Search

Introduction Crohn’s disease and ulcerative colitis are chronic inflammatory bowel diseases (IBD) with a relapsing-remitting nature. With adequate non-invasive prediction of mucosal inflammation, endoscopies can be prevented and treatment optimised earlier for better disease control. We aim to validate and recalibrate commonly used patient-reported symptom scores combined with a faecal calprotectin (FC) home test as non-invasive diagnostic tool for remote monitoring of IBD, both in daily practice and in a strict trial setting. Endoscopy will be used as the gold standard.Methods and analysis In this multicentre prospective validation study, adult IBD patients are asked to fill out questionnaires regarding disease activity (Monitor IBD At Home, mobile Health Index, Manitoba IBD Index, IBD control and patient-HBI/patient-Simple Clinical Colitis Activity Index), perform a FC home test and collect a stool sample for routine laboratory FC measurement, before the start of the bowel preparation for the ileocolonoscopy. Endoscopic disease activity will be scored according to the simplified endoscopic score for Crohn’s disease (CD) for CD patients or Ulcerative Colitis Endoscopic Index for Severity and Mayo Endoscopic Subscore for ulcerative colitis patients. The main study outcome is the diagnostic test accuracy of the various patient-reported scores to assess mucosal inflammation in combination with a FC home test.Ethics and dissemination This study is approved by the Medical Research Ethics Committee of azM/UM in Maastricht dated 03 March 2021 (METC 20–085) and is monitored by the Clinical Trial Centre Maastricht according to Good Clinical Practice guidelines. Written informed consent will be obtained from all patients. Study results will be published in international peer-reviewed medical journals.Trial registration number NCT05886322

Abstract Background Many patients with Inflammatory Bowel Diseases (IBD) suffer from psychological distress, fatigue and sleep disturbances, which are associated with reduced quality of life (QoL) and increased societal costs. Only limited psychosocial treatment options are available. As Mindfulness-Based Cognitive Therapy (MBCT) has demonstrated to improve psychological distress, QoL and sleep in other populations, MBCT might also be effective in patients with IBD. Methods The MindIBD study is a prospective, multicentre, randomised controlled trial comparing MBCT plus Treatment As Usual (TAU) versus TAU alone in a targeted number of 136 IBD patients in remission, aged 16 years and older with at least mild psychological distress (Hospital Anxiety and Depression Scale (HADS) total score ≥ 11). Primary outcome is reduction of psychological distress post-intervention, measured by the HADS. In addition, the effect of MBCT on sleep quality (including actigraphy and electroencephalography recordings), fatigue, disease activity, perceived disease control, QoL and positive mental health will be examined. Assessments will be conducted at baseline and at 3, 6, 9 and 12 months follow-up. Cost-effectiveness will be determined and a process evaluation will be conducted. Discussion This study will provide valuable insight into the clinical effect of MBCT on psychological distress, sleep quality, fatigue and QoL in IBD patients and into the cost-effectiveness. If effective, MBCT can be a valuable addition to the available psychosocial interventions for patients with IBD. Moreover, findings from this study may also be applicable in patients with other chronic conditions. Trial registration ClinicalTrials.gov: NCT04646785, registered on 30/11/2020.

Antibiotics are widely used in intensive animal husbandry in the Netherlands and are subsequently emitted to soil via manure. To predict degradation and mobility in soil, generic sorption models have been derived. However, most of the coefficients used in generic models are based on a limited range of soils and have not been validated for agricultural soils in the Netherlands. To improve model predictions and assess to what extent differences among soils affect sorption and degradation, an experimental study has been performed. Using a recently developed experimental approach, both the degradation (DT50) and mobility (Kd) of eight selected commonly used antibiotics were determined in 29 typical Dutch agricultural soils. Median DT50 values range from 5.3 days for Sulfadiazine to 120 days for Trimethoprim but are affected by soil type. The ratio of the lowest and highest DT50 for a given antibiotic among soils can be as large as 151, for Tylosin. Measured values of the logKd also range from 0.19 for Sulfadiazine to more than 2 for Doxycycline, Flumequine, Trimethoprim, Tylosin and Enrofloxacine. The impact of soil on Kd is large, especially for more mobile antibiotics such as Sulfadoxine and Sulfadiazine. Both the range in DT50 and Kd can be predicted reasonably well using a Freundlich type regression model that accounts for the variation in soil type and sampling depth. Organic matter, iron oxides, pH and clay content appear to be the main constituents and explain between 29 % (Trimethoprim) and 77 % of the variation in DT50 and between 64 % (Lincomycin) and 87 % (Sulfadoxine and Sulfadiazine) of the variation of Kd. The effect of depth on DT50 and Kd is however limited. The information thus obtained in combination with local data on soil type can be used to more accurately predict the potential risk of relevant antibiotics in soil and transport to ground- and nearby surface waters.

