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Valproic Acid Toxicity

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121. Brivaraceta

treatment ? 1 to 3 AEDs in a stable dosage with or without VNS from = 4 weeks (phenobarbital and primidone for at least 3 months) before baseline period: carbamazepine, clobazam, clonazepam, diazepam, ethosuximide, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, pregabalin, primidone, tiagabine, topiramate, valproic acid, zonisamide ? VNS was allowed and was not counted as AED VNS had to be in place = 9 months before study inclusion ? benzodiazepines were allowed (...) : Institute’s calculation: sodium valproate + valproic acid + magnesium valproate + valpromide. d: Institute’s calculation: phenytoin + phenytoin sodium. CBZ: carbamazepine; CLB: clobazam; CZP: clonazepam; FAS: full analysis set; GBP: gabapentin; ITT: intention to treat; LEV: levetiracetam; LTG: lamotrigine; OXC: oxcarbazepine; PB: phenobarbital; PGB: pregabalin; PHT: phenytoin; PRM: primidone; TPM: topiramate; VPA: valproate; ZNS: zonisamide The patient characteristics were balanced within the studies

2017 Institute for Quality and Efficiency in Healthcare (IQWiG)

122. Whole genome microarray analysis of neural progenitor C17.2 cells during differentiation and validation of 30 neural mRNA biomarkers for estimation of developmental neurotoxicity. (PubMed)

in neurogenesis (CHRDL1), axonal guidance (BMP4), neuronal connectivity (PLXDC2), axonogenesis (RTN4R) and astrocyte differentiation (S100B). The 30 biomarkers were further validated by exposure to non-cytotoxic concentrations of two DNT-inducing compounds (valproic acid and methylmercury) and one neurotoxic chemical possessing a possible DNT activity (acrylamide). Twenty-eight of the 30 biomarkers were altered by at least one of the neurotoxic substances, proving the importance of these biomarkers during (...) Whole genome microarray analysis of neural progenitor C17.2 cells during differentiation and validation of 30 neural mRNA biomarkers for estimation of developmental neurotoxicity. Despite its high relevance, developmental neurotoxicity (DNT) is one of the least studied forms of toxicity. Current guidelines for DNT testing are based on in vivo testing and they require extensive resources. Transcriptomic approaches using relevant in vitro models have been suggested as a useful tool

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2017 PLoS ONE

123. I love it when an antivax “study” meant to show how “dirty” vaccines are backfires so spectacularly

found dangerous contaminants, including red blood cells in one vaccine and metal toxicants in every single sample tested – except in one animal vaccine. Using extremely sensitive new technologies not used in vaccine manufacturing, Italian scientists reported they were “baffled” by their discoveries which included single particles and aggregates of organic debris including red cells of human or possibly animal origin and metals including lead, tungsten, gold, and chromium, that have been linked (...) for their research into toxic emissions. Grillo launched the campaign to raise €378,000 for a new EM that would allow the vital work to continue. All culminating in accusations that Gatti and Montanari are using their toy not for environmental activism, but for a profitable business selling analyses through their company Nanodiagnostic Ltd.; and accusations from Montanari that Grillo just raised all that money for them as a way of exploiting them for political gain. Lawyers and defamation suits are involved

2017 Respectful Insolence

124. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage

randomized trial of 1-month prophylactic treatment with valproic acid showed no reduc- tion in incident seizures over 1-year follow-up (19.5% in the treatment group, 22.2% in the placebo group; P=0.8). 168 Prophylactic anticonvulsant medication has thus not been demonstrated to be beneficial. Clinical seizures or electrographic seizures in patients with a change in mental status should be treated with antisei- zure drugs. Continuous EEG monitoring should be considered in ICH patients with depressed

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2015 American Heart Association

125. Management of Substance Use Disorder

in 2000 were tobacco (435,000 deaths; 18.1% of total U.S. deaths), poor diet and physical inactivity (365,000 deaths; 15.2%), and alcohol consumption (85,000 deaths; 3.5%). Other causes of death were microbial agents (75,000), toxic agents (55,000), motor vehicle crashes (43,000), incidents involving firearms (29,000), sexual behaviors (20,000), and illicit use of drugs (17,000).[7] From 1990-2010, the highest disability-adjusted life years, which accounted for years of life lost due to premature

