Category Archives: Pediatric Gastroenterology Intestinal Disorder

What does the law require with regard to food allergen labeling? (plus one)

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From APFED twitter feed: What does the Food Allergen Labeling and Consumer Protection Act require?: http://youtu.be/nhBd9iTYkUQ?a (<2 minute video)

Plus one more reference on Achalasia:

A recent review on achalasia highlights the recent advances in our understanding of this disorder (Gastroenterol 2013; 145: 954-65). This post is mainly to note it as a useful reference.

Specific topics covered include the following:

  • High-resolution manometry
  • Criteria for achalasia diagnosis
  • Physiology/pathogenesis/pathophysiology.  Achalasia is “an autoimmune disease targeting esophageal myenteric neurons with both a cell-mediated and antibody-mediated attack directed against an as yet unidentified antigen.”
  • Subtypes (Figure 2 shows, in color, manometric pattens with each subtype)

Related posts:

IBD Update 2014 (part 2)

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5. Inflamm Bowel Dis 2013; 19: 2927-36.  This reference is another article that tries to help discuss the risks and benefits of biologic therapy for pediatric inflammatory bowel disease.  After reviewing the potential risks, the authors provide their “Option Grid” (Page 2932).  The authors state, “in summary, the adult literature supports the concept of the early use of combination therapy…the risks associated with anti-TNF therapy are really not significantly different as compared with thiopurine therapy and perhaps in some cases safer.  Therefore, we should be moving closer to the idea of using anti-TNF therapy early, with or without an immunomodulator.  In the sickest patients, combination therapy probably adds benefit, and then once in remission, consideration can be given for stopping one of the medications, more likely the thiopurine.

6. Gut 2013; 62: 689-94.  Risk of ischemic heart disease in patients with inflammatory bowel disease: a nationwide Danish cohort study.  From 1997 to 2009, the authors compared 28,833 IBD persons to >4.5 million persons without IBD who were matched for age, gender, socioeconomic status, and calendar year.  With a mean follow-up of 13 years, they identified a 59% higher incidence rate of ischemic heart disease in patients with IBD.  Long-term use of immunosuppressive medications, such as azathioprine and anti-tumor necrosis factor-alpha agents, was not associated with an increased risk of ischemic heart disease.

7.   Gastroenterol 2013; 145: 1459-63.  AGA Guideline for Use of Thiopurines, Methotrexate, and Ant-TNF-alpha Biologic Drugs for the Induction and Maintenance of Remission in Inflammatory Crohn’s Disease. This reference was previously noted in blog (with a link) AGA Guidelines for the Use of Thiopurines and Anti … – gutsandgrowt.  The print version does have a nice algorithm (pg 1463).  The accompanying technical review: Gastroenterol 2013; 145: 1464-78.

8. BMJ 2013;347:f6633. Free full-text BMJ article PDF. (Thanks to Mike Hart for this reference) From the abstract:  During 3 421 972 person years of follow-up, we documented 284 cases of Crohn’s disease and 363 cases of ulcerative colitis. The risk of Crohn’s disease was inversely associated with physical activity (P for trend 0.02). Compared with women in the lowest fifth of physical activity, the multivariate adjusted hazard ratio of Crohn’s disease among women in the highest fifth of physical activity was 0.64 (95% confidence interval 0.44 to 0.94). Active women with at least 27 metabolic equivalent task (MET) hours per week of physical activity had a 44% reduction (hazard ratio 0.56, 95% confidence interval 0.37 to 0.84) in risk of developing Crohn’s disease compared with sedentary women with ❤ MET h/wk. Physical activity was not associated with risk of ulcerative colitis (P for trend 0.46). The absolute risk of ulcerative colitis and Crohn’s disease among women in the highest fifth of physical activity was 8 and 6 events per 100 000 person years compared with 11 and 16 events per 100 000 person years among women in the lowest fifth of physical activity, respectively. Age, smoking, body mass index, and cohort did not significantly modify the association between physical activity and risk of ulcerative colitis or Crohn’s disease (all P for interaction >0.35). Conclusion In two large prospective cohorts of US women, physical activity was inversely associated with risk of Crohn’s disease but not of ulcerative colitis.

Comment: While physical activity may directly reduce the risk of Crohn’s disease, it could also be an epiphenomenon of another unmeasured variable (eg. dietary habits) that modifies this risk.

