Coordination and collaboration in European research towards healthy and safe nanomaterials

Nanotechnology is becoming part of our daily life in a wide range of products such as computers, bicycles, sunscreens or nanomedicines. While these applications already become reality, considerable work awaits scientists, engineers, and policy makers, who want such nanotechnological products to yield a maximum of benefit at a minimum of social, environmental, economic and (occupational) health cost. Considerable efforts for coordination and collaboration in research are needed if one wants to reach these goals in a reasonable time frame and an affordable price tag. This is recognized in Europe by the European Commission which funds not only research projects but also supports the coordination of research efforts. One of these coordination efforts is NanoImpactNet, a researcher-operated network, which started in 2008 promote scientific cross-talk across all disciplines on the health and environmental impact of nanomaterials. Stakeholders contribute to these activities, notably the definition of research and knowledge needs. Initial discussions in this domain focused on finding an agreement on common metrics, and which elements are needed for standardized approaches for hazard and exposure identification. There are many nanomaterial properties that may play a role. Hence, to gain the time needed to study this complex matter full of uncertainties, researchers and stakeholders unanimously called for simple, easy and fast risk assessment tools that can support decision making in this rapidly moving and growing domain. Today, several projects are starting or already running that will develop such assessment tools. At the same time, other projects investigate in depth which factors and material properties can lead to unwanted toxicity or exposure, what mechanisms are involved and how such responses can be predicted and modelled. A vision for the future is that once these factors, properties and mechanisms are understood, they can and will be accounted for in the development of new products and production processes following the idea of "Safety by Design". The promise of all these efforts is a future with nanomaterials where most of their risks are recognized and addressed before they even reach the market.

Trabecular Bone Score (TBS)--A Novel Method to Evaluate Bone Microarchitectural Texture in Patients With Primary Hyperparathyroidism.

Context: In the milder form of primary hyperparathyroidism (PHPT), cancellous bone, represented by areal bone mineral density at the lumbar spine by dual-energy x-ray absorptiometry (DXA), is preserved. This finding is in contrast to high-resolution peripheral quantitative computed tomography (HRpQCT) results of abnormal trabecular microstructure and epidemiological evidence for increased overall fracture risk in PHPT. Because DXA does not directly measure trabecular bone and HRpQCT is not widely available, we used trabecular bone score (TBS), a novel gray-level textural analysis applied to spine DXA images, to estimate indirectly trabecular microarchitecture. Objective: The purpose of this study was to assess TBS from spine DXA images in relation to HRpQCT indices and bone stiffness in radius and tibia in PHPT. Design and Setting: This was a cross-sectional study conducted in a referral center. Patients: Participants were 22 postmenopausal women with PHPT. Main Outcome Measures: Outcomes measured were areal bone mineral density by DXA, TBS indices derived from DXA images, HRpQCT standard measures, and bone stiffness assessed by finite element analysis at distal radius and tibia. Results: TBS in PHPT was low at 1.24, representing abnormal trabecular microstructure (normal ≥1.35). TBS was correlated with whole bone stiffness and all HRpQCT indices, except for trabecular thickness and trabecular stiffness at the radius. At the tibia, correlations were observed between TBS and volumetric densities, cortical thickness, trabecular bone volume, and whole bone stiffness. TBS correlated with all indices of trabecular microarchitecture, except trabecular thickness, after adjustment for body weight. Conclusion: TBS, a measurement technology readily available by DXA, shows promise in the clinical assessment of trabecular microstructure in PHPT.

