Habit training versus habit training with direct visual biofeedback in adults with chronic constipation: A randomized controlled trial.

AIM: The aim was to determine whether specialist-led habit training using Habit Training with Biofeedback (HTBF) is more effective than specialist-led habit training alone (HT) for chronic constipation and whether outcomes of interventions are improved by stratification to HTBF or HT based on diagnosis (functional defaecation disorder vs. no functional defaecation disorder) by radio-physiological investigations (INVEST). METHOD: This was a parallel three-arm randomized single-blinded controlled trial, permitting two randomized comparisons: HTBF versus HT alone; INVEST- versus no-INVEST-guided intervention. The inclusion criteria were age 18-70 years; attending specialist hospitals in England; self-reported constipation for >6 months; refractory to basic treatment. The main exclusions were secondary constipation and previous experience of the trial interventions. The primary outcome was the mean change in Patient Assessment of Constipation Quality of Life score at 6 months on intention to treat. The secondary outcomes were validated disease-specific and psychological questionnaires and cost-effectiveness (based on EQ-5D-5L). RESULTS: In all, 182 patients were randomized 3:3:2 (target 384): HT n = 68; HTBF n = 68; INVEST-guided treatment n = 46. All interventions had similar reductions (improvement) in the primary outcome at 6 months (approximately -0.8 points of a 4-point scale) with no statistically significant difference between HT and HTBF (-0.03 points; 95% CI -0.33 to 0.27; P = 0.85) or INVEST versus no-INVEST (0.22; -0.11 to 0.55; P = 0.19). Secondary outcomes showed a benefit for all interventions with no evidence of greater cost-effectiveness of HTBF or INVEST compared with HT. CONCLUSION: The results of the study at 6 months were inconclusive. However, with the caveat of under-recruitment and further attrition at 6 months, a simple, cheaper approach to intervention may be as clinically effective and more cost-effective than more complex and invasive approaches.

Clinical Impact of Rectal Hyposensitivity: A Cross-Sectional Study of 2,876 Patients With Refractory Functional Constipation.

INTRODUCTION: Normal bowel function requires intact sensory pathways. Diminished rectal sensation (rectal hyposensitivity [RH]) is associated with constipation, although its clinical importance remains unclear. METHODS: Consecutive patients (aged 18-80) attending a tertiary center (2004-2016) for investigation of refractory functional constipation (Rome IV core criteria defined, applied post hoc) were included. Patients completed a clinical symptom questionnaire and underwent anorectal physiologic investigations, including rectal sensory testing (balloon distension) to determine 3 well-established sensory thresholds. Multivariate regression analyses were performed to evaluate associations between RH, symptomology, and allied physiologic investigations. RESULTS: Of 2,876 patients meeting inclusion criteria, 722 (25%) had RH based on ≥1 elevated sensory thresholds (0: n = 2,154 [74.9%]; 1: n = 327 [11.4%]; 2: n = 209 [7.3%]; and 3: n = 186 [6.5%]). A linear relationship existed between increasing number of elevated sensory thresholds and constipation severity (Cleveland Clinic constipation score: mean difference per threshold [95% confidence interval] 0.69 [0.48-0.90]; P < 0.001). Several symptoms were significantly (P < 0.05) associated with RH including: infrequent defecation (odds ratio 1.29 [1.17-1.42]), painful evacuation (1.15 [1.05-1.27]), prolonged toileting (1.14 [1.05-1.24]), and digitation or enema use (1.18 [1.08-1.30]). On defecography, a "functional" evacuation disorder was also associated with RH (1.37 [1.25-1.50], P < 0.001), as was megarectum (2.52 [2.08-3.05], P < 0.001). DISCUSSION: RH occurs in 25% of patients with refractory functional constipation. Increased number of elevated sensory thresholds is associated with more severe constipation phenotype. These data, in the largest study to date, provide for the first time evidence to show that RH is a major pathophysiologic mechanism in constipation, with recognized clinical impact (http://links.lww.com/AJG/B765).(Equation is included in full-text article.).

The effect of prunes on stool output, gut transit time and gastrointestinal microbiota: A randomised controlled trial.

