| 1. |
- Kaufmann, Tobias, et al.
(författare)
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Common brain disorders are associated with heritable patterns of apparent aging of the brain
- 2019
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Ingår i: Nature Neuroscience. - : Nature Publishing Group. - 1097-6256 .- 1546-1726. ; 22:10, s. 1617-
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Tidskriftsartikel (refereegranskat)abstract
- Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3-96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders.
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| 2. |
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| 3. |
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| 4. |
- Alnaes, Dag, et al.
(författare)
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Brain Heterogeneity in Schizophrenia and Its Association With Polygenic Risk
- 2019
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Ingår i: JAMA psychiatry. - : AMER MEDICAL ASSOC. - 2168-6238 .- 2168-622X. ; 76:7, s. 739-748
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Tidskriftsartikel (refereegranskat)abstract
- ImportanceBetween-individual variability in brain structure is determined by gene-environment interactions, possibly reflecting differential sensitivity to environmental and genetic perturbations. Magnetic resonance imaging (MRI) studies have revealed thinner cortices and smaller subcortical volumes in patients with schizophrenia. However, group-level comparisons may mask considerable within-group heterogeneity, which has largely remained unnoticed in the literature. ObjectivesTo compare brain structural variability between individuals with schizophrenia and healthy controls and to test whether respective variability reflects the polygenic risk score (PRS) for schizophrenia in an independent sample of healthy controls. Design, Setting, and ParticipantsThis case-control and polygenic risk analysis compared MRI-derived cortical thickness and subcortical volumes between healthy controls and patients with schizophrenia across 16 cohorts and tested for associations between PRS and MRI features in a control cohort from the UK Biobank. Data were collected from October 27, 2004, through April 12, 2018, and analyzed from December 3, 2017, through August 1, 2018. Main Outcomes and MeasuresMean and dispersion parameters were estimated using double generalized linear models. Vertex-wise analysis was used to assess cortical thickness, and regions-of-interest analyses were used to assess total cortical volume, total surface area, and white matter, subcortical, and hippocampal subfield volumes. Follow-up analyses included within-sample analysis, test of robustness of the PRS threshold, population covariates, outlier removal, and control for image quality. ResultsA comparison of 1151 patients with schizophrenia (mean [SD] age,33.8[10.6] years; 68.6% male [n=790] and 31.4% female [n=361]) with 2010 healthy controls (mean [SD] age,32.6[10.4] years; 56.0% male [n=1126] and 44.0% female [n=884]) revealed higher heterogeneity in schizophrenia for cortical thickness and area (t = 3.34), cortical (t=3.24) and ventricle (t range, 3.15-5.78) volumes, and hippocampal subfields (t range, 2.32-3.55). In the UK Biobank sample of 12 490 participants (mean [SD] age,55.9 [7.5] years; 48.2% male [n=6025] and 51.8% female [n=6465]), higher PRS was associated with thinner frontal and temporal cortices and smaller left CA2/3 (t=-3.00) but was not significantly associated with dispersion. Conclusions and RelevanceThis study suggests that schizophrenia is associated with substantial brain structural heterogeneity beyond the mean differences. These findings may reflect higher sensitivity to environmental and genetic perturbations in patients, supporting the heterogeneous nature of schizophrenia. A higher PRS was associated with thinner frontotemporal cortices and smaller hippocampal subfield volume, but not heterogeneity. This finding suggests that brain variability in schizophrenia results from interactions between environmental and genetic factors that are not captured by the PRS. Factors contributing to heterogeneity in frontotemporal cortices and hippocampus are key to furthering our understanding of how genetic and environmental factors shape brain biology in schizophrenia.
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| 5. |
- Annas, Anita, et al.
(författare)
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Basal and induced EROD activity in the chorioallantoic membrane during chicken embryo development
- 1999
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Ingår i: Environmental Toxicology and Pharmacology. - 1382-6689 .- 1872-7077. ; 8:1, s. 49-52
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The chorioallantoic membrane (CAM) is a highly vascularized tissue that takes part in the respiratory exchange of gases through the eggshell. Although the CAM may be exposed to environmental contaminants, its response to pollutants has not been studied. We examined the cytochrome P4501A (CYP1A)-catalyzed deethylation of 7-ethoxyresorufin (EROD) in the CAM during chicken embryo development. EROD was constitutively present and was inducible by the aryl hydrocarbon (Ah) receptor agonist 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126). Our results suggest the CAM as a first line of defence of the avian embryo against toxic compounds, but also as a target for CYP1A-activated chemicals.
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| 6. |
- Askling, Johan, et al.
(författare)
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Risk and case characteristics of tuberculosis in rheumatoid arthritis associated with tumor necrosis factor antagonists in Sweden
- 2005
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 52:7, s. 1986-1992
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:Because treatment with tumor necrosis factor (TNF) antagonists may increase the risk of tuberculosis (TB), and because knowledge of the risk of TB in rheumatoid arthritis (RA) not treated with biologics is scarce and of uncertain generalizability to low-risk populations, this study sought to determine the risk of TB among Swedish patients with RA.METHODS:Using data from Swedish nationwide and population-based registers and data from an ongoing monitoring program of TNF antagonists, the relative risks of TB in patients with RA (versus the general population) and of TB associated with TNF antagonists (versus RA patients not treated with biologics) were determined by comparing the incidence of hospitalization for TB in 3 RA cohorts and 2 general population cohorts from 1999 to 2001. We also reviewed the characteristics of all reported cases of TB in RA patients treated with TNF antagonists in Sweden and calculated the incidence of TB per type of TNF antagonist between 1999 and 2004.RESULTS:During 1999-2001, RA patients who were not treated with TNF antagonists were at increased risk of TB versus the general population (relative risk 2.0, 95% confidence interval [95% CI] 1.2-3.4). RA patients treated with TNF antagonists had a 4-fold increased risk of TB (relative risk 4.0, 95% CI 1.3-12) versus RA patients not treated with TNF antagonists. The reported TB cases during 1999-2004 in RA patients exposed to TNF antagonists (9 infliximab, 4 etanercept, 2 both) were predominantly pulmonary. TB occurred up to 3 years following the start of treatment.CONCLUSION:Irrespective of whether TNF antagonists are administered, Swedish patients with RA are at increased risk of TB. During 1999-2001, TNF antagonists were associated with an increased risk of TB, up to 4-fold in magnitude. This increased risk may persist over time during treatment and is related to both infliximab and etanercept.
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| 7. |
- Askling, Johan, et al.
(författare)
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Time-dependent increase in risk of hospitalisation with infection among Swedish RA patients treated with TNF antagonists
- 2007
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 66:10, s. 1339-1344
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES:The degree to which treatment with tumour necrosis factor (TNF) antagonists may be associated with increased risks for serious infections is unclear. An observational cohort study was performed using prospectively collected data from the Swedish Biologics Register (ARTIS) and other national Swedish registers.METHODS:First, in the ARTIS, all 4167 rheumatoid arthritis (RA) patients starting TNF antagonist treatment between 1999 and 2003 were identified. Secondly, in the Swedish Inpatient Register, all individuals hospitalised for any reason and who also carried a diagnosis of RA, between 1964 and 2003 (n = 44 946 of whom 2692 also occurred in ARTIS), were identified. Thirdly, in the Swedish Inpatient Register, all hospitalisations listing an infection between 1999 and 2003 were identified. By cross-referencing these three data sets, RRs for hospitalisation with infection associated with TNF antagonist treatment were calculated within the cohort of 44 946 RA patients, using Cox regression taking sex, age, geography, co-morbidity and use of inpatient care into account.RESULTS:Among the 4167 patients treated with TNF antagonists, 367 hospitalisations with infections occurred during 7776 person-years. Within the cohort of 44 496 RA patients, the RR for infection associated with TNF antagonists was 1.43 (95% CI 1.18 to 1.73) during the first year of treatment, 1.15 (95% CI 0.88 to 1.51) during the second year of treatment, and 0.82 (95% CI 0.62 to 1.08) for subjects remaining on their first TNF antagonist treatment after 2 years.CONCLUSION:Treatment with TNF antagonists may be associated with a small to moderate increase in risk of hospitalisation with infection, which disappears with increasing treatment duration.
