Constipation Syndrome Research Articles

Mediterranean Diet Adherence in People With Parkinson's Disease Reduces Constipation Symptoms and Changes Fecal Microbiota After a 5-Week Single-Arm Pilot Study.

Introduction: Non-motor symptoms of Parkinson's disease (PD) such as gastrointestinal (GI) dysfunction are common, yet little is known about how modifying dietary intake impacts PD symptoms. The aim of this study in individuals with PD was to determine whether a Mediterranean diet intervention is feasible and affects GI function, intestinal permeability and fecal microbial communities.Methods: A single-arm, 5-week Mediterranean diet intervention study was conducted in eight people with PD. Daily and weekly questionnaires were administered to determine changes in GI symptoms. Urine and stool samples were collected at baseline and after 5 weeks to assess intestinal permeability and fecal microbial communities. Additionally, live-in partners of the participants with PD were matched as controls (n = 8) for baseline urine and stool samples.Results: Participants with PD increased intake of Mediterranean diet based on adherence scores from baseline to week 5 (4.4 ± 0.6 vs. 11.9 ± 0.7; P < 0.01 with >10 representing good adherence), which was linked with weight loss (77.4 kg vs. 74.9 kg, P = 0.01). Constipation syndrome scores decreased after 5 weeks (2.3 ± 0.5 vs. 1.5 ± 0.3; P = 0.04). Bilophila, was higher at baseline in PD (0.6 ± 0.1% vs. 0.2 ± 0.1% P = 0.02) and slightly decreased after the diet intervention (0.5 ± 0.1%; P = 0.01). Interestingly, the proportion of Roseburia was significantly lower in PD compared to controls (0.6 ± 0.2% vs. 1.6 ± 0.3%; P = 0.02) and increased at week 5 (0.9 ± 0.2%; P < 0.01). No differences were observed for markers of intestinal permeability between the control and PD groups or post-intervention.Conclusions: Short-term Mediterranean diet adherence is feasible in participants with PD; correlated with weight loss, improved constipation, and modified gut microbiota.Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT03851861.

Interventions for preventing distal intestinal obstruction syndrome (DIOS) in cystic fibrosis.

Cystic fibrosis (CF) is the most common, life-limiting, genetically inherited disease. It affects multiple organs, particularly the respiratory system. However, gastrointestinal problems such as constipation and distal intestinal obstruction syndrome (DIOS) are also important and well-recognised complications in CF. They share similar symptoms e.g. bloating, abdominal pain, but are distinct conditions. Constipation occurs when there is gradual faecal impaction of the colon, but DIOS occurs when there is an accumulation of faeces and sticky mucus, forming a mass in the distal part of the small intestine. The mass may partially block the intestine (incomplete DIOS) or completely block the intestine (complete DIOS). Symptoms of DIOS can affect quality of life and other aspects of CF health, such as airway clearance, exercise, sleep and nutritional status. Treatment of constipation and prevention of complete bowel obstruction are required for gastrointestinal management in CF. However, many different strategies are used in clinical practice and there is a lack of consensus. The importance of this topic was highlighted in a recent research priority setting exercise by the James Lind Alliance. To evaluate the effectiveness and safety of laxative agents of differing types for preventing DIOS (complete and incomplete) in children and adults with CF. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of search: 09 September 2021. We also searched online trial registries. Date of last search: 12 October 2021. Randomised and quasi-randomised controlled parallel trials comparing laxative therapy for preventing DIOS (including osmotic agents, stimulants, mucolytics and substances with more than one action) at any dose to placebo, no treatment or an alternative laxative therapy, in people of any age with pancreatic sufficient or insufficient CF and any stage of lung disease. Randomised cross-over trials were judged on an individual basis. Two authors independently assessed trials for inclusion, extracted outcome data and performed a risk of bias assessment for the included data. We judged the certaintyof the evidence using GRADE criteria. We included one cross-over trial (17 participants) with a duration of 12 months, in which participants were randomly allocated to either cisapride (a gastro-prokinetic agent) or placebo for six months each. The trial had an unclear risk of bias for most domains but had a high risk of reporting bias. Radiograph scores revealed no difference in occurrence of DIOS between cisapride and placebo (narrative report, no data provided). There were no adverse effects. Symptom scores were the only secondary outcome within the review that were reported. Total gastrointestinal symptom scores favoured cisapride with a statistically significant mean difference (MD) of -7.60 (95% confidence interval (CI) -14.73 to -0.47). There was no significant difference at six months between cisapride and placebo for abdominal distension, MD -0.90 (95% CI -2.39 to 0.59) or abdominal pain, MD -0.4 (95% CI -2.05 to 1.25). The global symptom scores (whether individuals felt better or worse) were reported in the paper to favour cisapride and be statistically significant (P < 0.05). We assessed the available data to be very low certainty. There was a great deal of missing data from the included trial and the investigators failed to report numerical data for many outcomes. The overall risk of bias of the trial was unclear and it had a high risk for reporting bias. There was also indirectness; the trial drug (cisapride) has since been removed from the market in several countries due to adverse effects, thus it has no current applicability for preventing DIOS. The included trial also had very few participants, which downgraded the certaintya further level for precision. There is an absence of evidence for interventions for the prevention of DIOS. As there was only one included trial, we could not perform a meta-analysis of the data. Furthermore, the included trial compared a prokinetic agent (cisapride) that is no longer licensed for use in a number of countries due to the risk of serious cardiac events, a finding that came to light after the trial was conducted. Therefore, the limited findings from the trial are not applicable in current clinical practice. Overall, a great deal more research needs to be undertaken on gastrointestinal complications in CF, as this is a very poorly studied area compared to respiratory complications in CF.