Background and Aims: To determine how the health state of ulcerative colitis patients is impacted by their disease, different health state questionnaires are deployed. This study examines to what extent these health state questionnaires determine the same underlying health state concept and to what extent the complementary use of the health state questionnaires has added value for physicians. Methods: In total, 307 patients were enrolled in this cross-sectional multicenter cohort study. Medical, psychological, economic, and composite health state questionnaires were administered to determine reliability, convergent validity, and explained variance. Reliability was determined using Cronbach’s alpha. Convergent validity was measured using Spearman’s correlation coefficients. Explained variance was interpreted using R-squared coefficients. Results: All questionnaires can be considered reliable. The medical, psychological, and economic health state questionnaires show weak to moderate convergent validity with each other. The medical, psychological, and economic health state questionnaires also explain limited variance in each other’s outcomes. The composite health state questionnaire shows moderate to strong convergent validity with the other health state questionnaires. The composite health state questionnaire further explains considerable variance in the outcomes of the other health state questionnaires. Conclusion: Deploying divergent medical, psychological, and economic health state questionnaires may have added value as they provide a multiperspective holistic insight into patients’ health states. Deploying the composite health state questionnaire combined with other health state questionnaires may have added value as it provides additional understanding of their outcomes. Deploying an independent psychological health state questionnaire may have added value as it shows particularly limited convergent validity and explained variance regarding other health state questionnaires.

There are limited data on therapeutic drug monitoring (TDM) in inflammatory bowel disease (IBD) patients treated with vedolizumab (VDZ). Although an exposure–response relation has been demonstrated in the post-induction phase, this relationship is more uncertain in the maintenance phase of treatment. The aim of our study was to determine whether there is an association between VDZ trough concentration and clinical and biochemical remission in the maintenance phase. A prospective, observational multicenter study has been performed on patients with IBD on VDZ in the maintenance treatment (≥14 weeks). Patient demographics, biomarkers, and VDZ serum trough concentrations were collected. Clinical disease activity was scored by the Harvey Bradshaw Index (HBI) for Crohn’s disease (CD) and the Simple Clinical Colitis Activity Index (SCCAI) for ulcerative colitis (UC). Clinical remission was determined as HBI < 5 and SCCAI < 3. Biochemical remission was defined as fecal calprotectin p = 0.019). In this population, higher trough VDZ concentrations were associated with biochemical remission but not with clinical remission.

Abstract Background Pancreatic cancer has a very poor prognosis. Best practices for the use of chemotherapy, enzyme replacement therapy, and biliary drainage have been identified but their implementation in daily clinical practice is often suboptimal. We hypothesized that a nationwide program to enhance implementation of these best practices in pancreatic cancer care would improve survival and quality of life. Methods/design PACAP-1 is a nationwide multicenter stepped-wedge cluster randomized controlled superiority trial. In a per-center stepwise and randomized manner, best practices in pancreatic cancer care regarding the use of (neo)adjuvant and palliative chemotherapy, pancreatic enzyme replacement therapy, and metal biliary stents are implemented in all 17 Dutch pancreatic centers and their regional referral networks during a 6-week initiation period. Per pancreatic center, one multidisciplinary team functions as reference for the other centers in the network. Key best practices were identified from the literature, 3 years of data from existing nationwide registries within the Dutch Pancreatic Cancer Project (PACAP), and national expert meetings. The best practices follow the Dutch guideline on pancreatic cancer and the current state of the literature, and can be executed within daily clinical practice. The implementation process includes monitoring, return visits, and provider feedback in combination with education and reminders. Patient outcomes and compliance are monitored within the PACAP registries. Primary outcome is 1-year overall survival (for all disease stages). Secondary outcomes include quality of life, 3- and 5-year overall survival, and guideline compliance. An improvement of 10% in 1-year overall survival is considered clinically relevant. A 25-month study duration was chosen, which provides 80% statistical power for a mortality reduction of 10.0% in the 17 pancreatic cancer centers, with a required sample size of 2142 patients, corresponding to a 6.6% mortality reduction and 4769 patients nationwide. Discussion The PACAP-1 trial is designed to evaluate whether a nationwide program for enhanced implementation of best practices in pancreatic cancer care can improve 1-year overall survival and quality of life. Trial registration ClinicalTrials.gov, NCT03513705 . Trial opened for accrual on 22th May 2018.

