Showing papers in "Journal de la thérapeutique des populations et de la pharamcologie clinique in 2011"

A systematic review of treatment of drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in children.

Abstract: Stevens-Johnson (SJS) and Toxic Epidermal Necrolysis (TEN) are two uncommon mucocutaneous diseases usually considered as severe drug reactions and are characterized by different grades of epidermal necrosis. Several treatment modalities have been proposed with variable results but the lack of controlled studies makes difficult to analyze them objectively especially in children. All publications describing management for SJS and TEN in children were searched in MEDLINE, EMBASE, and the Cochrane Library. Reports included were divided in two categories: A, studies with 5 or more patients and observational studies; and B, reports with less than 5 patients. A formal meta-analysis was not feasible. Description was made using central tendency measures. From 1389 references only 31 references with a total of 128 cases were included, 88 category A and 40 category B. The 4 main treatment modalities were: intravenous immunoglobulin (IVIG), steroids (prednisolone, methylprednisolone, dexamethasone), dressings with or without surgical debridement, and support treatment alone. Miscellaneous treatments: Of 12 patients, 3 received ulinastatin, 4 patients plasmapheresis, 2 patients IV pentoxifylline and the last three patients received different treatment each (cyclosporine, methylprednisone/G-CSF and methylprednisolone/IVIG). Patients receiving IVIG and steroids showed similar findings while patients treated with dressing and support treatment alone, reported both longer time to achieve remission and hospitalization stays and appear to be associated with more complications and deaths. There is scant quality literature about management of SJS and TEN in children. Steroids and IVIG seem to improve the outcome of SJS and TEN patients but results from different reports are variable. Patients treated only with care support seem to have higher morbidity and mortality. Further studies are necessary to define optimal management.

Language impairments in children with fetal alcohol spectrum disorders.

Abstract: BACKGROUND: Fetal Alcohol Spectrum Disorder (FASD) is associated with a range of disabilities, including physical, behavioural, and cognitive deficits. One specific area of concern in children with FASD is the use and development of speech and language. Language deficits in FASD have been linked to learning problems and social difficulties. OBJECTIVES: The current study sought to examine the language difficulties of children with FASD, and to identify areas of deficit that may be particularly pronounced among these children. METHODS: Fifty children, aged 5 to 13, (27 with FASD, 23 control children) were tested on the CREVT-2, the TOLD-P:3, and the TOLD-I:3. RESULTS: Children with FASD had significantly lower scores than control children on both receptive and expressive subtests of the CREVT-2. Younger children scored significantly lower than controls on the Relational Vocabulary and Sentence Imitation subtests of the TOLD-P:3, and older children were significantly delayed on the Word Ordering, Grammatic Comprehension, and Malapropisms subtests of the TOLD-I:3. CONCLUSIONS: This study identified several areas of marked difficulty in children with FASD, adding to the current understanding of language development in this population. The results have implications for tailoring early interventions, and for providing evidence-based support to children prenatally exposed to alcohol.

The Canadian guidelines and the interdisciplinary clinical capacity of Canada to diagnose fetal alcohol spectrum disorder.

Abstract: Background In 2005, the CMAJ published the Fetal alcohol spectrum disorder: Canadian guidelines for diagnosis. The intent of this publication was to encourage a more consistent interdisciplinary team approach and diagnostic procedure for FASD diagnoses. That same year, the Canada Northwest FASD Research Network (CanFASD Northwest) determined the locations and capacity for interdisciplinary FASD diagnosis across Canada. Six years later, we wondered how successfully these Guidelines had been in bringing consistency to FASD clinical work. Method All clinical programs in Canada that routinely performed FASD evaluations were identified through membership in either our Network Action Team on FASD Diagnosis, professional meetings, organizational memberships, websites, programs lists available from Provincial or Federal offices or by word of mouth. Surveys were sent to all of the programs identified. Results A total of 55 clinics had been identified in seven provinces and one territory in 2005 that did FASD multidisciplinary diagnostics. In 2011 only 44 clinics were identified in six provinces and one territory using the same methodology. Survey responses were completed by 89% of these 44 clinics identified in 2011. The Guidelines were well known to all programs and actively referred to by most. Only 46% of respondents had a full staff of professionals on site for diagnosis, however 90% did use the team approach in determining final FASD diagnosis, while 79% used the team to help in developing a treatment plan. Among the clinics reporting, 74% of them used the new diagnostic schema proposed in the Guidelines and another 12% report using both the Guidelines and another system for diagnosis. Interpretation The Guidelines have become well known to the medical community. They have contributed to increased consistency in approach and in diagnosis. The variations in clinical ability to fully staff themselves, and the 20% decline in clinic numbers suggest important funding gaps. Many provinces and territories still have no local interdisciplinary programs for FASD diagnosis, and the need across Canada is still many times greater than what is currently available.

