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Aliu A, Bosch DHCA, Keszthelyi D, Rezazadeh Ardabili A, Colombel JF, Sawyer R, Törnblom H, Hart A, Jonkers DMAE, Pierik MJ, Mujagic Z. Review article: A practical approach to persistent gastrointestinal symptoms in inflammatory bowel disease in remission. Aliment Pharmacol Ther 2024; 59:1470-1488. [PMID: 38590140 DOI: 10.1111/apt.17988] [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: 10/16/2023] [Revised: 11/29/2023] [Accepted: 03/25/2024] [Indexed: 04/10/2024]
Abstract
BACKGROUND Persistent gastrointestinal symptoms are prevalent in adult patients with inflammatory bowel disease (IBD), even when endoscopic remission is reached. These symptoms can have profound negative effects on the quality of life of affected patients and can be difficult to treat. They may be caused by IBD-related complications or comorbid disorders, but they can also be explained by irritable bowel syndrome (IBS)-like symptoms. AIMS To provide a practical step-by-step guide to diagnose and treat persistent gastrointestinal symptoms in patients with IBD in remission via a personalised approach. METHODS We scrutinised relevant literature on causes, diagnostics and treatment of persistent gastrointestinal symptoms (abdominal pain or discomfort, bloating, abdominal distension, diarrhoea, constipation and faecal incontinence) in patients with IBD in remission. RESULTS A graphical practical guide for several steps in diagnosing, identifying potential triggers and adequate treatment of persistent gastrointestinal symptoms in IBD in remission is provided based on supporting literature. The first part of this review focuses on the diagnostic and treatment approaches for potential IBD-related complications and comorbidities. The second part describes the approach to IBS-like symptoms in IBD in remission. CONCLUSIONS Persistent gastrointestinal symptoms in IBD in remission can be traced back to potential pathophysiological mechanisms in individual patients and can be treated adequately. For both IBD-related complications and comorbidities and IBS-like symptoms in IBD in remission, pharmacological, dietary, lifestyle or psychological treatments can be effective. A systematic and personalised approach is required to reduce the burden for patients, healthcare systems, and society.
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Affiliation(s)
- Arta Aliu
- Department Gastroenterology and Hepatology, Maastricht University Medical Center+, Maastricht, the Netherlands
- NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands
| | - Daan H C A Bosch
- Department Gastroenterology and Hepatology, Maastricht University Medical Center+, Maastricht, the Netherlands
- NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands
| | - Daniel Keszthelyi
- Department Gastroenterology and Hepatology, Maastricht University Medical Center+, Maastricht, the Netherlands
- NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands
| | - Ashkan Rezazadeh Ardabili
- Department Gastroenterology and Hepatology, Maastricht University Medical Center+, Maastricht, the Netherlands
- NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands
| | - Jean-Frederic Colombel
- The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Rachel Sawyer
- IBD Patient Advocacy, Founder of the Bottom Line IBD and IBD Women, UK
| | - Hans Törnblom
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Ailsa Hart
- IBD Unit, St Mark's Hospital & Imperial College, London, UK
| | - Daisy M A E Jonkers
- Department Gastroenterology and Hepatology, Maastricht University Medical Center+, Maastricht, the Netherlands
- NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands
| | - Marieke J Pierik
- Department Gastroenterology and Hepatology, Maastricht University Medical Center+, Maastricht, the Netherlands
- NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands
| | - Zlatan Mujagic
- Department Gastroenterology and Hepatology, Maastricht University Medical Center+, Maastricht, the Netherlands
- NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands
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Zhang P, Mao R, Zhang C, Qiu Y, Chen M. Gastrointestinal injury induced by immunomodulators: A review article. Therap Adv Gastroenterol 2023; 16:17562848231158549. [PMID: 37113189 PMCID: PMC10126616 DOI: 10.1177/17562848231158549] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Accepted: 02/02/2023] [Indexed: 04/29/2023] Open
Abstract
An increasing number of immunomodulators, either anti-inflammatory or immunity-enhancing, have brought about a revolutionary effect in the management of a variety of autoimmune disorders and malignancies. However, their ability to cause gastrointestinal (GI) injury and induce GI symptoms has been increasingly and unexpectedly recognized. GI injury associated with immunomodulators may demonstrate various histologic and endoscopic patterns. Optimal diagnosis and treatment require a multidisciplinary approach. This review aims to provide an overview of the literature on its pathogenesis, the clinical, endoscopic, and histologic features, and suggested approaches to manage these newly recognized immunomodulator-induced GI adverse effects (AEs). We also reviewed current biomarkers predictive of GI toxicity and potential risk factors to identify susceptible patients. In addition, these immune-mediated AEs were compared with inflammatory bowel disease, a well-documented form of inflammation-driven GI injury. We hope this review will raise awareness and vigilance among clinicians of these entities to increase early diagnosis and rapid referral to specialist care.