Can We Rely on the Rome IV Questionnaire to Diagnose Children With Functional Gastrointestinal Disorders?

Background/AimsTo investigate the intra-rater (test-retest) reliability of the diagnosis of functional gastrointestinal disorders (FGIDs) as measured by the Questionnaire on Pediatric Functional Gastrointestinal Disorders, Rome IV version (QPGS-IV) in children.MethodsA prospective cohort study was conducted in a public school in Cali, Colombia. Children and adolescents between 11 and 18 years of age were given the self-report Spanish version of the QPGS-IV at day 0 (baseline) and at day 2 (48 hours later).ResultsThe study protocol was completed by 215 children, of which 97 (45%) were excluded from analysis due to the inability to follow the questionnaire’s instructions. The final analysis included data of 118 children (mean age 15.0 ± SD 1.8 years old, 58.5% boys). The most common diagnoses were functional dyspepsia, functional constipation, and irritable bowel syndrome. We found a moderate intra-rater reliability (κ = 0.61-0.65) for diagnosing an FGID in general, a functional abdominal pain disorder, and the diagnosis of functional dyspepsia. We found a weak intra-rater reliability (κ = 0.46-0.54) for diagnosing a functional defecation disorder, functional constipation, irritable bowel syndrome, and the postprandial distress syndrome subtype of functional dyspepsia.ConclusionsOur study shows that a large proportion of children cannot adequately complete the QPGS-IV and that the intra-rater reliability among those who did adequately follow the instructions is moderate. We advise to test the children’s understanding of the instructions prior to completion of questionnaires and recommend to not rely exclusively on a self-reported questionnaire to select, recruit, or evaluate pediatric patients for FGIDs for research purposes.

Systematic Review of Pediatric Functional Gastrointestinal Disorders (Rome IV Criteria).

Functional gastrointestinal disorders (FGID) are common among children and may cause a significant symptom burden. The Rome criteria are symptom-based guidelines for the assessment of FGID among children and adults. The aim of this systematic review was to estimate the prevalence of FGID utilizing the revised Rome IV criteria. Nine health databases were searched. The inclusion criteria were: prospective FGID prevalence data using the Rome IV criteria for children up to 18 years, and the exclusion criteria were: cohorts with known gastrointestinal or organic conditions. The data were presented as a percentage of children experiencing at least one FGID, as well as in individual categories. The searches identified 376 papers, with 20 included in the final analysis, providing a pooled cohort of 18,935 children. The median prevalence of FGID for children aged up to four years was 22.2% (range 5.8–40%), and aged four–eighteen years was 21.8% (range 19–40%). The most common FGID for children aged 0–12 months was infant regurgitation, the most common FGID for those aged 13–48 months were functional constipation and cyclic vomiting, and, for those aged over four years, functional constipation, functional dyspepsia, and irritable bowel syndrome. This reported overall incidence of FGID may be used as a benchmark of normative data among the general population and comparative data for those with comorbid disease.

