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- Bruze, Gustaf, et al.
(author)
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Mental health from 5 years before to 10 years after bariatric surgery in adolescents with severe obesity: a Swedish nationwide cohort study with matched population controls
- 2024
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In: LANCET CHILD & ADOLESCENT HEALTH. - : ELSEVIER SCI LTD. - 2352-4642 .- 2352-4650. ; 8:2, s. 135-146
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Journal article (peer-reviewed)abstract
- Background: The long-term effects of bariatric surgery on the mental health of adolescents with severe obesity remain uncertain. We aimed to describe the prevalence of psychiatric health-care visits and filled prescription psychiatric drugs among adolescents with severe obesity undergoing bariatric surgery in the 5 years preceding surgery and throughout the first 10 years after surgery, and to draw comparisons with matched adolescents in the general population. Methods: Adolescents with severe obesity and who underwent bariatric surgery were identified through the Scandinavian Obesity Surgery Registry. We included adolescents who had bariatric surgery between 2007 and 2017 and were younger than 21 years at time of surgery. Each adolescent patient was matched with ten adolescents from the general population by age, sex, and county of residence. Specialist psychiatric care and filled psychiatric prescriptions were retrieved from nationwide data registers. Findings: 1554 adolescents (<21 years) with severe obesity underwent bariatric surgery between 2007 and 2017, 1169 (75%) of whom were female. At time of surgery, the mean age was 19.0 years [SD 1.0], and the mean BMI was 43.7 kg/m(2) (SD 5.5). 15 540 adolescents from the general population were matched with adolescents in the surgery group. 5 years before the matched index date, 95 (6.2%) of 1535 surgery patients and 370 (2.5%) of 14 643 matched adolescents had a psychiatric health-care visit (prevalence difference 3.7%; 95% CI 2.4-4.9), whereas 127 (9.8%) of 1295 surgery patients and 445 (3.6%) of 12 211 matched adolescents filled a psychiatric drug prescription (prevalence difference 6.2%; 95% CI 4.5-7.8). The year before the matched index date, 208 (13.4%) of 1551 surgery patients and 844 (5.5%) of 15 308 matched adolescents had a psychiatric health-care visit (prevalence difference 7.9%; 95% CI 6.2-9.6), whereas 319 (20.6%) of 1551 surgery patients and 1306 (8.5%) of 15 308 matched adolescents filled a psychiatric drug prescription (prevalence difference 12.0%; 10.0-14.1). The prevalence difference in psychiatric health-care visits peaked 9 years after the matched index date (12.0%; 95% CI 9.0-14.9), when 119 (17.6%) of 675 surgery patients and 377 (5.7%) of 6669 matched adolescents had a psychiatric health-care visit. The prevalence difference in filled psychiatric drug prescription was highest 10 years after the matched index date (20.4%; 15.9-24.9), when 171 (36.5%) of 469 surgery patients and 739 (16.0%) of 4607 matched adolescents filled a psychiatric drug prescription. The year before the matched index date, 19 (1.2%) of 1551 surgery patients and 155 (1.0%) of 15304 matched adolescents had a health-care visit associated with a substance use disorder diagnosis (mean difference 0.2%, 95% CI -0.4 to 0.8). 10 years after the matched index date, the prevalence difference had increased to 4.3% (95% CI 2.3-6.4), when 24 (5.1%) of 467 surgery patients and 37 (0.8%) of 4582 matched adolescents had a health-care visit associated with a substance use disorder diagnosis. Interpretation: Psychiatric diagnoses and psychiatric drug prescriptions were more common among adolescents with severe obesity who would later undergo bariatric surgery than among matched adolescents from the general population. Both groups showed an increase in prevalence in psychiatric diagnoses and psychiatric drug prescriptions leading up to the time of surgery, but the rate of increase in the prevalence was higher among adolescents with severe obesity than among matched adolescents. With the exception of health-care visits for substance use disorders, these prevalence trajectories continued in the 10 years of follow-up. Realistic expectations regarding mental health outcomes should be set preoperatively. Funding: Swedish Research Council, Swedish Research Council for Health, Working Life and Welfare.
