Emotional distress in haemophilia: factors associated with the presence of anxiety and depression symptoms among adults

Introduction: Haemophilia is related to several clinical and psychosocial challenges that have been associated with increased emotional distress. These may impact on disease adjustment and health outcomes, reinforcing the attention given to psychosocial health of people with haemophilia (PWH), in the scope of optimal comprehensive care. Aim: To identify potentially modifiable factors associated with the presence of anxiety and depression symptoms among adult PWH. Methods: This was a cross-sectional observational study examining sociodemographic, clinical and psychosocial variables among 102 patients with haemophilia A or B who participated on a mail survey of haemophilia in Portugal. Results: People with haemophilia revealing higher anxiety and depression symptoms were more likely to have had, in the previous year, more urgent hospital visits due to haemophilia, more bleeding episodes, more affected joints and pain, as well as worst levels of perceived functionality and quality of life. After controlling for demographic (age and education) and clinical (haemophilia severity and joint deterioration) variables in multivariate hierarchical logistic regression analyses, professional status (OR = 4.646, P = .004; OR = 3.333, P = .029) and pain interference (OR = 1.397, P = .011; OR = .1.347, P = .037) were significantly associated with both anxiety and depression symptoms. Additionally, physical activity (OR = 0.302, P = .024) and the perception of consequences underlying haemophilia (OR = 1.600, P = .012) also emerged as key factors significantly associated with depression symptoms. Conclusion: Current findings increased knowledge on factors associated with anxiety and depression among PWH. These highlight potential intervention targets, which are amenable to change through evidence-based tailored interventions aiming to decrease emotional distress, promote well-being and improving haemophiliarelated health outcomes among these patients.Novo Nordisk HERO Research, Grant/Award Number: 2015; Portuguese Foundation for Science and Technology, Grant/Award Number: SFRH/BPD/103529/2014info:eu-repo/semantics/publishedVersio

Residual platelet ADP reactivity after clopidogrel treatment is dependent on activation of both the unblocked P2Y1 and the P2Y12 receptor and is correlated with protein expression of P2Y12

Two ADP receptors have been identified on human platelets: P2Y1 and P2Y12. The P2Y12 receptor blocker clopidogrel is widely used to reduce the risks in acute coronary syndromes, but, currently, there is no P2Y1 blocker in clinical use. Evidence for variable responses to clopidogrel has been described in several reports. The mechanistic explanation for this phenomenon is not fully understood. The aim of this study was to examine mechanisms responsible for variability of 2MeS-ADP, a stable ADP analogue, induced platelet reactivity in clopidogrel-treated patients. Platelet reactivity was assessed by flow cytometry measurements of P-selectin (CD62P) and activated GpIIb/IIIa complex (PAC-1). Residual 2MeS-ADP activation via the P2Y12 and P2Y1 receptors was determined by co-incubation with the selective antagonists AR-C69931 and MRS2179 in vitro. P2Y1 and P2Y12 receptor expression on both RNA and protein level were determined, as well as the P2Y12 H1 or H2 haplotypes. Our data suggest that the residual platelet activation of 2MeS-ADP after clopidogrel treatment is partly due to an inadequate antagonistic effect of clopidogrel on the P2Y12 receptor and partly due to activation of the P2Y1 receptor, which is unaffected by clopidogrel. Moreover, a correlation between increased P2Y12 protein expression on platelets and decreased response to clopidogrel was noticed, r2=0.43 (P<0.05). No correlation was found between P2Y12 mRNA levels and clopidogrel resistance, indicating post-transcriptional mechanisms. To achieve additional ADP inhibition in platelets, antagonists directed at the P2Y1 receptor could be more promising than the development of more potent P2Y12 receptor antagonists

Biomarker Analysis of Stored Blood Products: Emphasis on Pre-Analytical Issues

Millions of blood products are transfused every year; many lives are thus directly concerned by transfusion. The three main labile blood products used in transfusion are erythrocyte concentrates, platelet concentrates and fresh frozen plasma. Each of these products has to be stored according to its particular components. However, during storage, modifications or degradation of those components may occur, and are known as storage lesions. Thus, biomarker discovery of in vivo blood aging as well as in vitro labile blood products storage lesions is of high interest for the transfusion medicine community. Pre-analytical issues are of major importance in analyzing the various blood products during storage conditions as well as according to various protocols that are currently used in blood banks for their preparations. This paper will review key elements that have to be taken into account in the context of proteomic-based biomarker discovery applied to blood banking

Static platelet adhesion, flow cytometry and serum TXB2 levels for monitoring platelet inhibiting treatment with ASA and clopidogrel in coronary artery disease: a randomised cross-over study

