2,028 research outputs found
Combined Point of Care Tools Are Able to Improve Treatment Adherence and Health-Related Quality of Life in Patients with Severe Hemophilia: An Observational Prospective Study
Introduction: Ultrasound (US) assessment of joints is an evolving point of care tool for the detection of early joint arthropathy (Napolitano M, Kessler CM. Hemophilia A and B. Consultative Hemostasis and Thrombosis, Kitchens, 4th edition); population pharmacokinetic (pop-PK) studies are adopted as a useful instrument to set the prophylaxis regimen for patients with hemophilia, they may improve adherence (Nagao A.et al. Thromb Res. 2019 Jan; 173:79-84) and reduce the annual bleeding rate (ABR). Adherence to continuous intravenous administrations of factor VIII or Factor IX products is challenging, thus patients may experience breakthrough bleedings while on prophylaxis. Repeated US examinations of joint status have recently been advocated to attempt to remedy sub-optimal medication adherence (Di Minno A et al., Blood Rev. 2019 Jan;33:106-116). Aim of the current prospective analysis was to evaluate the impact of combined US assessment and pop-PK study on adherence to treatment and health related quality of life in patients with severe hemophilia A(HA) and B (HB) under regular prophylaxis. Material and methods: This prospective observational study was performed at a single tertiary center from January 2017 to June 2019. Research was conducted following the Helsinki Declaration. All patients included in the study provided a written informed consent for study participation. Patients with severe HA and HB routinely underwent, as part of regular 12-months follow-up visits, the following: US joints evaluation of elbows, knees and ankles using the HEAD-US protocol, treatment adherence evaluation by VERITAS-Pro questionnaire, health –related quality of life assessment by the standardized EQ-5D,EQ-VAS and pop-PK study (WAPPS-Hemo, McMaster University) as needed (i.e.in case of changes in life style, planned treatment switch); each patient visualised US and his estimated PK profile during medial encounters. Compliance to the prescribed treatment was also determined by analysis of patient diaries with infusion logs. Statistical analysis was performed using the SPSS software version 25.0 (SPSS Chicago, IL). Statistical tests were 2-sided, with a significance threshold of 0.05. Results: Twenty consecutive males with severe haemophilia were included in the current analysis, 13 with severe HA, 2 with HA with previous inhibitors and 5 HB, with a median age of 30 (range 14- 56) years and a median ABR of 5 (range:0-12). Nine patients were under primary prophylaxis, 8 under secondary prophylaxis and 3 under tertiary prophylaxis, they all self-infused at home. Four patients had one target joint and 3 patients had multiple target joints. For each enrolled subject, HEAD-US score, VERITAS-pro, EQ5D and EQ-VAS score were assessed at enrolment (T0) and at 12 (T12) and 24 (T24) months follow-up visits, respectively. Pop-PK was assessed in 11 patients: in 7 (5 HA,2 HB) it was assessed twice, before and after treatment switch to extended half-life (EHL) products, in 4 it was assessed once to modify prophylaxis treatment schedules for a more active life-style (N=2) or weight changes (N=2). Median ABR was 4 at T12 and 3.8 at T24. Reported breakthrough bleeds at T12 were 14, mainly trauma-related (N= 8) or affecting target joints (N=4), they were not reported at T24 in patients with PK-driven modified schedules (N=4) and in 4 patients under EHL treatments. Mean HEAD-US score at T0 resulted 8 (range:0-16), at T24 it was 6 (range:0-16). Mean Veritas-Pro score values were 42.7 at TO, 40.1 at T12 and 38.7 at T24. At T0, EQ-5D mean utility score was 0.82 (range: 0.68-1), at T24, the mean was 0.87 (range:0.72-1). In detail, at 24 months follow-up, there was a statistically significant (p<0.05) improvement in adherence to treatment with particular reference to the dimensions of communication and skipped doses. A tendency toward improved HEAD-US score, higher adherence and better quality of life scores, was observed in particular in patients switched to EHL products at T24, at a mean of 10 months after switching (range: 6-22 months). Conclusion: Several combined measures of haemophilia treatment monitoring, allowing visual assessment of joints status and PK profile estimates by patients have here shown to improve treatment adherence and quality of life in patients with HA and HB, this may be not only related to new available treatments but also to an increased awareness and education of patients
