|
1
|
Ng AP, Porter G, Vadlakonda A, Chervu N, Khan A, Benharash P, Lee H. Outcomes of surgery for inflammatory bowel disease among patients with psychiatric disorders. J Gastrointest Surg 2024; 28:2024-2030. [PMID: 39341587 DOI: 10.1016/j.gassur.2024.09.025] [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: 07/06/2024] [Revised: 09/01/2024] [Accepted: 09/23/2024] [Indexed: 10/01/2024]
Abstract
BACKGROUND Psychiatric disorders (PDs) are common among patients with inflammatory bowel disease (IBD). Brain-gut dysfunction and psychotropic medications may have adverse effects on postoperative outcomes in patients with IBD. This study aimed to evaluate the association between PD and outcomes after surgery for IBD. METHODS This was a retrospective study of adult patients with IBD who underwent small bowel, colon, or rectal resection in the 2016 to 2021 Nationwide Readmissions Database. PDs, including psychotic, mood, anxiety, eating, sleep, personality, and childhood-onset behavioral disorders, were identified. Records about colorectal cancer were excluded. Multivariate regressions were used to examine the association of PD with outcomes. RESULTS Of 81,955 patients included in the study, 21,800 (26.6%) had PDs. On risk adjustment, PD was associated with significantly increased postoperative ileus (adjusted odds ratio [AOR], 1.11; 95% CI, 1.03-1.19), length of stay (β, +1.4 days; 95% CI, 1.1-1.7), and costs (β, +$2100; 95% CI, $1200-$3100) compared with no PD. In addition, patients with PDs experienced increased odds of nonhome discharge (AOR, 1.23; 95% CI, 1.12-1.34) and 30-day readmission (AOR, 1.32; 95% CI, 1.22-1.43). Over the study period, the prevalence of PDs significantly increased from 24.3% to 28.5% (P < .001), along with an increase in the rates of ileus among patients with PDs (8.1%-15.8%; P < .001). CONCLUSION PD is associated with a significantly greater burden of adverse clinical and financial outcomes after IBD operations. Given the growing prevalence of mental health conditions among patients with IBD, further efforts to optimize preoperative psychiatric care may enhance the quality of colorectal surgery.
Collapse
Affiliation(s)
- Ayesha P Ng
- Cardiovascular Outcomes Research Laboratories, David Geffen School of Medicine at the University of California, Los Angeles, CA, United States
| | - Giselle Porter
- Cardiovascular Outcomes Research Laboratories, David Geffen School of Medicine at the University of California, Los Angeles, CA, United States
| | - Amulya Vadlakonda
- Cardiovascular Outcomes Research Laboratories, David Geffen School of Medicine at the University of California, Los Angeles, CA, United States
| | - Nikhil Chervu
- Cardiovascular Outcomes Research Laboratories, David Geffen School of Medicine at the University of California, Los Angeles, CA, United States; Department of Surgery, David Geffen School of Medicine at the University of California, Los Angeles, CA, United States
| | - Aimal Khan
- Division of Colon and Rectal Surgery, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Peyman Benharash
- Cardiovascular Outcomes Research Laboratories, David Geffen School of Medicine at the University of California, Los Angeles, CA, United States; Department of Surgery, David Geffen School of Medicine at the University of California, Los Angeles, CA, United States
| | - Hanjoo Lee
- Division of Colon and Rectal Surgery, Department of Surgery, Harbor-University of California Los Angeles Medical Center, Torrance, CA, United States.
| |
Collapse
|
|
2
|
Sturm A, Atreya R, Bettenworth D, Bokemeyer B, Dignass A, Ehehalt R, Germer CT, Grunert PC, Helwig U, Horisberger K, Herrlinger K, Kienle P, Kucharzik T, Langhorst J, Maaser C, Ockenga J, Ott C, Siegmund B, Zeißig S, Stallmach A. Aktualisierte S3-Leitlinie „Diagnostik und Therapie des Morbus Crohn“ der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) (Version 4.1) – living guideline. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1229-1318. [PMID: 39111333 DOI: 10.1055/a-2309-6123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/02/2024]
Affiliation(s)
- Andreas Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - Raja Atreya
- Medizinische Klinik 1, Universitätsklinikum Erlangen, Erlangen, Deutschland
| | | | - Bernd Bokemeyer
- Gastroenterologische Gemeinschaftspraxis Minden, Minden, Deutschland
| | - Axel Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt am Main, Deutschland
| | | | | | - P C Grunert
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Deutschland
| | - Ulf Helwig
- Internistische Praxengemeinschaft, Oldenburg, Deutschland
| | - Karoline Horisberger
- Universitätsmedizin Johannes Gutenberg, Universität Klinik f. Allgemein-,Visceral- und Transplantationschirurgie, Mainz, Deutschland
| | | | - Peter Kienle
- Allgemein- und Viszeralchirurgie, Theresienkrankenhaus und Sankt Hedwig-Klinik GmbH, Mannheim, Deutschland
| | - Torsten Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Klinikum Lüneburg, Lüneburg, Deutschland
| | - Jost Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Klinikum am Bruderwald, Bamberg, Deutschland
| | - Christian Maaser
- Gastroenterologie, Ambulanzzentrum Lüneburg, Lüneburg, Deutschland
| | - Johann Ockenga
- Medizinische Klinik II, Klinikum Bremen Mitte - Gesundheit Nord, Bremen, Deutschland
| | - Claudia Ott
- Gastroenterologie Facharztzentrum, Regensburg, Deutschland
| | - Britta Siegmund
- Medizinische Klinik I, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Deutschland
| | - Sebastian Zeißig
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Deutschland
| | - Andreas Stallmach
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Deutschland
| |
Collapse
|
|
3
|
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.
Collapse
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.)
| |
Collapse
|
|
4
|
Maltz RM, Marte-Ortiz P, McClinchie MG, Hilt ME, Bailey MT. T Cell-Induced Colitis Is Exacerbated by Prolonged Stress: A Comparison in Male and Female Mice. Biomedicines 2024; 12:214. [PMID: 38255320 PMCID: PMC10813177 DOI: 10.3390/biomedicines12010214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 01/09/2024] [Accepted: 01/12/2024] [Indexed: 01/24/2024] Open
Abstract
Psychological stress exposure is well recognized to exacerbate inflammatory bowel disease (IBD) but the mechanisms involved remain poorly understood. In this study, chronic T cell-mediated colitis was induced by adoptively transferring CD4+CD45RBhigh splenic T cells from C57BL/6 WT donor mice into Rag1tm1Mom mice. Two weeks after T cell transfer, mice were exposed to a prolonged restraint stressor (RST) for 8 h per day for 6 consecutive days. The colitis phenotype was assessed via histopathology and semi-quantitative rt-PCR at humane endpoints or 10 weeks post-T-cell transfer. Mice that received the T cell transplant developed chronic colitis marked by increases in colonic histopathology and inflammatory cytokines. Colonic histopathology was greater in males than females regardless of RST exposure but RST exposure increased histopathology scores in females such that they reached scores observed in the males. This pattern was consistent with cytokine gene expression and protein levels in the colon (especially for IFN-γ, IL-17A, and TNF-α). Serum cytokine levels were not strongly affected by exposure to the stressor. Using a murine model of chronic T cell-mediated colitis, this study demonstrates that biological sex strongly influences colonic inflammation and exposure to chronic stress has a more pronounced effect in females than in males.
Collapse
Affiliation(s)
- Ross M. Maltz
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Nationwide Children’s Hospital, Columbus, OH 43205, USA
- Department of Pediatrics, The Ohio State Wexner Medical Center, Columbus, OH 43210, USA
- The Center for Microbial Pathogenesis, The Research Institute, Nationwide Children’s Hospital, Columbus, OH 43205, USA
- Oral and Gastrointestinal Microbiology Research Affinity Group, Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH 43205, USA
| | - Pedro Marte-Ortiz
- The Center for Microbial Pathogenesis, The Research Institute, Nationwide Children’s Hospital, Columbus, OH 43205, USA
| | - Madeline G. McClinchie
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Nationwide Children’s Hospital, Columbus, OH 43205, USA
| | - Miranda E. Hilt
- The Center for Microbial Pathogenesis, The Research Institute, Nationwide Children’s Hospital, Columbus, OH 43205, USA
- Biomedical Sciences Graduate Program, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA
| | - Michael T. Bailey
- The Center for Microbial Pathogenesis, The Research Institute, Nationwide Children’s Hospital, Columbus, OH 43205, USA
- Oral and Gastrointestinal Microbiology Research Affinity Group, Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH 43205, USA
| |
Collapse
|
|
5
|
Glynn H, Knowles SR. A Phenomenological Investigation of Trauma in 18 Adults Living With Inflammatory Bowel Disease. Clin Nurs Res 2023; 32:159-170. [PMID: 35156407 DOI: 10.1177/10547738221075649] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
While trauma is recognized as being common in Inflammatory Bowel Disease (IBD) cohorts, limited research has explored how trauma impacts the lived experience of IBD. The aim of this study was to develop an understanding of how trauma impacts the experience of living with IBD and its subsequent management. An interpretative phenomenological analysis with thematic analysis was conducted. Eighteen adults with IBD participated in this qualitative research study. Key themes identified included: (1) Trauma was associated with the journey of IBD; (2) the impact of IBD and trauma, and (3) coping strategies. Pre-existing non-IBD trauma was prevalent, with several participants reporting links between traumatic events and their IBD diagnosis. Experiences of IBD trauma were described by participants across all stages of their illness journey. The study can assist healthcare professionals to better understand the experience of living with IBD and trauma and the factors that can contribute to traumatic responses.
Collapse
Affiliation(s)
- Heidi Glynn
- Swinburne University of Technology, Melbourne, Australia
| | - Simon R Knowles
- Swinburne University of Technology, Melbourne, Australia.,St Vincent's Hospital, Melbourne, Australia.,Department of Medicine, The University of Melbourne, Australia
| |
Collapse
|
|
6
|
Heisler C, Rohatinsky N, Mirza RM, Kits O, Zelinsky S, Veldhuyzen van Zanten S, Nguyen G, McCurdy J, MacMillan M, Lakatos PL, Targownik L, Fowler S, Rioux K, Jones J. Patient-Centered Access to IBD Care: A Qualitative Study. CROHN'S & COLITIS 360 2023; 5:otac045. [PMID: 36777367 PMCID: PMC9825304 DOI: 10.1093/crocol/otac045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND Canada has the highest global age-adjusted incidence and prevalence rates of inflammatory bowel disease (IBD). Due to IBD patient volumes and limited resources, challenges to timely access to specialty care have emerged. To address this gap, the aim of this paper was to understand the experiences and perspectives of persons living with IBD with a focus on accessing health care. METHODS Using a qualitative descriptive approach, patients diagnosed with IBD (≥18 years of age) were purposively sampled from rural and urban gastroenterology clinics and communities across Canada. Co-facilitated by a researcher and patient research partner, 14 focus groups were recorded, transcribed, and coded for themes. Thematic analysis was used to ascertain the congruence or discordance of IBD specialty care access experiences. RESULTS A total of 63 individuals participated in the study. The majority of participants were female (41/63, 65%) and from urban/suburban regions (33/63, 52%), with a mean age of 48.39 (range 16-77 years). The analysis generated three main themes: (1) need for patient to be partner, (2) adapting IBD care access to individual context, and (3) patient-defined care priorities should guide access to IBD care. CONCLUSIONS The complexity of specialty care access for IBD patients cannot be underestimated. It is vital to possess a robust understanding of healthcare system structures, processes, and the impact of these factors on accessing care. Using a patient-centered exploration of barriers and facilitators, IBD specialty care access in Canada can be better understood and improved on provincial and national levels.
Collapse
Affiliation(s)
- Courtney Heisler
- QEII Health Sciences Centre, Division of Digestive Care & Endoscopy, Halifax, Canada
| | - Noelle Rohatinsky
- QEII Health Sciences Centre, Division of Digestive Care & Endoscopy, Halifax, Canada
| | - Raza M Mirza
- University of Saskatchewan, College of Nursing, Saskatoon, Canada
| | - Olga Kits
- University of Toronto, Institute for Life Course and Aging, Toronto, Canada
| | - Sandra Zelinsky
- Dalhousie University, Research Methods Unit, Halifax, Canada
| | | | - Geoffrey Nguyen
- University of Alberta, Faculty of Medicine and Dentistry, Edmonton, Canada
| | | | | | | | - Laura Targownik
- University of Alberta, Faculty of Medicine and Dentistry, Edmonton, Canada
| | | | - Kevin Rioux
- University of Saskatchewan, Saskatoon, Canada
| | - Jennifer Jones
- University of Ottawa, Ottawa, Canada
- University of British Columbia, Vancouver, Canada
| |
Collapse
|
|
7
|
Black J, Sweeney L, Yuan Y, Singh H, Norton C, Czuber‐Dochan W. Systematic review: the role of psychological stress in inflammatory bowel disease. Aliment Pharmacol Ther 2022; 56:1235-1249. [PMID: 36082403 PMCID: PMC9825851 DOI: 10.1111/apt.17202] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Revised: 02/27/2022] [Accepted: 08/21/2022] [Indexed: 01/30/2023]
Abstract
BACKGROUND Psychological stress is a possible factor in the disease course and poor psychosocial outcomes in inflammatory bowel disease (IBD). Understanding the exact relationship between stress and health has been hampered by methodological issues and how stress has been defined and measured. AIMS To explore the association between stress and disease outcomes, investigate the impact of stress on psychosocial outcomes, and evaluate the efficacy of interventions in reducing stress for people with IBD METHODS: We performed a systematic review, searching Medline, CINAHL, Embase and PsycInfo databases on 21 January 2021. We included prospective studies that recruited people with IBD who were aged 16 or over and that measured psychological stress or distress. Analyses included Critical Appraisal Skills Programme quality assessments of included studies and narrative analyses against each research question. RESULTS We reviewed 38 studies with 4757 people with IBD, and included 23 observational and 15 interventional studies using 36 different instruments to measure stress. Perceived stress was the most frequently studied concept and preceded IBD exacerbation. Only three studies examined the relationship between stress and psychosocial factors. Cognitive behavioural interventions may reduce stress and other interventions with disease-specific stress, but more studies are needed where groups have comparable baseline characteristics and potential harms are considered alongside benefits. CONCLUSION Psychological stress appears to precede IBD exacerbation, although what role it plays in psychosocial outcomes and how it is best managed is unclear. Further research needs to examine the differential effects of stress on disease subtypes and IBD in flare and remission.
