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- Aboulatta, L, et al.
(author)
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Preterm birth and stillbirth rates associated with socioeconomic disparities during COVID-19 pandemic: a population-based cross-sectional study
- 2023
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In: BMJ paediatrics open. - : BMJ. - 2399-9772. ; 7:1
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Journal article (peer-reviewed)abstract
- Conflicting evidence exists on the impact of the COVID-19 pandemic restrictions on preterm birth (PTB) and stillbirth rates. We aimed to evaluate changes in PTB and stillbirth rates before and during the pandemic period and assess the potential effect modification of socioeconomic status (SES).MethodsUsing the linked administrative health databases from Manitoba, Canada, we conducted a cross-sectional study among all pregnant women, comparing 3.5 years pre-pandemic (1 October 2016 to 29 February 2020) to the first year of the pandemic (1 March 2020 to 31 March 2021). We used generalised linear models to assess the quarterly rates of PTB (<37 weeks) and stillbirths. We calculated the predicted trends based on pre-pandemic period data. Finally, we evaluated the PTB and stillbirth rates among lower and higher SES pregnant women (average annual household income) using subgroup analysis and interaction models.ResultsWe examined 70 931 pregnancies in Manitoba during the study period. The risk of PTB increased by 7.7% (95%CI 1.01 to 1.13) and stillbirths by 33% (95% CI 1.08 to 1.64) during the pandemic period. Following COVID-19 restrictions implemented in March 2020, there were increases in the quarterly rates of both PTB (immediate increase (β2)=1.37; p=0.0247) and stillbirths (immediate increase (β2)=0.12; p=0.4434). Among the lower income groups, the pandemic restrictions resulted in an immediate relative increase in PTB and stillbirth rates by 20.12% (immediate increase (β2)=3.17; p=0.0057) and 27.19% (immediate increase (β2)=0.48; p=0.0852). However, over the pandemic, the overall PTB rate significantly decreased as a rebound effect by 0.85% per quarter (p=0.0004), whereas the overall stillbirth rate did not decrease significantly (slope decrease (β3) =−0.01; p=0.8296) compared with the pre-pandemic period. The quarterly rates during the pandemic among the higher income group decreased by 0.39% (p=0.1296) for PTB and increased by 0.07% (p=0.1565) for stillbirth. We observed an effect modification by SES for PTB rates (p=0.047).ConclusionWhile the onset of COVID-19 pandemic restrictions was not associated with significant effects on stillbirth rates, we observed an immediate and rebound effect on PTB rates. The impact of COVID-19 on preterm birth was dependent on SES, with higher influence on families with lower SES. Further studies are needed to detect future trend changes during pandemic waves after 2021 and assess potential underlying mechanisms.
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- Hu, C, et al.
(author)
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Biostatistical Methods
- 2022
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In: MULTIPLE SCLEROSIS JOURNAL. - 1352-4585. ; 28:1_SUPPL, s. 52-52
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Conference paper (other academic/artistic)
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- Harroud, A, et al.
(author)
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Mendelian randomization provides no evidence for a causal role in the bidirectional relationship between depression and multiple sclerosis
- 2021
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In: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 27:13, s. 2077-2084
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Journal article (peer-reviewed)abstract
- Major depressive disorder (MDD) is common in multiple sclerosis (MS) and its incidence rises before MS diagnosis. However, the causality and direction of this association remain unclear. Objective: The objective is to investigate the bidirectional relationship between MS and MDD using Mendelian randomization (MR). Methods: We selected genetic instruments associated with risk of MDD ( n = 660,937 cases; 1,453,489 controls) and MS ( n = 47,429 cases; 68,374 controls). Using two-sample MR, we examined putative causal effects in either direction, with sensitivity analyses to assess pleiotropy. Also, we adjusted for body mass index (BMI) in multivariable MR. Results: We found no effect of genetic liability to MDD on the odds of MS (OR = 1.07/doubling in odds, 95% CI = 0.90–1.28). Similarly, our findings did not support a causal effect of genetic liability to MS on MDD (OR = 1.00/doubling in odds, 95% CI = 0.99–1.01). Despite heterogeneity, sensitivity analyses indicated that bias from pleiotropy was unlikely. Conversely, genetic predisposition toward higher BMI increased the odds of MS (OR = 1.34/SD increase, 95% CI = 1.09–1.65) and MDD (OR = 1.08, 95% CI = 1.01–1.15). Conclusion: This study does not support a causal association between MDD genetic liability and MS susceptibility, and vice versa. Genetic evidence suggesting commonality of obesity to both conditions may partly explain the increased incidence of depression pre-MS diagnosis.
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- Kowalec, K, et al.
