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Background Biological therapies have improved the care of patients with ulcerative colitis (UC). Tofacitinib, an oral small-molecule Janus kinase inhibitor, is potentially a new treatment option. Aim To comparatively assess efficacy and harm of tofacitinib and biologics (infliximab, adalimumab, golimumab and vedolizumab) in adult patients not previously exposed to TNF antagonists. Methods We performed a comprehensive search of PubMed, Embase, Scopus, clinical trial registries, regulatory authorities' websites and major conference proceedings, through August 2017, to identify randomised, placebo-controlled or head-to-head trials assessing tofacitinib or biologics as induction and/or maintenance therapy in moderate-to-severe UC. Two reviewers independently extracted study data and outcomes, and investigated each trial's risk-of-bias. We used conventional meta-analysis to synthesise direct evidence, and network meta-analysis for adjusted indirect treatment comparisons. Results Fifteen randomised, double-blind, placebo-controlled trials (n = 3130) contributed data for induction: All treatments are superior to placebo. Indirect treatment comparisons showed that infliximab is better than adalimumab (OR: 2.01, 95% CI: 1.36-2.98) and golimumab (1.67, 1.08-2.59) in clinical response, better than adalimumab (2.10, 1.21-3.64) in clinical remission, and better than adalimumab (1.87, 1.26-2.79) and golimumab (1.75, 1.13-2.73) in mucosal healing. No indirect comparisons between tofacitinib and biologics reached statistical significance. Nine studies (n = 1776) contributed maintenance data showing that all treatments have higher clinical efficacy than placebo. Safety analyses indicated no increased rates of adverse events for the treatments under evaluation (except for infliximab), while vedolizumab may have an advantage regarding the occurrence of serious adverse events. Conclusions Tofacitinib and biologics are efficacious and safe for UC. Further high-quality research is warranted to establish the best therapeutic option. 47 4 454 465

An overall long-term strategy for managing the coronavirus disease 2019 (COVID-19) pandemic is presented. This strategy will need to be maintained until herd immunity is achieved, hopefully through vaccination rather than natural infection. We suggest that a pure test-trace-isolate strategy is likely not practicable in most countries, and a degree of social distancing, ranging up to full lockdown, is the main public-health tool to mitigate the COVID-19 pandemic. Guided by reliable surveillance data, distancing should be continuously optimised down to the lowest sustainable level that guarantees a low and stable infection rate in order to balance its wide-ranging negative effects on public health. The qualitative mixture of social-distancing measures also needs to be carefully optimised in order to minimise social costs. © Author(s) 2020.

Objectives: To report on an active case finding (ACF) intervention that took place in the migrant camp of Oinofyta, Greece, upon suspicion of active TB transmission. Methods: Upon diagnosis of 3 TB cases among camp residents, an ACF intervention among contacts was implemented. All camp residents were offered two-step screening, that is tuberculin skin testing (TST) followed by chest X-ray in case of positive TST (defined as ≥5 mm). Results: 336 of 379 (89%) camp residents underwent TST testing, of whom 110 (33%) exhibited a positive skin reaction. The rate of positive TST results was particularly high in the elderly and significantly higher in adults than in children. Differences by sex or nationality were not observed. Of the 110 cases with positive TST, only 75 underwent chest X-ray, resulting in the detection of one pulmonary TB case in an adult woman. Conclusions: In the given intervention context, two-step ACF proved to be operationally cumbersome, with many residents lost to follow-up and a high Number Needed to Screen. Simpler ACF designs should be pilot-tested in similar settings in the future, and blanket screening of all camp residents should be reconsidered. Conclusions drawn by these exercises should pave the way for adopting a comprehensive, context-specific and evidence-based national strategy on TB in migrants. © 2021 John Wiley & Sons Ltd

Greece imposed a nationwide lockdown in March 2020 to mitigate transmission of severe acute respiratory syndrome coronavirus 2 during the first epidemic wave. We conducted a survey on age-specific social contact patterns to assess effects of physical distancing measures and used a susceptible-exposed-infectious-recovered model to simulate the epidemic. Because multiple distancing measures were implemented simultaneously, we assessed their overall effects and the contribution of each measure. Before measures were implemented, the estimated basic reproduction number (R0) was 2.38 (95% CI 2.01-2.80). During lockdown, daily contacts decreased by 86.9% and R0 decreased by 81.0% (95% credible interval [CrI] 71.8%-86.0%); each distancing measure decreased R0 by 10%-24%. By April 26, the attack rate in Greece was 0.12% (95% CrI 0.06%-0.26%), one of the lowest in Europe, and the infection fatality ratio was 1.12% (95% CrI 0.55%-2.31%). Multiple social distancing measures contained the first epidemic wave in Greece. © 2021 Centers for Disease Control and Prevention (CDC). All rights reserved.