Collapse
Affiliation(s)
- Jacqueline Black
- King's College LondonFlorence Nightingale Faculty of Nursing, Midwifery, and Palliative CareJames Clerk Maxwell BuildingLondonUK
| | - Louise Sweeney
- King's College LondonFlorence Nightingale Faculty of Nursing, Midwifery, and Palliative CareJames Clerk Maxwell BuildingLondonUK,King's College LondonInstitute of Psychiatry, Psychology & NeuroscienceLondonUK
| | - Yuhan Yuan
- King's College LondonFlorence Nightingale Faculty of Nursing, Midwifery, and Palliative CareJames Clerk Maxwell BuildingLondonUK
| | | | - Christine Norton
- King's College LondonFlorence Nightingale Faculty of Nursing, Midwifery, and Palliative CareJames Clerk Maxwell BuildingLondonUK
| | - Wladyslawa Czuber‐Dochan
- King's College LondonFlorence Nightingale Faculty of Nursing, Midwifery, and Palliative CareJames Clerk Maxwell BuildingLondonUK
| |
Collapse
|
|
8
|
Glynn H, Mikocka-Walus A, Knowles SR. Editorial: Hospitalization Experiences and Post-traumatic Stress in Inflammatory Bowel Disease: Opportunities for Change. Inflamm Bowel Dis 2022; 29:839-841. [PMID: 35894682 DOI: 10.1093/ibd/izac166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2022] [Indexed: 12/09/2022]
Affiliation(s)
- Heidi Glynn
- Department of Psychology, Swinburne University of Technology, Melbourne, VIC, Australia
| | | | - Simon R Knowles
- Department of Psychology, Swinburne University of Technology, Melbourne, VIC, Australia
| |
Collapse
|
|
9
|
Oddsson SJ, Gunnarsdottir T, Johannsdottir LG, Amundadottir ML, Frimannsdottir A, Molander P, Ylanne AK, Islind AS, Oskarsdottir M, Thorgeirsson T. A new Digital Health Program for Patients with Inflammatory Bowel Disease: Preliminary Program Evaluation (Preprint). JMIR Form Res 2022; 7:e39331. [PMID: 37115598 PMCID: PMC10182451 DOI: 10.2196/39331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Revised: 02/27/2023] [Accepted: 02/28/2023] [Indexed: 03/04/2023] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) causes chronic inflammation of the gastrointestinal tract. IBD is characterized by an unpredictable disease course that varies greatly between individuals and alternates between the periods of relapse and remission. A low energy level (fatigue) is a common symptom, whereas stress and reduced sleep quality may be the triggering factors. Therapeutic guidelines call for effective disease assessment, early intervention, and personalized care using a treat-to-target approach, which may be difficult to achieve through typical time- and resource-constrained standard care. Providing patients with a digital health program that incorporates helpful self-management features and patient support to complement standard care may be optimal for improving the disease course. OBJECTIVE This study aimed to perform a preliminary program evaluation, analyzing engagement and preliminary effectiveness and the effect on participants' energy levels (fatigue), stress, and sleep quality, of a newly developed 16-week digital health program (SK-311 and SK-321) for patients with IBD. METHODS Adults with IBD were recruited to participate in a real-world, live, digital health program via Finnish IBD patient association websites and social media. No inclusion or exclusion criteria were applied for this study. Baseline characteristics were entered by the participants upon sign-up. Platform engagement was measured by tracking the participants' event logs. The outcome measures of stress, energy levels (fatigue), and quality of sleep were reported by participants through the platform. RESULTS Of the 444 adults who registered for the digital health program, 205 (46.2%) were included in the intention-to-treat sample. The intention-to-treat participants logged events on average 41 times per week (5.9 times per day) during the weeks in which they were active on the digital platform. More women than men participated in the intervention (126/205, 88.7%). The mean age of the participants was 40.3 (SD 11.5) years, and their mean BMI was 27.9 (SD 6.0) kg/m2. In total, 80 people provided the required outcome measures during weeks 12 to 16 (completers). Treatment completion was strongly predicted by the number of active days in week 1. Analysis of the completers (80/205, 39%) showed significant improvements for stress (t79=4.57; P<.001; percentage change=-23.26%) and energy levels (t79=-2.44; P=.017; percentage change=9.48%); however, no significant improvements were observed for quality of sleep (t79=-1.32; P=.19). CONCLUSIONS These results support the feasibility of a digital health program for patients with IBD (SK-311 and SK-321) and suggest that treatment completion might have a substantial positive effect on patient-reported stress and energy levels in a real-world setting. These findings are promising and provide initial support for using the Sidekick Health digital health program to supplement standard care for patients with IBD.
Collapse
Affiliation(s)
| | | | | | | | | | - Pauliina Molander
- Abdominal Center, Gastroenterology, Helsinki University Hospital, Helsinki, Finland
- University of Helsinki, Helsinki, Finland
| | | | | | | | | |
Collapse
|
|
10
|
Su S, Marrie RA, Bernstein CN. Factors Associated With Social Participation in Persons Living With Inflammatory Bowel Disease. J Can Assoc Gastroenterol 2022; 5:59-67. [PMID: 35368323 PMCID: PMC8972209 DOI: 10.1093/jcag/gwab022] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Accepted: 06/29/2021] [Indexed: 12/25/2022] Open
Abstract
Background Inflammatory bowel disease (IBD) including Crohn’s disease (CD) and ulcerative colitis (UC) imposes a significant burden on health-related quality of life, particularly in social domains. We sought to investigate the factors that limit social participation in patients with IBD. Methods We assessed a cohort of 239 Manitobans with IBD. We collected sociodemographic information, medical comorbidities, disease phenotype, symptom activity and psychiatric comorbidity (using the Structured Clinical Interview for DSM-IV). Participants completed the eight-item Ability to Participate in Social Roles and Activities (APSRA) questionnaire, which assesses participation restriction, including problems experienced in social interaction, employment, transportation, community, social and civic life. Results Poorer social participation scores were associated with earning less than $50,000 CAD income annually (P < 0.001), actively smoking (P = 0.006), higher symptom scores (P < 0.001 for CD, P = 0.004 for UC), and having an increasing number of chronic medical conditions (R = −0.30). History of depression (P < 0.001) and anxiety (P = 0.001) and having active depression (P < 0.001) and anxiety (P = 0.001) all predicted poor social participation scores. IBD phenotype or disease duration was not predictive. Based on multivariable linear regression analysis, significant predictors of variability in social participation were medical comorbidity, psychiatric comorbidity, psychiatric symptoms and IBD-related symptoms. Conclusions The factors that predict social participation by IBD patients include income, smoking, medical comorbidities, IBD symptom burden, and psychiatric comorbidities. Multivariable linear regression suggests that the most relevant factors are medical comorbidity, psychiatric comorbidity, psychiatric symptoms and IBD symptoms.
Collapse
Affiliation(s)
- Samuel Su
- Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Ruth Ann Marrie
- Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Charles N Bernstein
- Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
| |
Collapse
|
|
11
|
Nass BYS, Dibbets P, Markus CR. Impact of the COVID‐19 pandemic on inflammatory bowel disease: The role of emotional stress and social isolation. Stress Health 2022; 38:222-233. [PMID: 34273129 PMCID: PMC8420478 DOI: 10.1002/smi.3080] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 07/01/2021] [Accepted: 07/06/2021] [Indexed: 12/17/2022]
Abstract
Inflammatory bowel disease (IBD) is a chronic health condition exacerbated by negative emotional stress experiences. In the current study, we examined whether the outbreak of the COVID-19 pandemic coincided with an increase in stress experiences and accordingly an aggravation of disease activity in IBD patients. Sixty-three IBD patients (30 Crohn's disease or CD, 33 ulcerative colitis) completed an online survey during the COVID-19-related lockdown, assessing clinical disease activity, disease-related quality of life, presence of functional gastrointestinal symptoms, social isolation and stress experiences. Scores were then compared to pre-lockdown baseline screening. The pandemic yielded a significant baseline-to-lockdown increase in emotional stress and social isolation. Stress increments, particularly those occasioned by interpersonal tension and excessive interpersonal proximity, were associated with a worsening of functional gastrointestinal symptoms. Exacerbations of loneliness coincided with an escalation of CD activity, functional gastrointestinal symptoms and a decline in subjective health. Lastly, COVID-19 anxiety was significantly related to CD symptom severity and social dysfunction. The findings show that shifts in IBD expression are closely linked to changes in emotional stress experiences and interpersonal relatedness. As such, they contribute to a better understanding of inter-individual differences in IBD progression and provide leads for therapeutic interventions.
Collapse
Affiliation(s)
- Boukje Yentl Sundari Nass
- Department of Neuropsychology and PsychopharmacologyFaculty of Psychology and NeuroscienceMaastricht UniversityMaastrichtThe Netherlands,Dr. Rath Health FoundationHeerlenThe Netherlands
| | - Pauline Dibbets
- Clinical Psychological ScienceMaastricht UniversityMaastrichtThe Netherlands
| | - C. Rob Markus
- Department of Neuropsychology and PsychopharmacologyFaculty of Psychology and NeuroscienceMaastricht UniversityMaastrichtThe Netherlands
| |
Collapse
|
|
12
|
Sturm A, Atreya R, Bettenworth D, Bokemeyer B, Dignaß A, Ehehalt R, Germer C, Grunert PC, Helwig U, Herrlinger K, Kienle P, Kreis ME, Kucharzik T, Langhorst J, Maaser C, Ockenga J, Ott C, Siegmund B, Zeißig S, Stallmach A. Aktualisierte S3-Leitlinie „Diagnostik und Therapie des Morbus Crohn“ der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – August 2021 – AWMF-Registernummer: 021-004. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:332-418. [PMID: 35263784 DOI: 10.1055/a-1713-3941] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Andreas Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - Raja Atreya
- Medizinische Klinik 1, Universitätsklinikum Erlangen, Deutschland
| | | | - Bernd Bokemeyer
- Gastroenterologische Gemeinschaftspraxis Minden, Deutschland
| | - Axel Dignaß
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt am Main, Deutschland
| | | | - Christoph Germer
- Chirurgische Klinik I, Universitätsklinikum Würzburg, Deutschland
| | - Philip C Grunert
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Deutschland
| | - Ulf Helwig
- Internistische Praxengemeinschaft, Oldenburg, Deutschland
| | | | - Peter Kienle
- Allgemein- und Viszeralchirurgie, Theresienkrankenhaus und Sankt Hedwig-Klinik GmbH, Mannheim, Deutschland
| | - Martin E Kreis
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Charité Campus Benjamin Franklin - Universitätsmedizin Berlin, Deutschland
| | - Torsten Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Klinikum Lüneburg, Deutschland
| | - Jost Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Klinikum am Bruderwald, Bamberg, Deutschland
| | | | - Johann Ockenga
- Medizinische Klinik II, Klinikum Bremen Mitte - Gesundheit Nord, Bremen, Deutschland
| | - Claudia Ott
- Gastroenterologie Facharztzentrum, Regensburg, Deutschland
| | - Britta Siegmund
- Medizinische Klinik I, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Deutschland
| | - Sebastian Zeißig
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Deutschland
| | - Andreas Stallmach
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Deutschland
| | | |
Collapse
|
|
13
|
Maltz RM, Marte-Ortiz P, Rajasekera TA, Loman BR, Gur TL, Bailey MT. Stressor-Induced Increases in Circulating, but Not Colonic, Cytokines Are Related to Anxiety-like Behavior and Hippocampal Inflammation in a Murine Colitis Model. Int J Mol Sci 2022; 23:ijms23042000. [PMID: 35216112 PMCID: PMC8877477 DOI: 10.3390/ijms23042000] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 01/31/2022] [Accepted: 02/08/2022] [Indexed: 01/27/2023] Open
Abstract
Stressor exposure increases colonic inflammation. Because inflammation leads to anxiety-like behavior, we tested whether stressor exposure in mice recovering from dextran-sulfate-sodium (DSS)-induced colitis enhances anxiety-like behavior. Mice received 2% DSS for five consecutive days prior to being exposed to a social-disruption (SDR) stressor (or being left undisturbed). After stressor exposure, their behavior was tested and colitis was assessed via histopathology and via inflammatory-cytokine measurement in the serum and colon. Cytokine and chemokine mRNA levels in the colon, mesenteric lymph nodes (MLNs), hippocampus, and amygdala were measured with RT-PCR. SDR increased anxiety-like behaviors, which correlated with serum and hippocampal IL-17A. The stressor also reduced IL-1β, CCL2, and iNOS in the colonic tissue, but increased iNOS, IFNγ, IL-17A, and TNFα in the MLNs. A network analysis indicated that reductions in colonic iNOS were related to elevated MLN iNOS and IFNγ. These inflammatory markers were related to serum and hippocampal IL-17A and associated with anxiety-like behavior. Our data suggest that iNOS may protect against extra-colonic inflammation, and when suppressed during stress it is associated with elevated MLN IFNγ, which may coordinate gut-to-brain inflammation. Our data point to hippocampal IL-17A as a key correlate of anxiety-like behavior.
Collapse
Affiliation(s)
- Ross M. Maltz
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Nationwide Children’s Hospital, Columbus, OH 43205, USA
- Department of Pediatrics, The Ohio State Wexner Medical Center, Columbus, OH 43210, USA;
- The Center for Microbial Pathogenesis, The Research Institute, Nationwide Children’s Hospital, Columbus, OH 43205, USA; (P.M.-O.); (B.R.L.)
- Oral and Gastrointestinal Microbiology Research Affinity Group, Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH 43205, USA
- Correspondence: ; Tel.: +1-614-722-5116; Fax: +1-614-722-2979
| | - Pedro Marte-Ortiz
- The Center for Microbial Pathogenesis, The Research Institute, Nationwide Children’s Hospital, Columbus, OH 43205, USA; (P.M.-O.); (B.R.L.)
| | - Therese A. Rajasekera
- Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; (T.A.R.); (T.L.G.)
- Department of Psychiatry & Behavioral Health, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
| | - Brett R. Loman
- The Center for Microbial Pathogenesis, The Research Institute, Nationwide Children’s Hospital, Columbus, OH 43205, USA; (P.M.-O.); (B.R.L.)
| | - Tamar L. Gur
- Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; (T.A.R.); (T.L.G.)
- Department of Psychiatry & Behavioral Health, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
| | - Michael T. Bailey
- Department of Pediatrics, The Ohio State Wexner Medical Center, Columbus, OH 43210, USA;
- The Center for Microbial Pathogenesis, The Research Institute, Nationwide Children’s Hospital, Columbus, OH 43205, USA; (P.M.-O.); (B.R.L.)
