| 1. |
- Ruilope, LM, et al.
(author)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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In: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Journal article (peer-reviewed)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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| 2. |
- Hageman, S., et al.
(author)
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SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe
- 2021
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In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 42:25, s. 2439-2454
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Journal article (peer-reviewed)abstract
- Aims The aim of this study was to develop, validate, and illustrate an updated prediction model (SCORE2) to estimate 10-year fatal and non-fatal cardiovascular disease (CVD) risk in individuals without previous CVD or diabetes aged 40-69 years in Europe. Methods and results We derived risk prediction models using individual-participant data from 45 cohorts in 13 countries (677 684 individuals, 30 121 CVD events). We used sex-specific and competing risk-adjusted models, including age, smoking status, systolic blood pressure, and total- and HDL-cholesterol. We defined four risk regions in Europe according to country-specific CVD mortality, recalibrating models to each region using expected incidences and risk factor distributions. Region-specific incidence was estimated using CVD mortality and incidence data on 10 776 466 individuals. For external validation, we analysed data from 25 additional cohorts in 15 European countries (1 133 181 individuals, 43 492 CVD events). After applying the derived risk prediction models to external validation cohorts, C-indices ranged from 0.67 (0.65-0.68) to 0.81 (0.76-0.86). Predicted CVD risk varied several-fold across European regions. For example, the estimated 10-year CVD risk for a 50-year-old smoker, with a systolic blood pressure of 140 mmHg, total cholesterol of 5.5 mmol/L, and HDL-cholesterol of 1.3 mmol/L, ranged from 5.9% for men in low- risk countries to 14.0% for men in very high-risk countries, and from 4.2% for women in low-risk countries to 13.7% for women in very high-risk countries. Conclusion SCORE2-a new algorithm derived, calibrated, and validated to predict 10-year risk of first-onset CVD in European populations-enhances the identification of individuals at higher risk of developing CVD across Europe.
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| 3. |
- Brunner, Fabian J., et al.
(author)
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Application of non-HDL cholesterol for population-based cardiovascular risk stratification : results from the Multinational Cardiovascular Risk Consortium
- 2019
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In: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 394:10215, s. 2173-2183
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Journal article (peer-reviewed)abstract
- Background: The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment.Methods: In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol.Findings: Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7–59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0–20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men; p<0·0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1·1, 95% CI 1·0–1·3 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9, 1·6–2·2 for ≥5·7 mmol/L in women and from 1·1, 1·0–1·3 to 2·3, 2·0–2·5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced.Interpretation: Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician–patient communication about primary prevention strategies.
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| 4. |
- Lee, S. D., et al.
(author)
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IDOL regulates systemic energy balance through control of neuronal VLDLR expression
- 2019
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In: Nature Metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 1:11
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Journal article (peer-reviewed)abstract
- Liver X receptors limit cellular lipid uptake by stimulating the transcription of inducible degrader of the low-density lipoprotein receptor (IDOL), an E3 ubiquitin ligase that targets lipoprotein receptors for degradation. The function of IDOL in systemic metabolism is incompletely understood. Here we show that loss of IDOL in mice protects against the development of dietinduced obesity and metabolic dysfunction by altering food intake and thermogenesis. Unexpectedly, analysis of tissue-specific knockout mice revealed that IDOL affects energy balance, not through its actions in peripheral metabolic tissues (liver, adipose tissue, endothelium, intestine, and skeletal muscle) but by controlling lipoprotein receptor abundance in neurons. Single-cell RNA sequencing of the hypothalamus demonstrated that IDOL deletion altered gene expression linked to the control of metabolism. Finally, we identified very low-density lipoprotein receptor (VLDLR) rather than low-density lipoprotein receptor (LDLR) as the primary mediator of the effects of IDOL on energy balance. These data identify a role for the neuronal IDOL-VLDLR pathway in metabolic homoeostasis and diet-induced obesity.
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| 5. |
- Bunck, M. C., et al.
(author)
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One-year treatment with exenatide improves beta-cell function, compared with insulin glargine, in metformin-treated type 2 diabetic patients: a randomized, controlled trial
- 2009
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In: Diabetes Care. - 1935-5548. ; 32:5, s. 762-8
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Traditional blood glucose-lowering agents do not sustain adequate glycemic control in most type 2 diabetic patients. Preclinical studies with exenatide have suggested sustained improvements in beta-cell function. We investigated the effects of 52 weeks of treatment with exenatide or insulin glargine followed by an off-drug period on hyperglycemic clamp-derived measures of beta-cell function, glycemic control, and body weight. RESEARCH DESIGN AND METHODS: Sixty-nine metformin-treated patients with type 2 diabetes were randomly assigned to exenatide (n = 36) or insulin glargine (n = 33). beta-Cell function was measured during an arginine-stimulated hyperglycemic clamp at week 0, at week 52, and after a 4-week off-drug period. Additional end points included effects on glycemic control, body weight, and safety. RESULTS: Treatment-induced change in combined glucose- and arginine-stimulated C-peptide secretion was 2.46-fold (95% CI 2.09-2.90, P < 0.0001) greater after a 52-week exenatide treatment compared with insulin glargine treatment. Both exenatide and insulin glargine reduced A1C similarly: -0.8 +/- 0.1 and -0.7 +/- 0.2%, respectively (P = 0.55). Exenatide reduced body weight compared with insulin glargine (difference -4.6 kg, P < 0.0001). beta-Cell function measures returned to pretreatment values in both groups after a 4-week off-drug period. A1C and body weight rose to pretreatment values 12 weeks after discontinuation of either exenatide or insulin glargine therapy. CONCLUSIONS: Exenatide significantly improves beta-cell function during 1 year of treatment compared with titrated insulin glargine. After cessation of both exenatide and insulin glargine therapy, beta-cell function and glycemic control returned to pretreatment values, suggesting that ongoing treatment is necessary to maintain the beneficial effects of either therapy.
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| 6. |
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| 7. |
- Jain, Ruchi, et al.