Uuden riskien arviointityökalun käyttöönotto metsäteollisuusyrityksessä

Vuonna 2003 uudistunut työturvallisuuslaki lisäsi yritysten vastuuta oman työympäristön riskien tunnistamisessa. Laki velvoittaa yritykset tunnistamaan, selvittämään ja arvioimaan työstä ja työolosuhteista johtuvat vaara- ja haittatekijät. Perinteisesti yritykset ovat suorittaneet riskien arviointia erilaisten tarkistuslistojen avulla, mutta nykyään tietotekniikan käytön lisääntyminen on tuonut tietotekniikan myös yhdeksi riskienhallinnan työvälineeksi. Tämän työn tavoitteena oli tutkia If Vahinkovakuutusyhtiön uuden riskien arviointiohjelman käyttöönottoa metsäteollisuuden yrityksessä, ja selvittää sen vaikutuksia turvallisuustoimenpiteiden hallintaan ja vastaavuutta sille ennakkoon asetettuihin käytettävyysvaatimuksiin. Riskien arviointiohjelmaa tutkittiin pilottikohteessa Stora Enson Anjalankoskentehtailla. Tietoa kerättiin mm. käyttäjäkoulutustilaisuuksien palautekyselyillä, haastattelemalla arvioijia ja osallistumalla riskien arviointikierroksille. Tutkimuksessa seurattiin mm. ohjelman avulla syntyneiden toimenpide-ehdotuksien määrää ja laatua, ja sitä kuinka hyvin ohjelmalle suunniteltu sisältö sopii käyttöön. Tämän tutkimuksen perusteella havaittiin, että riskien arviointiin tarkoitettu tietokoneohjelma voidaan suunnitella helppokäyttöiseksi ja toimivaksi. Myös ohjelman sisältö, joka oli tarkoitettu kattamaan työturvallisuuden eri osa-alueet, havaittiin tarkoitukseen sopivaksi. Riskien arvioinnin ongelmallisin alue, eli turvallisuustoimenpiteiden suunnittelu ja seuranta, havaittiin haasteelliseksi toteutettavaksi ohjelman avulla. Yritysten erilaisiin riskien arviointikäytäntöihinsopivan raportointijärjestelmän ja toimenpideseurannan kehittäminen tulee olemaan tulevaisuudessakin tärkeä osa-alue riskien arviointiohjelmien kehittämisessä.

Angiotensin converting enzyme inhibitor induced angio-oedema: a review of the pathophysiology and risk factors.

Angio-oedema (AE) is a known adverse effect of angiotensin converting enzyme inhibitor (ACE-I) therapy. Over the past several decades, evidence of failure to diagnose this important and potentially fatal reaction is commonly found in the literature. Because this reaction is often seen first in the primary care setting, a review was undertaken to analyse and document the keys to both diagnostic criteria as well as to investigate potential risk factors for ACE-I AE occurrence. A general review of published literature was conducted through Medline, EMBASE, and the Cochrane Database, targeting ACE-I-related AE pathomechanism, diagnosis, epidemiology, risk factors, and clinical decision making and treatment. The incidence and severity of AE appears to be on the rise and there is evidence of considerable delay in diagnosis contributing to significant morbidity and mortality for patients. The mechanism of AE due to ACE-I drugs is not fully understood, but some genomic and metabolomic information has been correlated. Additional epidemiologic data and clinical treatment outcome predictors have been evaluated, creating a basis for future work on the development of clinical prediction tools to aid in risk identification and diagnostic differentiation. Accurate recognition of AE by the primary care provider is essential to limit the rising morbidity associated with ACE-I treatment-related AE. Research findings on the phenotypic indicators relevant to this group of patients as well as basic research into the pathomechanism of AE are available, and should be used in the construction of better risk analysis and clinical diagnostic tools for ACE-I AE.

The last days of dying stroke patients referred to a palliative care consult team in an acute hospital.

BACKGROUND AND PURPOSE: Needs of patients dying from stroke are poorly investigated. We aim to assess symptoms of these patients referred to a palliative care consult team, and to review their treatment strategies. METHODS: All charts of patients dying from stroke in a tertiary hospital, and referred consecutively to a palliative care consultant team from 2000 to 2005, were reviewed retrospectively. Symptoms, ability to communicate, treatments, circumstances and causes of death were collected. RESULTS: Forty-two patients were identified. Median NIH Stroke Scale on admission was 21. The most prevalent symptoms were dyspnoea (81%), and pain (69%). Difficulties or inability to communicate because of aphasia or altered level of consciousness were present in 93% of patients. Pharmacological respiratory treatments consisted of anti-muscarinic drugs (52%), and opioids (33%). Pain was mainly treated by opioids (69%). During the last 48 h of life, 81% of patients were free of pain and 48% of respiratory distress. The main causes of death were neurological complications in 38% of patients, multiple medical complications in 36%, and specific medical causes in 26%. CONCLUSIONS: Patients dying from stroke and referred to a palliative care consult team have multiple symptoms, mainly dyspnoea and pain. Studies are warranted to develop specific symptoms assessment tools in non-verbal stroke patients, to accurately assess patients' needs, and to measure effectiveness of palliative treatments.

