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Goodwin SW, Wilk P, Yuan Y, Haan M, Jairath V. Increasing Rate of Hospitalization for Inflammatory Bowel Disease Is an Age-Related Effect: A Canadian Population Study. Am J Gastroenterol 2025:00000434-990000000-01619. [PMID: 40035436 DOI: 10.14309/ajg.0000000000003385] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Accepted: 02/07/2025] [Indexed: 03/05/2025]
Abstract
INTRODUCTION To understand trends in the risk of all-cause hospitalization for individuals with inflammatory bowel disease, we explored age, period, and cohort effects in Canada. METHODS Repeated cross-sectional survey data from the 2005-2014 Canadian Community Health Survey linked to the Discharge Abstract Database to capture the all-cause hospitalization within 3 years of entry into the study for eligible individuals. Random-effects 2-level models estimated fixed effects for age and random effects for time periods and birth cohorts on the risk of all-cause hospitalization within 3 years entry into the study. RESULTS An estimated 197,000 individuals were eligible for study inclusion. From this, an estimated 70,140 all-cause hospitalizations occurred within 3 years postentry into the study. The risk of hospitalization within 3 years increased with age and across birth cohorts, with older cohorts experiencing greater risks of hospitalization. A small temporal effect was identified for both inflammatory bowel disease groups. Within birth cohorts, the risk of hospitalization increased across ages for Crohn's disease, but in individuals with ulcerative colitis, the risk decreased across ages, except for the 2 oldest birth cohorts. DISCUSSION These data support the hypothesis that age effects are primarily responsible for increased risk of hospitalizations. As the prevalence of IBD continues to rise and age distribution of Canadians shifts toward an older-aged population, increasing the allocation of healthcare resources to prevent age-related risks of hospitalizations would be beneficial to reduce hospital burdens.
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Affiliation(s)
- Shane W Goodwin
- Department of Medicine, Lawson Health Research Institute, London Health Science Centre, London, Ontario, Canada
| | - Piotr Wilk
- Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada
- Department of Epidemiology, Maastricht University, Maastricht, the Netherlands
| | - Yuhong Yuan
- Department of Medicine, Lawson Health Research Institute, London Health Science Centre, London, Ontario, Canada
- Department of Medicine, Western University, London, Ontario, Canada
| | - Michael Haan
- Department of Sociology, Western University, London, Ontario, Canada
| | - Vipul Jairath
- Department of Medicine, Lawson Health Research Institute, London Health Science Centre, London, Ontario, Canada
- Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada
- Department of Medicine, Western University, London, Ontario, Canada
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2
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Anand R, George AT, Rubin DT, Spiegel BMR, Bernstein CN. The role of virtual reality in managing inflammatory bowel disease: a novel approach to bridging mental and physical health. J Can Assoc Gastroenterol 2025; 8:S15-S20. [PMID: 39990506 PMCID: PMC11842903 DOI: 10.1093/jcag/gwae060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/25/2025] Open
Abstract
Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, is characterized by symptoms such as fatigue, abdominal pain, and diarrhoea, which may persist even when inflammation is controlled. These symptoms are further exacerbated by psychological stress, which may complicate disease management that involves the gut-brain axis-a bidirectional communication pathway linking the gastrointestinal system and the central nervous system. While stress, anxiety, and depression are prevalent among patients with IBD, access to comprehensive mental health care is often limited, particularly in rural and underserved areas. Virtual reality (VR) has emerged as a promising tool in managing psychological comorbidities and enhancing the overall care of patients with IBD. The integration of VR in IBD care offers a novel, accessible approach to addressing both physical and mental health challenges, potentially improving the quality of life and clinical outcomes for IBD patients. Further research is warranted to evaluate the long-term benefits and broader applicability of VR-based interventions in diverse patient populations.
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Affiliation(s)
- Rajsavi Anand
- Department of Medicine, Division of Gastroenterology, Cedars-Sinai, Los Angeles, CA, 90048, United States
| | - Alvin T George
- The University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, IL, 60637, United States
| | - David T Rubin
- The University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, IL, 60637, United States
| | - Brennan M R Spiegel
- Department of Medicine, Division of Gastroenterology, Cedars-Sinai, Los Angeles, CA, 90048, United States
- Department of Medicine, Division of Health Services Research Virtual Medicine Program, Cedars-Sinai, Los Angeles, CA, 90048, United States
| | - Charles N Bernstein
- University of Manitoba IBD Clinical and Research Centre, Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada
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3
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Souaid C, Fares E, Primard P, Macaigne G, El Hajj W, Nahon S. A review investigating delays in Crohn's disease diagnosis. Clin Res Hepatol Gastroenterol 2025; 49:102500. [PMID: 39551466 DOI: 10.1016/j.clinre.2024.102500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Revised: 10/27/2024] [Accepted: 11/14/2024] [Indexed: 11/19/2024]
Abstract
Crohn's disease (CD) is a chronic inflammatory condition of the gastrointestinal tract where early diagnosis and timely, appropriate management are essential to prevent severe complications and reduce the need for surgery. This review sought to investigate factors contributing to diagnostic delays in CD, which typically ranged from 5 to 16 months. Delays were often due to nonspecific symptoms that could be mistaken for irritable bowel syndrome (IBS) and were influenced by various factors including age, education level, smoking, NSAID use, and disease characteristics like isolated ileal involvement. Healthcare system disparities also played a significant role, with delays varying by access to care. The review highlighted that delayed diagnosis was linked to worse disease outcomes, such as increased severity and complications, and underscored the importance of early intervention combined with timely management. Strategies to mitigate delays included implementing red flag tools, using inflammatory biomarkers like fecal calprotectin, and enhancing public and healthcare provider awareness. Addressing these factors and improving referral pathways and healthcare system efficiencies were crucial for enhancing early diagnosis and patient outcomes.
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Affiliation(s)
- Christophe Souaid
- Gastroenterology Unit, Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, France
| | - Eddy Fares
- Gastroenterology Unit, Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, France
| | - Paul Primard
- Gastroenterology Unit, Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, France
| | - Gilles Macaigne
- Gastroenterology Unit, Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, France
| | - Weam El Hajj
- Gastroenterology Unit, Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, France
| | - Stephane Nahon
- Gastroenterology Unit, Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, France.
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Madhvapathy SR, Bury MI, Wang LW, Ciatti JL, Avila R, Huang Y, Sharma AK, Rogers JA. Miniaturized implantable temperature sensors for the long-term monitoring of chronic intestinal inflammation. Nat Biomed Eng 2024; 8:1040-1052. [PMID: 38499643 DOI: 10.1038/s41551-024-01183-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Accepted: 02/09/2024] [Indexed: 03/20/2024]
Abstract
Diagnosing and monitoring inflammatory bowel diseases, such as Crohn's disease, involves the use of endoscopic imaging, biopsies and serology. These infrequent tests cannot, however, identify sudden onsets and severe flare-ups to facilitate early intervention. Hence, about 70% of patients with Crohn's disease require surgical intestinal resections in their lifetime. Here we report wireless, miniaturized and implantable temperature sensors for the real-time chronic monitoring of disease progression, which we tested for nearly 4 months in a mouse model of Crohn's-disease-like ileitis. Local measurements of intestinal temperature via intraperitoneally implanted sensors held in place against abdominal muscular tissue via two sutures showed the development of ultradian rhythms at approximately 5 weeks before the visual emergence of inflammatory skip lesions. The ultradian rhythms showed correlations with variations in the concentrations of stress hormones and inflammatory cytokines in blood. Decreasing average temperatures over the span of approximately 23 weeks were accompanied by an increasing percentage of inflammatory species in ileal lesions. These miniaturized temperature sensors may aid the early treatment of inflammatory bowel diseases upon the detection of episodic flare-ups.
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Affiliation(s)
- Surabhi R Madhvapathy
- Department of Materials Science and Engineering, Northwestern University, Evanston, IL, USA
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL, USA
| | - Matthew I Bury
- Division of Pediatric Urology, Department of Surgery, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA
- Stanley Manne Children's Research Institute, Louis A. Simpson and Kimberly K. Querrey Biomedical Research Center, Chicago, IL, USA
| | - Larry W Wang
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Joanna L Ciatti
- Department of Materials Science and Engineering, Northwestern University, Evanston, IL, USA
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL, USA
| | - Raudel Avila
- Department of Mechanical Engineering, Rice University, Houston, TX, USA
| | - Yonggang Huang
- Department of Mechanical Engineering, Northwestern University, Evanston, IL, USA
- Department of Civil Engineering, Northwestern University, Evanston, IL, USA
| | - Arun K Sharma
- Division of Pediatric Urology, Department of Surgery, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
- Stanley Manne Children's Research Institute, Louis A. Simpson and Kimberly K. Querrey Biomedical Research Center, Chicago, IL, USA.
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
- Simpson Querrey Institute, Northwestern University, Chicago, IL, USA.
- Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA.
| | - John A Rogers
- Department of Materials Science and Engineering, Northwestern University, Evanston, IL, USA.
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL, USA.
- Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA.
- Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
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5
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Belei O, Basaca DG, Olariu L, Pantea M, Bozgan D, Nanu A, Sîrbu I, Mărginean O, Enătescu I. The Interaction between Stress and Inflammatory Bowel Disease in Pediatric and Adult Patients. J Clin Med 2024; 13:1361. [PMID: 38592680 PMCID: PMC10932475 DOI: 10.3390/jcm13051361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2024] [Revised: 02/23/2024] [Accepted: 02/25/2024] [Indexed: 04/10/2024] Open
Abstract
Background: Inflammatory bowel diseases (IBDs) have seen an exponential increase in incidence, particularly among pediatric patients. Psychological stress is a significant risk factor influencing the disease course. This review assesses the interaction between stress and disease progression, focusing on articles that quantified inflammatory markers in IBD patients exposed to varying degrees of psychological stress. Methods: A systematic narrative literature review was conducted, focusing on the interaction between IBD and stress among adult and pediatric patients, as well as animal subjects. The research involved searching PubMed, Scopus, Medline, and Cochrane Library databases from 2000 to December 2023. Results: The interplay between the intestinal immunity response, the nervous system, and psychological disorders, known as the gut-brain axis, plays a major role in IBD pathophysiology. Various types of stressors alter gut mucosal integrity through different pathways, increasing gut mucosa permeability and promoting bacterial translocation. A denser microbial load in the gut wall emphasizes cytokine production, worsening the disease course. The risk of developing depression and anxiety is higher in IBD patients compared with the general population, and stress is a significant trigger for inducing acute flares of the disease. Conclusions: Further large studies should be conducted to assess the relationship between stressors, psychological disorders, and their impact on the course of IBD. Clinicians involved in the medical care of IBD patients should aim to implement stress reduction practices in addition to pharmacological therapies.
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Affiliation(s)
- Oana Belei
- First Pediatric Clinic, Disturbances of Growth and Development on Children Research Center, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania; (O.B.); (O.M.)
- Department of Pediatrics, First Pediatric Clinic, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania;
| | - Diana-Georgiana Basaca
- First Pediatric Clinic, Disturbances of Growth and Development on Children Research Center, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania; (O.B.); (O.M.)
- Department of Pediatrics, First Pediatric Clinic, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania;
| | - Laura Olariu
- Department of Pediatrics, First Pediatric Clinic, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania;
| | - Manuela Pantea
- Twelfth Department, Neonatology Clinic, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania; (M.P.); (I.E.)
| | - Daiana Bozgan
- Clinic of Neonatology, “Pius Brânzeu” County Emergency Clinical Hospital, 300723 Timișoara, Romania;
| | - Anda Nanu
- Third Pediatric Clinic, “Louis Țurcanu” Emergency Children Hospital, 300011 Timișoara, Romania; (A.N.); (I.S.)
| | - Iuliana Sîrbu
- Third Pediatric Clinic, “Louis Țurcanu” Emergency Children Hospital, 300011 Timișoara, Romania; (A.N.); (I.S.)
| | - Otilia Mărginean
- First Pediatric Clinic, Disturbances of Growth and Development on Children Research Center, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania; (O.B.); (O.M.)
- Department of Pediatrics, First Pediatric Clinic, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania;
| | - Ileana Enătescu
- Twelfth Department, Neonatology Clinic, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania; (M.P.); (I.E.)
