The Pediatric Autism Research Cohort (PARC) Study: protocol for a patient-oriented prospective study examining trajectories of functioning in children with autism.

INTRODUCTION: The developmentally variable nature of autism poses challenges in providing timely services tailored to a child's needs. Despite a recent focus on longitudinal research, priority-setting initiatives with stakeholders highlighted the importance of studying a child's day-to-day functioning and social determinants of health to inform clinical care. To address this, we are conducting a pragmatic multi-site, patient-oriented longitudinal investigation: the Pediatric Autism Research Cohort (PARC) Study. In young children (<7 years of age) newly diagnosed with autism, we will: (1) examine variability in trajectories of adaptive functioning from the point of diagnosis into transition to school; and (2) identify factors associated with trajectories of adaptive functioning. METHODS AND ANALYSIS: We aim to recruit 1300 children under 7 years of age with a recent (within 12 months) diagnosis of autism from seven sites: six in Canada; one in Israel. Participants will be followed prospectively from diagnosis to age 8 years, with assessments at 6-month intervals. Parents/caregivers will complete questionnaires administered via a customized online research portal. Following each assessment timepoint, families will receive a research summary report describing their child's progress on adaptive functioning and related domains. Analysis of the longitudinal data will map trajectories and examine child, family and service characteristics associated with chronogeneity (interindividual and intraindividual heterogeneity over time) and possible trajectory turning points around sensitive periods like the transition to school. ETHICS AND DISSEMINATION: Ethics approvals have been received by all sites. All parents/respondents will provide informed consent when enrolling in the study. Using an integrated knowledge translation approach, where stakeholders are directly engaged in the research process, the PARC Study will identify factors associated with trajectories of functioning in children with autism. Resulting evidence will be shared with government policy makers to inform provincial and national programs. Findings will be disseminated at conferences and published in peer-reviewed journals.

Association of alcohol use disorder on alcohol-related cancers, diabetes, ischemic heart disease and death: a population-based, matched cohort study.

BACKGROUND AND AIMS: High-risk alcohol consumption is associated with compromised health. This study aimed to compare the incidence of alcohol-related cancers, diabetes, ischemic heart disease (IHD) and mortality between those with and without an indication of alcohol use disorder (AUD). DESIGN: Retrospective, population-based, matched cohort study using data from the Manitoba Population Research Data Repository. Rates were modeled using generalized linear models with either negative binomial distribution or Poisson distribution and a log offset of person-years to account for each person's time to follow-up. SETTING: Manitoba, Canada. PARTICIPANTS: Individuals aged ≥ 12 years with a first indication of AUD (index date) between 1 April 1990 and 31 March 2015 were matched to five controls based on age, sex and geographical region at index. This study included 53 410 individuals with AUD and 264 857 matched controls. MEASUREMENTS: Adjusted rate ratios (aRR) and 95% confidence intervals (CI) were determined for each outcome from 5 years prior to and 20 years after AUD detection. FINDINGS: Alcohol-related cancers (aRR = 4.85, 95% CI = 3.88-6.07 and aRR = 1.85, 95% CI = 1.35-2.53 for men and women, respectively), diabetes (aRR = 1.74, 95% CI = 1.50-2.02 and aRR = 2.43, 95% CI = 2.20-2.68) and IHD (aRR = 3.59, 95% CI = 3.31-3.90 and aRR = 2.92, 95% CI = 2.50-3.41) peaked in the 1 year prior to index for those with AUD compared with matched controls. All-cause mortality (aRR = 3.31, 95% CI = 3.09-3.55 and aRR =3.61, 95% CI = 3.21-4.04) was highest in the year of index and remained higher among cases compared with controls throughout the 20-year follow-up. CONCLUSION: People with alcohol use disorder appear to have higher rates of adverse health outcomes in the year before alcohol use disorder recognition, and death at the time of alcohol use disorder recognition, compared with matched controls.

Use of pharmacotherapy for alcohol use disorder in Manitoba, Canada: A whole-population cohort study.

