Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1?year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn?s disease or ulcerative colitis who have achieved clinical remission for ?6?months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1?year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. Results: Enrolment began in 2016, and the study is expected to end in 2020. Conclusions: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. Clinical trial reference number: EudraCT 2015-001410-1

Open borders in the nineteenth century : constructing the national, the citizen and the foreigner in South America

This working paper describes and explains the historical origins of the division between the national and the foreigner in South America. In the early nineteenth century, all the previously Spanish possessions in South America as well as Brazil achieved independence. With this new freedom, countries turned their attention to asserting their statehood through the delineation of three constitutive elements: government, territory and population. The new governments had to define who were going to be considered as nationals, citizens and foreigners, and the rights that pertained to each of these categories. These countries were all concerned with attracting new settlers and very early on introduced constitutional provisions on open borders and equal treatment for foreigners. White, male Europeans were the principal addresses of open borders provisions in an effort to entice them to settle in territories presented as empty to the exclusion of indigenous groups, bring new industries, and contribute to the whitening of mixed race populations. Whilst weak statehood came with independence, forming nations was a much longer process and States used migration and citizenship policies as tools to define nationhood