A recent correspondence letter (CJ Black, AC Ford. AJG 2020; doi: 10.14309/ajg.0000000000000932. Full text: Efficacy of Ondansetron for Irritable Bowel Syndrome With Diarrhea) shows that ondansetron could be an effective option for irritable bowel syndrome with diarrhea. Thanks to Ben Gold for this reference.
A recent study (A Krasaelap et al. Clin Gastroenterol Hepatol 2020; 18: 1987-1994. Efficacy of Auricular Neurostimulation in Adolescents With Irritable Bowel Syndrome in a Randomized, Double-Blind Trial) with data from a double-blind trial provides evidence of short-term (4 week) efficacy of auricular neurostimulation therapy (aka. IB-Stim or Neuro-Stim).
- The IB-Stim group (n=27, median age 15 years) had a ≥30% reduction in abdominal pain in 59% compared to 26% of the sham group (n=23)
- A symptom response scale score of 2 or more was observed in 82% of patients who received IB-Stim vs 26% of patients in the sham group ( P ≤ .001)
- The authors indicate that the NNT for IB-Stim is 3 compared to 6-14 for other medical therapies (lubiprostone, linaclotide, and rifaximin)
- The effects of IB-Stim were NOT sustained at follow-up 8-12 weeks and there was no significant improvment in functional disability or anxiety. “The lack of long-term effect…likely reflects insufficient statistical power.” The authors indicate that longer or repeated courses could be needed
My take: This study indicates that IB-Stim can be helpful, at least in the short term, for adolescents with IBS. More studies showing long-term benefit would be helpful.
Related blog posts:
According to a recent study (RJ Shulman et al. J Pediatri 2020; 222: 134-40), the prevalence of joint hypermobility does NOT differ in children with irritable bowel syndrome, functional abdominal pain, or healthy control children.
Methods (to reach this conclusion):
- Children (median age ~9.5 years) with irritable bowel syndrome (n=109), functional abdominal pain (n=31), and healthy controls (n=69) completed a prospective 2-week pain and stooling diaries. In addition, children and parents reported on measures of anxiety, depression, and somatization. Children were recruited from both primary care and tertiary care settings
- Joint hypermobility was determined using Beighton criteria using a goniometer and examined cutoffs at both ≥4 or ≥6).
- Beighton scores were similar between the groups, as was the proportion with joint hypermobility. Beighton scores were not related to abdominal pain or stooling characteristics.
- Beighton score ≥4: IBS 35%, FAP 36%, healthy controls 36%.
- Beighton score ≥6: IBS 12%, FAP 13%, healthy controls 9%.
- Children reported depression more frequently in those with Beighton scores ≥6 and somatization was greater in those with a score ≥4.
- “It is well-recognized that patients with joint hypermobility syndromes (eg, Ehlers-Danlos syndrome, Marfan) commonly have GI symptoms.” However, joint hypermobility is common —in this study’s healthy control group 36% had a score ≥4 and 9% had a score ≥6.
- This study is in agreement with a school-based study (n=136) (M Saps et al. JPGN 2018; 66: 387-90).
- Limitations: This study population had a median age of ~9.5 years; thus, these findings need to be determined in an older children
My take: There does not appear to be an increased risk of functional GI disorders in children with joint hypermobility. Thus, looking for joint laxity/hypermobility in children with abdominal pain is not needed.
Related blog posts:
- Joint Mobility -Not Associated with Increased Functional GI Disorders
- NASPGHAN Postgraduate Course (part 5) RAP and Other Topics (with segment on POTS, joint hypermobility)
- #NASPGHAN19 Postgraduate Course -part 3)
- True red flags in recurrent abdominal pain
- Not Happy With Functional GI Diseases
- Change the Name: “Functional” is Lousy
Also, a link to Dr. Roy (Benaroch). Roy is an Atlanta pediatrician and he explains, with the help of Batman and Luigi, the term ‘index’ case and when one is considered exposed: Dr. Roy Covid Pathway
Here is a link to the EPUB draft of AGA clinical report (G Su et al. Gastroenterology DOI: https://doi.org/10.1053/j.gastro.2020.05.059): AGA Clinical Practice Guidelines on the Role of Probiotics in the Management of Gastrointestinal Disorders
Here is a link to the pre-draft technical review by GA Preidis et al. Gastroenterology DOI: https://doi.org/10.1053/j.gastro.2020.05.060 AGA Technical Review on the Role of Probiotics in the Management of Gastrointestinal Disorders
- The report recommends NOT using probiotics outside of clinical trials for irritable bowel syndrome, Clostridium difficile infection treatment, Crohn’s disease, and gastroenteritis.
