Development of a machine learning algorithm for early detection of opioid use disorder.

BACKGROUND: Opioid use disorder (OUD) affects an estimated 16 million people worldwide. The diagnosis of OUD is commonly delayed or missed altogether. We aimed to test the utility of machine learning in creating a prediction model and algorithm for early diagnosis of OUD. SUBJECTS AND METHODS: We analyzed data gathered in a commercial claim database from January 1, 2006, to December 31, 2018 of 10 million medical insurance claims from 550 000 patient records. We compiled 436 predictor candidates, divided to six feature groups - demographics, chronic conditions, diagnosis and procedures features, medication features, medical costs, and episode counts. We employed the Word2Vec algorithm and the Gradient Boosting trees algorithm for the analysis. RESULTS: The c-statistic for the model was 0.959, with a sensitivity of 0.85 and specificity of 0.882. Positive Predictive Value (PPV) was 0.362 and Negative Predictive Value (NPV) was 0.998. Significant differences between positive OUD- and negative OUD- controls were in the mean annual amount of opioid use days, number of overlaps in opioid prescriptions per year, mean annual opioid prescriptions, and annual benzodiazepine and muscle relaxant prescriptions. Notable differences were the count of intervertebral disc disorder-related complaints per year, post laminectomy syndrome diagnosed per year, and pain disorders diagnosis per year. Significant differences were also found in the episodes and costs categories. CONCLUSIONS: The new algorithm offers a mean 14.4 months reduction in time to diagnosis of OUD, at potential saving in further morbidity, medical cost, addictions and mortality.

Assessment of hair cortisol as a potential biomarker for possible adrenal suppression due to inhaled corticosteroid use in children with asthma: A retrospective observational study.

BACKGROUND: Inhaled corticosteroids (ICS) are the recommended long-term control therapy for asthma in children. However, concern exists regarding potential adrenal suppression with chronic ICS use. Our pilot study reported that hair cortisol in children was 50% lower during ICS therapy than prior to therapy, suggestive of adrenal suppression. OBJECTIVE: To evaluate hair cortisol concentration (HCC) as a potential biomarker for possible adrenal suppression from ICS use in children with asthma. METHODS: A retrospective observational study was performed at asthma clinics in Vancouver, Winnipeg, and Toronto, Canada. Children (n = 586) were recruited from July 2012 to December 2014 inclusive of those without asthma, with asthma not using ICS, and with asthma using ICS. The most recent three-month HCC was measured by enzyme immunoassay and compared among the groups. Quantile regression analysis was performed to identify factors potentially affecting HCC. RESULTS: The median HCC was not significantly different among the children: No ICS (n = 47, 6.7 ng/g, interquartile range (IQR) 3.7-9.8 ng/g), ICS Treated (n = 360, 6.5 ng/g, IQR 3.8-14.3 ng/g), and Controls (n = 53, 5.8 ng/g, IQR 4.6-16.7 ng/g). 5.6% of the children using ICS had hair cortisol <2.0 ng/g compared to none in the control groups (P < .05, comparing ICS Treated (20/360) to all Controls combined (0/100)) and only half had been exposed to systemic corticosteroids. Age, sex, BMI, and intranasal corticosteroid use were significantly associated with HCC. CONCLUSIONS: Results suggest HCC may be a potential biomarker for adrenal suppression as a population of children using ICS with HCC < 2.0 ng/g was identified compared to none in the control groups. Further research is needed to determine if those children have or are at risk of adrenal suppression or insufficiency.

Biobanking in Israel 2016-17; expressed perceptions versus real life enrollment.

