Category Archives: Pediatric Gastroenterology Intestinal Disorder

Magnetic Foreign Bodies –Still a Problem

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After reading a recent article on swallowed magnetic foreign bodies (J Pediatr 2014; 165: 332-35), I was thinking quite tangentially about an article from The Onion a few years ago: Falling Down Laundry Chute And Breaking Neck Remains America .‘s No. 548,221 Killer.  In this Onion article, the author sarcastically bemoans the attitude that many people adopt that “this could never happen to me.”

What this Journal of Pediatrics study adds to the literature is that swallowed magnetic foreign bodies remain a significant health threat and are likely to remain that way despite recent recalls.

Key finding: 94 pediatric patients were identified at this single center as having infested magnetic foreign bodies between 2002-2012, with increasing incidence in the last three years of the study period.  The median age was 4.5 years. Six patients required surgical removal.

Bottomline: Magnet ingestions are a much more serious health threat than falling down a laundry chute.

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Costs versus Quality

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So I can return to our radiology department without cowering, I wanted to elaborate on this morning’s post.  My focus for this morning’s blog was on cost transparency.  What our pediatric radiologists emphasized to me is that quality is another key issue for patients.  Everyday at our institution there are numerous CT scans, MRIs and xrays that are reviewed from outside institutions.  Many of these studies were performed poorly and may not be interpretable = “total crap.”  And, many of these studies were unnecessary to begin with.

A couple pointers:

  • Open MRIs usually produce lousy images.  They are mainly suitable for individuals too large to fit in conventional MRIs.
  • MRI quality is dependent on high strength magnets.  A minimal of 1.5 Tesla magnet, but preferably a 3 Tesla magnet, will produce better images.
  • It is not just the radiologist that matters.  If radiology techs are not certified/accomplished, then imaging results suffer.  Techs may not focus CT scanners properly and produce a much wider field of radiation then is necessary.
  • CT scans need to minimize radiation while producing good images.  Most children’s hospitals have adopted protocols to assure that this takes place.

Radiological tests are often a ‘black box’ for families –they have no idea what is really going on.  A CT scan/MRI at low quality place may be akin to a cold hamburger at a fast food restaurant whereas a study at a high quality institution may be more similar to the best steak in town.  In addition, the quality of the images can truly be life altering.  This is likely more of an issue in pediatrics than in adult medicine.

Bottomline: In our quest for price transparency, we also need to make sure we are truly comparing apples to apples.  Highlighting value of a particular study and quality are equally important.

If any radiologists reading this post have more pointers, please comment.

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Why Adding Vitamin D May Not Help IBD

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Despite all of the accolades that vitamin D has received, the fact that low vitamin D is associated with worse outcomes, in a number of disease states, does not prove causality. A recent article indicates that vitamin D is likely more of a marker of disease activity than a mediator of disease activity in inflammatory bowel disease (IBD), and specifically Crohn’s disease (CD) (Inflamm Bowel Dis 2014; 20: 856-60).

Background: Binding sites for the vitamin D receptor (VDR) have been “identified in genes associated with CD, and vitamin D has been shown to enhance the production of interleukin-10 (IL-10) and induction of regulatory T-cells.”

Design:The authors prospectively collected samples of 37 CD patients; the mean age in those with active disease (n=20) was 34 years and it was 30 years in those with inactive disease. In 8 patients with active disease, vitamin D levels were measured at the time of active inflammation (day 0) and at 14 days after receiving infliximab (day 14).

  • Key finding in these 8 patients: Vitamin D (25-OH) was 23 ng/mL on day 0 and 40 ng/mL 2 weeks later.  Only 1 of these 8 patients was taking a vitamin D supplement.
  • Key finding in the entire cohort: in the active disease group mean vitamin D level was 27 ng/mL compared with 38 ng/mL in those in remission (P=0.02).

Take-home point: There is an inverse relationship between vitamin D levels and disease activity.  However, the early increases in vitamin D levels with clinical response to anti-TNF therapy suggests that a major mechanism of vitamin D deficiency is related to the burden of systemic inflammation.  Hence, repeat testing when patients are in remission may obviate the need for vitamin D supplementation in many patients.

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Will This Change ALTE-GERD Practice?

