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  • Thomas, HS, et al. (författare)
  • 2019
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  • Burisch, J, et al. (författare)
  • Natural disease course of Crohn's disease during the first 5 years after diagnosis in a European population-based inception cohort: an Epi-IBD study
  • 2019
  • Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 68:3, s. 423-433
  • Tidskriftsartikel (refereegranskat)abstract
    • The Epi-IBD cohort is a prospective population-based inception cohort of unselected patients with inflammatory bowel disease from 29 European centres covering a background population of almost 10 million people. The aim of this study was to assess the 5-year outcome and disease course of patients with Crohn’s disease (CD).DesignPatients were followed up prospectively from the time of diagnosis, including collection of their clinical data, demographics, disease activity, medical therapy, surgery, cancers and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis.ResultsIn total, 488 patients were included in the study. During follow-up, 107 (22%) patients received surgery, while 176 (36%) patients were hospitalised because of CD. A total of 49 (14%) patients diagnosed with non-stricturing, non-penetrating disease progressed to either stricturing and/or penetrating disease. These rates did not differ between patients from Western and Eastern Europe. However, significant geographic differences were noted regarding treatment: more patients in Western Europe received biological therapy (33%) and immunomodulators (66%) than did those in Eastern Europe (14% and 54%, respectively, P<0.01), while more Eastern European patients received 5-aminosalicylates (90% vs 56%, P<0.05). Treatment with immunomodulators reduced the risk of surgery (HR: 0.4, 95% CI 0.2 to 0.6) and hospitalisation (HR: 0.3, 95% CI 0.2 to 0.5).ConclusionDespite patients being treated early and frequently with immunomodulators and biological therapy in Western Europe, 5-year outcomes including surgery and phenotype progression in this cohort were comparable across Western and Eastern Europe. Differences in treatment strategies between Western and Eastern European centres did not affect the disease course. Treatment with immunomodulators reduced the risk of surgery and hospitalisation.
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  • Dauvilliers, Y., et al. (författare)
  • Daridorexant, a New Dual Orexin Receptor Antagonist to Treat Insomnia Disorder
  • 2020
  • Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 87:3, s. 347-356
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To evaluate the dose-response relationship of daridorexant, a new dual orexin receptor antagonist, on sleep variables in subjects with insomnia disorder. Methods Adults (<= 64 years) with insomnia disorder were randomized (1:1:1:1:1:1) to receive daily oral placebo, daridorexant (5, 10, 25, or 50mg), or 10mg zolpidem for 30 days. The primary efficacy outcome was the change in wake time after sleep onset from baseline to days 1 and 2. Secondary outcome measures were change in latency to persistent sleep from baseline to days 1 and 2, change in subjective wake time after sleep onset, and subjective latency to sleep onset from baseline to week 4. Safety was also assessed. Results Of 1,005 subjects screened, 359 (64% female) were randomized and received >= 1 dose. A significant dose-response relationship (multiple comparison procedure-modeling, 2-sided p < 0.001) was found in the reduction of wake after sleep onset and latency to persistent sleep from baseline to days 1 and 2 with daridorexant. These reductions were sustained through to days 28 and 29 (p = 0.050 and p = 0.042, respectively). Similar dose-dependent relationships were observed for subjective wake after sleep onset and subjective latency to sleep onset. The incidence of treatment-emergent adverse events was 35%, 38%, 38%, and 34% in subjects treated with 5, 10, 25, and 50mg daridorexant, respectively, compared with 30% for placebo, and 40% for 10mg zolpidem. There were no clinically relevant treatment-related serious adverse events. Four subjects withdrew due to adverse events. Interpretation Daridorexant induced a dose-dependent reduction in wake time after sleep onset in subjects with insomnia disorder ( NCT02839200). ANN NEUROL 2020
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  • Duggan, E. C., et al. (författare)
  • A Multi-study Coordinated Meta-analysis of Pulmonary Function and Cognition in Aging
  • 2019
  • Ingår i: Journals of Gerontology Series a-Biological Sciences and Medical Sciences. - : Oxford University Press (OUP). - 1079-5006 .- 1758-535X. ; 74:11, s. 1793-1804
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Substantial research is dedicated to understanding the aging-related dynamics among Methods: We performed coordinated analysis of bivariate growth models in data from 20,586 Results: We found consistent but weak baseline and longitudinal associations in levels of pulmonary Conclusions: Results provide limited evidence for a consistent link between simultaneous changes in
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  • Gunawardana, L, et al. (författare)
  • Pre-conception inter-pregnancy interval and risk of schizophrenia
  • 2011
  • Ingår i: The British journal of psychiatry : the journal of mental science. - : Royal College of Psychiatrists. - 1472-1465. ; 199:4, s. 338-339
  • Tidskriftsartikel (refereegranskat)abstract
    • It is hypothesised that the risk of schizophrenia may be elevated in children conceived following a short interpregnancy interval, when maternal folate stores are still being replenished. We examined the relationship between inter-pregnancy interval and schizophrenia risk in a longitudinal, population-based cohort. Risk of schizophrenia was increased by approximately 150% in those born following a pregnancy interval of $6 months, but was not increased if the interval after birth of the participant, before conception of the subsequent sibling, was $6 months. These findings support the hypothesis that folate (or other micronutrient) deficiency during fetal development may be an important risk factor for schizophrenia.