WHOSE SHARED HUMANITY ?: THE TRIBAL LAW AND ORDER ACT (2010), BARACK OBAMA, AND THE POLITICS OF MULTICULTURALISM IN SETTLER COLONIAL STATES
This thesis advances a critical understanding of the ways in which neoliberal multiculturalism works to naturalize settler colonialism in the United States through the queer, feminist, and decolonial use of visual, historical, and legal analysis. The Tribal Law and Order Act (TLOA) of 2010, as well as the White House signing ceremony for the TLOA serve as the main sites for this analysis. The central argument of the thesis is that multiculturalism in the United States facilitates the ongoing naturalization of settler prerogatives and that Barack Obama, through his deployment of affect and analogy, is especially effective at normalizing multicultural settler domination of colonized lands and peoples. Subtending this argument are arguments about how settler colonialism is maintained through the use of sexual violence against Indigenous people and through heteronormativity, which must be continuously enforced. The thesis, therefore, interrogates the effects of the settler state\u27s gestures toward Indigenous women and sexual violence in the TLOA and the TLOA signing ceremony. The bulk of the evidence for the thesis comes from secondary historical sources, the genealogy of laws that constitutes Federal Indian Policy in the United States, and original legal analysis of the TLOA and the TLOA Congressional Hearings, as well as original visual and discourse analyses of the TLOA signing ceremony
Independent adjudicator assessments of platelet refractoriness and rFVIIa efficacy in bleeding episodes and surgeries from the multinational Glanzmann’s thrombasthenia registry
Glanzmann’s thrombasthenia (GT) is a rare congenital bleeding disorder associated with decreased platelet aggregation due to qualitative/quantitative deficiencies of the fibrinogen receptor. Severe bleeding episodes and perioperative bleeding are typically managed with platelet transfusions, although patients can develop antiâ platelet antibodies or experience clinical refractoriness. The GT Registry (GTR) was established to collect efficacy/safety data on hemostatic treatments for GT, including recombinant factor VIIa (rFVIIa). At the request of the United States Food and Drug Administration, three hematology experts evaluated platelet refractoriness, antibody status, and rFVIIa efficacy data on a caseâ byâ case basis to support a potential indication for rFVIIa in GT. Adjudication included 195 patients with 810 events (619 severe bleeding episodes, 192 surgeries), and a consensus algorithm was developed to describe adjudicators’ coding of refractoriness and antibody status based on treatment patterns over time. Most rFVIIaâ treated events were in patients without refractoriness or antibodies. Adjudicators rated most rFVIIaâ treated bleeding episodes as successful (251/266, 94.4%; rFVIIa only, 101/109, 92.7%; rFVIIaâ ±â plateletsâ ±â other agents, 150/157, 95.5%); efficacy was consistent in patients with platelet refractorinessâ ±â antibodies (75/79, 94.9%), antibodies only (10/10, 100.0%), and neither/unknown (166/177, 93.8%). Adjudicators also rated most rFVIIaâ treated surgeries as successful (159/160, 99.4%; rFVIIa only, 65/66, 98.5%; rFVIIaâ ±â plateletsâ ±â other agents, 94/94, 100.0%); efficacy was consistent in patients with platelet refractorinessâ ±â antibodies (69/70, 98.6%), antibodies only (24/24, 100.0%), and neither/unknown (66/66, 100.0%). Unblinding the adjudicators to investigator efficacy ratings changed few assessments. Doses of rFVIIa were narrowly distributed, regardless of other hemostatic agents used.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137322/1/ajh24741.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137322/2/ajh24741_am.pd
Haemostatic and fibrinolytic changes in obese subjects undergoing bariatric surgery: the effect of different surgical procedures.
Background
Little is known about effects of different bariatric surgery procedures on haemostatic and fibrinolytic parameters.
Material and methods
Consecutive obese subjects undergoing gastric bypass (GBP) or sleeve gastrectomy (SG) were enrolled. In all patients, levels of haemostatic factors (FII, FVII, FVIII, FIX, FX, vWF, fibrinogen), fibrinolytic variables (PAI-1, t-PA and D-dimer) and natural anticoagulants (AT, protein C and protein S) were evaluated before and 2 months after surgery.
