Treatment Of Chronic Constipation Research Articles

Safety/Efficacy of Prucalopride in Korean Patients with Chronic Constipation: Post-marketing Surveillance.

Constipation is a common gastrointestinal disorder. Prucalopride is a dihydrobenzofurancarboxamide derivative with gastrointestinal prokinetic activities and is recommended as an appropriate choice in patients unresponsive to laxatives. This study assessed the safety and efficacy of prucalopride in Korean patients with chronic constipation, in whom laxatives were ineffective. This prospective, non-interventional post-marketing surveillance of prucalopride was conducted from 2012 to 2018 at 28 hospitals in Korea. Adults who received prucalopride for the symptomatic treatment of chronic constipation were included. The patients received 2 mg of prucalopride once daily or 1 mg once daily in patients older than 65 years. The baseline characteristics, adverse events (AEs), and seven-point scale of Clinical Global Impression-Improvement were collected. Of 601 patients, 67.7% were female, and the mean age was 62.3 years. Three hundred patients (49.9%) were older than 65 years. At the baseline, 70.0% of patients reported less than two instances of spontaneous complete bowel movements per week. AEs were reported in 107 patients (17.7%), including headache (3.2%) and diarrhea (2.8%). Seven serious AEs (SAEs) were reported in five patients (0.8%). The SAEs were resolved without complications; there were no cases of death. All SAEs were assessed as 'unlikely' causality with prucalopride. In 72.7% of patients, chronic constipation was improved by the prucalopride treatment during the study period. This study demonstrated the promising safety and efficacy profile of prucalopride in clinical practice. Thus, prucalopride should be considered in patients with chronic constipation when bowel symptoms are refractory to simple laxatives.

MiR-128 participates in the pathogenesis of chronic constipation by regulating the p38α/M-CSF inflammatory signaling pathway.

Chronic constipation (CC) is a gastrointestinal disorder that adversely affects the quality of life. MicroRNAs are involved in the pathogenesis of functional gastrointestinal disorders. This study aims to investigate the molecular mechanism of microRNA-128 in CC. Here, we successfully constructed a murine model of CC based on morphine and rhubarb. The expression of stem cell factor (SCF) and neuron-specific enolase (NSE) was low in the models. Using miRNA array and bioinformatic analysis, we predicted and confirmed the expression of miR-128 and its downstream target genes in CC model. Compared with the control group, CC group showed a significant downregulation of miR-128 and upregulation of p38α and macrophage colony-stimulating factors (M-CSFs). Moreover, we observed elevated inflammatory cytokine and decreased anti-inflammatory cytokine levels in colonic tissues. Furthermore, coculture assays indicated that regulating expression of miR-128 in colonic epithelial cells induced the secretion of IL-6 and TNF-α by macrophages. In conclusion, our study demonstrated that miR-128 regulated the p38α/M-CSF signaling pathway to promote chronic inflammatory responses and changes in the immune microenvironment of the colon, thereby offering potential insights into the pathogenesis of CC and therapeutic targets for its treatment.NEW & NOTEWORTHY In this study, we constructed a murine model and identified a novel signaling mechanism involved in the chronic constipation progression. Our findings on the role of miR-128/p38α/M-CSF axis provide new insights into the treatment of chronic constipation.

Chronic Constipation: Is a Nutritional Approach Reasonable?

Chronic constipation (CC) is one of the most common gastroenterological diagnoses in clinical practice. Treatment includes several steps, depending on the severity of symptoms. Lifestyle modifications and increased intake of fiber and water are suggested by most health professionals. Unfortunately, the recommendations in this regard are the most varied, often conflicting with each other and not always based on solid scientific arguments. This paper aims to clarify this topic by providing practical indications for the management of these patients in every day clinical practice. The literature available on this topic is scarce, and dietary studies have important methodological biases. However, fiber, mainly by binding water and acting as bulking agents and/or as prebiotics for the intestinal microbiota, and mineral water, especially if rich in magnesium and/or bicarbonate, are useful tools. An adequate, well-designed diet should be a cornerstone of any effective treatment for chronic constipation. High-quality studies on larger samples are mandatory to give scientific validity to the role of the food in CC therapy and to enable professionals to choose the best approach for their patients, combining nutritional and pharmacological agents.

