This article is intended as a reference guide to various notions of monoidal categories and their associated string diagrams. It is hoped that this will be useful not just to mathematicians, but also ...to physicists, computer scientists, and others who use diagrammatic reasoning. We have opted for a somewhat informal treatment of topological notions, and have omitted most proofs. Nevertheless, the exposition is sufficiently detailed to make it clear what is presently known, and to serve as a starting place for more in-depth study. Where possible, we provide pointers to more rigorous treatments in the literature. Where we include results that have only been proved in special cases, we indicate this in the form of caveats.
Summary
Background
The optimal choice of biological agents after failure of anti‐tumour‐necrosis‐factor‐(TNF)α agent in Crohn’s disease (CD) is yet to be defined.
Aims
To assess the effectiveness and ...safety of ustekinumab compared to vedolizumab as second‐line treatment in CD patients who failed anti‐TNFα therapy.
Methods
Retrospective analysis of clinical response and remission at 14 and 52 weeks to ustekinumab by physician global assessment (PGA). A propensity score‐matched analysis with a cohort treated with vedolizumab was performed.
Results
Of 282 patients (mean age 40 ± 15, F:M ratio 1.7:1) treated with ustekinumab, clinical response or remission was reached by 200/282 patients (70.9%) at 14 weeks, and 162/259 patients (62.5%) at 52 weeks. Overall, 74 adverse events occurred, of which 26 were labelled as serious (8.3 per 100 person‐year). After exclusion of patients without prior anti‐TNFα exposure and patients previously exposed to vedolizumab or ustekinumab, we analysed 275/282 patients (97.5%) on ustekinumab and 118/135 patients (87.4%) on vedolizumab. Propensity score analysis revealed that at 14 weeks, patients treated with ustekinumab were 38% (95% CI 25%‐50%; P < 0.001) more likely to achieve clinical remission, while at 52 weeks, the difference of 9% (95% CI −15% to 33%; P = 0.462) was not significant.
Conclusions
Ustekinumab was effective and well tolerated in this real‐world cohort. While ustekinumab proved more effective at 14‐weeks, we found no statistically significant differences at 52 weeks compared to vedolizumab.
Ustekinumab was effective and well tolerated in a real‐world cohort, with no new safety signals. According to our propensity score‐matched analysis, vedolizumab should be first considered in older patients or with multimorbidity, while ustekinumab may be preferred in younger patients with psoriasis and for achieving remission more rapidly.
Summary Background Antibiotic-associated diarrhoea (AAD) is a frequent complication of systemic antibiotic therapy and Clostridium difficile -associated diarrhoea (CDAD) is its most serious form due ...to associated morbidity and mortality. Aim This trial aimed to investigate whether the probiotic VSL#3 prevents AAD and CDAD in average-risk hospital patients. Methods Adult hospital inpatients exposed to systemic antibiotics were recruited to this multicentre, randomized, double-blind, placebo-controlled trial. One sachet of VSL#3 or placebo was given twice daily for the length of the antibiotics course and for seven days thereafter. Primary outcomes were AAD and CDAD. Findings Patients randomized to active ( N = 117) and placebo ( N = 112) groups were well-matched for baseline demographic patient data. No cases of CDAD were detected. The rate of AAD was significantly lower in the active group on per protocol analysis (0% active vs 11.4% placebo; P = 0.006). On intention-to-treat analysis the difference in AAD incidence (4.3% active vs 8.9% placebo; P = 0.19) was not significant. Conclusions VSL#3 is associated with a significant reduction in the incidence of AAD in average-risk hospital inpatients exposed to systemic antibiotics. As the incidence of CDAD has fallen sharply, no cases of CDAD were found. Probiotic administration as prophylaxis for CDAD may not be indicated in average-risk hospital patients.
Abstract
The use of corticosteroids to treat patients with inflammatory bowel disease IBD has been the bedrock of IBD therapeutics since the pioneering work of Truelove and Witts in the UK in the ...1950s and subsequent large cohort studies in the USA and Europe. Nevertheless, although effective for induction of remission, these agents do not maintain remission and are associated with a long list of recognised side effects, including a risk of increased mortality. With the arrival of an increasing number of therapies for patients with IBD, the question arises as to whether we are using these agents appropriately in contemporary practice. This review discusses the historical background to steroid usage in IBD, and also provides a brief review of the literature on side effects of corticosteroid treatment as relevant to IBD patients. Data on licensed medications are presented with specific reference to the achievement of corticosteroid-free remission. We review available international data on the incidence of corticosteroid exposure and excess, and discuss some of the observations we and others have made concerning health care and patient-level factors associated with the risk of corticosteroid exposure, including identification of ‘at-risk’ populations.
