1. |
- Algaba, Juan-Carlos, et al.
(author)
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Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign
- 2021
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In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 911:1
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Research review (peer-reviewed)abstract
- In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M o˙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87's spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded.
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2. |
- Alexander, Stephen P. H., et al.
(author)
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The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors
- 2023
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In: BRITISH JOURNAL OF PHARMACOLOGY. - : British pharmacological society. - 0007-1188 .- 1476-5381. ; 180
-
Journal article (peer-reviewed)abstract
- The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at . G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
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3. |
- Christopoulos, Arthur, et al.
(author)
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THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors.
- 2021
-
In: British journal of pharmacology. - : Wiley. - 1476-5381 .- 0007-1188. ; 178 Suppl 1
-
Research review (peer-reviewed)abstract
- The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15538. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
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4. |
- Ghirardi, Laura, et al.
(author)
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Attention-Deficit/Hyperactivity Disorder Medication and Unintentional Injuries in Children and Adolescents
- 2020
-
In: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier. - 0890-8567 .- 1527-5418. ; 59:8, s. 944-951
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: Our objective was to determine whether ADHD medication is associated with a decreased risk of unintentional injuries in children and adolescents in the United States across sexes, age groups and injury types.METHOD: We used de-identified inpatient, outpatient, and filled prescription claims data from the Truven Health MarketScan® Research Databases. Individuals were followed from January 1, 2005, date of first ADHD diagnosis or medication prescription, or age 6, whichever occurred last, until December 31, 2014, first healthcare insurance disenrollment, or the first year at which their age was recorded as 19, whichever occurred first. A person was considered on ADHD medication during a given month if a prescription was filled in that month. The outcome was defined as emergency department visits for injuries, including traumatic brain injuries, with unintentional causes. Odds of having the outcome were compared between medicated and un-medicated months at the population-level and in within-individual analyses using logistic regression.RESULTS: Among 1 968 146 individuals diagnosed with ADHD or receiving ADHD medication, 87 154 had at least one event. At the population-level, medication use was associated a lower risk of injuries, both in boys (OR= 0.85; 95% CI: 0.84-0.86) and girls (OR=0.87; 95% CI: 0.85-0.89). Similar results were obtained from within-individual analysis among male (OR= 0.72; 95% CI: 0.70-0.74) and female (OR= 0.72; 95% CI: 0.69-0.75) children, and among male (OR= 0.64; 95% CI: 0.60-0.67) and female (OR= 0.65; 95% CI: 0.60-0.71) adolescents. Similar results were found for traumatic brain injuries.CONCLUSION: ADHD medication use was associated with a reduction of different types of unintentional injuries in children and adolescents of both sexes.
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5. |
- Pecunia, Vincenzo, et al.
(author)
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Roadmap on energy harvesting materials
- 2023
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In: Journal of Physics. - : IOP Publishing. - 2515-7639. ; 6:4
-
Journal article (peer-reviewed)abstract
- Ambient energy harvesting has great potential to contribute to sustainable development and address growing environmental challenges. Converting waste energy from energy-intensive processes and systems (e.g. combustion engines and furnaces) is crucial to reducing their environmental impact and achieving net-zero emissions. Compact energy harvesters will also be key to powering the exponentially growing smart devices ecosystem that is part of the Internet of Things, thus enabling futuristic applications that can improve our quality of life (e.g. smart homes, smart cities, smart manufacturing, and smart healthcare). To achieve these goals, innovative materials are needed to efficiently convert ambient energy into electricity through various physical mechanisms, such as the photovoltaic effect, thermoelectricity, piezoelectricity, triboelectricity, and radiofrequency wireless power transfer. By bringing together the perspectives of experts in various types of energy harvesting materials, this Roadmap provides extensive insights into recent advances and present challenges in the field. Additionally, the Roadmap analyses the key performance metrics of these technologies in relation to their ultimate energy conversion limits. Building on these insights, the Roadmap outlines promising directions for future research to fully harness the potential of energy harvesting materials for green energy anytime, anywhere.
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6. |
- Chang, Zheng, et al.
