| 1. |
- Dwibedi, Chinmay, 1987, et al.
(författare)
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Effect of Digital Lifestyle Management on Metabolic Control and Quality of Life in Patients with Well-Controlled Type 2 Diabetes
- 2022
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Ingår i: Diabetes Therapy. - : Springer Science and Business Media LLC. - 1869-6953 .- 1869-6961. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Introduction The lack of effective, scalable solutions for lifestyle treatment is a global clinical problem, causing severe morbidity and mortality. Digital tools could enable broad utility, but long-term metabolic outcomes and the influence on quality of life are unclear. Methods We developed a new method for lifestyle treatment that promotes self-reflection and iterative behavioural change, provided as a digital tool, and evaluated its effect on glycaemic control in patients with type 2 diabetes with HbA1c below 52 mmol/mol (n = 297). As a secondary analysis, its effect on quality of life (using SF-12) was examined in both participants with and without diabetes (total n = 1914). The tool was evaluated during a 12-week randomization period to assess the existence of effect, with a subsequent open-label follow-up to study long-term outcomes. Results Participants were randomized to wait or access the intervention tool. The mean difference in HbA1c was 2 mmol/mol (95% CI - 4 to 0; P = 0.02) after 12 weeks in participants with type 2 diabetes. The groups were then merged to enable all participants to use the tool. The mean HbA1c reduction from baseline in patients with type 2 diabetes using the tool was 2 mmol/mol compared with matched controls (95% CI - 3 to 0; P = 0.005). In users with HbA1c above 45 mmol/mol, the mean difference between the groups was 4 mmol/mol (95% CI - 7 to - 2). The improvements were sustained during the follow-up of 1 year on average. Users of the tool also had improved quality of life from baseline to 6 months, mainly observed in non-diabetic participants. Conclusion The tool does not require in-person reinforcement or increased healthcare resources, and the marginal cost is fundamentally lower than pharmacological treatment and most existing lifestyle interventions. The results therefore open a new means for self-managed lifestyle treatment with long-term metabolic efficacy that can benefit large numbers of people.
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| 2. |
- Dwibedi, Chinmay, 1987, et al.
(författare)
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Effect of self-managed lifestyle treatment on glycemic control in patients with type 2 diabetes
- 2022
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Ingår i: npj Digital Medicine. - : Nature Research. - 2398-6352. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- The lack of effective, scalable solutions for lifestyle treatment is a global clinical problem, causing severe morbidity and mortality. We developed a method for lifestyle treatment that promotes self-reflection and iterative behavioral change, provided as a digital tool, and evaluated its effect in 370 patients with type 2 diabetes (ClinicalTrials.gov identifier: NCT04691973). Users of the tool had reduced blood glucose, both compared with randomized and matched controls (involving 158 and 204 users, respectively), as well as improved systolic blood pressure, body weight and insulin resistance. The improvement was sustained during the entire follow-up (average 730 days). A pathophysiological subgroup of obese insulin-resistant individuals had a pronounced glycemic response, enabling identification of those who would benefit in particular from lifestyle treatment. Natural language processing showed that the metabolic improvement was coupled with the self-reflective element of the tool. The treatment is cost-saving because of improved risk factor control for cardiovascular complications. The findings open an avenue for self-managed lifestyle treatment with long-term metabolic efficacy that is cost-saving and can reach large numbers of people. © 2022, The Author(s).
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| 3. |
- Dwibedi, Chinmay, 1987, et al.
