. Ahlehoff O, Gislason GH, Charlot M, Jørgensen CH, Lindhardsen J, Olesen JB, Abildstrøm SZ, Skov L, Torp‐Pedersen C, Hansen PR. (Copenhagen University Hospital Gentofte, Hellerup; Copenhagen ...University Hospital Bispebjerg, Copenhagen; National Institute of Public Health, University of Southern Denmark, Copenhagen; Copenhagen University Hospital Gentofte, Hellerup; University of Copenhagen, Copenhagen, Denmark) Psoriasis is associated with clinically significant cardiovascular risk: a Danish nationwide cohort study. J Intern Med2011; 270: 147–157.
Objective. The magnitude of the cardiovascular risk from psoriasis and psoriatic arthritis is debated. We therefore investigated the psoriasis‐related risk of adverse cardiovascular events and mortality.
Design, setting and subjects. We conducted a cohort study of the entire Danish population aged ≥18 years followed from 1997 to 2006 by individual‐level linkage of nationwide registers. Psoriasis was defined by prescription claims and classified as severe if patients received hospital‐based treatment. Time‐dependent Poisson regression models were applied to assess cardiovascular risk in patients with psoriasis and psoriatic arthritis.
Main outcome measures. All‐cause mortality, cardiovascular mortality and hospitalizations for myocardial infarction (MI), stroke and coronary revascularization were recorded.
Results. A total of 34 371 patients with mild psoriasis and 2621 with severe psoriasis, including 607 with psoriatic arthritis, were identified and compared with 4 003 265 controls. The event rates and rate ratios (RRs) of all‐cause mortality, cardiovascular death, MI, coronary revascularization, stroke and a composite of MI, stroke and cardiovascular death were increased in patients with psoriasis. The rate ratio increased with disease severity and decreased with age of onset. The overall RRs for the composite endpoint were 1.20 (95% confidence interval CI 1.14–1.25) and 1.58 (95% CI 1.36–1.82) for mild and severe psoriasis, respectively. The corresponding RRs for cardiovascular death were 1.14 (95% CI 1.06–1.22) and 1.57 (95% CI1.27–1.94). The risk was similar in patients with severe skin affection alone and those with psoriatic arthritis.
Conclusions. Psoriasis is associated with increased risk of adverse cardiovascular events and all‐cause mortality. Young age, severe skin affection and/or psoriatic arthritis carry the most risk. Patients with psoriasis may be candidates for early cardiovascular risk factor modification.
Upregulation of the proto-oncogene plasminogen activator inhibitor-1 (PAI-1) is a common hallmark of various solid tumours, but the mechanisms controlling its expression are not fully understood.
We ...investigate microRNAs (miRNAs) regulating PAI-1 in a panel of normal bladder urothelial biopsies, superficial Ta bladder tumours and invasive T1-T4 tumours using expression microarrays and qRT-PCR. The prognostic implications of PAI-1 deregulation are established by tissue microarray staining of non-muscle-invasive bladder tumours. MicroRNA repression of PAI-1 is assayed by ectopic miRNA expression, argonaute immunoprecipitation and luciferase assays.
We found that the miR-143/-145 cluster is downregulated in all stages of bladder cancer and inversely correlated with PAI-1 expression. Mature miR-143 and miR-145 are coordinately expressed, and both directly target the PAI-1 3'UTR, leading to reduced PAI-1 mRNA and protein levels. Furthermore, we show that PAI-1 and miR-145 levels may serve as useful prognostic markers for non-muscle-invasive bladder tumours for which accurate progressive outcome is currently difficult to predict.
This report provides the first evidence for direct miRNA regulation of PAI-1 in bladder cancer. We also demonstrate mRNA co-targeting by a cluster of non-family miRNAs, and suggest miR-145 and PAI-1 as clinically relevant biomarkers in bladder cancer.
Essentials
Competing risk by death may lead to overestimation of venous thromboembolism (VTE) risk in cancers.
We assessed the risk of VTE in cancer with and without accounting for competing risk by ...death.
The risk of VTE was influenced by the mortality rate and the time since cancer diagnosis.
Competing risk by death should be taken into account when exploring VTE risk in cancer.
Summary
Background
Venous thromboembolism (VTE) is a common complication in cancer, and studies have suggested that aggressive cancers create the highest risk of VTE. However, competing risk by death may result in overestimation of VTE risk in patients with cancers associated with high mortality. Therefore, we estimated the risk of VTE by cancer site, accounting for the differential mortality between cancers.