Crohn’s disease [CD] is a chronic inflammatory bowel disease [IBD] that can result in progressive bowel damage and disability1. CD can affect individuals of any age, from children to the elderly, 2, 3 and may cause significant morbidity and impact on quality of life. Up to one-third of patients present with complicated behaviour [strictures, fistula, or abscesses] at diagnosis4. Most patients over time will develop a complication, with roughly 50% of patients requiring surgery within 10 years of diagnosis5-7. As the precise aetiology of CD remains unknown, a curative therapy is not yet available8. Several agents are available for the medical treatment of CD. Medical agents include mesalazine [5-ASA], locally active steroids [such as budesonide], systemic steroids, thiopurines such as azathioprine [AZA] and mercaptopurine [MP], methotrexate [MTX], and biological therapies [such as anti-TNF, anti-integrins, and anti-IL12/23]. The European Crohn’s and Colitis Organisation [ECCO] produces and regularly updates several guidelines aimed at providing evidence-based guidance on critical aspects of IBD care to all healthcare professionals who manage patients with IBD. To provide high-quality evidence-based recommendations on medical and surgical treatment in CD, ECCO decided to develop these guidelines by adopting the GRADE [Grading of Recommendations Assessment, Development, and Evaluation] approach9. GRADE is a systematic process for developing guidelines that addresses how to frame the healthcare questions, summarize the evidence, ..

Vaccine hesitancy has been recognized by the World Health Organization as one of ten threats to public health globally in 2019. Pregnant women constitute an extremely important group for the study of knowledge and attitudes towards pediatric vaccinations. This is a cross-sectional survey conducted in two maternity hospitals in Athens. A standardized questionnaire was used. A total of 814 pregnant women with a mean age of 33.1 years and a mean gestational age of 24.4 weeks were studied. Overall, 717 (89%) of 804 pregnant women reported that they intend to vaccinate their baby in accordance with the National Vaccination Program, 7 (1%) that they do not, while 80 (10%) reported that they have not decided yet. The women provided a mean of 11.4 correct replies out of 14 questions about vaccine-preventable diseases and vaccines (mean knowledge score: 81.5%). A pediatrician has been recognized as the source for information about vaccines in most cases (611/809, 75.5%), while in 215 (26.6%) the internet was also used. Overall, pregnant women trusted physicians about information for vaccines (“very much trusted” in 55.9% and “quite trusted” in 40% of cases). Lastly, 642 (81%) women agreed with the statement “vaccinations should be mandatory for school entry” while 70 (9%) women agreed with the statement “parents should have the right to refuse their children vaccinations”. A multivariate analysis found that a gestational age of ≤20 weeks (OR = 2.33, CIs: 1.27–4.28, p-value = 0.006), having another child (OR = 4.44, CIs: 2.30–8.58, p-value < 0.001), a history of influenza vaccination (OR = 2.54, CIs = 1.37–4.71, p-value = 0.003), and a higher knowledge score about vaccine-preventable diseases and vaccines (OR = 1.33, CIs: 1.23–1.45, p-value < 0.001) were significantly associated with an increased probability to get their child vaccinated in accordance with the National Vaccination Program. © 2020 Elsevier Ltd

Vaccination against rabies and routine antibody testing of subjects participating in programs for the surveillance and control of rabies in animals is strongly recommended. The scope of this study is to describe the antibody level as measured by a commercial enzyme-linked immunosorbent assay (ELISA) after primary and booster intramuscular vaccination with a purified vero-cell rabies vaccine (PVRV) in high-risk professionals and to determine the influence of an array of factors on antibody level, that is, time elapsed since primary immunization series and booster dose, sex, age, pathologic conditions, high-risk occupation, and peak antibody level after initial scheme and booster dose. A primary series of three doses of PVRV was administered and a commercial ELISA was recommended 14 days postimmunization with continuous repetition at 6 months and yearly intervals for the laboratory personnel and the rest of the professionals, respectively. The protective antibody titer was defined as a minimum of 0.5 equivalent units/mL (EU/mL) (seroconvertion) and a booster dose was applied if the titer was determined nonprotective. The seroconversion rate (SCR) after primary vaccination was 100%, with a geometric mean titer (GMT) of 2.90 EU/mL (interquartile range [IQR]: 1.85-3.45). After booster vaccination due to nonprotective titer, the SCR was 100% and the GMT increased by 678% (95% confidence interval [CI]: 514-887) reaching 4.25 EU/mL (IQR: 4.00-4.60), 2.5 times higher than the GMT elicited by the primary vaccine scheme in the respective recipients. The titer dropped by 1.20% per month (95% CI: 0.52-1.89) regardless of booster administration or any other factor. Women had 51% higher titer compared with men (95% CI: 6-116). High-risk professionals should be verified for adequate antibody titers, but routine administration of a single booster dose of PVRV 1 year after the primary series could be considered; more evidence is needed to support the benefit in terms of immunity and logistics. © Copyright 2020, Mary Ann Liebert, Inc., publishers 2020.

