Time trends, geographic variation and risk factors for gastroschisis in Canada: A population-based cohort study 2006-2017.

BACKGROUND: Previous studies showed increases in rates of gastroschisis in Canada in the first decade of the 21st century. OBJECTIVE: We sought to examine the epidemiologic characteristics of gastroschisis in Canada in recent years. METHODS: We conducted a retrospective population-based cohort study of all livebirths and stillbirths delivered in Canada (excluding Quebec) from 2006 to 2017, with information obtained from the Canadian Institute for Health Information. Gastroschisis rates by maternal age, region of residence, and maternal and infant characteristics were quantified using prevalence rate ratios (RR) and 95% confidence intervals (CI). Log-binomial regression was used to quantify the associations between risk factors and gastroschisis. RESULTS: There were 1314 gastroschisis cases among 3 364 116 births. The prevalence rate was 3.7 per 10 000 total births in 2006 and 3.4 per 10 000 total births in 2017, with substantial annual variation in rates. The proportion of mothers aged 20-24 years decreased from 16.5% in 2006 to 11.3% in 2017, while the proportion of mothers aged <20 years halved from 4.8% to 2.3%. The prevalence of gastroschisis at birth remained unchanged among mothers aged <20, 20-24 and 30-49 years but increased among mothers aged 25-29 years. The age-adjusted prevalence rate of gastroschisis increased across the period (for 2016-2017 versus 2006-2007 rate ratio [RR] 1.28, 95% CI 1.05, 1.56), and there was substantial regional variation. Risk factors included problematic use of substances (RR 2.61, 95% CI 2.01, 3.39) and hypothyroidism (RR 2.76, 95% CI 1.56, 4.88). There was a North-to-South difference in gastroschisis prevalence (adjusted RR Far North compared with South 1.54, 95% CI 1.11, 2.15). CONCLUSION: Gastroschisis birth prevalence rates in Canada have stabilised in recent years compared with the increase documented previously. The substantial geographic variation and North-to-South difference in gastroschisis prevalence may indicate variation in socio-economic status, lifestyle and nutritional patterns.

InSAR surface deformation and numeric modeling unravel an active salt diapir in southern Romania.

Salt diapirism is often associated with potential hydrocarbon energy resources, and detecting active diapirs can strongly affect the prospect to discover new gas and oilfields. Here we use InSAR techniques as a proxy to evaluate surface deformation in the Diapiric Fold Zone located in the East Carpathians Bend. Significant surface uplift (~ 5 mm/year) is identified in a relatively small region not previously known for the presence of an actively rising salt diapir. Using high-resolution two-dimensional thermomechanical numerical simulations of salt diapirs intrusions, we show that that the observed surface deformation can be induced by a relatively small salt diapir (1-2 km in diameter) rising from an initial salt layer located at < 7 km depth. We constrain the salt diapir viscosity by comparing the InSAR surface deformation pattern with results from numerical simulations and our best fitting model is obtained for a salt viscosity of 1 × 1017 Pa s. The best fitting model reveals the presence of a relatively small salt diapir that has not pierced yet the entire sedimentary layer and is located just 1-2 km below the surface.

Opioid and Cannabis Use During Pregnancy and Breastfeeding in Relation to Sociodemographics and Mental Health Status: A Descriptive Study.