BACKGROUND & AIM: Prunes (dried plums) are perceived to maintain healthy bowel function, however their effects on gastrointestinal (GI) function are poorly researched and potential mechanisms of action are not clear. We aimed to investigate the effect of prunes on stool output, whole gut transit time (WGTT), gut microbiota and short-chain fatty acids (SCFA) in healthy adults METHODS: We conducted a parallel group, randomised controlled trial with three treatment arms in 120 healthy adults with low fibre intakes and stool frequency of 3-6 stools/wk. Subjects were randomised to 80 g/d prunes (plus 300 ml/d water); 120 g/d prunes (plus 300 ml/d water) or control (300 ml/d water) for 4 weeks. Stool weight was the primary outcome and determined by 7-day stool collection. Secondary outcomes included stool frequency and consistency (stool diary), WGTT (radio-opaque markers), GI symptoms (diary), microbiota (quantitative PCR) and SCFA (gas liquid chromatography). Group assignment was concealed from the outcome assessors. RESULTS: There were significantly greater increases in stool weight in both the 80 g/d (mean + 22.2 g/d, 95% CI -1-45.3) and 120 g/d (+32.8 g/d, 95% CI 13.9-51.7) prune groups compared with control (-0.8 g/d, 95% CI -17.2 to 15.6, P = 0.026). Stool frequency was significantly greater following 80 g/d (mean 6.8 bowel movements/wk, SD 3.8) and 120 g/d (5.6, SD 1.9) prune consumption compared with control (5.4, SD 2.1) (P = 0.023), but WGTT was unchanged. The incidence of flatulence was significantly higher after prune consumption. There were no significant differences in any of the bacteria measured, except for a greater increase in Bifidobacteria across the groups (P = 0.046). Prunes had no effect on SCFA or stool pH. CONCLUSIONS: In healthy individuals with infrequent stool habits and low fibre intake, prunes significantly increased stool weight and frequency and were well tolerated. Prunes may have health benefits in populations with low stool weight. CLINICAL TRIAL REGISTRY NUMBER AND WEBSITE: ISRCTN42793297 http://www.isrctn.com/ISRCTN42793297.

Short-Term Daily Intake of Polydextrose Fiber Does Not Shorten Intestinal Transit Time in Constipated Adults: A Randomized Controlled Trial.

Chronic constipation (CC) remains a common gastrointestinal (GI) disorder that conveys a substantial healthcare burden. Expert guidelines recommend increasing fiber intake, yet the clinical evidence to support this needs strengthening for specific fibers. The aim was to evaluate changes in intestinal transit time and GI symptoms in CC patients who consumed polydextrose. In a randomized, double-blind, placebo-controlled trial, 128 adults with CC received 8 g or 12 g polydextrose, or placebo, daily for 4 weeks. Transit time, as primary outcome, was assessed by radiopaque marker distribution after 2-weeks intervention. Bowel habits, GI symptoms and quality of life (QOL) were assessed by questionnaire, including the Patient-Assessment of Constipation (PAC) Symptoms (SYM), and PAC-QOL. Following 2-weeks intervention, no reduction was seen in transit time in any group and following 2- or 4-weeks intervention, no improvements were seen in stool frequency or consistency in any group. After 2-weeks intervention with 8 g/day polydextrose an improvement was seen in the PAC-SYM rectal score (p = 0.041). After 4-weeks intervention both rectal (p = 0.049) and stool (p = 0.029) scores improved while improvement in the QOL satisfaction score did not reach significance (p = 0.071). Overall, the results suggest that 2-weeks consumption of 8 or 12 g/day polydextrose does not significantly improve physiological measures of gut function in CC adults. Longer term consumption may improve clinical measures, but further studies will be required to substantiate this.

Efficacy and mechanism of sub-sensory sacral (optimised) neuromodulation in adults with faecal incontinence: study protocol for a randomised controlled trial.

