Geographic Data Committee — A current, accurate spatial representation of all historic properties listed on the National Register of Historic Places is of interest to Federal agencies, the...

  5. Statement of Agreements Registered With The Agency

    International Nuclear Information System (INIS)

    1960-01-01

    This document contains a statement of all the agreements which had been registered with the Agency by 30 June 1960 under the Regulations for the Registration of Agreements adopted by the Board of Governors in implementation of Article XXII. B of the Statute. In compliance with Article VI of the Regulations this statement is hereby transmitted to all Members of the Agency for their information. A copy is also being sent to the Secretary-General of the United Nations

  6. Statement of Agreements Registered With The Agency

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1960-09-23

    This document contains a statement of all the agreements which had been registered with the Agency by 30 June 1960 under the Regulations for the Registration of Agreements adopted by the Board of Governors in implementation of Article XXII. B of the Statute. In compliance with Article VI of the Regulations this statement is hereby transmitted to all Members of the Agency for their information. A copy is also being sent to the Secretary-General of the United Nations.

  7. Time-to-event methodology improved statistical evaluation in register-based health services research.

    Science.gov (United States)

    Bluhmki, Tobias; Bramlage, Peter; Volk, Michael; Kaltheuner, Matthias; Danne, Thomas; Rathmann, Wolfgang; Beyersmann, Jan

    2017-02-01

    Complex longitudinal sampling and the observational structure of patient registers in health services research are associated with methodological challenges regarding data management and statistical evaluation. We exemplify common pitfalls and want to stimulate discussions on the design, development, and deployment of future longitudinal patient registers and register-based studies. For illustrative purposes, we use data from the prospective, observational, German DIabetes Versorgungs-Evaluation register. One aim was to explore predictors for the initiation of a basal insulin supported therapy in patients with type 2 diabetes initially prescribed to glucose-lowering drugs alone. Major challenges are missing mortality information, time-dependent outcomes, delayed study entries, different follow-up times, and competing events. We show that time-to-event methodology is a valuable tool for improved statistical evaluation of register data and should be preferred to simple case-control approaches. Patient registers provide rich data sources for health services research. Analyses are accompanied with the trade-off between data availability, clinical plausibility, and statistical feasibility. Cox' proportional hazards model allows for the evaluation of the outcome-specific hazards, but prediction of outcome probabilities is compromised by missing mortality information. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. RNA interference and Register Machines (extended abstract

    Directory of Open Access Journals (Sweden)

    Masahiro Hamano

    2012-11-01

    Full Text Available RNA interference (RNAi is a mechanism whereby small RNAs (siRNAs directly control gene expression without assistance from proteins. This mechanism consists of interactions between RNAs and small RNAs both of which may be single or double stranded. The target of the mechanism is mRNA to be degraded or aberrated, while the initiator is double stranded RNA (dsRNA to be cleaved into siRNAs. Observing the digital nature of RNAi, we represent RNAi as a Minsky register machine such that (i The two registers hold single and double stranded RNAs respectively, and (ii Machine's instructions are interpreted by interactions of enzyme (Dicer, siRNA (with RISC com- plex and polymerization (RdRp to the appropriate registers. Interpreting RNAi as a computational structure, we can investigate the computational meaning of RNAi, especially its complexity. Initially, the machine is configured as a Chemical Ground Form (CGF, which generates incorrect jumps. To remedy this problem, the system is remodeled as recursive RNAi, in which siRNA targets not only mRNA but also the machine instructional analogues of Dicer and RISC. Finally, probabilistic termination is investigated in the recursive RNAi system.

  9. [POISONING BY PSYCHOPHARMACOLOGICAL DRUGS IN AZERBAIJAN: THE RESULTS OF 8-YEAR PROSPECTIVE OBSERVATION].

    Science.gov (United States)

    Afandiyev, I; Azizov, V

    2017-11-01

    Acute poisoning of chemical etiology is a significant global public health problem. The aim of this study was the analysis of the toxicoepidemiological structure of psychopharmacological drugs poisoning in Azerbaijan. We collected and analyzed the data on all cases of acute poisoning by psychopharmacological drugs (codes of categories T42/T43 ICD-10) undergoing inpatient treatment at the Center of Clinical Toxicology in Baku, Azerbaijan in 2009-2016. The total number of patients with acute intoxication by psychopharmacological drugs was 3,413, which was 48.3% of all cases of poisoning by drugs, medicaments and biological substances (T36-T50). The predominance of women was registered in all age groups. 1114 patients or 32.6% were in 15-24 years old age group. The highest percentage of poisonings at category T42 of ICD-10 were benzodiazepine-type drugs (35.8%), and at category T43 - antipsychotic and neuroleptic drugs (19.2%). In the structure of benzodiazepine poisoning, the first and second ranked places belonged to phenazepam (71.0%) and clonazepam - 16.6%. In addition, another 120 cases (5.5%) of poisonings in the T42 cohort were caused by "Z drugs", which have similar therapeutic effect to benzodiazepines (zolpidem and zopiclone). Among the antipsychotic and neuroleptic poisonings, thioridazine, trifluoperazine, levomepromazine, chlorpromazine, and periciazine accounted for 91% of all cases of intoxication in this cohort. Barbiturates, in view of their toxicity and narrow range of therapeutic dosages, now lost their importance as antiepileptic and hypnotic drugs. Only 4.9% of all cases of poisoning, classified under category T42, was due to the use of barbiturates (mainly phenobarbital). Poisonings with iminostilbenes were presented by carbamazepine poisoning only. Most patients in this cohort received this anticonvulsant drug as prescribed by a doctor. Acute intoxications by tricyclic antidepressants in 91.5% were presented by cases of amitriptyline poisoning

  10. [Prevalence of psychoactive drug consumption in an obese population].

    Science.gov (United States)

    Cerdá Esteve, Maria A; Barral Tafalla, Diego; Gudelis, Mindaugas; Goday, Albert; Farre Albaladejo, Magi; Cano, Juan F

    2010-04-01

    To establish the prevalence of psychoactive drug consumption in an obese population. We collected data from the clinical records of obese patients attending the Endocrinology and Nutrition Department and Psychiatry Department of Hospital del Mar between June 2005 and May 2006 (n=259). We recorded anthropometric, epidemiological and toxicological data. We also investigated the prevalence of concomitant diseases in this population. Psychoactive drugs were consumed by 37% of obese patients, mainly antidepressants (27%), anxiolytics, sedatives and hypnotics, and anticonvulsants. Moreover, 15% of all patients received combination treatment with two or more psychoactive drugs, mostly the association of an antidepressant and an antiepileptic drug. The prevalence of psychoactive drug consumption in our sample was higher than prevalence data observed in the general population, with antidepressant consumption being three-fold higher. Copyright 2009 SEEN. Published by Elsevier Espana. All rights reserved.

  11. 78 FR 69133 - Drug Enforcement Administration

    Science.gov (United States)

    2013-11-18

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances..., California 94085, made application by renewal to the Drug Enforcement Administration (DEA) to be registered... Diversion Control, Drug Enforcement Administration. [FR Doc. 2013-27486 Filed 11-15-13; 8:45 am] BILLING...

  12. Direct Determination of a Small-Molecule Drug, Valproic Acid, by an Electrically-Detected Microcantilever Biosensor for Personalized Diagnostics

    Directory of Open Access Journals (Sweden)

    Long-Sun Huang

    2015-01-01

    Full Text Available Direct, small-molecule determination of the antiepileptic drug, valproic acid, was investigated by a label-free, nanomechanical biosensor. Valproic acid has long been used as an antiepileptic medication, which is administered through therapeutic drug monitoring and has a narrow therapeutic dosage range of 50–100 μg·mL−1 in blood or serum. Unlike labeled and clinically-used measurement techniques, the label-free, electrical detection microcantilever biosensor can be miniaturized and simplified for use in portable or hand-held point-of-care platforms or personal diagnostic tools. A micromachined microcantilever sensor was packaged into the micro-channel of a fluidic system. The measurement of the antiepileptic drug, valproic acid, in phosphate-buffered saline and serum used a single free-standing, piezoresistive microcantilever biosensor in a thermally-controlled system. The measured surface stresses showed a profile over a concentration range of 50–500 μg·mL−1, which covered the clinically therapeutic range of 50–100 μg·mL−1. The estimated limit of detection (LOD was calculated to be 45 μg·mL−1, and the binding affinity between the drug and the antibody was measured at around 90 ± 21 μg·mL−1. Lastly, the results of the proposed device showed a similar profile in valproic acid drug detection with those of the clinically-used fluorescence polarization immunoassay.

  13. Pattern of drug eruptions in a tertiary care hospital

    International Nuclear Information System (INIS)

    Tahir, Z.; Nadeem, N.; Aman, S.; Kazmi, A.H.

    2013-01-01

    Background: An adverse drug reaction is unintentional which occurs at doses used for prophylaxis, diagnosis or treatment. Objectives: To determine the frequency of various cutaneous drug eruptions that occur in patients in a tertiary care hospital setting. Patients and Methods: All patients with cutaneous drug eruptions seen at the Dermatology Department of Mayo Hospital, Lahore, over 6 months were enrolled and the pattern of drug eruptions like urticaria, angioedema, fixed drug eruption, maculopapular rash, erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis etc. were recorded, along with drugs that caused it. Results:A total of 160 patients (86 males, 74 females) were included in the study. Mean age of patients was 30.7+-15.4 years. Major eruptions were fixed drug eruption (21.3%) followed by urticaria without angioedema (10%), maculopapular rash (9.3%), lichenoid drug eruption (8.7%), acneiform drug eruption (7.5%), Stevens-Johnson syndrome (6.9%), vesiculobullous eruption (5.6%), erythema multiforme and eczematous eruption (5% each). Common drugs causing eruptions were sulfonamides (16.3%), followed by NSAIDs (14.4%), herbal and homeopathic medications (12.5%), penicillins (9.3%), tetracyclines (8.7%), antituberculous drugs, cephalosporins and antiepileptics (6.3% each). Conclusion: Fixed drug eruption and urticaria without angioedema were commonest eruptions while, sulfonamides and NSAIDs were the major causative drugs. Policy message: Reporting of adverse drug reactions is not done in Pakistan and needs to be done in each hospital. (author)

  14. Drug Facts

    Medline Plus

    Full Text Available ... Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard to Quit Drugs? ... Drug Use and Other People Drug Use and Families Drug Use and Kids Drug Use and Unborn ...

  15. Drug Facts

    Medline Plus

    Full Text Available ... Facts Search form Search Menu Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, ... Drugs? Effects of Drugs Drug Use and Other People Drug Use and Families Drug Use and Kids ...

  16. Drug Facts

    Medline Plus

    Full Text Available ... People Drug Use and Families Drug Use and Kids Drug Use and Unborn Children Drug Use and ... Children and Teens Stay Drug-Free Talking to Kids About Drugs: What to Say if You Used ...