(author)
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Medication for Attention-Deficit/Hyperactivity Disorder and Risk for Suicide Attempts
- 2020
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In: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 88:6, s. 452-458
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a risk factor for suicidal behavior, but the effect of ADHD medication on suicidal behavior remains unclear. This study aimed to examine the associations between medication treatment for ADHD and risk of suicide attempts.METHODS: We identified a large cohort of patients with ADHD (N = 3,874,728, 47.8% female patients) using data from commercial health care claims from 2005 to 2014 in the United States. We used population-level and within-individual analyses to compare risk of suicide attempts during months when individuals received prescribed stimulant or nonstimulant medication relative to months when they did not receive medication.RESULTS: In both population-level and within-individual analyses, ADHD medication was associated with lower odds of suicide attempts (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.66-0.73; and OR, 0.61; 95% CI, 0.57-0.66, respectively). Similar reductions were found in children to middle-aged adults and in clinically relevant subgroups, including patients with ADHD with preexisting depression or substance use disorder. The reduction was mainly seen for stimulant medication (OR, 0.72; 95% CI, 0.66-0.77); nonstimulant medication was not associated with statistically significant changes in risk of suicide attempts (OR, 0.94; 95% CI, 0.74-1.19). Sensitivity analyses assessing the influence of different exposure definitions, different outcome definitions, subsets of the cohort, and different analytic approaches provided comparable results.CONCLUSIONS: Stimulant medication was associated with a reduced risk of suicide attempts in patients with ADHD, and nonstimulant medication is unlikely to increase the risk of suicide attempts.
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7. |
- Chen, Hao Yu, et al.
(author)
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Association of FADS1/2 Locus Variants and Polyunsaturated Fatty Acids With Aortic Stenosis
- 2020
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In: JAMA cardiology. - : American Medical Association (AMA). - 2380-6583 .- 2380-6591. ; 5:6, s. 694-702
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Journal article (peer-reviewed)abstract
- Importance: Aortic stenosis (AS) has no approved medical treatment. Identifying etiological pathways for AS could identify pharmacological targets.Objective: To identify novel genetic loci and pathways associated with AS.Design, Setting, and Participants: This genome-wide association study used a case-control design to evaluate 44 703 participants (3469 cases of AS) of self-reported European ancestry from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort (from January 1, 1996, to December 31, 2015). Replication was performed in 7 other cohorts totaling 256 926 participants (5926 cases of AS), with additional analyses performed in 6942 participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Follow-up biomarker analyses with aortic valve calcium (AVC) were also performed. Data were analyzed from May 1, 2017, to December 5, 2019.Exposures: Genetic variants (615 643 variants) and polyunsaturated fatty acids (ω-6 and ω-3) measured in blood samples.Main Outcomes and Measures: Aortic stenosis and aortic valve replacement defined by electronic health records, surgical records, or echocardiography and the presence of AVC measured by computed tomography.Results: The mean (SD) age of the 44 703 GERA participants was 69.7 (8.4) years, and 22 019 (49.3%) were men. The rs174547 variant at the FADS1/2 locus was associated with AS (odds ratio [OR] per C allele, 0.88; 95% CI, 0.83-0.93; P = 3.0 × 10-6), with genome-wide significance after meta-analysis with 7 replication cohorts totaling 312 118 individuals (9395 cases of AS) (OR, 0.91; 95% CI, 0.88-0.94; P = 2.5 × 10-8). A consistent association with AVC was also observed (OR, 0.91; 95% CI, 0.83-0.99; P = .03). A higher ratio of arachidonic acid to linoleic acid was associated with AVC (OR per SD of the natural logarithm, 1.19; 95% CI, 1.09-1.30; P = 6.6 × 10-5). In mendelian randomization, increased FADS1 liver expression and arachidonic acid were associated with AS (OR per unit of normalized expression, 1.31 [95% CI, 1.17-1.48; P = 7.4 × 10-6]; OR per 5-percentage point increase in arachidonic acid for AVC, 1.23 [95% CI, 1.01-1.49; P = .04]; OR per 5-percentage point increase in arachidonic acid for AS, 1.08 [95% CI, 1.04-1.13; P = 4.1 × 10-4]).Conclusions and Relevance: Variation at the FADS1/2 locus was associated with AS and AVC. Findings from biomarker measurements and mendelian randomization appear to link ω-6 fatty acid biosynthesis to AS, which may represent a therapeutic target.
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8. |
- Fine, Kimberly L., et al.
(author)
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Association Between Early Prescribed Opioid Initiation and Risk of Suicidal Behavior
- 2020
-
Conference paper (other academic/artistic)abstract
- Prescription opioid use has been linked to increased risk of suicidal behavior in adults. However, little research exists examining the role of prescription opioid use on risk of suicidal behavior in children and adolescents. This population is at high risk for suicidal behavior, as suicide is the second leading cause of death for people ages 10 to 34. Using healthcare data from Swedish population registers, we aimed to characterize the extent to which exposure to opioids at a young age leads to an increased risk of new onset suicidal behavior, for those with no history of suicidal behavior. Compared to demographically matched non-recipients, young people who initiated prescription opioids had just under three times the rate of subsequent suicidal behavior (HR = 2.64, 95% CI, 2.47-2.81). Compared to their unexposed siblings, young people who initiated prescription opioids had roughly two times the rate of subsequent suicidal behavior (HR = 1.83, 95% CI, 1.67-2.01). Finally, compared to young people initiating prescription NSAIDs, young people who initiated prescription opioids had only 19% relatively greater rates of suicidal behavior (HR, 1.19, 95% CI, 1.11-1.27). These results suggest the association between prescription opioids and suicidal behavior may be driven by the underlying pain indication.