Phosphate binders such as sevelamer are widely used in patients with chronic kidney disease to lower serum phosphate levels. We present a case of a 67-year-old woman with lower gastrointestinal bleeding after 9 days of using sevelamer carbonate (Renvela ® ). Sigmoidoscopy revealed multiple deep ulcers (diameter 10–15 mm) and mucosal oedema. Histologic examination showed deposition of sevelamer crystals in these rectal ulcers. We hypothesized that the lower gastrointestinal bleeding was caused by deposition of sevelamer crystals. After cessation of sevelamer, gastrointestinal bleeding stopped. Deposition of sevelamer crystals in the gastrointestinal tract is a rare complication of sevelamer therapy. There are only 17 other recorded cases of gastrointestinal deposition of sevelamer crystals. This adverse effect should be considered in all patients taking sevelamer who present with gastrointestinal symptoms, such as gastrointestinal bleeding and abdominal pain. When sevelamer is discontinued, symptoms and mucosal damage appear to revert.

Introduction Adalimumab is effective for maintenance of remission in patients with Crohn’s disease (CD) at a dose of 40 mg subcutaneously every 2 weeks. However, adalimumab is associated with (long-term) adverse events and is costly. The aim of this study is to demonstrate non-inferiority and cost-effectiveness of disease activity guided adalimumab interval lengthening compared to standard dosing of every other week (EOW).Methods and analysis The Lengthening Adalimumab Dosing Interval (LADI) study is a pragmatic, multicentre, open label, randomised controlled non-inferiority trial. Non-inferiority is reached if the difference in cumulative incidence of persistent (>8 weeks) flares does not exceed the non-inferiority margin of 15%. 174 CD patients on adalimumab maintenance therapy in long-term (>9 months) clinical and biochemical remission will be included (C-reactive protein (CRP) 250 µg/g, CRP≥10 mg/l, HBI≥5. Secondary outcomes include cumulative incidence of transient flares, adverse events, predictors for successful dose reduction and cost-effectiveness.Ethics and dissemination The study is approved by the Medical Ethics Committee Arnhem-Nijmegen, the Netherlands (registration number NL58948.091.16). Results will be published in peer-reviewed journals and presented at international conferences.Trial registration numbers EudraCT registry (2016-003321-42); Clinicaltrials.gov registry (NCT03172377); Dutch trial registry (NTRID6417).

Hellen CS Römkens, Henny JM Beckers, Jan SAG Schouten, Tos TJM Berendschot, Carroll AB Webers Department of Ophthalmology, Maastricht University Medical Center+, Maastricht, the Netherlands Purpose: The aim of this study is to generate reference values for anterior chamber morphometrics to facilitate the interpretation of anterior chamber images acquired with swept-source optical coherence tomography (SS-OCT) in a Caucasian population.Materials and methods: Non-glaucomatous Caucasian subjects, who were newly referred to the outpatient department of the University Eye Clinic Maastricht UMC+, were asked to undergo anterior segment assessment with SS-OCT imaging prior to routine eye examination (including visual acuity and refractive error measurements, Goldmann applanation tonometry, slit lamp examination and funduscopy).Results: A total of 647 Caucasian subjects, aged 40–80 years, were included. Mean age (± standard deviation) was 61.7±10.3 years, and 294 were male (45%). Mean refractive error was -0.63±3.17 D. OCT images and measurements were obtained in all cases. The mean temporal trabecular iris angle at 500 µm (TIA500) was 27.04°±12.04°, the mean nasal TIA500 was 27.43°±11.75°, the mean anterior chamber depth (ACD) was 2.75±0.39 mm and the mean lens vault (LV) was 0.44±0.30 mm. A smaller temporal TIA500, shallower ACD and higher LV were found in female and hyperopic subjects.Conclusion: Reference values for anterior chamber morphometrics in Caucasians were generated, quantified and presented. These values offer tools for the interpretation of anterior segment images of Caucasians and differentiation between presumed mechanisms of angle closure. Keywords: reference value, anterior chamber, optical coherence tomography, Caucasian

