Search PubMed⌕ Search

Biomedical subjects

Gideon Koren

Publications and source records attributed to Gideon Koren.

At least 91 records · Page 5Linked to original sources
PubMed2005

Seven items were identified for inclusion when reporting a Bayesian analysis of a clinical study.

OBJECTIVE: (1) To generate a list of items that experts consider most important when reporting a Bayesian analysis of a clinical study, (2) to report on the extent to which we found these items in the literature, and (3) to identify factors related to the number of items in a report. STUDY DESIGN AND SETTING: Based on opinions from 23 international experts, we determined the items considered most important when publishing a Bayesian analysis. We then performed a literature search to identify articles in which a Bayesian analysis was performed and determined the extent to which we found these items in each report. Finally, we examined the relationship between the number of items in a report and journal- and article-specific attributes. RESULTS: Our final set of seven items described the prior distribution (specification, justification, and sensitivity analysis), analysis (statistical model and analytic technique), and presentation of results (central tendency and variance). There was >99% probability that more items were reported in studies with a noncontrolled study design and in journals with a methodological focus, lower impact factor, and absence of a word count limit. CONCLUSION: We developed a set of seven items that experts believe to be most important when reporting a Bayesian analysis.

Bayes Theorem↗
PubMed2005

Clopidogrel use in children.

OBJECTIVES: To review a pediatric experience with the antiplatelet agent clopidogrel and suggest a dosage regimen. STUDY DESIGN: A retrospective chart review of all infants and children treated with clopidogrel at The Hospital for Sick Children, Toronto between January 2001 and April 2004. Clopidogrel dosages, duration of therapy, complications, and adverse effects in a pediatric population were explored. RESULTS: Fifteen infants and children with congenital and acquired heart disease were treated with clopidogrel (median age, 3.5 years; range, 6 weeks to 16 years). Dosages ranged from 1 to 6 mg/kg/day for periods between 1 month and 6 months. Although no thrombotic events were reported, 1 child had a bleeding complication (gastrointestinal) while on triple antithrombotic therapy. Other complications reported in adults, including rash and clinical thrombocytopenia, were not noted in this pediatric series. CONCLUSIONS: Clopidogrel was well tolerated. We suggest a starting dose of 1 mg/kg/day for children.

Adolescent↗
PubMed2005

Gene-expression analysis after alcohol exposure in the developing mouse.

Exposure to alcohol in the embryonic mouse can lead to structural and neurophysiologic changes. The cause of these changes is poorly understood, but they are likely the result of numerous mechanisms. Here we investigate ethanol-induced alterations in gene expression in the fetal brain. Using complementary-DNA microarrays, we identified 25 genes that were down-regulated by prenatal ethanol exposure on days 7 and 9 of gestation. None were found to be up-regulated. Of those that were repressed, 6 (Timp4, Bmp15, Rnf25, Akt1, Tulp4, Dexras1) have been identified, and they are discussed here in the context of the developing fetus. The identified genes have been shown to be involved in cell proliferation, differentiation, and apoptosis, and they contribute to tissue growth and remodeling, as well as neuronal growth and survival. Microarray studies may be useful in the identification of a genetic marker for fetal alcohol syndrome, the discovery of novel pathways that may be involved in its origin, or both.

Animals↗
PubMed2005

Vision abnormalities in young children exposed prenatally to organic solvents.