  17. ANTIEPILEPTIC MEDICATION IN PREGNANCY - LATE EFFECTS ON THE CHILDRENS CENTRAL-NERVOUS-SYSTEM DEVELOPMENT

    NARCIS (Netherlands)

    VANDERPOL, MC; HADDERSALGRA, M; HUISJES, HJ; TOUWEN, BCL

    In a follow-up study long-term effects of antenatal exposure to two anticonvulsant drugs, phenobarbital and carbamazepine on central nervous system development were evaluated. Children aged 6 to 13 years of epileptic mothers who used phenobarbital (n = 13), carbamazepine (n = 12), phenobarbital plus

  18. Register-based studies on migration, ethnicity, and health

    DEFF Research Database (Denmark)

    Norredam, Marie; Kastrup, Marianne; Helweg-Larsen, Karin

    2011-01-01

    INTRODUCTION: Researchers in Denmark have unique possibilities of register-based research in relation to migration, ethnicity, and health. This review article outlines how these opportunities have been used, so far, by presenting a series of examples. RESEARCH TOPICS: We selected six registers...... it discriminatory. Although, we do not register ethnicity in relation to use of health care in Denmark, our possibilities of linkage between population registers and registers on diseases and healthcare utilisation appear to render the same potentials....... to highlight the process of how migrant study populations have been established and studied in relation to different registers: The Danish Cancer Registry, the Danish Central Psychiatric Research Register, the Danish National Patient Register, the Danish National Health Service Register, the Danish Injury...

  19. REGISTER PELAKU INDUSTRI BATIK DI KOTA PEKALONGAN: KAJIAN SOSIOLINGUISTIS

    Directory of Open Access Journals (Sweden)

    Afrinar Pramitasari

    2014-08-01

    Full Text Available Register merupakan pemakaian bahasa dalam setiap bidang kehidupan yang tiap-tiap bidang kehidupanmempunyai bahasa khusus yang tidak dimengerti oleh kelompok lain. Pekalongan dikenal sebagai kota dansebagian besar pekerjaan masyarakat di Kota Pekalongan adalah sebagai perajin batik, maka dalam tuturanmereka sehari-hari juga banyak menggunakan kosakata khas bidang industri batik. Sumber data dalampenelitian ini adalah penggalan percakapan masyarakat perajin batik di Kota Pekalongan yang di dugamengandung register. Pengumpulan data menggunakan metode simak yang dalam pelaksanaanya diwujudkanmelalui teknik dasar dan teknik lanjutan. Hasil yang diperoleh dari penelitian ini adalah ada dua bentuk registerindustri batik yang ditemukan dalam penelitian ini yaitu register berdasarkan satuan lingual bahasanya danberdasarkan jenis kata. Berdasarkan satuan lingual bahasa ditemukan dua bentuk register yaitu registerberbentuk kata tunggal dan register berbentuk kata kompleks. Register berbentuk kata kompleks mencakup 1register berbentuk frasa, 2 register berbentuk kata majemuk, 3 register bentuk reduplikasi, dan 4 registerbentuk berafiks. Register a use of language in every area of life, the life of each field specific language that is notunderstood by other groups. Pekalongan City is known as the city that have potential in the batikindustry, because most of the people work in the City Pekalongan batik is as crafters, then in theireveryday speech too much use of vocabulary typical batik industry. Data sources in the form ofpublic speech in Pekalongan batik artisans containing registers. Refer to the method of datacollection that the implementation is realized through basic techniques and advanced techniques.The results of this study was two are three forms of batik industry registers were found in thisstudy is based on the unit registers lingual languag and based on grammatical categories. Basedon unit lingual language, found two registers form the single

  20. Generating synthetic baseline populations from register data

    DEFF Research Database (Denmark)

    Rich, Jeppe; Mulalic, Ismir

    2012-01-01

    . A test on historical census data shows that a 2006 population could be predicted by a 1994 population with an overall percentage deviation of 5–6% given that targets were known. It is also indicated that the deviation is approximately a linear function of the length of the forecast period....... algorithm. The solution strategy consists in establishing a harmonisation process for the population targets, which combined with a linear programming approach, is applied to generate a consistent target representation. The model approach is implemented and tested on Danish administrative register data...

  1. Illinois I/O Register to FASTBUS Interface

    International Nuclear Information System (INIS)

    Downing, R.; Lesny, D.; Whitten, W.

    1983-01-01

    The I/O Register to FASTBUS Interface (IORFI) is connected to a processor via two 16-bit output registers (OR1,OR2) and two 16-bit output resisters (IR1,IR2). One of the output registers (OR1) is used to specify the interface function which is to be performed when the interface is accessed via the Data-in Register (IR2) or the Data-out Register (OR2). The other input register (IR1) is used to read the direct status of the FASTBUS lines independent of OR1. The changes made to the SLAC design at the University of Illinois are described

  2. Optimizing Instruction Scheduling and Register Allocation for Register-File-Connected Clustered VLIW Architectures

    Science.gov (United States)

    Tang, Haijing; Wang, Siye; Zhang, Yanjun

    2013-01-01

    Clustering has become a common trend in very long instruction words (VLIW) architecture to solve the problem of area, energy consumption, and design complexity. Register-file-connected clustered (RFCC) VLIW architecture uses the mechanism of global register file to accomplish the inter-cluster data communications, thus eliminating the performance and energy consumption penalty caused by explicit inter-cluster data move operations in traditional bus-connected clustered (BCC) VLIW architecture. However, the limit number of access ports to the global register file has become an issue which must be well addressed; otherwise the performance and energy consumption would be harmed. In this paper, we presented compiler optimization techniques for an RFCC VLIW architecture called Lily, which is designed for encryption systems. These techniques aim at optimizing performance and energy consumption for Lily architecture, through appropriate manipulation of the code generation process to maintain a better management of the accesses to the global register file. All the techniques have been implemented and evaluated. The result shows that our techniques can significantly reduce the penalty of performance and energy consumption due to access port limitation of global register file. PMID:23970841

  3. Optimizing Instruction Scheduling and Register Allocation for Register-File-Connected Clustered VLIW Architectures

    Directory of Open Access Journals (Sweden)

    Haijing Tang

    2013-01-01

    Full Text Available Clustering has become a common trend in very long instruction words (VLIW architecture to solve the problem of area, energy consumption, and design complexity. Register-file-connected clustered (RFCC VLIW architecture uses the mechanism of global register file to accomplish the inter-cluster data communications, thus eliminating the performance and energy consumption penalty caused by explicit inter-cluster data move operations in traditional bus-connected clustered (BCC VLIW architecture. However, the limit number of access ports to the global register file has become an issue which must be well addressed; otherwise the performance and energy consumption would be harmed. In this paper, we presented compiler optimization techniques for an RFCC VLIW architecture called Lily, which is designed for encryption systems. These techniques aim at optimizing performance and energy consumption for Lily architecture, through appropriate manipulation of the code generation process to maintain a better management of the accesses to the global register file. All the techniques have been implemented and evaluated. The result shows that our techniques can significantly reduce the penalty of performance and energy consumption due to access port limitation of global register file.

  4. Hepatitis C prevalence in Denmark -an estimate based on multiple national registers

    DEFF Research Database (Denmark)

    Christensen, Peer Brehm; Hay, Gordon; Jepsen, Peter

    2012-01-01

    ABSTRACT: BACKGROUND: A national survey for chronic hepatitis C has not been performed in Denmark and the prevalence is unknown. Our aim was to estimate the prevalence of chronic hepatitis C from public registers and the proportion of these patients who received specialized healthcare. METHODS...... by capture-recapture analysis. The population with undiagnosed hepatitis C was derived from the national register of drug users by comparing diagnosed and tested persons. RESULTS: A total of 6,935 patients diagnosed with chronic hepatitis C were identified in the four registers and the estimated population.......37-0.42) of the population over 15 years of age. CONCLUSIONS: The estimated prevalence of chronic hepatitis C in Denmark was 0.38%. Less than half of the patients with chronic hepatitis C in Denmark have been identified and among these patients, one in three has attended specialised care....

  5. Job satisfaction of registered dental practitioners.

    Science.gov (United States)

    Luzzi, L; Spencer, A J; Jones, K; Teusner, D

    2005-09-01

    This study was designed to measure job satisfaction among registered clinical dentists so as to identify issues which may influence recruitment and retention of dentists in active clinical practice. A questionnaire measuring dimensions of job satisfaction was mailed to a stratified random sample of 80 private and 80 public sector dentists selected from the 1999 Victorian Dental Register. An adjusted response rate of 60 per cent was achieved (n = 87). Analyses showed significant differences (ANOVA; p satisfaction for various dimensions of job satisfaction by gender, age group and practice type. Differences in job satisfaction between male and female dentists related to the personal time dimension. Differences in satisfaction between dentists of different age groups were attributable to six dimensions: relationships with colleagues, relationships with patients, relationships with staff, personal time, community and administrative responsibilities. Differences between levels of satisfaction among private and public dentists related to the autonomy, relationships with patients, pay and resources dimensions. There are various dimensions of job satisfaction that may be pertinent to issues influencing recruitment and retention of dentists. Differences that exist between levels of job satisfaction among private and public sector dentists, between male and female dentists and dentists of different age groups need to be addressed in order to improve recruitment and retention rates of dentists in active clinical practice in different sectors of the dental care system.

  6. Decoherence in large NMR quantum registers

    International Nuclear Information System (INIS)

    Krojanski, Hans Georg; Suter, Dieter

    2006-01-01

    Decoherence causes the decay of the quantum information that is stored in highly correlated states during quantum computation. It is thus a limiting factor for all implementations of a quantum computer. Because a scalable quantum computer with hundreds or thousands of qubits is not available yet, experimental data about decoherence rates was restricted to small quantum registers. With solid state nuclear magnetic resonance we create highly correlated multiqubit states that serve as a model quantum register and measure their decay. By measuring the decay as a function of the system size, we determined the scaling of the decoherence rate with the number of qubits. Using the same system, we also used decoupling techniques to reduce the coupling between system and environment and thereby the decoherence rate by more than an order of magnitude, independent of the system size. For the free decay as well as for the decoupled case, we found a relatively weak scaling with system size, which could be fitted to a power law ∝K p with an exponent p≅1/2. This raises the prospect for large-scale quantum computation

  7. Registered nurse buddies: Educators by proxy?

    Science.gov (United States)

    Rebeiro, Geraldine; Evans, Alicia; Edward, Karen-Leigh; Chapman, Rose

    2017-08-01

    The informal clinical teaching role of the buddy nurse seems to be a uniquely Australian title, with little consistency in terminology for informal nurse educator roles internationally. Not all registered nurses are professionally developed for the informal role of facilitating the clinical learning of students in clinical settings, yet these roles are expected by nursing professional bodies. In Australia the registered nurses (RN) experience of being a buddy nurse has been reported as lacking clarity, being unsupported and structureless. Whist there is a plethora of literature published about formal RN educator roles, little is available on the informal buddy nurse role. A view of the buddy nurse role in reference to the limited but available literature in the Australian context is offered in this paper. International perspectives are also gathered describing informal clinical education RN's roles with similar responsibilities to the Australian buddy nurse. The significance of this dialogue is to ignite debate about the role, potentially informing policy for the improved support of the role within the Australian nursing landscape. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Socio-Economic Characteristics of Registered Cocoa Farmers in ...

    African Journals Online (AJOL)

    PROF HORSFALL

    ABSTRACT: This study examined the socio-economic characteristics of registered cocoa farmers in Edo State; ... Key words: socio-economics, characteristics, registered cocoa farmers. ... international exchange market in two world currencies ...

  9. 7 CFR 57.690 - Person required to register.

    Science.gov (United States)

    2010-01-01

    ... business will be required to register before they start operations. [69 FR 571688, Sept. 24, 2004... hatcheries, are required to register with the Department by furnishing their name, place of business, and...