OBJECTIVE: This study of Canadian women estimates the prevalence of opioid and cannabis use during pregnancy and cannabis use during the breastfeeding period and explores the sociodemographic and mental health characteristics associated with use. METHODS: A total of 13 000 women who gave birth between January and June 2018 were invited to participate in the Survey on Maternal Health by Statistics Canada; 7111 women participated for a response rate of 54.7%. Participants were asked about their mental health, supports during pregnancy, and substance use. Multivariable logistic regression was used to describe the relationship between sociodemographic and mental health characteristics and substance use during pregnancy and while breastfeeding. RESULTS: The prevalence of self-reported opioid use during pregnancy was 1.4% (95% confidence interval [CI] 1.1%-1.8%). A higher proportion of women reported using cannabis during pregnancy and while breastfeeding, at 3.1% (95% CI 2.5%-3.6%) and 2.6% (95% CI 2.1%-3.1%), respectively. Younger age, not being in a relationship, lower level of education, and thoughts of self-harm were significantly associated with cannabis use during pregnancy. Lower level of education and thoughts of self-harm were also significantly associated with cannabis use while breastfeeding, as were symptoms of postpartum depression and/or generalized anxiety. Lower level of education and symptoms of postpartum depression and/or generalized anxiety were also significantly associated with opioid use during pregnancy. CONCLUSION: The results of this survey show relatively low levels of opioid and cannabis use during pregnancy and cannabis use while breastfeeding in Canada. Different sociodemographic and mental health characteristics are associated with the use of these substances, and public health interventions and policies should take into account these factors.

Symptoms of postpartum anxiety and depression among women in Canada: findings from a national cross-sectional survey.

OBJECTIVE: This study presents national estimates on symptoms consistent with postpartum anxiety (PPA) and postpartum depression (PPD) and the association between these conditions and possible risk and protective factors in women who gave birth in Canada. METHODS: Data were collected through the Survey on Maternal Health, a cross-sectional survey administered in Canada's ten provinces between November 2018 and February 2019 among women who gave birth between January 1 and June 30, 2018. A total of 6558 respondents were included. Weighted prevalence estimates were calculated, and logistic regression was used to model the relationship between symptoms consistent with PPA, PPD, and potential risk factors. RESULTS: Overall, 13.8% of women had symptoms consistent with PPA, while the prevalence of having symptoms consistent with PPD was 17.9%. Results of the logistic regression models indicated that women who had a history of depression were 3.4 times (95% CI 2.7-4.2) more likely to experience symptoms consistent with PPA and 2.6 times more likely to experience symptoms consistent with PPD (95% CI 2.2-3.2) compared with those who did not. Women who reported good, fair, or poor physical health were 2.4 times more likely to experience symptoms consistent with PPD (95% CI 2.0-2.9) and 2.0 times more likely to experience symptoms consistent with PPA (95% CI 1.7-2.4) compared with those who reported very good or excellent health. Maternal marital status, other postpartum maternal support, and sense of community belonging were also significant. CONCLUSION: This study highlights that a history of depression and good, fair, or poor physical health are associated with an increased odds of symptoms consistent with PPA and PPD, while other maternal support and sense of community belonging are associated with a decreased odds of these conditions.

RéSUMé: OBJECTIF: La présente étude présente des estimations nationales sur les symptômes correspondant à de l'anxiété post-partum (APP) et à une dépression post-partum (DPP) et sur l'association entre ces affections et les éventuels facteurs de risque et de protection chez les femmes ayant accouché au Canada. MéTHODOLOGIE: Les données ont été recueillies dans le cadre de l'Enquête sur la santé maternelle, une enquête transversale menée dans les dix provinces canadiennes entre novembre 2018 et février 2019 auprès des femmes ayant accouché entre le 1er janvier et le 30 juin 2018. Au total, 6 558 personnes ont répondu à l'enquête. Des estimations de la prévalence pondérée ont été calculées, et une régression logistique a été utilisée pour modéliser la relation entre les symptômes correspondant à de l'APP, à une DPP et aux facteurs de risque possibles. RéSULTATS: Dans l'ensemble, 13,8 % des femmes présentaient des symptômes compatibles avec de l'APP, tandis que la prévalence des symptômes compatibles avec une DPP était de 17,9 %. Les résultats des modèles de régression logistique ont indiqué que les femmes ayant des antécédents de dépression étaient 3,4 fois (IC à 95 % : 2,7 à 4,2) plus susceptibles de présenter des symptômes compatibles avec de l'APP et 2,6 fois plus susceptibles de présenter des symptômes compatibles avec une DPP (IC à 95 % : 2,2 à 3,2) par rapport à celles qui n'en avaient pas. Les femmes qui ont déclaré être en bonne, moyenne ou mauvaise santé physique étaient 2,4 fois plus susceptibles d'éprouver des symptômes correspondant à une DPP (IC à 95 % : 2,0 à 2,9) et 2,0 fois plus susceptibles d'éprouver des symptômes correspondant à de l'APP (IC à 95 % : 1,7 à 2,4) par rapport à celles qui ont déclaré être en très bonne ou en excellente santé. L'état matrimonial de la mère, les autres formes de soutien maternel post-partum et le sentiment d'appartenance à la collectivité étaient également significatifs. CONCLUSION: Cette étude souligne que des antécédents de dépression et une bonne, moyenne ou mauvaise santé physique sont associés à une augmentation de la probabilité de symptômes correspondant à de l'APP et à une DPP, tandis que d'autres formes de soutien maternel et le sentiment d'appartenance à la collectivité sont associés à une diminution de la probabilité de ces affections.

