| 1. |
- Lind, Marcus, 1976, et al.
(författare)
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Continuous Glucose Monitoring vs Conventional Therapy for Glycemic Control in Adults With Type 1 Diabetes Treated With Multiple Daily Insulin Injections The GOLD Randomized Clinical Trial
- 2017
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Ingår i: Jama-Journal of the American Medical Association. - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 317:4, s. 379-387
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE The majority of individuals with type 1 diabetes do not meet recommended glycemic targets. OBJECTIVE To evaluate the effects of continuous glucose monitoring in adults with type 1 diabetes treated with multiple daily insulin injections. DESIGN, SETTING, AND PARTICIPANTS Open-label crossover randomized clinical trial conducted in 15 diabetes outpatient clinics in Sweden between February 24, 2014, and June 1, 2016 that included 161 individuals with type 1 diabetes and hemoglobin A(1c) (HbA(1c)) of at least 7.5%(58 mmol/mol) treated with multiple daily insulin injections. INTERVENTIONS Participants were randomized to receive treatment using a continuous glucose monitoring system or conventional treatment for 26 weeks, separated by a washout period of 17 weeks. MAIN OUTCOMES AND MEASURES Difference in HbA(1c) between weeks 26 and 69 for the 2 treatments. Adverse events including severe hypoglycemia were also studied. RESULTS Among 161 randomized participants, mean age was 43.7 years, 45.3% were women, and mean HbA(1c) was 8.6%(70 mmol/mol). A total of 142 participants had follow-up data in both treatment periods. Mean HbA(1c) was 7.92%(63 mmol/mol) during continuous glucose monitoring use and 8.35%(68 mmol/mol) during conventional treatment (mean difference, -0.43% [95% CI, -0.57% to -0.29%] or -4.7 [-6.3 to -3.1 mmol/mol]; P < .001). Of 19 secondary end points comprising psychosocial and various glycemic measures, 6 met the hierarchical testing criteria of statistical significance, favoring continuous glucose monitoring compared with conventional treatment. Five patients in the conventional treatment group and 1 patient in the continuous glucose monitoring group had severe hypoglycemia. During washout when patients used conventional therapy, 7 patients had severe hypoglycemia. CONCLUSIONS AND RELEVANCE Among patients with inadequately controlled type 1 diabetes treated with multiple daily insulin injections, the use of continuous glucose monitoring compared with conventional treatment for 26 weeks resulted in lower HbA(1c). Further research is needed to assess clinical outcomes and longer-term adverse effects.
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| 2. |
- Olafsdottir, Arndis, 1978, et al.
(författare)
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A Randomized Clinical Trial of the Effect of Continuous Glucose Monitoring on Nocturnal Hypoglycemia, Daytime Hypoglycemia, Glycemic Variability, and Hypoglycemia Confidence in Persons with Type 1 Diabetes Treated with Multiple Daily Insulin Injections (GOLD-3)
- 2018
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Ingår i: Diabetes Technology & Therapeutics. - : Mary Ann Liebert Inc. - 1520-9156 .- 1557-8593. ; 20:4, s. 274-284
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Tidskriftsartikel (refereegranskat)abstract
- Background: To evaluate the effects of continuous glucose monitoring (CGM) on nocturnal and daytime hypoglycemia in persons with type 1 diabetes treated with multiple daily insulin injections (MDI); we also evaluated factors related to differences in hypoglycemia confidence in this population. Methods: Evaluations were performed from the GOLD randomized trial, an open-label multicenter crossover randomized clinical trial (n=161) over 69 weeks comparing CGM to self-measurement of blood glucose (SMBG) in persons with type 1 diabetes treated with MDI. Masked CGM and the hypoglycemia confidence questionnaire were used for evaluations. Results: Time with nocturnal hypoglycemia, glucose levels <70mg/dL was reduced by 48% (10.2 vs. 19.6min each night, P<0.001) and glucose levels <54mg/dL by 65%. (3.1 vs. 8.9min, P<0.001). For the corresponding glucose cutoffs, daytime hypoglycemia was reduced by 40% (29 vs. 49min, P<0.001) and 54% (8 vs. 18min., P<0.001), respectively. Compared with SMBG, CGM use improved hypoglycemia-related confidence in social situations (P=0.016) and confidence in more broadly avoiding serious problems due to hypoglycemia (P=0.0020). Persons also reported greater confidence in detecting and responding to decreasing blood glucose levels (thereby avoiding hypoglycemia) during CGM use (P=0.0033) and indicated greater conviction that they could more freely live their lives despite the risk of hypoglycemia (P=0.022). Conclusion: CGM reduced time in both nocturnal and daytime hypoglycemia in persons with type 1 diabetes treated with MDI and improved hypoglycemia-related confidence, especially in social situations, thus contributing to greater well-being and quality of life. Trial registration: ClinicalTrials.gov, number NCT02092051.
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| 3. |
- Cleland, J. G. F., et al.