Breast cancer incidence and overdiagnosis in Catalonia (Spain)

Introduction: Early detection of breast cancer (BC) with mammography may cause overdiagnosis and overtreatment, detecting tumors which would remain undiagnosed during a lifetime. The aims of this study were: first, to model invasive BC incidence trends in Catalonia (Spain) taking into account reproductive and screening data; and second, to quantify the extent of BC overdiagnosis. Methods: We modeled the incidence of invasive BC using a Poisson regression model. Explanatory variables were: age at diagnosis and cohort characteristics (completed fertility rate, percentage of women that use mammography at age 50, and year of birth). This model also was used to estimate the background incidence in the absence of screening. We used a probabilistic model to estimate the expected BC incidence if women in the population used mammography as reported in health surveys. The difference between the observed and expected cumulative incidences provided an estimate of overdiagnosis. Results: Incidence of invasive BC increased, especially in cohorts born from 1940 to 1955. The biggest increase was observed in these cohorts between the ages of 50 to 65 years, where the final BC incidence rates more than doubled the initial ones. Dissemination of mammography was significantly associated with BC incidence and overdiagnosis. Our estimates of overdiagnosis ranged from 0.4% to 46.6%, for women born around 1935 and 1950, respectively. Conclusions: Our results support the existence of overdiagnosis in Catalonia attributed to mammography usage, and the limited malignant potential of some tumors may play an important role. Women should be better informed about this risk. Research should be oriented towards personalized screening and risk assessment tools.

Bilateral deep brain stimulation: the placement of the second electrode is not necessarily less accurate than that of the first one.

BACKGROUND: Deep brain stimulation (DBS) is recognized as an effective treatment for movement disorders. We recently changed our technique, limiting the number of brain penetrations to three per side. OBJECTIVES: The first aim was to evaluate the electrode precision on both sides of surgery since we implemented this surgical technique. The second aim was to analyse whether or not the electrode placement was improved with microrecording and macrostimulation. METHODS: We retrospectively reviewed operation protocols and MRIs of 30 patients who underwent bilateral DBS. For microrecording and macrostimulation, we used three parallel channels of the 'Ben Gun' centred on the MRI-planned target. Pre- and post-operative MRIs were merged. The distance between the planned target and the centre of the implanted electrode artefact was measured. RESULTS: There was no significant difference in targeting precision on both sides of surgery. There was more intra-operative adjustment of the second electrode positioning based on microrecording and macrostimulation, which allowed to significantly approach the MRI-planned target on the medial-lateral axis. CONCLUSION: There was more electrode adjustment needed on the second side, possibly in relation with brain shift. We thus suggest performing a single central track with electrophysiological and clinical assessment, with multidirectional exploration on demand for suboptimal clinical responses.

Quantitative Analysis of Myelin and Axonal Remodeling in the Uninjured Motor Network After Stroke.

Contralesional brain connectivity plasticity was previously reported after stroke. This study aims at disentangling the biological mechanisms underlying connectivity plasticity in the uninjured motor network after an ischemic lesion. In particular, we measured generalized fractional anisotropy (GFA) and magnetization transfer ratio (MTR) to assess whether poststroke connectivity remodeling depends on axonal and/or myelin changes. Diffusion-spectrum imaging and magnetization transfer MRI at 3T were performed in 10 patients in acute phase, at 1 and 6 months after stroke, which was affecting motor cortical and/or subcortical areas. Ten age- and gender-matched healthy volunteers were scanned 1 month apart for longitudinal comparison. Clinical assessment was also performed in patients prior to magnetic resonance imaging (MRI). In the contralesional hemisphere, average measures and tract-based quantitative analysis of GFA and MTR were performed to assess axonal integrity and myelination along motor connections as well as their variations in time. Mean and tract-based measures of MTR and GFA showed significant changes in a number of contralesional motor connections, confirming both axonal and myelin plasticity in our cohort of patients. Moreover, density-derived features (peak height, standard deviation, and skewness) of GFA and MTR along the tracts showed additional correlation with clinical scores than mean values. These findings reveal the interplay between contralateral myelin and axonal remodeling after stroke.

E-Cigarettes: A Review of New Trends in Cannabis Use.

