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Biomedical subjects

Gideon Koren

Publications and source records attributed to Gideon Koren.

At least 235 records · Page 13Linked to original sources
PubMed2002

Single-dose and steady-state pharmacokinetics of celecoxib in children.

BACKGROUND AND OBJECTIVE: Celecoxib is a member of a novel group of agents that selectively inhibit cyclooxygenase 2 (COX-2). COX-2 inhibitors have emerged as an important class of drugs because of the lower incidence of side effects when compared with traditional nonsteroidal anti-inflammatory drugs, which inhibit both cyclooxygenase 1 and COX-2. Because children often differ from adults with respect to drug disposition, the objective of this study was to determine the single-dose and steady-state pharmacokinetics of celecoxib in pediatric patients. METHODS: Celecoxib plasma concentrations were determined at intervals over 12 hours after a 250-mg/m(2) dose and again 1 week later after twice-daily dosing (steady state). RESULTS: Peak plasma concentrations (1234 +/- 528 microg/L) were achieved 3 hours after drug administration. The area under the celecoxib plasma concentration-time curve was 7709 +/- 3176 microg/L x h, the elimination half-life (t(1/2)) was 3.7 +/- 1.1 hours, the apparent volume of distribution was 7.9 +/- 7.8 L/kg, and the lower oral clearance of the drug was 1.4 +/- 1.0 L x h(-1) x kg(-1). Statistical analysis revealed a significantly lower [corrected] apparent oral clearance and longer t(1/2) (P <.05) at steady state compared with pharmacokinetics after a single dose. In addition, when the results were compared in children and adults, the drug was cleared approximately twice as fast in children and had a t(1/2) that was approximately half as long. CONCLUSIONS: This is the first report of celecoxib pharmacokinetics in children, and the results indicate that there are significant differences between children and adults with respect to celecoxib disposition; hence these data may have implications when dosing schedules are planned for this population.

Adolescent↗
PubMed2002

Evidence-based view of safety and effectiveness of pharmacologic therapy for nausea and vomiting of pregnancy (NVP).

OBJECTIVE: Our goal was to review the safety and effectiveness of available antiemetics for treatment of nausea and vomiting of pregnancy. STUDY DESIGN: We performed a quantitative and qualitative overview of observational controlled studies for drug safety in pregnancy and randomized controlled trials for drug effectiveness for nausea and vomiting in pregnancy. RESULTS: All of the following are safe and effective for treatment of varying degrees of nausea and vomiting in pregnancy: Bendectin/Diclectin (doxylamine, pyridoxine, dicyclomine), antihistamine (H(1)) blockers, and phenothiazines; however, the magnitude of effect, particularly for phenothiazines, is in question and may differ among individual agents. Pyridoxine and vitamin B(12)are safe and may be effective. Metoclopramide, droperidol, and ondansetron may be effective, but safety data are insufficient to recommend them as first-line agents. Corticosteroids may not be as beneficial as first thought, and there may be a small teratogenic risk. The relative effectiveness of various agents is largely unknown. CONCLUSION: Many medications, particularly H(1)-antagonists and phenothiazines, are safe and effective for treatment of varying degrees of NVP.

Abnormalities, Drug-Induced↗
PubMed2002

The teratogenicity of drugs for nausea and vomiting of pregnancy: perceived versus true risk.

Women and health care providers commonly overestimate the teratogenic risk of medications in pregnancy. With regard to nausea and vomiting of pregnancy, this leads to an underutilization of pharmacologic therapy. Pregnancy termination has even been elected in some circumstances when safe and effective alternatives for nausea have not been attempted. The misperception of teratogenic risk is partly the result of the way data on safety are presented. An awareness of this can lead to more balanced patient and physician educational materials. To facilitate rational use of medicinal and nonmedicinal therapy for nausea and vomiting of pregnancy, we have developed an algorithm based on a recent systematic review of safety and efficacy in management of the problem. The hierarchical use of medication is based on strength of evidence of fetal safety.

Abnormalities, Drug-Induced↗
PubMed2002

Development of a health-related quality of life instrument for nausea and vomiting of pregnancy.