(author)
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Liver nucleotide biosynthesis is linked to protection from vascular complications in individuals with long-term type 1 diabetes
- 2020
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)abstract
- Identification of biomarkers associated with protection from developing diabetic complications is a prerequisite for an effective prevention and treatment. The aim of the present study was to identify clinical and plasma metabolite markers associated with freedom from vascular complications in people with very long duration of type 1 diabetes (T1D). Individuals with T1D, who despite having longer than 30 years of diabetes duration never developed major macro- or microvascular complications (non-progressors; NP) were compared with those who developed vascular complications within 25 years from diabetes onset (rapid progressors; RP) in the Scandinavian PROLONG (n = 385) and DIALONG (n = 71) cohorts. The DIALONG study also included 75 healthy controls. Plasma metabolites were measured using gas and/or liquid chromatography coupled to mass spectrometry. Lower hepatic fatty liver indices were significant common feature characterized NPs in both studies. Higher insulin sensitivity and residual beta-cell function (C-peptide) were also associated with NPs in PROLONG. Protection from diabetic complications was associated with lower levels of the glycolytic metabolite pyruvate and APOCIII in PROLONG, and with lower levels of thiamine monophosphate and erythritol, a cofactor and intermediate product in the pentose phosphate pathway as well as higher phenylalanine, glycine and serine in DIALONG. Furthermore, T1D individuals showed elevated levels of picolinic acid as compared to the healthy individuals. The present findings suggest a potential beneficial shunting of glycolytic substrates towards the pentose phosphate and one carbon metabolism pathways to promote nucleotide biosynthesis in the liver. These processes might be linked to higher insulin sensitivity and lower liver fat content, and might represent a mechanism for protection from vascular complications in individuals with long-term T1D.
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| 8. |
- Axelsson, Annika, et al.
(author)
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Sox5 regulates beta-cell phenotype and is reduced in type 2 diabetes
- 2017
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Journal article (peer-reviewed)abstract
- Type 2 diabetes (T2D) is characterized by insulin resistance and impaired insulin secretion, but the mechanisms underlying insulin secretion failure are not completely understood. Here, we show that a set of co-expressed genes, which is enriched for genes with islet-selective open chromatin, is associated with T2D. These genes are perturbed in T2D and have a similar expression pattern to that of dedifferentiated islets. We identify Sox5 as a regulator of the module. Sox5 knockdown induces gene expression changes similar to those observed in T2D and diabetic animals and has profound effects on insulin secretion, including reduced depolarization-evoked Ca 2+-influx and β-cell exocytosis. SOX5 overexpression reverses the expression perturbations observed in a mouse model of T2D, increases the expression of key β-cell genes and improves glucose-stimulated insulin secretion in human islets from donors with T2D. We suggest that human islets in T2D display changes reminiscent of dedifferentiation and highlight SOX5 as a regulator of β-cell phenotype and function.
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| 9. |
- Bunck, M. C., et al.
(author)
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Exenatide treatment did not affect bone mineral density despite body weight reduction in patients with type 2 diabetes
- 2011
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In: Diabetes, obesity & metabolism. - : Wiley. - 1463-1326 .- 1462-8902. ; 13:4, s. 374-377
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Journal article (peer-reviewed)abstract
- Preclinical studies suggest that incretin-based therapies may be beneficial for the bone; however, clinical data are largely lacking. We assessed whether the differential effects of these therapies on body weight differed with respect to their effect on bone mineral density (BMD) and markers of calcium homeostasis in patients with type 2 diabetes (T2D). Sixty-nine metformin-treated patients with T2D were randomized to exenatide twice daily (n = 36) or insulin glargine once daily (n = 33). Total body BMD, measured by dual-energy X-ray absorptiometry, and serum markers of calcium homeostasis were assessed before and after 44-week treatment. Exenatide or insulin glargine treatment decreased body weight by 6%. Endpoint BMD was similar in both groups after 44-week therapy (LSmean +/- s.e.m. between-group difference -0.002 +/- 0.007 g/cm(2) ; p = 0.782). Fasting serum alkaline phosphatase, calcium and phosphate remained unaffected. Forty-four-week treatment with exenatide or insulin glargine had no adverse effects on bone density in patients with T2D, despite differential effects on body weight.
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| 10. |
- He, W., et al.
(author)
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CYP2D6 genotype predicts tamoxifen discontinuation and drug response : a secondary analysis of the KARISMA trial
- 2021
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In: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 32:10, s. 1286-1293
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Journal article (peer-reviewed)abstract
- Background: Guidelines regarding whether tamoxifen should be prescribed based on women's cytochrome P450 2D6 (CYP2D6) genotypes are conflicting and have caused confusion. This study aims to investigate if CYP2D6 metabolizer status isa associated with tamoxifen-related endocrine symptoms, tamoxifen discontinuation, and mammographic density change. Patients and methods: We used data from 1440 healthy women who participated the KARISMA dose determination trial. Endocrine symptoms were measured using a modified Functional Assessment of Cancer Therapy – Endocrine Symptoms (FACT-ES) questionnaire. Change in mammographic density was measured and used as a proxy for tamoxifen response. Participants were genotyped and categorized as poor, intermediate, normal, or ultrarapid CYP2D6 metabolizers. Results: The median endoxifen level per mg oral tamoxifen among poor, intermediate, normal and ultrarapid CYP2D6 metabolizers were 0.18 ng/ml, 0.38 ng/ml, 0.56 ng/ml and 0.67 ng/ml, respectively. Ultrarapid CYP2D6 metabolizers were more likely than other groups to report a clinically relevant change in cold sweats, hot flash, mood swings, being irritable, as well as the overall modified FACT-ES score, after taking tamoxifen. The 6-month tamoxifen discontinuation rates among poor, intermediate, normal, and ultrarapid CYP2D6 metabolizers were 25.7%, 23.6%, 28.6%, and 44.4%, respectively. Among those who continued and finished the 6-month tamoxifen intervention, the mean change in dense area among poor, intermediate, normal, and ultrarapid CYP2D6 metabolizers were −0.8 cm2, −4.5 cm2, −4.1 cm2, and −8.0 cm2 respectively. Conclusions: Poor CYP2D6 metabolizers are likely to experience an impaired response to tamoxifen, measured through mammographic density reduction. In contrast, ultrarapid CYP2D6 metabolizers are at risk for exaggerated response with pronounced adverse effects that may lead to treatment discontinuation.
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| 11. |
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| 12. |
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| 13. |
- Bunck, M. C., et al.