OBJECTIVE: Update the evidence on use of pharmacotherapy for alcohol use disorder in a Canadian population. METHODS: Using whole-population administrative data from Manitoba, Canada, we identified all residents age 12+ who were first diagnosed with alcohol use disorder between April 1, 1996 and March 31, 2015, and compared characteristics of those who filled a prescription for naltrexone, acamprosate or disulfiram at least once during that period to those who did not fill a prescription for an alcohol use disorder medication. RESULTS: Only 1.3% of individuals with alcohol use disorder received pharmacotherapy (62.3% of prescriptions were for naltrexone, 39.4% for acamprosate, 7.5% for disulfiram). Most prescriptions came from family physicians in urban alcohol use disorder (53.6%) and psychiatrists (22.3%). Individuals were more likely to fill a prescription for alcohol use disorder medication if they lived in an urban vs rural environment (OR 2.25; 95% CI 1.83-2.77) or had a mood/anxiety disorder diagnosis vs no diagnosis (OR 2.40, 95% CI 1.98-2.90) in the five years before being diagnosed with alcohol use disorder. CONCLUSION: Despite established evidence for the effectiveness of pharmacotherapy for alcohol use disorder, these medications continue to be profoundly underutilized in Canada.

Health service use among Manitobans with alcohol use disorder: a population-based matched cohort study.

BACKGROUND: Alcohol is the drug most commonly used by Canadians, with multiple impacts on health and health service use. We examined patterns of short- and long-term health service use among people with a diagnosis of alcohol use disorder. METHODS: In this retrospective matched cohort study, we used population-based administrative data from the province of Manitoba, Canada, to identify individuals aged 12 years or older with a first indication of alcohol use disorder (index date) in the period 1990 to 2015. We matched cases (those with diagnosis of alcohol use disorder) to controls (those without this diagnosis), at a 1:5 ratio, on the basis of age, sex, geographic region and income quintile at the index date. The outcome measures were inpatient hospital admission, outpatient physician visits, emergency department visits and use of prescription medications. We modelled crude rates using generalized estimating equations with either a negative binomial or a Poisson distribution RESULTS: We identified 53 410 people with alcohol use disorder and 264 857 matched controls. All outcomes occurred at a higher rate among people with the disorder than among controls. For example, during the year of diagnosis, the rate ratio for hospital admission was 4.0 (95% confidence interval [CI] 3.9-4.2) for women and 4.5 (95% CI 4.4-4.7) for men. All rates of health service use peaked close to the index date, but remained significantly higher among people with alcohol use disorder than among controls for 20 years. Among people with alcohol use disorder, the most commonly filled prescriptions were for psycholeptics, whereas among controls, the most commonly filled prescriptions were for sex hormones (women) and antihypertensives (men). INTERPRETATION: Compared with controls, people with alcohol use disorder used significantly more health services from the time of diagnosis and over the next 20 years. This finding highlights the need for better detection and early intervention to reduce the need for acute and emergency care, as well as the need for improved management of alcohol use disorder over the longer term.

In Utero Antidepressants and Neurodevelopmental Outcomes in Kindergarteners.

OBJECTIVES: To determine if in utero selective serotonin reuptake inhibitor (SSRI) or selective serotonin norepinephrine inhibitor (SNRI) exposure is associated with developmental vulnerability in kindergarten among children whose mothers were diagnosed with prenatal mood or anxiety disorder. METHODS: Linkable administrative data were used to create a population-based cohort of 266 479 mother-child dyads of children born in Manitoba, Canada, between 1996 and 2014, with follow-up through 2015. The sample was restricted to mothers who had a mood or anxiety disorder diagnosis between 90 days before conception (N = 13 818). Exposed women had ≥2 SSRI or SNRI dispensations during pregnancy (n = 2055); unexposed mothers did not have a dispensation of an SSRI or SNRI during pregnancy (n = 10 017). The Early Development Instrument (EDI) was used to assess developmental health in kindergarten children. The EDI is a 104-component kindergarten teacher-administered questionnaire, encompassing 5 developmental domains. RESULTS: Of the 3048 children included in the study who met inclusion criteria and had an EDI, 21.43% of children in the exposed group were assessed as vulnerable on 2 or more domains versus 16.16% of children in the unexposed group (adjusted odds ratio = 1.43; 95% confidence interval 1.08-1.90). Children in the exposed group also had a significant risk of being vulnerable in language and/or cognition (adjusted odds ratio = 1.40; 95% confidence interval 1.03-1.90). CONCLUSIONS: Exposure to SSRIs or SNRIs during pregnancy was associated with an increased risk of developmental vulnerability and an increased risk of deficits in language and/or cognition. Replication of results is necessary before clinical implications can be reached.

