A survey of physicians knowledge regarding awareness of maternal alcohol use and the diagnosis of FAS.

BACKGROUND: Alcohol is the most widely used drug in the world that is a human teratogen whose use among women of childbearing age has been steadily increasing. It is also probable that Fetal Alcohol Syndrome is under diagnosed by physicians. The objectives of this study were twofold: 1) to evaluate the experience, knowledge and confidence of family physicians with respect to the diagnosis of FAS and 2) to evaluate physicians awareness of maternal drinking patterns. METHODS AND PARTICIPANTS: A multiple choice anonymous questionnaire was sent to a randomly selected group of family physicians in the Metropolitan Toronto area. RESULTS: There was a 73% (75/103) total response rate; Overall, 6/75 (8%) of family physicians reported that they had actually diagnosed a child with FAS. 17.9% had suspicions but did not make a diagnosis and 12.7% reported making a referral to confirm the diagnosis. Physician rated confidence in the ability to diagnosis FAS was low, with 49% feeling they had very little confidence. 75% reported counselling pregnant women and 60.8% reported counselling childbearing women in general on the use of alcohol. When asked what screening test they used to detect the use of alcohol, 75% described frequency/quantity. Not a single respondent identified using the current accepted screening method for alcohol use (TWEAK) which is recommended by The Centre for Addiction and Mental Health. CONCLUSIONS: Family physicians do not feel confident about diagnosing FAS. None of the physicians were aware of the current screening methods to accurately gage alcohol use in pregnant and childbearing wome

The interactions of age, genetics, and disease severity on tacrolimus dosing requirements after pediatric kidney and liver transplantation

Purpose: In children, data on the combined impact of age, genotype, and disease severity on tacrolimus (TAC) disposition are scarce. The aim of this study was to evaluate the effect of these covariates on tacrolimus dose requirements in the immediate post-transplant period in pediatric kidney and liver recipients. Methods: Data were retrospectively collected describing tacrolimus disposition, age, CYP3A5 and ABCB1 genotype, and pediatric risk of mortality (PRISM) scores for up to 14 days post-transplant in children receiving liver and renal transplants. Initial TAC dosing was equal in all patients and adjusted using therapeutic drug monitoring. We determined the relationship between covariates and tacrolimus disposition. Results: Forty-eight kidney and 42 liver transplant recipients (median ages 11.5 and 1.5 years, ranges 1.5-17.7 and 0.05-14.8 years, respectively) received TAC post-transplant. In both transplant groups, younger children (<5 years) needed higher TAC doses than older children [kidney: 0.15 (0.07-0.35) vs. 0.09 (0.02-0.20) mg/kg/12h, p = 0.046, liver: 0.12 (0.04-0.32) vs. 0.09 (0.01-0.18) mg/kg/12h, p

Methodology Challenges in Behavioural Teratology Drug Safety Studies on Depression

Numerous medical conditions in pregnancy require pharmacotherapy. A conflict between optimal maternal treatment and risk of fetal teratogenicity arises if drug safety is not assured. Behavioural teratology, the science of central nervous system impairments due to a variety of prenatal exposures, is an inseparable part of reproductive drug safety studies and addresses the long-term neurodevelopment of exposed children. Research in behavioural teratology is sparse due to lack of funding priorities and methodological obstacles related to statistical power, cost/time effectiveness, and multiple confounders (with the genetics being the most difficult to control for). Implementing an appropriate study design is critical in overcoming these challenges. Depression is the most common psychiatric disorder in women, and up to 16% of pregnant women with depression require pharmacotherapy. Selective transmitter reuptake inhibitors (STRIs) are widely used to control depression in pregnancy. The objectives of this thesis were to define the long-term neurodevelopment of children exposed in utero to STRI antidepressants and to develop an advanced methodology for behavioural teratology in order to achieve the highest possible degree of evidence. Three studies were conducted using different designs. The first study measured the intelligence of three groups of children exposed in utero to either the serotonin-norepinephrine reuptake inhibitor drug venlafaxine, other STRIs (a disease control), or children of healthy women exposed to non-teratogenic agents. The second study included an additional group of children prenatally exposed to maternal depression, but not pharmacotherapy, in order to separate the effects of maternal depression from the effects of the antidepressant medications. The third study compared long-term neurodevelopmental outcomes of children prenatally exposed to STRIs to their unexposed siblings. It was found that untreated depression is associated with adverse pregnancy outcome and increased rates of postpartum depression. Children of depressed mothers may be at risk of future psychopathology. Factors other than prenatal STRIs strongly predict children's intellect and behaviour. The sibling design was able to better control for genetic and environmental factors, was more cost-effective, and able to achieve more valid results with a much smaller sample size. This novel design should be implemented in behavioural teratology drug safety studies.Ph.D.2016-06-17 00:00:0

Effect of Lidocaine-Prilocaine Cream (EMLA®) on Pain of Intramuscular Fluzone® Injection