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Bhat MA, Usman I, Dhaneshwar S. Application of Drug Repurposing Approach for Therapeutic Intervention of Inflammatory Bowel Disease. Curr Rev Clin Exp Pharmacol 2024; 19:234-249. [PMID: 37859409 DOI: 10.2174/0127724328245156231008154045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 07/07/2023] [Accepted: 08/30/2023] [Indexed: 10/21/2023]
Abstract
Inflammatory bowel disease (IBD), represented by Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disorder of the gastrointestinal tract (GIT) characterized by chronic relapsing intestinal inflammation, abdominal pain, cramping, loss of appetite, fatigue, diarrhoea, and weight loss. Although the etiology of IBD remains unclear, it is believed to be an interaction between genes, and environmental factors, such as an imbalance of the intestinal microbiota, changing food habits, an ultra-hygiene environment, and an inappropriate immune system. The development of novel effective therapies is stymied by a lack of understanding of the aetiology of IBD. The current therapy involves the use of aminosalicylates, immunosuppressants, and corticosteroids that can effectively manage symptoms, induce and sustain remission, prevent complications, modify the course of the disease, provide diverse treatment options, showcase advancements in biologic therapies, and enhance the overall quality of life. However, the efficacy of current therapy is overshadowed by a plethora of adverse effects, such as loss of weight, mood swings, skin issues, loss of bone density, higher vulnerability to infections, and elevated blood pressure. Biologicals, like anti-tumour necrosis factor agents, can stimulate an autoimmune response in certain individuals that may diminish the effectiveness of the medication over time, necessitating a switch to alternative treatments. The response of IBD patients to current drug therapy is quite varied, which can lead to disease flares that underlines the urgent need to explore alternative treatment option to address the unmet need of developing new treatment strategies for IBD with high efficacy and fewer adverse effects. Drug repurposing is a novel strategy where existing drugs that have already been validated safe in patients for the management of certain diseases are redeployed to treat other, unindicated diseases. The present narrative review focuses on potential drug candidates that could be repurposed for the management of IBD using on-target and off-target strategies. It covers their preclinical, clinical assessment, mechanism of action, and safety profiles, and forecasts their appropriateness in the management of IBD. The review presents useful insights into the most promising candidates for repurposing, like anti-inflammatory and anti-apoptotic troxerutin, which has been found to improve the DSS-induced colitis in rats, an antiosteoarthritic drug diacetylrhein that has been found to have remarkable ameliorating effects on DSS-induced colitis via anti-oxidant and anti- inflammatory properties and by influencing both apoptosis and pyroptosis. Topiramate, an antiepileptic and anticonvulsant drug, has remarkably decreased overall pathophysiological and histopathological events in the experimental model of IBD in rodents by its cytokine inhibitory action.
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Affiliation(s)
- Mohammad Aadil Bhat
- Department of Pharmacology, Amity Institute of Pharmacy, Lucknow, Amity University Uttar Pradesh, UP, Noida, India
| | - Iqra Usman
- Department of Pharmacology, Amity Institute of Pharmacy, Lucknow, Amity University Uttar Pradesh, UP, Noida, India
| | - Suneela Dhaneshwar
- Department of Pharmaceutical Chemistry, Amity Institute of Pharmacy, Amity University Maharashtra, Mumbai, Maharashtra, India
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Holten KIA, Bernklev T, Opheim R, Johansen I, Olsen BC, Lund C, Strande V, Medhus AW, Perminow G, Bengtson MB, Cetinkaya RB, Vatn S, Frigstad SO, Aabrekk TB, Detlie TE, Hovde Ø, Kristensen VA, Småstuen MC, Henriksen M, Huppertz-Hauss G, Høivik ML, Jelsness-Jørgensen LP. Fatigue in Patients with Newly Diagnosed Inflammatory Bowel Disease: Results from a Prospective Inception Cohort, the IBSEN III Study. J Crohns Colitis 2023; 17:1781-1790. [PMID: 37279652 PMCID: PMC10673818 DOI: 10.1093/ecco-jcc/jjad094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 05/11/2023] [Accepted: 06/02/2023] [Indexed: 06/08/2023]
Abstract
BACKGROUND AND AIMS Although fatigue is common in inflammatory bowel disease [IBD], its pathogenesis remains unclear. This study aimed to determine the prevalence of fatigue and its associated factors in a cohort of patients newly diagnosed with IBD. METHODS Patients ≥18 years old were recruited from the Inflammatory Bowel Disease South-Eastern Norway [IBSEN III] study, a population-based, observational inception cohort. Fatigue was assessed using the Fatigue Questionnaire and compared with data from a Norwegian general population. Univariate and multivariate linear and logistic regression analyses were performed to evaluate the associations of total fatigue [TF; continuous score] and substantial fatigue [SF; dichotomized score ≥4] with sociodemographic, clinical, endoscopic, laboratory, and other relevant patient data. RESULTS In total, 983/1509 [65.1%] patients with complete fatigue data were included (ulcerative colitis [UC], 68.2%; Crohn's disease [CD], 31.8%). The prevalence of SF was higher in CD [69.6%] compared with UC [60.2%] [p < 0.01], and in both diagnoses when compared to the general population [p < 0.001]. In multivariate analyses, depressive symptoms, pain intensity, and sleep disturbances were associated with increased TF for both diagnoses. In addition, increased clinical disease activity and Mayo endoscopic score were significantly associated with TF in UC, whereas all disease-related variables were insignificant in CD. Similar findings were observed for SF, except regarding the Mayo endoscopic score. CONCLUSIONS SF affects approximately two-thirds of patients newly diagnosed with IBD. Fatigue was associated with depressive symptoms, sleep disturbances, and increased pain intensity in both diagnoses, while clinical and endoscopic activity were associated factors only in UC.
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Affiliation(s)
- Kristina I Aass Holten
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Department of Gastroenterology, Østfold Hospital Trust, Sarpsborg, Norway
| | - Tomm Bernklev
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Research and Development Department, Vestfold Hospital Trust, Tønsberg, Norway
| | - Randi Opheim
- Department of Gastroenterology, Oslo University Hospital, Oslo, Norway
- Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Ingunn Johansen
- Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway
- Department of Health Sciences, Østfold University College, Halden, Norway
| | - Bjørn C Olsen
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Department of Gastroenterology, Telemark Hospital Trust, Skien, Norway
| | - Charlotte Lund
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Department of Gastroenterology, Oslo University Hospital, Oslo, Norway
| | - Vibeke Strande
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Unger-Vetlesen Institute, Lovisenberg Diaconal Hospital, Oslo, Norway
- Department of Gastroenterology, Lovisenberg Diaconal Hospital, Oslo, Norway
| | - Asle W Medhus
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Department of Gastroenterology, Oslo University Hospital, Oslo, Norway
| | - Gøri Perminow
- Pediatric Department, Oslo University Hospital, Oslo, Norway
| | | | | | - Simen Vatn
- Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway
| | | | - Tone B Aabrekk
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Department of Medicine, Vestfold Hospital Trust, Tønsberg, Norway
| | - Trond Espen Detlie
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway
| | - Øistein Hovde
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Department of Medicine, Innlandet Hospital Trust, Gjøvik, Norway
| | | | | | - Magne Henriksen
- Department of Gastroenterology, Østfold Hospital Trust, Sarpsborg, Norway
| | | | - Marte Lie Høivik
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Department of Gastroenterology, Oslo University Hospital, Oslo, Norway
| | - Lars-Petter Jelsness-Jørgensen
- Department of Gastroenterology, Østfold Hospital Trust, Sarpsborg, Norway
- Department of Health Sciences, Østfold University College, Halden, Norway
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8
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Jayasooriya N, Baillie S, Blackwell J, Bottle A, Petersen I, Creese H, Saxena S, Pollok RC. Systematic review with meta-analysis: Time to diagnosis and the impact of delayed diagnosis on clinical outcomes in inflammatory bowel disease. Aliment Pharmacol Ther 2023; 57:635-652. [PMID: 36627691 DOI: 10.1111/apt.17370] [Citation(s) in RCA: 55] [Impact Index Per Article: 27.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 09/29/2022] [Accepted: 12/10/2022] [Indexed: 01/12/2023]
Abstract
BACKGROUND The impact of diagnostic delay on the clinical course of inflammatory bowel disease (IBD) remains uncertain. AIM To perform a systematic review of time to diagnosis and the impact of delayed diagnosis on clinical outcomes in Crohn's disease (CD) and ulcerative colitis (UC). METHODS We searched EMBASE and Medline from inception to 30th November 2022 for studies reporting diagnostic interval, from symptom onset to IBD diagnosis. We calculated the median, interquartile range (IQR) and pooled weighted median, of median diagnostic intervals of eligible studies. We defined delayed diagnosis as individuals above the 75th centile of longest time to diagnosis in each study. Using random effects meta-analysis, we pooled odds ratios (ORs) with 95% confidence intervals (CI) for studies reporting clinical outcomes, according to delayed diagnosis. RESULTS One hundred and one studies representing 112,194 patients with IBD (CD = 59,359; UC = 52,835) met inclusion criteria. The median of median times to diagnosis was 8.0 (IQR: 5.0-15.2) and 3.7 months (IQR: 2.0-6.7) in CD and UC, respectively. In high-income countries, this was 6.2 (IQR: 5.0-12.3) and 3.2 months (IQR: 2.2-5.3), compared with 11.7 (IQR: 8.3-18.0) and 7.8 months (IQR: 5.2-21.8) in low-middle-income, countries, for CD and UC respectively. The pooled weighted median was 7.0 (95% CI: 3.0-26.4) and 4.6 (95% CI: 1.0-96.0) months, for CD and UC respectively. Eleven studies, representing 6164 patients (CD = 4858; UC = 1306), were included in the meta-analysis that examined the impact of diagnostic delay on clinical outcomes. In CD, delayed diagnosis was associated with higher odds of stricturing (OR = 1.88; CI: 1.35-2.62), penetrating disease (OR = 1.64; CI: 1.21-2.20) and intestinal surgery (OR = 2.24; CI: 1.57-3.19). In UC, delayed diagnosis was associated with higher odds of colectomy (OR = 4.13; CI: 1.04-16.40). CONCLUSION Delayed diagnosis is associated with disease progression in CD, and intestinal surgery in both CD and UC. Strategies are needed to achieve earlier diagnosis of IBD.
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Affiliation(s)
- Nishani Jayasooriya
- Department of Gastroenterology, St George's Healthcare NHS Trust, St George's University, London, UK
- Institute of Infection and Immunity, St George's University, London, UK
- School of Public Health, Imperial College London, London, UK
| | - Samantha Baillie
- Department of Gastroenterology, St George's Healthcare NHS Trust, St George's University, London, UK
- Institute of Infection and Immunity, St George's University, London, UK
- School of Public Health, Imperial College London, London, UK
| | - Jonathan Blackwell
- Department of Gastroenterology, St George's Healthcare NHS Trust, St George's University, London, UK
- Institute of Infection and Immunity, St George's University, London, UK
- School of Public Health, Imperial College London, London, UK
| | - Alex Bottle
- School of Public Health, Imperial College London, London, UK
| | - Irene Petersen
- Department of Primary Care and Population Health, University College London, London, UK
- Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark
| | - Hanna Creese
- School of Public Health, Imperial College London, London, UK
| | - Sonia Saxena
- School of Public Health, Imperial College London, London, UK
| | - Richard C Pollok
- Department of Gastroenterology, St George's Healthcare NHS Trust, St George's University, London, UK
- Institute of Infection and Immunity, St George's University, London, UK
- School of Public Health, Imperial College London, London, UK
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9
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Stahnke A, Gioia P, Kumar D, Jha P. Crohn’s Disease Initially Presenting With Anterior Sclerouveitis. Cureus 2023; 15:e35373. [PMID: 36994295 PMCID: PMC10042547 DOI: 10.7759/cureus.35373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/22/2023] [Indexed: 02/25/2023] Open
Abstract
This report examines the case of a 32-year-old male who initially presented with symptoms of eye pain, redness, and vision changes, and was subsequently diagnosed with anterior sclerouveitis. One week after his initial visit, the patient presented to the emergency department (ED) with daily bloody stools and left lower quadrant (LLQ) pain. Further workup and examination revealed a diagnosis of Crohn's disease. This report expands on ocular manifestations of Crohn's disease and touches on the importance of early gastrointestinal examination in patients who present with ocular symptoms.
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10
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Cross E, Saunders B, Farmer AD, Prior JA. Diagnostic delay in adult inflammatory bowel disease: A systematic review. Indian J Gastroenterol 2023; 42:40-52. [PMID: 36715839 PMCID: PMC10038954 DOI: 10.1007/s12664-022-01303-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Accepted: 10/20/2022] [Indexed: 01/31/2023]
Abstract
BACKGROUND The extent of diagnostic delay in inflammatory bowel disease (IBD) is incompletely understood. We aimed to understand the extent of diagnostic delay of IBD in adults and identify associations between patient or healthcare characteristics and length of delay. METHODS Articles were sourced from EMBASE, Medline and CINAHL from inception to April 2021. Inclusion criteria were adult cohorts (18 ≥ years old) reporting median time periods between onset of symptoms for Crohn's disease (CD), ulcerative colitis (UC) or IBD (i.e. CD and UC together) and a final diagnosis (diagnostic delay). Narrative synthesis was used to examine the extent of diagnostic delay and characteristics associated with delay. Sensitivity analysis was applied by the removal of outliers. RESULTS Thirty-one articles reporting median diagnostic delay for IBD, CD or UC were included. After sensitivity analysis, the majority of IBD studies (7 of 8) reported a median delay of between 2 and 5.3 months. From the studies examining median delay in UC, three-quarters (12 of 16) reported a delay between 2 and 6 months. In contrast, three-quarters of the CD studies (17 of 23) reported a delay of between 2 and 12 months. No characteristic had been examined enough to understand their role in diagnostic delay in these populations. CONCLUSIONS This systematic review provides robust insight into the extent of diagnostic delay in IBD and suggests further intervention is needed to reduce delay in CD particularly. Furthermore, our findings provide a benchmark value range for diagnostic delay, which such future work can be measured against.
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Affiliation(s)
- Eleanor Cross
- School of Medicine, Keele University, Keele, Staffordshire, ST5 5BG, UK
- University of North Midlands (UHNM) NHS Trust, Stoke-On-Trent, UK
| | - Benjamin Saunders
- School of Medicine, Keele University, Keele, Staffordshire, ST5 5BG, UK
| | - Adam D Farmer
- School of Medicine, Keele University, Keele, Staffordshire, ST5 5BG, UK
- Department of Gastroenterology, University Hospital of North Midlands (UHNM) NHS Trust, Stoke-On-Trent, UK
| | - James A Prior
- School of Medicine, Keele University, Keele, Staffordshire, ST5 5BG, UK.
