Comparison of a Novel, Flavor-optimized, Polyethylene Glycol and Sulfate Bowel Preparation With Oral Sulfate Solution in Adults Undergoing Colonoscopy.

INTRODUCTION: A new bowel preparation for colonoscopy has been developed containing poorly absorbed sulfate salts and polyethylene glycol 3350, which retain water within the intestinal lumen resulting in copious diarrhea, thereby cleansing the bowel. The product was formulated to be safe and effective with a sports drink-like flavor. This study evaluated the new flavored polyethylene glycol and sulfate solution (FPSS) compared with a Food and Drug Administration-approved bowel preparation containing sulfate salts only [oral sulfate solution (OSS)]. METHODS: Five hundred adults were enrolled in this multicenter, noninferiority study. Subjects were assigned FPSS or OSS administered in split-dose regimens (PM/AM). FPSS subjects took 2 L of the flavored osmotic solution (1 L at night and 1 L in the morning). OSS was taken according to its approved labeling. Colonoscopies were graded globally and segmentally by blinded local investigators using a 4-point scale (excellent, good, fair, and poor), with "good" and "excellent" considered successful. Safety was assessed by adverse events (AEs) and laboratory testing. RESULTS: A high rate of cleansing success was seen with FPSS (94%), which was noninferior to OSS (94%). This conclusion was confirmed by blinded central readers. Segmental success rates were >90% for both preparations, including the right colon. Questionnaire ratings indicated the FPSS experience was preferred over OSS with 87% of FPSS subjects noting their preparation was "tolerable" to "very easy" to consume versus 74% for OSS. The majority of FPSS subjects agreed their preparation tasted like a sports drink. Gastrointestinal symptoms were the most common AEs. There was no difference between preparations for any AE and no clinically significant differences in laboratory parameters. CONCLUSIONS: The new sports drink-like flavored preparation achieved a high level of cleansing in the study, demonstrating noninferiority to OSS. FPSS was well-tolerated with low rates of expected gastrointestinal symptoms. The optimized flavor of FPSS resulted in significantly better acceptance ratings.

A Phase 2 evaluation of a new flavored peg and sulfate solution compared to an over-the-counter laxative, peg and sports drink bowel preparation combination.

BACKGROUND: Acceptability and tolerance of bowel preparation is critical to overcome patient hesitancy in undergoing colon cancer screening and surveillance colonoscopy. To improve patient experience, a new sports drink-flavored bowel preparation containing polyethylene glycol (PEG) and sulfate salts (FPSS) was developed to provide a similar experience to a commonly used but not United States Food and Drug Administration (FDA) approved PEG and sports drink bowel preparation (PEG-SD), while also achieving improved cleansing efficacy. METHODS: This FPSS preparation, approved by the FDA in June 2023, was evaluated in a non-randomized Phase 2 study in which 40 patients requiring colonoscopy were prepared with FPSS and 20 with PEG-SD. RESULTS: Overall cleansing success was high with FPSS based on unblinded local endoscopist assessment (93%) and blinded central reading (97%), exceeding PEG-SD which achieved success rates of 84% (local read), 74% and 68% (blinded central reads). Similar differences favoring FPSS were seen for excellent preparations and cleansing success by colon segment as rated by local endoscopists. Both preparations were well-tolerated, with 93% of FPSS patients rating their preparation as Tolerable to Very Easy to consume, compared to 100% of PEG-SD. Patients who had previously taken a preparation for colonoscopy found FPSS and PEG-SD better than their prior preparation (73% and 70%, respectively) and nearly all would request their assigned study preparation again in the future. About two thirds of FPSS patients agreed that the preparation tasted similar to a sports drink. CONCLUSION: The new sports drink-like flavored preparation compares favorably to PEG-SD for bowel cleansing efficacy while achieving similar patient satisfaction. The study was registered at www. CLINICALTRIALS: gov (NCT03328507) on 01/11/2017.

A Safety and Efficacy Comparison of a New Sulfate-Based Tablet Bowel Preparation Versus a PEG and Ascorbate Comparator in Adult Subjects Undergoing Colonoscopy.