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9. |
- Fine, Kimberly L., et al.
(author)
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Initiation of Opioid Prescription and Risk of Suicidal Behavior Among Youth and Young Adults
- 2022
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In: Pediatrics. - : American Academy of Pediatrics. - 0031-4005 .- 1098-4275. ; 149:3
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Journal article (peer-reviewed)abstract
- BACKGROUND AND OBJECTIVES: Opioids are involved in an increasing proportion of suicide deaths. This study examined the association between opioid analgesic prescription initiation and suicidal behavior among young people.METHODS: We analyzed Swedish population-register data on 1 895 984 individuals ages 9 to 29 years without prior recorded opioid prescriptions. We identified prescriptions dispensed from January 2007 onward and diagnosed self-injurious behavior and death by suicide through December 2013. We first compared initiators with demographically matched noninitiators. To account for confounding, we applied an active comparator design, which examined suicidal behavior among opioid initiators relative to prescription nonsteroidal antiinflammatory drug (NSAID) initiators while inverse-probability-of-treatment weighting with individual and familial covariates.RESULTS: Among the cohort, 201 433 individuals initiated opioid prescription. Relative to demographically matched noninitiators, initiators (N = 180 808) had more than doubled risk of incident suicidal behavior (hazard ratio = 2.64; 95% confidence interval [CI], 2.47-2.81). However, in the active comparator design, opioid initiators (N = 86 635) had only 19% relatively greater risk of suicidal behavior compared with NSAID initiators (N = 255 096; hazard ratio = 1.19; 95% CI,: 1.11-1.28), corresponding to a weighted 5-year cumulative incidence of 2.2% (95% CI, 2.1-2.4) for opioid and 1.9% (95% CI, 1.9-2.0) for NSAID initiators. Most sensitivity analyses produced comparable results.CONCLUSIONS: Opioid initiation may make only a small contribution to the elevated risk of suicidal behavior among young people receiving pharmacologic pain management. In weighing benefits and harms of opioid initiation, our results suggest that increased risk of suicidal behavior may not be a major concern.
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10. |
- Ghirardi, Laura, et al.
(author)
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Use of medication for attention-deficit/hyperactivity disorder and risk of unintentional injuries in children and adolescents with co-occurring neurodevelopmental disorders
- 2020
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In: Journal of Child Psychology and Psychiatry. - : Blackwell Publishing. - 0021-9630 .- 1469-7610. ; 61:2, s. 140-147
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is often associated with other neurodevelopmental disorders (NDs) and with risky behaviors and adverse health outcomes, including injuries. Treatment with ADHD medication has been associated with reduced risk of injuries. However, it is unknown whether the association is present in individuals with co-occurring NDs. The aim of the present study was to estimate the association between ADHD medication use and unintentional injuries in Sweden in children and adolescents with ADHD, including those with co-occurring NDs.METHODS: Using a linkage of several national registers via the unique personal identification number, we identified individuals with a diagnosis of ADHD and of other NDs, including autism spectrum disorder, intellectual disability, communication disorders, learning disorders and motor disorders. The primary outcome was unintentional injuries. Secondary outcome was traumatic brain injury (TBI). Individuals were followed from January 1st 2006 or their 5th birthday or the date of the first unintentional injury, whichever came last, to December 31st 2013 or their 18th birthday or death, whichever came first. We compared the rate of injuries during periods on-treatment with the rate of injuries during periods off-treatment within the same individual using stratified Cox regression to calculate hazard ratio (HR) with 95% confidence intervals (CIs).RESULTS: For children and adolescents with ADHD (N = 9,421) the rate of any unintentional injuries (HR = 0.85; 95% CI = 0.78-0.92) and TBIs (HR = 0.27; 95% CIs = 0.20-0.38) during medicated periods was lower than during non-medicated periods. Similar results were found among individuals with co-occurring NDs (N = 2,986), for unintentional injuries (HR = 0.88; 95% CI = 0.77-1.01) and for TBIs (HR = 0.27; 95% CI = 0.16-0.44).CONCLUSIONS: Beneficial effects of ADHD medication may extend beyond reduction of ADHD core symptoms to prevention of unintentional injuries in children and adolescents, including individuals with co-occurring NDs.
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11. |
- O'Reilly, Lauren, et al.
