| 1. |
- Bjerre, Mette, et al.
(författare)
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Serum osteoprotegerin as a long-term predictor for patients with stable coronary artery disease and its association with diabetes and statin treatment : A CLARICOR trial 10-year follow-up substudy
- 2020
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 301, s. 8-14
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Elevated circulating levels of osteoprotegerin (OPG) are known to add to the prediction of cardiovascular mortality. Our objective was to clarify the long-term risk associated with serum OPG and the possible influence of diabetes and statins on OPG levels in patients with stable coronary artery disease (CAD).METHODS: We assessed the placebo-treated group (n = 1998) from the CLARICOR trial (NCT00121550), a cohort with stable CAD. At entry, 15% of the participants had diabetes and 41% received statins. Serum OPG levels were measured in blood drawn at randomization. Participants were followed through public registers for 10 years.RESULTS: OPG levels correlated positively with diabetes status, age, CRP and female sex, but negatively with the use of statins. CAD participants with diabetes had significantly elevated serum OPG levels compared to participants without diabetes, p < 0.0001. The participants without diabetes treated with statins presented with significantly lower serum OPG levels than the corresponding non-statin-users (p < 0.0001). However, statin use showed no association with OPG levels in the participants with diabetes. High OPG levels at entry showed long-term associations with all-cause mortality and cardiovascular events (hazard ratio associated with factor 10 OPG increase 15.9 (95% CI 11.0-22.9) and 6.38 (4.60-8.90), p = 0.0001, even after adjustment for standard predictors (3.16 (1.90-5.25) and 2.29 (1.53-3.44), p < 0.0001).CONCLUSIONS: Circulating OPG holds long-term independent predictive ability for all-cause mortality and cardiovascular events in CAD participants. OPG levels were associated with diabetes, age, and female sex and statin treatment was associated with lower OPG levels in the absence of diabetes.
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| 2. |
- Blicharska, Malgorzata, 1979-, et al.
(författare)
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Between biodiversity conservation and sustainable forest management - A multidisciplinary assessment of the emblematic Bialowieza Forest case
- 2020
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Ingår i: Biological Conservation. - : Elsevier BV. - 0006-3207 .- 1873-2917. ; 248
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Tidskriftsartikel (refereegranskat)abstract
- The tension between biodiversity conservation and multipurpose forest management may lead to conflicts. An internationally prominent example is the Bialowieza Forest Massif (BFM), an extensive forest complex with high levels of naturalness. We apply a systematic, multidisciplinary assessment process to review empirical evidence on different dimensions of the BFM conflict. While there is broad consensus that this forest massif is an exceptional place worth conserving and that a way forward is a zonation system combining conservation with management, exactly how this should be done has yet to be agreed upon. Our assessment shows that the key reasons for the BFM controversy go beyond the availability of knowledge on the ecological status of the BFM and include: 1) evidence stemming from different sources, which is often contradictory and prone to different interpretations; 2) knowledge gaps, particularly with regard to socio-economic drivers and beneficiaries as well as uncertainties about future trends; 3) fundamentally different values and priorities among stakeholder groups, resulting in power struggles, and an overall lack of trust. We conclude that evidence-based knowledge alone is insufficient to cope with complex conservation conflicts. While more evidence may help assess the consequences of decisions, the actual management decisions depend on different actors' worldviews, which are rooted in their professional identities and power, and their political and legal realities. This calls for conflict management through a well-organized participatory process organized and supervised by a body deemed legitimate by the groups involved.
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| 3. |
- Carlsson, Axel C, et al.
(författare)
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10-Year Associations between Tumor Necrosis Factor Receptors 1 and 2 and Cardiovascular Events in Patients with Stable Coronary Heart Disease : A CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) Trial Substudy.
- 2018
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 7:9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We aimed to assess the associations and predictive powers between the soluble receptors for tumor necrosis factor (TNF)-α (TNFR1 and TNFR2) and cardiovascular outcomes in patients with stable coronary heart disease.METHODS AND RESULTS: CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) is a randomized clinical trial comparing clarithromycin with placebo in patients with stable coronary heart disease. The primary outcome was a composite of nonfatal acute myocardial infarction, unstable angina pectoris, cerebrovascular disease, and all-cause mortality. Patients were followed up for 10 years; discovery sample, those assigned placebo (1204 events in n=1998); and replication sample, those assigned clarithromycin (1220 events in n=1979). We used Cox regression adjusted for C-reactive protein level, established cardiovascular risk factors, kidney function, and cardiovascular drugs. After adjustments, higher serum levels of TNFR1 and TNFR2 were associated with the composite outcome in the discovery sample (hazard ratio per SD increase, 1.13; 95% confidence interval, 1.05-1.22; P=0.001 for TNFR1; hazard ratio, 1.16; 95% confidence interval, 1.08-1.24; P<0.001 for TNFR2). The associations were similar in the replication sample. The associations with the composite outcome were mainly driven by acute myocardial infarction, cardiovascular mortality, and noncardiovascular mortality. The addition of TNFR1 and TNFR2 to established cardiovascular risk factors improved prediction only modestly (<1%).CONCLUSIONS: Increased concentrations of circulating TNFR1 and TNFR2 were associated with increased risks of cardiovascular events and mortality in patients with stable coronary heart disease. Yet, the utility of measuring TNFR1 and TNFR2 to improve risk prediction in these patients appears limited.CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00121550.
