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By: Melissa R. Pleva, PharmD, BCPS, BCNSP

  • Clinical Pharmacist Specialist, Department of Pharmacy Services, University of Michigan Hospitals and Health Centers
  • Adjunct Clinical Assistant Professor, University of Michigan College of Pharmacy, Ann Arbor, Michigan

https://medicine.umich.edu/dept/pharmacy/melissa-pleva-pharmd-bcps-bcnsp

Comparative single-dose pharmacokinetics of topiramate in elderly versus young men and women [abstract] anxiety 4th sinequan 10mg without a prescription. Tolerability and safety of topiramate as first-line monotherapy in 1 anxiety symptoms 8 dpo generic 75 mg sinequan with amex,000 epilepsy patients [abstract] anxiety symptoms fear sinequan 25mg mastercard. A dose-comparison trial of topiramate as monotherapy in recently diagnosed partial epilepsy. Clinical experience with topiramate dosing and serum levels in children 12 years or under with epilepsy. The steady-state pharmacokinetics of phenytoin (Dilantin Kapseals brand) and of Topamax (topiramate) in male and female epileptic patients on monotherapy, and during combination therapy. Comparison of the steady-state pharmacokinetics of topiramate and valproate in patients with epilepsy during monotherapy and concomitant therapy. Topiramate and lamotrigine pharmacokinetics during repetitive monotherapy and combination therapy in epilepsy patients. Effect of topiramate or carbamazepine on the pharmacokinetics of an oral contraceptive containing norethindrone and ethinyl estradiol in healthy obese and nonobese female subjects. As first-line monotherapy in adults with newly or recently diagnosed epilepsy, 100 mg/day is an appropriate target dose to initially assess patient response. It appears the optimal starting dose in adults is 25 to 50 mg/day, with weekly or biweekly increases of 25 to 50 mg/day. As initial monotherapy in children, the recommended dose is 3 to 6 mg/kg/day, using a starting dose of 0. Cellular actions of topiramate blockade of kainate-evoked inward currents in cultured hippocampal neurons. Topiramate effects on excitatory amino acid-mediated responses in cultured hippocampal neurons: selective blockade of kainate currents [abstract]. Effects of topiramate on sustained repetitive firing and spontaneous recurrent seizure discharge in cultured hippocampal neurons. Effects of topiramate on sodiumdependent action-potential firing by mouse spinal cord neurons in cell culture. Inhibition of transient and persistent Na current fractions by the new anticonvulsant topiramate. Topiramate attenuates voltage-gated sodium currents in rat cerebellar granule cells. Frequency-dependent inhibition of neuronal activity by topiramate in rat hippocampal slices. Topiramate and phenytoin pharmacokinetics during repetitive monotherapy and combination therapy to epileptic patients. Topiramate, carbamazepine and valproate monotherapy: double-blind comparison in newly diagnosed epilepsy. Topiramate: effective as monotherapy in dose-response study in newly diagnosed epilepsy [abstract]. Topiramate placebo-controlled dose-ranging trial in refractory partial epilepsy using 200-, 400-, and 600-mg daily dosages. Topiramate placebo-controlled dose-ranging trial in refractory partial epilepsy using 600-, 800-, and 1000-mg daily dosages. Double-blind, placebocontrolled study of topiramate in patients with refractory partial epilepsy. Double-blind, placebocontrolled trial of topiramate (600 mg daily) for the treatment of refractory partial epilepsy. Double-blind, placebocontrolled trial of topiramate as add-on therapy in patients with refractory partial seizures. Placebo-controlled trial of topiramate as adjunctive therapy to carbamazepine or phenytoin for partialonset epilepsy [abstract]. Topiramate in medically intractable partial epilepsies: double-blind placebo-controlled randomized parallel group trial.

