We conducted a study to assess the effect of rosuvastatin use on fibrinolysis in patients with previous venous thromboembolism (VTE). This was a post hoc analysis within the STAtins Reduce ...Thrombophilia (START) study (NCT01613794). Plasma fibrinolytic potential, fibrinogen, plasmin inhibitor, plasminogen activator inhibitor‐1 (PAI‐1) and thrombin‐activatable fibrinolysis inhibitor (TAFI) were measured before and after four weeks of rosuvastatin or no treatment in participants with prior confirmed VTE, after ending anticoagulant therapy. In the non‐rosuvastatin group (n = 121), plasma fibrinolytic potential and individual fibrinolysis parameters did not change at the end of the study versus the baseline, whereas in the rosuvastatin group (n = 126), plasma fibrinolytic potential increased: the mean clot lysis time decreased by 8·75 min (95% CI −13·8 to −3·72), and plasmin inhibitor levels and TAFI activity were lower at the end of the study (−0·05 U/ml; 95% CI −0·07 to −0·02 and −4·77%; 95% CI −6·81 to −2·73, respectively). PAI‐1 levels did not change and fibrinogen levels were 0·17 g/l (95% CI 0·04–0·29) higher. In participants with prior VTE, rosuvastatin use led to an increased fibrinolytic potential compared with non‐statin use. Our findings support the need for further studies on the possible role for statins in the secondary prevention of VTE.
Background
D‐dimers are generated during endogenous fibrinolysis of a blood clot and have a central role in diagnostic algorithms to rule out venous thromboembolism. HMG‐CoA reductase inhibitors, ...more commonly called statins, are known to have effects independent of LDL‐cholesterol lowering, including antithrombotic properties. An effect of statins on D‐dimer levels has been reported in a prior systematic review and meta‐analysis, but methodological shortcomings might have led to an overestimated effect. To re‐evaluate the association between statins and D‐dimer levels, we systematically reviewed all published articles on the influence of statins on D‐dimer levels and conducted a novel meta‐analysis (PROSPERO registration number CRD42017058932).
Materials and methods
We electronically searched EMBASE, Medline Epub, Cochrane, Web of Science and Google Scholar (100 top relevance) (date of last search: 5 October 2017). We included randomized controlled trials, cohort studies and cross‐sectional studies. Two reviewers independently screened all articles retrieved and extracted data on study and patient characteristics, study quality and D‐dimer levels.
Results
Study‐level meta‐analysis involving 18,052 study participants showed lower D‐dimer levels in those receiving statin treatment than controls (SMD: −0.165, 95% CI −0.234; −0.096, P = <0.001). Sensitivity analyses and additional analyses on treatment duration (<12 weeks vs ≥12 weeks) and type of statin (lipophilic or hydrophilic) did not modify this overall result.
Conclusion
This meta‐analysis suggests an association between use of statins and reduction of D‐dimer levels, independent of treatment duration and type of statin used. This effect is small but robust, and should be interpreted with caution.
Background
Acute pulmonary embolism may be ruled out by combining nonhigh clinical probability and a normal D‐dimer level. Both antiplatelet drugs and HMG‐CoA reductase inhibitors (statins) have been ...associated with effects on thrombus formation, potentially influencing D‐dimer levels in this setting, leading to a higher rate of false‐negative tests. Therefore, we determined whether D‐dimer levels in patients with suspected pulmonary embolism are affected by concomitant use of antiplatelet drugs and/or statins and evaluated whether the effect of antiplatelet drugs or statins might affect diagnostic accuracy.
Materials and methods
We performed a posthoc analysis in the YEARS diagnostic study, comparing age‐ and sex‐adjusted D‐dimer levels among users of antiplatelet drugs, statins and nonusers. We then reclassified patients within the YEARS algorithm by developing a model in which we adjusted D‐dimer cut‐offs for statin use and evaluated diagnostic accuracy.
Results
We included 156 statins users, 147 antiplatelet drugs users and 726 nonusers of either drugs, all with suspected pulmonary embolism. Use of antiplatelet drugs did not have a significant effect, whereas statin use was associated with 15% decrease in D‐dimer levels (95% CI, −28% to −0.6%). An algorithm with lower D‐dimer thresholds in statin users yielded lower specificity (0.42 compared to 0.33) with no difference in false‐negative tests.
Conclusions
We conclude that use of statins but not of antiplatelet agents is associated with a modest decrease in D‐dimer levels. Adjusting D‐dimer cut‐offs for statin use did, however, not result in a safer diagnostic strategy in our cohort.
Since data on the safety and effectiveness of home telemonitoring and oxygen therapy started directly after Emergency Department (ED) assessment in COVID-19 patients are sparse but could have many ...advantages, we evaluated these parameters in this study.
All COVID-19 patients ≥18 years eligible for receiving home telemonitoring (November 2020-February 2022, Albert Schweitzer hospital, the Netherlands) were included: patients started directly after ED assessment (ED group) or after hospital admission (admission group). Safety (number of ED reassessments and hospital readmissions) and effectiveness (number of phone calls, duration of oxygen usage and home telemonitoring) were described in both groups.
278 patients were included (
= 65 ED group,
= 213 admission group). ED group: 23.8% (
= 15) was reassessed, 15.9% (
= 10) was admitted and 7.7% (
= 5) ICU admitted. Admission group: 15.8% (
= 37) was reassessed, 6.5% (
= 14) was readmitted and 2.4% (
= 5) ICU (re)admitted. Ten patients died, of whom 7 due to COVID-19 (1 in ED group; 6 in the admission group). ED group: median duration of oxygen therapy was 9 (IQR 7-13) days; the total duration of home telemonitoring was 14 (IQR 9-18) days. Admission group: duration of oxygen therapy was 10 (IQR 6-16) days; total duration of home telemonitoring was 14 (IQR 10-20) days.
it appears to be safe to start home telemonitoring and oxygen therapy directly after ED assessment.