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- Claesson, Andreas, et al.
(author)
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Defibrillation before EMS arrival in western Sweden
- 2017
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In: American Journal of Emergency Medicine. - : Elsevier. - 0735-6757 .- 1532-8171. ; 35:8, s. 1043-1048
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Journal article (peer-reviewed)abstract
- BACKGROUND: Bystanders play a vital role in public access defibrillation (PAD) in out-of-hospital cardiac arrest (OHCA). Dual dispatch of first responders (FR) alongside emergency medical services (EMS) can reduce time to first defibrillation. The aim of this study was to describe the use of automated external defibrillators (AEDs) in OHCAs before EMS arrival.METHODS: All OHCA cases with a shockable rhythm in which an AED was used prior to the arrival of EMS between 2008 and 2015 in western Sweden were eligible for inclusion. Data from the Swedish Register for Cardiopulmonary Resuscitation (SRCR) were used for analysis, on-site bystander and FR defibrillation were compared with EMS defibrillation in the final analysis.RESULTS: Of the reported 6675 cases, 24% suffered ventricular fibrillation (VF), 162 patients (15%) of all VF cases were defibrillated before EMS arrival, 46% with a public AED on site. The proportion of cases defibrillated before EMS arrival increased from 5% in 2008 to 20% in 2015 (p<0.001). During this period, 30-day survival increased in patients with VF from 22% to 28% (p=0.04) and was highest when an AED was used on site (68%), with a median delay of 6.5min from collapse to defibrillation. Adjusted odds ratio for on-site defibrillation versus dispatched defibrillation for 30-day survival was 2.45 (95% CI: 1.02-5.95).CONCLUSIONS: The use of AEDs before the arrival of EMS increased over time. This was associated with an increased 30-day survival among patients with VF. Thirty-day survival was highest when an AED was used on site before EMS arrival.
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- Dekkers, Koen, et al.
(author)
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An online atlas of human plasma metabolite signatures of gut microbiome composition.
- 2022
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Journal article (peer-reviewed)abstract
- Human gut microbiota produce a variety of molecules, some of which enter the bloodstream and impact health. Conversely, dietary or pharmacological compounds may affect the microbiota before entering the circulation. Characterization of these interactions is an important step towards understanding the effects of the gut microbiota on health. In this cross-sectional study, we used deep metagenomic sequencing and ultra-high-performance liquid chromatography linked to mass spectrometry for a detailed characterization of the gut microbiota and plasma metabolome, respectively, of 8583 participants invited at age 50 to 64 from the population-based Swedish CArdioPulmonary bioImage Study. Here, we find that the gut microbiota explain up to 58% of the variance of individual plasma metabolites and we present 997 associations between alpha diversity and plasma metabolites and 546,819 associations between specific gut metagenomic species and plasma metabolites in an online atlas ( https://gutsyatlas.serve.scilifelab.se/ ). We exemplify the potential of this resource by presenting novel associations between dietary factors and oral medication with the gut microbiome, and microbial species strongly associated with the uremic toxin p-cresol sulfate. This resource can be used as the basis for targeted studies of perturbation of specific metabolites and for identification of candidate plasma biomarkers of gut microbiota composition.
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- Ding, Mei, et al.
