150 research outputs found
Cardiovascular Disease and Osteoporosis in Psoriatic Arthritis
No full textPsoriatic arthritis (PsA) is an inflammatory joint disease (IJD) associated with psoriasis. The clinical presentation is heterogeneous and may involve the peripheral joints, the axial skeleton and the entheses, as well as skin and nails. The diagnosis is based on clinical manifestations, and the ClASsification of Psoriatic ARthritis (CASPAR) criteria can be used. PsA has been associated with several comorbid conditions, such as cardiovascular (CV) disease (CVD), osteoporosis, inflammatory bowel disease and depression.
This thesis focuses on two important comorbidities in rheumatic diseases, namely CVD and osteoporosis. Until now, patients with rheumatoid arthritis (RA), the most prevalent IJD, have been most extensively examined concerning both CVD and osteoporosis. However, PsA is a disease distinct from RA, clinically, radiologically and pathologically. Research findings from RA on disease course, comorbidity, treatment and outcome cannot be automatically translated to PsA patients.
In three of the papers included in this thesis we used data from the Health study in Nord -Trøndelag (HUNT). The HUNT studies are population-based cohorts established in the 1980ies, HUNT1 (1984 -86), HUNT2 (1995-97) and HUNT3 (2006-08). In Paper 4 we used data from the Department of Rheumatology, Hospital of Southern Norway Trust.
Increased CV burden has been documented in PsA patients, however the exact risk increase or causal relationship with inflammation is documented to a lesser degree. Paper 1 in this thesis showed that patients with PsA in the HUNT3 study had an increased burden of several CV risk factors, such as obesity, smoking, hypertension, CRP and high triglyceride levels. However, when it comes to established CVD, we observed only an increased risk of angina pectoris. Also, the estimated 10-years risk of a fatal CV event calculated with the Systematic Coronary Risk Evaluation (SCORE) was comparable to the background population. Whether CV risk factors are increased prior to diagnosis of PsA, co-existing or are a result of PsA itself has not been clarified. Longitudinal data from HUNT2 and HUNT3 in Paper 2 indicate that the unfavourable CV risk factors in PsA patients were present before the PsA diagnosis was established, which may be related to the patients already having psoriasis.
Because modifiable CV risk factors are often present in PsA patients, it is important to educate doctors and patients on how to manage their CV risk factors, to decrease their risk of CVD in the future.
Data from HUNT3 and the Rheumatology department of Hospital of Southern Norway Trust indicate that PsA patients did not have lower bone mineral density than the background population. The prevalence of osteoporosis according to the World Health Organization definition was low. This indicates that PsA patients may follow guidelines for osteoporosis assessment developed for the general population, in line with the current recommendations.
However, extra vigilance for patients with long-standing high disease activity or on high doses of glucocorticoids is probably needed.
Both osteoporosis and CVD may be silent conditions that the patients are unaware of. Therefore, to wisely target the use our health resources, it is important to know the risk of these conditions, so that we can identify the patients who need extra surveillance. Hopefully, the knowledge from this thesis may guide both doctors who care for patients with PsA, and the patients themselves, on how to manage important comorbid conditions
Pharmacological management of cardiovascular disease in patients with rheumatoid arthritis
No full textAtherosclerotic Cardiovascular Disease in Rheumatoid Arthritis: Impact of Inflammation and Antirheumatic Treatment
Full text linkPatients with rheumatoid arthritis (RA) are at approximately 1.5-fold risk of atherosclerotic cardiovascular disease (CVD) compared with the general population, a phenomenon resulting from combined effects of traditional CVD risk factors and systemic inflammation. Rheumatoid synovitis and unstable atherosclerotic plaques share common inflammatory mechanisms, such as expression of proinflammatory cytokines interleukin (IL)-1, tumour necrosis factor (TNF)-α and IL-6. RA patients are undertreated in terms of CVD prevention, and structured CVD prevention programmes are warranted. Alongside management of traditional risk factors, suppressing systemic inflammation with antirheumatic medication is fundamental for the reduction of CVD risk among this high-risk patient group. Many antirheumatic drugs, especially methotrexate, TNF-α-inhibitors and IL-6-inhibitors are associated with reduced risk of CVD in observational studies among RA patients, but randomised controlled trials with hard CVD endpoints are lacking. In patients without rheumatic disease, anti-inflammatory therapies targeting nucleotide-binding oligomerisation domain, leucine-rich repeat and pyrin domain-containing protein 3 inflammasome and the IL-1/IL-6 pathway arise as potential therapies after an atherosclerotic CVD event
Antithrombotic Therapy and Major Adverse Limb Events in Patients With Chronic Lower Extremity Arterial Disease: Systematic Review and Meta-analysis from the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy in Collaboration with the European Society of Cardiology Working Group on Aorta & Peripheral Vascular Diseases.