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This blog has highlighted several publications which have shown the lack of benefit and potential harm of pharmaceutical agents for gastroesophageal reflux “disease” (GERD) in infancy (see links below). However, in current practice, proton pump inhibitors and histamine receptor antagonists are used frequently.  Now, another influential study (J Pediatr 2014; 165: 250-5) has shown the lack of GERD as a causal mechanism in acute life-threatening events (ALTEs) and demonstrated other pathophysiologic mechanisms. However, changing physicians’ practice in this regard may prove to be as difficult as avoiding overprescribing antibiotics, or convincing reluctant parents to vaccinate their children.

So what did this study show?

This study of 20 infants (10 with proven ALTE and 10 healthy controls) had pharyngoesophageal manometry.  Key findings:

  • Infants with ALTE (vs controls) had delays in restoring aerodigestive normalcy (P=.03).  This was indicated by more frequent and prolonged spontaneous respiratory events (SREs)
  • Infants with ALTE had a lower magnitude of protective upper esophageal sphincter contractile reflexes (P=.01)
  • Infants with ALTE had swallowing as the most frequent esophageal event associated with SREs (84%), a higher proportion of failed esophageal propagation (10% vs 0%, P=.02), an more frequent mixed apnea mechanisms (P=<.01) along with gasping breaths (P=.04)

The associated editorial (pg 225-26) explains some of the limitations of the study, including the fact that the patients had a mean gestational age of 28 weeks.

The authors conclusion: “In infants with ALTE, prolonged SREs are associated with ineffective esophageal motility ,,,suggestive of dysfunctional regulation of swallow-respiratory junction interactions.  Hence, treatment should not target gastroesophageal reflux, but rather the proximal aerodigestive tract.”

Take-home message: (from the editorial): “Far too many low birth weight (and term) infants are being unnecessarily treated with a variety of antireflux medications that have serious side effects and few, if any, demonstrable benefits.”

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Enteral Fish Oil and Intestinal Adaptation in Premature Infants

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A provocative article (J Pediatr 2014; 165: 274-9) examines supplementation of enteral fat/fish oil in premature infants as a mechanism to reduce parenteral nutrition associated cholestasis (PNAC).  While the study’s limitations will prevent any dramatic conclusions, the article and associated editorial (pgs 226-27) do make several useful points.

Before discussing the limitations, the design of the study:

Infants were block randomized (block size of 8) into either a control group or treatment group.  While both groups received conventional PN, the treatment group received supplemental enteral fat as microlipid and fish oil after tolerating enteral feeds at 20 mL/kg/d.  Microlipid was started at 1 g/kg/d and advanced up to 2.5 g/kg/d; coinciding with microlipid increases, parenteral intralipid was decreased.  Fish oil was started at 0.2 g every 12 hours and was advanced to a maximum of 0.5 g every 6 hours.  The two fish oil products were Major Fish Oil 500 (Major Pharmaceuticals) and Rugby Sea Omega 50 (Rugby Laboratories).

The limitations include the following:

  • Small cohort of 18 patients in each arm
  • Due to the smell of fish oil, the study could not truly be blinded which introduces potential bias
  • Only 7 of the 36 patients could be considered to have short bowel syndrome as most of the infants had small amounts of intestine resected
  • Advancement of enteral feedings were halted if stoma output reached 20 mL/kg/d.  The editorialists note that 40 mL/kg/d would be more typical.  Thus, in both the treatment group and the control group, there was significant opportunity to reduce PN by more aggressive enteral nutrition advancement.

With these limitations in mind, there authors were able to show that supplemental fat (with fish oil) was associated with less parenteral intravenous lipid, and reduced conjugated bilirubin prior to anastomosis.  However, there was no significant difference in PN duration.  Growth parameters were similar prior to anastomosis, but improved in the treatment group after anastomosis.

In the editorial, it is noted that “enteral feeding with a high-fat diet has been demonstrated to enhance structural features of resection-associated adaptation, the underlying mechanisms for this phenomenon are still presently unknown.”

Take-home message: Enteral fat/fish oil supplementation helped decrease parenteral intravenous lipids in this study.  More broadly, advancing enteral nutrition by accepting higher ostomy outputs is likely the best strategy to avoid PNAC and other PN-associated complications.

