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- Huybrechts, KF, et al.
(författare)
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Association of In Utero Antipsychotic Medication Exposure With Risk of Congenital Malformations in Nordic Countries and the US
- 2023
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 80:2, s. 156-166
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Tidskriftsartikel (refereegranskat)abstract
- Psychiatric disorders are common among female individuals of reproductive age. While antipsychotic medication use is increasing, the safety of such medications in pregnancy is an area with large evidence gaps.ObjectiveTo evaluate the risk of first-trimester antipsychotic exposure with respect to congenital malformations, focusing on individual drugs and specific malformation subtypes.Design, Setting, and ParticipantsThis cohort study used data from nationwide health registers from the 5 Nordic countries and the US and spanned 1996 to 2018. The Nordic cohort included all pregnancies resulting in singleton live-born infants, and the US cohort consisted of publicly insured mothers linked to their live-born infants nested in the nationwide Medicaid Analytic eXtract. Data were analyzed from November 2020 to April 2022.ExposuresOne or more first-trimester dispensing of any atypical, any typical, and individual antipsychotic drugs.Main Outcomes and MeasuresAny major congenital malformation and specific malformation subtypes previously suggested to be associated with antipsychotic exposure in utero: cardiovascular malformations, oral clefts, neural tube defects, hip dysplasia, limb reduction defects, anorectal atresia/stenosis, gastroschisis, hydrocephalus, other specific brain anomalies, and esophageal disorders. Propensity score stratification was used to control for potential confounders. Pooled adjusted estimates were calculated using indirect standardization.ResultsA total of 6 455 324 unexposed mothers (mean maternal age range across countries: 24-31 years), 21 751 mothers exposed to atypical antipsychotic drugs (mean age range, 26-31 years), and 6371 mothers exposed to typical antipsychotic drugs (mean age range, 27-32 years) were included in the study cohort. Prevalence of any major malformation was 2.7% (95% CI, 2.7%-2.8%) in unexposed infants, 4.3% (95% CI, 4.1%-4.6%) in infants with atypical antipsychotic drug exposure, and 3.1% (95% CI, 2.7%-3.5%) in infants with typical antipsychotic drug exposure in utero. Among the most prevalent exposure-outcome combinations, adjusted relative risks (aRR) were generally close to the null. One exception was olanzapine exposure and oral cleft (aRR, 2.1 [95% CI, 1.1-4.3]); however, estimates varied across sensitivity analyses. Among moderately prevalent combinations, increased risks were observed for gastroschisis and other specific brain anomalies after atypical antipsychotic exposure (aRR, 1.5 [95% CI, 0.8-2.6] and 1.9 [95% CI, 1.1-3.0]) and for cardiac malformations after chlorprothixene exposure (aRR, 1.6 [95% CI, 1.0-2.7]). While the association direction was consistent across sensitivity analyses, confidence intervals were wide, prohibiting firm conclusions.Conclusions and RelevanceIn this study, considering the evidence from primary and sensitivity analyses and inevitable statistical noise for very rare exposure-outcome combinations, in utero antipsychotic exposure generally was not meaningfully associated with an increased risk of malformations. The observed increased risks of oral clefts associated with olanzapine, gastroschisis, and other specific brain anomalies with atypical antipsychotics and cardiac malformations with chlorprothixene requires confirmation as evidence continues to accumulate.
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| 2. |
- Huybrechts, KF, et al.