OBJECTIVE: To develop a questionnaire that measures change in symptoms of nausea and vomiting of pregnancy (NVP). METHODS: Eligible and consenting callers to the NVP Healthline at the Hospital for Sick Children, Toronto, underwent telephone interview by using a structured questionnaire. Callers were asked to indicate which of 195 items had been a problem for them and the importance of that problem. For each item, the "frequency" (of women who identified the item as problematic) and "mean importance" (mean importance score of women who indicated that the item was problematic) were multiplied to give the "overall impact." Patterns of response were examined by maternal characteristics. Factor analysis was used to explore relationships between factors. RESULTS: Among 500 women enrolled, areas of quality of life impairment were frequent and similar by maternal characteristics. The questionnaire contains 30 items in 4 domains (physical symptoms/aggravating factors, fatigue, emotions, and limitations) and takes 10 minutes to administer. CONCLUSIONS: This questionnaire contains topics of quality of life impairment important to women with NVP and shows promise for use as an outcome measure in clinical trials.

Adult↗
PubMed2002

Motherisk-PUQE (pregnancy-unique quantification of emesis and nausea) scoring system for nausea and vomiting of pregnancy.

OBJECTIVE: The morbidity of nausea and vomiting of pregnancy varies substantially. In addition to the physical symptoms, the emotional and psychosocial stress must be considered. The method available today to measure the severity of nausea and vomiting of pregnancy stems from chemotherapy-induced symptoms and is too complicated to use clinically. We sought to establish a simple and clinically relevant method for evaluation of the severity of nausea and vomiting of pregnancy that can be used for both clinical practice and research. METHODS: Women with nausea and vomiting of pregnancy were scored by use of the "gold standard" Rhodes' score, which includes 8 items. The Rhodes' score was compared with several short versions of 3 to 4 items. Patients were subsequently followed up a week later to monitor changes in scores. Changes in the Rhodes' scores were correlated with changes in the simplified scores. RESULTS: There was a very tight correlation between the Rhodes' score and the new pregnancy-unique quantification of emesis and nausea (PUQE) scoring system, which was based on the 3 items that included the number of daily vomiting episodes, the length of nausea per day in hours, and the number of retching episodes (r = 0.904; P <.0001). The distribution of severity of cases (between none, mild, moderate, and severe) did not differ between the Rhodes' and the PUQE. Comparing the changes in Rhodes' scores after a week of follow-up versus changes in the new PUQE score, there was a very high agreement (r = 0.95;P <.0001). CONCLUSION: The new PUQE score yields similar results to the gold standard, but more cumbersome, Rhode's score. Clinicians and researchers can easily use PUQE.

Female↗
PubMed2002

Aspirin consumption during the first trimester of pregnancy and congenital anomalies: a meta-analysis.

OBJECTIVE: The purpose of this study was to determine, on the basis of published reports, whether aspirin use during the first trimester of pregnancy is associated with an increased risk of congenital malformations. STUDY DESIGN: We reviewed the literature for published studies that reported exposure to aspirin during the first trimester of pregnancy and congenital malformations. Two reviewers independently determined whether a study should be included in the final analysis and extracted the data. We calculated the pooled odds ratio and 95% CI. RESULTS: Twenty-two studies met the inclusion criteria. In the eight studies that reported an overall risk, the risk of congenital malformations in offspring of women who were exposed to aspirin was not significantly higher than that in control subjects (odds ratio, 1.33; 95% CI, 0.94-1.89). However, a significantly increased risk of gastroschisis (odds ratio, 2.37; 95% CI, 1.44-3.88) was found. CONCLUSION: We found no evidence of an overall increase in the risk of congenital malformations that could be associated with aspirin. Aspirin exposure during the first trimester may be associated with an increased risk of gastroschisis.

Abnormalities, Drug-Induced↗
PubMed2002

Lung tissue concentrations of nicotine in sudden infant death syndrome (SIDS).