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Affiliation(s)
- Pingxin Zhang
- Department of Gastroenterology, The First
Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province,
China
| | - Ren Mao
- Department of Gastroenterology, The First
Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province,
China
| | - Chuhan Zhang
- Department of Gastroenterology, The First
Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province,
China
| | | | - Minhu Chen
- Department of Gastroenterology, The First
Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province,
China
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Hamdeh S, Micic D, Hanauer S. Review article: drug-induced small bowel injury. Aliment Pharmacol Ther 2021; 54:1370-1388. [PMID: 34668591 DOI: 10.1111/apt.16642] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 07/05/2021] [Accepted: 09/29/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND Drug-induced gastrointestinal injury has been increasingly reported, but its exact incidence is not known. The small and large intestines represent the most affected sites of injury, accounting for 20%-40% of all gastrointestinal side effects. AIM To provide an updated literature review detailing medications linked to the development of small bowel injury. METHODS We conducted a literature search on PubMed from its inception to May 1, 2021. We included English-language original studies, meta-analyses, systematic reviews, review articles and case reports. RESULTS Drug-induced enteropathy can range from asymptomatic histological changes resulting in a subtle, self-limited disease to a chronic inflammatory condition mimicking inflammatory bowel disease, or bowel perforation. Endoscopy can demonstrate erythema, mucosal friability, oedema, erosions, ulcers or strictures in severe cases. Histology may include mucosal erosions and ulcerations, focal active enteritis, villous atrophy, epithelial apoptosis or necrotising enteritis. A well-established association has been found with the use of nonsteroidal anti-inflammatory drugs, immunosuppressants, chemotherapeutic agents, antibiotics, immunotherapies, etanercept and olmesartan. Possible associations have been reported with other biologic agents, medications used for glycemic control, antihypertensives, cholinesterase inhibitors, potassium and iron supplements, with conflicting data regarding contraceptives/hormonal therapy and isotretinoin. CONCLUSION Physicians should be aware of the manifestations of drug-induced enteropathy as early recognition can lead to prompt discontinuation of the offending therapy and, therefore, a reduced risk of future complications.
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Affiliation(s)
- Shadi Hamdeh
- Department of Internal Medicine, Division of Gastroenterology, Hepatology and Motility, University of Kansas, Lawrence, KS, USA
| | - Dejan Micic
- Department of Internal Medicine, Section of Gastroenterology, Hepatology and Nutrition, University of Chicago, Chicago, IL, USA
| | - Stephen Hanauer
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
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Scarpignato C, Bjarnason I. Drug-Induced Small Bowel Injury: a Challenging and Often Forgotten Clinical Condition. Curr Gastroenterol Rep 2019; 21:55. [PMID: 31720893 DOI: 10.1007/s11894-019-0726-1] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE OF REVIEW Most drugs are given by the oral route. Oral intake allows direct contact between the drug and the entire GI tract mucosa, exposing it to potential topical damage until absorption. Medication-induced GI symptoms and lesions are therefore commonly encountered in clinical practice. This review will examine the most common drugs or classes of drugs affecting small bowel function and/or structure. RECENT FINDINGS Since non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used medicines, NSAID enteropathy is highly prevalent and brings about considerable morbidity. Antimicrobials and proton-pump inhibitors profoundly modify intestinal microbiota, affecting gut sensory and motor functions, while other drugs (like iron and gold derivatives) impair intestinal permeability. Olmesartan (and likely ACE inhibitors) induce villous atrophy and consequent malabsorption. Mycophenolate mofetil, cancer chemotherapeutic agents, and immune checkpoint inhibitors cause intestinal inflammation, abdominal pain, and diarrhea. Potassium chloride supplements may induce small bowel ulceration, stenosis, and perforation while the cotraceptive pill and anticoagulants are associated with intestinal ischemia and spontaneous intramural hematoma, respectively. In clinical practice, a deep knowledge of clinical pharmacology and toxicology and a high degree of suspicion of drug-related adverse events are mandatory. Only then, the practicing physician will be able to diagnose medication-induced small bowel lesions correctly and will implement the best strategies to treat them.