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  • Manrique-Garcia, E., et al. (författare)
  • Prognosis of schizophrenia in persons with and without a history of cannabis use
  • 2014
  • Ingår i: Psychological Medicine. - 0033-2917 .- 1469-8978. ; 44:12, s. 2513-2521
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. The aim of the study was to determinate whether schizophrenia patients with a history of cannabis use have a different prognosis, with regards to readmission and hospital duration, compared with those without a history of cannabis use. Method. The present investigation was a cohort study of 50087 Swedish men with data on cannabis use at the ages of 18-20 years. A total of 357 cases of schizophrenia were identified from in-patient care and followed up from 1973 to 2007. Results. Schizophrenia patients with a history of cannabis use had a higher median duration of first hospital episode (59 days v. 30 days). Patients with a history of cannabis use had a higher median rate of readmission (10 times v. four times). Also, total number of hospital days was higher in patients with a history of cannabis use compared with those without (547 days v. 184 days). Patients with a history of cannabis use had an increased odds of having more than 20 hospital readmissions compared with non-users [3.1, 95% confidence interval (CI) 1.3-7.3] as well as an increased odds of hospital admission lasting more than 2 years (2.4, 95% CI 1.1-7.4) after controlling for diagnosis of personality disorders, family socio-economic position, IQ score, civil status, place of residence, risky use of alcohol and use of other drugs. Patients with a history of cannabis use were less likely to have paranoid schizophrenia compared with never users (8% v. 17%) in the first admission. Conclusions. Schizophrenia patients with a history of cannabis use had a significantly higher burden of lifetime inpatient care than non-cannabis users. Not only does cannabis increase the risk of schizophrenia, but also our findings indicate that the course and prognosis of schizophrenia may be more severe than schizophrenia cases in general.
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  • Sarigul, Buse, et al. (författare)
  • Prognostication and Goals of Care Decisions in Severe Traumatic Brain Injury : A Survey of The Seattle International Severe Traumatic Brain Injury Consensus Conference Working Group
  • 2023
  • Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 40:15-16, s. 1707-1717
  • Tidskriftsartikel (refereegranskat)abstract
    • Best practice guidelines have advanced severe traumatic brain injury (TBI) care; however, there is little that currently informs goals of care decisions and processes despite their importance and frequency. Panelists from the Seattle International severe traumatic Brain Injury Consensus Conference (SIBICC) participated in a survey consisting of 24 questions. Questions queried use of prognostic calculators, variability in and responsibility for goals of care decisions, and acceptability of neurological outcomes, as well as putative means of improving decisions that might limit care. A total of 97.6% of the 42 SIBICC panelists completed the survey. Responses to most questions were highly variable. Overall, panelists reported infrequent use of prognostic calculators, and observed variability in patient prognostication and goals of care decisions. They felt that it would be beneficial for physicians to improve consensus on what constitutes an acceptable neurological outcome as well as what chance of achieving that outcome is acceptable. Panelists felt that the public should help to define what constitutes a good outcome and expressed some support for a "nihilism guard." More than 50% of panelists felt that if it was certain to be permanent, a vegetative state or lower severe disability would justify a withdrawal of care decision, whereas 15% felt that upper severe disability justified such a decision. Whether conceptualizing an ideal or existing prognostic calculator to predict death or an unacceptable outcome, on average a 64-69% chance of a poor outcome was felt to justify treatment withdrawal. These results demonstrate important variability in goals of care decision making and a desire to reduce this variability. Our panel of recognized TBI experts opined on the neurological outcomes and chances of those outcomes that might prompt consideration of care withdrawal; however, imprecision of prognostication and existing prognostication tools is a significant impediment to standardizing the approach to care-limiting decisions.