- Midlands Partnership NHS Foundation Trust, Trust Headquarters, St. George's Hospital, Stafford, UK.
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11
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Cohen NA, Kliper E, Zamstein N, Ziv-Baran T, Waterman M, Hodik G, Tov AB, Kariv R. Trends in Biochemical Parameters, Healthcare Resource and Medication Use in the 5 Years Preceding IBD Diagnosis: A Health Maintenance Organization Cohort Study. Dig Dis Sci 2023; 68:414-422. [PMID: 36221010 DOI: 10.1007/s10620-022-07714-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Accepted: 09/29/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND Few data describing pre-diagnosis changes in patients with inflammatory bowel disease (IBD) exist. We aimed to determine if there is a pattern of change in use of health resources, medications and laboratory results in the years preceding diagnosis. METHODS This retrospective study used electronic medical records of Maccabi Health Services (MHS). Patients with IBD ≥ 16 years of age and minimum of 5-years follow-up were identified by entry into the MHS IBD registry and included in the analysis. Demographic, clinical, medication and laboratory data were collected. Generalized estimating equation model was applied to study trends and compare between years. RESULTS This study included 5643 patients with IBD. Of these, 3039 (53.8%) had Crohn's disease (CD), 2322 (41.1%) had ulcerative colitis (UC) and 282 (5%) had indeterminate colitis (IC). Laboratory parameters including white blood cells, platelets and C-reactive protein showed significant increases while haemoglobin and mean cell volume showed significant decreases in mean values in the 2 years prior to diagnosis with stable values prior to that (p < 0.0001). Parameters such as creatinine, total protein and albumin showed significant, progressive decreases in mean values starting 5 years prior to diagnosis (p < 0.0001). Patients with CD had distinct laboratory trends when compared with patients with UC. CONCLUSIONS Changes in laboratory parameters, healthcare service and medication use occur during the 5-year period before IBD diagnosis. These data can have future clinical applicability by developing a composite score and referral algorithm introducing red flags into primary care visits and appropriate referral for specialist care.
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Affiliation(s)
- Nathaniel A Cohen
- Maccabi Institute for Research & Innovation, Maccabi Healthcare Services, 6 Weizmann Street, Tel Aviv, Israel.
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
- Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, Tel Aviv, Israel.
| | | | | | - Tomer Ziv-Baran
- School of Public Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel
| | - Matti Waterman
- Department of Gastroenterology, Rambam Health Care Campus, Haifa, Israel
- Bruce Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel
| | - Gabriel Hodik
- Maccabi Institute for Research & Innovation, Maccabi Healthcare Services, 6 Weizmann Street, Tel Aviv, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Amir Ben Tov
- Maccabi Institute for Research & Innovation, Maccabi Healthcare Services, 6 Weizmann Street, Tel Aviv, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
- Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Revital Kariv
- Maccabi Institute for Research & Innovation, Maccabi Healthcare Services, 6 Weizmann Street, Tel Aviv, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
- Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, Tel Aviv, Israel
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12
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Ribeiro BE, Breves J, de Souza HSP. Pathogenesis: Crohn’s disease and ulcerative colitis. NATURAL PLANT PRODUCTS IN INFLAMMATORY BOWEL DISEASES 2023:9-46. [DOI: 10.1016/b978-0-323-99111-7.00002-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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13
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Grace AG, Usman MA, Ochayi MO, Adams MD, Umar HD, Obalum CD, Akunna GG, Meraiyebu AB, Onwuchekwa C. Elucidating the anti-oxidant and anti-inflammatory potentials of Triticum aestivum against ulcerative colitis: An in vivo and in silico study. PHYTOMEDICINE PLUS 2022; 2:100350. [DOI: 10.1016/j.phyplu.2022.100350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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14
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Ulcerative Colitis in Adulthood and in Older Patients: Same Disease, Same Outcome, Same Risks? Drugs Aging 2022; 39:441-452. [PMID: 35641753 PMCID: PMC9155981 DOI: 10.1007/s40266-022-00943-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/09/2022] [Indexed: 02/07/2023]
Abstract
The number of patients with inflammatory bowel disease (IBD) approaching an older age, together with the number of over-60-year-old patients newly diagnosed with IBD, is steadily increasing, reaching 25% of all patients. The present review focuses on late-onset ulcerative colitis (UC) and its initial disease course in comparison with that observed in younger adults in terms of extension at onset and the risk of proximal disease progression, medical treatment, surgery and hospitalization in the first years after diagnosis. We summarize the clues pointing to a milder disease course in a population which frequently presents major frailty due to comorbidities. With increasing age and thus increasing comorbidities, medical and surgical therapies frequently represent a challenge for treating physicians. The response, persistence, and risks of adverse events of conventional therapies indicated for late onset/older UC patients are examined, emphasizing the risks in this particular population, who are still being treated with prolonged corticosteroid therapy. Finally, we concentrate on data on biotechnological agents for which older patients were mostly excluded from pivotal trials. Real-life data from newer agents such as vedolizumab and ustekinumab show encouraging efficacy and safety profiles in the population of older UC patients.
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15
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Buchanan F, Saleem S, Alsamman MA. A Controversial Relationship Between Crohn’s Disease and Hidradenitis Suppurativa: A Case Series and Literature Review. Cureus 2022; 14:e23422. [PMID: 35481292 PMCID: PMC9033643 DOI: 10.7759/cureus.23422] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/23/2022] [Indexed: 11/05/2022] Open
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16
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Crohn's Disease in a Patient With Fibrodysplasia Ossificans Progressiva. ACG Case Rep J 2022; 9:e00737. [PMID: 35097150 PMCID: PMC8791042 DOI: 10.14309/crj.0000000000000737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2021] [Accepted: 10/06/2021] [Indexed: 11/17/2022] Open
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17
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Louwies T, Meerveld BGV. Abdominal Pain. COMPREHENSIVE PHARMACOLOGY 2022:132-163. [DOI: 10.1016/b978-0-12-820472-6.00037-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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18
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Kim JY, Choi MJ, Ha S, Hwang J, Koyanagi A, Dragioti E, Radua J, Smith L, Jacob L, de Pablo GS, Lee SW, Yon DK, Thompson T, Cortese S, Lollo G, Liang CS, Chu CS, Fusar-Poli P, Cheon KA, Shin JI, Solmi M. Association between autism spectrum disorder and inflammatory bowel disease: A systematic review and meta-analysis. Autism Res 2021; 15:340-352. [PMID: 34939353 DOI: 10.1002/aur.2656] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2021] [Revised: 11/02/2021] [Accepted: 12/01/2021] [Indexed: 12/17/2022]
Abstract
Children with autism spectrum disorder (ASD) are frequently diagnosed with co-occurring medical conditions including inflammatory bowel disease (IBD). To investigate the association, we conducted a systematic review registered in PROSPERO (ID:CRD42021236263) with a random-effects meta-analysis. We searched PubMed, Embase, and PsycInfo (last search on January 25, 2021), and manually searched relevant publications. We included observational studies measuring the association between ASD and IBD. The primary outcome was the association (odds ratio, OR) between ASD and later development of IBD. Sensitivity analyses were conducted by quality, confounding adjustment, and study design. We performed meta-regression analyses and assessed heterogeneity, publication bias, and quality of studies with the Newcastle-Ottawa Scale. Overall, we included six studies consisting of eight datasets, including over 11 million participants. We found that ASD was significantly associated with subsequent incident IBD (any IBD, OR = 1.66, 95% confidence interval[CI] = 1.25-2.21, p < 0.001; ulcerative colitis, OR = 1.91, 95%CI = 1.41-2.6, p < 0.001; Crohn's disease, OR = 1.47, 95%CI = 1.15-1.88, p = 0.002). ASD and IBD were also associated regardless of temporal sequence of diagnosis (any IBD, OR = 1.57, 95%CI = 1.28-1.93, p < 0.001; ulcerative colitis, OR = 1.7, 95%CI = 1.36-2.12, p < 0.001; Crohn's disease, OR = 1.37, 95%CI = 1.12-1.69, p = 0.003). Sensitivity analyses confirmed the findings of the main analysis. Meta-regression did not identify any significant moderators. Publication bias was not detected. Quality was high in four datasets and medium in four. In conclusion, our findings highlight the need to screen for IBD in individuals with ASD, and future research should identify who, among those with ASD, has the highest risk of IBD, and elucidate the shared biological mechanisms between ASD and IBD.
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Affiliation(s)
- Jong Yeob Kim
- Yonsei University College of Medicine, Seoul, South Korea
| | - Min Je Choi
- Yonsei University College of Medicine, Seoul, South Korea
| | - Sungji Ha
- Department of Child and Adolescent Psychiatry, Department of Psychiatry, Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Jimin Hwang
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | - Ai Koyanagi
- Research and Development Unit, Parc Sanitari Sant Joan de Déu/CIBERSAM, Universitat de Barcelona, Fundació Sant Joan de Déu, Sant Boi de Llobregat, Barcelona, Spain.,ICREA, Barcelona, Spain
| | - Elena Dragioti
- Pain and Rehabilitation Centre, and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
| | - Joaquim Radua
- Mental Health Research Networking Center (CIBERSAM), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.,Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.,Department of Clinical Neuroscience, Centre for Psychiatric Research, Karolinska Institutet, Stockholm, Sweden
| | - Lee Smith
- Centre for Health, Performance, and Wellbeing, Anglia Ruskin University, Cambridge, UK
| | - Louis Jacob
- Research and Development Unit, Parc Sanitari Sant Joan de Déu/CIBERSAM, Universitat de Barcelona, Fundació Sant Joan de Déu, Sant Boi de Llobregat, Barcelona, Spain.,Faculty of Medicine, University of Versailles Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux, France
| | - Gonzalo Salazar de Pablo
- Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.,Child and Adolescent Mental Health Services, South London & Maudsley NHS Trust, London, UK.,Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
| | - Seung Won Lee
- Department of Data Science, Sejong University College of Software Convergence, Seoul, South Korea
| | - Dong Keon Yon
- Department of Pediatrics, Seoul National University College of Medicine, Seoul, South Korea
| | - Trevor Thompson
- Centre for Chronic Illness and Ageing, University of Greenwich, London, UK
| | - Samuele Cortese
- Centre for Innovation in Mental Health, School of Psychology, Faculty of Environmental and Life sciences & Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK.,Solent NHS Trust, Southampton, UK.,Division of Psychiatry and Applied Psychology, School of Medicine, University of Nottingham, Nottingham, UK.,Hassenfeld Children's Hospital at NYU Langone, New York University Child Study Center, New York, New York, USA
| | - Gianluca Lollo
- Department of Gastroenterology, Ospedale Regionale di Bellinzona e Valli (Ente Ospedaliero Cantonale: EOC), Bellinzona, Switzerland
| | - Chih-Sung Liang
- Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan.,Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
| | - Che-Sheng Chu
- Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.,Center for Geriatric and Gerontology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.,Society of Psychophysiology, Non-invasive Neuromodulation Consortium for Mental Disorders, Taipei, Taiwan.,Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Paolo Fusar-Poli
- Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.,OASIS Service, South London and Maudsley NHS Foundation Trust, London, UK.,Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.,National Institute for Health Research, Maudsley Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, London, UK
| | - Keun-Ah Cheon
- Department of Child and Adolescent Psychiatry, Department of Psychiatry, Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Jae Il Shin
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, South Korea
| | - Marco Solmi
- Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.,Centre for Innovation in Mental Health, School of Psychology, Faculty of Environmental and Life sciences & Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK.,Department of Psychiatry, University of Ottawa, Ottawa, Ontario, Canada.,Department of Mental Health, The Ottawa Hospital, Ottawa, Ontario, Canada.,Clinical Epidemiology Program, Ottawa Hospital Research Institute (OHRI), University of Ottawa, Ottawa, Ontario, Canada
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19
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Iwata K, Mikami Y, Kato M, Yahagi N, Kanai T. Pathogenesis and management of gastrointestinal inflammation and fibrosis: from inflammatory bowel diseases to endoscopic surgery. Inflamm Regen 2021; 41:21. [PMID: 34261521 PMCID: PMC8278771 DOI: 10.1186/s41232-021-00174-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Accepted: 06/30/2021] [Indexed: 12/26/2022] Open
Abstract
Gastrointestinal fibrosis is a state of accumulated biological entropy caused by a dysregulated tissue repair response. Acute or chronic inflammation in the gastrointestinal tract, including inflammatory bowel disease, particularly Crohn’s disease, induces fibrosis and strictures, which often require surgical or endoscopic intervention. Recent technical advances in endoscopic surgical techniques raise the possibility of gastrointestinal stricture after an extended resection. Compared to recent progress in controlling inflammation, our understanding of the pathogenesis of gastrointestinal fibrosis is limited, which requires the development of prevention and treatment strategies. Here, we focus on gastrointestinal fibrosis in Crohn’s disease and post-endoscopic submucosal dissection (ESD) stricture, and we review the relevant literature.