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| 4. |
- Hyttel-Sorensen, Simon, et al.
(författare)
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A phase II randomized clinical trial on cerebral near-infrared spectroscopy plus a treatment guideline versus treatment as usual for extremely preterm infants during the first three days of life (SafeBoosC) : study protocol for a randomized controlled trial
- 2013
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 14, s. 120-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Every year in Europe about 25,000 infants are born extremely preterm. These infants have a 20% mortality rate, and 25% of survivors have severe long-term cerebral impairment. Preventative measures are key to reduce mortality and morbidity in an extremely preterm population. The primary objective of the SafeBoosC phase II trial is to examine if it is possible to stabilize the cerebral oxygenation of extremely preterm infants during the first 72 hours of life through the application of cerebral near-infrared spectroscopy (NIRS) oximetry and implementation of an clinical treatment guideline based on intervention thresholds of cerebral regional tissue saturation rStO(2). Methods/Design: SafeBoosC is a randomized, blinded, multinational, phase II clinical trial. The inclusion criteria are: neonates born more than 12 weeks preterm; decision to conduct full life support; parental informed consent; and possibility to place the cerebral NIRS oximeter within 3 hours after birth. The infants will be randomized into one of two groups. Both groups will have a cerebral oximeter monitoring device placed within three hours of birth. In the experimental group, the cerebral oxygenation reading will supplement the standard treatment using a predefined treatment guideline. In the control group, the cerebral oxygenation reading will not be visible and the infant will be treated according to the local standards. The primary outcome is the multiplication of the duration and magnitude of rStO(2) values outside the target ranges of 55% to 85%, that is, the 'burden of hypoxia and hyperoxia' expressed in '%hours'. To detect a 50% difference between the experimental and control group in %hours, 166 infants in total must be randomized. Secondary outcomes are mortality at term date, cerebral ultrasound score, and interburst intervals on an amplitude-integrated electroencephalogram at 64 hours of life and explorative outcomes include neurodevelopmental outcome at 2 years corrected age, magnetic resonance imaging at term, blood biomarkers at 6 and 64 hours after birth, and adverse events. Discussion: Cerebral oximetry guided interventions have the potential to improve neurodevelopmental outcome in extremely preterm infants. It is a logical first step to test if it is possible to reduce the burden of hypoxia and hyperoxia.
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| 5. |
- Nilsson, Erik, 1975-, et al.
(författare)
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Pregnancy Associated Plasma Protein-A as a Cardiovascular Risk Marker in Patients with Stable Coronary Heart Disease During 10 Years Follow-Up-A CLARICOR Trial Sub-Study
- 2020
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Elevated pregnancy-associated plasma protein A (PAPP-A) is associated with mortality in acute coronary syndromes. Few studies have assessed PAPP-A in stable coronary artery disease (CAD) and results are conflicting. We assessed the 10-year prognostic relevance of PAPP-A levels in stable CAD. The CLARICOR trial was a randomized controlled clinical trial including outpatients with stable CAD, randomized to clarithromycin versus placebo. The placebo group constituted our discovery cohort (n = 1.996) and the clarithromycin group the replication cohort (n = 1.975). The composite primary outcome was first occurrence of cardiovascular event or death. In the discovery cohort, incidence rates (IR) for the composite outcome were higher in those with elevated PAPP-A (IR 12.72, 95% Confidence Interval (CI) 11.0-14.7 events/100 years) compared to lower PAPP-A (IR 8.78, 8.25-9.34), with comparable results in the replication cohort. Elevated PAPP-A was associated with increased risk of the composite outcome in both cohorts (discovery Hazard Ratio (HR) 1.45, 95% CI 1.24-1.70; replication HR 1.29, 95% CI 1.10-1.52). In models adjusted for established risk factors, these trends were attenuated. Elevated PAPP-A was associated with higher all-cause mortality in both cohorts. We conclude that elevated PAPP-A levels are associated with increased long-term mortality in stable CAD, but do not improve long-term prediction of death or cardiovascular events when added to established predictors.