(author)
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Examining protective factors for substance use problems and self-harm behavior during adolescence : A longitudinal co-twin control study
- 2022
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In: Development and psychopathology (Print). - : Cambridge University Press. - 0954-5794 .- 1469-2198. ; 34, s. 1781-1802
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Journal article (peer-reviewed)abstract
- Sports participation, physical activity, and friendship quality are theorized to have protective effects on the developmental emergence of substance use and self-harm behavior in adolescence, but existing research has been mixed. This ambiguity could reflect, in part, the potential for confounding of observed associations by genetic and environmental factors, which previous research has been unable to rigorously rule out. We used data from the prospective, population-based Child and Adolescent Twin Study in Sweden (n = 18,234 born 1994-2001) and applied a co-twin control design to account for potential genetic and environmental confounding of sports participation, physical activity, and friendship quality (assessed at age 15) as presumed protective factors for adolescent substance use and self-harm behavior (assessed at age 18). While confidence intervals widened to include the null in numerous co-twin control analyses adjusting for childhood psychopathology, parent-reported sports participation and twin-reported positive friendship quality were associated with increased odds of alcohol problems and nicotine use. However, parent-reported sports participation, twin-reported physical activity, and twin-reported friendship quality were associated with decreased odds of self-harm behavior. The findings provide a more nuanced understanding of the risks and benefits of putative protective factors for risky behaviors that emerge during adolescence.
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12. |
- Quinn, Patrick D., et al.
(author)
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Association of Opioid Prescription Initiation during Adolescence and Young Adulthood with Subsequent Substance-Related Morbidity
- 2020
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In: JAMA pediatrics. - : American Medical Association. - 2168-6203 .- 2168-6211. ; 174:11, s. 1048-1055
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Journal article (peer-reviewed)abstract
- Importance: Concerns about adverse outcomes associated with opioid analgesic prescription have led to major guideline and policy changes. Substantial uncertainty remains, however, regarding the association between opioid prescription initiation and increased risk of subsequent substance-related morbidity.Objective: To examine the association of opioid initiation among adolescents and young adults with subsequent broadly defined substance-related morbidity.Design, setting, and participants: This cohort study analyzed population-register data from January 1, 2007, to December 31, 2013, on Swedish individuals aged 13 to 29 years by January 1, 2013, who were naive to opioid prescription. To account for confounding, the analysis compared opioid prescription recipients with recipients of nonsteroidal anti-inflammatory drugs as an active comparator, compared opioid-recipient twins and other multiple birth individuals with their nonrecipient co-multiple birth offspring (co-twin control), examined dental prescription as a specific indication, and included individual, parental, and socioeconomic covariates. Data were analyzed from March 30, 2019, to January 22, 2020.Exposures: Opioid prescription initiation, defined as first dispensed opioid analgesic prescription.Main outcomes and measures: Substance-related morbidity, assessed as clinically diagnosed substance use disorder or overdose identified from inpatient or outpatient specialist records, substance use disorder or overdose cause of death, dispensed pharmacotherapy for alcohol use disorder, or conviction for substance-related crime.Results: Among the included cohort (n = 1 541 862; 793 933 male [51.5%]), 193 922 individuals initiated opioid therapy by December 31, 2013 (median age at initiation, 20.9 years [interquartile range, 18.2-23.6 years]). The active comparator design included 77 143 opioid recipients without preexisting substance-related morbidity and 229 461 nonsteroidal anti-inflammatory drug recipients. The adjusted cumulative incidence of substance-related morbidity within 5 years was 6.2% (95% CI, 5.9%-6.5%) for opioid recipients and 4.9% (95% CI, 4.8%-5.1%) for nonsteroidal anti-inflammatory drug recipients (hazard ratio, 1.29; 95% CI, 1.23-1.35). The co-twin control design produced comparable results (3013 opioid recipients and 3107 nonrecipients; adjusted hazard ratio, 1.43; 95% CI, 1.02-2.01), as did restriction to analgesics prescribed for dental indications and additional sensitivity analyses.Conclusions and relevance: Among adolescents and young adults analyzed in this study, initial opioid prescription receipt was associated with an approximately 30% to 40% relative increase in risk of subsequent substance-related morbidity in multiple designs that adjusted for confounding. These findings suggest that this increase may be smaller than previously estimated in some other studies.
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13. |
- Quinn, Patrick D., et al.
(author)
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Visual search : Heritability and association with general intelligence
- 2022
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In: Genes, Brain and Behavior. - : John Wiley & Sons. - 1601-1848 .- 1601-183X. ; 21:2
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Journal article (peer-reviewed)abstract
- Visual search guides goal-directed action in humans and many other species, and it has been studied extensively in the past. Yet, no study has investigated the relative contributions of genes and environments to individual differences in visual search performance, or to which extent etiologies are shared with broader cognitive phenotypes. To address this gap, we studied visual search and general intelligence in 156 monozygotic (MZ) and 158 same-sex dizygotic (DZ) twin pairs. We found that different indexes of visual search performance (response latency and visual search efficiency) were moderately heritable. Phenotypic correlations between visual search and intelligence were small-to-moderate, and only a small proportion of the genetic variance in visual search was shared with genetic variance in intelligence. We discuss these findings in the context of the ?generalist genes hypothesis? stating that different cognitive functions have a common genetic basis.
