| 1. |
- Bhatt, Deepak L., et al.
(författare)
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Rationale, design and baseline characteristics of the effect of ticagrelor on health outcomes in diabetes mellitus patients Intervention study
- 2019
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Ingår i: Clinical Cardiology. - : Wiley. - 0160-9289 .- 1932-8737. ; 42:5, s. 498-505
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Tidskriftsartikel (refereegranskat)abstract
- In the setting of prior myocardial infarction, the oral antiplatelet ticagrelor added to aspirin reduced the risk of recurrent ischemic events, especially, in those with diabetes mellitus. Patients with stable coronary disease and diabetes are also at elevated risk and might benefit from dual antiplatelet therapy. The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS, NCT01991795) is a Phase 3b randomized, double-blinded, placebo-controlled trial of ticagrelor vs placebo, on top of low dose aspirin. Patients >= 50 years with type 2 diabetes receiving anti-diabetic medications for at least 6 months with stable coronary artery disease as determined by a history of previous percutaneous coronary intervention, bypass grafting, or angiographic stenosis of >= 50% of at least one coronary artery were enrolled. Patients with known prior myocardial infarction (MI) or stroke were excluded. The primary efficacy endpoint is a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety endpoint is Thrombolysis in Myocardial Infarction major bleeding. A total of 19 220 patients worldwide have been randomized and at least 1385 adjudicated primary efficacy endpoint events are expected to be available for analysis, with an expected average follow-up of 40 months (maximum 58 months). Most of the exposure is on a 60 mg twice daily dose, as the dose was lowered from 90 mg twice daily partway into the study. The results may revise the boundaries of efficacy for dual antiplatelet therapy and whether it has a role outside acute coronary syndromes, prior myocardial infarction, or percutaneous coronary intervention.
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| 2. |
- Bergthorsdottir, Ragnhildur, 1971, et al.
(författare)
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Premature mortality in patients with Addison's disease: a population-based study.
- 2006
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 91:12, s. 4849-53
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The survival rate of patients with primary adrenal insufficiency (Addison's disease) undergoing currently accepted replacement therapy is not known, although well-informed patients are considered to have a normal survival rate. In this study, we evaluated the mortality of patients with Addison's disease in Sweden. METHODS: A population-based, retrospective, observational study was performed, using the National Swedish Hospital and Cause of Death Registers, covering the period from 1987-2001. After a diagnosis of Addison's disease, each patient was followed until the end of follow-up or death. Mortality was compared with that of the Swedish background population. FINDINGS: We identified 1675 patients (995 women and 680 men) diagnosed with primary adrenal insufficiency. The average follow-up from initial diagnosis was 6.5 yr. Five hundred seven patients died during the study period compared with an expected 199. The risk ratio for all-cause mortality was 2.19 (confidence interval 1.91-2.51) for men and 2.86 (confidence interval 2.54-3.20) for women. The excess mortality in both men and women was attributed to cardiovascular, malignant, and infectious diseases. Concomitant diabetes mellitus was observed in 12% of the patients, but only contributed to the increased mortality to a minor extent. INTERPRETATION: Compared with the background population, we observed that the risk ratio for death was more than 2-fold higher in patients with Addison's disease. Cardiovascular, malignant, and infectious diseases were responsible for the higher mortality rate.
