Category Archives: Pediatric Gastroenterology Intestinal Disorder

OpenBiome -Nation’s 1st Human Stool Bank

Posted on by

From NY Times: http://t.co/LIIk4JNMfl

An excerpt:
Around noon on a recent Friday, Donor Five, a healthy 31-year-old, walked across M.I.T.’s frigid, wind-swept campus to a third-floor restroom to make a contribution to public health.

Less than two hours later, a technician blended the donor’s stool into preparations that looked like chocolate milk. The material was separated and stored in freezers at an M.I.T. microbiology lab, awaiting shipment to hospitals around the country. Each container was carefully labeled: Fecal Microbiota Preparation.

Nearly a year ago, Mark Smith, a 27-year-old doctoral candidate, and three colleagues launched OpenBiome, the nation’s first human stool bank. Its mission: to provide doctors with safe, inexpensive fecal material from screened donors to treat patients with Clostridium difficile, a gastrointestinal infection that kills at least 14,000 Americans a year.

“People are dying, and it’s crazy because we know what the solution is,” Mr. Smith said. “People are doing fecal transplants in their basements and may not be doing any of the right screening or sterile preparation. We need an intermediate solution until there are commercial products on the market.”…

The bacteria are increasingly resistant to conventional treatments. But researchers have discovered an alternative: A donor’s stool can be transplanted in the intestine or colon of a sick patient via an enema, colonoscopy or nasogastric tube. The healthy bacteria fight off C. diff and re-establish a normal community in the gut.

A study published last year in The New England Journal of Medicine found that fecal transplants were nearly twice as effective as antibiotics in treating patients with recurring C. difficile.

But where to get healthy donor stool? For doctors, it’s a tedious, time-consuming process, and some patients turn awkwardly to relatives or friends. Since September, OpenBiome has delivered more than 135 frozen, ready-to-use preparations to 13 hospitals. The nonprofit project fields dozens of requests from doctors, hospitals and patients every week. (The preparations are not sent directly to patients.) 

Carol Capps, 75, a retired nurse in Clemmons, N.C., had been in and out of hospitals for months with a C. diff infection that was not going away despite multiple courses of antibiotics. After a recurrence, her doctor suggested OpenBiome, and she received a fecal transplant. By that afternoon, Ms. Capps said, she felt like a new person and has been healthy since…

Because of the legal ambiguity, some researchers are not preparing fecal microbiota for sale (usually at cost) …

At the same time, Mr. Smith and Eric J. Alm, an M.I.T. microbiologist and adviser to OpenBiome, said the F.D.A.’s classification of fecal transplants as drugs hinders research into their possible uses to treat inflammatory bowel diseases and obesity.

Related blog posts:

What NOT to say with functional pain

Posted on by

A recent article crossed my desk (from the “G-force”) which I hadn’t seen (or at least remembered).  So, although it is not new, it is a useful reference (Pain 2006; 122: 43-52).

In brief, the authors divided 223 children (n-104 with recurrent pain, n=119 healthy children) between ages 8-16 into 3 groups: attention, distraction, and no instruction.  After the children consumed water until they felt “completely full,” they were observed with their parents.  Parents in the attention and distraction groups had received video and written instructions; whereas the no instruction parents watched a video about the university.

Questions/statements that were typical in the attention group:

  • “I know it hurts now, but you’ll be OK later”
  • “What doe it feel like?”
  • “I can imagine it must feel really uncomfortable”

Questions/statements that were typical in the distraction group:

  • “Let’s talk about something else to get your mind off of it.  Tell me about ____”
  • “What would you like to do this evening?”

Key findings:

  1. Complaints nearly doubled under conditions of parent attention and were reduced by half under conditions of distraction (in comparison to the no instruction group).
  2. Female patients in this study had greater increase in pain complaints in the attention group than male patients.
  3. After water loading, children with a history of pain had significantly more complaints in the attention group than healthy children.
  4. “Unlike parents of well children, no parent of a pain patient rated attention as having any potential for negative impact on their child.”

Take home message (from Oscar Wilde -quoted in article): “While sympathy with joy intensifies the sum of joy in the world, sympathy with pain does not really diminish the amount of pain.”

