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2. |
- Alexandersson, Bjarki T., et al.
(author)
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Diverticulosis is not associated with altered gut microbiota nor is it predictive of future diverticulitis : a population-based colonoscopy study
- 2023
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In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 58:10, s. 1131-1138
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Journal article (peer-reviewed)abstract
- Background: The etiopathogenesis of diverticular disease is unknown.Objective: To compare the fecal and mucosa-associated microbiota between participants with and without diverticulosis and participants who later developed diverticulitis versus those that did not from a population-based study.Methods: The PopCol study, conducted in Stockholm, Sweden, invited a random sample of 3556 adults to participate, of which 745 underwent colonoscopy. Overall, 130 participants (17.5%) had diverticulosis. 16S rRNA gene sequencing was conducted on available sigmoid biopsy samples from 529 and fecal samples from 251 individuals. We identified individuals who subsequently developed acute diverticulitis up to 13 years after sample collection. In a case-control design matching for gender, age (+/−5 years), smoking and antibiotic exposure, we compared taxonomic composition, richness and diversity of the microbiota between participants with or without diverticulosis, and between participants who later developed acute diverticulitis versus those who did not.Results: No differences in microbiota richness or diversity were observed between participants with or without diverticulosis, nor for those who developed diverticulitis compared with those who did not. No bacterial taxa were significantly different between participants with diverticulosis compared with those without diverticulosis. Individuals who later developed acute diverticulitis (2.8%) had a higher abundance of genus Comamonas than those who did not (p = .027).Conclusions: In a population-based cohort study the only significant difference was that those who later develop diverticulitis had more abundance of genus Comamonas. The significance of Comamonas is unclear, suggesting a limited role for the gut microbiota in the etiopathogenesis of diverticular disease.
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3. |
- Alexandersson, Bjarki T., et al.
(author)
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Inflammatory Bowel Disease Is not Linked to a Higher Rate of Adverse Events in Colonoscopy : a Nationwide Population-based Study in Sweden
- 2023
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In: Journal of Crohn's & Colitis. - 1873-9946 .- 1876-4479. ; 17:12, s. 1962-1967
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Journal article (peer-reviewed)abstract
- Background and Aims: Inflammatory bowel disease may cause long-standing inflammation and fibrosis and may increase the risk of adverse events in colonoscopy. We evaluated whether inflammatory bowel disease and other potential risk factors are associated with bleeding or perforation in a nationwide, population-based, Swedish study.Methods: Data from 969 532 colonoscopies, including 164 012 [17%] on inflammatory bowel disease patients, between 2003 and 2019, were retrieved from the National Patient Registers. ICD-10 codes for bleeding [T810] and perforation [T812] within 30 days of the colonoscopy were recorded. Multivariable logistic regression was used to test if inflammatory bowel disease status, inpatient setting, time period, general anaesthesia, age, sex, endoscopic procedures, and antithrombotic treatment were associated with higher odds for bleeding and perforation.Results: Bleeding and perforation were reported in 0.19% and 0.11% of all colonoscopies, respectively. Bleeding [odds ratio 0.66, p <0.001] and perforation [odds ratio 0.79, p <0.033] were less likely in colonoscopies in individuals with inflammatory bowel disease status. Bleeding and perforation were more common in inpatient than in outpatient inflammatory bowel disease colonoscopies. The odds for bleeding but not perforation increased between 2003 to 2019. General anaesthesia was associated with double the odds for perforation.Conclusions: Individuals with inflammatory bowel disease did not have more adverse events compared with individuals without inflammatory bowel disease status. However, the inpatient setting was associated with more adverse events, particularly in inflammatory bowel disease status. General anaesthesia was associated with a greater risk of perforation.
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4. |
- Alme, Tomas Nordheim, et al.
(author)
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Chronic fatigue syndromes: real illnesses that people can recover from
- 2023
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In: Scandinavian Journal of Primary Health Care. - : TAYLOR & FRANCIS LTD. - 0281-3432 .- 1502-7724. ; 41:4, s. 372-376
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Journal article (peer-reviewed)abstract
- The Oslo Chronic Fatigue Consortium consists of researchers and clinicians who question the current narrative that chronic fatigue syndromes, including post-covid conditions, are incurable diseases. Instead, we propose an alternative view, based on research, which offers more hope to patients. Whilst we regard the symptoms of these conditions as real, we propose that they are more likely to reflect the brains response to a range of biological, psychological, and social factors, rather than a specific disease process. Possible causes include persistent activation of the neurobiological stress response, accompanied by associated changes in immunological, hormonal, cognitive and behavioural domains. We further propose that the symptoms are more likely to persist if they are perceived as threatening, and all activities that are perceived to worsen them are avoided. We also question the idea that the best way to cope with the illness is by prolonged rest, social isolation, and sensory deprivation.Instead, we propose that recovery is often possible if patients are helped to adopt a less threatening understanding of their symptoms and are supported in a gradual return to normal activities. Finally, we call for a much more open and constructive dialogue about these conditions. This dialogue should include a wider range of views, including those of patients who have recovered from them.