  10. The Danish nationwide clinical register for patients with rheumatoid arthritis: DANBIO.

    Science.gov (United States)

    Ibfelt, Else Helene; Jensen, Dorte Vendelbo; Hetland, Merete Lund

    2016-01-01

    DANBIO is a research register and a data source for rheumatologic diseases (rheumatoid arthritis [RA], axial spondyloarthritis, and psoriatic arthritis) for monitoring clinical quality at the national, regional, and hospital levels. The register includes patients with rheumatologic diseases who are treated at a hospital or a private rheumatologic clinic. Registration is mandatory for all patients with RA regardless of treatment and also for patients with other diagnoses if treated with biological disease-modifying antirheumatic drugs. Since 2006, the registration has been done electronically, including patient-reported outcome measures registered electronically by the patients with the use of touch screens. Core variables such as diagnosis, year of diagnosis, age, and sex are registered at the beginning. Data entered at later visits included the following: patient-reported outcomes for disease activity, pain, fatigue, functional status, and physician-reported objective measures of disease activity, treatment, C-reactive protein, and, when indicated, imaging. For subgroups of patients, the variables such as quality of life, sociodemographic factors, lifestyle, and comorbidity are also registered. The DANBIO cohort comprised ∼26,000 patients with RA, 3,200 patients with axial spondyloarthritis, and 6,200 patients with psoriatic arthritis in 2015. DANBIO has high nationwide coverage and completeness on key data variables. More than 60 original papers as well as annual reports of clinical quality (since 2005) have been published. DANBIO is a powerful register for research in rheumatologic diseases and furthermore serves as a Clinical Quality Register with the aim of monitoring treatment quality in patients with RA in Denmark.

  11. Universal Verification Methodology Based Register Test Automation Flow.

    Science.gov (United States)

    Woo, Jae Hun; Cho, Yong Kwan; Park, Sun Kyu

    2016-05-01

    In today's SoC design, the number of registers has been increased along with complexity of hardware blocks. Register validation is a time-consuming and error-pron task. Therefore, we need an efficient way to perform verification with less effort in shorter time. In this work, we suggest register test automation flow based UVM (Universal Verification Methodology). UVM provides a standard methodology, called a register model, to facilitate stimulus generation and functional checking of registers. However, it is not easy for designers to create register models for their functional blocks or integrate models in test-bench environment because it requires knowledge of SystemVerilog and UVM libraries. For the creation of register models, many commercial tools support a register model generation from register specification described in IP-XACT, but it is time-consuming to describe register specification in IP-XACT format. For easy creation of register model, we propose spreadsheet-based register template which is translated to IP-XACT description, from which register models can be easily generated using commercial tools. On the other hand, we also automate all the steps involved integrating test-bench and generating test-cases, so that designers may use register model without detailed knowledge of UVM or SystemVerilog. This automation flow involves generating and connecting test-bench components (e.g., driver, checker, bus adaptor, etc.) and writing test sequence for each type of register test-case. With the proposed flow, designers can save considerable amount of time to verify functionality of registers.

  12. Register Variation in Electronic Business Correspondence

    Directory of Open Access Journals (Sweden)

    Rosa Giménez Moreno

    2011-06-01

    Full Text Available Electronic correspondence is a highly dynamic genre within the business world in which Register Variation (RV is frequently used as a tool to improve communication but it often can lead to misunderstanding. In order to shed some light on this still unexplored area, the present study firstly offers a practical approach to classify and analyse RV within professional communication. After this, it reviews previous studies on email writing to apply their findings to this approach and, in the third part of the study, a corpus of recent business emails in English is analysed to examine how the key parameters of RV are currently used within this genre. The results will show that, not only the context, but also the roles and intentions of the senders influence an email’s register, often causing internal oscillations between different registers within the same text.La correspondencia electrónica es un género comunicativo de especial dinamismo dentro del mundo empresarial en el que la variación de registros se utiliza como herramienta para mejorar la interacción y las relaciones entre los interlocutores, pero que a menudo también genera confusión y malentendidos. Para aportar luz a esta área, el presente trabajo ofrece una aproximación práctica para la clasificación y el análisis de los registros lingüísticos dentro de la comunicación profesional. A continuación, revisa los estudios previos sobre este género con el fin de adaptar sus resultados a la teoría propuesta. Finalmente, se analiza un corpus de mensajes escritos en inglés para examinar el funcionamiento de los registros dentro de este género. Los resultados mostrarán que, no solo el contexto situacional, sino sobre todo los roles e intenciones de los emisores determinan el registro de un mensaje, provocando a menudo oscilación interna entre varios registros dentro del mismo texto.

  13. Drug Facts

    Medline Plus

    Full Text Available ... Treatment and Recovery Resources? Prevention Help Children and Teens Stay Drug-Free Talking to Kids About Drugs: What to Say if You Used Drugs in the Past Drug Use ... Videos Information About Drugs Alcohol ...

  14. Drug Allergy

    Science.gov (United States)

    ... Loss of consciousness Other conditions resulting from drug allergy Less common drug allergy reactions occur days or ... you take the drug. Drugs commonly linked to allergies Although any drug can cause an allergic reaction, ...

  15. Studies based on the Danish Adoption Register

    DEFF Research Database (Denmark)

    Petersen, Liselotte; Sørensen, Thorkild I A

    2011-01-01

    biological relatives to adoptees without schizophrenia. Clear trends in body mass index of biological relatives and the weight of adoptees were found in several settings. A genetic influence on smoking habits were found within a generation. A moderate genetic influence on the mortality rate has been found....... CONCLUSION: The Danish Adoption Register has contributed to the knowledge about environmental and genetic influence in various fields. Genetic influence on the risk of schizophrenia, body fatness, smoking habits, and on the mortality rate has been found........ RESEARCH TOPICS: To illustrate the adoption study approach in research, we present results achieved in schizophrenia, body fatness, smoking, and mortality. Significantly higher prevalence of schizophrenia and related conditions were found in biological relatives to adoptees with schizophrenia than among...

  16. Efficient sorting using registers and caches

    DEFF Research Database (Denmark)

    Wickremesinghe, Rajiv; Arge, Lars Allan; Chase, Jeffrey S.

    2002-01-01

    . Inadequate models lead to poor algorithmic choices and an incomplete understanding of algorithm behavior on real machines.A key step toward developing better models is to quantify the performance effects of features not reflected in the models. This paper explores the effect of memory system features...... on sorting performance. We introduce a new cache-conscious sorting algorithm, R-MERGE, which achieves better performance in practice over algorithms that are superior in the theoretical models. R-MERGE is designed to minimize memory stall cycles rather than cache misses by considering features common to many......Modern computer systems have increasingly complex memory systems. Common machine models for algorithm analysis do not reflect many of the features of these systems, e.g., large register sets, lockup-free caches, cache hierarchies, associativity, cache line fetching, and streaming behavior...

  17. Ambulatory care registered nurse performance measurement.

    Science.gov (United States)

    Swan, Beth Ann; Haas, Sheila A; Chow, Marilyn

    2010-01-01

    On March 1-2, 2010, a state-of-the-science invitational conference titled "Ambulatory Care Registered Nurse Performance Measurement" was held to focus on measuring quality at the RN provider level in ambulatory care. The conference was devoted to ambulatory care RN performance measurement and quality of health care. The specific emphasis was on formulating a research agenda and developing a strategy to study the testable components of the RN role related to care coordination and care transitions, improving patient outcomes, decreasing health care costs, and promoting sustainable system change. The objectives were achieved through presentations and discussion among expert inter-professional participants from nursing, public health, managed care, research, practice, and policy. Conference speakers identified priority areas for a unified practice, policy, and research agenda. Crucial elements of the strategic dialogue focused on issues and implications for nursing and inter-professional practice, quality, and pay-for-performance.

  18. Village registers for vital registration in rural Malawi.

    Science.gov (United States)

    Singogo, E; Kanike, E; van Lettow, M; Cataldo, F; Zachariah, R; Bissell, K; Harries, A D

    2013-08-01

    Paper-based village registers were introduced 5 years ago in Malawi as a tool to measure vital statistics of births and deaths at the population level. However, usage, completeness and accuracy of their content have never been formally evaluated. In Traditional Authority Mwambo, Zomba district, Malawi, we assessed 280 of the 325 village registers with respect to (i) characteristics of village headmen who used village registers, (ii) use and content of village registers, and (iii) whether village registers provided accurate information on births and deaths. All village headpersons used registers. There were 185 (66%) registers that were regarded as 95% completed, and according to the registers, there were 115 840 people living in the villages in the catchment area. In 2011, there were 1753 births recorded in village registers, while 6397 births were recorded in health centre registers in the same catchment area. For the same year, 199 deaths were recorded in village registers, giving crude death rates per 100 000 population of 189 for males and 153 for females. These could not be compared with death rates in health centre registers due to poor and inconsistent recording in these registers, but they were compared with death rates obtained from the 2010 Malawi Demographic Health Survey that reported 880 and 840 per 100 000 for males and females, respectively. In conclusion, this study shows that village registers are a potential source for vital statistics. However, considerable inputs are needed to improve accuracy of births and deaths, and there are no functional systems for the collation and analysis of data at the traditional authority level. Innovative ways to address these challenges are discussed, including the use of solar-powered electronic village registers and mobile phones, connected with each other and the health facilities and the District Commissioner's office through the cellular network and wireless coverage. © 2013 John Wiley & Sons Ltd.

  19. Eslicarbazepine acetate add-on for drug-resistant partial epilepsy.

    Science.gov (United States)

    Chang, Xian-Chao; Yuan, Hai; Wang, Yi; Xu, Hui-Qin; Hong, Wen-Ke; Zheng, Rong-Yuan

    2017-10-25

    This is an updated version of the Cochrane Review published in the Cochrane Library 2011, Issue 12.The majority of people with epilepsy have a good prognosis, but up to 30% of people continue to have seizures despite several regimens of antiepileptic drugs. In this review, we summarized the current evidence regarding eslicarbazepine acetate (ESL) when used as an add-on treatment for drug-resistant partial epilepsy. To evaluate the efficacy and tolerability of ESL when used as an add-on treatment for people with drug-resistant partial epilepsy. The searches for the original review were run in November 2011. Subsequently, we searched the Cochrane Epilepsy Group Specialized Register (6 December 2016), the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 11) and MEDLINE (1946 to 6 December 2016). There were no language restrictions. We reviewed the reference lists of retrieved studies to search for additional reports of relevant studies. We also contacted the manufacturers of ESL and experts in the field for information about any unpublished or ongoing studies. Randomized placebo controlled double-blind add-on trials of ESL in people with drug-resistant partial epilepsy. Two review authors independently selected trials for inclusion and extracted data. Outcomes investigated included 50% or greater reduction in seizure frequency, seizure freedom, treatment withdrawal, adverse effects, and drug interactions. Primary analyses were by intention to treat (ITT). The dose-response relationship was evaluated in regression models. We included five trials (1799 participants) rated at low risk of bias; all studies were funded by BIAL. The overall risk ratio (RR) with 95% confidence interval (CI) for 50% or greater reduction in seizure frequency was 1.71 (95% CI 1.42 to 2.05). Dose regression analysis showed evidence that ESL reduced seizure frequency with an increase in efficacy with increasing doses of ESL. ESL was significantly associated with seizure freedom

  20. An analysis of characteristics of post-authorisation studies registered on the ENCePP EU PAS Register [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Robert Carroll

    2017-11-01

    Full Text Available Background: The objective of this study was to investigate the study design characteristics of Post-Authorisation Studies (PAS requested by the European Medicines Agency which were recorded on the European Union (EU PAS Register held by the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP. Methods: We undertook a cross-sectional descriptive analysis of all studies registered on the EU PAS Register as of 18th October 2016. Results: We identified a total of 314 studies on the EU PAS Register, including 81 (26% finalised, 160 (51% ongoing and 73 (23% planned. Of those studies identified, 205 (65% included risk assessment in their scope, 133 (42% included drug utilisation and 94 (30% included effectiveness evaluation. Just over half of the studies (175; 56% used primary data capture, 135 (43% used secondary data and 4 (1% used a hybrid design combining both approaches. Risk assessment and effectiveness studies were more likely to use primary data capture (60% and 85% respectively as compared to 39% and 14% respectively for secondary. The converse was true for drug utilisation studies where 59% were secondary vs. 39% for primary. For type 2 diabetes mellitus, database studies were more commonly used (80% vs 3% chart review, 3% hybrid and 13% primary data capture study designs whereas for studies in oncology, primary data capture were more likely to be used (85% vs 4% chart review, and 11% database study designs. Conclusions: Results of this analysis show that PAS design varies according to study objectives and therapeutic area.