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| 6. |
- Perner, Anders, et al.
(författare)
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Hydroxyethyl Starch 130/0.4 versus Ringer's Acetate in Severe Sepsis
- 2012
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 367:2, s. 124-134
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Hydroxyethyl starch (HES) 130/0.4 is widely used for fluid resuscitation in intensive care units (ICUs), but its safety and efficacy have not been established in patients with severe sepsis. METHODS In this multicenter, parallel-group, blinded trial, we randomly assigned patients with severe sepsis to fluid resuscitation in the ICU with either 6% HES 130/0.4 or Ringer's acetate at a dose of up to 33 ml per kilogram of ideal body weight per day. The primary outcome measure was either death or end-stage kidney failure (dependence on dialysis) at 90 days after randomization. RESULTS Of the 804 patients who underwent randomization, 798 were included in the modified intention-to-treat population. The two intervention groups had similar baseline characteristics. At 90 days after randomization, 201 of 398 patients (51%) assigned to HES 130/0.4 had died, as compared with 172 of 400 patients (43%) assigned to Ringer's acetate (relative risk, 1.17; 95% confidence interval [CI], 1.01 to 1.36; P=0.03); 1 patient in each group had end-stage kidney failure. In the 90-day period, 87 patients (22%) assigned to HES 130/0.4 were treated with renal-replacement therapy versus 65 patients (16%) assigned to Ringer's acetate (relative risk, 1.35; 95% CI, 1.01 to 1.80; P=0.04), and 38 patients (10%) and 25 patients (6%), respectively, had severe bleeding (relative risk, 1.52; 95% CI, 0.94 to 2.48; P=0.09). The results were supported by multivariate analyses, with adjustment for known risk factors for death or acute kidney injury at baseline. CONCLUSIONS Patients with severe sepsis assigned to fluid resuscitation with HES 130/0.4 had an increased risk of death at day 90 and were more likely to require renal-replacement therapy, as compared with those receiving Ringer's acetate.
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| 7. |
- Perner, Anders, et al.
(författare)
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Long-term outcomes in patients with severe sepsis randomised to resuscitation with hydroxyethyl starch 130/0.42 or Ringer's acetate
- 2014
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 40:7, s. 927-934
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Tidskriftsartikel (refereegranskat)abstract
- We assessed long-term mortality and hospitalisation in patients with severe sepsis resuscitated with hydroxyethyl starch (HES) or Ringer's acetate. This was an investigator-initiated, parallel-grouped, blinded randomised trial using computer-generated allocation sequence and centralised allocation data that included 804 patients with severe sepsis needing fluid resuscitation in 26 general intensive care units (ICUs) in Scandinavia. Patients were allocated to fluid resuscitation using either 6 % HES 130/0.42 or Ringer's acetate during ICU admission. We assessed mortality rates at 6 months, 1 year and at the time of longest follow-up and days alive and out of hospital at 1 year. The vital status of all patients was obtained at a median of 22 (range 13-36) months after randomisation. Mortality rates in the HES versus Ringer's groups at 6 months were 53.3 (212/398 patients) versus 47.5 % (190/400) [relative risk 1.12; 95 % confidence interval (CI) 0.98-1.29; P = 0.10], respectively; at 1 year, 56.0 (223/398) versus 51.5 % (206/400) (1.09; 95 % CI 0.96-1.24; P = 0.20), respectively; at the time of longest follow-up, 59.8 (238/398) versus 56.3 % (225/400) (1.06; 95 % CI 0.94-1.20; P = 0.31), respectively. Percentage of days alive and out of hospital at 1 year in the HES versus Ringer's groups was 24 (0-87 days) versus 63 % (0-90) (P = 0.07). The long-term mortality rates did not differ in patients with severe sepsis assigned to HES 130/0.42 versus Ringer's acetate, but we could not reject a 24 % relative increased or a 4 % relative decreased mortality at 1 year with HES at the 95 % confidence level.
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| 8. |
- Ruge, Toralph, et al.