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5. |
- Andreasson, Anna, et al.
(author)
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An Increasing Incidence of Upper Gastrointestinal Disorders Over 23 Years : A Prospective Population-Based Study in Sweden
- 2021
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In: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270 .- 1572-0241. ; 116:1, s. 210-213
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Journal article (peer-reviewed)abstract
- INTRODUCTION: We hypothesized that the prevalence of functional dyspepsia and gastroesophageal reflux disease in the community may be increasing.METHODS: Randomly selected adults were surveyed on 4 occasions: 1988 (n = 1,151, 21–79 years, response rate [rr] = 90%), 1989 (n = 1,097, 22–80 years, rr = 87%), 1995 (n = 1,139, 20–85 years, rr = 76%), and 2011 (n = 1,175, 20–93 years, rr = 63%).RESULTS: In functional dyspepsia, the odds of postprandial distress syndrome tripled over 23 years' follow-up (odds ratio [OR]: 3.55; 95% confidence interval [CI]: 2.60–4.84, mixed-effect regression analysis), whereas a small decrease in epigastric pain syndrome was observed (OR: 0.65, 95% CI: 0.42–1.00). The odds of reporting gastroesophageal reflux disease doubled (OR: 2.02; 95% CI: 1.50–2.73).DISCUSSION: The underlying mechanisms behind the increase in postprandial distress syndrome and gastroesophageal reflux disease remain to be determined.
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6. |
- Andréasson, Frida
(author)
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Doing informal care : Identity, couplehood, social health and information and communication technologies in older people’s everyday lives
- 2021
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Doctoral thesis (other academic/artistic)abstract
- The aim of the thesis has been a) to analyse how informal care influences the identity of carers and care recipients, their sense of couplehood and social health, and b) to explore the use of Information and Communication Technology (ICT) in the context of informal care and the everyday lives of older people. Study I focused on how older carers conceptualised their identity as carers on a Swedish online social forum, using a netnographic methodology. The findings indicated a change in self-perception as the carer role was acquired. Carers’ capacities were filtered through the needs of the care recipient, making their carer identities into invisible selves. The findings revealed that online communication had the potential to create a virtual space of social recognition. Study II aimed to reflect on carers’ experiences of participation in a co-design process consisting of user group sessions with carers and researchers. The goal was to develop a web-based support programme for carers. The findings emphasised a need to consider carers’ lifeworlds and to develop flexible human-centred design methodologies, that are able to balance carers’ needs and ideas with proposed research outcomes. Studies III and IV utilised an ethnographic methodology. In study III, the notion of couplehood in informal care was analysed. The findings showed that in the process of becoming a carer and a care recipient previous (often gendered) responsibilities were re- negotiated and new practicalities emerged. Although these changes were understood as a natural part of family life, they nevertheless led to changes in the (power) balance between spouses, expressed in terms of a professionalised relationship and a sense of social isolation. ICT was used as a means to get a respite from caring and uphold a social connection with others. In study IV, the social implications and consequences of spousal informal care and carers and care recipients’ experiences of illness and the ill body was explored. The findings showed that the participants experienced barriers to living life as before. Thoughts about or the presence of ill and “leaking” bodies thus lead to “self-chosen” social isolation or social distancing by others. The thesis highlights that informal care needs to be understood as an identity forming practice, having a significant impact on involved parties’ sense of couplehood, their social health and that ICT can contribute to ease carers’ and care recipients’ daily life.
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7. |
- Andréasson, Måns, 1994-, et al.
(author)
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Exploring the dispersion and electrostatic components in arene-arene interactions between ligands and G4 DNA to develop G4-ligands
- 2024
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In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 67:3, s. 2202-2219
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Journal article (peer-reviewed)abstract
- G-Quadruplex (G4) DNA structures are important regulatory elements in central biological processes. Small molecules that selectively bind and stabilize G4 structures have therapeutic potential, and there are currently >1000 known G4 ligands. Despite this, only two G4 ligands ever made it to clinical trials. In this work, we synthesized several heterocyclic G4 ligands and studied their interactions with G4s (e.g., G4s from the c-MYC, c-KIT, and BCL-2 promoters) using biochemical assays. We further studied the effect of selected compounds on cell viability, the effect on the number of G4s in cells, and their pharmacokinetic properties. This identified potent G4 ligands with suitable properties and further revealed that the dispersion component in arene-arene interactions in combination with electron-deficient electrostatics is central for the ligand to bind with the G4 efficiently. The presented design strategy can be applied in the further development of G4-ligands with suitable properties to explore G4s as therapeutic targets.
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8. |
- Hugerth, Luisa W., et al.