S509 Plecanatide Provided Clinically Meaningful Improvements in Health-Related Quality of Life in Patients With Chronic Idiopathic Constipation and Irritable Bowel Syndrome With Constipation: A Post-Hoc Analysis

S509 Plecanatide Provided Clinically Meaningful Improvements in Health-Related Quality of Life in Patients With Chronic Idiopathic Constipation and Irritable Bowel Syndrome With Constipation: A Post-Hoc Analysis

S538 Plecanatide Improves Abdominal Symptoms in Individuals With Chronic Idiopathic Constipation and Irritable Bowel Syndrome With Constipation, Including Those Experiencing Severe Bloating, Pain, and Discomfort

S538 Plecanatide Improves Abdominal Symptoms in Individuals With Chronic Idiopathic Constipation and Irritable Bowel Syndrome With Constipation, Including Those Experiencing Severe Bloating, Pain, and Discomfort

Subjective Taste and Smell Changes in Conjunction with Anxiety and Depression Are Associated with Symptoms in Patients with Functional Constipation and Irritable Bowel Syndrome.

Background Patients with functional constipation (FC) and irritable bowel syndrome (IBS) often report psychological abnormalities and decreased eating enjoyment. Several patients also complain of changes in the sense of smell and taste, but these are often disregarded clinically. Aims Therefore, there is a need to determine whether taste/smell disturbances and psychological abnormalities are present in patients with FC or IBS and whether these are related to the severity of lower gastrointestinal symptoms. Methods A total of 337 subjects were recruited, including FC (n = 115), IBS (n = 126), and healthy controls (n = 96). All participants completed questionnaires evaluating taste and smell (taste and smell survey (TSS)), Lower Gastrointestinal Symptoms Rating Scale (LGSRS), Hamilton anxiety scale (HAMA), and Hamilton depression scale (HAMD). TSS recorded information on the nature of taste and smell changes (TSCs) and the impact of these changes on the quality of life. LGSRS was used to assess the severity of lower gastrointestinal symptoms; HAMA and HAMD scales were used to reflect the psychosocial state. This study protocol was registered on the Chinese Clinical Trial Registry (No. ChiCTR-2100044643). Results Firstly, we found that taste and smell scores were higher in patients with IBS than in healthy controls. Secondly, for FC and IBS patients, LGSRS was significantly correlated with the taste score (Spearman′s rho = 0.832, P < 0.001). LGSRS was also significantly correlated with HAMA (Spearman′s rho = 0.357, P = 0.017) and HAMD (Spearman′s rho = 0.377, P = 0.012). In addition, the taste score was significantly correlated with HAMD (Spearman′s rho = 0.479, P = 0.001), while the smell score was also significantly correlated with HAMD (Spearman′s rho = 0.325, P = 0.031). Thirdly, 60.87% and 71.43% of patients complained of taste abnormality, while 65.22% and 71.43% had smell abnormality in the FC and IBS groups, respectively. Meanwhile, 47.83% and 47.62% of patients suffered from anxiety, while 43.48% and 57.14% suffered from depression in the FC and IBS groups, respectively. Finally, we found significant differences in the taste, smell, HAMD, and LGSRS scores between the female and male IBS groups (P < 0.050). Conclusions TSCs and psychological disorders are prominent in FC and IBS patients. Taste abnormalities, as well as anxiety and depression, are significantly correlated with LGSRS. Awareness of this high prevalence of taste/smell abnormalities and the psychological changes among patients with FC and IBS may help better predict and understand the severity of symptoms.

Intestinal Guanylate Cyclase-C mRNA Expression in Duodenum and Colon of Children.

Guanylate cyclase-C (GC-C) agonists, which increase intestinal secretion and accelerate transit, are used to treat chronic constipation and constipation-predominant irritable bowel syndrome and are being evaluated for pediatric use. Prior studies suggest GC-C receptor density may be higher in young children, potentially amplifying GC-C agonism with treatment implications. We aimed to quantitate duodenal and colonic GC-C mRNA expression in children. Mucosal biopsies were obtained from subjects aged 6 months to 18 years during clinically indicated upper, that is, esophago-gastro-duodenal, and/or colonic endoscopy. Tissue samples without histologic abnormalities were grouped by subject age (<24 months, 24 months to <6 years, 6 to <12 years, and 12 to <18 years) and analyzed for GC-C mRNA expression by qPCR. The relationship between GC-C mRNA levels and age was modeled using regression analyses. Ninety-nine subjects underwent upper endoscopy/colonoscopy; 93 had evaluable samples. Mean relative GC-C mRNA expression was 2.36 (range 2.21-2.46) for duodenal samples and 1.56 (range 1.22-1.91) for colonic samples. Predicted and observed normalized GC-C mRNA expression in each region were comparable among age groups. Pooled expression by region demonstrated lower expression in colonic versus duodenal samples. Uniform levels of GC-C mRNA expression were detected in children aged >6 months in the duodenum and >12 months in the colon. Higher expression was observed in all age groups in duodenal versus colonic samples, indicating regional variability in GC-C receptor density. These data are reassuring for further studies of GC-C agonists in children.