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Affiliation(s)
- Carmelo Scarpignato
- LUdeS Lugano Campus, Lugano, Switzerland.
- United Campus of Malta, Gzira, Malta.
- Faculty of Medicine, Chinese University of Hong Kong, ShaTin, Hong Kong.
- Department of Medicine & Surgery, University of Parma, Parma, Italy.
| | - Ingvar Bjarnason
- Department of Gastroenterology, King's College Hospital, London, UK
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Ben Guebila M, Thiele I. Predicting gastrointestinal drug effects using contextualized metabolic models. PLoS Comput Biol 2019; 15:e1007100. [PMID: 31242176 PMCID: PMC6594586 DOI: 10.1371/journal.pcbi.1007100] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2018] [Accepted: 05/13/2019] [Indexed: 12/28/2022] Open
Abstract
Gastrointestinal side effects are among the most common classes of adverse reactions associated with orally absorbed drugs. These effects decrease patient compliance with the treatment and induce undesirable physiological effects. The prediction of drug action on the gut wall based on in vitro data solely can improve the safety of marketed drugs and first-in-human trials of new chemical entities. We used publicly available data of drug-induced gene expression changes to build drug-specific small intestine epithelial cell metabolic models. The combination of measured in vitro gene expression and in silico predicted metabolic rates in the gut wall was used as features for a multilabel support vector machine to predict the occurrence of side effects. We showed that combining local gut wall-specific metabolism with gene expression performs better than gene expression alone, which indicates the role of small intestine metabolism in the development of adverse reactions. Furthermore, we reclassified FDA-labeled drugs with respect to their genetic and metabolic profiles to show hidden similarities between seemingly different drugs. The linkage of xenobiotics to their transcriptomic and metabolic profiles could take pharmacology far beyond the usual indication-based classifications.
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Affiliation(s)
- Marouen Ben Guebila
- Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Ines Thiele
- Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
- School of Medicine, National University of Ireland, Galway, University Road, Galway, Ireland
- Discipline of Microbiology, School of Natural Sciences, National University of Ireland, Galway, University Road, Galway, Ireland
- * E-mail:
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Dumic I, Nordin T, Jecmenica M, Stojkovic Lalosevic M, Milosavljevic T, Milovanovic T. Gastrointestinal Tract Disorders in Older Age. Can J Gastroenterol Hepatol 2019; 2019:6757524. [PMID: 30792972 PMCID: PMC6354172 DOI: 10.1155/2019/6757524] [Citation(s) in RCA: 132] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2018] [Revised: 12/11/2018] [Accepted: 12/17/2018] [Indexed: 02/07/2023] Open
Abstract
Considering an increase in the life expectancy leading to a rise in the elderly population, it is important to recognize the changes that occur along the process of aging. Gastrointestinal (GI) changes in the elderly are common, and despite some GI disorders being more prevalent in the elderly, there is no GI disease that is limited to this age group. While some changes associated with aging GI system are physiologic, others are pathological and particularly more prevalent among those above age 65 years. This article reviews the most important GI disorders in the elderly that clinicians encounter on a daily basis. We highlight age-related changes of the oral cavity, esophagus, stomach, small and large bowels, and the clinical implications of these changes. We review epidemiology and pathophysiology of common diseases, especially as they relate to clinical manifestation in elderly. Details regarding management of specific disease are discussed in detail if they significantly differ from the management for younger groups or if they are associated with significant challenges due to side effects or polypharmacy. Cancers of GI tract are not included in the scope of this article.