(author)
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No distinct microbiome signature of irritable bowel syndrome found in a Swedish random population
- 2020
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In: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 69:6, s. 1076-1084
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Journal article (peer-reviewed)abstract
- Objective The ethiopathogenesis of irritable bowel syndrome (IBS) is unknown. While a link to the gut microbiome is postulated, the heterogeneity of the healthy gut makes it difficult to draw definitive conclusions. We aimed to describe the faecal and mucosa-associated microbiome (MAM) and health correlates on a community cohort of healthy and IBS individuals with no colonoscopic findings.Design The PopCol study recruited a random sample of 3556 adults; 745 underwent colonoscopy. IBS was defined by Rome IV criteria and organic disease excluded. 16S rRNA gene sequencing was conducted on sigmoid biopsy samples from 376 representative individuals (63 IBS cases) and faecal samples from 185 individuals (32 IBS cases).Results While sigmoid MAM was dominated by Lachnospiraceae, faeces presented a higher relative abundance of Ruminococcaceae. Microbial richness in MAM was linearly correlated to that in faeces from the same individual (R-2=0.255, p<3E-11) as was diversity (R-2=0.06, p=0.0022). MAM diversity decreased with increasing body mass index (BMI; Pearson's r=-0.1, p=0.08) and poorer self-rated health (r=-0.15, p=0.007), but no other health correlates. Faecal microbiome diversity was correlated to stool consistency (r=-0.16, p=0.043). Several taxonomic groups were correlated to age, BMI, depression and self-reported health, including Coprococcus catus associated with lower levels of depression (r=-0.003, p=0.00017). The degree of heterogeneity observed between IBS patients is higher than that observed between healthy individuals.Conclusions No distinct microbial signature was observed in IBS. Individuals presenting with low self-rated health or high BMI have lower gut microbiome richness.
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9. |
- Mancina, Rosellina Margherita, et al.
(author)
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PSD3 downregulation confers protection against fatty liver disease.
- 2022
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In: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 4:1, s. 60-75
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Journal article (peer-reviewed)abstract
- Fatty liver disease (FLD) is a growing health issue with burdening unmet clinical needs. FLD has a genetic component but, despite the common variants already identified, there is still a missing heritability component. Using a candidate gene approach, we identify a locus (rs71519934) at the Pleckstrin and Sec7 domain-containing 3 (PSD3) gene resulting in a leucine to threonine substitution at position 186 of the protein (L186T) that reduces susceptibility to the entire spectrum of FLD in individuals at risk. PSD3 downregulation by short interfering RNA reduces intracellular lipid content in primary human hepatocytes cultured in two and three dimensions, and in human and rodent hepatoma cells. Consistent with this, Psd3 downregulation by antisense oligonucleotides in vivo protects against FLD in mice fed a non-alcoholic steatohepatitis-inducing diet. Thus, translating these results to humans, PSD3 downregulation might be a future therapeutic option for treating FLD.
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10. |
- Talley, Nicholas J., et al.
(author)
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Role of smoking in functional dyspepsia and irritable bowel syndrome : three random population-based studies
- 2021
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In: Alimentary Pharmacology and Therapeutics. - : John Wiley & Sons. - 0269-2813 .- 1365-2036. ; 54:1, s. 32-42
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Journal article (peer-reviewed)abstract
- Background: It is uncertain if functional dyspepsia (FD) or irritable bowel syndrome (IBS) are linked to smoking, and smoking cessation is not part of the routine advice provided to these patients.Aim: To assess if smoking is an independent risk factor for FD and IBS.Methods: Three population-based endoscopy studies in Sweden with 2560 community individuals in total (mean age 51.5 years, 46% male). IBS (14.9%), FD (33.5%), and associated symptoms were assessed using the validated abdominal symptom questionnaire, and smoking (17.9%) was obtained from standardised questions during a clinic visit. The effect of smoking on symptom status was analysed in an individual person data meta-analysis using mixed effect logistic regression, adjusted for snuffing, age and sex.Results: Individuals smoking cigarettes reported significantly higher odds of postprandial distress syndrome (FD-PDS) (OR 10-19 cig/day = 1.42, 95% CI 1.04-1.98 P = 0.027, OR ≥20 cig/day = 2.16, 95% CI 1.38-3.38, P = 0.001) but not epigastric pain. Individuals smoking 20 or more cigarettes per day reported significantly higher odds of IBS-diarrhoea (OR = 2.40, 95% CI 1.12-5.16, P = 0.025), diarrhoea (OR = 2.01, 95%CI 1.28-3.16, P = 0.003), urgency (OR = 2.21, 95%CI 1.41-3.47, P = 0.001) and flatus (OR = 1.77, 95%CI 1.14-2.76, P = 0.012) than non-smokers. Smoking was not associated with IBS-constipation or IBS-mixed.Conclusion: Smoking is an important environmental risk factor for postprandial distress syndrome, the most common FD subgroup, with over a twofold increased odds of PDS in heavy smokers. The role of smoking in IBS-diarrhoea, but not constipation, is also likely important.
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11. |
- Ahlstrand, Erik, 1974-, et al.