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| 3. |
- Leonsson Zachrisson, Maria, 1968
(författare)
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Effects of growth hormone on cardiovascular risk factors and atherosclerosis
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hypopituitary patients with growth hormone (GH) deficiency (GHD) have increasedmorbidity and mortality from cardiovascular disease (CVD). GH treatment has both beneficialand potentially negative cardiovascular effects. The mechanism for the dyslipidemia observedin these patients is not completely understood and animal experiments indicate that GH isimportant for dietary effects on serum cholesterol. The aim was to investigate effects of GHon diet-induced changes in serum cholesterol and on other cardiovascular risk factors andatherosclerosis.Effects of GH on cholesterol metabolism were evaluated in a cross-over study of sixGHD patients during a high-fat and high-cholesterol 17-day diet with and without GHtreatment. GH attenuated the increase in cholesterol biosynthesis induced by the high-fat diet,probably due to maintained LDL receptor activity. In contrast to animal studies, GH did notinfluence serum LDL cholesterol levels during fat feeding in humans.Effects of GH on cardiovascular risk factors in relation to atherosclerosis were studiedin 34 cardiovascularly healthy hypopituitary patients with GHD, in an open prospective 3-year trial. Results were compared with two healthy control groups matched for age, sex andsmoking. Hypopituitary patients with GHD had higher waist-to-hip ratio, resting heart rate,fasting insulin levels, interleukin-6 (IL-6) concentrations and tissue plasminogen activatorantigen levels together with lipid disturbances including higher serum triglycerides, lowerHDL cholesterol and smaller LDL particles than both the BMI-matched and the non-obesecontrol group. Patients had higher intima-media thickness (IMT) of the carotid bulb (IMTCAB)than non-obese controls at baseline. Female patients had a more pronouncedcardiovascular risk profile compared to their BMI-matched controls. IMT of the commoncarotid artery (CCA) correlated to serum IL-6 levels at baseline in the patient group.Independent risk factors for high IMT-CAB were age and pituitary disease in the total cohort.The waist circumference and CRP levels decreased but insulin resistance increased inpatients after GH treatment. The IMT-CAB increased during three years in both controlgroups, but was unchanged in GH-treated patients. The IMT-CCA was unchanged in all threegroups. The change in IMT-CCA was independently correlated to the change in serum tumournecrosis factor-á in the patient group, but none of the measured variables correlatedindependently to the change in IMT-CAB.In conclusion, we found that GH attenuated the increased cholesterol synthesis inducedby fat feeding, but GH did not influence the increase in serum LDL cholesterol during diet.Pituitary-deficient GHD patients without manifest CVD demonstrated several cardiovascularrisk factors compared to controls independent of their BMI and female patients were at higherrisk. Despite this high risk pattern, GH treatment in GHD patients reduced the rate ofprogression of atherosclerosis in the CAB. The atherosclerosis progression rate in CCA wassimilar in patients to that observed in healthy BMI-matched as well as non-obese controls.
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| 4. |
- Löfdahl, Elisabet, et al.
(författare)
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Compromised quality of life in adult patients who have received a radiation dose towards the basal part of the brain. A case-control study in long-term survivors from cancer in the head and neck region.
- 2012
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Ingår i: Radiation oncology (London, England). - 1748-717X. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: Adult patients with hypothalamic-pituitary disorders have compromised quality of life (QoL). Whether this is due to their endocrine consequences (hypopituitarism), their underlying hypothalamic-pituitary disorder or both is still under debate. The aim of this trial was to measure quality of life (QoL) in long-term cancer survivors who have received a radiation dose to the basal part of the brain and the pituitary. METHODS: Consecutive patients (n=101) treated for oropharyngeal or epipharyngeal cancer with radiotherapy followed free of cancer for a period of 4 to10 years were identified. Fifteen patients (median age 56 years) with no concomitant illness and no hypopituitarism after careful endocrine evaluation were included in a case-control study with matched healthy controls. Doses to the hypothalamic-pituitary region were calculated. QoL was assessed using the Symptom check list (SCL)-90, Nottingham Health Profile (NHP), and Psychological Well Being (PGWB) questionnaires. Level of physical activity was assessed using the Baecke questionnaire. RESULTS: The median accumulated dose was 1.9 Gy (1.5--2.2 Gy) to the hypothalamus and 2.4 Gy (1.8--3.3 Gy) to the pituitary gland in patients with oropharyngeal cancer and 6.0--9.3 Gy and 33.5--46.1 Gy, respectively in patients with epipharyngeal cancer (n=2). The patients showed significantly more anxiety and depressiveness, and lower vitality, than their matched controls. CONCLUSION: In a group of long time survivors of head and neck cancer who hade received a low radiation dose to the hypothalamic-pituitary region and who had no endocrine consequences of disease or its treatment QoL was compromised as compared with well matched healthy controls.
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| 5. |
- Norjavaara, Ensio, et al.