(författare)
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Beta-blockers for heart failure with reduced, mid-range, and preserved ejection fraction: an individual patient-level analysis of double-blind randomized trials
- 2018
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 39:1, s. 26-35
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Tidskriftsartikel (refereegranskat)abstract
- Aims Recent guidelines recommend that patients with heart failure and left ventricular ejection fraction (LVEF) 40-49% should be managed similar to LVEF >= 50%. We investigated the effect of beta-blockers according to LVEF in double-blind, randomized, placebo-controlled trials. Methods and results Individual patient data meta-analysis of 11 trials, stratified by baseline LVEF and heart rhythm (Clinicaltrials.gov: NCT0083244; PROSPERO: CRD42014010012). Primary outcomes were all-cause mortality and cardiovascular death over 1.3 years median follow-up, with an intention-to-treat analysis. For 14 262 patients in sinus rhythm, median LVEF was 27% (interquartile range 21-33%), including 575 patients with LVEF 40-49% and 244 >= 50%. Beta-blockers reduced all-cause and cardiovascular mortality compared to placebo in sinus rhythm, an effect that was consistent across LVEF strata, except for those in the small subgroup with LVEF >= 50%. For LVEF 40-49%, death occurred in 21/292 [7.2%] randomized to beta-blockers compared to 35/283 [12.4%] with placebo; adjusted hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.34-1.03]. Cardiovascular death occurred in 13/292 [4.5%] with beta-blockers and 26/283 [9.2%] with placebo; adjusted HR 0.48 (95% CI 0.24-0.97). Over a median of 1.0 years following randomization (n = 4601), LVEF increased with beta-blockers in all groups in sinus rhythm except LVEF >= 50%. For patients in atrial fibrillation at baseline (n = 3050), beta-blockers increased LVEF when < 50% at baseline, but did not improve prognosis. Conculations Beta-blockers improve LVEF and prognosis for patients with heart failure in sinus rhythm with a reduced LVEF. The data are most robust for LVEF < 40%, but similar benefit was observed in the subgroup of patients with LVEF 40-49%.
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| 4. |
- Engström, Gunnar, et al.
(författare)
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The Swedish CArdioPulmonary BioImage Study : objectives and design
- 2015
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 278:6, s. 645-659
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Tidskriftsartikel (refereegranskat)abstract
- Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.
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| 5. |
- Kotecha, D., et al.
(författare)
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Effect of age and sex on efficacy and tolerability of beta blockers in patients with heart failure with reduced ejection fraction: individual patient data meta-analysis
- 2016
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Ingår i: Bmj-British Medical Journal. - : BMJ. - 1756-1833. ; 353
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES To determine the efficacy and tolerability of beta blockers in a broad age range of women and men with heart failure with reduced ejection fraction (HFrEF) by pooling individual patient data from placebo controlled randomised trials. Prospectively designed meta-analysis of individual patient data from patients aged 40-85 in sinus rhythm at baseline, with left ventricular ejection fraction < 0.45. The primary outcome was all cause mortality; the major secondary outcome was admission to hospital for heart failure. Analysis was by intention to treat with an adjusted one stage Cox proportional hazards model. Compared with placebo, beta blockers were effective in reducing mortality across all ages: hazard ratios were 0.66 (95% confidence interval 0.53 to 0.83) for the first quarter of age distribution (median age 50); 0.71 (0.58 to 0.87) for the second quarter (median age 60); 0.65 (0.53 to 0.78) for the third quarter (median age 68); and 0.77 (0.64 to 0.92) for the fourth quarter (median age 75). There was no significant interaction when age was modelled continuously (P=0.1), and the absolute reduction in mortality was 4.3% over a median follow-up of 1.3 years (number needed to treat 23). Admission to hospital for heart failure was significantly reduced by beta blockers, although this effect was attenuated at older ages (interaction P=0.05). There was no evidence of an interaction between treatment effect and sex in any age group. Drug discontinuation was similar regardless of treatment allocation, age, or sex (14.4% in those give beta blockers, 15.6% in those receiving placebo). Irrespective of age or sex, patients with HFrEF in sinus rhythm should receive beta blockers to reduce the risk of death and admission to hospital.
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| 6. |
- Kotecha, D., et al.