(författare)
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Circulating endostatin as a risk factor for cardiovascular events in patients with stable coronary heart disease : A CLARICOR trial sub-study
- 2019
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 284, s. 202-208
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Raised levels of serum endostatin, a biologically active fragment of collagen XVIII, have been observed in patients with ischemic heart disease but association with incident cardiovascular events in patients with stable coronary heart disease is uncertain.METHODS: The CLARICOR-trial is a randomized, placebo-controlled trial of stable coronary heart disease patients evaluating 14-day treatment with clarithromycin. The primary outcome was a composite of acute myocardial infarction, unstable angina pectoris, cerebrovascular disease or all-cause mortality. In the present sub-study using 10-year follow-up data, we investigated associations between serum endostatin at entry (randomization) and the composite outcome and its components during follow-up. The placebo group was used as discovery sample (1204 events, n = 1998) and the clarithromycin-treated group as replication sample (1220 events, n = 1979).RESULTS: In Cox regression models adjusting for cardiovascular risk factors, glomerular filtration rate, and current pharmacological treatment, higher serum endostatin was associated with an increased risk of the composite outcome in the discovery sample (hazard ratio per standard deviation increase 1.11, 95% CI 1.03-1.19, p = 0.004), but slightly weaker and not statistically significant in the replication sample (hazard ratio 1.06, 95% CI 1.00-1.14, p = 0.06). In contrast, strong and consistent associations were found between endostatin and cardiovascular and all-cause mortality in all multivariable models and sub-samples. Addition of endostatin to a model with established cardiovascular risk factors provided no substantial improvement of risk prediction (<1%).CONCLUSIONS: Raised levels of serum endostatin might be associated with cardiovascular events in patients with stable coronary heart disease. The clinical utility of endostatin measurements remains to be established.
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| 9. |
- Schroder, Jakob, et al.
(författare)
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Prognosis And Reclassification By YKL-40 In Stable Coronary Artery Disease
- 2020
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe inflammatory biomarker YKL‐40 has previously been studied as a potential risk marker in cardiovascular disease. We aimed to assess the prognostic reclassification potential of serum YKL‐40 in patients with stable coronary artery disease.Methods and ResultsThe main study population was the placebo group of the CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) trial. The primary outcome was a composite of acute myocardial infarction, unstable angina pectoris, cerebrovascular disease, and all‐cause mortality. We used Cox proportional hazards regression models adjusted for C‐reactive protein level and baseline cardiovascular risk factors. Improvement in prediction by adding serum YKL‐40 to the risk factors was calculated using the Cox‐Breslow method and c‐statistic. A total of 2200 patients were randomized to placebo, with a follow‐up duration of 10 years. YKL‐40 was associated with an increased risk of the composite outcome (hazard ratio per unit increase in (YKL‐40) 1.13, 95% CI 1.03–1.24, P=0.013) and all‐cause mortality (hazard ratio 1.32, 95% CI 1.17–1.49, P<0.0001). Considering whether a composite‐outcome event was more likely to have, or not have, occurred to date, we found 68.4% of such predictions to be correct when based on the standard predictors, and 68.5% when serum YKL‐40 was added as a predictor. Equivalent results were obtained with c‐statistics.ConclusionsHigher serum YKL‐40 was independently associated with an increased risk of adverse cardiovascular outcomes and mortality. Addition of YKL‐40 did not improve risk prediction in patients with stable coronary artery disease.
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| 10. |
- Winkel, Per, et al.
(författare)
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A screening method to spot biomarkers that may warn of serious events in a chronic disease - illustrated by cardiological CLARICOR trial data
- 2021
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter. - 1434-6621 .- 1437-4331. ; 59:11, s. 1852-1860
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To develop a crude screening method for detecting biomarkers which frequently exhibit a rise (or fall) in level prior to a serious event (e.g. a stroke) in patients with a chronic disease, signalling that the biomarker may have an alarm-raising or prognostic potential. The subsequent assessment of the marker's clinical utility requires costly, difficult longitudinal studies. Therefore, initial screening of candidate-biomarkers is desirable.METHODS: The method exploits a cohort of patients with biomarkers measured at entry and with recording of first serious event during follow-up. Copying those individual records onto a common timeline where a specific event occurs on the same day (Day 0) for all patients, the baseline biomarker level, when plotted against the patient's entry time on the revised timeline, will have a positive (negative) regression slope if biomarker levels generally rise (decline) the closer one gets to the event. As an example, we study 1,958 placebo-treated patients with stable coronary artery disease followed for nine years in the CLARICOR trial (NCT00121550), examining 11 newer biomarkers.RESULTS: Rising average serum levels of cardiac troponin T and of N-terminal pro-B-type natriuretic peptide were seen prior to a fatal cardiovascular outcome. C-reactive protein rose prior to non-cardiovascular death. Glomerular filtration rate, seven lipoproteins, and nine newer cardiological biomarkers did not show convincing changes.CONCLUSIONS: For early detection of biomarkers with an alarm-raising potential in chronic diseases, we proposed the described easy procedure. Using only baseline biomarker values and clinical course of participants with coronary heart disease, we identified the same cardiovascular biomarkers as those previously found containing prognostic information using longitudinal or survival analysis.
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