Full text linkINTRODUCTION: The role and selection of antithrombotic therapy to improve limb outcomes in chronic lower extremity artery disease (LEAD) is still debated. We conducted a meta-analysis to examine the efficacy and safety of anti-thrombotic and more intense antithrombotic therapy on limb outcomes and limb salvage in patients with chronic LEAD. METHODS: Study inclusion criteria were: enrollment of patients with LEAD, randomized allocation to more vs. less intense antithrombotic therapy [more vs. less intense single antiplatelet therapy (SAPT); dual antiplatelet therapy (DAPT) vs. SAPT; dual antithrombotic therapy vs. SAPT or oral anticoagulant]; enrolment of ≥ 200 patients; reporting of at least one of following outcomes: limb amputation or revascularization. Seven randomized studies enrolling 30'447 patients were included. RESULTS: Over a median follow-up of 24 months, more vs. less intense antithrombotic therapy or placebo significantly reduced the risk of limb revascularization (relative risk [RR]: 0.89; 95% confidence interval [CI]: 0.83 - 0.94) and limb amputation (RR: 0.63, 95% confidence interval [CI]: 0.46-0.86), as well as stroke (RR: 0.82, 95% CI: 0.70-0.97). There was no statistically significant effect on the risk of myocardial infarction (RR: 0.98, 95% CI: 0.87-1.11), all-cause (RR: 0.93, 95% CI: 0.86-1.01) and cardiovascular death (RR: 0.97, 95% CI: 0.86-1.08). Risk of major bleeding increased (RR: 1.23, 95% CI: 1.04-1.44). CONCLUSION: In patients with LEAD, more intense antithrombotic therapy reduces risk of limb amputation and revascularization as well as stroke, with an increase in the risk of bleeding events
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Effects of response bias on learning and memory tasks in squirrel monkeys
No full textSix squirrel monkeys were tested on short-term memory tasks assessing ability to suppress perseverative responses that had been previously reinforced. Each trial was divided into three parts: Initial Preference Assay (IPA), Bias-Conditioning (BC), and Reversal Conditioning (RC), and alternated between two conditions: experimental and control. Strength of response bias (based on choices of response during IPA) exceeded chance levels for each monkey. Eighty-four percent of responses to BC of the experimental trials were made to the response loci chosen in IPA even though that response was not rewarded. Monkeys made 38% correct responses during RC but shifted from making most errors during control trials in the beginning of the experiment to making most errors during experimental trials by the end of the experiment. Monkeys had developed a strategy of persevering from IPA to BC and then shifting to the other, not previously chosen window on RC, which led to correct responses in the experimental trials. (Abstract shortened with permission of author.
Engaging the manuscript: new editions and reading the 'whole book' in Chetham's Library MS 8009
Full text linkThis thesis considers the intersection of the manuscript and its literature through an examination of the late fifteenth century manuscript, Chetham’s Library 8009 (Mun. A.6.31) and provides four diplomatic editions. This manuscript contains fourteen texts in Middle English including romance, hagiography, courtesy literature, and a comic text. This thesis argues for the importance of reading medieval literature in its manuscript context. Although there is a growing trend to consider the ‘whole book’ and integrate analysis of the material artefact with interpretation, much work remains to be done.
In Part I, this thesis presents a new paradigm for reading medieval literature, and argues that the manuscript forms a very literal community of texts, and that each text acts as a co-creator of meaning with the others. It then demonstrates four brief contextual readings that may be made within Chetham 8009 across generic boundaries, and that produce a shift in interpretive focus .
Part II provides four diplomatic editions from Chetham 8009: the Life of St Katherine, the Liber Catonis, John Russell’s Book of Carving and Nurture, and the Book of the Duke and Emperor.
This thesis aims to contribute to the study of medieval literature by arguing for a methodological shift in the way the literature is approached and by providing access to four texts either previously unedited or not easily accessible
Long-term cardiovascular prognosis of patients with type 1 diabetes after myocardial infarction
Full text linkBackground To explore long-term cardiovascular prognosis after myocardial infarction (MI) among patients with type 1 diabetes. Methods Patients with type 1 diabetes surviving 90 days after MI (n = 1508; 60% male, mean age = 62.1 years) or without any type of diabetes (n = 62,785) in Finland during 2005-2018 were retrospectively studied using multiple national registries. The primary outcome of interest was a combined major adverse cardiovascular event (MACE; cardiovascular death, recurrent MI, ischemic stroke, or heart failure hospitalization) studied with a competing risk Fine-Gray analyses. Median follow-up was 3.9 years (maximum 12 years). Differences between groups were balanced by multivariable adjustments and propensity score matching (n = 1401 patient pairs). Results Cumulative incidence of MACE after MI was higher in patients with type 1 diabetes (67.6%) compared to propensity score-matched patients without diabetes (46.0%) (sub-distribution hazard ratio [sHR]: 1.94; 95% confidence interval [CI]: 1.74-2.17; p = 60 years, revascularized and non-revascularized patients, and patients with and without atrial fibrillation, heart failure, or malignancy. Conclusions Patients with type 1 diabetes have notably poorer long-term cardiovascular prognosis after an MI compared to patients without diabetes. These results underline the importance of effective secondary prevention after MI in patients with type 1 diabetes.Peer reviewe
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