(författare)
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Heart Rate and Rhythm and the Benefit of Beta-Blockers in Patients With Heart Failure
- 2017
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 69:24, s. 2885-2896
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND The relationship between mortality and heart rate remains unclear for patients with heart failure with reduced ejection fraction in either sinus rhythm or atrial fibrillation (AF). OBJECTIVES This analysis explored the prognostic importance of heart rate in patients with heart failure with reduced ejection fraction in randomized controlled trials comparing beta-blockers and placebo. METHODS The Beta-Blockers in Heart Failure Collaborative Group performed a meta-analysis of harmonized individual patient data from 11 double-blind randomized controlled trials. The primary outcome was all-cause mortality, analyzed with Cox proportional hazard ratios (HR) modeling heart rate measured at baseline and approximately 6 months post-randomization. RESULTS A higher heart rate at baseline was associated with greater all-cause mortality for patients in sinus rhythm (n = 14,166; adjusted HR: 1.11 per 10 beats/min; 95% confidence interval [CI]: 1.07 to 1.15; p < 0.0001) but not in AF (n = 3,034; HR: 1.03 per 10 beats/min; 95% CI: 0.97 to 1.08; p = 0.38). Beta-blockers reduced ventricular rate by 12 beats/min in both sinus rhythm and AF. Mortality was lower for patients in sinus rhythm randomized to beta-blockers (HR: 0.73 vs. placebo; 95% CI: 0.67 to 0.79; p < 0.001), regardless of baseline heart rate (interaction p = 0.35). Beta-blockers had no effect on mortality in patients with AF (HR: 0.96, 95% CI: 0.81 to 1.12; p = 0.58) at any heart rate (interaction p = 0.48). A lower achieved resting heart rate, irrespective of treatment, was associated with better prognosis only for patients in sinus rhythm (HR: 1.16 per 10 beats/min increase, 95% CI: 1.11 to 1.22; p < 0.0001). CONCLUSIONS Regardless of pre-treatment heart rate, beta-blockers reduce mortality in patients with heart failure with reduced ejection fraction in sinus rhythm. Achieving a lower heart rate is associated with better prognosis, but only for those in sinus rhythm. (C) 2017 by the American College of Cardiology Foundation.
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| 7. |
- Olafsdottir, Arndis, 1978, et al.
(författare)
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Excess risk of lower extremity amputations in people with type 1 diabetes compared with the general population: Amputations and type 1 diabetes
- 2019
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Ingår i: BMJ Open Diabetes Research and Care. - : BMJ. - 2052-4897. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective This study investigates how the excess risk of lower extremity amputations (amputations) in people with type 1 diabetes mellitus (DM) differs from the general population by diabetes duration, glycemic control, and renal complications. Research design and methods We analyzed data from people with type 1 DM from the Swedish National Diabetes Register without prior amputation from January 1998 to December 2013. Each person (n=36 872) was randomly matched with five controls by sex, age, and county (n=184 360) from the population without diabetes. All were followed until first amputation, death or end of follow-up. Results The overall adjusted HR for all amputation was 40.1 (95% CI 32.8 to 49.1) for type 1 DM versus controls. HR increased with longer diabetes duration. The incidence of amputation/1000 patient-years was 3.18 (95% CI 2.99 to 3.38) for type 1 DM and 0.07 (95% CI 0.05 to 0.08) for controls. The incidence decreased from 1998-2001 (3.09, 95% CI 2.56 to 3.62) to 2011-2013 (2.64, 95% CI 2.31 to 2.98). The HR for major amputations was lower than for minor amputations and decreased over the time period (p=0.0045). Worsening in glycemic control among patients with diabetes led to increased risk for amputation with an HR of 1.80 (95% CI 1.72 to 1.88) per 10 mmol/mol (1%) increase in hemoglobin A1c. Conclusions Although the absolute risk of amputation is relatively low, the overall excess risk was 40 times that of controls. Excess risk was substantially lower for those with good glycemic control and without renal complications, but excess risk still existed and is greatest for minor amputations. © 2019 Author(s) (or their employer(s)). Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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| 8. |
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| 9. |
- Schafmayer, Clemens, et al.
(författare)
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Genome-wide association analysis of diverticular disease points towards neuromuscular, connective tissue and epithelial pathomechanisms
- 2019
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 68:5, s. 854-865
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Tidskriftsartikel (refereegranskat)abstract
- Objective Diverticular disease is a common complex disorder characterised by mucosal outpouchings of the colonic wall that manifests through complications such as diverticulitis, perforation and bleeding. We report the to date largest genome-wide association study (GWAS) to identify genetic risk factors for diverticular disease. Design Discovery GWAS analysis was performed on UK Biobank imputed genotypes using 31 964 cases and 419 135 controls of European descent. Associations were replicated in a European sample of 3893 cases and 2829 diverticula-free controls and evaluated for risk contribution to diverticulitis and uncomplicated diverticulosis. Transcripts at top 20 replicating loci were analysed by real-time quatitative PCR in preparations of the mucosal, submucosal and muscular layer of colon. The localisation of expressed protein at selected loci was investigated by immunohistochemistry. Results We discovered 48 risk loci, of which 12 are novel, with genome-wide significance and consistent OR in the replication sample. Nominal replication (p< 0.05) was observed for 27 loci, and additional 8 in meta-analysis with a population-based cohort. The most significant novel risk variant rs9960286 is located near CTAGE1 with a p value of 2.3x10-10 and 0.002 (OR allelic = 1.14 (95% CI 1.05 to 1.24)) in the replication analysis. Four loci showed stronger effects for diverticulitis, PHGR1 (OR 1.32, 95% CI 1.12 to 1.56), FAM155A-2 (OR 1.21, 95% CI 1.04 to 1.42), CALCB (OR 1.17, 95% CI 1.03 to 1.33) and S100A10 (OR 1.17, 95% CI 1.03 to 1.33). Conclusion I n silico analyses point to diverticulosis primarily as a disorder of intestinal neuromuscular function and of impaired connective fibre support, while an additional diverticulitis risk might be conferred by epithelial dysfunction.
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