(författare)
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Glucokinase Activators AZD6370 and AZD1656 Do Not Affect the Central Counterregulatory Response to Hypoglycemia in Healthy Males
- 2012
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Endocrine Society. - 0021-972X .- 1945-7197. ; 97:9, s. 3319-3325
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Tidskriftsartikel (refereegranskat)abstract
- Context: Glucokinase is expressed in the hypothalamus, but effects of glucokinase activators (GKAs) on counterregulatory responses to hypoglycemia are unknown. less thanbrgreater than less thanbrgreater thanObjective: Two separate studies assessed the counterregulatory hormone responses to hypoglycemia induced by the GKAs, AZD6370 and AZD1656, compared with insulin infusion. less thanbrgreater than less thanbrgreater thanDesign and Setting: Both studies were randomized, open, two-way crossover studies, conducted in separate clinical research centers. less thanbrgreater than less thanbrgreater thanParticipants: Both studies involved 12 healthy adult male volunteers. less thanbrgreater than less thanbrgreater thanInterventions: Each subject received two treatments in randomized order, separated by a washout. In the AZD6370 study, overnight-fasted subjects received either a single oral AZD6370 dose (300 mg) or insulin infusion (0.8 mU/kg . min). In the AZD1656 study, overnight-fasted subjects received either a single oral dose of AZD1656 (80 mg) plus supporting insulin (1 mU/kg . min) or insulin alone (1 mU/kg . min). Insulin was added to support AZD1656 because AZD1656 alone did not produce the desired hypoglycemia. Plasma glucose was lowered during a stepwise hypoglycemic clamp with a glycemic nadir of 2.7 mmol/liter for 30 min. less thanbrgreater than less thanbrgreater thanMain Outcome Measures: Epinephrine, norepinephrine, GH, cortisol, and glucagon plasma levels were assessed. Results: No safety issues were raised. AZD6370 and AZD1656 had no effect on counterregulatory responses for norepinephrine, GH, or cortisol, but epinephrine increased slightly with AZD1656. Glucagon responses were reduced by approximately 30% with both GKAs vs. insulin. less thanbrgreater than less thanbrgreater thanConclusions: These data suggest the central nervous system-mediated counterregulatory response during GKA-induced hypoglycemia was preserved, whereas the glucagon response was attenuated; the latter was possibly mediated by a local pancreatic effect (intraislet hyperinsulinemia) rather than by impairment of the central nervous system-mediated response.
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| 6. |
- Steg, P. Gabriel, et al.
(författare)
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Ticagrelor in Patients with Stable Coronary Disease and Diabetes
- 2019
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Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 381:14, s. 1309-1320
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Tidskriftsartikel (refereegranskat)abstract
- Patients with stable coronary artery disease and diabetes were randomly assigned to receive either ticagrelor plus aspirin or placebo plus aspirin. At 40 months, the incidence of the composite efficacy outcome of cardiovascular death, myocardial infarction, or stroke was lower with ticagrelor than with placebo; the frequency of major bleeding was higher with ticagrelor. Background Patients with stable coronary artery disease and diabetes mellitus who have not had a myocardial infarction or stroke are at high risk for cardiovascular events. Whether adding ticagrelor to aspirin improves outcomes in this population is unclear. Methods In this randomized, double-blind trial, we assigned patients who were 50 years of age or older and who had stable coronary artery disease and type 2 diabetes mellitus to receive either ticagrelor plus aspirin or placebo plus aspirin. Patients with previous myocardial infarction or stroke were excluded. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety outcome was major bleeding as defined by the Thrombolysis in Myocardial Infarction (TIMI) criteria. Results A total of 19,220 patients underwent randomization. The median follow-up was 39.9 months. Permanent treatment discontinuation was more frequent with ticagrelor than placebo (34.5% vs. 25.4%). The incidence of ischemic cardiovascular events (the primary efficacy outcome) was lower in the ticagrelor group than in the placebo group (7.7% vs. 8.5%; hazard ratio, 0.90; 95% confidence interval [CI], 0.81 to 0.99; P=0.04), whereas the incidence of TIMI major bleeding was higher (2.2% vs. 1.0%; hazard ratio, 2.32; 95% CI, 1.82 to 2.94; P<0.001), as was the incidence of intracranial hemorrhage (0.7% vs. 0.5%; hazard ratio, 1.71; 95% CI, 1.18 to 2.48; P=0.005). There was no significant difference in the incidence of fatal bleeding (0.2% vs. 0.1%; hazard ratio, 1.90; 95% CI, 0.87 to 4.15; P=0.11). The incidence of an exploratory composite outcome of irreversible harm (death from any cause, myocardial infarction, stroke, fatal bleeding, or intracranial hemorrhage) was similar in the ticagrelor group and the placebo group (10.1% vs. 10.8%; hazard ratio, 0.93; 95% CI, 0.86 to 1.02). Conclusions In patients with stable coronary artery disease and diabetes without a history of myocardial infarction or stroke, those who received ticagrelor plus aspirin had a lower incidence of ischemic cardiovascular events but a higher incidence of major bleeding than those who received placebo plus aspirin. (Funded by AstraZeneca; THEMIS ClinicalTrials.gov number, NCT01991795.).
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