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| 8. |
- Bakkman, Linda, et al.
(författare)
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Reduced respiratory capacity in muscle mitochondria of obese subjects.
- 2010
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Ingår i: Obesity Facts. - : S. Karger AG. - 1662-4025 .- 1662-4033. ; 3:6, s. 371-5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIMS: The extent of weight gain varies among individuals despite equal calorie overconsumption. Furthermore, weight gain is often less than expected from energy excess. This suggests differences in metabolic efficiency and basal metabolism. Since mitochondrial uncoupling accounts for a substantial portion of the basal metabolic rate, we compared skeletal muscle mitochondrial respiration in obese subjects to normal-weight reference groups with various degrees of physical activity.METHODS: Muscle biopsies were taken from the vastus lateralis muscle of 9 healthy obese subjects (BMI 40 ± 3). Mitochondria were isolated and analyzed for coupled (state 3) and uncoupled (state 4) respirations as well as mitochondrial efficiency (P/O ratio) using pyruvate as a substrate. Respiratory data were compared to reference groups A, normal-weight untrained (BMI 24 ± 0.7), and B, normal-weight trained (BMI 24 ± 0.6).RESULTS: Obese subjects had a decreased respiratory capacity per mitochondrial volume compared to the reference groups: this was evident in state 4 (65% and 35% of reference group A and B, respectively) and state 3 (53% and 29% of A and B, respectively) (p < 0.05).CONCLUSION: Obese subjects had a low capacity for fuel oxidation, which may play a role in the predisposition of obesity. However, whether lower mitochondrial capacity is a cause or a consequence of obesity requires further research.
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| 9. |
- Bensing, Sophie, et al.
(författare)
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Increased death risk and altered cancer incidence pattern in patients with isolated or combined autoimmune primary adrenocortical insufficiency
- 2008
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Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 69:5, s. 697-704
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Primary adrenocortical insufficiency is mostly caused by an autoimmune destruction of the adrenal cortex. The disease may appear isolated or as a part of an autoimmune polyendocrine syndrome (APS). APS1 is a rare hereditary disorder with a broad spectrum of clinical manifestations. In APS2, primary adrenocortical insufficiency is often combined with autoimmune thyroid disease and/or type 1 diabetes. We analysed mortality and cancer incidence in primary adrenocortical insufficiency patients during 40 years. Data were compared with the general Swedish population. DESIGN AND PATIENTS: A population based cohort study including all patients with autoimmune primary adrenocortical insufficiency (3299) admitted to Swedish hospitals 1964-2004. MEASUREMENTS: Mortality risk was calculated as the standardized mortality ratio (SMR) and cancer incidence as the standardized incidence ratio (SIR). RESULTS: A more than 2-fold increased mortality risk was observed in both women (SMR 2.9, 95% CI 2.7-3.0) and men (SMR 2.5, 95% CI 2.3-2.7). Highest risks were observed in patients diagnosed in childhood. SMR was higher in APS1 patients (SMR 4.6, 95% CI 3.5-6.0) compared with patients with APS2 (SMR 2.1, 95% CI 1.9-2.4). Cancer incidence was increased (SIR 1.3, 95% CI 1.2-1.5). When tumours observed during the first year of follow-up were excluded, only the cancer risk among APS1 patients remained increased. Cause-specific cancer incidence analysis revealed significantly higher incidences of oral cancer, nonmelanoma skin cancer, and male genital system cancer among patients. Breast cancer incidence was lower than in the general population. CONCLUSIONS: Our study shows a reduced life expectancy and altered cancer incidence pattern in patients with autoimmune primary adrenocortical insufficiency.
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| 10. |
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| 11. |
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| 12. |
- Björnsdottir, Sigridur, et al.
(författare)
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Addison's Disease in Women Is a Risk Factor for an Adverse Pregnancy Outcome
- 2010
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 95:12, s. 5249-5257
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Tidskriftsartikel (refereegranskat)abstract
- Context: Autoimmune Addison's disease(AAD) tends to affect young and middle-aged women. It is not known whether the existence of undiagnosed or diagnosed AAD influences the outcome of pregnancy. Objective: The aim of the study was to compare the number of children and pregnancy outcomes in individuals with AAD and controls. Design and Setting: We conducted a population-based historical cohort study in Sweden. Patients: Through the Swedish National Patient Register and the Total Population Register, we identified 1,188 women with AAD and 11,879 age-matched controls who delivered infants between 1973 and 2006. Main Outcome Measures: We measured parity and pregnancy outcome. Results: Adjusted odds ratios (ORs) for infants born to mothers with deliveries 3 yr or less before the diagnosis of AAD were 2.40 [95% confidence interval (Cl), 1.27-4.53] for preterm birth (<= 37 wk), 3.50 (95% Cl, 1.83-6.67) for low birth weight (<2500 g), and 1.74 (95% Cl, 1.02-2.96) for cesarean section. Compared to controls, women who gave birth after their AAD diagnosis were at increased risk of both cesarean delivery (adjusted OR, 2.35; 95% Cl, 1.68-3.27) and preterm delivery (adjusted OR, 2.61; 95% Cl, 1.69-4.05). Stratifying by isolated AAD and concomitant type 1 diabetes and/or autoimmune thyroid disease in the mother did not essentially influence these risks. There were no differences in risks of congenital malformations or infant death. Women with AAD had a reduced overall parity compared to controls (P < 0.001). Conclusion: Clinically undiagnosed and diagnosed AAD both entail increased risks of unfavorable pregnancy outcomes. AAD also influences the number of childbirths.
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| 13. |
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| 14. |
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| 15. |
- Bodén, Robert, et al.
(författare)
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Antipsychotics During Pregnancy Relation to Fetal and Maternal Metabolic Effects
- 2012
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Ingår i: Archives of General Psychiatry. - : American Medical Association (AMA). - 0003-990X .- 1538-3636. ; 69:7, s. 715-721
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Tidskriftsartikel (refereegranskat)abstract
- Context: Knowledge about the effects of exposure to the newer antipsychotics during pregnancy is limited. Objective: To investigate the effects of maternal use of antipsychotics during pregnancy on gestational diabetes and fetal growth. Design: Population-based cohort study comparing women exposed and not exposed to antipsychotics during pregnancy. Exposure was defined as prescriptions filled. Setting: Swedish national health registers. Participants: All women giving birth in Sweden from July 1, 2005, through December 31, 2009, grouped by filled prescriptions for (1) olanzapine and/or clozapine, the most obesogenic and diabetogenic antipsychotics (n=169), (2) other antipsychotics (n=338), or (3) no antipsychotics (n=357 696). Main Outcome Measures: Odds ratios (ORs) with 95% CIs for gestational diabetes and being small for gestational age (SGA) and large for gestational age for birth weight, birth length, and head circumference. Results: Exposure to other antipsychotics was associated with an increased risk of gestational diabetes (adjusted OR, 1.77 [95% CI, 1.04-3.03]). The risk increase with olanzapine and/or clozapine was of similar magnitude but not statistical significance (adjusted OR, 1.94 [95% CI, 0.97-3.91]). Infants exposed to either group of antipsychotics had increased risks of being SGA on birth weight, whereas only exposure to other antipsychotics yielded increased risks of being SGA for birth length and head circumference. None of the risks for SGA measurements remained significant after adjusting for maternal factors. There were no increased risks of being large for gestational age for birth weight or birth length after exposure to olanzapine and/or clozapine, but the risk increased for head circumference (OR, 3.02 [95% CI, 1.60-5.71]). Conclusions: Women who used antipsychotics during pregnancy had increased risks of gestational diabetes. The increased risks of giving birth to an SGA infant seemed to be an effect of confounders, such as smoking. Except for macrocephaly, olanzapine and/or clozapine exposure was not associated with anabolic fetal growth.