Gastrointestinal disorders in patients with COVID-19: diagnoses and treatment during the pandemic

Background. The pandemic caused by the coronavirus disease 2019 (COVID-19) is a topic that is currently in the spotlight of the world community. The use of non-steroidal anti-inflammatory drugs (NSAIDs) in combination with new oral anticoagulants (dabigatran, rivaroxaban, apixaban, etc.) and acetylsalicylic acid by the significant number of patients during the pandemic, caused by COVID-19, raises the question about the safety of the influence of each drug on the occurrence of gastrointestinal complications. The development of algorithms to prevent damage to the gastrointestinal mucosa on the background of these drugs is becoming a priority. The purpose was to examine the presence of gastrointestinal disorders using the Gastrointestinal Symptom Rating Scale (GSRS) in convalescents after COVID-19 and to evaluate the effectiveness of esomeprazole for correction of these disorders. Materials and methods. We surveyed 92 (48 men and 44 women) convalescents after COVID-19. The mean age of individuals was (49.2±2.0) years. To conduct a survey of patients who had COVID-19, we developed a questionnaire which included patient’s passport data, age, gender. In addition, patients reported how COVID-19 was diagnosed, what drugs they were taking during treatment, and whether they needed oxygen therapy. Subsequently, convalescents after COVID-19 answered questions from the GSRS. Information was collected and the questionnaire was completed by telephone survey. Depending on the data of GSRS, esomeprazole (Ezonexa) was prescribed to patients at a dose of 20 mg 1 time per day, 30 minutes before meals, for 30 days. During the follow-up survey on day 30 of esomeprazole intake, patients re-answered the GSRS questions. Results. Thirty days after starting esomeprazole intake at a dose of 20 mg 1 time per day, 92 convalescents after COVID-19 showed a significant reduction (p&lt;0.001) in the manifestations of reflux, abdominal pain and dyspeptic syndromes compared to the results before treatment ((2.3±0.1), (4.3±0.2), (5.7±0.3) versus (4.3±0.3), (9.3±0.4), (8.6±0.6), respectively). Esomeprazole was equally effective (p&gt;0.05) in influencing the severity of reflux, abdominal pain, dyspeptic, diarrheal and constipation syndromes in both men and women: (2.3±0.1), (4.3±0.2), (5.7±0.3), (3.9±0.3), (3.0±0.1) versus (2.4±0.1), (4.2±0.2), (6.0±0.4), (4.0±0.4), (3.1±0.1), respectively. Esomeprazole was also equally effective (p&gt;0.05) in the impact on the severity of reflux, abdominal pain, dyspeptic, diarrheal and constipation syndromes among patients receiving acetylsalicylic acid and those treated with rivaroxaban: (2.5±0.2), (4.2±0.2), (5.6±0.2), (3.9±0.4), (3.1±0.1) versus (2.2±0.1), (4.4±0.3), (6.4±0.6), (4.2±0.4), (3.0±0.1), respectively. Esomeprazole at a dose of 20 mg 1 time per day was equally effective (p&gt;0.05) in relation to the dynamics of the severity of syndromes in patients receiving paracetamol and one NSAID and in those receiving paracetamol and 2 NSAIDs. In particular, in people receiving paracetamol and one NSAID, on the background of esomeprazole administration, the severity of reflux, abdominal pain, dyspeptic, diarrheal and constipation syndromes were (2.4±0.1), (4.3±0.2), (5.8±0.3), (4.1±0.3), (3.1±0.1) and in patients taking paracetamol and 2 NSAIDs— (2.1±0.2), (4.5±0.4), (6.7±0.7), (4.4±0.7), (3.0±0.1), respectively. Conclusions. Esomeprazole (Ezonexa) effectively reduces (p&lt;0.001) the severity of reflux, abdominal pain and dyspeptic syndromes in convalescents after COVID-19. The use of Esomeprazole (Ezonexa) demonstrates the same efficacy (p&gt;0.05) in men and women when receiving both ASA and rivaroxaban and during the treatment with both paracetamol and one NSAID and paracetamol and 2 NSAIDs.