INTRODUCTION: A new tablet-based bowel prep for colonoscopy has been developed containing poorly absorbed sulfate salts which act to retain water within the intestinal lumen resulting in a copious diarrhea, thereby cleansing the bowel. This study evaluated the safety and efficacy of these oral sulfate tablets (OST) compared with a US FDA-approved bowel prep solution containing PEG3350, electrolytes, and ascorbate (polyethylene glycol and ascorbate [PEG-EA]). METHODS: Five hundred fifteen adult patients (mean 57y) were enrolled in this single-blind, multicenter, noninferiority study. Subjects were assigned either PEG-EA or OST to be administered in a split-dose regimen starting the evening before colonoscopy. PEG-EA was taken according to its approved labeling (1 L of prep solution with 16 oz. of additional water) in the evening and again in the morning. OST patients took a total of 24 tablets. OST patients were administered 12 tablets in the evening, and the following morning. Patients consumed 16 ounces of water with each dose of 12 tablets and drank an additional 32 oz. of water with each dose. Colonoscopies were performed by blinded investigators. Cleansing efficacy was evaluated globally and segmentally using a 4-point scale (Excellent-no more than small bits of feces/fluid which can be suctioned easily; achieves clear visualization of the entire colonic mucosa. Good-feces and fluid requiring washing and suctioning, but still achieves clear visualization of the entire colonic mucosa. Fair-enough feces even after washing and suctioning to prevent clear visualization of the entire colonic mucosa. Poor-large amounts of fecal residue and additional bowel preparation required). Scores of Good or Excellent were considered to be a success. Safety was assessed by spontaneously reported adverse events, solicited ratings of expected prep symptoms, and laboratory testing. RESULTS: A high rate of cleansing success was seen with OST (92%), which was noninferior to PEG-EA (89%). Only a small proportion of subjects rated their expected gastrointestinal symptoms as severe (<5% for both preps). No clinically significant differences were seen between preps for chemistry and hematology parameters. No serious adverse experiences were reported with OST. DISCUSSION: Sulfate tablets achieved a high level of cleansing in the study, comparable with US FDA-approved preps. OST was noninferior to PEG-EA in this study and achieved significantly more Excellent preps overall and in the proximal colon. The OST prep was well-tolerated, with a similar rate of spontaneously reported adverse experiences to PEG-EA and a low rate of severe expected gastrointestinal symptoms.

Effect of individualized feedback on learning curves in EGD and colonoscopy: a cluster randomized controlled trial.

BACKGROUND AND AIMS: Gastroenterology fellowships need to ensure that trainees achieve competence in upper endoscopy (EGD) and colonoscopy. Because the impact of structured feedback remains unknown in endoscopy training, this study compared the effect of structured feedback with standard feedback on trainee learning curves for EGD and colonoscopy. METHODS: In this multicenter, cluster, randomized controlled trial, trainees received either individualized quarterly learning curves or feedback standard to their fellowship. Assessment was performed in all trainees using the Assessment of Competency in Endoscopy tool on 5 consecutive procedures after every 25 EGDs and colonoscopies. Individual learning curves were created using cumulative sum (CUSUM) analysis. The primary outcome was the mean CUSUM score in overall technical and overall cognitive skills. RESULTS: In all, 13 programs including 132 trainees participated. The intervention arm (6 programs, 51 trainees) contributed 558 EGD and 600 colonoscopy assessments. The control arm (7 programs, 81 trainees) provided 305 EGD and 468 colonoscopy assessments. For EGD, the intervention arm (-.7 [standard deviation {SD}, 1.3]) had a superior mean CUSUM score in overall cognitive skills compared with the control arm (1.6 [SD, .8], P = .03) but not in overall technical skills (intervention, -.26 [SD, 1.4]; control, 1.76 [SD, .7]; P = .06). For colonoscopy, no differences were found between the 2 arms in overall cognitive skills (intervention, -.7 [SD, 1.3]; control, .7 [SD, 1.3]; P = .95) or overall technical skills (intervention, .1 [SD, 1.5]; control, -.1 [SD, 1.5]; P = .77). CONCLUSIONS: Quarterly feedback in the form of individualized learning curves did not affect learning curves for EGD and colonoscopy in a clinically meaningful manner. (Clinical trial registration number: NCT02891304.).