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  • Wallin, A. S., et al. (författare)
  • Academic performance, externalizing disorders and depression: 26,000 adolescents followed into adulthood
  • 2019
  • Ingår i: Social Psychiatry and Psychiatric Epidemiology. - : Springer Science and Business Media LLC. - 0933-7954 .- 1433-9285. ; 54:8, s. 977-986
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThe incidence of major depression among adults has been shown to be socially differentiated, and there are reasons to seek explanations for this before adulthood. In this cohort study, we examined whether academic performance in adolescence predicts depression in adulthood, and the extent to which externalizing disorders explain this association.MethodsWe followed 26,766 Swedish women and men born 1967-1982 from the last year of compulsory school, at age about 16, up to 48years of age. We investigated the association between grade point average (GPA, standardized by gender) and first diagnosis of depression in national registers of in- or out-patient psychiatric care. We used Cox proportional hazards models, adjusting for lifetime externalizing diagnoses and potential confounders including childhood socioeconomic position and IQ.ResultsDuring follow-up, 7.0% of the women and 4.4% of the men were diagnosed with depression. A GPA in the lowest quartile, compared with the highest, was associated with an increased risk in both women (hazard ratio 95% confidence interval 1.7, 1.3-2.1) and men (2.9, 2.2-3.9) in models controlling for potential confounders. Additional control for externalizing disorders attenuated the associations, particularly in women.ConclusionsThe findings suggest that poor academic performance is associated with depression in young adulthood and that the association is partly explained by externalizing disorders. Our results indicate the importance of early detection and management of externalizing disorders among children and adolescents.
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  • Zammit, A. R., et al. (författare)
  • A Coordinated Multi-study Analysis of the Longitudinal Association Between Handgrip Strength and Cognitive Function in Older Adults
  • 2021
  • Ingår i: The journals of gerontology. Series B, Psychological sciences and social sciences. - : Oxford University Press (OUP). - 1758-5368 .- 1079-5014. ; 76:2, s. 229-241
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Handgrip strength, an indicator of overall muscle strength, has been found to be associated with slower rate of cognitive decline and decreased risk for cognitive impairment and dementia. However, evaluating the replicability of associations between aging-related changes in physical and cognitive functioning is challenging due to differences in study designs and analytical models. A multiple-study coordinated analysis approach was used to generate new longitudinal results based on comparable construct-level measurements and identical statistical models and to facilitate replication and research synthesis. METHODS: We performed coordinated analysis on 9 cohort studies affiliated with the Integrative Analysis of Longitudinal Studies of Aging and Dementia (IALSA) research network. Bivariate linear mixed models were used to examine associations among individual differences in baseline level, rate of change, and occasion-specific variation across grip strength and indicators of cognitive function, including mental status, processing speed, attention and working memory, perceptual reasoning, verbal ability, and learning and memory. Results were summarized using meta-analysis. RESULTS: After adjustment for covariates, we found an overall moderate association between change in grip strength and change in each cognitive domain for both males and females: Average correlation coefficient was 0.55 (95% CI = 0.44-0.56). We also found a high level of heterogeneity in this association across studies. DISCUSSION: Meta-analytic results from nine longitudinal studies showed consistently positive associations between linear rates of change in grip strength and changes in cognitive functioning. Future work will benefit from the examination of individual patterns of change to understand the heterogeneity in rates of aging and health-related changes across physical and cognitive biomarkers. Published by Oxford University Press on behalf of The Gerontological Society of America 2019.
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  • Zammit, Mark C., et al. (författare)
  • Laser-driven production of the antihydrogen molecular ion
  • 2019
  • Ingår i: Physical Review A: covering atomic, molecular, and optical physics and quantum information. - 2469-9926 .- 2469-9934. ; 100:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The feasibility of producing the molecular antihydrogen anion (H) over bar (-)(2) in the laboratory is investigated. Utilizing reaction rates calculated here involving the interaction of laser excited-state antihydrogen atoms held in magnetic minimum traps, key processes are identified that could lead to anion production, as well as competing effects leading to anti-atom loss. These are discussed in the context of present-day and near-future experimental capabilities.