(författare)
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Randomized open-label trial of semaglutide and dapagliflozin in patients with type 2 diabetes of different pathophysiology
- 2024
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Ingår i: Nature Metabolism. - 2522-5812. ; 6:1, s. 50-60
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Tidskriftsartikel (refereegranskat)abstract
- The limited understanding of the heterogeneity in the treatment response to antidiabetic drugs contributes to metabolic deterioration and cardiovascular complications 1,2, stressing the need for more personalized treatment 1. Although recent attempts have been made to classify diabetes into subgroups, the utility of such stratification in predicting treatment response is unknown 3. We enrolled participants with type 2 diabetes (n = 239, 74 women and 165 men) and features of severe insulin-deficient diabetes (SIDD) or severe insulin-resistant diabetes (SIRD). Participants were randomly assigned to treatment with the glucagon-like peptide 1 receptor agonist semaglutide or the sodium–glucose cotransporter 2 inhibitor dapagliflozin for 6 months (open label). The primary endpoint was the change in glycated haemoglobin (HbA1c). Semaglutide induced a larger reduction in HbA1c levels than dapagliflozin (mean difference, 8.2 mmol mol−1; 95% confidence interval, −10.0 to −6.3 mmol mol−1), with a pronounced effect in those with SIDD. No difference in adverse events was observed between participants with SIDD and those with SIRD. Analysis of secondary endpoints showed greater reductions in fasting and postprandial glucose concentrations in response to semaglutide in participants with SIDD than in those with SIRD and a more pronounced effect on postprandial glucose by dapagliflozin in participants with SIDD than in those with SIRD. However, no significant interaction was found between drug assignment and the SIDD or SIRD subgroup. In contrast, continuous measures of body mass index, blood pressure, insulin secretion and insulin resistance were useful in identifying those likely to have the largest improvements in glycaemic control and cardiovascular risk factors by adding semaglutide or dapagliflozin. Thus, systematic evaluation of continuous pathophysiological variables can guide the prediction of the treatment response to these drugs and provide more information than stratified subgroups (NCT04451837).
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| 4. |
- Gennemark, Peter, et al.
(författare)
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An oral antisense oligonucleotide for PCSK9 inhibition
- 2021
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Ingår i: Science Translational Medicine. - : AMER ASSOC ADVANCEMENT SCIENCE. - 1946-6234 .- 1946-6242. ; 13:593
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Tidskriftsartikel (refereegranskat)abstract
- Inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) reduce low-density lipoprotein (LDL) cholesterol and are used for treatment of dyslipidemia. Current PCSK9 inhibitors are administered via subcutaneous injection. We present a highly potent, chemically modified PCSK9 antisense oligonucleotide (ASO) with potential for oral delivery. Past attempts at oral delivery using earlier-generation ASO chemistries and transient permeation enhancers provided encouraging data, suggesting that improving potency of the ASO could make oral delivery a reality. The constrained ethyl chemistry and liver targeting enabled by N-acetylgalactosamine conjugation make this ASO highly potent. A single subcutaneous dose of 90 mg reduced PCSK9 by >90% in humans with elevated LDL cholesterol and a monthly subcutaneous dose of around 25 mg is predicted to reduce PCSK9 by 80% at steady state. To investigate the feasibility of oral administration, the ASO was coformulated in a tablet with sodium caprate as permeation enhancer. Repeated oral daily dosing in dogs resulted in a bioavailability of 7% in the liver (target organ), about fivefold greater than the plasma bioavailability. Target engagement after oral administration was confirmed by intrajejunal administration of a rat-specific surrogate ASO in solution with the enhancer to rats and by plasma PCSK9 and LDL cholesterol lowering in cynomolgus monkey after tablet administration. On the basis of an assumption of 5% liver bioavailability after oral administration in humans, a daily dose of 15 mg is predicted to reduce circulating PCSK9 by 80% at steady state, supporting the development of the compound for oral administration to treat dyslipidemia.
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| 5. |
- Giordanetto, Fabrizio, et al.
(författare)
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Design of Selective sPLA2-X Inhibitor (-)-2-{2-[Carbamoyl-6-(trifluoromethoxy)-1 H-indol-1-yl]pyridine-2-yl}propanoic Acid
- 2018
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Ingår i: ACS Medicinal Chemistry Letters. - : American Chemical Society. - 1948-5875 .- 1948-5875. ; 9:7, s. 600-605
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Tidskriftsartikel (refereegranskat)abstract
- A lead generation campaign identified indole-based sPLA2-X inhibitors with a promising selectivity profile against other sPLA2 isoforms. Further optimization of sPLA2 selectivity and metabolic stability resulted in the design of (-)-17, a novel, potent, and selective sPLA2-X inhibitor with an exquisite pharmacokinetic profile characterized by high absorption and low clearance, and low toxicological risk. Compound (-)-17 was tested in an ApoE-/- murine model of atherosclerosis to evaluate the effect of reversible, pharmacological sPLA2-X inhibition on atherosclerosis development. Despite being well tolerated and achieving adequate systemic exposure of mechanistic relevance, (-)-17 did not significantly affect circulating lipid and lipoprotein biomarkers and had no effect on coronary function or histological markers of atherosclerosis.
