|
1
|
Song J, Sun H, Pan L, Wang D, Wang J, Su F. Metal-organic cages based catalytic hybrid hydrogels for enhanced wound healing: Antibacterial and regenerative effects of Zr-MOC/chitosan composites hydrogel. Int J Biol Macromol 2025; 301:139851. [PMID: 39826748 DOI: 10.1016/j.ijbiomac.2025.139851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2024] [Revised: 01/06/2025] [Accepted: 01/12/2025] [Indexed: 01/22/2025]
Abstract
Metal-organic cages (MOCs), assembled by the coordination of metal nodes with organic ligands, offer excellent solvent dispersion, functionalization potential, and abundant binding sites, making them ideal for hybrid hydrogel synthesis. Herrin, a novel Zr-MOC/CS hybrid hydrogel was developed by crosslinking Zr-based metal-organic cages (Zr-MOC) and chitosan (CS) using dibenzaldehyde-functionalized polyethylene glycol (DF-PEG) as crosslinker, marking the first instance of incorporating Zr-MOC into a hydrogel matrix. The composite hydrogel leverages the catalytic activity of Zr-MOC to convert trace H2O2 into hydroxyl radicals (·OH), delivering enhanced antibacterial performance. Characterization via XRD, FT-IR, XPS, SEM and SEM-EDS confirmed the successful integration of Zr-MOC within the hydrogel matrix. Antibacterial assays demonstrated superior efficacy against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) compared to conventional hydrogels. Cytotoxicity tests (MTT and live-dead staining) confirmed excellent biocompatibility. Furthermore, in vivo experiments using an infected wound model revealed that the Zr-MOC/CS hydrogel significantly accelerated wound healing. These results highlight the potential of Zr-MOC/CS hydrogel as a multifunctional wound dressing material for antibacterial therapy in clinical applications.
Collapse
Affiliation(s)
- Jie Song
- State Key Laboratory Base of Eco-chemical Engineering, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China; Institute of High Performance Polymers, Qingdao University of Science and Technology, Qingdao 266042, China
| | - Haozhi Sun
- State Key Laboratory Base of Eco-chemical Engineering, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China
| | - Lixia Pan
- State Key Laboratory Base of Eco-chemical Engineering, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China
| | - Dandan Wang
- State Key Laboratory Base of Eco-chemical Engineering, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China
| | - Jinjun Wang
- Qingdao Traditional Chinese Medicine Hospital (Qingdao Hiser Hospital), Qingdao 266033, China.
| | - Feng Su
- State Key Laboratory Base of Eco-chemical Engineering, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China; Institute of High Performance Polymers, Qingdao University of Science and Technology, Qingdao 266042, China.
| |
Collapse
|
|
2
|
Lee YM, Kim JY, Lee KJ. Weaning strategies for osmotic laxatives in children with functional constipation: a pilot multicenter randomized controlled trial. Transl Pediatr 2025; 14:252-261. [PMID: 40115451 PMCID: PMC11921306 DOI: 10.21037/tp-24-436] [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: 10/17/2024] [Accepted: 02/09/2025] [Indexed: 03/23/2025] Open
Abstract
Background Long-term maintenance of laxatives is crucial for treating functional constipation (FC) in children. This study aimed to compare the success rates of discontinuation based on different drug reduction methods, in order to identify the optimal strategy for discontinuing laxative use. Methods This open-label randomized controlled trial was conducted from September 2020 to September 2021. Children with FC who had been successfully treated with lactulose for more than three months were included. Patients were randomly assigned to one of two groups: dose reduction or frequency reduction over a three-month period. The primary outcome was the weaning success rate at week 12. Participants were divided into two subgroups based on the pre-weaning lactulose dosage: the low-dose group (≤1.5 g/kg/day) and the high-dose group (>1.5 g/kg/day). Results A total of 16 patients were enrolled, with a median age of 43 months and 11 boys. There were no significant differences in baseline characteristics between the two groups. The primary outcome showed no significant difference: 66.7% for dose reduction vs. 57.1%. for frequency reduction. Weaning success rates decreased at week 16 (33.3% vs. 57.1%) and week 24 (33.3% vs. 42.9%) without significant differences. In the subgroup analysis, the high-dose group showed a significantly higher weaning success rate at 12 weeks compared to the low-dose group (81.8% vs. 20%, P=0.04). Other measures, including median defecation frequency, incontinence episodes, stool consistency, painful defecations, and compliance, were also similar between the groups. Patient satisfaction was 77.8% for dose reduction and 57.1% for frequency reduction, with no significant difference. Conclusions The method of reducing the dose or frequency of lactulose did not affect the weaning success rate in children with FC. However, a pre-weaning lactulose dose exceeding 1.5 g/kg/day may lead to better outcomes at week 12. Despite gradual reduction over more than 3 months, the weaning success rate remained low, highlighting the importance of careful drug discontinuation and follow-up. Trial Registration The Clinical Research Information Service of the Korea Center for Disease Control and Prevention (https://cris.nih.go.kr/cris, registration No. KCT0006286).
Collapse
Affiliation(s)
- Yoo Min Lee
- Department of Pediatrics, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Republic of Korea
| | - Ju Young Kim
- Department of Pediatrics, Daejeon Eulji Medical Center, Eulji University, Daejeon, Republic of Korea
| | - Kyung Jae Lee
- Department of Pediatric, Hallym University College of Medicine, Chuncheon, Republic of Korea
- Department of Pediatrics, Seoul National University Hospital, Seoul, Republic of Korea
| |
Collapse
|
|
3
|
Yang L, Zong Y, Meng F, Wu Y, Zhang S. Comparative Efficacy and Safety of Lubiprostone and Osmotic Laxatives in Chronic Idiopathic Constipation: A Systematic Review and Network Meta-Analysis. J Gastroenterol Hepatol 2025; 40:387-397. [PMID: 39660667 DOI: 10.1111/jgh.16844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Accepted: 11/22/2024] [Indexed: 12/12/2024]
Abstract
OBJECTIVE The objective of this study is to compare the efficacy and safety of lubiprostone (Lub) with osmotic laxatives in the treatment of chronic idiopathic constipation (CIC). METHODS A comprehensive literature search was conducted using PubMed, EMBASE, and the Cochrane Library in May 2024. Studies that met the inclusion criteria were manually searched by two independent reviewers. The efficacy was assessed by the proportion of patients with spontaneous bowel movements (SBMs) within 24 h after the first administration of the medication and SBMs in Weeks 1 and 4. Safety was evaluated based on adverse events including nausea, diarrhea, and abdominal distension. Optimal probability values and the surface under the cumulative ranking area (SUCRA) were also calculated for all interventions. Higher SUCRA values indicate better efficacy and safety of the intervention. RESULTS Following a thorough search and screening process, 25 articles were included. Among the selected trials, 8 compared Lub to placebo, 10 compared polyethylene glycol (PEG) to placebo, 4 compared lactulose (Lac) to placebo, and 3 compared PEG to Lac. The meta-analysis results indicated that Lub and osmotic laxatives were significantly more effective than placebo. According to the SUCRA results, the highest rank probabilities were for Lub in increasing the SBMs and reducing abdominal distension. CONCLUSION Lubiprostone is more effective than PEG and Lactulose for treating CIC, with comparable safety profiles. However, this conclusion requires further validation through large-scale, high-quality studies.
Collapse
Affiliation(s)
- Luoyao Yang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Ye Zong
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Fandong Meng
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yongdong Wu
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Shutian Zhang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| |
Collapse
|
|
4
|
Chen Y, Ding M. Novel insights into carbohydrate-to-fiber ratio and constipation: NHANES findings suggest a turning point. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2025. [PMID: 39784686 DOI: 10.17235/reed.2024.10306/2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/12/2025]
Abstract
BACKGROUND Constipation, a widespread global issue, prompted an investigation into the intricate relationship between dietary factors and this condition. This study delves into the association between carbohydrate-to-fiber (CF) ratio and constipation, employing data from the National Health and Nutrition Examination Survey (NHANES) and a comprehensive meta-analysis. METHODS Utilizing NHANES data (2005-2010) from 7752 adults, constipation was defined based on stool type (Bristol Stool Form Scale types 1 or 2). The CF ratio was calculated, revealing an L-shaped, non-linear association with constipation. A meta-analysis of 16 studies (1626 participants) confirmed a positive effect of dietary fiber on constipation, emphasizing the robustness of the findings. RESULTS Among participants, constipation prevalence stood at 13.98%. The CF ratio exhibited a turning point at 26.92/day, with adjusted odds ratios for constipation indicating a decrease with higher CF ratios. Meta-analysis results supported these findings, demonstrating a significant positive effect of dietary fiber on constipation. CONCLUSION This study illuminates a nuanced relationship between CF ratio and constipation, suggesting a critical turning point at 26.92/day. These findings underscore the importance of dietary assessment, offering valuable insights for clinicians and individuals. Further prospective research is warranted to validate the CF ratio as a robust dietary assessment tool.
Collapse
Affiliation(s)
- Yin Chen
- Proctology, The Affiliated Xuancheng Hospital of Wannan Medical College
| | - Meisheng Ding
- Proctology, The Affiliated Xuancheng Hospital of Wannan Medica, china
| |
Collapse
|
|
5
|
Hojo M, Shibuya T, Nagahara A. Management of Chronic Constipation: A Comprehensive Review. Intern Med 2025; 64:7-15. [PMID: 37952945 PMCID: PMC11781917 DOI: 10.2169/internalmedicine.2867-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Accepted: 09/21/2023] [Indexed: 11/14/2023] Open
Abstract
Traditionally, the treatment of chronic constipation has focused on lifestyle modification, dietary guidance and therapy, and osmotic and stimulant laxatives. Recently, several drugs with new mechanisms of action have been introduced as treatments for chronic constipation. In Japan, polyethylene glycol and lactulose can now be administered under insurance coverage. The number of treatment options for constipation has increased dramatically. First, lifestyle modifications and dietary therapies must be implemented. If constipation does not improve sufficiently, specialized functional tests are performed to diagnose physiological subgroups. If functional tests are not available, patients are classified as having the "decreased frequency of defecation" type or the "difficult defecation" type based on the patient's symptoms, with treatment applied according to each type. Medical therapy includes osmotic laxatives, secretagogues, bile acid transporter inhibitors, probiotics, prokinetics, and Kampo medicines. The temporary use of stimulant laxatives, suppositories, enemas, and digital evacuation is also recommended. The usefulness of biofeedback is yet to be determined.
Collapse
Affiliation(s)
- Mariko Hojo
- Department of Gastroenterology, Juntendo University School of Medicine, Japan
| | - Tomoyoshi Shibuya
- Department of Gastroenterology, Juntendo University School of Medicine, Japan
| | - Akihito Nagahara
- Department of Gastroenterology, Juntendo University School of Medicine, Japan
| |
Collapse
|
|
6
|
Quitadamo P, Tambucci R, Mancini V, Campanozzi A, Caldaro T, Giorgio V, Pensabene L, Isoldi S, Mallardo S, Fusaro F, Staiano A, Salvatore S, Borrelli O. Diagnostic and therapeutic approach to children with chronic refractory constipation: Consensus report by the SIGENP motility working group. Dig Liver Dis 2024; 56:406-420. [PMID: 38104028 DOI: 10.1016/j.dld.2023.11.037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Revised: 11/15/2023] [Accepted: 11/29/2023] [Indexed: 12/19/2023]
Abstract
Constipation is a common problem in children, accounting for about 3% of all primary care visits and up to 25% of referrals to paediatric gastroenterologists. Although polyethylene glycol often proves effective, most children require prolonged treatment and about 50% of them have at least one relapse within the first 5 years after initial recovery. When conventional treatment fails, children are considered to have refractory constipation. Children with refractory constipation deserve specialist management and guidance. Over the last decades, there has been a remarkable increase in our knowledge of normal and abnormal colonic and anorectal motility in children, and a number of different techniques to measure transit and motility have been developed. The present review analyses the possible diagnostic investigations for children with refractory constipation, focusing on their actual indications and their utility in clinical practice. Moreover, we have also analytically reviewed medical and surgical therapeutic options, which should be considered in selected patients in order to achieve the best clinical outcome.