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There were several patterns in which the diagnostic results differ from the parameter-based method anxiety quotes buy cheap sinequan 10mg. The risk color map marked safe anxiety symptoms before period purchase sinequan 25 mg visa, intermediate anxiety symptoms in 2 year old cheap sinequan 10 mg amex, and dangerous as red, green, and blue. Figure 3 Risk color map result of artificial intelligence based real-time analysis microperfusion on the indocyanine green video. Red region means risk-safe, green region means riskintermediate, and blue region means risk-dangerous. Patient data consists of a large number of normal patient data and a small number of complication risk patient data. Since patient data are not of the same distribution, some of the normal patient data were distributed to a test set and some of the complication risk patient data were distributed to a test set. The risk classification was divided into two levels where safe and intermediate risk levels were true and dangerous was false. Mann-Whitney test, Chi-square test and Fisher exact test were used as analyzing tools for these clinical factors. Three patient (3/50, 6%) had transection line change after perfusion test during the surgery, and no one among them had occurred the anastomotic complications. In testing group, there was no anastomotic complication, but three patients had changed the transection line before separating the colon from the distal margin. Statistically, there were no significant differences in clinical characteristics between training and test group (Table 2). The red color of the region represented low-risk (labeled risk-safe), green indicated intermediate-risk (labeled risk-intermediate), and blue indicated high-risk (labeled risk-dangerous). Since we had tested with such a small sampled size, the accuracy was not a suitable evaluation metrics. T1/2max is the time it takes for the indocyanine green fluorescence intensity change to become Fmax/2. Figure 7 Statistical performance verification using classification performance evaluation metrics between artificial intelligence-based analysis and perfusion parameter of quantitative analysis. F1 score represents a harmonized average of recall and precision, artificial intelligence analysis was evaluated as the most accurate parameter to predict the risk of anastomotic complications. When right hemicolectomy is performed, the left branch of the middle colic artery is usually preserved, so favorable perfusion conditions are maintained in most patients. This perfusion properties are considered to be one of the reasons for the higher anastomotic complication in anterior resection than in right hemicolectomy. The perfusion status was labeled by comprehensively considering patient complications and parameters. In this study, we could have discriminated the colonic hypoperfusion phenomenon into two types; type 1 as segmental hypoperfusion and type 2 as collateral hypoperfusion (Figure 8). Type 1 hypoperfusion refers to the segmental hypoperfusion around the planed transection line after division of colonic mesentery. Precise assessment of segmental perfusion status plays an important role in the determination of the transection line with favorable perfusion segment. To refer perfusion color map for determining the transection line in the surgical field, colonic microcirculation analysis should be performed in real-time. Type 2 hypoperfusion indicates the insufficient collateral circulation of colonic mesentery. In the classification performance evaluation metrics, performance verification was improved and the visualization verification was more accurate than the conventional parameter-based method. So, real-time analysis and intuitive visualization could be helpful for inexperienced surgeons to determine the microperfusion status[32]. Since intraoperative angiography has not been easy to date, surgeons could not easily access perfusion status of the anastomosis site using objective methods. Since the number of patients in the training group was small sized, the process was hard enough to indicate perfusion with the high reliability. Especially, clinical trials and large-scale multi-center studies should follow for composing standard applications. In this study, all patients were evaluated using laboratory liver function test panel before surgery, and liver function was normal in all patients. Research perspectives Real-time analysis of perfusion during surgery may reduce the probability of postlaparoscopic colorectal anastomotic complications. Altered microperfusion at the rectal stump is predictive for rectal anastomotic leak.