Despite an accumulating body of evidence demonstrating that the visual system is an important target for organic solvent toxicity in adults, little attention has been paid to the visual functioning of children with prenatal exposure to organic solvents. The present study aimed to: (1) determine prospectively whether prenatal solvent exposure increases the risk of visual deficits in infants and (2) assess the relationship between estimates of exposure level and integrity of visual responses. A sample of 21 infants born to women who were occupationally exposed to solvents during pregnancy was compared with 27 non-exposed age-matched control infants. All mothers were recruited from Motherisk, an antenatal counseling service in Toronto, Canada. Contrast sensitivity and grating acuity were assessed using a sweep visual evoked potential (VEP) technique whereas chromatic- and achromatic mechanisms were assessed using a transient VEP technique. Exposure level was estimated from questionnaire data obtained during pregnancy. Testers were masked to exposure status. Results showed a significant reduction in contrast sensitivity in the low and intermediate spatial frequency range in solvent-exposed infants compared to controls (p<0.001). With respect to grating acuity, there was a significant effect of exposure level, with children in the high exposed having reduced grating acuity compared with children in the low exposed group (p<0.025) and controls (p=0.02). Regarding color vision, 26.3% of infants in the exposed group versus 0% of the controls produced abnormal VEP responses to the red-green onset stimulus (p<0.01), but not to either blue-yellow or achromatic stimuli. No differences were found with respect to latency or amplitude of chromatic and achromatic response. These findings suggest that prenatal solvent exposure is associated with selective visual deficits, including reduced contrast sensitivity and abnormal red-green vision. Increasing levels of exposure may lead to further visual deficits affecting grating acuity. These findings support the need for a re-evaluation of current occupational exposure standards for pregnant women.

Adult↗
PubMed2005

Maternal hyperthermia and the risk for neural tube defects in offspring: systematic review and meta-analysis.

BACKGROUND: In animals, excessive core body temperatures have been documented to cause malformations; neural tube defects (NTDs) are among the most frequently reported. In humans, data are inconclusive and often conflicting. The objective of our report is to determine the risk for neural tube defects associated with maternal hyperthermia in early pregnancy. METHODS: We conducted a systematic review and meta-analysis to evaluate available evidence on this topic in humans. MEDLINE, EMBASE, references from published reports, and biologic abstracts from meetings were searched for relevant studies. Reviewers evaluated all the retrieved articles and extracted the relevant data. Individual and summary odds ratios and relative risks were calculated using the Mantel-Haenszel method. RESULTS: Fifteen studies, reporting on 1,719 cases and 37,898 noncases, were included in the meta-analysis. The overall odds ratio for neural tube defects associated with maternal hyperthermia was 1.92 (95% confidence interval = 1.61-2.29). When analyzed separately, the 9 case-control studies had an odds ratio of 1.93 (1.53-2.42). The summary relative risk for the 6 cohort studies was 1.95 (1.30-2.92). CONCLUSIONS: Maternal hyperthermia in early pregnancy is associated with increased risk for neural tube defects and may be a human teratogen.

Adult↗
PubMed2005

Baseline measures of fatty acid ethyl esters in hair of neonates born to abstaining or mild social drinking mothers.

Elevated levels of fatty acid ethyl esters have been documented in the meconium of neonates born to heavily drinking mothers. Recently, accumulation of FAEE has been documented in the hair of drinking adults. To be able to use this test in the diagnosis of Fetal Alcohol Spectrum Disorder, one needs to establish baseline FAEE levels in infants born to nonalcoholic women because ethanol occurs in the baby naturally even without drinking. Scalp hair of 56 infants born to nonalcoholic women attending a well-baby clinic was obtained. Levels of FAEE were measured by GC-MS. FAEE were detected in almost all hair samples. Offspring of women admitting to mild, infrequent drinking did not differ in FAEE hair levels from infants of total abstainers. Baseline levels of FAEE in neonatal hair of nonalcoholic mothers have been established. Mild infrequent maternal drinking does not elevate these baseline levels. This may help avoid false-positive determinations when assessing infants born to problem drinking mothers.

Adult↗
PubMed2005

A tubule cell model for ifosfamide nephrotoxicity.