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Affiliation(s)
- Kentaro Iwata
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.,Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, Tokyo, Japan
| | - Yohei Mikami
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
| | - Motohiko Kato
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.,Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, Tokyo, Japan
| | - Naohisa Yahagi
- Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, Tokyo, Japan
| | - Takanori Kanai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
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20
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Abstract
PURPOSE OF REVIEW Irritable bowel syndrome (IBS) is a very common disorder whose clinical presentation varies considerably between patients as well as within the same individual over time. Many of its symptoms, such as pain, diarrhea, constipation and bloating, may be manifestations of a host of other gastrointestinal diseases; some accompanied by increased mortality. This presents the clinician with a real dilemma: how to sensibly investigate the patient in which one suspects IBS but there is a nagging doubt that 'it could be something else'? Could one miss 'something serious'? This short review attempts to provide both an evidence-based response to these vexing questions and a practical guide to detecting alternative diagnoses in the subject with IBS-type symptoms. RECENT FINDINGS Clinical features, patient demographics and the clinical context can help to significantly narrow the differential diagnosis of the individual with IBS-type symptoms and may permit a positive diagnosis of IBS. The advent of noninvasive serological and stool tests has greatly facilitated differentiation from celiac disease and inflammatory bowel disease, respectively. In the older, female diarrhea sufferer microscopic colitis should be considered. The role of bile acid diarrhea in the individual with diarrhea-predominant IBS is emphasized; the status of small intestinal bacterial overgrowth in IBS remain uncertain. SUMMARY Attention to detail in the clinical evaluation of the individual with IBS-like symptoms will facilitate a selective and targeted approach to investigation. Wherever indicated, widely available serological and fecal tests will serve to bolster the diagnosis by excluding other options. Proceeding to more invasive testing should be dictated by clinical presentation and scenario with the threshold for intervention being generally lower among those with prominent diarrhea.
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21
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Alkhatry M, Al-Rifai A, Annese V, Georgopoulos F, Jazzar AN, Khassouan AM, Koutoubi Z, Nathwani R, Taha MS, Limdi JK. First United Arab Emirates consensus on diagnosis and management of inflammatory bowel diseases: A 2020 Delphi consensus. World J Gastroenterol 2020; 26:6710-6769. [PMID: 33268959 PMCID: PMC7684461 DOI: 10.3748/wjg.v26.i43.6710] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 07/15/2020] [Accepted: 10/12/2020] [Indexed: 02/06/2023] Open
Abstract
Ulcerative colitis and Crohn's disease are the main entities of inflammatory bowel disease characterized by chronic remittent inflammation of the gastrointestinal tract. The incidence and prevalence are on the rise worldwide, and the heterogeneity between patients and within individuals over time is striking. The progressive advance in our understanding of the etiopathogenesis coupled with an unprecedented increase in therapeutic options have changed the management towards evidence-based interventions by clinicians with patients. This guideline was stimulated and supported by the Emirates Gastroenterology and Hepatology Society following a systematic review and a Delphi consensus process that provided evidence- and expert opinion-based recommendations. Comprehensive up-to-date guidance is provided regarding diagnosis, evaluation of disease severity, appropriate and timely use of different investigations, choice of appropriate therapy for induction and remission phase according to disease severity, and management of main complications.
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Affiliation(s)
- Maryam Alkhatry
- Gastroenterology and Endoscopy Department, Ibrahim Bin Hamad Obaid Allah Hospital, Ministry of Health and Prevention, Ras Al Khaiman, United Arab Emirates
| | - Ahmad Al-Rifai
- Department of Gastroenterology, Sheikh Shakbout Medical City, Abu Dhabi, United Arab Emirates
| | - Vito Annese
- Department of Gastroenterology, Valiant Clinic, Dubai, United Arab Emirates
- Department of Gastroenterology and Endoscopy, American Hospital, Dubai, United Arab Emirates
| | | | - Ahmad N Jazzar
- Gastroenterology Division, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates
| | - Ahmed M Khassouan
- Digestive Disease Unit, Rashid Hospital, Dubai, United Arab Emirates
| | - Zaher Koutoubi
- Digestive Disease Institute, Cleveland Clinic, Abu Dhabi, United Arab Emirates
| | - Rahul Nathwani
- Department of Gastroenterology, Mediclinic City Hospital, Dubai, United Arab Emirates
- Department of Gastroenterology, Mohammed Bin Rashid University, Dubai, United Arab Emirates
| | - Mazen S Taha
- Gastroenterology and Hepatology, Tawam Hospital, Al Ain, United Arab Emirates
| | - Jimmy K Limdi
- Department of Gastroenterology, The Pennine Acute Hospitals NHS Trust, Manchester Academic Health Sciences, University of Manchester, Manchester M8 5RB, United Kingdom
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22
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Moulton CD, Norton C, Powell N, Mohamedali Z, Hopkins CWP. Depression in inflammatory bowel disease: risk factor, prodrome or extraintestinal manifestation? Gut 2020; 69:609-610. [PMID: 30808645 DOI: 10.1136/gutjnl-2019-318444] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2019] [Accepted: 02/08/2019] [Indexed: 12/08/2022]
Affiliation(s)
- Calum D Moulton
- Department of Psychological Medicine, King's College London, London, UK
| | - Christine Norton
- Florence Nightingale School of Nursing & Midwifery, King's College London, London, UK
| | - Nick Powell
- Centre for Inflammation Biology and Cancer Immunology, King's College London, London, UK
| | - Zahra Mohamedali
- GKT School of Medical Education, King's College London, London, UK
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23
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Alharbi R, Almahmudi F, Makhdoom Y, Mosli M. Knowledge and attitudes of primary healthcare physicians toward the diagnosis and management of inflammatory bowel disease following an educational intervention: A comparative analysis. Saudi J Gastroenterol 2019; 25:277-285. [PMID: 31187783 PMCID: PMC6784430 DOI: 10.4103/sjg.sjg_169_19] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND/AIMS Inflammatory bowel disease (IBD) is a chronic inflammatory condition that requires early diagnosis and proper management. Patients with early symptoms of IBD are typically evaluated first by primary healthcare (PHC) physicians, who in turn refer patients with suspected IBD to specialists. Therefore, we aimed to assess the knowledge and attitude of PHC physicians toward IBD. MATERIALS AND METHODS We conducted a comparative cross-sectional survey of PHC physicians practicing at the Ministry of Health PHC centers in Jeddah, KSA. Demographics and data on the knowledge and practices of physicians were collected through a predefined and tested questionnaire that included three domains (Eaden, Leong, and Sign/Symptom Awareness). A subgroup of the cohort was educated about IBD referral criteria (group A, n = 65) prior to study initiation and their responses were compared with those from the remaining group (group B, n = 135). Regression analysis was used to test associations with the significance threshold set at 5%. RESULTS A total of 211 PHC physicians were surveyed with a response rate of 95%. Female physicians comprised 66.5% of the cohort and the mean age was 32.26 ± 6.6 years. About 91% of physicians were Saudi nationals, and 75.5% were MBBS degree holders. The majority of the respondents (93%) reported seeing zero to five patients with IBD per month, and almost half of the physicians preferred to always refer patients to specialists (49.5%). Most of the respondents were uncomfortable (3.27 ± 1.4 to 4.35 ± 1.2) with initiating or managing specific medical therapies (maintenance therapy, therapy for acute flare, corticosteroids, immunomodulators, and biologics) for patients with IBD. With regard to knowledge, group A had higher scores in all three domains especially in the Sign/Symptom Awareness domain (mean score 6.17 ± 1.1 vs. 3.5 ± 1.01, P < 0.001). According to multivariate analyses, both groups' knowledge showed no significant relationship with any of the medical therapies, except for the Sign/Symptom Awareness domain which was shown to be significantly affecting the comfort of doctors in managing maintenance therapy among patients with IBD [odds ratio (OR) =1.61, P = 0.008]. Gender, nationality, and qualifications were found to have a significant influence on the comfort in initiating specific medical therapies. Group A was identified as a significant factor in predicting comfort with managing corticosteroids (OR = 8.25, P = 0.006) and immunomodulators (OR = 6.03, P = 0.02) on patients with IBD. CONCLUSION The knowledge and comfort of PHC physicians with IBD medication prescription appears to be higher when education is provided. This observation is important, since PHC physicians are responsible for early identification and referral of patients suspected of having IBD, to specialists.
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Affiliation(s)
- Rwan Alharbi
- The Joint Program of Family Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Faizah Almahmudi
- The Joint Program of Family Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Yahya Makhdoom
- The Joint Program of Family Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Mahmoud Mosli
- Department of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
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24
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Seyedian SS, Nokhostin F, Malamir MD. A review of the diagnosis, prevention, and treatment methods of inflammatory bowel disease. J Med Life 2019; 12:113-122. [PMID: 31406511 PMCID: PMC6685307 DOI: 10.25122/jml-2018-0075] [Citation(s) in RCA: 391] [Impact Index Per Article: 65.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2018] [Accepted: 01/27/2019] [Indexed: 12/11/2022] Open
Abstract
Ulcerative colitis (UC) and Crohn's disease (CD) are classified as chronic inflammatory bowel diseases (IBD) which have similar symptoms and lead to digestive disorders and inflammation in the digestive system. The reason why they occur is still a mystery. A number of factors can be attributed to the prevalence of CD and UC, some of which include geographical location, inappropriate diet, genetics, and inappropriate immune response. Both diseases are more often diagnosed in urban areas compared to rural areas and both have their own challenges and side effects, but the patients can still have a good quality of life. Given the fact that the prevalence of this disease is higher at younger ages and that it disrupts half the life of the patient, it will, most likely, become a major health problem in the near future, even in developing countries. By reviewing valid scientific resources and evaluating new methods of addressing this disease, the present study aims to provide researchers and patients with new insights into this field and facilitate access to new treatments.
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Affiliation(s)
- Seyed Saeid Seyedian
- Alimentary Tract Research Center, Ahvaz Jundishapur University of Medical Science, Ahvaz, Iran
| | - Forogh Nokhostin
- Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mehrdad Dargahi Malamir
- Faculty of Medicine, Medical doctor of Internal Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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Gajula P, Quigley EM. Overlapping irritable bowel syndrome and inflammatory bowel disease. MINERVA GASTROENTERO 2019; 65:107-115. [PMID: 30746927 DOI: 10.23736/s1121-421x.19.02559-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The pathogenesis of irritable bowel-type symptoms occurring in patients with inflammatory bowel disease who are in apparent remission continues to generate scientific controversy and the interpretation and management of these symptoms, so distressing to the sufferer, represent major challenges for the clinician. On the one hand, these symptoms often satisfy Rome IV criteria for IBS and their occurrence correlates highly with anxiety, a known trigger for IBS. On the other hand, recent studies have shown that many of these patients exhibit subtle inflammatory changes. These observations beg the question: are these symptoms "true" IBS superimposed on IBD, or an active but subclinical form of IBD? While it is certain that earlier studies failed to detect subclinical inflammation, it is also evident that even with the use of sensitive biomarkers for inflammation, such as calprotectin and lactoferrin backed up by pan-endoscopy and biopsy to exclude ongoing inflammatory activity in its most subtle form, the prevalence of IBS-type symptoms remains higher than expected in the IBD patient. Pending further definition of its etiology and pathology, we coined the term irritable inflammatory bowel syndrome (IIBS) to refer to this phenomenon. Here we explore the risk factors for this entity, sift through clues to its pathogenesis and attempt to provide, albeit bereft of a robust evidence base, an approach to its management.
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Affiliation(s)
- Prianka Gajula
- Department of Medicine, Houston Methodist Hospital and Weill Cornell Medical College, Houston, TX, USA
| | - Eamonn M Quigley
- Division of Gastroenterology and Hepatology, Lynda K. and David M. Underwood Center for Digestive Disorders, Houston Methodist Hospital and Weill Cornell Medical College, Houston, TX, USA -
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Abstract
Most of us live blissfully unaware of the orchestrated function that our internal organs conduct. When this peace is interrupted, it is often by routine sensations of hunger and urge. However, for >20% of the global population, chronic visceral pain is an unpleasant and often excruciating reminder of the existence of our internal organs. In many cases, there is no obvious underlying pathological cause of the pain. Accordingly, chronic visceral pain is debilitating, reduces the quality of life of sufferers, and has large concomitant socioeconomic costs. In this review, we highlight key mechanisms underlying chronic abdominal and pelvic pain associated with functional and inflammatory disorders of the gastrointestinal and urinary tracts. This includes how the colon and bladder are innervated by specialized subclasses of spinal afferents, how these afferents become sensitized in highly dynamic signaling environments, and the subsequent development of neuroplasticity within visceral pain pathways. We also highlight key contributing factors, including alterations in commensal bacteria, altered mucosal permeability, epithelial interactions with afferent nerves, alterations in immune or stress responses, and cross talk between these two adjacent organs.