- Oral and Gastrointestinal Microbiology Research Affinity Group, Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH 43205, USA
- Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; (T.A.R.); (T.L.G.)
| |
Collapse
|
|
14
|
Ahmed S, Travis SD, Díaz-Bahamonde FV, Porter DDL, Henry SN, Mykins J, Ravipati A, Booker A, Ju J, Ding H, Ramesh AK, Pickrell AM, Wang M, LaConte S, Howell BR, Yuan L, Morton PD. Early Influences of Microbiota on White Matter Development in Germ-Free Piglets. Front Cell Neurosci 2022; 15:807170. [PMID: 35027884 PMCID: PMC8751630 DOI: 10.3389/fncel.2021.807170] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Accepted: 11/29/2021] [Indexed: 11/13/2022] Open
Abstract
Abnormalities in the prefrontal cortex (PFC), as well as the underlying white matter (WM) tracts, lie at the intersection of many neurodevelopmental disorders. The influence of microorganisms on brain development has recently been brought into the clinical and research spotlight as alterations in commensal microbiota are implicated in such disorders, including autism spectrum disorders, schizophrenia, depression, and anxiety via the gut-brain axis. In addition, gut dysbiosis is common in preterm birth patients who often display diffuse WM injury and delayed WM maturation in critical tracts including those within the PFC and corpus callosum. Microbial colonization of the gut aligns with ongoing postnatal processes of oligodendrogenesis and the peak of brain myelination in humans; however, the influence of microbiota on gyral WM development remains elusive. Here, we develop and validate a neonatal germ-free swine model to address these issues, as piglets share key similarities in WM volume, developmental trajectories, and distribution to humans. We find significant region-specific reductions, and sexually dimorphic trends, in WM volume, oligodendrogenesis, and mature oligodendrocyte numbers in germ-free piglets during a key postnatal epoch of myelination. Our findings indicate that microbiota plays a critical role in promoting WM development during early life when the brain is vulnerable to environmental insults that can result in an array of disabilities manifesting later in life.
Collapse
Affiliation(s)
- Sadia Ahmed
- Graduate Studies in Biomedical and Veterinary Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States
| | - Sierrah D Travis
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States
| | - Francisca V Díaz-Bahamonde
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States
| | - Demisha D L Porter
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States.,Virginia Tech Graduate Program in Translational Biology, Medicine and Health, Virginia Tech, Roanoke, VA, United States
| | - Sara N Henry
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States
| | - Julia Mykins
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States
| | - Aditya Ravipati
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States
| | - Aryn Booker
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States
| | - Jing Ju
- Graduate Studies in Biomedical and Veterinary Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States
| | - Hanzhang Ding
- Virginia Tech Graduate Program in Translational Biology, Medicine and Health, Virginia Tech, Roanoke, VA, United States
| | - Ashwin K Ramesh
- Graduate Studies in Biomedical and Veterinary Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States.,Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States.,Molecular Microbiology and Immunology, University of Missouri, Columbia, MO, United States
| | - Alicia M Pickrell
- School of Neuroscience, Virginia Tech, Blacksburg, VA, United States
| | - Maosen Wang
- Fralin Biomedical Research Institute at Virginia Tech Carilion (VTC), Virginia Tech, Roanoke, VA, United States
| | - Stephen LaConte
- Fralin Biomedical Research Institute at Virginia Tech Carilion (VTC), Virginia Tech, Roanoke, VA, United States.,Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA, United States
| | - Brittany R Howell
- Fralin Biomedical Research Institute at Virginia Tech Carilion (VTC), Virginia Tech, Roanoke, VA, United States.,Department of Human Development and Family Science, Virginia Tech, Roanoke, VA, United States
| | - Lijuan Yuan
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States
| | - Paul D Morton
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States
| |
Collapse
|
|
15
|
Graff LA, Fowler S, Jones JL, Benchimol EI, Bitton A, Huang JG, Kuenzig ME, Kaplan GG, Lee K, Mukhtar MS, Tandon P, Targownik LE, Windsor JW, Bernstein CN. Crohn's and Colitis Canada's 2021 Impact of COVID-19 and Inflammatory Bowel Disease in Canada: Mental Health and Quality of Life. J Can Assoc Gastroenterol 2021; 4:S46-S53. [PMID: 34755039 PMCID: PMC8570421 DOI: 10.1093/jcag/gwab031] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Accepted: 08/11/2021] [Indexed: 12/13/2022] Open
Abstract
There has been a dramatic rise in mental health difficulties during the coronavirus disease 2019 (COVID-19) pandemic. While young adults have the lowest risk of hospitalization and mortality due to COVID-19, they have been identified as being at highest risk of detrimental mental health outcomes during the pandemic, along with women, those with lower socioeconomic status and those with pre-existing mental health conditions. Somewhat of a crisis in mental health has emerged across the general population through the evolution of the pandemic. A national Canadian survey identified a quadrupling of those experiencing pervasive elevated anxiety symptoms early in the pandemic compared to pre-pandemic levels, and a doubling of those with pervasive elevated depressive symptoms. Independent of the pandemic, persons with inflammatory bowel disease (IBD) can face multiple challenges related to their disease, which can result in a significant psychosocial burden and psychologic distress. Anxiety and depression have been found to be more prevalent in persons with IBD. Many potential factors contribute to the increased psychologic distress and negative impacts on mental health of the COVID-19 pandemic on persons with IBD. These include the fears of contracting COVID-19 or infecting other people. Many believe that IBD or its treatments predispose them to an increased risk of COVID-19 or a worse outcome if acquired. Concerns about access to health care add to mental distress. People with IBD generally report lower quality of life (QOL) compared to community controls. Psychologic interventions, in addition to adequate disease control, have been shown to improve health-related QOL. Uncertainty is another factor associated with reduced health-related QOL. Most studies suggest that persons with IBD have suffered QOL impairment during the pandemic in comparison to the pre-pandemic period. Uncertainties brought on by the pandemic are important contributors for some of the reduction in QOL.
Collapse
Affiliation(s)
- Lesley A Graff
- Department of Clinical Health Psychology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
- University of Manitoba IBD Clinical and Research Centre, Winnipeg, Manitoba, Canada
| | - Sharyle Fowler
- Department of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Jennifer L Jones
- Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Eric I Benchimol
- SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- Child Health Evaluative Sciences, SickKids Research Institute, Toronto, Ontario, Canada
- ICES, Toronto, Ontario, Canada
- Department of Paediatrics and Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
| | - Alain Bitton
- Department of Medicine, McGill University Health Centre, McGill University, Montreal, Quebec, Canada
| | - James Guoxian Huang
- SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - M Ellen Kuenzig
- SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- Child Health Evaluative Sciences, SickKids Research Institute, Toronto, Ontario, Canada
| | - Gilaad G Kaplan
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada
- Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Kate Lee
- Crohn’s and Colitis Canada, Toronto, Ontario, Canada
| | - Mariam S Mukhtar
- Department of Internal Medicine, King Abdulaziz University Hospital, Jeddah, Saudi Arabia
| | - Parul Tandon
- Division of Gastroenterology and Hepatology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Laura E Targownik
- Division of Gastroenterology and Hepatology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Joseph W Windsor
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Charles N Bernstein
- University of Manitoba IBD Clinical and Research Centre, Winnipeg, Manitoba, Canada
- Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
| |
Collapse
|
|
16
|
Maget A, Dalkner N, Hamm C, Bengesser SA, Fellendorf FT, Platzer M, Queissner R, Birner A, Lenger M, Mörkl S, Kohlhammer-Dohr A, Rieger A, Seidl M, Mendel L, Färber T, Wetzlmair L, Schwalsberger K, Amberger-Otti DV, Schöggl H, Lahousen T, Leitner-Afschar B, Unterweger R, Zelzer S, Mangge H, Reininghaus EZ. Sex differences in zonulin in affective disorders and associations with current mood symptoms. J Affect Disord 2021; 294:441-446. [PMID: 34320451 DOI: 10.1016/j.jad.2021.07.021] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 07/09/2021] [Accepted: 07/12/2021] [Indexed: 11/28/2022]
Abstract
INTRODUCTION The bidirectional connection between the brain and the gut within psychiatric entities has gained increasing scientific attention over the last years. As a regulator of intestinal permeability, zonulin acts as a key player on the interface of this interplay. Like several psychiatric disorders, intestinal permeability was associated with inflammation in previous findings. METHODS In this study we explored differences in zonulin serum levels in currently depressed (n = 55) versus currently euthymic (n = 37) individuals with an affective disorder. Further, we explored sex differences and possible influences on zonulin and affective symptoms like medication, age, body mass index, and smoking status. RESULTS Serum zonulin was significantly higher in females than in men independent from affective status (z = -2.412, p = .016). More specifically, females in the euthymic subgroup had higher zonulin levels than euthymic men (z = -2.114, p = .035). There was no difference in zonulin serum levels in individuals taking or not taking a specific psychopharmacotherapy. We found no correlation between zonulin serum levels and depression severity. DISCUSSION Increased serum zonulin levels as a proxy for increased intestinal permeability in women may indicate a state of elevated susceptibility for depression-inducing stimuli.
Collapse
Affiliation(s)
- A Maget
- Departement for Psychiatry and Psychotherapeutic Medicine, Medical University Graz, Graz, Austria
| | - N Dalkner
- Departement for Psychiatry and Psychotherapeutic Medicine, Medical University Graz, Graz, Austria
| | - C Hamm
- Departement for Psychiatry and Psychotherapeutic Medicine, Medical University Graz, Graz, Austria
| | - S A Bengesser
- Departement for Psychiatry and Psychotherapeutic Medicine, Medical University Graz, Graz, Austria
| | - F T Fellendorf
- Departement for Psychiatry and Psychotherapeutic Medicine, Medical University Graz, Graz, Austria.
| | - M Platzer
- Departement for Psychiatry and Psychotherapeutic Medicine, Medical University Graz, Graz, Austria
| | - R Queissner
- Departement for Psychiatry and Psychotherapeutic Medicine, Medical University Graz, Graz, Austria
| | - A Birner
- Departement for Psychiatry and Psychotherapeutic Medicine, Medical University Graz, Graz, Austria
| | - M Lenger
- Departement for Psychiatry and Psychotherapeutic Medicine, Medical University Graz, Graz, Austria
| | - S Mörkl
- Departement for Psychiatry and Psychotherapeutic Medicine, Medical University Graz, Graz, Austria
| | - A Kohlhammer-Dohr
- Departement for Psychiatry and Psychotherapeutic Medicine, Medical University Graz, Graz, Austria
| | - A Rieger
- Departement for Psychiatry and Psychotherapeutic Medicine, Medical University Graz, Graz, Austria
| | - M Seidl
- Departement for Psychiatry and Psychotherapeutic Medicine, Medical University Graz, Graz, Austria
| | - L Mendel
- Departement for Psychiatry and Psychotherapeutic Medicine, Medical University Graz, Graz, Austria
| | - T Färber
- Departement for Psychiatry and Psychotherapeutic Medicine, Medical University Graz, Graz, Austria
| | - L Wetzlmair
- Departement for Psychiatry and Psychotherapeutic Medicine, Medical University Graz, Graz, Austria
| | - K Schwalsberger
- Departement for Psychiatry and Psychotherapeutic Medicine, Medical University Graz, Graz, Austria
| | - D V Amberger-Otti
- Departement for Psychiatry and Psychotherapeutic Medicine, Medical University Graz, Graz, Austria
| | - H Schöggl
- Departement for Psychiatry and Psychotherapeutic Medicine, Medical University Graz, Graz, Austria
| | - T Lahousen
- Departement for Psychiatry and Psychotherapeutic Medicine, Medical University Graz, Graz, Austria
| | - B Leitner-Afschar
- Departement for Psychiatry and Psychotherapeutic Medicine, Medical University Graz, Graz, Austria
| | - R Unterweger
- Departement for Psychiatry and Psychotherapeutic Medicine, Medical University Graz, Graz, Austria
| | - S Zelzer
- Institute of Medical and Chemical Laboratory Diagnostics, Medical University Graz, Graz, Austria
| | - H Mangge
- Institute of Medical and Chemical Laboratory Diagnostics, Medical University Graz, Graz, Austria
| | - E Z Reininghaus
- Departement for Psychiatry and Psychotherapeutic Medicine, Medical University Graz, Graz, Austria
| |
Collapse
|
|
17
|
Hu S, Chen Y, Chen Y, Wang C. Depression and Anxiety Disorders in Patients With Inflammatory Bowel Disease. Front Psychiatry 2021; 12:714057. [PMID: 34690829 PMCID: PMC8531580 DOI: 10.3389/fpsyt.2021.714057] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Accepted: 08/30/2021] [Indexed: 12/12/2022] Open
Abstract
Mental health is a significant yet overlooked aspect of inflammatory bowel disease (IBD) patient care, with challenges in determining optimal treatments and psychological health resources. The most common psychological conditions in patients with IBD are anxiety and depression. The increased prevalence of these mental disorders appeals to mental screening of each person diagnosed with IBD at initial consultation. There are simple and clinically viable methods available to screen for mental problems. Psychological methods may be as or even more significant as a therapeutic modality. Herein we discuss the three major areas of psychological co-morbidity in IBD: (1) the prevalence and risk factors associated with anxiety and depression disorders for patients with IBD; (2) diagnosis of psychological disorders for patients with IBD; (3) treatment with patients with IBD and mental disorders. The gastroenterologists are encouraged to screen and treat these patients with IBD and mental disorders, which may improve outcomes.
Collapse
Affiliation(s)
- Shurong Hu
- Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yiping Chen
- Department of Psychiatry, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yan Chen
- Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Caihua Wang
- Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| |
Collapse
|
|
18
|
Banfi D, Moro E, Bosi A, Bistoletti M, Cerantola S, Crema F, Maggi F, Giron MC, Giaroni C, Baj A. Impact of Microbial Metabolites on Microbiota-Gut-Brain Axis in Inflammatory Bowel Disease. Int J Mol Sci 2021; 22:1623. [PMID: 33562721 PMCID: PMC7915037 DOI: 10.3390/ijms22041623] [Citation(s) in RCA: 75] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 01/29/2021] [Accepted: 02/02/2021] [Indexed: 02/07/2023] Open
Abstract
The complex bidirectional communication system existing between the gastrointestinal tract and the brain initially termed the "gut-brain axis" and renamed the "microbiota-gut-brain axis", considering the pivotal role of gut microbiota in sustaining local and systemic homeostasis, has a fundamental role in the pathogenesis of Inflammatory Bowel Disease (IBD). The integration of signals deriving from the host neuronal, immune, and endocrine systems with signals deriving from the microbiota may influence the development of the local inflammatory injury and impacts also more distal brain regions, underlying the psychophysiological vulnerability of IBD patients. Mood disorders and increased response to stress are frequently associated with IBD and may affect the disease recurrence and severity, thus requiring an appropriate therapeutic approach in addition to conventional anti-inflammatory treatments. This review highlights the more recent evidence suggesting that alterations of the microbiota-gut-brain bidirectional communication axis may concur to IBD pathogenesis and sustain the development of both local and CNS symptoms. The participation of the main microbial-derived metabolites, also defined as "postbiotics", such as bile acids, short-chain fatty acids, and tryptophan metabolites in the development of IBD-associated gut and brain dysfunction will be discussed. The last section covers a critical evaluation of the main clinical evidence pointing to the microbiome-based therapeutic approaches for the treatment of IBD-related gastrointestinal and neuropsychiatric symptoms.
