Pacifiers & Reflux in Preterm Infants Plus Swallow Syncope

Posted on May 14, 2016 by gutsandgrowth

In a crossover study (J Pediatr 2016; 172: 205-8) with 30 preterm infants (adjusted age 33 weeks at time of study) showed that non-nutritive sucking with a pacifier had no effect on acid and nonacid gastroesophageal reflux based on esophageal pH-impedance.

My take: It is good that sucking a pacifier did not effect reflux. What would the authors have proposed if it had?

Another curious report: “Syncope with Swallowing” J Pediatr 2016; 172: 209-11. Case report of a teenager who had syncope with drinking and eating along with atrial septal defect; after repair of ASD, the symptoms persisted and ultimately the patient had a pacemaker placed due to an exaggerated vagoglossopharyngeal reflex leading to high-grade AV block.

Gibbs Gardens

Why a Diet History Can Be Helpful

Posted on May 13, 2016 by gutsandgrowth

A recent clinical problem-solving case report (D Hafez, et al. NEJM 2016; 374: 1369-74) highlights why a dietary history is important. The initial paragraph indicated that a 2 year old with delayed speech and a picky eater presented with a 6 week history of progressive inability to bear weight.

The authors of this report explained the entire sequence of diagnosis which included extensive studies like bloodwork, radiographs, MRI, and bone marrow biopsy. The last paragraph indicates that finally someone asked about the child’s diet: “approximately 1.4 liters of chocolate milk and ate two to four graham crackers per day. His mother acknowledged that these items were the mainstay of his diet.”

It turns out that the patient had vitamin C deficiency causing scurvy. “Unfortunately, a comprehensive dietary review was performed only after an exhaustive and costly workup had been pursued.” Personally, if I were involved in such a case, I would be embarrassed if it were published.

My take: While scurvy is interesting and rare in this country, the broader lesson of this report is to get a better dietary history before pursuing a huge workup.

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Gibbs Gardens

What happens when anti-TNF therapy is stopped

Posted on May 12, 2016 by gutsandgrowth

Another study (NA Kennedy et al. Aliment Pharmacol Ther 2016; 43: 910-23) has examined the issue of outcomes after anti-TNF therapy withdrawal among patients with inflammatory bowel disease.

This study included 166 UK patient cohort (117 with Crohn’s disease [median 31 yrs], 19 with ulcerative colitis [median 40 years]) as part of a retrospective observational study and a meta-analysis incorporating 11 further cohorts totalling 746 patients (624 with Crohn’s dissease, 122 with ulcerative colitis).

Key findings:

In the UK cohort, relapse rates were 36% at year and 56% at 2 years for Crohn’s disease
In the UK cohort, relapse rates were 42% at year and 47% at 2 years for ulcerative colitis
Increased relapse rates were noted for those with a diagnosis prior to age 22 years (hazard ratio (HR) 2.78), calprotectin >50 mcg/g (HR 2.95).
In meta-analysis, 1-year relapse rates were 39% for CD and 35% for UC/IBDU patients
Retreatment with anti-TNF was successful in 88% for CD and 76% of UC/IBDU patients

To understand this study, it is important to note some of the study criteria. In the UK cohort, inclusion criteria required the patient to have had at least 12 months of ant-TNF therapy and be in corticosteroid-remission for at least 6 months. In addition, the relapse rate is likely to be underestimated due to using a definition of relapse that required either commencement of steroids, immunomodulator or anti-TNF therapy. The meta-anlaysis cohort studies also used clinical relapse rather than endoscopic or other objective markers.

My take: Relapse of clinical symptoms occur in about 40% after withdrawal in highly-selected groups who were doing well prior. Significantly higher rates of endoscopic relapse are likely. This study provides strong reasons for not interrupting therapy when it is working.

The “EAT” Study

Posted on May 11, 2016 by gutsandgrowth

A recent study from MR Perkin et al (NEJM 2016; 374: 1733-43) examined whether early introduction (3 months) of allergenic foods in 1303 infants lowered the rate of allergies to these foods at 3 years of life compared to standard introduction (after 6 months). The six foods: peanut, egg, cow’s milk, sesame, whitefish, and wheat.