Beyond Metoclopramide for Gastroparesis

Beyond Metoclopramide for Gastroparesis

Oral bisacodyl is effective and safe for short term treatment of chronic constipation

A clinical decision report using: Kamm MA, Mueller-Lissner S, Wald A, Richter E, Swallow R, Gessner U. Oral bisacodyl is effective and well-tolerated in patients with chronic constipation. Clin Gastroenterol Hepatol. 2011;9(7):577-583. https://doi.org/10.1016/j.cgh.2011.03.026 to evaluate potential long term treatment with oral Bisacodyl in a patient with a history of chronic constipation and recent non-surgical treatment of ischemic colitis.

Safety of elobixibat and lubiprostone in Japanese patients with chronic constipation: a retrospective cohort study

ABSTRACT Background We aimed to discuss and compare reported adverse reactions and drug add-ons associated with elobixibat and lubiprostone use in chronic constipation treatment, as the safety of these drugs has not been well examined in post-marketing clinical settings. Research Design and Methods In this retrospective cohort study, using records of community pharmacies in Japan, we identified new users of elobixibat and lubiprostone. The Japan Pharmaceutical Association sent questionnaires regarding baseline and event data to community pharmacists. The incidence of events and hazard ratio (HR) associated with the study drugs were evaluated. Results New users of elobixibat (n = 979) and lubiprostone (n = 829) were identified (mean age: 74 and 77 years; females: 59% and 53%, respectively). Although the crude risk ratio of adverse events for elobixibat was 0.79 (95% confidence interval: 0.63–0.99), there was no significant difference in the HR for any of the common events, including drug add-ons (n ≥ 5), compared with those for lubiprostone. Conclusion No new safety concerns have been raised in relation to elobixibat and lubiprostone use for treating chronic constipation, although the HR of different events varied. Further larger-scale study is needed as the estimates for events of small numbers were unstable

Effects of linaclotide in the treatment of chronic constipation and irritable bowel syndrome with constipation: a meta-analysis.

Linaclotide is a guanylate cyclase-C (GCC) agonist that is found in intestinal epithelial cells and is used when treating chronic constipation (CC) and irritable bowel syndrome with constipation (IBS-C). Several randomized controlled trials (RCTs) were conducted for evaluating its efficacy and safety. The PubMed, EMBASE, and Cochrane databases and the Web of Science were searched to find multiple RCTs of patients with CC or IBS-C. The Jadad scoring system was used for evaluating each study's methodological quality, and RevMan5.3 was used for meta-analysis. The composite endpoint reaction approved by the FDA, abdominal pain and discomfort relief, symptom improvement, and diarrhea-related adverse reactions were chosen as observation indicators, and relative risk (RR) and 95% confidence interval (CI) were obtained for quantitative and comprehensive evaluation. Eleven randomized controlled studies were included, consisting of 5 cases of CC and 6 cases of IBS-C. Linaclotide reached the composite endpoint response approved by FDA in the treatment of CC (RR = 3.26, 95% CI: 2.45-4.33), and the composite endpoint response approved by FDA for the treatment of IBS-C (RR = 2.26, 95% CI: 1.86-2.74) was greater than the placebo (both p < 0.00001). The main adverse reactions of linaclotide were gastrointestinal, mostly diarrhea, which was higher than that of the placebo when treating CC (RR = 3.56, 95% CI: 2.76-4.60) and IBS-C (RR = 8.23, 95% CI: 5.69-11.90) (both p < 0.00001). Linaclotide proved to be effective and safe for the treatment of CC and IBS-C compared to the placebo. However, diarrhea is the primary adverse reaction.