  1. Identifying victims of violence using register-based data

    DEFF Research Database (Denmark)

    Kruse, Marie; Sørensen, Jan; Brønnum-Hansen, Henrik

    2010-01-01

    AIMS: The aim of this study was twofold. Firstly we identified victims of violence in national registers and discussed strengths and weaknesses of this approach. Secondly we assessed the magnitude of violence and the characteristics of the victims using register-based data. METHODS: We used three...... nationwide registers to identify victims of violence: The National Patient Register, the Victim Statistics, and the Causes of Death Register. We merged these data and assessed the degree of overlap between data sources. We identified a reference population by selecting all individuals in Denmark over 15....... RESULTS: In 2006, 22,000 individuals were registered as having been exposed to violence. About 70% of these victims were men. Most victims were identified from emergency room contacts and police records, and few from the Causes of Death Register. There was some overlap between the two large data sources...

  2. A small trapped-ion quantum register

    International Nuclear Information System (INIS)

    Kielpinski, D

    2003-01-01

    We review experiments performed at the National Institute of Standards and Technology on entanglement, Bell's inequality and decoherence-free subspaces (DFSs) in a quantum register of trapped 9 Be + ions. The group of Dr David Wineland has demonstrated entanglement of up to four ions using the technique of Molmer and Sorensen. This method produces the state (|↓↓> + |↑↑>)/√2 for two ions and the state (|↓↓↓↓> + |↑↑↑↑>)/√2 for four ions. The entanglement was generated deterministically in each shot of the experiment. Measurements on the two-ion entangled state violate Bell's inequality at the 8σ level. Because of the high detector efficiency of the apparatus, this experiment closes the detector loophole for Bell's inequality measurements for the first time. This measurement is also the first violation of Bell's inequality by massive particles that does not implicitly assume results from quantum mechanics. The group also demonstrated measurement of an interferometric phase with precision better than the shot-noise limit using a two-ion entangled state. A large-scale version of this scheme could improve the signal-to-noise ratio of atomic clocks by orders of magnitude. Further experiments demonstrated reversible encoding of an arbitrary qubit, originally contained in one ion, into a DFS of two ions. The DFS-encoded qubit resists applied collective dephasing noise and retains coherence under ambient conditions 3.6 times longer than does an unencoded qubit. The encoding method, which uses single-ion gates and the two-ion entangling gate, demonstrates all the elements required for two-qubit universal quantum logic. Finally, we describe an architecture for a large-scale ion trap quantum computer. By performing logic gates on small numbers of ions trapped in separate regions of the array, we take advantage of existing techniques for manipulating small trapped-ion quantum registers while enabling massively parallel gate operation. Encoding the

  3. Transitioning from military medics to registered nurses

    Directory of Open Access Journals (Sweden)

    Keita MD

    2015-11-01

    Full Text Available Mohamed D Keita,1 Valerie J Diaz,1,2 Audrey P Miller,1 Maria Olenick,1 Sharon R Simon1 1Department of Undergraduate Nursing, Nicole Wertheim College of Nursing and Health Sciences, Florida International University, Miami, 2Operational Health Support Unit Jacksonville, United States Navy Nurse Corps, Jacksonville, FL, USA Abstract: The nursing shortage in the USA is expected to reach 260,000 registered nurses (RNs by 2025. The most profound shortages are expected in California and Florida, translating into 109,779 and 128,364 RN jobs, respectively. Despite a foreseen growth in nursing career opportunities nationwide, the supply of nurses will be insufficient to meet the corresponding demand. Capitalizing on prior education, experience, and skills of military clinical personnel to fill these jobs could significantly reduce the projected nursing shortage. Florida International University's Nicole Wertheim College of Nursing and Health Sciences is circumventing barriers to recruit, retain, and graduate transitioning veteran medics and corpsmen as Bachelor of Science in Nursing prepared RNs who reintegrate into the civilian workforce. The Veteran Bachelor of Science in Nursing (VBSN program is in the form of a cooperative agreement between Florida International University and the US Health Resources and Services Administration. The VBSN program's main objective is to build upon the unique leadership skills, clinical education, and training of military medics and corpsmen to ensure successful completion of the Bachelor of Science in Nursing curriculum. VBSN students, as veterans themselves, have unique knowledge and exposure to the specific health issues and needs of the veteran population overall. They are poised and best prepared to effectively care for the US population, particularly the current 22 million US veterans and 1.6 million Florida veterans. Additionally, the VBSN program will alleviate the challenges, such as the lack of recognition of

  4. Danish Register of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Lange P

    2016-10-01

    Full Text Available Peter Lange,1,2 Sandra Søgaard Tøttenborg,1 Anne Dichmann Sorknæs,3 Jørgen Steen Andersen,4 Mette Søgaard,5 Henrik Nielsen,5 Reimar Wernich Thomsen,5 Katrine Abildtrup Nielsen6 1Section of Social Medicine, Department of Public Health, University of Copenhagen, 2Lung Diseases Department, Respiratory Medicine Section, Lung Diseases Department, Hvidovre Hospital, University of Copenhagen, Copenhagen, 3Medical Department, Odense Universitetshospital–Svendborg Hospital, Svendborg, 4Danish College of General Practitioners, Copenhagen, 5Department of Clinical Epidemiology, Aarhus University Hospital, 6Registry Support Centre of Clinical Quality and Health Informatics (West, Århus, Denmark Aim of database: The Danish Register of Chronic Obstructive Pulmonary Disease (DrCOPD is a nationwide database aiming to describe the quality of treatment of all patients with chronic obstructive pulmonary disease (COPD in Denmark. Study population: DrCOPD comprises data on all patients with a diagnosis of COPD. In the hospital setting, both in- and outpatients are included. In the setting of the general practice (GP, DrCOPD aims to include all patients with a COPD diagnosis who attend an annual control visit for COPD. Main variables: DrCOPD includes information on forced expiratory volume in 1 second, smoking status, body mass index, dyspnea, treatment modalities such as rehabilitation, smoking cessation, medical treatment, and the use of noninvasive ventilation during hospitalization due to exacerbations. The outcome variables include frequency of readmission and death 30 days after discharge from hospital. Descriptive data: Since 2008, the registration in the Danish hospitals has gradually become more comprehensive. In 2014, ~90% of 16,106 eligible patients had complete data sets that showed an improvement in the processes describing quality of care, including increased offering of smoking cessation, rehabilitation, and correct treatment with inhaled

  5. Your brain on drugs: imaging of drug-related changes in the central nervous system.

    Science.gov (United States)

    Tamrazi, Benita; Almast, Jeevak

    2012-01-01

    Drug abuse is a substantial problem in society today and is associated with significant morbidity and mortality. Various drugs are associated with serious complications affecting the brain, and it is critical to recognize the imaging findings of these complications to provide prompt medical management. The central nervous system (CNS) is a target organ for drugs of abuse as well as specific prescribed medications. Drugs of abuse affecting the CNS include cocaine, heroin, alcohol, amphetamines, toluene, and cannabis. Prescribed medications or medical therapies that can affect the CNS include immunosuppressants, antiepileptics, nitrous oxide, and total parenteral nutrition. The CNS complications of these drugs include neurovascular complications, encephalopathy, atrophy, infection, changes in the corpus callosum, and other miscellaneous changes. Imaging abnormalities indicative of these complications can be appreciated at both magnetic resonance (MR) imaging and computed tomography (CT). It is critical for radiologists to recognize complications related to drugs of abuse as well as iatrogenic effects of various medications. Therefore, diagnostic imaging modalities such as MR imaging and CT can play a pivotal role in the recognition and timely management of drug-related complications in the CNS.

  6. Registered Replication Report: Strack, Martin, & Stepper (1988).

    Science.gov (United States)

    Acosta, Alberto; Adams, Reginald B; Albohn, Daniel N; Allard, Eric S; Beek, Titia; Benning, Stephen D; Blouin- Hudon, Eve-Marie; Bulnes, Luis Carlo; Caldwell, Tracy L; Calin-Jageman, Robert J; Capaldi, Colin A; Carfagno, Nicholas S; Chasten, Kelsie T; Cleeremans, Axel; Connell, Louise; DeCicco, Jennifer M.; Dijkhoff, Laura; Dijkstra, Katinka; Fischer, Agneta H; Foroni, Francesco; Gronau, Quentin F; Hess, Ursula; Holmes, Kevin J; Jones, Jacob L H; Klein, Olivier; Koch, Christopher; Korb, Sebastian; Lewinski, Peter; Liao, Julia D; Lund, Sophie; Lupiáñez, Juan; Lynott, Dermot; Nance, Christin N; Oosterwijk, Suzanne; Özdog˘ru, Asil Ali; Pacheco-Unguetti, Antonia Pilar; Pearson, Bethany; Powis, Christina; Riding, Sarah; Roberts, Tomi-Ann; Rumiati, Raffaella I; Senden, Morgane; Shea-Shumsky, Noah B; Sobocko, Karin; Soto, Jose A; Steiner, Troy G; Talarico, Jennifer M; vanAllen, Zack M; Wagenmakers, E-J; Vandekerckhove, Marie; Wainwright, Bethany; Wayand, Joseph F; Zeelenberg, Rene; Zetzer, Emily E; Zwaan, Rolf A

    2016-11-01

    According to the facial feedback hypothesis, people's affective responses can be influenced by their own facial expression (e.g., smiling, pouting), even when their expression did not result from their emotional experiences. For example, Strack, Martin, and Stepper (1988) instructed participants to rate the funniness of cartoons using a pen that they held in their mouth. In line with the facial feedback hypothesis, when participants held the pen with their teeth (inducing a "smile"), they rated the cartoons as funnier than when they held the pen with their lips (inducing a "pout"). This seminal study of the facial feedback hypothesis has not been replicated directly. This Registered Replication Report describes the results of 17 independent direct replications of Study 1 from Strack et al. (1988), all of which followed the same vetted protocol. A meta-analysis of these studies examined the difference in funniness ratings between the "smile" and "pout" conditions. The original Strack et al. (1988) study reported a rating difference of 0.82 units on a 10-point Likert scale. Our meta-analysis revealed a rating difference of 0.03 units with a 95% confidence interval ranging from -0.11 to 0.16. © The Author(s) 2016.

  7. Quantum logic between remote quantum registers

    Science.gov (United States)

    Yao, N. Y.; Gong, Z.-X.; Laumann, C. R.; Bennett, S. D.; Duan, L.-M.; Lukin, M. D.; Jiang, L.; Gorshkov, A. V.