(author)
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Highly Reduced Survival in Essential Thrombocythemia and Polycythemia Vera Patients with Vascular Complications during Follow-up
- 2020
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In: European Journal of Haematology. - : Munksgaard Forlag. - 0902-4441 .- 1600-0609. ; 104:3, s. 271-278
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To explore the relative importance of risk factors, treatments and blood counts for the occurrence of vascular complications and their impact on life expectancy in Essential Thrombocythemia (ET) and Polycythemia Vera (PV).METHODS: Nested case-control study within the Swedish MPN registry. From a cohort of 922 ET patients and 763 PV patients, 71 ET and 81 PV cases with vascular complications were compared to matched controls.RESULTS: Incidence of vascular complications were 2.0 and 3.4 events per 100 patient-years in ET and PV, respectively. At diagnosis, no significant risk factor differences were observed between cases and controls in neither of the diseases. At the time of vascular event, ET complication cases did not differ significantly from controls but in PV, cases had significantly higher WBCs and were to a lesser extent treated with antithrombotic and cytoreductive therapy. Life expectancy was significantly decreased in both ET and PV cases compared to controls.CONCLUSIONS: The risk of vascular complications is high in both ET and PV and these complications have a considerable impact on life expectancy. The protective effect of antithrombotic and cytoreductive therapy for vascular complications in PV underscores the importance of avoiding undertreatment.
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12. |
- Alexandersson, Bjarki, et al.
(author)
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High-Definition Chromoendoscopy Superior to High-Definition White-Light Endoscopy in Surveillance of Inflammatory Bowel Diseases in a Randomized Trial
- 2020
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In: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565 .- 1542-7714. ; 18:9, s. 2101-2107
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Journal article (peer-reviewed)abstract
- BACKGROUND & AIMS: There is debate over the optimal method for colonoscopic surveillance of patients with inflammatory bowel diseases. Guidelines recommend chromoendoscopy, but the value of chromoendoscopy in high-definition colonoscopy has not been proven. Furthermore, the value of random biopsies is controversial. METHODS: We performed a prospective study of 305 patients with ulcerative colitis or Crohn's colitis referred for surveillance colonoscopy at a university hospital in Sweden, from March 2011 through April 2016. Patients randomly assigned to a group that received high-definition chromoendoscopy with indigo carmine (HD-CE; n=152), collection of 32 random biopsies, and targeted biopsies or polypectomies or to a group that received high-definition white light endoscopy (HD-WLE; n=153), collection of 32 random biopsies, and targeted biopsies or polypectomies. The primary endpoint was number of patients with dysplastic lesions. RESULTS: Dysplastic lesions were detected in 17 patients with HD-CE and 7 patients with HD-WLE (P=.032). Dysplasias in random biopsies (n=9760) were detected in 9 patients: 6 (3.9%) in the HD-CE group and 3 (2.0%) in the HD-WLE group (P=.72). Of the 9 patients with dysplasia, 3 patients (33%) had primary sclerosing cholangitis-only 18% of patients (54/305) included in the study had primary sclerosing cholangitis. The number of dysplastic lesions per 10 min of withdrawal time was 0.066 with HD-CE and 0.027 with HD-WLE (P=.056). CONCLUSIONS: In a randomized trial, we found HD-CE with collection of random biopsies to be superior to HD-WLE with random biopsies for detection of dysplasia per colonoscopy. These results support the use of chromoendoscopy for surveillance of patients with inflammatory bowel diseases. ClinicalTrials.gov no: NCT01505842.
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13. |
- Alifier, Marek, et al.
(author)
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Cardiac Surgery is Associated with Biomarker Evidence of Neuronal Damage.
- 2020
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In: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 74:4, s. 1211-1220
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Journal article (peer-reviewed)abstract
- Anesthesia and surgery is commonly associated with central nervous system sequelae and cognitive symptoms, which may be caused by neuronal injury. Neuronal injury can be monitored by plasma concentrations of the neuronal biomarkers tau and neurofilament light protein (NFL). Currently, there are no studies examining whether neuronal injury varies between surgical procedures.Our aim was to investigate if neuronal damage is more frequent after cardiac than after otolaryngeal surgery, as estimated by tau and NFL concentrations in plasma.Blood samples were drawn before, during, and after surgery and concentrations of tau, NFL, Aβ40, and Aβ42 were measured in 25 patients undergoing cardiac surgery (9 off-pump and 16 on-pump) and 26 patients undergoing otolaryngeal surgery.Tau increased during surgery (1752%, p=0.0001) and NFL rose seven days post-surgery (1090%, p<0.0001) in patients undergoing cardiac surgery; even more in patients on-pump than off-pump. No changes were observed in patients undergoing otolaryngeal surgery and only minor fluctuations were observed for Aβ40 and Aβ42.Cardiac surgery is associated with neuronal injury, which is aggravated by extracorporeal circulation. Analyses of NFL and tau in blood may guide development of surgical procedures to minimize neuronal damage, and may also be used in longitudinal clinical studies to assess the relationship of surgery with future neurocognitive impairment or dementia.
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14. |
- Allemann, Hanna, et al.