BACKGROUND: Faecal incontinence (FI) is a substantial health problem with a prevalence of approximately 8% in community-dwelling populations. Sacral neuromodulation (SNM) is considered the first-line surgical treatment option in adults with FI in whom conservative therapies have failed. The clinical efficacy of SNM has never been rigorously determined in a trial setting and the underlying mechanism of action remains unclear. METHODS/DESIGN: The design encompasses a multicentre, randomised, double-blind crossover trial and cohort follow-up study. Ninety participants will be randomised to one of two groups (SNM/SHAM or SHAM/SNM) in an allocation ratio of 1:1. The main inclusion criteria will be adults aged 18-75 years meeting Rome III and ICI definitions of FI, who have failed non-surgical treatments to the UK standard, who have a minimum of eight FI episodes in a 4-week screening period, and who are clinically suitable for SNM. The primary objective is to estimate the clinical efficacy of sub-sensory SNM vs. SHAM at 32 weeks based on the primary outcome of frequency of FI episodes using a 4-week paper diary, using mixed Poisson regression analysis on the intention-to-treat principle. The study is powered (0.9) to detect a 30% reduction in frequency of FI episodes between sub-sensory SNM and SHAM stimulation over a 32-week crossover period. Secondary objectives include: measurement of established and new clinical outcomes after 1 year of therapy using new (2017 published) optimised therapy (with standardised SNM-lead placement); validation of new electronic outcome measures (events) and a device to record them, and identification of potential biological effects of SNM on underlying anorectal afferent neuronal pathophysiology (hypothesis: SNM leads to increased frequency of perceived transient anal sphincter relaxations; improved conscious sensation of defaecatory urge and cortical/subcortical changes in afferent responses to anorectal electrical stimulation (main techniques: high-resolution anorectal manometry and magnetoencephalography). DISCUSSION: This trial will determine clinical effect size for sub-sensory chronic electrical stimulation of the sacral innervation. It will provide experimental evidence of modifiable afferent neurophysiology that may aid future patient selection as well as a basic understanding of the pathophysiology of FI. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number: ISRCTN98760715 . Registered on 15 September 2017.

Habit training versus habit training with direct visual biofeedback in adults with chronic constipation: study protocol for a randomised controlled trial.

BACKGROUND: Constipation affects up to 20% of adults. Chronic constipation (CC) affects 1-2% of adults. Patient dissatisfaction is high; nearly 80% feel that laxative therapy is unsatisfactory and symptoms have significant impact on quality of life. There is uncertainty about the value of specialist investigations and whether equipment-intensive therapies using biofeedback confer additional benefit when compared with specialist conservative advice. METHODS/DESIGN: A three-arm, parallel-group, multicentre randomised controlled trial. OBJECTIVES: to determine whether standardised specialist-led habit training plus pelvic floor retraining using computerised biofeedback is more clinically effective than standardised specialist-led habit training alone; to determine whether outcomes are improved by stratification based on prior investigation of anorectal and colonic pathophysiology. Primary outcome measure is response to treatment, defined as a 0.4-point (10% of scale) or greater reduction in Patient Assessment of Constipation-Quality of Life (PAC-QOL) score 6 months after the end of treatment. Other outcomes up to 12 months include symptoms, quality of life, health economics, psychological health and qualitative experience. HYPOTHESES: (1) habit training (HT) with computer-assisted direct visual biofeedback (HTBF) results in an average reduction in PAC-QOL score of 0.4 points at 6 months compared to HT alone in unselected adults with CC, (2) stratification to either HT or HTBF informed by pathophysiological investigation (INVEST) results in an average 0.4-point reduction in PAC-QOL score at 6 months compared with treatment not directed by investigations (No-INVEST). Inclusion: chronic constipation in adults (aged 18-70 years) defined by self-reported symptom duration of more than 6 months; failure of previous laxatives or prokinetics and diet and lifestyle modifications. Consenting participants (n = 394) will be randomised to one of three arms in an allocation ratio of 3:3:2: [1] habit training, [2] habit training and biofeedback or [3] investigation-led allocation to one of these arms. Analysis will be on an intention-to-treat basis. DISCUSSION: This trial has the potential to answer some of the major outstanding questions in the management of chronic constipation, including whether costly invasive tests are warranted and whether computer-assisted direct visual biofeedback confers additional benefit to well-managed specialist advice alone. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number: ISRCTN11791740. Registered on 16 July 2015.

Prospective randomized double-blind study of temporary sacral nerve stimulation in patients with rectal evacuatory dysfunction and rectal hyposensitivity.