- It recommends a specific probiotic for pouchitis and for prevention of necrotizing enterocolitis in preterm infants <37 weeks and 3 probiotics for patients who are receiving antibiotics (to prevent Clostridium difficile infection)
“While our guideline does highlight a few use cases for probiotics, it more importantly underscores that the public’s assumptions about the benefits of probiotics are not well-founded,” said Dr. Grace L. Su, a professor of medicine and chief of gastroenterology at the University of Michigan, Ann Arbor, in a news statement. She was the chair of the panel that issued the new guidance….
“The industry is largely unregulated and marketing of product is often geared directly at consumers without providing direct and consistent proof of effectiveness,” said the new guidelines. “This has led to widespread use of probiotics with confusing evidence for clinical efficacy,” it said…
“Not all probiotics are created equal. Some probiotic strains and mixtures are very effective for some types of diseases and should not be overlooked due to studies that lump all probiotics together as one”
My take: Probiotics are overhyped and underperform for most conditions. This report suggests that most people should NOT be taking probiotics.
Related blog posts:
- Those Probiotics May Actually Be Hurting Your Gut Heatlh
- Are Probiotics Effective in Changing the Microbiome?
- Our Food is Killing Too Many of Us
- “Low quality of evidence; strong recommendation” for Probiotics in Gastroenteritis
- Bad diets –>High Mortality
- Better Diet, Lower Mortality
- Big Data for Personalized Diets
- Why Fiber Matters?
- Buyer Beware: Supplement at Your Own Risk | gutsandgrowt
- Probiotics for Crohn’s Disease -No Beneficial Effects …
- Do Probiotics Really Help Crying Infants? | gutsandgrowth
Here are some selected slides and notes from this year’s NASPGHAN’s postrgraduate course. There may be some errors of omission or transcription.
Link to the full NASPGHAN PG Syllabus 2019 (Borrowed with permission)
95 Carlo Di Lorenzo, MD, Nationwide Children’s Hospital. Evaluation Testing for functional disorders: The indispensable, the useless, the dangerous and treatment strategies in NERD and functional dyspepsia.
This was the best lecture of the day!!! (Hence a lot of slides follow)
- Families never complain about doctors missing irritable bowel syndrome and anxiety. They may complain about missing diagnosis which are controversial with regarding to chronic pain (‘chronic appendicitis, gallbladder dyskinesia, ‘mild’ IBD, median arcuate ligament syndrome, and food allergies)
- Functional disorders, but not organic disorders, can cause ‘constant’ pain. “Tried everything.” Functional disorder patients frequently have side effects with everything.
- Listen to patient and sit while listening.
- Early diagnosis of functional disorder associated with higher long-term resolution
- Testing –only tests that are cost-effective: celiac disease and stool calprotectin. “Don’t get KUB for constipation.”
- Endoscopy does not improve outcomes in children with functional GI disorder (FGID)
- Eosinophilic esophagitis (EoE) treatment does not help abdominal pain but can help if patient has dysphagia
- Abdominal wall pain is often overlooked. Check Carnett sign.
112 Peter Kahrilas, MD, Northwestern Medicine Achalasia
- Achalasia likely develops after an infection in a susceptible host
- Discussed POEM as newer treatment. It appears to be more effective than either Heller myotomy or pneumatic dilatation in adults. So far, there is limited experience in pediatrics though it appears to mirror adult experience
124 Julie Khlevner, MD, Morgan Stanley Children’s Hospital Evaluation and treatment strategies in NERD and functional dyspepsia
- In patients with NERD, hypermetabolizers of PPIs may need higher dosing.
- Neuromodulators (not FDA approved) used for PPI-nonresponders. Cognitive behavioral therapies may be helpful as well.
- Functional dyspepsia with reflux symptoms are more likely to respond to PPIs than those with dyspepsia symptoms
- A Japanese herb, rikkunshito, may be helpful for functional dyspepsia
136 Robert J. Shulman, MD, Children’s Nutrition Research Center Role of diet in managing of IBS
- Vast majority of low FODMAPs studies show “too much bias” due to lack of blinding in study designs.
- Nutritionists are needed to guide diet. Kids (families) do not follow these diets well.
- Most who are going to respond to diet will do so within 7-10 days.
Disclaimer: NASPGHAN/gutsandgrowth assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. The discussion, views, and recommendations as to medical procedures, choice of drugs and drug dosages herein are the sole responsibility of the authors. Because of rapid advances in the medical sciences, the Society cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure. Some of the slides reproduced in this syllabus contain animation in the power point version. This cannot be seen in the printed version.
Briefly noted: GR D’Haens, C Jobin. Gastroenterol 2019; 157: 624-36. This review sums up the emerging evidence for use of fecal microbial transplantation for conditions besides recurrent Clostridium difficile infection.