This EAT study (“Enquiring about Tolerance”) required parents in the intervention group to give 3 rounded teaspoons of smooth peanut butter, one small egg, two portions (40-60 g) of cow’s milk yogurt, 3 teaspoons of sesame paste, 24 g of white fish, and two wheat-based cereal biscuits every week.

While the study did not reach a statistical significance, the absolute rate of allergies was modestly lower in those in the early introduction group (5.6% compared with 7.1%). In a per-protocol analysis of those who strictly adhered to the assigned treatment regimen, there was an even lower rate of 2.4% (compared to 7.3% in the standard group). The associated editorial (pg 1783-84) indicates that the demanding protocol limited those who adhered to the protocol and points out that those who were not adherent could have been due to reverse causation (eg. subtle avoidance to certain foods due to reactions). The editorial conclusion: “evidence is building that early consumption rather than delayed introduction of foods is likely to be more beneficial as a strategy for the primary prevention of food allergy.”

My take: Early introduction of allergenic solids at ~3 months of age probably lowers the risk of developing allergies to these foods.

Here’s a link to <2 minute quick take summary: The EAT Study NEJM

Reference on consensus for guidance on introducing peanuts: J Allergy Clin Immunol 2015; 136: 258-61.

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Antibiotic Overuse and Allergic Antibiotic Challenge

Posted on May 10, 2016 by gutsandgrowth

A recent study by Fleming-Dutra K et al (JAMA, May 2016), that has been widely reported, estimates that 1 in 3 antibiotic prescriptions in U.S. are unnecessary. Here’s a CDC media release link: CDC: 1 in 3 antibiotic prescriptions unnecessary

“About 44 percent of outpatient antibiotic prescriptions are written to treat patients with acute respiratory conditions, such as sinus infections, middle ear infections, pharyngitis, viral upper respiratory infections (i.e., the common cold), bronchitis, bronchiolitis, asthma, allergies, influenza, and pneumonia. An estimated half of these outpatient prescriptions are unnecessary.”

Some of the downside of unnecessary antibiotics:

Allergic reactions and other adverse reactions
Infections become more difficult to treat due to increased resistance
Expense
Clostridium difficile infection

My take: This study’s findings are NOT surprising. Antibiotics are often prescribed without a clear indication.

Many children are labelled allergic to antibiotics like amoxicillin due to the development of a rash but have not undergone formal evaluation. However, a recent study (Mill C et al. JAMA Pediatr 2016 Apr 4) shows that an oral provocative challenge that most will be able to tolerate amoxicillin. Here is a summary of the article by DocAlert (forwarded to me by Mike Hart) -I highlighted in bold the key finding:

In an observational study, researchers offered a graded oral provocation test to all children referred to an allergy clinic in Montreal with suspected allergy to amoxicillin. Children were given 10% of the therapeutic dose of amoxicillin, observed for 20 minutes, then given 90% of the therapeutic dose and observed for at least 1 hour. Parents were instructed to report reactions that occurred the next week.

Of 818 participants (mean age, 1.7 years), 94% tolerated the provocation test and therefore were not allergic to amoxicillin. Of the others, 2% had immediate reactions (within 1 hour of the last dose) — all mild urticaria that resolved with antihistamines — and 4% had nonimmediate reactions (median of 12 hours after the last dose) — all mild maculopapular rash. Only 1 of the 17 children with immediate reactions tested positive on skin prick and intradermal testing 2 to 3 months later.

History of a rash lasting longer than 7 days and parental history of drug allergy were associated with nonimmediate reactions on the provocation test (adjusted odds ratios, 5 and 3, respectively); history of allergic reaction within 5 minutes was associated with immediate reactions (AOR, 10). During 3-year follow-up of children who tolerated the test, 55 received a subsequent full course of amoxicillin and 6 (11%) had nonimmediate reactions. All patients with reactions to amoxicillin tolerated cefixime.

My take (from summary): An oral provocation challenge to confirm either an immediate or nonimmediate allergic reaction to amoxicillin was found to be safe and more accurate than skin testing.

How Likely is Reflux in Infants with “Reflux-like” Behaviors?

