Showing papers in "Journal de la thérapeutique des populations et de la pharamcologie clinique in 2010"

Role of central nervous system insulin resistance in fetal alcohol spectrum disorders

Abstract: Fetal alcohol spectrum disorder (FASD) is the most common preventable cause of mental retardation in the USA Ethanol impairs neuronal survival and function by two major mechanisms: 1) it inhibits insulin signaling required for viability, metabolism, synapse formation, and acetylcholine production; and 2) it functions as a neurotoxicant, causing oxidative stress, DNA damage and mitochondrial dysfunction Ethanol inhibition of insulin signaling is mediated at the insulin receptor (IR) level and caused by both impaired receptor binding and increased activation of phosphatases that reverse IR tyrosine kinase activity As a result, insulin activation of PI3K-Akt, which mediates neuronal survival, motility, energy metabolism, and plasticity, is impaired The neurotoxicant effects of ethanol promote DNA damage, which could contribute to mitochondrial dysfunction and oxidative stress Therefore, chronic in utero ethanol exposure produces a dual state of CNS insulin resistance and oxidative stress, which we postulate plays a major role in ethanol neurobehavioral teratogenesis We propose that many of the prominent adverse effects of chronic prenatal exposure to ethanol on CNS development and function may be prevented or reduced by treatment with peroxisome-proliferated activated receptor (PPAR) agonists which enhance insulin sensitivity by increasing expression and function of insulin-responsive genes, and reducing cellular oxidative stress

Depression and anxiety in pregnancy.

Abstract: The risk of depression in women is greatest during the child-bearing years. Considering that about 50% of pregnancies are unplanned, women may become pregnant while on antidepressants, may have their depression or anxiety relapse during pregnancy or postpartum, or may be unwell and untreated before and during pregnancy and the postpartum period. The impact of the symptoms of depression and anxiety can cause risk to the mother and also have a negative effect on child development. This presentation is intended to assist in understanding the impact of untreated maternal depression and anxiety on fetus, neonate, child and mother; to review the effects of fetal exposure to psychotropic medications (antidepressants); and to summarize general management of perinatal mood/anxiety disorders.

Drinking alcohol during pregnancy: evidence from Canadian Community Health Survey 2007/2008.

Abstract: Background Dinking alcohol during pregnancy may cause many health problems for the child, one of which is fetal alcohol spectrum disorder (FASD). Since FASD is incurable, actions meant to prevent the occurrence of the disability by targeting drinking women become more important. Epidemiological data on drinking among pregnant women, including prevalence and determinants/risk factors, is essential for designing and evaluating prevention programs. Objectives To estimate the prevalence of drinking alcohol during pregnancy and examine the determinants of this behaviour. Methods Using the 2007/8 Canadian Community Health Survey (CCHS) data, we estimated the weighted prevalence of women who drank alcohol during their last pregnancy by provinces. We used a weighted logistic regression to examine associations between drinking patterns, substance abuse behaviours, healthrelated and socio-demographic characteristics of the women, and the outcome variable. Results There were two main findings of this study. One was that the 2007/8 prevalence of drinking alcohol during pregnancy in ON, BC, and Canada was estimated at 5.4%, 7.2%, and 5.8%, respectively. The other was that the use of general practitioners (GP) or family physicians (FP) associated with a decreased risk of drinking alcohol during pregnancy. Discussion The results suggest that interventions that involve GP or FP and that increase the use of GP or FP by pregnant women can be effective in reducing drinking alcohol during pregnancy.

Herbal medicines and pregnancy.

Abstract: The prevalence of herbal medicine use during pregnancy is between 7% and 55%, depending upon the geographic area surveyed and the surveyed group's socio-cultural aspects and ethnicity. Why are women taking natural health products (NHPs) in pregnancy? Women who learn they are pregnant are concerned about the safety of their fetus and may turn to NHPs rather than prescription medication. Use of NHPs in pregnancy is an area where more research is needed. The importance of knowing about these products is to understand their potential dangers in women of childbearing age, particularly when it is known that they are trying to conceive. Information on select NHPs is provided in this presentation.

A systematic review of medication safety outcomes related to drug interaction software.

Abstract: Background Adverse drug events (ADEs) represent an important problem for hospital and primary care. Software that detects potential adverse drug interactions has been widely implemented in an effort to reduce the rate of ADEs. However, the impact of drug interaction detection software (DIS) on patient safety outcomes remains unknown. Objectives To systematically review the literature on DIS in preventing adverse drug events and determine the effectiveness and cost-effectiveness of DIS. Methods A literature search of MEDLINE, EMBASE, CINAHL, IPA and Healthstar, using terms “Computer, Software or Decision Support” combined with “Drug Interactions, Drug Errors or Drug Monitoring” sought English language, post-1990 prospective studies that examined drug interaction (drug-drug) software as an intervention and adverse drug interactions as an outcome. Relevant studies were analyzed using a Bayesian meta-analysis approach. Results Of 5848 citations, only four studies met our inclusion criteria. Most of the excluded studies were not prospective or measured only prescriber attitudes, implementation success or changes in workflow. No study examined the impact of drug interaction software exclusively, rather as a component of decision support software. A Bayesian meta-analysis of these studies showed no significant difference in event rate between intervention and control groups (relative risk 0.66, 95% CI 0.33 to 1.18). The posterior median Isquared was 52%.