(author)
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Methylation age acceleration does not predict mortality in schizophrenia
- 2019
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In: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9:1, s. 157-
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Journal article (peer-reviewed)abstract
- Schizophrenia (SCZ) is associated with high mortality. DNA methylation levels vary over the life course, and pre-selected combinations of methylation array probes can be used to estimate “methylation age” (mAge). mAge correlates highly with chronological age but when it differs, termed mAge acceleration, it has been previously associated with all-cause mortality. We tested the association between mAge acceleration and mortality in SCZ and controls. We selected 190 SCZ cases and 190 controls from the Sweden Schizophrenia Study. Cases were identified from the Swedish Hospital Discharge Register with ≥5 specialist treatment contacts and ≥5 antipsychotic prescriptions. Controls had no psychotic disorder or antipsychotics. Subjects were selected if they had died or survived during follow-up (2:1 oversampling). Extracted DNA was assayed on the Illumina MethylationEPIC array. mAge was regressed on age at sampling to obtain mAge acceleration. Using Cox proportional hazards regression, the association between mAge acceleration and mortality was tested. After quality control, the following were available: n = 126 SCZ died, 63 SCZ alive, 127 controls died, 62 controls alive. In the primary analyses, we did not find a significant association between mAge acceleration and SCZ mortality (adjusted p > 0.005). Sensitivity analyses excluding SCZ cases with pre-existing cancer demonstrated a significant association between the Hannum mAge acceleration and mortality (hazard ratio = 1.13, 95% confidence interval = 1.04–1.22, p = 0.005). Per our pre-specified criteria, we did not confirm our primary hypothesis that mAge acceleration would predict subsequent mortality in people with SCZ, but we cannot rule out smaller effects or effects in patient subsets.
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- Leong, C, et al.
(author)
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Psychotropic Medication Use Before and During COVID-19: A Population-Wide Study
- 2022
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In: Frontiers in pharmacology. - : Frontiers Media SA. - 1663-9812. ; 13, s. 886652-
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Journal article (peer-reviewed)abstract
- Background: The coronavirus disease 2019 (COVID-19) pandemic and public health measures that took place have led to concerns regarding mental health and receipt of psychotropic medications. We aimed to study the changes in psychotropic medication dispensation rates before and during the COVID-19 pandemic in the general population.Methods: Administrative health data from the Canadian province of Manitoba was used to describe the quarterly incidence and prevalence of antipsychotics, antidepressants, and anxiolytic/sedative-hypnotics from January 1, 2015 to December 31, 2020. Individuals who received at least one prescription within each quarter were considered exposed to the medication. The denominator was the total population within each quarter. Incidence was defined as no receipt of medication in the 3 years prior to the quarter of interest. Autoregression models for time series data plus indicator variables were used to compare each quarter of 2020 after public health measures were implemented in March 2020 in relation to the expected trend. Analyses were stratified by age and sex.Results: There were 1,394,885 individuals in the first quarter of 2020, with a mean (SD) age of 38.9 (23.4) years, 50.3% were female, and 36.1% had a psychiatric diagnosis in the previous 5 years. A significant decrease was observed for incident antidepressant use (p < 0.05 for both sexes and all age groups except for those 65 years and older) and anxiolytic use (p < 0.05 for both sexes and all age groups except 80 years and older) in the second quarter (April-June) of 2020 compared to the expected trend. Females and those aged 40 years and older had a significantly higher incidence of antidepressant and antipsychotic use in the final quarter of 2020 compared to the expected trend (p < 0.05).Conclusion: Our findings indicate a decrease in new prescriptions for antidepressants and anxiolytics in the 3 months after COVID-19 in-person restrictions were first implemented. We then observed an increase in the new use of antidepressants and antipsychotics at the end of 2020, in females and people aged 40 years and older, with the highest rates of use in the population 80 years and older.
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- Shouman, W, et al.