Related blog post:

Understanding IBD Therapy Risks -A Good Link | gutsandgrowth  Provides link to useful 6-minute internet video for families.

IBD Update 2014 (part 1)

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A number of recent articles that may be helpful for clinicians who help patients with inflammatory bowel disease.

1. Inflamm Bowel Dis 2013; 19: 2778-86.  “The Incidence and Predictors of Lupus-Like Reaction in Patients with IBD treated with Anti-TNF therapies.”  Key result: 20 of 289 (6.9%) developed lupus-like reactions (LLRs).  Female gender and IBD-unclassified were more prevalent in this group.  Clinical features included arthropathy (100%); fatigue and dermatitis were common.  All tested positive for ANA, 16 of 20 also had anti-dsDNA.  LLRs resolved with cessation of culprit agent and steroids.  Only one patient had recurrence who had switched to an alternative anti-TNF.

2. Inflamm Bowel Dis 2013; 19: 2753-62. This phase 3, randomized open-label multicenter study enrolled 60 children and provided data regarding infliximab pharmacokinetics in patients with moderate-to-severe ulcerative colitis.  The findings indicate that infliximab exposure-response is similar to adult patients.  At week 8, those with higher serum infliximab levels (≥41.1 mcg/mL) had higher efficacy (response 92.9%, remission 64.3%) compared with those with a lower levels <18.1 mcg/mL (response 53.9%, remission 30.8%).  Trough levels (at week 30) for q8 week-dosing was 1.9 mcg/mL compared with 0.8 mcg/mL for q12 week-dosing.

3. Inflamm Bowel Dis 2013; 19: 2744-52. A lot of pediatric IBD patients are colonized with Clostridium difficile.  In this prospective study of 85 outpatient IBD pediatric patients and 78 age-matched controls, asymptomatic C difficile carriage was noted in 17% of IBD patients compared with 3% of controls.  Use of proton pump inhibitors was associated with an increased carriage rate.

4. Inflamm Bowel Dis 2013; 19: 2937-48.  Excellent review article regarding fertility and pregnancy for women with IBD.  This review includes a discussion about the timing of pregnancy with regard to remission, effects of surgery and medications, acceptable radiology testing in pregnant patients, and issues regarding delivery.

Updated Pediatric Expert Constipation Guidelines

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Updated guidelines for the diagnosis and treatment of constipation by NASPGHAN and ESPGHAN have undergone formal peer review are likely to be published soon (available online with the following link: bit.ly/1geLxrk).  “Evidence-Based Recommendations from ESPGHAN and NASPGHAN for Evaluation and Treatment of Functional Constipation in Infants and Children” by Merti Tabbers, Carlo DiLorenzo et al. The following are some of their recommendations.

Diagnostic recommendations:

  • The ROME III criteria are recommended for the definition of functional constipation for all age  groups.
  • Diagnosis of functional constipation is based on history and physical examination.
  • There is no role for the routine use of an abdominal X-ray to diagnose functional constipation.
  • A plain abdominal  radiography may be used in a child in whom fecal impaction is  suspected but in whom physical examination is unreliable/not possible.
  • Based on expert opinion, a 2-4 weeks trial of avoidance of cow’s milk protein may be indicated in the child with intractable constipation.
  • Routine laboratory testing to screen for hypothyroidism, celiac disease and hypercalcemia is not recommended in children with constipation in the absence of alarm symptoms. 

Treatment Recommendations:

  • We do not recommend the use of biofeedback as additional treatment in childhood constipation.
  • Polyethylene glycol (PEG) with or without electrolytes orally 1-1.5 gr/kg/day for 3-6 days is recommended as first-line treatment for children presenting with fecal impaction
  • An enema once a day for 3-6 days is recommended for children with fecal impaction if PEG is not available.
  • PEG with or without electrolytes is recommended as first-line maintenance treatment. A starting dose of 0.4 gr/kg/day is recommended and the dose should be adjusted according to the clinical response.
  • Addition of enemas to the chronic use of PEG is not recommended.
  • Based on expert opinion, use of milk of magnesia, mineral oil and stimulant laxatives may be considered as additional or second line treatment.
  • Antegrade enemas are recommended in the treatment of selected children with intractable constipation.

Related blog posts:

Less Red Meat, More Anemia

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The title of this entry is not particularly surprising.  A recent study (JPGN 2013; 57: 722-27) showed that among 263 children (1.5-6 years in age) in Jerusalem, that anemia was present in 11.2%, iron deficiency in 22%, and iron-deficiency anemia in 3.7%.