(author)
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Exenatide affected circulating cardiovascular risk biomarkers independently of changes in body composition
- 2010
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In: Diabetes Care. - 0149-5992. ; 33:8, s. 1734-1737
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Journal article (peer-reviewed)abstract
- OBJECTIVE To study the effect of exenatide on body composition and circulating cardiovascular risk biomarkers. RESEARCH DESIGN AND METHODS Metformin-treated patients with type 2 diabetes (N = 69) were randomized to exenatide or insulin glargine and treated for 1 year. Body composition was evaluated by dual-energy X-ray absorptiometry. Additionally, body weight, waist circumference, and cardiovascular biomarkers were measured. RESULTS Treatment with exenatide for 1 year significantly reduced body weight, waist circumference, and total body and trunkal fat mass by 6, 5, 11, and 13%, respectively. In addition, exenatide increased total adiponectin by 12% and reduced high-sensitivity C-reactive protein by 61%. Insulin glargine significantly reduced endothelin-1 by 7%. These changes were statistically independent of the change in total body fat mass and body weight. CONCLUSIONS Exenatide treatment for 1 year reduced body fat mass and improved the profile of circulating biomarkers of cardiovascular risk. No significant changes were seen with insulin glargine except a trend for reduced endothelin-1 levels.
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| 14. |
- Efe, C., et al.
(author)
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Validation of Risk Scoring Systems in Ursodeoxycholic Acid-Treated Patients With Primary Biliary Cholangitis
- 2019
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In: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270 .- 1572-0241. ; 114:7, s. 1101-1108
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Risk stratification based on biochemical variables is a useful tool for monitoring ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC). Several UDCA response criteria and scoring systems have been proposed for risk prediction in PBC, but these have not been validated in large external cohorts. METHODS: We performed a study on data of 1746 UDCA-treated patients with PBC from 25 centers in Europe, United States, and Canada. The prognostic performance of the risk scoring systems (GLOBE and UK-PBC) and the UDCA response criteria (Barcelona, Paris I, Paris II, Rotterdam, and Toronto) were evaluated. We regarded cirrhosis-related complications (ascites, variceal bleeding, and/or hepatic encephalopathy) as clinical end points. RESULTS: A total of 171 patients reached a clinical end point during a median 7 years (range 1-16 years) of follow-up. The 5-, 10- and 15-year adverse outcome-free survivals were 95%, 85%, and 77%. The GLOBE and UK-PBC scores predicted cirrhosis-related complications better than the UDCA response criteria. The hazard ratio (HR) for a 1 standard deviation increase was HR 5.05 (95% confidence interval (CI): 4.43-5.74, P < 0.001) for the GLOBE score and HR 3.39 (95% CI: 3.10-3.72, P < 0.001) for the UK-PBC score. Overall, the GLOBE and UK-PBC risk scores showed similar and excellent prognostic performance (C-statistic, 0.93; 95% CI: 0.91%-95% vs 0.94; 95% CI: 0.91%-0.96%). DISCUSSION: In our international, multicenter PBC cohort, the GLOBE and UK-PBC risk scoring systems were good predictors of future cirrhosis-related complications.
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| 15. |
- Eliasson, H., et al.
(author)
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Modeling of high power impulse magnetron sputtering discharges with graphite target
- 2021
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In: Plasma sources science & technology. - : IOP Publishing Ltd. - 0963-0252 .- 1361-6595. ; 30:11
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Journal article (peer-reviewed)abstract
- The ionization region model (IRM) is applied to model a high power impulse magnetron sputtering discharge in argon with a graphite target. Using the IRM, the temporal variation of the various species and the average electron energy, as well as internal parameters such as the ionization probability, back-attraction probability, and the ionized flux fraction of the sputtered species, is determined. It is found that thedischarge develops into working gas recycling and most of the discharge current at the cathode target surface is composed of Ar+ ions, which constitute over 90% of the discharge current, while the contribution of the C+ ions is always small (<5%), even for peak current densities close to 3 A cm(-2). For the target species, the time-averaged ionization probability is low, or 13-27%, the ion back-attraction probability during the pulse is high (>92%), and the ionized flux fraction is about 2%. It is concluded that in the operation range studied here it is a challenge to ionize carbon atoms, that are sputtered off of a graphite target in a magnetron sputtering discharge, when depositing amorphous carbon films.
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| 16. |
- Elofsson, Ulla, et al.
(author)
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Adsorption studies of interaction between water-extractable nonstarch polysaccharides and prolamins in cereals
- 2000
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In: Cereal Chemistry. - 0009-0352. ; 77:5, s. 679-684
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Journal article (peer-reviewed)abstract
- Adsorption of cereal storage protein and nonstarch polysaccharides onto methylated silica surfaces, as measured by ellipsometry, was used to study possible interactions between those components. All fractions, rye secalin, wheat gliadin, rye arabinoxylan, and wheat arabinogalactan peptide, were surface- oxylan and wheat arabinogalactan peptide on top of gliadin and secalin, respectively, indicated that an interaction occurred. As ionic strength and pH influenced both the adsorption and the interaction of the components studied, these phenomena are believed to be of electrostatic nature.
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| 17. |
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| 18. |
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| 19. |
- Muskiet, M H A, et al.
(author)
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Exenatide twice-daily does not affect renal function or albuminuria compared to titrated insulin glargine in patients with type 2 diabetes mellitus: A post-hoc analysis of a 52-week randomised trial.
- 2019
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In: Diabetes research and clinical practice. - : Elsevier BV. - 1872-8227 .- 0168-8227. ; 153, s. 14-22
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Journal article (peer-reviewed)abstract
- To compare the effects of long-term treatment with the GLP-1RA exenatide twice-daily versus titrated insulin glargine (iGlar) on renal function and albuminuria in type 2 diabetes (T2DM) patients.We post-hoc evaluated renal outcome-data of 54 overweight T2DM patients (mean ±SD age 60±8years, HbA1c 7.5±0.9%, eGFR 86±16mL/min/1.73m2, median [IQR] urinary albumin-to-creatinine-ratio (UACR) 0.75 [0.44-1.29]mg/mmol) randomised to exenatide 10µg twice-daily or titrated iGlar on-top-of metformin for 52-weeks. Renal efficacy endpoints were change in creatinine clearance (CrCl) and albuminuria (urinary albumin-excretion [UAE] and UACR) based on 24-h urines, collected at baseline and Week-52. eGFR and exploratory endpoints were collected throughout the intervention-period, and after a 4-week wash-out.HbA1c-reductions were similar with exenatide (mean±SEM -0.80±0.10%) and iGlar (-0.79±0.14%; treatment-difference 0.02%; 95% CI -0.31 to 0.42%). Change from baseline to Week-52 in CrCl, UAE or UACR did not statistically differ; only iGlar reduced albuminuria (P<0.05; within-group). eGFR decreased from baseline to Week-4 with exenatide (-3.9±2.1mL/min/1.73m2; P=0.069) and iGlar (-2.7±1.2mL/min/1.73m2; P=0.034), without treatment-differences in ensuing trajectory. Exenatide versus iGlar reduced bodyweight (-5.4kg; 2.9-7.9; P<0.001), but did not affect blood pressure, lipids or plasma uric acid.Among T2DM patients without overt nephropathy, one-year treatment with exenatide twice-daily does not affect renal function-decline or onset/progression of albuminuria compared to titrated iGlar.ClinicalTrials.gov ID: NCT00097500.
