The Impact of Interface Quality on Trust in Web Retailers

Web retailing is expected to grow at aggressive rates in future years. One of the most important factors that is slowing down this growth is the lack of trust of potential customers. So, as transactions through the internet develop and mature, success will largely be dependent on gaining and0501ntaining this trust. It has been suggested that the quality of the user interface of the Web site is a determinant of the initial establishment of trust. In this article, we describe a study where 66 subjects were asked to perform some predefined book purchasing task in a series of sites with varying interface quality. We found a strong relationship between interface quality and trust. We also found some components of user interface quality to be more important than others and discuss the implications for Web site design. Le manque de confiance constitue une des barrières les plus importantes à l'adoption et au développement du commerce électronique. Centré sur le commerce électronique de détail, ce travail présente un modèle permettant d'analyser le développement de la confiance du consommateur en fonction des caractéristiques de ce dernier - sa propension - et de la perception qu'il a de certaines caractéristiques du commerçant, soit l'intégrité, l'habilité et la bienveillance de ce dernier. L'utilisabilité de l'interface graphique a été retenue comme étant le facteur-clé en ce qui concerne la perception de ces caractéristiques. Le rôle de chacune des dimensions composant l'utilisabilité a donc été étudié et mis en évidence relativement à la confiance développée par le consommateur.User interface, laboratory experiment, trust, usability, electronic retailing, web design, Interface utilisateur, expérimentation en laboratoire, confiance, b2c, commerce électronique (détail), design de site web

Preference for a prefilled syringe or an auto-injection device for delivering golimumab in patients with moderate-to-severe ulcerative colitis: a randomized crossover study.

Purpose: Simponi((R)) (golimumab, MSD) is a fully human monoclonal antibody against tumor necrosis factor alpha administered subcutaneously using an autoinjector or a prefilled syringe. This study examined preference for administration of golimumab by autoinjector or prefilled syringe in patients with moderate-to-severe ulcerative colitis (UC). Patients and methods: This was a multicenter, open-label, randomized crossover trial (EudraCT no 2014-000656-29). Patients with moderate-to-severe UC were randomized 1:1 to receive 2 subcutaneous injections of 50 mg golimumab with the autoinjector followed by 2 injections of 50 mg with the prefilled syringe or the same 4 injections administered in the opposite order. Patients assessed preference, ease of use, and discomfort immediately after the injections and 2 weeks later. Results: Ninety-one patients were included (median age=42.7 years [range, 19.7-93.7]; 58% male). The autoinjector was preferred by 76.9% of patients immediately after injections and by 71.4% 2 weeks later. The autoinjector was more often considered extremely easy or easy to use (94.5%) than the prefilled syringe (73.6%). Moderate discomfort or worse was reported by more patients when using the prefilled syringe (20.9%) than when using the autoinjector (5.5%), and severe discomfort or discomfort preventing injection of future doses was reported by 8.8% for the pre-filled syringe but not at all when using the autoinjector. A favorable or extremely favorable overall impression was reported by 89.0% for the autoinjector and 72.5% for the prefilled syringe. Conclusion: Most patients with moderate-to-severe UC preferred to self-administer golimumab with the autoinjector over a prefilled syringe

Novel Crohn Disease Locus Identified by Genome-Wide Association Maps to a Gene Desert on 5p13.1 and Modulates Expression of PTGER4