Key finding:

Children with extremely low red meat consumption had 4-fold higher rates of iron deficiency than those who consumed ≥2 servings per week.  Poultry intake was not protective.

Bottomline: As more families choose a ‘health-conscious diet,’ iron deficiency may become more frequent.

Related blog entry: Help with hepcidin | gutsandgrowth

JAMA Thalidomide Study for Crohn’s Disease

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The link (from KT Park’s twitter feed): media.jamanetwork.com/news-item/drug-improves-remission-crohn-disease-among-children-adolescents/ …

An except:

The study included 56 children and was conducted August 2008-September 2012 in 6 pediatric care centers in Italy. Children were randomized to thalidomide or placebo once daily for 8 weeks. The primary measured outcomes were a reduction in the Pediatric Crohn Disease Activity Index (PCDAI) score of ≥ 25 percent or ≥ 75 percent at weeks 4 and 8 (clinical remission). Nonresponders to placebo received thalidomide for an additional 8 weeks. All responders continued to receive thalidomide for an additional minimum 52 weeks.

The researchers found that clinical remission was achieved by more children treated with thalidomide (13/28 [46.4 percent] vs. 3/26 [11.5 percent]). Responses were not different at 4 weeks, but greater improvement was observed at 8 weeks in the thalidomide group. Of the nonresponders to placebo who began receiving thalidomide, 11 of 21 (52.4 percent) subsequently reached remission at week 8. Overall, 31 of 49 children treated with thalidomide (63.3 percent) achieved clinical remission, and 32 of 49 (65.3 percent) achieved 75 percent response.

Average duration of clinical remission in the thalidomide group was 181 weeks vs. 6.3 weeks in the placebo group.

Related blog post:

How to Change Your Microbiome Quickly?

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Change your diet.

From NPR, http://n.pr/JeWCh4, an excerpt:

Switching to a diet packed with meat and cheese — and very few carbohydrates — alters the trillions of microbes living in the gut, scientists report Wednesday [12/111/13] in the journal Nature.

The change happens quickly. Within two days, the types of microbes thriving in the gut shuffle around. And there are signs that some of these shifts might not be so good for your gut: One type of bacterium that flourishes under the meat-rich diet has been linked to inflammation and intestinal diseases in mice.

“I mean, I love meat,” says microbiologist Lawrence David, who contributed to the study and is now at Duke University.

[The researchers] wanted to know whether fiber — or lack of it — could alter gut bacteria more rapidly.

To figure that out, the researchers got nine volunteers to go on two extreme diets for five days each.

The first diet was all about meat and cheese. “Breakfast was eggs and bacon,” David says. “Lunch was ribs and briskets, and then for dinner, it was salami and prosciutto with an assortment of cheeses. The volunteers had pork rinds for snacks.”

Then, after a break, the nine volunteers began a second, fiber-rich diet at the other end of the spectrum: It all came from plants. “Breakfast was granola cereal,” David says. “For lunch, it was jasmine rice, cooked onions, tomatoes, squash, garlic, peas and lentils.” Dinner looked similar, and the volunteers could snack on bananas and mangoes.

“The animal-based diet is admittedly a little extreme,” he says. “But the plant-based diet is one you might find in a developing country.”

David and the team analyzed the volunteers’ microbiomes before, during and after each diet. And the effects of all that meat and cheese were immediately apparent.

“The relative abundance of various bacteria species looked like it shifted within a day after the food hit the gut,” David says. After the volunteers had spent about three days on each diet, the bacteria in the gut even started to change their behavior. “The kind of genes turned on in the microbes changed in both diets,” he says.

In particular, microbes that “love bile” — the Bilophila — started to dominate the volunteers’ guts during the animal-based diet. Bile helps the stomach digest fats. So people make more bile when their diet is rich in meat and dairy fats.

A study last year found that blooms of Bilophila cause inflammation and colitis in mice. “But we didn’t measure levels of inflammation in our subjects,” David says. “That’s the next step.”

Malignancy Risk with Thiopurines

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Based on a large retrospective, nationwide cohort study, it has been estimated that patients with ulcerative colitis have a 4-fold increase in the risk of lymphoma compared with patients who have not been treated with thiopurines (Gastroenterol 2013; 145: 1007-15).  While this study enrolled data from 36,891 patients followed for a median of 6.7 years, this study should not be interpreted in isolation.  The editorial (pages 927-30) provides some important context.

