Category Archives: Pediatric Gastroenterology Intestinal Disorder

What is Wrong with the Glimmer of “Precision Medicine”

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Several thought leaders, including Francis Collins, have heralded the age of “precision medicine.” A recent commentary provides compelling arguments why “enthusiasm is premature.”

The greatest problems we face in improving health care do not require precision medicine.

“In 2013, the National Research Council (NRC) and the Institute of Medicine (IOM) issued a bleak report on life expectancy and well-being in the United States.  Shorter Lives, Poorer Health documented the extent to which Americans were at a disadvantage at every stage of life compared with their counterparts in peer countries.”  Americans fared worse in all of the following:

  • Birth outcomes
  • Heart disease
  • Motor vehicle accidents
  • Violence
  • Sexually transmitted disease
  • Chronic lung disease

The NRC notes that “health is determined by far more than health care.”

Other points:

  • While the U.S. may have the most advanced healthcare in the world, the “whiz-bang technology just cannot fix what ails us.” (NY T-inequality-is-costing-the-us-on-social issues.html)
  • “Precision medicine itself may ultimately make critical contributions to a narrow set of conditions, but the challenge we face…entails…willingness to address certain persistent social realities”
  • “Our public investments in broad, cross-sectional efforts to minimize…foundational drivers of poor health as poverty…are pitifully few in comparison with those of other countries.”
  • Take-home message from authors: “We worry that an unstinting focus on precision medicine by trusted spokespeople for health is a mistake — and a distraction from the goal of producing a healthier population.”

My view: The challenges posed by the authors do seem monumentally greater than those facing the development of precision medicine.

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Is It a Good Idea for Pregnant Mothers to Take Probiotics?

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A previous study has indicated that maternal probiotic administration was associated with a lower rate of atopic dermatitis.  The overall quality of evidence supporting this association is considered low.

A recent study (CK Dotterud et al. JPGN 2015; 61: 200-7) examined the effect on the intestinal microbiota in both mother and child following maternal perinatal probiotic supplementation. This randomized, double-blind trial examined the effect of probiotic administration (or placebo) from 36 weeks of gestation up to 3 months postnatally while breastfeeding. Stool microbiome was examined in both mother and child.

Key findings:

  • The changes in the infants microbiome were quite limited. “Only the Lactobacillus rhamnosus GG bacteria colonized the children at 10 days and at 3 months of age. There were no significant differences in the abundance of administered probiotic bacteria between the groups at 1 and 2 years of age.”

My take: We know very little about probiotics and their effects on the GI tract. We often do not even the basics: which strains? which dosage?  optimal timing/when to use?  Given the lack of persistent change in the infant’s microbiome, does administration to pregnant mothers really make any sense (outside of research endeavors)?

Disaccharidase Deficiencies in Recurrent Abdominal Pain

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Question for pediatric gastroenterologists (first poll I’ve placed in this blog): Do you think disaccharidases are needed routinely for patients with abdominal pain in the absence of bloating, or diarrhea?

A recent report indicated a high rate of disaccharidase deficiencies among children with recurrent abdominal pain. Here’s the abstract link: Disaccharidase Deficiencies in Children With Chronic Abdominal Pain (K El-Chammas, SE Williams, A Miranda. Published online before print July 9, 2015, doi: 10.1177/0148607115594675JPEN J Parenter Enteral Nutr July 9, 2015 0148607115594675).  Thanks to Kipp Ellsworth for this reference.

Here’s an excerpt:

Data on disaccharidase activity and histology of endoscopic biopsies were collected retrospectively. Only patients with normal histology were included in the study.

Results: A total of 203 pediatric patients with CAP were included. The mean (SD) age was 11.5 (3.1) years, and 32.5% were male. The percentages of abnormally low disaccharidase levels using the standard laboratory cutoffs were lactase, 37%; sucrase, 21%; glucoamylase, 25%; and palatinase, 8%. Thirty-nine percent of the patients with low lactase also had low sucrase, and 67% of the patients with low sucrase had low lactase…Also, no association was found between stool consistency, stool frequency, or location of pain and low disaccharidase activity.