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| 16. |
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| 17. |
- Boden, Robert, et al.
(författare)
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Early non-adherence to medication and other risk factors for rehospitalization in schizophrenia and schizoaffective disorder
- 2011
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Ingår i: Schizophrenia Research. - : Elsevier BV. - 0920-9964 .- 1573-2509. ; 133:1-3, s. 36-41
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Tidskriftsartikel (refereegranskat)abstract
- Non-adherence to antipsychotic medication and hospitalization in psychotic disorders are common and costly problems. Our aim was to identify risk factors for rehospitalization of patients with recent onset schizophrenia or schizoaffective disorder in a population-based cohort study. All patients with a first hospitalization for schizophrenia or schizoaffective disorder between 2006 and 2007 were included (n = 861). Patients were identified through and data retrieved from national Swedish health and population registers. We investigated how socio-demographic variables, duration of first hospitalization and prescription fills of antipsychotics were associated with rehospitalization in Cox regression models. A higher risk for rehospitalization within 28 days was observed in patients with a first hospitalization that was shorter than two weeks compared with patients who were hospitalized for more than four weeks: hazard ratio (HR) 2.30,95% confidence interval (CI) 1.42 to 3.74. Further, patients who did not fill a prescription of antipsychotics within the first week after discharge had a higher risk of early rehospitalization than patients who were given antipsychotics (HR 1.75, 95% CI 1.13 to 2.72). More than 12 years of education was associated with a lower risk of early rehospitalization (HR 0.44,95% CI 0.26 to 0.77). Sex, age, being born in Sweden, urban area residence and prescription fills of antipsychotics prior to first admission did not significantly affect the risk of early rehospitalization. In conclusion, we identified two potentially modifiable risk factors for rehospitalization: short duration of initial hospitalization and early non-adherence to medication.
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| 18. |
- Bodén, Robert, et al.
(författare)
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Factors associated with pregabalin dispensing at higher than the approved maximum dose
- 2014
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Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 70:2, s. 197-204
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Tidskriftsartikel (refereegranskat)abstract
- Concerns have been raised about the abuse potential of pregabalin. Therefore, the aim of our study was to characterize patients dispensed pregabalin at higher than the maximum allowed dose in a cohort study based on data extracted from Swedish national registers. All patients dispensed at least three prescriptions of pregabalin between July 2006 and December 2009 were included (n = 48,550). The daily dose was defined as the amount of pregabalin dispensed divided by the number of days between the second and third dispensings. Associations between sociodemographic and clinical variables and dispensing pregabalin at a dose exceeding the maximum daily allowed dose (600 mg) were investigated in multivariate regression models. Of the patients dispensed pregabalin during the study period, 8.5 % were dispensed a dose that exceeded the maximum daily allowed dose. A previous addictive disorder drug treatment or diagnosis was present in 20 and 31 % of patients dispensed pregabalin within and exceeding the recommended dose range, respectively. Our analysis revealed that those patients at increased risk of being dispensed pregabalin at higher than the maximum allowed dose were male [adjusted odds ratio (aOR) 1.40, 95 % confidence interval (CI) 1.31-1.49], were between 18 and 29 years of age compared with those aged a parts per thousand yen65 years (aOR 1.62, 95 % CI 1.45-1.82), had a low income (aOR 1.24, 95 % CI 1.10-1.40), had epilepsy compared with no diagnosis (aOR 1.41, 95 % CI 1.10-1.81), had a previous substance use disorder treatment or diagnosis (aOR 1.41, 95 % CI 1.31-1.52) or had previously been dispensed high doses of drugs with abuse potential (aOR 1.77, 95 % CI 1.62-1.94). Based on our results we conclude that patients at a high risk of addiction and patients with epilepsy are more likely to be dispensed pregabalin at higher than the maximum approved daily dose.
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| 19. |
- Boden, Robert, et al.
(författare)
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Risks of adverse pregnancy and birth outcomes in women treated or not treated with mood stabilisers for bipolar disorder : population based cohort study
- 2012
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Ingår i: The BMJ. - : BMJ. - 1756-1833. ; 345, s. e7085-
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate the risks of adverse pregnancy and birth outcomes for treated and untreated bipolar disorder during pregnancy. Design Population based cohort study using data from national health registers. Setting Sweden. Participants 332 137 women with a last menstrual period anytime after 1 July 2005 and giving birth anytime before the end of 31 December 2009. Women with a record of at least two bipolar diagnoses were identified and grouped as treated (n=320)-those who had filled a prescription for mood stabilisers (lithium, antipsychotics, or anticonvulsants) during pregnancy-or untreated (n=554). Both groups were compared with all other women giving birth (n=331 263). Main outcome measures Preterm birth, mode of labour initiation, gestational diabetes, infants born small or large for gestational age, neonatal morbidity, and congenital malformations. Results Of the untreated women, 30.9% (n=171) were induced or had a planned caesarean delivery compared with 20.7% (n=68 533) without bipolar disorder (odds ratio 1.57, 95% confidence interval 1.30 to 1.90). The corresponding values for the treated women were 37.5% (n=120) (2.12, 1.68 to 2.67). The risks of preterm birth in both treated and untreated women were increased by 50%. Of the untreated women, 3.9% (n=542) had a microcephalic infant compared with 2.3% (324 844) of the women without bipolar disorder (1.68, 1.07 to 2.62). The corresponding values for the treated women were 3.3% (n=311) (1.26, 0.67 to 2.37). Similar trends were observed for risks of infants being small for gestational age infants for weight and length. Among infants of untreated women, 4.3% (n=24) had neonatal hypoglycaemia compared with 2.5% (n=8302) among infants of women without bipolar disorder (1.51, 1.04 to 2.43), and 3.4% (n=11) of the treated women (1.18, 0.64 to 2.16). The analyses of variation in outcomes did not support any significant differences between treated and untreated women. Conclusions Bipolar disorder in women during pregnancy, whether treated or not, was associated with increased risks of adverse pregnancy outcomes.
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| 20. |
- Brauner, Annelie, et al.
(författare)
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Is there a risk of cancer development after Campylobacter infection?