Association between abuse and neglect with functional constipation and irritable bowel syndrome in adolescents

Objectives To evaluate the association between violence exposure, abuse, and neglect victimization with functional constipation and irritable bowel syndrome in adolescents. Methods Observational cross-sectional case–control study conducted with adolescents from two public schools in the municipality of Osasco, metropolitan region of São Paulo, Brazil. A self-administered questionnaire validated for Brazilian Portuguese Child Abuse Screening Tools – Children’s version (ICAST-C) was used to screen the different types of violence. The definition of functional constipation and irritable bowel syndrome was performed using the Rome IV criteria for adolescents. Parents or legal guardians completed the questionnaire for socioeconomic assessment and signed the informed consent form. Results 265 students aged 11–17 years, 157 females, were evaluated. Functional constipation and irritable bowel syndrome were found in 74 (27.9%) of the 265 adolescents. Violence exposure was found in 82.6% of the 265 screened adolescents, physical abuse in 91.3%, psychological abuse in 93.2%, sexual abuse in 12.1%, and neglect in 53.6%. The multiple logistic regression analysis showed an association (p < .05) between functional constipation and irritable bowel syndrome with violence exposure (OR = 2.77), physical abuse (OR = 2.17), psychological abuse (OR = 2.95), and neglect (OR= 2.31). There was no association with sexual abuse. Conclusions Functional constipation and irritable bowel syndrome were associated with violence exposure, physical abuse, psychological abuse, and neglect in adolescent students from public schools. No association was found with sexual abuse. Further studies are necessary to investigate the causal relationship between violence and functional gastrointestinal disorders.

Understanding the physiology of human defaecation and disorders of continence and evacuation.

The act of defaecation, although a ubiquitous human experience, requires the coordinated actions of the anorectum and colon, pelvic floor musculature, and the enteric, peripheral and central nervous systems. Defaecation is best appreciated through the description of four phases, which are, temporally and physiologically, reasonably discrete. However, given the complexity of this process, it is unsurprising that disorders of defaecation are both common and problematic; almost everyone will experience constipation at some time in their life and many will develop faecal incontinence. A detailed understanding of the normal physiology of defaecation and continence is critical to inform management of disorders of defaecation. During the past decade, there have been major advances in the investigative tools used to assess colonic and anorectal function. This Review details the current understanding of defaecation and continence. This includes an overview of the relevant anatomy and physiology, a description of the four phases of defaecation, and factors influencing defaecation (demographics, stool frequency/consistency, psychobehavioural factors, posture, circadian rhythm, dietary intake and medications). A summary of the known pathophysiology of defaecation disorders including constipation, faecal incontinence and irritable bowel syndrome is also included, as well as considerations for further research in this field.

Kabızlık ve Üfürümle Tespit Edilen Williams-Beuren Sendromu

Williams-Beuren Syndrome Detected with Constipation and Murmur Williams-Beuren syndrome (WBS) is a rare disease that occurs as a result of microdeletion of 11.23 of the long arm of chromosome 7, with a frequency of 1/20.000-30.000. Typical facial appearance, mental retardation, various congenital cardiovascular anomalies and endocrinological disorders may accompany this syndrome. In cases suspected as a result of clinical and laboratory findings, the diagnosis is made by showing the deletion of the mentioned region using the fluorescent in situ hybridization (FISH) method. We detected WBS in a 17-month-old male patient who presented with chronic constipation and had peripheral pulmonary stenosis in echocardiography performed with accompanying clinical findings, and aimed to emphasize the importance of multidimensional evaluation and early diagnosis. Keywords: Congenital heart disease, pulmonary stenosis, microdeletion syndromes, constipation, Williams-Beuren syndrome