    2013-02-01

    We consider two approaches to dark-spin-mediated quantum computing in hybrid solid-state spin architectures. First, we review the notion of eigenmode-mediated unpolarized spin-chain state transfer and extend the analysis to various experimentally relevant imperfections: quenched disorder, dynamical decoherence, and uncompensated long-range coupling. In finite-length chains, the interplay between disorder-induced localization and decoherence yields a natural optimal channel fidelity, which we calculate. Long-range dipolar couplings induce a finite intrinsic lifetime for the mediating eigenmode; extensive numerical simulations of dipolar chains of lengths up to L=12 show remarkably high fidelity despite these decay processes. We further briefly consider the extension of the protocol to bosonic systems of coupled oscillators. Second, we introduce a quantum mirror based architecture for universal quantum computing that exploits all of the dark spins in the system as potential qubits. While this dramatically increases the number of qubits available, the composite operations required to manipulate dark-spin qubits significantly raise the error threshold for robust operation. Finally, we demonstrate that eigenmode-mediated state transfer can enable robust long-range logic between spatially separated nitrogen-vacancy registers in diamond; disorder-averaged numerics confirm that high-fidelity gates are achievable even in the presence of moderate disorder.

  8. Pre-surgical register of tobacco consumption.

    Science.gov (United States)

    Gavilán, Eva; Moreno, Montse; Pérez, Àngels; Castellano, Yolanda; Fernández, Esteve; Martínez, Cristina

    2018-03-24

    Smoking cessation before surgery decreases the risk of complications. The aim of this study was to analyse the smoking register, associated variables and a short talk given to smokers in pre-surgical visits. Cross-sectional study. The pre-surgical records of 680 patients were assessed. We selected patient sociodemographic variables, surgical intervention characteristics, smoking status and consumption pattern. Logistic regression was used to study the variables association with smoking. A percentage of 97.2 of the pre-surgical records include information on tobacco consumption. Overall 20% of surgical patients are smokers. The probability of smoking is higher among men (adjusted odds ratio [aOR] 2.6, 95% confidence interval [CI] 1.7-4.0) and≤60 years (aOR 5.4, 95% CI 3.2-9.1). None of the records had information regarding a short talk given to patients to give up smoking. Smoking consumption was prevalent, but the characterisation of a smoker's profile and short talk given to patient before surgery was practically nonexistent. Ensuring that patients who smokes receives a short talk to give up smoking before surgery is necessary. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

  9. Generational differences among newly licensed registered nurses.

    Science.gov (United States)

    Keepnews, David M; Brewer, Carol S; Kovner, Christine T; Shin, Juh Hyun

    2010-01-01

    Responses of 2369 newly licensed registered nurses from 3 generational cohorts-Baby Boomers, Generation X, and Generation Y-were studied to identify differences in their characteristics, work-related experiences, and attitudes. These responses revealed significant differences among generations in: job satisfaction, organizational commitment, work motivation, work-to-family conflict, family-to-work conflict, distributive justice, promotional opportunities, supervisory support, mentor support, procedural justice, and perceptions of local job opportunities. Health organizations and their leaders need to anticipate intergenerational differences among newly licensed nurses and should provide for supportive working environments that recognize those differences. Orientation and residency programs for newly licensed nurses should be tailored to the varying needs of different generations. Future research should focus on evaluating the effectiveness of orientation and residency programs with regard to different generations so that these programs can be tailored to meet the varying needs of newly licensed nurses at the start of their careers. Copyright 2010 Mosby, Inc. All rights reserved.

  10. THE CAPABILITIES OF A REGISTER AS A QUALITY CONTROL OF THE PHARMACOTHERAPY IN OUTPATIENTS AT HIGH RISK OF CARDIOVASCULAR COMPLICATIONS (THE "LIS-1" REGISTER

    Directory of Open Access Journals (Sweden)

    M. L. Ginzburg

    2014-01-01

    Full Text Available Aim. To evaluate the frequency of the prescription of cardiovascular drugs in patients before the reference acute myocardial infarction (AMI based on the register "LIS-1" (Lubertsy mortality study of patients after myocardial infarction.Material and methods. Stage 1: development of the Register of patients with AMI admitted to cardiology departments of hospitals in Luberets district, Moscow region (2005-2007 and discharged for outpatient treatment. Median follow-up – 1.6 years (1.0, 2.4. The primary endpoint – total mortality. Stage 2: the continuation of register "LIS-1" (2011-2012.Results.1133 patients (mean age of men 60.1±0.5, women – 71.4±0.4 years were included in the 1st stage of the study; 172 (15.2% died in the hospital. Before the reference hospitalization 21.4% of patients had been receiving b-blockers, 35.3% - renin-angiotensin-aldosterone system (RAAS inhibitors, 15.7% - antiplatelet agents, 1.9% - statins, 13% of patients - diuretics. Statistically significant (adjusted for sex and age positive impact on hospital mortality reduction had a treatment with b-blockers [OR=0.542, CI=0.357-0.824, p=0.004] and RAAS inhibitors [OR=0.710; CI=0.512-0.986, p=0.040] prior to the development of acute myocardial infarction. As the number of patients receiving statins and antiplatelet agents was small, the contribution these drugs intake on hospital mortality was not identified. 272 patients (mean age 63.6±12.6 years were included on the second phase of the study. The information about the received therapy before reference hospitalization was reported by 173 patients: 39% of patients used b-blockers, 47% - RAAS inhibitors, 37% - antiplatelet agents, 15% - statins, 15% of patients - diuretics. Positive changes in the frequency of the prescription of essential drugs were observed in 5 years: a significant increase in number of patients with b-blockers (p<0.001, RAAS inhibitors (p<0.01, antiplatelet agents (p<0.05 and statins (p<0.001. The

  11. THE CAPABILITIES OF A REGISTER AS A QUALITY CONTROL OF THE PHARMACOTHERAPY IN OUTPATIENTS AT HIGH RISK OF CARDIOVASCULAR COMPLICATIONS (THE "LIS-1" REGISTER

    Directory of Open Access Journals (Sweden)

    M. L. Ginzburg

    2015-09-01

    Full Text Available Aim. To evaluate the frequency of the prescription of cardiovascular drugs in patients before the reference acute myocardial infarction (AMI based on the register "LIS-1" (Lubertsy mortality study of patients after myocardial infarction.Material and methods. Stage 1: development of the Register of patients with AMI admitted to cardiology departments of hospitals in Luberets district, Moscow region (2005-2007 and discharged for outpatient treatment. Median follow-up – 1.6 years (1.0, 2.4. The primary endpoint – total mortality. Stage 2: the continuation of register "LIS-1" (2011-2012.Results.1133 patients (mean age of men 60.1±0.5, women – 71.4±0.4 years were included in the 1st stage of the study; 172 (15.2% died in the hospital. Before the reference hospitalization 21.4% of patients had been receiving b-blockers, 35.3% - renin-angiotensin-aldosterone system (RAAS inhibitors, 15.7% - antiplatelet agents, 1.9% - statins, 13% of patients - diuretics. Statistically significant (adjusted for sex and age positive impact on hospital mortality reduction had a treatment with b-blockers [OR=0.542, CI=0.357-0.824, p=0.004] and RAAS inhibitors [OR=0.710; CI=0.512-0.986, p=0.040] prior to the development of acute myocardial infarction. As the number of patients receiving statins and antiplatelet agents was small, the contribution these drugs intake on hospital mortality was not identified. 272 patients (mean age 63.6±12.6 years were included on the second phase of the study. The information about the received therapy before reference hospitalization was reported by 173 patients: 39% of patients used b-blockers, 47% - RAAS inhibitors, 37% - antiplatelet agents, 15% - statins, 15% of patients - diuretics. Positive changes in the frequency of the prescription of essential drugs were observed in 5 years: a significant increase in number of patients with b-blockers (p<0.001, RAAS inhibitors (p<0.01, antiplatelet agents (p<0.05 and statins (p<0.001. The

  12. Fighting Fire with Fire: Surgical Options for Patients with Drug-Resistant Epilepsy.

    Science.gov (United States)

    Bayer, Alina D; Blum, Andrew S; Asaad, Wael F; Roth, Julie; Toms, Steven A; Deck, Gina M

    2018-03-01

    While antiepileptic drugs (AEDs) provide adequate seizure control for most patients with epilepsy, ~30% continue to have seizures despite treatment with two or more AEDs.1 In addition to direct harm from seizures, poor epilepsy control correlates with higher mortality, morbidity, 2, 3 and cost to the healthcare system.4 In the subset of patients with persistent seizures despite medical management, surgical intervention and neuromodulation may be more effective. Primary care physicians and general neurologists should be aware of non-AED treatment options that are standard of care for drug- resistant epilepsy (DRE). [Full article available at http://rimed.org/rimedicaljournal-2018-03.asp].

  13. Comorbidity and temporal ordering of alcohol use disorders and other psychiatric disorders: results from a Danish register-based study

    DEFF Research Database (Denmark)

    Flensborg-Madsen, Trine; Mortensen, Erik Lykke; Knop, Joachim

    2009-01-01

    AUD in individuals who were already registered with another psychiatric disorder; these differences in risk were especially noticeable for anxiety disorders, personality disorders, and drug abuse. CONCLUSIONS: AUD is frequently comorbid with other psychiatric disorders, and it is likely that AUD...

  14. [Neonatal risks of drugs exposure at the end of pregnancy].

    Science.gov (United States)

    Autret-Leca, Elisabeth; Cissoko, Hawaré; Jonville-Béra, Annie Pierre

    2011-01-01

    Foetal drugs exposure consequences depend according to the drug involved and to the length of the exposure which in the sum of length of treatment and of drug elimination (5 half life). Decisions are based upon risk evaluation and are a compromise between a risk banalisation and an excess of carefully. We described risks management for drugs used for a disease due to the pregnancy (glucocorticoïdes, antibiotics) then for drugs used for a chronic disease often preceding the pregnancy (non steroidal anti-inflammatory, serotonin recapture inhibitors, benzodiazepines, antiepileptics, conversion enzyme inhibitors/renine angiotensine antagonists, betabloquants). We also present the elements to take in account for the best drug choice at the end of pregnancy and/or for an adapted advice if the drug has been already taken: the drug itself (pharmacological effects, kinetics in neonate, toxicity marker, risk detection tool), drug amount possibly received by the neonate and literature data about neonatal manifestations due to the drug. © 2011 Société Française de Pharmacologie et de Thérapeutique.

  15. 76 FR 51310 - Branded Prescription Drug Fee

    Science.gov (United States)

    2011-08-18

    ... Branded Prescription Drug Fee AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice of proposed... issue of the Federal Register, the IRS is issuing temporary regulations relating to the branded... business of manufacturing or importing certain branded prescription drugs. The text of the temporary...

  16. Drug Safety

    Science.gov (United States)

    ... over-the-counter drug. The FDA evaluates the safety of a drug by looking at Side effects ... clinical trials The FDA also monitors a drug's safety after approval. For you, drug safety means buying ...

  17. Drug Abuse

    Science.gov (United States)

    ... Cocaine Heroin Inhalants Marijuana Prescription drugs, including opioids Drug abuse also plays a role in many major social problems, such as drugged driving, violence, stress, and child abuse. Drug abuse can lead to ...

  18. Drug Facts

    Medline Plus

    Full Text Available ... Use and Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug ...

  19. Drug Facts

    Medline Plus

    Full Text Available ... Drug Use and Kids Drug Use and Unborn Children Drug Use and Your Health Other Effects on ... Someone Find Treatment and Recovery Resources? Prevention Help Children and Teens Stay Drug-Free Talking to Kids ...