ABSTRACTThe efficacy of lidocaine-prilocaine cream (EMLA® — Eutectic mixture of Local Anesthetics) in alleviating the pain of intramuscular injections was investigated in a randomized, double-blind, placebo-controlled, parallel group trial. EMLA® or placebo cream was applied to the arms of 60 adult volunteers before receiving influenza virus vaccine (Fluzone®). Twenty-nine subjects received approximately 2.5 g of EMLA® cream and 31 subjects received approximately 2.5 g of an inert placebo cream under occlusion for 60-90 minutes. The cream was then removed and each subject received one 0.5 mL intramuscular injection of influenza virus vaccine using a 22 gauge one inch needle. Pain of needle puncture and pain of injection were both assessed by the subjects using a visual analog scale. EMLA® was associated with decreased needle puncture pain (p &lt; 0.0002) and decreased pain of injection when compared to placebo (p = 0.0139). There was a significant correlation between scores of needle puncture pain and injection pain. Mild skin pallor was a common skin reaction from EMILA®· While the efficacy of EMLA® to alleviate pain of venipuncture is well documented, this is the first study to show the efficacy of EMLA ® for intramuscular injections.RESUMÉUne étude randomisée à double insu, en contrôle parallèle avec placebo a permis d'évaluer la capacité de la Lidocaïne-Prilocaïne (crème EMLA® — mélange eutectique d'anesthésiques locaux) à soulager la douleur causée par les injections intramusculaires. On a appliqué la crème EMLA® ou un placebo sur le bras de 60 volontaires adultes avant de leur injecter un vaccin viral contre la grippe (Fluzone®). Vingt-neuf (29) sujets ont été traités avec la crème EMLA® et 31 avec le placebo. Tous ont reçu une application d'environ 2,5 g de crème sous un pansement occlusif pendant 60 à 90 minutes. Après l'élimination de la crème, on leur a injecté 0,5 mL de vaccin par voie intramusculaire au moyen d'une aiguille calibre 22 d'un pouce. Les sujets ont évalué la douleur causée par l’insertion de l'aiguille et par l'injection au moyen d'une échelle visuelle analogique. Comparativement au placebo, la crème EMLA® a atténué la douleur associée à l'insertion de l’aiguille (p &lt; 0.0002) et à l’injection (P = 0,0139). On a noté une corrélation significative entre les cotes se rapportant à la douleur provoquée par l'insertion de l'aiguille et celles relatives à la douleur causée par l'injection. L'apparition d'une légère pâleur fut une réaction cutanée courante à l'application de la crème EMLA®. Il est bien établi que cette dernière soulage la douleur due à la ponction veineuse, mais la présente étude est la premièree à démontrer son efficacité en cas d'injection intramusculaire

Long-term neurodevelopment of children exposed in utero to ciclosporin after maternal renal transplant

Background: Immunosuppressant therapy is essential in the prevention of organ transplant rejection. Objective: To evaluate the long-term neurodevelopmental outcomes of children following in utero ciclosporin (cyclosporine) exposure after maternal renal transplantation. Methods: A cohort study with matched controls using a prospectively collected database was conducted to assess neurocognitive and behavioral outcomes using standardized measures. Thirty-nine children exposed in utero to ciclosporin therapy following maternal renal transplantation were assessed (15 single pregnancies, 24 multiple pregnancies) and compared with 38 matched unexposed children. Intelligence, visuomotor abilities, and psychologic adjustment were measured using the Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R), the Beery Developmental Test of Visual-Motor Integration (VMI-4) and the Wide Range Assessment of Visual Motor Abilities (WRAVMA), and the Child Behavior Checklist (CBCL), respectively. Statistical analysis, including regression, was performed to determine the significant predictors for the main outcome, full-scale IQ (FIQ). Results: There were no significant differences in FIQ, verbal IQ (VIQ), performance IQ (PIQ) or behavioral outcomes between exposed and unexposed children or between single and multiple delivery groups. Thirty-three percent of exposed children were premature versus 0.5% in unexposed controls (p < 0.01). Prematurity was associated with lowbirthweight, high rates of perinatal complications, and instrumental deliveries. Relative to fullterm children, premature, low birthweight children in the ciclosporin-exposed group had significantly lower FIQ and VIQ scores (101.04 vs 111.31 [p = 0.008] and 102.31 vs 113.08 [p = 0.021], respectively). Maternal IQ and socioeconomic status were positive and significant predictors for childrens IQ (p < 0.001 and p = 0.03, respectively). Therewere no statistically significant differences in exposed childrens IQwho were andwere not breastfed. Conclusion: In this cohort, there was no association between in utero exposure to ciclosporin and long-term neurocognitive and behavioral development in children after maternal renal transplantation. Maternal IQ and socioeconomic status are positive predictors for childrens intelligence. However, maternal renal transplantation and associated co-morbidity is associated with higher rates of premature delivery and consequent poorer neurocognitive and behavioral outcomes. Proper management of maternal morbidity and improved obstetric care may improve the childs profile