Background and Aims We aimed to assess cost-effectiveness of increasing adalimumab dose intervals compared to the conventional dosing interval in patients with Crohn's disease [CD] in stable clinical and biochemical remission. Design We conducted a pragmatic, open-label, randomized controlled non-inferiority trial, comparing increased adalimumab intervals with the 2-weekly interval in adult CD patients in clinical remission. Quality of life was measured with the EQ-5D-5L. Costs were measured from a societal perspective. Results are shown as differences and incremental net monetary benefit [iNMB] at relevant willingness to accept [WTA] levels. Results We randomized 174 patients to the intervention [ n  = 113] and control [ n  = 61] groups. No difference was found in utility (difference: −0.017, 95% confidence interval [−0.044; 0.004]) and total costs (−€943, [−€2226; €1367]) over the 48-week study period between the two groups. Medication costs per patient were lower (−€2545, [−€2780; −€2192]) in the intervention group, but non-medication healthcare (+€474, [+€149; +€952]) and patient costs (+€365 [+€92; €1058]) were higher. Cost–utility analysis showed that the iNMB was €594 [−€2099; €2050], €69 [−€2908; €1965] and −€455 [−€4,096; €1984] at WTA levels of €20 000, €50 000 and €80 000, respectively. Increasing adalimumab dose intervals was more likely to be cost-effective at WTA levels below €53 960 per quality-adjusted life year. Above €53 960 continuing the conventional dose interval was more likely to be cost-effective. Conclusion When the loss of a quality-adjusted life year is valued at less than €53 960, increasing the adalimumab dose interval is a cost-effective strategy in CD patients in stable clinical and biochemical remission. Clinical Trial Registration Number ClinicalTrials.gov , number NCT03172377. [ABSTRACT FROM AUTHOR]

Background and Aims Both methotrexate and tioguanine can be considered as treatment options in patients with Crohn's disease after failure of conventional thiopurines. This study aimed to compare tolerability and drug survival of methotrexate and tioguanine therapy after failure of conventional thiopurines in patients with Crohn's disease. Methods We conducted a retrospective, multicentre study, including patients with Crohn's disease initiating monotherapy methotrexate or tioguanine after failure [all causes] of conventional thiopurines. Follow-up duration was 104 weeks or until treatment discontinuation. The primary outcome was cumulative therapy discontinuation incidence due to adverse events. Secondary outcomes included total number of [serious] adverse events, and ongoing monotherapy. Results In total, 219 patients starting either methotrexate [ n  = 105] or tioguanine [ n  = 114] were included. In all 65 [29.7%] patients (methotrexate 43.8% [46/105 people], tioguanine 16.7% [19/114 people], p  <0.001) discontinued their treatment due to adverse events during follow-up. Median time until discontinuation due to adverse events was 16 weeks (interquartile range [IQR] 7-38, p  = 0.812). Serious adverse events were not significantly different. Patients treated with methotrexate experienced adverse events more often [methotrexate 83%, tioguanine 46%, p  <0.001]. Total monotherapy drug survival after 104 weeks was 22% for methotrexate and 46% for tioguanine [ p  <0.001]. Conclusions We observed a higher cumulative discontinuation incidence due to adverse events for methotrexate [44%] compared with tioguanine [17%] in Crohn's disease patients after failure of conventional thiopurines. The total adverse events incidence during methotrexate use was higher, whereas serious adverse events incidence was similar. These favourable results for tioguanine treatment may guide the selection of immunosuppressive therapy after failure of conventional thiopurines. [ABSTRACT FROM AUTHOR]