  20. Club Drugs

    Science.gov (United States)

    ... uses. Other uses of these drugs are abuse. Club drugs are also sometimes used as "date rape" drugs, to make someone unable to say no to or fight back against sexual assault. Abusing these drugs can ...

  1. Validity of dementia diagnoses in the danish hospital registers

    DEFF Research Database (Denmark)

    Phung, T.K.T.; Andersen, B.B.; Phung, T.K.T.

    2007-01-01

    .24-0.48). Conclusion: The validity of dementia syndrome in the Danish hospital registers was high and allows for epidemiological studies about dementia. Alzheimer's disease, although underregistered, also had a good validity once the diagnosis was registered. In general, other ICD-10 dementia subtypes in the registers......Background:The validity of dementia diagnoses in the Danish nationwide hospital registers was evaluated to determine the value of these registers in epidemiological research about dementia. Methods: Two hundred patients were randomly selected from 4,682 patients registered for the first time...... with a dementia diagnosis in the last 6 months of 2003. The patients' medical journals were reviewed to evaluate if they fulfilled ICD-10 and/or DSM-IV criteria for dementia and specific dementia subtypes. The patients who were still alive in 2006 were invited to an interview. Results: One hundred and ninety...

  2. REGISTER PERCAKAPAN ANGGOTA KESATUAN LALU LINTAS POLRESTA PONTIANAK: KAJIAN SOSIOLINGUISTIK

    Directory of Open Access Journals (Sweden)

    Wahyu Damayanti

    2017-10-01

    Full Text Available Register adalah variasi bahasa berdasarkan penggunaannya. Variasi bahasa merupakan wujud keanekaragaman bahasa yang ditampilkan berdasarkan konteks yang menyertainya, termasuk penutur dan penggunaannya. Tujuan penelitian ini adalah mendiskripsikan bentuk register yang terdapat pada percakapan anggota kesatuan lalu lintas Polresta Pontianak. Metode yang digunakan dalam penelitian ini adalah metode kualitatif. Teknik pengumpulan data dengan cara simak dan catat. Data penelitian ini berupa kata, abreviasi, kode, istilah, dan wacana yang termasuk register dalam percakapan komunitas Satlantas Polresta Pontianak melalui jejaring sosial WhatsApp pada bulan Agustus dan September 2016. Teknik analisis data menggunakan analisis interaktif. Hasil dan pembahasaan penelitian ini menunjukkan bahwa karakteristik bentuk register dalam percakapan anggota melalui jejaring sosial WhatsApp berupa bentuk dasar, bentuk berafiks, bentuk ulang, bentuk majemuk, pemendekan atau abreviasi, pemenggalan, singkatan, akronim, kontraksi, sapaan, kode, dan istilah khusus. Dengan demikian, penelitian register dalam percakapan anggota Satlantas merupakan satu di antara bentuk register yang terjadi di masyarakat, dalam hal ini kajian sosiolinguistik.

  3. Transitioning from military medics to registered nurses.

    Science.gov (United States)

    Keita, Mohamed D; Diaz, Valerie J; Miller, Audrey P; Olenick, Maria; Simon, Sharon R

    2015-01-01

    The nursing shortage in the USA is expected to reach 260,000 registered nurses (RNs) by 2025. The most profound shortages are expected in California and Florida, translating into 109,779 and 128,364 RN jobs, respectively. Despite a foreseen growth in nursing career opportunities nationwide, the supply of nurses will be insufficient to meet the corresponding demand. Capitalizing on prior education, experience, and skills of military clinical personnel to fill these jobs could significantly reduce the projected nursing shortage. Florida International University's Nicole Wertheim College of Nursing and Health Sciences is circumventing barriers to recruit, retain, and graduate transitioning veteran medics and corpsmen as Bachelor of Science in Nursing prepared RNs who reintegrate into the civilian workforce. The Veteran Bachelor of Science in Nursing (VBSN) program is in the form of a cooperative agreement between Florida International University and the US Health Resources and Services Administration. The VBSN program's main objective is to build upon the unique leadership skills, clinical education, and training of military medics and corpsmen to ensure successful completion of the Bachelor of Science in Nursing curriculum. VBSN students, as veterans themselves, have unique knowledge and exposure to the specific health issues and needs of the veteran population overall. They are poised and best prepared to effectively care for the US population, particularly the current 22 million US veterans and 1.6 million Florida veterans. Additionally, the VBSN program will alleviate the challenges, such as the lack of recognition of military skills, unemployment, the substandard income, and homelessness that many former service members face after separation from the military.

  4. Pollutant Release and Transfer Register; Emissieregistratie

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2008-07-01

    Since 1974 a number of organisations have been working closely together in this pollutant register (PRTR) project to collect and formally establish the yearly releases of pollutants to air, water and soil in the Netherlands. Results of this project serve to underpin the national environmental policy. Data is in this way also provided for the many environmental reports to international organisations such as the European Union and the United Nations, e.g. the National Inventory Report for the Kyoto Protocol. This website shows the yearly releases (emissions) of the most important pollutants in the Netherlands. You can explore the emission data through various channels, such as maps, graphs and tables. But you can also download all the details into your own database. The data shown in this website is updated 2 to 3 times a year. The current release shows emissions for 1990, 1995, 2000, 2004, 2005 and 2006 The 2006 emissions are preliminary data and not yet shown in the maps. We expect to add an extra year in August 2008. [Dutch] Sinds 1974 werkt een groot aantal organisaties hecht samen in het project Emissieregistratie. Doel is het jaarlijks verzamelen en vaststellen van de uitstoot van verontreinigende stoffen naar lucht, water en bodem. Het project levert zo de emissiegegevens voor onderbouwing van milieubeleid. Het vormt de basis voor vele rapportages, bijvoorbeeld die in het kader van het Kyoto protocol. Deze website toont de geregionaliseerde uitstoot (emissie) van ruim 300 verontreinigende stoffen in Nederland. U vindt deze emissies op diverse manieren: als kaart, grafiek en tabel maar ook in de vorm van een database voor eigen gebruik. U vindt hier de emissies uit de inventarisatieronde vastgesteld in juli 2007 voor de emissiejaren 1990, 1995, 2000, 2004, 2005 en de voorlopige cijfers van 2006. De emissies uit 2006 zijn wel gedetailleerd per bron aanwezig maar u vindt ze nog niet op de kaart gepresenteerd. In augustus 2008 verwachten we de volgende ronde te

  5. Drug-induced status epilepticus.

    Science.gov (United States)

    Cock, Hannah R

    2015-08-01

    Drug-induced status epilepticus (SE) is a relatively uncommon phenomenon, probably accounting for less than 5% of all SE cases, although limitations in case ascertainment and establishing causation substantially weaken epidemiological estimates. Some antiepileptic drugs, particularly those with sodium channel or GABA(γ-aminobutyric acid)-ergic properties, frequently exacerbate seizures and may lead to SE if used inadvertently in generalized epilepsies or less frequently in other epilepsies. Tiagabine seems to have a particular propensity for triggering nonconvulsive SE sometimes in patients with no prior history of seizures. In therapeutic practice, SE is most commonly seen in association with antibiotics (cephalosporins, quinolones, and some others) and immunotherapies/chemotherapies, the latter often in the context of a reversible encephalopathy syndrome. Status epilepticus following accidental or intentional overdoses, particularly of antidepressants or other psychotropic medications, has also featured prominently in the literature: whilst there are sometimes fatal consequences, this is more commonly because of cardiorespiratory or metabolic complications than as a result of seizure activity. A high index of suspicion is required in identifying those at risk and in recognizing potential clues from the presentation, but even with a careful analysis of patient and drug factors, establishing causation can be difficult. In addition to eliminating the potential trigger, management should be as for SE in any other circumstances, with the exception that phenobarbitone is recommended as a second-line treatment for suspected toxicity-related SE where the risk of cardiovascular complications is higher anyways and may be exacerbated by phenytoin. There are also specific recommendations/antidotes in some situations. The outcome of drug-induced status epilepticus is mostly good when promptly identified and treated, though less so in the context of overdoses. This article is

  6. A comparison of registered and unregistered female sex workers in Tijuana, Mexico.

    Science.gov (United States)

    Sirotin, Nicole; Strathdee, Steffanie A; Lozada, Remedios; Nguyen, Lucie; Gallardo, Manuel; Vera, Alicia; Patterson, Thomas L

    2010-01-01

    Sex work is regulated in Tijuana, Mexico, but only half of the city's female sex workers (FSWs) are registered with the municipal health department, which requires regular screening for sexually transmitted infections (STIs) and human immunodeficiency virus (HIV). We examined correlates of registration to determine if it confers measurable health benefits. From 2004 to 2006, we interviewed FSWs in Tijuana > or = 18 years of age who reported recent unprotected sex with at least one client and were not knowingly HIV-positive, and tested them for HIV, syphilis, gonorrhea, and chlamydia. Logistic regression identified factors associated with registration. Of 410 FSWs, 44% were registered, 69% had been tested for HIV, 6% were HIV-positive, and 44% tested positive for any STI. Compared with unregistered FSWs, registered FSWs were more likely to have had HIV testing (86% vs. 56%, p $30 per transaction without a condom (AOR = 2.41), whereas working on the street (AOR = 0.34), injecting cocaine (AOR = 0.06), snorting or smoking methamphetamine (AOR = 0.27), and being born in the Mexican state of Baja California (AOR = 0.35) were inversely associated with registration. Registered FSWs were more likely than unregistered FSWs to have had HIV testing and to engage in less drug use, but did not have significantly lower HIV or STI prevalence after adjusting for confounders. Current regulation of FSWs in Tijuana should be further examined to enhance the potential public health benefits of registration.

  7. The Danish nationwide clinical register for patients with rheumatoid arthritis: DANBIO

    Directory of Open Access Journals (Sweden)

    Ibfelt EH

    2016-10-01

    Full Text Available Else Helene Ibfelt,1 Dorte Vendelbo Jensen,2,3 Merete Lund Hetland2,4 1Registry Support Centre (East, Epidemiology and Biostatistics, Research Centre for Prevention and Health, Rigshospitalet, Glostrup University Hospital, 2DANBIO Registry and Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Centre of Head and Orthopedics, Rigshospitalet, Glostrup, 3Department of Rheumatology, Herlev and Gentofte University Hospital, Hellerup, 4Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Introduction: DANBIO is a research register and a data source for rheumatologic diseases (rheumatoid arthritis [RA], axial spondyloarthritis, and psoriatic arthritis for monitoring clinical quality at the national, regional, and hospital levels. Study population: The register includes patients with rheumatologic diseases who are treated at a hospital or a private rheumatologic clinic. Registration is mandatory for all patients with RA regardless of treatment and also for patients with other diagnoses if treated with biological disease-modifying antirheumatic drugs. Since 2006, the registration has been done electronically, including patient-reported outcome measures registered electronically by the patients with the use of touch screens. Main variables: Core variables such as diagnosis, year of diagnosis, age, and sex are registered at the beginning. Data entered at later visits included the following: patient-reported outcomes for disease activity, pain, fatigue, functional status, and physician-reported objective measures of disease activity, treatment, C-reactive protein, and, when indicated, imaging. For subgroups of patients, the variables such as quality of life, sociodemographic factors, lifestyle, and comorbidity are also registered. Descriptive data: The DANBIO cohort comprised ~26,000 patients with RA, 3,200 patients with axial spondyloarthritis, and 6

  8. The Austrian breast implant register: recent trends in implant-based breast surgery.

    Science.gov (United States)

    Wurzer, Paul; Rappl, Thomas; Friedl, Herwig; Kamolz, Lars-Peter; Spendel, Stephan; Hoflehner, Helmut; Parvizi, Daryousch