BACKGROUND: As part of the preparations to establish a population-based biobank in a large Israeli health organization, we aimed to investigate through focus groups the knowledge, perceptions and attitudes of insured Israelis, toward biobanking, and then, after input from focus groups' participants, to empirically assess the impact of a revised recruitment process on recruitment rates. METHODS: 1) Six Focus group discussions were conducted (n = 10 per group) with individuals who had routine blood laboratory tests taken in the last 2 years. 2) After addressing the issues raised in the focus groups and revising the recruitment process, individuals undergoing routine blood tests in phlebotomy clinics (N = 10,262) were invited to participate in the future biobank. RESULTS: At the outset of the focus groups there was an overall positive response to the prospect of a population-based biobank. Concerns revolved around infringement on privacy, fears of the "big brother"(e.g. insurance companies), and anxiety about inequality. Reaction to the language of the informed consent document revolved around concerns over ability to maintain anonymity, to withdraw consent, involvement of commercial entities, and the general tenor of the informed consent, which was perceived as legalistic and unilateral. In general, the longer participants were exposed to discussion about the biobank, the less likely they were to consent to sign in. Overall, only 20% (12) of the 60 participants stated they would agree to sign in by the end of the 2 hour group session. The feedback obtained from the focus groups was used in the second stage ("real life") of the study. A team of recruiters received extensive training to enable fruitful discussion and a detailed explanation to questions and concerns raised during the recruitment process. During the second stage of the study, after revising the consent form and training recruiters, a 53% consent rate was observed among 10,262 participants, more than 4 fold higher than estimated at the focus group stage. CONCLUSIONS: The qualitative focus group research helped identify important perceptions and concerns, which were subsequently addressed in the revised consent form and in the discussion the recruiters had with potential biobank donors.

No. 245-Alcohol Use and Pregnancy Consensus Clinical Guidelines.

OBJECTIVE: To establish national standards of care for the screening and recording of alcohol use and counselling on alcohol use of women of child-bearing age and pregnant women based on the most up-to-date evidence. EVIDENCE: Published literature was retrieved through searches of PubMed, CINAHL, and the Cochrane Library in May 2009 using appropriate controlled vocabulary (e.g., pregnancy complications, alcohol drinking, prenatal care) and key words (e.g., pregnancy, alcohol consumption, risk reduction). Results were restricted to literature published in the last five years with the following research designs: systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no language restrictions. Searches were updated on a regular basis and incorporated in the guideline to May 2010. Grey (unpublished) literature was identified through searching the websites of health technology assessment (HTA) and HTA-related agencies, national and international medical specialty societies, clinical practice guideline collections, and clinical trial registries. Each article was screened for relevance and the full text acquired if determined to be relevant. The evidence obtained was reviewed and evaluated by the members of the Expert Workgroup established by the Society of Obstetricians and Gynaecologists of Canada. The quality of evidence was evaluated and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care. VALUES: The quality of evidence was rated using the criteria described by the Canadian Task Force on Preventive Health Care (Table 1). SPONSOR: The Public Health Agency of Canada and the Society of Obstetricians and Gynaecologists of Canada. ENDORSEMENT: These consensus guidelines have been endorsed by the Association of Obstetricians and Gynecologists of Quebec; the Canadian Association of Midwives; the Canadian Association of Perinatal, Women's Health and Neonatal Nurses (CAPWHN); the College of Family Physicians of Canada; the Federation of Medical Women of Canada; the Society of Rural Physicians of Canada; and Motherisk. SUMMARY STATEMENTS: RECOMMENDATIONS.

Association Between Use of Oral Contraceptives and Folate Status: A Systematic Review and Meta-Analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis of the effect of oral contraceptive use on plasma and red blood cell (RBC) folate concentrations. METHODS: We searched Medline, EMBASE, Web of Science, and the Cochrane library for human studies published from inception to June 2013 evaluating oral contraceptive use and folate status. Case-control studies, cohort studies, and clinical trials were included. A random-effects model of outcomes was used for the meta-analysis. RESULTS: A total of 2831 women in 17 studies were included in the analysis. In those whose plasma folate concentrations were available, there was a significant folate-lowering effect of oral contraceptives observed (mean reduction 1.27 µg/L; 95% CI 1.85 to 0.69, P < 0.001). Similarly, after analyzing data from 1389 women in 12 studies whose RBC folate concentrations were available, significantly lower folate status was observed among oral contraceptive users (mean reduction 59.32 µg/L; 95% CI 58.03 to 23.04, P < 0.001). CONCLUSION: Because of the reduction in blood folate concentrations associated with the use of oral contraceptives, it is critical for women of childbearing age to continue folate supplementation during oral contraceptive use.

