| 1. |
- Aasa, Jenny, et al.
(författare)
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Cancer risk estimation of glycidol based on rodent carcinogenicity studies, a multiplicative risk model and in vivo dosimetry
- 2019
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Ingår i: Food and Chemical Toxicology. - : Elsevier BV. - 0278-6915 .- 1873-6351. ; 128, s. 54-60
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Tidskriftsartikel (refereegranskat)abstract
- Here we evaluate a multiplicative (relative) risk model for improved cancer risk estimation of genotoxic compounds. According to this model, cancer risk is proportional to the background tumor incidence and to the internal dose of the genotoxic compound. Furthermore, the relative risk coefficient per internal dose is considered to be approximately the same across tumor sites, sex, and species. In the present study, we demonstrate that the relative risk model is valid for cancer risk estimation of glycidol, a common food contaminant. Published tumor data from glycidol carcinogenicity studies in mice and rats were evaluated in combination with internal dose estimates from hemoglobin adduct measurements in blood from mice and rats treated with glycidol in short-term studies. A good agreement between predicted and observed tumor incidence in responding sites was demonstrated in the animals, supporting a relative risk coefficient that is independent of tumor site, sex, and species. There was no significant difference between the risk coefficients for mice (5.1% per mMh) and rats (5.4% per mMh) when considering internal doses of glycidol. Altogether, this mechanism-based risk model gives a reliable risk coefficient, which then was extrapolated to humans considering internal dose, and background cancer incidence.
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| 3. |
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| 4. |
- Carr, Hanna, et al.
(författare)
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Preterm Birth and Risk of Heart Failure Up to Early Adulthood
- 2017
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Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 69:21, s. 2634-2642
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In small clinical studies, preterm birth was associated with altered cardiac structure and increased cardiovascular mortality in the young.OBJECTIVES: The goal of this study was to determine the association between preterm birth and risk of incident heart failure (HF) in children and young adults.METHODS: This register-based cohort study included 2,665,542 individuals born in Sweden from 1987 to 2012 who were followed up from 1 year of age to December 31, 2013. The main study outcome was diagnosis of HF in the National Patient Register or the Cause of Death Register. The association between preterm birth and risk of incident HF was analyzed by using a Poisson regression model. Estimates were adjusted for maternal and pregnancy characteristics, socioeconomic status, and maternal and paternal cardiovascular disease.RESULTS: During 34.8 million person-years of follow-up (median 13.1 years), there were 501 cases of HF. After exclusion of 52,512 individuals with malformations (n = 196 cases), 305 cases of HF remained (0.88 per 100,000 person-years). Gestational age was inversely associated with the risk of HF. Compared with individuals born at term (>= 37 weeks' gestation), adjusted incidence relative risks for HF were 17.0 (95% confidence interval [CI]: 7.96 to 36.3) after extremely preterm birth (<28 weeks) and 3.58 (95% CI: 1.57 to 8.14) after very preterm birth (28 to 31 weeks). There was no risk increase after moderately preterm birth (32 to 36 weeks) (relative risk: 1.36; 95% CI: 0.87 to 2.13).CONCLUSIONS: There was a strong association between preterm birth before 32 weeks of gestation and HF in childhood and young adulthood. Although the absolute risk of HF is low in young age, our findings indicate that preterm birth may be a previously unknown risk factor for HF. (J Am Coll Cardiol 2017;69:2634-42) (C) 2017 by the American College of Cardiology Foundation.
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| 5. |
- Hammarström, Lars G. J., et al.
(författare)
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The Oncolytic Efficacy and in Vivo Pharmacokinetics of [2-(4-Chlorophenyl)quinolin-4-yl](piperidine-2-yl)methanol (Vacquinol-1) Are Governed by Distinct Stereochemical Features
- 2016
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 59:18, s. 8577-8592
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Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma remains an incurable brain cancer. Drugs developed in the past 20 years have not improved the prognosis for patients, necessitating the development of new treatments. We have previously reported the therapeutic potential of the quinoline methanol Vacquinol-1 (1) that targets glioblastoma cells and induces cell death by catastrophic vacuolization. Compound 1 is a mixture of four stereoisomers due to the two adjacent stereogenic centers in the molecule, complicating further development in the preclinical setting. This work describes the isolation and characterization of the individual isomers of 1 and shows that these display stereospecific pharmacokinetic and pharmacodynamic features. In addition, we present a stereoselective synthesis of the active isomers, providing a basis for further development of this compound series into a novel experimental therapeutic for glioblastoma.
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| 6. |
- Johansson, Kari, et al.