To identify novel susceptibility loci for Crohn disease (CD), we undertook a genome-wide association study with more than 300,000 SNPs characterized in 547 patients and 928 controls. We found three chromosome regions that provided evidence of disease association with p-values between 10(−6) and 10(−9). Two of these (IL23R on Chromosome 1 and CARD15 on Chromosome 16) correspond to genes previously reported to be associated with CD. In addition, a 250-kb region of Chromosome 5p13.1 was found to contain multiple markers with strongly suggestive evidence of disease association (including four markers with p < 10(−7)). We replicated the results for 5p13.1 by studying 1,266 additional CD patients, 559 additional controls, and 428 trios. Significant evidence of association (p < 4 × 10(−4)) was found in case/control comparisons with the replication data, while associated alleles were over-transmitted to affected offspring (p < 0.05), thus confirming that the 5p13.1 locus contributes to CD susceptibility. The CD-associated 250-kb region was saturated with 111 SNP markers. Haplotype analysis supports a complex locus architecture with multiple variants contributing to disease susceptibility. The novel 5p13.1 CD locus is contained within a 1.25-Mb gene desert. We present evidence that disease-associated alleles correlate with quantitative expression levels of the prostaglandin receptor EP4, PTGER4, the gene that resides closest to the associated region. Our results identify a major new susceptibility locus for CD, and suggest that genetic variants associated with disease risk at this locus could modulate cis-acting regulatory elements of PTGER4

Open-label extension of a phase 2 trial of risankizumab in patients with moderate-to-severe Crohn's disease

Background: Risankizumab, an anti-interleukin-23 antibody, was superior to placebo in achieving clinical and endoscopic remission at week 12 in a randomised, phase 2 induction study in patients with moderately to severely active Crohn’s disease. The efficacy and safety of extended intravenous induction and/or subcutaneous maintenance therapy with risankizumab was assessed. Methods: Following 12-week, double-blind, randomised, induction treatment comparing 200 mg or 600 mg intravenous risankizumab to placebo every 4 weeks, patients without deep remission, defined as clinical (Crohn’s Disease Activity Index <150) and endoscopic remission (Crohn’s Disease Endoscopic Index of Severity [CDEIS] ≤4 [≤2 for patients with isolated ileitis]), received open-label 600 mg intravenous risankizumab (every 4 weeks) and patients in deep remission underwent washout until week 26 (Period 2). At week 26, patients in clinical remission received maintenance treatment (Period 3) with 180 mg subcutaneous risankizumab (every 8 weeks). Efficacy endpoints included clinical and endoscopic response and remission at weeks 26 (Period 2) and 52 (Period 3) respectively; safety was assessed through both periods. Study registration: ClinicalTrials.gov, NCT02031276. Findings: In Period 2, 101 patients were treated with 600 mg risankizumab resulting in an increase in clinical remission rates at week 26 versus week 12 for all original designated treatment groups: 55% versus 18%, 59% versus 21%, and 47% versus 26% for placebo, 200, and 600 mg risankizumab, respectively. Of the 62 patients receiving maintenance treatment, 54 completed treatment. At week 52, clinical remission was maintained by 71% of patients; endoscopic remission and response (>50% CDEIS reduction from baseline) was achieved by 35% and 55% of patients, respectively, and 29% of patients achieved deep remission. Risankizumab was well tolerated with no new safety signals. Interpretation: Extended induction treatment with open-label intravenous risankizumab was effective in increasing clinical response and remission rates at week 26. Open-label subcutaneous risankizumab maintained remission till week 52 in most patients who were in clinical remission at week 26. Selective blockade of interleukin-23 warrants further evaluation as treatment for Crohn’s disease.Boehringer Ingelhei

Evolution of Endoscopic Lesions in Steroid-Refractory Acute Severe Ulcerative Colitis Responding to Infliximab or Cyclosporine

BACKGROUND/AIMS: Few data on the evolution of endoscopic findings are available in patients with acute severe ulcerative colitis (ASUC). The aim of this study was to describe this evolution in a prospective cohort. METHODS: Patients admitted for a steroid-refractory ASUC and included in a randomized trial comparing infliximab and cyclosporine were eligible if they achieved steroid-free clinical remission at day 98. Flexible sigmoidoscopies were performed at baseline, days 7, 42 and 98. Ulcerative colitis endoscopic index of severity (UCEIS) and its sub-scores - vascular pattern, bleeding and ulceration/erosion - were post-hoc calculated. Global endoscopic remission was defined by a UCEIS of 0, and partial endoscopic remission by any UCEIS sub-score of 0. RESULTS: Among the 55 patients analyzed (29 infliximab and 26 cyclosporine), 49 (83%) had UCEIS >= 6 at baseline at baseline. Partial endoscopic remission rates were higher for bleeding than for vascular pattern and for ulcerations/erosions at day 7 (20% vs. 4% and 5% (n = 55); p CONCLUSION: In steroid-refractory ASUC patients responding to a second-line medical therapy, endoscopic remission process started with bleeding remission and was not achieved in half the patients at day 98 for vascular pattern. Infliximab provided a higher endoscopic remission rate than cyclosporine at day 98.Peer reviewe

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Usefulness of thiopurine methyltransferase and thiopurine metabolite analysis in clinical practice in patients with inflammatory bowel diseases.