Bowel function and quality of life following surgery for deep endometriosis

Objective To assess the influence of surgical approach, complications and patient characteristics and their postoperative functional outcomes on (sexual) quality of life (QoL) in patients with deep endometriosis (DE) with bowel involvement. Methods Retrospective cohort study on patients surgically treated for DE in a Dutch tertiary referral hospital. Data are based on surgical records and questionnaires covering current postoperative bowel function and (sexual) QoL. Results Postoperative functional score outcomes: constipation, fecal incontinence and Low Anterior Resection Syndrome (LARS) did not differ between patients treated with rectal shaving or segmental resection. Thirty percent of women treated with rectal shaving experienced LARS-like symptoms as well. Women who underwent segmental resection had a worse sexual QoL compared to patients managed by shaving. Patients who suffered from complications had a worse postoperative QoL. A higher postoperative constipation score was correlated with a significantly higher pain score and a lower overall and sexual QoL. LARS-score was correlated with a worsened sexual QoL. Conclusion Women who underwent surgery for deep endometriosis rated their overall QoL as lower when a complication occurred. Segmental resection resulted in a lower sexual QoL compared to shaving. We showed that a higher LARS-score correlates with a lower sexual QOL, and postoperative constipation with more pain and a lower overall and sexual QoL. Interestingly, after using the shaving technique one-third of the patients experienced LARS-like symptoms as well.

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.

Psyllium

Psyllium is a natural, predominantly soluble isolated fiber that forms a gel when hydrated. The psyllium gel is not fermented and transits the entire gastrointestinal tract intact. In the small intestine, the psyllium gel increases chyme viscosity, which slows the degradation and absorption of nutrients, which significantly improves fasting blood glucose and hemoglobin A1c levels in individuals with metabolic syndrome and type 2 diabetes mellitus (eg, −37 mg/dL). This delay in nutrient absorption prolongs satiety/delays hunger, leading to decreased energy intake and weight loss in overweight and obese patients. In the distal small intestine (terminal ileum), psyllium becomes more concentrated as water is absorbed, and the highly viscous gel interferes with the active reuptake of bile acids, which are captured in the gel and eliminated via stool. This decrease in the bile acid pool stimulates the liver to produce more bile. As cholesterol is a component of bile, the liver expresses low-density lipoprotein (LDL) cholesterol receptors to harvest LDL-cholesterol from the blood, thereby lowering both LDL-cholesterol (up to 24%) and total cholesterol (up to 20%) levels without affecting high-density lipoprotein cholesterol level. The cholesterol-lowering benefit of psyllium is also additive to the effects of statin drugs, with an effect equivalent to doubling the statin dose. In the large intestine, the nonfermented psyllium gel has a paradoxical “stool normalizing” effect: psyllium softens hard stool in constipation, firms loose/liquid stool in diarrhea, and normalizes stool form/reduces symptoms in irritable bowel syndrome. Psyllium is the only fiber recommended for treatment of constipation and irritable bowel syndrome by the American College of Gastroenterology. Taken together, psyllium is the only fiber supplement that provides 5 of the major health benefits identified by the Food and Drug Administration (cholesterol lowering, improved glycemic control, decreased energy intake/weight loss, decreased blood pressure secondary to weight loss, and laxation/regularity). Psyllium has also been shown clinically to be effective in disease states (eg, hypercholesterolemia, type 2 diabetes, obesity, chronic constipation, chronic diarrhea, hemorrhoids, ulcerative colitis, enteral nutrition–induced diarrhea, fecal incontinence, and irritable bowel syndrome). Taken together, the clinical data support the conclusion that “Fiber needs to gel to keep your patients well.”

A Collaborative Effort to Advance Drug Development in Pediatric Constipation and Irritable Bowel Syndrome.

Pediatric functional gastrointestinal disorders including irritable bowel syndrome with constipation and functional constipation are common conditions in childhood, but no drugs are U.S. Food and Drug Administration (FDA) approved for chronic use in pediatric patients with these disorders. Despite efforts to better standardize the diagnosis of these conditions in children (including recent modifications to the Rome criteria), conducting pediatric clinical trials to support drug approval remains a challenge. In March 2018, FDA, in collaboration with the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition, American Gastroenterological Association, and American College of Gastroenterology, convened a public workshop to discuss the challenges and opportunities in conducting pediatric clinical trials in functional gastrointestinal conditions. The workshop assembled gastroenterologists, psychologists, patients, patient advocates, regulators, and industry representatives to discuss trial design and conduct including alternative designs, eligibility criteria, instruments for patient- and observer-reported outcomes, and optimal primary endpoints to support regulatory approval. This report summarizes the workshop, key challenges and knowledge gaps identified, and outlines areas where further research efforts are needed to overcome barriers to developing drugs to treat these conditions.

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.