(författare)
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Outcomes of pregnancy after bariatric surgery
- 2015
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 372:9, s. 814-824
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Maternal obesity is associated with increased risks of gestational diabetes, large-for-gestational-age infants, preterm birth, congenital malformations, and stillbirth. The risks of these outcomes among women who have undergone bariatric surgery are unclear.METHODS: We identified 627,693 singleton pregnancies in the Swedish Medical Birth Register from 2006 through 2011, of which 670 occurred in women who had previously undergone bariatric surgery and for whom presurgery weight was documented. For each pregnancy after bariatric surgery, up to five control pregnancies were matched for the mother's presurgery body-mass index (BMI; we used early-pregnancy BMI in the controls), age, parity, smoking history, educational level, and delivery year. We assessed the risks of gestational diabetes, large-for-gestational-age and small-for-gestational-age infants, preterm birth, stillbirth, neonatal death, and major congenital malformations.RESULTS: Pregnancies after bariatric surgery, as compared with matched control pregnancies, were associated with lower risks of gestational diabetes (1.9% vs. 6.8%; odds ratio, 0.25; 95% confidence interval [CI], 0.13 to 0.47; P< 0.001) and large-for-gestational-age infants (8.6% vs. 22.4%; odds ratio, 0.33; 95% CI, 0.24 to 0.44; P< 0.001). In contrast, they were associated with a higher risk of small-for-gestational-age infants (15.6% vs. 7.6%; odds ratio, 2.20; 95% CI, 1.64 to 2.95; P< 0.001) and shorter gestation (273.0 vs. 277.5 days; mean difference -4.5 days; 95% CI, -2.9 to -6.0; P< 0.001), although the risk of preterm birth was not significantly different (10.0% vs. 7.5%; odds ratio, 1.28; 95% CI, 0.92 to 1.78; P = 0.15). The risk of stillbirth or neonatal death was 1.7% versus 0.7% (odds ratio, 2.39; 95% CI, 0.98 to 5.85; P = 0.06). There was no significant between-group difference in the frequency of congenital malformations.CONCLUSIONS: Bariatric surgery was associated with reduced risks of gestational diabetes and excessive fetal growth, shorter gestation, an increased risk of small-for-gestational-age infants, and possibly increased mortality.
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| 7. |
- Ludvigsson, Jonas F., 1969-, et al.
(författare)
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Maternal vaccination against H1N1 influenza and offspring mortality : population based cohort study and sibling design
- 2015
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Ingår i: BMJ. British Medical Journal. - London, United Kingdom : BMJ Publishing Group Ltd. - 0959-8146 .- 0959-535X. ; 351
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Tidskriftsartikel (refereegranskat)abstract
- Study question: What is the mortality in offspring of mothers who hadinfluenza A(H1N1)pdm09 vaccination during pregnancy?Methods: This was a prospective population based cohort study in seven healthcare regions in Sweden based on vaccinations taking place between 2 October 2009 and 26 November 2010. H1N1 vaccination data were linked with pregnancy and birth characteristics and offspring mortality data in 275 500 births (of which 1203 were stillbirths) from 137 886 mothers. Of these offspring, 41 183 had been exposed to vaccination with Pandemrix, a monovalent AS03 adjuvanted H1N1 influenza vaccine, during fetal life. A primary comparison group consisted of pregnancies of women who were not vaccinated during the same calendar period. In a second comparison, non-exposed siblings of infants prenatally exposed to vaccination were used as controls. Cox regression was used to estimate hazard ratios for stillbirth, early neonatal mortality (days 0-6 after birth), and subsequent mortality (beginning on day 7) in vaccinated versus nonvaccinated women, adjusting for mother’s age at delivery, body mass index, parity, smoking, country of birth, and disposable income and for sex of offspring.Study answer and limitations: The results of this study suggest that AS03 adjuvanted H1N1 vaccination during pregnancy does not affect the risk of stillbirth, early neonatal death, or later mortality in the offspring. During follow-up, 1172 stillbirths, 380 early neonatal deaths, and 706 deaths thereafter occurred. Compared with general population controls, this corresponded to adjusted hazard ratios of 0.83 (95% confidence interval 0.65 to 1.04) for stillbirth, 0.71 (0.44 to 1.14) for early neonatal death, and 0.97 (0.69 to 1.36) for later death. When siblings were used as controls, adjusted hazard ratios were 0.88 (0.59 to 1.30) for stillbirth, 0.82 (0.46 to 1.49) for early neonatal death, and 0.78 (0.52 to 1.19) for later death. Limitations of the study include lack of data on miscarriage before gestational week 22, inability to ascertain which mothers had pandemic flu during pregnancy, and lack of data on factors influencing the decision to vaccinate during pregnancy.What this study adds: H1N1 vaccination during pregnancy is not associated with adverse fetal outcome or offspring mortality, including when familial factors are taken into account.
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| 8. |
- Ludvigsson, Jonas F., 1969-, et al.
