Showing papers by "Gideon Koren published in 2007"

Measurement of cortisol in human Hair as a biomarker of systemic exposure

Abstract: Purpose: Current methods for measuring long-term endogenous production of cortisol can be challenging due to the need to take multiple urine, saliva or serum samples. Hair grows approximately 1 centimeter per month, and hair analysis accurately reflects exposure to drug abuse and environmental toxins. Here we describe a new assay for measurement of cortisol in hair, and determined a reference range for non-obese subjects. Methods: For measurement of cortisol in hair we modified an immunoassay originally developed for measuring cortisol in saliva. We compared hair samples obtained from various parts of the head, and assessed the effect of hair dying. We analyzed hair samples from non-obese subjects, in whom we also obtained urine, saliva and blood samples for cortisol measurements. Results: The mean extraction recovery for hair cortisol standards of 100 ng/ml, 50 ng/ml and 2 ng/ml (n=6) was 87.9%, 88.9% and 87.4%, respectively. Hair cortisol levels were not affected by hair color or by dying hair samples after they were obtained. Cortisol levels were decreased in hair that was artificially colored before taking the sample. The coefficient of variation was high for cortisol levels in hair from different sections of the head (30.5 %), but was smaller when comparing between hair samples obtained from the vertex posterior (15.6%). The reference range for cortisol in hair was 17.7-153.2 pg/mg of hair (median 46.1 pg/mg). Hair cortisol levels correlated significantly with cortisol in 24-hour urine (r=0.33; P=0.041). Conclusion: The correlation of hair cortisol with 24-hour urine cortisol supports its relevance as biomarker for long-term exposure.

Pre-conceptional Vitamin/Folic Acid Supplementation 2007: The Use of Folic Acid in Combination With a Multivitamin Supplement for the Prevention of Neural Tube Defects and Other Congenital Anomalies