The emergence of electronic cigarettes (e-cigs) has given cannabis smokers a new method of inhaling cannabinoids. E-cigs differ from traditional marijuana cigarettes in several respects. First, it is assumed that vaporizing cannabinoids at lower temperatures is safer because it produces smaller amounts of toxic substances than the hot combustion of a marijuana cigarette. Recreational cannabis users can discretely "vape" deodorized cannabis extracts with minimal annoyance to the people around them and less chance of detection. There are nevertheless several drawbacks worth mentioning: although manufacturing commercial (or homemade) cannabinoid-enriched electronic liquids (e-liquids) requires lengthy, complex processing, some are readily on the Internet despite their lack of quality control, expiry date, and conditions of preservation and, above all, any toxicological and clinical assessment. Besides these safety problems, the regulatory situation surrounding e-liquids is often unclear. More simply ground cannabis flowering heads or concentrated, oily THC extracts (such as butane honey oil or BHO) can be vaped in specially designed, pen-sized marijuana vaporizers. Analysis of a commercial e-liquid rich in cannabidiol showed that it contained a smaller dose of active ingredient than advertised; testing our laboratory-made, purified BHO, however, confirmed that it could be vaped in an e-cig to deliver a psychoactive dose of THC. The health consequences specific to vaping these cannabis preparations remain largely unknown and speculative due to the absence of comprehensive, robust scientific studies. The most significant health concerns involve the vaping of cannabinoids by children and teenagers. E-cigs could provide an alternative gateway to cannabis use for young people. Furthermore, vaping cannabinoids could lead to environmental and passive contamination.

Ability of physicians to diagnose influenza and usefulness of a rapid influenza antigen test in febrile returning travelers: A randomized controlled trial.

BACKGROUND: Fever is a frequent cause of medical consultation among returning travelers. The objectives of this study were to assess whether physicians were able to identify patients with influenza and whether the use of an influenza rapid diagnostic test (iRDT) modified the clinical management of such patients. METHODS: Randomized controlled trial conducted at 2 different Swiss hospitals between December 2008 and November 2012. Inclusion criteria were 1) age ≥18 years, 2) documented fever of ≥38 °C or anamnestic fever + cough or sore throat within the last 4 days, 3) illness occurring within 14 days after returning from a trip abroad, 4) no definitive alternative diagnosis. Physicians were asked to estimate the likelihood of influenza on clinical grounds, and a single nasopharyngeal swab was taken. Thereafter patients were randomized into 2 groups: i) patients with iRDT (BD Directigen A + B) performed on the nasopharyngeal swab, ii) patients receiving usual care. A quantitative PCR to detect influenza was done on all nasopharyngeal swabs after the recruitment period. Clinical management was evaluated on the basis of cost of medical care, number of X-rays requested and prescription of anti-infective drugs. RESULTS: 100 eligible patients were referred to the investigators. 93 patients had a naso-pharyngeal swab for a PCR and 28 (30%) swabs were positive for influenza. The median probability of influenza estimated by the physician was 70% for the PCR positive cases and 30% for the PCR negative cases (p < 0.001). The sensitivity of the iRDT was only 20%, and specificity 100%. Mean medical cost for the patients managed with iRDT and without iRDT were USD 581 (95%CI 454-707) and USD 661 (95%CI 522-800) respectively. 14/60 (23%) of the patients managed with iRDT were prescribed antibiotics versus 13/33 (39%) in the control group (p = 0.15). No patient received antiviral treatment. CONCLUSION: Influenza was a frequent cause of fever among these febrile returning travelers. Based on their clinical assessment, physicians had a higher level of suspicion for influenza in PCR positive cases. The iRDT used in this study showed a disappointingly low sensitivity and can therefore not be recommended for the management of these patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT00821626.

Safety of human immunisation with a live-attenuated Mycobacterium tuberculosis vaccine: a randomised, double-blind, controlled phase I trial.