Substance use and related harms in the context of COVID-19: a conceptual model. / Consommation de substances et méfaits connexes dans le contexte de la COVID-19 : un modèle conceptuel.

As the effects of COVID-19 have been unfolding, growing attention has been paid to the intersection of COVID-19 and substance use and the related harms. However, there are few theories and little empirical evidence to guide investigations in this area. To advance this emerging area of inquiry, we present a conceptual model that synthesizes evidence, information and knowledge on substance use and related harms in the context of the pandemic. The conceptual model offers a visual representation of the connections between the pandemic and substance use and related harms, and can be used to identify areas for future research.

As of June 2020, substance use and related harms in the context of a pandemic remained largely uninvestigated. The COVID-19 pandemic may impact how Canadians use substances and may present specific challenges and harms among people who use substances. The conceptual model in this paper offers a synthesis of evidence, information and knowledge of the concepts and associations relevant to substance use and harms in the context of the pandemic. Relevant concepts were synthesized into five interrelated domains that can be used to identify areas for future research into substance use and related harms in the context of COVID-19: substance use as a means of coping; changes in social support and networks; availability and accessibility of services; increased risk of COVID-19 transmission among people who use substances; and increased risk of severe outcomes.

En juin 2020, la consommation de substances et les méfaits connexes dans le contexte de la pandémie restaient largement inexplorés. La pandémie de COVID-19 peut avoir une incidence sur la façon dont les Canadiens consomment des substances, ce qui pourrait entraîner des défis et des méfaits particuliers chez ces personnes. Le modèle conceptuel présenté dans le présent document offre une synthèse des données probantes, de l'information et des connaissances sur les concepts et les associations relatifs à la consommation de substances et aux méfaits dans le contexte de la pandémie. Les concepts pertinents ont été synthétisés en cinq domaines interreliés qui peuvent être utilisés pour déterminer les futurs domaines de recherche sur la consommation de substances et les méfaits connexes dans le contexte de la COVID-19, soit la consommation de substances comme stratégie d'adaptation, les changements relatifs au soutien social et aux réseaux; la disponibilité et l'accessibilité des services; le risque accru de transmission de la COVID-19 chez les personnes qui consomment des substances; et le risque accru de conséquences graves.

Prevalence of Positive Mental Health and Associated Factors Among Postpartum Women in Canada: Findings from a National Cross-Sectional Survey.