Abstract: Objective To provide information regarding the use of folic acid in combination with a multivitamin supplement for the prevention of neural tube defects and other congenital anomalies, so that physicians, midwives, nurses, and other health care workers can assist in the education of women in the pre-conception phase of their health care. Option Supplementation with folic acid and vitamins is problematic, since 50% of pregnancies are unplanned, and women's health status may not be optimal when they conceive. Outcomes Folic acid in combination with a multivitamin supplement has been associated with a decrease in specific birth defects. Evidence Medline, PubMed, and Cochrane Database were searched for relevant English language articles published between 1985 and 2007. The previous Society of Obstetricians and Gynaecologists of Canada (SOGC) Policy Statement of November 1993 and statements from the American College of Obstetrics and Gynecology and Canadian College of Medical Geneticists were also reviewed in developing this clinical practice guideline. Values The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Benefits, Harms, and Costs Promoting the use of folic acid and a multivitamin supplement among women of reproductive age will reduce the incidence of birth defects. The costs are those of daily vitamin supplementation and eating a healthy diet. Recommendations 1.Women in the reproductive age group should be advised about the benefits of folic acid in addition to a multivitamin supplement during wellness visits (birth control renewal, Pap testing, yearly examination) especially if pregnancy is contemplated. (III-A) 2.Women should be advised to maintain a healthy diet, as recommended in Eating Well With Canada's Food Guide (Health Canada). Foods containing excellent to good sources of folic acid are fortified grains, spinach, lentils, chick peas, asparagus, broccoli, peas, Brussels sprouts, corn, and oranges. However, it is unlikely that diet alone can provide levels similar to folate-multivitamin supplementation. (III-A) 3.Women taking a multivitamin containing folic acid should be advised not to take more than one daily dose of vitamin supplement, as indicated on the product label. (II-2-A) 4.Folic acid and multivitamin supplements should be widely available without financial or other barriers for women planning pregnancy to ensure the extra level of supplementation. (III-B) 5.Folic acid 5mg supplementation will not mask vitamin B12 deficiency (pernicious anemia), and investigations (examination or laboratory) are not required prior to initiating supplementation. (II-2-A) 6.The recommended strategy to prevent recurrence of a congenital anomaly (anencephaly, myelomeningocele, meningocele, oral facial cleft, structural heart disease, limb defect, urinary tract anomaly, hydrocephalus) that has been reported to have a decreased incidence following preconception / first trimester folic acid +/- multivitamin oral supplementation is planned pregnancy +/- supplementation compliance. A folate-supplemented diet with additional daily supplementation of multivitamins with 5mg folic acid should begin at least three months before conception and continue until 10 to 12weeks post conception. From 12weeks post-conception and continuing throughout pregnancy and the postpartum period (4–6 weeks or as long as breastfeeding continues), supplementation should consist of a multivitamin with folic acid (0.4–1.0mg). (I-A) 7.The recommended strategy(ies) for primary prevention or to decrease the incidence of fetal congenital anomalies will include a number of options or treatment approaches depending on patient age, ethnicity, compliance, and genetic congenital anomaly risk status. ●Option A: Patients with no personal health risks, planned pregnancy, and good compliance require a good diet of folate-rich foods and daily supplementation with a multivitamin with folic acid (0.4–1.0mg) for at least two to three months before conception and throughout pregnancy and the postpartum period (4–6 weeks and as long as breastfeeding continues). (II-2-A) ●Option B: Patients with health risks, including epilepsy, insulin dependent diabetes, obesity with BMI >35kg/m 2 , family history of neural tube defect, belonging to a high-risk ethnic group (e.g., Sikh) require increased dietary intake of folate-rich foods and daily supplementation, with multivitamins with 5mg folic acid, beginning at least three months before conception and continuing until 10 to 12weeks post conception. From 12weeks post-conception and continuing throughout pregnancy and the postpartum period (4-6 weeks or as long as breastfeeding continues), supplementation should consist of a multivitamin with folic acid (0.4-1.0mg). (II-2-A) ●Option C: Patients who have a history of poor compliance with medications and additional lifestyle issues of variable diet, no consistent birth control, and possible teratogenic substance use (alcohol, tobacco, recreational non-prescription drugs) require counselling about the prevention of birth defects and health problems with folic acid and multivitamin supplementation. The higher dose folic acid strategy (5mg) with multivitamin should be used, as it may obtain a more adequate serum red blood cell folate level with irregular vitamin / folic acid intake but with a minimal additional health risk. (III-B) 8.The Canadian Federal Government could consider an evaluation process for the benefit/risk of increasing the level of national folic acid flour fortification to 300mg/100g (present level 140mg/100g). (III-B) 9.The Canadian Federal Government could consider an evaluation process for the benefit/risk of additional flour fortification with multivitamins other than folic acid. (III-B) 10.The Society of Obstetricians and Gynaecologists of Canada will explore the possibility of a Canadian Consensus conference on the use of folic acid and multivitamins for the primary prevention of specific congenital anomalies. The conference would include Health Canada/Congenital Anomalies Surveillance, Canadian College of Medical Geneticists, Canadian Paediatric Society, Motherisk, and pharmaceutical industry representatives. Validation This is a revision of a previous guideline and information from other consensus reviews from medical and government publications has been used. Sponsor The Society of Obstetricians and Gynaecologists of Canada.

The relationship between stress and hair cortisol in healthy pregnant women.

Abstract: Purpose: Stress has been shown to cause a large range of adverse fetal effects. This pilot study is the first attempt to examine cortisol level in the hair of pregnant women and assess its potential as a biomarker of gestational stress. Patients and Methods: Twenty-five healthy pregnant women, in whom hair cortisol levels and the Perceived Stress Scale (PSS) were measured and correlated. Results: Maternal hair cortisol levels, ranging between 0.06 and 0.23 nmol/g of hair correlated positively and significantly with measures of perceived stress (ranging between 2-22); (Rs=0.47) (P < 0.05). Conclusions: Our findings corroborate recent primate studies with induced stress, and suggest that hair cortisol is a potential biomarker of chronic stress in pregnancy. This new long term biological marker may have important implications in research and clinical practice.

Pregnancy outcome of women exposed to azathioprine during pregnancy.