My take: I am highly skeptical regarding these findings–see Twyman’s Law | gutsandgrowth. For sucrase deficiency, for example, this report represents an extraordinarily high rate of deficiency compared with previous reports. In addition, there are numerous errors which can occur in the handling of tissue specimens.  With regard to lactase deficiency, of course, this is common but having lactose intolerance does not prove causality with regard to abdominal pain.  Many physicians encourage families to see if there is a link between milk ingestion and GI symptoms to help determine if lactose intolerance is a likely contributor to stomach pain (before endoscopy). Stomach pain in the absence of milk ingestion is not due to lactose intolerance.

Before accepting these high rates, improved methodology (eg. control group and duplicating results) would be helpful.

Related blog post: Congenital Sucrase Isomaltase Deficiency

 

Enteral Autonomy in Pediatric Intestinal Failure

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A recent study (FA Khan et al. J Pediatr 2015; 167: 29-34 -thanks to Mike Hart for forwarding this reference) provides data from a multicenter retrospective cohort of 272 infants.  These infants had of IF were defined by requiring >60 days of PN; they were enrolled in the Pediatric Intestinal Failure Consortium.  The median followup was 33.5 months.  The most common etiologies of IF were necrotizing enterocolitis (NEC), gastroschisis, small bowel atresia, and volvulus. Key findings:

  • 43% achieved enteral autonomy (EA), defined as freedom from PN for >3 months, 13% remained dependent on PN, and 43% had died, undergone intestinal transplantation, or both.
  • Infants with EA were more likely to have had NEC, preserved ileocecal valve, longer preserved small bowel length, and care at a non-transplant center (with retrospective study, high likelihood of a selection bias).

The associated editorial by Valeria Cohran (pages 6-8) notes that pediatric intestinal transplants peaked in frequency in 2007, but in 2014 there only 56 performed.  She also notes that the care of these children with short bowel syndrome in the first year of life is approximately $500,000 ± $250,000!  The improved survival is attributed to minimizing cholestasis with new lipid strategies, minimizing blood stream infections with better care and ethanol locks, and the use of autologous bowel reconstruction surgery. Bottomline: This study and several others show that meticulous care and advances in the treatment of intestinal failure improve the likelihood of survival without the need for intestinal transplantation. FULL CITATION: Khan FA et al. Predictors of enteral autonomy in children with intestinal failure: A multicenter cohort study. J Pediatr 2015 Jul; 167:29-34. [Free full-text J Pediatr article PDF | PubMed® abstract] Related blog posts:

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FODMAPS Advice From Harvard

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A recent post from Harvard Health Publications offers a succinct explanation of a low FODMAPs diet for irritable bowel syndrome.

Here’s the link: Try a FODMAPs diet to manage irritable bowel syndrome

 

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“Fat Report Cards” –Do They Help?

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Probably not.

From NY Times: Body Report Cards Aren’t Influencing Arkansas Teenagers,   Excerpt:

It is one of the boldest and most controversial tactics in the battle against childhood obesity: A growing number of schools are monitoring their students’ weight and sending updates home, much like report cards.

Ten states, including Ohio, Pennsylvania and Illinois, now require schools to send such notifications, sometimes called “B.M.I. letters,” or less charitably “fat letters.” But a new study of the first state to adopt the practice shows that the letters have had almost no effect, at least on older teenagers…

The Arkansas study by Dr. Gee looked at the B.M.I. results of juniors and seniors who had been evaluated and, after the 2007 legislative changes, those who had not. It found that students whose families had received the letters showed no appreciable improvement in B.M.I. scores after two years, compared with those who had not been screened. Another peer-reviewed study of such letters, a 2011 examination of younger students in California, had similar findings.

Empire State Building

Empire State Building

Low FODMAPs Diet in Pediatric Irritable Bowel

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A low FODMAPs diet has been associated with clinical improvement in adults with irritable bowel syndrome and “gluten sensitivity” (see links below).  Now, there is more data that this diet can be effective in the pediatric population (Chumpitazi BP, et al. Aliment Pharm Ther DOI: 10.1111/apt.13286. Article first published online: 24 JUN 2015 -Thanks to KT Park for this reference).  In addition, this small study (n=33) tries to correlate changes in symptoms with changes in the gut microbiome. Interestingly, the dietary trials were only 48 hours.