    2014-12-01

    Due to the fact that the number of breast implant surgeries for cosmetic and medical purposes is rising yearly, a discussion about the quality of service for both patients and physicians is more important than ever. To this end, we reviewed the Austrian Breast Implant Register with one specific question in mind: What are the trends? In the statistical analysis of the Austrian Breast Implant Register, we were able to identify 13,112 registered breast implants between 2004 and 2012. The whole dataset was then divided into medical and cosmetic groups. We focused on device size, surface characteristics, filling material, device placement and incision site. All factors were considered for all examined years. In summary, the most used device had a textured surface (97 %) and silicone gel as the filling material (93 %). The mean size of implants for the cosmetic group was 240 cc, placement was submuscular (58 %) and the incision site was inframammary (67 %). In the medical group, the mean size was 250 cc. Yearly registrations had their peak in 2008 (1,898 registered devices); from this year on, registrations decreased annually. A slight trend away from subglandular placement in the cosmetic group was noted. Also, the usage of implants with polyurethane surface characteristics has increased since 2008. The smooth surface implants had a peak usage in 2006 and their usage decreased steadily from then on whereas the textured surface was steady over the years. Keeping the problems related to the quality of breast implants in mind, we could recommend an obligatory national register. Organisations of surgeons and governments should develop and establish these registers. Furthermore, an all-encompassing international register should be established by the European Union and the American FDA (Food and Drug Administration); this might be useful in comparing the individual country registers and also would help in delivering "evidence based" medicine in cosmetic and medical procedures

  9. Evaluation of anti-epileptic activity of leaf extracts of Punica granatum on experimental models of epilepsy in mice.

    Science.gov (United States)

    Viswanatha, Gollapalle L; Venkataranganna, Marikunte V; Prasad, Nunna Bheema Lingeswara; Ashok, Godavarthi

    2016-01-01

    This study was aimed to examine the anti-epileptic activity of leaf extracts of Punica granatum in experimental models of epilepsy in Swiss albino mice. Petroleum ether leaf extract of P. granatum (PLPG), methanolic LPG (MLPG), and aqueous LPG (ALPG) extracts of P. granatum leaves was initially evaluated against 6-Hz-induced seizure model; the potent extract was further evaluated against maximal electroshock (MES) and pentylenetetrazole (PTZ)-induced convulsions. Further, the potent extract was evaluated for its influence on Gamma amino butyric acid (GABA) levels in brain, to explore the possible mechanism of action. In addition, the potent extract was subjected to actophotometer test to assess its possible locomotor activity deficit inducing action. In 6-Hz seizure test, the MLPG has alleviated 6-Hz-induced seizures significantly and dose dependently at doses 50, 100, 200, and 400 mg/kg. In contrast, PLPG and ALPG did not show any protection, only high dose of ALPG (400 and 800 mg/kg, p.o.) showed very slight inhibition. Based on these observations, only MLPG was tested in MES and PTZ models. Interestingly, the MLPG (50, 100, 200 and 400 mg/kg) has offered significant and dose-dependent protection against MES ( P < 0.01) and PTZ-induced ( P < 0.01) seizures in mice. Further, MLPG showed a significant increase in brain GABA levels ( P < 0.01) compared to control and showed insignificant change in locomotor activity in all tested doses (100, 200 and 400 mg/kg). Interestingly, higher dose of MLPG (400 mg/kg, p.o.) and Diazepam (5 mg/mg, p.o.) have completely abolished the convulsions in all the anticonvulsant tests. These findings suggest that MLPG possesses significant anticonvulsant property, and one of the possible mechanisms behind the anticonvulsant activity of MLPG may be through enhanced GABA levels in the brain.

  10. The European Register of Specialists in Clinical Chemistry and Laboratory Medicine: guide to the Register, version 3-2010

    DEFF Research Database (Denmark)

    McMurray, Janet; Zérah, Simone; Hallworth, Michael

    2010-01-01

    In 1997, the European Communities Confederation of Clinical Chemistry and Laboratory Medicine (EC4) set up a Register for European Specialists in Clinical Chemistry and Laboratory Medicine. The operation of the Register is undertaken by a Register Commission (EC4RC). During the last 12 years, more...... than 2200 specialists in Clinical Chemistry and Laboratory Medicine have joined the Register. In 2007, EC4 merged with the Forum of European Societies of Clinical Chemistry and Laboratory Medicine (FESCC) to form the European Federation of Clinical Chemistry and Laboratory Medicine (EFCC). Two previous...

  11. Making Decisions about Workforce Development in Registered Training Organisations

    Science.gov (United States)

    Hawke, Geof

    2008-01-01

    The purpose of this research activity is to understand further how large and small registered training organisations (RTOs) make decisions about the allocation of resources for developing their workforces. Six registered training organisations--four technical and further education (TAFE) institutes and two private providers--were selected for…

  12. Homophobia in Registered Nurses: Impact on LGB Youth

    Science.gov (United States)

    Blackwell, Christopher W.; Kiehl, Ermalynn M.

    2008-01-01

    This study examined registered nurses' overall attitudes and homophobia towards gays and lesbians in the workplace. Homophobia scores, represented by the Attitudes Toward Lesbians and Gay Men (ATLG) Scale, was the dependent variable. Overall homophobia scores were assessed among a randomized stratified sample of registered nurses licensed in the…

  13. 12 CFR 528.6 - Loan application register.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Loan application register. 528.6 Section 528.6 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY NONDISCRIMINATION... Mortgage Disclosure Act Loan Application Registers with the Office of Thrift Supervision in accordance with...

  14. Measuring the Accuracy of Survey Responses using Administrative Register Data

    DEFF Research Database (Denmark)

    Kreiner, Claus Thustrup; Lassen, David Dreyer; Leth-Petersen, Søren

    2015-01-01

    This paper shows how Danish administrative register data can be combined with survey data at the person level and be used to validate information collected in the survey. Register data are collected by automatic third party reporting and the potential errors associated with the two data sources...

  15. Nursing career fulfillment: statistics and statements from registered nurses.

    Science.gov (United States)

    Reineck, Carol; Furino, Antonio

    2005-01-01

    A state-level survey of registered nurses confirmed national findings and raised new issues. Findings revealed that while nurses love the intrinsic reward of nursing, they report workplace, relationship, and stress issues which contribute to frustration and exhaustion. These issues may prevent registered nurses from giving the nursing care they desire to deliver, hastening preventable retirement and costly turnover decisions.

  16. 7 CFR 3015.204 - Federal Register publications.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Federal Register publications. 3015.204 Section 3015.204 Agriculture Regulations of the Department of Agriculture (Continued) OFFICE OF THE CHIEF FINANCIAL... Register publications. (a) Program regulations. Most grant programs have program-specific regulations...

  17. Critical points based register-concurrency autotuning for GPUs

    NARCIS (Netherlands)

    Li, A.; Song, S.L.; Kumar, A.; Zhang, E.Z.; Chavarría-Miranda, D.; Corporaal, H.

    2016-01-01

    The unprecedented prevalence of GPGPU is largely attributed to its abundant on-chip register resources, which allow massively concurrent threads and extremely fast context switch. However, due to internal memory size constraints, there is a tradeoff between the per-thread register usage and the

  18. 30 CFR 45.4 - Independent contractor register.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Independent contractor register. 45.4 Section... ADMINISTRATIVE REQUIREMENTS INDEPENDENT CONTRACTORS § 45.4 Independent contractor register. (a) Each independent contractor shall provide the production-operator in writing the following information: (1) The independent...

  19. Socio-economic characteristics of registered cocoa farmers in Edo ...

    African Journals Online (AJOL)

    This study examined the socio-economic characteristics of registered cocoa farmers in Edo State; Nigeria. Primary data was collected using a well structured questionnaire administered to 180 registered cocoa farmers selected using a multi-stage sampling technique. Data were analyzed using descriptive statistics and ...

  20. PENGGUNAAN REGISTER DALAM WACANA RESEP MASAKAN BLUE BAND

    Directory of Open Access Journals (Sweden)

    Asri Soraya Afsari

    2018-03-01

    Full Text Available AbstractOn its using, language has diverse variation. Language in formal situation will be different from the informal one. Likewise the language for advertisement is different from scientific paper. In Sociolinguistics, the application of a language variant is called as Register. The food recipe discourse is one type of the register for it has specific characteristics in particular grammar and structure. This writing tries to review the application of the register in Blue Band  food recipe discourse. The result of the research indicates that it comprises vocabularies, morphology of derivatives and phrases, and also clauses. The finding register shows ingredients, tools, processing, and, serving.Keyword: register, food recipe discourse, sociolinguistics, vocabulary, morphology

  1. Validity of dementia diagnoses in the danish hospital registers

    DEFF Research Database (Denmark)

    Phung, T.K.T.; Andersen, B.B.; Phung, T.K.T.

    2007-01-01

    Background:The validity of dementia diagnoses in the Danish nationwide hospital registers was evaluated to determine the value of these registers in epidemiological research about dementia. Methods: Two hundred patients were randomly selected from 4,682 patients registered for the first time...... with a dementia diagnosis in the last 6 months of 2003. The patients' medical journals were reviewed to evaluate if they fulfilled ICD-10 and/or DSM-IV criteria for dementia and specific dementia subtypes. The patients who were still alive in 2006 were invited to an interview. Results: One hundred and ninety......-seven journals were available for review and 51 patients were interviewed. A registered diagnosis of dementia was found to be correct in 169 (85.8%) cases. Regarding dementia subtypes, the degree of agreement between the registers and the results of the validating process was low with a kappa of 0.36 (95% CI 0...

  2. Clarithromycine-Induced Ventricular Tachycardia in a Geriatric Patient Using Multiple Drugs

    Directory of Open Access Journals (Sweden)

    Gulsah Karaoren

    2016-07-01

    Full Text Available Long QT syndrome is a cardiac repolarization disorder, which can be either idiopathic or congenital, and cause sudden cardiac death. The iatrogenic form is generally associated with drugs or electrolyte imbalance. Although prolonged QT interval is frequently seen due to antiarrhythmic agents, it can also be seen with antibiotics or anti-epileptics. Adverse drug interaction can manifest in several clinicopathological forms in elder individuals. In such cases, potential adverse effects of drugs used should be taken into consideration before prescribing additional drugs. Here, we present a case of clarithromycine-induced ventricular arrhythmia accompanied by QT prolongation on the third day of therapy, and the subsequent therapeutic approach, in a 91-year-old man. The patient was taking multiple drugs due to comorbid conditions and was prescribed clarithromycine therapy in the intensive care unit.

  3. Drug-related mortality in Denmark 1970-93

    DEFF Research Database (Denmark)

    Juel, K; Helweg-Larsen, K

    1999-01-01

    We analysed drug-related mortality in Denmark with respect to secular trends, gender, and regional variations, for the period 1970-93, for all deaths from poisoning and among drug addicts. The study was based on the Register of Causes of Death in Denmark and included 6,229 drug-related deaths...

  4. [Salivary flow and psychoactive drug consumption in elderly people].