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Affiliation(s)
- Igor Dumic
- Division of Hospital Medicine, Mayo Clinic Health System, Eau Claire, WI, USA
- Mayo Clinic College of Medicine and Sciences, Rochester, MN, USA
| | - Terri Nordin
- Mayo Clinic College of Medicine and Sciences, Rochester, MN, USA
- Department of Family Medicine, Mayo Clinic Health System, Eau Claire WI, USA
| | - Mladen Jecmenica
- Gastroenterology Fellowship Program, The Wright Center for Graduate Medical Education, Scranton, PA, USA
| | | | - Tomica Milosavljevic
- Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia, Belgrade, Serbia
- School of Medicine, Belgrade University, Belgrade, Serbia
| | - Tamara Milovanovic
- Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia, Belgrade, Serbia
- School of Medicine, Belgrade University, Belgrade, Serbia
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Wells CI, O’Grady G, Bissett IP. Acute colonic pseudo-obstruction: A systematic review of aetiology and mechanisms. World J Gastroenterol 2017; 23:5634-5644. [PMID: 28852322 PMCID: PMC5558126 DOI: 10.3748/wjg.v23.i30.5634] [Citation(s) in RCA: 72] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2017] [Revised: 06/29/2017] [Accepted: 07/22/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To critically review the literature addressing the definition, epidemiology, aetiology and pathophysiology of acute colonic pseudo-obstruction (ACPO). METHODS A systematic search was performed to identify articles investigating the aetiology and pathophysiology of ACPO. A narrative synthesis of the evidence was undertaken. RESULTS No consistent approach to the definition or reporting of ACPO has been developed, which has led to overlapping investigation with other conditions. A vast array of risk factors has been identified, supporting a multifactorial aetiology. The pathophysiological mechanisms remain unclear, but are likely related to altered autonomic regulation of colonic motility, in the setting of other predisposing factors. CONCLUSION Future research should aim to establish a clear and consistent definition of ACPO, and elucidate the pathophysiological mechanisms leading to altered colonic function. An improved understanding of the aetiology of ACPO may facilitate the development of targeted strategies for its prevention and treatment.
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Abstract
The evaluation of a patient with chronic diarrhea can be quite frustrating, as it is expensive and involves multiple diagnostic studies. Moreover, identification of a drug as a cause of chronic diarrhea is a challenge in patients taking multiple medications. The disease may either be associated with intestinal mucosal changes, mimicking diseases such as celiac disease, or purely functional, with no histopathologic change. Drug-induced diarrhea may or may not be associated with malabsorption of nutrients, and a clinical improvement may occur within days of discontinuation of the drug, or may take longer when associated with mucosal injury. Diarrhea in diabetics, often attributed to poor management and lack of control, may be due to oral hypoglycaemic agents. Chemotherapy can result in diffuse or segmental colitis, whereas olmesartan and a few other medications infrequently induce a disease that mimics celiac disease, but is not associated with gluten intolerance. In short, increased awareness of a drug, as a cause for diarrhea and a clear understanding of the clinical manifestations will help clinicians to solve this challenging problem. This article aims to review drug-induced diarrhea to (a) understand known pathophysiological mechanisms; (b) assess the risk associated with frequently prescribed medications, and discuss the pathogenesis; and
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Affiliation(s)
- Nissy A Philip
- Division of Gastroenterology, Hepatology, Saint Peter's University Hospital, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ
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9
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Logrippo S, Ricci G, Sestili M, Cespi M, Ferrara L, Palmieri GF, Ganzetti R, Bonacucina G, Blasi P. Oral drug therapy in elderly with dysphagia: between a rock and a hard place! Clin Interv Aging 2017; 12:241-251. [PMID: 28203065 PMCID: PMC5293185 DOI: 10.2147/cia.s121905] [Citation(s) in RCA: 58] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Demographic indicators forecast that by 2050, the elderly will account for about one-third of the global population. Geriatric patients require a large number of medicines, and in most cases, these products are administered as solid oral solid dosage forms, as they are by far the most common formulations on the market. However, this population tends to suffer difficulties with swallowing. Caregivers in hospital geriatric units routinely compound in solid oral dosage forms for dysphagic patients by crushing the tablets or opening the capsules to facilitate administration. The manipulation of a tablet or a capsule, if not clearly indicated in the product labeling, is an off-label use of the medicine, and must be supported by documented scientific evidence and requires the patient's informed consent. Compounding of marketed products has been recognized as being responsible for an increased number of adverse events and medical errors. Since extemporaneous compounding is the rule and not the exception in geriatrics departments, the seriousness and scope of issues caused by this daily practice are probably underestimated. In this article, the potential problems associated with the manipulation of authorized solid oral dosage forms are discussed.