Crohn's disease affects many women of childbearing age. Fecundity rates are often lower than in the general population due to reduced fertility during active inflammation, effects of pelvic surgery ...or voluntary childlessness. Many women have concerns regarding the effects of pregnancy on their Crohn's, any potential effect of medication on the fetus, and passing on Crohn's disease to the offspring. International guidelines on reproduction for women with Crohn's disease provide evidence-based advice to patients and health care professionals. There is an increasing literature on the safety of advanced medication for Crohn's disease during pregnancy. This review article therefore focuses on obstetric considerations beyond medication safety. We provide information on fertility, factors affecting pregnancy and fetal outcomes, obstetric complications, factors influencing mode of delivery, management of intestinal stomas during pregnancy and general considerations around breast feeding.
Summary
Background
Smoking demonstrates divergent effects in Crohn's disease (CD) and ulcerative colitis (UC). Smoking frequency is greater in CD and deleterious to its disease course. Conversely, UC ...is primarily a disease of nonsmokers and ex‐smokers, with reports of disease amelioration in active smoking.
Aim
To determine the prevalence of smoking and its effects on disease progression and surgery in a well‐characterised cohort of inflammatory bowel diseases (IBD) patients.
Methods
Patients with smoking data of the Sydney IBD Cohort were included. Demographic, phenotypic, medical, surgical and hospitalisation data were analysed and reported on the basis of patient smoking status.
Results
1203 IBD patients were identified comprising 626 CD and 557 UC with 6725 and 6672 patient‐years of follow‐up, respectively. CD patients were more likely to smoke than UC patients (19.2% vs. 10.2%, P < 0.001). A history of smoking in CD was associated with an increased proportional surgery rate (45.8% vs. 37.8%, P = 0.045), requirement for IBD‐related hospitalisation (P = 0.009) and incidence of peripheral arthritis (29.8% vs. 22.0%, P = 0.027). Current smokers with UC demonstrated reduced corticosteroid utilisation (24.1% vs. 37.5%, P = 0.045), yet no reduction in the rates of colectomy (3.4% vs. 6.6%, P = 0.34) or hospital admission (P = 0.25) relative to nonsmokers. Ex‐smokers with UC required proportionately greater immunosuppressive (36.2% vs. 26.3%, P = 0.041) and corticosteroid (43.7% vs. 34.5%, P = 0.078) therapies compared with current and never smokers.
Conclusions
This study confirms the detrimental effects of smoking in CD, yet failed to demonstrate substantial benefit from smoking in UC. These data should encourage all patients with IBD to quit smoking.
Surgery is an important treatment for Crohn's disease CD, but recurrence occurs in up to 80% of individuals post-operatively. The efficacy of several drugs to prevent post-operative recurrence has ...been studied in previous meta-analyses, but a number of randomized controlled trials RCTs have recently been published. We therefore performed an updated systematic review and network meta-analysis to investigate this issue.
We performed a comprehensive literature search through to July 2018 to identify RCTs investigating the endoscopic and clinical recurrence of CD at 12 months post-operatively. We performed a random-effects network meta-analysis to produce a pooled relative risk RR with 95% confidence intervals CIs. We ranked the treatments according to their P-score.
We included 10 RCTs, containing 751 patients, in our primary analysis of endoscopic recurrence of CD at 12 months. Anti-tumour necrosis factor TNF-α therapies were significantly better than placebo, either alone P-score 0.98, RR 0.13; 95% CI 0.04-0.39 or in combination with 5-aminosalicylates 5-ASAs P-score 0.81, RR 0.30; 95% CI 0.12-0.75, or 5-nitroimidazoles P-score 0.75, RR 0.40; 95% CI 0.23-0.69. Combination therapy with a thiopurine and 5-nitroimidazole was also more effective than placebo P-score 0.59, RR 0.56; 95% CI 0.40-0.80, as was thiopurine monotherapy P-score 0.31, RR 0.84; 95% CI 0.74-0.94. However, neither 5-nitroimidazoles nor 5-ASAs alone were superior to placebo.
