| 1. |
- Thuesen, Anne Cathrine Baun, et al.
(författare)
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Identification of pathogenic GCK variants in patients with common type 2 diabetes can lead to discontinuation of pharmacological treatment
- 2023
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Ingår i: Molecular Genetics and Metabolism Reports. - : Elsevier BV. - 2214-4269. ; 35
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Tidskriftsartikel (refereegranskat)abstract
- Background: Functionally disruptive variants in the glucokinase gene (GCK) cause a form of mild non-progressive hyperglycemia, which does not require pharmacological treatment. A substantial proportion of patients with type 2 diabetes (T2D) carry GCK variants. We aimed to investigate whether carriers of rare GCK variants diagnosed with T2D have a glycemic phenotype and treatment response consistent with GCK-diabetes. Methods: Eight patients diagnosed with T2D from the Danish DD2 cohort who had previously undergone sequencing of GCK participated. Clinical examinations at baseline included an oral glucose tolerance test and continuous glucose monitoring. Carriers with a glycemic phenotype consistent with GCK-diabetes took part in a three-month treatment withdrawal. Results: Carriers of pathogenic and likely pathogenic variants had lower median fasting glucose and C-peptide levels compared to carriers of variants of uncertain significance and benign variants (median fasting glucose: 7.3 (interquartile range: 0.4) mmol/l vs. 9.5 (1.6) mmol/l, p = 0.04; median fasting C-peptide 902 (85) pmol/l vs. 1535 (295) pmol/l, p = 0.03). Four participants who discontinued metformin treatment and one diet-treated participant were reevaluated after three months. There was no deterioration of HbA1c or fasting glucose (median baseline HbA1c: 49 (3) vs. 51 (6) mmol/mol after three months, p = 0.4; median baseline fasting glucose: 7.3 (0.4) mmol/l vs. 7.0 (0.6) mmol/l after three months, p = 0.5). Participants did not consistently fulfill best practice guidelines for GCK screening nor clinical criteria for monogenic diabetes. Discussion: Carriers of pathogenic or likely pathogenic GCK variants identified by unselected screening in T2D should be reported, as they have a glycemic phenotype and treatment response consistent with GCK-diabetes. Variants of uncertain significance should be interpreted with care. Systematic genetic screening of patients with common T2D receiving routine care can lead to the identification and precise care of patients with misclassified GCK-diabetes who are not identifiable through common genetic screening criteria.
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| 2. |
- Andersen, Sören M., et al.
(författare)
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A scalable route to 5-substituted 3-isoxazolol fibrinolysis inhibitor AZD6564
- 2014
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Ingår i: Organic Process Research & Development. - : American Chemical Society (ACS). - 1083-6160 .- 1520-586X. ; 18:8, s. 952-959
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Tidskriftsartikel (refereegranskat)abstract
- A practical and chromatography-free multikilogram synthesis of a 3-isoxazolol containing antifibrinolytic agent, AZD6564, has been developed in eight steps and 7% overall yield starting from methyl 2-chloroisonicotinate. Highlights in the synthesis are a Negishi coupling and an enzymatic resolution of a racemic ester.
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| 3. |
- Axelrad, Jordan E., et al.
(författare)
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Inflammatory bowel disease and risk of small bowel cancer : a binational population-based cohort study from Denmark and Sweden
- 2021
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Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 70:2, s. 297-308
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Crohn's disease (CD) is associated with increased risk of small bowel cancer (SBC), but previous studies have been small. We aimed to examine the risk of incident SBC and death from SBC in patients with inflammatory bowel disease (IBD).DESIGN: In a binational, population-based cohort study from Sweden and Denmark of patients with IBD during 1969-2017 and matched reference individuals from the general population, we evaluated the risk of incident SBC and death from SBC. Cox regression was used to estimate adjusted hazard ratios (aHRs).RESULTS: We identified 161 896 individuals with IBD (CD: 47 370; UC: 97 515; unclassified IBD: 17 011). During follow-up, 237 cases of SBC were diagnosed in patients with IBD (CD: 24.4/100 000 person-years; UC: 5.88/100 000 person-years), compared with 640 cases in reference individuals (2.81/100 000 person-years and 3.32/100 000 person-years, respectively). This corresponded to one extra case of SBC in 385 patients with CD and one extra case in 500 patients with UC, followed up for 10 years. The aHR for incident SBC was 9.09 (95% CI 7.34 to 11.3) in CD and 1.85 (95% CI 1.43 to 2.39) in UC. Excluding the first year after an IBD diagnosis, the aHRs for incident SBC decreased to 4.96 in CD and 1.69 in UC. Among patients with CD, HRs were independently highest for recently diagnosed, childhood-onset, ileal and stricturing CD. The relative hazard of SBC-related death was increased in both patients with CD (aHR 6.59, 95% CI 4.74 to 9.15) and patients with UC (aHR 1.57; 95% CI 1.07 to 2.32).CONCLUSION: SBC and death from SBC were more common in patients with IBD, particularly among patients with CD, although absolute risks were low.
