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1.
Benefit-Risk Assessment of Plecanatide in the Treatment of Chronic Idiopathic Constipation.
Miner, PB
Drug safety. 2019;(5):603-615
Abstract
Plecanatide, a uroguanylin analog, activates the guanylate cyclase C receptors in the epithelial lining of the gastrointestinal tract in a pH-dependent fashion initiating (1) the conversion of intracellular guanosine triphosphate to cyclic guanosine monophosphate, which increases the activity of the cystic fibrosis transmembrane conductance regulator to increase chloride and bicarbonate secretion into the intestinal lumen and (2) a decrease in activity of the sodium-hydrogen ion exchanger. The resulting ionic shifts cause an increase in lumenal fluid to facilitate digestion. Plecanatide has been approved by the FDA for use in chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation. This manuscript is a critical assessment of the therapeutic efficacy and potential risks associated with the use of plecanatide in CIC. The discussion of CIC as a clinical and investigative disorder focuses on the importance of this problem as well and the difficulties involved in clinical management and scholarly investigation of a symptom arising from multiple pathophysiologic mechanisms. Clinical data from studies of recently approved drugs for CIC are utilized to construct a platform for thoughtful understanding of CIC and of how changes in investigation guidelines influence the interpretation of study data and guide symptom management. Plecanatide is a safe and effective medication for the management of adults with CIC.
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2.
Obesity, Motility, Diet, and Intestinal Microbiota-Connecting the Dots.
Fayfman, M, Flint, K, Srinivasan, S
Current gastroenterology reports. 2019;(4):15
Abstract
PURPOSE OF REVIEW The goal of the present review is to explore the relationship between dietary changes and alterations in gut microbiota that contribute to disorders of gut motility and obesity. RECENT FINDINGS We review the microbiota changes that are seen in obesity, diarrhea, and constipation and look at potential mechanisms of how dysbiosis can predispose to these. We find that microbial metabolites, particularly short chain fatty acids, can lead to signaling changes in the host enterocytes. Microbial alteration leading to both motility disorders and obesity may be mediated by the release of hormones including glucagon-like peptides 1 and 2 (GLP-1, GLP-2) and polypeptide YY (PYY). These pathways provide avenues for microbiota-targeted interventions that can treat both disorders of motility and obesity. In summary, multiple mechanisms contribute to the interplay between the microbial dysbiosis, obesity, and dysmotility.
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3.
Neurogenic bowel dysfunction.
Emmanuel, A
F1000Research. 2019
Abstract
The symptoms of neurogenic bowel dysfunction (NBD) comprise constipation and fecal incontinence. These have a major impact on quality of life and dignity. Bowel symptoms occur in the majority of patients with chronic neurological diseases like multiple sclerosis, spinal cord injury, and Parkinson's disease. Management relies on obtaining a careful bowel history, including assessment of bowel function prior to the onset of neurological symptoms. Objective measures of NBD are available and important in terms of monitoring response for what are often intensely personal and difficult-to-elicit symptoms. Conservative management begins by establishing an effective and regular bowel regime by optimizing diet and laxative use. If this is insufficient, as seen in about half of patients, transanal irrigation has been shown to reduce NBD symptoms and improve quality of life. Failing that, there are more invasive surgical options available. This review aims to provide practical guidance for the clinician who encounters these patients, focusing on a stepwise approach to assessment, interventions, and monitoring.
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4.
Relationship Between Constipation and Medication.
Ueki, T, Nakashima, M
Journal of UOEH. 2019;(2):145-151
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Abstract
Constipation is very common and can be caused by adverse drug reactions as a result of many drugs. While the adverse effects of several medications such as opioids and anticholinergic agents are well established and well known, other commonly prescribed drugs, such as hypnotics, are less well understood. This review presents the results of an analysis of the relationship between constipation and drugs.
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5.
Putative mechanisms of kiwifruit on maintenance of normal gastrointestinal function.
Bayer, SB, Gearry, RB, Drummond, LN
Critical reviews in food science and nutrition. 2018;(14):2432-2452
Abstract
Kiwifruits are recognized as providing relief from constipation and symptoms of constipation-predominant irritable bowel syndrome (IBS-C). However, the underlying mechanisms, specifically in regards to gastrointestinal transit time and motility, are still not completely understood. This review provides an overview on the physiological and pathophysiological processes underlying constipation and IBS-C, the composition of kiwifruit, and recent advances in the research of kiwifruit and abdominal comfort. In addition, gaps in the research are highlighted and scientific studies of other foods with known effects on the gastrointestinal tract are consulted to find likely mechanisms of action. While the effects of kiwifruit fiber are well documented, observed increases in gastrointestinal motility caused by kiwifruit are not fully characterized. There are a number of identified mechanisms that may be activated by kiwifruit compounds, such as the induction of motility via protease-activated signaling, modulation of microflora, changes in colonic methane status, bile flux, or mediation of inflammatory processes.
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Recommendations for pharmacological clinical trials in children with functional constipation: The Rome foundation pediatric subcommittee on clinical trials.