551 EASING THE STRAIN OF CONSTIPATION IN CARE HOMES

Abstract Introduction Older individuals are particularly prone to constipation with a reported prevalence of up 50% for those living in community with the prevalence rising to 70% within nursing homes (De Giorgio et al, 2015 1). Objectives To assess impact of staff education &amp; pharmacist intervention on appropriateness of laxative use: Staff education: Examine the baseline knowledge of care home staff on constipation and laxative use: Formulate an education package to deliver to care home staff on key aspects of laxative use: Evaluate the staff knowledge, post the educational intervention.: Impact of pharmacist medication review on laxative use: Evaluate impact of pharmacist review on appropriateness of laxative use in care Homes. Method Three BHSCT Care Homes being case managed by the Medicines Optimisation Pharmacist were included in the study. Staff Education: The baseline knowledge of care home staff was examined by questionnaire, pre- and post-educational intervention on key aspects of laxative use. Staff directly administering medication or directly impacting on patients’ care in were included. An education package on key aspects of laxative use for delivery in nursing homes was designed and implemented. Impact of Pharmacist medication review on laxative use: We retrospectively examined if 30 patients were prescribed multiple laxatives from the same group as an indicator of inappropriate laxative use, pre and post pharmacist intervention. Results Staff education: Thirty-three staff completed the questionnaires. The educational package developed on laxative use had a positive impact on the knowledge of the staff on constipation and laxative use with statistically significant improvements in staff knowledge post education, with p-value &amp;lt;0.05. Healthcare assistants’ mean percentage increase in knowledge following education mirrored that of nursing staff at almost 50%. Impact of Pharmacist medication review on laxative use: There was a statistically significant improvement in appropriateness of laxative prescribing following the pharmacist led medication review of 30 residents. Fewer patients were prescribed laxatives from the same class following medication reviews with a p value of &amp;lt; 0.00001, the result is significant at p &amp;lt; 0.05. Discussion The positive impact of this study supports the conclusion by Chen et al 2 (2014) that patient and carer education should be first line treatment for non-severe constipation. Shen Q et al 3 (2018) suggested that educational intervention for patients can effectively improve constipation symptoms, treatment and result in improved health habits however this study provides further evidence that the education of care home staff plays a significant role in improving the appropriate management of constipation for care home residents. Pharmacist-led review of laxatives has the potential to improve a Care Home resident’s quality of life, as previously suggested by Dennison et al 4 (2005), with the potential to reduce the risk of complications or hospital admissions from ineffective treatment of chronic constipation. Conclusion The development &amp; delivery of a bespoke laxative educational package along with pharmacist medication review of residents’ current laxatives regimes resulted in a statistically improved appropriateness in laxative use. The education package developed will be shared with Medicines Optimisation for Older People (MOOP) Care Home Pharmacists for delivery in NI trusts.

Effectiveness of an herbaceous derivatives, PHGG, plus sodium hyaluronate in the treatment of chronic constipation in patients with Parkinson's disease: a pilot study.

Chronic constipation is a highly prevalent and often under-appreciated gastrointestinal disorder in PD associated with significant impairment in quality of life. In this study, we investigated the efficacy and safety of PHGG plus hyaluronate (PHGG+) in patients suffering from PD and constipation. Thirty-four PD patients have been recruited in an open-label pilot study and measured symptoms and quality of life instruments related to constipation. PHGG+ showed to have a minimal still significant effect in improving constipation as measured by PAC Symp and CGI-S. PHGG+ is safe and well tolerated. Data suggests that PHGG+ may be considered efficacious in alleviating symptoms of constipation in PD patients. Trial registration number: NCT04569656/24 Sept. 2020.

Current Opinion on Prucalopride in Gastroparesis and Chronic Constipation Treatment: A Focus on Patient Selection and Safety.

Prucalopride is a third-generation, highly selective 5-hydroxytryptamine 4 (5-HT4) receptor agonist. Many recent studies indicate prucalopride may play an important role in various motility disorders. The aim of this study was to investigate safety and patient selection considerations when using prucalopride as gastroparesis and chronic constipation treatment. We systematically searched PubMed, Embase, the Cochrane Central Register and ClinicalTrials.gov, and we reviewed all studies that evaluated prucalopride for the treatment of gastroparesis and chronic idiopathic constipation in adults. Prucalopride is an effective and safe option based on all the studies currently conducted. Thus, it may be the first-line treatment in the future. Prucalopride has the potential to be useful in the treatment of functional constipation and other forms of gastrointestinal diseases (eg, gastroparesis). Through the research on this potential, prucalopride is expected to be a useful and versatile option for treating gastrointestinal diseases in the future.