(author)
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The co-design of an online support programme with and for informal carers of people with heart failure : A methodological paper
- 2023
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In: Journal of Clinical Nursing. - : John Wiley & Sons. - 0962-1067 .- 1365-2702. ; 32:19-20, s. 7589-7604
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Journal article (peer-reviewed)abstract
- Abstract AimTo describe the co-designing process of an online support programme with and for informal carers of people with heart failure.DesignA co-design process built on core concepts and ideas embedded in co-design methodology.Data sources Our co-design process included three phases involving 32 informal caregivers and 25 content creators; (1) Identification of topics and content through literature searches, focus group interviews and user group sessions; (2) Development of the online support programme and; (3) Refinement and finalization which included testing a paper prototype followed by testing the online version and testing and approval of the final version of the support programme.Outcomes The co-design process resulted in a support programme consisting of 15 different modules relevant to informal carers, delivered on a National Health Portal.Conclusion Co-design is an explorative process where researchers need to balance a range of potentially conflicting factors and to ensure that the end users are genuinely included in the process.Relevance to clinical practice Emphasizing equal involvement of end users (e.g. carers or patients) in the design and development of healthcare interventions aligns with contemporary ideas of person-centred care and provides a valuable learning opportunity for those involved. Furthermore, a co-designed online support programme has the capacity to be both accessible and meet end users' information and support needs, thereby optimizing their self-care abilities. Additionally, an online support programme provides the opportunity to address current challenges regarding scarce resources and the lack of healthcare personnel.Reporting methodsConsolidated criteria for reporting qualitative research (COREQ).Patient or public contributionBoth informal carers and content creators were involved in developing the support programme.
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15. |
- Andreasson, Anna, 1980-, et al.
(author)
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Assessing sickness behavior in the French : Validation of the French translation of the sickness questionnaire (SicknessQ) in a non-clinical French population
- 2023
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In: Brain, Behavior, & Immunity - Health. - 2666-3546. ; 34
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Journal article (peer-reviewed)abstract
- The Sickness Questionnaire (SicknessQ) is a questionnaire developed to assess symptoms of sickness behavior, including somatic, behavioral, and affective dimensions. To promote cross-cultural assessments of sickness behavior, we aim to expand the use of this questionnaire to other populations and languages. The aim of the present study was to evaluate the French translation of SicknessQ in a French-speaking general population during the COVID-19 pandemic. One hundred and thirty-nine individuals completed the SicknessQ online, along with the construct criteria measures of self-rated health, state anxiety (STAI-S), and depressive symptoms (PHQ-9). The principal component analyses revealed two components: the first component included seven items concerning mood, motivation and experiences of fatigue and pain; the second component included three items concerning somatic sickness symptoms. Higher scores on the total scale and the two component subscales were associated with poorer self-rated health and higher STAI-S and PHQ-9 scores. Since the associations with construct criteria variables were relatively similar between the single- and the two-dimensional solutions, both the total scale and the subscales of the two components of the French SicknessQ can be used in future studies to measure sickness behavior in French-speaking populations.
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16. |
- Andreasson, Anna, 1980-, et al.
(author)
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Effect of on-demand vs continuous prescription of proton pump inhibitors on symptom burden and quality of life : results of a real-world randomized controlled trial in primary care patients with gastroesophageal reflux disease
- 2024
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In: Annals of Medicine. - 0785-3890 .- 1365-2060. ; 56:1
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Journal article (peer-reviewed)abstract
- Objectives: This study aimed to assess the impact of on-demand versus continuous prescribing of proton pump inhibitors (PPIs) on symptom burden and health-related quality of life in patients with gastroesophageal reflux disease (GERD) presenting to primary care.Methods: Thirty-six primary care centres across Europe enrolled adult GERD patients from electronic health records. Participants were randomised to on-demand or continuous PPI prescriptions and were followed for 8 weeks. PPI intake, symptom burden, and quality of life were compared between the two groups using mixed-effect regression analyses. Spearman’s correlation was used to assess the association between changes in PPI dose and patient-reported outcomes.Results: A total of 488 patients (median age 51 years, 58% women) completed the initial visit, with 360 attending the follow-up visit. There was no significant difference in PPI use between the continuous and on-demand prescription groups (b=.57, 95%CI:0.40-1.53), although PPI use increased in both groups (b = 1.33, 95%CI:0.65 − 2.01). Advice on prescribing strategy did not significantly affect patient-reported outcomes. Both symptom burden (Reflux Disease Questionnaire, b=-0.61, 95%CI:-0.73 − -0.49) and quality of life (12-item Short Form Survey physical score b = 3.31, 95%CI:2.17 − 4.45) improved from baseline to follow-up in both groups. Increased PPI intake correlated with reduced reflux symptoms (n = 347, ρ=-0.12, p = 0.02) and improved quality of life (n = 217, ρ = 0.16, p = 0.02).Conclusion: In real-world settings, both continuous and on-demand PPI prescriptions resulted in similar increases in PPI consumption with no difference in treatment effects. Achieving an adequate PPI dose to alleviate reflux symptom burden improves quality of life in GERD patients. EudraCT number 2014-001314-25.