(author)
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Secretome screening reveals immunomodulating functions of IFNα-7, PAP and GDF-7 on regulatory T-cells
- 2021
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In: Scientific Reports. - : Springer Nature. - 2045-2322. ; , s. 16767-
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Journal article (peer-reviewed)abstract
- Regulatory T cells (Tregs) are the key cells regulating peripheral autoreactive T lymphocytes. Tregs exert their function by suppressing effector T cells. Tregs have been shown to play essential roles in the control of a variety of physiological and pathological immune responses. However, Tregs are unstable and can lose the expression of FOXP3 and suppressive functions as a consequence of outer stimuli. Available literature suggests that secreted proteins regulate Treg functional states, such as differentiation, proliferation and suppressive function. Identification of secreted proteins that affect Treg cell function are highly interesting for both therapeutic and diagnostic purposes in either hyperactive or immunosuppressed populations. Here, we report a phenotypic screening of a human secretome library in human Treg cells utilising a high throughput flow cytometry technology. Screening a library of 575 secreted proteins allowed us to identify proteins stabilising or destabilising the Treg phenotype as suggested by changes in expression of Treg marker proteins FOXP3 and/or CTLA4. Four proteins including GDF-7, IL-10, PAP and IFNα-7 were identified as positive regulators that increased FOXP3 and/or CTLA4 expression. PAP is a phosphatase. A catalytic-dead version of the protein did not induce an increase in FOXP3 expression. Ten interferon proteins were identified as negative regulators that reduced the expression of both CTLA4 and FOXP3, without affecting cell viability. A transcriptomics analysis supported the differential effect on Tregs of IFNα-7 versus other IFNα proteins, indicating differences in JAK/STAT signaling. A conformational model experiment confirmed a tenfold reduction in IFNAR-mediated ISG transcription for IFNα-7 compared to IFNα-10. This further strengthened the theory of a shift in downstream messaging upon external stimulation. As a summary, we have identified four positive regulators of FOXP3 and/or CTLA4 expression. Further exploration of these Treg modulators and their method of action has the potential to aid the discovery of novel therapies for both autoimmune and infectious diseases as well as for cancer.
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- Neovius, Martin, et al.
(author)
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Risk of suicide and non-fatal self-harm after bariatric surgery: results from two matched cohort studies.
- 2018
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In: The lancet. Diabetes & endocrinology. - : Elsevier. - 2213-8595 .- 2213-8587. ; 6:3, s. 197-207
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Journal article (peer-reviewed)abstract
- Bariatric surgery reduces mortality, but might have adverse effects on mental health. We assessed the risk of suicide and self-harm after bariatric surgery compared with non-surgical obesity treatment.Suicide and non-fatal self-harm events retrieved from nationwide Swedish registers were examined in two cohorts. The non-randomised, prospective Swedish Obese Subjects (SOS) study compared bariatric surgery (n=2010; 1369 vertical-banded gastroplasty, 376 gastric banding, and 265 gastric bypass) with usual care (n=2037; recruitment 1987-2001). The second cohort consisted of individuals from the Scandinavian Obesity Surgery Registry (SOReg; n=20256 patients who had gastric bypass) matched to individuals treated with intensive lifestyle modification (n=16162; intervention 2006-13) on baseline BMI, age, sex, education level, diabetes, cardiovascular disease, history of self-harm, substance misuse, antidepressant use, anxiolytics use, and psychiatric health-care contacts.During 68528 person-years (median 18; IQR 14-21) in the SOS study, suicides or non-fatal self-harm events were higher in the surgery group (n=87) than in the control group (n=49; adjusted hazard ratio [aHR] 1·78, 95% CI 1·23-2·57; p=0·0021); of these events, nine and three were suicides, respectively (3·06, 0·79-11·88; p=0·11). In analyses by primary procedure type, increased risk of suicide or non-fatal self-harm was identified for gastric bypass (3·48, 1·65-7·31; p=0·0010), gastric banding (2·43, 1·23-4·82; p=0·011), and vertical-banded gastroplasty (2·25, 1·37-3·71; p=0·0015) compared with controls. Out of nine deaths by suicide in the SOS surgery group, five occurred after gastric bypass (two primary and three converted procedures). During 149582 person-years (median 3·9; IQR 2·8-5·2), more suicides or non-fatal self-harm events were reported in the SOReg gastric bypass group (n=341) than in the intensive lifestyle group (n=84; aHR 3·16, 2·46-4·06; p<0·0001); of these events, 33 and five were suicides, respectively (5·17, 1·86-14·37; p=0·0017). In SOS, substance misuse during follow-up was recorded in 48% (39/81) of patients treated with surgery and 28% (13/47) of controls with non-fatal self-harm events (p=0·023). Correspondingly, substance misuse during follow-up was recorded in 51% (162/316) of participants in the SOReg gastric bypass group and 29% (23/80) of participants in the intensive lifestyle group with non-fatal self-harm events (p=0·0003). The risk of suicide and self-harm was not associated with poor weight loss outcome.Bariatric surgery was associated with suicide and non-fatal self-harm. However, the absolute risks were low and do not justify a general discouragement of bariatric surgery. The findings indicate a need for thorough preoperative psychiatric history assessment along with provision of information about increased risk of self-harm following surgery. Moreover, the findings call for postoperative surveillance with particular attention to mental health.US National Institutes of Health and Swedish Research Council.