Besides the risk of lymphoma in patients treated with the thiopurines, the editorial briefly states the potential for life-threatening infections, primarily varicella and hemophagocytic lymphohistiocytosis which may complicate primary EBV infection.  The latter is much more common in younger patients.

With regard to malignancy, besides lymphoma, thiopurines also increase the frequency of nonmelanoma skin cancer.  Since these are not life-threatening, in many patients the risk of lymphoma is “the major limiting factor for the prolonged use of thiopurines.”  Furthermore, the risk of lymphoma may increase relative to treatment duration according to the above-referenced study. The editorial notes that there are three types of lymphoma to be considered:

  1. Posttransplant-like lymphoma associated with EBV seropositivity. Absolute risk in all IBD patients ~ 1 per 1000 patient-years.  All EBV-seropositive patients are at risk.
  2. Early post-mononucleosis lymphomas. Absolute risk in all IBD patients ~0.1 per 1000 patient-years; however, the risk in young men who are seronegative for EBV (<35 years) is ~3 per 1000 patient-years.
  3. Hepatosplenic T-cell lymphomas.  Absolute risk in all IBD in all IBD patients ~0.05 per 1000 patient-years; again, in young patients (mostly men) the risk is ~0.1 per 1000 patient-years.

The second and third types of lymphomas can be reduced by limiting thiopurines in young men.

Despite the risks posed by thiopurines, the overall benefit-risk balance needs to consider the fact that the risk of colorectal cancer “is markedly reduced in patients with long-standing extensive colitis exposed to thiopurines.”  Thus, the lowered risk of colorectal cancer “may outweigh the excess risk of lymphoma.”

Also, in considering thiopurines:

Inflamm Bowel Dis 2013; 19: 2801-08.  “Thiopurines are Associated with a Reduction in Surgical Re-resections in Patient’s with Crohn’s Disease.”  This study was a retrospective review of 567 patients of whom 237 (41.8%) developed a surgical recurrence after a median of 70 months.  Taking thiopurine was associated with a hazard ratio of 0.51.  Due to small numbers, the results with anti-TNF therapy was not conclusive, but “seems promising as well.”

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MIRTH Study -Laughter in Medicine

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From NY times review of a recent BMJ study:  http://t.co/RavJd8FgSJ

An excerpt:

Just in time to protect patients from the dangers of holiday cheer, a new scholarly review from a British medical journal describes many harmful effects wrought by laughter. 

Among the alarms it sounds: The force of laughing can dislocate jaws, prompt asthma attacks, cause headaches, make hernias protrude. It can provoke cardiac arrhythmia, syncope or even emphysema (this last, according to a clinical lecturer in 1892).

Laughter can trigger the rare but possibly grievous Pilgaard-Dahl and Boerhaave’s syndromes…

And ponder, briefly, the mortifying impact of sustained laughter on the urinary tract (detailed in a 1982 The Lancet paper entitled “Giggle Incontinence”).

At the very least, the new review could be considered an affirmation for the perpetually dour….

The analysis, “Laughter and MIRTH (Methodical Investigation of Risibility, Therapeutic and Harmful),” was drawn from about 5,000 studies. It appears in BMJ, formerly known as The British Medical Journal, which for more than 30 years has traditionally featured rigorously researched but lighthearted articles in its Christmas issue. A deputy editor, Dr. Tony Delamothe, said that the MIRTH study was indeed peer-reviewed — presumably by a doctor with a carefully managed sense or humor (or humour).

This year, companion studies in the issue include “Were James Bond’s drinks shaken because of alcohol induced tremor?” , “The survival time of chocolates on hospital wards: covert observational study,”  and “Operating room safety: the 10 point plan to safe flinging”  (among the cautions: “Before flinging, identify your target and the area beyond it” and “Never fling an instrument straight up into the air”).

Dr. Ferner and Dr. Aronson considered holiday foods, for example, but their tastes were not in concert. “He likes sweet wines and I like dry wines,” Dr. Ferner explained. Then they found common cause: ”But we both like dry humor.”…

They winnowed down the papers that mentioned laughter to 785, putting them into three categories: benefits (85), harms (114) and conditions causing pathological laughter (586).