In network meta-analysis, anti-TNF-α therapies alone, or in combination, appear to be the best medications for preventing endoscopic post-operative recurrence of CD.
AIM To examine patient knowledge and factors influencing knowledge about pregnancy in British women with inflammatory bowel disease(IBD).METHODS This is a post hoc analysis of a study of female ...members of Crohn’s and Colitis United Kingdom, aged 18-45 years who were sent an online questionnaire recording patient demographics, education, employment, marital status, and disease characteristics. Disease related pregnancy knowledge was recorded using Crohn’s and colitis pregnancy knowledge score(CCPKnow).RESULTS Of 1324 responders, 776(59%) suffered from Crohn’s disease, 496(38%) from ulcerative colitis and 52(4%) from IBD-uncategorised. CCPKnow scores were poor(0-7) in 50.8%, adequate(8-10) in 23.6%, good(11-13) in 17.7% and very good(≥ 14) in 7.8%. Multiple linear regression analysis revealed that higher CCPKnow scores were independently associated with higher educational achievement(P < 0.001), younger age at diagnosis(P = 0.003) and having consulted a health care professional about pregnancy and IBD(P = 0.001). CONCLUSION Knowledge was poor in 50%. Speaking with healthcare professionals was a modifiable factor associated with better knowledge. This illustrates the importance of disease related pregnancy education
Summary
Background
Healthcare service provision in inflammatory bowel disease (IBD) is often designed to meet targets set by healthcare providers rather than those of patients. It is unclear whether ...this meets the needs of patients, as assessed by patients themselves. Aims: To assess patients' experience of IBD and the healthcare they received, aiming to identify factors in IBD healthcare provision associated with perceived high‐quality care.
Methods
Using the 2019 IBD standards as a framework, a national benchmarking tool for quality assessment in IBD was developed by IBD UK, comprising a patient survey and service self‐assessment.
Results
134 IBD services and 9757 patients responded. Perceived quality of care was lowest in young adults and increased with age, was higher in males and those >2 years since diagnosis. No hospital services met all the national IBD standards for recommended workforce numbers. Key metrics associated with patient‐reported high‐ quality care were: identification as a tertiary centre, patient information availability, shared decision‐ making, rapid response to contact for advice, access to urgent review, joint medical/surgical clinics, and access to research (all p < 0.001). Higher numbers of IBD nurse specialists in a service was strongly associated with patients receiving regular reviews and having confidence in self‐management and reporting high‐ quality care.
Conclusions
This extensive patient and healthcare provider survey emphasises the importance of aspects of care less often measured by clinicians, such as communication, shared decision‐ making and provision of information. It demonstrates that IBD nurse specialists are crucial to meeting the needs of people living with IBD.
Maintenance of remission during pregnancy is vital for women with inflammatory bowel disease (IBD). The antenatal safety of novel small molecules for IBD is yet to be ascertained. We aimed to ...describe the current evidence on reproductive data regarding small-molecule drugs. We performed a systematic review searching Embase Classic + Embase and Ovid MEDLINE for reproductive outcomes for tofacitinib, filgotinib, upadacitininb, and ozanimod. Additionally, we asked the manufacturers for available data on file regarding reproduction. We analysed data from 10 sources; six studies and four manufacturer reports were identified from our search. Significant malformation risks were reported for tofacitinib, filgotinib, upadacitininb, and ozanimod in animal studies. In 126 tofacitinib-exposed pregnancies, there were 55 live births with 2 congenital malformations and 1 serious infant infection, 14 terminations, 15 miscarriages, and 42 outcomes unknown. In 50 filgotinib-exposed pregnancies, there were 20 healthy babies, 1 congenital malformation, 9 terminations, 10 miscarriages, and 10 outcomes unknown. In 78 upadacitinib-exposed pregnancies, there were 30 healthy babies, 15 terminations, 15 miscarriages, and 18 outcomes unknown. In 60 ozanimod-exposed pregnancies, there were 31 live births with 1 congenital malformation, 1 case of intra-uterine growth restriction, 1 case of neonatal icterus, 13 terminations, 9 miscarriages, and 8 unknown outcomes. Animal data suggest significant risks of malformations for tofacitinib, filgotinib, upadacitininb, and ozanimod. Human data from clinical trials and real-world observations do not show concerning data so far, but these are very limited. Currently, alternative treatments should be used for IBD during pregnancy.
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