Abstract: BACKGROUND Azathioprine (AZP) interferes with nucleic acid synthesis and is teratogenic in animals. In view of the paucity of information on the use of AZP during pregnancy we investigated this subject in a prospective, controlled, multicenter study. Our objective was too determine whether exposure to AZP during pregnancy increases the risk for major malformations and to determine the effect on pregnancy outcome. METHODS Pregnant women on AZP who contacted one of seven teratogen information services were compared to a cohort of pregnant women who contacted two of the seven teratogen information services and took nonteratogenic treatments during their pregnancy. RESULTS Follow-up was completed on 189 women in the AZP group and compared to 230 women in the control group. The rate of major malformations did not differ between groups with six neonates in each; the AZP rate was 3.5% and the control group rate was 3.0% (p = .775; OR 1.17; CI: 0.37, 3.69). The mean birth weight and gestational age were lower in the AZP group (2,995 g vs. 3,252 g [p = .001, difference of mean: 257, 95% CI: 106.3, 408.1] and 37.8 weeks vs. 39.1 weeks [p = .001, difference of mean: 1.3, 95% CI: .5, 2.0], respectively). The AZP group had more cases of prematurity (21.4% vs. 5.2% [p < .001; OR 4.0; 95% CI: 2.0, 8.06]) and low birth weight (23% vs. 6.0% [p < .001; OR 3.81; 95% CI: 2.0, 7.2]). CONCLUSIONS These results suggest that AZP (50–100 mg/day) does not triple the rate of birth defects; however, it is associated with lower birth weight, gestational age, and prematurity. Larger studies are needed to confirm these observations. © 2007 Wiley-Liss, Inc.

Hair Cortisol as a Potential Biologic Marker of Chronic Stress in Hospitalized Neonates

Abstract: Background: As preterm and term infants in the neonatal intensive care unit (NICU) undergo multiple stressful/painful procedures, research is required that addresses chronic stress.

Safety of codeine during breastfeeding Fatal morphine poisoning in the breastfed neonate of a mother prescribed codeine

Abstract: QUESTION Recently a newborn died from morphine poisoning when hismother used codeine while breastfeeding. Many patients receive codeine for postlabour pain. Is it safe to prescribe codeine for nursing mothers? ANSWER When a mother is an ultrarapid metabolizer of cytochrome P450 2D6, she produces much more morphine when taking codeine than most people do. In this situation, newborns might be exposed to toxic levels of morphine when breastfeeding. Options to reduce this risk include discontinuing codeine after 2 to 3 days of use and being aware of symptoms of potential opioid toxicity in both mothers and newborns.

From type 2 diabetes to antioxidant activity : a systematic review of the safety and efficacy of common and cassia cinnamon bark

Abstract: Common (Cinnamomum verum, C. zeylanicum) and cassia (C. aromaticum) cinnamon have a long history of use as spices and flavouring agents. A number of pharmacological and clinical effects have been observed with their use. The objective of this study was to systematically review the scientific literature for preclinical and clinical evidence of safety, efficacy, and pharmacological activity of common and cassia cinnamon. Using the principles of evidence-based practice, we searched 9 electronic databases and compiled data according to the grade of evidence found. One pharmacological study on antioxidant activity and 7 clinical studies on various medical conditions were reported in the scientific literature including type 2 diabetes (3), Helicobacter pylori infection (1), activation of olfactory cortex of the brain (1), oral candidiasis in HIV (1), and chronic salmonellosis (1). Two of 3 randomized clinical trials on type 2 diabetes provided strong scientific evidence that cassia cinnamon demonstrates a thera...