Background and Aims The COVID-19 risk and disease course in inflammatory bowel disease [IBD] patients remains uncertain. Therefore, we aimed to assess the clinical presentation, disease course, and outcomes of COVID-19 in IBD patients. Second, we determined COVID-19 incidences in IBD patients and compared this with the general population. Methods We conducted a multicentre, nationwide IBD cohort study in The Netherlands and identified patients with COVID-19. First, we assessed the COVID-19 disease course and outcomes. Second, we compared COVID-19 incidences between our IBD study cohort and the general Dutch population. Results We established an IBD cohort of 34 763 patients. COVID-19 was diagnosed in 100/34 763 patients [0.29%]; 20/100 of these patients [20%] had severe COVID-19 defined as admission to the intensive care unit, mechanical ventilation, and/or death. Hospitalisation occurred in 59/100 [59.0%] patients and 13/100 [13.0%] died. All patients who died had comorbidities and all but one were ≥65 years old. In line, we identified ≥1 comorbidity as an independent risk factor for hospitalisation (odds ratio [OR] 4.20, 95% confidence interval [CI] 1.58–11.17,; p = 0.004). Incidences of COVID-19 between the IBD study cohort and the general population were comparable (287.6 [95% CI 236.6–349.7] versus 333.0 [95% CI 329.3–336.7] per 100000 patients, respectively; p = 0.15). Conclusions Of 100 cases with IBD and COVID-19, 20% developed severe COVID-19, 59% were hospitalised and 13% died. A comparable COVID-19 risk was found between the IBD cohort [100/34 763 = 0.29%] and the general Dutch population. The presence of ≥1 comorbidities was an independent risk factor for hospitalisation due to COVID-19. [ABSTRACT FROM AUTHOR]

Copyright of Markt en Mededinging is the property of Boom uitgevers Den Haag and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and Aims There is paucity of data on safety and efficacy of anti-tumour necrosis factor [TNF] in elderly inflammatory bowel disease [IBD] patients. We aimed to compare the long-term treatment failure rates and safety of a first anti-TNF agent in IBD patients between different age groups [<40 years/40–59 years/≥60 years]. Methods IBD patients who started a first anti-TNF agent were identified through IBDREAM, a multicentre prospective IBD registry. Competing risk regression was used to study treatment failure, defined as time to drug discontinuation due to adverse events [AEs] or lack of effectiveness, with discontinuation due to remission as a competing risk. Results A total of 895 IBD patients were included; 546 started anti-TNF at age <40 [61.0%], 268 at age 40–59 [29.9%], and 81 at age ≥60 [9.1%]. Treatment failure rate was higher in the two older groups (subhazard rate [SHR] age ≥60 1.46, SHR age 40–59 1.21; p  = 0.03). The SHR in the elderly [>60] was 1.52 for discontinuation due to AEs and 1.11 for lack of effectiveness. Concomitant thiopurine use was associated with a lower treatment failure rate (SHR 0.78, 95% confidence interval [CI] 0.62–0.98, p  = 0.031). Serious adverse event [SAE] rate, as well as serious infection rate, were significantly higher in elderly IBD patients [61.2 versus 16.0 and 12.4 per 1000 patient-years, respectively] whereas the malignancy rate was low in all age groups. Conclusions Elderly IBD patients starting a first anti-TNF agent showed higher treatment failure rates, but concomitant thiopurine use at baseline was associated with lower failure rates. Elderly IBD patients demonstrated higher rates of SAEs and serious infections. [ABSTRACT FROM AUTHOR]

Background and Aims The long-term risk of high-grade dysplasia [HGD] and colorectal cancer [CRC] following low-grade dysplasia [LGD] in inflammatory bowel disease [IBD] patients is relatively unknown. We aimed to determine the long-term cumulative incidence of advanced neoplasia [HGD and/or CRC], and to identify risk factors for advanced neoplasia in a nationwide IBD cohort with a history of LGD. Methods This is a nationwide cohort study using data from the Dutch National Pathology Registry [PALGA] to identify all IBD patients with LGD between 1991 and 2010 in the Netherlands. Follow-up data were collected until January 2016. We determined the cumulative incidence of advanced neoplasia and identified risk factors via multivariable Cox regression analysis. Results We identified 4284 patients with colonic LGD with a median follow-up of 6.4 years after initial LGD diagnosis. The cumulative incidence of subsequent advanced neoplasia was 3.6, 8.5, 14.4 and 21.7%, after 1, 5, 10 and 15 years, respectively. The median time to develop advanced neoplasia after LGD was 3.6 years. Older age [≥ 55 years] at moment of LGD (hazard ratio [HR] 1.73, 95% confidence interval [CI] 1.44–2.06), male sex [HR 1.33, 95% CI 1.10–1.60], and follow-up at an academic [vs non-academic] medical centre [HR 1.37, 95% CI 1.07–1.76] were independent risk factors for advanced neoplasia following LGD. Conclusions In a large nationwide cohort with long-term follow-up of IBD patients with LGD, the cumulative incidence of advanced neoplasia was 21.7% after 15 years. Older age at LGD [≥55 years], male sex and follow-up by a tertiary IBD referral centre were independent risk factors for advanced neoplasia development after initial LGD. [ABSTRACT FROM AUTHOR]