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Hattig and colleagues (165) reported greater cognitive impairment with polytherapy compared with monotherapy and with valproate as monotherapy anxiety related to order sinequan 25 mg with visa. Two retrospective studies from Denmark (166) examined the effects of in utero phenobarbital exposure on intelligence in adult men of mothers without epilepsy anxiety krizz kaliko lyrics cheap 25mg sinequan with amex. Special education was required in 30% of children exposed to anxiety symptoms checklist buy 75 mg sinequan with amex valproate monotherapy, compared with 3% to 6% for other monotherapies, and 11% with no drug. Two retrospective and one prospective study have also reported an increased risk for autistic spectrum disorder or behavioral abnormalities in children exposed to valproate (170­172). Possible Mechanisms of Antiepileptic Drug Effects on Neurodevelopment A teratogen operates on a susceptible genotype, and this process may involve the interaction of multiple-liability genes (173). For example, discordant outcomes have been observed for dizygotic twin fetuses exposed to phenytoin (174). It is unclear whether similar mechanisms may be involved in both functional and anatomical defects since anatomical risks are related to first trimester exposure, but functional deficits may be related primarily to third trimester exposure. Chapter 92: Cognitive Effects of Epilepsy and Antiepileptic Medications 1033 Ischemia/Hypoxia Ischemia-induced embryopathy in animals resembles phenytoininduced defects, and hyperoxic chamber treatment reduces malformations caused by phenytoin (179). Phenobarbital, phenytoin, and primidone, but not carbamazepine, deplete folate (180­183), and valproate affects folate-dependent onecarbon metabolism (184). Blood folate concentrations are significantly lower in women with epilepsy who have abnormal pregnancy outcomes (185). In addition, Biale and Lewenthal (186) found that infants of mothers with epilepsy who received no folate supplementation had a 15% rate of malformation, but no congenital abnormalities were identified in 33 folate-supplemented children. Reduction of neuronal excitation in utero might alter synaptic growth and connectivity during these early stages of neurodevelopment, resulting in long-term deficits in cognition and behavior. Apoptosis-Related Mechanisms In utero ethanol exposure can result in widespread apoptotic neurodegeneration, reduced brain mass, and neurobehavioral deficits (187). Studies in neonatal rats reveal widespread apoptosis in the developing brain as a result of exposure to clonazepam, diazepam, phenobarbital, phenytoin, vigabatrin, or valproate (188­190). The effect is dose-dependent, occurs at therapeutically relevant blood levels, and requires only relatively brief exposure. The effect appeared to be caused by reduced expression of neurotrophins and levels of protein kinases that promote neuronal growth and survival. Of note, the adverse effects were ameliorated by -estradiol, which has neurotrophic effects. With polypharmacy, the effects are additive and can occur even when all anticonvulsant blood levels are within "standard therapeutic ranges. However, the treatment goal in each patient is to achieve the best control of seizures while producing the fewest side effects. For an individual patient, the best risk-to-benefit ratio may be obtained with judicious use of polypharmacy or with anticonvulsant blood level above "standard therapeutic ranges. Effect of major motor seizure frequency upon cognitive-intellectual functions in adults. Seizures accelerate forgetting in patients with left-sided temporal lobe epilepsy. Comparative cognitive effects of phenobarbital, phenytoin and valproate in healthy subjects. Results of a nationwide Veterans Administration Cooperative Study comparing the efficacy and toxicity of carbamazepine, phenobarbital, phenytoin, and primidone. Neurobehavioral effects of phenytoin and carbamazepine in patients recovering from brain trauma: a comparative study. Influence of major antiepileptic drugs on neuropsychological function: results from a randomized, doubleblind, placebo-controlled withdrawal study of seizure-free epilepsy patients on monotherapy. Neuropsychological abilities before and after 5 years of stable antiepileptic drug therapy. Effect of gabapentin (Neurontin) [corrected] on mood and well-being in patients with epilepsy. Comparative cognitive effects of carbamazepine and gabapentin in healthy senior adults. Randomized double-blind parallel-group study comparing cognitive effects of a low-dose lamotrigine with valproate and placebo in healthy volunteers.

