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Introduction Constipation is commonly treated with over-the-counter (OTC) products whose efficacy and safety remain unclear. We performed a systematic review of OTC therapies for chronic constipation and provide evidence-based recommendations. Methods We searched PubMed and Embase for randomized controlled trials of ≥4-week duration that evaluated OTC preparations between 2004 and 2020. Studies were scored using the US Preventive Services Task Force criteria (0-5 scale) including randomization, blinding, and withdrawals. The strengths of evidence were adjudicated within each therapeutic category, and recommendations were graded (A, B, C, D, and I) based on the level of evidence (level I, good; II, fair; or III, poor). Results Of 1,297 studies identified, 41 met the inclusion criteria. There was good evidence (grade A recommendation) for the use of the osmotic laxative polyethylene glycol (PEG) and the stimulant senna; moderate evidence (grade B) for psyllium, SupraFiber, magnesium salts, stimulants (bisacodyl and sodium picosulfate), fruit-based laxatives (kiwi, mango, prunes, and ficus), and yogurt with galacto-oligosaccharide/prunes/linseed oil; and insufficient evidence (grade I) for polydextrose, inulin, and fructo-oligosaccharide. Diarrhea, nausea, bloating, and abdominal pain were common adverse events, but no serious adverse events were reported. Discussion The spectrum of OTC products has increased and quality of evidence has improved, but methodological issues including variability in study design, primary outcome measures, trial duration, and small sample sizes remain. We found good evidence to recommend polyethylene glycol or senna as first-line laxatives and moderate evidence supporting fiber supplements, fruits, stimulant laxatives, and magnesium-based products. For others, further validation with more rigorously designed studies is warranted.

Objectives: Breath tests (BTs) are important for the diagnosis of carbohydrate maldigestion syndromes and small intestinal bacterial overgrowth (SIBO). However, standardization is lacking regarding indications for testing, test methodology and interpretation of results. A consensus meeting of experts was convened to develop guidelines for clinicians and research. Methods: Pre-meeting survey questions encompassing five domains; indications, preparation, performance, interpretation of results, and knowledge gaps, were sent to 17 clinician-scientists, and 10 attended a live meeting. Using an evidence-based approach, 28 statements were finalized and voted on anonymously by a working group of specialists. Results: Consensus was reached on 26 statements encompassing all five domains. Consensus doses for lactulose, glucose, fructose and lactose BT were 10, 75, 25 and 25 g, respectively. Glucose and lactulose BTs remain the least invasive alternatives to diagnose SIBO. BT is useful in the diagnosis of carbohydrate maldigestion, methane-associated constipation, and evaluation of bloating/gas but not in the assessment of oro-cecal transit. A rise in hydrogen of ≥20 p.p.m. by 90 min during glucose or lactulose BT for SIBO was considered positive. Methane levels ≥10 p.p.m. was considered methane-positive. SIBO should be excluded prior to BT for carbohydrate malabsorption to avoid false positives. A rise in hydrogen of ≥20 p.p.m. from baseline during BT was considered positive for maldigestion. Conclusions: BT is a useful, inexpensive, simple and safe diagnostic test in the evaluation of common gastroenterology problems. These consensus statements should help to standardize the indications, preparation, performance and interpretation of BT in clinical practice and research.

This is the second of a two-part summary of a National Institutes of Health conference on fecal incontinence (FI) that summarizes current treatments and identifies research priorities. Conservative medical management consisting of patient education, fiber supplements or antidiarrheals, behavioral techniques such as scheduled toileting, and pelvic floor exercises restores continence in up to 25% of patients. Biofeedback, often recommended as first-line treatment after conservative management fails, produces satisfaction with treatment in up to 76% and continence in 55%; however, outcomes depend on the skill of the therapist, and some trials are less favorable. Electrical stimulation of the anal mucosa is ineffective, but continuous electrical pulsing of sacral nerves produces a ≥50% reduction in FI frequency in a median 73% of patients. Tibial nerve electrical stimulation with needle electrodes is promising but remains unproven. Sphincteroplasty produces short-term clinical improvement in a median 67%, but 5-year outcomes are poor. Injecting an inert bulking agent around the anal canal led to ≥50% reductions of FI in up to 53% of patients. Colostomy is used as a last resort because of adverse effects on quality of life. Several new devices are under investigation but not yet approved. FI researchers identify the following priorities for future research: (1) trials comparing the effectiveness, safety, and cost of current therapies; (2) studies addressing barriers to consulting for care; and (3) translational research on regenerative medicine. Unmet patient needs include FI in special populations (e.g., neurological disorders and nursing home residents) and improvements in behavioral treatments.