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  • Borg, Jonathan, et al. (författare)
  • An Industry 4.0 Training Framework Addressing ‘COVID-19 Type’ Disruptions on Manufacturing
  • 2021
  • Ingår i: Digital Manufacturing Technology. - : Universal Wiser Publisher Pte. Ltd. - 2810-9309 .- 2810-9317.
  • Tidskriftsartikel (refereegranskat)abstract
    • Although digitization in the manufacturing industry has been going on for some years, the recent COVID-19 pandemic helped reveal a number of bottlenecks and challenges that still need to be overcome. Joint ongoing research by a number of European Universities aimed at developing a systematic training framework on Industry 4.0 happened to be performed in the midst of the pandemic. COVID-19 meant that suddenly, internal and external workers of different educational backgrounds and in different roles had to rapidly adapt to new working procedures and environments whilst learning to use new technologies. This disruption helped this research group to generate specifications of a Higher Education Industry 4.0 Training Framework (HEI4.0) that is relevant to foster skills and competencies that make manufacturing more resilient to other possible scenarios requiring social distancing limitations. This paper outlines the details of the research performed and contributes the concept and value of establishing what is termed as the ‘flow-cognitive profile chart’ of a manufacturing organization to effectively help it in its transition towards digital manufacturing. Based on this concept, the paper passes on to prescribe a HEI4.0 Training Framework intended to guide manufacturing organizations in addressing ‘COVID-19 type’ manufacturing disruptions that can take place in other future unforeseen circumstances.
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  • Chesnut, Randall, et al. (författare)
  • A management algorithm for adult patients with both brain oxygen and intracranial pressure monitoring : the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC)
  • 2020
  • Ingår i: Intensive Care Medicine. - : Springer. - 0342-4642 .- 1432-1238. ; 46:5, s. 919-929
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Current guidelines for the treatment of adult severe traumatic brain injury (sTBI) consist of high-quality evidence reports, but they are no longer accompanied by management protocols, as these require expert opinion to bridge the gap between published evidence and patient care. We aimed to establish a modern sTBI protocol for adult patients with both intracranial pressure (ICP) and brain oxygen monitors in place.Methods: Our consensus working group consisted of 42 experienced and actively practicing sTBI opinion leaders from six continents. Having previously established a protocol for the treatment of patients with ICP monitoring alone, we addressed patients who have a brain oxygen monitor in addition to an ICP monitor. The management protocols were developed through a Delphi-method-based consensus approach and were finalized at an in-person meeting.Results: We established three distinct treatment protocols, each with three tiers whereby higher tiers involve therapies with higher risk. One protocol addresses the management of ICP elevation when brain oxygenation is normal. A second addresses management of brain hypoxia with normal ICP. The third protocol addresses the situation when both intracranial hypertension and brain hypoxia are present. The panel considered issues pertaining to blood transfusion and ventilator management when designing the different algorithms.Conclusions: These protocols are intended to assist clinicians in the management of patients with both ICP and brain oxygen monitors but they do not reflect either a standard-of-care or a substitute for thoughtful individualized management. These protocols should be used in conjunction with recommendations for basic care, management of critical neuroworsening and weaning treatment recently published in conjunction with the Seattle International Brain Injury Consensus Conference.
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  • Chesnut, Randall M., et al. (författare)
  • Perceived Utility of Intracranial Pressure Monitoring in Traumatic Brain Injury : A Seattle International Brain Injury Consensus Conference Consensus-Based Analysis and Recommendations
  • 2023
  • Ingår i: Neurosurgery. - : Oxford University Press. - 0148-396X .- 1524-4040. ; 93:2, s. 399-408
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Intracranial pressure (ICP) monitoring is widely practiced, but the indications are incompletely developed, and guidelines are poorly followed. OBJECTIVE: To study the monitoring practices of an established expert panel (the clinical working group from the Seattle International Brain Injury Consensus Conference effort) to examine the match between monitoring guidelines and their clinical decision-making and offer guidance for clinicians considering monitor insertion.METHODS: We polled the 42 Seattle International Brain Injury Consensus Conference panel members' ICP monitoring decisions for virtual patients, using matrices of presenting signs (Glasgow Coma Scale [GCS] total or GCS motor, pupillary examination, and computed tomography diagnosis). Monitor insertion decisions were yes, no, or unsure (traffic light approach). We analyzed their responses for weighting of the presenting signs in decision-making using univariate regression.RESULTS: Heatmaps constructed from the choices of 41 panel members revealed wider ICP monitor use than predicted by guidelines. Clinical examination (GCS) was by far the most important characteristic and differed from guidelines in being nonlinear. The modified Marshall computed tomography classification was second and pupils third. We constructed a heatmap and listed the main clinical determinants representing 80% ICP monitor insertion consensus for our recommendations.CONCLUSION: Candidacy for ICP monitoring exceeds published indicators for monitor insertion, suggesting the clinical perception that the value of ICP data is greater than simply detecting and monitoring severe intracranial hypertension. Monitor insertion heatmaps are offered as potential guidance for ICP monitor insertion and to stimulate research into what actually drives monitor insertion in unconstrained, real-world conditions.