The question was timely, they argue, because BMJ had not addressed laughter in a serious fashion in over a century. In 1898, it had published a case study of heart failure in a 13-year-old girl following prolonged laughter. The next year, the laughter problem was raised again, when an editorial writer, in response to an Italian doctor’s suggestion that telling jokes could treat bronchitis, dismissively proposed the term “gelototherapy” (Gelos was the Greek god of laughter; in Italian, gelato is ice cream.)…

The harms, however, have been scrutinized. A 1997 discussion of Boerhaave’s syndrome, a spontaneous perforation of the esophagus, a rare though potentially lethal event, mentioned that one unusual precipitating cause is laughter.

Then there is the mysterious Pilgaard-Dahl syndrome, identified in a 2010 article  as a pneumothorax in middle-aged male smokers induced by laughter. It takes its name from Ulf Pilgaard and Lisbet Dahl, the Danish revue performers….

There were other respiratory threats occasioned by laughter, he said. The popping of alveoli (the air sacs in the lungs, which together typically contain about 600 million):  “If you’re going to make asthmatics laugh heartily,” Dr. Ferner said, “they might want to have an inhaler by their side.” (This, extrapolated from a 1936 experiment on the mechanism of laughter in asthmatics.)

There are choking hazards, such as ingesting food during belly laughs.

The MIRTH review did take an even-handed, cost-benefit approach to laughter, noting ample evidence of its salutary effects. It concluded that laughter’s benefits included reduced anger, anxiety and stress; reduced cardiovascular tension, blood glucose concentration and risk of myocardial infarction. “The benefit-harm balance,” the authors wrote, “is probably favourable.”

Studies in recent years concluded that laughter “reduces arterial wall stiffness” and “improves endothelial function.” And a 2008 study of patients with chronic obstructive pulmonary disease concluded that laughter inspired by Pello the clown improved lung function….

Despite such a comprehensive look at the medical literature on laughter, Dr. Ferner felt there was still territory to be charted. “We don’t know how much laughter is safe,” he said. “There’s probably a U-shaped curve: laughter is good for you, but enormous amounts are bad, perhaps. It’s not a problem in England.”

When to Screen Patients Taking Ondansetron (Zofran)

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A recent study indicates that a single oral dose of ondansetron (Zofran®) is safe.

This excerpt from Eric Benchimol’s twitter feed: ow.ly/rBaV0:

New research from The Hospital for Sick Children (SickKids) and the University of Calgary’s Alberta Children’s Hospital Research Institute helps to clarify the actual risk of ondansetron administration and cardiac arrhythmias in both children and adults. The study is published in the December issue of Annals of Emergency Medicine. 

In 2011, the Food and Drug Administration notified health-care professionals and patients of an ongoing safety review and labelling changes for the anti-nausea drug linking its use to the possibility of inducing abnormal and potentially fatal arrhythmias.  The warning also implied that doctors needed to rule out conditions that might place patients at risk for developing an abnormal heart rhythm prior to giving patients the drug.  Screening all patients for such conditions requires ECG monitoring and blood testing, which are associated with discomfort, delayed care and may lead to additional unnecessary investigations and anxiety.  In 2012, the FDA issued an update linking the risk only to the administration of the drug in high doses intravenously. However, there was no change in the universal screening recommendations to all patients before receiving ondansetron, in any dose or route…

Through an in-depth post-marketing analysis which included a systematic review of published literature, the FDA Adverse Events Reporting System and the World Health Organization Individual Safety Case Reports Database, Drs. Yaron Finkelstein and Stephen Freedman explored this association. They did not find any reports of arrhythmia related to the administration of a single oral dose of ondansetron, the most common administration route, employed in over 85 per cent of doses given to children in emergency departments…

The study’s principal investigator, Dr. Yaron Finkelstein, staff physician in Paediatric Emergency Medicine and Clinical Pharmacology and Toxicology and Associate Scientist at SickKids. “Despite more than 22 years of use and hundreds of millions of ondansetron doses administered worldwide, we did not find evidence to support screening of patients without known risk factors before administering a single oral ondansetron dose.” 

Bottomline:  “The authors concluded that ECG screening and electrolyte testing should be targeted to patients with known risk factors such as patients with cardiac diseases or those concomitantly receiving other arrhythmia-inducing medications and those receiving ondansetron intravenously or repeated doses, while it is not warranted in low-risk individuals who are receiving a single oral dose.”

Related blog post: A drug that makes a difference: ondansetron | gutsandgrowth