Linaclotide is a minimally absorbed guanylate cyclase-C agonist. The objective of this trial was to determine the efficacy and safety of linaclotide in patients with irritable bowel syndrome with constipation (IBS-C).This phase 3, double-blind, parallel-group, placebo-controlled trial randomized IBS-C patients to placebo or 290 μ g oral linaclotide once daily in a 12-week treatment period, followed by a 4-week randomized withdrawal (RW) period. There were four primary end points, the Food and Drug Administration ’ s (FDA ’ s) primary end point for IBS-C (responder: improvement of ≥ 30 % in average daily worst abdominal pain score and increase by ≥ 1 complete spontaneous bowel movement (CSBM) from baseline (same week) for at least 50 % of weeks assessed) and three other primary end points, based on improvements in abdominal pain and CSBMs for 9 / 12 weeks. Adverse events (AEs) were monitored.The trial evaluated 800 patients (mean age = 43.5 years, female = 90.5 % , white = 76.9 % ). The FDA end point was met by 136 / 405 linaclotide-treated patients (33.6 % ), compared with 83 / 395 placebo-treated patients (21.0 % ) ( P0.0001) (number needed to treat: 8.0, 95 % confidence interval: 5.4, 15.5). A greater percentage of linaclotide patients, compared with placebo patients, reported for at least 6 / 12 treatment period weeks, a reduction of ≥ 30 % in abdominal pain (50.1 vs. 37.5 % , P = 0.0003) and an increase of ≥ 1 CSBM from baseline (48.6 vs. 29.6 % , P0.0001). A greater percentage of linaclotide patients vs. placebo patients were also responders for the other three primary end points ( P0.05). Significantly greater improvements were seen in linaclotide vs. placebo patients for all secondary end points ( P0.001). During the RW period, patients remaining on linaclotide showed sustained improvement; patients re-randomized from linaclotide to placebo showed return of symptoms, but without worsening of symptoms relative to baseline. Diarrhea, the most common AE, resulted in discontinuation of 5.7 % of linaclotide and 0.3 % of placebo patients.Linaclotide significantly improved abdominal pain and bowel symptoms associated with IBS-C for at least 12 weeks; there was no worsening of symptoms compared with baseline following cessation of linaclotide during the RW period.

Despite a lack of supportive data, stool form and stool frequency are often used as clinical surrogates for gut transit in constipated patients. The aim of this study was to assess the correlation between stool characteristics (form and frequency) and gut transit in constipated and healthy adults.A post hoc analysis was performed on 110 subjects (46 chronic constipation) from nine US sites recording stool form (Bristol Stool Scale) and frequency during simultaneous assessment of whole-gut and colonic transit by wireless motility capsule (WMC) and radio-opaque marker (ROM) tests. Stool form and frequency were correlated with transit times using Spearman's rank correlation. Accuracy of stool form in predicting delayed transit was assessed by receiver operating characteristic analysis.In the constipated adults (42 females, 4 males), moderate correlations were found between stool form and whole-gut transit measured by WMC (r=-0.61, P0.0001) or ROM (-0.45, P=0.0016), as well as colonic transit measured by WMC (-0.62, P0.0001). A Bristol stool form value3 predicted delayed whole-gut transit with a sensitivity of 85% and specificity of 82% and delayed colonic transit with a sensitivity of 82% and specificity of 83%. No correlation between stool form and measured transit was found in healthy adults, regardless of gender. No correlation was found between stool frequency and measured transit in constipated or healthy adults. The correlation between stool frequency and measured transit remained poor in constipated adults with3 bowel movements per week.Stool form predicts delayed vs. normal transit in adults. However, only a moderate correlation exists between stool form and measured whole-gut or colonic transit time in constipated adults. In contrast, stool frequency is a poor surrogate for transit, even in those with reduced stool frequency.

Objectives Although the role of lactose intolerance in the pathogenesis of abdominal symptoms is well known, the role of fructose intolerance is unclear. Our aims were 1) to examine the prevalence of fructose intolerance in patients with unexplained abdominal symptoms, and 2) to explore whether fructose concentration influences fructose breath test. Methods Over 2 yr, patients with unexplained symptoms answered questionnaires and underwent fructose breath tests. Patients received 50 g fructose in 150 ml water (33% solution). Breath samples were collected for hydrogen and methane. In a second study, breath test was performed after giving either 10%, 20%, or 33% fructose solution. Data were analyzed retrospectively. Results A total of 183 patients (50 male, 133 female) had breath tests, of whom 134 (73%) were positive. Among these, 119 (89%) had elevated H2, and 15 (11%) had elevated CH4 or both gases. Questionnaires showed that flatus (83%), pain (80%), bloating (78%), belching (70%), and altered bowel habit (65%) were the most common symptoms. Breath test reproduced symptoms in 101 patients (75%). In the second study, 14/36 (39%) tested positive with a 10% solution, 23/33 (70%) with a 20% solution, and 16/20 (80%) with a 33% solution (10% versus 20% or 33%, p Conclusions Fructose intolerance may cause unexplained GI symptoms. The higher yield of positive tests in our initial study may be due to referral bias or testing conditions; lower test dose produced a lower yield. Nonetheless, recognition and treatment of fructose intolerance may help many patients.