- 2010
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Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 45:7-8, s. 893-897
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: All Campylobacter jejuni species produce a genotoxin, which induce DNA double strand breaks, could lead to an increased risk of cancer especially in the gastro-intestinal tract.MATERIAL AND METHODS: All individuals in Stockholm County who tested positive with C. jejuni between 1989 and 2006 were included. The cohort was followed-up until December 31, 2007 for the occurrence of cancer, overall and site specific. Standard incidence ratios (SIR) with 95% confidence intervals (CI) were calculated by comparisons with the background population.RESULTS: There were 16,276 individuals who tested positive for C. jejuni generating 124,387 person years. Excluding the first year of follow-up the overall risk for cancer did neither differ from that expected SIR = 0.95 (95% CI 0.82-1.09) nor after 10 years or more of follow-up; SIR = 0.91 (95% CI 0.71-1.16). There was no increased risk for cancer in the gastro-intestinal tract, but there were significantly increased risks for melanomas SIR = 1.84 (95% CI 1.27-2.57) and squamous cell skin cancer SIR = 1.52 (95% CI 1.01-2.19) while a significantly decreased risk of respiratory cancers among males SIR = 0.32 (95% CI 0.12-0.70) was observed.CONCLUSIONS: Our results indicate no excess risks of malignancies following an infection by C. jejuni at least during the first decade. Furthermore, the finding of a decreased risk of respiratory cancers could be of interest, if the results are reproduced in future studies in other populations.
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| 21. |
- Brenner, Philip, et al.
(författare)
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Substance use disorders and risk for treatment resistant depression : a population-based, nested case-control study
- 2020
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Ingår i: Addiction. - : Wiley. - 0965-2140 .- 1360-0443. ; 115:4, s. 768-777
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Treatment-resistant depression (TRD), defined as inadequate treatment response after at least two adequate treatment trials, is common among patients initiating antidepressant treatment. Current or previous substance use disorders (SUD) are common among patients with depression and often lead to worse treatment outcomes. However, in clinical studies, SUD have not been found to increase the risk for TRD. The aim of this study was to investigate the association between SUD and TRD.Design: Nested case-control study.Setting: Nation-wide governmental health-care registers in Sweden.Cases and controls: Data on prescribed drugs and diagnoses from specialized health care were used to establish a prospectively followed cohort of antidepressant initiators with depression (n = 121 669) from 2006 to 2014. Of these, 15 631 patients (13%) were defined as TRD cases, with at least three treatment trials within a single depressive episode. Each case with TRD was matched on socio-demographic data with five controls with depression.Measurements: Crude and adjusted odds ratios (aOR) with 95% confidence intervals (CI) estimated the association between TRD and SUD diagnosis and/or treatment in five different time intervals until the time for fulfillment of TRD definition for the case. The analysis was adjusted for clinical and socio-demographic covariates.Findings: Having any SUD during, or <= 180 days before start of, antidepressant treatment was associated with almost double the risk for TRD [<= 180 days before: adjusted OR (aOR) = 1.86, CI = 1.70-2.05]. Increased risks for TRD were found <= 180 days before treatment start for the subcategories of sedative use (aOR = 2.37; 1.88-2.99), opioids (aOR = 2.02; 1.48-2.75), alcohol (aOR = 1.77; CI = 1.59-1.98) and combined substance use (aOR = 2.31; 1.87-2.99).Conclusions: Recent or current substance use disorders is positively associated with treatment resistance among patients initiating treatment for depression.
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| 22. |
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| 23. |
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| 24. |
- Brenner, Philip, et al.
(författare)
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Treatment-resistant depression as risk factor for substance use disorders : a nation-wide register-based cohort study
- 2019
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Ingår i: Addiction. - : Wiley. - 0965-2140 .- 1360-0443. ; 114:7, s. 1274-1282
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims Treatment-resistant depression (TRD) is common among patients with major depressive disorder (MDD). MDD may increase the risk for developing substance use disorders (SUD). The aim of this study was to investigate the risk for developing SUD among patients with TRD compared with other depressed patients.Design Observational cohort study.Setting Nation-wide governmental health registers in Sweden.Participants All patients aged 18-69 years with an MDD diagnosis in specialized health care who had received at least one antidepressant prescription during 2006-14 were identified. Patients with at least three treatment trials within a single depressive episode were classified with TRD.Measurements Patients with TRD were compared with the whole MDD cohort regarding risk for obtaining a SUD diagnosis or medication using survival analyses adjusted for socio-demographics and comorbidities.Findings Of 121 669 MDD patients, 13% were classified with TRD. Among the patients without any history of SUD, patients with TRD had a risk increase for any SUD both ≤ 1 and > 1 year after antidepressant initiation [> 1 year hazard ratio (HR) = 1.4; 95% confidence interval (CI) = 1.3-1.5]. Risks were elevated for the subcategories of opioid (HR = 1.9, 95% CI = 1.4-2.5) and sedative SUD (HR = 2.7, 95% CI = 2.2-3.2). Patients with a history of SUD had a risk increase for any SUD ≤ 1 year after start of treatment (HR = 1.2, 95% CI = 1.1-1.4), and both ≤ 1 year and > 1 year for sedative (> 1 year HR = 2.0, 95% CI = 1.3-3.0) and multiple substance SUD (HR = 1.9, 95% CI = 1.4-2.5).Conclusions Patients with treatment-resistant depression may be at greater risk for substance use disorders compared with other patients with major depressive disorder. Patterns may differ for patients with and without a history of substance use disorders, and for different categories of substance use disorder.
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| 26. |
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| 27. |
- Clapham, Eric, et al.
(författare)
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Suicide Ideation and Behavior as Risk Factors for Subsequent Suicide in Schizophrenia : A Nested Case-Control Study
- 2019
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Ingår i: Journal of Suicide and Life-threatening Behaviour. - : WILEY. - 0363-0234 .- 1943-278X. ; 49:4, s. 996-1005
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate suicide ideation and behavior as risk factors for suicide in schizophrenia during varying time periods. Method Cases were 84 patients who died by suicide within 5 years from diagnosis in a source population of patients discharged for the first time from psychiatric hospitals in Stockholm County, Sweden, with a schizophrenia spectrum diagnosis. One control was individually matched with each suicide case. Data were retrieved from clinical records in a blind fashion. Thoughts of death, thoughts of suicide, suicide plan, and suicide attempt during varying time periods were investigated as risk factors for subsequent completed suicide. Results In adjusted analyses, thoughts of suicide, suicide plan, and suicide attempt were significantly associated with subsequent completed suicide in the following year. The highest suicide risk was found within a year following suicide attempt (adjusted OR 9.9, 95% confidence interval 2.5-39.0). The association between suicide ideation and behavior and subsequent suicide declined over time. Conclusions Several types of suicide ideation and behavior were associated with suicide, and the association was stronger for suicidal behavior. The clinical significance of suicidal communication appears highest during the following month or/and year. Many suicides occurred without recorded short-term suicidal communication.
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| 28. |
- Clapham, Eric, et al.
(författare)
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The association between exposure to clozapine, olanzapine, and quetiapine and the outcomes perimyocarditis and heart failure : A population-based cohort study
- 2023
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Ingår i: Psychiatry Research. - : Elsevier. - 0165-1781 .- 1872-7123. ; 326
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Tidskriftsartikel (refereegranskat)abstract
- The risk of cardiac adverse events following clozapine use is debated and is unknown for the chemically related and widely used antipsychotics olanzapine and quetiapine. National Swedish registers were used to identify all patients 16-75 years old with antipsychotic dispensations between 2005 and 2018. The short-term outcome was a diagnosis of perimyocarditis (pericarditis and/or myocarditis) within two months of first dispensation, and the long-term outcome was heart failure (including cardiomyopathy) within three years. Cox regressions with time varying exposure were used to estimate hazard rates (HR) and their 95% confidence intervals (CI). A total of 201,045 individuals were included in the cohort. The risk of developing perimyocarditis during clozapine treatment tripled compared to no antipsychotic treatment (HR 3.4, CI 1.6-7.3), although the absolute rate remained comparably low. The long-term risk of heart failure during clozapine treatment was also elevated (HR 1.3, CI 1.1-1.7). Treatment with either or both olanzapine or quetiapine was not associated with an increased relative risk of perimyocarditis, or heart failure compared to no antipsychotic treatment. Clozapine use is therefore associated with a substantially elevated short-term risk of perimyocarditis and an increased risk of heart failure within three years.