Making Contributions and Defining Success: An eDelphi Study of the Inaugural Cohort of CIHR Health System Impact Fellows, Host Supervisors and Academic Supervisors.

CONTEXT: The Health System Impact (HSI) Fellowship, an innovative training program developed by the Canadian Institutes of Health Research's Institute of Health Services and Policy Research, provides PhD-trained health researchers with an embedded, experiential learning opportunity within a health system organization. METHODS/DESIGN: An electronic Delphi (eDelphi) study was conducted to: (1) identify the criteria used to define success in the program and (2) elucidate the main contributions fellows made to their organizations. Through an iterative, two-round eDelphi process, perspectives were elicited from three stakeholder groups in the inaugural cohort of the HSI Fellowship: HSI fellows, host supervisors and academic supervisors. DISCUSSION: A consensus was reached on many criteria of success for an embedded research fellowship and on several perceived contributions of the fellows to their host organization and academic institutions. This work begins to identify specific criteria for success in the fellowship that can be used to improve future iterations of the program.

Prenatal care of women who give birth to children with fetal alcohol spectrum disorder in a universal health care system: a case-control study using linked administrative data.

BACKGROUND: Few studies have investigated prenatal care use among women who use alcohol during pregnancy. The objective of this study was to investigate rates of prenatal care usage of women who have given birth to children with fetal alcohol spectrum disorder (FASD). METHODS: We conducted a case-control study of women with children born in Manitoba between Apr. 1, 1984, and Mar. 31, 2012, with follow-up until 2013, using linkable administrative data. The study group included women whose child(ren) was (were) diagnosed with FASD (n = 702) between Apr. 1, 1999, and Mar. 31, 2012, at a centralized diagnostic clinic. The comparison group included women whose child(ren) did not have an FASD diagnosis (n = 2097), exact matched on the index child's birthdate, postal code and socioeconomic status. Adequacy of prenatal care was defined using the Revised Graduated Prenatal Care Utilization Index. RESULTS: Women in the study group had lower socioeconomic status than women in the comparison group and were more likely to have mental disorders and involvement with the child welfare system. Rates of inadequate prenatal care were higher among women in the study group (adjusted relative risk 2.47, 95% confidence interval [CI] 2.08-2.94), as were rates of no prenatal care (adjusted relative risk 3.55, 95% CI 2.42-5.22). In the study group, 41% of women accessed inadequate or no prenatal care, and 59% received intermediate, adequate or intensive prenatal care. INTERPRETATION: Women who give birth to children with FASD have higher rates of inadequate prenatal care and significant social complexities. Socioeconomic disparities in the use of prenatal care should be addressed; multisector interventions are needed that facilitate the uptake of prenatal care by high-risk women who use alcohol.

Health, Social, Education, and Justice Outcomes of Manitoba First Nations Children Diagnosed with Fetal Alcohol Spectrum Disorder: A Population-Based Cohort Study of Linked Administrative Data.

OBJECTIVE: To examine health services, social services, education, and justice system outcomes among First Nations children and youth with fetal alcohol spectrum disorder (FASD). METHODS: In this retrospective cohort study, health and social services, education, and justice data were linked with clinical records on First Nations (FN) individuals aged 1 to 25 and diagnosed with FASD between 1999 and 2010 (n = 743). We compared the FN FASD group to non-FN individuals with FASD (non-FN FASD; n = 315) and to First Nations individuals (matched on age, sex, and income) not diagnosed with FASD (FN non-FASD; n = 2229). Rates and relative risks (RRs) were calculated using generalized linear models. RESULTS: FN FASD individuals had similar health services use to non-FN FASD individuals but had greater involvement with child welfare (RR, 1.20; 95% confidence interval [CI], 1.02 to 1.41) and the justice system (RR, 1.37; 95% CI, 1.07 to 1.74) and were more likely to be charged with a crime (RR, 1.40; 95% CI, 1.05 to 1.86). There were no suicides/suicide attempts among the non-FN FASD individuals during the study, but the crude rate/100 person-years of suicides among FN FASD individuals (0.22 for females; 1.06 for males) was substantially higher than for FN non-FASD individuals (0.08 for females; 0.32 for males). There were no significant differences between groups in the education outcomes we measured. CONCLUSIONS: Young people with FASD are at risk for poor health, education, and social outcomes, but First Nations young people with FASD face comparably higher risks, particularly with child welfare and justice system involvement. The study emphasizes a critical need for appropriate resources for First Nations children with FASD.