The characterization, management, and future considerations for ErbB-family TKI-associated diarrhea.

PURPOSE: Diarrhea is recognized as a common adverse event associated with tyrosine kinase inhibitors (TKIs), with those targeting the ErbB family of receptors being associated with the highest rate of diarrhea. METHODS: This paper reviews data on the incidence, timing, and duration of diarrhea associated with US Food and Drug Administration-approved ErbB family-targeted TKIs from the published literature, and sets forth recommendations for management. RESULTS: In the absence of anti-diarrheal prophylaxis the incidence of any-grade diarrhea varies and typically occurs early during the course of treatment. Although it is difficult to determine if the incidence and severity of diarrhea is related to inhibition of a particular kinase target because of the multi-targeted and overlapping activity of many agents, evidence suggests that second-generation TKIs with broader target profiles (i.e., afatinib, lapatinib, neratinib) result in a higher incidence of diarrhea compared with highly specific first- (erlotinib, gefitinib) or third- (osimertinib) generation agents. The mechanisms responsible for TKI-associated diarrhea are not fully understood and are likely multi-factorial, involving dysregulated ion transport, inflammation, and mucosal injury. Management strategies have been developed-and continue to be refined-to prevent and reduce the severity and duration of TKI-associated diarrhea. For agents associated with more significant symptoms, anti-diarrheal prophylaxis reduces the incidence and severity of diarrhea, and ongoing studies are evaluating specific strategies to further reduce incidence and duration of TKI-associated diarrhea. CONCLUSIONS: Continued investigations into risk factors and pharmacogenomic markers for diarrhea may further improve management of this common toxicity.

Does Carbohydrate Challenge Testing Predict Clinical Response in Small Intestinal Bacterial Overgrowth?

OBJECTIVES: Small intestinal bacterial overgrowth (SIBO) is considered a frequent cause of abdominal symptoms in patients with surgically altered intestinal anatomy or dysmotility conditions and is recognized as a contributing factor in the exacerbation of irritable bowel syndrome symptoms. Diagnostic testing can be used to detect the condition. METHODS: The study group comprised patients who had breath hydrogen and methane lactulose challenge testing. All of the patients were treated with antibiotic regimens that have shown benefit for SIBO. The lactulose challenge was administered orally at 15 g. Hydrogen and methane in expired air were measured and hydrogen values were recorded as the hydrogen plus twice the methane result. Breath tests were analyzed for positivity based on single and multiple criteria of fasting baseline elevation, early rise, and second peak hydrogen rise. Global improvement of gastrointestinal symptoms was assessed by telephone contact or record review. RESULTS: One hundred participants (78 women) were included in the analysis. The mean age was 51 years. A total of 15% of participants did not meet any criteria on breath testing for SIBO; 73% had a fasting baseline elevation >10 ppm; and 19% had an increase of >20 ppm above baseline in the first 20 minutes, 48% had a 20-ppm increase in the first 60 minutes, and 32% had a second increase, reflecting a colon peak. Overall, 74% responded to a course of antibiotics, determined by reported improvement in more than half of the symptoms within 3 months. In total, 67% (10/15) of the subjects who tested negative for SIBO, by all criteria, had a favorable response to antibiotics. Among those with positive hydrogen increases, 76.3% with 1 criterion responded, 66.7% with 2 criteria responded, 84.6% with 3 responded, and 76.9% with 4 responded. After antibiotic treatment, 88.7% (47/53) of those who had diarrhea reported improvement, 63.3% (19/30) with constipation reported improvement, and 74.3% (52/70) with baseline bloating experienced improvement. Sixty-five of the 82 patients with pain or discomfort reported improvement (79.3%). Of those treated with a rifaximin regimen, 74.2% (49/66) reported a response to treatment. Twenty of 28 (71.4%) treated with amoxicillin/clavulanate experienced a clinical response. CONCLUSIONS: These data suggest that the response to antibiotic therapy in patients with suspected SIBO is not predicted by carbohydrate SIBO testing results and bring into question the value of such testing.