Collapse
Affiliation(s)
- Davide Banfi
- Department of Medicine and Surgery, University of Insubria, via H Dunant 5, 21100 Varese, Italy; (D.B.); (A.B.); (M.B.); (F.M.); (A.B.)
| | - Elisabetta Moro
- Department of Internal Medicine and Therapeutics, Section of Pharmacology, University of Pavia, via Ferrata 9, 27100 Pavia, Italy; (E.M.); (F.C.)
| | - Annalisa Bosi
- Department of Medicine and Surgery, University of Insubria, via H Dunant 5, 21100 Varese, Italy; (D.B.); (A.B.); (M.B.); (F.M.); (A.B.)
| | - Michela Bistoletti
- Department of Medicine and Surgery, University of Insubria, via H Dunant 5, 21100 Varese, Italy; (D.B.); (A.B.); (M.B.); (F.M.); (A.B.)
| | - Silvia Cerantola
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Largo Meneghetti 2, 35131 Padova, Italy; (S.C.); (M.C.G.)
| | - Francesca Crema
- Department of Internal Medicine and Therapeutics, Section of Pharmacology, University of Pavia, via Ferrata 9, 27100 Pavia, Italy; (E.M.); (F.C.)
| | - Fabrizio Maggi
- Department of Medicine and Surgery, University of Insubria, via H Dunant 5, 21100 Varese, Italy; (D.B.); (A.B.); (M.B.); (F.M.); (A.B.)
| | - Maria Cecilia Giron
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Largo Meneghetti 2, 35131 Padova, Italy; (S.C.); (M.C.G.)
| | - Cristina Giaroni
- Department of Medicine and Surgery, University of Insubria, via H Dunant 5, 21100 Varese, Italy; (D.B.); (A.B.); (M.B.); (F.M.); (A.B.)
- Centre of Neuroscience, University of Insubria, 21100 Varese, Italy
| | - Andreina Baj
- Department of Medicine and Surgery, University of Insubria, via H Dunant 5, 21100 Varese, Italy; (D.B.); (A.B.); (M.B.); (F.M.); (A.B.)
| |
Collapse
|
|
19
|
Clemente-Suárez VJ, Dalamitros AA, Beltran-Velasco AI, Mielgo-Ayuso J, Tornero-Aguilera JF. Social and Psychophysiological Consequences of the COVID-19 Pandemic: An Extensive Literature Review. Front Psychol 2020; 11:580225. [PMID: 33391099 PMCID: PMC7772398 DOI: 10.3389/fpsyg.2020.580225] [Citation(s) in RCA: 79] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2020] [Accepted: 10/16/2020] [Indexed: 12/11/2022] Open
Abstract
The Coronavirus Disease 2019 (COVID-19) pandemic, now a global health crisis, has surprised health authorities around the world. Recent studies suggest that the measures taken to curb the spread of the COVID-19 outbreak have generated issues throughout the population. Thus, it is necessary to establish and identify the possible risk factors related to the psychosocial and psychophysiological strain during the COVID-19 outbreak. The present extensive literature review assesses the social, psychological, and physiological consequences of COVID-19, reviewing the impact of quarantine measures, isolation, vast human loss, social and financial consequences in the family's economies, and its impact on the psychological health of the population. We also discussed the effect of psychophysiological factors, considering the impact of physical inactivity and modifications in nutritional habits, at psychological and physiological levels. The present review includes an actualized to date bibliography, articles for which were methodologically analyzed to verify they met the standards of quality and scientific accuracy. Authors understand the pandemic as a multifactorial event for which only a profound and extensive analysis would lead to better compression and efficient intervention in the near future.
Collapse
Affiliation(s)
- Vicente Javier Clemente-Suárez
- Faculty of Sports Sciences, Universidad Europea de Madrid, Madrid, Spain
- Grupo de Investigación en Cultura, Educación y Sociedad, Universidad de la Costa, Barranquilla, Colombia
- Studies Centre in Applied Combat, Toledo, Spain
| | - Athanasios A. Dalamitros
- Laboratory of Evaluation of Human Biological Performance, School of Physical Education and Sport Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | | | - Juan Mielgo-Ayuso
- Department of Biochemistry, Molecular Biology and Physiology, Faculty of Health Sciences, University of Valladolid, Soria, Spain
| | | |
Collapse
|
|
20
|
Expressive writing to combat distress associated with the COVID-19 pandemic in people with inflammatory bowel disease (WriteForIBD): A trial protocol. J Psychosom Res 2020; 139:110286. [PMID: 33171431 PMCID: PMC7609228 DOI: 10.1016/j.jpsychores.2020.110286] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Revised: 10/26/2020] [Accepted: 10/31/2020] [Indexed: 12/13/2022]
Abstract
OBJECTIVE A large proportion of patients with inflammatory bowel disease (IBD) receive immunosuppressive medication, may be at higher risk of complications if they contract SARS-CoV-2 virus, and therefore report high levels of COVID-19-related distress. This trial will evaluate a brief, evidence-based, online, group-based expressive writing intervention to reduce COVID-19-related distress in people living with IBD at the time of pandemic. METHODS A parallel double-blind randomised controlled trial will be conducted. Overall, up to 154 adult participants with IBD and mild-moderate distress will be recruited via patient organisations. Participants will be allocated to the expressive writing intervention or an active control group. All participants will complete questionnaires including measures of distress, quality of life, resilience, self-efficacy, social support and disease activity before and after the intervention (1 week) and at 3 months post-intervention. The expressive writing group will participate in the evidenced-based 4-day writing program adapted from Pennebaker and Beall, 1986. The active control group will write about untherapeutic topics provided by researchers. Statistical analysis will be carried out on an intention-to-treat basis and will involve linear mixed effects models. CONCLUSIONS If successful, this simple intervention may bring personal and societal benefits, particularly because it is low cost, can be easily implemented online, ensuring social distancing, and be made widely available, during future disasters and to help with trauma-related distress in IBD. TRIAL REGISTRATION The trial has been prospectively registered in the Australian New Zealand Trial Registry - ACTRN12620000448943p.
Collapse
|
|
21
|
Association of Alterations in Intestinal Microbiota With Impaired Psychological Function in Patients With Inflammatory Bowel Diseases in Remission. Clin Gastroenterol Hepatol 2020; 18:2019-2029.e11. [PMID: 31546058 DOI: 10.1016/j.cgh.2019.09.022] [Citation(s) in RCA: 84] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Revised: 09/13/2019] [Accepted: 09/15/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Depression and anxiety are frequent comorbidities with inflammatory bowel diseases (IBD). Alterations to the intestinal microbiome promote not only intestinal inflammation but also psychologic function. We studied the interactions between the composition of the intestinal microbiota and psychological outcomes in patients with IBD in Switzerland. METHODS We performed a prospective study of psychological comorbidities and quality of life (QoL) in 171 participants in the Swiss IBD Cohort Study with IBD in remission. Participants complete the Hospital Anxiety and Depression Scale, Perceived Stress Questionnaire, the 36-Item Short Form Survey, and the IBD QoL Questionnaire. Microbes were collected from intestinal biopsies and analyzed by 16S rRNA high-throughput sequencing. RESULTS Microbiomes of patients with higher perceived stress had significantly lower alpha diversity. Anxiety and depressive symptoms were significantly associated with beta diversity. We found a negative correlation between psychological distress and abundance of Clostridia, Bacilli, Bacteroidia, and Beta- and Gamma-proteobacteria. Psychological distress was also associated with decreases in operational taxonomic units from the lineages of Lachnospiraceae, Fusobacteriaceae, Ruminococcaceae, Veillonellaceae, Alcaligenaceae, Desulfovibrionaceae, and Bacteroidaceae families. The relative abundance of Bifidobacterium in patients with Crohn's disease and Desulfovibrio in patients with ulcerative colitis correlated with depression, whereas abundance of Sutterella, RF 32, and Lactococcus correlated with quality of life in patients with Crohn's disease. CONCLUSIONS We identified correlations between the composition of the intestinal microbiota in patients with IBD and remission, psychological well-being, and QoL. Further studies should investigate how intestinal inflammation, the microbiome, and microbial metabolites affect psychological well-being and whether these components are mono- or bi-directionally linked.
Collapse
|
|
22
|
Silva NOE, Brito BBD, Silva FAFD, Santos MLC, Melo FFD. Probiotics in inflammatory bowel disease: Does it work? World J Meta-Anal 2020; 8:54-66. [DOI: 10.13105/wjma.v8.i2.54] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2019] [Revised: 03/26/2020] [Accepted: 04/14/2020] [Indexed: 02/06/2023] Open
|
|
23
|
Sinagra E, Utzeri E, Morreale GC, Fabbri C, Pace F, Anderloni A. Microbiota-gut-brain axis and its affect inflammatory bowel disease: Pathophysiological concepts and insights for clinicians. World J Clin Cases 2020; 8:1013-1025. [PMID: 32258072 PMCID: PMC7103973 DOI: 10.12998/wjcc.v8.i6.1013] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 02/14/2020] [Accepted: 03/05/2020] [Indexed: 02/05/2023] Open
Abstract
Despite the bi-directional interaction between gut microbiota and the brain not being fully understood, there is increasing evidence arising from animal and human studies that show how this intricate relationship may facilitate inflammatory bowel disease (IBD) pathogenesis, with consequent important implications on the possibility to improve the clinical outcomes of the diseases themselves, by acting on the different components of this system, mainly by modifying the microbiota. With the emergence of precision medicine, strategies in which patients with IBD might be categorized other than for standard gut symptom complexes could offer the opportunity to tailor therapies to individual patients. The aim of this narrative review is to elaborate on the concept of the gut-brain-microbiota axis and its clinical significance regarding IBD on the basis of recent scientific literature, and finally to focus on pharmacological therapies that could allow us to favorably modify the function of this complex system.
Collapse
Affiliation(s)
- Emanuele Sinagra
- Gastroenterology and Endoscopy Unit, Fondazione Istituto Giuseppe Giglio, Contrada Pietra Pollastra Pisciotto, Cefalù 90015, Italy
- Euro-Mediterranean Institute of Science and Technology, Palermo 90100, Italy
| | - Erika Utzeri
- Nuova Casa di Cura di Decimomannu, Cagliari 09100, Italy
| | | | - Carlo Fabbri
- Gastroenterology and Digestive Endoscopy Unit, Forlì-Cesena, Azienda USL Romagna, Forlì 47121, Italy
| | - Fabio Pace
- Unit of Gastroenterology, Bolognini Hospital, Bergamo 24100, Italy
| | - Andrea Anderloni
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital, Rozzano 20089, Italy
| |
Collapse
|
|
24
|
Mackner LM, Hatzakis E, Allen JM, Davies RH, Kim SC, Maltz RM, Bailey MT. Fecal microbiota and metabolites are distinct in a pilot study of pediatric Crohn's disease patients with higher levels of perceived stress. Psychoneuroendocrinology 2020; 111:104469. [PMID: 31654986 PMCID: PMC6956257 DOI: 10.1016/j.psyneuen.2019.104469] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Revised: 08/14/2019] [Accepted: 09/30/2019] [Indexed: 12/14/2022]
Abstract
Stress is associated with increased Crohn's Disease (CD) activity. This pilot study tested whether pediatric patients with CD reporting higher levels of perceived stress exhibited differences in the fecal microbiome and metabolome. The perceived stress scale (PSS) questionnaire was administered within 2 days of collecting a stool sample for microbiome (using 16S rRNA gene sequencing) and metabolome (using NMR metabolomics) analyses. Higher levels of perceived stress were correlated with increased disease activity on the short Pediatric Crohn's Disease Activity Index (sPCDAI). Patients with High PSS scores vs. Low PSS scores based on a median split had significantly lower relative abundances of Firmicutes and Anaerostipes, as well as higher relative abundances of Parabacteroides. Fecal alanine and nicotinate were also significantly different in patients with High vs. Low PSS Scores. This pilot study suggests that the fecal microbiome and metabolome differs in pediatric patients with CD and high perceived stress.
Collapse
Affiliation(s)
- Laura M. Mackner
- Center for Biobehavioral Health, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205,Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43210
| | - Emmanuel Hatzakis
- Department of Food Science, The Ohio State University, Columbus, OH 43205
| | - Jacob M. Allen
- Center for Microbial Pathogenesis, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205
| | - Ronald H. Davies
- Center for Microbial Pathogenesis, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205
| | - Sandra C. Kim
- Gastroenterology, Hepatology, and Nutrition; UPMC Children’s Hospital of Pittsburgh and the University of Pittsburgh School of Medicine, Pittsburgh, PA 1522
| | - Ross M. Maltz
- Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43210.,Center for Microbial Pathogenesis, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205.,Gastroenterology, Hepatology and Nutrition, Nationwide Children’s Hospital, Columbus, OH 43205.,Oral and GI Research Affinity Group, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205
| | - Michael T. Bailey
- Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43210.,Center for Microbial Pathogenesis, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205.,Oral and GI Research Affinity Group, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205
| |
Collapse
|
|
25
|
Modelo de intervención psicológica para pacientes con enfermedad inflamatoria intestinal. REVISTA MÉDICA CLÍNICA LAS CONDES 2019. [DOI: 10.1016/j.rmclc.2019.06.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
|
|
26
|
Chandra N, Srivastava A, Kumar S. Bacterial biofilms in human gastrointestinal tract: An intricate balance between health and inflammatory bowel diseases. World J Pharmacol 2019; 8:26-40. [DOI: 10.5497/wjp.v8.i3.26] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2019] [Revised: 07/05/2019] [Accepted: 07/16/2019] [Indexed: 02/06/2023] Open
Affiliation(s)
- Niharika Chandra
- Faculty of Biotechnology, Institute of Bio-Sciences and Technology, Shri Ramswaroop Memorial University, Uttar Pradesh 225003, India
| | - Ankita Srivastava
- Faculty of Bio-Sciences, Institute of Bio-Sciences and Technology, Shri Ramswaroop Memorial University, Uttar Pradesh 225003, India
| | - Sunil Kumar
- Faculty of Bio-Sciences, Institute of Bio-Sciences and Technology, Shri Ramswaroop Memorial University, Uttar Pradesh 225003, India
| |
Collapse
|
|
27
|
Lores T, Goess C, Mikocka-Walus A, Collins KL, Burke ALJ, Chur-Hansen A, Delfabbro P, Andrews JM. Integrated Psychological Care is Needed, Welcomed and Effective in Ambulatory Inflammatory Bowel Disease Management: Evaluation of a New Initiative. J Crohns Colitis 2019; 13:819-827. [PMID: 30721977 DOI: 10.1093/ecco-jcc/jjz026] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Revised: 12/12/2018] [Accepted: 01/31/2019] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Inflammatory bowel disease is associated with psychosocial issues which reduce quality of life and impair medical management. However, these issues are rarely addressed in routine care. A model of integrated psychological screening and intervention was trialled to measure prevalence, patient participation, and potential benefits to mental health and/or quality of life. METHODS During a 12-month period, 490 adult patients at an established hospital-based service were approached to complete screening instruments for anxiety, depression, general distress, quality of life and medication adherence. Disease-specific and demographic data were also collected. Patients who scored highly on screening questionnaires were offered psychological intervention (in-service or externally referred). Participants were reassessed after 12 months. RESULTS Psychological screening was well accepted with 68% (N = 335) participating. Psychological care was 'needed', with 55% (N = 183) scoring highly for anxiety, depression and/or general distress. Half of those 'in need' (N = 91) accepted intervention. In those who accepted, levels of anxiety (mean at intake [M1] = 12.11 vs mean at follow-up [M2] = 9.59, p < 0.001), depression (M1 = 8.38 vs M2 = 6.42, p < 0.001), general distress (M1 = 17.99 vs M2 = 13.96, p < 0.001), mental health quality of life (M1 = 54.64 vs M2 = 59.70, p < 0.001) and overall quality of life (M1 = 57.60 vs M2 = 64.10, p < 0.001) each improved between intake and follow-up. Engagement in psychological intervention was six times greater for those treated in-service vs externally referred (χ2[1] = 13.06, p < 0.001, odds ratio = 6.47). CONCLUSIONS Mental health issues are highly prevalent in people with inflammatory bowel disease. Patients are open to psychological screening and treatment. Psychological care can improve patient mental health and quality of life, and works best when integrated into routine management.