Methods
The Scandinavian Thrombosis and Cancer cohort included 144 952 participants followed from 1993–1997 to 2008–2012. Incidence rates, cause‐specific hazard ratios (HRs) and subdistribution HRs (SHRs) were assessed for overall cancer and by cancer site according to time intervals since cancer diagnosis.
Results
During follow‐up, 14 272 subjects developed cancer, and 567 had cancer‐related VTE. In cause‐specific analyses, the VTE risk was highest in the first 6 months after cancer diagnosis (HR 17.5, 95% confidence interval CI 15.1–20.3), and declined rapidly thereafter. However, when mortality was taken into account, the risk was similar in the periods 6 months before (SHR 4.8, 95% CI 3.6–6.4) and 6 months after (SHR 4.6, 95% CI 3.9–5.4) cancer diagnosis. The range of the 2‐year cumulative VTE incidence rates was substantially narrowed for all cancer sites after competing risk by death was taken into account (from 1–10% to 1–4%).
Conclusion
VTE risk by cancer site was influenced by the mortality rate and the time since cancer diagnosis. Our findings suggest that the cancer itself is a major contributor to VTE risk, and that competing risk by death should be taken into account when VTE risk in cancer is explored.
In contemporary post‐operative pain management, patients are most often treated with combinations of non‐opioid analgesics, to enhance pain relief and to reduce opioid requirements and opioid‐related ...adverse effects. A diversity of combinations is currently employed in clinical practice, and no well‐documented ‘gold standards’ exist. The aim of the present topical, narrative review is to provide an update of the evidence for post‐operative analgesic efficacy with the most commonly used, systemic non‐opioid drugs, paracetamol, non‐steroidal anti‐inflammatory drugs (NSAIDs)/COX‐2 antagonists, glucocorticoids, gabapentinoids, and combinations of these. The review is based on data from previous systematic reviews with meta‐analyses, investigating effects of non‐opioid analgesics on pain, opioid‐requirements, and opioid‐related adverse effects. Paracetamol, NSAIDs, COX‐2 antagonists, and gabapentin reduced 24 h post‐operative morphine requirements with 6.3 (95% confidence interval: 3.7 to 9.0) mg, 10.2 (8.7, 11.7) mg, 10.9 (9.1, 12.8) mg, and ≥ 13 mg, respectively, when administered as monotherapy. The opioid‐sparing effect of glucocorticoids was less convincing, 2.33 (0.26, 4.39) mg morphine/24 h. Trials of pregabalin > 300 mg/day indicated a morphine‐sparing effect of 13.4 (4, 22.8) mg morphine/24 h. Notably, though, the available evidence for additive or synergistic effects of most combination regimens was sparse or lacking. Paracetamol, NSAIDs, selective COX‐2 antagonists, and gabapentin all seem to have well‐documented, clinically relevant analgesic properties. The analgesic effects of glucocorticoids and pregabalin await further clarification. Combination regimens are sparsely documented and should be further investigated in future studies.
Context. The planck satellite will map the full sky at nine frequencies from 30 to 857 GHz. The CMB intensity and polarization that are its prime targets are contaminated by foreground emission. ...Aims. The goal of this paper is to compare proposed methods for separating CMB from foregrounds based on their different spectral and spatial characteristics, and to separate the foregrounds into “components” with different physical origins (Galactic synchrotron, free-free and dust emissions; extra-galactic and far-IR point sources; Sunyaev-Zeldovich effect, etc.). Methods. A component separation challenge has been organised, based on a set of realistically complex simulations of sky emission. Several methods including those based on internal template subtraction, maximum entropy method, parametric method, spatial and harmonic cross correlation methods, and independent component analysis have been tested. Results. Different methods proved to be effective in cleaning the CMB maps of foreground contamination, in reconstructing maps of diffuse Galactic emissions, and in detecting point sources and thermal Sunyaev-Zeldovich signals. The power spectrum of the residuals is, on the largest scales, four orders of magnitude lower than the input Galaxy power spectrum at the foreground minimum. The CMB power spectrum was accurately recovered up to the sixth acoustic peak. The point source detection limit reaches 100 mJy, and about 2300 clusters are detected via the thermal SZ effect on two thirds of the sky. We have found that no single method performs best for all scientific objectives. Conclusions. We foresee that the final component separation pipeline for planck will involve a combination of methods and iterations between processing steps targeted at different objectives such as diffuse component separation, spectral estimation, and compact source extraction.