From the methods: Following a 7-day baseline period, “we employed a randomised, double-blind, crossover study design. Subjects received either a low FODMAP or typical American childhood diet (TACD) for 48 h. After 48 h on the first assigned diet, they returned to their habitual diet for 5 days. Following this 5-day washout period, they were crossed over to the other intervention diet for 48 h.”

Here is the abstract and a link to the full text: Randomised clinical trial: gut microbiome biomarkers are associated with clinical response to a low FODMAP diet in children with the irritable bowel syndrome

Abstract:

Background

A low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet can ameliorate symptoms in adult irritable bowel syndrome (IBS) within 48 h.

Aim

To determine the efficacy of a low FODMAP diet in childhood IBS and whether gut microbial composition and/or metabolic capacity are associated with its efficacy.

Methods

In a double-blind, crossover trial, children with Rome III IBS completed a 1-week baseline period. They then were randomised to a low FODMAP diet or typical American childhood diet (TACD), followed by a 5-day washout period before crossing over to the other diet. GI symptoms were assessed with abdominal pain frequency being the primary outcome. Baseline gut microbial composition (16S rRNA sequencing) and metabolic capacity (PICRUSt) were determined. Metagenomic biomarker discovery (LEfSe) compared Responders (≥50% decrease in abdominal pain frequency on low FODMAP diet only) vs. Nonresponders (no improvement during either intervention).

Results

Thirty-three children completed the study. Less abdominal pain occurred during the low FODMAP diet vs. TACD [1.1 ± 0.2 (SEM) episodes/day vs. 1.7 ± 0.4, P < 0.05]. Compared to baseline (1.4 ± 0.2), children had fewer daily abdominal pain episodes during the low FODMAP diet (P < 0.01) but more episodes during the TACD (P < 0.01). Responders were enriched at baseline in taxa with known greater saccharolytic metabolic capacity (e.g. Bacteroides, Ruminococcaceae, Faecalibacterium prausnitzii) and three Kyoto Encyclopedia of Genes and Genomes orthologues, of which two relate to carbohydrate metabolism.

Conclusions

In childhood IBS, a low FODMAP diet decreases abdominal pain frequency. Gut microbiome biomarkers may be associated with low FODMAP diet efficacy.

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Selective Data Mining: Reflux and Bronchopulmonary Dysplasia

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With some studies, the abstract may suggest a more compelling result than is truly evident.  That’s how I feel about a recent report (Nobile S, et al. J Pediatr 2015; 167: 279-85).

Here’s the conclusion (verbatim) from the abstract: “The increased number of (and sensitivity for) pH-only events among infants with BPD may be explained by several factors, including lower milk intake, impaired esophageal motility, and a peculiar autonomic nervous system response pattern.”

To me, it sounds like this prospective study of pH-multichannel intraluminal impedance (pH-MII) of 46 infants born ≤32 weeks gestation (12 with bronchopulmonary dysplasia (BPD) and 34 without BPD) must have identified something important linking gastroesophageal reflux disease (GERD) and BPD.  But, the real findings, in my view, are that this is a negative study. Period.

Here are the results reported in the abstract:

  • “Infants with BPD…had increased numbers of pH-only events (median number 21 v 9) and a higher symptom symptom sensitivity index for pH-only events (9% vs. 4.9%)”
  • They also state: “the number and characteristics of acid, weakly acid, nonacid and gas gastroesophageal reflux events, acid exposure, esophageal clearance, and recorded symptoms did not significantly differ between the 2 groups.”

Here’s a little more data –not in the abstract:

  • The P value for the difference in pH-only events was .360
  • The authors could just have easily pointed out (in the abstract) that infants without BPD had increased acid exposure: 40.5 min compared with 27.0 min (P = .599)

What should have been in the abstract conclusion? Perhaps, the first line of their discussion: “Infants with BPD did not have significantly higher GER features compared with infants without BPD as measured by esophageal pH-MII monitoring, except for higher occurrence of pH-only events and higher SSI for pH-only events.”