Collapse
Affiliation(s)
- Paolo Quitadamo
- Pediatric Gastroenterology and Epatology Unit, Santobono-Pausilipon Children's Hospital, Naples, Italy.
| | - Renato Tambucci
- Digestive Endoscopy and Surgery Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Valentina Mancini
- Department of Pediatrics and Neonatology, San Carlo Hospital, Milan, Italy
| | - Angelo Campanozzi
- Pediatrics, Department of Medical and Surgical Sciences, University of Foggia
| | - Tamara Caldaro
- Digestive Endoscopy and Surgery Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Valentina Giorgio
- UOC Pediatria, Fondazione Policlinico Universitario A. Gemelli IRCSS, Roma, Italy
| | - Licia Pensabene
- Department of Medical and Surgical Sciences, Pediatric Unit, University "Magna Graecia" of Catanzaro, Catanzaro, Italy
| | - Sara Isoldi
- Pediatric Gastroenterology and Epatology Unit, Santobono-Pausilipon Children's Hospital, Naples, Italy; Maternal and Child Health Department, Sapienza - University of Rome, Santa Maria Goretti Hospital, Polo Pontino, Latina, Italy
| | - Saverio Mallardo
- Maternal and Child Health Department, Sapienza - University of Rome, Santa Maria Goretti Hospital, Polo Pontino, Latina, Italy
| | - Fabio Fusaro
- Department of Medical and Surgical Neonatology, Newborn Surgery Unit, Digestive and Endoscopic Surgery, Gastroenterology and Nutrition, Intestinal Failure Rehabilitation Research Group, Bambino Gesù Children's Hospital Research Institute, Rome, Italy
| | - Annamaria Staiano
- Department of Translational Medical Science, Section of Pediatrics, University "Federico II", Naples, Italy
| | - Silvia Salvatore
- Pediatric Department, Ospedale "F. Del Ponte", University of Insubria, Varese, Italy
| | - Osvaldo Borrelli
- Division of Neurogastroenterology and Motility, Department of Paediatric Gastroenterology, UCL Institute of Child Health and Great Ormond Street Hospital, London, UK
| |
Collapse
|
|
7
|
Quigley EMM. Constipation in Parkinson's Disease. Semin Neurol 2023; 43:562-571. [PMID: 37579786 DOI: 10.1055/s-0043-1771457] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/16/2023]
Abstract
Constipation is one of the most common gastrointestinal features of Parkinson's disease (PD), occurring in over 50% of all PD patients during the course of their disease. Furthermore, constipation is now recognized as an important, prodromal symptom and may predate the onset of the classical motor symptoms by decades. Thereafter, the prevalence and severity of constipation in PD tend to parallel the course of both motor and nonmotor phenomena such as cognitive decline and depression. Difficult defecation (obstructed defecation, dyssynergia) is the primary pathophysiology underlying constipation and likely reflects involvement by the PD process of one or more of the many skeletal muscle groups that are involved in effecting defecation. Management of constipation in PD may be complicated by several patient factors including dysphagia, cognitive impairment, depression, and weak sphincter tone. While the armamentarium available to those who treat constipation, in general, has expanded considerably in recent years, the evidence supporting any therapy in the management of this symptom in PD has remained slim.
Collapse
Affiliation(s)
- Eamonn M M Quigley
- Division of Gastroenterology and Hepatology, Lynda K and David M Underwood Center for Digestive Disorders, Houston Methodist Hospital, Houston, Texas
| |
Collapse
|
|
8
|
Chang L, Chey WD, Imdad A, Almario CV, Bharucha AE, Diem S, Greer KB, Hanson B, Harris LA, Ko C, Murad MH, Patel A, Shah ED, Lembo AJ, Sultan S. American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation. Am J Gastroenterol 2023; 118:936-954. [PMID: 37204227 PMCID: PMC10544839 DOI: 10.14309/ajg.0000000000002227] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Accepted: 02/27/2023] [Indexed: 05/20/2023]
Abstract
INTRODUCTION Chronic idiopathic constipation (CIC) is a common disorder associated with significant impairment in quality of life. This clinical practice guideline, jointly developed by the American Gastroenterological Association and the American College of Gastroenterology, aims to inform clinicians and patients by providing evidence-based practice recommendations for the pharmacological treatment of CIC in adults. METHODS The American Gastroenterological Association and the American College of Gastroenterology formed a multidisciplinary guideline panel that conducted systematic reviews of the following agents: fiber, osmotic laxatives (polyethylene glycol, magnesium oxide, lactulose), stimulant laxatives (bisacodyl, sodium picosulfate, senna), secretagogues (lubiprostone, linaclotide, plecanatide), and serotonin type 4 agonist (prucalopride). The panel prioritized clinical questions and outcomes and used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence for each intervention. The Evidence to Decision framework was used to develop clinical recommendations based on the balance between the desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS The panel agreed on 10 recommendations for the pharmacological management of CIC in adults. Based on available evidence, the panel made strong recommendations for the use of polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride for CIC in adults. Conditional recommendations were made for the use of fiber, lactulose, senna, magnesium oxide, and lubiprostone. DISCUSSION This document provides a comprehensive outline of the various over-the-counter and prescription pharmacological agents available for the treatment of CIC. The guidelines are meant to provide a framework for approaching the management of CIC; clinical providers should engage in shared decision making based on patient preferences as well as medication cost and availability. Limitations and gaps in the evidence are highlighted to help guide future research opportunities and enhance the care of patients with chronic constipation.
Collapse
Affiliation(s)
- Lin Chang
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - William D. Chey
- Division of Gastroenterology & Hepatology, Michigan Medicine, Ann Arbor, Michigan, USA
| | - Aamer Imdad
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, SUNY Upstate Medical University, Syracuse, New York, USA
| | - Christopher V. Almario
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Adil E. Bharucha
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Susan Diem
- Minneapolis VA Healthcare System, Minneapolis, Minnesota, USA
- University of Minnesota School of Medicine, Minneapolis, Minnesota, USA
| | - Katarina B. Greer
- Cleveland VA Healthcare System, Cleveland, Ohio, USA
- Case Western Reserve University, Cleveland, Ohio, USA
| | - Brian Hanson
- Minneapolis VA Healthcare System, Minneapolis, Minnesota, USA
- Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA
| | - Lucinda A. Harris
- Division of Gastroenterology & Hepatology, Mayo Clinic, Phoenix, Arizona, USA
| | - Cynthia Ko
- Division of Gastroenterology & Hepatology, University of Washington, Washington, DC, USA
| | | | - Amit Patel
- Division of Gastroenterology, Duke University School of Medicine and the Durham Veterans Affairs Medical Center, Durham, North Carolina, USA
| | - Eric D. Shah
- Division of Gastroenterology & Hepatology, Michigan Medicine, Ann Arbor, Michigan, USA
- Division of Gastroenterology & Hepatology, Department of Medicine, DartMouth Health, Lebanon, New Hampshire, USA
| | - Anthony J. Lembo
- Department of Gastroenterology, Hepatology & Nutrition, Digestive Disease and Surgery Institute; Cleveland Clinic, Cleveland, Ohio, USA
| | - Shahnaz Sultan
- Minneapolis VA Healthcare System, Minneapolis, Minnesota, USA
- University of Minnesota, Minneapolis, Minnesota, USA
| |
Collapse
|
|
9
|
Chang L, Chey WD, Imdad A, Almario CV, Bharucha AE, Diem S, Greer KB, Hanson B, Harris LA, Ko C, Murad MH, Patel A, Shah ED, Lembo AJ, Sultan S. American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation. Gastroenterology 2023; 164:1086-1106. [PMID: 37211380 PMCID: PMC10542656 DOI: 10.1053/j.gastro.2023.03.214] [Citation(s) in RCA: 52] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Accepted: 02/27/2023] [Indexed: 05/23/2023]
Abstract
INTRODUCTION Chronic idiopathic constipation (CIC) is a common disorder associated with significant impairment in quality of life. This clinical practice guideline, jointly developed by the American Gastroenterological Association and the American College of Gastroenterology, aims to inform clinicians and patients by providing evidence-based practice recommendations for the pharmacological treatment of CIC in adults. METHODS The American Gastroenterological Association and the American College of Gastroenterology formed a multidisciplinary guideline panel that conducted systematic reviews of the following agents: fiber, osmotic laxatives (polyethylene glycol, magnesium oxide, lactulose), stimulant laxatives (bisacodyl, sodium picosulfate, senna), secretagogues (lubiprostone, linaclotide, plecanatide), and serotonin type 4 agonist (prucalopride). The panel prioritized clinical questions and outcomes and used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence for each intervention. The Evidence to Decision framework was used to develop clinical recommendations based on the balance between the desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS The panel agreed on 10 recommendations for the pharmacological management of CIC in adults. Based on available evidence, the panel made strong recommendations for the use of polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride for CIC in adults. Conditional recommendations were made for the use of fiber, lactulose, senna, magnesium oxide, and lubiprostone. DISCUSSION This document provides a comprehensive outline of the various over-the-counter and prescription pharmacological agents available for the treatment of CIC. The guidelines are meant to provide a framework for approaching the management of CIC; clinical providers should engage in shared decision making based on patient preferences as well as medication cost and availability. Limitations and gaps in the evidence are highlighted to help guide future research opportunities and enhance the care of patients with chronic constipation.
Collapse
Affiliation(s)
- Lin Chang
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, California.
| | - William D Chey
- Division of Gastroenterology & Hepatology, Michigan Medicine, Ann Arbor, Michigan
| | - Aamer Imdad
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, SUNY Upstate Medical University, Syracuse, New York
| | - Christopher V Almario
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California
| | - Adil E Bharucha
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | - Susan Diem
- Minneapolis VA Healthcare System, Minneapolis, Minnesota; University of Minnesota School of Medicine, Minneapolis, Minnesota
| | - Katarina B Greer
- Cleveland VA Healthcare System, Cleveland, Ohio; Case Western Reserve University, Cleveland, Ohio
| | - Brian Hanson
- Minneapolis VA Healthcare System, Minneapolis, Minnesota; Department of Medicine, University of Minnesota, Minneapolis, Minnesota
| | - Lucinda A Harris
- Division of Gastroenterology & Hepatology, Mayo Clinic, Phoenix, Arizona
| | - Cynthia Ko
- Division of Gastroenterology & Hepatology, University of Washington, Washington, DC
| | | | - Amit Patel
- Division of Gastroenterology, Duke University School of Medicine and the Durham Veterans Affairs Medical Center, Durham, North Carolina
| | - Eric D Shah
- Division of Gastroenterology & Hepatology, Michigan Medicine, Ann Arbor, Michigan; Division of Gastroenterology & Hepatology, Department of Medicine, DartMouth Health, Lebanon, New Hampshire
| | - Anthony J Lembo
- Department of Gastroenterology, Hepatology & Nutrition, Digestive Disease and Surgery Institute; Cleveland Clinic, Cleveland, Ohio
| | - Shahnaz Sultan
- Minneapolis VA Healthcare System, Minneapolis, Minnesota; University of Minnesota, Minneapolis, Minnesota
| |
Collapse
|
|
10
|
Grinevich VB, Lazebnik LB, Kravchuk YA, Radchenko VG, Tkachenko EI, Pershko AM, Seliverstov PV, Salikova CP, Zhdanov KV, Kozlov KV, Makienko VV, Potapova IV, Ivanyuk ES, Egorov DV, Sas EI, Korzheva MD, Kozlova NM, Ratnikova AK, Ratnikov VA, Sitkin SI, Bolieva LZ, Turkina CV, Abdulganieva DI, Ermolova TV, Kozhevnikova SA, Tarasova LV, Myazin RG, Khomeriki NM, Pilat TL, Kuzmina LP, Khanferyan RA, Novikova VP, Polunina AV, Khavkin AI. Gastrointestinal disorders in post-COVID syndrome. Clinical guidelines. EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2023:4-68. [DOI: 10.31146/1682-8658-ecg-208-12-4-68] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/26/2023]
Abstract
Summary Post- COVID syndrome refers to the long-term consequences of a new coronavirus infection COVID-19, which includes a set of symptoms that develop or persist after COVID-19. Symptoms of gastrointestinal disorders in post- COVID syndrome, due to chronic infl ammation, the consequences of organ damage, prolonged hospitalization, social isolation, and other causes, can be persistent and require a multidisciplinary approach. The presented clinical practice guidelines consider the main preventive and therapeutic and diagnostic approaches to the management of patients with gastroenterological manifestations of postCOVID syndrome. The Guidelines were approved by the 17th National Congress of Internal Medicine and the 25th Congress of Gastroenterological Scientifi c Society of Russia.