(författare)
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Association of In Utero Antipsychotic Medication Exposure With Risk of Congenital Malformations in Nordic Countries and the US
- 2023
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 80:2, s. 156-166
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Tidskriftsartikel (refereegranskat)abstract
- Psychiatric disorders are common among female individuals of reproductive age. While antipsychotic medication use is increasing, the safety of such medications in pregnancy is an area with large evidence gaps.ObjectiveTo evaluate the risk of first-trimester antipsychotic exposure with respect to congenital malformations, focusing on individual drugs and specific malformation subtypes.Design, Setting, and ParticipantsThis cohort study used data from nationwide health registers from the 5 Nordic countries and the US and spanned 1996 to 2018. The Nordic cohort included all pregnancies resulting in singleton live-born infants, and the US cohort consisted of publicly insured mothers linked to their live-born infants nested in the nationwide Medicaid Analytic eXtract. Data were analyzed from November 2020 to April 2022.ExposuresOne or more first-trimester dispensing of any atypical, any typical, and individual antipsychotic drugs.Main Outcomes and MeasuresAny major congenital malformation and specific malformation subtypes previously suggested to be associated with antipsychotic exposure in utero: cardiovascular malformations, oral clefts, neural tube defects, hip dysplasia, limb reduction defects, anorectal atresia/stenosis, gastroschisis, hydrocephalus, other specific brain anomalies, and esophageal disorders. Propensity score stratification was used to control for potential confounders. Pooled adjusted estimates were calculated using indirect standardization.ResultsA total of 6 455 324 unexposed mothers (mean maternal age range across countries: 24-31 years), 21 751 mothers exposed to atypical antipsychotic drugs (mean age range, 26-31 years), and 6371 mothers exposed to typical antipsychotic drugs (mean age range, 27-32 years) were included in the study cohort. Prevalence of any major malformation was 2.7% (95% CI, 2.7%-2.8%) in unexposed infants, 4.3% (95% CI, 4.1%-4.6%) in infants with atypical antipsychotic drug exposure, and 3.1% (95% CI, 2.7%-3.5%) in infants with typical antipsychotic drug exposure in utero. Among the most prevalent exposure-outcome combinations, adjusted relative risks (aRR) were generally close to the null. One exception was olanzapine exposure and oral cleft (aRR, 2.1 [95% CI, 1.1-4.3]); however, estimates varied across sensitivity analyses. Among moderately prevalent combinations, increased risks were observed for gastroschisis and other specific brain anomalies after atypical antipsychotic exposure (aRR, 1.5 [95% CI, 0.8-2.6] and 1.9 [95% CI, 1.1-3.0]) and for cardiac malformations after chlorprothixene exposure (aRR, 1.6 [95% CI, 1.0-2.7]). While the association direction was consistent across sensitivity analyses, confidence intervals were wide, prohibiting firm conclusions.Conclusions and RelevanceIn this study, considering the evidence from primary and sensitivity analyses and inevitable statistical noise for very rare exposure-outcome combinations, in utero antipsychotic exposure generally was not meaningfully associated with an increased risk of malformations. The observed increased risks of oral clefts associated with olanzapine, gastroschisis, and other specific brain anomalies with atypical antipsychotics and cardiac malformations with chlorprothixene requires confirmation as evidence continues to accumulate.
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| 11. |
- Bagardi, M, et al.
(författare)
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Influence of Morphometry on Echocardiographic Measurements in Cavalier King Charles Spaniels: An Inverse Probability Weighting Analysis
- 2021
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Ingår i: Veterinary sciences. - : MDPI AG. - 2306-7381. ; 8:10
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Tidskriftsartikel (refereegranskat)abstract
- The development and progression of myxomatous mitral valve disease (MMVD) in Cavalier King Charles Spaniels (CKCS) are difficult to predict. Thus, the identification of dogs with a morphotype associated with more severe mitral disease at a young age is desirable. The aims of this study were to: (1) describe the physical, morphometric, and echocardiographic features of class B1 MMVD-affected Cavalier King Charles Spaniels (CKCS) according to the American College of Veterinary Internal Medicine (ACVIM) guidelines; (2) evaluate the influence of morphometric physical measurements on murmur intensity, mitral valve prolapse (MVP), regurgitant jet size, and indexed mitral valve and annulus measurements. Fifty-two MMVD-affected CKCS were included in the ACVIM class B1. This is a prospective clinical cross-sectional study. Morphometric measurements, which included the body, thorax, and head sizes of each dog, were investigated to establish the association with heart murmur intensity, valvular and annular echocardiographic measurements, MVP, and regurgitant jet size, using inverse probability weighting (IPW) analyses to adjust for confounding. The IPW analyses showed that when the head length and nose length decreased, dogs had a more severe regurgitant jet size. Furthermore, subjects with a more pronounced head stop angle had thicker anterior mitral valve leaflets. A brachycephalic morphotype, as seen in dogs similar to the King Charles Spaniel breed in terms of cephalic morphology, is associated with a more severe regurgitant jet size and with valvular characteristics that are related to the most severe forms of MMVD.
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- Cesta, CE, et al.