The authors try to explain the differences in the BPD patients by highlighting some of the potential mechanisms of reflux and/or autonomic dysfunction.  I think the limitations of this study deserve careful scrutiny.  This was a small study with only 12 BPD infants.  There was a significant selection bias -only ‘symptomatic’ infants were included.  Some of the factors affecting BPD directly could have an indirect effect on reflux (eg. caffeine).

The authors make one other point: “we believe pharmacologic treatment for GER should be initiated only after the demonstration of pathologic pH-MII monitoring to avoid unnecessary drug therapy, adverse events, and costs.”

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Stress and IBD Flareups

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Over the years, I’ve had several experiences in which some patients had flareups of their inflammatory bowel disease (IBD) in relation to specific stresses (eg. going to away camp).  This was not just stomach pain but instead bloody diarrhea.  While this is very infrequent, I’ve come to believe that there may be some individuals who develop IBD flareups in response to stress. A recent study (Targownik LE, et al. AJG 2015; 110, 1001-1012 | doi:10.1038/ajg.2015.147) suggests that most of the time when individuals report a flareup in response to stress, that there is not objective evidence of increased inflammation.

The Relationship Among Perceived Stress, Symptoms, and Inflammation in Persons With Inflammatory Bowel Disease

From Abstract:

METHODS:

Participants were recruited from a population-based registry of individuals with known IBD. Symptomatic disease activity was assessed using validated clinical indices: the Manitoba IBD Index (MIBDI) and Harvey Bradshaw Index (HBI) for Crohn’s disease (CD), and Powell Tuck Index (PTI) for ulcerative colitis (UC). Perceived stress was measured using Cohen’s Perceived Stress Scale (CPSS). Intestinal inflammation was determined through measurement of fecal calprotectin (FCAL), with a level exceeding 250 μg/g indicating significant inflammation. Logistic regressions were used to evaluate the association between intestinal inflammation, perceived stress, and disease activity.

RESULTS:

Of the 478 participants with completed surveys and stool samples, perceived stress was associated with symptomatic activity (MIBDI) for both CD and UC (1.07 per 1-point increase on the CPSS, 95% confidence interval (CI) 1.03–1.10 and 1.03–1.11, respectively). There was no significant association between perceived stress and intestinal inflammation for either CD or UC. Active symptoms (MIBDI ≤3) were associated with intestinal inflammation in UC (odds ratio (OR) 3.94, 95% CI 1.65–9.43), but not in CD (OR 0.98, 95% CI 0.51–1.88).

CONCLUSIONS:

Symptomatic disease activity was unrelated to intestinal inflammation in CD and only weakly associated in UC. Although there was a strong relationship between perceived stress and gastrointestinal symptoms, perceived stress was unrelated to concurrent intestinal inflammation. Longitudinal investigation is required to determine the directionality of the relationship between perceived stress, inflammation, and symptoms in IBD.

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Magnetic Placement of NJ Feeding Tubes

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From ASPEN twitter feed: Placement of a Magnetic Small Bowel Feeding Tube at the Bedside

Abstract

Background: Current methods of achieving postpyloric enteral access for feeding are fraught with difficulties, which can markedly delay enteral feeding and cause complications. Bedside tube placement has a low success rate, often requires several radiographs to confirm position, and delays feeding by many hours. Although postpyloric enteral tubes can reliably be placed in interventional radiology (IR), this involves greater resource utilization, delays, cost, and inconvenience. We assessed the utility of bedside enteral tube placement using a magnetic feeding tube (Syncro-BlueTube; Syncro Medical Innovations, Macon, GA, USA) as a means to facilitate initial tube placement. Methods: We recorded the time to insertion, location of tube, success rate, and need for radiographs in a series of patients given magnetic feeding tubes (n = 46) inserted by our hospitalist service over an 8-month interval. Results: Of the 46 attempted magnetic tube placements, 76% were successfully placed in the postpyloric position, 13% were in the stomach, and 11% could not be placed. In 83% of the magnetic tubes, only 1 radiograph was needed for confirmation. The median time to placement was 12 minutes (range, 4–120 minutes). Conclusion: The use of a magnetic feeding tube can increase the success rate of bedside postpyloric placement, decrease the time to successful placement, and decrease the need for supplemental radiographs and IR

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