Epidemiology and risk factors for IBD Ananthakrishnan, Ashwin N
Nature reviews. Gastroenterology & hepatology,
04/2015, Volume:
12, Issue:
4
Journal Article
Peer reviewed
IBD, comprising Crohn's disease and ulcerative colitis, is a chronic immunologically mediated disease at the intersection of complex interactions between genetics, environment and gut microbiota. ...Established high-prevalence populations of IBD in North America and Europe experienced the steepest increase in incidence towards the second half of the twentieth century. Furthermore, populations previously considered 'low risk' (such as in Japan and India) are witnessing an increase in incidence. Potentially relevant environmental influences span the spectrum of life from mode of childbirth and early-life exposures (including breastfeeding and antibiotic exposure in infancy) to exposures later on in adulthood (including smoking, major life stressors, diet and lifestyle). Data support an association between smoking and Crohn's disease whereas smoking cessation, but not current smoking, is associated with an increased risk of ulcerative colitis. Dietary fibre (particularly fruits and vegetables), saturated fats, depression and impaired sleep, and low vitamin D levels have all been associated with incident IBD. Interventional studies assessing the effects of modifying these risk factors on natural history and patient outcomes are an important unmet need. In this Review, the changing epidemiology of IBD, mechanisms behind various environmental associations and interventional studies to modify risk factors and disease course are discussed.
Inflammatory bowel diseases comprising Crohn’s disease (CD) and ulcerative colitis (UC) are chronic immunologically mediated diseases. The key mechanism underlying the pathogenesis of these diseases ...is a dysregulated immune response to commensal flora in a genetically susceptible host. Thus intestinal microbial dysbiosis, host genetics, and the external environment all play an important role in the development of incident disease and in determining subsequent disease behavior and outcomes. There are several well-defined or putative environmental risk factors including cigarette smoking, appendectomy, diet, stress and depression, vitamin D as well as hormonal influence. The effect of some of the risk factors appears to differ between CD and UC suggesting that despite shared genetic and immunologic mechanisms, distinct pathways of pathogenesis exist. There is a growing body of literature identifying risk factors for incident disease. There is less rigorous literature defining triggers of relapse, and few controlled clinical trials examining if modification of such risk factors results in an improvement in patient outcomes. This is an area of considerable patient, physician, and scientific interest, and there is an important unmet need for rigorous studies of the external environment in disease pathogenesis and subsequent course.
Ulcerative colitis (UC) is an idiopathic inflammatory disorder. These guidelines indicate the preferred approach to the management of adults with UC and represent the official practice ...recommendations of the American College of Gastroenterology. The scientific evidence for these guidelines was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process. In instances where the evidence was not appropriate for GRADE, but there was consensus of significant clinical merit, "key concept" statements were developed using expert consensus. These guidelines are meant to be broadly applicable and should be viewed as the preferred, but not only, approach to clinical scenarios.
The epidemiology of Clostridium difficile infection (CDI) has changed over the past decade. There has been a dramatic worldwide increase in its incidence, and new CDI populations are emerging, such ...as those with community-acquired infection and no previous exposure to antibiotics, children, pregnant women and patients with IBD. Diagnosis of CDI requires identification of C. difficile toxin A or B in diarrheal stool. The accuracy of current diagnostic tests remains inadequate and the optimal diagnostic testing algorithm has not been defined. The first-line agents for CDI treatment are metronidazole and vancomycin, with the latter being the preferred agent in patients with severe disease as it has significantly superior efficacy. The incidence of metronidazole treatment failures has increased, emphasizing the need to find alternative treatment options. Disease recurrence continues to occur in 20-40% of patients and its treatment remains challenging. In patients with CDI who develop fulminant colitis, early surgical consultation is essential. Intravenous immunoglobulin and tigecycline have been used in patients with severe refractory disease but delaying surgery may be associated with worse outcomes. Infection control measures are key to prevent horizontal transmission of infection. Ongoing research into effective treatment protocols and prevention is essential.
Clostridium difficile infection (CDI) is the most common healthcare associated infection and is highly prevalent in Europe and North America. Limited data is available on the prevalence of CDI in ...Asia. However, secular increases in prevalence of risk factors for CDI suggest that it may be emerging as a major cause of morbidity, highlighting the urgent need for a systematic study of the prevalence of CDI in Asia.
We systematically searched PubMed/Medline and Embase for publications from Asia between 2000-16 examining prevalence of CDI. A random-effects meta-analysis was performed to calculate the pooled prevalence of CDI in Asia and to identify subgroups and regions at high risk.
Our meta-analysis included 51 studies from throughout Asia including 37,663 patients at risk among whom confirmed CDI was found in 4,343 patients. The pooled proportion of confirmed CDI among all patients with diarrhea was 14.8% with a higher prevalence in East Asia (19.5%), compared with South Asia (10.5%) or the Middle East (11.1%). There were an estimated 5.3 episodes of CDI per 10,000 patient days, similar to rates reported from Europe and North America. Infections due to hypervirulent strains were rare. CDI-related mortality was 8.9%.
In a meta-analysis of 51 studies, we observed similar rates of CDI in Asia in comparison to Europe and North America. Increased awareness and improved surveillance of Clostridium difficile is essential to reduce incidence and morbidity.
Upadacitinib for ulcerative colitis Ananthakrishnan, Ashwin N
The Lancet (British edition),
06/2022, Volume:
399, Issue:
10341
Journal Article
Peer reviewed
In The Lancet, Silvio Danese and colleagues1 report the results of induction and maintenance trials for upadacitinib, a selective inhibitor of the Janus kinase 1 (JAK1) enzyme, within the broader JAK ...enzyme family. In addition to their promising efficacy, which positions them as favoured treatments for ulcerative colitis in indirect comparison network meta-analyses,4 their oral route offers greater convenience and might be preferred by patients whereas their small molecule (as opposed to monoclonal antibody) composition avoids the immunogenicity and loss of response, which is an issue with many biologics. In a post-authorisation safety trial in patients with rheumatoid arthritis aged 50 years or older with at least one cardiovascular risk factor, tofacitinib was associated with a higher incidence of major adverse cardiovascular events (MACE), cancers, and venous thromboembolism compared with anti-TNFα.6 The decreased risk of venous thromboembolism might be particularly relevant in younger cohorts with IBD who have increased thrombotic risk at baseline.
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