Objectif : Mener une analyse systématique et une méta-analyse quant à l'effet du recours à la contraception orale sur les concentrations plasmatiques et érythrocytaires en folate. Méthodes : Nous avons mené des recherches dans Medline, EMBASE, Web of Science et la Cochrane library en vue d'en tirer les études menées chez l'homme, publiées entre le début de nos travaux et juin 2013, qui ont évalué l'utilisation de contraceptifs oraux et les taux de folate. Les études cas-témoins, les études de cohorte et les essais cliniques ont été admis aux fins de notre analyse. Un modèle à effets aléatoires quant aux issues a été utilisé dans le cadre de la méta-analyse. Résultats : Au total, 2 831 femmes issues de 17 études ont été admises à l'analyse. Chez les femmes pour lesquelles les concentrations plasmatiques en folate étaient disponibles, nous avons constaté que les contraceptifs oraux exerçaient un effet considérable d'atténuation de ces concentrations (baisse moyenne, 1,27 µg/l; IC à 95 %, 1,85 - 0,69, P < 0,001). De façon semblable, après avoir analysé les données traitant de 1 389 femmes issues de 12 études pour lesquelles les concentrations érythrocytaires en folate étaient disponibles, nous avons constaté une baisse considérable de ces concentrations chez les utilisatrices de contraceptifs oraux (baisse moyenne, 59,32 µg/l; IC à 95 %, 58,03 - 23,04, P < 0,001). Conclusion : En raison de la baisse des concentrations sanguines en folate qui sont associées à l'utilisation de contraceptifs oraux, il est crucial que les femmes en âge de procréer qui ont recours à une telle contraception continuent à prendre une supplémentation en folate.

Labetalol for hypertension in pregnancy.

INTRODUCTION: Labetalol is one of the most commonly used antihypertensive medications for the treatment of hypertension during pregnancy, an increasingly common and leading cause of maternal mortality and morbidity worldwide. AREAS COVERED: The literature reviewed included the 2014 Canadian national pregnancy hypertension guideline and its references. The additional published literature was retrieved through searches of Medline, CINAHL, and The Cochrane Library using appropriate controlled vocabulary (e.g., pregnancy, hypertension, pre-eclampsia, pregnancy toxemias) and key words (e.g., diagnosis, evaluation, classification, prediction, prevention, prognosis, treatment, and postpartum follow-up).Results were restricted to systematic reviews, randomized controlled trials, controlled clinical trials, and observational studies published in French or English, Jan-Mar/14. The unpublished literature was identified by searching websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. We evaluated the impact of interventions on substantive clinical outcomes for mothers and babies. EXPERT OPINION: Labetalol is a reasonable choice for treatment of severe or non-severe hypertension in pregnancy. However, we should continue our search for other therapeutic options.

Cost effectiveness of teratology counseling - the Motherisk experience.