Related blog post:

Anxiety and Functional Abdominal Pain | gutsandgrowth

Gluten-free diet “has legs”

Posted on by

From NY Times: http://t.co/5cQijw7do9

An excerpt:

The Girl Scouts recently introduced a gluten-free chocolate chip shortbread cookie to their annually anticipated line of sweet treats…And Trader Joe’s recently joked in an advertising flier promoting gluten-free foods that it was selling “Gluten Free Greeting Cards 99 Cents Each! Every Day!” — even though it then went on to say the cards were not edible.

Makers of products that have always been gluten-free, including popcorn, potato chips, nuts and rice crackers, are busy hawking that quality in ads and on their packaging.

And consumers are responding with gusto. The portion of households reporting purchases of gluten-free food products to Nielsen hit 11 percent last year, rising from 5 percent in 2010.

In dollars and cents, sales of gluten-free products were expected to total $10.5 billion last year, according to Mintel, a market research company, which estimates the category will produce more than $15 billion in annual sales in 2016…

“About 30 percent of the public says it would like to cut back on the amount of gluten it’s eating, and if you find 30 percent of the public doing anything, you’ll find a lot of marketers right there, too.”

Never mind that a Mayo Clinic survey in 2012 concluded that only 1.8 million Americans have celiac disease, an autoimmune disorder that causes the body to attack the small intestine when gluten is ingested and can lead to other debilitating medical problems if not diagnosed.

An additional 18 million people, or about 6 percent of the population, is believed to have gluten sensitivity, a less severe problem with the protein in wheat, barley and rye and their relatives that gives elasticity to dough and stability to the shape of baked goods.

“There are truly people out there who need gluten-free foods for health reasons, but they are not the majority of consumers who are driving this market,” said Virginia Morris, vice president for consumer strategy and insights at Daymon Worldwide, a private brand and consumer interactions company…

“The reason I do believe this has legs is that it ties into this whole naked and ‘free from’ trend,” she said. “I think we as a country and as a globe will continue to be concerned about what’s going into our food supply.”

Rebecca Thompson, a marketing manager at General Mills, said ..“When you think about the dynamics in a household, where there are likely to be three other people eating at the same time as one person with celiac or gluten sensitivity, it’s much easier to prepare one meal for everyone.”…

General Mills, whose brands include Bisquick, Pillsbury and Betty Crocker, might seem like the least likely company to embrace gluten-free. But in the mid-2000s, more and more customers began seeking alternatives to its traditional products.

So in 2008, it began reformulating its Chex cereals, underscoring the first change, to Rice Chex, with a major marketing effort. It was relatively easy to tweak Chex by switching a few minor ingredients. But the next year, Betty Crocker introduced gluten-free brownies, cookies and cakes in a far more complicated process…

Gluten-free customers are valuable, ringing up roughly $100 in sales with their average grocery basket compared with $33 for the overall average basket, according to Catalina Marketing…

Last August, the Food and Drug Administration, which oversees food labeling, ruled that products labeled gluten free were permitted to contain no more than 20 parts of gluten per million, which made it more difficult for large food companies to get into the business. “You really need to have a captive facility because wheat floats,” Mr. Hughes said.

Sales of Udi’s and Glutino were up 50 percent last year, and Boulder Brands is finding more demand from regional food service businesses and institutions. Udi’s hot dog buns are available now in most major baseball parks, and Dunkin’ Donuts and others are turning to the company for individually wrapped gluten-free bagels and muffins…

Mr. Hughes said. “We think this is a trend with long legs because there is some insulation from the big players — it’s hard to produce gluten-free — and because so much of the category is represented by $10- and $15-million mom-and-pop businesses.”

Interest in gluten-free products also has been a boon for fruits and vegetables and other foods that are inherently gluten-free. Popcorn Indiana, for example, has labeled its ready-to-eat popcorn gluten-free since before the fad began, in part because the chief executive, Hitesh Hajarnavis, has children who have food allergies. “I had become an avid reader of labels, and so when I came over to Popcorn Indiana, I knew the value of having a clear gluten-free label for what was then a very small number of people with gluten allergies,” Mr. Hajarnavis said… “But there is a growing population of people who have somehow heard that gluten-free is healthier or think of it as fashionable, and when they remove gluten from their diet, they’re inadvertently taking out a lot of processed foods and are really feeling the benefits of eating healthier foods.”