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Probiotics for NEC -More Work is Needed (part 2)

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For very low birth weight (VLBW) premature infants, there is even more evidence that probiotics are effective (The Journal of Pediatrics Volume 165, Issue 2 , Pages 285-289.e1, August 2014 -thanks to Kipp Ellsworth for abstract link).

Abstract ():

Study design

Within the observational period (September 1, 2010, until December 31, 2012, n = 5351 infants) study centers were categorized into 3 groups based on their choice of Lactobacillus acidophilus/Bifidobacterium infantis use: (1) no prophylactic use (12 centers); (2 a/b) change of strategy nonuser to user during observational period (13 centers); and (3) use before start of observation (21 centers). 

Results

The use of probiotics was associated with a reduced risk for necrotizing enterocolitis surgery (group 1 vs group 3: 4.2 vs 2.6%,P = .028; change of strategy: 6.2 vs 4.0%, P < .001), any abdominal surgery, and hospital mortality. Infants treated with probiotics had improved weight gain/day, and probiotics had no effect on the risk of blood-culture confirmed sepsis. In a multivariable logistic regression analysis, probiotics were protective for necrotizing enterocolitis surgery (OR 0.58, 95% CI 0.37-0.91; P = .017), any abdominal surgery (OR 0.7, 95% CI 0.51-0.95; P = .02), and the combined outcome abdominal surgery and/or death (OR 0.43; 95% CI 0.33-0.56; P < .001).

Probiotics For NEC -More Work is Needed (part 1)

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From Kipp Ellsworth’s Twitter Feed:

The Time for a Confirmatory NEC Probiotic Prevention Trial in ELBW Infants is Now. Editorial in J Peds  (The Journal of Pediatrics
Volume 165, Issue 2 , Pages 389-394, August 2014)

This editorial reviews previous studies and recommends implementing a Probiotic Trial in North America. Here’s an excerpt:

“An adequately powered double-blinded placebo-controlled trial replicating a previous effective NEC prevention study in VLBW infants was published (the ProPrem trial)…the study revealed a significant reduction of NEC: from 4.4%-2.0% but no effect on mortality (4.9% vs 5.1%)…A closer look at the results of the ProPrem study, however, reveals that the probiotic supplementation did not have any effect on NEC in the ELBW (<1000 g) infants, which is consistent with two small previous studies reporting data on these infants separately.36, 42 Thus, there is currently no compelling evidence for recommending prophylactic probiotics to prevent NEC in infants with a birth weight <1000 g. Especially important is the lack of safety information in these most immature and highly vulnerable babies…Probiotics appear promising for use as prevention strategy for NEC, but there is still insufficient data for general recommendation of the use of probiotics in the ELBW infant. We argue, therefore, that now is the time to conduct in the North American setting, a high quality confirmative NEC prevention trial using probiotics in at-risk ELBW infants.”

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Use of Gluten-Free Diet with Inflammatory Bowel Diseases

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As noted in a previous blog (The Search for a Dietary Culprit in IBD | gutsandgrowth), alternative diets have been explored both for symptom improvement and in efforts to improve inflammation in individuals with inflammatory bowel diseases (IBD).  A new study from North Carolina indicates that nearly 20% of patients have tried a gluten-free diet (GFD) to help control clinical symptoms in IBD (Inflamm Bowel Dis 2014; 20: 1194-97).

While adoption of a GFD clearly is effective for celiac disease, it has become popular, along with a low FODMAPs diet, as an alternative treatment for irritable bowel syndrome (IBS)/and “non-celiac gluten sensitivity.”  Since IBS is a common comorbidity with IBD (see recent blog: New Biomarker for Crohn’s Disease (Plus Two …), it is not surprising that a GFD would be used by some with IBD.  In this study, the authors performed a cross-sectional study using a GFD questionnaire in 1647 IBD patients though a CCFA longitudinal internet-based cohort.

Results:

  • 19.1% had previously tried a GFD and 8.2% reported current use of GFD.
  • 65.6% described improvement while on a GFD.  Improved symptoms included fatigue, nausea, bloating, abdominal pain, and diarrhea.
  • 0.6% of patients reported a concurrent diagnosis of celiac disease (which is similar to overall celiac prevalence in U.S.)

