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| 2. |
- Wormser, David, et al.
(författare)
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Adult height and the risk of cause-specific death and vascular morbidity in 1 million people : individual participant meta-analysis
- 2012
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 41:5, s. 1419-1433
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe extent to which adult height, a biomarker of the interplay of genetic endowment and early-life experiences, is related to risk of chronic diseases in adulthood is uncertain.MethodsWe calculated hazard ratios (HRs) for height, assessed in increments of 6.5 cm, using individual-participant data on 174 374 deaths or major non-fatal vascular outcomes recorded among 1 085 949 people in 121 prospective studies.ResultsFor people born between 1900 and 1960, mean adult height increased 0.5-1 cm with each successive decade of birth. After adjustment for age, sex, smoking and year of birth, HRs per 6.5 cm greater height were 0.97 (95% confidence interval: 0.96-0.99) for death from any cause, 0.94 (0.93-0.96) for death from vascular causes, 1.04 (1.03-1.06) for death from cancer and 0.92 (0.90-0.94) for death from other causes. Height was negatively associated with death from coronary disease, stroke subtypes, heart failure, stomach and oral cancers, chronic obstructive pulmonary disease, mental disorders, liver disease and external causes. In contrast, height was positively associated with death from ruptured aortic aneurysm, pulmonary embolism, melanoma and cancers of the pancreas, endocrine and nervous systems, ovary, breast, prostate, colorectum, blood and lung. HRs per 6.5 cm greater height ranged from 1.26 (1.12-1.42) for risk of melanoma death to 0.84 (0.80-0.89) for risk of death from chronic obstructive pulmonary disease. HRs were not appreciably altered after further adjustment for adiposity, blood pressure, lipids, inflammation biomarkers, diabetes mellitus, alcohol consumption or socio-economic indicators.ConclusionAdult height has directionally opposing relationships with risk of death from several different major causes of chronic diseases.
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| 3. |
- Arridge, Christopher S., et al.
(författare)
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Uranus Pathfinder : exploring the origins and evolution of Ice Giant planets
- 2012
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Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 33:2-3, s. 753-791
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Tidskriftsartikel (refereegranskat)abstract
- The "Ice Giants" Uranus and Neptune are a different class of planet compared to Jupiter and Saturn. Studying these objects is important for furthering our understanding of the formation and evolution of the planets, and unravelling the fundamental physical and chemical processes in the Solar System. The importance of filling these gaps in our knowledge of the Solar System is particularly acute when trying to apply our understanding to the numerous planetary systems that have been discovered around other stars. The Uranus Pathfinder (UP) mission thus represents the quintessential aspects of the objectives of the European planetary community as expressed in ESA's Cosmic Vision 2015-2025. UP was proposed to the European Space Agency's M3 call for medium-class missions in 2010 and proposed to be the first orbiter of an Ice Giant planet. As the most accessible Ice Giant within the M-class mission envelope Uranus was identified as the mission target. Although not selected for this call the UP mission concept provides a baseline framework for the exploration of Uranus with existing low-cost platforms and underlines the need to develop power sources suitable for the outer Solar System. The UP science case is based around exploring the origins, evolution, and processes at work in Ice Giant planetary systems. Three broad themes were identified: (1) Uranus as an Ice Giant, (2) An Ice Giant planetary system, and (3) An asymmetric magnetosphere. Due to the long interplanetary transfer from Earth to Uranus a significant cruise-phase science theme was also developed. The UP mission concept calls for the use of a Mars Express/Rosetta-type platform to launch on a Soyuz-Fregat in 2021 and entering into an eccentric polar orbit around Uranus in the 2036-2037 timeframe. The science payload has a strong heritage in Europe and beyond and requires no significant technology developments.
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| 5. |
- Astermark, Jan, et al.
(författare)
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Non-genetic risk factors and the development of inhibitors in haemophilia: a comprehensive review and consensus report.
- 2010
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Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; May 4, s. 747-766
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Tidskriftsartikel (refereegranskat)abstract
- Summary. The development of inhibitors to the infused factor in patients with haemophilia is a serious clinical problem. Recent evidence suggests that alongside the strong genetic contribution to inhibitor formation, there are a number of non-genetic factors - perceived by the immune system as danger signals - which promote formation of inhibitors. This study provides a comprehensive review of clinical studies relating to these factors and also presents a survey of opinion concerning their importance and clinical influence, conducted among the members of the European Haemophilia Treatment Standardisation Board (EHTSB). Taken together, this information highlights the lack of robust data concerning the influence of several non-genetic risk factors on inhibitor development, and an urgent need for prospective, well-conducted studies that adhere to recommendations made by the European Medicines Agency (EMEA) for studying inhibitors. Based on current literature, the EHTSB formulated consensus recommendations. It is desirable to minimize intensive treatment wherever possible, given the clinical situation. Prophylaxis should be offered to all children, although we still need to determine optimal dosing with respect to inhibitor development, and age for starting treatment. Vaccinations should be given subcutaneously and concomitant factor concentrate infusions avoided. According to the board, there is no evidence in the literature supporting suggestions that the type of concentrate influences inhibitor risk; but all patients should be monitored during their first exposures. Furthermore, there is no evidence to support an association between pregnancy-related issues, breast feeding and treatment-related factors (e.g. route of administration, or use of blood components) and inhibitor development.