Background: Surgical site infection (SSI) following spinal surgery is a frequent clinical problem with significant clinical and socio-economic consequences. Malnutrition has been linked with SSI in various other surgical procedures. Aim: To investigate whether malnutrition is a risk factor for SSI following spinal surgery. Methods: Two electronic databases (PUBMED and SCOPUS) and the Cochrane Library were searched systematically from inception to May 2019. Cohort and case–control studies assessing malnutrition as a risk factor for SSI in patients undergoing spinal procedures were considered eligible. Μalnutrition was defined according to laboratory measurements or by relevant International Classification of Diseases-9 codes. SSI was the outcome of interest. Two reviewers independently abstracted study data and assessed the risk of bias for each study. Pooled effect estimates were calculated using random effects models. Findings: In total, 22 studies (20 retrospective cohort and two case–control) with over 175,000 participants (of whom 2.14% developed postoperative SSI) were analysed. SSIs were more likely to develop in malnourished patients [odds ratio (OR) 2.31, 95% confidence interval (CI) 1.75–3.05]. While pre-operative malnutrition was significantly associated with SSI in patients undergoing thoracolumbar spinal and sacral surgery, no significant difference was seen in patients undergoing cervical spinal surgery. In subgroup analyses, similar results were observed for both hospital-based (OR 3.16, 95% CI 1.84–5.43) and population-based (OR 2.00, 95% CI 1.63–2.46) studies. Conclusions: Malnutrition is associated with increased risk of developing SSI after spinal surgery. Further high-quality research is warranted to investigate whether improvement of pre-operative nutritional status can decrease SSI rates. © 2019 The Healthcare Infection Society

Objectives: Excess population mortality during winter is most often associated with influenza A(H3N2), though susceptibility differs by age. We examined differences between influenza types/subtypes in their association with severe laboratory -confirmed cases, overall and by age group, to determine which type is the most virulent. Methods: We used nine seasons of comprehensive nationwide surveillance data from Greece (2010 - 2011 to 2018-2019) to examine the association, separately for influenza A(H1N1)pdm09, A(H3N2) and B, between the number of laboratory -confirmed severe cases (intensive care hospitalizations or deaths) per type/subtype and the overall type -specific circulation during the season (expressed as a cumulative incidence proxy). Quasi -Poisson models with identity link were used, and multiple imputation to handle missing influenza A subtype. Results: For the same level of viral circulation and across all ages, influenza A(H1N1)pdm09 was asso- ciated with twice as many intensive care hospitalizations as A(H3N2) (rate ratio (RR) 1.89, 95% CI 1.38 - 2.74) and three times more than influenza B (RR 3.27, 95%CI 2.54-4.20). Similar associations were observed for laboratory -confirmed deaths. A(H1N1)pdm09 affected adults over 40 years at similar rates, whereas A(H3N2) affected elderly people at a much higher rate than younger persons ( 65 vs. 40 - 64 years, RR for intensive care 5.42, 95% CI 3.45-8.65, and RR for death 6.19, 95%CI 4.05-9.38). Within the 40-64 years age group, A(H1N1)pdm09 was associated with an approximately five times higher rate of severe disease than both A(H3N2) and B. Discussion: Influenza A(H1N1)pdm09 is associated with many more severe laboratory -confirmed cases, likely due to a more typical clinical presentation and younger patient age, leading to more testing. A(H3N2) affects older people more, with cases less often recognized and confirmed. T. Lytras, Clin Microbiol Infect 2020;26:922