(författare)
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Antidiabetic medication use during pregnancy: an international utilization study
- 2019
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Ingår i: BMJ open diabetes research & care. - : BMJ. - 2052-4897. ; 7:1, s. e000759-
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Tidskriftsartikel (refereegranskat)abstract
- Diabetes in pregnancy and consequently the need for treatment with antidiabetic medication (ADM) has become increasingly prevalent. The prevalence and patterns of use of ADM in pregnancy from 2006 onward in seven different countries was assessed.Research design and methodsData sources included individually linked data from the nationwide health registers in Denmark (2006–2016), Finland (2006–2016), Iceland (2006–2012), Norway (2006–2015), Sweden (2006–2015), state-wide administrative and claims data for New South Wales, Australia (2006–2012) and two US insurance databases: Medicaid Analytic eXtract (MAX; 2006–2012, public) and IBM MarketScan (2012–2015, private). The prevalence of ADM use was calculated as the proportion of pregnancies with at least one filled prescription of an ADM in the 90 days before pregnancy or within the three trimesters of pregnancy.ResultsPrevalence of any ADM use in 5 279 231 pregnancies was 3% (n=147 999) and varied from under 2% (Denmark, Norway, and Sweden) to above 5% (Australia and US). Insulin was the most used ADM, and metformin was the most used oral hypoglycemic agent with increasing use over time in all countries. In 11.4%–62.5% of pregnancies with prepregnancy use, ADM (primarily metformin) was discontinued. When ADM treatment was initiated in late pregnancy for treatment of gestational diabetes mellitus, insulin was most often dispensed, except in the US, where glibenclamide was most often used.ConclusionsPrevalence and patterns of use of ADM classes varied between countries and over time. While insulin remained the most common ADM used in pregnancy, metformin use increased significantly over the study period.
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| 17. |
- Karampelias, C, et al.
(författare)
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Reinforcing one-carbon metabolism via folic acid/Folr1 promotes β-cell differentiation
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 3362-
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Tidskriftsartikel (refereegranskat)abstract
- Diabetes can be caused by an insufficiency in β-cell mass. Here, we performed a genetic screen in a zebrafish model of β-cell loss to identify pathways promoting β-cell regeneration. We found that both folate receptor 1 (folr1) overexpression and treatment with folinic acid, stimulated β-cell differentiation in zebrafish. Treatment with folinic acid also stimulated β-cell differentiation in cultures of neonatal pig islets, showing that the effect could be translated to a mammalian system. In both zebrafish and neonatal pig islets, the increased β-cell differentiation originated from ductal cells. Mechanistically, comparative metabolomic analysis of zebrafish with/without β-cell ablation and with/without folinic acid treatment indicated β-cell regeneration could be attributed to changes in the pyrimidine, carnitine, and serine pathways. Overall, our results suggest evolutionarily conserved and previously unknown roles for folic acid and one-carbon metabolism in the generation of β-cells.
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- Pazzagli, L, et al.
(författare)
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Causal inference in pharmacoepidemiology
- 2019
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Ingår i: PHARMACOEPIDEMIOLOGY AND DRUG SAFETY. - 1053-8569. ; 28, s. 414-415
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 26. |
- Pazzagli, L, et al.
(författare)
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Erratum
- 2018
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Ingår i: Pharmacoepidemiology and drug safety. - : Wiley. - 1099-1557 .- 1053-8569. ; 27:3, s. 356-356
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Tidskriftsartikel (refereegranskat)
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- Pazzagli, L, et al.
(författare)
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Rationale and performances of a data-driven method for computing the duration of pharmacological prescriptions using secondary data sources
- 2022
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1, s. 6245-
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Tidskriftsartikel (refereegranskat)abstract
- The assessment of the duration of pharmacological prescriptions is an important phase in pharmacoepidemiologic studies aiming to investigate persistence, effectiveness or safety of treatments. The Sessa Empirical Estimator (SEE) is a new data-driven method which uses k-means algorithm for computing the duration of pharmacological prescriptions in secondary data sources when this information is missing or incomplete. The SEE was used to compute durations of exposure to pharmacological treatments where simulated and real-world data were used to assess its properties comparing the exposure status extrapolated with the method with the “true” exposure status available in the simulated and real-world data. Finally, the SEE was also compared to a Researcher-Defined Duration (RDD) method. When using simulated data, the SEE showed accuracy of 96% and sensitivity of 96%, while when using real-world data, the method showed sensitivity ranging from 78.0 (nortriptyline) to 95.1% (propafenone). When compared to the RDD, the method had a lower median sensitivity of 2.29% (interquartile range 1.21–4.11%). The SEE showed good properties and may represent a promising tool to assess exposure status when information on treatment duration is not available.
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