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| 6. |
- Holme, I, et al.
(författare)
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Cardiovascular outcomes and their relationships to lipoprotein components in patients with and without chronic kidney disease: results from the IDEAL trial
- 2010
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Ingår i: JOURNAL OF INTERNAL MEDICINE. - : Blackwell Publishing Ltd. - 0954-6820. ; 267:6, s. 567-575
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Tidskriftsartikel (refereegranskat)abstract
- Cardiovascular outcomes and their relationships to lipoprotein components in patients with and without chronic kidney disease: Results from the IDEAL trial. J Intern Med 2010; 267:567-575. Objectives. In Incremental Decrease in Endpoints through Aggressive Lipid-lowering (IDEAL), we compared cardiovascular outcomes in patients with and without chronic kidney disease (CKD) (estimated glomerular filtration rate andlt; 60 mL min-1 1.73 m-2) and analysed relationships between lipoprotein components (LC) and major coronary events (MCE) and other cardiovascular (CV) events. Design. Exploratory analysis of CV endpoints in a randomized trial comparing high dose of atorvastatin to usual dose of simvastatin on MCE. Settings. Patients with CKD were compared with the non-CKD patients. Cox regression models were used to study the relationships between on-treatment levels of LC and incident MCE. Findings. Chronic kidney disease was strongly associated with cardiovascular end-points including total mortality. In patients with CKD, a significant benefit of high dose atorvastatin treatment was found for any CV events, stroke and peripheral artery disease, but not for MCE. However, all cardiovascular end-points except stroke and CV mortality were reduced in the non-CKD group. Differential changes in LC or relationships to LC could not explain the different treatment outcomes in MCE in the two groups. Interpretation. Chronic kidney disease was a powerful risk factor for all cardiovascular end-points. The reason why the significant reductions achieved by high-dose statin treatment in most CV end-points in the non-CKD group were only in part matched by similar reductions in the CKD patients is not apparent. This difference did not result from differential changes in or relations to LC, but limited power may have increased the possibility of chance findings.
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| 7. |
- Kranendijk, Martijn, et al.
(författare)
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IDH2 Mutations in Patients with D-2-Hydroxyglutaric Aciduria.
- 2010
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 330:6002
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Tidskriftsartikel (refereegranskat)abstract
- Heterozygous somatic mutations in the genes encoding isocitrate dehydrogenase- 1 and -2 (IDH1 and IDH2) were recently discovered in human neoplastic disorders. These mutations disable the enzymes' normal ability to convert isocitrate to 2-ketoglutarate (2-KG) and confer on the enzymes a new function: the ability to convert 2-KG to d-2-hydroxyglutarate (D-2-HG). We have detected heterozygous germline mutations in IDH2 that alter enzyme residue R140 in 15 unrelated patients with d-2-hydroxyglutaric aciduria (D-2-HGA), a rare neurometabolic disorder characterized by supraphysiological levels of D-2-HG. These findings provide additional impetus for investigating the role of D-2-HG in the pathophysiology of metabolic disease and cancer.
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| 8. |
- Lassila, Riitta, et al.
(författare)
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Practical Viewpoints on the Diagnosis and Management of Heparin-Induced Thrombocytopenia
- 2011
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Ingår i: Seminars in Thrombosis and Hemostasis. - : Georg Thieme Verlag KG. - 1098-9064 .- 0094-6176. ; 37:3, s. 328-335
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Tidskriftsartikel (refereegranskat)abstract
- Heparin-induced thrombocytopenia (HIT, type II) is an immune-mediated disorder due to antibodies formed against heparin platelet factor 4 complexes, usually appearing at days 5 to 14 after initiation of heparin. It is important to recognize HIT because heparin prophylaxis or treatment paradoxically associates with new venous and/or arterial thrombosis. Early clinical suspicion and diagnosis together with proper pharmacotherapy and close laboratory monitoring are the cornerstones for successful management. This includes monitoring of Thrombocytopenia, its Timing to heparin administration, appearance of new Thrombosis or resistance to treatment, and differential diagnosis by exclusion of oTher causes (the 4T's). Specific attention should be paid to the absence or presence of thrombosis and to tailoring thromboprophylaxis or anticoagulant therapy with a nonheparin alternative. Even in the absence of HIT-associated thrombosis, an active policy for prolonged thromboprophylaxis is demanded. Rapid and reliable assays should be developed for diagnosis and anticoagulation monitoring to secure safe management with nonheparins. Semiquantitative testing for on-call hours should be available and later confirmed as clinically needed. Alternative therapeutic options are available, but because their use is infrequent, experienced coagulation treatment centers should provide guidance in the treatment and in laboratory monitoring. Most of the evidence in HIT is grade IC, and thus the best evidence is provided by clinical experience. New anticoagulants and platelet inhibitors may offer future alternatives in the management of HIT, but the current treatment options provide the best experience and benefit. The joint clinical and laboratory guidelines provided in this article along with two practical case scenarios were prepared by a Nordic expert panel. They will be valuable for hematologists and colleagues who do not routinely encounter HIT.