BACKGROUND: Tuberculosis remains one of the world's deadliest transmissible diseases despite widespread use of the BCG vaccine. MTBVAC is a new live tuberculosis vaccine based on genetically attenuated Mycobacterium tuberculosis that expresses most antigens present in human isolates of M tuberculosis. We aimed to compare the safety of MTBVAC with BCG in healthy adult volunteers. METHODS: We did this single-centre, randomised, double-blind, controlled phase 1 study at the Centre Hospitalier Universitaire Vaudois (CHUV; Lausanne, Switzerland). Volunteers were eligible for inclusion if they were aged 18-45 years, clinically healthy, HIV-negative and tuberculosis-negative, and had no history of active tuberculosis, chemoprophylaxis for tuberculosis, or BCG vaccination. Volunteers fulfilling the inclusion criteria were randomly assigned to three cohorts in a dose-escalation manner. Randomisation was done centrally by the CHUV Pharmacy and treatments were masked from the study team and volunteers. As participants were recruited within each cohort, they were randomly assigned 3:1 to receive MTBVAC or BCG. Of the participants allocated MTBVAC, those in the first cohort received 5 × 10(3) colony forming units (CFU) MTBVAC, those in the second cohort received 5 × 10(4) CFU MTBVAC, and those in the third cohort received 5 × 10(5) CFU MTBVAC. In all cohorts, participants assigned to receive BCG were given 5 × 10(5) CFU BCG. Each participant received a single intradermal injection of their assigned vaccine in 0·1 mL sterile water in their non-dominant arm. The primary outcome was safety in all vaccinated participants. Secondary outcomes included whole blood cell-mediated immune response to live MTBVAC and BCG, and interferon γ release assays (IGRA) of peripheral blood mononuclear cells. This trial is registered with ClinicalTrials.gov, number NCT02013245. FINDINGS: Between Jan 23, 2013, and Nov 6, 2013, we enrolled 36 volunteers into three cohorts, each of which consisted of nine participants who received MTBVAC and three who received BCG. 34 volunteers completed the trial. The safety of vaccination with MTBVAC at all doses was similar to that of BCG, and vaccination did not induce any serious adverse events. All individuals were IGRA negative at the end of follow-up (day 210). After whole blood stimulation with live MTBVAC or BCG, MTBVAC was at least as immunogenic as BCG. At the same dose as BCG (5×10(5) CFU), although no statistical significance could be achieved, there were more responders in the MTBVAC group than in the BCG group, with a greater frequency of polyfunctional CD4+ central memory T cells. INTERPRETATION: To our knowledge, MTBVAC is the first live-attenuated M tuberculosis vaccine to reach clinical assessment, showing similar safety to BCG. MTBVAC seemed to be at least as immunogenic as BCG, but the study was not powered to investigate this outcome. Further plans to use more immunogenicity endpoints in a larger number of volunteers (adults and adolescents) are underway, with the aim to thoroughly characterise and potentially distinguish immunogenicity between MTBVAC and BCG in tuberculosis-endemic countries. Combined with an excellent safety profile, these data support advanced clinical development in high-burden tuberculosis endemic countries. FUNDING: Biofabri and Bill & Melinda Gates Foundation through the TuBerculosis Vaccine Initiative (TBVI).

EEG as an Indicator of Cerebral Functioning in Postanoxic Coma.

Postanoxic coma after cardiac arrest is one of the most serious acute cerebral conditions and a frequent cause of admission to critical care units. Given substantial improvement of outcome over the recent years, a reliable and timely assessment of clinical evolution and prognosis is essential in this context, but may be challenging. In addition to the classic neurologic examination, EEG is increasingly emerging as an important tool to assess cerebral functions noninvasively. Although targeted temperature management and related sedation may delay clinical assessment, EEG provides accurate prognostic information in the early phase of coma. Here, the most frequently encountered EEG patterns in postanoxic coma are summarized and their relations with outcome prediction are discussed. This article also addresses the influence of targeted temperature management on brain signals and the implication of the evolution of EEG patterns over time. Finally, the article ends with a view of the future prospects for EEG in postanoxic management and prognostication.