Sex ratios at birth among second-generation mothers of South Asian ethnicity in Ontario, Canada: a retrospective population-based cohort study.

BACKGROUND: Son-biased sex ratios at birth (M:F), an extreme manifestation of son preference, are predominately found in East and South Asia. Studies have examined sex ratios among first-generation migrants from these regions, but few have examined second-generation descendants. Our objective was to determine whether son-biased sex ratios persist among second-generation mothers with South Asian ethnicity in Ontario, Canada. METHODOLOGY: A surname algorithm identified a population-based cohort of mothers with South Asian ethnicity who gave birth in Ontario between 1993 and 2014 (n=59 659). Linking to official immigration data identified births to first-generation mothers (ie, immigrants). Births not to immigrants were designated as being to second-generation mothers (ie, born in Canada) (n=10 273). Sex ratios and 95% CI were stratified by the sex of previous live births and by whether it was preceded by ≥1 abortion for both first-generation and second-generation mothers. RESULTS: Among mothers with two previous daughters and at least one prior abortion since the second birth, both second-generation mothers and first-generation mothers had elevated sex ratios at the third birth (2.80 (95% CI 1.36 to 5.76) and 2.46 (95% CI 1.93 to 3.12), respectively). However, among mothers with no prior abortion, second-generation mothers had a normal sex ratio, while first-generation mothers gave birth to 142 boys for every 100 girls (95% CI 125 to 162 boys for every 100 girls). CONCLUSION: Son preference persists among second-generation mothers of South Asian ethnicity. Culturally sensitive and community-driven gender equity interventions are needed.

The Cycle of Child Protection Services Involvement: A Cohort Study of Adolescent Mothers.

OBJECTIVES: To determine if adolescent mothers who were in the care of child protection services (CPS) when they gave birth to their first child are more likely to have that child taken into CPS care before the child's second birthday than adolescent mothers who were not in the care of CPS. METHODS: Linkable administrative data were used to create a population-based cohort of adolescent mothers whose first child was born in Manitoba, Canada between April 1, 1998, and March 31, 2013 (n = 5942). Adjusted odds ratios (aOR) of having that first child taken into care before their second birthday were compared between mothers who were in care (n = 576) and mothers who were not in care (n = 5366) at the birth of their child by using logistic regression models. RESULTS: Adolescent mothers who were in care had greater odds of having their child taken into care before the child's second birthday (aOR = 7.53; 95% confidence interval [CI] = 6.19-9.14). Specifically, their children had higher odds of being taken into care in their first week of life (aOR = 11.64; 95% CI = 8.83-15.34), between 1 week and their first birthday (aOR = 3.63; 95% CI = 2.79-4.71), and between their first and second birthday (aOR = 2.21; 95% CIl = 1.53-3.19). CONCLUSIONS: Findings support an intergenerational cycle of involvement with CPS. More and better services are required for adolescent mothers who give birth while in care of CPS.

Effectiveness of evidence-based treatments of fetal alcohol spectrum disorders in children and adolescents: a systematic review protocol.

INTRODUCTION: The aim of this paper is to provide a protocol for a systematic review assessing the effectiveness of evidence from randomised controlled trials comparing fetal alcohol spectrum disorders pharmacological and non-pharmacological interventions with placebo/dummy interventions or usual standards of care in children and adolescents (<18 years old). METHODS AND ANALYSIS: The following electronic databases will be searched: Medline (Ovid), Cumulative Index of Nursing and Allied Health Plus with Full text (EBSCO), Cochrane Central Register of Controlled Trials (Cochrane Library-Wiley), PsycINFO (ProQuest) and Proquest DissertationsandTheses will be searched from inception to March 2017 for relevant citations of published trials using individualised search strategies prepared for database. We will also search the reference lists of relevant articles and conference proceedings. Two reviewers will independently assess each study against predetermined inclusion/exclusion criteria and extract data including population characteristics, types and duration of interventions and outcomes from included trials. Internal validity will be assessed using the Cochrane Risk of Bias Tool. Primary outcome measures will be improvements in symptoms, including: hyperactivity, impulsivity and attention as measured by standard rating scales. Secondary outcome measures will include improvements in physical and mental health domains, as well as cognitive, behavioural, social and educational skills as measured by rating scales, standardised psychometric tests of IQ and memory, grade repetition, literacy tests and diagnosis of mental health disorder. ETHICS AND DISSEMINATION: Ethical approval will not be obtained since it is not required for systematic reviews as there are no concerns regarding patient privacy. The results of this review will be disseminated through publication in a peer-review journal and presented at relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42013005996.

