Effectiveness and safety of tofacitinib for ulcerative colitis: two-year results of the ICC Registry

Background Tofacitinib is an oral Janus kinase (JAK) inhibitor and is registered for the treatment of ulcerative colitis (UC). The effectiveness of tofacitinib has been evaluated up to 12 months of treatment. Aim The aim of this study was to assess the effectiveness and safety of 24 months of tofacitinib use in UC patients in the Netherlands. Methods Patients initiating tofacitinib treatment were included in the ICC Registry, a nationwide, observational registry. Patients were prospectively evaluated for up to 24 months. The primary outcome was corticosteroid-free clinical remission (CSFR, Simple Clinical Colitis Activity Index [SCCAI] <= 2) at week 104. Secondary outcomes included biochemical remission (C-reactive protein (CRP) <= 5 mg/L and faecal calprotectin (FC) <= 250 mu g/g), safety, and discontinuation rate. Results We included 110 patients of whom 104 (94.5%) were anti-TNF experienced. After 104 weeks of tofacitinib, 31.8% (34/107) were in CSFR, 23.4% (25/107) in biochemical remission and 18.7% (20/107) in combined clinical and biochemical remission. Of the patients in CSFR at week 52, 76.5% (26/34) remained so after 104 weeks of treatment. Sixty-one patients (55.5%) discontinued tofacitinib after a median duration of 13 weeks (IQR 7-34). The main reasons for discontinuation were non-response (59%), loss of response (14.8%), and adverse events (18%). There were 33.9 possible tofacitinib-related adverse events per 100 patient-years during follow-up. Adverse events most probably related to tofacitinib were skin reactions and headaches. There were 6.4 herpes zoster infections per 100 patient-years. Conclusion Tofacitinib was effective in 31.8% of patients after 24 months of treatment.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Changing practices: The specialised domestic violence court process

Specialised domestic violence courts, initially developed in the United States of America, have been recognised by other jurisdictions including Canada, Australia and the United Kingdom. This article presents a case study of K Court in Toronto, drawing upon documentary evidence, direct observations and interviews with key informants. It is argued that the specialised domestic violence court process includes changing practices of some of the key stakeholders. Learning lessons from abroad can offer jurisdictions insights that can steer implementation of appropriate practices in the field

Mucosal Healing in Ulcerative Colitis: A Comprehensive Review

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by periods of remission and periods of relapse. Patients often present with symptoms such as rectal bleeding, diarrhea and weight loss, and may require hospitalization and even colectomy. Long-term complications of UC include decreased quality of life and productivity and an increased risk of colorectal cancer. Mucosal healing (MH) has gained progressive importance in the management of UC patients. In this article, we review the endoscopic findings that define both mucosal injury and MH, and the strengths and limitations of the scoring systems currently available in clinical practice. The basic mechanisms behind colonic injury and MH are covered, highlighting the pathways through which different drugs exert their effect towards reducing inflammation and promoting epithelial repair. A comprehensive review of the evidence for approved drugs for UC to achieve and maintain MH is provided, including a section on the pharmacokinetics of anti-tumor necrosis factor (TNF)-alpha drugs. Currently approved drugs with proven efficacy in achieving MH in UC include salicylates, corticosteroids (induction only), calcineurin inhibitors (induction only), thiopurines, vedolizumab and anti-TNF alpha drugs (infliximab, adalimumab, and golimumab). MH is of crucial relevance in the outcomes of UC, resulting in lower incidences of clinical relapse, the need for hospitalization and surgery, as well as reduced rates of dysplasia and colorectal cancer. Finally, we present recent evidence towards the need for a more strict definition of complete MH as the preferred endpoint for UC patients, using a combination of both endoscopic and histological findings.info:eu-repo/semantics/publishedVersio

Soil mobility of surface applied polyaromatic hydrocarbons in response to simulated rainfall

Polyaromatic hydrocarbons (PAHs) are emitted from a variety of sources and can accumulate on and within surface soil layers. To investigate the level of potential risk posed by surface contaminated soils, vertical soil column experiments were conducted to assess the mobility, when leached with simulated rainwater, of six selected PAHs (naphthalene, phenanthrene, fluoranthene, pyrene, benzo(e)pyrene and benzo(ghi)perylene) with contrasting hydrophobic characteristics and molecular weights/sizes. The only PAH found in the leachate within the experimental period of 26 days was naphthalene. The lack of migration of the other applied PAHs were consistent with their low mobilities within the soil columns which generally parallelled their log Koc values. Thus only 2.3% of fluoranthene, 1.8% of pyrene, 0.2% of benzo(e)pyrene and 0.4% of benzo(ghi)perylene were translocated below the surface layer. The PAH distributions in the soil columns followed decreasing power relationships with 90% reductions in the starting levels being shown to occur within a maximum average depth of 0.94 cm compared to an average starting depth of 0.5 cm. A simple predictive model identifies the extensive time periods, in excess of 10 years, required to mobilise 50% of the benzo(e)pyrene and benzo(ghi)perylene from the surface soil layer. Although this reduces to between 2 and 7 years for fluoranthene and pyrene, it is concluded that the possibility of surface applied PAHs reaching and contaminating a groundwater aquifer is unlikely

Superior effectiveness of tofacitinib compared to vedolizumab in anti-TNF-experienced ulcerative colitis patients: a nationwide Dutch registry study

BACKGROUND & AIMS: Clinicians face difficulty in when and in what order to position biologics and Janus kinase in-hibitors in patients with anti-tumor necrosis factor-alpha (TNF) refractory ulcerative colitis (UC). We aimed to compare the effectiveness and safety of vedolizumab and tofacitinib in anti-TNF-exposed patients with UC in our prospective nationwide Initiative on Crohn and Colitis Registry. METHODS: Patients with UC who failed anti-TNF treatment and initiated vedolizumab or tofacitinib treatment were identified in the Initiative on Crohn and Colitis Registry in the Netherlands. We selected patients with both clinical as well as biochemical or endoscopic disease activity at initiation of therapy. Patients previously treated with vedolizumab or tofacitinib were excluded. Corticosteroid-free clinical remission (Simple Clinical Colitis Activity Index 52), biochemical remission (C-reactive protein 55 mg/L or fecal calprotectin 5250 mg/g), and safety outcomes were compared after 52 weeks of treatment. Inverse propensity score-weighted comparison was used to adjust for confounding and selection bias. RESULTS: Overall, 83 vedolizumab-and 65 tofacitinib-treated patients were included. Propensity score -weighted analysis showed that tofacitinib-treated patients were more likely to achieve corticosteroid-free clinical remission and biochemical remission at weeks 12, 24, and 52 compared with vedolizumab-treated patients (odds ratio [OR], 6.33; 95% confidence interval [CI], 3.81-10.50; P Cellular mechanisms in basic and clinical gastroenterology and hepatolog