478-P: Effect of Nonpharmacological Management of Chronic Constipation in Diabetic Patients

Background: Chronic constipation is highly prevalent in diabetic patients. The treatment of chronic constipation in general patients is mainly lifestyle modification and pharmacological therapy. The efficacy of non-pharmacological treatment, i.e., behavioral therapy to improve lifestyle and defecation habits, for chronic constipation in diabetic patients is not well known. This study aimed to determine the efficacy of non-pharmacological management for chronic constipation in diabetic patients. Methods: We conducted a questionnaire on defecation for diabetic patients aged 20 to 75 years at Asama General Hospital outpatient clinic. Patients diagnosed with chronic constipation according to Rome IV criteria were randomly assigned to two groups. The intervention group instructed behavior therapy to improve constipation. Specifically, we provided guidance on defecation behavior, exercise, water and dietary fiber intake, and guidance on a defecation diary recording daily defecation status. The other group received usual medical care as a control group. The questionnaire was conducted again at the next outpatient clinic. Results: Eighty of 545 diabetic patients (14.7%) had chronic constipation. The average age of constipated patients was 59.3 years, frequency of defecation 3.7 times/week, stool form (Bristol Stool Form Scale) 2.8, straining during defecations 78,8% and sensation of incomplete evacuation of defecations 42.5%. After the intervention, there was a significant increase in the frequency of defecation (4.8 vs. 3.9 times/week, P=0.008) and improvement in constipation symptoms (P=0.018) in the intervention group compared to the control group. In addition, stool form and straining during defecations were significantly improved before and after comparison within the intervention group (P &amp;lt;0.05). Conclusion: Our findings suggest that non-pharmacological management, including behavioral therapy for chronic constipation in diabetic patients, was effective. Disclosure E. Nishimori: None. M. Naka: None.

Evaluation of efficacy and safety of lubiprostone in patients with chronic constipation

Objectives Lubiprostone is an apical type 2 chloride channel activator approved for the treatment of chronic constipation (CC), and nausea is the most common adverse symptom. However, the associated factors with the efficacy and the precise mechanism of nausea remain unclear. The aim of this study is to characterize clinical backgrounds related with the efficacy and the adverse symptoms of lubiprostone. Materials and methods Subjects were patients with CC who were prescribed lubiprostone from April 2017 to October 2019. The efficacy and safety of lubiprostone were retrospectively examined using the electronic medical record. Results Hundred and fifty-five patients (76 men, and mean age 69) were evaluated. Lubiprostone was effective in 74 patients (47.8%), and the discontinuation due to adverse in 34 patients (21.9%). including nausea, diarrhea and abdominal pain in 16, 12 and 3 patients, respectively. The efficacy was significantly associated with gender, age, body mass index (BMI), diabetes mellitus, hypertension, calcium channel blockers and antipsychotics. In multivariate analysis, the efficacy was significantly associated with men (odds ratio [OR], 3.21; 95% confidence interval (CI), 1.42–7.27) and BMI (OR, 1.14; 95% CI, 1.02–1.28). The incidence of nausea was higher in patients under 65 years old, and hypertension was the significant protective factor for nausea. Conclusions Lubiprostone was effective for men patients with CC, and hypertension seems to be the protective factor for nausea.