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Affiliation(s)
- Luke Grundy
- Visceral Pain Research Group, College of Medicine and Public Health, Centre for Neuroscience, Flinders University, Bedford Park, South Australia 5042, Australia; .,Centre for Nutrition and Gastrointestinal Diseases, University of Adelaide, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, South Australia 5000, Australia
| | - Andelain Erickson
- Visceral Pain Research Group, College of Medicine and Public Health, Centre for Neuroscience, Flinders University, Bedford Park, South Australia 5042, Australia; .,Centre for Nutrition and Gastrointestinal Diseases, University of Adelaide, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, South Australia 5000, Australia
| | - Stuart M Brierley
- Visceral Pain Research Group, College of Medicine and Public Health, Centre for Neuroscience, Flinders University, Bedford Park, South Australia 5042, Australia; .,Centre for Nutrition and Gastrointestinal Diseases, University of Adelaide, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, South Australia 5000, Australia
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Novacek G, Gröchenig HP, Haas T, Wenzl H, Steiner P, Koch R, Feichtenschlager T, Eckhardt G, Mayer A, Kirchgatterer A, Ludwiczek O, Platzer R, Papay P, Gartner J, Fuchssteiner H, Miehsler W, Peters PG, Reicht G, Vogelsang H, Dejaco C, Waldhör T. Diagnostic delay in patients with inflammatory bowel disease in Austria. Wien Klin Wochenschr 2019; 131:104-112. [PMID: 30715607 DOI: 10.1007/s00508-019-1451-3] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2018] [Accepted: 01/12/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Delayed diagnosis seems to be common in inflammatory bowel diseases (IBD). The study was carried out to investigate the diagnostic delay and associated risk factors in Austrian IBD patients. METHODS In a multicenter cross-sectional study adult patients with IBD attending 18 Austrian outpatient clinics completed a multi-item questionnaire that recorded medical and socioeconomic characteristics. The study outcome was diagnostic delay defined as the period from symptom onset to diagnosis of IBD. RESULTS A total of 1286 patients (Crohn's disease 830, ulcerative colitis 435, inflammatory bowel disease unclassified 21; females 651) with a median age of 40 years (interquartile range 31-52 years) and a median disease duration of 10 years (4-18 years) were analyzed. The median diagnostic delay was 6 months (2-23 months) in Crohn's disease and 3 months (1-10 months) in ulcerative colitis (p < 0.001). In the multivariable regression analysis Crohn's disease, greater age at diagnosis and a high educational level (compared to middle degree level) were independently associated with longer diagnostic delay. CONCLUSION The diagnostic delay was longer in Crohn's disease than in ulcerative colitis patients and was associated with greater age at diagnosis and a higher educational level.
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Affiliation(s)
- Gottfried Novacek
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
| | - Hans Peter Gröchenig
- Department of Internal Medicine, Brothers of St. John of God Hospital, St. Veit an der Glan, Spitalgasse 26, 9300, St. Veit an der Glan, Austria
| | - Thomas Haas
- Darmpraxis Salzburg, Bayernstraße 17, 5020, Salzburg, Austria
| | - Heimo Wenzl
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Auenbruggerplatz 2, 8036, Graz, Austria
| | - Pius Steiner
- Department of Internal Medicine I, Wels-Grieskirchen Hospital, Grieskirchnerstraße 42, 4600, Wels, Austria
| | - Robert Koch
- Department of Internal Medicine I, Medical University of Innsbruck, Christoph-Probst-Platz 1, Innrain 52, 6020, Innsbruck, Austria
| | - Thomas Feichtenschlager
- Department of Internal Medicine IV, Rudolfstiftung Hospital, Juchgasse 25, 1030, Vienna, Austria
| | - Gerald Eckhardt
- Department of Internal Medicine, Oberpullendorf Hospital, Spitalstraße 32, 7350, Oberpullendorf, Austria
| | - Andreas Mayer
- Department of Internal Medicine II, Universitätsklinikum St. Pölten, Dunant-Platz 1, 3100, St. Pölten, Austria
| | - Andreas Kirchgatterer
- Department of Internal Medicine V, Wels-Grieskirchen Hospital, Wagnleithnerstraße 27, 4710, Grieskirchen, Austria
| | - Othmar Ludwiczek
- Department of Internal Medicine, Hall in Tirol Hospital, Milserstraße 10, 6060, Hall in Tirol, Austria
| | - Reingard Platzer
- Department of Internal Medicine I, Wiener Neustadt Hospital, Corvinusring 3-5, 2700, Wiener Neustadt, Austria
| | - Pavol Papay
- Department of Internal Medicine, Franziskus Hospital, Nikolsdorfergasse 32, 1050, Vienna, Austria
| | - Johanna Gartner
- Department of Internal Medicine, Hanusch Hospital, Heinrich-Collin-Straße 30, 1140, Vienna, Austria
| | - Harry Fuchssteiner
- Department of Internal Medicine IV, Elisabethinen Hospital, Fadingerstraße 1, 4020, Linz, Austria
| | - Wolfgang Miehsler
- Department of Internal Medicine, Brothers of St. John of God Hospital, Kajetanerplatz 1, 5010, Salzburg, Austria
| | - Paul-Gerhard Peters
- Department of Internal Medicine, Feldkirch Hospital, Carinagasse 47, 6800, Feldkirch, Austria
| | - Gerhard Reicht
- Department of Internal Medicine II, Brothers of St. John of God Hospital, Marschallgasse 12, 8020, Graz, Austria
| | - Harald Vogelsang
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Clemens Dejaco
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Thomas Waldhör
- Department of Epidemiology, Center for Public Health, Medical University of Vienna, Kinderspitalgasse 15, 1090, Vienna, Austria
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Impact of Diagnostic Delay and Associated Factors on Clinical Outcomes in a U.S. Inflammatory Bowel Disease Cohort. Inflamm Bowel Dis 2017; 23:1825-1831. [PMID: 28885229 DOI: 10.1097/mib.0000000000001257] [Citation(s) in RCA: 81] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND The impact of diagnostic delay in inflammatory bowel disease, including Crohn's disease (CD) and ulcerative colitis (UC), on disease course remains uncertain. This study examines factors that may influence time to diagnosis and disease outcomes in a U.S. patient cohort. METHODS We retrospectively collected data on patient characteristics, time to diagnosis, disease phenotype, and complications in 177 patients with inflammatory bowel disease (110 CD and 67 UC) diagnosed at our institution from 2008 to 2015. Factors potentially affecting time to diagnosis were analyzed. Association between disease complications (perianal disease, intestinal strictures, surgery, fistula, abscess, and perforation) and time to diagnosis was tested by multivariable analysis. RESULTS The median time to diagnosis was longer for patients with CD compared with patients with UC (median 9.5 versus 3.1 months; P < 0.001). The median time from symptom onset to initial physician visit was similar for patients with CD and patients with UC (1 month). However, the median time from symptom onset to specialist evaluation was longer for patients with CD compared with patients with UC: 7 months (interquartile range: 3-23) versus 3 months (interquartile range: 1-8), respectively (P < 0.001). In CD, ileal disease and hematochezia were positively and negatively correlated, respectively, with longer time to diagnosis (P < 0.05). Compared with patients with time to diagnosis ≤4 months, patients with time >26 months had increased overall complications (odds ratio, 8.22; P = 0.007) and intestinal strictures (odds ratio, 8.96; P = 0.012) at time of diagnosis. Such correlation persisted at follow-up. CONCLUSIONS Time to diagnosis was long in CD. Physician-related delay in diagnosing CD was associated with increased overall complications and intestinal strictures (See Video Abstract, Supplemental Digital Content 1, http://links.lww.com/IBD/B646).
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Lee DW, Koo JS, Choe JW, Suh SJ, Kim SY, Hyun JJ, Jung SW, Jung YK, Yim HJ, Lee SW. Diagnostic delay in inflammatory bowel disease increases the risk of intestinal surgery. World J Gastroenterol 2017; 23:6474-6481. [PMID: 29085197 PMCID: PMC5643273 DOI: 10.3748/wjg.v23.i35.6474] [Citation(s) in RCA: 72] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2017] [Revised: 07/28/2017] [Accepted: 08/15/2017] [Indexed: 02/07/2023] Open
Abstract
AIM To investigate the factors affecting diagnostic delay and outcomes of diagnostic delay in inflammatory bowel disease (IBD)
METHODS We retrospectively studied 165 patients with Crohn’s disease (CD) and 130 patients with ulcerative colitis (UC) who were diagnosed and had follow up durations > 6 mo at Korea University Ansan Hospital from January 2000 to December 2015. A diagnostic delay was defined as the time interval between the first symptom onset and IBD diagnosis in which the 76th to 100th percentiles of patients were diagnosed.
RESULTS The median diagnostic time interval was 6.2 and 2.4 mo in the patients with CD and UC, respectively. Among the initial symptoms, perianal discomfort before di-agnosis (OR = 10.2, 95%CI: 1.93-54.3, P = 0.006) was associated with diagnostic delays in patients with CD; however, no clinical factor was associated with diagnostic delays in patients with UC. Diagnostic delays, stricturing type, and penetrating type were associated with increased intestinal surgery risks in CD (OR = 2.54, 95%CI: 1.06-6.09; OR = 4.44, 95%CI: 1.67-11.8; OR = 3.79, 95%CI: 1.14-12.6, respectively). In UC, a diagnostic delay was the only factor associated increased intestinal surgery risks (OR = 6.81, 95%CI: 1.12-41.4).
CONCLUSION A diagnostic delay was associated with poor outcomes, such as increased intestinal surgery risks in patients with CD and UC.
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Affiliation(s)
- Dong-won Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan-si, Gyeonggi-do 15355, South Korea
| | - Ja Seol Koo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan-si, Gyeonggi-do 15355, South Korea
| | - Jung Wan Choe
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan-si, Gyeonggi-do 15355, South Korea
| | - Sang Jun Suh
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan-si, Gyeonggi-do 15355, South Korea
| | - Seung Young Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan-si, Gyeonggi-do 15355, South Korea
| | - Jong Jin Hyun
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan-si, Gyeonggi-do 15355, South Korea
| | - Sung Woo Jung
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan-si, Gyeonggi-do 15355, South Korea
| | - Young Kul Jung
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan-si, Gyeonggi-do 15355, South Korea
| | - Hyung Joon Yim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan-si, Gyeonggi-do 15355, South Korea
| | - Sang Woo Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan-si, Gyeonggi-do 15355, South Korea
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Cantoro L, Di Sabatino A, Papi C, Margagnoni G, Ardizzone S, Giuffrida P, Giannarelli D, Massari A, Monterubbianesi R, Lenti MV, Corazza GR, Kohn A. The Time Course of Diagnostic Delay in Inflammatory Bowel Disease Over the Last Sixty Years: An Italian Multicentre Study. J Crohns Colitis 2017; 11:975-980. [PMID: 28333328 DOI: 10.1093/ecco-jcc/jjx041] [Citation(s) in RCA: 71] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2016] [Accepted: 03/16/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Inflammatory bowel disease [IBD] patients are still under-diagnosed or diagnosed with serious delay. We examined whether diagnostic delay [DD] in IBD has changed over the last 60 years, and explored the risk factors of longer DD. METHODS In total, 3392 IBD patients recorded in the registry of four IBD Italian centres were divided according to the year of diagnosis into a historical cohort [HC: 1955-84] and modern cohort [MC: 1985-2014]. DD, i.e. time lapse between onset of symptoms indicative of IBD and definitive diagnosis, was divided into four sub-periods [0-6, 7-12, 13-24, >24 months], which were correlated with age and disease location/behaviour at diagnosis. RESULTS Median DD in IBD was 3.0 months, it was significantly [P < 0.0001] higher in Crohn's disease [CD] [7.1 months] than in ulcerative colitis [UC] [2.0 months], and did not differ either between the HC and the MC or over the last three decades. However, the proportion of patients with a DD>24 months was significantly [P < 0.0001] higher in the HC [26.0%] than in the MC [18.2%], and the same trend was evident over the last three decades [1985-94: 19.9%; 1995-2004: 16.4%; 2005-14: 13.9%; P = 0.04]. At logistic regression analysis, age at diagnosis >40 years (CD: odds ratio 1.73, 95% confidence interval [CI] 1.31-2.28, P < 0.0001; UC: 1.41, 95% CI 1.02-1.96, P = 0.04) and complicated disease at CD diagnosis [1.39, 95% CI 1.06-1.82, P = 0.02] were independently associated with a DD>24 months. CONCLUSIONS DD duration has not changed over the last 60 years in Italy, but the number of IBD patients with a longer DD significantly decreased. Older age at diagnosis and a complicated disease at CD diagnosis are risk factors for longer DD.