Table 2 succinctly provides list of disease, types of study/evidence, and potential effect.
- Among gastrointestinal diseases, the authors note that there is an “overall positive” effect for ulcerative colitis, “suggestive” benefits for IBS, GVHD, post-antibiotic diarrhea, constipation, and hepatic encephalopathy. No effect has been evident with Crohn’s disease or pouchitis.
- Among nongastrointestinal diseases, the authors note a “suggestive” benefit in autism and metabolic syndrome and “unknown” effect with psoriasis and multiple sclerosis.
My take: The review indicates a need for more studies and the need to define which factors in fecal material mediate the therapeutic effects.
Related article: OC Aroniadis. Lancet Gastroenterology and Hepatology; 2019. https://doi.org/10.1016/S2468-1253(19)30198-0. In this double-blind, randomized, placebo-controlled crossover trial in patients aged 18–65 years with moderate-to-severe IBS-D with 48 patients, FMT (capsule study) was safe, but did not induce symptom relief at 12 weeks compared with placebo.
Related blog posts:
- “Intestinal Microbiota Transplant” -better terminology for FMT
- Experimental Use of FMT for Ulcerative Colitis
- FDA Warning for FMT
- Consensus Guidelines on FMT
- Clostridium difficile/Fecal Microbiota Transplantation Video
- OpenBiome -Nation’s 1st Human Stool Bank
W Smalley et al. Gastroenterol 2019; 157: 851-54. Full Text Link: AGA Clinical Practice Guidelines on the Laboratory Evaluation of Functional Diarrhea and Diarrhea-Predominant Irritable Bowel Syndrome in Adults (IBS-D)
Clinical support tool on pg 855, Patient Summary 856-57, and Technical Review 859-80.
These guidelines/recommendations (listed below) do NOT apply to patients with any of the following:
- Alarm features such as gross blood, weight loss, anemia, and hypoalbuminemia
- Family history of of IBD, colon cancer, or celiac disease
- Travel to areas with high prevalence of infectious diarrhea
- Immune suppression
- Ingestion of medications or substances known to cause diarrhea
|Statement||Strength of recommendation||Quality of evidence|
|Recommendation 1: In patients presenting with chronic diarrhea, the AGA suggests the use of either fecal calprotectin or fecal lactoferrin to screen for IBD.||Conditional||Low|
|Recommendation 2: In patients presenting with chronic diarrhea, the AGA suggests against the use of ESR or CRP to screen for IBD.||Conditional||Low|
|Recommendation 3: In patients presenting with chronic diarrhea, the AGA recommends testing for Giardia.||Strong||High|
|Recommendation 4: In patients presenting with chronic diarrhea with no travel history to or recent immigration from high-risk areas, the AGA suggests against testing stools for ova and parasites (other than Giardia).||Conditional||Low|
|Recommendation 5: In patients presenting with chronic diarrhea, the AGA recommends testing for celiac disease with IgA-tTG and a second test to detect celiac disease in the setting of IgA deficiency||Strong||Moderate|
|Recommendation 6: In patients presenting with chronic diarrhea, the AGA suggests testing for bile acid diarrhea.||Conditional||Low|
|Recommendation 7. In patients presenting with chronic diarrhea, the AGA makes no recommendation for the use of currently available serologic tests for diagnosis of IBS||None||Knowledge gap|
For recommendation #6, the authors note that tests for bile acid mediated diarrhea in the U.S. include total bile acid in a 48-hour stool collection and serum fibroblalt growth factor 19.
Image available online:
In a recent study (A Fritscher-Ravens et al. Gastroenterol 2019; 157: 109-18) uses confocal laser endomicroscopy (CLE) for “real-time detection and quantification of changes in intestinal tissues” related to food challenges. The authors previously had used this technique in a feasibility study (Gastroenterol 2014; 147: 1012-20). In this study, two-thirds of patients with CLE+ IBS showed improvement of IBS symptoms after a 12-month exclusion diet.
In the current study, the authors prospectively examined patients (n=108 completed study) who had irritable bowel syndrome and were convinced that this was triggered by foods (with negative IgE food allergy testing). The CLE testing evaluated four food components
- 76 of 108 (70%) had abnormal CLE; 46 of these reactions were to wheat
- In those with CLE+ reactions, intraepithelial lymphocytes were significantly higher compared to those with CLE-negative (normal evaluations).
- Other biomarkers associated with CLE+ included increased claudin-2 expression from crypt to villous tip, lower levels of occludin, and higher eosinophilic cationic protein.
Abnormal CLE indicated abnormal mucosal appearance including formation of epithelial leaks/gaps and widening of the intervillous spaces after food challenge.