Investigating the effects of low to moderate levels of prenatal alcohol exposure on child behaviour: a critical review.

Abstract: Conflicting findings exist regarding the risks of low to moderate levels of alcohol use during pregnancy. A recent study from Australia has suggested that mild gestational drinking is not associated with adverse fetal effects, and may even be associated with favorable outcomes as compared to "no drinking".The study may lead women to continue consuming alcohol throughout pregnancy, despite methodological limitations that render its conclusions uncertain. This review discusses the challenges of assessing long-term effects of moderate drinking during pregnancy. Recommendations are provided for researchers investigating the effects of prenatal alcohol consumption on subsequent developmental outcomes in children.

Toward improved pregnancy labelling.

Abstract: Information about the use of a medication in pregnancy is part of overall drug labelling as prepared by the pharmaceutical company and approved by the regulators. It is aimed at assisting clinicians in prescribing, however, very few drugs are labelled for specific indications in pregnancy, since there is rarely information about the use of a drug in this condition. Recently the FDA has drafted new guidelines for the labeling of drugs in pregnancy and breastfeeding, to replace the A,B,C,D,X system that was used for more than 30 years. Here we document the use of the new system through 3 different medications; each representing a different clinical situation in pregnancy- acute infection, chronic pain, and drug use during labor. Advantages and challenges in the new system are being highlighted.

Training needs of healthcare providers related to Centers for Disease Control and Prevention core competencies for fetal alcohol spectrum disorders.

Abstract: Background Fetal alcohol spectrum disorders (FASDs) are birth defects directly linked to consumption of alcohol during pregnancy and hence completely preventable. Many health and allied health professionals are in prime positions for primary prevention of FASDs through work with women of childbearing age and secondary prevention through work with affected individuals whose lives can be greatly improved via tailored intervention. Objectives To develop educational guidelines for FASD prevention. Methods Interviews were conducted with 26 individuals representing eight health or allied health professions. Participants were asked about professional groups with which they had sufficient experience to describe FASD-related competencies and educational needs for the given group(s). For each group, participants were asked for their perceptions of group members’ FASD awareness, knowledge, and skills application as related to the seven core competencies for FASD practice developed by the Centers for Disease Control and Prevention (CDC). Results Findings revealed that competence, especially when viewed separately in terms of knowledge versus capacity for application of information, in the area of FASDs is unevenly distributed among and throughout healthcare provider groups. Conclusion Based on this information, recommendations are offered for optimal health and allied health education efforts to prevent and treat FASDs, framed along FASD core competencies recommended by the CDC.

Cholinesterase inhibitors and the risk of pulmonary disorders in hospitalized dementia patients

Abstract: Objective To evaluate whether Cholinesterase inhibitors (ChEI) are associated with an increased risk of pulmonary disorders (PD) in hospitalized dementia patients. Methods We conducted an observational cross-sectional study by examining the medical records of all the dementia patients hospitalized in the acute geriatric ward at the Bertinot Juel Hospital between January 1, 2005 and June 30, 2009. First, we examined whether there were any differences between the patients receiving ChEIs and those who were not. Second, we measured whether the patients had any type of PD outcome, including pneumonia, persistent cough, bronchitis, and asthma. Finally, we studied the association between ChEIs and PD. We used a logistic regression analysis preceded by a univariate analysis to adjust for other variables, such as age, weight, severity of dementia, length of stay in hospital, and history of asthma. Results The study included 183 patients with a mean age of 83 years. There were 131 females and 52 males. There were 55 patients with PD, including 37 with pneumonia, 11 with bronchitis, 4 with asthma, 2 with acute respiratory failure and 1 with a persistent cough. In 38 of these cases, the PD was present before hospitalization and was considered the cause of hospitalization. In 17 cases, the PD was not present at admission but occurred during hospitalization. Only ChEI treatment and age (> 80 years) were associated with an increased risk of pulmonary disorders. The adjusted relative risk was 1.98 [1.21, 3.23] for ChEI and 1.30 [1.10, 1.54] for age. Conclusion When prescribing ChEIs, physicians should be aware about the risk of PD. As well, withdrawing ChEIs in patients who present repeated PD should be discussed. Prospective studies need to be conducted to confirm our findings.

Medication Exposure in Pregnancy Risk Evaluation Program (MEPREP).