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  • Hawryluk, Gregory W. J., et al. (författare)
  • A management algorithm for patients with intracranial pressure monitoring : the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC)
  • 2019
  • Ingår i: Intensive Care Medicine. - : Springer. - 0342-4642 .- 1432-1238. ; 45:12, s. 1783-1794
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Management algorithms for adult severe traumatic brain injury (sTBI) were omitted in later editions of the Brain Trauma Foundation's sTBI Management Guidelines, as they were not evidence-based.Methods: We used a Delphi-method-based consensus approach to address management of sTBI patients undergoing intracranial pressure (ICP) monitoring. Forty-two experienced, clinically active sTBI specialists from six continents comprised the panel. Eight surveys iterated queries and comments. An in-person meeting included whole- and small-group discussions and blinded voting. Consensus required 80% agreement. We developed heatmaps based on a traffic-light model where panelists' decision tendencies were the focus of recommendations.Results: We provide comprehensive algorithms for ICP-monitor-based adult sTBI management. Consensus established 18 interventions as fundamental and ten treatments not to be used. We provide a three-tier algorithm for treating elevated ICP. Treatments within a tier are considered empirically equivalent. Higher tiers involve higher risk therapies. Tiers 1, 2, and 3 include 10, 4, and 3 interventions, respectively. We include inter-tier considerations, and recommendations for critical neuroworsening to assist the recognition and treatment of declining patients. Novel elements include guidance for autoregulation-based ICP treatment based on MAP Challenge results, and two heatmaps to guide (1) ICP-monitor removal and (2) consideration of sedation holidays for neurological examination.Conclusions: Our modern and comprehensive sTBI-management protocol is designed to assist clinicians managing sTBI patients monitored with ICP-monitors alone. Consensus-based (class III evidence), it provides management recommendations based on combined expert opinion. It reflects neither a standard-of-care nor a substitute for thoughtful individualized management.
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  • O'Gorman, A., et al. (författare)
  • Identification of a plasma signature of psychotic disorder in children and adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort
  • 2017
  • Ingår i: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • The identification of an early biomarker of psychotic disorder is important as early treatment is associated with improved patient outcome. Metabolomic and lipidomic approaches in combination with multivariate statistical analysis were applied to identify plasma alterations in children (age 11) (38 cases vs 67 controls) and adolescents (age 18) (36 cases vs 117 controls) preceeding or coincident with the development of psychotic disorder (PD) at age 18 in the Avon Longitudinal Study of Parents and Children (ALSPAC). Overall, 179 lipids were identified at age 11, with 32 found to be significantly altered between the control and PD groups. Following correction for multiple comparisons, 8 of these lipids remained significant (lysophosphatidlycholines (LPCs) LPC(18: 1), LPC(18: 2), LPC(20: 3); phosphatidlycholines (PCs) PC(32: 2; PC(34: 2), PC(36: 4), PC(0-34-3) and sphingomyelin (SM) SM(d18: 1/24: 0)), all of which were elevated in the PD group. At age 18, 23 lipids were significantly different between the control and PD groups, although none remained significant following correction for multiple comparisons. In conclusion, the findings indicate that the lipidome is altered in the blood during childhood, long before the development of psychotic disorder. LPCs in particular are elevated in those who develop PD, indicating inflammatory abnormalities and altered phospholipid metabolism. These findings were not found at age 18, suggesting there may be ongoing alterations in the pathophysiological processes from prodrome to onset of PD.