Aim: Limited data are available regarding the clinical relevance of platelet function measurements in stable patients with coronary artery disease (CAD). Our aim is to evaluate the agreement between multiple electrode aggregometry (MEA) and light transmittance aggregometry (LTA) in detecting clopidogrel low responders and their prognostic value in CAD patients with type 2 diabetes mellitus (T2DM) on dual platelet inhibition. Methods: LTA and MEA were performed in 122 stable cardiovascular patients with T2DM. The upper quartile of patients according to maximum LTA (LTAmax) and MEA measurements were defined as clopidogrel low responders. Agreement between the two methods was evaluated by kappa statistics. We assessed the potential correlation between antiplatelet response and clinical outcome and the optimal cutoff value according to ROC analysis to predict the occurrence of major adverse cardiovascular events (MACE), during 1-year follow-up period. Results: Cohen's kappa coefficients (0.214) indicated fair agreement (70.2%) between LTA and MEA. A total of 25 MACE occurred in 108 patients (23.1%). Patients with MACE had higher LTAmax than those without (57.1 ± 16.5 vs 49.3 ± 18.3, respectively, p = 0.023). MEA measurements were similar between patients with and without MACE (30.1 ± 15.4 vs 30.6 ± 20.8, respectively; p = 0.84). Multiple logistic regression showed LTAmax response as an independent predictor of death from cardiovascular causes (Odds Ratio, adjusted:0.2;0.05–0.81). ROC analysis indicated that LTAmax cutoff of 62.5% best predicted death (AUC = 0.67, sensitivity = 78%, specificity = 61.5%). Conclusions: The assessment of platelet responsiveness remains highly test-specific. Our results support the prognostic role of LTA, but not MEA testing, for death risk evaluation in stable cardiovascular T2DM patients. © 2019 Elsevier Ltd

Background: A growing body of evidence associates malnutrition with several adverse outcomes. Aim: To investigate the link between malnutrition with surgical site and periprosthetic joint infections (SSIs and PJIs) following total knee and hip arthroplasty (TKA and THA) through a comprehensive meta-analysis of observational studies. Methods: A systematic search was conducted on PubMed and Scopus databases through December 2018, and recent proceedings of major orthopaedic meetings. Data from eligible studies were extracted and synthesized; pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. Findings: Seven publications were included, reporting eight independent cohort studies with >250,000 subjects. SSIs and PJIs were more likely to develop in malnourished patients (OR: 2.49; 95% CI: 2.13–2.90; and 3.62; 2.33–5.64, respectively). The association of SSI with malnutrition was evident both after TKA (2.42; 1.94–3.02) and after THA (2.66; 1.64–4.30). Similarly, PJI was associated with malnutrition after TKA (2.55; 1.10–5.91) and after THA (3.10; 1.84–5.25). Finally, PJI correlated with malnutrition both after primary arthroplasty (3.58; 1.82–7.03) and revision arthroplasty (3.96; 2.47–6.33). The subgroup analysis by study setting confirmed the relationship between PJI and malnutrition in hospital (6.02; 3.07–11.81) and population-based (2.80; 1.76–4.44) studies. Conclusion: Malnutrition is associated with PJIs and SSIs after total joint arthroplasty. Further high-quality research is warranted to confirm or refute these findings. © 2019 The Healthcare Infection Society

Our aim was to evaluate the potential role of standard extrinsically activated thromboelastometry (EXTEM) assay in the early detection of neonatal sepsis. We studied 91 hospitalized neonates categorized in two groups: group A included 35 neonates with confirmed sepsis, while group B included 56 neonates with suspected sepsis; 274 healthy neonates served as controls. Whenever sepsis was suspected, EXTEM assay was performed, Score for Neonatal Acute Physiology Perinatal Extension (SNAPPE) and Tοllner score were calculated, and clinical findings and laboratory results were recorded. Septic neonates had significantly prolonged clotting time (CT) and clot formation time (CFT), and reduced maximum clot firmness (MCF), compared to neonates with suspected sepsis (p values 0.001, 0.001, and 0.009, respectively) or healthy neonates (p values 0.001, 0.001, and 0.021, respectively). EXTEM parameters (CT, CFT, MCF) demonstrated a more intense hypocoagulable profile in septic neonates with hemorrhagic diathesis than those without (p values 0.021, 0.007, and 0.033, respectively). In septic neonates, CFT was correlated with platelet count, SNAPPE, Tollner score, and day of full enteral feeding (p values 0.01, 0.02, 0.05, and 0.03, respectively). Conclusions: A ROTEM hypocoagulable profile at admission seems promising for the early detection of sepsis in neonates while the degree of hypocoagulation may be associated with sepsis severity.What is Known:• The early phase of septicemia might be difficult to be recognized in neonates. In adult septic patients, the diagnostic and prognostic role of thromboelastometry (ROTEM) have been extensively investigated.• Limited data are available on the role of ROTEM as an indicator of early neonatal sepsis.What is New:• ROTEM measurements indicate an early appearance of hypocoagulability in neonatal sepsis, while the degree of hypocoagulation might be associated with severity of sepsis.• ROTEM could be a useful tool in the early detection of sepsis in neonates. © 2017, Springer-Verlag GmbH Germany, part of Springer Nature.