Collapse
Affiliation(s)
- Taryn Lores
- IBD Service, Department of Gastroenterology & Hepatology, Royal Adelaide Hospital, Adelaide, Australia
| | - Charlotte Goess
- IBD Service, Department of Gastroenterology & Hepatology, Royal Adelaide Hospital, Adelaide, Australia
| | | | - Kathryn L Collins
- Psychology Department, Central Adelaide Local Health Network, Adelaide, Australia
| | - Anne L J Burke
- Psychology Department, Central Adelaide Local Health Network, Adelaide, Australia
| | - Anna Chur-Hansen
- School of Psychology, University of Adelaide, Adelaide, Australia
| | - Paul Delfabbro
- School of Psychology, University of Adelaide, Adelaide, Australia
| | - Jane M Andrews
- IBD Service, Department of Gastroenterology & Hepatology, Royal Adelaide Hospital, Adelaide, Australia
| |
Collapse
|
|
28
|
Inflammatory Bowel Disease: A Stressed "Gut/Feeling". Cells 2019; 8:cells8070659. [PMID: 31262067 PMCID: PMC6678997 DOI: 10.3390/cells8070659] [Citation(s) in RCA: 74] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Revised: 06/22/2019] [Accepted: 06/28/2019] [Indexed: 12/21/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic and relapsing intestinal inflammatory condition, hallmarked by a disturbance in the bidirectional interaction between gut and brain. In general, the gut/brain axis involves direct and/or indirect communication via the central and enteric nervous system, host innate immune system, and particularly the gut microbiota. This complex interaction implies that IBD is a complex multifactorial disease. There is increasing evidence that stress adversely affects the gut/microbiota/brain axis by altering intestinal mucosa permeability and cytokine secretion, thereby influencing the relapse risk and disease severity of IBD. Given the recurrent nature, therapeutic strategies particularly aim at achieving and maintaining remission of the disease. Alternatively, these strategies focus on preventing permanent bowel damage and concomitant long-term complications. In this review, we discuss the gut/microbiota/brain interplay with respect to chronic inflammation of the gastrointestinal tract and particularly shed light on the role of stress. Hence, we evaluated the therapeutic impact of stress management in IBD.
Collapse
|
|
29
|
Torres J, Ellul P, Langhorst J, Mikocka-Walus A, Barreiro-de Acosta M, Basnayake C, Ding NJS, Gilardi D, Katsanos K, Moser G, Opheim R, Palmela C, Pellino G, Van der Marel S, Vavricka SR. European Crohn's and Colitis Organisation Topical Review on Complementary Medicine and Psychotherapy in Inflammatory Bowel Disease. J Crohns Colitis 2019; 13:673-685e. [PMID: 30820529 DOI: 10.1093/ecco-jcc/jjz051] [Citation(s) in RCA: 98] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2019] [Accepted: 02/26/2019] [Indexed: 12/11/2022]
Abstract
Patients with inflammatory bowel disease [IBD] increasingly use alternative and complementary therapies, for which appropriate evidence is often lacking. It is estimated that up to half of all patients with IBD use various forms of complementary and alternative medicine during some point in their disease course. Considering the frequent use of such therapies, it is crucial that physicians and patients are informed about their efficacy and safety in order to provide guidance and evidence-based advice. Additionally, increasing evidence suggests that some psychotherapies and mind-body interventions may be beneficial in the management of IBD, but their best use remains a matter of research. Herein, we provide a comprehensive review of some of the most commonly used complementary, alternative and psychotherapy interventions in IBD.
Collapse
Affiliation(s)
- Joana Torres
- Department of Gastroenterology, Hospital Beatriz Ângelo, Loures, Portugal
| | - Pierre Ellul
- Department of Medicine, Division of Gastroenterology, Mater Dei Hospital, Msida, Malta
| | - Jost Langhorst
- Department of Internal Medicine and Integrative Gastroenterology, Kliniken Essen-Mitte and Chair for Integrative Medicine and Translational Gastroenterology, Klinikum Bamberg, University Duisburg-Essen, Germany
| | | | - Manuel Barreiro-de Acosta
- Department of Gastroenterology, IBD Unit, University Hospital Santiago De Compostela (CHUS), Santiago De Compostela, Spain
| | - Chamara Basnayake
- Department of Gastroenterology, St. Vincent's Hospital Melbourne, Fitzroy, Melbourne, Australia
| | - Nik John Sheng Ding
- Department of Gastroenterology, St. Vincent's Hospital Melbourne, Fitzroy, Melbourne, Australia
| | - Daniela Gilardi
- IBD Centre, Department of Gastroenterology, Humanitas Clinical and Research Institute, Rozzano, Milan, Italy
| | - Konstantinos Katsanos
- Department of Gastroenterology and Hepatology, Division of Internal Medicine, University and Medical School of Ioannina, Ioannina, Greece
| | - Gabriele Moser
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
| | - Randi Opheim
- Department of Gastroenterology, Oslo University Hospital, and Department of Nursing Science, Institute of Health and Society, University of Oslo, Oslo, Norway
| | - Carolina Palmela
- Department of Gastroenterology, Hospital Beatriz Ângelo, Loures, Portugal
| | - Gianluca Pellino
- Department of Advanced Medical and Surgical Sciences, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy
| | - Sander Van der Marel
- Department of Gastroenterology and Internal Medicine, Haaglanden Medisch Centrum, The Hague, The Netherlands
| | | |
Collapse
|
|
30
|
Ewais T, Begun J, Kenny M, Rickett K, Hay K, Ajilchi B, Kisely S. A systematic review and meta-analysis of mindfulness based interventions and yoga in inflammatory bowel disease. J Psychosom Res 2019; 116:44-53. [PMID: 30654993 DOI: 10.1016/j.jpsychores.2018.11.010] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2018] [Revised: 11/12/2018] [Accepted: 11/14/2018] [Indexed: 12/22/2022]
Abstract
BACKGROUND Mindfulness interventions are increasingly used as a part of integrated treatment in inflammatory bowel disease (IBD) but there are limited data and a lack of consensus regarding effectiveness. OBJECTIVES We explored the efficacy of mindfulness interventions compared to treatment as usual (TAU), or other psychotherapeutic interventions, in treating physical and psychosocial symptoms associated with IBD. METHODS We conducted a systematic review and meta-analysis of relevant randomized controlled trials (RCTs). We included a broad range of mindfulness interventions including mindfulness-based interventions and yoga, with no restrictions on date of publication, participants' age, language or publication type. We searched the following electronic databases: MEDLINE, EMBASE, PsycINFO, CINAHL and WHO ICTRP database. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines in conducting the review. RESULTS We included eight studies in the meta-analysis. Mindfulness interventions showed a statistically significant effect on stress in both the short(SMD = -0.48; 95%CI:-0.97, 0.00; P = .05), and long term(SMD = -0.55; 95%CI:-0.78, -0.32; P < .00001), significant long term effects on depression (SMD = -0.36; 95%CI:-0.66, -0.07; P = .02) and quality of life (SMD = 0.38; 95%CI:0.08, 0.68; P = .01),and small but not statistically significant improvements in anxiety (SMD = -0.27; 95%CI:-0.65, 0.11; P = .16).Effects on physical outcomes were equivocal and not statistically significant. CONCLUSIONS Mindfulness interventions are effective in reducing stress and depression and improving quality of life and anxiety, but do not lead to significant improvements in the physical symptoms of IBD. Further research involving IBD-tailored interventions and more rigorously designed trials is warranted.
Collapse
Affiliation(s)
- Tatjana Ewais
- School of Medicine, Mater Clinical School and Princess Alexandra Clinical School, Raymond Terrace, The University of Queensland, South Brisbane, QLD 4101, Australia; The Mater Young Adult Health Centre, Mater Misericordiae Ltd, Raymond Terrace, South Brisbane, QLD 4101, Australia.
| | - Jake Begun
- School of Medicine, Mater Clinical School and Princess Alexandra Clinical School, Raymond Terrace, The University of Queensland, South Brisbane, QLD 4101, Australia; The Mater Young Adult Health Centre, Mater Misericordiae Ltd, Raymond Terrace, South Brisbane, QLD 4101, Australia.
| | - Maura Kenny
- The University of Adelaide, Adelaide, SA 5005, Australia
| | - Kirsty Rickett
- The UQ/Mater McAuley Library, Mater Misericordiae Ltd, South Brisbane, QLD 4101, Australia.
| | - Karen Hay
- QIMR Berghofer, Mater Misericordiae Ltd, South Brisbane, QLD 4006, Australia.
| | - Bita Ajilchi
- Department of Psychology, Faculty of Human Science, Science and Research Branch, Islamic Azad University (IAU), Tehran, Iran
| | - Steve Kisely
- School of Medicine, Mater Clinical School and Princess Alexandra Clinical School, Raymond Terrace, The University of Queensland, South Brisbane, QLD 4101, Australia.
| |
Collapse
|
|
31
|
Benchimol EI, Bernstein CN, Bitton A, Murthy SK, Nguyen GC, Lee K, Cooke-Lauder J, Siddiq S, Windsor JW, Carroll MW, Coward S, El-Matary W, Griffiths AM, Jones JL, Kuenzig ME, Lee L, Mack DR, Mawani M, Otley AR, Singh H, Targownik LE, Weizman AV, Kaplan GG. The Impact of Inflammatory Bowel Disease in Canada 2018: A Scientific Report from the Canadian Gastro-Intestinal Epidemiology Consortium to Crohn's and Colitis Canada. J Can Assoc Gastroenterol 2018; 2:S1-S5. [PMID: 31294380 PMCID: PMC6512240 DOI: 10.1093/jcag/gwy052] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2018] [Accepted: 09/06/2018] [Indexed: 02/06/2023] Open
Abstract
Canada has among the highest rates of IBD in the world, and the number of people living with these disorders is growing rapidly. This has placed a high burden on the health care system and on the Canadian economy—a burden that is only expected to grow in the future. It is important to understand IBD and its impact on Canadian society in order to appropriately plan for health care expenditures, reduce the burden on patients and their families, and improve the quality of life for those afflicted with IBD. In Canada, there is a lack of public awareness of the impact of Crohn’s disease and ulcerative colitis. Raising awareness is crucial to reducing the social stigma that is common with these diseases and to help individuals maximize their overall quality of life. A better public understanding of IBD can also help to raise and direct funds for research, which could lead to improved treatments and, ultimately, to a cure. This report from Canadian clinicians and researchers to Crohn’s and Colitis Canada makes recommendations aimed at the public, policy-makers, scientific funding agencies, charitable foundations and patients regarding future directions for advocacy efforts and areas to emphasize for research spending. The report also identifies gaps in knowledge in the fields of clinical, health systems and epidemiological research.
Collapse
Affiliation(s)
- Eric I Benchimol
- Canadian Gastro-Intestinal Epidemiology Consortium, Canada.,Children's Hospital of Eastern Ontario IBD Centre, Department of Pediatrics and School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
| | - Charles N Bernstein
- Canadian Gastro-Intestinal Epidemiology Consortium, Canada.,University of Manitoba IBD Clinical and Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Alain Bitton
- Canadian Gastro-Intestinal Epidemiology Consortium, Canada.,McGill University Health Centre IBD Centre, McGill University, Montreal, Quebec, Canada
| | - Sanjay K Murthy
- Canadian Gastro-Intestinal Epidemiology Consortium, Canada.,Ottawa Hospital Research Institute, Department of Medicine and School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
| | - Geoffrey C Nguyen
- Canadian Gastro-Intestinal Epidemiology Consortium, Canada.,Mount Sinai Hospital Centre for IBD, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Kate Lee
- Crohn's and Colitis Canada, Toronto, Ontario, Canada
| | | | - Shabnaz Siddiq
- Children's Hospital of Eastern Ontario IBD Centre, Department of Pediatrics and School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
| | - Joseph W Windsor
- Canadian Gastro-Intestinal Epidemiology Consortium, Canada.,Department of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Matthew W Carroll
- Canadian Gastro-Intestinal Epidemiology Consortium, Canada.,Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
| | - Stephanie Coward
- Canadian Gastro-Intestinal Epidemiology Consortium, Canada.,Department of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Wael El-Matary
- Canadian Gastro-Intestinal Epidemiology Consortium, Canada.,University of Manitoba IBD Clinical and Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Anne M Griffiths
- SickKids IBD Centre, The Hospital for Sick Children, Department of Paediatrics, University of Toronto, Ontario, Canada
| | - Jennifer L Jones
- Canadian Gastro-Intestinal Epidemiology Consortium, Canada.,Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
| | - M Ellen Kuenzig
- Canadian Gastro-Intestinal Epidemiology Consortium, Canada.,Children's Hospital of Eastern Ontario IBD Centre, Department of Pediatrics and School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
| | - Lawrence Lee
- Ottawa Hospital Research Institute, Department of Medicine and School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
| | - David R Mack
- Canadian Gastro-Intestinal Epidemiology Consortium, Canada.,Children's Hospital of Eastern Ontario IBD Centre, Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada
| | - Mina Mawani
- Crohn's and Colitis Canada, Toronto, Ontario, Canada
| | - Anthony R Otley
- Canadian Gastro-Intestinal Epidemiology Consortium, Canada.,Division of Gastroenterology and Nutrition, Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Harminder Singh
- Canadian Gastro-Intestinal Epidemiology Consortium, Canada.,University of Manitoba IBD Clinical and Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Laura E Targownik
- Canadian Gastro-Intestinal Epidemiology Consortium, Canada.,University of Manitoba IBD Clinical and Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Adam V Weizman
- Mount Sinai Hospital Centre for IBD, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Gilaad G Kaplan
- Canadian Gastro-Intestinal Epidemiology Consortium, Canada.,Department of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| |
Collapse
|
|
32
|
Jones JL, Nguyen GC, Benchimol EI, Bernstein CN, Bitton A, Kaplan GG, Murthy SK, Lee K, Cooke-Lauder J, Otley AR. The Impact of Inflammatory Bowel Disease in Canada 2018: Quality of Life. J Can Assoc Gastroenterol 2018; 2:S42-S48. [PMID: 31294384 PMCID: PMC6512247 DOI: 10.1093/jcag/gwy048] [Citation(s) in RCA: 69] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2018] [Accepted: 10/23/2018] [Indexed: 02/07/2023] Open
Abstract
Inflammatory bowel disease (IBD) has a substantial impact on quality of life. It causes considerable personal, emotional and social burdens. The impact of IBD on quality of life cannot readily be quantified as a cost; however, the impact places a significant burden on the patient and caregivers. Numerous studies have shown that health-related quality of life is impaired in patients living with IBD as compared with the general population. While disease activity and severity is an important driver of physical and mental health–related quality of life, patients may experience psychological distress even during clinical remission. Reduced quality of life can impact persons living with IBD as they pursue employment, family planning and personal milestones. Further, the impact of IBD extends to the patient influencing the quality of lives of those around them, including their caregivers. Improving quality of life requires a multidisciplinary approach that includes screening for and managing psychological distress. Adaptive coping mechanisms help manage illness perceptions and reduce psychosocial distress. Highlights Key Summary Points Gaps in Knowledge and Future Directions
Collapse
Affiliation(s)
- Jennifer L Jones
- Canadian Gastro-Intestinal Epidemiology Consortium, Canada.,Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Geoffrey C Nguyen
- Canadian Gastro-Intestinal Epidemiology Consortium, Canada.,Mount Sinai Hospital Centre for IBD, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Eric I Benchimol
- Canadian Gastro-Intestinal Epidemiology Consortium, Canada.,Children's Hospital of Eastern Ontario IBD Centre, Department of Pediatrics and School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
| | - Charles N Bernstein
- Canadian Gastro-Intestinal Epidemiology Consortium, Canada.,University of Manitoba IBD Clinical and Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Alain Bitton
- Canadian Gastro-Intestinal Epidemiology Consortium, Canada.,McGill IBD Centre of Excellence, McGill University Health Centre, Montreal, Quebec, Canada
| | - Gilaad G Kaplan
- Canadian Gastro-Intestinal Epidemiology Consortium, Canada.,Department of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Sanjay K Murthy
- Canadian Gastro-Intestinal Epidemiology Consortium, Canada.,Ottawa Hospital Research Institute, Department of Medicine and School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
| | - Kate Lee
- Crohn's and Colitis Canada, Toronto, Ontario, Canada
| | | | - Anthony R Otley
- Canadian Gastro-Intestinal Epidemiology Consortium, Canada.,Division of Gastroenterology and Nutrition, Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada
| |
Collapse
|
|
33
|
Desai D. Psychiatric morbidity in inflammatory bowel disease: Time to screen all the patients. Indian J Gastroenterol 2018; 37:281-283. [PMID: 30196517 DOI: 10.1007/s12664-018-0891-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- Devendra Desai
- Division of Gastroenterology, P D Hinduja Hospital, Veer Savarkar Marg, Mahim, Mumbai, 400 016, India.