Pharmacogenomics of serious adverse drug reactions in pediatric oncology

Abstract: Adverse drug reactions (ADRs) rank as one of the top ten leading causes of death and illness in the developed world. In cancer therapy, more patients are surviving cancer than ever before, but 40% of cancer survivors suffer life-threatening or permanently disabling severe ADRs and are left with long-term sequelae. ADRs are often more frequent and more severe in children, and the consequences for children who experience a severe ADR can be catastrophic. Pharmacogenomics has the potential to improve the safety of these drugs. This review highlights severe ADRs that can occur in cancer therapy that are more frequent and more severe in children, and the pharmacogenomics research that aims to understand, predict, and ultimately prevent these severe reactions.

Executive functioning and working memory deficits on the CANTAB among children with prenatal alcohol exposure.

Abstract: Background Children with prenatal alcohol exposure (PAE) and Fetal Alcohol Spectrum Disorders (FASD) display numerous neuropsychological impairments, including deficits on measures of executive functioning (EF) and working memory. Objectives The goal of this project was to examine whether children with PAE and FASD demonstrate EF and working memory deficits on the CANTAB ® (a computerized neuropsychological test).

Improving pediatric drug safety: need for more efficient clinical translation of pharmacovigilance knowledge.

Abstract: There is an urgency to improve the evaluation of pediatric drug safety in the pre-market and post-market phases of drug evaluation. The need to improve pharmacovigilance methods concerns not only new drugs but also existing drugs that have been used for many years in an off-label manner in children. Effective methods for early detection of adverse drug reactions (ADRs) and drug safety epidemiologic studies are a pressing need in pediatrics. Moreover, the nature and severity of an ADR as well as the extent to which the suspected drug is being used, will determine how quickly the information about risk needs to be made available to users and what would be the most appropriate method of communication. Based on our experience through the Genotype-specific Approaches to Therapy in Children study, an active ADR surveillance network of pediatric hospitals across Canada, we present five strategic elements that should be included in pharmacovigilance initiatives in pediatrics: active ADR surveillance; drug or ADR targeted pharmacovigilance; trained surveillance clinicians; case-control methodology and standardized procedures for recognition; reporting and evaluating drug-induced harm. In addition, linking pharmacovigilance with pharmacogenomics to find drug safety solutions is presented as a promising strategy for knowledge generation. Finally, we discuss the importance of an efficient translation of the pharmacovigilance knowledge into clinical practice to achieve safer drug therapy in children.

A differential approach for examining the behavioural phenotype of fetal alcohol spectrum disorders.