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| 20. |
- Novak, Iona, et al.
(author)
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Early, Accurate Diagnosis and Early Intervention in Cerebral Palsy : Advances in Diagnosis and Treatment
- 2017
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In: JAMA pediatrics. - : American Medical Association. - 2168-6203 .- 2168-6211. ; 171:9, s. 897-907
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Research review (peer-reviewed)abstract
- Importance: Cerebral palsy describes the most common physical disability in childhood and occurs in 1 in 500 live births. Historically, the diagnosis has been made between age 12 and 24 months but now can be made before 6 months' corrected age.Objectives: To systematically review best available evidence for early, accurate diagnosis of cerebral palsy and to summarize best available evidence about cerebral palsy-specific early intervention that should follow early diagnosis to optimize neuroplasticity and function.Evidence Review: This study systematically searched the literature about early diagnosis of cerebral palsy in MEDLINE (1956-2016), EMBASE (1980-2016), CINAHL (1983-2016), and the Cochrane Library (1988-2016) and by hand searching. Search terms included cerebral palsy, diagnosis, detection, prediction, identification, predictive validity, accuracy, sensitivity, and specificity. The study included systematic reviews with or without meta-analyses, criteria of diagnostic accuracy, and evidence-based clinical guidelines. Findings are reported according to the PRISMA statement, and recommendations are reported according to the Appraisal of Guidelines, Research and Evaluation (AGREE) II instrument.Findings: Six systematic reviews and 2 evidence-based clinical guidelines met inclusion criteria. All included articles had high methodological Quality Assessment of Diagnostic Accuracy Studies (QUADAS) ratings. In infants, clinical signs and symptoms of cerebral palsy emerge and evolve before age 2 years; therefore, a combination of standardized tools should be used to predict risk in conjunction with clinical history. Before 5 months' corrected age, the most predictive tools for detecting risk are term-age magnetic resonance imaging (86%-89% sensitivity), the Prechtl Qualitative Assessment of General Movements (98% sensitivity), and the Hammersmith Infant Neurological Examination (90% sensitivity). After 5 months' corrected age, the most predictive tools for detecting risk are magnetic resonance imaging (86%-89% sensitivity) (where safe and feasible), the Hammersmith Infant Neurological Examination (90% sensitivity), and the Developmental Assessment of Young Children (83% C index). Topography and severity of cerebral palsy are more difficult to ascertain in infancy, and magnetic resonance imaging and the Hammersmith Infant Neurological Examination may be helpful in assisting clinical decisions. In high-income countries, 2 in 3 individuals with cerebral palsy will walk, 3 in 4 will talk, and 1 in 2 will have normal intelligence.Conclusions and Relevance: Early diagnosis begins with a medical history and involves using neuroimaging, standardized neurological, and standardized motor assessments that indicate congruent abnormal findings indicative of cerebral palsy. Clinicians should understand the importance of prompt referral to diagnostic-specific early intervention to optimize infant motor and cognitive plasticity, prevent secondary complications, and enhance caregiver well-being.
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| 21. |
- Nystrom, T., et al.
(author)
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PCI Versus CABG in Patients With Type 1 Diabetes and Multivessel Disease
- 2017
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In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 70:12, s. 1441-1451
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Journal article (peer-reviewed)abstract
- BACKGROUND It is unknown if coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) may offer a survival benefit in patients with type 1 diabetes (T1D) in need of multivessel revascularization. OBJECTIVES This study sought to determine if patients with T1D and multivessel disease may benefit from CABG compared with PCI. METHODS In an observational cohort study, the authors included all patients with T1D who underwent a first multivessel revascularization in Sweden from 1995 to 2013. The authors used the SWEDEHEART (Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies) register, the Swedish National Diabetes Register, and the Swedish National Patient Register to retrieve information about patient characteristics and outcomes. They estimated hazard ratios (HRs) adjusted for confounders with 95% confidence intervals (CIs) for all-cause and coronary heart disease mortality, myocardial infarction, repeat revascularization, stroke, and heart failure using inverse probability of treatment weighting based on propensity scores. RESULTS In total, 683 patients whounderwent CABGand 1,863 patientswho underwent PCI were included. During a mean follow-up of 10.6 years, 53% of patients in the CABG group and 45% in the PCI group died. PCI, compared with CABG, was associated with a similar risk of all-cause mortality (HR: 1.14; 95% CI: 0.99 to 1.32), but higher risks of death from coronary heart disease (HR: 1.45; 95% CI: 1.21 to 1.74), myocardial infarction (HR: 1.47; 95% CI: 1.23 to 1.78), and repeat revascularization (HR: 5.64; 95% CI: 4.67 to 6.82). No differences in risks of stroke or heart failure were found. CONCLUSIONS Notwithstanding the inclusion of patients with T1D who might not have been able to undergo CABG in the PCI group we found that PCI, compared with CABG, was associated with higher rates and risks of coronary heart disease mortality, myocardial infarction, and repeat revascularizations. Our findings indicate that CABG may be the preferred strategy in patients with T1D in need of multivessel revascularization. (J Am Coll Cardiol 2017; 70: 1441-51) (C) 2017 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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| 22. |
- Salomonsson, S., et al.