| |
Collapse
|
|
34
|
Rohr M, Narasimhulu CA, Sharma D, Doomra M, Riad A, Naser S, Parthasarathy S. Inflammatory Diseases of the Gut. J Med Food 2018; 21:113-126. [PMID: 29389238 DOI: 10.1089/jmf.2017.0138] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, are chronic inflammatory disorders of the gastrointestinal tract whose prevalence has been dramatically increasing over the past decade. New studies have shown that IBD is the second most common chronic inflammatory disease worldwide after rheumatoid arthritis, affecting millions of people mainly in industrialized countries. Symptoms of IBD include frequent bloody diarrhea, abdominal cramping, anorexia, abdominal distension, and emesis. Although the exact etiology is unknown, it has been postulated that immunological, microbial, environmental, nutritional, and genetic factors contribute to the pathogenesis and severity of IBD. Today, no treatment has consistently been shown to be successful in treating IBD. This review summarizes current research on the epidemiology, etiology, pathophysiology, and existing treatment approaches, including pharmaceutical and nutritional options for IBD.
Collapse
Affiliation(s)
- Michael Rohr
- Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida , Orlando, Florida, USA
| | | | - Dhara Sharma
- Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida , Orlando, Florida, USA
| | - Mitsushita Doomra
- Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida , Orlando, Florida, USA
| | - Aladdin Riad
- Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida , Orlando, Florida, USA
| | - Saleh Naser
- Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida , Orlando, Florida, USA
| | - Sampath Parthasarathy
- Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida , Orlando, Florida, USA
| |
Collapse
|
|
35
|
Jordan C, Ohlsen R, Hayee B, Chalder T. A qualitative study exploring the experience of people with IBD and elevated symptoms of anxiety and low mood and the type of psychological help they would like. Psychol Health 2017; 33:634-651. [PMID: 28948842 DOI: 10.1080/08870446.2017.1381958] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND People with inflammatory bowel disease (IBD) are at increased risk of developing anxiety and low mood. We sought to explore the experience of people with IBD and moderate-severe symptoms of anxiety/low mood to identify psychological processes which could be targeted in psychological interventions, as well as the kind of psychological support preferred. METHODS Twenty-five participants with IBD and moderate-severe symptoms of anxiety/low mood were recruited for interview. Template analysis was utilised to analyse interview data. We explored the situations, cognitions and behaviour linked to symptoms of anxiety and low mood by people with IBD, as well as the kind of psychological help preferred. RESULTS Two themes were identified within participants accounts of symptoms of anxiety; 'under performance' and 'preventing an accident'. Two further themes were identified for symptoms of low mood; 'lack of understanding' and 'stigma'. Expertise and understanding was the main theme identified for the type of psychological help desired. CONCLUSION The analysis highlights situations, cognitions and behaviour linked to anxiety and low mood by people with IBD and the type of psychological support desired. Our findings link to the knowledge and competencies set for psychological therapist working with long-term conditions.
Collapse
Affiliation(s)
- Cheryl Jordan
- a Faculty of Nursing and Midwifery , King's College London , London , UK
| | - Ruth Ohlsen
- a Faculty of Nursing and Midwifery , King's College London , London , UK
| | - Bu'Hussain Hayee
- b Department of Gastroenterology , King's College Hospital , London , UK
| | - Trudie Chalder
- c Department of Psychological Medicine , King's College London, Weston Education Centre , London , UK
| |
Collapse
|
|
36
|
Coretti L, Cristiano C, Florio E, Scala G, Lama A, Keller S, Cuomo M, Russo R, Pero R, Paciello O, Mattace Raso G, Meli R, Cocozza S, Calignano A, Chiariotti L, Lembo F. Sex-related alterations of gut microbiota composition in the BTBR mouse model of autism spectrum disorder. Sci Rep 2017; 7:45356. [PMID: 28349974 PMCID: PMC5368984 DOI: 10.1038/srep45356] [Citation(s) in RCA: 130] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2016] [Accepted: 02/23/2017] [Indexed: 12/13/2022] Open
Abstract
Alterations of microbiota-gut-brain axis have been invoked in the pathogenesis of autism spectrum disorders (ASD). Mouse models could represent an excellent tool to understand how gut dysbiosis and related alterations may contribute to autistic phenotype. In this study we paralleled gut microbiota (GM) profiles, behavioral characteristics, intestinal integrity and immunological features of colon tissues in BTBR T + tf/J (BTBR) inbred mice, a well established animal model of ASD. Sex differences, up to date poorly investigated in animal models, were specifically addressed. Results showed that BTBR mice of both sexes presented a marked intestinal dysbiosis, alterations of behavior, gut permeability and immunological state with respect to prosocial C57BL/6j (C57) strain. Noticeably, sex-related differences were clearly detected. We identified Bacteroides, Parabacteroides, Sutterella, Dehalobacterium and Oscillospira genera as key drivers of sex-specific gut microbiota profiles associated with selected pathological traits. Taken together, our findings indicate that alteration of GM in BTBR mice shows relevant sex-associated differences and supports the use of BTBR mouse model to dissect autism associated microbiota-gut-brain axis alteration.
Collapse
Affiliation(s)
- Lorena Coretti
- Institute of Endocrinologia ed Oncologia Sperimentale, IEOS, Consiglio Nazionale delle Ricerche CNR, Via S. Pansini, 5, 80131, Naples, Italy
| | - Claudia Cristiano
- Department of Pharmacy, University of Naples Federico II, Via D. Montesano, 49, 80131, Naples, Italy
| | - Ermanno Florio
- Department of Medicina Molecolare e Biotecnologie Mediche, University of Naples Federico II, Via S. Pansini, 5, 80131, Naples, Italy
| | - Giovanni Scala
- Istituto Nazionale di Fisica Nucleare, Sezione di Napoli, Naples, Italy
| | - Adriano Lama
- Department of Pharmacy, University of Naples Federico II, Via D. Montesano, 49, 80131, Naples, Italy
| | - Simona Keller
- Department of Medicina Molecolare e Biotecnologie Mediche, University of Naples Federico II, Via S. Pansini, 5, 80131, Naples, Italy
| | - Mariella Cuomo
- Department of Medicina Molecolare e Biotecnologie Mediche, University of Naples Federico II, Via S. Pansini, 5, 80131, Naples, Italy
| | - Roberto Russo
- Department of Pharmacy, University of Naples Federico II, Via D. Montesano, 49, 80131, Naples, Italy
| | - Raffaela Pero
- Department of Medicina Molecolare e Biotecnologie Mediche, University of Naples Federico II, Via S. Pansini, 5, 80131, Naples, Italy
| | - Orlando Paciello
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Napoli, Italy
| | - Giuseppina Mattace Raso
- Department of Pharmacy, University of Naples Federico II, Via D. Montesano, 49, 80131, Naples, Italy
| | - Rosaria Meli
- Department of Pharmacy, University of Naples Federico II, Via D. Montesano, 49, 80131, Naples, Italy
| | - Sergio Cocozza
- Institute of Endocrinologia ed Oncologia Sperimentale, IEOS, Consiglio Nazionale delle Ricerche CNR, Via S. Pansini, 5, 80131, Naples, Italy.,Department of Medicina Molecolare e Biotecnologie Mediche, University of Naples Federico II, Via S. Pansini, 5, 80131, Naples, Italy
| | - Antonio Calignano
- Department of Pharmacy, University of Naples Federico II, Via D. Montesano, 49, 80131, Naples, Italy
| | - Lorenzo Chiariotti
- Institute of Endocrinologia ed Oncologia Sperimentale, IEOS, Consiglio Nazionale delle Ricerche CNR, Via S. Pansini, 5, 80131, Naples, Italy.,Department of Medicina Molecolare e Biotecnologie Mediche, University of Naples Federico II, Via S. Pansini, 5, 80131, Naples, Italy
| | - Francesca Lembo
- Department of Pharmacy, University of Naples Federico II, Via D. Montesano, 49, 80131, Naples, Italy
| |
Collapse
|
|
37
|
Regueiro M, Greer JB, Szigethy E. Etiology and Treatment of Pain and Psychosocial Issues in Patients With Inflammatory Bowel Diseases. Gastroenterology 2017; 152:430-439.e4. [PMID: 27816599 DOI: 10.1053/j.gastro.2016.10.036] [Citation(s) in RCA: 91] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2016] [Revised: 10/07/2016] [Accepted: 10/27/2016] [Indexed: 12/15/2022]
Abstract
There is increasing evidence that brain-gut interactions are altered during development of inflammatory bowel diseases (IBDs). Understanding the relationship between the neurobiology, psychological symptoms, and social ramifications of IBD can guide comprehensive care for the whole patient. The most common psychological conditions in patients with IBD are chronic abdominal pain, anxiety, and depression. We review the evidence-based data and rates of these conditions and their respective relationship to IBD and the diagnostic approaches to identify patients with these conditions. Different treatment options for pain and psychosocial conditions are discussed, and new models of team-based IBD care are introduced. Providing the health care provider with tools to diagnose and manage psychological conditions in patients with Crohn's disease or ulcerative colitis is necessary for their total care and should be part of quality-improvement initiatives.
Collapse
Affiliation(s)
- Miguel Regueiro
- Division of Gastroenterology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Julia B Greer
- Division of Gastroenterology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Eva Szigethy
- Division of Gastroenterology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.
| |
Collapse
|
|
38
|
Wilburn J, Twiss J, Kemp K, McKenna SP. A qualitative study of the impact of Crohn's disease from a patient's perspective. Frontline Gastroenterol 2017; 8:68-73. [PMID: 28839887 PMCID: PMC5369426 DOI: 10.1136/flgastro-2015-100678] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2016] [Revised: 04/12/2016] [Accepted: 04/15/2016] [Indexed: 02/04/2023] Open
Abstract
OBJECTIVE To understand how the lives of people with Crohn's disease (CD) are affected. Most research in CD has focused on symptoms and functioning rather than on how these outcomes influence quality of life (QoL). DESIGN As part of a study to develop a CD-specific patient-reported outcome measure, qualitative interviews were conducted with patients from Manchester Royal Infirmary to determine how CD affects QoL. The needs-based model was adopted for the study. The interviews, which took the form of focused conversations covering all aspects of the impact of CD and its treatment, were audio-recorded. Theoretical thematic analysis of the transcripts identified needs affected by CD. RESULTS Thirty patients (60% female) aged 25-68 years were interviewed. Participants had experienced CD for between 2 and 40 years. Nearly 1300 statements relating to the impact of CD were identified. Thirteen main need themes were identified: nutrition, hygiene, continence, freedom from infection, security, self-esteem, role, attractiveness, relationships, intimacy, clear-mindedness, pleasure and autonomy. CONCLUSIONS The findings from the interviews indicate that CD has a major impact on need-fulfilment. Such issues should be addressed in CD audit, clinical trials and when evaluating clinical practice.
Collapse
Affiliation(s)
| | | | - Karen Kemp
- Department of Gastroenterology, Manchester Royal Infirmary, Manchester, UK
| | | |
Collapse
|
|
39
|
Patient-reported Anxiety: A Possible Predictor of Pediatric Inflammatory Bowel Disease Health Care Use. Inflamm Bowel Dis 2016; 22:2127-33. [PMID: 27482980 DOI: 10.1097/mib.0000000000000864] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
BACKGROUND Anxiety is linked with adverse health-related outcomes and increased health-seeking behaviors among patients with chronic illness. Yet, this relationship has received little attention in pediatric inflammatory bowel disease. The aim of this study was to examine whether anxiety symptoms predicted youth at increased risk for repeated disease relapse and greater gastrointestinal health care use over the subsequent 12 months. METHODS Eighty-six pediatric patients aged 11 to 18 years (M = 14.7, SD = 2.0), and their caregivers completed a validated anxiety questionnaire during a gastrointestinal specialty appointment (baseline). Medical records were reviewed for the subsequent year to record the number of disease relapses and gastrointestinal health care services and generate disease activity scores at baseline and 12 months. Analysis of variance was used to examine anxiety levels between those who experienced ≤1 versus ≥2 disease relapses. Poisson regressions were used to model the relationship between child- and caregiver-reported anxiety and health care use, controlling for disease activity. RESULTS The sample was predominantly white (81%) and male (56%). Patients with higher anxiety at baseline (M = 19.6; SD = 13.7) had more frequent (≥2) disease relapses compared with those with lower anxiety at baseline (M = 12.6; SD = 10.3). Higher anxiety, irrespective of reporter, also predicted greater total gastrointestinal health care use (P < 0.01). This included hospital-based interventions (P < 0.01), but not office encounters or outpatient endoscopic procedures. Findings remained significant after controlling for disease severity (P < 0.05). CONCLUSIONS Assessment of anxiety may be one mechanism by which to identify those youth who are most vulnerable for disease exacerbation and costly interventions in the near future.