Abstract: Background In 2006, Nash and colleagues published results suggesting that individual items from the Child Behavior Checklist (CBCL) could be used as a screening tool that was highly sensitive in differentiating children with FASD from controls and children with Attention Deficit Hyperactivity Disorder (ADHD). Since many of the items referred to features of Oppositional Defiant/Conduct Disorder (ODD/CD), it was not clear whether the items reflected comorbidity with ODD/CD, or were unique to children with FASD. Objectives The present study sought to replicate the results of our 2006 paper using a new and larger sample, which also includes a group of children diagnosed with ODD/CD. Methods Retrospective psychological chart review was conducted on 56 children with FASD, 50 with ADHD, 60 with ODD/CD, and 50 normal control (NC) children. Receiver operating characteristic curve (ROC) analysis of CBCL items discriminating FASD from NC was used to compare FASD to the ADHD and ODD/CD groups. Results ROC analyses showed scores of a) 3 or higher on 10 items differentiated FASD from NC with a sensitivity of 98%, specificity of 42% and b) 2 or higher on 5 items reflecting oppositional behaviors differentiated FASD from ADHD with a sensitivity of 89% and specificity of 42%. Conclusion Our findings partially replicate the results of our 2006 study and additionally elucidate the behavioural differences between children with FASD and those with ODD/CD. The proposed screening tool is currently the only tool available that is empirically derived and able to differentiate children with FASD from children with clinically similar profiles.

Pharmacokinetics in pregnancy; clinical significance.

Abstract: In pharmacokinetics drug absorption, distribution, clearance, and bioequivalence are usually considered, but during pregnancy the most important variable is adherence or compliance. Pharmacokinetic changes during pregnancy that may lead to changes in maternal drug use are described through presentation of cases highlighting the relevance of these changes. Non-invasive methods of pharmacokinetic analysis, such as determining concentrations of drug in hair, are now being tested and used.Pharmacokinetics are important, but one needs to consider the entire pregnant state and its circumstances when treating women. One treats people, not a "volume of distribution" or a drug level. Therapy should be individualized as much as possible, addressing kinetic changes in the context of dynamic alterations and the effects of underlying medical conditions. To ensure that women are not orphaned from advances in drug therapy, much more research is needed into the determinants of pharmacokinetic and pharmacodynamic changes in pregnancy.

Cutaneous adverse drug reactions in children: an analysis of reports from the Canadian Pharmacogenomics Network for Drug Safety (CPNDS).

Abstract: Cutaneous adverse drug reactions (CADRs) are the most prevalent adverse drug reactions (ADRs) in hospitalized children, with an estimated rate of 2-3%. The Canadian Pharmacogenomics Network for Drug Safety (CPNDS) is a pan-Canadian active surveillance network identifying genomic biomarkers of risk for serious ADRs. The purpose of this paper is to describe the characteristics of paediatric CADR cases reported to the CPNDS from February 2005 to December 2008. The CPNDS database was mined and details of CADRs and key clinical data from cases were extracted. Reports were individually analyzed and classified in two main groups: severe and non-severe CADRs, with subcategories. In total, 326 CADR cases were included in the study; 214 (65.6%) severe and 112 (34.4%) non-severe CADRs. Overall L-asparaginase (n=56, 16%), amoxicillin (n=29, 8.3%), cotrimoxazole (n=25, 7.2%), carbamazepine (n=17, 4.9%) and lamotrigine (n=13, 3.7%) accounted for 40% of all suspected medications. We have demonstrated the ability to comprehensively collect clinical data on a wide range of severe and non-severe CADRs to drugs commonly used in the care of children. Our study provides additional real world evidence to promote the proactive detection, collection, reporting and assessment of CADRs in children.

A need for closer examination of FASD by the criminal justice system: has the call been answered?

Abstract: Individuals with FASD exhibit deficits in many domains that can include memory, learning, behavioural inhibition, executive functioning, interpersonal skills, and language. These deficits have serious implications for affected persons when they become engaged in the legal system. In 2004, Moore and Green reviewed case law and psychological literature which suggested that FASD-related deficits placed affected individuals at a significant disadvantage in the justice system. According to them, this disadvantage stemmed from the limited awareness and knowledge of FASD demonstrated by key players in the justice system, as well as the scarcity of effective interventions in place to rehabilitate affected defendants. The aim of the current paper is to assess the extent to which awareness of FASD-related issues in the Canadian justice system has advanced since the publication of Moore and Green’s conclusions. First, the deficits associated with FASD and their implications for the justice system are described. Next, recent case law and psychological evidence are reviewed as we consider issues of witness reliability and false confessions. The significance of FASD for sentencing, fitness to stand trial, and the Not Criminally Responsible by Reason of Mental Disorder defence are also briefly discussed. Finally, emerging system wide responses to FASD-related issues are presented. Overall, it appears that the call for closer examination of FASD by the justice system has been answered, but a need for increased education and awareness remains.