Collapse
Affiliation(s)
| | - L. B. Lazebnik
- A. I. Yevdokimov Moscow State University of Medicine and Dentistry
| | | | | | | | | | | | | | | | - K. V. Kozlov
- Military Medical Academy named after S. M. Kirov
| | | | | | | | - D. V. Egorov
- Military Medical Academy named after S. M. Kirov
| | - E. I. Sas
- Military Medical Academy named after S. M. Kirov
| | | | | | - A. K. Ratnikova
- North-West District Scientifi c and Clinical Center named after L. G. Sokolov Federal Medical and Biological Agency
| | - V. A. Ratnikov
- North-West District Scientifi c and Clinical Center named after L. G. Sokolov Federal Medical and Biological Agency
| | - S. I. Sitkin
- North-Western state medical University named after I. I. Mechnikov;
Almazov National Medical Research Centre
| | | | | | | | - T. V. Ermolova
- North-Western state medical University named after I. I. Mechnikov
| | | | | | | | - N. M. Khomeriki
- Moscow Regional Research Clinical Institute n. a. M. F. Vladimirsky”
| | - T. L. Pilat
- Scientifi c Research Institute of labour medicine named after academician N. F. Izmerov
| | - L. P. Kuzmina
- Scientifi c Research Institute of labour medicine named after academician N. F. Izmerov;
I. M. Sechenov First Moscow State Medical University (Sechenov University)
| | | | | | | | - A. I. Khavkin
- Russian National Research Medical University named after N. I. Pirogov
| |
Collapse
|
|
11
|
Rajindrajith S, Devanarayana NM, Thapar N, Benninga MA. Myths and misconceptions about childhood constipation. Eur J Pediatr 2023; 182:1447-1458. [PMID: 36689003 DOI: 10.1007/s00431-023-04821-8] [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: 11/02/2022] [Revised: 01/09/2023] [Accepted: 01/13/2023] [Indexed: 01/24/2023]
Abstract
Many widely held beliefs and assumptions concerning childhood constipation continue to interfere with rational management of childhood constipation. Although many still believe that constipation is not a common disease, about 9.5% of the world's children suffer from chronic constipation. Most of these children live in non-Western countries. There are major misconceptions about the etiology of constipation as a significant proportion of clinicians still believe that constipation is caused by some form an organic pathology, whereas in reality, the majority have functional constipation. Contrary to a commonly held belief that children outgrow constipation without long-term problems, there is evidence that constipation leads to significant bowel and psychological consequences and has a major impact on the quality of life which detrimentally affects future health and education. Finally, ineffective management strategies such as increasing fiber and water in the diet, and short duration of treatment owing to the fear that long-term laxative treatment leads to colonic dysfunction, interfere with effective therapeutic strategies. Conclusions: It is apparent that myths and misconception often lead to wrong assumptions regarding the distribution of the disease, its etiology, pathophysiology, and management leading to ordering incorrect investigations and ineffective therapeutic strategies while spending large sums of public funds unnecessarily. Poorly treated constipation leads to deleterious psychological consequences predisposing children to develop significant psychological damage and bowel dysfunctions. This review aims to challenge these myths about various elements of constipation by exploring the existing literature and encouraging clinicians to have a fresh look at old concepts that could interfere with the well-being of children with constipation. What is Known: • Childhood constipation is a growing problem in the world leading to significant suffering and high healthcare expenditure • Myths and misconceptions lead to poor management strategies causing psychological and bowel damage What is New: • Organic, systemic, and bowel disorders leading to constipation are uncommon, and in the majority, it arises due to deliberate fecal withholding and most investigations ordered by clinicians are not very helpful in the management • Most non-pharmacological interventions are not effective in the day-to-day management of childhood constipation. The use of laxatives is considered to be the first-line management strategy.
Collapse
Affiliation(s)
- Shaman Rajindrajith
- Department of Pediatrics, Faculty of Medicine, University of Colombo, Colombo, 00800, Sri Lanka.
| | | | - Nikhil Thapar
- Department of Gastroenterology, Hepatology and Liver Transplant, Queensland Children's Hospital, Brisbane, Australia
| | - Marc Alexander Benninga
- Department of Pediatric Gastroenterology and Nutrition, Emma Children's Hospital, Amsterdam University Medical Center, University, of Amsterdam, Amsterdam, The Netherlands
| |
Collapse
|
|
12
|
Efficacy, safety, and acceptability of polyethylene glycol 3350 without electrolytes vs magnesium hydroxide in functional constipation in children from six months to eighteen years of age: A controlled clinical trial. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2021; 88:107-117. [PMID: 34961695 DOI: 10.1016/j.rgmxen.2021.12.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Accepted: 05/18/2021] [Indexed: 11/23/2022] Open
Abstract
INTRODUCTION AND AIMS There are few studies that compare polyethylene glycol (PEG) 3350 and magnesium hydroxide (MH), as long-term treatment of functional constipation (FC) in children, and they do not include infants as young as 6 months of age. Our aim was to determine the efficacy, safety, and acceptability of PEG vs MH in FC, in the long term, in pediatric patients. METHODS An open-label, parallel, controlled clinical trial was conducted on patients from 6 months to 18 years of age, diagnosed with FC, that were randomly assigned to receive PEG 3350 or MH for 12 months. Success was defined as: ≥ 3 bowel movements/week, with no fecal incontinence, fecal impaction, abdominal pain, or the need for another laxative. We compared adverse events and acceptability, measured as rejected doses of the laxative during the study, in each group and subgroup. RESULTS Eighty-three patients with FC were included. There were no differences in success between groups (40/41 PEG vs 40/42 MH, p = 0.616). There were no differences in acceptability between groups, but a statistically significant higher number of patients rejected MH in the subgroups > 4 to 12 years and > 12 to 18 years of age (P = .037 and P = .020, respectively). There were no differences regarding adverse events between the two groups and no severe clinical or biochemical adverse events were registered. CONCLUSIONS The two laxatives were equally effective and safe for treating FC in children from 0.5 to 18 years of age. Acceptance was better for PEG 3350 than for MH in patients above 4 years of age. MH can be considered first-line treatment for FC in children under 4 years of age.
Collapse
|
|
13
|
De Giorgio R, Zucco FM, Chiarioni G, Mercadante S, Corazziari ES, Caraceni A, Odetti P, Giusti R, Marinangeli F, Pinto C. Management of Opioid-Induced Constipation and Bowel Dysfunction: Expert Opinion of an Italian Multidisciplinary Panel. Adv Ther 2021; 38:3589-3621. [PMID: 34086265 PMCID: PMC8279968 DOI: 10.1007/s12325-021-01766-y] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Accepted: 04/28/2021] [Indexed: 12/14/2022]
Abstract
The prescribing and use of opioid analgesics is increasing in Italy owing to a profusion in the number and types of opioid analgesic products available, and the increasing prevalence of conditions associated with severe pain, the latter being related to population aging. Herein we provide the expert opinion of an Italian multidisciplinary panel on the management of opioid-induced constipation (OIC) and bowel dysfunction. OIC and opioid-induced bowel dysfunction are well-recognised unwanted effects of treatment with opioid analgesics that can profoundly affect quality of life. OIC can be due to additional factors such as reduced mobility, a low-fibre diet, comorbidities, and concomitant medications. Fixed-dose combinations of opioids with mu (μ) opioid receptor antagonists, such as oxycodone/naloxone, have become available, but have limited utility in clinical practice because the individual components cannot be independently titrated, creating a risk of breakthrough pain as the dose is increased. A comprehensive prevention and management strategy for OIC should include interventions that aim to improve fibre and fluid intake, increase mobility or exercise, and restore bowel function without compromising pain control. Recommended first-line pharmacological treatment of OIC is with an osmotic laxative (preferably polyethylene glycol [macrogol]), or a stimulant laxative such as an anthraquinone. A second laxative with a complementary mechanism of action should be added in the event of an inadequate response. Second-line treatment with a peripherally acting μ opioid receptor antagonist (PAMORA), such as methylnaltrexone, naloxegol or naldemedine, should be considered in patients with OIC that has not responded to combination laxative treatment. Prokinetics or intestinal secretagogues, such as lubiprostone, may be appropriate in the third-line setting, but their use in OIC is off-label in Italy, and should therefore be restricted to settings such as specialist centres and clinical trials.
Collapse
Affiliation(s)
- Roberto De Giorgio
- Department of Translational Medicine, University of Ferrara, Via Aldo Moro 8, 44124, Ferrara, Italy.
| | | | - Giuseppe Chiarioni
- Division of Gastroenterology of the University of Verona, Azienda Ospedaliera Universitaria Integrata (AOUI) Verona, Verona, Italy
- UNC Center for Functional GI and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | | | | | - Augusto Caraceni
- High-Complexity Unit of Palliative Care, Pain Therapy and Rehabilitation, IRCSS Foundation National Cancer Institute, Milan, Italy
| | - Patrizio Odetti
- Department of Geriatrics and Gerontology, University of Genoa, Genoa, Italy
| | - Raffaele Giusti
- High-Complexity Medical Oncology Unit, Sant'Andrea University Hospital, Rome, Italy
| | - Franco Marinangeli
- Department of Anesthesiology, Pain Treatment, Intensive and Palliative Care, University of L'Aquila, L'Aquila, Italy
| | - Carmine Pinto
- High-Complexity Oncology Unit, Clinical Cancer Center, IRCCS Reggio Emilia, Reggio Emilia, Italy
| |
Collapse
|
|
14
|
Sharma A, Rao SSC, Kearns K, Orleck KD, Waldman SA. Review article: diagnosis, management and patient perspectives of the spectrum of constipation disorders. Aliment Pharmacol Ther 2021; 53:1250-1267. [PMID: 33909919 PMCID: PMC8252518 DOI: 10.1111/apt.16369] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 12/24/2020] [Accepted: 03/31/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND Chronic constipation is a common, heterogeneous disorder with multiple symptoms and pathophysiological mechanisms. Patients are often referred to a gastroenterology provider after laxatives fail. However, there is limited knowledge of the spectrum and management of constipation disorders. AIM To discuss the latest understanding of the spectrum of constipation disorders, tools for identifying a pathophysiologic-based diagnosis in the specialist setting, treatment options and the patient's perspective of constipation. METHODS Literature searches were conducted using PubMed for constipation diagnostic criteria, diagnostic tools and approved treatments. The authors provided insight from their own practices. RESULTS Clinical assessment, stool diaries and Rome IV diagnostic criteria can facilitate diagnosis, evaluate severity and distinguish between IBS with constipation, chronic idiopathic constipation and dyssynergic defecation. Novel smartphone applications can help track constipation symptoms. Rectal examinations, anorectal manometry and balloon expulsion, assessments of neuromuscular function with colonic transit time and colonic manometry can provide mechanistic understanding of underlying pathophysiology. Treatments include lifestyle and diet changes, biofeedback therapy and pharmacological agents. Several classes of laxatives, as well as prokinetic and prosecretory agents, are available; here we describe their mechanisms of action, efficacy and side effects. CONCLUSIONS Constipation includes multiple overlapping subtypes identifiable using detailed history, current diagnostic tools and smartphone applications. Recognition of individual subtype(s) could pave the way for optimal, evidence-based treatments by a gastroenterology provider.
Collapse
Affiliation(s)
- Amol Sharma
- Division of Gastroenterology/HepatologyMedical College of GeorgiaAugusta UniversityAugustaGAUSA
| | - Satish S. C. Rao
- Division of Gastroenterology/HepatologyMedical College of GeorgiaAugusta UniversityAugustaGAUSA
| | | | | | - Scott A. Waldman
- Department of Pharmacology and Experimental TherapeuticsThomas Jefferson UniversityPhiladelphiaPAUSA
| |
Collapse
|
|
15
|
Managing functional constipation: the course doesn’t always run smooth. DRUGS & THERAPY PERSPECTIVES 2021. [DOI: 10.1007/s40267-020-00803-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
|
|
16
|
Abstract
Chronic constipation is one of the five most common symptoms seen by gastroenterologist. In the absence of alarm symptoms, a confident symptom-based diagnosis can often be made using the Rome criteria. Three different subtypes have been identified to date: normal transit constipation, defaecatory disorders and slow transit constipation. Differentiation between these subtypes can be made through functional testing using tests such as anorectal manometry with balloon expulsion and a radio-opaque marker test. In general, patients are initially advised to increase their fluid and fibre intake. When these general lifestyle recommendations do not improve patients' symptoms, a step-wise and add-on treatment approach should be applied. This review summarises the diagnostic criteria to differentiate functional constipation from other causes of chronic constipation. In addition, current drug treatment options, including discussion of new therapeutic targets are discussed. Further, practical treatment approaches (choice and dosing), include discussion of combination/augmentation, treatment failure (adherence/expectations), and relapse prevention are mentioned. Finally, treatment and management of pain and bloating aspects are included.
Collapse
Affiliation(s)
- Jasper Pannemans
- Translational Research Centre for Gastrointestinal Disorders, University of Leuven, Herestraat 49, Box 701, 3000, Leuven, Belgium
| | - Imke Masuy
- Translational Research Centre for Gastrointestinal Disorders, University of Leuven, Herestraat 49, Box 701, 3000, Leuven, Belgium
| | - Jan Tack
- Translational Research Centre for Gastrointestinal Disorders, University of Leuven, Herestraat 49, Box 701, 3000, Leuven, Belgium.
| |
Collapse
|
|
17
|
Abstract
Primary care physicians frequently evaluate patients with constipation. The history is crucial in uncovering warning symptoms and signs that warrant colonoscopy. Particular elements in the history and rectal examination also can provide clues regarding the underlying etiology. Regardless of etiology, lifestyle modifications, fiber, and laxatives are first-line therapies. Patients who fail first-line therapies can be offered second-line treatments and/or referred for testing of defecatory function. In those with severely refractory symptoms, referrals to a gastroenterologist and a surgeon should be considered.