Abstract: Knowledge about safe medication use during pregnancy is limited, yet about two of every three women take at least one prescription medication during pregnancy, furthermore, there is a lack of rigorous studies evaluating birth outcomes associated with in utero exposure to medications. The Medication Exposure in Pregnancy Risk Evaluation Program (MEPREP) is intended to provide a mechanism for collaborative pharmacoepidemiological research to address the safety of pharmaceutical product exposure during pregnancy, through the development of standardized data requirements and of the necessary data linkages of mother-infant pairs to conduct multi-site investigations. This presentation will describe the program, the types of data collected, and progress to date. The current MEPREP population includes female health plan members of 11 distinct health management entities within three research centres who have delivered an infant between January 1, 2001 and December 31, 2007, along with the administrative and birth certificate data on over one million children linked to mothers. There is information on all the medications those mothers took, as well as most of the outcomes of the babies. One of the benefits of this dataset is the information that could be investigated, such as birth weight, fetal growth, congenital anomalies, perinatal conditions, etc., against various demographics of the women in the dataset. The population size within the dataset suggests that various parameters could be studied with at least a modest degree of power.

The motherisk alcohol and substance use helpline: 10 years of experience and counting

Abstract: The Motherisk Alcohol and Substance Use Helpline at The Hospital for Sick Children in Toronto, Canada, is a unique telephone service providing evidence-based information on the negative effects associated with alcohol and substance use in pregnancy and lactation. We describe the characteristics of the service, the demographics of the callers, and the inquiries made during its first ten years of service. Since its inception in November 1998 until November 2008, almost 20,000 calls had been received with 60% of calls initiated by pregnant and breastfeeding women, the remainder from various health care providers. Most women exposed to alcohol and substances were of Caucasian descent (80%), employed (65%), and married (46%) with some level of post-secondary education (52%). The demographics of the callers deviate from the well-documented cohort of women at risk of engaging in alcohol and substance use in pregnancy and lactation, confirming that a selective group of women is more likely to use the services offered by the Motherisk program. Thus, further efforts are required to reach out to the subgroup of women at high risk of continuing their harmful behaviors during pregnancy and lactation.

Pandemic influenza H1N1 2009--the Canadian experience.

Abstract: The cornerstone of Canadian response to the pandemic H1N1 outbreak was the Canadian Pandemic Influenza Plan. The Plan was based on a moderate scenario, articulated around 7 pillars: surveillance, antiviral drugs, vaccines, public health measures, clinical care, communications, and research. This presentation provides an overview of Canada's response to pandemic H1N1. It presents the context (Who did what? How? …), what happened (focusing on pregnant women), addresses making decisions together, and includes some post-H1N1 reflections.

Drugs in pregnancy--the issues for 2010.

Abstract: A Motherisk symposium on establishing benchmarks for the evaluation of medications during pregnancy, was held on May 10, 2006, under the auspices of the Canadian Society of Pharmacology and Therapeutics. From that symposium came a consensus on the need for collection and analysis of data on fetal safety and ongoing post-marketing surveillance, which in turn led to the establishment of CaseMed-Pregnancy--the Canadian Alliance for Safe and Effective Medication During Pregnancy and Breastfeeding.

Oral dosing requirements for phenytoin in the first three months of life.

Abstract: Background Historically, physicians have been reluctant to maintain infants on phenytoin (PHT) following initial stabilization with intravenous loading doses, as therapeutic blood levels are difficult to achieve with conventional oral doses, and there is concern that high doses will result in toxicity. Objectives To determine the oral dose of PHT required to achieve therapeutic blood concentrations, without clinical toxicity, in the first weeks of life. Methods Eight infants with seizures were treated with phenytoin from 2 weeks to 3 months of age. Total and free phenytoin concentrations, and urine phenytoin metabolite (p-hydroxyphenytoin) were measured every 2 weeks. Parents were asked to note seizure frequency and complete a questionnaire about possible side effects every 2 weeks. Results No infants had seizures and no clinical side effects were noted. Doses required to achieve therapeutic serum concentrations ranged from 10-20mg/kg/day, considerably higher than doses required in adults. Free phenytoin levels were 8-13% of total serum concentrations, similar to ratios reported in adults. Conclusion To achieve therapeutic serum phenytoin levels in infants, doses of 10-20 mg/kg/day are required. These higher doses can be safely administered without clinical toxicity.

A multi-case report of acute renal failure in patients treated with Aggrenox.

Abstract: Background Aggrenox® is used in the secondary prevention of stroke. Acute renal failure, potentially associated with Aggrenox®, has been observed in several patients. Objective The objective of this study was to determine if Aggrenox® was associated with acute renal failure and to determine whether it was acetylsalicylic acid, dipyridamole or the combination that led to decline in renal function. Methods A case series of three patients suffering severe nausea, vomiting, diarrhea, renal dysfunction and clinical decline during Aggrenox® therapy was examined. Serum creatinine and Blood Urea Nitrogen (BUN) were measured to evaluate renal function. Results Analysis of this patient group revealed that Patient 1 experienced nausea, emesis, anorexia, diarrhea and significant clinical decline during treatment with Aggrenox®. Patients 2 and 3 also presented with complaints of nausea and emesis. Lab measurements along with clinical symptoms indicated that all three patients experienced acute renal failure, having increases in serum creatinine of 186%, 144% and 249%, respectively. Symptoms and lab work returned to baseline following discontinuation of Aggrenox®. Conclusion It is biologically plausible that Aggrenox® may contribute to renal dysfunction in patients under certain pathophysiological circumstances.