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17. |
- Andreasson, Anna, et al.
(author)
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Poor sleep quality is associated with worse self-rated health in long sleep duration but not short sleep duration
- 2021
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In: Sleep Medicine. - : Elsevier BV. - 1389-9457 .- 1878-5506. ; 88, s. 262-266
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Journal article (peer-reviewed)abstract
- Unhealthy sleep duration, either short or long, is associated with worse health and central subjective dimensions of sleep and health such as fatigue. It has been argued that the link between sleep duration and health may depend on the quality of the slept hours, and on its functional impact (ie, fatigue). The present study therefore assessed whether the relationship between last night's sleep duration and general self-rated health (SRH) differs as a function of sleep quality, and secondly, whether current fatigue and sleep quality are factors linking sleep duration and SRH. The present cross-sectional dataset involved 1304 individuals (57% female, M age = 28.8, range 18-79). Participants completed surveys for general SRH, previous night's sleep duration and sleep quality, and current fatigue. Results showed the expected inverted U-shaped (ie, quadratic) relation between last night's sleep duration and SRH and a linear relation between last night's sleep quality and SRH. However, long sleep duration was only associated with poorer SRH in individuals who also reported poor sleep quality. Further, the quadratic relationship between sleep duration and SRH was partially mediated by fatigue and sleep quality. The results of this multi-study analysis suggest that SRH is particularly poor in those who slept both long and with poor quality the night before, while good sleep quality may protect those with a long sleep duration from poor SRH. Thus, last night's long sleep does not seem to be associated with poor subjective health unless it is coupled with poor sleep quality. Furthermore, fatigue and sleep quality are potential pathways linking short and long sleep duration with SRH. Different dimensions of sleep interact in their association with health, and future research will benefit from an integrative approach.
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18. |
- Andreasson, Anna, et al.
(author)
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Properties of the Sickness Questionnaire in an Australian sample with chronic medically unexplained symptoms
- 2020
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In: Brain, Behavior, & Immunity - Health. - : Elsevier BV. - 2666-3546. ; 3
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Journal article (peer-reviewed)abstract
- Sickness behavior including malaise, fatigue and increased pain sensitivity is thought to be adaptive and facilitate recovery from disease. However, it may also reduce functioning and health if symptoms persists, which is why validated instruments for its assessment are needed. We evaluated the English translation of the Sickness Questionnaire (SicknessQ) in an Australian population of 156 participants with high level of persistent musculoskeletal pain and/or gastrointestinal symptoms without an organic explanation. The SicknessQ total score had an adequate model fit and no other models were found to fit data better. The SicknessQ correlated most strongly with fatigue, stress, anxiety and depression, which explained 62% of the variance in SicknessQ, but not with physical functioning. The mean score (8.9; 95 %CI: 8.0–9.8) was in between those previously reported in a general population sample and in primary care patients. In conclusion, the evaluation of the English version of the SicknessQ in an Australian sample with significant, chronic unexplained medical symptoms supports the use of the English version of the total SicknessQ score as an overall measure of sickness behavior.
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19. |
- Andreasson, Jesper, 1977-, et al.
(author)
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Perceptions of gender equality and engaged fatherhood among young fathers: parenthood and the welfare state in Sweden and the UK
- 2023
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In: Families, Relationships and Societies. - : Policy Press. - 2046-7435 .- 2046-7443. ; 12:3, s. 323-340
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Journal article (peer-reviewed)abstract
- This article presents analyses from an international empirical study of young fatherhood in Sweden and the UK to interrogate how welfare contexts and family policies shape young fathers’ views of parenthood. Our analyses demonstrate that despite differences in constructions of young fatherhood, whereby young parenthood is problematised in UK family policy, more so than in Sweden, young fathers in both countries express an encouraging commitment to contemporary cultural imperatives for engaged fatherhood. However, differences in welfare and parental leave systems have a clear influence on the extent to which the young men in the respective countries fulfil their parental commitments and act as local agents of change in the wider social project of gender equality. We argue that while policy processes and discourses in support of young parenthood and gender equality are currently treated as disparate concerns, their articulations with one another may instead be seen as complementary and symbiotic.