Suicide Attempts and Completions among Mothers Whose Children Were Taken into Care by Child Protection Services: A Cohort Study Using Linkable Administrative Data.

OBJECTIVE: The objective of this study is to examine suicide attempts and completions among mothers who had a child taken into care by child protection services (CPS). These mothers were compared with their biological sisters who did not have a child taken into care and with mothers who received services from CPS but did not have a child taken into care. METHODS: A retrospective cohort of mothers whose first child was born in Manitoba, Canada, between April 1, 1992, and March 31, 2015, is used. Rates among discordant biological sisters (1872 families) were compared using fixed-effects Poisson regression models, and mothers involved with CPS (children in care [ n = 1872] and received services [ n = 9590]) were compared using a Poisson regression model. RESULTS: Compared with their biological sisters and mothers who received services, the adjusted incidence rate ratio (aIRR) of death by suicide was greater among mothers whose child was taken into care by CPS (aIRR = 4.46 [95% confidence interval (CI), 1.39-14.33] and ARR = 3.45 [95% CI, 1.61-7.40], respectively). Incidence rates of suicide attempts were higher among mothers with a child taken into care compared with their sisters (aIRR = 2.15; 95% CI, 1.40-3.30) and mothers receiving services (aIRR = 2.82; 95% CI, 2.03-3.92). CONCLUSIONS: Mothers who had a child taken into care had significantly higher rates of suicide attempts and completions. When children are taken into care, physician and social workers should inquire about maternal suicidal behaviour and provide appropriate mental health.

Suicide and suicide attempts among women in the Manitoba Mothers and Fetal Alcohol Spectrum Disorder cohort: a retrospective matched analysis using linked administrative data.

BACKGROUND: Women who give birth to children with fetal alcohol spectrum disorder (FASD) may be at increased risk for suicide; however, there are few data in this area. The objective of this study was to compare rates of suicide between women who had given birth to children with FASD and women who had not given birth to children with FASD during critical periods in their lives, including before pregnancy, during pregnancy, during the postpartum period (maternal death) and until the end of the study period. METHODS: We conducted a retrospective cohort analysis of women with children born in Manitoba between Apr. 1, 1984, and Mar. 31, 2012 in whom FASD was diagnosed between Apr. 1, 1999, and Mar. 31, 2012, with follow-up until Dec. 1, 2013 (FASD group; n = 702). We generated a comparison group of women who had not given birth to children with FASD (n = 2097), matched up to 1:3 on date of birth of the index child, socioeconomic status and region of residence. We used linked administrative data to investigate suicide attempt and completion rates in the 2 groups. Regression modelling produced relative rates (RRs) adjusted for socioeconomic status and age at birth of the index child and was used to assess suicide risk. RESULTS: The 2799 participants produced 40 390.21 person-years until the end of the study period. Compared to the comparison group, the FASD group had higher rates of suicide completion (adjusted RR 6.20 [95% confidence interval (CI) 2.36-16.31]), a higher number of women who attempted suicide after the postpartum period until the end of the study period (adjusted RR 4.62 [95% CI 2.53-8.43]) and a higher number of attempts after the postpartum period until the end of the study period (adjusted RR 3.92 [95% CI 2.30-6.09]). INTERPRETATION: This study identified a group of women with increased rates of social complexities, mental disorders and alcohol use, which places them at risk for suicide. Interventions are needed that screen for suicidal behaviour in women who are at high risk to consume alcohol during pregnancy and have mental disorders.

The Psychiatric Morbidity of Women Who Give Birth to Children with Fetal Alcohol Spectrum Disorder (FASD): Results of the Manitoba Mothers and FASD Study.