OBJECTIVE: To compare lung concentrations of nicotine and cotinine in cases of sudden infant death syndrome (SIDS) and controls. DESIGN/METHODS: We measured lung tissue concentrations of nicotine and cotinine in SIDS (n = 44) and non-SIDS cases (n = 29) stratified according to household smoking status. RESULTS: When all the SIDS and non-SIDS cases were compared regardless of smoking status, there was a significantly higher nicotine concentration in the SIDS cases than in the non-SIDS cases, (P =.0001). Upon stratifying for smoking status, there was a nonsignificant trend toward more nicotine in SIDS versus non-SIDS lungs that had come from a reported smoking environment. In the nonsmoking group, there were significantly higher nicotine concentrations in SIDS than non-SIDS cases (P =.001). CONCLUSIONS: Children who died from SIDS tended to have higher concentrations of nicotine in their lungs than control children, regardless of whether smoking was reported. These results are based on an objective, biochemical test rather than history, and they further support the relationship between environmental tobacco smoke and the risk of SIDS.

Cotinine↗
PubMed2002

The stability of a ketamine-morphine solution.

UNLABELLED: Recent advances in acute pain mechanisms and management have implicated the N-methyl D-aspartate receptor-ion channel complex in the development of postoperative hyperalgesia and acute opioid tolerance. N-methyl D-aspartate receptor antagonists such as ketamine have been used increasingly in clinical studies in an effort to minimize acute postoperative pain and reduce opioid requirements. A mixture of ketamine and an opioid administered in the same solution and syringe would be a practical and useful technique for postoperative epidural analgesia, continuous IV infusion, or patient-controlled IV analgesia. We investigated the stability of a morphine sulfate and racemic ketamine solution in saline at pH 5.5-7.5 over a period of 4 days. Our study demonstrates that the ketamine-morphine mixture at a clinically relevant concentration seems to be stable at room temperature, at a wide range of pH values, for at least 4 days. IMPLICATIONS: Small-dose ketamine is used with increasing frequency in the acute postoperative setting as an adjunct to traditional opioid analgesics. We show that a racemic ketamine and morphine solution at a clinically relevant concentration seems to be stable at room temperature at a wide range of pH values for at least 4 days.

Analgesics↗
PubMed2002

Activated protein C in normal human pregnancy and pregnancies complicated by severe preeclampsia: a therapeutic opportunity?

OBJECTIVES: Given the efficacy and safety of recombinant human activated protein C (rhAPC) in the systemic inflammatory response syndrome, this study was designed to review the evidence for a role for APC in the pathogenesis of preeclampsia. Preeclampsia is a proinflammatory and procoagulant state, and it is a pregnancy-specific condition that mimics the systemic inflammatory response syndrome. rhAPC reduces mortality in patients with systemic inflammatory response syndrome and could potentially have a role as disease-modifying therapy in preeclampsia. To determine which patients would be offered rhAPC, the literature pertaining to fetal/neonatal outcomes for preeclampsia remote from term, transplacental transport of protein C, and pregnancy experience with the compound were reviewed. DATA SOURCES: MEDLINE, review papers, hand searches of relevant nonindexed journals, and the bibliographies of relevant textbooks and articles reviewed. STUDY SELECTION: Randomized controlled trials were considered to provide the best quality of clinical data. Case-control series were considered over uncontrolled data. Some data were not available in the published literature (e.g., neonatal outcomes at various gestational ages and birthweights after a hypertensive pregnancy; and transplacental transfer of protein C), and these data were determined by us. DATA EXTRACTION: Data were extracted by systematic review onto data collection sheets. Because of the quality of the data, this review is primarily qualitative. DATA SYNTHESIS: APC levels fall during normal gestation, returning to normal values by 6 wks postpartum. Limited data suggest that early onset preeclampsia is a state of further, and inappropriate, reduction in APC. Preeclampsia resembles systemic inflammatory response syndrome in this regard. After hypertensive pregnancies, neonates have a 50% chance of intact survival if delivered after 27 + 0 wks of gestation with a birthweight of >600 g. It would seem ethical to offer women with preeclampsia with <50% chance of intact perinatal survival novel and potentially disease-modifying therapy such as rhAPC, especially as there is no transplacental transfer of protein C. Limited evidence would support the use of rhAPC in women with severe postpartum preeclampsia. CONCLUSIONS: Sufficient data exist to support the use of rhAPC in phase II clinical studies for women with either early onset preeclampsia or severe or deteriorating postpartum disease.

Case-Control Studies↗
PubMed2002

Estimation of fetal exposure to drugs of abuse, environmental tobacco smoke, and ethanol.