2015 VA/DoD Clinical Practice Guidelines

126. Management of an unprovoked first seizure in adults

appear to be mild and reversible when an affected patient is switched to another AED. , AEDs included phenytoin, phenobarbital, carbamazepine, valproic acid, and lamotrigine, , , , , some of which may now be considered older AEDs but were standard, commonly used AEDs at the time of the studies. Although AEDs may cause different AEs, most events are known to be dose-related and reversible through dose reduction or discontinuation of the responsible drug. , Evidence from reports of AED AEs (...) ” seizure). We excluded studies of provoked seizures, which are defined as seizures due to an acute symptomatic condition (e.g., a metabolic or toxic disturbance, cerebral trauma, stroke) and differ in prognosis from unprovoked seizures. , , , This practice guideline considers the evidence for prognosis and treatment of adults with an unprovoked first seizure; a 2003 guideline addresses this for children. We posed 3 questions: (1) What are the risks for seizure recurrence after a first seizure? (2) Does

2015 American Academy of Neurology

127. Guidelines for the management of spontaneous intracerebral hemorrhage

reports. A small randomized trial of 1-month prophylactic treatment with valproic acid showed no reduction in incident seizures over 1-year follow-up (19.5% in the treatment group, 22.2% in the placebo group; P =0.8). Prophylactic anticonvulsant medication has thus not been demonstrated to be beneficial. Clinical seizures or electrographic seizures in patients with a change in mental status should be treated with antiseizure drugs. Continuous EEG monitoring should be considered in ICH patients

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2015 American Academy of Neurology

128. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage

randomized trial of 1-month prophylactic treatment with valproic acid showed no reduc- tion in incident seizures over 1-year follow-up (19.5% in the treatment group, 22.2% in the placebo group; P=0.8). 168 Prophylactic anticonvulsant medication has thus not been demonstrated to be beneficial. Clinical seizures or electrographic seizures in patients with a change in mental status should be treated with antisei- zure drugs. Continuous EEG monitoring should be considered in ICH patients with depressed

2015 Congress of Neurological Surgeons

129. Evidence-based Guideline: Management of First Unprovoked Seizure in Adults

appear to be mild and reversible when an affected patient is switched to another AED. , AEDs included phenytoin, phenobarbital, carbamazepine, valproic acid, and lamotrigine, , , , , some of which may now be considered older AEDs but were standard, commonly used AEDs at the time of the studies. Although AEDs may cause different AEs, most events are known to be dose-related and reversible through dose reduction or discontinuation of the responsible drug. , Evidence from reports of AED AEs (...) ” seizure). We excluded studies of provoked seizures, which are defined as seizures due to an acute symptomatic condition (e.g., a metabolic or toxic disturbance, cerebral trauma, stroke) and differ in prognosis from unprovoked seizures. , , , This practice guideline considers the evidence for prognosis and treatment of adults with an unprovoked first seizure; a 2003 guideline addresses this for children. We posed 3 questions: (1) What are the risks for seizure recurrence after a first seizure? (2) Does

2015 American Epilepsy Society

130. Acute Pain Management: Scientific Evidence

4.4.3 Local anaesthetic toxicity 109 4.5 Inhalational agents 111 4.5.1 Nitrous oxide 111 4.5.2 Methoxyflurane 114 4.6 NMDA-receptor antagonists 116 4.6.1 Systemic NMDA-receptor antagonists 116 4.6.2 Regional NMDA-receptor antagonists 121 4.7 Antidepressant medicines 122 4.7.1 Acute pain 122 4.7.2 Chronic pain 123 4.7.3 Specific pain conditions 123 4.8 Anticonvulsant medicines 125 4.8.1 Acute pain 125 4.8.2 Chronic pain 126 4.9 Alpha-2 agonists 127 4.9.1 Systemic alpha-2 agonists 127 4.9.2 Regional

2015 Clinical Practice Guidelines Portal

132. Autism

signi?cant response c for repetitive behavior and stereotypy on risperidone Risperidone vs. haloperidol b Miral et al., 2008 126 behavior, social, sensory, language 0.01-0.08 mg/kg/d 30 children 8-18 y old EPS, weight gain, gynecomastia risperidone reported superior to haloperidol only on ABC total score, no subscales reported Mood stabilizers Valproic acid Hellings et al., 2005 127 irritability 20 mg/kg/d, average level 75-78 30 subjects 6-20 y old increased appetite, skin rash no signi?cant (...) .,homocystinuria), traumatic (e.g., head injury), toxic (e.g., fetal alcohol syndrome), 4 or genetic (e.g., chromosomal abnormality). Certain developmental disorders, most notably Landau-Kleffner syndrome, also should be ruled out. In this condition, a highly distinctive EEG abnormality is present and asso- ciated with development of a marked aphasia. 71 Genetic or neurologic consultation, neuroimaging, EEG, and additional laboratory tests should be obtained when relevant, based on examination or history(e.g