Thiopurines (TP) are widely used in the management of inflammatory bowel diseases. Side-effects and inefficacy are a major concern as they lead to withdrawal of the drug. Tools investigating TP metabolism are useful to avoid inadequate cessation of TP therapy. TP metabolism is complex and many enzymes are involved. Among them, Thiopurine methyltransferase (TPMT) is the only one routinely measured by pheno- or genotyping. In this review, the rationale for TPMT and thiopurine metabolites, 6-thioguanine nucleotides and 6-methylmercaptopurine, determination in clinical practice is discussed, specifically in case of thiopurine failure and recommendations are given about their interpretation and potential dose optimization of TP drugs

L’azathioprine dans les maladies inflammatoires chroniques intestinales : impact de son métabolisme sur l’efficacité et la sécurité thérapeutique

Thiopurines (TP) are widely used in the management of inflammatory bowel diseases. Side effects and inefficacy are a major concern as they lead to withdrawal of the drug. Tools investigating TP metabolism are useful to avoid inadequate cessation of TP therapy. TP metabolism is complex and many enzymes are involved. Among them, Thiopurine methyl transferase is the only one routinely measured by pheno- or genotyping. A decreased TPMT activity results in a potential overdosing of TP drugs leading to myelotoxicity, whereas an ultra-high activity leads to TP ineffectiveness and overproduction of methylated compounds responsible for hepatotoxicity. TPMT determination prior to TP treatment results in an individual adapted dose. Xanthine oxidase ⁄ dehydrogenase (XOD), inosine triphosphate pyrophosphatase (ITPA) and glutathion-S-transferase (GST) are other promising enzyme targets that might help to explain TP efficacy or toxicity. ITPA and GST polymorphisms might potentially be related to some TP side effects. Drug interactions are discussed and, specifically allopurinol and aminosalicylates in terms of benefits and inconvenients. XOD inhibition by allopurinol could avoid TP-related hepatotoxicity if TP and allopurinol doses are adjusted. Utilization of thiopurine metabolites, 6-thioguanine nucleotides and 6-methylmercaptopurine, is discussed, specifically, in case of thiopurine failure and recommendations are given about their interpretation and potential dose optimization. These enzymes and metabolites tests are complementary to the regular monitoring of blood cells count and liver tests which remains mandatory.(SBIM 3) -- UCL, 201

Le traitement des fistules anales dans la maladie de Crohn [Treatment of anal fistula in Crohn's disease]

Crohn's disease (CD) is complicated by perianal fistulas in up to 40 % of patients at some time during the course of their disease. Perianal fistulas are particularly frequent when the distal portion of the digestive tract is involved and are one of the most difficult sequelae of Crohn's disease, with an often incomplete response to treatment. The goal of the treatment is symptom relief and improved quality of life in an attempt to cure the lesions, prevent relapse, and reduce the risk of sphincter destruction. Modalities used to diagnose and classify Crohn's perianal fistulas tracks with a high diagnostic accuracy include examination under anaesthesia, pelvic magnetic resonance imaging and endoanal ultrasonography. The classification of the fistula as simple or complex depends on the anatomical fistula track, the activity and the clinical severity of the disease. A combined medical and surgical approach in the management of such patients is the optimal treatment bearing higher success rate. A simple fistula is usually treated by antibiotics and fistulotomy. A complex fistula is often treated by noncutting scions, antibiotics, azathioprine and in many cases by anti-TNF agents such as infliximab. In a second step, fibrin glue or rectal advancement flap can be considered