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| 29. |
- De Rosa, Maria, et al.
(författare)
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Design, synthesis and in vitro biological evaluation of oligopeptides targeting E. coli type I signal peptidase (LepB)
- 2017
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Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896 .- 1464-3391. ; 25:3, s. 897-911
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Tidskriftsartikel (refereegranskat)abstract
- Type I signal peptidases are potential targets for the development of new antibacterial agents. Here we report finding potent inhibitors of E. coli type I signal peptidase (LepB), by optimizing a previously reported hit compound, decanoyl-PTANA-CHO, through modifications at the N- and C-termini. Good improvements of inhibitory potency were obtained, with IC50s in the low nanomolar range. The best inhibitors also showed good antimicrobial activity, with MICs in the low μg/mL range for several bacterial species. The selection of resistant mutants provided strong support for LepB as the target of these compounds. The cytotoxicity and hemolytic profiles of these compounds are not optimal but the finding that minor structural changes cause the large effects on these properties suggests that there is potential for optimization in future studies.
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| 30. |
- DiBernardo, Allitia, et al.
(författare)
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Humanistic outcomes in treatment resistant depression : a secondary analysis of the STAR*D study
- 2018
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Ingår i: BMC Psychiatry. - : BMC. - 1471-244X. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIn the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, a third of patients did not achieve remission or adequate response after two treatment trials, fulfilling requirements for treatment resistant depression (TRD). The present study is a secondary analysis of the STAR*D data conducted to compare the humanistic outcomes in patients with TRD and non-TRD MDD.MethodsPatients with major depressive disorder who entered level 3 of the STAR*D were included in the TRD group, while patients who responded to treatment and entered follow-up from level 1 or 2 were included in the non-TRD group. The first visit in level 1 was used for baseline assessments. The time-point of assessments for comparison was the first visit in level 3 for TRD patients (median day: 141), and the visit closest to 14160days from baseline for non-TRD patients. Outcomes were assessed by the 12-item Short Form Health Survey (SF12), 16-item Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), Work and Social Adjustment Scale (WSAS), and Work Productivity and Activity Impairment scale (WPAI). Scores were compared in a linear model with adjustment for covariates including age, gender, and depression severity measured by the 17-item Hamilton Rating Scale for Depression (HDRS17) and Quick Inventory of Depressive Symptomatology (QIDS).ResultsA total of 2467 (TRD: 377; non-TRD: 2090) patients were studied. TRD patients were slightly older (mean age 44 vs 42years), had a higher proportion of men (49% vs 37%, p<.0001), and baseline depression severity (HDRS17: 24.4 vs 22.0, p<.0001) vs non-TRD patients. During follow-up, TRD patients had lower health-related quality of life (HRQOL) scores on mental (30 vs 45.7) and physical components (47.7 vs 48.9) of the SF12, and lower Q-LES-Q scores (43.6 vs 63.7), greater functional and work impairments and productivity loss vs non-TRD patients (all p<0.05).Conclusion Patients with TRD had worse HRQOL, work productivity, and social functioning than the non-TRD patients.
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| 31. |
- Egesten, Arne, et al.
(författare)
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Increased Prevalence of Multiple Sclerosis Among COPD Patients and Their First-Degree Relatives: A Population-based Study.
- 2008
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Ingår i: Lung. - : Springer Science and Business Media LLC. - 1432-1750 .- 0341-2040. ; 186, s. 173-178
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Tidskriftsartikel (refereegranskat)abstract
- In both chronic obstructive pulmonary disease (COPD) and multiple sclerosis (MS), combinations of environmental and genetic factors are likely to increase the vulnerability to acquire disease. This study was undertaken to investigate any possible comorbidity of COPD and MS, thus indicating common inflammatory vulnerability. Individuals with a diagnosis of COPD (including chronic bronchitis and emphysema) during 1987-2002, according to the Swedish Inpatient and Cause of Death Registers, were identified (180,239 individuals). Thereafter, controls and first-degree relatives of both cases and controls were identified. Finally, all individuals were compared with the Inpatient Register to identify individuals discharged with a diagnosis of MS. In the COPD cohort, there was a more than twofold increased risk of MS compared with controls (HR 2.51; 95% CI 2.13-2.98). The risk of MS was even more pronounced among individuals discharged with a diagnosis of COPD before 60 years of age (HR 6.37; 95% CI 3.58-9.68). There was also an increased risk of MS among mothers (HR 2.24; 95% CI 1.04-4.61) and siblings (HR 1.50; 95% CI 1.08-2.08) of COPD patients. This study indicates that COPD and MS have an inflammatory vulnerability in common, at least in a subgroup of patients. These diseases may share inflammatory pathways, including predisposing variants of genes.
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| 32. |
- Ejeby, Kersti, et al.
(författare)
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Randomized controlled trial of transdiagnostic group treatments for primary care patients with common mental disorders
- 2014
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Ingår i: Family Practice. - : Oxford University Press (OUP). - 0263-2136 .- 1460-2229. ; 31:3, s. 273-280
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Tidskriftsartikel (refereegranskat)abstract
- Background. The purpose was to test the effectiveness of two transdiagnostic group interventions compared to care as usual (CAU) for patients with anxiety, depressive or stress-related disorders within a primary health care context. Objectives. To compare the effects of cognitive-based-behavioural therapy (CBT) and multimodal intervention (MMI) on the quality of life and relief of psychological symptoms of patients with common mental disorders or problems attending primary health care centre. Methods. Patients (n = 278), aged 18-65 years, were referred to the study by the GPs and 245 were randomized to CAU or one of two group interventions in addition to CAU: (i) group CBT administered by psychologists and (ii) group MMI administered by assistant nurses. The primary outcome measure was the Mental Component Summary score of short form 36. Secondary outcome measures were Perceived Stress Scale and Self-Rating Scale for Affective Syndromes. The data were analysed using intention-to-treat with a linear mixed model. Results. On the primary outcome measure, the mean improvement based on mixed model analyses across post-and follow-up assessment was significantly larger for the MMI group than for the CBT (4.0; P = 0.020) and CAU (7.5; P = .001) groups. Participants receiving CBT were significantly more improved than those in the CAU group. On four of the secondary outcome measures, the MMI group was significantly more improved than the CBT and CAU groups. The course of improvement did not differ between the CBT group and the CAU group on these measures. Conclusions. Transdiagnostic group treatment can be effective for patients with common mental disorders when delivered in a primary care setting. The group format and transdiagnostic approach fit well with the requirements of primary care.
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| 33. |
- Ejeby, Kersti, et al.