<p>Abstract</p> <p>Background</p> <p>Despite the use of anti-platelet agents such as acetylsalicylic acid (ASA) and clopidogrel in coronary heart disease, some patients continue to suffer from atherothrombosis. This has stimulated development of platelet function assays to monitor treatment effects. However, it is still not recommended to change treatment based on results from platelet function assays. This study aimed to evaluate the capacity of a static platelet adhesion assay to detect platelet inhibiting effects of ASA and clopidogrel. The adhesion assay measures several aspects of platelet adhesion simultaneously, which increases the probability of finding conditions sensitive for anti-platelet treatment.</p> <p>Methods</p> <p>With a randomised cross-over design we evaluated the anti-platelet effects of ASA combined with clopidogrel as well as monotherapy with either drug alone in 29 patients with a recent acute coronary syndrome. Also, 29 matched healthy controls were included to evaluate intra-individual variability over time. Platelet function was measured by flow cytometry, serum thromboxane B₂(TXB₂)-levels and by static platelet adhesion to different protein surfaces. The results were subjected to Principal Component Analysis followed by ANOVA, t-tests and linear regression analysis.</p> <p>Results</p> <p>The majority of platelet adhesion measures were reproducible in controls over time denoting that the assay can monitor platelet activity. Adenosine 5'-diphosphate (ADP)-induced platelet adhesion decreased significantly upon treatment with clopidogrel compared to ASA. Flow cytometric measurements showed the same pattern (r²= 0.49). In opposite, TXB₂-levels decreased with ASA compared to clopidogrel. Serum TXB₂and ADP-induced platelet activation could both be regarded as direct measures of the pharmacodynamic effects of ASA and clopidogrel respectively. Indirect pharmacodynamic measures such as adhesion to albumin induced by various soluble activators as well as SFLLRN-induced activation measured by flow cytometry were lower for clopidogrel compared to ASA. Furthermore, adhesion to collagen was lower for ASA and clopidogrel combined compared with either drug alone.</p> <p>Conclusion</p> <p>The indirect pharmacodynamic measures of the effects of ASA and clopidogrel might be used together with ADP-induced activation and serum TXB₂for evaluation of anti-platelet treatment. This should be further evaluated in future clinical studies where screening opportunities with the adhesion assay will be optimised towards increased sensitivity to anti-platelet treatment.</p

Vem äter kakan? : En kvalitativ studie kring klädbranschens nyttjande av personlig data i marknadsföringssyfte i relation till kundens integritet online

History: Digitalization brings great benefits to companies regardless of market. One of the markets that is undergoing change is the retail sector where e-commerce services are the new environment. This environment benefits from the innovative solutions that the consumer uses, such as smartphones. These and other connected devices are constantly generating user data that companies can then take advantage of. This, in turn, has sparked discussions about the individual's integrity in relation to companies' use of this data. Purpose: The purpose of the study is to investigate how retail companies in Sweden use personal data for marketing purposes and how important it is for the consumer to maintain their online integrity and how personalized advertising is perceived by the consumer. Theory: The theories and concepts that are explored are personal data, big data, data-driven marketing, CRM, the marketing mix as well as integrity and security. Every theory is described thoroughly and summarized to create an understanding as to why these are selected.  Methodology: Methodical choices have been made in the form of targeting the Swedish clothing industry and Swedish consumers. A qualitative approach was used. Two semi-structured interviews were conducted with representatives from a company and a trade organization selected through a benchmarked selection of candidates. Semi-structured interviews were also carried out with eight consumers close or related to the researchers. Results: The results show an uncertainty of customers when it comes to what companies are allowed to do and how they actually use their personal data. Some also find it unsettling to receive personalized advertisements. Others appreciate advertisement based on their preferences. The company representatives saw an overarching possibility to create better personalized experiences for the customer thanks to the data generated.  Conclusions: Based on the study's results, it can be concluded that companies in the clothing industry in Sweden use data from the consumer for marketing purposes to both retain customers and create new customer relationships. The personal data collected has proven to be very important for companies from a competitive perspective. The study suggests that the consumer values his or her integrity highly but does not act accordingly and is largely unaware of any restrictions on his or her online privacy. The general attitude the consumer has towards personalized advertising is that it is unpleasant. However, the study also shows that it can be appreciated, given that the content is interesting for the consumer. Should opportunities for financial compensation from the companies to access individual personal data, the consumer would not choose to take advantage of this.Bakgrund: Digitaliseringen för med sig stora fördelar för företag oavsett marknad. En av dessa marknader som är i förändring är detaljhandeln där e-handelstjänster är den nya miljön. Denna miljö gynnas av de innovativa lösningar som konsumenten nyttjar, exempelvis smartphones. Dessa och andra uppkopplade enheter genererar ständigt data om användaren som företagen sedan kan dra nytta av. Det här har i sin tur väckt diskussioner kring individens integritet i förhållande till företagens användande av denna data. Syfte: Syftet med studien är att undersöka hur företag inom detaljhandeln i Sverige använder sig av personlig data i marknadsföringssyfte samt hur viktigt det är för konsumenten att bibehålla sin integritet online och hur personanpassad reklam upplevs av konsumenten. Teori: De teorier och begrepp som behandlas i studien är datadriven marknadsföring, CRM, marknadsföringsmixen samt integritet och säkerhet. Varje teori beskrivs ingående och sammanfattas i en teoretisk referensram i slutet av kapitlet för att skapa en förståelse till varför just dessa är valda.  Metod: Metodmässiga val har gjort i form av att rikta in sig på svenska klädesbranschen och svenska konsumenter. En kvalitativ ansats har använts i studien och två semistrukturerade intervjuer har genomförts med representanter från ett företag samt en branschorganisation som valts genom ett målstyrt urval. Semistrukturerade intervjuer har även utförts med åtta konsumenter genom ett bekvämlighetsurval. Empiri: Övergripande ansåg representanterna för företaget samt branschorganisationen att data gör det möjligt att skapa bättre upplevelser för kunden då man kan individanpassa erbjudanden. Studiens resultat visar även på en viss osäkerhet hos konsumenterna gällande vad företagen får göra och faktiskt gör med deras personliga data. Vissa respondenter tycker att det är obehagligt att få personifierad reklam, andra respondenter uppskattar reklam baserad på deras preferenser.  Slutsats: Utifrån studiens resultat kan man konstatera att företag inom klädbranschen i Sverige använder data från konsumenten i marknadsföringssyfte för att både behålla kunder samt skapa nya kundrelationer. Den personliga datan som samlas in har visat sig vara väldigt betydelsefull för företagen utifrån ett konkurrensmässigt perspektiv. Studien tyder på att konsumenten värderar sin integritet högt men agerar dock inte därefter och är i stor utsträckning inte medveten om inskränkningar i sin integritet online. Den genomgående inställningen konsumenten har till personanpassad reklam är att det är obehagligt. Dock visar studien även på att den kan uppskattas om respondenten finner innehållet intressant. Skulle möjligheten till ekonomisk ersättning från företagen för att ta del av individens personliga data skulle konsumenten inte välja att ta del av detta