Collapse
Affiliation(s)
- David B Snell
- Division of Gastroenterology & Hepatology, Department of Medicine, New York University, 550 First Avenue, New York, NY 10016, USA.
| | - Saamia Faruqui
- Division of Gastroenterology & Hepatology, Department of Medicine, New York University, 550 First Avenue, New York, NY 10016, USA
| | - Brian P Bosworth
- Department of Medicine, New York University, 550 First Avenue, HCC 3-15, New York, NY 10016, USA
| |
Collapse
|
|
18
|
Lucak S, Lunsford TN, Harris LA. Evaluation and Treatment of Constipation in the Geriatric Population. Clin Geriatr Med 2020; 37:85-102. [PMID: 33213776 DOI: 10.1016/j.cger.2020.08.007] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Chronic constipation affects one-third of the US population and occurs disproportionately in the elderly and female individuals, increasing in older individuals who are institutionalized. This condition has a significant impact on health care costs and quality of life. Clinicians need to consider primary as well as secondary causes of constipation in elderly individuals because the cause is often multifactorial. Diagnostic algorithms should eliminate red-flag symptoms that may indicate a malignancy but also consider pelvic floor dysfunction, which is more common in this age group. An appropriate treatment plan is tailored to the severity of the patient's symptoms.
Collapse
Affiliation(s)
- Susan Lucak
- Weill Cornell Medicine, Columbia University Medical Center
| | - Tisha N Lunsford
- Division of Gastroenterology & Hepatology, Alix School of Medicine, Mayo Clinic, 13400 East Shea Boulevard, Scottsdale, AZ 85259, USA
| | - Lucinda A Harris
- Division of Gastroenterology & Hepatology, Alix School of Medicine, Mayo Clinic, 13400 East Shea Boulevard, Scottsdale, AZ 85259, USA.
| |
Collapse
|
|
19
|
Mokhtare M, Karimi S, Bahardoust M, Sotoudeheian M, Ghazi A, Babaei-Ghazani A. How adding the abdominal massage to polyethylene glycol can improve symptom and quality of life in patients with functional constipation in comparison with each one of the treatment modalities alone: A randomized clinical trial. Complement Ther Med 2020; 52:102495. [PMID: 32951744 DOI: 10.1016/j.ctim.2020.102495] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Revised: 05/11/2020] [Accepted: 06/22/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND A variety of medical and non-medical treatments have been introduced for functional constipation relief. Here, we aimed to compare the efficacy of a combination of polyethylene glycol (PEG) and abdominal massage with each one of the treatments alone. MATERIALS AND METHODS Patients with functional constipation based on Rome IV criteria were randomly assigned into the three treatment groups: group A (abdominal massage for 15 min daily), group B (PEG 20 g daily), and group C (PEG 20 g plus abdominal massage for 15 min daily) for 14 days. PAC-QOL questionnaire, Bristol stool scale were evaluated at baseline and two weeks after treatment. Constipation-associated symptom scores were recorded at baseline, two weeks and four weeks after treatment beginning. Descriptive statistics were provided as the mean ± standard deviation or number and percentage. P-value<0.05 was considered statistically significant. RESULTS Forty eight, 47 and 48 patients in group A, B, and C completed the study, respectively. PAC-QOL, Bristol and Constipation-associated symptom scores showed a significant improvement in all study groups two weeks after the treatment compared to the baseline. At the end of treatment, the rate of straining, incomplete evacuation sensation, finger evacuation and the number of defecation was significantly lower in the group C (P < 0.04). Bristol score were significantly improved in group B (P = 0.029) in compare to other groups. The total quality of life score was also significantly improved in the group C (P = 0.028). CONCLUSION A combination of abdominal massage and PEG is safe, tolerable and more effective than each one of the treatments alone.
Collapse
Affiliation(s)
- Marjan Mokhtare
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran.
| | - Shahdieh Karimi
- Internal Medicine, Iran University of Medical Sciences, Tehran, Iran.
| | - Mansour Bahardoust
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Epidemiology, School of Public Health, Iran University of Medical Science, Tehran, Iran.
| | | | - Ayoub Ghazi
- Fellowship of Gastroenterology, Iran University of Medical Sciences, Tehran, Iran.
| | - Arash Babaei-Ghazani
- Neuromusculoskeletal Research Center, Department of Physical Medicine and Rehabilitation, Iran University of Medical Sciences, Tehran, Iran; Department of Physical Medicine and Rehabilitation, University of Montreal Health Center, Montreal, Canada.
| |
Collapse
|
|
20
|
Wong MYW, Hebbard G, Gibson PR, Burgell RE. Chronic constipation and abdominal pain: Independent or closely interrelated symptoms? J Gastroenterol Hepatol 2020; 35:1294-1301. [PMID: 31900961 DOI: 10.1111/jgh.14970] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Revised: 12/20/2019] [Accepted: 01/02/2020] [Indexed: 02/06/2023]
Abstract
Constipation is both a symptom and a disorder, seen in both functional constipation and irritable bowel syndrome with constipation predominance (IBS-C). Despite the Rome IV criteria distinguishing between these conditions, they share many therapeutic approaches. This review aims to explore the relationship between constipation and abdominal pain and assess the evidence surrounding whether laxation improves abdominal pain and whether such a response to laxation differs between IBS-C and functional constipation. In patients with functional constipation, increasing frequency of bowel motions by laxatives regardless of mechanism of action is associated with reductions in the severity of abdominal pain, supporting the role of constipation as a contributor to abdominal discomfort. In patients with IBS-C, evidence from systematic reviews indicates that abdominal pain is driven by factors additional to constipation alone and that visceral analgesic modulation is also needed to optimize pain. Changing definitions of IBS-C and heterogeneity in clinical trial design including endpoints have raised uncertainty about the comparative ability of older laxatives without known neuromodulatory effects to improve chronic abdominal pain compared with new secretagogues and prokinetics for the management of IBS-C. While it is known that abdominal pain is associated with constipation and laxation contributes to relief of that pain, it remains unproven whether proposed visceral analgesic properties of new laxatives provide greater pain relief than laxation alone. However, it is likely that the response to laxation in IBS-C is only part of the puzzle.
Collapse
Affiliation(s)
- May Y W Wong
- Department of Gastroenterology, Alfred Health and Monash University, Melbourne, Victoria, Australia.,Department of Gastroenterology, The Royal Melbourne Hospital and Melbourne University, Melbourne, Victoria, Australia
| | - Geoffrey Hebbard
- Department of Gastroenterology, The Royal Melbourne Hospital and Melbourne University, Melbourne, Victoria, Australia
| | - Peter R Gibson
- Department of Gastroenterology, Alfred Health and Monash University, Melbourne, Victoria, Australia
| | - Rebecca E Burgell
- Department of Gastroenterology, Alfred Health and Monash University, Melbourne, Victoria, Australia
| |
Collapse
|
|
21
|
Serra J, Pohl D, Azpiroz F, Chiarioni G, Ducrotté P, Gourcerol G, Hungin APS, Layer P, Mendive JM, Pfeifer J, Rogler G, Scott SM, Simrén M, Whorwell P. European society of neurogastroenterology and motility guidelines on functional constipation in adults. Neurogastroenterol Motil 2020; 32:e13762. [PMID: 31756783 DOI: 10.1111/nmo.13762] [Citation(s) in RCA: 120] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Revised: 10/14/2019] [Accepted: 10/18/2019] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Chronic constipation is a common disorder with a reported prevalence ranging from 3% to 27% in the general population. Several management strategies, including diagnostic tests, empiric treatments, and specific treatments, have been developed. Our aim was to develop European guidelines for the clinical management of constipation. DESIGN After a thorough review of the literature by experts in relevant fields, including gastroenterologists, surgeons, general practitioners, radiologists, and experts in gastrointestinal motility testing from various European countries, a Delphi consensus process was used to produce statements and practical algorithms for the management of chronic constipation. KEY RESULTS Seventy-three final statements were agreed upon after the Delphi process. The level of evidence for most statements was low or very low. A high level of evidence was agreed only for anorectal manometry as a comprehensive evaluation of anorectal function and for treatment with osmotic laxatives, especially polyethylene glycol, the prokinetic drug prucalopride, secretagogues, such as linaclotide and lubiprostone and PAMORAs for the treatment of opioid-induced constipation. However, the level of agreement between the authors was good for most statements (80% or more of the authors). The greatest disagreement was related to the surgical management of constipation. CONCLUSIONS AND INFERENCES European guidelines on chronic constipation, with recommendations and algorithms, were developed by experts. Despite the high level of agreement between the different experts, the level of scientific evidence for most recommendations was low, highlighting the need for future research to increase the evidence and improve treatment outcomes in these patients.
Collapse
Affiliation(s)
- Jordi Serra
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Badalona, Spain
- Motility and Functional Gut Disorders Unit, University Hospital Germans Trias i Pujol, Badalona, Spain
- Department of Medicine, Autonomous University of Barcelona, Badalona, Spain
| | - Daniel Pohl
- Division of Gastroenterology, University Hospital Zurich, Zurich, Switzerland
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Fernando Azpiroz
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Badalona, Spain
- Digestive System Research Unit, University Hospital Vall d'Hebron, Barcelona, Spain
| | - Giuseppe Chiarioni
- Division of Gastroenterology B, AOUI Verona, Verona, Italy
- UNC Center for Functional GI and Motility Disorders, University of North Carolina, Chapel Hill, NC, USA
| | - Philippe Ducrotté
- Department of Gastroenterology, UMR INSERM 1073, Rouen University Hospital, Rouen, France
| | - Guillaume Gourcerol
- Department of Physiology, UMR INSERM 1073 & CIC INSERM 1404, Rouen University Hospital, Rouen, France
| | - A Pali S Hungin
- General Practice, Faculty of Medical Sciences, Newcastle University, Newcastle, UK
| | - Peter Layer
- Department of Medicine, Israelitic Hospital, Hamburg, Germany
| | - Juan-Manuel Mendive
- Sant Adrià de Besòs (Barcelona) Catalan Institut of Health (ICS), La Mina Primary Health Care Centre, Badalona, Spain
| | - Johann Pfeifer
- Department of Surgery, Division of General Surgery, Medical University of Graz, Graz, Austria
| | - Gerhard Rogler
- Division of Gastroenterology, University Hospital Zurich, Zurich, Switzerland
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - S Mark Scott
- Neurogastroenterology Group, Centre for Neuroscience, Surgery and Trauma, Blizard Institute, Barts, UK
- The London School of Medicine & Dentistry, Queen Mary University London, London, UK
| | - Magnus Simrén
- Department of Internal Medicine & Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Peter Whorwell
- Division of Diabetes, Endocrinology & Gastroenterology, Neurogastroenterology Unit, Wythenshawe Hospital, University of Manchester, Manchester, UK
| |
Collapse
|
|
22
|
Nee J, Sugarman MA, Ballou S, Katon J, Rangan V, Singh P, Zubiago J, Kaptchuk TJ, Lembo A. Placebo Response in Chronic Idiopathic Constipation: A Systematic Review and Meta-Analysis. Am J Gastroenterol 2019; 114:1838-1846. [PMID: 31592782 DOI: 10.14309/ajg.0000000000000399] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Chronic idiopathic constipation (CIC), like other functional gastrointestinal disorders, has been associated with a high placebo response rate. However, the placebo response in randomized controlled trials has not been described. METHODS We conducted a search of the medical literature following the protocol outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement using MEDLINE, EMBASE and EMBASE Classic, Web of Science, and the Cochrane Central Register of Controlled Trials for all drugs used for the treatment of CIC. Two independent reviewers performed eligibility assessment and data extraction. The mean response rate was examined for the following 2 responder endpoints: (i) greater than or equal to 3 complete spontaneous bowel movements (CSBMs)/wk (≥3 CSBMs/wk responders) and (ii) mean increase of ≥1 CSBM/wk compared with baseline (increase in ≥1 CSBM/wk responders). RESULTS A total of 23 placebo-controlled trials met our inclusion criteria and were included in this meta-analysis. The placebo response in CIC trials ranged from 4% to 44%. The magnitude of the placebo response was 13% (95% confidence interval 11%-16%) with the ≥3 CSBM/wk responder endpoint and 28% (95% confidence interval 21%-30%) with the increase of ≥1 in the CSBM responder endpoint. Higher baseline CSBM, older age, and trials with more male participants were significantly associated with a stronger placebo response for both the ≥3 CSBMs/wk endpoint and increase in the ≥1 CSBM/wk endpoint. Trial characteristics such as location (Europe vs Asia/United States) and laxative class (prokinetic vs secretagogue) revealed key differences in the placebo response for both endpoints. The placebo response was not significantly affected by the number of study visits, study duration, year of publication, number of drop outs, or likelihood of receiving active drug. DISCUSSION The placebo response in CIC trials ranges from 4% to 44% depending on the endpoint. Modifying factors of the placebo response include multiple subject and trial characteristics.