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20. |
- Andréasson, Måns, 1994-
(author)
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Redefining the essential molecular aspects that drive interactions between small molecules and G-quadruplex DNA
- 2023
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Doctoral thesis (other academic/artistic)abstract
- G-Quadruplex (G4) structures are secondary nucleic acid structures located in guanine-rich regions of DNA and RNA sequences, involved in gene regulation and cellular maintenance. Efforts to target G4s in a therapeutic setting are scarce, mainly due to vague details about the binding interactions between the ligands and the G4 structure combined with the lack of emphasis on drug-like properties early in the ligand development process. Furthermore, the ability to target specific G4 structures with small drug-like molecules remains a big challenge to overcome in the field. In this thesis, extensive organic synthesis developments coupled with computational-aided design and orthogonal in vitro assays has been used in tandem to reveal in-depth knowledge about ligand-to-G4 interactions. First, a macrocyclic approach was applied to design and discover novel G4 ligands which showed that macrocycles offer a solid foundation for ligand design. Next, computational tools to optimise the macrocyclic molecular conformation were used based on the macrocycles' abilities to stack on the G4 surface. In addition, macrocyclic, and non-macrocyclic ligands that bound G4 with high potency were shown to correlate with electron-deficient electrostatic potential (ESP) maps. The frequent inclusion of cationic residues in G4 ligands and their enhancement on ligand-to-G4 binding was, thereof, ascribed to their impact on the electrostatic character of the ligands' arene-arene interactions with the G4 surface, and not through direct electrostatic ionic interactions. In addition, the dispersion energetic component in the arene-arene interactions between the G4 ligand and the G4 was discovered to be paramount for ligand-to-G4 binding. The implementation of these descriptors in practice resulted in the discovery of potent G4 binders with adequate pharmacokinetic (PK) properties, accentuating the significance of understanding the molecular interactions between ligands and G4s in rational ligand design. Finally, a G4 ligand conjugated to an oligonucleotide was demonstrated as a modular approach to achieve selective binding of a ligand to a specific G4 structure.
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21. |
- Arvidsson Rådestig, Maya, et al.
(author)
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Cerebrospinal fluid biomarkers of axonal and synaptic degeneration in a population-based sample
- 2023
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In: Alzheimers Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 15:1
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Journal article (peer-reviewed)abstract
- BackgroundNeurofilament light (NfL) and neurogranin (Ng) are promising candidate AD biomarkers, reflecting axonal and synaptic damage, respectively. Since there is a need to understand the synaptic and axonal damage in preclinical Alzheimer's disease (AD), we aimed to determine the cerebrospinal fluid (CSF) levels of NfL and Ng in cognitively unimpaired elderly from the Gothenburg H70 Birth Cohort Studies classified according to the amyloid/tau/neurodegeneration (A/T/N) system.MethodsThe sample consisted of 258 cognitively unimpaired older adults (age 70, 129 women and 129 men) from the Gothenburg Birth Cohort Studies. We compared CSF NfL and Ng concentrations in A/T/N groups using Student's T-test and ANCOVA.ResultsCSF NfL concentration was higher in the A-T-N+ group (p=0.001) and the A-T+N+ group (p=0.006) compared with A-T-N-. CSF Ng concentration was higher in the A-T-N+, A-T+N+, A+T-N+, and A+T+N+ groups (p<0.0001) compared with A-T-N-. We found no difference in NfL or Ng concentration in A+ compared with A- (disregarding T- and N- status), whereas those with N+ had higher concentrations of NfL and Ng compared with N- (p<0.0001) (disregarding A- and T- status).ConclusionsCSF NfL and Ng concentrations are increased in cognitively normal older adults with biomarker evidence of tau pathology and neurodegeneration.
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22. |
- Bonfiglio, Ferdinando, et al.
(author)
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GWAS of stool frequency provides insights into gastrointestinal motility and irritable bowel syndrome
- 2021
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In: Cell Genomics. - Cambridge, MA, United States : Elsevier. - 2666-979X. ; 1:3
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Journal article (peer-reviewed)abstract
- Gut dysmotility is associated with constipation, diarrhea, and functional gastrointestinal disorders like irritable bowel syndrome (IBS), although its molecular underpinnings are poorly characterized. We studied stool frequency (defined by the number of bowel movements per day, based on questionnaire data) as a proxy for gut motility in a GWAS meta-analysis including 167,875 individuals from UK Biobank and four smaller population-based cohorts. We identify 14 loci associated with stool frequency (p ≤ 5.0 × 10-8). Gene set and pathway analyses detected enrichment for genes involved in neurotransmitter/neuropeptide signaling and preferentially expressed in enteric motor neurons controlling peristalsis. PheWAS identified pleiotropic associations with dysmotility syndromes and the response to their pharmacological treatment. The genetic architecture of stool frequency correlates with that of IBS, and UK Biobank participants from the top 1% of stool frequency polygenic score distribution were associated with 5× higher risk of IBS with diarrhea. These findings pave the way for the identification of actionable pathological mechanisms in IBS and the dysmotility syndromes.
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23. |
- Boza-serrano, Antonio, et al.
(author)
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Galectin-3 is elevated in CSF and is associated with Aβ deposits and tau aggregates in brain tissue in Alzheimer’s disease
- 2022
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In: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 1432-0533 .- 0001-6322.