Nutcracker esophagus is a manometric pattern that is commonly seen in patients with functional (noncardiac) chest pain. However, this pattern is often unassociated with pain. Consequently, the pathophysiology of chest pain in these patients is unclear.We prospectively examined the sensory perception and biomechanical properties of the esophagus in 10 patients with chest pain and a nutcracker esophagus, along with those properties in 12 healthy controls using impedance planimetry.Stepwise balloon distentions reproduced typical chest pain in 9/10 (90%) patients. The threshold for chest pain was lower (p0.05) in patients than in controls (mean +/- SD 43+/-5 vs 62+/-4 cm H2O) but only 2/12 controls experienced pain. The thresholds for first perception and moderate discomfort were also lower (18+/-8 vs 30+/-11 cm H2O, p0.01 and 28+/-9 vs 62+/-5 cm H2O, p0.001) in patients than in controls, but only 3/12 controls experienced moderate discomfort. The esophageal reactivity to balloon distention was higher in patients than in controls (p0.001). The tension-strain curve shifted to the left in the patient group when compared to that in the controls (p0.05).Patients with a nutcracker esophagus demonstrate a hypersensitive and stiff esophagus. Because balloon distention reproduced their chest pain, visceral hyperalgesia of the esophagus may be relevant to the pathogenesis of their pain. Balloon distention test may be more useful in the evaluation of patients with functional chest pain and a nutcracker esophagus.

Objective: Traditionally, barium paste has been used for performing defecography. Because this substance is not stool-like, barium defecography may not accurately represent defecatory function. Our aim was to prospectively compare the utility of a new artificial stool, “FECOM”—a silicon-filled and barium-coated, deformable device the shape and consistency of which mimicked a normal formed stool with that of barium paste. Methods: Defecography was performed after placing FECOM or barium paste in a random order in 12 healthy subjects (two men and 10 women). We evaluated the changes in anorectal angle, rectal morphology, rectal sensation, and the subjects’ preference for a “stool-like” device. Results: Anorectal angle at rest, during squeeze, cough, and straining were each greater with the FECOM when compared with the barium paste (p < 0.006). Anterior rectocele (nine), mucosal intussusception (four), and incontinence (three) were identified only with barium defecography. Nine (75%) subjects preferred FECOM to barium paste (p < 0.001) and reported that expulsion of this device mimicked more closely their stools at home (p < 0.05). Conclusion: The anorectal angle is influenced by the form and consistency of stool material and is lower with barium paste. The detection of rectocele, mucosal intussusception, and barium leakage in normal subjects during barium defecography questions the significance of these findings. FECOM appears to be a realistic alternative to barium paste for performing defecography.

Objective: The pathophysiology of obstructive defecation is unclear. We investigated whether impaired rectoanal coordination causes obstructive defecation and if this dysfunction can be corrected by biofeedback therapy. Methods: We prospectively studied 25 healthy subjects and 35 consecutive patients with constipation (>1 year) with anorectal manometry and balloon expulsion test. Symptoms were assessed from diary cards. Patients found to have obstructive defecation were offered biofeedback therapy. After treatment, their defecation dynamics and symptoms were reassessed. Results: Eighteen patients had obstructive defecation and 17 had normal defecation dynamics (nonobstructive). Five normals (20%) exhibited obstructive pattern but only one failed to expel balloon. In the obstructive group, during straining, the intrarectal pressure and defecation index were lower (p < 0.05), and anal residual pressure was higher (p < 0.01) when compared with the nonobstructive group or normals. After biofeedback therapy, the intrarectal pressure and defecation index increased (p < 0.02) and anal residual pressure decreased (p < 0.001); stool frequency, degree of straining, and bowel satisfaction scores improved (p < 0.05); 67% stopped laxatives and 11 patients discontinued stooling with digitation. Conclusion: Patients with obstructive defecation showed impaired rectal contraction, paradoxical anal contraction, or inadequate anal relaxation. These features suggest that rectoanal coordination was impaired. Biofeedback therapy rectified these pathophysiological disturbances and improved constipation.