Teratogenic determinants of first-trimester exposure to antiepileptic medications.

Abstract: Objective To investigate the potential impact of exposure to anti epileptic medications during the first-trimester of pregnancy on major malformations. Study Design A retrospective cohort study comparing all pregnancies of women with and without exposure to antiepileptic medications during pregnancy was performed. A computerized database of medications dispensed from 1998 to 2008 to all women registered in the "Clalit" health maintenance organization, was linked with computerized and non computerized databases containing maternal and infant hospitalization records from the district hospital. Exposed women were further analyzed by mono and poly- antiepileptic therapy during pregnancy. Stratified analyses, using multiple logistic regression models were performed to control for confounders. Results During the study period 99,724 deliveries and 1012 pregnancy terminations occurred; of those, 421 (0.42%) were exposed to one or more antiepileptic medications during the first trimester. A higher rate of major congenital malformations was detected among women who were exposed, as compared to those unexposed to antiepileptic medications during the first trimester (10.0% vs. 7.0%; P=0.02). The association remained significant after adjusting for maternal age, ethnicity, smoking, diabetes and parity (adjusted OR= 1.50; 95% CI 1.06-2.12; p=0.02). Specifically, the risk was significant for antiepileptic anti folate drugs (n=210; adjusted OR= 1.95; 95% CI 1.25-3.03; P=0.003). Poly-antiepileptic therapy was significantly associated with major congenital malformations (26.5% vs. 5.7%, P<0.001). Using a multiple logistic regression model, controlling for ethnicity, diabetes, smoking, maternal age and parity, poly-antiepileptic therapy was an independent risk factor for major congenital malformations (adjusted OR= 7.98; 95% CI 3.4-18.7; P<0.001), while mono-therapy lost its independent association with major congenital malformations (adjusted OR= 1.23; 95% CI 0.8-1.8; P=0.28). Conclusion First-trimester exposure to antiepileptic medications is an independent risk factor for major congenital malformations. The risk is significantly higher for anti folate antiepileptic drugs and for poly-antiepileptic therapy.

Feeling different: the experience of living with fetal alcohol spectrum disorder.

Abstract: Background In Canada the incidences of Fetal Alcohol Spectrum Disorder (FASD) is estimated to be in 1 in 100 live births Caused by prenatal exposure to alcohol, the disorder is the leading cause of developmental and cognitive disabilities among Canadian children and its effects are life lasting. No research has attempted to describe the experience of living with FASD from the perspective of Canadian children. Purpose The main purpose of this study was to describe the children's experience of living with FASD. Methods A qualitative method was used to examine the children's experiences. Twenty-two (22) children, aged 6 to 18 years, living in urban and rural communities across Canada participated in an unstructured in-depth interview. Data was analysed using Colaizzi's qualitative method. Results For all children in this study, living day-to-day with FASD meant feeling different. Within this construct knowing the disability; feeling alone-feeling supported, and overcoming the disability were dominant themes which emerged. Conclusion

Perpetuating fears: bias against the null hypothesis in fetal safety of drugs as expressed in scientific citations.