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| 6. |
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| 7. |
- Löwhagen Hendén, Pia, et al.
(författare)
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General Anesthesia Versus Conscious Sedation for Endovascular Treatment of Acute Ischemic Stroke: The AnStroke Trial (Anesthesia During Stroke).
- 2017
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Ingår i: Stroke. - 1524-4628. ; 48:6, s. 1601-1607
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Tidskriftsartikel (refereegranskat)abstract
- Retrospective studies have found that patients receiving general anesthesia for endovascular treatment in acute ischemic stroke have worse neurological outcome compared with patients receiving conscious sedation. In this prospective randomized single-center study, we investigated the impact of anesthesia technique on neurological outcome in acute ischemic stroke patients.Ninety patients receiving endovascular treatment for acute ischemic stroke in 2013 to 2016 were included and randomized to general anesthesia or conscious sedation. Difference in neurological outcome at 3 months, measured as modified Rankin Scale score, was analyzed (primary outcome) and early neurological improvement of National Institutes of Health Stroke Scale and cerebral infarction volume. Age, sex, comorbidities, admission National Institutes of Health Stroke Scale score, intraprocedural blood pressure, blood glucose, Paco2 and Pco2 modified Thrombolysis in Cerebral Ischemia score, and relevant time intervals were recorded.In the general anesthesia group 19 of 45 patients (42.2%) and in the conscious sedation group 18 of 45 patients (40.0%) achieved a modified Rankin Scale score ≤2 (P=1.00) at 3 months, with no differences in intraoperative blood pressure decline from baseline (P=0.57); blood glucose (P=0.94); PaCO2 (P=0.68); time intervals (P=0.78); degree of successful recanalization, 91.1% versus 88.9% (P=1.00); National Institutes of Health Stroke Scale score at 24 hours 8 (3-5) versus 9 (2-15; P=0.60); infarction volume, 20 (10-100) versus 20(10-54) mL (P=0.53); and hospital mortality (13.3% in both groups; P=1.00).In endovascular treatment for acute ischemic stroke, no difference was found between general anesthesia and conscious sedation in neurological outcome 3 months after stroke.URL: https://www.clinicaltrials.gov. Unique identifier: NCT01872884.
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| 8. |
- Rosengren, Erika, et al.
(författare)
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Miniatyren : ingen småsak. En presentation av en alternativ tolkning till vapen- och redskapsminiatyrer i Uppåkra.
- 2010
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Ingår i: Uppåkrastudier 11. Från romartida skalpeller till senvikingatida urnesspännen. Nya materialstudier från Uppåkra. ACTA Archaeologica LUNDENSIA Series in 8, NO 61. - 9789189578333 ; , s. 201-212
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Bokkapitel (refereegranskat)abstract
- In recent years two new finds of miniature weapons and tools have been made on the Iron Age site of Uppåkra. Because of this it is my intention to present an alternative interpretation that might perhaps supplement earlier studies of these objects. The idea came to me while reading about the Iron Age woman being adopted into her husband 's family in connection with the wedding and the rituals linked with this practice. For example, there is an account of how the man gives his future wife a set of weapons as well as a fully equipped warhorse in some Gerrnanic tribes in the first century AD. It is my conviction that the custom was rationalized over time and the costly full-size weapons, of no practical use for the woman, were replaced with the miniatures. This would explain why they are exclusively found in women's graves, since they would constitute status symbols associated with the female significance as a wife.
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| 9. |
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| 10. |
- Rosengren, Lars, 1954, et al.
(författare)
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Värna utförarens kompetens vid intrakraniell trombektomi
- 2018
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Ingår i: Läkartidningen. - 0023-7205. ; 2018:115
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Den snabbkurs för kardiologer om 3–6 månader som föreslås av Sjögren och medförfattare utgör endast en bråkdel av den utbildningsinsats som det finns konsensus om, skriver 12 medlemmar i Nationella arbetsgruppen för stroke i en replik om trombektomi. De föreslår att ett modernt nationellt ambulanshelikoptersystem etableras.
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