(author)
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A Population-based Investigation of the Autoantibody Profile in Mothers of Children with Atrioventricular Block
- 2011
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In: Scandinavian Journal of Immunology. - Oxford : Blackwell Publishing. - 0300-9475 .- 1365-3083. ; 74:5, s. 511-517
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Journal article (peer-reviewed)abstract
- The objective of the study was to investigate the antigen specificity and occurrence of individual autoantibodies in mothers of children diagnosed with atrioventricular (AV) block in a nation-wide setting. Patients with AV block detected before 15 years of age were identified using national quality registries as well as a network of pediatric and adult cardiologists and rheumatologists at the six university hospitals in Sweden. Patients with gross heart malformations, surgically or infectiously induced blocks were excluded. Blood samples were obtained from the mothers and maternal autoantibody profile, including the occurrence of antibodies against Ro52, Ro60, La, SmB, SmD, RNP-70k, RNP-A, RNP-C, CENP-C, Scl-70, Jo-1, ribosomal RNP and histones was investigated in 193 mothers of children with AV block by immunoblotting and ELISA. Autoantibody reactivity was detected in 48% (93/193) of the mothers of children with AV block. In autoantibody-positive mothers, the vast majority, 95% (88/93), had antibodies against Ro52, while 63% (59/93) had autoantibodies to Ro60 and 58% (54/93) had autoantibodies to La. In addition, 13% (12/93) of the autoantibody-positive mothers had antibodies to other investigated antigens besides Ro52, Ro60 and La, and of these anti-histone antibodies were most commonly represented, detected in 8% (7/93) of the mothers. In conclusion, this Swedish population-based study confirms that maternal autoantibodies may associate with heart block in the child. Further, our data demonstrate a dominant role of Ro52 antibodies in association with AV block.
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| 23. |
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| 24. |
- Taimour, S., et al.
(author)
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Survival, cardiovascular morbidity, and reinterventions after elective endovascular aortic aneurysm repair in patients with and without diabetes: A nationwide propensity-adjusted analysis
- 2019
-
In: Vascular Medicine. - : SAGE Publications. - 1358-863X .- 1477-0377. ; 24:6, s. 539-546
-
Journal article (peer-reviewed)abstract
- Epidemiological data indicate decreased risk for development and growth of abdominal aortic aneurysm (AAA) among patients with diabetes mellitus (DM). On the other hand, DM adds to increased cardiovascular (CV) morbidity and mortality. In a nationwide observational cohort study of patients registered in the Swedish Vascular Register and the Swedish National Diabetes Register, we evaluated potential effects of DM on total mortality, CV morbidity, and the need for reintervention after elective endovascular aneurysm repair (EVAR) for AAA. We compared 748 patients with and 2630 without DM with propensity score-adjusted analysis, during a median 4.22 years of follow-up for patients with DM, and 4.05 years for those without. In adjusted analysis, diabetic patients showed higher rates of acute myocardial infarction (AMI) during follow-up (relative risk (RR) 1.44, 95% CI 1.06-1.95; p = 0.02), but lower need for reintervention (RR 0.12, CI 0.02-0.91; p = 0.04). There were no differences in total (RR 0.88, CI 0.74-1.05; p = 0.15) or CV (RR 1.58, CI 0.87-2.86; p = 0.13) mortality, or stroke (RR 0.95, CI 0.68-1.32; p = 0.75) during follow-up. In conclusion, patients with DM had higher rates of AMI and lower need for reintervention after elective EVAR than those without DM, whereas neither total nor CV mortality differed between groups. The putative protective effects of DM towards further AAA enlargement and late sac rupture may help explain the lower need for reintervention and absence of excess mortality.
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| 25. |
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| 26. |
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| 27. |
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| 28. |
- Adamsson Eryd, Samuel, et al.
(author)
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Risk of future microvascular and macrovascular disease in people with Type 1 diabetes of very long duration : A national study with 10-year follow-up
- 2017
-
In: Diabetic Medicine. - : Wiley. - 0742-3071. ; 34:3, s. 411-418
-
Journal article (peer-reviewed)abstract
- Aims: To describe factors associated with prevalence or absence of microvascular and macrovascular complications in people with Type 1 diabetes of very long duration and to investigate the risk factors associated with the incidence of such complications. Methods: We included individuals with Type 1 diabetes who had been entered in the Swedish National Diabetes Register between 2002 and 2004 (n = 18 450). First, risk factor distribution in people with diabetes duration of ≥ 50 years was compared between people with and without complications. Second, the incidence of complications during a 10-year follow-up period was studied in all individuals who had no complications at baseline. Results: Among people with a diabetes duration of ≥ 50 years (n = 1023), 453 (44%) had macrovascular disease, 534 (52%) had microvascular disease and 319 (31%) did not have either of the diagnoses. Factors that differed significantly between people with and without macrovascular disease were gender, age, HbA1c, BMI, LDL cholesterol, HDL cholesterol, triglycerides, systolic blood pressure, albuminuria, antihypertensive medication and lipid-lowering medication. The same factors differed significantly between people with and without microvascular disease, with the exception of gender and HDL cholesterol. During the follow-up period, 6.1% of the study cohort were diagnosed with macrovascular disease and 19.6% with microvascular disease. Incidence of macrovascular disease was significantly associated with HbA1c levels. Hazard ratios decreased with longer diabetes duration. Conclusions: People with Type 1 diabetes who have survived ≥ 50 years without complications are significantly younger, and have significantly lower HbA1c levels, BMI and triglyceride levels than survivors with complications. HbA1c level is a predictor of macrovascular disease, independently of diabetes duration.
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| 29. |
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| 30. |
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| 31. |
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| 32. |
- Alonso, Lorena, et al.
(author)
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TIGER : The gene expression regulatory variation landscape of human pancreatic islets
- 2021
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In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 37:2
-
Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWASs) identified hundreds of signals associated with type 2 diabetes (T2D). To gain insight into their underlying molecular mechanisms, we have created the translational human pancreatic islet genotype tissue-expression resource (TIGER), aggregating >500 human islet genomic datasets from five cohorts in the Horizon 2020 consortium T2DSystems. We impute genotypes using four reference panels and meta-analyze cohorts to improve the coverage of expression quantitative trait loci (eQTL) and develop a method to combine allele-specific expression across samples (cASE). We identify >1 million islet eQTLs, 53 of which colocalize with T2D signals. Among them, a low-frequency allele that reduces T2D risk by half increases CCND2 expression. We identify eight cASE colocalizations, among which we found a T2D-associated SLC30A8 variant. We make all data available through the TIGER portal (http://tiger.bsc.es), which represents a comprehensive human islet genomic data resource to elucidate how genetic variation affects islet function and translates into therapeutic insight and precision medicine for T2D.
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| 33. |
- Axelsson, K. F., et al.