Mechanisms leading to ifosfamide (IF)-induced renal damage have not been fully elucidated. Recent work suggests that localized renal tubular metabolism of IF and the production of the nephrotoxic chloroacetaldehyde may lead to nephrotoxicity. Presently no pharmacological method to reduce IF nephrotoxicity has been identified. The objectives of this study were to establish a tubule cell model for IF nephrotoxicity, to verify whether renal proximal tubular cells have the necessary cytochrome P450 (CYP) enzymes to oxidize IF, and whether they can metabolize IF to chloroacetaldehyde. CYP3A, and 2B mRNA and protein were identified in LLCPK-1 cells. The cells metabolized the R- and S-IF enantiomers to their respective 2- and 3-dechloroethylifosfamide metabolites, by-products of chloroacetaldehyde formation. Metabolite production was both time and concentration-dependent. IF did not affect cell viability. In contrast, glutathione-depleted cells showed time and dose-dependent damage. The presence of the relevant CYP enzymes in renal tubular cells along with their ability to metabolize IF to its 2- and 3-dechloroethylifosfamide metabolites suggests that nephrotoxic damage may result from the localized production of chloroacetaldehyde. Glutathione is a major defence mechanism against IF toxicity, thus pharmacological methods for replenishing intracellular glutathione may be effective in modulating IF-induced nephrotoxicity.

Animals↗
PubMed2005

A Guinea pig model for the identification of in utero alcohol exposure using fatty acid ethyl esters in neonatal hair.

Measuring levels of fatty acid ethyl esters (FAEE) in hair has been a useful way to discriminate between adult heavy and nondrinkers. Extending the use of FAEE into neonatal hair to objectively identify children exposed to alcohol in utero may revolutionize current methods used to diagnose fetal alcohol spectrum disorder (FASD). Here we confirm for the first time that chronic exposure to alcohol during pregnancy in guinea pigs leads to increased levels of FAEE in both maternal and neonatal hair. The mean cumulative FAEE concentration in exposed maternal samples taken at GD57 was 0.431+/-0.140 pmol/mg (mean+/-SEM); levels observed in corresponding sucrose and water controls were 10-fold lower. Similarly, FAEE concentrations in exposed offspring samples taken at postnatal d 1 (mean cumulative FAEE=0.491+/-0.177 pmol/mg) were more than 15-fold higher than control counterparts. Sixty percent of all alcohol-exposed animal samples contained two or more quantifiable FAEE, whereas close to 90% of either water or sucrose control samples did not have more than one quantifiable level of a single FAEE. Results of this study suggest that FAEE in neonatal hair may be useful biomarkers in identifying in utero alcohol exposure and may facilitate the early diagnosis and treatment of FASD.

Animals↗
PubMed2005

Ontogeny of renal P-glycoprotein expression in mice: correlation with digoxin renal clearance.

Digoxin is eliminated mainly by the kidney through glomerular filtration and P-glycoprotein (P-gp) mediated tubular secretion. Toddlers and young children require higher doses of digoxin per kilogram of bodyweight than adults, although the reasons for this have not been elucidated. We hypothesized there is an age-dependant increase in P-gp expression in young children. The objectives of this study were to elucidate age-dependant expression of renal P-gp and its correlation with changes in the clearance rate of digoxin. FVB mice were killed at different ages to prepare total RNA for P-gp expression studies. Semi-quantitative RT-PCR was conducted to analyze mdr1a and mdr1b ontogeny in the kidney at: birth, 7, 14, 21, 28 and 45-d old adults. The pharmacokinetics of digoxin (7 microg/kg) was studied in mice of the same age groups. Newborn and Day 7 levels of both mdr1a and mdr1b were marginal. Day 21 mdr1b levels were significantly higher than both Day 14 and Day 28 levels. Digoxin clearance rates were the highest at Day 21, with significant correlation between P-gp expression and clearance values. Increases in digoxin clearance rates after weaning may be attributed, at least in part, to similar increases in P-gp expression.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2005

Natural health product-HIV drug interactions: a systematic review.

The use of natural health products (NHPs) within the HIV community is high. Several NHPs have demonstrated interactions with HIV medications that could contribute to drug failure. We aimed to conduct a systematic review of clinical trials examining NHP-HIV drug interactions and their methodological characteristics. We searched electronic databases and unpublished resources independently, in duplicate. Nine studies were identified, eight clinical pharmacokinetics trials and one population-pharmacokinetics trial. Investigators studied four different herbal medicines (St John's wort, garlic, goldenseal and milk thistle) and one vitamin (vitamin C). Significant interactions were observed with St John's wort, garlic and vitamin C. However, methodological challenges exist to making the results directly generalizable to patients. This review finds that important drug level changes exist when NHPs are combined with HIV medications. Considering patient values and the implications of these studies, further research is urgently required to determine the extent of interactions with other commonly used NHPs.