OBJECTIVES: The objectives of this study were to compare the prevalence of three positive mental health (PMH) outcomes (self-rated mental health, life satisfaction, sense of community belonging) in postpartum women to the general population, and to examine the relationship between protective factors and the three PMH outcomes among postpartum women. METHODS: The national cross-sectional Survey on Maternal Health (n = 6558) was analyzed. Analyses were weighted and 95% confidence intervals were calculated. Three adjusted logistic regression models were generated. To compare this sample to the general population of women, estimates from the Canadian Community Health Survey-Annual Component (2018) were used. RESULTS: Compared to the general population of women, a larger proportion of postpartum women reported a strong sense of community belonging. The odds of postpartum women with high self-rated physical health having high self-rated mental health were approximately seven times greater (aOR 6.9, 95% confidence interval [CI] 5.9, 8.1) than postpartum women with lower self-rated physical health. The absence of symptoms of postpartum depression (PPD) or generalized anxiety disorder (GAD) and high self-rated physical health were significantly associated with all three PMH outcomes. Frequent availability of maternal support was associated with greater odds of high life satisfaction (aOR 1.6, 95% CI 1.4, 1.9) and sense of community belonging (aOR 1.4, 95% CI 1.2, 1.6). CONCLUSIONS: Our study demonstrated that availability of maternal support, self-rated physical health and absence of symptoms of PPD or GAD were associated with PMH among postpartum women. As physical health had the strongest association with mental health, we encourage further examination of this relationship.

Identification of Biological Hazards in Produce Consumed in Industrialized Countries: A Review.

Microbial contamination of fresh produce (fresh fruits and vegetables) poses serious public health concerns worldwide. This study was conducted as a comprehensive analysis of biological hazards in the global fresh produce chain. Data about produce-related outbreaks and illness were collected from the annual reports and databases of foodborne outbreak surveillance systems in different regions and countries from 2010 to 2015. The global patterns of and regional differences in documented outbreaks and cases were analyzed, and produce commodities and pathogens of greatest concern were identified. Data on sporadic illnesses were also collected through a comprehensive literature review of case-control studies. We found 988 produce-related outbreaks (with known agents) and 45,723 cases in all regions and countries. The numbers of produce-related outbreaks per million person-years were approximately 0.76, 0.26, 0.25, 0.13, 0.12, and 0.05 in New Zealand, Australia, the United States, the European Union, Canada, and Japan, respectively. The top three food categories and pathogens contributing to produce-related outbreaks were vegetables and nonfruits (i.e., food other than fruits; 27.0%), unspecified vegetables (12.2%), and vegetable row crops (11.7%) and norovirus (42.4%), Salmonella enterica (19.9%), and Staphylococcus aureus (7.9%), respectively. Produce consumption was identified as a protective factor, a risk factor, and either a protective or risk factor for sporadic illnesses in 11, 5, and 5 studies, respectively, among 21 case-control studies. Risks associated with produce consumption in the United States and the European Union have been linked to various factors such as irrigation water, cross-contamination, storage time and temperature abuse, infected food handlers, and unprocessed contaminated ingredients. The results of the current study indicate the complexity of produce products consumed across the globe and the difficulty in tracing illnesses back to specific food ingredients.

Long-term ground deformation patterns of Bucharest using multi-temporal InSAR and multivariate dynamic analyses: a possible transpressional system?

The aim of this exploratory research is to capture spatial evolution patterns in the Bucharest metropolitan area using sets of single polarised synthetic aperture radar (SAR) satellite data and multi-temporal radar interferometry. Three sets of SAR data acquired during the years 1992-2010 from ERS-1/-2 and ENVISAT, and 2011-2014 from TerraSAR-X satellites were used in conjunction with the Small Baseline Subset (SBAS) and persistent scatterers (PS) high-resolution multi-temporal interferometry (InSAR) techniques to provide maps of line-of-sight displacements. The satellite-based remote sensing results were combined with results derived from classical methodologies (i.e., diachronic cartography) and field research to study possible trends in developments over former clay pits, landfill excavation sites, and industrial parks. The ground displacement trend patterns were analysed using several linear and nonlinear models, and techniques. Trends based on the estimated ground displacement are characterised by long-term memory, indicated by low noise Hurst exponents, which in the long-term form interesting attractors. We hypothesize these attractors to be tectonic stress fields generated by transpressional movements.