Collapse
Affiliation(s)
- Judy Nee
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
| | | | - Sarah Ballou
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
| | - Jesse Katon
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
| | - Vikram Rangan
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
| | - Prashant Singh
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
| | - Julia Zubiago
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
| | - Ted J Kaptchuk
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
| | - Anthony Lembo
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
| |
Collapse
|
|
23
|
Bassotti G, Usai Satta P, Bellini M. Plecanatide for the treatment of chronic idiopathic constipation in adult patients. Expert Rev Clin Pharmacol 2019; 12:1019-1026. [PMID: 31575291 DOI: 10.1080/17512433.2019.1670057] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Accepted: 09/17/2019] [Indexed: 12/14/2022]
Abstract
Introduction. Chronic idiopathic constipation (CIC) is a functional gastrointestinal disorder that is associated with an increased healthcare cost and an abnormally poor quality of life. Plecanatide is a natural analog to the peptide agonist of the guanylate cyclase-C (GC-C) receptor, uroguanylin. The conversion of guanosine 5-triphosphate to cyclic guanosine monophosphate results in an increased bowel fluid secretion. Plecanatide is a promising new agent for CIC unresponsive to current therapeutic regimes.Areas covered. A comprehensive online search of Medline and the Science Citation Index was made using the keywords 'plecanatide', 'guanylate cyclase-C agonists', and 'constipation', in various combinations. We reviewed the pharmacodynamics, pharmacokinetics, and metabolism of this agent, and the most significant studies regarding the clinical efficacy and safety of plecanatide in CIC therapy.Expert opinion. Experimental studies showed that plecanatide was significantly better than placebo in reducing CIC severity, straining, stool consistency, bowel movements and quality of life. Apart from limited cases of diarrhea, no serious adverse events were reported. However, few data are available on its long-term safety. Furthermore, patients' affordability of plecanatide can be limited by its costs. Finally, this new agent with a different way of action can be proposed in patients refractory to common therapy.
Collapse
Affiliation(s)
- Gabrio Bassotti
- Gastroenterology & Hepatology Section, Department of Medicine, University of Perugia Medical School, Perugia, Italy
| | | | - Massimo Bellini
- Gastrointestinal Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| |
Collapse
|
|
24
|
Luthra P, Camilleri M, Burr NE, Quigley EMM, Black CJ, Ford AC. Efficacy of drugs in chronic idiopathic constipation: a systematic review and network meta-analysis. Lancet Gastroenterol Hepatol 2019; 4:831-844. [DOI: 10.1016/s2468-1253(19)30246-8] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Revised: 06/30/2019] [Accepted: 07/02/2019] [Indexed: 12/13/2022]
|
|
25
|
Abstract
Constipation is a common symptom that may be primary (idiopathic or functional) or associated with a number of disorders or medications. Although most constipation is self-managed by patients, 22% seek health care, mostly to primary care physicians (>50%) and gastroenterologists (14%), resulting in large expenditures for diagnostic testing and treatments. There is strong evidence that stimulant and osmotic laxatives, intestinal secretagogues, and peripherally restricted μ-opiate antagonists are effective and safe; the lattermost drugs are a major advance for managing opioid-induced constipation. Constipation that is refractory to available laxatives should be evaluated for defecatory disorders and slow-transit constipation using studies of anorectal function and colonic transit. Defecatory disorders are often responsive to biofeedback therapies, whereas slow-transit constipation may require surgical intervention in selected patients. Both efficacy and cost should guide the choice of treatment for functional constipation and opiate-induced constipation. Currently, no studies have compared inexpensive laxatives with newer drugs that work by other mechanisms.
Collapse
Affiliation(s)
- Adil E. Bharucha
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Arnold Wald
- Division of Gastroenterology and Hepatology, University of Wisconsin School of Medicine and Public Health, Madison
| |
Collapse
|
|
26
|
Sheikh-Taha M, Dimassi H. Use of over the counter products in older cardiovascular patients admitted to a tertiary care center in USA. BMC Geriatr 2018; 18:301. [PMID: 30514238 PMCID: PMC6278107 DOI: 10.1186/s12877-018-0989-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2018] [Accepted: 11/21/2018] [Indexed: 01/25/2023] Open
Abstract
BACKGROUND In recent years there has been a substantial increase in the use of over-the-counter (OTC) products around the world. While they are assumed to be safe by consumers, they can potentially lead to adverse effects and drug interactions particularly in older adults. METHODS We assessed the patterns of OTC products used by older adults admitted to the cardiology service in a tertiary care medical center in the USA over a three month period. We conducted a retrospective chart review where older adults with cardiovascular diseases (CVD) who were taking at least one OTC product at home were included. RESULTS Out of 404 patients who were admitted to the cardiology service, 281 (69.6%) were taking OTC products. Patients were taking a total of 659 OTC products; mean of 2.35 ± 1.57 and the range varied from 1 to 9 products. The most commonly used products were vitamins (37.3%), followed by laxatives (17%), minerals (13.6%), stomach acid reducers (9%), and analgesics (3.6%). OTC users were found to be suffering from more comorbidities and received more prescription medications as compared to non-users. Gender and age did not have an impact on the use of OTC products while patients with atrial fibrillation, sleep apnea and gastro-esophageal reflux disease were more likely to use OTC products. CONCLUSION Use of OTC products is quite frequent in older adults with CVD in our study. Clinicians should ask about OTC product usage and counsel patients about the risks and benefits associated with their use.
Collapse
Affiliation(s)
- Marwan Sheikh-Taha
- Department of Pharmacy Practice, Lebanese American University, Byblos, Lebanon.
| | - Hani Dimassi
- Department of Pharmaceutical Sciences, Lebanese American University, Byblos, Lebanon
| |
Collapse
|
|
27
|
Zhu L, Ma Y, Deng X. Comparison of acupuncture and other drugs for chronic constipation: A network meta-analysis. PLoS One 2018; 13:e0196128. [PMID: 29694378 PMCID: PMC5918910 DOI: 10.1371/journal.pone.0196128] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2018] [Accepted: 04/06/2018] [Indexed: 01/19/2023] Open
Abstract
The objective of this study was to compare the efficacy and side effects of acupuncture, sham acupuncture and drugs in the treatment of chronic constipation. Randomized controlled trials (RCTs) assessing the effects of acupuncture and drugs for chronic constipation were comprehensively retrieved from electronic databases (such as PubMed, Cochrane Library, Embase, CNKI, Wanfang Database, VIP Database and CBM) up to December 2017. Additional references were obtained from review articles. With quality evaluations and data extraction, a network meta-analysis (NMA) was performed using a random-effects model under a frequentist framework. A total of 40 studies (n = 11032) were included: 39 were high-quality studies and 1 was a low-quality study. NMA showed that (1) acupuncture improved the symptoms of chronic constipation more effectively than drugs; (2) the ranking of treatments in terms of efficacy in diarrhoea-predominant irritable bowel syndrome was acupuncture, polyethylene glycol, lactulose, linaclotide, lubiprostone, bisacodyl, prucalopride, sham acupuncture, tegaserod, and placebo; (3) the ranking of side effects were as follows: lactulose, lubiprostone, bisacodyl, polyethylene glycol, prucalopride, linaclotide, placebo and tegaserod; and (4) the most commonly used acupuncture point for chronic constipation was ST25. Acupuncture is more effective than drugs in improving chronic constipation and has the least side effects. In the future, large-scale randomized controlled trials are needed to prove this. Sham acupuncture may have curative effects that are greater than the placebo effect. In the future, it is necessary to perform high-quality studies to support this finding. Polyethylene glycol also has acceptable curative effects with fewer side effects than other drugs.
Collapse
Affiliation(s)
- Lingping Zhu
- General Practice Department of Shenzhen Longhua District Central Hospital, Shenzhen, Guangdong Province, China
- General Practice Department of Zhongshan Hospital of Fudan University, Shanghai City, China
| | - Yunhui Ma
- General Practice Department of Shenzhen Longhua District Central Hospital, Shenzhen, Guangdong Province, China
| | - Xiaoyan Deng
- Endocrinology Department of Shenzhen Longhua District Central Hospital, Shenzhen, Guangdong Province, China
| |
Collapse
|
|
28
|
The Mexican consensus on chronic constipation. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2018. [DOI: 10.1016/j.rgmxen.2018.05.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
|
|
29
|
Clinical practice guidelines from the French National Society of Coloproctology in treating chronic constipation. Eur J Gastroenterol Hepatol 2018; 30:357-363. [PMID: 29406436 DOI: 10.1097/meg.0000000000001080] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Chronic constipation is a common symptom that regularly affects the quality of life of adult patients. Its treatment is mainly based on dietary rules, laxative drugs, perineal rehabilitation and surgical treatment. The French National Society of Coloproctology offers clinical practice recommendations on the basis of the data in the current literature, including those on recently developed treatments. Most are noninvasive, and the main concepts include the following: stimulant laxatives are now considered safe drugs and can be more easily prescribed as a second-line treatment; biofeedback therapy remains the gold standard for the treatment of anorectal dyssynergia that is resistant to medical treatment; transanal irrigation is the second-line treatment of choice in patients with neurological diseases, but it may also be proposed for patients without neurological diseases; and although interferential therapy may be a new promising treatment, it needs further evaluation.
Collapse
|
|
30
|
The Mexican consensus on chronic constipation. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2018; 83:168-189. [PMID: 29555103 DOI: 10.1016/j.rgmx.2017.12.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/29/2017] [Accepted: 12/08/2017] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Significant advances have been made in the knowledge and understanding of the epidemiology, pathophysiology, diagnosis, and treatment of chronic constipation, since the publication of the 2011 guidelines on chronic constipation diagnosis and treatment in Mexico from the Asociación Mexicana de Gastroenterología. AIMS To present a consensus review of the current state of knowledge about chronic constipation, providing updated information and integrating the new scientific evidence. METHODS Three general coordinators reviewed the literature published within the time frame of January 2011 and January 2017. From that information, 62 initial statements were formulated and then sent to 12 national experts for their revision. The statements were voted upon, using the Delphi system in 3 voting rounds (2 electronic and one face-to-face). The statements were classified through the GRADE system and those that reached agreement >75% were included in the consensus. RESULTS AND CONCLUSIONS The present consensus is made up of 42 final statements that provide updated knowledge, supplementing the information that had not been included in the previous guidelines. The strength of recommendation and quality (level) of evidence were established for each statement. The current definitions of chronic constipation, functional constipation, and opioid-induced constipation are given, and diagnostic strategies based on the available diagnostic methods are described. The consensus treatment recommendations were established from evidence on the roles of diet and exercise, fiber, laxatives, new drugs (such as prucalopride, lubiprostone, linaclotide, plecanatide), biofeedback therapy, and surgery.
Collapse
|
|
31
|
Long-term follow-up of the effects of fecal microbiota transplantation in combination with soluble dietary fiber as a therapeutic regimen in slow transit constipation. SCIENCE CHINA-LIFE SCIENCES 2018; 61:779-786. [PMID: 29441452 DOI: 10.1007/s11427-017-9229-1] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2017] [Accepted: 11/22/2017] [Indexed: 02/07/2023]
Abstract
As some studies have reported that strategies targeting the gut microbiota such as fecal microbiota transplantation (FMT) with or without other microecological therapy might have efficacy in treating slow transit constipation (STC), we conducted a single-center, open-label trial to study the long-term effect of FMT combined with soluble dietary fiber (pectin) on STC. Thirty-one adult patients with STC were enrolled into the trial. Patients received 6-day FMT procedures repeatedly for the first 3 months and soluble dietary fiber (pectin) daily during the follow-up. The rate of clinical remission and improvement, stool consistency, the Wexner constipation scale, and assessment of constipation-related symptoms were evaluated at week 4 and 1 year later. The clinical remission and improvement rates at week 4 were 69.0% (20/29) and 75.9% (22/29), respectively. At the end of the study, 48.3% (14/29) of patients continued to have at least three complete spontaneous bowel movements per week and 58.6% (17/29) of patients showed clinical improvements. Stool consistency, the Wexner constipation scale, and constipation symptoms improved both at short-term and long-term follow-up. The results indicated that FMT in combination with soluble dietary fiber (pectin) had both short-term and long-term efficacy in treating STC.