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| 4. |
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| 5. |
- Berlin, Henrik, et al.
(författare)
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A grounded theory study on Swedish 10 to 16-year-olds’ perceptions of pain in conjunction with orthodontically indicated tooth extraction
- 2023
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Ingår i: Acta Odontologica Scandinavica. - : Taylor & Francis. - 0001-6357 .- 1502-3850. ; 81:3, s. 235-240
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Children frequently experience pain and/or discomfort during dental treatment. Still, pain research in dentistry has mainly been performed on adults using quantitative methods while research on the child's perspective is scarce. This study aims to explore and describe children's experiences and/or thoughts regarding pain in conjunction with tooth extraction.Material and methods: Interviews were carried out with twelve Swedish 10-16-year-olds who had recently undergone tooth extractions due to orthodontic reasons. Interviews were transcribed verbatim and analysed according to grounded theory.Results: A core category was identified and named 'handling the unavoidable unknown'. The informants recalled experiences of pain and discomfort during extractions. However, instead of focussing on pain, they described an urge for more information about the procedure and what to expect in terms of pain and/or discomfort, during and/or after treatment. They stated that the levels of pain/discomfort were manageable, while the lack of information negatively affected their coping abilities, causing feelings of unease.Conclusions: To improve patients' ability to deal with pain in conjunction with dental extraction, the dental team should ensure better and individually tailored information about the treatment. Thus, the use of psychological techniques is a cornerstone in pain management and must be reflected in clinical guidelines.
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| 6. |
- Berlin, Henrik, et al.
(författare)
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Postoperative pain profile in 10-15-year-olds after bilateral extraction of maxillary premolars
- 2019
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Ingår i: European Archives of Paediatric Dentistry. - : Springer. - 1818-6300 .- 1996-9805. ; 20:6, s. 545-555
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To study pain perception in 10-15-year-olds, during and after uncomplicated extractions of bilateral maxillary premolars. The study investigated pain's natural course and made comparisons between the first and second extractions. METHODS: 31 Swedish children in need of orthodontic treatment were identified and consecutively enrolled. Tooth extractions followed a standardised protocol and the two teeth were extracted with at least 10 days between. The participants rated pain intensity using visual analogue scale (VAS) at 14 different time points from treatment and 7 days forward. RESULTS: The pain intensity profile followed the same pattern for all patients. Pain intensity peaked 2 h after extractions (mean VASPI 27.3, SD 20.8; median 23.0) when moderate pain intensity (VASPI >/= 40) was registered for 16 (28%) of 57 cases. After that, there was a rapid decrease in pain intensity notable already at 4 h after extractions. There were no statistically significant differences in any VASPI measurements between the first and second extractions, sexes, or different age groups. CONCLUSIONS: The majority of the participants who undergo uncomplicated bilateral extraction of maxillary premolars experience mild to moderate levels of postoperative pain during a short period of time, with no differences between the first and second extractions. Bilateral tooth extractions is a suitable model for further studies on pain management.
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| 7. |
- Bjørge, Tone, et al.
(författare)
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Reproductive history and risk of colorectal adenocarcinoma in parous women : a Nordic population-based case-control study
- 2016
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 115:11, s. 1416-1420
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Tidskriftsartikel (refereegranskat)abstract
- Background: Data are conflicting regarding the role of endogenous sex hormones in colorectal carcinogenesis. In this large population-based study, we pooled data from birth and cancer registries in four Nordic countries, to evaluate the risk of colorectal adenocarcinoma in relation to women's reproductive history. Methods: We conducted a population-based case-control study among women registered in Nordic birth registries. The study included colorectal adenocarcinoma cases diagnosed in Denmark, Finland, Norway, and Sweden during 1967-2013 and up to 10 matched controls per case, in total 22 185 cases and 220 246 controls. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were derived from conditional logistic regression models. We had limited information available on possible confounders. Results: We found no evidence for associations between colorectal adenocarcinoma and parity, age at first and last birth, and time since first and last birth. The risk estimates were also close to unity for specific cancer subsites (proximal and distal colon and rectum). As well, when the analyses were stratified on menopausal status, parity, and mother's year of birth, no indication of associations was found. Conclusions: In this large, Nordic population-based study, no evidence for associations was found between women's reproductive history and colorectal adenocarcinoma in parous women.