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Affiliation(s)
- Laura Cantoro
- IBD Unit, San Camillo-Forlanini Hospital, Rome, Italy
| | - Antonio Di Sabatino
- First Department of Internal Medicine, San Matteo Hospital Foundation, University of Pavia, Pavia, Italy
| | - Claudio Papi
- IBD Unit, San Filippo Neri Hospital, Rome, Italy
| | | | - Sandro Ardizzone
- Gastroenterology Unit, Department of Biomedical and Clinical Sciences, Luigi Sacco University Hospital, Italy
| | - Paolo Giuffrida
- First Department of Internal Medicine, San Matteo Hospital Foundation, University of Pavia, Pavia, Italy
| | - Diana Giannarelli
- Biostatistics Unit, Regina Elena National Cancer Institute, Rome, Italy
| | - Alessandro Massari
- Gastroenterology Unit, Department of Biomedical and Clinical Sciences, Luigi Sacco University Hospital, Italy
| | | | - Marco Vincenzo Lenti
- First Department of Internal Medicine, San Matteo Hospital Foundation, University of Pavia, Pavia, Italy
| | - Gino Roberto Corazza
- First Department of Internal Medicine, San Matteo Hospital Foundation, University of Pavia, Pavia, Italy
| | - Anna Kohn
- IBD Unit, San Camillo-Forlanini Hospital, Rome, Italy
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Feuerstein JD, Cheifetz AS. Crohn Disease: Epidemiology, Diagnosis, and Management. Mayo Clin Proc 2017; 92:1088-1103. [PMID: 28601423 DOI: 10.1016/j.mayocp.2017.04.010] [Citation(s) in RCA: 298] [Impact Index Per Article: 37.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2017] [Revised: 03/30/2017] [Accepted: 04/12/2017] [Indexed: 12/20/2022]
Abstract
Crohn disease is a chronic idiopathic inflammatory bowel disease condition characterized by skip lesions and transmural inflammation that can affect the entire gastrointestinal tract from the mouth to the anus. For this review article, we performed a review of articles in PubMed through February 1, 2017, by using the following Medical Subject Heading terms: crohns disease, crohn's disease, crohn disease, inflammatory bowel disease, and inflammatory bowel diseases. Presenting symptoms are often variable and may include diarrhea, abdominal pain, weight loss, nausea, vomiting, and in certain cases fevers or chills. There are 3 main disease phenotypes: inflammatory, structuring, and penetrating. In addition to the underlying disease phenotype, up to a third of patients will develop perianal involvement of their disease. In addition, in some cases, extraintestinal manifestations may develop. The diagnosis is typically made with endoscopic and/or radiologic findings. Disease management is usually with pharmacologic therapy, which is determined on the basis of disease severity and underlying disease phenotype. Although the goal of management is to control the inflammation and induce a clinical remission with pharmacologic therapy, most patients will eventually require surgery for their disease. Unfortunately, surgery is not curative and patients still require ongoing therapy even after surgery for disease recurrence. Importantly, given the risks of complications from both Crohn disease and the medications used to treat the disease process, primary care physicians play an important role in optimizing the preventative care management to reduce the risk of complications.
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Affiliation(s)
- Joseph D Feuerstein
- Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
| | - Adam S Cheifetz
- Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
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Wehkamp J, Götz M, Herrlinger K, Steurer W, Stange EF. Inflammatory Bowel Disease. DEUTSCHES ARZTEBLATT INTERNATIONAL 2017; 113:72-82. [PMID: 26900160 DOI: 10.3238/arztebl.2016.0072] [Citation(s) in RCA: 58] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/28/2015] [Revised: 12/14/2015] [Accepted: 12/14/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND Inflammatory bowel diseases are common in Europe, with prevalences as high as 1 in 198 persons (ulcerative colitis) and 1 in 310 persons (Crohn's disease). METHODS This review is based on pertinent articles retrieved by a search in PubMed and in German and European guidelines and Cochrane reviews of controlled trials. RESULTS Typically, the main clinical features of inflammatory bowel diseases are diarrhea, abdominal pain, and, in the case of ulcerative colitis, peranal bleeding. These diseases are due to a complex immunological disturbance with both genetic and environmental causes. A defective mucosal barrier against commensal bowel flora plays a major role in their pathogenesis. The diagnosis is based on laboratory testing, ultrasonography, imaging studies, and, above all, gastrointestinal endoscopy. Most patients with Crohn's disease respond to budesonide or systemic steroids; aminosalicylates are less effective. Refractory exacerbations may be treated with antibodies against tumor necrosis factor (TNF) or, more recently, antibodies against integrin, a protein of the cell membrane. In ulcerative colitis, aminosalicylates are given first; if necessary, steroids or antibodies against TNF-α or integrin are added. Maintenance therapy to prevent further relapses often involves immunosuppression with thiopurines and/or antibodies. Once all conservative treatment options have been exhausted, surgery may be necessary. CONCLUSION The treatment of chronic inflammatory bowel diseases requires individually designed therapeutic strategies and the close interdisciplinary collaboration of internists and surgeons.
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Affiliation(s)
- Jan Wehkamp
- Department of Internal Medicine I - Gastroenterology, Hepatology, Infectiology, University Hospital of Tübingen, Asklepios Klinik Nord - Heidberg, Hamburg, Department of Internal Medicine I (Gastroenterology, Hepatology and Endocrinology), Robert-Bosch-Krankenhaus, Stuttgart
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The diagnostic accuracy of faecal calprotectin and small bowel capsule endoscopy and their correlation in suspected isolated small bowel Crohn's disease. Eur J Gastroenterol Hepatol 2016; 28:1145-50. [PMID: 27384306 DOI: 10.1097/meg.0000000000000696] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Faecal calprotectin (FC) is less accurate at identifying inflammation in the small bowel than in the colon. Small bowel capsule endoscopy (SBCE) is a useful tool to detect small bowel inflammation. We investigated the diagnostic accuracy of FC and SBCE and their correlation in patients with suspected isolated small bowel Crohn's disease. PATIENTS AND METHODS This was performed as a prospective single centre study including patients attending for SBCE with suspected small bowel Crohn's disease. Patient demographics, symptoms, medications and blood parameters were collected. Capsule endoscopy findings were analysed against calprotectin values, final diagnosis and blood parameters. RESULTS A total of 146 patients were included (99 females and 47 males) with a mean age of 38±14 years. FC of more than 50 mg/kg was not significantly associated with clinically relevant capsule endoscopy findings (P=0.25), correlation coefficient was 0.11. Sensitivity, specificity, positive and negative predictive values for FC at a cut-off of more than 50 mg/kg were 88.9% [95% confidence interval (CI): 65.3-98.6], 25.0% (95% CI: 17.8-33.4), 14.3 (95% CI: 8.4-22.2) and 94.1% (95% CI: 80.3-99.3), respectively. A raised FC was not significantly associated with an elevated C-reactive protein or the presence of anaemia (P=0.19 and 0.10, respectively). CONCLUSION FC performs modestly as a screening test to exclude small bowel inflammation. However, we recommend interpretation within the overall clinical context to avoid overlooking the infrequent patient with small bowel inflammation and a negative FC.
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Abstract
The acute phase of IBD with inflamed gut and often ulcerated mucosa is clearly different from the apparently normal mucosa characteristic of IBS. However, more detailed assessment has detected immune activation, increased gut permeability, increased mucosal serotonin availability, abnormalities of enteric nerve structure and function, and dysbiosis in gut microbiota in IBS - all features seen in IBD. Furthermore, as treatments for inflammation in IBD have become more effective it is now apparent that ∼1 in 3 patients with IBD in remission from inflammation still have persistent abnormalities of sensation, motility and gut microbiota, which might cause IBS-like symptoms. This Perspective explores the overlap between IBS and IBD and their treatments, proposing future directions for research in this stimulating area.
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Affiliation(s)
- Robin Spiller
- NIHR Biomedical Research Unit in Gastrointestinal and Liver Diseases at Nottingham University Hospitals NHS Trust and The University of Nottingham, Queens Medical Centre, E Floor West Block, Nottingham NG7 2UH, UK
| | - Giles Major
- NIHR Biomedical Research Unit in Gastrointestinal and Liver Diseases at Nottingham University Hospitals NHS Trust and The University of Nottingham, Queens Medical Centre, E Floor West Block, Nottingham NG7 2UH, UK
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Thornton GCD, Goldacre MJ, Goldacre R, Howarth LJ. Diagnostic outcomes following childhood non-specific abdominal pain: a record-linkage study. Arch Dis Child 2016. [PMID: 26220924 DOI: 10.1136/archdischild-2015-308198] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
AIMS Non-specific abdominal pain (NSAP) is the most common diagnosis on discharge following admission for abdominal pain in childhood. Our aim was to determine the risk of subsequent hospital diagnosis of organic and functional gastroenterological conditions following a diagnosis of NSAP, and to assess the persistence of this risk. METHODS An NSAP cohort of 268,623 children aged 0-16 years was constructed from linked English Hospital Episode Statistics from 1999 to 2011. The control cohort (1,684,923 children, 0-16 years old) comprised children hospitalised with unrelated conditions. Clinically relevant outcomes were selected and standardised rate ratios were calculated. RESULTS From the NSAP cohort, 15,515 (5.8%) were later hospitalised with bowel pathology and 13,301 (5%) with a specific functional disorder. Notably, there was a 4.84 (95% CI 4.45 to 5.27) times greater risk of Crohn's disease following NSAP and a 4.23 (4.13 to 4.33) greater risk of acute appendicitis than in the control cohort. The risk of irritable bowel syndrome (IBS) was 7.22 (6.65 to 7.85) times greater following NSAP. The risks of inflammatory bowel disease (IBD), IBS and functional disorder (unspecified) were significantly increased in all age groups except <2-year-olds. The risk of underlying bowel pathology remained raised up to 10 years after first diagnosis with NSAP. CONCLUSIONS Only a small proportion of those with NSAP go on to be hospitalised with underlying bowel pathology. However, their risk is increased even at 10 years after the first hospital admission with NSAP. Diagnostic strategies need to be assessed and refined and active surveillance employed for children with NSAP.
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Affiliation(s)
- G C D Thornton
- Department of Paediatric Gastroenterology, Oxford University Hospitals Trust, Oxford, UK
| | - M J Goldacre
- Unit of Health-Care Epidemiology, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - R Goldacre
- Unit of Health-Care Epidemiology, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - L J Howarth
- Department of Paediatric Gastroenterology, Oxford University Hospitals Trust, Oxford, UK
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Quigley EMM. Overlapping irritable bowel syndrome and inflammatory bowel disease: less to this than meets the eye? Therap Adv Gastroenterol 2016; 9:199-212. [PMID: 26929782 PMCID: PMC4749858 DOI: 10.1177/1756283x15621230] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Though distinct in terms of pathology, natural history and therapeutic approach, irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) have some features in common. These include shared symptomatology and largely similar demographics. However, in most instances, clinical presentation, together with laboratory, imaging and endoscopic findings will readily permit the differentiation of active IBD from IBS. More problematic is the situation where a subject with IBD, in apparent remission, continues to complain of symptoms which, in aggregate, satisfy commonly employed criteria for the diagnosis of IBS. Access to methodologies, such the assay for levels of calprotectin in feces, now allows identification of ongoing inflammation in some such individuals and prompts appropriate therapy. More challenging is the IBD patient with persisting symptoms and no detectable evidence of inflammation; is this coincident IBS, IBS triggered by IBD or an even more subtle level of IBD activity unrecognized by available laboratory or imaging methods? Arguments can be advanced for each of these proposals; lacking definitive data, this issue remains unresolved. The occurrence of IBS-type symptoms in the IBD patient, together with some data suggesting a very subtle level of 'inflammation' or 'immune activation' in IBS, raises other questions: is IBS a prodromal form of IBD; and are IBS and IBD part of the spectrum of the same disease? All of the available evidence indicates that the answer to both these questions should be a resounding 'no'. Indeed, the whole issue of overlap between IBS and IBD should be declared moot given their differing pathophysiologies, contrasting natural histories and divergent treatment paths. The limited symptom repertoire of the gastrointestinal tract may well be fundamental to the apparent confusion that has, of late, bedeviled this area.
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Zaharie R, Tantau A, Zaharie F, Tantau M, Gheorghe L, Gheorghe C, Gologan S, Cijevschi C, Trifan A, Dobru D, Goldis A, Constantinescu G, Iacob R, Diculescu M. Diagnostic Delay in Romanian Patients with Inflammatory Bowel Disease: Risk Factors and Impact on the Disease Course and Need for Surgery. J Crohns Colitis 2016; 10:306-14. [PMID: 26589956 PMCID: PMC4957477 DOI: 10.1093/ecco-jcc/jjv215] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Accepted: 11/16/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND The epidemiology of inflammatory bowel disease [IBD] in Eastern Europe is poorly understood, particularly with regard to diagnostic delay. Here we investigated the factors leading to delayed diagnosis and the effect of the delay on several disease progression and outcome measures. METHODS A total of 1196 IBD cases [682 ulcerative colitis [UC], 478 Crohn's disease [CD], 36 indeterminate colitis] from the Romanian national registry IBDPROSPECT were reviewed. Standard clinical and demographic factors were evaluated as predictors of a long diagnostic delay in both CD and UC. Diagnostic delay was subsequently evaluated as a potential risk factor for bowel stenoses, bowel fistulas, perianal fistulas, perianal surgery, and intestinal surgery in CD patients. RESULTS The median diagnostic delay was significantly longer in CD [5 months] than in UC [1 month] patients [p < 0.001]. Compared with 5 months for UC patients, 75% of CD patients were diagnosed within 18 months of symptom onset. In CD patients, extra-ileal location was a protective factor (odds ratio [OR], 0.5; p = 0.03), whereas being an active smoker [OR, 2.09; p = 0.01] and symptom onset during summer [OR, 3.35; p < 0.001] were independent risk factors for a long diagnostic delay [> 18 months]. In UC patients, an age > 40 years was a protective factor [OR, 0.68; p = 0.04] for a long delay. Regarding outcomes, a long diagnostic delay in CD patients positively correlated with bowel stenoses [OR, 3.38; p < 0.01] and any IBD-related surgery [OR, 1.95; p = 0.03] and had a positive trend for intestinal fistulas [OR, 2.64; p = 0.08] and perianal fistulas [OR, 2.9; p = 0.07]. Disease duration since diagnosis positively correlated with bowel stenoses [OR, 1.04; p = 0.04], any IBD-related surgery [OR, 1.04; p = 0.02], and intestinal surgery [OR, 1.07; p < 0.01]. CONCLUSIONS A long diagnostic delay in IBD correlates with an increased frequency of bowel stenoses and need for IBD-related surgery.