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| 9. |
- Olsson, Anders, et al.
(författare)
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LDL cholesterol goals and cardiovascular risk during statin treatment: the IDEAL study
- 2011
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Ingår i: EUROPEAN JOURNAL OF CARDIOVASCULAR PREVENTION and REHABILITATION. - : Lippincott Williams and Wilkins. - 1741-8267. ; 18:2, s. 262-269
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Tidskriftsartikel (refereegranskat)abstract
- Aims: We assessed the proportion of patients treated with either simvastatin 20 or 40 mg or atorvastatin 80 mg who achieved low-density lipoprotein cholesterol (LDL-C) goals of 2.5 or 2.0 mmol/l in the Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) study. We explored how lipoprotein components related to cardiovascular disease (CVD) outcomes in these groups. Methods and results: For subjects who reached on-treatment LDL-C goals, Cox regression models were used to assess the ability of lipoprotein components to predict CVD events. Treatment with simvastatin or atorvastatin resulted in 40 per cent and 80 per cent of patients, respectively, reaching the 2.5 mmol/l goal and 12 per cent and 52 per cent, respectively, reaching the 2.0 mmol/l goal, after 1 year (all p andlt; 0.001 between groups). Adjusting for baseline LDL-C levels, hazard ratio (HR) for those reaching 2.0-2.5 mmol/l LDL-C versus those reaching andlt; 2.0 mmol/l was 1.16 (95% confidence interval [CI], 1.02-1.33, p = 0.023). An increase of the apolipoprotein B/A1 (apoB/A1) ratio by 1 standard deviation in participants who reached 2.0 mmol/l showed a HR for CVD of 1.14 (95% CI, 1.04-1.25, p = 0.004). Conclusion: More CVD patients treated with atorvastatin than simvastatin achieved either LDL-C goal and those reaching the 2.0 mmol/l goal exhibited significantly less CVD than those only reaching 2.5 mmol/l. In those reaching the 2.0 mmol/l goal, the apoB/A1 ratio still bears a relation to CVD outcome. The use of apoB/A1 ratio may provide additional predictive value to that of LDL-C.
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| 10. |
- Pedersen, Terje R, et al.
(författare)
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Comparison of Atorvastatin 80 mg/day Versus Simvastatin 20 to 40 mg/day on Frequency of Cardiovascular Events Late (Five Years) After Acute Myocardial Infarction (from the Incremental Decrease in End Points Through Aggressive Lipid Lowering [IDEAL] Trial)
- 2010
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Ingår i: AMERICAN JOURNAL OF CARDIOLOGY. - : Elsevier Science B. V., Amsterdam. - 0002-9149. ; 106:3, s. 354-359
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have demonstrated that benefits of intensive statin therapy compared to standard statin therapy begin shortly after an acute event and are continued up to 2 years of follow-up. However, whether efficacy and safety of intensive statin therapy in patients with a recent cardiac event are maintained in longer-term follow-up has not been evaluated. We conducted a post hoc analysis of a subgroup of 999 patients who had a first acute myocardial infarction (MI) andlt;2 months before randomization in a prospective, open-label, blinded end-point evaluation trial of 8,888 patients with a history of MI that compared intensive statin therapy (atorvastatin 80 mg) to standard statin therapy (simvastatin 20 to 40 mg) over approximately 5 years of follow-up. We analyzed the same composite end point used in the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT) trial (death, MI, hospitalization for unstable angina, revascularization, and stroke). Rates of the composite end point were 44.7% (n = 226) in the simvastatin group and 37.9% (n = 187) in the atorvastatin group (hazard ratio 0.82, 95% confidence interval 0.67 to 0.99, p = 0.04). Although statistical power was smaller than that of the PROVE IT trial, the relative risk decrease observed at 5 years is consistent with that in the 2-year follow-up in PROVE IT. The 2 treatment regimens were well tolerated. In conclusion, our analysis provides support for the strategy of placing patients with recent MI on intensive statin therapy and maintaining the high dose over the long term, beyond 2 years.
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