(författare)
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Symptom reduction due to psychosocial interventions is not accompanied by a reduction in sick leave : Results from a randomized controlled trial in primary care
- 2014
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Ingår i: Scandinavian Journal of Primary Health Care. - : Informa UK Limited. - 0281-3432 .- 1502-7724. ; 32:2, s. 67-72
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To investigate whether interventions that have positive effects on psychological symptoms and quality of life compared with usual care would also reduce days on sick leave. Design. A randomized controlled trial. Setting. A large primary health care centre in Stockholm, Sweden. Intervention. Patients with common mental disorders were recruited by their GPs and randomized into one of two group interventions that took place in addition to usual care. These group interventions were: (a) group cognitive behavioural therapy (CBT), and (b) group multimodal intervention (MMI). Both types of intervention had previously shown significant effects on quality of life, and MMI had also shown significant effects on psychological symptoms. Patients. Of the 245 randomized patients, 164 were employed and had taken sick leave periods of at least two weeks in length during the study period of two years. They comprised the study group. Main outcome measures. The odds, compared with usual care, for being sick-listed at different times relative to the date of randomization. Results. The mean number of days on sick leave increased steadily in the two years before randomization and decreased in the two years afterwards, showing the same pattern for all three groups. The CBT and MMI interventions did not show the expected lower odds for sick-listing compared with usual care during the two-year follow-up. Conclusion. Reduction in psychological symptoms and increased well-being did not seem to be enough to reduce sickness absence for patients with common mental problems in primary care. The possibility of adding workplace-oriented interventions is discussed.
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| 34. |
- Ekbom, Anders, et al.
(författare)
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Increased risk of both ulcerative colitis and Crohn's disease in a population suffering from COPD
- 2008
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Ingår i: Lung. - : Springer Science and Business Media LLC. - 1432-1750 .- 0341-2040. ; 186:3, s. 167-172
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Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation of the airways. In the majority of cases, the inflammation is triggered by tobacco smoke. Smoking also affects the pathogenesis of inflammatory bowel disease (IBD), protecting against ulcerative colitis (UC) and promoting development of Crohn's disease (CD). The present study was undertaken to investigate occurrence of IBD among COPD patients, indicating common inflammatory pathways and shared vulnerability on a genetic basis. The study was designed as a population-based cohort study. All individuals discharged with a diagnosis of COPD from 1987 to 2002 were identified in the Swedish Inpatient Register (n = 180,239). Controls and first-degree relatives of both cases and controls were identified using the Multi-Generation Register. Finally, all individuals (n = 1,174,557) were compared with the Inpatient Register, identifying discharges with a diagnosis of UC or CD. Hazard ratios (HR) for IBD were determined by Cox proportional hazards regression analysis. COPD patients had a significantly higher risk of both UC (HR 1.83; 95% CI 1.61-2.09) and CD (HR 2.72; 95% CI 2.33-3.18). Among first-degree relatives of COPD patients, there was also an overall increased risk of CD (HR 1.25; 95% CI 1.09-1.43) but not of UC (HR 1.09; 95% CI 0.96-1.23). The kinship of first-degree relatives displayed an increased risk of both UC and CD among siblings (HR 1.49; 95% CI 1.15-1.91 and HR 1.46; 95% CI 1.12-1.89, respectively). The results suggest that COPD and IBD may have inflammatory pathways in common, including genetic variants of genes predisposing for disease.
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| 35. |
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| 36. |
- Fernström, Maria, 1960-, et al.
(författare)
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Improved Muscle Mitochondrial Capacity Following Gastric Bypass Surgery in Obese Subjects
- 2016
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Ingår i: Obesity Surgery. - New York, USA : Springer. - 0960-8923 .- 1708-0428. ; 26:7, s. 1391-1397
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Tidskriftsartikel (refereegranskat)abstract
- Background: Weight loss resulting from low-calorie diets is often less than expected. We hypothesized that energy restriction would influence proton leakage and improve mitochondrial efficiency, leading to reduced energy expenditure, partly explaining the difficulties in weight loss maintenance.Methods: Eleven women with a median BMI of 38.5 kg/m(2) (q-range 37-40), and referred to gastric bypass surgery participated. Before surgery, and at 6 months of follow-up, muscle biopsies were collected from the vastus lateralis muscle. Mitochondria were isolated and analyzed for coupled (state 3) and uncoupled (state 4) respiration and mitochondrial capacity (P/O ratio).Results: At follow-up, the participants had a median BMI of 29.6 kg/m(2) (28.3-32.0). State 3 increased from 20.6 (17.9-28.9) to 34.9 nmol O2/min/U citrate synthase (CS) (27.0-49.0), p = 0.01, while state 4 increased from 2.8 (1.8-4.2) to 4.2 nmol O2/min/U CS (3.1-6.1), although not statistically significant. The P/O ratio increased from 2.7 (2.5-2.8) to 3.2 (3.0-3.4), p = 0.02, indicating improved mitochondrial efficiency.Conclusions: Six months after gastric bypass surgery, the mitochondrial capacity for coupled, i.e., ATP-generating, respiration increased, and the P/O ratio improved. Uncoupled respiration was not enhanced to the same extent. This could partly explain the decreased basal metabolism and the reduced inclination for weight loss during energy restriction.
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| 37. |
- Gyllenhammar, Irina, 1978-
(författare)
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Endocrine Disruption in Amphibians : Developmental Effects of Ethynylestradiol and Clotrimazole on the Reproductive System
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Amphibian populations are declining world-wide and one of the suggested reasons is environmental pollutants. Studies of long-term effects on the reproductive system in frogs following larval exposure to environmental pollutants are scarce. It is therefore important to develop methods to study developmental reproductive toxicity in amphibians. In this thesis the usefulness of Xenopus tropicalis (the West African clawed frog) as a model species for a test system was investigated. Effects on the reproductive system after larval exposure to the pharmaceuticals ethynylestradiol (EE2) and clotrimazole were evaluated. The susceptibility to EE2 exposure was compared between the model species and a wild species, the European common frog (Rana temporaria). Larval exposure to EE2 caused female-biased sex ratios in both examined frog species, indicating male-to-female sex-reversal. In adult Xenopus tropicalis, male frogs that were not sex-reversed had reduced fertility and decreased amount of mature spermatozoa in the seminiferous tubules. The proportion of frogs with ovaries but lacking oviducts increased with increasing EE2-concentrations. A female frog without oviducts is sterile. The development of ovaries in sex-reversed male frogs was implied to be similar to control females. The combination of a reduced number of males, due to sex-reversal, and impaired fertility could have severe effects on frog populations. Larval exposure to clotrimazole modulated aromatase activity in gonads and brain in Xenopus tropicalis. Brain aromatase activity was decreased at the time for gonadal differentiation and gonadal aromatase activity was increased at metamorphosis. The findings in this thesis indicate that reproduction in wild frogs might be impaired by estrogenic compounds in the environment. The results combined with the short generation time supports the use of Xenopus tropicalis as a model species when evaluating long term effects of endocrine disruptors on the reproductive system in amphibians.
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| 38. |
- Hagg, David, et al.
(författare)
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A register-based approach to identifying treatment-resistant depression : Comparison with clinical definitions
- 2020
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:7
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Tidskriftsartikel (refereegranskat)abstract
- Background Several definitions of treatment-resistant depression (TRD) are used for clinical research, but no verified model for use in register data exists. We aimed to compare a novel model created for use in register data-the Karolinska Institutet Model (KIM)-to the clinical definitions regarding the proportion of patients identified with TRD, their characteristics and clinical outcomes. Methods All patients in Sweden initiating antidepressant treatment with a diagnosis of depression in specialized healthcare 2006-2014 were identified and followed in national registers. In KIM, patients who initiated a third sequential, >28-day antidepressant treatment trial were defined as having TRD. Proportion of TRD and patient characteristics were compared with register adaptations of the European Staging Model (ESM), Massachusetts General Hospital Staging Method (MGH-s), and Maudsley Staging Model (MSM). Differences in patient characteristics were assessed with Chi-square tests and one-way ANOVAs. Hazard ratios for psychiatric hospitalization and for death from external causes were estimated by Cox proportional hazard regressions. Results Out of 127,108 antidepressant initiators with depression, the highest proportion of TRD was found using the MGH-s (19.0%), followed by MSM (15.3%), KIM (12.9%), and ESM (9.5%). Clinical characteristics were similar across the models. Compared with TRD patients identified by KIM, those identified by ESM had a marginally higher risk for psychiatric hospitalization (adjusted hazard ratio [aHR] 1.03, 95%CI 1.00-1.05), whereas those identified by MGH-s (aHR 0.92; 0.90-0.94) and MSM (aHR 0.95; 0.94-0.97) had a slightly reduced risk. Patients identified by MGH-s showed a reduced mortality compared with KIM (aHR 0.84; 0.72-0.98). Conclusions This study provides insight into the differing characteristics of patients captured by various TRD models when used for register research. Models yielding lower proportions of TRD seemed to identify patients with greater morbidity. The KIM may be useful for register based research in TRD.