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Journal article (peer-reviewed)abstract
- Galectin-3 (Gal-3) is a beta-galactosidase binding protein involved in microglial activation in the central nervous system(CNS). We previously demonstrated the crucial deleterious role of Gal-3 in microglial activation in Alzheimer’s disease(AD). Under AD conditions, Gal-3 is primarily expressed by microglial cells clustered around Aβ plaques in both humanand mouse brain, and knocking out Gal-3 reduces AD pathology in AD-model mice. To further unravel the importance ofGal-3-associated infammation in AD, we aimed to investigate the Gal-3 infammatory response in the AD continuum. First,we measured Gal-3 levels in neocortical and hippocampal tissue from early-onset AD patients, including genetic and sporadiccases. We found that Gal-3 levels were signifcantly higher in both cortex and hippocampus in AD subjects. Immunohistochemistry revealed that Gal-3+microglial cells were associated with amyloid plaques of a larger size and more irregularshape and with neurons containing tau-inclusions. We then analyzed the levels of Gal-3 in cerebrospinal fuid (CSF) fromAD patients (n=119) compared to control individuals (n=36). CSF Gal-3 levels were elevated in AD patients comparedto controls and more strongly correlated with tau (p-Tau181 and t-tau) and synaptic markers (GAP-43 and neurogranin)than with amyloid-β. Lastly, principal component analysis (PCA) of AD biomarkers revealed that CSF Gal-3 clustered andassociated with other CSF neuroinfammatory markers, including sTREM-2, GFAP, and YKL-40. This neuroinfammatory component was more highly expressed in the CSF from amyloid-β positive (A+), CSF p-Tau181 positive (T+), andbiomarker neurodegeneration positive/negative (N+/−) (A+T+N+/−) groups compared to the A+T−N− group. Overall,Gal-3 stands out as a key pathological biomarker of AD pathology that is measurable in CSF and, therefore, a potential targetfor disease-modifying therapies involving the neuroinfammatory response.
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24. |
- Brew, Bronwyn K., et al.
(author)
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Comorbidity of atopic diseases and gastro-oesophageal reflux evidence of a shared cause
- 2022
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In: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 52:7, s. 868-877
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Journal article (peer-reviewed)abstract
- Introduction: Gastro-oesophageal reflux disease (GERD) is the most common non-allergic comorbidity in adults with asthma; however, comorbidity with other atopic diseases such as eczema and hay fever is unclear. The objective was to assess the comorbidity of GERD with asthma and atopic diseases and to investigate possible mechanisms, including genetic and/or affective factors.Methods: A co-twin control study harnessing 46 583 adult twins. Questionnaires on health status were linked to national patient and prescribed drug register data. Analyses tested associations of comorbidity between multiple definitions of atopic diseases (self-report and register-based) with GERD. Comparisons were made between unpaired, monozygotic (MZ) and dizygotic (DZ) twins to assess genetic liability. Affective traits (depression, anxiety and neuroticism) were added to models as possible explanatory factors.Results: The risk of GERD in those with asthma was OR (odds ratio) 1.52 (95% CI 1.38, 1.68), hay fever OR 1.22 (95%CI 1.12, 1.34) and eczema OR 1.23 (95%CI 1.10, 1.38). Adjusting for affective traits completely attenuated the comorbidity associations for hay fever and eczema with GERD, and partly for asthma with GERD. Co-twin control associations attenuated suggesting a shared cause for both GERD and atopic diseases. For example, all twins adjOR 1.32 (95%CI 1.00, 1.74), 0.97 (95% CI 0.76–1.23) and 1.11 (95%CI 0.85–1.45) for self-report asthma, hay fever and eczema with GERD respectively.Conclusions: GERD is a common comorbidity in adults with asthma, hay fever and/or eczema. We found evidence for shared mechanisms suggesting common underlying causes that may involve affective traits requiring further investigation.
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25. |
- Broberg, Ellen, et al.
(author)
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Mechanically ventilated patients exhibit decreased particle flow in exhaled breath as compared to normal breathing patients
- 2020
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In: Erj Open Research. - : European Respiratory Society (ERS). - 2312-0541. ; 6:1
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Journal article (peer-reviewed)abstract
- Introduction: In this cohort study, we evaluated whether the particles in exhaled air (PExA) device can be used in conjunction with mechanical ventilation during surgery. The PExA device consists of an optical particle counter and an impactor that collects particles in exhaled air. Our aim was to establish the feasibility of the PExA device in combination with mechanical ventilation (MV) during surgery and if collected particles could be analysed. Patients with and without nonsmall cell lung cancer (NSCLC) undergoing lung surgery were compared to normal breathing (NB) patients with NSCLC. Methods: A total of 32 patients were included, 17 patients with NSCLC (MV-NSCLC), nine patients without NSCLC (MV-C) and six patients with NSCLC and not intubated (NB). The PEx samples were analysed for the most common phospholipids in surfactant using liquid-chromatography-mass-spectrometry (LCMS). Results: MV-NSCLC and MV-C had significantly lower numbers of particles exhaled per minute ( particle flow rate; PFR) compared to NB. MV-NSCLC and MV-C also had a siginificantly lower amount of phospholipids in PEx when compared to NB. MV-NSCLC had a significantly lower amount of surfactant A compared to NB. Conclusion: We have established the feasibility of the PExA device. Particles could be collected and analysed. We observed lower PFR from MV compared to NB. High PFR during MV may be due to more frequent opening and closing of the airways, known to be harmful to the lung. Online use of the PExA device might be used to monitor and personalise settings for mechanical ventilation to lower the risk of lung damage.
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