BACKGROUND: While the benefits of evidence-based counseling to large numbers of women and physicians are intuitively evident, there is an urgent need to document that teratology counseling, in addition to improving the quality of life of women and families, also leads to cost saving. The objective of the present study was to calculate the cost effectiveness of the Motherisk Program, a large teratology information and counseling service at The Hospital for Sick Children and the University of Toronto. METHODS: We analyzed data from the Motherisk Program on its 2012 activities in two domains: 1) Calculation of cost-saving in preventing unjustified pregnancy terminations; and 2) prevention of major birth defects. Cost of pregnancy termination and lifelong cost of specific birth defects were identified from primary literature and prorated for cost of living for the year 2013. RESULTS: Prevention of 255 pregnancy terminations per year led to cost savings of $516,630. The total estimated number of major malformations prevented by Motherisk counseling in 2012 was 8.41 cases at a total estimated cost of $9,032,492. CONCLUSIONS: With an estimated minimum annual prevention of 8 major malformations, and numerous unnecessary terminations of otherwise- wanted pregnancies, a cost saving of $10 million can be calculated. In 2013 the operating budget of Motherisk counseling totaled $640,000. Even based on the narrow range of activities for which we calculated cost, this service is highly cost- effective. Because most teratology counseling services are operating in a very similar method to Motherisk, it is fair to assume that these results, although dependent on the size of the service, are generalizable to other countries.

Cultural and socio-economic conditions as factors contributing to chronic stress in sub-Saharan African communities.

Stress is known to contribute to overall health status. Many individuals in sub-Saharan Africa are believed to be stressed about their employment, income, and health. This study aimed to investigate hair cortisol as a biomarker of chronic stress in settlement communities in Kenya. Hair samples were collected from 108 volunteers from settlement communities in Kenya. An enzyme-linked immunosorbent assay technique was used to measure hair cortisol concentrations. In parallel, a health survey was completed. The mean ± SD for the cortisol concentration in the hair of volunteers from the settlement communities in Naivasha was 639 ± 300 ng/g, which was higher than found for a Caucasian reference group (299 ± 110 ng/g; one-way ANOVA, P = 0.0003). There were no differences in hair cortisol concentrations between members of slum settlements adjacent to large floriculture farms in Naivasha (Karagita, Kamere/Kwa Muhia/DCK, and Kasarani) compared with those well-removed from all floriculture in Mogotio (Mogotio and Westlands/Katorongot). However, hair cortisol concentrations were significantly higher in females, divorced volunteers, those who made below minimum wage, and those who reported feeling unsafe collecting water or using sanitation facilities within these 2 settlement groups. We found no evidence for increased chronic stress (measured by hair cortisol content) between members of slum settlements adjacent to versus distant to large floriculture farms. Cultural and socio-economic conditions that prevail in much of sub-Saharan Africa were found to be factors contributing to chronic stress.

Screening and referral to identify children at risk for FASD: Search for new methods 2006-2013.

As part of the Canadian Association of Paediatric Health Centres Taskforce on FASD Screening commitment to further pilot, validate and evaluate the multiple components of the Canadian FASD Screening Tool Kit, it was deemed necessary that recent developments and/or improvements in FASD screening were identified and considered. In 2008 a literature review of methods for screening for FASD was published until 2006 and identified five tools which met pre-set criteria. A review of all new papers was published from the period January 2006 until July 1, 2013. Out of 1392 papers, two new screening methods met the inclusion criteria: Clarren et al's new norms for palpebral fissure length by age in Canada; and Breiner et al's extension of the Neurobehavioral Screening Test (NST) to age 4 years. Further work is needed to validate these methods in other settings. 

Hair cortisol as a biomarker of stress among a first nation in Canada.

BACKGROUND: Cortisol level in hair is increasingly being used as a biomarker of chronic stress. Members of First Nation communities in Canada are experiencing stress related to a higher incidence of chronic diseases, socioeconomic factors, the state of their environment, and cultural oppression. This study aimed to investigate hair cortisol as a biomarker of stress in this population. MATERIALS AND METHODS: Hair samples were collected from the posterior vertex of 55 Walpole Island First Nation (WIFN) volunteers and compared with white volunteers living in and around London, ON, Canada. An enzyme-linked immunosorbent assay technique was used to measure cortisol content in 1 cm of hair, considered to represent 1 month of growth. In parallel, the Perceived Stress Scale (PSS), which measures short-term stress, was also completed. RESULTS: Median hair cortisol level (range) in WIFN volunteers was 177 (93-273) ng/g, significantly higher than the median hair cortisol in the healthy white controls of 116 (26-204) ng/g (P < 0.0001, Mann-Whitney U test). Hair cortisol correlated positively with gender, smoking status, and self-reported diabetes. Unlike hair cortisol, the Perceived Stress Scale did not differentiate between the First Nation and control population. CONCLUSIONS: The increased hair cortisol concentrations among WIFN volunteers compared with volunteers from a non-First Nation community suggests higher levels of chronic stress. The causes for this apparent increased stress are likely due to factors such as socioeconomic and poorer health and are worthy of further evaluation. The results highlight the difference between acute stress measured for short periods of time compared with chronic stress, measured by hair analysis.