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Affiliation(s)
| | | | - Matteo Sestili
- Italian National Research Centers on Ageing (INRCA), Ancona, Italy
| | | | - Letizia Ferrara
- Italian National Research Centers on Ageing (INRCA), Ancona, Italy
| | | | - Roberta Ganzetti
- Italian National Research Centers on Ageing (INRCA), Ancona, Italy
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Ikarashi N, Kon R, Sugiyama K. Aquaporins in the Colon as a New Therapeutic Target in Diarrhea and Constipation. Int J Mol Sci 2016; 17:ijms17071172. [PMID: 27447626 PMCID: PMC4964543 DOI: 10.3390/ijms17071172] [Citation(s) in RCA: 104] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2016] [Revised: 07/12/2016] [Accepted: 07/14/2016] [Indexed: 12/29/2022] Open
Abstract
Aquaporins (AQPs) play important roles in the water transport system in the human body. There are currently 13 types of AQP, AQP0 through AQP12, which are expressed in various organs. Many members of the AQP family are expressed in the intestinal tract. AQP3 is predominantly expressed in the colon, ultimately controlling the water transport. Recently, it was clarified that several laxatives exhibit a laxative effect by changing the AQP3 expression level in the colon. In addition, it was revealed that morphine causes severe constipation by increasing the AQP3 expression level in the colon. These findings have shown that AQP3 is one of the most important functional molecules in water transport in the colon. This review will focus on the physiological and pathological roles of AQP3 in the colon, and discuss clinical applications of colon AQP3.
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Affiliation(s)
- Nobutomo Ikarashi
- Department of Clinical Pharmacokinetics, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
| | - Risako Kon
- Department of Clinical Pharmacokinetics, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
| | - Kiyoshi Sugiyama
- Department of Clinical Pharmacokinetics, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
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12
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Tenner S. Drug induced acute pancreatitis: Does it exist? World J Gastroenterol 2014; 20:16529-16534. [PMID: 25469020 PMCID: PMC4248195 DOI: 10.3748/wjg.v20.i44.16529] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2014] [Revised: 05/08/2014] [Accepted: 07/16/2014] [Indexed: 02/06/2023] Open
Abstract
As the incidence of acute pancreatitis continues to rise, establishing the etiology in order to prevent recurrence is important. Although the etiology of acute pancreatitis is not difficult in the majority of patients, almost a quarter of patients are initially labeled as having idiopathic acute pancreatitis. When confronted with a patient with acute pancreatitis and no clear etiology defined as an absence alcoholism, gallstones (ultrasound and/or MRI), a normal triglyceride level, and absence of tumor, it often appears reasonable to consider a drug as the cause of acute pancreatitis. Over 100 drugs have been implicated by case reports as causing acute pancreatitis. While some of these case reports are well written, many case reports represent poorly written experiences of the clinician simply implicating a drug without a careful evaluation. Over-reliance on case reports while ignoring randomized clinical trials and large pharmacoepidemiologic surveys has led to confusion about drug induced acute pancreatitis. This review will explain that drug induced acute pancreatitis does occur, but it is rare, and over diagnosis leads to misconceptions about the disease resulting in inappropriate patient care, increased litigation and a failure to address the true entity: idiopathic acute pancreatitis.
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Tenner S. Isotretinoin and inflammatory bowel disease: trial lawyer misuse of science and FDA warnings. Am J Gastroenterol 2014; 109:570-1. [PMID: 24698863 DOI: 10.1038/ajg.2014.34] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2014] [Accepted: 01/28/2014] [Indexed: 12/11/2022]
Abstract
Based on the Food and Drug Administration Adverse Event Reporting System (FAERS), the FDA and Hoffman La Roche issued warnings of a possible causal association between isotretinoin and inflammatory bowel disease. While scientists studied the association, trial lawyers used the courts to award large sums of money to plaintiffs despite the absence of clear scientific evidence of a causal effect. In this Issue of the Journal, a well-designed, large pharmaco-epidemiologic study shows no association. The story of isotretinoin highlights the problems that occur when the FAERS is used in litigation prior to further study and scientific analysis.