Celiac Update: Quinoa –probably OK for gluten-free diet based on small study.  Here’s the link: nature.com/ajg/journal/vaop/ncurrent/full/ajg2013431a.html … (from KT Park twitter feed)

Related blog posts:

‘Little’ Knowledge Exists Regarding Medicines for Neonates

Posted on by

Despite federal legislation encouraging the study of products used in the pediatric population, very little of these studies has translated into meaningful information regarding neonates (JAMA Pediatr 2014; 168: 130-36, thanks to Ben Gold for this reference).

This publication reviewed studies submitted to the FDA between 1997-2010.  The authors identified all drugs with pediatric studies that included neonates.  Subsequently, the use of these drugs was examined in a oohort of neonates admitted to 290 neonatal intensive care units (NICU) (Pediatrix Data Warehouse) in the U.S. form 2005-2010.

Key findings:

  • 28 drugs (in 41 studies) were examined in neonates. This led to 24 labeling changes.
  • 11 of 24 neonatal labeling changes included an approval for use in neonates, including 4 for HIV and 3 for anesthesia.
  • 13 of 24 labeling changes were the following: “safety and effectiveness have not been established.”  These drugs included several reflux medications: esomeprazole, lansoprazole, pantoprazole, and ranitidine.
  • In the Pediatrix database involving 446,335 hospitalized neonates, there were 399 different drugs identified that had been administered.  Of the 28 studied drugs, the gastroesophageal reflux medicines were used most frequently.  13 of the 28 studied drugs were not used at all in the NICUs.
  • Of the 11 drugs with a neonatal indication, 7 were never used in the Pediatrix neonatal population and the other 4 drugs were used infrequently.

Conclusions:

  • Neonates are a vulnerable and an understudied population
  • Most of the exposure to drugs was off-label for neonates.
  • Most often, off-label drugs were prescribed “despite studies indicating they were not effective…For example, ranitidine, lansoprazole, and inhaled nitric oxide (for the prevention of bronchpulmonary dysplasia) were the top 3 drugs used in neonates…none have FDA labelling for the indication studied because of lack of efficacy.”
  • Furthermore, drugs like ranitidine and lansoprazole” are associated with serious adverse effects in neonates.” (Clin Perinatol 2012; 39: 99-109)

Related blog entries:

UC SUCCESS

Posted on by

The results of the “UC SUCCESS” trial show that combination therapy with infliximab and azathioprine is more effective than either medication as monotherapy in ulcerative colitis (UC) (Gastroenterol 2014; 146: 392-400). This study findings are similar to the SONIC trial in Crohn’s disease (CD).

Study Design: randomized, double-blind trial with evaluation at 16 weeks with a total of 239 patients.  In patients assigned to infliximab (IFX) alone, they were given daily oral placebo pills. In patients with azathioprine monotherapy (AZA), dosed at 2.5 mg/kg/day, they also received placebo infusions.  Patients had moderate to severe UC as defined by Mayo scores at baseline and had not responded adequately to a course of corticosteroids.  All patients were naive to tumor necrosis factor α antagonists (anti-TNFα).  Mean age was approximately 40 years.

Results:

  • IFX/AZA had a 39.7% corticosteroid-free remission at week 16 compared with 22.1% with IFX monotherapy and 23.8% with AZA monotherapy.
  • Mucosal healing at week 16 was evident in 62.8% of combination group compared with 54.6% IFX monotherapy and 36.8% with AZA monotherapy.
  • Serious adverse events were noted more frequently in the AZA monotherapy group, though this did not reach statistical significance.
  • A subset of patients had antibodies to infliximab (ATIs) measured.  ATI-positivity was more common with IFX monotherapy (19%, 7 of 37) than for IFX/AZA combination (3%, 1 of 31)

While this study indicates that for moderate to severe UC combination therapy with IFX/AZA was superior in this age group, there were several limitations.  Given the slow onset of action of azathioprine, more patients may have responded to this therapy if longer treatment duration was studied.

Take-home message: Combination therapy for UC, like CD, is more effective.  In this small study population, the adverse events were not increased. In the pediatric population, particularly males, the concern for malignancy in patients (especially males) treated with combination therapy may limit the frequency of combination therapy.