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- Ng, Winda L., et al.
(author)
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Change in Use of Sleep Medications After Gastric Bypass Surgery or Intensive Lifestyle Treatment in Adults with Obesity
- 2017
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In: Obesity. - : WILEY. - 1930-7381 .- 1930-739X. ; 25:8, s. 1451-1459
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Journal article (peer-reviewed)abstract
- Objective: To examine the change in use of hypnotics and/or sedatives after gastric bypass surgery or intensive lifestyle modification in adults with obesity.Methods: Adults with obesity who underwent gastric bypass surgery or initiated intensive lifestyle modification between 2007 and 2012 were identified through the Scandinavian Obesity Surgery Registry and a Swedish commercial weight loss database. The two cohorts were matched on BMI, age, sex, education, history of hypnotics and/or sedatives use, and treatment year (surgery n = 20,626; lifestyle n = 11,973; 77% women, mean age 41 years, mean BMI 41 kg/m(2)). The proportion of participants with filled hypnotics and/or sedatives prescriptions was compared yearly for 3 years.Results: In the matched treatment cohorts, 4% had filled prescriptions for hypnotics and/or sedatives during the year before treatment. At 1 year follow-up, following an average weight loss of 37 kg and 18 kg in the surgery and intensive lifestyle cohorts, respectively, this proportion had increased to 7% in the surgery cohort but remained at 4% in the intensive lifestyle cohort (risk ratio 1.7; 95% CI: 1.4-2.1); at 2 years, the proportion had increased to 11% versus 5% (risk ratio 2.0; 95% CI: 1.7-2.4); and at 3 years, it had increased to 14% versus 6% (risk ratio 2.2; 95% CI: 1.9-2.6).Conclusions: Gastric bypass surgery was associated with increased use of hypnotics and/or sedatives compared with intensive lifestyle modification.
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- Sayols-Baixeras, Sergi, et al.
(author)
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Streptococcus Species Abundance in the Gut Is Linked to Subclinical Coronary Atherosclerosis in 8973 Participants From the SCAPIS Cohort
- 2023
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In: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 148:6, s. 459-472
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Journal article (peer-reviewed)abstract
- Background: Gut microbiota have been implicated in atherosclerotic disease, but their relation with subclinical coronary atherosclerosis is unclear. This study aimed to identify associations between the gut microbiome and computed tomography-based measures of coronary atherosclerosis and to explore relevant clinical correlates.Methods: We conducted a cross-sectional study of 8973 participants (50 to 65 years of age) without overt atherosclerotic disease from the population-based SCAPIS (Swedish Cardiopulmonary Bioimage Study). Coronary atherosclerosis was measured using coronary artery calcium score and coronary computed tomography angiography. Gut microbiota species abundance and functional potential were assessed with shotgun metagenomics sequencing of stool, and associations with coronary atherosclerosis were evaluated with multivariable regression models adjusted for cardiovascular risk factors. Associated species were evaluated for association with inflammatory markers, metabolites, and corresponding species in saliva.Results: The mean age of the study sample was 57.4 years, and 53.7% were female. Coronary artery calcification was detected in 40.3%, and 5.4% had at least 1 stenosis with >50% occlusion. Sixty-four species were associated with coronary artery calcium score independent of cardiovascular risk factors, with the strongest associations observed for Streptococcus anginosus and Streptococcus oralis subsp oralis (P<1×10-5). Associations were largely similar across coronary computed tomography angiography-based measurements. Out of the 64 species, 19 species, including streptococci and other species commonly found in the oral cavity, were associated with high-sensitivity C-reactive protein plasma concentrations, and 16 with neutrophil counts. Gut microbial species