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Affiliation(s)
- Scott Tenner
- Department of Gastroenterology, Downstate Medical Center, Brooklyn, New York, USA
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Seminerio J, McGrath K, Arnold CA, Voltaggio L, Singhi AD. Medication-associated lesions of the GI tract. Gastrointest Endosc 2014; 79:140-50. [PMID: 24119504 DOI: 10.1016/j.gie.2013.08.027] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2013] [Accepted: 08/22/2013] [Indexed: 02/08/2023]
Affiliation(s)
- Jennifer Seminerio
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Kevin McGrath
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Christina A Arnold
- Department of Pathology, Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Lysandra Voltaggio
- Department of Pathology, George Washington University, Washington, District of Columbia
| | - Aatur D Singhi
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
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15
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Dumkow LE, Voss JR, Peters M, Jennings DL. Reversal of dabigatran-induced bleeding with a prothrombin complex concentrate and fresh frozen plasma. Am J Health Syst Pharm 2012; 69:1646-50. [DOI: 10.2146/ajhp120055] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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16
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Swallowing dysfunction and dysphagia is an unrecognized challenge for oral drug therapy. Int J Pharm 2012; 430:197-206. [DOI: 10.1016/j.ijpharm.2012.04.022] [Citation(s) in RCA: 149] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2012] [Revised: 03/30/2012] [Accepted: 04/02/2012] [Indexed: 01/03/2023]
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Bartel B, Gau E. Nosocomial diarrhea: a review of pathophysiology, etiology, and treatment strategies. Hosp Pract (1995) 2012; 40:130-8. [PMID: 22406888 DOI: 10.3810/hp.2012.02.953] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Diarrhea is a frequent complication among hospitalized patients. Nosocomial diarrhea is generally diagnosed as increased frequency and decreased consistency of stools developing after 72 hours of hospitalization. The causes of nosocomial diarrhea may be infectious or noninfectious. Noninfectious etiologies occur most commonly, and are often adverse effects of medications or enteral nutrition therapies. Infectious etiologies are most concerning and include Clostridium difficile and norovirus. Patients with nosocomial diarrhea should be placed in isolation with contact precautions in place until the presence of C difficile infection is determined. Irrespective of etiology, diarrhea can cause serious complications in hospitalized patients, including malnutrition, hemodynamic instability, metabolic acidosis, and potentially fatal pseudomembranous colitis. This article reviews nosocomial diarrhea, including its pathophysiology, infectious and noninfectious causes, and treatment strategies based on identified cause.
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Affiliation(s)
- Billie Bartel
- Avera McKennan Hospital and University Health Center, Sioux Falls, SD 57117, USA.
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Dequito AB, Mol PGM, van Doormaal JE, Zaal RJ, van den Bemt PMLA, Haaijer-Ruskamp FM, Kosterink JGW. Preventable and non-preventable adverse drug events in hospitalized patients: a prospective chart review in the Netherlands. Drug Saf 2011; 34:1089-100. [PMID: 21981436 DOI: 10.2165/11592030-000000000-00000] [Citation(s) in RCA: 61] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
Abstract
BACKGROUND Medication safety research and clinical pharmacy practice today is primarily focused on managing preventable adverse drug events (pADEs). Determinants of both pADEs and non-preventable adverse drug reactions (ADRs) have been identified. However, relatively little is known on the overlap between these determinants and the balance of preventable and non-preventable harm inpatients experience in modern computerized hospitals. OBJECTIVE The aim of this study was to analyse the prevalence of pADEs and non-preventable ADRs as well as the determinants, including multimorbidity, of these ADEs, i.e. both pADEs and ADRs. METHODS Adverse events experienced by patients admitted to two Dutch hospitals with functioning computerized physician order entry (CPOE) systems were prospectively identified through chart review. Adverse events were divided into pADEs (i.e. as a result of a medication error) and non-preventable ADRs. In both cases, a causal relationship between adverse events and patients' drugs was established using the simplified Yale algorithm. Study data were collected anytime between April 2006 and May 2008 over a 5-month period at each hospital ward included in the study, beginning from 8 weeks after CPOE was implemented at the ward. RESULTS pADEs and non-preventable ADRs were experienced by 349 (58%) patients, of whom 307 (88%) had non-preventable ADRs. Multimorbidity (adjusted odds ratio [OR(adj)] 1.90; 95% CI 1.44, 2.50; OR(adj) 1.28; 95% CI 1.14, 1.45, respectively), length of stay (OR(adj) 1.13; 95% CI 1.06, 1.21; OR(adj) 1.11; 95% CI 1.07, 1.16, respectively), admission to the geriatric ward (OR(adj) 7.78; 95% CI 2.15, 28.13; OR(adj) 3.82; 95% CI 1.73, 8.45, respectively) and number of medication orders (OR(adj) 1.25; 95% CI 1.16, 1.35; OR(adj) 1.13; 95% CI 1.06, 1.21, respectively) were statistically significantly associated with pADEs and ADRs. Admission to the gastroenterology/rheumatology ward (OR(adj) 0.22; 95% CI 0.06, 0.77; OR(adj) 0.40; 95% CI 0.24, 0.65, respectively) was inversely related to both pADEs and ADRs. Other determinants for ADRs only were female sex (OR(adj) 1.77; 95% CI 1.12, 2.80) and use of drugs affecting the nervous system (OR(adj) 1.83; 95% CI 1.09, 3.07). Age was a significant determinant for pADEs only (OR(adj) 1.07; 95% CI 1.03, 1.11). CONCLUSIONS In this study more than half of the patients admitted to the hospitals are harmed by drugs, of which most are non-serious, non-preventable ADRs (after the introduction of CPOE). Determinants of both pADEs and ADRs overlap to a large extent. Our results imply the need for signalling early potential adverse events that occur during the normal use of drugs in multimorbid patients or those in geriatric wards. Subsequent therapeutic interventions may improve the well-being of hospitalized patients to a greater extent than focusing on errors in the medication process only.
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Affiliation(s)
- Aileen B Dequito
- Department of Hospital and Clinical Pharmacy, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands
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Triantafyllou K, Vlachogiannakos J, Ladas SD. Gastrointestinal and liver side effects of drugs in elderly patients. Best Pract Res Clin Gastroenterol 2010; 24:203-215. [PMID: 20227033 DOI: 10.1016/j.bpg.2010.02.004] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2009] [Revised: 02/07/2010] [Accepted: 02/08/2010] [Indexed: 01/31/2023]
Abstract
It is expected that the percentage of people >60 years of age will be 22% worldwide by the year 2050. Multi-morbidity and poly-pharmacy are common in individuals during old age, while adverse drug reactions are at least twice as common in the elderly compared to younger adults. Publications related to drug side effects are rather rare in this age group since most clinical trials exclude patients >75-80 years of age. Gastrointestinal adverse drug reactions studied in the elderly include non-steroidal anti-inflammatory drugs (NSAIDs) and anticoagulant-induced gastrointestinal tract mucosal injuries. Malabsorption, diarrhoea and constipation are common side effects of laxatives, antibiotics, anticholinergics and calcium channel blockers. Drug (amoxycilin/clavulanic acid, isoniazide, nitrofurantoin, diclifenac and methotrexate)-induced hepatotoxicity in the elderly is four times more common than in younger adults and may simulate almost all known liver disorders. Further clinical studies are needed to investigate gastrointestinal and hepatic side effects of drugs in elderly patients.
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Affiliation(s)
- Konstantinos Triantafyllou
- Hepatogastroenterology Unit, 2nd Department of Internal Medicine - Propaedeutic, Attikon University General Hospital, Medical School, Athens University, Chaidari, Greece
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Olyaei AJ, Bennett WM. Drug Dosing in the Elderly Patients with Chronic Kidney Disease. Clin Geriatr Med 2009; 25:459-527. [DOI: 10.1016/j.cger.2009.04.004] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
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Current awareness: Pharmacoepidemiology and drug safety. Pharmacoepidemiol Drug Saf 2009. [DOI: 10.1002/pds.1650] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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