Collapse
|
|
32
|
Advancements in the Treatment of Constipation in Hospitalized Older Adults: Utilizing Secretagogues and Peripherally Acting Mu-Opioid Receptor Antagonists. Am J Ther 2018. [DOI: 10.1097/mjt.0000000000000665] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
|
|
33
|
Mínguez M, López Higueras A, Júdez J. Use of polyethylene glycol in functional constipation and fecal impaction. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2017; 108:790-806. [PMID: 27871178 DOI: 10.17235/reed.2016.4571/2016] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
OBJECTIVE The objective of this study was to evaluate in an analytical and descriptive manner the evidence published so far on the use of polyethylene glycol (PEG), with or without electrolytes, in the management of functional constipation and the treatment of fecal impaction. METHODOLOGY Search on MEDLINE, EMBASE and Cochrane databases until May 2016 of all publications adjusted to the following terms: constipation AND/OR fecal impaction AND (PEG OR polyethylene glycol OR macrogol OR movicol OR idralax OR miralax OR transipeg OR forlax OR golytely OR isocolan OR mulytely) NOT colonoscopy. Critical reading of selected articles (English or Spanish), sorting their description according to group age (adult/pediatric age) and within those, in accordance with study features (efficacy evaluation versus placebo, doses query, safety, comparison with other laxatives, observational studies and monographic review articles of polyethylene glycol or meta-analysis). RESULTS Fifty-eight publications have been chosen for descriptive analysis; of them, 41 are clinical trials, eight are observational studies and nine are systematic reviews or meta-analysis. Twelve clinical trials evaluate PEG efficacy versus placebo, eight versus lactulose, six are dose studies, five compare polyethylene glycol with and without electrolytes, two compare its efficacy with respect to milk of magnesia, and the rest of the trials evaluate polyethylene glycol with enemas (two), psyllium (one), tegaserod (one), prucalopride (one), paraffin oil (one), fiber combinations (one) and Descurainia sophia (one). CONCLUSIONS Polyethylene glycol with or without electrolytes is more efficacious than placebo for the treatment of functional constipation, either in adults or in pediatric patients, with great safety and tolerability. These preparations constitute the most efficacious osmotic laxatives (more than lactulose) and are the first-line treatment for functional constipation in the short and long-term. They are as efficacious as enemas in fecal impaction, avoid the need for hospital admission and are well tolerated by patients (mainly when administered without electrolytes).
Collapse
Affiliation(s)
- Miguel Mínguez
- Servicio de Medicina Digestiva, Hospital Clínico de Valencia
| | | | | |
Collapse
|
|
34
|
Nelson AD, Camilleri M, Chirapongsathorn S, Vijayvargiya P, Valentin N, Shin A, Erwin PJ, Wang Z, Murad MH. Comparison of efficacy of pharmacological treatments for chronic idiopathic constipation: a systematic review and network meta-analysis. Gut 2017; 66:1611-1622. [PMID: 27287486 DOI: 10.1136/gutjnl-2016-311835] [Citation(s) in RCA: 113] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2016] [Revised: 04/15/2016] [Accepted: 05/17/2016] [Indexed: 12/16/2022]
Abstract
OBJECTIVE To compare efficacy of pharmacotherapies for chronic idiopathic constipation (CIC) based on comparisons to placebo using Bayesian network meta-analysis. DATA SOURCES We conducted searches (inception to May 2015) of MEDLINE, EMBASE, Scopus and Cochrane Central, as well as original data from authors or drug companies for the medications used for CIC. STUDY SELECTION Phase IIB and phase III randomised, placebo-controlled trials (RCT) of ≥4 weeks' treatment for CIC in adults with Rome II or III criteria for functional constipation; trials included at least one of four end points. DATA EXTRACTION AND SYNTHESIS Two investigators independently evaluated all full-text articles that met inclusion criteria and extracted data for primary and secondary end points, risk of bias and quality of evidence. OUTCOMES Primary end points were ≥3 complete spontaneous bowel movements (CSBM)/week and increase over baseline by ≥1 CSBM/week. Secondary end points were change from baseline (Δb) in the number of SBM/week and Δb CSBM/week. RESULTS Twenty-one RCTs (9189 patients) met inclusion and end point criteria: 9 prucalopride, 3 lubiprostone, 3 linaclotide, 2 tegaserod, 1 each velusetrag, elobixibat, bisacodyl and sodium picosulphate (NaP). All prespecified end points were unavailable in four polyethylene glycol studies. Bisacodyl, NaP, prucalopride and velusetrag were superior to placebo for the ≥3 CSBM/week end point. No drug was superior at improving the primary end points on network meta-analysis. Bisacodyl appeared superior to the other drugs for the secondary end point, Δb in number of SBM/week. CONCLUSIONS Current drugs for CIC show similar efficacy. Bisacodyl may be superior to prescription medications for Δb in the number of SBM/week in CIC.
Collapse
Affiliation(s)
- Alfred D Nelson
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, Minnesota, USA
| | - Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, Minnesota, USA
| | - Sakkarin Chirapongsathorn
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, Minnesota, USA
| | - Priya Vijayvargiya
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, Minnesota, USA
| | - Nelson Valentin
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, Minnesota, USA
| | - Andrea Shin
- Indiana University, Indianapolis, Indiana, USA
| | - Patricia J Erwin
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, Minnesota, USA
| | - Zhen Wang
- Mayo Clinic Evidence-Based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - M Hassan Murad
- Mayo Clinic Evidence-Based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| |
Collapse
|
|
35
|
Serrano-Falcón B, Rey E. The safety of available treatments for chronic constipation. Expert Opin Drug Saf 2017; 16:1243-1253. [PMID: 28756692 DOI: 10.1080/14740338.2017.1361402] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Affiliation(s)
- Blanca Serrano-Falcón
- Department of Digestive Diseases, Hospital Clinico San Carlos, Complutense University, Instituto de Investigacion Sanitaria San Carlos (IdISSC), Madrid, Spain
| | - Enrique Rey
- Department of Digestive Diseases, Hospital Clinico San Carlos, Complutense University, Instituto de Investigacion Sanitaria San Carlos (IdISSC), Madrid, Spain
| |
Collapse
|
|
36
|
Krogh K, Chiarioni G, Whitehead W. Management of chronic constipation in adults. United European Gastroenterol J 2017; 5:465-472. [PMID: 28588875 PMCID: PMC5446139 DOI: 10.1177/2050640616663439] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2016] [Accepted: 07/15/2016] [Indexed: 12/21/2022] Open
Abstract
Chronic constipation (CC) is an extremely common condition with an estimated prevalence of up to 24%. Most patients with CC should be treated in primary care. Changes in lifestyle, including increased intake of dietary fibre, fluid, and exercise, should be attempted in most patients. Osmotic or stimulant laxatives are indicated if there are insufficient effects of lifestyle changes. Prokinetics and secretagogues should be restricted to those not responding to basic treatment. Anorectal physiology tests and assessment of colorectal transit time are indicated if medical treatment fails or if symptoms indicate severely obstructed defecation. If symptoms indicate an underlying structural disorder, barium or magnetic resonance evacuation proctography is indicated. Biofeedback therapy is effective in patients with dyssynergic defecation. In patients with other evacuation disorders, rectally administered laxatives or transanal irrigation should be attempted. Surgery is restricted to the minority of CC patients with very severe symptoms not responding to conservative treatment.
Collapse
Affiliation(s)
- K Krogh
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - G Chiarioni
- Gastroenterology Division, University of Verona, Verona, Italy
| | - W Whitehead
- Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| |
Collapse
|
|
37
|
Treatment Algorithm for Chronic Idiopathic Constipation and Constipation-Predominant Irritable Bowel Syndrome Derived from a Canadian National Survey and Needs Assessment on Choices of Therapeutic Agents. Can J Gastroenterol Hepatol 2017; 2017:8612189. [PMID: 28271055 PMCID: PMC5320366 DOI: 10.1155/2017/8612189] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2016] [Revised: 11/23/2016] [Accepted: 12/18/2016] [Indexed: 12/15/2022] Open
Abstract
Background. Chronic idiopathic constipation (CIC) and constipation-predominant irritable bowel syndrome (IBS-C) are common functional lower gastrointestinal disorders that impair patients' quality of life. In a national survey, we aimed to evaluate (1) Canadian physician practice patterns in the utilization of therapeutic agents listed in the new ACG and AGA guidelines; (2) physicians satisfaction with these agents for their CIC and IBS-C patients; and (3) the usefulness of these new guidelines in their clinical practice. Methods. A 9-item questionnaire was sent to 350 Canadian specialists to evaluate their clinical practice for the management of CIC and IBS-C. Results. The response rate to the survey was 16% (n = 55). Almost all (96%) respondents followed a standard, stepwise approach for management while they believed that only 24% of referring physicians followed the same approach. Respondents found guanylyl cyclase C (GCC) agonist most satisfying when treating their patients. Among the 69% of respondents who were aware of published guidelines, only 50% found them helpful in prioritizing treatment choices and 69% of respondents indicated that a treatment algorithm, applicable to Canadian practice, would be valuable. Conclusion. Based on this needs assessment, a treatment algorithm was developed to provide clinical guidance in the management of IBS-C and CIC in Canada.
Collapse
|
|
38
|
Prasad VGM, Abraham P. Management of chronic constipation in patients with diabetes mellitus. Indian J Gastroenterol 2017; 36:11-22. [PMID: 27987136 DOI: 10.1007/s12664-016-0724-2] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2016] [Accepted: 11/27/2016] [Indexed: 02/04/2023]
Abstract
AIM The aim of this review is to provide an overview of the clinical assessment and evidence-based treatment options for managing diabetes-associated chronic constipation. METHODS A literature search of published medical reports in English language was performed using the OVID Portal, from PUBMED and the Cochrane Database of Systematic Reviews, from inception to October 2015. A total of 145 abstracts were identified; duplicate publications were removed and 95 relevant full-text articles were retrieved for potential inclusion. RESULTS Chronic constipation is one of the most common gastrointestinal symptoms in patients with diabetes, and occurs more frequently than in healthy individuals. Treatment goals include improving symptoms and restoring bowel function by accelerating colonic transit and facilitating defecation. Based on guidelines and data from published literature, food and dietary change with exercise and lifestyle change should be the first step in management. For patients recalcitrant to these changes, laxatives should be the next step of treatment. Treatment should begin with bulking agents such as psyllium, bran or methylcellulose followed by osmotic laxatives if response is poor. Lactulose, polyethylene glycol and lactitol are the most frequently prescribed osmotic agents. Lactulose has a prebiotic effect and a carry-over effect (continued laxative effect for at least 6 to 7 days, post cessation of treatment). Stimulants such as bisacodyl, sodium picosulphate and senna are indicated if osmotic laxatives are not effective. Newer agents such as chloride-channel activators and 5-HT4 agonist can be considered for severe or resistant cases. CONCLUSION The primary aim of intervention in diabetic patients with chronic constipation is to better manage the diabetes along with management of constipation. The physician should explain the rationale for prescribing laxatives and educate patients about the potential drawbacks of long-term use of laxatives. They should contact their physician if short-term use of prescribed laxative fails to provide relief.
Collapse
Affiliation(s)
- V G M Prasad
- VGM Hospital, 2100, Trichy Road, Coimbatore, 641 005, India.
| | - Philip Abraham
- P D Hinduja National Hospital and Medical Research Centre, Veer Savarkar Marg, Mahim, Mumbai, 400 016, India
| |
Collapse
|
|
39
|
Abstract
INTRODUCTION Chronic constipation is a frequent complaint in daily clinical practice. Notwithstanding the availability of numerous drugs, its treatment it is still unsatisfactory. However, new emerging treatments are in the pipeline and some drugs seem to be promising; among these velusetrag, a selective 5-HT4 receptors agonist. AREAS COVERED An in depth Medline literature search was performed concerning topics related to the treatment of constipated patients with velusetrag. In addition, abstracts concerning the topic were searched by hand in our libraries. EXPERT OPINION After analyzing the available data, the authors feel that velusetrag may likely improve symptoms and the quality of life of chronically constipated subjects. However, additional data is needed to fully understand the safety and efficacy of velusetrag, particularly in patients on long-term therapy. Thanks to the once-daily dosing and the pharmacologic properties, velusetrag could be used as a single agent or in association with other drugs. In the future, this drug holds the potential to be an effective adjunct to the therapeutic armamentarium for chronic constipation.