Bias in the case-only design applied to studies of gene-environment and gene-gene interaction: a systematic review and meta-analysis.

BACKGROUND: The case-only study, proposed as a design specifically for assessing departure from multiplicative gene-environment and gene-gene interactions, is of considerable potential value but there are concerns about its validity. The objective of this study was to evaluate the extent and sources of bias in the case-only design by means of a systematic review and meta-regression analysis. METHODS: The MEDLINE, CINAHL, EMBASE and PUBMED databases were searched through to 7 October 2009. Studies that assessed bias in the case-only design applied to the study of gene-environment and gene-gene interaction were identified. Qualitative comments on the sources and extent of bias were extracted. A meta-regression analysis of the ratio (IOR(CC)/IOR(CO)) of the case-control (IOR(CC)) and case-only (IOR(CO)) interaction odds ratios was conducted based on studies in which both methods were applied to the same data set. RESULTS: The search yielded 365 unique articles of which 38 met the inclusion criteria. Potential sources of bias in the case-only design included non-independence of genotype and exposure in the source population. Meta-regression analysis, based on 24 evaluations, produced a mean IOR(CC)/IOR(CO) of 1.06 [95% confidence interval (95% CI) 0.93-1.22], suggesting that bias in case-only designs is not common in practice. The I(2) statistic indicated that 23.9% (95% uncertainty interval 0-53.9%) of the observed variation was due to heterogeneity between studies, which was not explained by any methodological characteristics of the included studies. CONCLUSION: As understanding of the relationships between genes and environmental exposures in the population improves, the case-only design may prove to be of considerable value.

Development and validation of an HPLC-MS/MS method to quantify clopidogrel acyl glucuronide, clopidogrel acid metabolite, and clopidogrel in plasma samples avoiding analyte back-conversion.

A new sensitive and fast quantitative analytical method for the simultaneous determination of clopidogrel, its main metabolite clopidogrel carboxylic acid, and the newly described acyl glucuronide metabolite, in human plasma samples, is presented. The analytical procedures (plasma storage, handling, and extract storage in the autosampler) were optimized in order to avoid back-conversion; a known drawback in measurements of clopidogrel. Clopidogrel acyl glucuronide was confirmed as a major source of back-conversion to the parent drug in the presence of methanol, and thorough stability experiments were carried out to find the most appropriate conditions for an accurate analysis of clopidogrel and the two metabolites. The method was validated by assessing selectivity, sensitivity, linearity, accuracy, and precision for all three analytes, in accordance to Food and Drug Administration guidelines. Spiked quality controls in plasma as well as incurred samples were used to verify back-conversion in the selected conditions, with results meeting European Medicines Agency acceptance criteria (concentrations within 80-120% of the first reading). The method was then applied to a pharmacokinetic study, and for the first time, a pharmacokinetic curve of clopidogrel acyl glucuronide in human plasma is presented. The concentrations ranged up to 1,048.684 ng/mL, with a mean of 470.268 ng/mL, while clopidogrel had a mean C(max) of 1.348 ng/mL; these orders of magnitude show how much the back-conversion of this metabolite may influence clopidogrel quantification if it is not properly controlled.

Incurred sample reanalysis: different evaluation approaches on data obtained for spironolactone and its active metabolite canrenone.