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| 8. |
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| 9. |
- Bröms, Gabriella, et al.
(författare)
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Paediatric infections in the first 3 years of life after maternal anti-TNF treatment during pregnancy
- 2020
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Ingår i: Alimentary Pharmacology and Therapeutics. - : John Wiley & Sons. - 0269-2813 .- 1365-2036. ; 52:5, s. 843-854
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Tidskriftsartikel (refereegranskat)abstract
- Background: Most anti‐tumour necrosis factor (anti‐TNF) agents are transferred across the placenta and may increase paediatric susceptibility to infections.Aims: To assess the risk of paediatric infections after maternal anti‐TNF treatment.Methods: Population‐based cohort study in Denmark, Finland and Sweden 2006‐2013 in which 1027 children born to women with rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis or inflammatory bowel disease, treated with anti‐TNF, and 9346 children to women with nonbiologic systemic treatment, were compared to 1 617 886 children of the general population. Children were followed for 3 years.Results: Adjusted by maternal age, parity, smoking, body mass index, country and calendar year, the incidence rate ratios with 95% confidence interval (CI) for hospital admissions for infection in the first year were 1.43 (1.23‐1.67) for anti‐TNF and 1.14 (1.07‐1.21) for non‐biologic systemic treatment, and 1.29 (1.11‐1.50) and 1.09 (1.02‐1.15), respectively, when additionally adjusting for adverse birth outcomes. There was a slight increase in antibiotic prescriptions in the second year for anti‐TNF, 1.19 (1.11‐1.29), and for non‐biologic systemic treatment, 1.10 (1.07‐1.13). There was no difference among anti‐TNF agents, treatment in the third trimester, or between mono/combination therapy with non‐biologic systemic treatment.Conclusions: Both anti‐TNF and non‐biologic systemic treatment were associated with an increased risk of paediatric infections. However, reassuringly, the increased risks were present regardless of treatment in the third trimester, with combination of treatments, and were not persistent across the first 3 years of life. Our findings may indicate a true risk, but could also be due to unadjusted confounding by disease severity and healthcare‐seeking behaviour. This may in turn shift the risk‐benefit equation towards continuation of treatment even in the third trimester.
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| 10. |
- Christensen, Steffen, et al.
(författare)
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Preadmission beta-blocker use and 30-day mortality among patients in intensive care : a cohort study
- 2011
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Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535 .- 1466-609X. ; 15:2, s. R87-
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Beta-blockers have cardioprotective, metabolic and immunomodulating effects that may be beneficial to patients in intensive care. We examined the association between preadmission beta-blocker use and 30-day mortality following intensive care. Methods: We identified 8,087 patients over age 45 admitted to one of three multidisciplinary intensive care units (ICUs) between 1999 and 2005. Data on the use of beta-blockers and medications, diagnosis, comorbidities, surgery, markers of socioeconomic status, laboratory tests upon ICU admission, and complete follow-up for mortality were obtained from medical databases. We computed probability of death within 30 days following ICU admission for beta-blocker users and non-users, and the odds ratio (OR) of death as a measure of relative risk using conditional logistic regression and also did a propensity score-matched analysis. Results: Inclusion of all 8,087 ICU patients in a logistic regression analysis yielded an adjusted OR of 0.82 (95% confidence interval (CI): 0.71 to 0.94) for beta-blocker users compared with non-users. In the propensity score-matched analysis we matched all 1,556 beta-blocker users (19.2% of the entire cohort) with 1,556 non-users; the 30-day mortality was 25.7% among beta-blocker users and 31.4% among non-users (OR 0.74 (95% CI: 0.63 to 0.87)]. The OR was 0.69 (95% CI: 0.54 to 0.88) for surgical ICU patients and 0.71 (95% CI: 0.51 to 0.98) for medical ICU patients. The OR was 0.99 (95% CI: 0.67 to 1.47) among users of non-selective beta-blockers, and 0.70 (95% CI: 0.58 to 0.83) among users of cardioselective beta-blockers. Conclusions: Preadmission beta-blocker use is associated with reduced mortality following ICU admission.
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