Prenatal Multivitamin Supplementation and Rates of Pediatric Cancers: A Meta-Analysis

Abstract: Prenatal supplementation of folic acid has been shown to decrease the risk of several congenital malformations. Several studies have recently suggested a potential protective effect of folic acid on certain pediatric cancers. The protective role of prenatal multivitamins has not been elucidated. We conducted a systematic review and meta-analysis to assess the potential protective effect of prenatal multivitamins on several pediatric cancers. Medline, PubMed, EMBASE, Toxline, Healthstar, and Cochrane databases were searched for studies published in all languages from 1960 to July 2005 on multivitamin supplementation and pediatric cancers. References from all articles collected were reviewed for additional articles. Two blinded independent reviewers assessed the articles for inclusion and exclusion. Rates of cancers in women supplemented with multivitamins were compared with unsupplemented women using a random effects model. Sixty-one articles were identified in the initial search, of which, seven articles met the inclusion criteria. There was an apparent protective effect for leukemia (odds ratio (OR)=0.61, 95% confidence interval (CI)=0.50-0.74), pediatric brain tumors (OR=0.73, 95% CI=0.60-0.88) and neuroblastoma (OR=0.53, 95% CI=0.42-0.68). In conclusion, maternal ingestion of prenatal multivitamins is associated with a decreased risk for pediatric brain tumors, neuroblastoma, and leukemia. Presently, it is not known which constituent(s) among the multivitamins confer this protective effect.

The treatment of Hodgkin's and non-Hodgkin's lymphoma in pregnancy.

Abstract: Lymphoma is the fourth most frequent malignancy diagnosed during pregnancy, occurring in approximately 1:6000 of deliveries. Its occurrence may increase due to the current trend to postpone pregnancy until later in life and the suggested high incidence of AIDS-related non-Hodgkin's lymphoma in developing countries. The relatively rare occurrence of pregnancy-associated lymphoma precludes the conduction of large, prospective studies to examine diagnostic, management and outcome issues. Chemotherapy and radiotherapy during the first trimester are associated with increased risk of congenital malformations and this risk diminishes as pregnancy advances. In the vast majority of cases, when lymphoma is diagnosed during the first trimester, treatment with a standard chemotherapy regimen, following pregnancy termination should be recommended. In the rare patients at low risk, such as those with stage 1 Hodgkin's lymphoma or indolent non-Hodgkin's lymphoma, therapy can be delayed until the end of the first trimester and of embryogenesis while keeping the patients under close observation. When lymphoma is diagnosed during the second and third trimesters, evidence exists suggesting that full-dose chemotherapy can be administered safely without apparent increased risk of severe adverse fetal outcome.

Motherisk Rounds: Risks of Statin Use During Pregnancy: A Systematic Review

Abstract: Although statins have been identified as potential teratogens on the basis of theoretical considerations and small case series, the available evidence is far from conclusive. In fact, epidemiological data collected to date suggest that statins are not major teratogens. The actual risk for an exposed pregnancy seems to be small, if present at all, and does not by itself warrant termination of pregnancy. Nevertheless, given the scarcity of available data, it is still advisable to avoid use of these drugs in patients who are planning pregnancy in order to reduce the risks as much as possible.

Isotretinoin, pregnancies, abortions and birth defects: a population‐based perspective