    Science.gov (United States)

    Cabrera, Marcos Aparecido Sarria; Mesas, Arthur Eumann; Rossato, Luiz Angelo; Andrade, Selma Maffei de

    2007-01-01

    To analyze the association between low saliva flow rates and the use of psychoactive drugs among the elderly. A cross-sectional study was carried out with 267 elderly people from 60 to 74 years of age who lived in a borough of the city of Londrina, Paraná State, Brazil. Individuals with high functional dependence or restricted to bed were excluded. Saliva flow rate was the dependent variable with values under the first tercile being considered as low flow rates (less than 0.44 ml/min). The continuous use of psychoactive drugs (antidepressant, antiepileptic, sedative, antipsychotic, hypnotic or sedative-hypnotic drugs) was the independent variable. Multivariate analysis was performed taking into account gender, age and smoking status. The majority of the elderly were women (80.5%), with a mean age of 66.5 years. Use of psychoactive drugs was observed among 31 elderly (11.6%). Mean saliva flow rate was 0.76 ml/min, lower among users of psychoactive drugs (0.67 ml/min). In the multivariate analysis, use of psychoactive drugs was associated with low saliva flow rates (psychoactive drugs and low saliva flow rates in this group of independent and non-institutionalized elderly. These conclusions stress the need of a rational use of these drugs, particularly among the elderly.

  5. 78 FR 8446 - Center for Drug Evaluation and Research; Prescription Drug Labeling Improvement and Enhancement...

    Science.gov (United States)

    2013-02-06

    ... utility of the prescription drug labeling as a communication tool and to discuss strategies for making it... the Web site after this document publishes in the Federal Register.) All holders of marketing... before June 30, 2001, and for generic drugs. The initiative is anticipated to take place over several...

  6. The European Register of Specialists in Clinical Chemistry and Laboratory Medicine: guide to the Register, version 3-2010.

    LENUS (Irish Health Repository)

    McMurray, Janet

    2010-07-01

    In 1997, the European Communities Confederation of Clinical Chemistry and Laboratory Medicine (EC4) set up a Register for European Specialists in Clinical Chemistry and Laboratory Medicine. The operation of the Register is undertaken by a Register Commission (EC4RC). During the last 12 years, more than 2200 specialists in Clinical Chemistry and Laboratory Medicine have joined the Register. In 2007, EC4 merged with the Forum of European Societies of Clinical Chemistry and Laboratory Medicine (FESCC) to form the European Federation of Clinical Chemistry and Laboratory Medicine (EFCC). Two previous Guides to the Register have been published, one in 1997 and another in 2003. The third version of the Guide is presented in this article and is based on the experience gained and development of the profession since the last revision. Registration is valid for 5 years and the procedure and criteria for re-registration are presented as an Appendix at the end of the article.

  7. Drug allergies

    Science.gov (United States)

    Allergic reaction - drug (medication); Drug hypersensitivity; Medication hypersensitivity ... A drug allergy involves an immune response in the body that produces an allergic reaction to a medicine. The first time ...

  8. Study Drugs

    Science.gov (United States)

    ... to quit, they may have withdrawal symptoms like depression, thoughts of suicide, intense drug cravings, sleep problems, and fatigue. The health risks aren't the only downside to study drugs. Students caught with illegal prescription drugs may get suspended ...

  9. Drug Facts

    Medline Plus

    Full Text Available ... symptoms of someone with a drug use problem? How Does Drug Use Become an Addiction? What Makes Someone More Likely to Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard to ...

  10. Drug Facts

    Medline Plus

    Full Text Available ... Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen ... to prescription drugs. The addiction slowly took over his life. I need different people around me. To ...

  11. Drug Reactions

    Science.gov (United States)

    ... problem is interactions, which may occur between Two drugs, such as aspirin and blood thinners Drugs and food, such as statins and grapefruit Drugs and supplements, such as ginkgo and blood thinners ...

  12. Drug Facts

    Science.gov (United States)

    ... Makes Someone More Likely to Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard ... the text to you. This website talks about drug abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol ...

  13. Editorial : Clinical drug interactions | Kokwaro | East African Medical ...

    African Journals Online (AJOL)

    Journal Home > Vol 78, No 10 (2001) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Editorial: Clinical drug interactions. G. O. Kokwaro. Abstract. (East African Medical Journal 2001 78 (10): 505-506). Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT

  14. Registered nurses' perceptions of rewarding and its significance.

    Science.gov (United States)

    Seitovirta, Jaana; Lehtimäki, Aku-Ville; Vehviläinen-Julkunen, Katri; Mitronen, Lasse; Kvist, Tarja

    2017-11-07

    To examine reward type preferences and their relationships with the significance of rewarding perceived by registered nurses in Finland. Previous studies have found relationships between nurses' rewarding and their motivation at work, job satisfaction and organisational commitment. Data were collected in a cross-sectional, descriptive, questionnaire survey from 402 registered nurses using the Registered Nurses' Perceptions of Rewarding Scale in 2015, and analysed with descriptive and multivariate statistical methods. Registered nurses assigned slightly higher values to several non-financial than to financial rewards. The non-financial reward types appreciation and feedback from work community, worktime arrangements, work content, and opportunity to develop, influence and participate were highly related to the significance of rewarding. We identified various rewards that registered nurses value, and indications that providing an appropriate array of rewards, particularly non-financial rewards, is a highly beneficial element of nursing management. It is important to understand the value of rewards for nursing management. Nurse managers should offer diverse rewards to their registered nurses to promote excellent performance and to help efforts to secure and maintain high-quality, safe patient care. The use of appropriate rewards is especially crucial to improving registered nurses' reward satisfaction and job satisfaction globally in the nursing profession. © 2017 John Wiley & Sons Ltd.

  15. Registered Nurses' perceptions of their work and professional development.

    Science.gov (United States)

    Hallin, Karin; Danielson, Ella

    2008-01-01

    This paper is a report of a study to elucidate Registered Nurses' perceptions of their work and professional development 6 years after graduation. Nursing education and health care has rapidly changed in the last two decades. Education and experience are important components in Registered Nurses' ability to promote a high quality of care, but a great deal depends on their work circumstances. This study emphasizes Registered Nurses' view of their work in health care, at a time in their career when they have several years of experience. Data were collected in 2003 from in-depth interviews with 15 Registered Nurses 6 years after their graduation. The interviews were semi-structured and analysed with interpretive content analysis. The findings revealed two themes and five sub-themes. The first theme, An appropriate but demanding profession, consisted of two sub-themes: 'having found one's niche' and 'growing old in nursing may be difficult'. The second theme, A profession with opportunities and obstacles, consisted of three sub-themes: 'being aware of Registered Nurses' potential', 'having knowledge that is seldom made use of' and 'attaining professional growth is no matter of course'. Keeping Registered Nurses' satisfied and avoiding their dissatisfaction is crucial for both educators and employers. It is essential that employers give priority to Registered Nurses' time with patients and to motivate and support them in professional development. Further intervention studies regarding a change of the balance between obstacles and opportunities are needed.

  16. Obesity research based on the Copenhagen School Health Records Register

    DEFF Research Database (Denmark)

    Baker, Jennifer L; Sørensen, Thorkild I A

    2011-01-01

    INTRODUCTION: To summarise key findings from research performed using data from the Copenhagen School Health Records Register over the last 30 years with a main focus on obesity-related research. The register contains computerised anthropometric information on 372,636 schoolchildren from the capi......INTRODUCTION: To summarise key findings from research performed using data from the Copenhagen School Health Records Register over the last 30 years with a main focus on obesity-related research. The register contains computerised anthropometric information on 372,636 schoolchildren from...... the capital city of Denmark. Additional information on the cohort members has been obtained via linkages with population studies and national registers. RESEARCH TOPICS: Studies using data from the register have made important contributions in the areas of the aetiology of obesity, the development...... of the obesity epidemic, and the long-term health consequences of birth weight as well as body size and growth in childhood. CONCLUSION: Research using this unique register is ongoing, and its contributions to the study of obesity as well as other topics will continue for years to come....

  17. External review and validation of the Swedish national inpatient register

    Directory of Open Access Journals (Sweden)

    Kim Jeong-Lim

    2011-06-01

    Full Text Available Abstract Background The Swedish National Inpatient Register (IPR, also called the Hospital Discharge Register, is a principal source of data for numerous research projects. The IPR is part of the National Patient Register. The Swedish IPR was launched in 1964 (psychiatric diagnoses from 1973 but complete coverage did not begin until 1987. Currently, more than 99% of all somatic (including surgery and psychiatric hospital discharges are registered in the IPR. A previous validation of the IPR by the National Board of Health and Welfare showed that 85-95% of all diagnoses in the IPR are valid. The current paper describes the history, structure, coverage and quality of the Swedish IPR. Methods and results In January 2010, we searched the medical databases, Medline and HighWire, using the search algorithm "validat* (inpatient or hospital discharge Sweden". We also contacted 218 members of the Swedish Society of Epidemiology and an additional 201 medical researchers to identify papers that had validated the IPR. In total, 132 papers were reviewed. The positive predictive value (PPV was found to differ between diagnoses in the IPR, but is generally 85-95%. Conclusions In conclusion, the validity of the Swedish IPR is high for many but not all diagnoses. The long follow-up makes the register particularly suitable for large-scale population-based research, but for certain research areas the use of other health registers, such as the Swedish Cancer Register, may be more suitable.

  18. Pollutant emission registers-INES and EPER toward PRTR

    International Nuclear Information System (INIS)

    Caricchia, A.M.; Cirillo, M.C.; Gagna, A.

    2005-01-01

    PRTRs (Pollutant Release and Transfer Registers) are information systems collecting and providing public access to information on pollutant releases in the environment. These registers are based on a scheduled reporting by the manufacturing facilities. Since the establishment of the TRI (Toxic Release lnventory) at the end of the '80s in the USA, international interest grew focussing on the definition of the features of national PRTRs as environmental management systems. The Protocol on PRTRs, the first international legally binding agreement, was signed in 2003 in the frame of the UNECE-Convention on Access to Information, Public Participation in Decision-making and Access to Justice in Environmental Matters (Aarhus Convention, 1999). The European register EPER (European Pollutant Emission Register), established in the Directive 96/61/EC, represents the first step at a European level towards a truly integrated pollutant emissions register, an experience which is going to improve further with the forthcoming introduction of the E-PRTR (European Pollutant Release and Transfer Register). Operating since 2003, EPER collects the information provided by 9377 facilities spread over EU15 countries plus Norway and Hungary. Concerning Italy, in accordance with European EPER, a national pollutant emission register has been established, called INES ('Inventario Nazionale delle Emissioni e loro Sorgenti'). INES can be currently browsed and queried on the following web-page: http://www.sinanet.apat.it [it

  19. Subdural hematoma cases identified through a Danish patient register

    DEFF Research Database (Denmark)

    Poulsen, Frantz Rom; Halle, Bo; Pottegård, Anton

    2016-01-01

    PURPOSE: This study aimed to assess the usefulness of Danish patient registers for epidemiological studies of subdural hematoma (SDH) and to describe clinical characteristics of validated cases. METHODS: Using a patient register covering a geographically defined area in Denmark, we retrieved...... use did not vary by SDH type (OR 0.9, 95%CI 0.6-1.2). CONCLUSIONS: Danish patient registers are a useful resource for SDH studies. However, choice of International Classification of Diseases code markedly influences diagnostic validity. Distinction between cSDH and aSDH is not possible based on SDH...

  20. Register-based statistics statistical methods for administrative data

    CERN Document Server

    Wallgren, Anders

    2014-01-01

    This book provides a comprehensive and up to date treatment of  theory and practical implementation in Register-based statistics. It begins by defining the area, before explaining how to structure such systems, as well as detailing alternative approaches. It explains how to create statistical registers, how to implement quality assurance, and the use of IT systems for register-based statistics. Further to this, clear details are given about the practicalities of implementing such statistical methods, such as protection of privacy and the coordination and coherence of such an undertaking. Thi