Abstract: Background Bias against negative studies (i.e., those showing no issues with fetal safety of drugs) may cause distorted interpretation with apparently safe drugs being labeled as teratogenic, causing women to terminate pregnancy or not to treat serious medical conditions. Objective To investigate whether “positive” studies, claiming teratogenic effects of drugs, which were later shown to be safe, have been cited more often than “negative” studies on the same topic. Methods We reviewed published studies on the fetal safety of 6 drugs, which were the focus of appreciable controversy over the last 5 decades (oral contraceptives, bendectin  , benzodiazepines, paroxetine, ACE inhibitors and statins). While initial highly publicized papers claimed teratogenic effects, these were subsequently contradicted by large numbers of “negative” studies. We compared medical citation patterns of the “positive” vs. “negative” papers related to these 6 drugs. Results “Positive” papers were 70% more likely to be cited than “negative” articles (median 39 vs. 23, p=0.04). In multivariate linear regression, “positivity” of results (p=0.04), the number of years since publication (p=0.01) and journal citation impact (p<0.001) all independently predicted the total number of medical citations. Conclusions We documented bias against the null hypothesis in medical citations of fetal drug safety. Acknowledging this source of bias is critical in trying to avert the distortion of the medical knowledge created by it.

Severe bullous hypersensitivity reactions after exposure to carbamazepine in a Han-Chinese child with a positive HLA-B*1502 and negative in vitro toxicity assays: evidence for different pathophysiological mechanisms.

Abstract: BACKGROUND Drug hypersensitivity syndrome (DHS) can present in several clinical forms ranging from simple maculopapular skin rash to severe bullous reactions and multi-system dysfunction. Genetic analysis of DHS patients has revealed a striking association between carbamazepine (CBZ)-induced severe bullous reactions, such as Steven-Johnson Syndrome, and toxic epidermal necrolysis in individuals from Southeast Asia who carry a specific HLA allele (HLA-B*1502). This ethnic-specific relationship with a disease phenotype has raised the question of the commonality of the pathogenesis mechanisms of these diseases. The aim of this study was to investigate the genetic and metabolic bases of DHS development to help predict patient susceptibility. METHOD A case of carbamazepine-induced Steven-Johnson Syndrome reaction in a HLA-B*1502 positive child of Han Chinese origin, a carbamazepine-induced DHS case in a Caucasian patient and 3 healthy controls were investigated. We performed two types of in vitro toxicity assay, the lymphocyte toxicity assay (LTA) and the novel in vitro platelet toxicity assay (iPTA) on cells taken from the Chinese child 3 and 9 months after recovery from the reaction and from two healthy volunteers. We also tested the Caucasian patient, who developed CBZ-induced DHS, 3 months after the reaction. RESULTS Both LTA and iPTA tests were negative 3 and 9 months after the reaction on samples from the Chinese child whereas the tests were positive in the Caucasian patient. CONCLUSION These results strongly suggest more than one mechanistic pathway for different CBZ-induced hypersensitivity reactions in patients with different ethnic backgrounds.

Outcomes of infants exposed to multiple antidepressants during pregnancy: results of a cohort study.

Abstract: Background A single study has been published documenting an increased risk for adverse pregnancy outcomes following use of more than one antidepressant during pregnancy. Objective To examine whether multiple antidepressant use is associated with increased rates of major malformations, spontaneous abortions (SA), therapeutic abortions (TA), stillbirths, preterm birth, low birth weight, small for gestational age (SGA) and admission to the neonatal intensive care unit (NICU). Methods Information from the Motherisk Program’s prospectively collected database of 1243 women with gestational exposure to antidepressants. We compared pregnancy outcomes of 89 women exposed to >1 antidepressants, 89 taking one antidepressant, and 89 women not exposed to antidepressants (n= 267). Women were matched for maternal age, smoking and alcohol use. Groups were compared using odds ratios and ANOVA. Results 11/89 (12%) took 3 and 78 (88%) took 2 antidepressants. There were no statistically significant differences in any of the outcomes analyzed among the 3 groups except for a lower mean gestational age at birth in the multi-antidepressant group (0.9 week, P=0.036). There were 9 admissions to NICU from the antidepressant groups and 3 from the non-exposed group; but this did not reach statistical significance. Conclusions There is a small risk of preterm delivery that is associated with exposure to antidepressant therapy, although the clinical relevance remains to be determined.

Alcohol consumption during pregnancy among women in Israel.