(author)
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Fracture Risk After Gastric Bypass Surgery : A Retrospective Cohort Study
- 2018
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In: Osteoporosis International. - : Springer London. - 0937-941X .- 1433-2965. ; 29:Suppl. 1, s. S491-S491
-
Journal article (other academic/artistic)abstract
- Objectives: Gastric bypass surgery constitutes the most common and effective bariatric surgery to treat obesity. Gastric bypass leads to bone oss but fracture risk following surgery has been insufficiently studied. Our objective was to investigate if gastric bypass surgery in obese patients, with and without diabetes, was associated with fracture risk, and if the fracture risk was associated with post-surgery weight loss or insufficient calcium and vitamin D supplementation.Methods: Using large databases, 38 971 obese patients undergoing gastric bypass were identified, 7758 with diabetes and 31 213 without. Through multivariable 1:1 propensity score matching, well-balanced controls were identified. The risk of fracture and fall injury was investigated using Cox proportional hazards and flexible parameter models. Fracture risk according to weight loss and degree of calcium and vitamin D supplementation one year post-surgery was investigated.Results: 77 942 patients had a median and total follow-up time of 3.1 (IQR 1.7-4.6) and 251 310 person-years, respectively. Gastric bypass was associated with increased risk of any fracture, in patients with diabetes and without diabetes using a multivariable Cox model (HR 1.26, 95%CI 1.05-1.53 and HR 1.32, 95%CI 1.18-1.47, respectively). The risk of fall injury without fracture was also increased after gastric bypass, both in patients with (HR 1.26 95%CI 1.04-1.52) and without diabetes (HR 1.24 95%CI 1.12-1.38). Weight loss or degree of calcium and vitamin D supplementation after gastric bypass were not associated with fracture risk.Conclusions: Gastric bypass was associated with an increased risk of fracture and fall injury. Weight loss or calcium and vitamin D supplementation following surgery were not associated with fracture risk. These findings indicate that gastric bypass increases fracture risk, which could at least partly be due to increased susceptibility to falls.
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| 34. |
- Balintescu, A., et al.
(author)
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Glycaemic control and sepsis risk in adults with type 1 diabetes
- 2023
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In: Diabetes Obesity & Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 25:7, s. 1942-1949
-
Journal article (peer-reviewed)abstract
- Aims: To study the association between glycated haemoglobin (HbA1c) and sepsis in adults with type 1 diabetes, and to explore the relationship between HbA1c and mortality among individuals who developed sepsis.Materials and Methods: We included 33 549 adult individuals with type 1 diabetes recorded in the Swedish National Diabetes Register between January 2005 and December 2015. We used multivariable Cox regression and restricted cubic spline analyses to study the relationship between HbA1c values and sepsis occurrence and association between HbA1c and mortality among those with sepsis.Results: In total, 713 (2.1%) individuals developed sepsis during the study period. Com-pared with the HbA1c reference interval of 48-52 mmol/mol (6.5-6.9%), the adjusted hazard ratio for sepsis was: 2.50 [95% confidence interval (CI) 1.18-5.29] for HbA1c <43 mmol/mol; 1.88 (95% CI 0.96-3.67) for HbA1c 43-47 mmol/mol; 1.78 (95% CI 1.09-2.89) for HbA1c 53-62 mmol/mol; 1.86 (95% CI 1.14-3.03) for HbA1c 63-72 mmol/mol; 3.15 (95% CI 1.91-5.19) for HbA1c 73-82 mmol/mol; and 4.26 (95% CI 2.53-7.16) for HbA1c >82 mmol/mol. On multivariable restricted cubic spline analy-sis, we found a J-shaped association between HbA1c and sepsis risk, with the lowest risk observed at HbA1c of approximately 53 mmol/mol. We found no association between HbA1c and mortality among those individuals who developed sepsis.Conclusions: In our nationwide observational study of adult individuals with type 1 diabetes we found a J-shaped relationship between HbA1c and risk of sepsis, with the lowest risk at HbA1c levels about 53 mmol/mol (7.0%). HbA1c was not associ-ated with mortality in individuals affected by sepsis.
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| 35. |
- Balintescu, A., et al.
(author)
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Glycemic Control and Risk of Sepsis and Subsequent Mortality in Type 2 Diabetes
- 2022
-
In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 45:1, s. 127-133
-
Journal article (peer-reviewed)abstract
- OBJECTIVE To investigate the nature of the relationship between HbA1c and sepsis among individuals with type 2 diabetes, and to assess the association between sepsis and all-cause mortality in such patients. RESEARCH DESIGN AND METHODS We included 502,871 individuals with type 2 diabetes recorded in the Swedish National Diabetes Register and used multivariable Cox regression and restricted cubic spline analyses to assess the association between time-updated HbA1c values and sepsis occurrence between 1 January 2005 and 31 December 2015. The association between sepsis and death was examined using multivariable Cox regression analysis. RESULTS Overall, 14,534 (2.9%) patients developed sepsis during the study period. On multivariable Cox regression analysis, compared with an HbA1c of 48–52 mmol/mol (6.5–6.9%), the adjusted hazard ratio for sepsis was 1.15 (95% CI 1.07–1.24) for HbA1c <43 mmol/mol (6.1%), 0.93 (0.87–0.99) for HbA1c 53–62 mmol/mol (7.0–7.8%), 1.05 (0.97–1.13) for HbA1c 63–72 mmol/mol (7.9–8.7%), 1.14 (1.04–1.25) for HbA1c 73–82 mmol/mol (8.8–9.7%), and 1.52 (1.37–1.68) for HbA1c >82 mmol/mol (9.7%). In the cubic spline model, a reduction of the adjusted risk was observed within the lower HbA1c range until 53 mmol/mol (7.0%), with a hazard ratio of 0.78 (0.73–0.82) per SD; it increased thereafter (P for nonlinearity <0.001). As compared with patients without sepsis, the adjusted hazard ratio for death among patients with sepsis was 4.16 (4.03–4.30). CONCLUSIONS In a nationwide cohort of individuals with type 2 diabetes, we found a U-shaped association between HbA1c and sepsis and a fourfold increased risk of death among those developing sepsis. © 2021 by the American Diabetes Association.
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| 36. |
- Barg, Sebastian, et al.