2014 American Academy of Child and Adolescent Psychiatry

133. Liver Transplantation, evaluation of the pediatric patient

reliable anthropometric assessments to judge nutritional status, as reliance on weight alone may overestimate nutritional adequacy in children with chronic liver disease. 24,25,28 Fat soluble vitamin (FSV) de?ciency is common and dosing and monitoring recommendations to prevent FSV de?- ciency are available. 24,25,29,30 Enteral formulas that contain medium chain triglycerides (MCT) are pre- ferred in cholestatic patients, but excessive administra- tion of MCT can lead to essential fatty acid de?ciency (...) and a normal serum gamma-glutamyl transferase (GGT). Vitamin D- de?cient rickets and intracerebral bleeding as a conse- quence of vitamin K de?ciency may be presenting fea- tures of FIC1 disease. Other symptoms include chronic diarrhea, asthma-like symptoms, and sensori- neural hearing loss, likely as a result of abnormal microvilli in affected cells in the intestine, lungs, and cochlear hair cells. Ursodeoxycholic acid may improve cholestasis to the degree that other interventions can be delayed

2014 American Association for the Study of Liver Diseases

134. Prevention of Acute Nausea and Vomiting due to Antineoplastic Medication in Pediatric Cancer Patients

summary or in which the emetogenicity of the antineoplastic therapy administered was not able to be determined. Headache 44, 96, 97 and constipation 96 were often reported to be the most common adverse effects. Abnormal liver function tests were reported in 4 of 22 children in one study. 31 Two studies prospectively evaluated cardiovascular toxicity including continuous electrocardiographic monitoring for 24 hours after receipt of granisetron. 95, 98 No dysrhythmias were observed in 64 children

2013 SickKids Supportive Care Guidelines

135. Clinical practice guideline for care in pregnancy and puerperium

creatinine level in a biochemical test? 8. What is the purpose of determining the plasma uric acid level in a biochemical test? 9. What is the purpose of universal screening for syphilis in pregnant women and at what stage of pregnancy should it be done? 10. What is the purpose of universal screening for Chagas disease in pregnant women and at what stage of pregnancy should it be done? 11. What is the purpose of universal screening for chlamydia in pregnant women and at what stage of pregnancy should (...) pregnancy? 39. With a varied diet, are micronutrient needs as iron, vitamins or iodine covered? Pharmacological supplementation of nutrients 40. What is the effect of iron prophylaxis in women during pregnancy? 41. Is a pharmacological iodine supplementation necessary during pregnancy? 42. Is a pharmacological folic acid supplementation necessary during pregnancy? 43. Is a pharmacological vitamin complex supplementation necessary during pregnancy? 44. How safe are food supplements (omega3 fatty acids

2014 GuiaSalud

136. Atopic dermatitis – Treatment with phototherapy and systemic agents

. Guidelines of care for the management of psoriasis and psoriatic arthritis, section 5: guidelines of care for the treatment of psoriasis with phototherapy and photochemotherapy. J Am Acad Dermatol . 2010 ; 62 : 114–135 | | | | | , x 19 Morison, W.L., Baughman, R.D., Day, R.M., Forbes, P.D., Hoenigsmann, H., Krueger, G.G. et al. Consensus workshop on the toxic effects of long-term PUVA therapy. Arch Dermatol . 1998 ; 134 : 595–598 | | | , x 22 Uetsu, N. and Horio, T. Treatment of persistent severe atopic (...) arthritis, section 5: guidelines of care for the treatment of psoriasis with phototherapy and photochemotherapy. J Am Acad Dermatol . 2010 ; 62 : 114–135 | | | | | , x 19 Morison, W.L., Baughman, R.D., Day, R.M., Forbes, P.D., Hoenigsmann, H., Krueger, G.G. et al. Consensus workshop on the toxic effects of long-term PUVA therapy. Arch Dermatol . 1998 ; 134 : 595–598 | | | , x 20 Goldsmith LK, Katz SI, Gilchrest B, Paller A, Lefell D, Wolff K. Fitzpatrick's dermatology in general medicine. 8th ed. New