Abstract: BACKGROUND Fetal alcohol spectrum disorder (FASD) is a range of disabilities caused by gestational exposure of the fetus to alcohol. Alcohol consumption in Israel has increased dramatically in the last decades. Our previous study revealed limited knowledge among Israeli medical professionals of the risks and potential long-term effects of FASD. OBJECTIVES To evaluate the awareness and knowledge of women regarding the current recommendations on alcohol consumption during pregnancy, evaluate how many of the women received information regarding alcohol consumption during pregnancy from medical professionals, and their personal drinking habits during pregnancy. METHODS A cross-sectional sample of new mothers in 3 large hospitals in Israel were asked to complete an ad hoc questionnaire on aspects of alcohol consumption during pregnancy. RESULTS A total of 3815 women of mean age 30.4 years participated in the study; 82% were Jewish. Alcohol consumption during pregnancy was reported by 14.1%, including more than 17% of the Jewish women, 11.1% of the Christian women, and none of the Muslim women. Rates were higher among nonsecular and younger women and first-time mothers. 71.6% of the sample claimed that women should not drink alcohol at all during pregnancy, and 21.4% thought that it was permissible if limited to 2 drinks per week. Seventy-five percent had received no formal information from medical professionals regarding alcohol consumption during pregnancy. CONCLUSIONS Alcohol consumption is frequent among pregnant women in Israel, especially young secular Jewish women with first pregnancies. Improved educational programs on the dangers of FASD are needed for both professionals and the general public.

The effect of ascertainment bias in evaluating gestational antidepressant exposure.

Abstract: Several administrative database studies have reported on a positive association between first trimester exposure to paroxetine and ventricular septal defects (VSD). Using multiple source data we have shown that depressed women utilize significantly more health care resources, including ultrasound, echocardiogram and emergency room visits for their babies. Hence, there is much higher chance to identify VSD in their babies than among healthy controls. Moreover, paroxetine has been used more specifically than other SSRI for anxiety, further increasing the chance of ascertainment bias.

Prediction of placental drug transfer using the human placental perfusion model.

Abstract: The placental perfusion model and a newly developed complementary computational model are reviewed. Examples are provided, where the computational model can be applied to adjust drug pharmacokinetic data obtained from the perfusion model to more closely resemble the in vivo placental transfer of therapeutic agents. After modelling the data, placental perfusion experiments can be used to predict placental drug transfer and can be useful for clinical assessment of the risks and benefits of drug therapy in pregnancy.

Reinforcement learning in children with FASD.

Abstract: BACKGROUND It is often said that children with Fetal Alcohol Spectrum Disorder (FASD) have difficulty learning from reinforcement. However, there is little empirical evidence to support or deny this claim. OBJECTIVES To examine reinforcement learning in children with FASD, specifically: (1) the rate of learning from reinforcement; and (2) the impact of concreteness of the reinforcer. METHODS Participants included 18 children with FASD (IQ ≥ 70), ages 11-17, and 18 age- and sex-matched controls. Participants each completed a novel reinforcement learning discrimination task that involved visual probabilistic learning (70% contingent feedback). The task was completed twice, once with tokens, and once with points (counterbalanced). RESULTS The control group demonstrated significantly stronger overall reinforcement learning, although rates of improvement and effect of concreteness of the reinforcer (tokens vs. points) were not different between groups. The FASD group's responses were more likely to be guided by the most recent information, rather than based on integration of reward status over multiple trials. CONCLUSIONS Reinforcement learning does not appear to occur in a functionally different manner in children with FASD, but does take longer, and is more impacted by recent reward than an integration of overall reinforcement information. Children with FASD without an intellectual disability may be able to learn from reinforcement given sufficient consistent repetition. However, other failures associated with learning difficulties such as the complexity of the material, transfer of learning, or impulsivity were not addressed in this study.

Safety and efficacy of drugs in pregnancy.