A randomized, controlled trial of oral sulfate solution plus polyethylene glycol as a bowel preparation for colonoscopy.

BACKGROUND: No bowel preparation for colonoscopy is optimal with regard to efficacy, safety, and tolerability. New options for bowel preparation are needed. OBJECTIVE: To compare a new hybrid preparation consisting of a reduced dose of oral sulfate solution (OSS) plus 2 L of sulfate-free electrolyte lavage solution (SF-ELS) with 2 low-volume preparations based on polyethylene glycol electrolyte lavage solution (PEG-ELS). DESIGN: Two randomized, controlled trials. SETTING: Twenty-four U.S. centers. PATIENTS: A total of 737 outpatients undergoing colonoscopy. INTERVENTIONS: In study 1, OSS plus SF-ELS was given as a split dose, and in study 2, OSS plus SF-ELS was given in its entirety the evening before colonoscopy. In study 1, the active control was 2 L of PEG-ELS plus ascorbic acid (PEG-EA) given as a split dose. In study 2, the control was 10 mg of bisacodyl plus 2 L of SF-ELS taken the evening before colonoscopy. MAIN OUTCOME MEASUREMENTS: Rates of successful (good or excellent) bowel preparation. RESULTS: In study 1, the rates of successful (excellent or good) preparation with OSS plus SF-ELS and PEG-EA were identical at 93.5% for split-dose preparation. OSS plus SF-ELS was noninferior to PEG-EA (P < .001). In study 2, OSS plus SF-ELS resulted in successful preparation in 89.8% of patients compared with 83.5% with bisacodyl plus SF-ELS in a same-day preparation regimen. OSS plus SF-ELS was noninferior to bisacodyl plus SF-ELS (P <.001). In study 1, vomiting was more frequent with OSS plus SF-ELS (13.5% vs 6.7%; P = .042), and bloating was rated worse with PEG-EA (P = .025). In study 2, overall discomfort was rated worse with OSS plus SF-ELS (mean score 2.1 vs 1.8; P = .032). There were no deaths in either study and no serious adverse events considered related to the preparation. LIMITATIONS: Bowel cleansing was not scored by colon segment. Adenoma detection was not compared between the regimens. CONCLUSION: OSS plus SF-ELS is a new, safe, and effective bowel preparation for colonoscopy.

Preclinical and clinical evaluation through serial colonoscopic evaluation of neratinib-induced diarrhea in HER2-positive breast cancer-A pilot study.

The irreversible pan-HER tyrosine kinase inhibitor neratinib is approved for patients with HER2-positive, early-stage and metastatic breast cancer (BC). Neratinib-associated diarrhea is the most common reason for early discontinuation. Preclinical studies identified mechanisms of neratinib-induced diarrhea and rationale for prophylactic and preventive measures. We studied effects of neratinib on rat intestines and conducted a phase 2 study of colon pathogenesis in patients with HER2-positive BC treated with neratinib (NCT04366713). Colon samples from female albino Wistar rats receiving neratinib or vehicle were examined for histopathological changes. Patients with HER2-positive BC received neratinib 240 mg once daily for up to 1 year. Colonoscopy biopsies were collected at baseline and at Day 28 to identify changes consistent with rat pathologies. Rat colons were markedly altered in appearance, with similar short circuit currents (Isc) and responses to carbachol and forskolin. Mucosal barrier loss and/or significant increase in secretory propensity in neratinib- versus control-treated animals were not seen. Two of four endpoint-evaluable patients presented with mild pathological changes, largely comparable with the rat model. Preclinical evidence supports an inflammatory component of neratinib-induced diarrhea without mucosal barrier function loss. Colonoscopy findings in patients with BC indicate mild or no pathological changes in the colon due to neratinib treatment.

Colon cleansing for colonoscopy 2013: current status.

Colonoscopy requires adequate bowel cleansing to be safe and effective. There are a variety of options available. This review will focus on highlighting new products, administration techniques emphasizing the value of split-dose and same-day regimens, safety, and options for inadequate cleansing.

The role of effective clinician-patient communication in the management of irritable bowel syndrome and chronic constipation.