OBJECTIVE: To investigate differences in physician-diagnosed psychiatric disorders between women who gave birth to children with a fetal alcohol spectrum disorder (FASD) diagnosis (study group) compared to women who gave birth to children without FASD (comparison group). METHODS: We linked population-level health and social services data to clinical data on FASD diagnoses to identify study group ( n = 702) and comparison group ( n = 2097) women matched 1:3 on date of birth of index child, region of residence, and socioeconomic status. Regression modeling produced relative rates (RRs) for outcomes. RESULTS: Mothers who gave birth to children with FASD had higher adjusted rates of substance use disorder (RR, 12.65; 95% confidence interval [CI], 8.99-17.80), personality disorder (RR, 12.93; 95% CI, 4.88-34.22), and mood and anxiety disorders (RR, 1.75; 95% CI, 1.49-2.07) before the pregnancy of the child. These mothers also had higher adjusted rates of maternal psychological distress during pregnancy (RR, 5.35; 95% CI, 4.58-6.35) and higher rates of postpartum psychological distress (RR, 1.71; 95% CI, 1.53-1.90). These women also had higher adjusted rates for antidepressant prescriptions before, during, and after the pregnancy. CONCLUSIONS: A significant psychiatric burden exists for women giving birth to children with FASD. Clinicians should recognise the high rates of psychiatric concerns facing mothers who give birth to children with FASD and should offer treatment and support to these women to improve their health and well-being and prevent further alcohol-exposed pregnancies.

Sex determination from mesiodens of Indian children by amelogenin gene.

CONTEXT: The identification of sex is the first and the foremost step in forensic science. Teeth consist of enamel which is the hardest tissue available in the body, protector of DNA presents in pulp tissue at the time of exposure of tooth to adverse conditions. Teeth can be stated as a sealed box of mystery as it contains various human and bacterial DNA for molecular utilization. AIM AND OBJECTIVE: The aim is to determine sex from mesiodens on the basis of gene identification by the polymerase chain reaction (PCR). SETTINGS AND DESIGN: Total number of sample was 8 human-extracted mesiodens. DNA was isolated and was subjected to PCR analysis with use of predesigned primers for amelogenin (AMEL) X and AMEL Y genes. RESULTS: Isolation of genomic and mitochondrial DNA from mesiodens was successful in six samples (75%). In samples, quantity of DNA present was also calculated. CONCLUSION: Mesiodens are a good source of DNA and are a very useful tool in identification of sex using PCR analysis which was simple and effective. Hence, the procedure presented in the present study can be applied for extraction of DNA and identification of sex for forensic purpose.

Current and Future Status of Extracorporeal Cardiopulmonary Resuscitation for In-Hospital Cardiac Arrest.

Numerous series, propensity-matched trials, and meta-analyses suggest that appropriate use of extracorporeal cardiopulmonary resuscitation (E-CPR) for in-hospital cardiac arrest (IHCA) can be lifesaving. Even with an antecedent cardiopulmonary resuscitation (CPR) duration in excess of 45 minutes, 30-day survival with favourable neurologic outcome using E-CPR is approximately 35%-45%. Survival may be related to age, duration of CPR, or etiology. Associated complications include sepsis, renal failure, limb and neurologic complications, hemorrhage, and thrombosis. However, methodological biases-including small sample size, selection bias, publication bias, and inability to control for confounders-in these series prevent definitive conclusions. As such, the 2015 American Heart Association Advanced Cardiac Life Support guidelines update recommended E-CPR as a Level of Evidence IIb recommendation in appropriate cases. The absence of high-quality evidence presents an opportunity for clinician/scientists to generate practice-defining data through collaborative investigation and prospective trials. A multidisciplinary dialogue is required to standardize the field and promote multicentre investigation of E-CPR with data sharing and the development of a foundation for high-quality trials. The objectives of this review are to (1) provide an overview of the strengths and limitations of currently available studies investigating the use of E-CPR in patients with IHCA and highlight knowledge gaps; (2) create a framework for the standardization of terminology, clinical practice, data collection, and investigation of E-CPR for patients with IHCA that will help ensure congruence in future work in this area; and (3) propose suggestions to guide future research by the cardiovascular community to advance this important field.

Neonatal and childhood neurodevelopmental, health and educational outcomes of children exposed to antidepressants and maternal depression during pregnancy: protocol for a retrospective population-based cohort study using linked administrative data.