Diabetes type 2: relationships between lysosomal exocytosis of circulating normal-sized platelets and in vitro alpha-thrombin-evoked platelet responses

Background/objective: Type 2 diabetes is a major risk factor for atherosclerotic disease. It is well agreed that the reactivity of diabetic platelets is increased but how platelet reactivity regulates is unknown. In our laboratory, density separated platelets have been investigated extensively and high- and low-density platelets circulate in an activated state. The density distribution of circulating platelets is altered in diabetes type 2 as well. We hypothesize that such platelets modify whole blood (WB) in vitro a-thrombin-evoked (10 mu M/mL) activity in type 2 diabetes. Thus, the study aims to identify features of circulating normal-sized density subpopulations affecting whole blood (WB) platelet reactivity in type 2 diabetes. Patients and methods: Patients with type 2 diabetes (n = 16) were enrolled. Their normal-sized platelets were divided into density subfractions (n = 16) using continuous polyvinylpyrrolidone-coated silica (Percoll (TM)) gradients (density span, 1.090-1.040 kg/L) containing prostaglandin E-1. The proportions (%) of such density-separated platelets expressing lysosomal-associated membrane protein 1 (LAMP-1) were analyzed using a flow cytometer. Further, determinations of WB alpha-thrombin-evoked (10 U/mL) surface LAMP-1 (an assessment of lysosomal release), the fibrinogen (a(IIb)beta(3)) receptor activity, annexin V (binds to exposed membrane phosphatidylserine), and mitochondrial transmembrane potentials (an estimate of organelle integrity) were performed. Surface LAMP-1 expressions of individual normal-sized platelet density subpopulations were stratified into equal-sized groups (n = 2) depending on reactivity, as judged from the alpha-thrombin-induced WB activity markers. Results: With some exceptions, the proportion of normal-sized circulating platelets showing spontaneous LAMP-1 was strongly associated with WB alpha-thrombin-evoked (10 U/mL) surface LAMP-1 and a(IIb)beta(3) receptor activity. LAMP-1-expressing normal-sized platelets also displayed inverse associations with WB alpha-thrombin-induced surface annexin V and mitochondrial damage, which are features of procoagulant platelets. Conclusions: From the current descriptive work only involving type 2 diabetes, it is impossible to judge whether the findings are features of the disease or if they occur in healthy individuals as well. However, the study describes LAMP-1 expressing subpopulations of circulating normal-sized platelets that associate with WB a-thrombin (10 U/mL) responses in vitro. Increased proportions of such platelets induced lysosomal release and a(IIb)beta(3) receptor activity, whereas lower proportions promoted WB agonist-induced procoagulant platelet creation. It is to hypothesize that the new described regulatory mechanism could in the future offer a possibility to influence platelet behavior in type 2 diabetes. KEY MESSAGES circle Lysosomal exocytosis of circulating platelets influences reactivity, as determined by agonistinduced platelet reactions in vitro circle Thus, the low release of lysosomes by normal-sized platelets in vivo increases agonist-evoked procoagulant platelet production. circle Higher lysosomal exocytosis of circulating normal-sized platelets promotes platelet aggregation and secretion.Funding Agencies|OEstergoetland County Council, Sweden</p