Related blog posts:

Other recent IBD articles of interest:

Inflamm Bowel Dis 2014; 20: 291-300. “Malignancy and Mortality in Pediatric Patients with Inflammatory Bowel Disease”  This article presented the results of a survey of 20 European countries and Israel.  Key finding: 18 cases of cancer and 31 deaths in 44 children. 5 of the deaths were due to cancer; the most common cause of mortality was infectious (n=14).  In this cohort, all HSTCL or EBV-positive lymphomas were treated with thiopurine monotherapy.

Inflamm Bowel Dis 2014; 20: 196-212.  “Opportunistic Infections Due to Inflammatory Bowel Disease Therapy”  This review article covers a broad range of pathogens and includes recommendations for prophylaxis and treatment (Table 3).  In addition the authors  provide suggestions for checking for several infections prior to treatment and vaccinations.

Sometimes more is not better

Posted on by

‘More is not better’ may be the case with trimethoprim/sulfamethoxazole (TMP/SMX) Pneumocystis prophylaxis (PCP) (J Pediatr 2014; 164: 389-92).  This study indicates that a single-day course of TMP/SMX prophylaxis is as effective as other regimens.

Design: Prospective survey of 20 centers with newly diagnosed cancer between 2009-2011.  This included 1093 with solid tumors and 1373 with leukemia/lymphoma.  55.6% received 3-day/week prophylaxis, 16.5% received 2-day/week regimen, and 27.9% received 1-day/week regimen (5-10 mg/kg/day into 2 doses).

Key result:

  • Incidence of PCP at 3 years was 0.09% overall.  The two cases occurred in the 2-day regimen (though both had withdrawn from treatment)

The authors note the need for PCP prophylaxis has been questioned for solid tumor patients.  However, the lack of PCP among the 439  children with leukemia/lymphoma indicates that a single day per week regimen is effective.

Bottomline: In GI/liver patients who need TMP/SMX prophylaxis, 1-day per week regimen is likely effective (as it is in leukemia/lymphoma patients).  One-day/week is easier and should help with compliance, which is the key to preventing PCP.

Why an ERCP Study Matters to Pediatric Care

Posted on by

While there are pediatric patients who undergo endoscopic retrograde cholangiopancreatography (ERCP), this is a relatively infrequent occurrence. Nevertheless, a recent study has a couple useful clinical pearls that may have broader application.

  1. Clin Gastroenterol Hepatol 2014; 12: 303-07.
  2. Clin Gastroenterol Hepatol 2014; 12: 308-10 Associated editorial
  3. Gastroenterol 2014; 146: 581-82. Associated summary

Key points/Implications:

  • Aggressive hydration may prevent post-ERCP pancreatitis. In the study, the treatment group received an average of 3290 mL over the 9-hour period compared with 945 mL in the standard infusion group.
  • Implication: The speculation from the study and the editorials is that improved pancreatic perfusion will result in better oxygenation and reduce the likelihood of  pancreatitis. In the 2nd reference, the author states that his practice is to administer “at least 3 L of crystalloid in recovery to young, healthy patients who have undergone high-risk ERCP and an additional 3 to 5 L within the first 12 hospital hours to those admitted with postprocedure pain”
  • The best fluid (for post-ERCP and acute pancreatitis) may be lactated Ringer’s (LR).
  • Implication: The lactate in LR may help reduce pancreatitis by avoiding acidosis which could promote zymogen activation and pancreatic inflammation. A previous small trial (n=40) of acute pancreatitits from any cause showed lesser degrees of systemic inflammatory response with LR in compared with normal saline (Clin Gastroenterol Hepatol 2011; 9: 710-17e1).
  • This study adds aggressive IVFs as another intervention to prevent ERCP.  Rectal indomethacin and prophylactic stent placement (in high-risk patients) are other accepted treatments.

Study details:

This pilot study randomly assigned 39 patients to aggressive hydration and 23 to standard hydration; all patients were inpatients who were not at risk for fluid overload. The aggressive group received 3 mL/kg/h during the procedure, a 20 mL/kg bolus after the procedure, and then continued on 3 mL/kg/hr for 8 hours.  In contrast, the standard group received LR at 1.5 mL/kg/h during and for 8 hours afterwards.

Demographics: The average age was 43 years in the aggressive hydration group and 45 years in the standard group. 78% were hispanic.  The ERCP procedures were mostly “average risk.”  74% had ERCP for choledocholithiasis.  Only 2 subjects needed precut sphinterotomy (3%).

