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

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:

Training for Tomorrow

To those in the Pediatric GI community who follow this blog, particularly fellowship directors, I would urge you to have a forthright discussion about training in our field with your fellows.

After reading a recent NASPGHAN newsletter, I was concerned to find more than 110 first-year trainees (a significant increase over the last few years).  While some of these trainees have international origins and will return to their home countries, many others will be looking for job positions across the USA.  I personally think that the type of available job openings will be disappointing for many, though I recognize that “manpower” (is there a more politically correct word?) predictions have a poor track record.

My belief is that it is the ethical responsibility of each program to inform their applicants and their trainees of their potential job prospects. Ultimately, the number of pediatric gastroenterologists will adjust based on job openings and satisfaction along with other “market forces.”  Unfortunately, some in training may not be aware that their job prospects may be quite limited due to an overabundance of trainees.  Perhaps, trainees with specific niche area training such as neurogastroenterology or hepatology will have less difficulty.

The upside of the increase in trainees will be the availability of pediatric gastroenterologists to fill the spots repeatedly vacated by more senior physicians due to dissatisfaction.

My two cents…

IBD Update 2014 (part 2)

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)

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

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:

Could you recruit your patients to climb a mountain for research?

Amazingly, a group of investigators enrolled 25 healthy climbers to determine how hypoxia affects the expression of iron transporters in the duodenal mucosa (Hepatology 2013; 58: 2135-62).

Methods: In a nonblinded, prospective study, blood and duodenal samples were taken at three timepoints: baseline (446 meters) and at 4559 meters two days later after a rapid ascent and then at day four while remaining at high altitude. 14 subjects received dexamethasone on day 2 to avoid high-altitude sickness. The duodenal biopsies were obtained by unseated transnasal small-caliber duodenoscopy.  Numerous other assays were checked as well.

Key finding: Hypoxemia was associated with a 10-fold increase in duodenal expression of divalent metal-ion transporter 1 and ferroportin 1 which promote iron intake.  In addition, there was decreased serum hepcidin levels.

Take-home message: Hypoxic conditions such as high-altitude quickly lead to an activation of changes that lead to compensatory erythropoeisis.

Related blog post: Help with hepcidin | gutsandgrowth

Less Red Meat, More Anemia

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

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?

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.”