Background and Aims: Histological remission [HR] is a potential treatment target in ulcerative colitis [UC]. Limited 'real world' data are available on the reliability of histological scoring when assessing minimal histological inflammation. The aim of this study was to investigate the reliability of UC histological scores in colonic biopsies showing mucosal healing [MH] and limited histological inflammation, and to compare the 'daily practice' histological assessment with expert reviews by gastrointestinal [GI] pathologists. Methods: We performed a retrospective single-centre study. Colonic biopsies from UC patients with MH [Mayo score = 1] were included. All biopsies assessed in daily practice were reassessed by three blinded GI pathologists using three histological scores (Geboes score [GS], Riley score [RS], Harpaz [Gupta] Index [HGI]) and a global visual scale [GVS]. We evaluated inter- and intraobserver variation between GI pathologists and correlations between scores including the initial histological assessment using Cronbach's alpha and Spearman rho analysis. Results: In total, 270 biopsies from 39 UC patients were included. The inter-observer concordance for all histological indexes was substantial to almost perfect [GS 0.84; HGI 0.61; GVS 0.74, RS 0.91]. Correlation between the RS and GS was almost perfect [R = 0.86], but we found no correlation between the primary histological assessment and reassessment by GI pathologists. Conclusions: Current UC histological scores reliably assess limited histological inflammation in UC patients. The discrepancy between the initial histological assessment and the reassessment by dedicated GI pathologists suggests a gap between daily practice and academic expertise. This issue may limit the implementation of HR as a treatment target for UC in daily practice. [ABSTRACT FROM AUTHOR]

Discontinuation of anti–tumor necrosis factor-α treatment (anti-TNF) (infliximab and adalimumab) in patients with inflammatory bowel disease (IBD) is associated with a high relapse risk that may be influenced by endoscopic activity at the time of stopping. We assessed the relapse rate after anti-TNF withdrawal in patients with endoscopic healing and studied predictors of relapse including the depth of endoscopic healing. This was a multicenter, prospective study in adult patients with Crohn's disease (CD), ulcerative colitis (UC), or IBD-unclassified (IBDU), with ≥6 months of corticosteroid-free clinical remission (confirmed at baseline) and endoscopic healing (Mayo <2/SES-CD <5 without large ulcers), who discontinued anti-TNF between 2018 and 2020 in the Netherlands. We performed Kaplan-Meier and Cox regression analyses to assess the relapse rate and evaluate potential predictors: partial (Mayo 1/SES-CD 3–4) versus complete (Mayo 0/SES-CD 0–2) endoscopic healing, anti-TNF trough levels, and immunomodulator and/or mesalamine use. Among 81 patients (CD: n = 41, 51%) with a median follow-up of 2.0 years (interquartile range, 1.6–2.1), 40 patients (49%) relapsed. Relapse rates in CD and UC/IBDU patients were comparable. At 12 months, 70% versus 35% of patients with partial versus complete endoscopic healing relapsed, respectively (adjusted hazard rate [aHR], 3.28; 95% confidence interval [CI], 1.43–7.50). Mesalamine use was associated with fewer relapses in UC/IBDU patients (aHR, 0.08; 95% CI, 0.01–0.67). Thirty patients restarted anti-TNF, and clinical remission was regained in 73% at 3 months. The relapse risk was high after anti-TNF withdrawal in IBD patients with endoscopic healing, but remission was regained in most cases after anti-TNF reintroduction. Complete endoscopic healing and mesalamine treatment in UC/IBDU patients decreased the risk of relapse. [Display omitted] [ABSTRACT FROM AUTHOR]