OBJECTIVE: Prospective randomized double-blind placebo-controlled crossover trial of 14 female patients (median age 52 [30-69] years) with proctographically defined evacuatory dysfunction (ED) and demonstrable rectal hyposensitivity (elevated thresholds to balloon distension in comparison with age- and sex-matched controls). BACKGROUND: Sacral nerve stimulation (SNS) is an evolving treatment for constipation. However, variable outcomes might be improved by better patient selection. Evidence that the effect of SNS may be mediated by modulation of afferent signaling promotes a role in patients with ED associated with rectal hyposensation. METHODS: SNS was performed by the standard 2-stage technique (temporary then permanent implantation). During a 4-week period of temporary stimulation, patients were randomized ON-OFF/OFF-ON for two 2-week periods. Before insertion (PRE), and during each crossover period, primary (rectal sensory thresholds) and secondary (bowel diaries, constipation, and GIQoL [gastrointestinal quality of life] scores) outcome variables were blindly assessed. RESULTS: Thirteen patients completed the trial. Following stimulation, defecatory desire volumes to rectal balloon distension were normalized in 10 of 13 patients (PRE: mean 277 mL [234-320] vs ON: 163 mL [133-193] vs OFF: 220 mL [183-257 mL]; P = 0.006) and maximum tolerable volume in 9 of 13 (PRE: mean 350 mL [323-377] vs ON: 262 mL [219-305] vs OFF: 298 mL [256-340 mL]; P = 0.012). There was a significant increase in the percentage of successful bowel movements (PRE: median 43% [0-100] vs ON: 89% [11-100] vs OFF: 83% [11-100]; P = 0.007) and Wexner constipation scores improved (PRE: median 19 [9-26] vs ON: 10 [6-27] vs OFF: 13 [5-29]; P = 0.01). There were no significant changes in disease-specific or generic quality of life measures. Eleven patients progressed to permanent stimulation (9/11 success at 19 months). CONCLUSIONS: Most patients with chronic constipation secondary to ED with rectal hyposensitivity responded to temporary SNS. The physiological results presented support a mechanistic role for rectal afferent modulation.

Efficacy of sacral nerve stimulation for fecal incontinence in patients with anal sphincter defects.

PURPOSE: Sacral nerve stimulation has traditionally been used to treat patients with fecal incontinence with intact anal sphincters. This rationale has been challenged, but it remains unknown if its efficacy is related to the extent of the sphincter injury. METHODS: This was a prospective study of 15 patients with sphincter defects (9 combined, 2 external only, and 4 internal only) undergoing sacral nerve stimulation for fecal incontinence. Endoanal ultrasound scans were reviewed and defects scored (0-16) with use of a system published by two independent observers. These were correlated with the following outcomes: 1) reduction in fecal incontinence episodes, 2) reduction in soiling, 3) improvement in Cleveland Clinic scores, and 4) improvement in ability to defer defecation. All patients were studied after temporary stimulation and again at three to six months after permanent implantation. RESULTS: Thirteen patients (87%) progressed to permanent stimulation. Median fecal incontinence episodes per two weeks decreased from 15 (range, 1-53) to 3 (range, 0-16; P = 0.01). Median soiling episodes were reduced from 10 (range, 1-14) to 6 (range, 0-14; P = 0.009). Median Cleveland Clinic scores decreased from 12 (range, 9-18) to 9 (range, 4-14; P = 0.0005). The ability to defer defecation was improved significantly (P = 0.05). There were no relationships between sphincter defect scores and outcome measures after sacral nerve stimulation (r = 0.001-0.10; P = 0.28-0.94). CONCLUSION: Sacral nerve stimulation is an effective treatment in patients with fecal incontinence who have anal sphincter defects, and outcome is not associated with severity of sphincter disruption.

Rectal augmentation: short- and mid-term evaluation of a novel procedure for severe fecal urgency with associated incontinence.