Many women worldwide use recreational drugs and alcohol. Details on the amounts and schedule of such exposures in pregnancy are often unreliable because of recall issues and shame and fears of legal action. Even when the report on maternal dose is correct, it does not necessarily reflect the amount reaching the fetus. Drugs of abuse accumulate in meconium and are incorporated into fetal hair on its growth. Recent work has documented the sensitivity and specificity of these assays for cocaine and other recreational drugs. Dose-response relationships between cocaine as measured in neonatal hair and head circumference or neurologic sequelae have been recently established. For ethanol, which cannot be measured in hair or meconium, accumulation of its fatty acid ethyl esters in meconium is emerging as a promising test for heavy maternal drinking in the second part of pregnancy. The identification of biologic markers of intrauterine exposure to xenobiotics will allow better understanding of etiology and dose-response relationships.

Central Nervous System Depressants↗
PubMed2002

How high can we go with phenytoin?

Phenytoin is an effective anticonvulsant, but high serum phenytoin concentrations may be associated with serious toxicity. The upper limit for the therapeutic serum concentration of phenytoin is considered to be 80 micromol/L. However, in some situations higher serum concentrations are needed to control seizures. The authors describe a 9-year-old girl who needed concentrations twice the normal amount to control recurrent episodes of decreased levels of consciousness. Except for nystagmus, she had no other signs of phenytoin toxicity. This patient highlights the critical principle in therapeutic drug monitoring of individualizing drug therapy. Although some patients receiving phenytoin may achieve seizure control with "subtherapeutic" levels (i.e., <40 micromol/L), others may need supratherapeutic levels, as was the case with this patient. Clinicians should be careful not to treat "numbers" (i.e., serum concentrations), but rather the patient's clinical condition, with a careful balance between therapeutic advantage and adverse effects.

Anticonvulsants↗
PubMed2002

Potential prevention of neural tube defects by assessment of women of childbearing age through monitoring of folate.

BACKGROUND: Three quarters of neural tube defects (NTD) can be prevented by sufficient dietary folate supplementation. Despite this knowledge, most women do not supplement their diet effectively. Red cell folate concentrations correlate with the risk of NTD, and levels of less than 900 nM are associated with an increased risk of these serious congenital anomalies. OBJECTIVE: Laboratory tests to assess anemia include testing for folate. This study was conducted to estimate the potential benefits of informing women of reproductive age who are unaware of their low folate levels, uncovered in their anemia tests. METHODS: The number of Ontario women of reproductive age who undergo folate tests and are at an increased risk of NTD was calculated. In addition, the authors calculated the number of NTD cases that could have been prevented if these women were informed of the possible consequences of their low folate levels should they become pregnant. RESULTS: In 1998, red cell folate concentrations were measured in 23,109 women of childbearing age (15-45 y). Approximately half of the women [n = 11,392 (49.3%)] had folate levels below 900 nM and thus were at an increased risk of giving birth to a child with NTD should they have become pregnant. Their overall mean relative risk (RR) of NTD was 1.95, or 1:512 births. If they would have been informed of this risk and subsequently increased their consumption of folate before becoming pregnant, 22.3 cases of NTD per year could have possibly been prevented at no extra cost, since the folic acid results were a part of investigational blood tests performed for another reason (anemia). CONCLUSIONS: Women of reproductive age who are being evaluated for the cause of anemia and have low red cell folate results constitute a high-risk group for NTD in their children. These women should be informed of the increased risk and of methods of dietary folate supplementation.

Adolescent↗
PubMed2002

Agreement between prospective and retrospective reports of maternal exposure to chemicals during pregnancy.

As part of a prospective study of solvent exposure and child behavior, it occurred that women's responses about exposure history during pregnancy differed from the information documented during the postpartum period. The objective of the study was to examine the levels of agreement in 29 self-reports of exposure information obtained before and 3- to 7-years after pregnancy. Percent agreement was low for duration of exposure (41%), protective barrier use (48%), and symptomatology (41%). When reports were not in perfect agreement, women tended to report longer durations of exposure (r = 0.67), increased use of protective barriers (r = 0.39), and more symptoms at time of follow-up (r = 0.57). Agreement of report was not substantially associated with time since pregnancy or concurrent child behavior. Low levels of agreement may reflect response biases in the data collected at time of pregnancy or recall biases at time of follow-up. These variations in self-reports are of concern because they can severely affect estimates of human teratological risk.