2014 American Academy of Dermatology

137. Image-guided Targeted Doxorubicin Delivery With Hyperthermia to Optimize Loco-regional Control in Breast Cancer

, cyclosporine, carbamazepine, phenytoin, valproic acid, paclitaxel, trastuzumab and other liposomal drugs (Abelect, Ambisome, Nyotran, etc.) or lipid-complexed drugs. Caution will be exercised with all the medications mentioned in appendix C, for interactions are theoretically possible. Contraindications to MR imaging (e.g., pacemaker in situ, severe claustrophobia, metal implants incompatible with the MRI-scan, body size incompatible with MR bore). Contraindications to gadolinium-based contrast agent (...) that by substituting doxorubicin (A) in the AC-chemotherapy regimen for the combination of LTLD and MR-HIFU induced hyperthermia, optimal local tumour control can be achieved without compromising systemic toxicity or efficacy. This will be the first study to evaluate LTLD with MR-HIFU hyperthermia in breast cancer patients. Condition or disease Intervention/treatment Phase Metastatic Breast Cancer Breast Cancer Breast Neoplasms Stage IV Breast Cancer Metastatic Cancer Invasive Ductal Carcinoma of Female Breast

2018 Clinical Trials

138. Anticonvulsant and reproductive toxicological studies of the imidazole-based histamine H3R antagonist 2-18 in mice (PubMed)

Anticonvulsant and reproductive toxicological studies of the imidazole-based histamine H3R antagonist 2-18 in mice The imidazole-based H3R antagonist 2-18 with high in vitro H3R antagonist affinity, excellent in vitro selectivity profile, and high in vivo H3R antagonist potency was tested for its anticonvulsant effect in maximal electroshock (MES)-induced convulsions in mice having valproic acid (VPA) as a reference antiepileptic drug (AED). Additionally, H3R antagonist 2-18 was evaluated (...) for its reproductive toxicity in the same animal species. The results show that acute systemic administration (intraperitoneal; i.p.) of H3R antagonist 2-18 (7.5, 15, 30, and 60 mg/kg, i.p.) significantly and dose dependently protected male as well as female mice against MES-induced convulsion. The protective action observed for H3R antagonist 2-18 in both mice sexes was comparable to that of VPA and was reversed when mice were pretreated with the selective H3R agonist (R)-alpha-methylhistamine (RAMH

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2018 Drug design, development and therapy

139. Assessment of new HDAC inhibitors for immunotherapy of malignant pleural mesothelioma (PubMed)

of cancer cells. We previously showed that a hypomethylating agent (decitabine) and a histone deacetylase inhibitor (HDACi) (valproic acid (VPA)) combination was immunogenic and led to the induction of an anti-tumor immune response in a mice model of mesothelioma. However, VPA is not very specific, is active at millimolar concentrations and is responsible for side effects in clinic. To improve this approach, we studied four newly synthetized HDACi, two hydroxamates (ODH and NODH) and two benzamides (ODB (...) and NODB), in comparison with VPA and SAHA. We evaluated their toxicity on immune cells and their immunogenicity on MPM cells in combination with decitabine.All the tested HDACi were toxic for immune cells at high concentrations. Combination with decitabine increased toxicity of HDACi only towards T-cell clone. A decrease in the proportion of regulatory T cells and natural killer cells was observed in particular with VPA and ODH. In MPM cells, all HDACi combinations induced NY-ESO-1 cancer testis

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2018 Clinical epigenetics

140. LRAs United as a Novel Anti-HIV Strategy.

the size of the reservoir as measured by TILDA, HIV-DNA, HIV-RNA and level of acetylation/BAF expression after stimulation by pyrimethamine, valproic acid or both, and this will be correlated to these observed reservoir measurements outcomes in vivo at week 2 and week 6. Incidence of Treatment-Emergent Adverse Events [ Time Frame: 6 week ] The clinical and biochemical adverse events will be assessed by the Common Toxicity Criteria. Plasma HIV-RNA [ Time Frame: 6 week ] The proportion of subjects (...) , Erasmus Medical Center Study Details Study Description Go to Brief Summary: A translational proof of concept study in humans on the primary research question whether novel anti-human immunodeficiency virus (HIV) latency strategies, including a BAF inhibitor and a histone deacetylase inhibitor, result in HIV reservoir reduction in HIV patients on antiretroviral therapy. Condition or disease Intervention/treatment Phase HIV-1-infection Drug: Valproic Acid Drug: Pyrimethamine Phase 1 Phase 2 Detailed

2018 Clinical Trials

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