Rotational thromboelastometry (ROTEM) is an attractive method for rapid evaluation of hemostasis in neonates. Currently, no reference values exist for ROTEM assays in full-term and pre-term neonates. Our aim was to establish reference ranges for standard extrinsically activated ROTEM assay (EXTEM) in arterial blood samples of healthy full-term and pre-term neonates. In the present study, EXTEM assay was performed in 198 full-term (≥37 weeks' gestation) and 84 pre-term infants (

Anemia is the most prevalent extraintestinal complication of inflammatory bowel disease (IBD). Our aim was to evaluate the comparative efficacy and harm of intravenous (IV) versus oral iron supplementation for correcting anemia in adult IBD patients. We conducted a systematic review and meta-analysis to integrate evidence from randomized controlled trials having enrolled adults with IBD, and comparing IV versus oral iron (head-to-head) for correcting iron-deficiency anemia. Medline, Embase, Scopus, and the Web of Science database were searched through July 2015. The Cochrane Central Register of Controlled Trials, the WHO International Clinical Trials Registry Platform, the ClinicalTrials.gov, and international conference proceedings were also investigated. Two reviewers independently abstracted study data and outcomes, and rated each trial's risk-of-bias. Pooled odds ratio (OR) estimates with their 95% CIs were calculated using fixed- and random-effects models. Five eligible studies, including 694 IBD patients, were identified. In meta-analysis, IV iron demonstrated a higher efficacy in achieving a hemoglobin rise of ≥2.0 g/dL as compared to oral iron (OR: 1.57, 95% CI: 1.13, 2.18). Treatment discontinuation rates, due to adverse events or intolerance, were lower in the IV iron groups (OR: 0.27, 95% CI: 0.13, 0.59). Similarly, the occurrence of gastrointestinal adverse events was consistently lower in the IV iron groups. On the contrary, serious adverse events (SAEs) were more frequently reported among patients receiving IV iron preparations (OR: 4.57, 95% CI: 1.11, 18.8); however, the majority of the reported SAEs were judged as unrelated or unlikely to be related to the study medication. We found no evidence of publication bias, or between-study heterogeneity, across all analyses. Risk of bias was high across primary studies, because patients and personnel were not blinded to the intervention. IV iron appears to be more effective and better tolerated than oral iron for the treatment of IBD-associated anemia. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

Aim: To investigate the association between statin use and colorectal cancer risk, we conducted an updated meta-analysis of published studies. Methods: We performed a comprehensive search for studies published up to July 2013. Eligible studies for this meta-analysis were either randomized controlled trials (RCTs) or observational studies (casecontrol or cohort) evaluating any exposure to statins and the risk of colorectal cancer. Two reviewers selected studies based on predefined inclusion criteria, and abstracted the data. Pooled relative risk (RR) estimates with their 95%CI were calculated using fixedand random-effects models. Then, we assessed the potential presence of publication bias and betweenstudies heterogeneity. To evaluate the results, we also performed a "leave-one-out" sensitivity analysis. Results: A total of 40 studies, involving more than eight million subjects, contributed to the analysis. They were grouped on the basis of study design and, consequently, three separate meta-analyses were conducted. A similar modest reduction in the risk of colorectal cancer with statin use was observed, which was not statistically significant among RCTs (RR = 0.89, 95%CI: 0.74-1.07; n = 8), but reached statistical significance among cohort studies (RR = 0.91, 95%CI: 0.83-1.00; n = 13) and case-control studies (RR = 0.92, 95%CI: 0.87-0.98; n = 19). While we did not find significant evidence of selective outcome reporting or publication bias, substantial heterogeneity was detected, mainly among the observational studies. The sensitivity analysis confirmed the stability of our results. Conclusion: A modest reduction in risk of colorectal cancer among statin users cannot be disproved. Further targeted research is warranted. © 2014 Baishideng Publishing Group Co., Limited. All rights reserved.

We systematically reviewed randomized controlled trials (RCTs) assessing the effectiveness ofcomputerized decision support systems (CDSSs) featuring rule- or algorithm-based software integrated with electronic health records (EHRs) and evidence-based knowledge. We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Abstracts of Reviews of Effects. Information on system design, capabilities, acquisition, implementation context, and effects on mortality, morbidity, and economic outcomes were extracted. Twenty-eight RCTs were included. CDSS use did not affect mortality (16 trials, 37395 patients; 2282 deaths; risk ratio [RR] = 0.96; 95%confidence interval [CI] = 0.85, 1.08; I2 = 41%).Astatistically significant effect was evident in the prevention ofmorbidity, any disease (9 RCTs; 13868 patients;RR = 0.82; 95% CI = 0.68, 0.99; I2 = 64%), but selectiveoutcomereporting or publication bias cannot be excluded. We observed differences for costs and health service utilization, although these were often small in magnitude. Across clinical settings, new generation CDSSs integrated with EHRs do not affect mortality and might moderately improvemorbidity outcomes. © 2013 American Public Health Association.

