Evidence-based selection on the appropriate FIT cut-off point in CRC screening programs in the COVID pandemic

Background: The COVID pandemic has forced the closure of many colorectal cancer (CRC) screening programs. Resuming these programs is a priority, but fewer colonoscopies may be available. We developed an evidence-based tool for decision-making in CRC screening programs, based on a fecal hemoglobin immunological test (FIT), to optimize the strategy for screening a population for CRC. Methods: We retrospectively analyzed data collected at a regional CRC screening program between February/2014 and November/2018. We investigated two different scenarios: not modifying vs. modifying the FIT cut-off value. We estimated program outcomes in the two scenarios by evaluating the numbers of cancers and adenomas missed or not diagnosed in due time (delayed). Results: The current FIT cut-off (20-mu g hemoglobin/g feces) led to 6, 606 colonoscopies per 100, 000 people invited annually. Without modifying this FIT cut-off value, when the optimal number of individuals invited for colonoscopies was reduced by 10-40%, a high number of CRCs and high-risk adenomas (34-135 and 73-288/100.000-people invited, respectively) will be undetected every year. When the FIT cut-off value was increased to where the colonoscopy demand matched the colonoscopy availability, the number of missed lesions per year was remarkably reduced (9-36 and 29-145/100.000 people, respectively). Moreover, the unmodified FIT scenario outcome was improved by prioritizing the selection process based on sex (males) and age, rather than randomly reducing the number invited. Conclusions: Assuming a mismatch between the availability and demand for annual colonoscopies, increasing the FIT cut-off point was more effective than randomly reducing the number of people invited. Using specific risk factors to prioritize access to colonoscopies should be also considered

Diversity in olfactory bulb size in birds reflects allometry, ecology, and phylogeny

The relative size of olfactory bulbs (OBs) is correlated with olfactory capabilities across vertebrates and is widely used to assess the relative importance of olfaction to a species’ ecology. In birds, variations in the relative size of OBs are correlated with some behaviors; however, the factors that have led to the high level of diversity seen in OB sizes across birds are still not well understood. In this study, we use the relative size of OBs as a neuroanatomical proxy for olfactory capabilities in 135 species of birds, representing 21 orders. We examine the scaling of OBs with brain size across avian orders, determine likely ancestral states and test for correlations between OB sizes and habitat, ecology, and behavior. The size of avian OBs varied with the size of the brain and this allometric relationship was for the most part isometric, although species did deviate from this trend. Large OBs were characteristic of more basal species and in more recently derived species the OBs were small. Living and foraging in a semiaquatic environment was the strongest variable driving the evolution of large OBs in birds; olfaction may provide cues for navigation and foraging in this otherwise featureless environment. Some of the diversity in OB sizes was also undoubtedly due to differences in migratory behavior, foraging strategies and social structure. In summary, relative OB size in birds reflect allometry, phylogeny and behavior in ways that parallel that of other vertebrate classes. This provides comparative evidence that supports recent experimental studies into avian olfaction and suggests that olfaction is an important sensory modality for all avian species

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