Results
A total of 77 GBP and 79 SG subjects completed the study. At baseline no difference in coagulation parameters was found between the two groups. After both GBP and SG, subjects showed significant changes in haemostatic and fibrinolytic variables and in natural anticoagulant levels. The Δ% changes in FVII, FVIII, FIX, vWF, fibrinogen, D-dimer, protein C and protein S levels were significantly higher in subjects who underwent GBP than in those who underwent SG. Multivariate analysis confirmed that GBP was a predictor of higher Δ% changes in FVII (β=0.268, p=0.010), protein C (β=0.274, p=0.003) and protein S (β=0.297, p<0.001), but not in all the other variables. Following coagulation factor reduction, 31 subjects (25.9% of GBP and 13.9% of SG; p=0.044) showed overt FVII deficiency; protein C deficiency was reported by 34 subjects (32.5% of GBP vs 11.4% of SG, p=0.033) and protein S deficiency by 39 (37.6% of GBP vs 12.6% of SG, p=0.009). Multivariate analyses showed that GBP was associated with an increased risk of deficiency of FVII (OR: 3.64; 95% CI: 1.73–7.64, p=0.001), protein C (OR: 4.319; 95% CI: 1.33–13.9, p=0.015) and protein S (OR: 5.50; 95% CI: 1.71–17.7, p=0.004).
Discussion
GBP is associated with an increased risk of post-operative deficiency in some vitamin K-dependent coagulation factors. Whereas such deficiency is too weak to cause bleeding, it is significant enough to increase the risk of thrombosis
8-Hydroxy-2-Deoxyguanosine Levels and Cardiovascular Disease: A Systematic Review and Meta-Analysis of the Literature
Significance: 8-Hydroxy-2-deoxyguanosine (8-OHdG) is generated after the repair of ROS-mediated DNA damages and, thus, is one of the most widely recognized biomarkers of oxidative damage of DNA because guanosine is the most oxidized among the DNA nucleobases. In several pathological conditions, high urinary levels of oxidized DNA-derived metabolites have been reported (e.g., cancer, atherosclerosis, hypertension, and diabetes). Recent Advances: Even if published studies have shown that DNA damage is significantly associated with the development of atherosclerosis, the exact role of this damage in the onset and progression of this pathology is not fully understood, and the association of oxidative damage to DNA with cardiovascular disease (CVD) still needs to be more extensively investigated. We performed a meta-analysis of the literature to investigate the association among 8-OHdG levels and CVD. Critical Issues: Fourteen studies (810 CVD patients and 1106 controls) were included in the analysis. We found that CVD patients showed higher 8-OHdG levels than controls (SMD: 1.04, 95%CI: 0.61, 1.47, p < 0.001, I2 = 94%, p < 0.001). The difference was confirmed both in studies in which 8-OHdG levels were assessed in urine (MD: 4.43, 95%CI: 1.71, 7.15, p = 0.001) and in blood samples (MD: 1.42, 95%CI: 0.64, 2.21, p = 0.0004). Meta-regression models showed that age, hypertension, and male gender significantly impacted on the difference in 8-OHdG levels among CVD patients and controls. Future Directions: 8-OHdG levels are higher in patients with CVD than in controls. However, larger prospective studies are needed to test 8-OHdG as a predictor of CVD. Antioxid. Redox Signal. 24, 548-555
Impact of body weight on the achievement of minimal disease activity in patients with rheumatic diseases: a systematic review and meta-analysis
An untargeted lipidomic analysis reveals depletion of several phospholipid classes in patients with familial hypercholesterolemia on treatment with Evolocumab
Familial hypercholesterolemia (FH) is caused by mutations in genes involved in low-density lipoprotein cholesterol (LDL-C) metabolism, including those for pro-protein convertase subtilisin/kexin type 9 (PCSK-9). The effect of PCSK-9 inhibition on the plasma lipidome has been poorly explored. Objective: Using an ultra-high-performance liquid chromatography-electrospray ionization-quadrupole-time of flight-mass spectrometry method, the plasma lipidome of FH subjects before and at different time intervals during treatment with the PCSK-9 inhibitor Evolocumab was explored. Methods and Results: In 25 FH subjects, heterozygotes or compound heterozygotes for different LDL receptor mutations, untargeted lipidomic revealed