INTRODUCTION: Antidepressants are commonly prescribed during pregnancy; however, there are inconsistent data on the safety of these medications during the prenatal period. To address this gap, this study will investigate short-term and long-term neurodevelopmental, physical and mental health, and educational outcomes of children who have been exposed to selective serotonin reuptake inhibitors (SSRIs) or selective serotonin norepinephrine reuptake inhibitors (SNRIs) and/or maternal depression during pregnancy. METHODS AND ANALYSIS: Administrative data will be linked to generate 4 population-based exposed groups from all children born in Manitoba between 1996 and 2014 whose mother had at least 2 prescriptions for either an SSRI or SNRI: (1) throughout the prenatal period (beginning of pregnancy until birth); (2) in the first trimester (≤14 weeks gestation); (3) in the second trimester (15-26 weeks gestation); (4) in the third trimester (≥27 weeks gestation) and 1 population-based unexposed group consisting of children whose mothers had a diagnosis of mood or anxiety disorder during pregnancy but did not use antidepressants. Propensity scores and inverse probability treatment weights will be used to adjust for confounding. Multivariate regression modelling will determine whether, compared with untreated mood/anxiety disorder, prenatal exposure to antidepressant medications is associated with: (1) adverse birth and neonatal outcomes, including: preterm birth, low birth weight, low Apgar scores, respiratory distress, congenital malformations and persistent pulmonary hypertension; (2) adverse early childhood outcomes, including: early childhood education challenges, diagnosis of neurodevelopmental disorders and diagnosis of mental disorders. We will determine if exposure effects differ between SSRIs and SRNIs, and determine if exposure effects differ between gestation timing of exposure to antidepressants. ETHICS AND DISSEMINATION: Ethical approval was obtained from the University of Manitoba Health Research Ethics Board. Dissemination of results will include engagement of stakeholders and patients, writing of reports for policymakers and patients, and publication of scientific papers.

Manitoba mothers and fetal alcohol spectrum disorders study (MBMomsFASD): protocol for a population-based cohort study using linked administrative data.

INTRODUCTION: Fetal alcohol spectrum disorder (FASD) is a significant public health concern. To prevent FASD, factors that place women at risk for giving birth to children with FASD must be investigated; however, there are little data in this area. This paper describes the development of the Manitoba mothers and FASD study, a retrospective cohort of mothers whose children were diagnosed with FASD, generated to investigate: (1) risk factors associated with giving birth to children with FASD; (2) maternal physical and health outcomes, as well as the usage of health and social services. METHODS: The study population will be identified by linking children diagnosed with FASD from a provincially centralised FASD assessment clinic (from 31 March 1999 to 31 March 2012) to their birth mothers using de-identified administrative health data housed at the Manitoba Centre for Health Policy. Preliminary analysis has identified over 700 mothers, which is the largest sample size in this field to date. A comparison cohort of women with children who did not have an FASD diagnosis matched on the region of residence, date of birth of child with FASD and socioeconomic status will be generated to compare exposures and outcomes. Potential demographic, socioeconomic, family history, and physical and mental health risk factors will be investigated by linking a range of health and social databases, furthering insight into the root causes of drinking during pregnancy. The longitudinal data will allow us to document the usage patterns of healthcare and social services throughout significant periods in these women's lives to identify opportunities for prevention. ETHICS AND DISSEMINATION: Ethical approval has been obtained by the University of Manitoba's Health Research Ethics Board and the Manitoba Health Information Privacy Committee. Dissemination of study results will include engagement of stakeholders and policymakers through presentations and reports for policymakers, in parallel with scientific papers.

An Immature Type II Dens Invaginatus in a Mandibular Lateral Incisor with Talon's Cusp: A Clinical Dilemma to Confront.

Dens invaginatus (DI) is a malformation of teeth probably resulting from an infolding of the dental papilla during tooth development. DI is classified as type I, II, and III by Oehlers depending on the severity of malformation. The maxillary lateral incisor is the most commonly affected tooth. Structural defects do exist in the depth of the invagination pits, and as a consequence, the early development of caries and the subsequent necrosis of the dental pulp, as well as abscess and cyst formation are clinical implications associated with DI. Occasionally, we can see more than one developmental anomaly occurring in a single tooth. In such cases it becomes important to identify the anomalies and initiate a proper treatment plan for good prognosis. In this paper, an unusual case of DI which clinically presented as a huge talons cusp affecting a mandibular lateral incisor tooth is described. This case report illustrates grinding of the talons cusp followed by nonsurgical endodontic management of dens invaginatus type II with an immature apex and periapical lesions, in which Mineral Trioxide Aggregate (MTA) shows a complete periapical healing with bone formation at the site of the lesions.