(författare)
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Risk for Congenital Malformation With H1N1 Influenza Vaccine : A Cohort Study With Sibling Analysis
- 2016
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Ingår i: Annals of Internal Medicine. - Philadelphia, USA : American College of Physicians. - 0003-4819 .- 1539-3704. ; 165:12, s. 848-855
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Tidskriftsartikel (refereegranskat)abstract
- Background: Earlier studies reporting varying risk estimates for congenital malformation in offspring of mothers undergoing vaccination against H1N1 influenza during pregnancy did not consider the potential role of confounding by familial (genetic and shared environmental) factors.Objective: To evaluate an association between maternal H1N1 vaccination during pregnancy and offspring malformation, with familial factors taken into account.Design: Population-based prospective study.Setting: Sweden.Participants: Liveborn offspring born between 1 October 2009 and 1 October 2011 to mothers receiving monovalent AS03-adjuvanted H1N1 influenza vaccine (Pandemrix [GlaxoSmithKline]) during pregnancy. A total of 40 983 offspring were prenatally exposed to the vaccine, 14 385 were exposed within the first trimester (14 weeks), and 7502 were exposed during the first 8 weeks of pregnancy. Exposed offspring were compared with 197 588 unexposed offspring. Corresponding risks in exposed versus unexposed siblings were also estimated.Measurements: Congenital malformation, with subanalyses for congenital heart disease, oral cleft, and limb deficiency.Results: Congenital malformation was observed in 2037 (4.97%) exposed offspring and 9443 (4.78%) unexposed offspring. Adjusted risk for congenital malformation was 4.98% in exposed offspring versus 4.96% in unexposed offspring (risk difference, 0.02% [95% CI, -0.26% to 0.30%]). The corresponding risk differences were 0.16% (CI, -0.23% to 0.56%) for vaccination during the first trimester and 0.10% (CI, -0.41% to 0.62%) for vaccination in the first 8 weeks. Using siblings as comparators yielded no statistically significant risk differences.Limitations: The study was based on live births, and the possibility that data on miscarriage or induced abortion could have influenced the findings cannot be ruled out. Study power was limited in analyses of specific malformations.Conclusion: When intrafamilial factors were taken into consideration, H1N1 vaccination during pregnancy did not seem to be linked to overall congenital malformation in offspring, although risk increases for specific malformations could not be ruled out completely.
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| 9. |
- Neovius, Martin, et al.
(författare)
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Risk of suicide and non-fatal self-harm after bariatric surgery: results from two matched cohort studies.
- 2018
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Ingår i: The lancet. Diabetes & endocrinology. - : Elsevier. - 2213-8595 .- 2213-8587. ; 6:3, s. 197-207
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Tidskriftsartikel (refereegranskat)abstract
- Bariatric surgery reduces mortality, but might have adverse effects on mental health. We assessed the risk of suicide and self-harm after bariatric surgery compared with non-surgical obesity treatment.Suicide and non-fatal self-harm events retrieved from nationwide Swedish registers were examined in two cohorts. The non-randomised, prospective Swedish Obese Subjects (SOS) study compared bariatric surgery (n=2010; 1369 vertical-banded gastroplasty, 376 gastric banding, and 265 gastric bypass) with usual care (n=2037; recruitment 1987-2001). The second cohort consisted of individuals from the Scandinavian Obesity Surgery Registry (SOReg; n=20256 patients who had gastric bypass) matched to individuals treated with intensive lifestyle modification (n=16162; intervention 2006-13) on baseline BMI, age, sex, education level, diabetes, cardiovascular disease, history of self-harm, substance misuse, antidepressant use, anxiolytics use, and psychiatric health-care contacts.During 68528 person-years (median 18; IQR 14-21) in the SOS study, suicides or non-fatal self-harm events were higher in the surgery group (n=87) than in the control group (n=49; adjusted hazard ratio [aHR] 1·78, 95% CI 1·23-2·57; p=0·0021); of these events, nine and three were suicides, respectively (3·06, 0·79-11·88; p=0·11). In analyses by primary procedure type, increased risk of suicide or non-fatal self-harm was identified for gastric bypass (3·48, 1·65-7·31; p=0·0010), gastric banding (2·43, 1·23-4·82; p=0·011), and vertical-banded gastroplasty (2·25, 1·37-3·71; p=0·0015) compared with controls. Out of nine deaths by suicide in the SOS surgery group, five occurred after gastric bypass (two primary and three converted procedures). During 149582 person-years (median 3·9; IQR 2·8-5·2), more suicides or non-fatal self-harm events were reported in the SOReg gastric bypass group (n=341) than in the intensive lifestyle group (n=84; aHR 3·16, 2·46-4·06; p<0·0001); of these events, 33 and five were suicides, respectively (5·17, 1·86-14·37; p=0·0017). In SOS, substance misuse during follow-up was recorded in 48% (39/81) of patients treated with surgery and 28% (13/47) of controls with non-fatal self-harm events (p=0·023). Correspondingly, substance misuse during follow-up was recorded in 51% (162/316) of participants in the SOReg gastric bypass group and 29% (23/80) of participants in the intensive lifestyle group with non-fatal self-harm events (p=0·0003). The risk of suicide and self-harm was not associated with poor weight loss outcome.Bariatric surgery was associated with suicide and non-fatal self-harm. However, the absolute risks were low and do not justify a general discouragement of bariatric surgery. The findings indicate a need for thorough preoperative psychiatric history assessment along with provision of information about increased risk of self-harm following surgery. Moreover, the findings call for postoperative surveillance with particular attention to mental health.US National Institutes of Health and Swedish Research Council.
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