BACKGROUND: Rectal augmentation (RA) with or without electrically stimulated gracilis neosphincter (ESGN) was developed to address the physiologic and anatomic abnormalities present in a subset of patients with incapacitating fecal urgency and associated urge fecal incontinence (UFI). This study evaluated the short- and medium-term clinical and physiologic results. METHODS: Eleven patients with fecal urgency and UFI underwent RA, 6 with concomitant ESGN formation. Patients were evaluated preoperatively, and at a median of 12.5 and 54 months after surgery. RESULTS: At 4.5 years, 7/11 patients had avoided stoma construction. Symptoms recurred leading to permanent stoma formation in 1 patient, whereas one other developed evacuatory difficulty with overflow incontinence. Median ability to defer defecation improved from seconds preoperatively to 10 minutes at 1 year (P = 0.0002), and 15 minutes at 4.5 years (P = 0.002). Median Wexner incontinence scores improved from 15 preoperatively to 3 at 1 year (P = 0.002), and 4 at 4.5 years (P = 0.02). At 1 year, 2 of the rectal sensory thresholds (DDV: P = 0.008; MTV: P = 0.008) and compliance were normalized (P = 0.008), whereas at 4.5 years, all sensation thresholds improved (FCS: P = 0.002; DDV: P = 0.002; MTV: P = 0.002), but changes in compliance were not significant. CONCLUSION: RA with or without ESGN improved reported symptoms and normalized rectal sensation. Improvements were sustained in the medium term. The procedure had no associated morbidity or mortality, and should be considered in the surgical management of a select group of patients presenting with severe urgency and UFI.

A novel technique to identify patients with megarectum.

PURPOSE: Traditional methods of identifying patients with persistent dilation of the rectum, or megarectum, are associated with inherent methodologic limitations. The purpose of this study was to use a barostat to establish criteria for the diagnosis of megarectum and to assess rectal diameter during isobaric (barostat) and volumetric (barium contrast) distention protocols in constipated patients with megarectum on anorectal manometry. METHODS: During fluoroscopic screening, rectal diameter was measured at minimum distending pressure of the rectum, achieved using a barostat. It was also measured during evacuation proctography (volumetric distention). Having established a normal range in 25 healthy volunteers, 30 constipated patients with evidence of megarectum on anorectal manometry (elevated maximum tolerable volume on latex balloon distention) were studied. A further 10 constipated patients without evidence of megarectum were studied (normal rectum). RESULTS: Megarectum was diagnosed when the rectal diameter was greater than 6.3 cm at minimum distending pressure. Rectal diameter at minimum distending pressure was increased in 20 patients (67 percent) with megarectum on anorectal manometry, but was normal in the remaining 10 patients (33 percent) and all patients with a normal rectum on anorectal manometry. Rectal diameter was increased at evacuation proctography in only 15 patients (50 percent) with evidence of megarectum on anorectal manometry. CONCLUSIONS: The prevalence of megarectum is overestimated and underestimated when rectal diameter is assessed using anorectal manometry and contrast studies, respectively. Controlled (pressure-based) distention combined with fluoroscopic imaging allowed accurate identification of patients with megarectum on the basis of a rectal diameter greater than 6.3 cm at the minimum distention pressure. Measurement of rectal diameter at minimum distention pressure may be useful in those patients with an elevated maximum tolerable volume on anorectal manometry when surgery is being contemplated.

Rectal heat thresholds: a novel test of the sensory afferent pathway.

PURPOSE: Currently, rectal sensation may be measured by balloon distention or mucosal electrostimulation. This study investigated the application of a graded heat stimulus to the rectum using a novel thermal probe as a further method of evaluating rectal sensory afferent mechanisms. METHODS: A thermal probe specially designed in our institution was used to test rectal heat sensitivity in 31 healthy subjects. This was compared with all other standard anorectal physiologic measurements. Repeatability studies were also performed. RESULTS: Heat stimulation of the mid rectum elicited sensory responses in all subjects. The most common reported response was not heat but a sharp or prickling sensation. The median rectal heat threshold was similar in males (median, 47 degrees C; range, 44-50 degrees C) compared with females (median, 45 degrees C; range, 43-50 degrees C; P > 0.05). There was a high degree of repeatability with rectal heat and balloon distention thresholds, but not electrostimulation thresholds. A strong correlation was found between rectal heat thresholds and defecatory desire (r = 0.71; P < 0.001) and maximum tolerable volumes (r = 0.8; P < 0.001) measured with balloon distention. CONCLUSION: This is the first demonstration of a repeatable sensory response to heat stimulation in the rectum of normal subjects. Strong correlation between heat thresholds and balloon distention to maximum tolerable volumes and defecatory desire suggest common sensory afferent pathway excitation. Heat stimulation is a simple technique that has a high degree of repeatability and may be an objective assessment of polymodal nociceptor function in the rectum.