(author)
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Trends of Utilization of Antiseizure Medications Among Pregnant Women in Manitoba, Canada: A 20-Year Population-Based Study
- 2022
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In: Frontiers in pharmacology. - : Frontiers Media SA. - 1663-9812. ; 13, s. 871136-
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Journal article (peer-reviewed)abstract
- Background: Evidence from developed countries demonstrates that the use of antiseizure medications (ASMs) has been increasing in the last decade. Pregnant women have a very challenging risk benefit trade-off in terms of ASM utilization, and it is crucial to know if increased utilization is seen among pregnant women.Objective: To examine time-trends of utilization of ASM therapies among pregnant women in Manitoba, Canada.Methods: We conducted a population-based cohort study using de-identified, linked administrative databases from Manitoba. Pregnancies between 1995 and 2018 were included. Four groups of pregnant people were created based on ASM exposure and epilepsy diagnosis.Results: Of 273,492 pregnancies, 812 (3/1000) had epilepsy diagnosis and were exposed to ASMs, 963 (3.5/1000) had epilepsy diagnosis and were unexposed, and 2742 (10/1000) were exposed to ASMs and did not have epilepsy diagnosis. Overall, the number of pregnancies exposed to ASMs increased significantly from 0.56% in 1997 to 2.21% in 2018 (p < 0.0001). Subgroup analysis by epilepsy diagnosis showed no significant change in ASMs exposure among pregnant women with epilepsy [the proportion of women exposed to ASM from all pregnancies was 0.37% (in 1997) and 0.36% (in 2018), p = 0.24]. A drop in carbamazepine use was observed, while the number of lamotrigine prescriptions increased from 6.45% in 1997 to 52% by 2018. ASM use among pregnant women without epilepsy increased significantly from 0.19% in 1997 to 1.85% in 2018 (p < 0.0001). In the total cohort of pregnancies, 1439 (0.53%) were exposed during their entire pregnancy, and 1369 (0.5%) were exposed only in their first trimester. Clonazepam was the most used ASM during the study period (1953 users, 0.71%), followed by gabapentin (785 users, 0.29%) and carbamazepine (449 users, 0.16%).Conclusion: No major shifts in the quantity of ASM use over the study period were observed among pregnant women with epilepsy. However, there was a significant increase in ASM use among pregnant women without epilepsy. The study results warrant further investigation into the implications of ASM use in pregnancy for indications other than epilepsy.
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| 40. |
- Song, J, et al.
(author)
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The impact of educational attainment, intelligence and intellectual disability on schizophrenia: a Swedish population-based register and genetic study
- 2022
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In: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 27:5, s. 2439-2447
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Journal article (peer-reviewed)abstract
- Schizophrenia (SCZ) is highly heterogenous and no subtypes characterizing treatment response or longitudinal course well. Cognitive impairment is a core clinical feature of SCZ and a determinant of poorer outcome. Genetic overlap between SCZ and cognitive traits is complex, with limited studies of comprehensive epidemiological and genomic evidence. To examine the relation between SCZ and three cognitive traits, educational attainment (EDU), premorbid cognitive ability, and intellectual disability (ID), we used two Swedish samples: a national cohort (14,230 SCZ cases and 3,816,264 controls) and a subsample with comprehensive genetic data (4992 cases and 6009 controls). Population-based analyses confirmed worse cognition as a risk factor for SCZ, and the pedigree and SNP-based genetic correlations were comparable. In the genotyped cases, those with high EDU and premorbid cognitive ability tended to have higher polygenetic risk scores (PRS) of EDU and intelligence and fewer rare exonic variants. Finally, by applying an empirical clustering method, we dissected SCZ cases into four replicable subgroups characterized by EDU and ID. In particular, the subgroup with higher EDU in the national cohort had fewer adverse outcomes including long hospitalization and death. In the genotyped subsample, this subgroup had higher PRS of EDU and no excess of rare genetic burdens than controls. In conclusion, we found extensive evidence of a robust relation between cognitive traits and SCZ, underscoring the importance of cognition in dissecting the heterogeneity of SCZ.
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| 43. |
- Xiong, Y., et al.
(author)
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Polygenic risk scores of lithium response and treatment resistance in major depressive disorder
- 2023
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In: Translational Psychiatry. - 2158-3188. ; 13:1
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Journal article (peer-reviewed)abstract
- Treatment response and resistance in major depressive disorder (MDD) are suggested to be heritable. Due to significant challenges in defining treatment-related phenotypes, our understanding of their genetic bases is limited. This study aimed to derive a stringent definition of treatment resistance and to investigate the genetic overlap between treatment response and resistance in MDD. Using electronic medical records on the use of antidepressants and electroconvulsive therapy (ECT) from Swedish registers, we derived the phenotype of treatment-resistant depression (TRD) and non-TRD within similar to 4500 individuals with MDD in three Swedish cohorts. Considering antidepressants and lithium are first-line treatment and augmentation used for MDD, respectively, we generated polygenic risk scores (PRS) of antidepressants and lithium response for individuals with MDD and evaluated their associations with treatment resistance by comparing TRD with non-TRD. Among 1778 ECT-treated MDD cases, nearly all (94%) used antidepressants before their first ECT and the vast majority had at least one (84%) or two (61%) antidepressants of adequate duration, suggesting these MDD cases receiving ECT were resistant to antidepressants. We did not observe a significant difference in the mean PRS of antidepressant response between TRD and non-TRD; however, we found that TRD cases had a significantly higher PRS of lithium response compared to non-TRD cases (OR = 1.10-1.12 under various definitions). The results support the evidence of heritable components in treatment-related phenotypes and highlight the overall genetic profile of lithium-sensitivity in TRD. This finding further provides a genetic explanation for lithium efficacy in treating TRD.
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