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Syndromes

  • Esophageal varices usually from cirrhosis
  • Defects of the proteins that make up the internal framework of red blood cells
  • Focus on behavioral changes.
  • Clotting blood
  • Magnetoencephalography (MEG)
  • Clean the skin with mild, dilute soap and water. Rinse well, and gently pat dry.
  • Stretching exercises may be needed. These are done if the foot can be easily moved into a normal position. The family will be taught how to do these exercises at home.
  • Seizures or unexplained, small strokes (from bleeding into the brain)

For example anxiety symptoms dry lips cheap sinequan 25 mg without a prescription, it is estimated that up to anxiety chest pain proven 25 mg sinequan 50% of all pregnancies affected with a neural tube defect may be discontinued and would thus not be included in hospital records (Cragan 2000) anxiety attack help buy 25mg sinequan with amex. In addition, postnatal tests such as echocardiograms and ultrasounds may identify internal organ defects not diagnosed in the birthing hospital. Spontaneous abortions that are delivered prior to 20 weeks of gestation and less than 350 grams are not included in the case definition. Another example, Fetal Alcohol Syndrome, may not be detected until developmental delays become evident when a child is much older. Deliveries and diagnoses that occurred in other out-ofstate facilities are not included at this time. Factors such as differences in the demographics of the two populations, the environments in which they live, and the methods of surveillance conducted by the two programs may contribute to differences in the prevalence of birth defects. Glossary A glossary of selected birth defect terms is included in the appendices of this report. The lower rates for the other defects may reflect differences in defect criteria between surveillance systems as well as regional differences. Spontaneous deliveries of stillbirths equal to or greater than 20 weeks of gestation were reported by birthing hospitals but limited information about the stillbirth is included in the maternal record. Thus, some birth defects are not well documented and are unable to be confirmed for inclusion in state surveillance. For the two years 1994 and 1999, 40-80% of pregnancies with either lethal or very severe defects were terminated (Peller 2004). The overall prevalence of reported birth defects in Massachusetts in 2002-2003 was 157. This increase was due to better reporting from hospitals and improved ascertainment of cases. Three of the ten most common defects were cardiovascular defects: Atrial Septal Defects, Ventricular Septal Defects and Pulmonary Stenosis (Valvular). Common non-cardiovascular defects included Trisomy 21, Polydactyly/Syndactyly, Hypospadias, Clubfoot, Cleft Lip with and without Cleft Palate, Cleft Palate alone, and Obstructive Genitourinary Defects. Cardiovascular Defects were the most commonly occurring birth defects in both Massachusetts and in the nation. They also contribute more to infant deaths than any other defect category (Petrini 1998). Multiple Defects Table 4 shows the distribution of birth defects by whether they appeared as a single diagnosis or in combination (multiple) with other defects. A case was defined as having multiple defects, if it had more than one defect from among those that are included in this surveillance report. Anencephaly, Cleft Lip with and without Cleft Palate, Gastroschisis, Hirschsprung Disease, Clubfoot, and Hypospadias appeared more often as a single defect rather than in combination with other defects. Limb Reductions, Hydrocephalus, Esophageal Atresia/Tracheoesophageal Fistula, Intestinal Atresias, and Obstructive Genitourinary Defects were some of the birth defects that appeared more often with other defects. Overall, Cardiovascular Defects were five times more likely to occur as one of multiple defects than as a single defect. Selected Pregnancy Outcomes Figure 2 compares selected pregnancy outcomes (C-sections, birthweight, gestational age, multiple birth and infant death) among infants born with birth defects to those born without birth defects in 2002-2003 by percentage. While numbers of infants with birth defects are relatively small, it is important to recognize the impact of these outcomes when diagnosing and treating a baby with a birth defect. These rates are from surveillance systems that include prenatally diagnosed and terminated pregnancies. C hr om C en tra lN er om M os G vo us en i 26 27 28 29 30 31 32 33 Figure 2 Pregnancy Outcomes: Birth Defect Cases Compared to Unaffected Live Births, Massachusetts: 2002-2003 45. Birth defects that occurred more frequently in multiple births included Esophageal Atresia/Tracheoesophageal Fistula, Hypospadias, Coarctation of Aorta, Diaphragmatic Hernia and Polydactyly/Syndactyly. Examining birth defects by plurality is important since the number of multiple births has been increasing over time in Massachusetts.

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