Abstract: Although most drugs are used to treat chronic or pregnancy-induced conditions during pregnancy and lactation, very few are studied in pregnant or breastfeeding women. The information we have on drugs taken during pregnancy and lactation is usually obtained after market approval through published case reports or case series and from pregnancy exposure or retrospective birth defect registries. Furthermore, generic drugs approved for use in this vulnerable population may be approved based on results from a male trial population. This disregards the changes that can occur during pregnancy which can affect the pharmacokinetics of drugs. In an effort to improve the information provided to prescribers, in 2008 the United States Food and Drug Administration proposed a change in product labelling where information from pregnancy exposure registries would be required. As of 2009, European Medicines Agency requires additional statements on use during pregnancy within drug labelling information. In Canada, it is anticipated that the efficacy and safety of drugs in pregnancy will be included under the Drug Safety and Effectiveness Network initiative, and that this will offer a unified approach for such assessments. Pregmedic, a non-profit organization for the advancement of safe and effective use of drugs in pregnancy, has presented a number of proposals and draft guidelines to Health Canada on the inclusion of pregnant women in pharmacokinetic studies and the establishment of registries for women who take drugs during pregnancy. Pregmedic advocates for ensuring that drugs indicated for women are studied in women.

Anorectal symptom management in pregnancy: development of a severity scale.

Abstract: BACKGROUND Anorectal conditions are very common and under-diagnosed in pregnancy, with severe implications on quality of life. Presently no validated scale is available to quantify the severity of symptoms and their response to therapy. The objective of this study was to create and validate a scale for symptoms associated with anal/rectal conditions. METHODS Patients attending a colorectal clinic were assessed twice, for severity of anorectal symptoms; once by the new questionnaire-ColoRectal Evaluation of Clinical Therapeutics Scale (CORECTS)--followed by a direct examination by a proctologist. Linear regression analysis was performed to correlate the clinician's and CORECTS scores. In parallel, 209 pregnant women with hemorrhoids were assessed using CORECTS before and after treatment with Proctofoam-HC®. We evaluated whether scores' improvement corresponded to changes in quality of life. RESULTS There was a significant concordance between each component of the CORECTS scale as well as impact on quality of life, with direct clinical examination of a proctologist. Significant reduction in symptoms, as measured by the scale following use of Proctofoam-HC® highly correlated with changes in quality of life before and after treatment. CONCLUSION CORECTS is a reliable tool in capturing the severity of symptoms associated with colorectal symptoms in pregnancy and is highly sensitive in detecting changes in symptom severity following treatment.

Teratogen information service for pharmacists: a pilot study

Abstract: We report on the first Helpline for pharmacists dealing with the safety of medications in pregnancy and during breastfeeding. Pharmacists from all parts of Canada participated in this pilot, receiving guidance in approximately 90% of cases. There were 472 inquiries relating to 598 products with regards to safety in pregnancy and 197 calls relating to 249 products regarding exposure in breastfeeding. All callers who were surveyed found the service helpful in counseling both patients and physicians.

Legal and ethical considerations in meconium testing for fetal exposure to alcohol

Abstract: In Canadian law, pregnant women are held to owe no enforceable duties of care to their children before birth, but healthcare providers may be held accountable once children are born alive for causing injuries prenatally. When children are born in hospitals, recovered meconium may be tested without consent, but there may be an ethical duty to inform mothers. Meconium belongs to the newborns, and mothers may be required to make decisions about its use in their children’s best interests. Proposals to test meconium from particular populations raise concern about stigmatization.

The communication of pharmacogenetic research results: participants weigh in on their informational needs in a pilot study.

Abstract: In this brief investigation, the informational needs of research participants (n = 62; mothers who had breastfed, taken codeine, and participated in a pharmacogenetic study) were probed during a counselling session in which they received their CYP2D6 pharmacogenetic research results and overall study results In addition to the standard information, developed by a multidisciplinary team and provided to the participants, 38% of individuals had further questions related to potential adverse effects in babies, future codeine or medication use, heredity, and consequences for policies and programmes The diversity and complexity of the questions raised support the need to communicate the results in the context of personalized genetic counselling information sessions

Reporting on the prevalence of drug and alternative health product use for mental health reasons: results from a national population survey.