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| 39. |
- Hermansson, Ulric, et al.
(författare)
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Screening for high-risk and elevated alcohol consumption in day and shift workers by use of the AUDIT and CDT
- 2003
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Ingår i: Occupational Medicine. - : Oxford University Press (OUP). - 0962-7480 .- 1471-8405. ; 53:8, s. 518-526
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Tidskriftsartikel (refereegranskat)abstract
- The present findings on employees who attended for regular health examinations suggest that shift workers did not show a higher level of risky alcohol consumption than day workers, according to the results with the AUDIT, CDT and GGT. On the contrary, the two-shift workers appeared to drink significantly less.
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| 40. |
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| 41. |
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| 42. |
- Holm, Lena, et al.
(författare)
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Embryonic exposure to o,p'-DDT causes eggshell thinning and altered shell gland carbonic anhydrase expression in the domestic hen
- 2006
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Ingår i: Environmental Toxicology and Chemistry. - 0730-7268 .- 1552-8618. ; 25:10, s. 2787-2793
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Tidskriftsartikel (refereegranskat)abstract
- The mechanism for contaminant-induced eggshell thinning in wild birds remains to be clarified. It is generally assumed, however, that it results from exposure of the adult laying female. We have reported that embryonic exposure to the synthetic estrogen ethynylestradiol (EE2) results in eggshell thinning in the domestic hen. The objective of this study was to investigate whether eggshell thinning can be induced following in ovo exposure to a bioaccumulating estrogenic environmental contaminant, o,p '-DDT. Ethynylestradiol was used as a positive control. Domestic hens exposed in ovo to o,p '-DDT (37 or 75 mu g/g egg) or EE2 (60 ng/g egg) laid eggs with thinner shells than the control birds. The hens from these exposure groups also had a significantly reduced frequency of shell gland capillaries with carbonic anhydrase (CA) activity, a key enzyme in eggshell formation. The decreased number of capillaries with CA activity suggests that a developmentally induced disruption of CA expression in the shell gland was involved in the eggshell thinning found in this study. Egg laying was not affected in hens exposed embryonically to 37 or 75 mu g o,p '-DDT/g egg, whereas it was inhibited in hens exposed to higher doses. Decreased lengths of the left oviduct and its infundibulum were seen after embryonic treatment with o,p '-DDT or EE2. In addition, o,p '-DDT exposure resulted in right oviduct retention. The results support our hypothesis that eggshell thinning in avian wildlife can result from a functional malformation in the shell gland, induced by embryonic exposure to estrogenic substances.
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| 43. |
- Karamanis, Georgios, et al.
(författare)
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Cancer incidence and mortality patterns in women with anorexia nervosa
- 2014
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 134:7, s. 1751-1757
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Tidskriftsartikel (refereegranskat)abstract
- Caloric restriction in animals is an effective way to reduce carcinogenesis. Anorexia nervosa (AN) is considered a model of extreme caloric restriction in humans. The aim of our study was to assess cancer incidence and mortality in women with AN. A total of 6,009 women with at least one inpatient treatment for AN during the period 1973-2003 were included in the study. Standardized incidence ratios (SIR) and standardized mortality ratios (SMR) were calculated. Overall, there was no statistically significant difference in cancer incidence compared to women in the general population. At a statistically significant or borderline significant level, a higher incidence for lung cancer and cancer of lymphoid, hematopoietic and related tissue was observed along with a reduced breast cancer incidence. Women with AN had twice as high mortality from cancer in general, and more specifically from melanoma, cancers of genital organs and cancers of ill-defined, secondary and unspecified sites. The increased lung cancer incidence may be due to smoking habits among women with AN. The worse prognosis with higher mortality from melanoma, cancers of genital organs and cancers of ill-defined, secondary and unspecified sites may be explained by AN-specific attitudes toward seeking medical care, adherence to treatment or worse biological precondition due to starvation and cachexia.
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| 44. |
- Kask, Jan, et al.
(författare)
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Mortality in Women With Anorexia Nervosa : The Role of Comorbid Psychiatric Disorders
- 2016
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Ingår i: Psychosomatic Medicine. - 0033-3174 .- 1534-7796. ; 78:8, s. 910-919
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate mortality in anorexia nervosa (AN) with a psychiatric comorbidity. Methods Using Swedish registers, data for 8069 female inpatients with AN were retrospectively collected for 1973-2010. Mortality patterns were assessed using standardized mortality ratios (SMRs), Cox regression-derived hazard ratios, and incidence rate ratios. A control cohort of 76,995 women was used. Results Patients with AN and a psychiatric comorbidity had higher mortality rates did than those without a comorbidity. The SMRs for patients with AN and a psychiatric comorbidity were 5.4 (95% confidence interval [CI] = 4.6-6.4) and 18.1 (95% CI = 15.2-21.3) for natural and unnatural causes of death, respectively. The SMRs for patients with AN without a comorbidity were 2.8 (95% CI = 2.3-3.5) and 3.1 (95% CI = 2.2-4.1) for natural and unnatural causes of death, respectively. The adjusted hazard ratios for mortality from natural or unnatural causes were 2.0 (95% CI = 1.5-2.7) and 5.7 (95% CI = 3.9-8.2), respectively. Incidence rate ratios comparing patients with AN and controls, both with psychiatric comorbidities, suggest a negative synergistic effect of comorbid AN and psychiatric disorder on mortality, which was greater for unnatural causes of death. Conclusions Mortality in patients with AN was greater in the presence of a psychiatric comorbidity, and even more pronounced for unnatural causes of death and suicides. Substance abuse, especially alcohol use disorder, increased mortality from natural causes of death. These findings highlight the need for early detection and treatment of psychiatric comorbidity in AN, to potentially improve long-term outcomes.
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| 45. |
- Knight, Ann, et al.
(författare)
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Increasing Incidence of Wegener´s granulomatosis in Sweden 1975-2001
- 2006
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Ingår i: Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 33:10, s. 2060-2063
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Studies of Wegener's granulomatosis (WG) since the late 1980s indicate a probable increase in incidence of unknown cause and significance, possibly related to antineutrophil cytoplasmic antibody (ANCA) testing. To extend these observations and to include calendar periods before ANCA was introduced, we assessed time trends in the incidence of WG in Sweden in the period 1975-2001. Methods. In the population-based Swedish Inpatient Register, we identified 1938 individuals diagnosed with WG in the period 1975-2001, and calculated the annual age and sex adjusted incidences. Results. The incidence increased from 0.33 (95% CI 0.28-0.39) in the period 1975-85 to 0.77 (95% CI 0.69-0.85) in 1986-90, to 1.19 (95% CI 1.12-1.26) in 1991-2001, resulting in a mean incidence of 0.78 (95% CI 0.74-0.82). Conclusion. WG displays a strong temporal trend. While the increase coincides to some extent with the implementation of ANCA testing, suggestive of increased disease recognition, ANCA testing remains an incomplete explanation as increasing incidences were noted before as well as after their introduction.