Patient with constipation syndrome at the ambulatory-polyclinic reception: actual aspects of differential diagnosis and treatment

Constipation is a serious medical and social problem due to the widespread prevalence of this condition, a decrease in the quality of life and social activity of patients. For the successful treatment of constipation, it is necessary to establish the causes leading to the violation of the stool in the patient. And this task is a priority for the doctor at the outpatient stage.The clinical features of constipation largely depend on their cause, duration, severity and characteristics of intestinal damage. Constipation is often accompanied by general somatic and other gastroenterological symptoms.Within the framework of the review article, the main conditions and diseases are considered, in the clinical picture of which there is constipation syndrome, which must be considered by the doctor at the outpatient stage when conducting differential diagnosis and prescribing appropriate treatment, which also presupposes impact on causal factors. Currently, drugs based on high molecular weight polyethylene glycol 4000 are widely used to treat chronic constipation in adults and children in most countries of the world. Preparations based on polyethylene glycol 4000 are affordable and easy to use, they can be used both on an outpatient basis and in a hospital. Polyethylene glycol 4000 preparations act quickly, are highly effective and well tolerated, have a high safety profile (practically does not affect homeostasis) both for adult patients and in pediatric practice. International clinical trials have shown the possibility of long-term use of polyethylene glycol 4000 preparations.Current international clinical guidelines and domestic clinical guidelines for the treatment of constipation recommend the use of polyethylene glycol 4000 preparations instead of lactulose and volume-forming laxatives in the symptomatic treatment of constipation in children and adults. In the second part of the review, the possibilities of polyethylene glycol 4000 and the first domestic drug polyethylene glycol 4000 in the treatment of chronic constipation are considered.

New Drugs on the Horizon for Functional and Motility Gastrointestinal Disorders

New Drugs on the Horizon for Functional and Motility Gastrointestinal Disorders

Probiotics for treatment of chronic constipation in children

Probiotics for treatment of chronic constipation in children

Positioning of Bristol Stool Form Scale type 3 in constipation treatment satisfaction: A multicenter study in Japan.

Many patients are not satisfied with chronic constipation (CC) treatments. The aim of this study was to identify factors linked to CC treatment satisfaction or dissatisfaction. Our study population included patients who received CC treatment at a clinic or hospital. CC was diagnosed by a physician based on the patient's complaint. Treatment satisfaction was evaluated using the 28th question of the Patient Assessment of Constipation Quality of Life questionnaire. We conducted this study at 28 facilities. We included 167 patients (mean age 66.7±15.2years, male:female ratio is 1:3.07). Sixty-eight (40.7%) of patients were satisfied with their constipation treatment. Treatment dissatisfaction of CC was significantly associated with frequency of bowel movement <3/week (odds ratio [OR]=0.376, 95% confidence interval [CI]: 0.156-0.904, P=0.029) or Bristol Stool Form Scale (BSFS) type 3 (OR=0.401, 95% CI: 0.170-0.946, P=0.037). Our study showed that CC patients with BSFS type3 were not satisfied with constipation treatment. In general, BSFS types 3-5 are defined as normal stools. Therefore, BSFS type 3 may be set as a treatment goal even though the patient is not satisfied. The pathophysiology of CC differs by region and patient background. Therefore, parameters used to define successful treatment will be different by patient or region. We should reconsider the positioning of BSFS type 3 to improve treatment satisfaction for CC.

Exploratory Comparative Effectiveness Trial of Green Kiwifruit, Psyllium, or Prunes in US Patients With Chronic Constipation.

Psyllium and prunes are proven treatments for chronic constipation (CC). Asian studies suggest that kiwifruit may also benefit CC symptoms. We report a partially randomized, comparative effectiveness trial evaluating kiwifruit, psyllium, and prunes in US patients with CC. Adults with CC at a US medical center were randomized to 3 natural treatments. Eligible patients had ≤3 complete spontaneous bowel movements (CSBMs) per week and were partially randomized to green kiwifruit (2/d), prunes (100 g/d), or psyllium (12 g/d) for 4 weeks. The primary endpoint was the proportion of patients in each group reporting an increase of ≥1 CSBM per week compared with baseline for at least 2 of 4 treatment weeks. Key secondary outcomes included stool frequency, stool consistency, and straining assessed daily. Treatment satisfaction and adverse events (AEs) were also measured. Standard statistical methods were used, and a P < 0.05 was considered significant. Seventy-nine patients with CC (mean age = 42.7 years, 87% female, and 77% white) were partially randomized. Complete data were available for 75 patients (kiwifruit 29, prunes 24, and psyllium 22). For the primary endpoint, proportions of CSBM responders were similar for the treatments. For secondary outcomes comparing treatment weeks 3 and 4 to baseline, there was a significant increase in weekly CSBM rate with all 3 treatments (P ≤ 0.003); stool consistency significantly improved with kiwifruit (P = 0.01) and prunes (P = 0.049); and straining significantly improved with kiwifruit (P = 0.003), prunes (P < 0.001), and psyllium (P = 0.04). Patients randomized to the kiwifruit group reported significant improvement in bloating scores (P = 0.02). AEs were most common with psyllium and least common with kiwifruit. At the end of treatment, a smaller proportion of patients were dissatisfied with kiwifruit compared with prunes or psyllium (P = 0.02). Kiwifruit, prunes, and psyllium improve constipation symptoms in patients with CC. Kiwifruit was associated with the lowest rate of AEs and dissatisfaction with therapy.