Abstract: BACKGROUND Concomitant use of alternative health products with commonly prescribed medications has been associated with elevated risks of adverse effects. OBJECTIVE The aim of this study was to determine the prevalence and determinants of the use of alternative health products and psychotropic drugs in the same year for mental health reasons and to examine this for specific psychiatric and physical conditions. METHODS This study used data from the Canadian Community Health Survey: Mental Health and Well-Being cycle 1.2 carried out by Statistics Canada in 2002 on 36,984 Canadians. Multivariate analyses were carried out to identify determinants of health product use. RESULTS Overall, 13% of Canadians reported the use of alternative health products. Among respondents with a psychiatric diagnosis, heart disease, high blood pressure and diabetes the rate was 20.0%, 12.0%, 12.6% and 9.4% respectively. Use of alternative health products and psychotropic drugs within the same year was reported by 21.3%. Determinants of alternative health product use included older age, female sex, higher education, and mental disorder, the use of cardiovascular drugs, consulting a health care provider for mental health reasons and reporting an unmet mental health need. People with diabetes were less likely to be users. CONCLUSIONS Concomitant use of alternative health products and psychotropic drugs for mental health reasons are prevalent. This increases the risk for potential drug-herb interactions. Health professionals need to be aware of patient alternative health product use, especially in the presence of co-morbid mental and physical conditions. Public health campaigns aimed towards increasing awareness and education may incite discussions between health professionals and patients on the risks and benefits of these products.

Low systemic ganciclovir exposure and preemptive treatment failure of cytomegalovirus reactivation in a transplanted child.

Abstract: Prevention of cytomegalovirus (CMV) disease with ganciclovir has led to decrease morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. In the present report, we describe a case of ganciclovir treatment failure in a HSCT child who presented a refractory CMV infection despite harbouring a susceptible strain. The failure was partly attributed to sub-therapeutic plasma ganciclovir levels. Our experience emphasizes the importance of drug monitoring in immunocompromised patients.

Meconium testing for fatty acid ethyl esters: a 2011 status report.

Abstract: The Canadian Association of Pediatric Health Centres, working in partnership with the Public Health Agency of Canada has recently published a toolkit to guide screening for identification of risk of FAS/FASD. One of the tools highlighted is the testing of meconium for fatty acid ethyl esters to identify high risk pregnancies and to support associated prevention programs. This paper describes the conclusions of a workshop held in Prince Edward Island in September 2011 to discuss key issues surrounding the wider deployment of meconium testing for assessment of population risk for FAS/FASD.

A survey of Canadian medical student attitudes towards the ethics of pediatric clinical trials: are they different from Canadian and British health care professionals?

Abstract: BACKGROUND Due to ethical concerns and constraints inherent to research in children, the conduct of clinical trials in children has often been difficult. The views of medical professionals and trainees towards conducting clinical trials in children have been largely unexplored and are potentially important towards working to increase the number of appropriate trials conducted in children. OBJECTIVE To explore the views of Canadian medical school trainees towards paediatric clinical trials and to compare these views with that of an earlier pilot study conducted amongst Canadian and British health care professionals. METHODS Participants were given a questionnaire which consisted of direct questions as well as scenarios with ethical dilemmas. Responders were asked to state whether they would enter children in the trial documented in the scenario and to justify their reasons. RESULTS 89 questionnaires were collected (74% response rate). 42% had formal teaching regarding paediatric ethical dilemmas but only 2% had formal teaching on pharmaceutical testing in children. The students were divided on whether children should only participate in trials where they receive direct benefit. Most students (85%; 95% CI: 77% to 91%) were comfortable with non-inferiority trials even with post-hoc consent. Only a third (33%; 95% CI: 24% to 43%) agreed with the use of placebo in an analgesia trial. CONCLUSION Teaching on the ethics of paediatric clinical trials still appears to be lacking amongst medical trainees. However, there does seem to be increased willingness on the part of trainees compared to practicing medical professionals in enrolling children in clinical trials.