Irritable bowel syndrome (IBS) and chronic constipation (CC) are common functional bowel disorders that are among the most frequent reasons for referral to a gastroenterologist. Diagnosis and management of these conditions can be challenging for both the clinician and the patient for a number of reasons. Diagnosis can be complicated by the lack of a specific diagnostic test and the fact that IBS and CC are multisymptomatic conditions, whereas management can be suboptimal, because the conditions are often undiagnosed and self-managed by the patient. Furthermore, these are chronic conditions that must be managed over the long term, which can often lead to frustration both on the part of the patient and the clinician. As such, the role of the therapeutic clinician-patient relationship in diagnosis and management of these conditions has been attracting increasing attention. A patient-centered approach with a strong focus on effective communication between the clinician and the patient has been recommended for management of functional bowel diseases such as IBS and CC and has been associated with improved outcomes, increased patient satisfaction, and decreased utilization of care. The potential benefit of such practices as asking open-ended questions, actively listening to the patient, and displaying empathy in strengthening the clinician-patient relationship are highlighted in this manuscript. These skills have broad application in clinical medicine and can be used to improve clinician-patient communication in the management of patients with chronic illnesses.

Carbohydrate challenge tests: do you need to measure methane?

OBJECTIVE: Breath tests that measure hydrogen (H2) have been judged reliable for the detection of lactose maldigestion (LM) and fructose malabsorption (FM). Recently, methane (CH4) testing has been advocated and measurement of CH4 in addition to H2 has been shown to increase the diagnostic accuracy for LM. PURPOSE: This study was designed to consider the additional yield from CH4 measurement in patients tested for LM and FM. METHODS: Patients reported for testing after an overnight fast, not smoking and with their prior evening meal carbohydrate restricted. After challenge with 50 g lactose or 25 g fructose in water, end-alveolar breath samples collected over a 4-hour duration were analyzed for H2 and CH4. Diagnostic positivity was compared using a cutoff level of 20 ppm increase above fasting baseline for H2 alone, which is consistent with consensus guidelines, versus H2 plus twice CH4, which recognizes that CH4 consumes twice the hydrogen. RESULTS: There were 406 LM performed in 93 men and 313 women. Of those tested, 124 (30%) had a positive test for H2 and 139 (34%) had a positive test for H2 + CH4 ×2. There were 178 FM tests performed in 31 men and 147 women. Of those tested, 17 (9%) had a positive test for H2 and 42 (23%) had a positive test for H2 + CH4 ×2. CONCLUSION: If H2 alone was measured without additional CH4 analysis, 4% of patients with LM and 14% patients with FM would not have been identified.

Endoscopist-directed administration of propofol: a worldwide safety experience.

BACKGROUND & AIMS: Endoscopist-directed propofol sedation (EDP) remains controversial. We sought to update the safety experience of EDP and estimate the cost of using anesthesia specialists for endoscopic sedation. METHODS: We reviewed all published work using EDP. We contacted all endoscopists performing EDP for endoscopy that we were aware of to obtain their safety experience. These complications were available in all patients: endotracheal intubations, permanent neurologic injuries, and death. RESULTS: A total of 646,080 (223,656 published and 422,424 unpublished) EDP cases were identified. Endotracheal intubations, permanent neurologic injuries, and deaths were 11, 0, and 4, respectively. Deaths occurred in 2 patients with pancreatic cancer, a severely handicapped patient with mental retardation, and a patient with severe cardiomyopathy. The overall number of cases requiring mask ventilation was 489 (0.1%) of 569,220 cases with data available. For sites specifying mask ventilation risk by procedure type, 185 (0.1%) of 185,245 patients and 20 (0.01%) of 142,863 patients required mask ventilation during their esophagogastroduodenoscopy or colonoscopy, respectively (P < .001). The estimated cost per life-year saved to substitute anesthesia specialists in these cases, assuming they would have prevented all deaths, was $5.3 million. CONCLUSIONS: EDP thus far has a lower mortality rate than that in published data on endoscopist-delivered benzodiazepines and opioids and a comparable rate to that in published data on general anesthesia by anesthesiologists. In the cases described here, use of anesthesia specialists to deliver propofol would have had high costs relative to any potential benefit.