Koppen, IJN, Saps, M, Lavigne, JV, Nurko, S, Taminiau, JAJM, Di Lorenzo, C, Benninga, MA
Neurogastroenterology and motility. 2018;(4):e13294
Abstract
BACKGROUND Evidence for the efficacy of commonly used drugs in the treatment of childhood functional constipation (FC) is scarce, studies are often of low quality and study designs are heterogeneous. Thus, recommendations for the design of clinical trials in childhood FC are needed. PURPOSE Members of the Rome Foundation and a member of the Pediatric Committee of the European Medicines Agency formed a committee to create recommendations for the design of clinical trials in children with FC. KEY RECOMMENDATIONS This committee recommends conducting randomized, double-blind, placebo-controlled, parallel-group clinical trials to assess the efficacy of new drugs for the treatment of childhood FC. Pediatric study participants should be included based on fulfilling the Rome IV criteria for FC. A treatment free run-in period for baseline assessment is recommended. The trial duration should be at least 8 weeks. Treatment success is defined as no longer meeting the Rome IV criteria for FC. Stool consistency should be reported based on the Bristol Stool Scale. Endpoints of drug efficacy need to be tailored to the developmental age of the patient population.
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Magnesium poisoning, multi-organ failure and ischemic colitis secondary to chronic ingestion of a parapharmacy product.
Díaz Gómez, C, López Amor, L, García Prieto, E, Escudero Augusto, D
Revista espanola de enfermedades digestivas. 2018;(6):404-406
Abstract
The article describes the clinical case of a patient with multi-organ failure and ischemic colitis secondary to magnesium poisoning, due to the chronic intake of a parapharmacy product, used for the treatment of chronic constipation. The clinical case is described and a review of the literature is made.
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8.
Systematic review and meta-analysis of the effect of probiotic supplementation on functional constipation in children.
Jin, L, Deng, L, Wu, W, Wang, Z, Shao, W, Liu, J
Medicine. 2018;(39):e12174
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Abstract
BACKGROUND To evaluate the effect of probiotic supplementation on functional constipation in children. METHODS We performed electronic searches in PubMed, Embase, and Cochrane Library without language restriction to identify relevant studies from the time of inception of these databases to March 2018. The relative risk or weighted mean difference was calculated to evaluate the treatment effect of probiotics using random-effects model. RESULTS We included 4 trials reporting data on 382 children with functional constipation. Overall, there were no significant differences in treatment success (P = .697), spontaneous bowel movements per week (P = .571), fecal soiling episodes per week (P = .642), straining at defecation (P = .408), use of lactulose (P = .238), use of laxatives (P = .190), fecal incontinence (P = .139), pain during defecation (P = .410), flatulence (P = .109), and adverse events (P = .979) between probiotics and placebo. Further, the use of probiotics was associated with lower frequency of glycerin enema use (weighted mean difference -2.40, P = .004) and abdominal pain (weighted mean difference -4.80, P < .001). CONCLUSION The findings of this study suggested that the use of probiotics was associated with significant improvement in glycerin enema use and abdominal pain but did not affect the treatment success and other function indices.
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9.
Plecanatide: First Global Approval.
Al-Salama, ZT, Syed, YY
Drugs. 2017;(5):593-598
Abstract
Plecanatide (TrulanceTM) is an oral guanylate cyclase-C agonist that is being developed by Synergy Pharmaceuticals for the treatment of gastrointestinal disorders, such as chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C). It is a synthetic analogue of human uroguanylin, a 16 amino acid peptide that regulates ion and fluid transport in the gastrointestinal tract. In January 2017, plecanatide received its first global approval in the USA for the treatment of adult patients with CIC. Plecanatide is undergoing phase III investigation in IBS-C. This article summarizes the milestones in the development of plecanatide leading to this first approval in CIC.
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10.
The effect of probiotics as a treatment for constipation in elderly people: A systematic review.
Martínez-Martínez, MI, Calabuig-Tolsá, R, Cauli, O
Archives of gerontology and geriatrics. 2017;:142-149
Abstract
PURPOSE Treating constipation in elderly people remains a challenge; the administration of probiotics may be a valid therapy for this problem as an alternative to traditional drug-based treatments. The objective of this systematic review was to evaluate the efficiency of probiotics in treating constipation in elderly people. METHODS Articles related to this topic and published, without any time limitations, in the Medline, Embase, Scopus, Lilacs, or Cochrane databases were systematically reviewed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The primary search terms were 'constipation' and 'probiotics'. The main inclusion criteria were: 1) the article was original and the whole text was published in English or Spanish and 2) included the primary search terms in the title, summary, or body text; 3) the studies had to have included 60 or more participants defined as 'elderly' and 4) have specifically evaluated the effect of the administration of probiotics. RESULTS Of the 475 articles consulted, 9 met the inclusion criteria. Among the selected studies, there were four randomised and placebo-controlled trials and the remaining five reports were observational. Overall, our analysis of the randomised and placebo-controlled trials suggests that administration of probiotics significantly improved constipation in elderly individuals by 10-40% compared to placebo controls in which no probiotic was administered. The strain of bacteria most commonly tested was Bifidobacterium longum. However, caution is needed when interpreting these reports because of the heterogeneity of the original study designs, populations, and the risk of bias. Therefore, further placebo-controlled trials are necessary to determine the most efficient strains, doses, and the optimal treatment duration.