3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) have been proved highly effective treatments for primary and secondary prevention of cardiovascular diseases. Despite widespread and long-term use of statins, there is still a debate concerning their association with cancer at various sites, including breast. As of today, the accumulated epidemiological evidence does not support the hypothesis that statin use affects the risk of developing breast cancer when taken at low doses for managing hypercholesterolemia. However, current evidence cannot exclude an increased risk of breast cancer with statin use in subsets of individuals, for example, the elderly. On the other hand, some studies show that statins might be useful to prevent recurrence and improve survival in patients already suffering from certain breast cancer types. They could also be combined with certain anticancer drugs and potentiate their effects, ameliorate their side effects or prevent the development of resistance. Further research is warranted to clarify these issues. © 2014 Informa UK, Ltd.

The quality of guidelines is often modest and highly variable. We searched the Medline database for occupational asthma (OA) guidelines meeting our inclusion criteria and undertook a systematic appraisal of them. Six appraisers independently evaluated these guidelines using the AGREE II (Appraisal of Guidelines, Research and Evaluation II) instrument. Standardised scores for each domain and for overall quality were calculated, as well as intraclass correlation coefficients to assess agreement among appraisers. Seven relevant guidelines were identified. Three were based on a systematic review of the evidence. Most guidelines scored high on the domains 'Scope and purpose' and 'Clarity and presentation', but scores on the other domains were variable. The lowest scores were for 'Applicability', suggesting that guideline developers did not pay sufficient attention to practical problems affecting the implementation of their recommendations. We also observed a trend toward improved scores in guidelines published after 2000. Inter-rater agreement was good for most domains, and particularly for ' Rigour of development'. This domain was most strongly correlated with the overall assessment scores, together with 'Scope and purpose' and 'Editorial independence'. The quality of OA guidelines is variable, both within and across guidelines. There is significant room for improvement, and greater efforts to produce high-quality guidelines are warranted, in order to assist clinical decision-making.

hese recommendations summarise the current evidence on the medical management of adult patients with UC. Gaps were iden-tified during the analysis of the data, which should be addressed by further research. Where evidence is lacking or is very weak and evidence-based recommendations cannot be given, ECCO provides alternative tools, such as Topical Reviews28,95,153–158 or Position Papers.159–161 It is important that clinicians use these guidelines within the framework of local regulations, and seek to understand and address the individual needs and expectations of every patient. We recognise that constraints on health care resources are an im-portant factor in determining whether recommendations can be implemented for patients in many countries. The recommendations outlined here should be used to inform treatment decisions and form part of an overall multidisciplinary treatment plan for patients with UC, which may also encompass psychological, nutritional, and other non-pharmacological interventions.

ECCO reviewed the available high-quality evidence on the medical management of CD and developed evidence-based recommendations on the medical treatment of adult patients with CD. These guidelines do not cover specific situations, such as postoperative management of adult patients with CD, which was already covered in the latest ECCO Guidelines on Crohn’s disease.

This is the second of a series of two articles reporting the European Crohn’s and Colitis Organisation [ECCO] evidence-based consensus on the management of adult patients with ulcerative colitis [UC]. The first article is focused on medical management, and the present article addresses medical treatment of acute severe ulcerative colitis [ASUC] and surgical management of medically refractory UC patients, including preoperative optimisation, surgical strategies, and technical issues. The article provides advice for a variety of common clinical and surgical conditions. Together, the articles represent an update of the evidence-based recommendations of the ECCO for UC.

This article is the second in a series of two publications relating to the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of Crohn's disease. The first article covers medical management; the present article addresses surgical management, including preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations. Both articles together represent the evidence-based recommendations of the ECCO for Crohn's disease and an update of previous guidelines. ispartof: JOURNAL OF CROHNS & COLITIS vol:14 issue:2 pages:155-168 ispartof: location:England status: published