(author)
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The stimulatory action of tolbutamide on Ca2+-dependent exocytosis in pancreatic beta cells is mediated by a 65-kDa mdr-like P-glycoprotein
- 1999
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In: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 96:10, s. 5539-5544
-
Journal article (peer-reviewed)abstract
- Intracellular application of the sulfonylurea tolbutamide during whole-cell patch-clamp recordings stimulated exocytosis >5-fold when applied at a cytoplasmic Ca2+ concentration of 0.17 microM. This effect was not detectable in the complete absence of cytoplasmic Ca2+ and when exocytosis was elicited by guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS). The stimulatory action could be antagonized by the sulfonamide diazoxide, by the Cl--channel blocker 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), by intracellular application of the antibody JSB1 [originally raised against a 170-kDa multidrug resistance (mdr) protein], and by tamoxifen (an inhibitor of the mdr- and volume-regulated Cl- channels). Immunocytochemistry and Western blot analyses revealed that JSB1 recognizes a 65-kDa protein in the secretory granules. This protein exhibited no detectable binding of sulfonylureas and is distinct from the 140-kDa sulfonylurea high-affinity sulfonylurea receptors also present in the granules. We conclude that (i) tolbutamide stimulates Ca2+-dependent exocytosis secondary to its binding to a 140-kDa high-affinity sulfonylurea receptor in the secretory granules; and (ii) a granular 65-kDa mdr-like protein mediates the action. The processes thus initiated culminate in the activation of a granular Cl- conductance. We speculate that the activation of granular Cl- fluxes promotes exocytosis (possibly by providing the energy required for membrane fusion) by inducing water uptake and an increased intragranular hydrostatic pressure.
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| 37. |
- Bastholm Rahmner, Pia, et al.
(author)
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Physicians perceptions of possibilities and obstacles prior to implementing a computerised drug prescribing support system
- 2004
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In: International journal of health care quality assurance incorporating leadership in helath services. - : Emerald. - 1366-0756 .- 2051-3135. ; 17:4, s. 173-179
-
Journal article (peer-reviewed)abstract
- Seeks to identify physicians' perceptions of possibilities and obstacles prior to implementing a computerised drug prescribing support system. Details a descriptive, qualitative study, with semi-structured individual interviews of 21 physicians in the Accident and Emergency Department of South Stockholm General Hospital. Identifies four descriptive categories for possibilities and obstacles. Concludes that gaining access to patient drug history enables physicians to carry out work in a professional way – a need the computerised prescription support system was not developed for and thus cannot fulfil. Alerts and producer-independent drug information are valuable in reducing workload. However, technical prerequisites form the base for a successful implementation. Time must be given to adapt to new ways of working.
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| 38. |
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| 39. |
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| 40. |
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| 41. |
- Broman, T, et al.
(author)
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Molecular Detection of Persistent Francisella tularensis Subspecies holarctica in Natural Waters
- 2011
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In: International Journal of Microbiology. - : Hindawi Publishing Corporation. - 1687-918X .- 1687-9198. ; 2011, s. Article ID 851946-
-
Journal article (peer-reviewed)abstract
- Tularemia, caused by the bacterium Francisella tularensis, where F. tularensis subspecies holarctica has long been the cause of endemic disease in parts of northern Sweden. Despite this, our understanding of the natural life-cycle of the organism is still limited. During three years, we collected surface water samples (n = 341) and sediment samples (n = 245) in two areas in Sweden with endemic tularemia. Real-time PCR screening demonstrated the presence of F. tularenis lpnA sequences in 108 (32%) and 48 (20%) of the samples, respectively. The 16S rRNA sequences from those samples all grouped to the species F. tularensis. Analysis of the FtM19InDel region of lpnA-positive samples from selected sampling points confirmed the presence of F. tularensis subspecies holarctica-specific sequences. These sequences were detected in water sampled during both outbreak and nonoutbreak years. Our results indicate that diverse F. tularensis-like organisms, including F. tularensis subsp. holarctica, persist in natural waters and sediments in the investigated areas with endemic tularemia.
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| 42. |
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| 43. |
- Dakhel, Ardwan, et al.
(author)
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Worse cardiovascular prognosis after endovascular surgery for intermittent claudication caused by infrainguinal atherosclerotic disease in patients with diabetes
- 2020
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In: Therapeutic Advances in Endocrinology and Metabolism. - : SAGE Publications. - 2042-0188 .- 2042-0196. ; 11
-
Journal article (peer-reviewed)abstract
- Background: Diabetes mellitus (DM) is an established risk factor for intermittent claudication (IC) and other manifestations of atherosclerotic peripheral arterial disease. Indications for surgery in infrainguinal IC are debated, and there are conflicting reports regarding its outcomes in patients with DM. Aims of this study were to compare both short- and long-term effects on total- and cardiovascular (CV) mortality, major adverse cardiovascular events (MACEs), acute myocardial infarction (AMI), stroke, and major amputation following infrainguinal endovascular surgery for IC in patients with and without DM. We also evaluated potential relationships between diabetic control and outcomes in patients with DM. Methods: Nationwide observational cohort study of patients registered in the Swedish Vascular Registry and the Swedish National Diabetes Registry. Propensity score adjusted comparison of total and CV mortality, MACE, AMI, stroke, and major amputation after elective infrainguinal endovascular surgery for IC in 626 patients with and 1112 without DM at 30 postoperative days and after median 5.2 [interquartile range (IQR) 4.2-6.3] years of follow-up for patients with DM, and 5.4 (IQR 4.3-6.5) years for those without. Results: In propensity score adjusted Cox regression after 30 postoperative days, there were no differences between groups in morbidity or mortality. At last follow-up, patients with DM showed higher rates of MACE [hazard ratio (HR) 1.26, confidence interval (CI) 1.07-1.48;p < 0.01], AMI (HR 1.48, CI 1.09-2.00;p = 0.01), and major amputation (HR 2.31, CI 1.24-4.32;p < 0.01). Among patients with DM, higher HbA1c was associated with higher total mortality during follow-up (HR 1.01, CI 1.00-1.03;p = 0.045). Conclusion: Patients with DM have higher rates of MACE, AMI, and major amputation in propensity score adjusted analysis during 5 years of follow-up after infrainguinal endovascular surgery for IC. Furthermore, HbA1c is associated with total mortality in patients with DM. Prevention and treatment of DM is important to improve cardiovascular and limb outcomes.
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| 44. |
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| 45. |
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| 46. |
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| 47. |
- Elfstrand, Lidia, et al.