Economic burden of nausea and vomiting of pregnancy in the USA.

BACKGROUND: Nausea and vomiting of pregnancy (NVP) is the most common medical condition during gestation, affecting 50%-90% of women during their first trimester, and many in the second and third trimester. NVP affects women's quality of life and exerts a large economic impact on patients, caregivers and society. OBJECTIVES: To estimate the overall economic burden of illness of NVP in the USA. METHODS: A spreadsheet model was utilized to estimate this burden including direct and indirect costs. Costs are reported in 2012 US dollars and were estimated from the perspective of society. Cost centers included drug treatments for mild to severe NVP and hospitalizations for hyperemesis gravidarum (HG), as well as time lost from work and caregiver time. Clinical, epidemiologic, and economic data were obtained from the literature to populate the model. Rates of drug use were multiplied by unit costs and summed. RESULTS: The estimated total economic burden in 2012 in the USA was $1,778,473,782 which included $1,062,847,276 (60%) in direct costs and $715,626,506 (40%) in indirect costs. Overall, the average cost to manage one woman for NVP was $1827. Costs increased with increasing severity of NVP. The estimates were conservative, as not all applicable costs could be included. CONCLUSIONS: NVP results in a significant economic impact, and hence effective therapy should be sought. Future prospective research should determine in more detail what resources are utilized in the USA to manage women with NVP.

Neonatal screening for prenatal alcohol exposure: assessment of voluntary maternal participation in an open meconium screening program.

Meconium fatty acid ethyl esters (FAEEs) are validated biomarkers of fetal alcohol exposure. Meconium FAEE testing can potentially be used as a screen by health-care professionals to identify neonates at-risk for Fetal Alcohol Spectrum Disorder, thereby permitting diagnostic follow-up of these children and early intervention in those who develop disabilities. The purpose of this study was to assess whether women would willingly partake in a screening program of this nature. This was determined by launching a pilot screening program for prenatal alcohol exposure in a high-risk obstetric unit previously shown to have a high prevalence of FAEE-positive meconium via anonymous meconium testing. The program involved voluntary testing of meconium for FAEEs and long-term developmental follow-up of positive cases through an existing public health program. The participation rate in the screening program was significantly lower than when testing was conducted anonymously (78% vs. 95%, respectively; p < 0.05), and the positivity rate was 3% in contrast to 30% observed under anonymous conditions (p < 0.001). These low rates suggest that the majority of mothers who consumed alcohol in pregnancy refused to participate. We conclude that despite the potential benefits of such screening programs, maternal unwillingness to consent, likely due to fear, embarrassment, and guilt, may limit the effectiveness of meconium testing for population-based open screening, highlighting the need for public education and social marketing efforts for such programs to be of benefit.

Safety assessment in pediatric studies.

It typically takes many years before an association of a drug with a rare, serious adverse reaction is established. As related to pediatric drug use, evidence is even more erratic, as most drugs are used off labels. To enhance child safety, there is an urgent need to develop robust and rapid methods to identify such associations in as timely a manner as possible. In this chapter, several novel methods, both clinically based pharmacoepidemiological approaches and laboratory-based methods, are described.

Systemic bioavailability and pharmacokinetics of the doxylamine-pyridoxine delayed-release combination (Diclectin).