Collapse
|
|
40
|
Mikocka-Walus A, Pittet V, Rossel JB, von Känel R, Bauerfeind P, Beglinger C, Begré S, Belli D, Bengoa JM, Biedermann L, Bigler B, Binek J, Blattmann M, Boehm S, Borovicka J, Braegger CP, Brunner N, Bühr P, Burnand B, Burri E, Buyse S, Cremer M, Criblez DH, de Saussure P, Degen L, Delarive J, Doerig C, Dora B, Dorta G, Egger M, Ehmann T, El-Wafa A, Engelmann M, Ezri J, Felley C, Fliegner M, Fournier N, Fraga M, Frei P, Frei R, Fried M, Froehlich F, Funk C, Ivano Furlano R, Gallot-Lavallée S, Geyer M, Girardin M, Golay D, Grandinetti T, Gysi B, Haack H, Haarer J, Helbling B, Hengstler P, Herzog D, Hess C, Heyland K, Hinterleitner T, Hiroz P, Hirschi C, Hruz P, Iwata R, Jost R, Juillerat P, Kessler Brondolo V, Knellwolf C, Knoblauch C, Köhler H, Koller R, Krieger-Grübel C, Kullak-Ublick G, Künzler P, Landolt M, Lange R, Serge Lehmann F, Macpherson A, Maerten P, Maillard MH, Manser C, Manz M, Marbet U, Marx G, Matter C, McLin V, Meier R, Mendanova M, Meyenberger C, Michetti P, Misselwitz B, Moradpour D, Morell B, Mosler P, Mottet C, Müller C, Müller P, Müllhaupt B, Münger-Beyeler C, Musso L, Nagy A, et alMikocka-Walus A, Pittet V, Rossel JB, von Känel R, Bauerfeind P, Beglinger C, Begré S, Belli D, Bengoa JM, Biedermann L, Bigler B, Binek J, Blattmann M, Boehm S, Borovicka J, Braegger CP, Brunner N, Bühr P, Burnand B, Burri E, Buyse S, Cremer M, Criblez DH, de Saussure P, Degen L, Delarive J, Doerig C, Dora B, Dorta G, Egger M, Ehmann T, El-Wafa A, Engelmann M, Ezri J, Felley C, Fliegner M, Fournier N, Fraga M, Frei P, Frei R, Fried M, Froehlich F, Funk C, Ivano Furlano R, Gallot-Lavallée S, Geyer M, Girardin M, Golay D, Grandinetti T, Gysi B, Haack H, Haarer J, Helbling B, Hengstler P, Herzog D, Hess C, Heyland K, Hinterleitner T, Hiroz P, Hirschi C, Hruz P, Iwata R, Jost R, Juillerat P, Kessler Brondolo V, Knellwolf C, Knoblauch C, Köhler H, Koller R, Krieger-Grübel C, Kullak-Ublick G, Künzler P, Landolt M, Lange R, Serge Lehmann F, Macpherson A, Maerten P, Maillard MH, Manser C, Manz M, Marbet U, Marx G, Matter C, McLin V, Meier R, Mendanova M, Meyenberger C, Michetti P, Misselwitz B, Moradpour D, Morell B, Mosler P, Mottet C, Müller C, Müller P, Müllhaupt B, Münger-Beyeler C, Musso L, Nagy A, Neagu M, Nichita C, Niess J, Noël N, Nydegger A, Obialo N, Oneta C, Oropesa C, Peter U, Peternac D, Marie Petit L, Piccoli-Gfeller F, Beatrice Pilz J, Pittet V, Raschle N, Rentsch R, Restellini S, Richterich JP, Rihs S, Alain Ritz M, Roduit J, Rogler D, Rogler G, Rossel JB, Sagmeister M, Saner G, Sauter B, Sawatzki M, Schäppi M, Scharl M, Schelling M, Schibli S, Schlauri H, Schmid Uebelhart S, Schnegg JF, Schoepfer A, Seibold F, Seirafi M, Semadeni GM, Semela D, Senning A, Sidler M, Sokollik C, Spalinger J, Spangenberger H, Stadler P, Steuerwald M, Straumann A, Straumann-Funk B, Sulz M, Thorens J, Tiedemann S, Tutuian R, Vavricka S, Viani F, Vögtlin J, Von Känel R, Vonlaufen A, Vouillamoz D, Vulliamy R, Wermuth J, Werner H, Wiesel P, Wiest R, Wylie T, Zeitz J, Zimmermann D. Symptoms of Depression and Anxiety Are Independently Associated With Clinical Recurrence of Inflammatory Bowel Disease. Clin Gastroenterol Hepatol 2016; 14:829-835.e1. [PMID: 26820402 DOI: 10.1016/j.cgh.2015.12.045] [Show More Authors] [Citation(s) in RCA: 262] [Impact Index Per Article: 29.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2015] [Revised: 12/14/2015] [Accepted: 12/23/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS We examined the relationship between symptoms of depression and anxiety and clinical recurrence of inflammatory bowel disease (IBD) in a large patient cohort. We considered the progression of depression and anxiety over time. METHODS We collected clinical and treatment data on 2007 adult participants of the Swiss IBD study (56% with Crohn's disease [CD], 48% male) performed in Switzerland from 2006 through 2015. Depression and anxiety symptoms were quantified by using the Hospital Anxiety and Depression Scale. The relationship between depression and anxiety scores and clinical recurrence was analyzed by using survival-time techniques. RESULTS We found a significant association between symptoms of depression and clinical recurrence over time (for all patients with IBD, P = .000001; for subjects with CD, P = .0007; for subjects with ulcerative colitis, P = .005). There was also a significant relationship between symptoms of anxiety and clinical recurrence over time in all subjects with IBD (P = .0014) and in subjects with CD (P = .031) but not ulcerative colitis (P = .066). CONCLUSIONS In an analysis of a large cohort of subjects with IBD, we found a significant association between symptoms of depression or anxiety and clinical recurrence. Patients with IBD should therefore be screened for clinically relevant levels of depression and anxiety and referred to psychologists or psychiatrists for further evaluation and treatment.
Collapse
Affiliation(s)
- Antonina Mikocka-Walus
- Department of Health Sciences, University of York, York, United Kingdom; School of Psychology, University of Adelaide, Adelaide, Australia; Foundation Brocher, Geneva, Switzerland.
| | - Valerie Pittet
- Health Care Evaluation Unit, Institute of Social and Preventive Medicine, University of Lausanne, Lausanne, Switzerland
| | - Jean-Benoît Rossel
- Health Care Evaluation Unit, Institute of Social and Preventive Medicine, University of Lausanne, Lausanne, Switzerland
| | - Roland von Känel
- Department of Clinical Research, University of Bern, Bern, Switzerland; Department of Neurology, Inselspital, Bern University Hospital, Bern, Switzerland; Department of Psychosomatic Medicine, Clinic Barmelweid, Barmelweid, Switzerland
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
41
|
Jang SH, Ryu HS, Choi SC, Lee SY. Psychological factors influence the overlap syndrome in functional gastrointestinal disorders and their effect on quality of life among firefighters in South Korea. J Dig Dis 2016; 17:236-43. [PMID: 26896638 DOI: 10.1111/1751-2980.12330] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2015] [Revised: 02/05/2016] [Accepted: 02/17/2016] [Indexed: 12/11/2022]
Abstract
OBJECTIVE The aim of this study was to investigate the predictor variables that could influence overlap syndrome in functional gastrointestinal disorders (FGID) among firefighters in Korea. METHODS Data collected from 1217 firefighters in Korea were reviewed. FGID were diagnosed according to the Rome III diagnostic criteria. Psychological factors were measured by self-reported questionnaires. The scores for depression, anxiety, quality of life (QOL) and occupational job stress were analyzed. The correlation between psychological factors and QOL was analyzed and a stepwise multiple regression analysis was performed. RESULTS FGID were observed in 461 (37.9%) participants. In those with FGID, functional heartburn (FH) was most common (32.2%), followed by functional dyspepsia (12.2%). Patients with overlap syndrome had the highest depression, anxiety and occupational stress score than those having non-overlap syndrome and healthy controls, respectively (depression: F = 142.29, η(2) = 0.190; anxiety: F = 88.33, η(2) = 0.127; occupational stress: F = 43.68, η(2) = 0.067; all P < 0.001). Healthy controls had the highest QOL score (F = 73.39, P < 0.001, η(2) = 0.108). Pychological factors were significantly correlated with QOL in the overlap syndrome of FGID. After the stepwise selection, the final model explained 45.6% of predictable variance and contained four significant variables: depression, self-esteem, occupational stress and anxiety. CONCLUSIONS Psychological factors are associated with the overlap syndrome of FGID. Acknowledging this common comorbidity may facilitate the recognition and treatment of patients with FGID.
Collapse
Affiliation(s)
- Seung-Ho Jang
- Department of Psychiatry, School of Medicine, Wonkwang University, Iksan, Korea
| | - Han-Seung Ryu
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Wonkwang University, Iksan, Korea
| | - Suck-Chei Choi
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Wonkwang University, Iksan, Korea
| | - Sang-Yeol Lee
- Department of Psychiatry, School of Medicine, Wonkwang University, Iksan, Korea
| |
Collapse
|
|
42
|
Moloney RD, Johnson AC, O'Mahony SM, Dinan TG, Greenwood‐Van Meerveld B, Cryan JF. Stress and the Microbiota-Gut-Brain Axis in Visceral Pain: Relevance to Irritable Bowel Syndrome. CNS Neurosci Ther 2016; 22:102-17. [PMID: 26662472 PMCID: PMC6492884 DOI: 10.1111/cns.12490] [Citation(s) in RCA: 257] [Impact Index Per Article: 28.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2015] [Revised: 11/05/2015] [Accepted: 11/05/2015] [Indexed: 02/06/2023] Open
Abstract
Visceral pain is a global term used to describe pain originating from the internal organs of the body, which affects a significant proportion of the population and is a common feature of functional gastrointestinal disorders (FGIDs) such as irritable bowel syndrome (IBS). While IBS is multifactorial, with no single etiology to completely explain the disorder, many patients also experience comorbid behavioral disorders, such as anxiety or depression; thus, IBS is described as a disorder of the gut-brain axis. Stress is implicated in the development and exacerbation of visceral pain disorders. Chronic stress can modify central pain circuitry, as well as change motility and permeability throughout the gastrointestinal (GI) tract. More recently, the role of the gut microbiota in the bidirectional communication along the gut-brain axis, and subsequent changes in behavior, has emerged. Thus, stress and the gut microbiota can interact through complementary or opposing factors to influence visceral nociceptive behaviors. This review will highlight the evidence by which stress and the gut microbiota interact in the regulation of visceral nociception. We will focus on the influence of stress on the microbiota and the mechanisms by which microbiota can affect the stress response and behavioral outcomes with an emphasis on visceral pain.
Collapse
Affiliation(s)
- Rachel D. Moloney
- Laboratory of NeurogastroenterologyAPC Microbiome InstituteUniversity College CorkCorkIreland
- Present address:
Oklahoma Center for NeuroscienceUniversity of Oklahoma Health Science CenterOklahoma CityOKUSA
| | - Anthony C. Johnson
- Oklahoma Center for NeuroscienceUniversity of Oklahoma Health Science CenterOklahoma CityOKUSA
| | - Siobhain M. O'Mahony
- Laboratory of NeurogastroenterologyAPC Microbiome InstituteUniversity College CorkCorkIreland
- Department of Anatomy and NeuroscienceUniversity College CorkCorkIreland
| | - Timothy G. Dinan
- Laboratory of NeurogastroenterologyAPC Microbiome InstituteUniversity College CorkCorkIreland
- Department of Psychiatry and Neurobehavioural ScienceUniversity College CorkCorkIreland
| | - Beverley Greenwood‐Van Meerveld
- Oklahoma Center for NeuroscienceUniversity of Oklahoma Health Science CenterOklahoma CityOKUSA
- V.A. Medical CenterOklahoma CityOKUSA
| | - John F. Cryan
- Laboratory of NeurogastroenterologyAPC Microbiome InstituteUniversity College CorkCorkIreland
- Department of Anatomy and NeuroscienceUniversity College CorkCorkIreland
| |
Collapse
|
|
43
|
Burkhalter H, Stucki-Thür P, David B, Lorenz S, Biotti B, Rogler G, Pittet V. Assessment of inflammatory bowel disease patient's needs and problems from a nursing perspective. Digestion 2015; 91:128-41. [PMID: 25677558 DOI: 10.1159/000371654] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2014] [Accepted: 12/18/2014] [Indexed: 02/04/2023]
Abstract
BACKGROUND In this study, we aimed at assessing Inflammatory Bowel Disease patients' needs and current nursing practice to investigate to what extent consensus statements (European Crohn's and Colitis Organization) on the nursing roles in caring for patients with IBD concur with local practice. METHODS We used a mixed-method convergent design to combine quantitative data prospectively collected in the Swiss IBD cohort study and qualitative data from structured interviews with IBD healthcare experts. Symptoms, quality of life, and anxiety and depression scores were retrieved from physician charts and patient self-reported questionnaires. Descriptive analyses were performed based on quantitative and qualitative data. RESULTS 230 patients of a single center were included, 60% of patients were males, and median age was 40 (range 18-85). The prevalence of abdominal pain was 42%. Self-reported data were obtained from 75 out of 230 patients. General health was perceived significantly lower compared with the general population (p < 0.001). Prevalence of tiredness was 73%; sleep problems, 78%; issues related to work, 20%; sexual constraints, 35%; diarrhea, 67%; being afraid of not finding a bathroom, 42%; depression, 11%; and anxiety symptoms, 23%. According to experts' interviews, the consensus statements are found mostly relevant with many recommendations that are not yet realized in clinical practice. CONCLUSION Identified prevalence may help clinicians in detecting patients at risk and improve patient management.