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14. |
- Sujan, Ayesha C., et al.
(author)
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A nation-wide Swedish study of opioid analgesic prescribing patterns during pregnancy and associated preexisting mental health conditions
- 2022
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In: The Journal of Maternal-Fetal & Neonatal Medicine. - : Informa Healthcare. - 1476-7058 .- 1476-4954. ; 35:25, s. 5161-5167
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Research has consistently shown individuals with mental health conditions are more likely to be prescribed opioid analgesic medications and to engage in heavier utilization. However, it is unclear whether these findings apply to pregnant women.STUDY DESIGN: We explored opioid analgesic prescription in 689,400 pregnancies occurring in Sweden between 2007 and 2013. We investigated prescription patterns across time and type of source clinic for any opioid analgesic and for strong and weak opioid analgesics. We further evaluated the extent to which receipt of opioid analgesic medications was associated with previous mental health diagnoses and prescriptions of other psychoactive medications.RESULTS: The prevalence of pregnant women who filled prescriptions for opioid analgesics (4.5%) was relatively stable across the assessed years. However, among pregnant women who filled opioid analgesic prescriptions, there was a large increase in strong opioid analgesic prescriptions-from 6.1% in 2007 to 17.1% in 2013. The main source of opioid analgesic prescriptions were primary care and obstetrics and gynecology clinics-38.7% of all filled prescriptions originated from primary care providers and 25.3% from obstetrics and gynecology practitioners. Compared to pregnant women who did not fill any opioid analgesic prescriptions, those who did were more likely to have a wide range of pre-existing mental health diagnoses (e.g., anxiety disorder odds ratio[OR] = 3.13, 95% confidence interval[CI]:2.98,3.29) and to utilize a wide range of other psychoactive medications (e.g., benzodiazepines OR =4.26, 95% CI:4.10,4.43). Similarly, those who received strong opioids were more likely to have a wide range of mental health diagnoses and be prescribed a wide range of psychoactive medications compared to those who received weak opioids.CONCLUSIONS: These results highlight the need for physicians treating pregnant women and women of childbearing age for painful conditions to obtain detailed histories of mental health problems, screen for symptoms of mental health problems, and facilitate integrated care and evidence-based mental health interventions if needed.
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15. |
- Sujan, Ayesha C., et al.
(author)
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A population-based study of concurrent prescriptions of opioid analgesic and selective serotonin reuptake inhibitor medications during pregnancy and risk for adverse birth outcomes
- 2021
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In: Paediatric and Perinatal Epidemiology. - : Blackwell Science Ltd.. - 0269-5022 .- 1365-3016. ; 35:2, s. 184-193
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Journal article (peer-reviewed)abstract
- BACKGROUND: Pregnant women with painful conditions often have mental health problems, including depression and anxiety. Co-morbid conditions may cause pregnant women to use multiple medications, although safety of such practice is poorly understood.OBJECTIVES: We investigated the influence of combined prescriptions of opioid analgesics and selective serotonin reuptake inhibitors (SSRIs) during pregnancy on two adverse birth outcomes.METHODS: We analysed Swedish population-based births (n = 688 914) between 2007 and 2013. Using national registers, we obtained data on filled medication prescriptions, birth outcomes, and a wide range of parental characteristics. We estimated preterm birth and small-for-gestational-age risk following independent or combined prescriptions of the two medications compared with no filled prescriptions for either medication. We adjusted for confounders using inverse probability of treatment weights.RESULTS: After adjusting for confounders, preterm birth risk was higher among women with opioid analgesic prescriptions only (5.9%; risk ratio [RR] 1.27, 95% confidence interval [CI] 1.22, 1.33), SSRIs only (6.2%; RR 1.34, 95% CI 1.27, 1.42), and both medications (7.8%; RR 1.70, 95% CI 1.47, 1.96) compared with unexposed women (4.6%). The interaction between the medications on preterm birth was small (risk difference [RD] 0.4%, 95% CI -0.8%, 1.6%); relative excess risk due to interaction [RERI] 0.09, 95% CI -0.17, 0.34; RR 1.00, 95% CI 0.85, 1.17). For small for gestational age, risk was approximately 2% across all groups, and there was no interaction between the medications (RD 0.3%, 95% CI -0.4%, 1.1%); RERI 0.15, 95% CI -0.16, 0.47; RR 1.15, 95% CI 0.87, 1.52).CONCLUSIONS: Compared with unexposed pregnancies, those with either medication alone had a small increased risk for preterm birth but no increased risk for small for gestational age. The magnitude of associations with combined exposure to both medications were not greater than the sum of the associations with each medication considered individually.