BACKGROUND & AIMS: Multiple environmental factors have been associated with the development of inflammatory bowel diseases (IBDs). We performed an umbrella review of meta-analyses to summarize available epidemiologic evidence and assess its credibility. METHODS: We systematically identified and appraised meta-analyses of observational studies examining environmental factors and risk of IBD (Crohn's disease [CD] or ulcerative colitis [UC]). For each meta-analysis, we considered the random effects estimate, its 95% confidence interval, the estimates of heterogeneity, and small-study effects, and we graded the evidence according to prespecified criteria. Methodologic quality was assessed with AMSTAR (ie, A Measurement Tool to Assess Systematic Reviews) 2. RESULTS: We examined 183 estimates in 53 meta-analyses of 71 environmental factors related to lifestyles and hygiene, surgeries, drug exposures, diet, microorganisms, and vaccinations. We identified 9 factors that increase risk of IBD: smoking (CD), urban living (CD and IBD), appendectomy (CD), tonsillectomy (CD), antibiotic exposure (IBD), oral contraceptive use (IBD), consumption of soft drinks (UC), vitamin D deficiency (IBD), and non-Helicobacter pylori-like enterohepatic Helicobacter species (IBD). We identified 7 factors that reduce risk of IBD: physical activity (CD), breastfeeding (IBD), bed sharing (CD), tea consumption (UC), high levels of folate (IBD), high levels of vitamin D (CD), and H pylori infection (CD, UC, and IBD). Epidemiologic evidence for all of these associations was of high to moderate strength we identified another 11 factors associated with increased risk and 16 factors associated with reduced risk with weak credibility. Methodologic quality varied considerably among meta-analyses. Several associations were based on findings from retrospective studies, so it is not possible to determine if these are effects of IBD or the results of recall bias. CONCLUSIONS: In an umbrella review of meta-analyses, we found varying levels of evidence for associations of different environmental factors with risk of IBD. High-quality prospective studies with analyses of samples from patients with recent diagnoses of IBD are needed to determine whether these factors cause or are results of IBD and their pathogenic mechanisms. 157 3 647 659.e4

Aims The comparative efficacy, safety and tolerability of budesonide-MMX and oral mesalamine in active, mild-to-moderate ulcerative colitis (UC) are unclear. We conducted a network meta-analysis to fill this evidence gap. Methods We searched PubMed, Scopus, Embase, the Cochrane Library, clinical trial registries, regulatory agencies' websites and international conference proceedings, up to July 2018, to identify randomized controlled trials of adult patients with active, mild-to-moderate UC, comparing budesonide-MMX or mesalamine against placebo, or against each other, or different dosing strategies, for induction of remission. Two reviewers independently abstracted study data and outcomes, and assessed each trial's risk-of-bias. Results We identified and synthesized evidence from 15 eligible trials including 4083 participants. Budesonide-MMX 9 mg/day and mesalamine >2.4 g/day had similar efficacy for induction of clinical and endoscopic remission (OR = 0.97 0.59–1.60), both showing superiority over placebo (OR = 2.68 1.75–4.10, and OR = 2.75 1.94–3.90, respectively). Furthermore, mesalamine >2.4 g/day was more efficacious than mesalamine 1.6–2.4 g/day (odds ratio = 1.27 1.03–1.56). Secondary analyses showed that mesalamine >2.4 g/day ranks at the top among comparator treatments regarding safety (serious adverse events surface under the cumulative ranking area [SUCRA] 79.2%) and tolerability (treatment discontinuations or withdrawals from the study due to adverse events SUCRA 96.7%). There was no evidence of inconsistency, while heterogeneity between studies and risk of publication bias were low. Conclusion Budesonide-MMX and mesalamine >2.4 g/day had similar efficacy for induction of clinical and endoscopic remission in active, mild-to-moderate UC however, mesalamine >2.4 g/day showed better tolerability. Further high-quality research is warranted. 85 10 2244 2254

Background & Aims Vedolizumab is effective and safe for the treatment of Crohn’s disease (CD) and ulcerative colitis (UC). Little is known about the incidence rate of loss of response to vedolizumab maintenance therapy or whether dose intensification restores response to this drug. Methods We searched PubMed, Scopus and conference abstracts (Digestive Disease Week, European Crohn’s and Colitis Organization, and United European Gastroenterology Week), through December 2017, for experimental or observational cohort studies of vedolizumab use in adult patients with CD or UC; we identified studies that provided sufficient data to determine the incidence rate of loss of response among initial responders and the ability of dose intensification to restore response. Two reviewers independently abstracted study data and outcomes and rated each study’s risk of bias. The studies were evaluated for heterogeneity and publication bias. Summary estimates were calculated using random effects models. Results We analyzed data from 10 eligible cohorts; most patients had received prior treatment with a tumor necrosis factor antagonist. The pooled incidence rates of loss of response were 47.9 per 100 person-years of follow up (95% CI, 26.3‒87.0; I2 = 74%) among patients with CD and 39.8 per 100 person-years of follow up (95% CI, 35.0‒45.3; I2 = 0%) among patients with UC. Dose intensification restored response to the drug in 53.8% of secondary non-responders (95% CI, 21.8%‒82.9%; I2 = 77%). Conclusions In a systematic review and meta-analysis, we found high proportions of patients with CD or UC to lose responsiveness to vedolizumab maintenance therapy. Dose intensification restores responsiveness to more than half of these patients. Additional studies are warranted to inform clinical decision making.

