External validation of risk prediction models for incident colorectal cancer using UK Biobank.

BACKGROUND: This study aimed to compare and externally validate risk scores developed to predict incident colorectal cancer (CRC) that include variables routinely available or easily obtainable via self-completed questionnaire. METHODS: External validation of fourteen risk models from a previous systematic review in 373 112 men and women within the UK Biobank cohort with 5-year follow-up, no prior history of CRC and data for incidence of CRC through linkage to national cancer registries. RESULTS: There were 1719 (0.46%) cases of incident CRC. The performance of the risk models varied substantially. In men, the QCancer10 model and models by Tao, Driver and Ma all had an area under the receiver operating characteristic curve (AUC) between 0.67 and 0.70. Discrimination was lower in women: the QCancer10, Wells, Tao, Guesmi and Ma models were the best performing with AUCs between 0.63 and 0.66. Assessment of calibration was possible for six models in men and women. All would require country-specific recalibration if estimates of absolute risks were to be given to individuals. CONCLUSIONS: Several risk models based on easily obtainable data have relatively good discrimination in a UK population. Modelling studies are now required to estimate the potential health benefits and cost-effectiveness of implementing stratified risk-based CRC screening

Quantifying Vegetation Biophysical Variables from Imaging Spectroscopy Data: A Review on Retrieval Methods

An unprecedented spectroscopic data stream will soon become available with forthcoming Earth-observing satellite missions equipped with imaging spectroradiometers. This data stream will open up a vast array of opportunities to quantify a diversity of biochemical and structural vegetation properties. The processing requirements for such large data streams require reliable retrieval techniques enabling the spatiotemporally explicit quantification of biophysical variables. With the aim of preparing for this new era of Earth observation, this review summarizes the state-of-the-art retrieval methods that have been applied in experimental imaging spectroscopy studies inferring all kinds of vegetation biophysical variables. Identified retrieval methods are categorized into: (1) parametric regression, including vegetation indices, shape indices and spectral transformations; (2) nonparametric regression, including linear and nonlinear machine learning regression algorithms; (3) physically based, including inversion of radiative transfer models (RTMs) using numerical optimization and look-up table approaches; and (4) hybrid regression methods, which combine RTM simulations with machine learning regression methods. For each of these categories, an overview of widely applied methods with application to mapping vegetation properties is given. In view of processing imaging spectroscopy data, a critical aspect involves the challenge of dealing with spectral multicollinearity. The ability to provide robust estimates, retrieval uncertainties and acceptable retrieval processing speed are other important aspects in view of operational processing. Recommendations towards new-generation spectroscopy-based processing chains for operational production of biophysical variables are given

Systematic review: the safety of vedolizumab for the treatment of inflammatory bowel disease.

Background Vedolizumab specifically recognizes the 47 integrin and selectively blocks gut lymphocyte trafficking: potentially, it offers gut-specific immunosuppression. Aims To review the safety of vedolizumab and summarise post-marketing data to assess if any safety concerns that differ from registration trials have emerged. Method A systematic bibliographic search identified six registration trials and nine cohort studies. Results Integrated data from registration trials included 2830 vedolizumab-exposed patients (4811 person-years exposure (PYs)) and 513 placebo patients. This reported lower exposure-adjusted incidence rates of infection (63.5/100 PYs; 95% CI 59.6 to 67.3) and serious adverse events (20.0/100 PYs; 95% CI 18.5 to 21.5) compared to placebo (82.9/100 PYs; 95% CI 68.3 to 97.5) and (28.3/100 PYs 95% CI 20.6 to 35.9) respectively. Higher, but statistically insignificant rates of enteric infections occurred in vedolizumab-exposed patients (7.4/100 PYs; 95% CI 6.6 to 8.3) compared to placebo (6.7 PYs; 95% CI 3.2 to 10.1). Six post-marketing cohort studies (1049 patients, 403 PYs) demonstrated rates of infection of 8% (82/1049); enteric infection of 2% (21/1049) and adverse events of 16% (166/1049). Multivariate analysis in one cohort study suggested increased risk of surgical site infection with perioperative VDZ. Human experience in pregnancy is limited. Conclusions Post-marketing data confirm the excellent safety of vedolizumab observed in registration trials. The signal of post-operative complications should be interpreted with caution, but warrants further study. Although comparative studies are needed, Vedolizumab may be a safe alternative in patients who best avoid systematic immunosuppression, including those predisposed to infection, malignancy, or the elderly.</p

Editorial: gut selective immunosuppression-is it a double edged sword? Authors' reply.

The Editorial on the safety of vedolizumab by Sheridan and Doherty in response to our safety review is thoughtful and well balanced, but there are post-marketing data on malignancy after >25000 patient-years of experience with vedolizumab that they do not mentio

Systematic review: the safety of vedolizumab for the treatment of inflammatory bowel disease.

Background Vedolizumab specifically recognizes the 47 integrin and selectively blocks gut lymphocyte trafficking: potentially, it offers gut-specific immunosuppression. Aims To review the safety of vedolizumab and summarise post-marketing data to assess if any safety concerns that differ from registration trials have emerged. Method A systematic bibliographic search identified six registration trials and nine cohort studies. Results Integrated data from registration trials included 2830 vedolizumab-exposed patients (4811 person-years exposure (PYs)) and 513 placebo patients. This reported lower exposure-adjusted incidence rates of infection (63.5/100 PYs; 95% CI 59.6 to 67.3) and serious adverse events (20.0/100 PYs; 95% CI 18.5 to 21.5) compared to placebo (82.9/100 PYs; 95% CI 68.3 to 97.5) and (28.3/100 PYs 95% CI 20.6 to 35.9) respectively. Higher, but statistically insignificant rates of enteric infections occurred in vedolizumab-exposed patients (7.4/100 PYs; 95% CI 6.6 to 8.3) compared to placebo (6.7 PYs; 95% CI 3.2 to 10.1). Six post-marketing cohort studies (1049 patients, 403 PYs) demonstrated rates of infection of 8% (82/1049); enteric infection of 2% (21/1049) and adverse events of 16% (166/1049). Multivariate analysis in one cohort study suggested increased risk of surgical site infection with perioperative VDZ. Human experience in pregnancy is limited. Conclusions Post-marketing data confirm the excellent safety of vedolizumab observed in registration trials. The signal of post-operative complications should be interpreted with caution, but warrants further study. Although comparative studies are needed, Vedolizumab may be a safe alternative in patients who best avoid systematic immunosuppression, including those predisposed to infection, malignancy, or the elderly.</p

Editorial: gut selective immunosuppression-is it a double edged sword? Authors' reply.

The Editorial on the safety of vedolizumab by Sheridan and Doherty in response to our safety review is thoughtful and well balanced, but there are post-marketing data on malignancy after &gt;25000 patient-years of experience with vedolizumab that they do not mentio