Abstract: What is already known about this subject • As of now, no population-based data exist on the incidence of pregnancy, elective abortions, and birth defects while on isotretinoin. • From surveys or interventional studies, it is known that pregnancy rates while on isotretinoin are comparable to the baseline rate, and that birth defect rates associated with first-trimester exposure are 10 times greater than in the general population. • Given that women decide to terminate pregnancies based on the available data, population-based estimates are needed. What this study adds • This first non-interventional population-based study on the risk of pregnancy while being exposed to isotretinoin has shown that the rate of pregnancy is four times greater than what has been published to date (32.7/1000 person-years). • Any pregnancy while using isotretinoin is the result of a failure of pregnancy prevention strategies, hence, thus far, pregnancy prevention programmes have failed. • The rate of elective abortions is much higher than previously reported (84%). • Women of a lower socio-economic level and high users of healthcare services are more likely to become pregnant while on isotretinoin, suggesting that high use of health services increase the opportunity of having a prescription for isotretinoin or of having a pregnancy diagnosis. Aims To estimate the population-based incidence rates of pregnancy, spontaneous and elective abortions, and birth defects associated with isotretinoin use, and to determine predictors of pregnancy while on isotretinoin. Methods Using the RAMQ (medical and pharmaceutical data), MED-ECHO (hospitalizations) and ISQ (births and deaths) databases for the period 1984–2002, a cohort of 8609 women between 13 and 45 years of age and with a first prescription for isotretinoin (date of entry in the cohort) was identified. Women were eligible if they were insured by RAMQ for their medications at least 12 months before entry in the cohort and until 1 month after the end of their isotretinoin treatment. Pregnancies, spontaneous and elective abortions, and birth defects were identified using procedure codes and medical diagnoses. Results Of the 8609 women included, 90 became pregnant, an annual incident pregnancy rate during isotretinoin treatment of 32.7 per 1000 person-years of treatment (95% confidence interval 26.6, 40.1). Of the 90 women who became pregnant while on the drug, 76 terminated the pregnancy (84%), three had a spontaneous abortion (3%), two had trauma during delivery resulting in neonatal deaths (2%) and nine had a live birth (10%). Among the live births, only one had a congenital anomaly of the face and neck (11%). Adjusting for potential confounders, predictors of becoming pregnant while on isotretinoin were lower socio-economic level, one or more visits to the doctor or to the emergency department, or one or more hospitalization while on isotretinoin; concomitant isotretinoin and oral contraceptive use had a preventive effect. Conclusions This first non-interventional population-based study generated incidence rates of pregnancy while on isotretinoin four times greater than what has been reported in the literature thus far; elective abortion rates were also much higher in our study. This shows the importance of using population-based data for public health purposes.

Treatment of Nausea and Vomiting in Pregnancy: An Updated Algorithm

Abstract: QUESTION My patient has severe nausea and vomiting of pregnancy (NVP). I am having difficulty treating her, as nothing she has tried so far has been really effective. I heard that there is some new information regarding the treatment of this condition. ANSWER Even a less severe case of NVP can have serious adverse effects on the quality of a woman’s life, affecting her occupational, social, and domestic functioning, and her general well-being; therefore, it is very important to treat this condition appropriately and effectively. There are safe and effective treatments available. We have updated Motherisk’s NVP algorithm to include recent relevant published data, and we describe some other strategies that deal with secondary symptoms related to NVP.

Fetal Safety of Letrozole and Clomiphene Citrate for Ovulation Induction

Abstract: Letrozole is a third-generation selective aromatase inhibitor that blocks the rate-limiting step in the production of estrogen from androstenedione and testosterone substrates. Letrozole is approved in Canada for use in the treatment of postmenopausal women with breast cancer.1 Letrozole has no significant active metabolites. It is completely absorbed after oral administration and has a mean terminal half-life of approximately 45 hours (range 30–60 hours). It is cleared from the systemic circulation mainly by the liver.

Oral Antidiabetic Agents in Pregnancy and Lactation: A Paradigm Shift?

Abstract: Objective:To provide information on the use of oral antidiabetic agents in pregnancy and breast-feeding.Data Sources:Primary articles were identified by a MEDLINE search (1966–March 2007) using the MeSH headings: pregnancy in diabetics, pregnancy, polycystic ovary syndrome, hypoglycemic agents, glipizide, glyburide, metformin, rosiglitazone, pioglitazone, clinical trial, controlled clinical trial, multicenter study, randomized controlled trial, case–control studies, and cohort studies.Study Selection and Data Extraction:All studies using oral antidiabetic agents in pregnancy were evaluated and relevant data were included in the discussion.Data Synthesis:Studies of glyburide and glipizide have found little or no transfer of these drugs across the placenta, whereas metformin and rosiglitazone cross readily. Animal studies have found no evidence to suggest that glyburide, glipizide, metformin, or rosiglitazone are teratogenic. In gestational diabetes, glyburide was safe and efficacious; however, 16–19% of wo...

Reference values for hair cotinine as a biomarker of active and passive smoking in women of reproductive age, pregnant women, children, and neonates: systematic review and meta-analysis.