Genetic selection for body temperature during heat stress might be a useful approach to reduce the magnitude of heat stress effects on production and reproduction. Objectives of the study were to ...estimate the genetic parameters of rectal temperature (RT) in dairy cows in freestall barns under heat stress conditions and to determine the genetic and phenotypic correlations of rectal temperature with other traits. Afternoon RT were measured in a total of 1,695 lactating Holstein cows sired by 509 bulls during the summer in North Florida. Genetic parameters were estimated with Gibbs sampling, and best linear unbiased predictions of breeding values were predicted using an animal model. The heritability of RT was estimated to be 0.17±0.13. Predicted transmitting abilities for rectal temperature changed 0.0068±0.0020°C/yr from (birth year) 2002 to 2008. Approximate genetic correlations between RT and 305-d milk, fat, and protein yields, productive life, and net merit were significant and positive, whereas approximate genetic correlations between RT and somatic cell count score and daughter pregnancy rate were significant and negative. Rectal temperature during heat stress has moderate heritability, but genetic correlations with economically important traits mean that selection for RT could lead to lower productivity unless methods are used to identify genes affecting RT that do not adversely affect other traits of economic importance.
Background: Oral anticoagulation (OAC) in patients with atrial fibrillation (AF) is a double‐edged sword, because it decreases the risk of stroke at the cost of an increased risk of bleeding. We ...compared the performance of a new bleeding prediction scheme, HAS‐BLED, with an older bleeding prediction scheme, HEMORR2HAGES, in a cohort of ‘real‐world’ AF patients. Methods: By individual‐level‐linkage of nationwide registers, we identified all patients (n = 118 584) discharged with non‐valvular AF in Denmark during the period 1997–2006, with and without OAC. Major bleeding rates during 1 year of follow‐up were determined, and the predictive capabilities of the two schemes were compared by c‐statistics. The risk of bleeding associated with individual risk factors composing HAS‐BLED was estimated using Cox proportional‐hazard analyses. Results: Of AF patients receiving OAC (n = 44 771), 34.8% and 47.3% were categorized as ‘low bleeding risk’ by HAS‐BLED and HEMORR2HAGES, respectively, and the bleeding rates per 100 person‐years were 2.66 (95% confidence interval CI, 2.40–2.94) and 3.06 (2.83–3.32), respectively. C‐statistics for the two schemes were 0.795 (0.759–0.829) and 0.771 (0.733–0.806), respectively. The risk factors composing HAS‐BLED were associated with varying risks, with a history of bleeding (hazard ratio HR 2.98; 95% CI 2.68–3.31) and being elderly (HR 1.93; 95% CI 1.71–2.18) being associated with the highest risks. Comparable results were found in AF patients not receiving OAC (n = 77 813). Conclusions: In an unselected nationwide cohort of hospitalized patients with atrial fibrillation, the HAS‐BLED score performs similarly to HEMORR2HAGES in predicting bleeding risk but HAS‐BLED is much simpler and easier to use in everyday clinical practise.
Summary
Essentials
The relationship between atherosclerosis and venous thromboembolism (VTE) is controversial.
In total, 10 426 participants recruited from the general population were included.
...Carotid intima media thickness and total plaque area was not associated with VTE.
There was no association between plaque initiation or plaque progression and subsequent VTE.
Summary
Background
Whether a relationship between atherosclerosis and subsequent venous thromboembolism (VTE) exists is controversial.
Objective
To investigate the association between carotid atherosclerosis and VTE by using repeated measurements of intima media thickness (IMT) and total plaque area (TPA) in participants recruited from the general population.
Methods
Participants were recruited from the fourth (1994–1995), fifth (2001–2002) and sixth (2007–2008) surveys of the Tromsø Study. In total, 10 426 participants attended, for whom measurements of carotid IMT and TPA and potential confounders were updated at each available survey. Time‐varying Cox regression models were used to calculate hazard ratios (HRs) of VTE across various levels of IMT and TPA adjusted for age, sex, and body mass index.