Collapse
Affiliation(s)
- Gabrio Bassotti
- a Gastroenterology & Hepatology Section, Department of Medicine , University of Perugia Medical School , Perugia , Italy
| | - Dario Gambaccini
- b Gastrointestinal Unit, Department of Gastroenterology , University of Pisa , Pisa , Italy
| | - Massimo Bellini
- b Gastrointestinal Unit, Department of Gastroenterology , University of Pisa , Pisa , Italy
| |
Collapse
|
|
40
|
Sajid MS, Hebbar M, Baig MK, Li A, Philipose Z. Use of Prucalopride for Chronic Constipation: A Systematic Review and Meta-analysis of Published Randomized, Controlled Trials. J Neurogastroenterol Motil 2016; 22:412-22. [PMID: 27127190 PMCID: PMC4930296 DOI: 10.5056/jnm16004] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2016] [Revised: 02/14/2016] [Accepted: 03/05/2016] [Indexed: 12/22/2022] Open
Abstract
This article highlights the role of prucalopride in the management of chronic constipation based upon the principles of meta-analysis using data reported in the published randomized, controlled trials. Sixteen randomized, controlled trials on 3943 patients reported the effectiveness of prucalopride in patients with chronic constipation. Prucalopride successfully increased the frequency of spontaneous bowel movements per week in all variable doses of 1 mg (standardized mean difference [SMD], 0.42 [95% CI, 0.18-0.66; P = 0.006]), 2 mg (SMD, 0.34 [95% CI, 0.11-0.56; P = 0.003]), and 4 mg (SMD, 0.33 [95% CI, 0.22-0.44; P = 0.00001]). The risks of adverse events or side effects such as headache, abdominal cramps, excessive flatulence, dizziness, diarrhea, and rash were higher (odds ratio, 1.70 [95% CI, 1.27 to -2.27; P = 0.0004]) in prucalopride group. Prucalopride is clinically a beneficial pharmacotherapy for chronic constipation and its routine use may be considered in patients with chronic simple laxative-resistant constipation.
Collapse
Affiliation(s)
- Muhammad S Sajid
- Department of General, Endoscopic and Laparoscopic Colorectal Surgery, Western Sussex Hospitals NHS Foundation Trust, Worthing Hospital, Worthing,
UK
| | - Madhu Hebbar
- Department of General, Endoscopic and Laparoscopic Colorectal Surgery, Western Sussex Hospitals NHS Foundation Trust, Worthing Hospital, Worthing,
UK
| | - Mirza K Baig
- Department of General, Endoscopic and Laparoscopic Colorectal Surgery, Western Sussex Hospitals NHS Foundation Trust, Worthing Hospital, Worthing,
UK
| | - Andy Li
- Department of Gastroenterology, Gastrointestinal Endoscopy and Hepatology, Western Sussex Hospitals NHS Foundation Trust, Worthing Hospital, Worthing,
UK
| | - Zinu Philipose
- Department of Gastroenterology, Gastrointestinal Endoscopy and Hepatology, Western Sussex Hospitals NHS Foundation Trust, Worthing Hospital, Worthing,
UK
| |
Collapse
|
|
41
|
Shin JE, Jung HK, Lee TH, Jo Y, Lee H, Song KH, Hong SN, Lim HC, Lee SJ, Chung SS, Lee JS, Rhee PL, Lee KJ, Choi SC, Shin ES. Guidelines for the Diagnosis and Treatment of Chronic Functional Constipation in Korea, 2015 Revised Edition. J Neurogastroenterol Motil 2016; 22:383-411. [PMID: 27226437 PMCID: PMC4930295 DOI: 10.5056/jnm15185] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2015] [Revised: 03/13/2016] [Accepted: 04/03/2016] [Indexed: 12/13/2022] Open
Abstract
The Korean Society of Neurogastroenterology and Motility first published guidelines for chronic constipation in 2005 and was updated in 2011. Although the guidelines were updated using evidence-based process, they lacked multidisciplinary participation and did not include a diagnostic approach for chronic constipation. This article includes guidelines for diagnosis and treatment of chronic constipation to realistically fit the situation in Korea and to be applicable to clinical practice. The guideline development was based upon the adaptation method because research evidence was limited in Korea, and an organized multidisciplinary group carried out systematical literature review and series of evidence-based evaluations. Six guidelines were selected using the Appraisal of Guidelines for Research & Evaluation (AGREE) II process. A total 37 recommendations were adopted, including 4 concerning the definition and risk factors of chronic constipation, 8 regarding diagnoses, and 25 regarding treatments. The guidelines are intended to help primary physicians and general health professionals in clinical practice in Korea, to provide the principles of medical treatment to medical students, residents, and other healthcare professionals, and to help patients for choosing medical services based on the information. These guidelines will be updated and revised periodically to reflect new diagnostic and therapeutic methods.
Collapse
Affiliation(s)
- Jeong Eun Shin
- Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea
| | - Hye-Kyung Jung
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
| | - Tae Hee Lee
- Institute for Digestive Research, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Yunju Jo
- Division of Gastroenterology, Department of Internal Medicine, Eulji General Hospital, Eulji University School of Medicine, Seoul, Korea
| | - Hyuk Lee
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kyung Ho Song
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Konyang University Hospital, Daejeon, Korea
| | - Sung Noh Hong
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hyun Chul Lim
- Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Gyeonggi-do, Korea
| | - Soon Jin Lee
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Soon Sup Chung
- Department of Surgery, Ewha Womans University School of Medicine, Seoul, Korea
| | - Joon Seong Lee
- Institute for Digestive Research, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Poong-Lyul Rhee
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kwang Jae Lee
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Suck Chei Choi
- Department of Internal Medicine and Digestive Disease Research Institute, Wonkwang University School of Medicine, Iksan, Korea
| | - Ein Soon Shin
- Steering Committee for Clinical Practice Guideline, Korean Academy of Medical Science, Korea
| | | |
Collapse
|
|
42
|
McGraw T. Polyethylene glycol 3350 in occasional constipation: A one-week, randomized, placebo-controlled, double-blind trial. World J Gastrointest Pharmacol Ther 2016; 7:274-282. [PMID: 27158544 PMCID: PMC4848251 DOI: 10.4292/wjgpt.v7.i2.274] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2015] [Revised: 12/23/2015] [Accepted: 01/13/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the efficacy and safety of polyethylene glycol (PEG) 3350 in subjects with self-reported occasional constipation.
METHODS: Eligible subjects ≥ 17 years of age were randomized to receive either placebo or PEG 3350 17 g once daily in this multicenter, double-blind trial. Evaluations were conducted before (baseline) and after a 7-d treatment period. The primary efficacy variable was the proportion of subjects reporting complete resolution of straining and hard or lumpy stools. Secondary efficacy variables assessed the severity of the subjects’ daily bowel movement (BM) symptoms, and preference of laxatives based on diary entries, visual analog scale scores, and questionnaires.
RESULTS: Of the 203 subjects enrolled in the study, 11 had major protocol violations. Complete resolution was noted by 36/98 (36.7%) subjects in the PEG 3350 group and 23/94 (24.5%) in the placebo group (P = 0.0595). The number of complete BMs without straining or lumpy stools was similar between both groups. Subjects receiving PEG 3350 experienced significant relief in straining and reduction in hardness of stools over a 7-d period (P < 0.0001). Subjects reported that PEG 3350 had a better effect on their daily lives, provided better control over a BM, better relief from constipation, cramping, and bloating, and was their preferred laxative. Adverse events (AEs) were balanced between the PEG 3350 and the placebo groups. No deaths, serious AEs, or discontinuations due to AEs were reported. This trial is registered at clinicaltrials.gov as NCT00770432.
CONCLUSION: Oral administration of 17 g PEG 3350 once daily for a week is effective, safe, and well tolerated in subjects with occasional constipation.
Collapse
|
|
43
|
Comparison of the effectiveness of polyethylene glycol with and without electrolytes in constipation: a systematic review and network meta-analysis. BMC Gastroenterol 2016; 16:42. [PMID: 27029340 PMCID: PMC4815254 DOI: 10.1186/s12876-016-0457-9] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2015] [Accepted: 03/19/2016] [Indexed: 01/19/2023] Open
Abstract
Background Polyethylene glycol is commonly used to manage constipation and is available with or without electrolytes. The addition of electrolytes dates back to its initial development as lavage solutions in preparation for gastrointestinal interventions. The clinical utility of the addition of electrolytes to polyethylene glycol for the management of constipation is not established. The objective of this systematic review and network meta-analysis (NMA) was to assess the relative effectiveness of polyethylene glycol with (PEG + E) or without electrolytes (PEG) in the management of functional constipation in adults. Methods A systematic review was conducted to identify randomised controlled clinical trials that assessed the use of polyethylene glycol in functional constipation. The primary outcome was the mean number of bowel movements per week. Results Nineteen studies were included in the NMA (PEG N = 9, PEG + E N = 8, PEG versus PEG + E N = 2; involving 2247 patients). PEG and PEG + E are both effective, increasing the number of bowel movements per week by 1.8 (95 % Crl 1.0, 2.8) and 1.9 (95 % Crl 0.9, 3.0) respectively versus placebo and by 1.8 (95 % Crl 0.0, 3.5) and 1.9 (95 % Crl 0.2, 3.6) respectively versus lactulose. There was no efficacy difference between PEG + E and PEG (0.1, 95 % Crl −1.1, 1.2) and there were no differences in safety or tolerability. Conclusions Polyethylene glycol with and without electrolytes are effective and safe treatments for constipation in adults. The addition of electrolytes to polyethylene glycol does not appear to offer any clinical benefits over polyethylene glycol alone in the management of constipation.
Collapse
|
|
44
|
Bielefeldt K, Levinthal DJ, Nusrat S. Effective Constipation Treatment Changes More Than Bowel Frequency: A Systematic Review and Meta-Analysis. J Neurogastroenterol Motil 2015; 22:31-45. [PMID: 26717930 PMCID: PMC4699720 DOI: 10.5056/jnm15171] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2015] [Revised: 11/20/2015] [Accepted: 12/03/2015] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND/AIMS The marketing of newer agents for treatment of constipation and irritable bowel syndrome with constipation (IBS-C) emphasize improvements in abdominal pain. However, it is not clear whether this observation reflects a unique visceral analgesic effect of these agents or is a general feature of effective laxation. We sought to determine the relationship between improvements in bowel frequency and decreases in abdominal pain in clinical trials of patients with constipation or IBS-C. METHODS We searched "PubMed" and "Embase" databanks for clinical trials in patients with constipation or IBS-C, targeting publications that provided detailed data on bowel movement frequency and pain intensity before and after an intervention. We abstracted the results and performed meta-analytic and meta-regression analyses. RESULTS Twenty-seven trials (16 constipation and 11 IBS) met entry criteria. Baseline weekly bowel movement frequency was low with 2.35 (2.07-2.64) with differences between constipation (2.00 [1.62-2.38]) and IBS-C (2.77 [2.40-3.14]; Q = 8.18; P = 0.002). Studies reported moderate pain levels (2.12 [1.81-2.42]) with comparable baseline levels in constipation (2.02 [1.63-2.42]) and IBS-C (2.35 [2.10-2.60]; Q = 1.92; P = 0.167). Treatments increased bowel frequency by 2.17 [1.88-2.47] and lowered pain ratings by 0.58 [0.49-0.68]. Meta-regression demonstrated a significant correlation between treatment-induced increases in bowel frequency and decreased pain ratings. CONCLUSIONS Our analysis suggests that reduction of abdominal pain observed in clinical trials of constipation and IBS-C is associated with laxation, and may not require specific drug mechanisms, thus arguing against a unique advantage of newer agents over traditional laxatives in the treatment of constipation and IBS-C.
Collapse
Affiliation(s)
| | | | - Salman Nusrat
- University of Oklahoma Health Sciences Center, Oklahoma, OK, USA
| |
Collapse
|
|
45
|
Quigley EMM, Neshatian L. Advancing treatment options for chronic idiopathic constipation. Expert Opin Pharmacother 2015; 17:501-11. [PMID: 26630260 DOI: 10.1517/14656566.2016.1127356] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Chronic constipation is a global problem affecting all ages and associated with considerable morbidity and significant financial burden for society. Though formerly defined on the basis of a single symptom, infrequent defecation; constipation is now viewed as a syndrome encompassing several complaints such as difficulty with defecation, a sense of incomplete evacuation, hard stools, abdominal discomfort and bloating. AREAS COVERED The expanded concept of constipation has inevitably led to a significant change in outcomes in clinical trials, as well as in patient expectations from new therapeutic interventions. The past decades have also witnessed a proliferation in therapeutic targets for new agents. Foremost among these have been novel prokinetics, a new category, prosecretory agents and innovative approaches such as inhibitors of bile salt transport. In contrast, relatively few effective therapies exist for the management of those anorectal and pelvic floor problems that result in difficult defecation. EXPERT OPINION Though constipation is a common and often troublesome disorder, many of those affected can resolve their symptoms with relatively simple measures. For those with more resistant symptoms a number of novel, effective and safe options now exist. Those with defecatory difficulty (anismus, pelvic floor dysfunction) continue to represent a significant management challenge.