Abstract: Exposure to environmental tobacco smoke (ETS) is most often estimated using questionnaires, but they are unreliable. Biomarkers can provide valid information on ETS exposure, the preferred biomarker being cotinine. However, no reference range of hair cotinine exists to distinguish among active, passive, and unexposed nonsmokers. This study identifies cutoffs to validate cotinine as a marker for exposure to ETS. Data were obtained from six databases (four US, one Canada, one France). Active smoking and exposure to ETS were measured in the hair of women of reproductive age, pregnant women, their children, and neonates. Subjects were classified into active smokers, passively exposed to ETS, and unexposed nonsmokers. A total of 1746 cases were available for analysis. For active smokers, mean hair cotinine concentrations (95% confidence interval) were 2.3 to 3.1 ng/mg for nonpregnant women and 1.5 to 1.9 ng/mg for pregnant women. In the group of passive smokers, mean hair cotinine concentrations were 0.5 to 0.7 ng/mg for nonpregnant women, 0.04 to 0.09 ng/mg for pregnant women, 0.9 to 1.1 for children, and 1.2 to 1.7 for neonates. Among unexposed nonsmokers, mean hair cotinine was 0.2 to 0.4 ng/mg in nonpregnant women, 0.06 to 0.09 ng/mg in pregnant women, and 0.3 to 0.4 ng/mg in children. Cutoff values for hair cotinine were established to distinguish active smokers from passive or unexposed (0.8 ng/mg for nonpregnant women and 0.2 ng/mg for pregnant women). A cutoff value of 0.2 ng/mg was accurate in discriminating between exposed children and unexposed. These new values should facilitate clinical diagnosis of active and passive exposure to tobacco smoke. Such diagnosis is critical in pregnancy and in a large number of tobacco-induced medical conditions.

The weekly cost of nausea and vomiting of pregnancy for women calling the Toronto Motherisk Program

Abstract: Background: Nausea with or without vomiting of pregnancy (NVP) is the most common medical condition in pregnancy. NVP, even with mild symptoms, is associated with costs to society, patients, and the health care system.Objective: The main objective of this study was to estimate the total direct and indirect costs per woman-week associated with the onset of NVP in Canada from the perspective of society.Methods: A cost of illness study was performed to estimate the cost per woman-week associated with the onset of NVP in Canada, stratified according to the severity of NVP. Data were collected from 139 pregnant women, who called the Motherisk Program at the Hospital for Sick Children in Toronto. Results are reported in 2005 Canadian dollars.Results: From the perspective of society, the total cost per woman-week was $132 ($114 indirect and $18 direct costs), $355 ($271 indirect and $84 direct costs), and $653 ($494 indirect and $159 direct costs) for women with mild, moderate, and severe NVP, respective...

Methamphetamine detection in maternal and neonatal hair: implications for fetal safety

Abstract: Background: Methamphetamine misuse is a serious health problem of epidemic proportions. Use of this drug, particularly during pregnancy, is difficult to ascertain. Sparse information is available on gestational exposure. Objectives: To quantify methamphetamine accumulation in hair, identify the use of methamphetamine with other drugs of abuse and characterise correlations between concentrations of methamphetamine in maternal and neonatal hair. Subjects and methods: Motherisk laboratory at the Hospital for Sick Children routinely carries out analysis of methamphetamine in hair. Mothers and infants with positive results for methamphetamine in hair were identified. Drugs present in hair were analysed by ELISA and positive results were confirmed by gas chromatgraphy/mass spectrometry. Results: 396 people positive for methamphetamine in their hair were identified from our database. Almost 85% of them were positive for at least one other drug of abuse, mostly cocaine. Eleven mother–baby pairs with hair positive for methamphetamine were identified. Methamphetamine levels in hair ranged between 0.13 and 51.97 ng/mg in the mothers and between 0 and 22.73 ng/mg in the neonates. Methamphetamine levels in mothers and neonates correlated significantly. One (9%) neonate was negative for methamphetamine even though the mother was positive. Conclusion: To our knowledge, this is the first report on fetal exposure to methamphetamine during pregnancy, showing transplacental transfer of the drug, with accumulation in fetal hair. Hair measurement for methamphetamine in neonates is a useful screening method to detect intra-uterine exposure to the drug. The data also indicate that positive exposure to methamphetamine strongly suggests that the person is a polydrug user, which may have important implications for fetal safety.