D-dimer is a product of fibrinolysis. In clinical practice, D-dimer levels are commonly used to rule out venous thromboembolism. Antiplatelet drugs may influence D-dimer levels, potentially affecting ...the accuracy of this diagnostic tool. To evaluate the effect of antiplatelet drugs on D-dimer levels, we performed a systematic review and meta-analysis of all published articles on this topic (PROSPERO registration number CRD42017058932).
We electronically searched EMBASE, MEDLINE Epub, Cochrane, Web of Science, and Google Scholar (100 top relevance) (last search on October 5, 2017). We included randomized controlled trials, cohort studies, and cross-sectional studies conducted in humans, with a drug exposure time of at least 7 days. Two reviewers independently selected eligible articles and extracted the data. Five controlled trials, 7 cohort studies, and 5 cross-sectional studies were finally included. Meta-analysis involving all 1117 participants showed no change in dimer levels (standardized mean difference: -0.015, 95% confidence interval, 0.182-0.151, P = 0.855).
In conclusion, antiplatelet drugs do not seem to influence D-dimer levels.
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Statins are generally believed to have cardiovascular protective effects independent of low-density lipoprotein-cholesterol (LDL-C) lowering, such as antithrombotic effects ...characterized by a decrease in D-dimer levels. For the recently introduced Proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors antithrombotic effects are yet unknown. We determined the effect of starting PCSK9 inhibitors on D-dimer and fibrinogen levels as most robust markers for thrombogenicity in statin-intolerant patients with familial hypercholesterolemia. We determined D-dimer and fibrinogen levels before and after start of evolocumab (n = 19) or alirocumab (n = 11). Baseline median D-dimer levels were 0.34 mg/L (IQR 0.24–0.59 mg/L) and baseline median fibrinogen levels 3.2 g/L (IQR 2.88–3.63 g/L). At follow-up D-dimer levels (median 0.31 mg/L (IQR 0.25-0.59 mg/L); p = 0.37), and fibrinogen levels (median 3.4 g/L (IQR 2.98–3.62 g/L); p = 0.38) did not change significantly. We therefore conclude PCSK9 inhibitors do not seem to have a profound antithrombotic effect, although a more subtle effect can not been excluded.
The aim of this study was to determine the efficacy of early tocilizumab treatment for hospitalized patients with COVID-19 disease. Open-label randomized phase II clinical trial investigating ...tocilizumab in patients with proven COVID-19 admitted to the general ward and in need of supplemental oxygen. The primary endpoint of the study was 30-day mortality with a prespecified 2-sided significance level of alpha = 0.10. A post-hoc analysis was performed for a combined endpoint of mechanical ventilation or death at 30 days. Secondary objectives included comparing the duration of hospital stay, ICU admittance and duration of ICU stay and the duration of mechanical ventilation. A total of 354 patients (67% men; median age 66 years) were enrolled of whom 88% received dexamethasone. Thirty-day mortality was 19% (95% CI 14%-26%) in the standard arm versus 12% (95% CI: 8%-18%) in the tocilizumab arm, hazard ratio (HR) = 0.62 (90% CI 0.39-0.98; p = 0.086). 17% of patients were admitted to the ICU in each arm (p = 0.89). The median stay in the ICU was 14 days (IQR 9-28) in the standard arm versus 9 days (IQR 5-14) in the tocilizumab arm (p = 0.014). Mechanical ventilation or death at thirty days was 31% (95% CI 24%-38%) in the standard arm versus 21% (95% CI 16%-28%) in the tocilizumab arm, HR = 0.65 (95% CI 0.42-0.98; p = 0.042). This randomized phase II study supports efficacy for tocilizumab when given early in the disease course in hospitalized patients who need oxygen support, especially when concomitantly treated with dexamethasone.
Background Depression has a strong genetic component but candidate gene studies conducted to date have not shown consistent associations. Methods We conducted a genome-wide parametric and ...nonparametric linkage analysis in a large-scale family-based study including 115 individuals with depression who were identified based on the Hospital Anxiety Depression Scale, Center for Epidemiologic Studies Depression Rating Scale, or use of antidepressive medication. Further, we investigated the most promising chromosomal regions found in the genome-wide linkage analysis with an association analysis in 734 individuals in the family-based study and 2373 individuals in the population-based study. Results Our study demonstrated evidence for significant linkage of depression to chromosome 2p16.1-15 (logarithm of odds LOD = 5.13; parametric analysis) and suggestive evidence for linkage in nonparametric analysis to chromosome 5p15.33 (LOD = 2.14), 11q25 (LOD = 2.27), and 19p13.3 (LOD = 2.66). The subsequent association analysis in the family-based study showed region-wide significant association in intron 1 of the OPCML gene on chromosome 11q25 (empirical p value = .04). The association analysis in the population-based study did not show any region-wide significant association, yet showed suggestive association in intron 1 of the APLP2 gene on chromosome 11q25. Conclusions Our linkage and association studies suggest a locus for depression on chromosomes 2p16.1-15 and 11q25. The linkage to chromosome 11q25 may be, in part, explained by the OPCML or the APLP2 gene. Further, there is evidence for a role of the GNG7 gene (chromosome 19p13.3).
A woman with an ulcer of the leg Schol-Gelok, Suzanne; Bode, Willem A
Nederlands tijdschrift voor geneeskunde,
2012, Letnik:
156, Številka:
43
Journal Article
A 47-year-old woman with a history of ulcerative colitis and rheumatoid arthritis presented with a large ulcer with an erythematous halo of the right lower leg. The clinical course and the ...histopathological results were indicative of pyoderma gangrenosum.
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