My take: This study shows that in individuals with a strong suspicion of food-triggered IBS, immediate reactions in the mucosa can be detected with CLE in more than 50%. Whether this type of approach could/should be developed for wider use in targeting a specific diet is unclear. More studies are needed.
Related blog posts:
- Looking More Closely at a Persistent Problem
- An Unexpected Twist for “Gluten Sensitivity” | gutsandgrowth
- Mechanism for FODMAPs diet | gutsandgrowth
1.From John Pohl Twitter Feed: FDA Warns of One Death Linked to Fecal Transplants (6/13/19)
The consent should include, at a minimum, a statement that the use of FMT to treat C. difficile is investigational and a discussion of its potential risks.
“Two immunocompromised adults who received investigational FMT developed invasive infections caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E.coli). One of the individuals died,” the agency said Thursday…
Openbiome, a nonprofit stool bank based in Cambridge, MA, told Focus: “We are saddened to hear of the recent patient death due to an infection from a multi-drug resistant organism (MDRO) transmitted through a fecal transplant. OpenBiome material was not involved. OpenBiome screens its donors and fecal transplant material for MDROs and related risk factors, and this serious event further highlights the importance of rigorous screening and clinical oversight for all fecal transplant procedures.”
2. FDA approval for IB-stim (a.k.a. Neuro-stim) device.
IB-Stim treatment resulted in at least a 30% decrease in usual pain at the end of three weeks in 52% of treated patients compared to 30% of patients who received the placebo, and at least a 30% decrease in worst pain in 59% of treated patients compared with 26% of patients who received the placebo.
:Kovacic K1, Hainsworth K2, Sood M1, Chelimsky G1, Unteutsch R1, Nugent M3, Simpson P3, Miranda A4. Lancet Gastroenterol Hepatol. 2017 Oct;2(10):727-737. doi: 10.1016/S2468-1253(17)30253-4. Epub 2017 Aug 18.
3. FDA Approves Gattex (Teduglutide) for Pediatric SBS
From CenterWatch: Gattex New FDA Drug Approval
Pediatric SBS: “In a 24-week pediatric study 59 pediatric patients with SBS aged 1 year through 17 years chose whether to receive Gattex or standard of care (SOC)…Based on patient-diary data, patients who received Gattex 0.05 mg/kg/day experienced a 42% mean reduction in PS volume (mL/kg/day) from baseline (-23 mL/kg/day from baseline). At week 24, 38% of patients (10/26) were able to reduce PS infusion by at least 1 day per week. Patients reduced their PS infusion time by 3 hours per day on average compared to baseline.”
Related blog post: Teduglutide for SBS
Jeppesen PB, Pertkiewicz M, Messing B, Iyer K, Seidner DL, O’keefe SJ, Forbes A, Heinze H, Joelsson B Teduglutide reduces need for parenteral support among patients with short bowel syndrome with intestinal failure. Gastroenterology 2012 Dec;143(6):1473-1481
Jeppesen PB, Gilroy R, Pertkiewicz M, Allard JP, Messing B, O’Keefe SJ Randomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndrome. Gut 2011 Jul;60(7):902-14.
A recent study (CJ Black et al. Gastroenterol 2018; 155: 1753-63) examined the effectiveness of secretagogues for constipation-predominant irritable bowel syndrome (IBS-C). The authors conducted a systematic review and network meta-analysis with 15 eligible randomized controlled trials (8462 patients).
- Linaclotide (290 mcg per day) was ranked first in efficacy using the end point recommended by the FDA for IBS-C trials
- Tenapanor (50 mg twice a day) was ranked first for bloating
- Plecanatide (6 mg per day) ranked first for safety
- Diarrhea was significantly more common with all of the secretagogues except for lubiprostone; nausea was significantly more common with lubiprostone
The authors acknowledge the limitations in comparing medicines without direct head-to-head trials (which may never occur). They state that linaclotide being superior to other treatments had a probability of 88%.
My take: This study indicates that linaclotide may be more likely to be effective than other IBS-C medications; all of these secretagogues have been shown to be superior to placebo.
In this same issue, pgs 1666-9 (J Ruddy), a patient describes her long journey with abdominal pain/GI symptoms. She describes her initial experiences with physicians who were dismissive and not attentive. Ultimately, a physician listened to her and helped her improve after explaining that she had a postinfectious IBS and provided treatment.
Related study: S Ishague et al. BMC Gastroenterol 2018; 18:71. This randomized controlled trial which compared a multistrain probiotic (Bio-Kult, n=181) to placebo (n=179). The probiotic group had a 69% decrease in abdominal pain compared to a 47% decrease in placebo group.