International journal of engineering education

This work presents an analysis of the assessment tools used by professors at the Universitat Politécnica de Catalunya to assess the generic competencies introduced in the Bachelor’s Degrees in Engineering. In order to conduct this study, a survey was designed and administered anonymously to a sample of the professors most receptive to educational innovation at their own university. All total, 80 professors responded to this survey, of whom 26% turned out to be members of the university’s own evaluation innovation group (https://www.upc.edu/rima/grups/grapa), GRAPA. This percentage represents 47% of the total GRAPA membership, meaning that nearly half of the professors most concerned about evaluation at the university chose to participate. The analysis of the variables carried out using the statistical program SPSS v19 shows that for practically 49% of those surveyed, rubrics are the tools most commonly used to assess generic competencies integrated in more specific ones. Of those surveyed, 60% use them either frequently or always. The most frequently evaluated generic competencies were teamwork (28%), problem solving (26%), effective oral and written communication (24%) and autonomous learning (13%), all of which constitute commonly recognized competencies in the engineering profession. A two-dimensional crosstabs analysis with SPSS v19 shows a significant correlation (Asymp. Sig. 0.001) between the type of tool used and the competencies assessed. However, no significant correlation was found between the type of assessment tool used and the type of subject, type of evaluation (formative or summative), frequency of feedback given to the students or the degree of student satisfaction, and thus none of these variables can be considered to have an influence on the kind of assessment tool used. In addition, the results also indicate that there are no significant differences between the instructors belonging to GRAPA and the rest of those surveyed

A Meta-Analysis of Trabecular Bone Score in Fracture Risk Prediction and Its Relationship to FRAX.

Trabecular bone score (TBS) is a gray-level textural index of bone microarchitecture derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images. TBS is a bone mineral density (BMD)-independent predictor of fracture risk. The objective of this meta-analysis was to determine whether TBS predicted fracture risk independently of FRAX probability and to examine their combined performance by adjusting the FRAX probability for TBS. We utilized individual-level data from 17,809 men and women in 14 prospective population-based cohorts. Baseline evaluation included TBS and the FRAX risk variables, and outcomes during follow-up (mean 6.7 years) comprised major osteoporotic fractures. The association between TBS, FRAX probabilities, and the risk of fracture was examined using an extension of the Poisson regression model in each cohort and for each sex and expressed as the gradient of risk (GR; hazard ratio per 1 SD change in risk variable in direction of increased risk). FRAX probabilities were adjusted for TBS using an adjustment factor derived from an independent cohort (the Manitoba Bone Density Cohort). Overall, the GR of TBS for major osteoporotic fracture was 1.44 (95% confidence interval [CI] 1.35-1.53) when adjusted for age and time since baseline and was similar in men and women (p > 0.10). When additionally adjusted for FRAX 10-year probability of major osteoporotic fracture, TBS remained a significant, independent predictor for fracture (GR = 1.32, 95% CI 1.24-1.41). The adjustment of FRAX probability for TBS resulted in a small increase in the GR (1.76, 95% CI 1.65-1.87 versus 1.70, 95% CI 1.60-1.81). A smaller change in GR for hip fracture was observed (FRAX hip fracture probability GR 2.25 vs. 2.22). TBS is a significant predictor of fracture risk independently of FRAX. The findings support the use of TBS as a potential adjustment for FRAX probability, though the impact of the adjustment remains to be determined in the context of clinical assessment guidelines. © 2015 American Society for Bone and Mineral Research.

Efficacy of methotrexate to prevent postoperative recurrence of Crohn's disease

BACKGROUND: endoscopic postoperative recurrence (POR) of Crohn’s disease (CD) is the presence of lesions in previously unaffected intestinal segments and occurs in up to 85% of patients one year after bowel resection. Patients at low risk for POR can either remain untreated until lesions recur or receive immediate prevention after surgery with mesalazine, azathioprine (AZA) and/or metronidazole, although with moderate benefit. Out of the postoperative setting, methotrexate (MTX) has been shown to be efficacious for induction and maintenance of remission and has been established as the second-line immunosuppressant for patients with CD unresponsive or intolerant to AZA.AIMS: to determine the efficacy and safety of MTX to prevent endoscopic and clinical POR at 24 weeks after surgery in low risk patientsMETHODS: the study consists on a multicenter, randomized, double-blind and placebo-controlled clinical trial that will enroll 132 patients at low risk for POR (non-smokers, first intestinal resection, non-penetrating behavior). Patients will be randomized to receive subcutaneous MTX at doses of 25 mg/week or an identical placebo, for 24 weeks. Endoscopic and clinical assessment of POR will be performed after 24 weeks (6 months) of treatment. The main outcome is endoscopic POR, defined as a Rutgeerts score of >i2, and secondary outcomes include clinical POR, defined as >i2 lesions plus a Crohn’s Disease Activity Index (CDAI) >150, and description of adverse events