A randomized clinical study comparing reduced-volume oral sulfate solution with standard 4-liter sulfate-free electrolyte lavage solution as preparation for colonoscopy.

BACKGROUND: Low-volume bowel preparations for colonoscopy improve tolerability. OBJECTIVE: We compared the efficacy, tolerability, and safety of a new low-volume sulfate solution with a standard 4-L polyethylene glycol electrolyte lavage solution as bowel preparation for colonoscopy. DESIGN: Multicenter, single-blind, randomized, noninferiority study. SETTING: Five academic and community endoscopy centers in the United States. PATIENTS: One hundred thirty-six outpatients undergoing colonoscopy. INTERVENTIONS: Patients were randomized to receive 4 L sulfate-free electrolyte lavage solution (SF-ELS) given the night before colonoscopy versus 12 oz oral sulfate solution (OSS) given in equally divided doses the evening before and the morning of colonoscopy. MAIN OUTCOME MEASUREMENTS: Successful (ie, good or excellent) bowel preparation. RESULTS: Successful bowel preparation was more frequent with OSS than with SF-ELS (98.4% vs 89.6%; P = .04). Excellent preparation also was achieved more frequently with OSS (71.4% vs 34.3%; P < .001). Patients receiving OSS had less residual stool in the cecum and ascending colon and less residual fluid in the cecum and ascending, transverse, and descending colon compared with SF-ELS. The percentage of patients with GI side effects and adverse events was not significantly different between the 2 groups. LIMITATIONS: The OSS was administered in split doses, whereas the SF-ELS was administered the evening before (which is its FDA-approved regimen). CONCLUSIONS: Oral sulfate solution is promising as a safe low-volume preparation for colonoscopy. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT00856843.).

Update on preparation for colonoscopy.

Colonoscopy requires adequate bowel cleansing to be safe and effective. Current options for preparation include dietary restrictions plus cathartics and purgatives, large-volume gut lavage solutions, and sodium phosphate preparations. Gut lavage with or without a stimulant laxative is safe and effective, and traditionally is taken the evening before the procedure. Sodium phosphate formulations also provide effective cleansing, but fluid and electrolyte disturbances can occur. Recent advances include split administration of gut lavage solutions-ingesting only half of the solution the evening prior to, and the rest the morning of, the procedure. Split administration can yield adequate preparations in inpatients, traditionally a difficult group for proper cleansing. A new oral sulfate solution, when commercially available, should provide safe, effective cleaning with a lower ingested volume. This review discusses the current clinical experience of available preparation options and the efforts to make preparation for colonoscopy more tolerable.

Deep enteroscopy.

Obscure gastrointestinal bleeding has long been a challenging dilemma for gastroenterologists and primary care providers alike. Although many abnormalities can be localized to the small bowel by traditional endoscopic evaluation, deep enteroscopy is often needed to evaluate persistent bleeding of unknown etiology and other conditions. New technology and developments in endoscopic evaluation now provide the necessary tools to explore the small bowel further. These techniques, along with the ability to perform therapeutic interventions, have significantly advanced the management of patients with occult gastrointestinal bleeding and have led to a decline in intraoperative enteroscopy and exploratory laparotomy.

A Prospective Multicenter Study Evaluating Endoscopy Competence Among Gastroenterology Trainees in the Era of the Next Accreditation System.

PURPOSE: The Next Accreditation System requires training programs to demonstrate competence among trainees. Within gastroenterology (GI), there are limited data describing learning curves and structured assessment of competence in esophagogastroduodenoscopy (EGD) and colonoscopy. In this study, the authors aimed to demonstrate the feasibility of a centralized feedback system to assess endoscopy learning curves among GI trainees in EGD and colonoscopy. METHOD: During academic year 2016-2017, the authors performed a prospective multicenter cohort study, inviting participants from multiple GI training programs. Trainee technical and cognitive skills were assessed using a validated competence assessment tool. An integrated, comprehensive data collection and reporting system was created to apply cumulative sum analysis to generate learning curves that were shared with program directors and trainees on a quarterly basis. RESULTS: Out of 183 fellowships invited, 129 trainees from 12 GI fellowships participated, with an overall trainee participation rate of 72.1% (93/129); the highest participation level was among first-year trainees (90.9%; 80/88), and the lowest was among third-year trainees (51.2%; 27/53). In all, 1,385 EGDs and 1,293 colonoscopies were assessed. On aggregate learning curve analysis, third-year trainees achieved competence in overall technical and cognitive skills, while first- and second-year trainees demonstrated the need for ongoing supervision and training in the majority of technical and cognitive skills. CONCLUSIONS: This study demonstrated the feasibility of using a centralized feedback system for the evaluation and documentation of trainee performance in EGD and colonoscopy. Furthermore, third-year trainees achieved competence in both endoscopic procedures, validating the effectiveness of current training programs.