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Affiliation(s)
- Roxana Zaharie
- University of Medicine and Pharmacy 'Iuliu Hatieganu', Regional Institute of Gastroenterology and Hepatology ' O. Fodor' Cluj-Napoca, Romania
| | - Alina Tantau
- University of Medicine and Pharmacy 'Iuliu Hatieganu', 4th Medical Clinic, Cluj-Napoca, Romania
| | - Florin Zaharie
- University of Medicine and Pharmacy 'Iuliu Hatieganu', Regional Institute of Gastroenterology and Hepatology ' O. Fodor' Cluj-Napoca, Romania
| | - Marcel Tantau
- University of Medicine and Pharmacy 'Iuliu Hatieganu', Regional Institute of Gastroenterology and Hepatology ' O. Fodor' Cluj-Napoca, Romania
| | - Liana Gheorghe
- Carol Davila University of Medicine and Pharmacy, Fundeni Clinical Institute, Digestive and Liver Disease, Bucuresti, Romania
| | - Cristian Gheorghe
- Carol Davila University of Medicine and Pharmacy, Fundeni Clinical Institute, Digestive and Liver Disease, Bucuresti, Romania
| | - Serban Gologan
- Carol Davila University of Medicine and Pharmacy, Elias University Hospital, Gastroenterology, Bucuresti, Romania
| | - Cristina Cijevschi
- University of Medicine and Pharmacy 'Gr. T. Popa', Gastroenterology and Hepatology Institute, Iasi, Romania
| | - Anca Trifan
- University of Medicine and Pharmacy 'Gr. T. Popa', Gastroenterology and Hepatology Institute, Iasi, Romania
| | - Daniela Dobru
- University of Medicine and Pharmacy, Municipal Hospital, Gastroenterology, Targu-Mures, Romania
| | - Adrian Goldis
- University of Medicine and Pharmacy 'Victor Babes', District Hospital, Gastroenterology, Timisoara, Romania
| | - Gabriel Constantinescu
- Carol Davila University of Medicine and Pharmacy, Floreasca Emergency Hospital, Gastroenterology Department, Bucuresti, Romania
| | - Razvan Iacob
- Carol Davila University of Medicine and Pharmacy, Fundeni Clinical Institute, Digestive and Liver Disease, Bucuresti, Romania
| | - Mircea Diculescu
- Carol Davila University of Medicine and Pharmacy, Fundeni Clinical Institute, Digestive and Liver Disease, Bucuresti, Romania
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Abstract
Little is known on the natural history of Crohn's disease (CD) before diagnosis. By the time the patient is diagnosed, the disease has often produced considerable damage to the intestinal mucosa and sometimes other organs. Such period before diagnosis might involve both a silent and a symptomatic phase. The silent phase, or preclinical CD, might last several years after the biological disease onset. Evidence is accumulating that the symptomatic phase might also go undiagnosed for months or years. In fact, for each established case of CD, there are probably several undiagnosed cases, a classic iceberg phenomenon of disease. Such status quo--lagging behind diagnostic standards for many other diseases--effectively hampers efforts to block disease evolution and the development of complications. This is no longer tenable because CD is a debilitating, severe, and costly affection, whose incidence is rapidly rising worldwide. Here, we will review what is currently known on preclinical and undiagnosed CD and what could be done to improve accuracy and timeliness of diagnosis.
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Wilson A, Teft WA, Morse BL, Choi YH, Woolsey S, DeGorter MK, Hegele RA, Tirona RG, Kim RB. Trimethylamine-N-oxide: A Novel Biomarker for the Identification of Inflammatory Bowel Disease. Dig Dis Sci 2015; 60:3620-30. [PMID: 26160437 DOI: 10.1007/s10620-015-3797-3] [Citation(s) in RCA: 70] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2015] [Accepted: 06/30/2015] [Indexed: 12/18/2022]
Abstract
BACKGROUND The gastrointestinal (GI) microbiome is recognized for potential clinical relevance in inflammatory bowel disease (IBD). Data suggest that there is a disease-dependent loss of microbial diversity in IBD. Trimethylamine-N-oxide (TMAO) is generated by GI anaerobes through the digestion of dietary phosphatidylcholine and carnitine in a microbial-mammalian co-metabolic pathway. IBD-related changes in the gut microbiome may result in disease-specific changes in TMAO plasma concentrations. AIM To determine whether TMAO plasma levels in IBD are altered compared to controls and whether they correlate with disease presence or activity. METHODS Liquid chromatography-tandem mass spectrometry was used to measure TMAO, choline, and carnitine plasma levels in 479 subjects (373 non-IBD controls, 106 IBD). Subjects were also genotyped for the flavin monooxygenase (FMO)3 variants, E158K and E308G. RESULTS Plasma TMAO levels were 2.27 µM lower in the IBD population compared to the control population (p = 0.0001). Lower TMAO levels were similarly seen in active ulcerative colitis (UC) (1.56 µM) versus inactive disease (3.40 µM) (p = 0.002). No difference was seen in active Crohn's disease (CD) versus inactive CD. No intergroup variation existed in plasma TMAO levels based on FMO3 genotype. Choline levels were higher in IBD, while carnitine levels were similar between the two groups, suggesting that lower TMAO levels in IBD were not due to dietary differences. CONCLUSIONS Decreased TMAO levels are seen in IBD compared to a non-IBD population. These data suggest that TMAO may have potential as a biomarker to support IBD diagnosis as well as to assess disease activity in UC.
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Affiliation(s)
- Aze Wilson
- Division of Clinical Pharmacology, Department of Medicine, Western University, 339 Windermere Road B9-130, London, ON, N6A 5A5, Canada
- Division of Gastroenterology, Department of Medicine, Western University, 339 Windermere Road, London, ON, N6A 5A5, Canada
- Department of Physiology and Pharmacology, Western University, Medical Sciences Building, Rm 216, London, ON, N6A 5C1, Canada
| | - Wendy A Teft
- Division of Clinical Pharmacology, Department of Medicine, Western University, 339 Windermere Road B9-130, London, ON, N6A 5A5, Canada
| | - Bridget L Morse
- Division of Clinical Pharmacology, Department of Medicine, Western University, 339 Windermere Road B9-130, London, ON, N6A 5A5, Canada
| | - Yun-Hee Choi
- Department of Epidemiology and Biostatistics, Western University, Kresge Building, Rm K201, London, ON, N6A 5C1, Canada
| | - Sarah Woolsey
- Department of Physiology and Pharmacology, Western University, Medical Sciences Building, Rm 216, London, ON, N6A 5C1, Canada
| | - Marianne K DeGorter
- Division of Clinical Pharmacology, Department of Medicine, Western University, 339 Windermere Road B9-130, London, ON, N6A 5A5, Canada
| | - Robert A Hegele
- Division of Endocrinology, Department of Medicine, Western University, 339 Windermere Road, London, ON, N6A 5A5, Canada
| | - Rommel G Tirona
- Division of Clinical Pharmacology, Department of Medicine, Western University, 339 Windermere Road B9-130, London, ON, N6A 5A5, Canada
- Department of Physiology and Pharmacology, Western University, Medical Sciences Building, Rm 216, London, ON, N6A 5C1, Canada
| | - Richard B Kim
- Division of Clinical Pharmacology, Department of Medicine, Western University, 339 Windermere Road B9-130, London, ON, N6A 5A5, Canada.
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Maconi G, Orlandini L, Asthana AK, Sciurti R, Furfaro F, Bezzio C, de Franchis R. The impact of symptoms, irritable bowel syndrome pattern and diagnostic investigations on the diagnostic delay of Crohn's disease: A prospective study. Dig Liver Dis 2015; 47:646-51. [PMID: 26004215 DOI: 10.1016/j.dld.2015.04.009] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2014] [Revised: 03/20/2015] [Accepted: 04/15/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND We investigated symptoms and tests performed prior to a formal diagnosis of Crohn's disease and the reasons for diagnostic delay. METHODS Consecutive patients recently diagnosed with Crohn's disease were enrolled between October 2012 and November 2013. Clinical data, symptoms including Rome III criteria at onset and at diagnosis, location and disease phenotype were recorded. Faecal calprotectin, radiological and endoscopic examinations performed prior to diagnosis were analysed. Diagnostic delay, stratified into tertiles and median time, was analysed using parametric and nonparametric tests. RESULTS 83 patients (49.4% males, median age 31 years) were enrolled. The median diagnostic delay was 8 (0-324) months. Twenty-six patients did not consult a general practitioner until diagnosis (31.3%), 18 presented to the emergency department (21.7%) and 8 directly to a gastroenterologist (9.6%). Diagnostic delay was not associated with specific symptoms. However, patients with bloating at presentation had a longer delay compared to those who did not (median, 6.1 vs. 16.8 months, respectively; p=0.016). Nineteen patients underwent incomplete ileocolonoscopies (22.9%) and 7 had no biopsies (8.4%), with a consequent diagnostic delay (median, 24 and 24 vs. 6 months, respectively; p=0.025 and p=0.008). CONCLUSION Diagnostic delay for Crohn's disease is significantly associated with incomplete ileocolonoscopies, but not with symptoms, except bloating at presentation.
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Affiliation(s)
- Giovanni Maconi
- Gastroenterology Unit, Department of Biomedical and Clinical Sciences, L. Sacco University Hospital, Milan, Italy.
| | - Laura Orlandini
- Gastroenterology Unit, Department of Biomedical and Clinical Sciences, L. Sacco University Hospital, Milan, Italy
| | - Anil K Asthana
- Department of Gastroenterology, The Alfred Hospital and Monash University, Melbourne, VIC, Australia
| | - Roberta Sciurti
- Gastroenterology Unit, Department of Biomedical and Clinical Sciences, L. Sacco University Hospital, Milan, Italy
| | - Federica Furfaro
- Gastroenterology Unit, Department of Biomedical and Clinical Sciences, L. Sacco University Hospital, Milan, Italy
| | - Cristina Bezzio
- Gastroenterology Unit, Department of Biomedical and Clinical Sciences, L. Sacco University Hospital, Milan, Italy
| | - Roberto de Franchis
- Gastroenterology Unit, Department of Biomedical and Clinical Sciences, L. Sacco University Hospital, Milan, Italy
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Ford AC, Moayyedi P, Bercik P, Morgan DG, Bolino C, Pintos-Sanchez MI, Reinisch W. Lack of utility of symptoms and signs at first presentation as predictors of inflammatory bowel disease in secondary care. Am J Gastroenterol 2015; 110:716-24. [PMID: 25916225 DOI: 10.1038/ajg.2015.117] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2014] [Accepted: 03/02/2015] [Indexed: 12/11/2022]
Abstract
OBJECTIVES There are few data concerning the utility of symptoms and signs at first presentation in predicting a diagnosis of ulcerative colitis (UC) or Crohn's disease (CD). We conducted a study to examine this issue in secondary care. METHODS We collected complete symptom, colonoscopy, and histology data prospectively from 1,981 consecutive adult patients with lower gastrointestinal symptoms at two hospitals in Hamilton, Ontario. Assessors were blinded to symptom status. The reference standard used to define the presence of UC or CD was according to accepted histological criteria. Patients without UC or CD served as controls. Sensitivity, specificity, and positive and negative likelihood ratios (LRs) were calculated for individual items from the clinical history, as well as combinations of these. RESULTS In identifying 302 patients with inflammatory bowel diseases (IBD), positive LRs for individual items ranged from 1.18 (incomplete emptying) to 2.30 (passage of stools more than four times per day at least most of the time) and negative LRs from 0.70 (bloody stools) to 0.96 (incomplete emptying). Combinations of items had a high specificity, but at the expense of sensitivity. Items that were independent predictors of IBD after logistic regression analysis were family history of IBD, younger age, passage of stools more than four times per day ≥75% of the time, urgency most of the time, and anemia. CONCLUSIONS Individual items from the clinical history are not helpful in predicting a diagnosis of UC or CD. However, this may be because some items lacked sufficient detail. Combinations of symptoms and computer models had a high specificity, but overall were only modestly useful diagnostically. Future studies should evaluate biological markers in combination with symptoms to improve accuracy.
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Affiliation(s)
- Alexander C Ford
- 1] Leeds Gastroenterology Institute, St James's University Hospital, Leeds, UK [2] Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, UK
| | - Paul Moayyedi
- Gastroenterology Division, Health Sciences Center, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Premysl Bercik
- Gastroenterology Division, Health Sciences Center, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - David G Morgan
- Gastroenterology Department, St Joseph's Healthcare, Hamilton, Ontario, Canada
| | - Carolina Bolino
- Gastroenterology Division, Health Sciences Center, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Maria I Pintos-Sanchez
- Gastroenterology Division, Health Sciences Center, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Walter Reinisch
- Gastroenterology Division, Health Sciences Center, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
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43
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Maconi G, Magro F. Comparing techniques to achieve high accuracy and low cost: how should we first diagnose Crohn's disease? J Comp Eff Res 2015; 4:75-8. [DOI: 10.2217/cer.15.2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Affiliation(s)
- Giovanni Maconi
- Gastroenterology Unit, Department of Biomedical & Clinical Sciences, L. Sacco University Hospital, Via G.B. Grassi, 74, 20157 Milan, Italy
| | - Ferdinando Magro
- Department of Pharmacology & Therapeutics Porto Medical School, Gastroenterology Department of Centro Hospitalar São João, Porto, Portugal
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Del Valle-Pinero AY, Sherwin LB, Anderson EM, Caudle RM, Henderson WA. Altered vasoactive intestinal peptides expression in irritable bowel syndrome patients and rats with trinitrobenzene sulfonic acid-induced colitis. World J Gastroenterol 2015; 21:155-163. [PMID: 25574088 PMCID: PMC4284331 DOI: 10.3748/wjg.v21.i1.155] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2014] [Revised: 10/29/2014] [Accepted: 11/19/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the vasoactive intestinal peptides (VIP) expression in irritable bowel syndrome (IBS) and trinitrobenzene sulfonic acid (TNBS) induced colitis.