Results
There were 368 incident VTE events during a median follow‐up of 10.8 years. Participants with increasing IMT were, on average, older and had a less favorable cardiovascular risk profile. There was no association between tertiles of increasing TPA and the risk of VTE in the time‐varying model, and increasing IMT was not associated with an increased risk of VTE (HR 0.96, 95% confidence interval CI 0.86–1.07). Neither plaque formation nor plaque progression was associated with the risk of VTE (respectively: HR 1.00, 95% CI 0.98–1.02; and HR 0.96, 95% CI 0.84–1.11).
Conclusion
Carotid IMT and TPA were not associated with an increased risk of VTE in time‐varying analyses. Furthermore, there was no association between plaque initiation or plaque progression and subsequent VTE.
Post‐operative pain affects millions of patients worldwide and the post‐operative period has high rates of morbidity and mortality. Some of this morbidity may be related to analgesics. The aim of ...this review was to provide an update of current knowledge of adverse events (AE) associated with the most common perioperative non‐opioid analgesics: paracetamol, non‐steroidal anti‐inflammatory drugs (NSAIDs), glucocorticoids (GCCs), gabapentinoids and their combinations. The review is based on data from systematic reviews with meta‐analyses of analgesic efficacy and/or adverse effects of perioperative non‐opioid analgesics, and randomised trials and cohort/retrospective studies. Generally, data on AE are sparse and related to the immediate post‐operative period. For paracetamol, the incidence of AEs appears trivial. Data are inconclusive regarding an association of NSAIDs with mortality, cardiovascular events, surgical bleeding and renal impairment. Anastomotic leakage may be associated with NSAID usage. No firm evidence exists for an association of NSAIDs with impaired bone healing. Single‐dose GCCs were not significantly related to increased infection rates or delayed wound healing. Gabapentinoid treatment was associated with increased sedation, dizziness and visual disturbances, but the clinical relevance needs clarification. Importantly, data on AEs of combinations of the above analgesics are sparse and inconclusive. Despite the potential adverse events associated with the most commonly applied non‐opioid analgesics, including their combinations, reporting of such events is sparse and confined to the immediate perioperative period. Knowledge of benefit and harm related to multimodal pain treatment is deficient and needs clarification in large trials with prolonged observation.
Essentials
Whether D‐dimer at incident venous thromboembolism (VTE) can predict recurrence‐risk is unknown.
We explored this association in 454 cancer‐free patients with a first lifetime VTE.
A low ...D‐dimer at first VTE diagnosis was associated with a low recurrence risk.
The association was predominant in patients with deep vein thrombosis and unprovoked VTE.
Click to hear Dr Cannegieter's presentation on venous thrombosis: prediction of recurrence
Summary
Background
Venous thromboembolism (VTE) is a common disease with a high recurrence rate. D‐dimer measured after cessation of anticoagulant therapy predicts recurrence, and is used to decide on treatment prolongation. However, whether D‐dimer measured at first VTE diagnosis can be used to assess recurrence‐risk is unknown.
Aims
To investigate the association between D‐dimer, measured at first VTE diagnosis and risk of recurrent VTE.
Methods
Information on clinical risk factors and laboratory markers were collected in 454 cancer‐free patients with a first VTE. Recurrent VTEs and deaths during follow‐up (1994–2012) were recorded.
Results
During a median follow‐up of 3.9 years, 84 patients experienced a recurrent VTE. The crude recurrence rate was 1.7 (95% confidence interval CI, 1.0–2.9) per 100 person‐years in the lower quartile of D‐dimer (≤ 1500 ng mL−1), and 4.9 (95% CI, 3.9–6.1) per 100 person‐years in the upper three quartiles combined, yielding an absolute risk difference of 3.2 per 100 person‐years. Patients with D‐dimer ≤ 1500 ng mL−1 had 54% lower recurrence‐risk than patients with D‐dimer > 1500 ng mL−1 (HR, 0.46; 95% CI, 0.25–0.82). The association was particularly pronounced among patients with unprovoked events and deep vein thrombosis, showing a 66% (HR, 0.34; 95% CI, 0.15–0.74) and 68% (HR, 0.32; 95% CI, 0.14–0.71) lower recurrence risk among patients with D‐dimer ≤ 1500 ng mL−1, respectively.
Conclusions
A low D‐dimer (≤ 1500 ng mL−1) measured at first VTE diagnosis was associated with a low recurrence risk, particularly among patients with DVT and unprovoked events. Our findings suggest that a clinical decision to avoid prolonged anticoagulant treatment could be considered based on low D‐dimer at the time of VTE diagnosis.
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