A randomized clinical study evaluating the safety and efficacy of a new, reduced-volume, oral sulfate colon-cleansing preparation for colonoscopy.

OBJECTIVES: We sought to evaluate a new, low-volume, oral sulfate solution as a bowel preparation for colonoscopy in adult patients. METHODS: The investigations were designed as two multicenter, single-blind, randomized, non-inferiority studies to show that the sulfate regimen would effect cleansing that is acceptable and equivalent to polyethylene glycol electrolyte solution with ascorbic acid (PEG-EA), and would be suitable for colonoscopy. One study evaluated same-day administration; the other compared the two study preparations given by split-dose administration in which the first portion was taken the evening before colonoscopy and the second portion on the morning of the procedure. The primary efficacy variable was based on bowel cleansing graded by an investigator who was unaware of the preparation method received. RESULTS: Study 1 randomized 408 outpatients scheduled for colonoscopy for routine indications, with 387 subjects taking the preparation. In all, 364 subjects were randomized and took the preparation in study 2. The demographics of the enrolled subjects were similar across both treatment groups in the two studies, including gender, race, and ethnic characteristics. The primary efficacy analysis supports the conclusion that the oral sulfate solution produces the same degree of cleansing as PEG-EA. Successful preparations were seen in 82.4% and 80.3% in study 1 and 97.2% and 95.6% in study 2 for the oral sulfate solution and the PEG-EA regimen, respectively. Although no difference in excellent preparations was seen in the 1-day preparation, split-dose administration resulted in more excellent preparations in the sulfate group than in the PEG-EA group (63.3 vs. 52.5%, P=0.043). Preparation-related symptoms of cramping, bloating, nausea, and vomiting were generally mild and infrequent. Sulfate subjects reported slightly increased gastrointestinal events and higher vomiting scores (P=0.009) in the 1-day preparation but not in the split-dose regimen. There were no other differences for adverse events or clinically significant laboratory findings, including no increased creatinine. CONCLUSIONS: The new 960 -ml oral sulfate solution is effective for colonoscopy cleansing and has an acceptable safety profile.

Lubiprostone neither decreases gastric and small-bowel transit time nor improves visualization of small bowel for capsule endoscopy: a double-blind, placebo-controlled study.