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16. |
- Summit, Alynna G., et al.
(author)
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Preliminary Validation of a General Factor Model of Chronic Overlapping Pain Conditions
- 2024
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In: Journal of Pain. - : Elsevier. - 1526-5900 .- 1528-8447. ; 25:8
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Journal article (peer-reviewed)abstract
- Chronic overlapping pain conditions (COPCs) by definition frequently co-occur, perhaps reflecting their shared etiologies. Their overlapping nature presents a methodological challenge, possibly masking associations between COPCs and health outcomes attributable to either general or specific processes. To address this challenge, we used population-based cohort data to evaluate the predictive validity of a bifactor model of nine self-reported COPCs by assessing its association with incident pain-related clinical diagnoses; pain-relevant pharmacotherapy; and other health outcomes. We obtained data from a 2005-2006 study of Swedish adult twins linked with health data from nationwide registers through 2016 (N = 25,418). We then fit a bifactor model comprising a general COPC factor and two independent specific factors measuring pain-related somatic symptoms and neck and shoulder pain. Accounting for age, biological sex, and cancer, the general factor was associated with increased risk of all pain-related outcomes (e.g., COPC diagnosis aOR, 1.71; 95% CI [1.62, 1.81]), most mental health-related outcomes (e.g., depression aOR, 1.72 [1.60, 1.85]), and overdose and mortality (e.g., all-cause mortality aOR, 1.25 [1.09, 1.43]). The somatic symptoms specific factor was associated with pain-relevant pharmacotherapy (e.g., prescribed opioids aOR, 1.25 [1.15, 1.36]), most mental health-related outcomes (e.g., depression aOR, 1.95 [1.70, 2.23]), and overdose (e.g., nonfatal overdose aOR, 1.66 [1.31, 2.10]). The neck and shoulder pain specific factor was weakly and inconsistently associated with the outcomes. Findings provide initial support for the validity and utility of a general-factor model of COPCs as a tool to strengthen understandings of co-occurrence, etiology, and consequences of chronic pain. PERSPECTIVE: This article presents associations between a novel measurement model of chronic overlapping pain conditions (COPCs) and various health outcomes. Findings provide support for measuring pain across multiple domains rather than only measuring pain specific to one physical location in both research and clinical contexts.
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17. |
- Svanberg, Mikael, 1958-, et al.
(author)
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Opioid Prescriptions in Chronic Pain Rehabilitation : A Prospective Study on the Prevalence and Association between Individual Patient Characteristics and Opioids
- 2021
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In: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 10:10
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Journal article (peer-reviewed)abstract
- While against recommendations, long-term opioid therapy (LTOT) for chronic pain is common. This study aimed to describe the prevalence of opioid prescriptions and to study the association of patient characteristics (demographics, pain characteristics, anxiety, depressive symptoms and pain coping) with future LTOT. The sample included N = 1334 chronic musculoskeletal pain patients, aged 18–65, who were assessed for Interdisciplinary Multimodal Pain Rehabilitation (IMMR) in Swedish specialist rehabilitation. Prescriptions were tracked across a two-year target period after assessment. In total, 9100 opioid prescriptions were prescribed to 55% of the sample (Mmedian = 6, IQR = 14). Prediction of LTOT was analyzed separately for those who did (24%) and did not (76%) receive IMMR. The odds of receiving opioids was similar for these subsamples, after controlling for differences in baseline characteristics. In both samples, there were significant associations between patient characteristics and future opioid prescriptions. Dysfunctional pain coping was a unique predictor of LTOT in those who received IMMR while pain intensity and depressive symptoms were unique predictors in those who did not receive IMMR. The results underscore that opioid treatment is common among patients in chronic pain rehabilitation and relates to pain and psychological factors. Understanding in detail why these factors relate to opioid prescription patterns is an important future study area as it is a prerequisite for better management and fundamental for preventing overuse.
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18. |
- Wiggs, Kelsey K., et al.