Given the structure of this study, which is mainly an internet survey, there are many limitations in its interpretation.  Certainly, this study does not prove that a GFD is effective for IBD.  However, it is clear that a GFD is used frequently and may improve IBD/IBS symptoms.

Take-home message: Particularly in patients who have ongoing symptoms despite  mucosal healing, pursuing either a low FODMAPs diet or a GFD may be helpful.

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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects), implementation of diets and specific medical management interventions should be confirmed by prescribing physician.  Application of the information in a particular situation remains the professional responsibility of the practitioner.

Pushback on Probiotics

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I had not paid much attention to a study last year (Lancet 2013; 382: 1249-57) titled, “Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhea and Clostridium difficile diarrhea in older patients (PLACIDE): a randomized, double-blind, placebo-controlled, multcentre trial.”

A useful review (Gastroenterol 2014; 146: 1822-23) of this study provides some useful insight into the use of probiotics.  The authors state that “in the last decade, medical and non medical professionals have endorsed the use of probiotics as a means of preventing AAD through a dogma that adding ‘good bacteria’ will prevent dysbiosis caused by ‘bad bacteria.'”  They note that several meta-analysis have supported a positive benefit for probiotics in this setting; yet, the “results merit cautious interpretation owing to a high risk of bias and notable heterogeneity of included studies.”

The PLACIDE study overcomes many of the previous limitations in this well-designed study design which enrolled a large cohort of 2,981 patients (≥65 years old).  The probiotics used in this trial were lactobacillus acidophilus along with bidodbacterium bifidum and lactis.  Ultimately, “patients receiving probiotics were as likely to develop AAD as patients in the placebo arm (relative risk 1.04).”  The rate of C difficile infection was ~1% and lower than expected.

While this study did not demonstrate any benefit from probiotics, there was no significant harm identified from probiotics; though, patients receiving probiotics were more likely to develop flatus and bloating in comparison to placebo.

Take-home message: “This study now also points away from probiotics being of benefit…probiotics use will not diminish as a result of this trial.  Parties will, argue rightly or wrongly, that the wrong strains were chosen…However, what the PLACIDE trial does point is that there is no clear evidence for use of probiotics in this setting until high-quality RCTs are conducted.”

Another probiotic reference:

JAMA Pediatr 2014; 168: 228-33.  This randomized double-blind, controlled trial conducted in 9 neonatal units in Italy compared L reuteri DSM 17938 to placebo for prevention of colic.  Mean duration of daily crying was 38 min in probiotic group compared with 71 min in placebo-treated patients, though these measures were with a nonvalidated diary.  Conclusions of authors: “prophylactic use of L reuteri DSM 17938 during the first 3 months of life reduced the magnitude of crying and functional gastrointestinal disorders.”

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Clostridium difficile Epidemiology

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A recent study shows that Clostridium difficile infection (CDI) is identified frequently in young children and that approximately three-fourths had recent preceding antibiotics (Pediatrics 2014; 133: 651-58). Abstract link.

Methods: “Data from an active population- and laboratory-based CDI surveillance in 10 US geographic areas during 2010–2011 were used to identify cases.”

Key findings:

  • Of 944 pediatric CDI cases identified, 71% were community-acquired
  • CDI incidence per 100 000 children was highest among 1-year-olds (66.3)
  • Using a representative sample (n=84) who reported diarrhea on the day of stool collection, 73% received antibiotics during the previous 12 weeks.

Despite the frequency of CDI, understanding a couple of key diagnostic pearls is crucial. According to the American Academy of Pediatrics Committee on Infectious Disease policy guideline: (Link to AAP guideline PDF)

  • Recommends avoid routine testing in pediatric patients less than 1 year of age due to high carriage rates.
  • “Testing for C difficile can be considered in children 1 to 3 years of age with diarrhea, but testing for other causes of diarrhea, particularly viral, is recommended first>
  • “A common mistake is to… test for cure. C difficile, its toxins, and genome are shed for long periods after resolution of diarrheal symptoms.”
  • “An interval greater than 4 weeks since last testing should be used for testing with a recurrence.”

Bottomline: This most recent study reinforces the notion that about 1/4th of pediatric CDI occurs in the absence of recent antibiotics; nevertheless, understanding the limitations of testing for CDI could prevent a fair amount of aggravation.

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