BACKGROUND: The inherent reproducibility of a bioanalytical approach is usually sustained through incurred sample reanalysis (ISR). Questions relating to the number of ISRs, the right moment for performing reanalysis, the way of performing an appropriate statistical refinement of experimental data and actions to be taken in the case of failure are frequently raised. RESULTS: Data resulting from ISR following a bioequivalence study for spironolactone formulations are discussed. Reanalysis of samples was carried out twice: immediately after the end of the study and after a period that overcame the long-term stability study achieved during method validation. The Bland-Altman approach was used to assess experimental results. ISR was successful over the short reanalysis period for both compounds. Data produced through reanalysis after the long-term period indicated a systematic positive bias for the metabolite canrenone (although results supported reproducibility). The results obtained for spironolactone were affected by a strong negative systematic bias and failed to support reproducibility. The explanation deals with the continuous conversion of spironolactone to canrenone in plasma samples. However, reproducibility of the method may be sustained by comparing original and repeated differences between concentration values in samples by means of a paired t-test, Wilcoxon sign rank-sum test and linear regression. CONCLUSIONS: Different statistical approaches for making data comparisons are discussed and may be successfully applied during reanalysis of samples from a bioequivalence study. Results of the evaluations may differ in accordance with the statistical procedure being applied, thus a definitive conclusion requires consideration of all specific experimental circumstances arising during production of the processed data.

Development and validation of an HPLC-MS/MS method to determine clopidogrel in human plasma. Use of incurred samples to test back-conversion.

Quantitative methods using LC-MS/MS allow achievement of adequate sensitivity for pharmacokinetic studies with clopidogrel; three such methods, with LLOQs as low as 5 pg/mL, were developed and fully validated according to the well established FDA 2001 guidelines. The chromatographic separations were performed on reversed phase columns Ascentis RP-Amide (15 cm x 2.1 mm, 5 µm), Ascentis Express C8 (10 cm x 2.1 mm, 2.7 µm) and Ascentis Express RP Amide (10 cm x 2.1 mm, 2.7 µm), respectively. Positive electrospray ionization in MRM mode was employed for the detection and a deuterated analogue (d3-clopidogrel) was used as internal standard. Linearity, precision, extraction recovery, matrix effects and stability tests on blank plasma spiked with clopidogrel and stored in different conditions met the acceptance criteria. During the analysis of the real samples from the first pharmacokinetic study, a significant increase (>100%) of the measured clopidogrel concentrations in the extracts kept in the autosampler at 10 °C was observed. Investigations led to the conclusion that most probably a back-conversion of one or more of the clopidogrel metabolites is occurring. The next methods were optimized in order to minimize this back-conversion. After a series of experiments, the adjustment of the sample preparation (e.g. processing at low temperature and introducing a clean-up step on Supelco HybridSPE-Precipitation cartridges) has proven to be the most effective in order to improve the stability of the extracts. Incurred samples of real subjects were successfully used in the validation of the last two analytical methods to evaluate the back-conversion, while tests using only the known metabolites could not detect this important problem.

High-throughput HPLC-MS/MS method to determine ibandronate in human plasma for pharmacokinetic applications.

A sensitive high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the quantification of ibandronate in human plasma. In a previous study, we have analyzed alendronate in urine samples of subjects treated at therapeutic dosages, using a derivatization approach; a similar derivatization was adapted and improved to determine ibandronate in plasma. The bisphosphonate was isolated from the biological matrix by liquid-liquid extraction, and derivatized with trimethylsilyldiazomethane prior to separation on a reversed-phase column (Supelco Discovery HSC18) and detection on a quadrupole-linear ion trap mass spectrometer (API 4000 QTrap). Various parameters of extraction and derivatization were optimized in order to get adequate recovery, high derivatization yield and minimal ion suppression; a deuterated analogue, d3-ibandronate, was used as internal standard. The transitions 376.1-->114.2 and 379.1-->61.0 were acquired to monitor ibandronate and d3-ibandronate derivatives, respectively. A multiplexing LC system made possible the overlapping of two chromatographic runs, thus the interval between injections being reduced to only 2min, a very short analysis time for compounds of this class. The method was fully validated over the quantification range 0.2-175.0ng/ml, allowing an appropriate evaluation of the plasma concentrations of ibandronate, expected at therapeutic dosage, as proved by application to a pharmacokinetic study. A good linearity over the selected range (r>0.99), accuracy and precision within +/-15% of the target values and a recovery over 50% were obtained.