METHODS: The VIP gene expression and protein plasma levels were measured in adult participants (45.8% male) who met Rome III criteria for IBS for longer than 6 mo and in a rat model of colitis as induced by TNBS. Plasma and colons were collected from naïve and inflamed rats. Markers assessing inflammation (i.e., weight changes and myeloperoxidase levels) were assessed on days 2, 7, 14 and 28 and compared to controls. Visceral hypersensitivity of the rats was assessed with colo-rectal distension and mechanical threshold testing on hind paws. IBS patients (n = 12) were age, gender, race, and BMI-matched with healthy controls (n = 12). Peripheral whole blood and plasma from fasting participants was collected and VIP plasma levels were assayed using a VIP peptide-enzyme immunoassay. Human gene expression of VIP was analyzed using a custom PCR array.
RESULTS: TNBS induced colitis in the rats was confirmed with weight loss (13.7 ± 3.2 g) and increased myeloperoxidase activity. Visceral hypersensitivity to colo-rectal distension was increased in TNBS treated rats up to 21 d and resolved by day 28. Somatic hypersensitivity was also increased up to 14 d post TNBS induction of colitis. The expression of an inflammatory marker myeloperoxidase was significantly elevated in the intracellular granules of neutrophils in rat models following TNBS treatment compared to naïve rats. This confirmed the induction of inflammation in rats following TNBS treatment. VIP plasma concentration was significantly increased in rats following TNBS treatment as compared to naïve animals (P < 0.05). Likewise, the VIP gene expression from peripheral whole blood was significantly upregulated by 2.91-fold in IBS patients when compared to controls (P < 0.00001; 95%CI). VIP plasma protein was not significantly different when compared with controls (P = 0.193).
CONCLUSION: Alterations in VIP expression may play a role in IBS. Therefore, a better understanding of the physiology of VIP could lead to new therapeutics.
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Card TR, Siffledeen J, Fleming KM. Are IBD patients more likely to have a prior diagnosis of irritable bowel syndrome? Report of a case-control study in the General Practice Research Database. United European Gastroenterol J 2014; 2:505-12. [PMID: 25452846 DOI: 10.1177/2050640614554217] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2014] [Accepted: 08/25/2014] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) patients are sometimes first diagnosed with irritable bowel syndrome (IBS), which may be construed as a misdiagnosis. OBJECTIVE The objective of this article is to determine if this occurs more than expected by chance. METHODS We conducted a case-control study nested in the General Practice Research Database. We selected incident cases of IBD and up to 10 matched controls for each. We assessed the proportions with IBS recorded prior to the IBD diagnosis and variation by age, sex, and calendar time. We compared proportions affected in fixed time periods and conducted conditional logistic regression to derive odds ratios. RESULTS The 20, 193 cases were three times as likely as controls to have a prior record of IBS. Fifteen per cent of IBD cases and 5% of controls had IBS coded before diagnosis with 11% having a code for IBS over one year before IBD (cf. 5% of controls) and 6% over five years earlier (cf. 3%). These figures roughly doubled if typical antispasmodic therapies were assumed to represent IBS diagnoses. CONCLUSION If excess IBS diagnoses represent misdiagnoses of IBD, our results suggest that about 10% of IBD patients are misdiagnosed and in 3% of cases this may persist for five or more years.
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Affiliation(s)
- Timothy R Card
- University of Nottingham, Division of Epidemiology and Public Health, Nottingham City Hospital, UK
| | - Jesse Siffledeen
- Translational Gastroenterology Unit, John Radcliffe Hospital, University of Oxford, UK
| | - Kate M Fleming
- University of Nottingham, Division of Epidemiology and Public Health, Nottingham City Hospital, UK
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46
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Maconi G, Bolzoni E, Giussani A, Friedman AB, Duca P. Accuracy and cost of diagnostic strategies for patients with suspected Crohn's disease. J Crohns Colitis 2014; 8:1684-92. [PMID: 25179579 DOI: 10.1016/j.crohns.2014.08.005] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2014] [Revised: 08/06/2014] [Accepted: 08/08/2014] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To evaluate accuracy and cost of non-invasive diagnostic strategies including magnetic resonance imaging, intestinal ultrasonography, ileocolonoscopy and video-capsule endoscopy in suspected Crohn's disease. METHODS A decision-analytic model was used to assess the costs in low (25%), intermediate (50%) or high (75%) pre-test probability of Crohn's disease. Based on the published accuracy of diagnostic modalities and Bayes' rule, we calculated post-test probability of Crohn's disease using different strategies, starting from ileocolonoscopy, ultrasonography or magnetic resonance. Each strategy was considered successful when post-test probability was >95% or <5%. RESULTS With low pre-test probability, only ileocolonoscopy as the first investigation could exclude or confirm Crohn's disease while a normal ultrasonography may exclude Crohn's disease. With high pre-test probability, ileocolonoscopy or ultrasonography as the first test may confirm Crohn's disease, but at least 3 negative tests are required to exclude Crohn's disease. The cost to diagnose one patient was cheapest utilising an ultrasonography-based strategy both in low (ultrasonography €1076; ileocolonoscopy €2005; magnetic resonance €4515) and high pre-test probability of Crohn's disease (ultrasonography €321; ileocolonoscopy €712; magnetic resonance €1412). CONCLUSION The accuracy and cost of these strategies depend on pre-test probability of Crohn's disease and vary according to the first test used. Ileocolonoscopy plus ultrasonography is the most accurate and less expensive initial diagnostic strategy.
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Affiliation(s)
- Giovanni Maconi
- Gastroenterology Unit, Department of Biomedical and Clinical Sciences, L. Sacco University Hospital, Milan, Italy.
| | - Enrico Bolzoni
- Department of Decision Sciences, Bocconi University, Milan, Italy
| | - Andrea Giussani
- Department of Decision Sciences, Bocconi University, Milan, Italy
| | - Antony B Friedman
- Department of Gastroenterology, The Alfred Hospital and Monash University, Melbourne, Victoria, Australia
| | - Piergiorgio Duca
- Medical Statistics and Biometry Unit, Department of Biomedical and Clinical Sciences, L. Sacco University Hospital, Milan, Italy
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Targownik LE, Nugent Z, Singh H, Bugden S, Bernstein CN. The prevalence and predictors of opioid use in inflammatory bowel disease: a population-based analysis. Am J Gastroenterol 2014; 109:1613-20. [PMID: 25178702 DOI: 10.1038/ajg.2014.230] [Citation(s) in RCA: 101] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2013] [Accepted: 06/17/2014] [Indexed: 02/06/2023]
Abstract
OBJECTIVES Opioids are commonly used in the treatment of pain and associated symptoms of inflammatory bowel disease (IBD). The continuous use of opioids has been associated with adverse outcomes, including death. The prevalence and the risk factors for opioid use in IBD are poorly characterized. METHODS We used the population-based Manitoba IBD Epidemiology Database to identify all individuals in Manitoba with IBD who were prescribed opioids both before and following diagnosis. We determined the point prevalence of any opioid use, as well as the risk of becoming a heavy opioid user (defined as continuous use for 30 days at a dose exceeding 50 mg morphine/day or equivalent). Logistic regression and Cox proportional hazards models were generated to assess whether IBD was an independent risk factor for opioid use, the risk factors for opioid use in individuals with IBD, and to determine whether opioid use was associated with excess mortality in IBD. RESULTS Within 10 years of diagnosis, 5% of individuals with IBD had become heavy opioid users. Moderate use of opioids before diagnosis was strongly predictive of future heavy use. Individuals with IBD were significantly more likely to become heavy opioid users than their matched controls (odds ratio (OR) 2.91, 95% confidence interval (CI) 2.19-3.85). Heavy opioid use was strongly associated with mortality (OR 2.82, 95% CI 1.58-5.02). CONCLUSIONS IBD is an independent risk factor for becoming a heavy opioid user, and heavy opioid use is associated with excess mortality in IBD patients. Clinicians should recognize risk factors for future heavy opioid use among their patients with IBD.
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Affiliation(s)
- Laura E Targownik
- 1] Section of Gastroenterology, Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada [2] University of Manitoba IBD Clinical and Research Centre, Winnipeg, Manitoba, Canada
| | - Zoann Nugent
- 1] Section of Gastroenterology, Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada [2] CancerCare Manitoba, Winnipeg, Manitoba, Canada
| | - Harminder Singh
- 1] Section of Gastroenterology, Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada [2] University of Manitoba IBD Clinical and Research Centre, Winnipeg, Manitoba, Canada
| | - Shawn Bugden
- Faculty of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Charles N Bernstein
- 1] Section of Gastroenterology, Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada [2] University of Manitoba IBD Clinical and Research Centre, Winnipeg, Manitoba, Canada
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48
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Abstract
The gastrointestinal tract is innervated by several distinct populations of neurons, whose cell bodies either reside within (intrinsic) or outside (extrinsic) the gastrointestinal wall. Normally, most individuals are unaware of the continuous, complicated functions of these neurons. However, for patients with gastrointestinal disorders, such as IBD and IBS, altered gastrointestinal motility, discomfort and pain are common, debilitating symptoms. Although bouts of intestinal inflammation underlie the symptoms associated with IBD, increasing preclinical and clinical evidence indicates that infection and inflammation are also key risk factors for the development of other gastrointestinal disorders. Notably, a strong correlation exists between prior exposure to gut infection and symptom occurrence in IBS. This Review discusses the evidence for neuroplasticity (structural, synaptic or intrinsic changes that alter neuronal function) affecting gastrointestinal function. Such changes are evident during inflammation and, in many cases, long after healing of the damaged tissues, when the nervous system fails to reset back to normal. Neuroplasticity within distinct populations of neurons has a fundamental role in the aberrant motility, secretion and sensation associated with common clinical gastrointestinal disorders. To find appropriate therapeutic treatments for these disorders, the extent and time course of neuroplasticity must be fully appreciated.
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Ahn JY, Lee KH, Choi CH, Kim JW, Lee HW, Kim JW, Kim MK, Kwon GY, Han S, Kim SE, Kim SM, Chang SK. Colonic mucosal immune activity in irritable bowel syndrome: comparison with healthy controls and patients with ulcerative colitis. Dig Dis Sci 2014; 59:1001-11. [PMID: 24282051 DOI: 10.1007/s10620-013-2930-4] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2013] [Accepted: 10/18/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM Mucosal immune activity may participate in irritable bowel syndrome (IBS) pathogenesis. Mast- and T cell numbers from patients with IBS or ulcerative colitis (UC) and healthy controls were determined. METHODS Between November 2007 and May 2012, patients with diarrhea-predominant IBS (D-IBS, n = 83), 49 patients with UC, and 25 healthy controls were recruited. Of the UC group, 28 were in remission and 21 had mildly active UC. Biopsies from each colon segment were subjected to immunohistochemical analysis. The mast cells, intraepithelial lymphocytes (IELs), and lamina proprial lymphocytes (LPLs) were counted. RESULTS Compared to the healthy controls, the patients with D-IBS, UC in remission, and mildly active UC had significantly higher mean colorectal mucosal mast-cell, IEL, and LPL counts. Comparison with the colon segments (ascending, transverse, descending, and sigmoid segments) that had once been involved in UC (in the patients with remission) revealed that the D-IBS colons had similar immune-cell counts. However, they had significantly fewer immune cells than the colon segments that presently showed involvement in the patients with mildly-activated UC. The mast-cell and IEL counts were similar in the D-IBS rectums and once-involved UC rectums but significantly higher in the presently-involved UC rectums. However, both the once-involved and presently-involved UC rectums had significantly higher LPL counts than the D-IBS rectums. CONCLUSIONS Patients with D-IBS had significantly higher colonic mucosal immune-cell counts than healthy controls but had similar counts to patients with UC in remission. The symptoms in both conditions may originate from low-grade inflammation in the colonic mucosa.
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Affiliation(s)
- Ji Yong Ahn
- Department of Internal Medicine, Chung-Ang University College of Medicine, 221 Heukseok-dong, Dongjak-gu, Seoul, 156-756, Republic of Korea,
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50
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Stein AC, Cohen RD. Dietary fiber intake and Crohn's disease. Gastroenterology 2014; 146:1133. [PMID: 24576734 DOI: 10.1053/j.gastro.2013.12.044] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2013] [Accepted: 12/23/2013] [Indexed: 12/12/2022]
Affiliation(s)
- Adam C Stein
- Advanced Clinical Nutrition Fellow, Section of Gastroenterology, Hepatology, and Nutrition, The University of Chicago Medicine, Chicago, Illinois
| | - Russell D Cohen
- Department of Medicine, Pritzker School of Medicine and Inflammatory Bowel Disease Center, The University of Chicago Medicine, Chicago, Illinois
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