significant reductions in 26 lipid classes belonging to phosphatidylcholine (PC), sphingomyelin (SM), ceramide (CER), cholesteryl ester (CE), triacylglycerol (TG) and phosphatidylinositol (PI). Lipid changes were graded between baseline and 4- and 12-week treatment. At 12-week treatment, five polyunsaturated diacyl PC, accounting for 38.6 to 49.2% of total PC at baseline; two ether/vinyl ether forms; seven SM; five CER and glucosyl/galactosyl-ceramide (HEX-CER) were reduced, as was the unsaturation index of HEX-CER and lactosyl—CER (LAC-CER). Although non quantitative modifications were observed in phosphatidylethanolamine (PE) during treatment with Evolocumab, shorter and more saturated fatty acyl chains were documented. Conclusions: Depletion of several phospholipid classes occurs in plasma of FH patients during treatment with the PCSK-9 inhibitor Evolocumab. The mechanism underlying these changes likely involves the de novo synthesis of SM and CER through the activation of the key enzyme sphingomyelin synthase by oxidized LDL and argues for a multifaceted system leading to vascular improvement in users of PCSK-9 inhibitor
Lipid profile changes in patients with rheumatic diseases receiving a treatment with TNF-α blockers: a meta-analysis of prospective studies.
Some studies showed an anti-atherogenic effect of TNF-α blockers on lipid profile, but these data have been challenged.To perform a meta-analysis on lipid profile changes induced by TNF-α blocker treatment.Prospective studies on rheumatic patients receiving TNF-α blockers and providing before-and-after treatment values of triglycerides (TGs), total cholesterol (TC), HDL-cholesterol (HDLc), LDL-cholesterol (LDLc), and atherogenic index (AI) were included. Standardized mean differences (SMD) in lipid profile were analyzed at short-term (2-12 weeks), middle-term (13-24 weeks), and long-term (25-52 weeks) assessments.Thirty articles (1707 patients) were included. TNF-α blockers determined an increase in TC at short-term, middle-term, and long-term assessments (SMD: 0.20 mmol/L [95% CI: 0.04, 0.35]; SMD: 0.27 mmol/L [95% CI: 0.08, 0.46]; SMD: 0.22 mmol/L [95% CI: 0.01, 0.43]). HDLc increased only at the short-term assessment (SMD: 0.19 mmol/L [95% CI: 0.10, 0.28]), and TGs achieved a significant increase at the long-term assessment (SMD: 0.19 mmol/L [95% CI: 0.04, 0.34]). LDLc and AI were not affected by TNF-α blocker treatment.Slight but significant increases in TC occurred without any significant change in LDLc and AI. Changes in HDLc and TGs were not consistent among the different time point assessments. These quantitative changes in lipid profile do not seem to be able to explain cardiovascular risk improvement reported in patients receiving TNF-α blockers. Further studies on other mechanisms are needed to address this issue
Mesoglycan: Clinical Evidences for Use in Vascular Diseases
Vascular glycosaminoglycans (GAG) are essential components of the endothelium and vessel wall and have been shown to be involved in several biologic functions. Mesoglycan, a natural GAG preparation, is a polysaccharide complex rich in sulphur radicals with strong negative electric charge. It is extracted from porcine intestinal mucosa and is composed of heparan sulfate, dermatan sulfate, electrophoretically slow-moving heparin, and variable and minimal quantities of chondroitin sulfate. Data on antithrombotic and profibrinolytic activities of the drug show that mesoglycan, although not indicated in the treatment of acute arterial or venous thrombosis because of the low antithrombotic effect, may be useful in the management of vascular diseases, when combined with antithrombotics in the case of disease of cerebral vasculature, and with antithrombotics and vasodilator drugs in the case of chronic peripheral arterial disease. The protective effect of mesoglycan in patients with venous thrombosis and the absence of side effects, support the use of GAG in patients with chronic venous insufficiency and persistent venous ulcers, in association with compression therapy (zinc bandages, multiple layer bandages, etc.), elastic compression stockings, and local care, and in the prevention of recurrences in patients with previous DVT following the standard course of oral anticoagulation treatment
- …