Cost of fetal alcohol spectrum disorder in Canada

Abstract: QUESTION I have heard that thousands of Canadian kids are affected by fetal alcohol spectrum disorders. Has there been any attempt to estimate what it costs our society? ANSWER In a recent Canadian study, the lifetime cost of fetal alcohol spectrum disorders was estimated at $1 million per case. With an estimated 4000 new cases yearly, this translates to $4 billion annually.

Amitriptyline to relieve pain in juvenile idiopathic arthritis: a pilot study using Bayesian metaanalysis of multiple N-of-1 clinical trials.

Abstract: OBJECTIVE: Using serial N-of-1 trials and subsequent analysis with Bayesian methods may allow study of therapies using small numbers of subjects. Our research questions were: (1) Can serial N-of-1 trials analyzed with Bayesian statistical techniques be used to estimate the population effect of a therapeutic intervention? (2) Compared to placebo, how likely is it that low-dose amitriptyline therapy in children aged 10-18 years with active polyarticular-course juvenile idiopathic arthritis (JIA) results in a significant improvement in pain? METHODS: Six children (age 10.3-16.3 yrs, 4 girls) were enrolled. There were 3 pairs of randomized, double-blinded treatments (amitriptyline 25 mg or placebo) per participant. Each treatment lasted 2 weeks, with a 1 week washout. The primary outcome was pain, measured by 10 cm visual analog scale. Assessments were at the beginning and end of each treatment. A Bayesian statistical model was used to determine the treatment effect. Values

Validation of the oral mucositis assessment scale in pediatric cancer.

Abstract: Background Our objective was to examine the construct validity of the Oral Mucositis Assessment Scale (OMAS) in children receiving doxorubicin chemotherapy. Methods Children between 6 and 18 years of age with cancer receiving doxorubicin-containing chemotherapy were included. OMAS was measured on days 7, 10, 14, and 17 after chemotherapy. Other measures of mucositis obtained concurrent with OMAS were the World Health Organization (WHO) mucositis scale and pain visual analogue scale (VAS). We also recorded analgesia administration. Results Sixteen children were studied for 45 post-chemotherapy cycles and 156 OMAS assessments were performed. OMAS was moderately correlated with WHO scores (r = 0.56; P = 0.0006) whereas correlation with the pain VAS was fair (r = 0.37; P = 0.002). OMAS also had fair correlation with the number of doses of topical analgesia (r = 0.43; P = 0.001) and with the cumulative dose of opioid analgesia (r = 0.38; P = 0.003). Conclusions The OMAS is valid for use in mucositis clinical trials for children at least 6 years of age. Pediatr Blood Cancer 2007;49:149–153. © 2006 Wiley-Liss, Inc.

Exposure to attention deficit hyperactivity disorder medications during pregnancy

Abstract: QUESTION An 18-year-old patient of mine, currently under treatment for attention deficit hyperactivity disorder (ADHD) with methylphenidate, just found out that she is pregnant. What are the risks for the baby when the mother uses ADHD medications during pregnancy? ANSWER Available evidence for amphetamines suggests no increased risk of malformations with use of therapeutic doses, and inadvertent exposure during pregnancy is unlikely to be harmful. Human data for methylphenidate and atomoxetine treatment in pregnancy are very limited. Documented cases do not suggest teratogenicity, but we cannot rule out this risk with the information available.

Cocaine detection in maternal and neonatal hair: implications to fetal toxicology.

Abstract: :Cocaine use during pregnancy is difficult to ascertain, and maternal reports are likely to be inaccurate. Presently, the dose-response characteristics between maternal cocaine use and fetal exposure and adverse effects are unknown. Clinically, some babies are harmed, whereas others are not

Human teratogens and evidence-based teratogen risk counseling: the Motherisk approach.

Abstract: There are only a limited number of drugs proven to be human teratogens including thalidomide, isotretinoin, coumarin derivates, valproic acid, and folate antagonists. In some cases, the combination of 2 drugs may increase the teratogenic risk. The risk of birth defects may also vary with the time at