BACKGROUND: Diclectin, composed of 10 mg doxylamine succinate (DOX) and 10 mg pyridoxine hydrochloride, is the drug combination of choice for the management of nausea and vomiting during pregnancy in Canada. However, there is large variability in its onset and duration of action among women. To understand and improve its effectiveness, the variability in the pharmacokinetics of the ingredients in this doxylamine succinate/pyridoxine hydrochloride combination must be studied. OBJECTIVES: To determine the pharmacokinetics of DOX and pyridoxine after oral administration of two tablets of this drug combination in the form of Diclectin and to calculate their respective relative bioavailability by comparison with intravenous administration in another population. METHODS: Eighteen nonpregnant, nonlactating, healthy females between 18 and 45 years of age were administered two tablets of Diclectin with 240 mL of water under empty stomach conditions. Blood samples were analyzed for DOX and pyridoxine along with its four active metabolites: pyridoxal, pyridoxal-5'-phosphate (PLP), pyridoxamine, and pyridoxamine-5'-phosphate using tandem mass spectrometry. For the purpose of this study, pharmacokinetic values for DOX and PLP were adjusted for body weight. RESULTS: The mean DOX-AUC0→∞ was calculated to be 3137.22 ± 633.57 ng·hr/mL (range, 2056.59-4376.06 ng·hr/mL). The mean PLP-AUC0→∞ was calculated to be 5513.10 ± 2362.35 ng·hr/mL (range, 1572.56-10,153.77 ng·hr/mL). Based on literature values of the PLP-AUC0→∞ after intravenous administration and data from the current study, the relative bioavailability of pyridoxine in Diclectin was calculated at 100%. CONCLUSION: There was a 2.1-fold variability in the DOX-AUC0→∞ and 6.5-fold variability in the PLP-AUC0→∞ after oral administration of 20 mg Diclectin. Using literature values and data from the current study, we estimated the oral bioavailability of pyridoxine to be 100%. Therefore, interindividual differences in metabolism, and not in bioavailability, may be important sources of variability that need to be addressed in dosing guidelines.

Alcohol use and pregnancy consensus clinical guidelines.

OBJECTIVE: to establish national standards of care for the screening and recording of alcohol use and counselling on alcohol use of women of child-bearing age and pregnant women based on the most up-to-date evidence. EVIDENCE: published literature was retrieved through searches of PubMed, CINAHL, and the Cochrane Library in May 2009 using appropriate controlled vocabulary (e.g., pregnancy complications, alcohol drinking, prenatal care) and key words (e.g., pregnancy, alcohol consumption, risk reduction). Results were restricted to literature published in the last five years with the following research designs: systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no language restrictions. Searches were updated on a regular basis and incorporated in the guideline to May 2010. Grey (unpublished) literature was identified through searching the websites of health technology assessment (HTA) and HTA-related agencies, national and international medical specialty societies, clinical practice guideline collections, and clinical trial registries. Each article was screened for relevance and the full text acquired if determined to be relevant. The evidence obtained was reviewed and evaluated by the members of the Expert Workgroup established by the Society of Obstetricians and Gynaecologists of Canada. The quality of evidence was evaluated and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care. VALUES: the quality of evidence was rated using the criteria described by the Canadian Task Force on Preventive Health Care (Table 1). SPONSOR: the Public Health Agency of Canada and the Society of Obstetricians and Gynaecologists of Canada. ENDORSEMENT: these consensus guidelines have been endorsed by the Association of Obstetricians and Gynecologists of Quebec; the Canadian Association of Midwives; the Canadian Association of Perinatal, Women's Health and Neonatal Nurses (CAPWHN); the College of Family Physicians of Canada; the Federation of Medical Women of Canada; the Society of Rural Physicians of Canada; and Motherisk. SUMMARY STATEMENTS: 1. There is evidence that alcohol consumption in pregnancy can cause fetal harm. (II-2) There is insufficient evidence regarding fetal safety or harm at low levels of alcohol consumption in pregnancy. (III) 2. There is insufficient evidence to define any threshold for low-level drinking in pregnancy. (III) 3. Abstinence is the prudent choice for a woman who is or might become pregnant. (III) 4. Intensive culture-, gender-, and family-appropriate interventions need to be available and accessible for women with problematic drinking and/or alcohol dependence. (II-2). RECOMMENDATIONS: 1. Universal screening for alcohol consumption should be done periodically for all pregnant women and women of child-bearing age. Ideally, at-risk drinking could be identified before pregnancy, allowing for change. (II-2B) 2. Health care providers should create a safe environment for women to report alcohol consumption. (III-A) 3. The public should be informed that alcohol screening and support for women at risk is part of routine women's health care. (III-A) 4. Health care providers should be aware of the risk factors associated with alcohol use in women of reproductive age. (III-B) 5. Brief interventions are effective and should be provided by health care providers for women with at-risk drinking. (II-2B) 6. If a woman continues to use alcohol during pregnancy, harm reduction/treatment strategies should be encouraged. (II-2B) 7. Pregnant women should be given priority access to withdrawal management and treatment. (III-A) 8. Health care providers should advise women that low-level consumption of alcohol in early pregnancy is not an indication for termination of pregnancy. (II-2A).