BACKGROUND: Lubiprostone, a selective activator of type 2 chloride channels, is approved for treatment of chronic idiopathic constipation and recently constipation-predominant irritable bowel syndrome. It has been suggested that lubiprostone has a prokinetic effect. OBJECTIVE: This investigation was designed to evaluate lubiprostone as a preparation and propulsive agent for small-bowel capsule endoscopy. The PillCam Small Bowel capsule endoscopy system with the PillCam SB1 capsule and Rapid 5 software platform were used. DESIGN: The study was designed as a double-blind, placebo-controlled trial. PATIENTS: Forty healthy adults. MAIN OUTCOME MEASURES: Gastric transit time (GTT), small-bowel transit time (SBTT), and adequacy of small-bowel cleansing preparation. INTERVENTIONS: The study subjects received 24 mug lubiprostone or placebo 30 minutes before PillCam capsule ingestion. METHODS: Capsule endoscopy studies were read by 2 independent investigators unaware of the study medication received, and differences in interpretation were resolved by consensus. Anatomical landmarks were identified, and GTT and SBTT were calculated. Overall preparation quality assessment of the proximal, mid, and distal small bowel was determined by using a 4-step scale. The percentage of visualized bowel was determined by review of 10-minute video segments at 1-hour intervals after the capsule passed through the pylorus. RESULTS: In the lubiprostone group (n = 20), 2 subjects did not pass the capsule through the pylorus in the 8-hour battery life of the capsule. An additional 3 capsules did not pass into the colon. In the placebo group (n = 20), all capsules passed into the small bowel, but 1 did not pass into the colon. The subjects in whom the capsule did not pass into the small bowel were excluded from the small-bowel analysis. In the subjects in whom the capsule did reach the colon, the SBTT could not be calculated and they were excluded from SBTT analysis. The mean GTT in the lubiprostone group was 126 minutes and 43 minutes in the placebo group (P = .0095). The mean SBTT in the lubiprostone group was 188 minutes and 219 minutes in the placebo group (P = .130). The overall preparation assessment of the small bowel was not statistically significant between the 2 groups in the proximal, mid, or distal small bowel (proximal, P = .119; mid, P = .118; distal, P = .121). There was no significant difference in lubiprostone compared with placebo in the percentage of visualized small bowel. LIMITATIONS: Some capsules did not leave the stomach or reach the cecum. CONCLUSION: Lubiprostone produced a significant increase in GTT but did not result in a significant decrease in SBTT compared with placebo. The administration of lubiprostone before capsule ingestion did not result in improved overall preparation of the small bowel for capsule endoscopy or increase the percentage of visualized small bowel. (The trial was registered at www.clinicaltrials.gov, identifier NCT00746395.).

Clinical impact of identifying lactose maldigestion or fructose malabsorption in irritable bowel syndrome or other conditions.

BACKGROUND: The role of carbohydrate maldigestion or malabsorption remains unclear in patients with irritable bowel syndrome (IBS). The purpose of this study was to examine the impact of identifying lactose maldigestion (LM) and fructose malabsorption (FM) on patients with and without IBS. METHODS: Patients who received lactose and fructose challenge testing formed the study group. Carbohydrate challenge testing was performed with 50 g lactose and 25 g fructose. Breath samples were collected and analyzed for hydrogen, methane, and CO2 (for correction) using a MicroLyzer Model SC (QuinTron Instrument Company, Milwaukee, WI). Questionnaires were used to assess Rome III IBS criteria, compliance with carbohydrate dietary modifications, and changes in symptoms. RESULTS: One hundred and twenty-one of the 181 (67%) study subjects were able to be contacted 8 months to 4 years after carbohydrate testing. LM (21) and FM (2) were seen in 33% of the 66 IBS subjects. LM (12) and FM (9) were seen in 33% of the 55 subjects without IBS. Seventy-seven percent of IBS and 72% of those without IBS reported compliance with dietary advice. Of the subjects who reported compliance, 47% of IBS and 77% of those without IBS reported that, after identifying LM or FM, their symptoms resolved or improved. CONCLUSIONS: Carbohydrate maldigestion has a similar incidence in patients with and without IBS and both populations have similar compliance with therapeutic diets. However, patients without IBS are more likely to have improvement in symptoms when dietary changes are instituted when compared to IBS patients.

Faecal microbiota transplantation: applications and limitations in treating gastrointestinal disorders.

The process of stool transfer from healthy donors to the sick, known as faecal microbiota transplantation (FMT), has an ancient history. However, only recently researchers started investigating its applications in an evidence-based manner. Current knowledge of the microbiome, the concept of dysbiosis and results of preliminary research suggest that there is an association between gastrointestinal bacterial disruption and certain disorders. Researchers have studied the effects of FMT on various gastrointestinal and non-gastrointestinal diseases, but have been unable to precisely pinpoint specific bacterial strains responsible for the observed clinical improvement or futility of the process. The strongest available data support the efficacy of FMT in the treatment of recurrent Clostridium difficile infection with cure rates reported as high as 90% in clinical trials. The use of FMT in other conditions including inflammatory bowel disease, functional gastrointestinal disorders, obesity and metabolic syndrome is still controversial. Results from clinical studies are conflicting, which reflects the gap in our knowledge of the microbiome composition and function, and highlights the need for a more defined and personalised microbial isolation and transfer.