Dermatological conditions during TNF-α-blocking therapy in patients with rheumatoid arthritis: a prospective study

Various dermatological conditions have been reported during tumor necrosis factor (TNF)-α-blocking therapy, but until now no prospective studies have been focused on this aspect. The present study was set up to investigate the number and nature of clinically important dermatological conditions during TNF-α-blocking therapy in patients with rheumatoid arthritis (RA). RA patients starting on TNF-α-blocking therapy were prospectively followed up. The numbers and natures of dermatological events giving rise to a dermatological consultation were recorded. The patients with a dermatological event were compared with a group of prospectively followed up RA control patients, naive to TNF-α-blocking therapy and matched for follow-up period. 289 RA patients started TNF-α-blocking therapy. 128 dermatological events were recorded in 72 patients (25%) during 911 patient-years of follow-up. TNF-α-blocking therapy was stopped in 19 (26%) of these 72 patients because of the dermatological event. More of the RA patients given TNF-α-blocking therapy (25%) than of the anti-TNF-α-naive patients (13%) visited a dermatologist during follow-up (P < 0.0005). Events were recorded more often during active treatment (0.16 events per patient-year) than during the period of withdrawal of TNF-α-blocking therapy (0.09 events per patient-year, P < 0.0005). The events recorded most frequently were skin infections (n = 33), eczema (n = 20), and drug-related eruptions (n = 15). Other events with a possible relation to TNF-α-blocking therapy included vasculitis, psoriasis, drug-induced systemic lupus erythematosus, dermatomyositis, and a lymphomatoid-papulosis-like eruption. This study is the first large prospective study focusing on dermatological conditions during TNF-α-blocking therapy. It shows that dermatological conditions are a significant and clinically important problem in RA patients receiving TNF-α-blocking therapy

European clinical practice guidelines for the definition, diagnosis, and treatment of oligometastatic esophagogastric cancer (OMEC-4)

Introduction: The OligoMetastatic Esophagogastric Cancer (OMEC) project aims to provide clinical practice guidelines for the definition, diagnosis, and treatment of esophagogastric oligometastatic disease (OMD). Methods: Guidelines were developed according to AGREE II and GRADE principles. Guidelines were based on a systematic review (OMEC-1), clinical case discussions (OMEC-2), and a Delphi consensus study (OMEC-3) by 49 European expert centers for esophagogastric cancer. OMEC identified patients for whom the term OMD is considered or could be considered. Disease-free interval (DFI) was defined as the time between primary tumor treatment and detection of OMD. Results: Moderate to high quality of evidence was found (i.e. 1 randomized and 4 non-randomized phase II trials) resulting in moderate recommendations. OMD is considered in esophagogastric cancer patients with 1 organ with ≤ 3 metastases or 1 involved extra-regional lymph node station. In addition, OMD continues to be considered in patients with OMD without progression in number of metastases after systemic therapy. 18F-FDG PET/CT imaging is recommended for baseline staging and for restaging after systemic therapy when local treatment is considered. For patients with synchronous OMD or metachronous OMD and a DFI ≤ 2 years, recommended treatment consists of systemic therapy followed by restaging to assess suitability for local treatment. For patients with metachronous OMD and DFI &gt; 2 years, upfront local treatment is additionally recommended. Discussion: These multidisciplinary European clinical practice guidelines for the uniform definition, diagnosis and treatment of esophagogastric OMD can be used to standardize inclusion criteria in future clinical trials and to reduce variation in treatment.</p

Circulating tumor cell enumeration and characterization in metastatic castration-resistant prostate cancer patients treated with cabazitaxel

(1) Background: Markers identifying which patients with metastatic, castration-resistant prostate cancer (mCRPC) will benefit from cabazitaxel therapy are currently lacking. Therefore, the aim of this study was to identify markers associated with outcome to cabazitaxel therapy based on counts and gene expression profiles of circulating tumor cells (CTCs). (2) Methods: From 120 mCRPC patients, CellSearch enriched CTCs were obtained at baseline and after 6 weeks of cabazitaxel therapy. Furthermore, 91 genes associated with prostate cancer were measured in mRNA of these CTCs. (3) Results: In 114 mCRPC patients with an evaluable CTC count, the CTC count was independently associated with poor progression-free survival (PFS) and overall survival (OS) in multivariable analysis with other commonly used variables associated with outcome in mCRPC (age, prostate specific antigen (PSA), alkaline phosphatase, lactate dehydrogenase (LDH), albumin, hemoglobin), together with alkaline phosphatase and hemoglobin. A five-gene expression profile was generated to predict for outcome to cabazitaxel therapy. However, even though this signature was associated with OS in univariate analysis, this was not the case in the multivariate analysis for OS nor for PFS. (4) Conclusion: The established five-gene expression profile in CTCs was not independently associated with PFS nor OS. However, along with alkaline phosphatase and hemoglobin, CTC-count is independently associated with PFS and OS in mCRPC patients who are treated with cabazitaxel

Impact of nationwide enhanced implementation of best practices in pancreatic cancer care (PACAP-1): A multicenter stepped-wedge cluster randomized controlled trial