Results:

  • No patients in the aggressive hydration group developed acute pancreatitis compared with 4 (17%) in the standard hydration group
  • Elevated amylase (23% vs. 39%) and epigastric pain (8% vs 22%) were also less frequent in the aggressive hydration group.

Numerous Limitations: This was a small pilot study with an atypical population; thus, the findings are difficult to generalize.  A false-positive (type 1 error) can easily occur due to the small numbers, especially as the standard hydration group had a rate of acute pancreatitis that was about double from previous studies. In addition, this study was not blinded and could have been susceptible to bias.  Furthermore, the authors defined acute pancreatitis differently than in previous studies.  In this study, the authors required enzyme increases 2 or 8 hours after ERCP with new abdominal pain; in previous studies, the definition of acute pancreatitis relied on enzyme increases for at least 24 hours after the ERCP.

Take-home message for those not doing ERCPs: Think about using lactated ringer’s and aggressive hydration in otherwise-well patients who present with acute pancreatitis.

Related blog entries:

Eosinophilic Esophagitis and Psychosocial Dysfunction

Posted on by

There are many medical challenges in treating patients with eosinophilic esophagitis (EoE) and this has been discussed extensively in this blog (some links below).  What is striking in managing these patients and families is how often there are significant psychosocial problems.  Does this disorder serve as an excuse for other issues? Does the altered diet create enormous stress and isolation? Is the diagnosis of EoE an epiphenomenon for many of these patients?

While these questions are not answered, a recent retrospective study from a tertiary care center does provide some data on the frequency of psychosocial dysfunction in children and adolescents with EoE (JPGN 2013; 57: 500-05).

Psychosocial evaluation was offered as part of these patients’ clinical evaluation; this took place in 64 of 152 patients during the study timeframe.  Subsequently, a retrospective review of these patients, who had been offered a 1-hour behavioral health assessment by either a psychologist or social worker, were analyzed.

Key findings:

  • 69% had some psychosocial impairment
  • 64% had social difficulties
  • 41% had anxiety
  • 33% had sleep difficulties
  • 28% had depression
  • 26% had school problems
  • 44% had adjustment problems; this was more common in older children and in children with gastrostomy tubes

The main limitations of this study are its retrospective nature and the fact that only a minority of patients were analyzed; the latter indicates a high likelihood of a selection bias. The severity of EoE was not correlated with these problems, but could have been higher  at a tertiary center.

Take-home message: As with other chronic diseases, EoE patients have frequent psychosocial health problems –this study starts to define the extent of the problem.

The Genius of Breastmilk

Posted on by

While there has been a lot of talk about how breastmilk improves IQ/development (see links below), there are many other reasons why breastmilk is amazing.  For example, breastmilk reduces the risk of necrotizing enterocolitis (NEC).  A recent study on this effect: J Pediatr 2013; 163: 1592-5.

In this multicenter randomized controlled trial involving 7 NICUs, the authors studied extremely premature infants whose mothers did not provide their breastmilk.  Infants were fed either a cows-milk based preterm formula (COW, n=24) or pasteurized donor human milk (HUM, n=29). Birth weight and gestational age were similar in both groups, approximately 990 g and 27.5 weeks respectively.

Results:

  • HUM patients had fewer days of parenteral nutrition: 27 vs. 36, P=.04
  • HUM patients had fewer bouts of NEC: 1 (3%) vs. 5 (21%), P=.08; surgical NEC occurred 4 times in COW group compared with 0 in HUM patients (P=.04)

Take-home message: The data from this study are in line with recent American Academy of Pediatrics policy statement that recommends the following: “premature infants should receive only human milk from their mother and that, if it is not available, pasteurized donor human milk should be used.”

Another relevant study: J Pediatr 2010; 156: 562-7.

Related blog posts:

Polyps: Clinical Decision Tool

Posted on by

The best approach to polyps from the U.S. Multi-Society Task Force: Gastroenterology 2014; 146: 305-306.  This paper’s simple chart on page 306 could help reduce many follow-up colonoscopies that are performed at shorter than recommended intervals.

Polyp Guideline

Related blog post:  Consensus guidelines after polypectomy | gutsandgrowth)