Collapse
Affiliation(s)
- Eamonn M M Quigley
- a Lynda K. and David M. Underwood Center for Digestive Disorders, Division of Gastroenterology and Hepatology , Houston Methodist Hospital, Weill Cornell Medical College , Houston , TX , USA
| | - Leila Neshatian
- a Lynda K. and David M. Underwood Center for Digestive Disorders, Division of Gastroenterology and Hepatology , Houston Methodist Hospital, Weill Cornell Medical College , Houston , TX , USA
| |
Collapse
|
|
46
|
De Giorgio R, Ruggeri E, Stanghellini V, Eusebi LH, Bazzoli F, Chiarioni G. Chronic constipation in the elderly: a primer for the gastroenterologist. BMC Gastroenterol 2015; 15:130. [PMID: 26467668 PMCID: PMC4604730 DOI: 10.1186/s12876-015-0366-3] [Citation(s) in RCA: 105] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2015] [Accepted: 10/04/2015] [Indexed: 02/07/2023] Open
Abstract
Constipation is a frequently reported bowel symptom in the elderly with considerable impact on quality of life and health expenses. Disease-related morbidity and even mortality have been reported in the affected frail elderly. Although constipation is not a physiologic consequence of normal aging, decreased mobility, medications, underlying diseases, and rectal sensory-motor dysfunction may all contribute to its increased prevalence in older adults. In the elderly there is usually more than one etiologic mechanism, requiring a multifactorial treatment approach. The majority of patients would respond to diet and lifestyle modifications reinforced by bowel training measures. In those not responding to conservative treatment, the approach needs to be tailored addressing all comorbid conditions. In the adult population, the management of constipation continues to evolve as well as the understanding of its complex etiology. However, the constipated elderly have been left behind while gastroenterology consultations for this common conditions are at a rise for the worldwide age increment. Aim of this review is to provide an update on epidemiology, quality of life burden, etiology, diagnosis, current approaches and limitations in the management of constipation in the older ones to ease the gastroenterologists' clinic workload.
Collapse
Affiliation(s)
- Roberto De Giorgio
- Department of Medical and Surgical Sciences/Digestive system, University of Bologna and St. Orsola-Malpighi Hospital, Bologna, Italy.
| | - Eugenio Ruggeri
- Department of Medical and Surgical Sciences/Digestive system, University of Bologna and St. Orsola-Malpighi Hospital, Bologna, Italy.
| | - Vincenzo Stanghellini
- Department of Medical and Surgical Sciences/Digestive system, University of Bologna and St. Orsola-Malpighi Hospital, Bologna, Italy.
| | - Leonardo H Eusebi
- Department of Medical and Surgical Sciences/Digestive system, University of Bologna and St. Orsola-Malpighi Hospital, Bologna, Italy.
| | - Franco Bazzoli
- Department of Medical and Surgical Sciences/Digestive system, University of Bologna and St. Orsola-Malpighi Hospital, Bologna, Italy.
| | - Giuseppe Chiarioni
- Division of Gastroenterology of the University of Verona, AOUI Verona, Verona, Italy.
- UNC Center for Functional GI & Motility Disorder, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
- Division of Gastroenterology of the University of Verona, Ospedale Policlinico GB Rossi, Piazzale LA Scuro, 10, 37134, Verona, Italy.
| |
Collapse
|
|
47
|
Rungsiprakarn P, Laopaiboon M, Sangkomkamhang US, Lumbiganon P, Pratt JJ. Interventions for treating constipation in pregnancy. Cochrane Database Syst Rev 2015; 2015:CD011448. [PMID: 26342714 PMCID: PMC8958874 DOI: 10.1002/14651858.cd011448.pub2] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Constipation is a common symptom experienced during pregnancy. It has a range of consequences from reduced quality of life and perception of physical health to haemorrhoids. An understanding of the effectiveness and safety of treatments for constipation in pregnancy is important for the clinician managing pregnant women. OBJECTIVES To assess the effectiveness and safety of interventions (pharmacological and non-pharmacological) for treating constipation in pregnancy. SEARCH METHODS We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2015), ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (30 April 2015) and reference lists of retrieved studies. SELECTION CRITERIA We considered all published, unpublished and ongoing randomised controlled trials (RCTs), cluster-RCTs and quasi-RCTs, evaluating interventions (pharmacological and non-pharmacological) for constipation in pregnancy. Cross-over studies were not eligible for inclusion in this review. Trials published in abstract form only (without full text publication) were not eligible for inclusion.We compared one intervention (pharmacological or non-pharmacological) against another intervention, placebo or no treatment. DATA COLLECTION AND ANALYSIS Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS Four studies were included, but only two studies with a total of 180 women contributed data to this review. It was not clear whether they were RCTs or quasi-RCTs because the sequence generation was unclear. We classified the overall risk of bias of three studies as moderate and one study as high risk of bias. No meta-analyses were carried out due to insufficient data.There were no cluster-RCTs identified for inclusion. Comparisons were available for stimulant laxatives versus bulk-forming laxatives, and fibre supplementation versus no intervention. There were no data available for any other comparisons.During the review process we found that studies reported changes in symptoms in different ways. To capture all data available, we added a new primary outcome (improvement in constipation) - this new outcome was not prespecified in our published protocol. Stimulant laxatives versus bulk-forming laxativesNo data were identified for any of this review's prespecified primary outcomes: pain on defecation, frequency of stools and consistency of stools.Compared to bulk-forming laxatives, pregnant women who received stimulant laxatives had significantly more improvement in constipation (risk ratio (RR) 1.59, 95% confidence interval (CI) 1.21 to 2.09; 140 women, one study, moderate quality of evidence), but also significantly more abdominal discomfort (RR 2.33, 95% CI 1.15 to 4.73; 140 women, one study, low quality of evidence), and borderline difference in diarrhoea (RR 4.50, 95% CI 1.01 to 20.09; 140 women, one study, moderate quality of evidence). In addition, there was no significant difference in women's satisfaction (RR 1.06, 95% CI 0.77 to 1.46; 140 women, one study, moderate quality of evidence).No usable data were identified for any of this review's secondary outcomes: quality of life; dehydration; electrolyte imbalance; acute allergic reaction; or asthma. Fibre supplementation versus no interventionPregnant women who received fibre supplementation had significantly higher frequency of stools compared to no intervention (mean difference (MD) 2.24 times per week, 95% CI 0.96 to 3.52; 40 women, one study, moderate quality of evidence). Fibre supplementation was associated with improved stool consistency as defined by trialists (hard stool decreased by 11% to 14%, normal stool increased by 5% to 10%, and loose stool increased by 0% to 6%).No usable data were reported for either the primary outcomes of pain on defecation and improvement in constipation or any of this review's secondary outcomes as listed above. Quality Five outcomes were assessed with the GRADE software: improvement in constipation, frequency of stools, abdominal discomfort, diarrhoea and women's satisfaction. These were assessed to be of moderate quality except for abdominal discomfort which was assessed to be of low quality. The results should therefore be interpreted with caution. There were no data available for evaluation of pain on defecation or consistency of stools. AUTHORS' CONCLUSIONS There is insufficient evidence to comprehensively assess the effectiveness and safety of interventions (pharmacological and non-pharmacological) for treating constipation in pregnancy, due to limited data (few studies with small sample size and no meta-analyses). Compared with bulk-forming laxatives, stimulant laxatives appear to be more effective in improvement of constipation (moderate quality evidence), but are accompanied by an increase in diarrhoea (moderate quality evidence) and abdominal discomfort (low quality evidence) and no difference in women's satisfaction (moderate quality evidence). Additionally, fibre supplementation may increase frequency of stools compared with no intervention (moderate quality evidence), although these results were of moderate risk of bias.There were no data for a comparison of other types of interventions, such as osmotic laxatives, stool softeners, lubricant laxatives and enemas and suppositories.More RCTs evaluating interventions for treating constipation in pregnancy are needed. These should cover different settings and evaluate the effectiveness of various interventions (including fibre, osmotic, and stimulant laxatives) on improvement in constipation, pain on defecation, frequency of stools and consistency of stools.
Collapse
Affiliation(s)
- Phassawan Rungsiprakarn
- Khon Kaen UniversityThai Cochrane Network123 Mittapharp RoadAmphur MuengKhon KaenThailand40002
| | - Malinee Laopaiboon
- Khon Kaen UniversityDepartment of Biostatistics and Demography, Faculty of Public Health123 Mitraparb RoadAmphur MuangKhon KaenThailand40002
| | - Ussanee S Sangkomkamhang
- Khon Kaen HospitalDepartment of Obstetrics and GynaecologySrichan RoadMaungKhon KaenThailand40000
| | - Pisake Lumbiganon
- Khon Kaen UniversityDepartment of Obstetrics and Gynaecology, Faculty of Medicine123 Mitraparb RoadAmphur MuangKhon KaenThailand40002
| | - Jeremy J Pratt
- Bunbury Regional HospitalRobertson DriveBunburyAustraliaWA 6230
| | | |
Collapse
|
|
48
|
Hussain ZH, Everhart K, Lacy BE. Treatment of Chronic Constipation: Prescription Medications and Surgical Therapies. Gastroenterol Hepatol (N Y) 2015; 11:104-114. [PMID: 27099579 PMCID: PMC4836568] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
Constipation is a highly prevalent disorder that affects people regardless of age, race, gender, or socioeconomic status. For many patients, constipation is a chronic condition that reduces quality of life. Chronic constipation also imposes a significant economic burden on the health care system. The treatment of constipation remains problematic for both patients and providers for a variety of reasons, including a lack of specificity of symptoms, an inconsistent relationship between underlying pathophysiology and symptom generation, and different and unpredictable patient responses to medications. A large number of over-the-counter agents are used to treat symptoms of constipation, although many of these agents are not effective, and data to support their use are limited and generally of poor quality. Patients referred for consultation typically have failed therapy with over-the-counter agents and require prescription medications or possibly even surgical therapy. This article discusses medical treatments and surgical options for chronic idiopathic constipation.
Collapse
Affiliation(s)
- Zilla H Hussain
- Dr Hussain is a gastroenterology fellow, Ms Everhart is a medical student, and Dr Lacy is a professor of medicine and chief of the Section of Gastroenterology and Hepatology at the Geisel School of Medicine at Dartmouth and the Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire
| | - Kelly Everhart
- Dr Hussain is a gastroenterology fellow, Ms Everhart is a medical student, and Dr Lacy is a professor of medicine and chief of the Section of Gastroenterology and Hepatology at the Geisel School of Medicine at Dartmouth and the Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire
| | - Brian E Lacy
- Dr Hussain is a gastroenterology fellow, Ms Everhart is a medical student, and Dr Lacy is a professor of medicine and chief of the Section of Gastroenterology and Hepatology at the Geisel School of Medicine at Dartmouth and the Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire
| |
Collapse
|
|
49
|
Rungsiprakarn P, Laopaiboon M, Sangkomkamhang US, Lumbiganon P, Pratt JJ. Interventions for treating constipation in pregnancy. THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS 2014. [DOI: 10.1002/14651858.cd011448] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
|
|
50
|
Diederen K, Mugie SM, Benninga MA. Efficacy and safety of prucalopride in adults and children with chronic constipation. Expert Opin Pharmacother 2014; 16:407-16. [PMID: 25539475 DOI: 10.1517/14656566.2015.996547] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Chronic constipation (CC) is a debilitating condition with high prevalence rates both in children and adults. Despite the broad range of medical and pharmaceutical treatments, the bowel function does not restore in a fair amount of patients. Prucalopride is a first-in-class selective, high affinity serotonin 5-hydroxytryptamine type 4 (5-HT4) receptor agonist promoting gastro-intestinal prokinetic activity and has been evaluated for the treatment of CC. AREAS COVERED A PubMed search (1965 - 2014) using the following terms alone or in combination: prucalopride, 5-HT4, R093877, safety, toxicity, pharmacokinetics, pharmacodynamics, transit, cardiac, human ether-a-go-go related gene (hERG), arrhythmia, potassium current, elderly, children. EXPERT OPINION Prucalopride, a highly selective 5-HT4 receptor agonist, stimulates gastrointestinal motility and has been proven to be effective in the treatment of CC in adults by increasing stool frequency, reducing constipation-related symptoms and improving quality of life (QoL). The safety and tolerability have been proven to be excellent. More research would be preferable on the effect of prucalopride on men, children and in other gastrointestinal motility disorders.
Collapse
Affiliation(s)
- Kay Diederen
- Emma Children's Hospital, Academic Medical Centre, Department of Paediatric Gastroenterology and Nutrition , Meibergdreef 9, 1105 AZ Amsterdam , The Netherlands +31 20 5665270 ; +31 20 6917033 ;
| | | | | |
Collapse
|