Impact of Parental Illness and Injury on Pediatric Disorders of Gut–Brain Interaction

To evaluate the relationship between parental injury and illness and disorders of gut-brain interaction (DGBI) in children. A self-controlled case series using data from the Military Health System Data Repository compared International Classification of Diseases, Ninth Revision-identified DGBI-related outpatient visits and prescriptions in 442 651 children aged 3-16years in the 2years before and the 2years after the injury and/or illness of their military parent. Negative binomial regression was used to compare visit rates for constipation, fecal incontinence, abdominal pain, irritable bowel syndrome, and a composite of these before and after parental injury and/or illness. Logistic regression, clustered by child, compared the odds of stooling agent and antispasmodic prescription before and after parental injury and/or illness. In the 2years following parental injury and/or illness, children had increased visits for DGBIs (adjusted incidence rate ratio [aIRR] 1.09; 95% CI 1.07-1.10), constipation (aIRR 1.07; 95% CI 1.04-1.10), abdominal pain (aIRR 1.09; 95% CI 1.07-1.12), and irritable bowel syndrome (aIRR 1.37; 95% CI 1.19-1.58). Following parental injury and/or illness, the odds of stooling agent prescription decreased (aOR 0.95; 95% CI 0.93-0.97) and the odds of antispasmodic prescription increased (aOR 1.26; 95% CI 1.18-1.36). Parental injury and/or illness is associated with increased healthcare use for DGBIs. Parental health should be considered by clinicians when assessing DGBIs, counseling patients, and formulating treatment plans.

An Innovative Synbiotic Formulation Decreases Free Serum Indoxyl Sulfate, Small Intestine Permeability and Ameliorates Gastrointestinal Symptoms in a Randomized Pilot Trial in Stage IIIb-IV CKD Patients.

Proteolytic dysbiosis of the gut microbiota has been recognized as both a typical feature of chronic kidney disease (CKD) and a risk factor for its progression. Blood accumulation of gut-derived uremic toxins (UTs) like indoxyl sulfate (IS) and p-cresyl sulfate (PCS), intestinal permeability and constipation are typical features accompanying CKD progression and triggering chronic inflammation. In order to verify the efficacy of the innovative synbiotic formulation NATUREN G® in modulating the levels of circulating UTs, intestinal permeability and gastrointestinal symptoms, we set up a randomized, single-blind, placebo-controlled, pilot trial in stage IIIb-IV CKD patients and in healthy controls. Two-month administration of the synbiotic resulted in a decrease of free IS, as compared with the placebo-treated arm, only in the CKD group. The other UTs did not significantly change, although different trends in time (increase in the placebo arm and decrease in the synbiotic arm) were observed. Moreover, after supplementation, reduction of small intestinal permeability and amelioration of abdominal pain and constipation syndromes were observed only in the CKD group. The obtained results suggest the specificity of action of NATUREN G® in CKD and justify further validation in a wider study population.

The Use of Linaclotide in Children with Functional Constipation or Irritable Bowel Syndrome: A Retrospective Chart Review.

BackgroundLinaclotide is a well-tolerated and effective agent for adults with functional constipation (FC) or irritable bowel syndrome with constipation (IBS-C). However, data in children are lacking. The aim of this study is to examine the efficacy and safety of linaclotide in children.MethodsWe performed a retrospective review of children < 18 years old who started linaclotide at our institution (Nationwide Children's Hospital, Columbus, Ohio). We excluded children already using linaclotide or whom had an organic cause of constipation or abdominal pain. We recorded information on patient characteristics, medical and surgical history, symptoms, clinical response, course of treatment, and adverse events at baseline, first follow-up, and after 1 year of linaclotide use. A positive clinical response was based on the physician’s global assessment of symptoms at the time of the visit as documented.ResultsWe included 93 children treated with linaclotide for FC (n = 60) or IBS-C (n = 33); 60% were female; median age was 14.7 years (IQR 13.2–16.6). Forty-five percent of patients with FC and 42% with IBS-C had a positive clinical response at first follow-up a median of 2.5 and 2.4 months after starting linaclotide, respectively. Approximately a third of patients experienced adverse events and eventually 27% stopped using linaclotide due to adverse events. The most common adverse events were diarrhea, abdominal pain, nausea, and bloating.ConclusionNearly half of children with FC or IBS-C benefited from linaclotide, but adverse events were relatively common. Further prospective, controlled studies are needed to confirm these findings and to identify which patients are most likely to benefit from linaclotide.