In the field of international human rights, we currently face a paradox. Even with regional human rights instruments like the European Convention of Human Rights, or the recent Convention on preventing and combating violence against women and domestic violence (Istanbul Convention) many Dutch consider human rights mainly as intended for foreign consumption. In the field of violence against women this creates a stark contrast between national and international developments. In this inaugural speech, delivered on the occasion of the acceptance of the first Chair on gender based violence at the University of Amsterdam, several of the core issues in the social and legal debate on gender based violence are explored. The women's movements in the 1970s have been writing history when violence against women was reframed as a political concern instead of a personal problem. The recognition that the epidemic proportions of violence against women worldwide, regardless of culture, are both cause and effect of gender-based inequalities, was underlying this paradigm shift. The call on governments was to take measures against violence and simultaneously to address wider inequality concerns. Both social discourse and policy and legal measures in the 1980s and 1990s were resting upon these premises. In the new millennium, this very paradigm shift has become the subject of increasing debate in the Netherlands. Three intersecting counter-narratives on violence against women have evolved: minimization, culturalization (foregrounding violence against women in migrant muslim communities) and gender neutralization (foregrounding the domestic victimization of men by women in native white Dutch communities). These discourses have entered policy research and policy measures, as reflected in current social support structures as set up by local authorities. The net effect implies a de-politicization of violence against women since the recognition that violence against women is a form of discrimination is considered neither relevant nor valid anymore. It is argued that these narratives illustrate a profound ambiguity that entered public Dutch discourse and policies. This ambiguity has become more manifest with the Netherlands ratifying the Istanbul Convention early 2016. This human rights convention unambiguously frames violence against women as a form of gender based discrimination, requiring a coherent gender sensitive set of policy and other measures. In recent years, jurisprudence of the European Court of Human Rights, has increasingly underlined the discriminatory nature of domestic violence and how it obliges states to specifically address women's needs when victimized by their partner or ex-partner. It is concluded that two crucial questions deserve more attention in research. What is the impact of the tendency to minimize severity and gender neutralize domestic violence against white women, while selectively culturalizing violence against migrant women? A more fundamental question concerns the meaning and impact of binding international human rights law, when on a national level the relevance of gender to understand violence against women is contested. [ABSTRACT FROM AUTHOR]

There is a growing need to recover degraded soils to restore their essential ecosystem services and limit damages of anthropic activities onto these systems. Safe and sustainable solutions for long-term recovery must be designed, ideally by recycling existing resources. Using ash from combustion of residual forest biomass at the pulp and paper industry is an interesting and sustainable strategy to recover mining soils. However, formulations must be found to limit the potential toxicity associated with soluble salts and chloride that ash contains. Here, we assessed the effectiveness of three field ash-based amendments for the recovery of three highly acidic soils from Portuguese abandoned mines. Three amendments were tested: an un-stabilized mixture of ash and biological sludge, granulated ash, and granulated ash mixed with composted sludge. One year after application in open field plots (in the scope of LIFE No_Waste project), soil health restoration was evaluated through (i) soil physico-chemical characterization and (ii) soil habitat functions though standardized ecotoxicological tests. This study highlights that stabilized materials provided nutrients, organic matter and alkalinity that corrected soil pH and decreased metal bioavailability, while controlling the release of soluble salts and chloride from ash. This soil improvement correlated with improved soil model organisms' reproduction and survival. For similar amendment, the native soil properties studied (as soil native electrical conductivity) affected the level of organism response. This work provides evidence that ash stabilization, formulation and supplementation with organic matter could be sustainable strategies to restore highly degraded mining soils and to recover their ecological functions. It further highlights the importance of analyzing combined effects on soil physico-chemical properties and ecological function recovery to assess restoration strategy efficiencies in complex multi-stressor environments. • Ash-based formulations improved physico-chemical conditions in highly degraded mining soils. • Invertebrate reproduction benefits from stabilized ash granules and composted sludge application. • Organic carbon addition with composted sludge promotes E. crypticus reproduction. • Ash granulation reduced EC and soluble chloride-related hazard for model invertebrates. Ash-based amendments are a promising strategy to contribute to the recovery of mining soils' capacity to support ecosystems function and to recycling nutrients in relevant waste streams. [ABSTRACT FROM AUTHOR]