Adolescent↗
PubMed2005

Effectiveness of bupropion for smoking cessation during pregnancy.

Gestational smoking has been established as a risk to the fetus. However, many pregnant smokers are unable to quit due to the highly addictive nature of nicotine. Nicotine replacement therapy has failed in several studies in pregnant women. In a prospective matched, controlled observational study, of 22 pregnant smokers receiving bupropion, 10 (45%) ceased smoking, as compared to 3 (14%) of 22 controls (P = 0.047). Bupropion appears to be effective for smoking cessation therapy during pregnancy.

Adult↗
PubMed2005

Using a preprinted order sheet to reduce prescription errors in a pediatric emergency department: a randomized, controlled trial.

OBJECTIVE: Medication errors are common among pediatric patients and in emergency departments (EDs). Such errors may lead to prolonged hospitalization, unnecessary diagnostic tests and treatments, and death. The objective of this study was to determine whether the use of a structured order sheet reduces the incidence of medication errors in a pediatric ED. METHODS: The study was a randomized, controlled study that was conducted in a tertiary care pediatric hospital. Eighteen days were randomized into 2 study groups: days during which the regular blank order sheets were used and days during which preprinted, formatted, order sheets were used. All patients' charts from these days were reviewed by 2 medical students, who extracted demographic, clinical, and therapeutic data into a database. Two pediatric emergency physicians, blinded to the form used, reviewed the database and independently decided whether an error had occurred and the severity of the error. RESULTS: Within the study period, there were 2157 visits to the ED. A total of 2058 (95.4%) charts were available for review. A total of 411 (52.2%) orders for drugs in the ED were ordered on the regular form, and 376 (47.8%) were given on the new form. Drug errors were identified in 68 (16.6%) orders when the regular form was used and in 37 (9.8%) of the orders on the new form. Using the new form was associated with a significant reduction in the risk for an error (odds ratio: 0.55; 95% confidence interval: 0.34-0.90). CONCLUSIONS: The use of a preprinted structured order form significantly reduces medication errors among pediatric patients in the ED.

Child↗
PubMed2005

Fetal safety of drugs used in the treatment of allergic rhinitis: a critical review.

Allergic rhinitis is the most common allergic disease. Pharmacological interventions are often not used in pregnancy because of alarming information in drug labels and patient information, even when evidence for safety exists.Low-risk therapies could include immunotherapy, intranasal sodium cromoglycate (cromolyn sodium), beclometasone, budesonide and first-generation antihistamines. In a meta-analysis examining the safety of first-generation antihistamines in pregnancy, 200 000 first trimester exposures failed to show increased teratogenic risk. Loratadine is the most studied second-generation antihistamine (with a total patient cohort of 2147 women who were exposed) and does not appear to increase the risk of major congenital malformations; however, it has not been as well studied as the earlier antihistamines. Since desloratadine is the principal metabolite of loratadine, it can be assumed that a similar safety profile would fit for desloratadine as was described for loratadine although no direct human studies have been done. Decongestants have not been conclusively proven to affect the fetal outcome and may be used for short-term relief when no other safer alternatives are available. Intranasal corticosteroids have not been associated with an increase in congenital malformations in humans. Based on efficacy and the fact that there would be little systemic absorption, they can be considered a first-line treatment over oral antihistamines, decongestants and mast cell stabilisers; however, the number of controlled trials in pregnancy is limited. Intranasal corticosteroids are associated with minimal systemic effects in adults and are the most effective therapy for allergic rhinitis. Benefit-risk considerations must, therefore, be done but favour their first-line use during pregnancy. Because fetal safety is paramount, recommendations should be based both on the safety of the drugs during pregnancy and the comparative efficacy of the agent in the treatment of the underlying condition. This review exemplifies the fact that there are many safe treatment options for the clinician when dealing with allergic rhinitis during pregnancy.

Animals↗