(author)
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A nationwide study of initiation of antidepressant pharmacotherapy and the risk of seizures
- 2023
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In: Epilepsy Research. - : Elsevier. - 0920-1211 .- 1872-6844. ; 192
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Journal article (peer-reviewed)abstract
- OBJECTIVE: The present study aimed to examine whether antidepressant initiation increases the risk of hospitalizations and unplanned outpatient visits for seizures. Research has provided conflicting evidence as to whether antidepressant initiation causes seizures. Because epilepsy and depression are comorbid, this remains an important question, particularly in the care of those already at-risk for seizures.METHODS: We used Swedish-register data, including 658,766 antidepressant initiators and 1:1 age-, region-, and sex-matched non-initiators, ages 12-65. We used filled prescriptions to identify any antidepressant and serotonergic antidepressant and inpatient hospitalizations and unplanned outpatient (to avoid coding routine epilepsy maintenance as a seizure) visits to identify seizures, respectively. We first compared seizure visit incidence between antidepressant-initiators and matched non-users in the year following initiation from 2006 to 2013. To examine seizure risk over months pre- and post-initiation, within-individual analyses compared risk during the month one year prior to initiation with all subsequent months. We examined associations for any antidepressant and serotonergic antidepressants, as well as for any initiator and initiators with a history of seizures.RESULTS: Our matched-cohort results showed higher incidence of seizure visits among antidepressant users compared with non-users (e.g., adjusted incidence rate ratio [IRR]=3.14, 95% confidence interval [CI]=2.83-3.49). In within-individual analyses, the months after initiation were associated with higher incidence of seizure visits when compared with the month one year prior to initiation (e.g., one month after initiation IRR=1.96, 95%CI=1.64-2.34), but in individuals with a seizure history we observed weaker or no associations in the months after initiation (e.g., two months after initiation IRR=1.12, 95%CI=0.87-1.45). Notably, irrespective of potential seizure history, the months preceding initiation were associated with the greatest risk (e.g., one month before initiation IRR=2.86, 95% CI=2.42-3.38).CONCLUSIONS: Our findings suggest that there may be an elevated risk of seizures during antidepressant treatment, though the period of highest risk was before the initiation of antidepressants. Risk for seizure visits was lower among individuals with a history of prior seizures, which may be reassuring for the clinical care of these patients or indicate lack of treatment seeking following seizures. This study highlights the need to consider seizure risk across time; the failure to account for these dynamics may help account for discrepant findings in previous studies.
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19. |
- Wiggs, Kelsey K., et al.
(author)
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Antiseizure medication use during pregnancy and risk of ASD and ADHD in children
- 2020
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In: Neurology. - : Wolters Kluwer. - 0028-3878 .- 1526-632X. ; 95:24, s. e3232-e3240
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Journal article (peer-reviewed)abstract
- Objective: To determine whether children born to women who use antiseizure medications (ASMs) during pregnancy have higher risk of autism spectrum disorder (ASD) and attention-deficit/ hyperactivity disorder (ADHD) independent of confounding factors.Methods: We used Swedish register data (n = 14,614 children born 1996-2011 and followed up through 2013) to examine associations in children of women with epilepsy, using the largest sample to date and adjusting for a range of measured confounders. We examined maternal-reported first-trimester use of any ASM (22.7%) and the 3 most commonly reported individual drugs (valproic acid 4.8%, lamotrigine 6.8%, and carbamazepine 9.7%). We identified ASD with ICD10 diagnoses and ADHD with ICD-10 diagnoses or filled prescriptions of ADHD medication.Results: Examination of individual drugs revealed that after adjustment for confounding, use of valproic acid was associated with ASD (hazard ratio [HR] 2.30, 95% confidence interval [CI] 1.53-3.47) and ADHD (HR 1.74, 95% CI 1.28-2.38). Whereas a small, nonstatistically significant association with ASD (HR 1.25, 95% CI = 0.88-1.79) and ADHD (HR 1.18, 95% CI 0.91-1.52) remained for reported use of carbamazepine, confounding explained all of the associations with lamotrigine (HRASD 0.86, 95% CI 0.67-1.53; HRADHD 1.01, 95% CI 0.67-1.53).Conclusions: We found no evidence of risk related to exposure to lamotrigine, whereas we observed elevated risk of ASD and ADHD related to maternal use of valproic acid. Associations with carbamazepine were weak and not statistically significant. Our findings add to a growing body of evidence that suggests that certain ASMs may be safer than others in pregnancy.
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20. |
- Wiggs, Kelsey Kathleen, et al.
(author)
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Maternal Serotonergic Antidepressant Use in Pregnancy and Risk of Seizures in Children
- 2022
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In: Neurology. - : Wolters Kluwer. - 0028-3878 .- 1526-632X. ; 98:23, s. E2329-E2336
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Journal article (peer-reviewed)abstract
- Background and Objectives: To evaluate whether children born to women who use serotonergic antidepressants during pregnancy have higher risk of neonatal seizures and epilepsy.Methods: We used Swedish register-based data to examine associations between maternal reported use of selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) in pregnancy and diagnosis of neonatal seizures or epilepsy in >1.2 million children. To account for systematic differences between exposed and unexposed children, we adjusted for a wide range of measured confounders. After first evaluating the role of maternal indication for SSRI/SNRI use (i.e., depression or anxiety) and parental epilepsy, we adjusted for remaining parental background factors (e.g., age, comorbidities, education, and family socioeconomic indices) and pregnancy-specific characteristics (e.g., maternal use of other psychotropic medications and tobacco smoking in early pregnancy).Results: Compared with all other children, children of women who reported use of SSRI/SNRI in pregnancy had an elevated risk of neonatal seizures and epilepsy (risk ratio [RR] 1.41, 95% CI 1.03-1.94; hazard ratio [HR] 1.21, 95% CI 1.03-1.43, respectively). The estimates of association were attenuated by adjustment for maternal indications for SSRI/SNRI use (RR 1.30, 95% CI 0.94-1.80; HR 1.13, 95% CI 0.95-1.33), but not by additional adjustment for parental history of epilepsy. Full adjustment for all measured parental and pregnancy-specific factors resulted in substantial attenuation of the remaining associations (RR 1.10, 95% CI 0.79-1.53; HR 0.96, 95% CI 0.81-1.14).Discussion: We found no support for the concern that maternal SSRI/SNRI use in pregnancy increases children's risk for neonatal seizures or epilepsy.Classification of Evidence: This study provides Class II evidence that exposure to SSRIs/SNRIs in the first trimester of pregnancy is not associated with an increased incidence of neonatal seizures/epilepsy.