Collapse
Affiliation(s)
- Hanna Burkhalter
- Department of Abdominal Surgery, University Hospital Zurich, Zurich, Switzerland
| | | | | | | | | | | | | |
Collapse
|
|
44
|
Mikocka-Walus A, Bampton P, Hetzel D, Hughes P, Esterman A, Andrews JM. Cognitive-behavioural therapy has no effect on disease activity but improves quality of life in subgroups of patients with inflammatory bowel disease: a pilot randomised controlled trial. BMC Gastroenterol 2015; 15:54. [PMID: 25934170 PMCID: PMC4427935 DOI: 10.1186/s12876-015-0278-2] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2014] [Accepted: 04/13/2015] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Studies have demonstrated usefulness of cognitive-behavioural therapy (CBT) in managing distress in inflammatory bowel disease (IBD); however, few have focused on IBD course. The present trial aimed to investigate whether adding CBT to standard treatment prolongs remission in IBD in comparison to standard therapy alone. METHODS A 2-arm parallel pragmatic randomised controlled trial (+CBT - standard care plus either face-to-face (F2F) or online CBT over 10 weeks versus standard care alone (SC)) was conducted with adult patients in remission. IBD remission at 12 months since baseline was the primary outcome measure while the secondary outcome measures were mental health status and quality of life (QoL). Linear mixed-effect models were used to compare groups on outcome variables while controlling for baseline. RESULTS Participants were 174 patients with IBD (90 +CBT, 84 SC). There was no difference in remission rates between groups, with similar numbers flaring at 12 months. Groups did not differ in anxiety, depression or coping at 6 or 12 months (p >0.05). When only participants classified as 'in need' (young, high baseline IBD activity, recently diagnosed; poor mental health) were examined in the post-hoc analysis (n = 74, 34 CBT and 40 controls), CBT significantly improved mental QoL (p = .034, d = .56) at 6 months. Online CBT group had a higher score on Precontemplation than the F2F group, which is consistent with less developed coping with IBD in the cCBT group (p = .045). CONCLUSIONS Future studies should direct psychological interventions to patients 'in need' and attempt to recruit larger samples to compensate for significant attrition when using online CBT. TRIAL REGISTRATION The protocol was registered on 21/10/2009 with the Australian New Zealand Clinical Trials Registry (ID: ACTRN12609000913279).
Collapse
Affiliation(s)
- Antonina Mikocka-Walus
- School of Nursing and Midwifery and Sansom Institute for Health Research, University of South Australia, Adelaide, Australia. .,Department of Health Sciences, University of York, Area 4, ARRC Building, Heslington, YO10 5DD, UK. .,School of Psychology, University of Adelaide, Adelaide, Australia.
| | - Peter Bampton
- School of Medicine, Flinders University, Adelaide, Australia. .,Department of Gastroenterology and Hepatology, Flinders Medical Centre, Bedford Park, Australia.
| | - David Hetzel
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, Australia.
| | - Patrick Hughes
- Nerve-Gut Research Laboratory, Discipline of Medicine, University of Adelaide, Adelaide, Australia.
| | - Adrian Esterman
- School of Nursing and Midwifery and Sansom Institute for Health Research, University of South Australia, Adelaide, Australia.
| | - Jane M Andrews
- School of Medicine, Flinders University, Adelaide, Australia. .,Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, Australia. .,School of Medicine, University of Adelaide, Adelaide, Australia.
| |
Collapse
|
|
45
|
Carding S, Verbeke K, Vipond DT, Corfe BM, Owen LJ. Dysbiosis of the gut microbiota in disease. MICROBIAL ECOLOGY IN HEALTH AND DISEASE 2015; 26:26191. [PMID: 25651997 PMCID: PMC4315779 DOI: 10.3402/mehd.v26.26191] [Citation(s) in RCA: 785] [Impact Index Per Article: 78.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
There is growing evidence that dysbiosis of the gut microbiota is associated with the pathogenesis of both intestinal and extra-intestinal disorders. Intestinal disorders include inflammatory bowel disease, irritable bowel syndrome (IBS), and coeliac disease, while extra-intestinal disorders include allergy, asthma, metabolic syndrome, cardiovascular disease, and obesity. In many of these conditions, the mechanisms leading to disease development involves the pivotal mutualistic relationship between the colonic microbiota, their metabolic products, and the host immune system. The establishment of a ‘healthy’ relationship early in life appears to be critical to maintaining intestinal homeostasis. Whilst we do not yet have a clear understanding of what constitutes a ‘healthy’ colonic microbiota, a picture is emerging from many recent studies identifying particular bacterial species associated with a healthy microbiota. In particular, the bacterial species residing within the mucus layer of the colon, either through direct contact with host cells, or through indirect communication via bacterial metabolites, may influence whether host cellular homeostasis is maintained or whether inflammatory mechanisms are triggered. In addition to inflammation, there is some evidence that perturbations in the gut microbiota is involved with the development of colorectal cancer. In this case, dysbiosis may not be the most important factor, rather the products of interaction between diet and the microbiome. High-protein diets are thought to result in the production of carcinogenic metabolites from the colonic microbiota that may result in the induction of neoplasia in the colonic epithelium. Ever more sensitive metabolomics methodologies reveal a suite of small molecules produced in the microbiome which mimic or act as neurosignallers or neurotransmitters. Coupled with evidence that probiotic interventions may alter psychological endpoints in both humans and in rodent models, these data suggest that CNS-related co-morbidities frequently associated with GI disease may originate in the intestine as a result of microbial dysbiosis. This review outlines the current evidence showing the extent to which the gut microbiota contributes to the development of disease. Based on evidence to date, we can assess the potential to positively modulate the composition of the colonic microbiota and ameliorate disease activity through bacterial intervention.
Collapse
Affiliation(s)
- Simon Carding
- Institute of Food Research, Norwich, UK.,Norwich Medical School, University of East Anglia, Norwich, UK
| | - Kristin Verbeke
- Translational Research in GastroIntestinal Disorders, KU Leuven, Leuven, Belgium
| | - Daniel T Vipond
- Institute of Food Research, Norwich, UK.,Norwich Medical School, University of East Anglia, Norwich, UK
| | - Bernard M Corfe
- Molecular Gastroenterology Research Group, Department of Oncology, University of Sheffield, Sheffield, UK.,Insigneo Institute for in silico Medicine, University of Sheffield, Sheffield, UK;
| | - Lauren J Owen
- Human Nutrition Unit, Department of Oncology, University of Sheffield, Sheffield, UK
| |
Collapse
|
|
46
|
Abstract
It is generally agreed that environmental factors trigger the onset and cause flares of inflammatory bowel disease. Although we have learned much about genetic susceptibility factors of inflammatory bowel disease in recent years, our knowledge on these environmental factors is limited. The sum of all environmental factors a human is exposed to during lifetime has been termed the exposome. The challenge of investigating the exposome is discussed in this overview. The environmental exposure of a subject causes changes in the intestinal microbiota and subsequently changes the epigenetic imprinting of the mucosa and the associated immune system. Some relevant environmental factors have been investigated in recent years in inflammatory bowel disease and other (auto)inflammatory disease. These factors can be categorized in air pollution, diet, drugs, stress, infections, water pollution, food additives, and lifestyle. Examples from those categories and their potential pathophysiological mechanism are discussed.
Collapse
|
|
47
|
Rodiño-Janeiro BK, Alonso-Cotoner C, Pigrau M, Lobo B, Vicario M, Santos J. Role of Corticotropin-releasing Factor in Gastrointestinal Permeability. J Neurogastroenterol Motil 2015; 21:33-50. [PMID: 25537677 PMCID: PMC4288093 DOI: 10.5056/jnm14084] [Citation(s) in RCA: 83] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2014] [Revised: 10/06/2014] [Accepted: 10/07/2014] [Indexed: 12/11/2022] Open
Abstract
The interface between the intestinal lumen and the mucosa is the location where the majority of ingested immunogenic particles face the scrutiny of the vast gastrointestinal immune system. Upon regular physiological conditions, the intestinal micro-flora and the epithelial barrier are well prepared to process daily a huge amount of food-derived antigens and non-immunogenic particles. Similarly, they are ready to prevent environmental toxins and microbial antigens to penetrate further and interact with the mucosal-associated immune system. These functions promote the development of proper immune responses and oral tolerance and prevent disease and inflammation. Brain-gut axis structures participate in the processing and execution of response signals to external and internal stimuli. The brain-gut axis integrates local and distant regulatory networks and super-systems that serve key housekeeping physiological functions including the balanced functioning of the intestinal barrier. Disturbance of the brain-gut axis may induce intestinal barrier dysfunction, increasing the risk of uncontrolled immunological reactions, which may indeed trigger transient mucosal inflammation and gut disease. There is a large body of evidence indicating that stress, through the brain-gut axis, may cause intestinal barrier dysfunction, mainly via the systemic and peripheral release of corticotropin-releasing factor. In this review, we describe the role of stress and corticotropin-releasing factor in the regulation of gastrointestinal permeability, and discuss the link to both health and pathological conditions.
Collapse
Affiliation(s)
- Bruno K Rodiño-Janeiro
- Neuro-Immuno-Gastroenterology Group, Digestive Diseases Research Unit, Gastroenterology Department, Hospital Universitari Vall d'Hebron, Vall d' Hebron Research Institute; and Department of Medicine, Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Barcelona, Spain
| | - Carmen Alonso-Cotoner
- Neuro-Immuno-Gastroenterology Group, Digestive Diseases Research Unit, Gastroenterology Department, Hospital Universitari Vall d'Hebron, Vall d' Hebron Research Institute; and Department of Medicine, Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Barcelona, Spain
| | - Marc Pigrau
- Neuro-Immuno-Gastroenterology Group, Digestive Diseases Research Unit, Gastroenterology Department, Hospital Universitari Vall d'Hebron, Vall d' Hebron Research Institute; and Department of Medicine, Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Barcelona, Spain
| | - Beatriz Lobo
- Neuro-Immuno-Gastroenterology Group, Digestive Diseases Research Unit, Gastroenterology Department, Hospital Universitari Vall d'Hebron, Vall d' Hebron Research Institute; and Department of Medicine, Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Barcelona, Spain
| | - María Vicario
- Neuro-Immuno-Gastroenterology Group, Digestive Diseases Research Unit, Gastroenterology Department, Hospital Universitari Vall d'Hebron, Vall d' Hebron Research Institute; and Department of Medicine, Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Barcelona, Spain
| | - Javier Santos
- Neuro-Immuno-Gastroenterology Group, Digestive Diseases Research Unit, Gastroenterology Department, Hospital Universitari Vall d'Hebron, Vall d' Hebron Research Institute; and Department of Medicine, Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Barcelona, Spain
| |
Collapse
|
|
48
|
Prinsloo S, Lyle RR. The Microbiome, Gut-Brain-Axis, and Implications for Brain Health. NEUROREGULATION 2015; 2:158-161. [PMID: 28955721 DOI: 10.15540/nr.2.4.158] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
As Antonio Damasio highlighted back in 1994, Descartes' division of mind and body slowed the full realization of the connectedness of the brain and the body by centuries. The simple fact that homeostasis in the brain was fully interconnected with the body has eluded researchers and clinicians even after the connection was well established. Recent studies reporting the central role in dysfunction of mental systems as a result of inflammation in the gut and the autonomic nervous system (ANS) was yet one more reminder that the entire system is connected and interdependent. Central to this discovery and its application to mental function has been the growing field of study of the microbiome. This article is an attempt to situate those who are active in the variety of ways and means of treating the brain in the essential role that is likely being played by a vast community of bacteria living in the bowels of the human being and influencing all of the higher and most "sophisticated" aspects of human interchange and thought. It is the authors hope that this brief introduction will remind and inform researchers and clinicians that the organism is more interconnected and more complex than we have tended to think and that disorders of the mind are likely also, often disorders of the gut.
Collapse
Affiliation(s)
- Sarah Prinsloo
- The University of Texas MD Anderson Cancer Center, Houston, Texas
| | | |
Collapse
|
|
49
|
Moloney RD, O'Mahony SM, Dinan TG, Cryan JF. Stress-induced visceral pain: toward animal models of irritable-bowel syndrome and associated comorbidities. Front Psychiatry 2015; 6:15. [PMID: 25762939 PMCID: PMC4329736 DOI: 10.3389/fpsyt.2015.00015] [Citation(s) in RCA: 102] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2014] [Accepted: 01/28/2015] [Indexed: 12/12/2022] Open
Abstract
Visceral pain is a global term used to describe pain originating from the internal organs, which is distinct from somatic pain. It is a hallmark of functional gastrointestinal disorders such as irritable-bowel syndrome (IBS). Currently, the treatment strategies targeting visceral pain are unsatisfactory, with development of novel therapeutics hindered by a lack of detailed knowledge of the underlying mechanisms. Stress has long been implicated in the pathophysiology of visceral pain in both preclinical and clinical studies. Here, we discuss the complex etiology of visceral pain reviewing our current understanding in the context of the role of stress, gender, gut microbiota alterations, and immune functioning. Furthermore, we review the role of glutamate, GABA, and epigenetic mechanisms as possible therapeutic strategies for the treatment of visceral pain for which there is an unmet medical need. Moreover, we discuss the most widely described rodent models used to model visceral pain in the preclinical setting. The theory behind, and application of, animal models is key for both the understanding of underlying mechanisms and design of future therapeutic interventions. Taken together, it is apparent that stress-induced visceral pain and its psychiatric comorbidities, as typified by IBS, has a multifaceted etiology. Moreover, treatment strategies still lag far behind when compared to other pain modalities. The development of novel, effective, and specific therapeutics for the treatment of visceral pain has never been more pertinent.
Collapse
Affiliation(s)
- Rachel D Moloney
- Laboratory of Neurogastroenterology, Alimentary Pharmabiotic Centre, Biosciences Institute, University College Cork , Cork , Ireland
| | - Siobhain M O'Mahony
- Laboratory of Neurogastroenterology, Alimentary Pharmabiotic Centre, Biosciences Institute, University College Cork , Cork , Ireland ; Department of Anatomy and Neuroscience, University College Cork , Cork , Ireland
| | - Timothy G Dinan
- Laboratory of Neurogastroenterology, Alimentary Pharmabiotic Centre, Biosciences Institute, University College Cork , Cork , Ireland ; Department of Psychiatry, University College Cork , Cork , Ireland
| | - John F Cryan
- Laboratory of Neurogastroenterology, Alimentary Pharmabiotic Centre, Biosciences Institute, University College Cork , Cork , Ireland ; Department of Anatomy and Neuroscience, University College Cork , Cork , Ireland
| |
Collapse
|
|
50
|
van Assche G, Dignass A, Bokemeyer B, Danese S, Gionchetti P, Moser G, Beaugerie L, Gomollón F, Häuser W, Herrlinger K, Oldenburg B, Panes J, Portela F, Rogler G, Stein J, Tilg H, Travis S, Lindsay JO. [Second European evidence-based consensus on the diagnosis and management of ulcerative colitis Part 3: Special situations (Spanish version)]. REVISTA DE GASTROENTEROLOGIA DE MEXICO 2015; 80:74-106. [PMID: 25769216 DOI: 10.1016/j.rgmx.2014.10.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/16/2014] [Accepted: 10/23/2014] [Indexed: 12/12/2022]
Affiliation(s)
- G van Assche
- En nombre de la ECCO; G.V.A. y A.D. actúan como coordinadores del consenso y han contribuido igualmente para este trabajo.
| | - A Dignass
- G.V.A. y A.D. actúan como coordinadores del consenso y han contribuido igualmente para este trabajo.
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|