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  • Price, C, et al. (författare)
  • Cannabis and suicide: longitudinal study
  • 2009
  • Ingår i: The British journal of psychiatry : the journal of mental science. - : Royal College of Psychiatrists. - 1472-1465. ; 195:6, s. 492-497
  • Tidskriftsartikel (refereegranskat)abstract
    • Some studies suggest that cannabis use is associated with suicidal ideation, but no detailed longitudinal study has examined suicide as an outcome.AimsTo examine the association between cannabis use and completed suicide.MethodA longitudinal study investigated 50 087 men conscripted for Swedish military service, with cannabis use measured non-anonymously at conscription. Suicides during 33 years of follow-up were identified by linkage with the National Cause of Death Register.ResultsThere were 600 (1.2% of cohort) suicides or deaths from undetermined causes. Cannabis use was associated with an increased risk of suicide (crude OR for ‘ever use’ 1.62, 95% CI 1.28–2.07), but this association was eliminated after adjustment for confounding (adjusted OR = 0.88, 95% CI 0.65–1.20).ConclusionsAlthough there was a strong association between cannabis use and suicide, this was explained by markers of psychological and behavioural problems. These results suggest that cannabis use is unlikely to have a strong effect on risk of completed suicide, either directly or as a consequence of mental health problems secondary to its use.
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  • Sadik, A, et al. (författare)
  • Parental inflammatory bowel disease and autism in children
  • 2022
  • Ingår i: Nature medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 28:7, s. 1406-
  • Tidskriftsartikel (refereegranskat)abstract
    • Evidence linking parental inflammatory bowel disease (IBD) with autism in children is inconclusive. We conducted four complementary studies to investigate associations between parental IBD and autism in children, and elucidated their underlying etiology. Conducting a nationwide population-based cohort study using Swedish registers, we found evidence of associations between parental diagnoses of IBD and autism in children. Polygenic risk score analyses of the Avon Longitudinal Study of Parents and Children suggested associations between maternal genetic liability to IBD and autistic traits in children. Two-sample Mendelian randomization analyses provided evidence of a potential causal effect of genetic liability to IBD, especially ulcerative colitis, on autism. Linkage disequilibrium score regression did not indicate a genetic correlation between IBD and autism. Triangulating evidence from these four complementary approaches, we found evidence of a potential causal link between parental, particularly maternal, IBD and autism in children. Perinatal immune dysregulation, micronutrient malabsorption and anemia may be implicated.
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  • Williams, N M, et al. (författare)
  • A systematic genomewide linkage study in 353 sib pairs with schizophrenia.
  • 2003
  • Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 73:6, s. 1355-1367
  • Tidskriftsartikel (refereegranskat)abstract
    • We undertook a genomewide linkage study in a total of 353 affected sib pairs (ASPs) with schizophrenia. Our sample consisted of 179 ASPs from the United Kingdom, 134 from Sweden, and 40 from the United States. We typed 372 microsatellite markers at approximately 10-cM intervals. Our strongest finding was a LOD score of 3.87 on chromosome 10q25.3-q26.3, with positive results being contributed by all three samples and a LOD-1 interval of 15 cM. This finding achieved genomewide significance (P<.05), on the basis of simulation studies. We also found two regions, 17p11.2-q25.1 (maximum LOD score [MLS] = 3.35) and 22q11 (MLS = 2.29), in which the evidence for linkage was highly suggestive. Linkage to all of these regions has been supported by other studies. Moreover, we found strong evidence for linkage (genomewide P<.02) to 17p11.2-q25.1 in a single pedigree with schizophrenia. In our view, the evidence is now sufficiently compelling to undertake detailed mapping studies of these three regions.
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  • Zammit, S, et al. (författare)
  • Examining interactions between risk factors for psychosis
  • 2010
  • Ingår i: The British journal of psychiatry : the journal of mental science. - : Royal College of Psychiatrists. - 1472-1465. ; 197:3, s. 207-211
  • Tidskriftsartikel (refereegranskat)abstract
    • For complex multifactorial diseases it seems likely that co-exposure to two risk factors will show a greater than additive relationship on disease risk.AimsTo test whether greater than additive relationships occur between risk factors for psychosis.MethodA cohort study of 50 053 Swedish conscripts. Data on IQ, cannabis use, psychiatric diagnoses, disturbed behaviour and social relations assessed at age 18 were linked to admissions with any non-affective psychoses over a 27-year follow-up period. Statistical interactions between risk factors were examined under both additive and multiplicative models.ResultsThere was some evidence of interaction for eight of the ten combinations of risk factors under additive models, but for only one combination under multiplicative models.ConclusionsMultiplicative models describe the joint effect of risk factors more adequately than additive ones do. However, the implications of finding interactions as observed here, or for most interactions reported to date, remain very limited.
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