Efficacy of oral magnesium therapy in the treatment of chronic constipation in spastic cerebral palsy children: a randomized controlled trial.

Constipation is a common problem in children with spastic cerebral palsy (sCP) with a prevalence that reaches 75%. We hypothesized that treating constipation in those children will improve their health and shorten time spent in daily care. Our aim was to evaluate the efficacy and safety of oral magnesium sulfate for treating chronic constipation in children with sCP. A prospective, double-blinded randomized control trial was carried out involving 100 children aged 2-12years with sCP (level III-V of the Gross Motor Functional Classification system) and chronic constipation. They were followed up in the Pediatric neurology clinic, Children's hospital, Ain Shams University, May 2017- January 2019. The intervention group (O-Mg) received oral magnesium sulfate 1mL/kg/day daily for 1month compared to the placebo. Outcome measures were constipation improvement and decrease in bowel evacuation time after 1month. Initially, weekly bowel movements, constipation scores and stool consistency were comparable in both groups. After 1 month of regular administration of oral magnesium sulfate, the constipation score, stool frequency and consistency improved compared to the placebo group (P < 0.001). Effective safe treatment was achieved in 31 (68%) and 4 (9.5%) patients in the O-Mg and placebo groups, respectively (RR, 2.95; 95% CI 2.0-4.5) (P < 0.001). Painful bowel evacuation attempts spent by mothers decreased from 25 (55.6%) of the cases initially to 10 (22%) cases after onemonth in the O-Mg group (P = 0.001). In contrast, in the placebo group, the decrease went from 21 (50%) cases initially to 18 (42.9%) after 1month and was not significant (P = 0.5). Oral magnesium sulfate seems effective in alleviating chronic constipation and pain experience in children with sCP. Consequently, saving maternal time spent in daily bowel evacuation attempts.

Lubiprostone and linaclotide as treatments for chronic constipation in hemodialysis patients at a long‒term care hospital

【目的】長期療養入院血液透析患者の難治性便秘症に対する上皮機能変容薬（ルビプロストン，リナクロチド）の有用性を検討した．【対象・方法】刺激性下剤で改善を認めない便秘症患者25名に対し上皮機能変容薬に変更後1か月間投与し，その有用性を検討した．【結果】ルビプロストン投与期では，Constipation Scoring Systemは投与前後で有意な変化はみられなかったが，非糖尿病性腎臓病群ではs‒Crは開始時6.3±2.45 mg/dL，1か月後は5.9±2.2 mg/dL，IPは開始時4.5±1.4 mg/dLであったが，1か月後は3.8±1.0 mg/dLと有意な改善を認めた．リナクロチド投与非糖尿病性腎臓病群では，Constipation Scoring Systemは開始時6.4±6.0点であったが，1か月後は4.7±5.3点と有意な改善が認められた．【結語】上皮機能変容薬は長期療養入院血液透析患者の非糖尿病性腎臓病群において有用性のある下剤と思われる．

A new approach to the treatment of chronic constipation and diagnosed dysbacteriosis in children with dolichosigma

A new approach to the treatment of chronic constipation and diagnosed dysbacteriosis in children with dolichosigma