Adult↗
PubMed2002

Use of atypical antipsychotics during pregnancy and the risk of neural tube defects in infants.

OBJECTIVE: Folate deficiency in early pregnancy and maternal adiposity, independent of folate intake, lead to a greater risk of neural tube defects in infants. Atypical antipsychotics cause various degrees of weight gain. The authors assessed folate status and obesity among patients with schizophrenia receiving atypical antipsychotics. METHOD: A sample of 70 inpatients and outpatients (21 of them women) who were taking antipsychotics was randomly selected. Body weight, body mass index, daily folate intake, and folate serum concentrations were determined. RESULTS: The majority of the patients were overweight. Only eight of 37 patients had folate intake above 400 microg/day, the level shown to be protective against neural tube defects. Mean serum folate was significantly lower than in a general hospital group of 810 patients. CONCLUSIONS: Women with schizophrenia who take atypical antipsychotics have a higher risk of neural tube defects in their infants because of the associated low intake of folate and obesity.

Adult↗
PubMed2002

Child development following exposure to tricyclic antidepressants or fluoxetine throughout fetal life: a prospective, controlled study.

OBJECTIVE: Previous work suggested that first-trimester exposure to tricyclic antidepressants or fluoxetine does not affect adversely child IQ and language development. However, many women need antidepressants throughout pregnancy to avoid morbidity and suicide attempts. Little is known about the fetal safety of tricyclic antidepressants and fluoxetine when taken throughout pregnancy. The goal of this study was to assess the effects of tricyclic antidepressants and fluoxetine used throughout gestation on child IQ, language, and behavior. METHOD: In a prospective study, mother-child pairs exposed throughout gestation to tricyclic antidepressants (N=46) or fluoxetine (N=40) and an unexposed, not depressed comparison group (N=36) were blindly assessed. The three groups were compared in terms of the children's IQ, language, behavior, and temperament between ages 15 and 71 months. The authors adjusted for independent variables such as duration and severity of maternal depression, duration of pharmacological treatment, number of depression episodes after delivery, maternal IQ, socioeconomic status, cigarette smoking, and alcohol use. RESULTS: Neither tricyclic antidepressants nor fluoxetine adversely affected the child's global IQ, language development, or behavior. IQ was significantly and negatively associated with duration of depression, whereas language was negatively associated with number of depression episodes after delivery. CONCLUSIONS: Exposure to tricyclic antidepressants or fluoxetine throughout gestation does not appear to adversely affect cognition, language development, or the temperament of preschool and early-school children. In contrast, mothers' depression is associated with less cognitive and language achievement by their children. When needed, adequate antidepressant therapy should be instituted and maintained during pregnancy and postpartum.

Antidepressive Agents↗
PubMed2002

Serum concentrations, efficacy, and safety of a new, intravenously administered varicella zoster immune globulin in pregnant women.

Chickenpox is teratogenic in humans, and varicella zoster immune globulin (VZIG) is given to pregnant women believed to be susceptible to the virus after contact with chickenpox. Available VZIG is given as intramuscular injections. The objective of this study was to evaluate the efficacy, safety, and serum concentrations of a new VZIG that can be given intravenously. The new VZIG (Cangene Pharm., Inc.) was compared to the standard VZIG (Massachusetts Public Health Biologic Laboratories) in a randomized protocol in 57 pregnant women seronegative to varicella zoster virus (VZV). Pregnant women received 125 units per 10 kg body weight to a maximal dose of 625 units. Women were evaluated on days 2, 7, 14, and 28 and at other times if symptoms developed into clinical varicella, which was scored by the Constitutional Illness Score. The new VZIG was comparable to the standard VZIG on all parameters of efficacy and safety. Levels of VZV antibodies at day 2 postinjection were significantly higher among those receiving the new preparation intravenously. The authors concluded that the new intravenous form of VZIG confers higher initial levels of VZV antibodies and is comparable in terms of its maternal efficacy and safety to the standard form of VZIG.

Adult↗