Toward improved pregnancy labelling.

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.

Estimating the economic costs of antidepressant discontinuation during pregnancy.

OBJECTIVE: Depression is a major public health concern that results in a wide range of economic costs to people, their families, and the health care system. Our study sought to determine the direct medical costs incurred by the Ontario government owing to cessation of antidepressant therapy during pregnancy. METHODS: We conducted an economic evaluation by making assumptions based on data obtained from Statistics Canada, federal and provincial government reports, and relevant depression literature. The analysis included the number of pregnant women with depression residing in Ontario and, subsequently, the number of those women who experienced depressive relapse during pregnancy owing to discontinuation of antidepressant medication. The cost of physician services, hospitalizations, and the birth of preterm and low birth weight infants (2 adverse outcomes associated with untreated depression during pregnancy) were also taken into consideration. RESULTS: An estimated 2953 pregnant women with depression in Ontario annually discontinue antidepressant therapy and subsequently have a depressive relapse. An estimated $20 546 982 is spent annually in Ontario on untreated maternal depression in pregnancy; this is the total after subtracting the cost of risks associated with treated depression during pregnancy ($3 144 053). CONCLUSIONS: Safe treatment options for the management of depression during pregnancy should be actively explored as treated depression translates into cost savings for the Ontario government and society as a whole. Beyond this cost, depression interferes with the quality of childrearing, maternal responsiveness to infants, and other determinants essential for optimal child development.

Periconceptional folic acid supplementation: a new indication for therapeutic drug monitoring.

The role of periconceptional folic acid supplementation in the prevention of neural tube defects (NTDs) has been well established. Maternal red blood cell (RBC) folate concentration is inversely associated with NTD risk, and concentrations above 906 nmol/L are associated with a low risk of NTDs. Current guidelines call for a minimum of 0.4 mg of folic acid per day for all women who could become pregnant and higher levels of supplementation for women with a family history of NTDs or risk factors associated with NTDs. However, there is variability in supplement adherence and lack of knowledge of conditions that may elevate folate requirements or NTD risk. Therefore, guidance provided to the population as a whole may be inappropriate for individual women. Current data show that a significant proportion of women of childbearing age have RBC folate concentrations below 906 nmol/L, rendering a higher-than-baseline risk for NTDs. Therapeutic drug monitoring (TDM) of RBC folate could be used to identify these women and to help them improve their folate status, thus reducing their risk for having a child with an NTD.This review describes the evolution of the evidence for TDM of RBC folate and preliminary experience with TDM in a population of 12 women who were planning a pregnancy and who were being treated with an atypical antipsychotic.