AIM: To determine the efficacy of calcium supplementation in reducing the recurrence of colorectal adenomas. " METHODS: We conducted a systematic review and meta-analysis of published studies. We searched PubMed, Scopus, the Cochrane Library, the WHO International Clinical Trials Registry Platform, and the ClinicalTrials. gov website, through December 2015. Randomized, placebo-controlled trials assessing supplemental calcium intake for the prevention of recurrence of adenomas were eligible for inclusion. Two reviewers independently selected studies based on predefined criteria, extracted data and outcomes (recurrence of colorectal adenomas, and advanced or ""high-risk"" adenomas), and rated each trial's risk-of-bias. Between-study heterogeneity was assessed, and pooled risk ratio (RR) estimates with their 95% confidence intervals (95% CI) were calculated using fixed-and random-effects models. To express the treatment effect in clinical terms, we calculated the number needed to treat (NNT) to prevent one adenoma recurrence. We also assessed the quality of evidence using GRADE." RESULTS: Four randomized, placebo-controlled trials met the eligibility criteria and were included. Daily doses of elemental calcium ranged from 1200 to 2000 mg, while the duration of treatment and follow-up of participants ranged from 36 to 60 mo. Synthesis of intention-to-treat data, for participants who had undergone follow-up colonoscopies, indicated a modest protective effect of calcium in prevention of adenomas (fixed-effects, RR = 0.89, 95% CI: 0.82-0.96 random-effects, RR = 0.87, 95% CI: 0.77-0.98 high quality of evidence). The NNT was 20 (95% CI: 12-61) to prevent one colorectal adenoma recurrence within a period of 3 to 5 years. On the other hand, the association between calcium treatment and advanced adenomas did not reach statistical significance (fixed-effects, RR = 0.92, 95% CI: 0.75-1.13 random-effects, RR = 0.92, 95% CI: 0.71-1.18 moderate quality of evidence). CONCLUSION: Our results suggest a modest chemo-preventive effect of calcium supplements against recurrent colorectal adenomas over a period of 36 to 60 mo. Further research is warranted. AIM: To determine the efficacy of calcium supplementation in reducing the recurrence of colorectal adenomas. METHODS: We conducted a systematic review and meta-analysis of published studies. We searched PubMed, Scopus, the Cochrane Library, the WHO International Clinical Trials Registry Platform, and the ClinicalTrials.gov website, through December 2015. Randomized, placebo-controlled trials assessing supplemental calcium intake for the prevention of recurrence of adenomas were eligible for inclusion. Two reviewers independently selected studies based on predefined criteria, extracted data and outcomes (recurrence of colorectal adenomas, and advanced or "high-risk" adenomas), and rated each trial's riskof- bias. Between-study heterogeneity was assessed, and pooled risk ratio (RR) estimates with their 95% confidence intervals (95%CI) were calculated using fixed- and random-effects models. To express the treatment effect in clinical terms, we calculated the number needed to treat (NNT) to prevent one adenoma recurrence. We also assessed the quality of evidence using GRADE. RESULTS: Four randomized, placebo-controlled trials met the eligibility criteria and were included. Daily doses of elemental calcium ranged from 1200 to 2000 mg, while the duration of treatment and follow-up of participants ranged from 36 to 60 mo. Synthesis of intention-to-treat data, for participants who had undergone follow-up colonoscopies, indicated a modest protective effect of calcium in prevention of adenomas (fixed-effects, RR = 0.89, 95%CI: 0.82-0.96; randomeffects, RR = 0.87, 95%CI: 0.77-0.98; high quality of evidence). The NNT was 20 (95%CI: 12-61) to prevent one colorectal adenoma recurrence within a period of 3 to 5 years. On the other hand, the association between calcium treatment and advanced adenomas did not reach statistical significance (fixed-effects, RR = 0.92, 95%CI: 0.75-1.13; random-effects, RR = 0.92, 95%CI: 0.71-1.18; moderate quality of evidence). CONCLUSION: Our results suggest a modest chemopreventive effect of calcium supplements against recurrent colorectal adenomas over a period of 36 to 60 mo. Further research is warranted.