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| 46. |
- Knight, Ann, et al.
(författare)
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What is the significance in routine care of c-ANCA/PR3-ANCA in the abscence of systemic vasculitis? : A case series
- 2008
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Ingår i: Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 26:3, s. S53-S56
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Tidskriftsartikel (refereegranskat)abstract
- Objective. ANCA has come to play an important role in diagnosing vasculitis. In selected populations c-ANCA/PR3-ANCA has a high specificity and sensitivity for vasculitis. In clinical practice, how individuals with c-ANCA/PR3-ANCA but without sufficient evidence of systemic vasculitis should be managed is unclear. We therefore retrospectively assessed the disease panorama and outcome in a consecutive series of individuals with c-ANCA/PR3-ANCA, and studied in detail those individuals who turned out not to fulfil criteria for vasculitic disease.Methods. The study population consisted of 74 consecutive patients who all had a positive test for C-ANCA and PR3-ANCA between 1992 and 2002 at the Immunology laboratory at Uppsala University Hospital, Sweden. The patients' medical files were reviewed and their diagnosis re-evaluated through June 2006.Results. 18 of the 74 ANCA-positive individuals did not present clinical evidence supportive of, or insufficient to support, a diagnosis of systemic vasculitis, but presented a range of other diseases. During a mean follow-up of 6.8 years, none of these 18 patients developed vasculitis.Conclusions. Individuals with a positive c-ANCA and PR3-ANCA but no vasculitis at the time of testing run an unknown but likely small risk of later developing vasculitis. In this group, a positive ANCA may represent background noise (borderline titres) or be a marker of inflammatory activity rather than of vasculitic disease (high titres).
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| 47. |
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| 48. |
- Lagerros, Ylva Trolle, et al.
(författare)
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Suicide, Self-harm, and Depression After Gastric Bypass Surgery : A Nationwide Cohort Study
- 2017
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Ingår i: Annals of Surgery. - 0003-4932 .- 1528-1140. ; 265:2, s. 235-243
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to examine risk of self-harm, hospitalization for depression and death by suicide after gastric bypass surgery (GBP).SUMMARY OF BACKGROUND DATA: Concerns regarding severe adverse psychiatric outcomes after GBP have been raised.METHODS: This nationwide, longitudinal, self-matched cohort encompassed 22,539 patients who underwent GBP during 2008 to 2012. They were identified through the Swedish National Patient Register, the Prescribed Drug Register, and the Causes of Death Register. Follow-up time was up to 2 years. Main outcome measures were hazard ratios (HRs) for post-surgery self-harm or hospitalization for depression in patients with presurgery self-harm and/or depression compared to patients without this exposure; and standardized mortality ratio (SMR) for suicide post-surgery.RESULTS: A diagnosis of self-harm in the 2 years preceding surgery was associated with an HR of 36.6 (95% confidence interval [CI] 25.5-52.4) for self-harm during the 2 years of follow up, compared to GBP patients who had no self-harm diagnosis before surgery. Patients with a diagnosis of depression preceding GBP surgery had an HR of 52.3 (95% CI 30.6-89.2) for hospitalization owing to depression after GBP, compared to GBP patients without a previous diagnosis of depression. The SMR for suicide after GBP was increased among females (n = 13), 4.50 (95% CI 2.50-7.50). The SMR among males (n = 4), was 1.71 (95% CI 0.54-4.12).CONCLUSIONS: The increased risk of post-surgery self-harm and hospitalization for depression is mainly attributable to patients who have a diagnosis of self-harm or depression before surgery. Raised awareness is needed to identify vulnerable patients with history of self-harm or depression, which may be in need of psychiatric support after GBP.
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| 49. |
- Li, Gang, et al.
(författare)
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All-cause mortality in patients with treatment-resistant depression : a cohort study in the US population
- 2019
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Ingår i: Annals of General Psychiatry. - : BMC. - 1744-859X. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Treatment-resistant depression (TRD) may represent a substantial proportion of major depressive disorder (MDD); however, the risk of mortality in TRD is still incompletely assessed. Methods Data were obtained from Optum Clinformatics (TM) Extended, a US claims database. Date of the first antidepressant (AD) dispensing was designated as the index date for study entry and 6 months prior to that was considered the baseline period. Patients with MDD aged >= 18 years, index date between January 1, 2008 and September 30, 2015, no AD claims during baseline, and continuous enrollment in the database during baseline were included. Patients who started a third AD regimen after two regimens of appropriate duration were included in the TRD cohort. All-cause mortality was compared between patients with TRD and non-TRD MDD using a proportional hazards model and Kaplan-Meier estimate with TRD status being treated as a time-varying covariate. The model was adjusted for study year, age, gender, depression diagnosis, substance use disorder, psychiatric comorbidities, and Charlson comorbidity index. Results Out of 355,942 patients with MDD, 34,176 (9.6%) met the criterion for TRD. TRD was associated with a significantly higher mortality compared with non-TRD MDD (adjusted HR: 1.29; 95% CI 1.22-1.38; p < 0.0001). Survival time was significantly shorter in the TRD cohort compared with the non-TRD MDD cohort (p < 0.0001). Conclusions Patients with TRD had a higher all-cause mortality compared with non-TRD MDD patients.
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- Ludvigsson, Jonas F., et al.
(författare)
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Small-intestinal histopathology and mortality risk in celiac disease
- 2009
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 302:11, s. 1171-1178
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Studies of mortality in celiac disease have not taken small-intestinal pathology into account. OBJECTIVE: To examine mortality in celiac disease according to small-intestinal histopathology. DESIGN, SETTING, AND PATIENTS: Retrospective cohort study. We collected data from duodenal/jejunal biopsies taken between July 1969 and February 2008 on celiac disease (Marsh stage 3: villous atrophy; n = 29,096 individuals) and inflammation (Marsh stage 1-2; n = 13,306) from all 28 pathology departments in Sweden. A third cohort consisted of individuals with latent celiac disease from 8 university hospitals (n = 3719). Latent celiac disease was defined as positive celiac disease serology in individuals with normal mucosa (Marsh stage 0). Through linkage with the Swedish Total Population Register, we estimated the risk of death through August 31, 2008, compared with age- and sex-matched controls from the general population. MAIN OUTCOME MEASURE: All-cause mortality. RESULTS: There were 3049 deaths among patients with celiac disease, 2967 with inflammation, and 183 with latent celiac disease. We found an increased hazard ratio (HR) for death in celiac disease (HR, 1.39; 95% confidence interval [CI], 1.33-1.45; median follow-up, 8.8 years), inflammation (HR, 1.72; 95% CI, 1.64-1.79; median follow-up, 7.2 years), and latent celiac disease (HR, 1.35; 95% CI, 1.14-1.58; median follow-up, 6.7 years). The absolute mortality rate was 10.4 (95% CI, 10.0-10.8) per 1000 person-years in celiac disease, 25.9 (95% CI, 25.0-26.8) in inflammation, and 6.7 (95% CI, 5.7-7.6) in latent celiac disease. Excess mortality was 2.9 per 1000 person-years in celiac disease, 10.8 in inflammation, and 1.7 in latent celiac disease. This risk increase was also seen in children. Excluding the first year of follow-up, HRs decreased somewhat. CONCLUSION: Risk of death among patients with celiac disease, inflammation, or latent celiac disease is modestly increased.
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