Background: Pancreatic cancer has a very poor prognosis. Best practices for the use of chemotherapy, enzyme replacement therapy, and biliary drainage have been identified but their implementation in daily clinical practice is often suboptimal. We hypothesized that a nationwide program to enhance implementation of these best practices in pancreatic cancer care would improve survival and quality of life. Methods/design: PACAP-1 is a nationwide multicenter stepped-wedge cluster randomized controlled superiority trial. In a per-center stepwise and randomized manner, best practices in pancreatic cancer care regarding the use of (neo)adjuvant and palliative chemotherapy, pancreatic enzyme replacement therapy, and metal biliary stents are implemented in all 17 Dutch pancreatic centers and their regional referral networks during a 6-week initiation period. Per pancreatic center, one multidisciplinary team functions as reference for the other centers in the network. Key best practices were identified from the literature, 3 years of data from existing nationwide registries within the Dutch Pancreatic Cancer Project (PACAP), and national expert meetings. The best practices follow the Dutch guideline on pancreatic cancer and the current state of the literature, and can be executed within daily clinical practice. The implementation process includes monitoring, return visits, and provider feedback in combination with education and reminders. Patient outcomes and compliance are monitored within the PACAP registries. Primary outcome is 1-year overall survival (for all disease stages). Secondary outcomes include quality of life, 3- and 5-year overall survival, and guideline compliance. An improvement of 10% in 1-year overall survival is considered clinically relevant. A 25-month study duration was chosen, which provides 80% statistical power for a mortality reduction of 10.0% in the 17 pancreatic cancer centers, with a required sample size of 2142 patients, corresponding to a 6.6% mortality reduction and 4769 patients nationwide. Discussion: The PACAP-1 trial is designed to evaluate whether a nationwide program for enhanced implementation of best practices in pancreatic cancer care can improve 1-year overall survival and quality of life. Trial registration: ClinicalTrials.gov, NCT03513705. Trial opened for accrual on 22th May 2018

The Role of Information Technology in Ex-ante Transaction Processes

The electronic market hypothesis (EMH) has found little support in research practice. Alternative hypotheses have been formulated and tested with more satisfactory results. However, today’s Internet successes (e.g. Amazon bookshop) seem to support the original EMH. This implies that the EMH may be correct in forecasting electronic markets, but wrong in determining the conditions under which these markets would arise. This article re-investigates the EMH conditions, and proposes a framework, based on marketing and transaction cost theory. The framework is used to score and compare some 50 electronic market sites on the Internet (books, cds and mortgages)

The move to ex-ante

The electronic market hypothesis (EMH) has found little support in research practice. Alternative hypotheses have been formulated and tested with more satisfactory results. However, today's Internet creates new business opportunities which seem to support the original EMH (e.g. Amazon bookshop). This implies that the EMH may be correct in forecasting electronic markets, but wrong in determining the conditions under which this would take place. Moreover, modern electronic markets appear not always to evolve along the predicted process (biased, unbiased, personalized markets). This article investigates former EMH-related research (Hess & Kemerer, 1994) and analyzes a few modern Internet business successes and failures, concluding that (1) the EMH-condition 'complexity of the product description' appears to be equivocal and (2) the degree to which ICT supports Ex-Ante actions (such as exchanging product and supplier information, advise, quotes and negotiating) seems to be an important discriminating factor between success and failure in electronic commerce (whether in markets or in hierarchies). Furthermore, it is shown that virtual communities, the evolution of which is not covered by the EMH, may play an important role as electronic markets too. It is shown that augmentation of the EMH can not solve the problems, and a new hypothesis, the Move to Ex-Ante hypothesis, is formulated.electronic markets; transaction costs; virtual communities.

Predicting online purchase behavior : replications and tests of competing models

Online purchase behavior is definitely an interesting and relevant issue for marketeers today. In this paper, we report on a study into the antecedents of online purchase intention for B2C websites. In particular, this research juxtaposes two competing models that explain online purchase intention. The first model is trust-oriented and argues that online purchase intention is primarily predicted by trust in the company. The second model is website-oriented and argues that purchase intention is primarily predicted by usefulness and ease-of-use of the e-commerce website. In order to test to what extent each of these orientations has merit, a replication was carried out of the trust-oriented study by Jarvenpaa, Tractinsky, and Vitale (2000). The model was extended with the website-oriented constructs from by Chau, Au, and Tam (2000), first developed by Davis (1989). The replication study involved 227 undergraduate students. 64.4% of them had never bought online; 8.8% had bought on the intemet at least four times. Consequently, the results of the study are somewhat biased towards initiaZ purchase intention as opposed to repeat purchase intention. The research has a number of important findings. First, online purchase intention at the website is strongly determined by attitude towards online shopping at the website, providing support for the Theory of Reasoned Action in a website context. Second, perceived risk of shopping strongly influences attitude towards shopping. Trust in the company does not influence attitude directly, but indirectly through a significant impact on perceived risk. Third, perceived reputation influences trust, whereas perceived size does not, at least not in the case of low-value products. Fourth, website ease-of-use strongly and positively influences website usefulness. Finally, website usefulness does not significantly influence attitude towards shopping and online purchase intention. We conclude that trust-oriented models appear to be more appropriate to explain online purchase intention than website-oriented models.