(author)
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Molecular characterization of native and processed waxy maize starch in relation to the recrystallization behavior of model systems and starch microspheres
- 2004
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In: Starch: from polysaccharides to granules, simple and mixture gels. - 1594540136 ; , s. 203-214
-
Conference paper (peer-reviewed)abstract
- The recrystallization behavior of five starch materials, native waxy maize starch, and starches modified by acid hydrolysis and mechanical treatments, were investigated by DSC (differential scanning calorimetry) and electron microscopy (SEM). The starches were known to vary significantly in molecular weights but not in the degree of branching. Microspheres manufactured from one of these starches were also studied by both methods. The acid hydrolysis did not produce major breakdown of the granular structure of starch as evidenced by SEK or the amount of crystalline amylopectin, as measured by DSC, but broadened the melting temperature range compared to native starch. No crystallinity could be detected in the material after the mechanical treatment, which also seemed to destroy the granular structure. The crystallinity was regained after the material had been dispersed in 70 % water during heating followed by 20 hour storage at 6 degreesC, called as one-step temperature treatment, while within the set of samples stored at 20 degreesC only one of the starches showed presence of regained crystallinity. No significant differences could be observed with regard to endothermic transition temperature or temperature range between the samples of native starch and both the acid hydrolysed and the mechanically treated samples, as measured by DSC. Apparently from the enthalpy values and presence of endothermic transitions, amylopectin molecular weight and modification method seemed to affect the amount of starch crystallites formed and/or the recrystallization rates, with acid hydrolysed samples showing higher enthalpy values compared to mechanically treated samples. The same conclusion, as for one-step temperature treatment of starch materials, was done for a two-steps temperature treatment of the starch materials, regarding transitions temperatures within the set of experiment. The two-steps treatment with nucleation at a lower temperature and crystal growth and perfection at a higher temperature resulted in an increase in the melting temperatures and narrower melting intervals. This treatment is also similar to the actual microsphere manufacture process. DSC thermogram of placebo starch microspheres revealed that the crystallites, obtained in production process of the microspheres, melted at temperatures similar to melting temperatures of the starch dispersion after 14 days/6 degreesC- storage but showed higher enthalpy value and smaller melting interval.
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| 48. |
- Elfstrand, Lidia, et al.
(author)
-
Recrystallisation behaviour of native and processed waxy maize starch in relation to the molecular characteristics
- 2004
-
In: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617. ; 57:4, s. 389-400
-
Journal article (peer-reviewed)abstract
- Molecular characteristics were determined for native waxy maize starch and maize starch modified in different way (by mechanical treatment or/and acid hydrolysis). Recrystallisation behaviour was studied. Methods used in this study were MALLS, HPAEC-PAD, NMR, DSC, SEM, light microscopy. Five starch materials were subjected to storage under the same conditions in the presence of water (70 w/w%). Molecular weight, radius of gyration, initial crystallinity, and degree of polymerisation, degree of branching, chain length distribution profiles, were related to nucleation rate during the recrystallisation process, rate of recrystallisation, thermal stability and amount of obtained crystallinity. This allowed the following connections between the molecular characteristics and kinetic of recrystallisation to be proposed: Amylopectin molecular weight appeared to affect the number of starch crystallites formed and amount of crystallinity but not the stability of the rebuilt crystallites. The stability of rebuilt crystallites can be controlled by degree of polymerization, degree of branching and unit chain length distribution, characteristics which were similar for the starches. A mixture of two starches, with and without crystalline structure in initial state but with molecular weight in same range, were stored and scanned in order to understand possible cocrystallisation effects. (C) 2004 Elsevier Ltd. All rights reserved.
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| 49. |
- Eliasson, Ann-Christin, 1950-, et al.
(author)
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Guidelines for future research in constraint-induced movement therapy for children with unilateral cerebral palsy : an expert consensus
- 2014
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In: Developmental Medicine & Child Neurology. - : Mac Keith Press. - 0012-1622 .- 1469-8749. ; 56:2, s. 125-137
-
Journal article (peer-reviewed)abstract
- AIM: The aim of this study was to provide an overview of what is known about constraintinduced movement therapy (CIMT) in children with unilateral cerebral palsy (CP), to identify current knowledge gaps, and to provide suggestions for future research.METHOD: Nine experts participated in a consensus meeting. A comprehensive literature search was conducted and data were summarized before the meeting. The core model produced by the European network for Health Technology Assessment was used as a framework for discussion and to identify critical issues for future research.RESULTS: All models of CIMT have demonstrated improvements in the upper limb abilities of children with unilateral CP. A consensus was reached on 11 important questions to be further explored in future studies. The areas of highest priority included the effect of dosage, the effect of repeated CIMT, and the impact of predictive factors, such as age, on the response to CIMT. Consensus suggestions for future study designs and the use of validated outcome measures were also provided.INTERPRETATION: The CIMT construct is complex, and much remains unknown. It is unclear whether a specific model of CIMT demonstrates superiority over others and whether dosage of training matters. Future research should build upon existing knowledge and aim to provide information that will help implement CIMT in various countries with different healthcare resources and organizational structures.
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| 50. |
- Eliasson, A. C., et al.
(author)
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The Manual Ability Classification System (MACS) for children with cerebral palsy: scale development and evidence of validity and reliability
- 2006
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In: Dev Med Child Neurol. - 0012-1622 .- 1469-8749. ; 48:7, s. 549-54
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Journal article (peer-reviewed)abstract
- The Manual Ability Classification System (MACS) has been developed to classify how children with cerebral palsy (CP) use their hands when handling objects in daily activities. The classification is designed to reflect the child's typical manual performance, not the child's maximal capacity. It classifies the collaborative use of both hands together. Validation was based on the experience within an expert group, a review of the literature, and thorough analysis of children across a spectrum of function. Discussions continued until consensus was reached, first about the constructs, then about the content of the five levels. Parents and therapists were interviewed about the content and the description of levels. Reliability was tested between pairs of therapists for 168 children (70 females, 98 males; with hemiplegia [n=52], diplegia [n=70], tetraplegia [n=19], ataxia [n=6], dyskinesia [n=19], and unspecified CP [n=2]) between 4 and 18 years and between 25 parents and their children's therapists. The results demonstrated that MACS has good validity and reliability. The intraclass correlation coefficient between therapists was 0.97 (95% confidence interval 0.96-0.98), and between parents and therapist was 0.96 (0.89-0.98), indicating excellent agreement.
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