that are commonly found in the oral cavity were negatively associated with plasma indole propionate and positively associated with plasma secondary bile acids and imidazole propionate. Five species, including 3 streptococci, correlated with the same species in saliva and were associated with worse dental health in the Malmö Offspring Dental Study. Microbial functional potential of dissimilatory nitrate reduction, anaerobic fatty acid β-oxidation, and amino acid degradation were associated with coronary artery calcium score.Conclusions: This study provides evidence of an association of a gut microbiota composition characterized by increased abundance of Streptococcus spp and other species commonly found in the oral cavity with coronary atherosclerosis and systemic inflammation markers. Further longitudinal and experimental studies are warranted to explore the potential implications of a bacterial component in atherogenesis.
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- Sayols-Baixeras, Sergi, et al.
(author)
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Streptococcus Species Abundance in the Gut Is Linked to Subclinical Coronary Atherosclerosis in 8973 Participants From the SCAPIS Cohort
- 2023
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In: Circulation. - : American Heart Association. - 0009-7322 .- 1524-4539. ; 148:6, s. 459-472
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Journal article (peer-reviewed)abstract
- BACKGROUND: Gut microbiota have been implicated in atherosclerotic disease, but their relation with subclinical coronary atherosclerosis is unclear. This study aimed to identify associations between the gut microbiome and computed tomography–based measures of coronary atherosclerosis and to explore relevant clinical correlates.METHODS: We conducted a cross-sectional study of 8973 participants (50 to 65 years of age) without overt atherosclerotic disease from the population-based SCAPIS (Swedish Cardiopulmonary Bioimage Study). Coronary atherosclerosis was measured using coronary artery calcium score and coronary computed tomography angiography. Gut microbiota species abundance and functional potential were assessed with shotgun metagenomics sequencing of fecal samples, and associations with coronary atherosclerosis were evaluated with multivariable regression models adjusted for cardiovascular risk factors. Associated species were evaluated for association with inflammatory markers, metabolites, and corresponding species in saliva.RESULTS: The mean age of the study sample was 57.4 years, and 53.7% were female. Coronary artery calcification was detected in 40.3%, and 5.4% had at least 1 stenosis with >50% occlusion. Sixty-four species were associated with coronary artery calcium score independent of cardiovascular risk factors, with the strongest associations observed for Streptococcus anginosus and Streptococcus oralis subsp oralis (P<1×10–5). Associations were largely similar across coronary computed tomography angiography–based measurements. Out of the 64 species, 19 species, including streptococci and other species commonly found in the oral cavity, were associated with high-sensitivity C-reactive protein plasma concentrations, and 16 with neutrophil counts. Gut microbial species that are commonly found in the oral cavity were negatively associated with plasma indole propionate and positively associated with plasma secondary bile acids and imidazole propionate. Five species, including 3 streptococci, correlated with the same species in saliva and were associated with worse dental health in the Malmö Offspring Dental Study. Microbial functional potential of dissimilatory nitrate reduction, anaerobic fatty acid β-oxidation, and amino acid degradation were associated with coronary artery calcium score.CONCLUSIONS: This study provides evidence of an association of a gut microbiota composition characterized by increased abundance of Streptococcus spp and other species commonly found in the oral cavity with coronary atherosclerosis and systemic inflammation markers. Further longitudinal and experimental studies are warranted to explore the potential implications of a bacterial component in atherogenesis.
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