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21. |
- Zhang, Le, et al.
(author)
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Attention-Deficit/Hyperactivity Disorder Medications and Long-Term Risk of Cardiovascular Diseases
- 2024
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In: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 81:2, s. 178-187
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Journal article (peer-reviewed)abstract
- IMPORTANCE: Use of attention-deficit/hyperactivity disorder (ADHD) medications has increased substantially over the past decades. However, the potential risk of cardiovascular disease (CVD) associated with long-term ADHD medication use remains unclear.OBJECTIVE: To assess the association between long-term use of ADHD medication and the risk of CVD.DESIGN, SETTING, AND PARTICIPANTS: This case-control study included individuals in Sweden aged 6 to 64 years who received an incident diagnosis of ADHD or ADHD medication dispensation between January 1, 2007, and December 31, 2020. Data on ADHD and CVD diagnoses and ADHD medication dispensation were obtained from the Swedish National Inpatient Register and the Swedish Prescribed Drug Register, respectively. Cases included individuals with ADHD and an incident CVD diagnosis (ischemic heart diseases, cerebrovascular diseases, hypertension, heart failure, arrhythmias, thromboembolic disease, arterial disease, and other forms of heart disease). Incidence density sampling was used to match cases with up to 5 controls without CVD based on age, sex, and calendar time. Cases and controls had the same duration of follow-up.EXPOSURE: Cumulative duration of ADHD medication use up to 14 years.MAIN OUTCOMES AND MEASURES: The primary outcome was incident CVD. The association between CVD and cumulative duration of ADHD medication use was measured using adjusted odds ratios (AORs) with 95% CIs.RESULTS: Of 278 027 individuals with ADHD aged 6 to 64 years, 10 388 with CVD were identified (median [IQR] age, 34.6 [20.0-45.7] years; 6154 males [59.2%]) and matched with 51 672 control participants without CVD (median [IQR] age, 34.6 [19.8-45.6] years; 30 601 males [59.2%]). Median (IQR) follow-up time in both groups was 4.1 (1.9-6.8) years. Longer cumulative duration of ADHD medication use was associated with an increased risk of CVD compared with nonuse (0 to ≤1 year: AOR, 0.99 [95% CI, 0.93-1.06]; 1 to ≤2 years: AOR, 1.09 [95% CI, 1.01-1.18]; 2 to ≤3 years: AOR, 1.15 [95% CI, 1.05-1.25]; 3 to ≤5 years: AOR, 1.27 [95% CI, 1.17-1.39]; and >5 years: AOR, 1.23 [95% CI, 1.12-1.36]). Longer cumulative ADHD medication use was associated with an increased risk of hypertension (eg, 3 to ≤5 years: AOR, 1.72 [95% CI, 1.51-1.97] and >5 years: AOR, 1.80 [95% CI, 1.55-2.08]) and arterial disease (eg, 3 to ≤5 years: AOR, 1.65 [95% CI, 1.11-2.45] and >5 years: AOR, 1.49 [95% CI, 0.96-2.32]). Across the 14-year follow-up, each 1-year increase of ADHD medication use was associated with a 4% increased risk of CVD (AOR, 1.04 [95% CI, 1.03-1.05]), with a larger increase in risk in the first 3 years of cumulative use (AOR, 1.08 [95% CI, 1.04-1.11]) and stable risk over the remaining follow-up. Similar patterns were observed in children and youth (aged <25 years) and adults (aged ≥25 years).CONCLUSIONS AND RELEVANCE: This case-control study found that long-term exposure to ADHD medications was associated with an increased risk of CVDs, especially hypertension and arterial disease. These findings highlight the importance of carefully weighing potential benefits and risks when making treatment decisions about long-term ADHD medication use. Clinicians should regularly and consistently monitor cardiovascular signs and symptoms throughout the course of treatment.
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