Posted on May 9, 2016 by gutsandgrowth

Another study (Funderburk et al. JPGN 2016; 62: 556-61) has shown that gastroesophageal reflux disease is infrequent in infants with a “strong clinical suspicion for reflux.” This is a good to know since we also know that pharmacologic therapy for gastroesophageal reflux has not been proven to be effective in infancy either.

This retrospective study with 58 infants, including 40 preterm infants, evaluated for GERD with MII-pH studies. Characteristics of cohort: median gestational age 31 weeks, median birth wt 1683 gm, and median age at study: 70 days. 10 patients were receiving acid suppression therapy.

Indications for testing:

Irritability 55%
Bradycardia 34%
Desaturation 31%
Cough 21%
Gagging 12%
Difficulty feeding 12%
Arching 10%
Apnea 5%

Key findings:

Only 6 infants (~10%) had abnormal MII-pH studies (defined as >95th percentile for reflux episodes/hours or >95th percentile for acid exposure time)
None of the symptom indices correlated with symptoms. SI, SSI, or SAP
The majority of reflux episodes did not correlate with clinical “reflux” behaviors
Small bore (5 Fr) NG tubes were not associated with increased reflux.

In the related commentary by Rachel Rosen (pgs 517-18), she noted that “there is little to no evidence to show that the 3 indices predict any meaningful clinical outcome…including response to fundoplication, or medications.” “The current literature fails to support the use of symptom indices to prove causality when resolution of symptoms with medical or surgical therapies is used as the criterion standard.”

My take: The vast majority of infants with “reflux behaviors” do not have reflux. Even if they do, current pharmacologic therapies have not been shown to work. So, there is little value in reflux testing in most infants. Finally, given the failure of symptom indices, does the addition of the impedance data to the pH data add any value?

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Jerusalem Collage -Made from hundreds of postcards. Vik Muniz

Jerusalem Collage -Made from hundreds of pictures/postcards. Look closely -it’s amazing. by Vik Muniz

Another Rare Cause of Neonatal Diarrhea

Posted on May 8, 2016 by gutsandgrowth

A well-described case report (B Harter et al. JPGN 2016; 62: 577-80) provides a description of proprotein convertase 1/3 (PC1/3) deficiency. To date, only 21 cases have been reported.

Clinical features: congenital diarrhea and polyuria; normal endoscopy/histology. This patient required parenteral nutrition until 11 months of age. Her polyuria resolved at 13 months of age. Low serum levels of c-peptide and insulin along with elevated pro-insulin, combined with the polyuria, were suspicious for PC1/3 deficiency. This patient’s diagnosis was established with genetic analysis of the PCSK1 gene.

PC1/3 is responsible for peptide hormone processing in endocrine cells in the gut, and has targets in the hypothalamus and pancreas. Growth hormone deficiency, adrenal insufficiency, diabetes insipidus, and hypogonadism are commonly observed.

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Gibbs Gardens

Get Here If You Can: Improved Vitamin D Status

Posted on May 7, 2016 by gutsandgrowth

“I don’t care how you get here
Just get here if you can”

–Oleta Adams, “Get Here”

A recent study (Kugathasan et al. JPGN 2016; 62: 252-8) reminded me of the aforementioned song lyrics. (Full lyrics: Get Here)

This randomized pilot study comparing two regimens for low Vitamin D levels (serum 25-OH Vit D <30 ng/mL). During a treatment period of 6 weeks, patients were randomized to treatment with Vitamin D3 (cholecalciferol) at 10,000 units or to 5,000 units per 10 kg per week. The maximum weekly dose in the first group was 50,000 units (IU) and the maximum dose in the latter group was 25,000 IU.

Both treatments were associated with improvement; in the higher dose group the mean serum level reached 49.2 whereas it was 41.5 in the lower dose group. Of note, this repletion effect was nearly lost by the 12-week followup.

Other points:

This study used Vitamin D3 (cholecalciferol) which has greater bioavailability than Vitamin D2 (ergocalciferol).
No serious adverse effects were noted. The study monitored Calcium, and parathyroid hormone concentrations.
The authors did not report any correlation with CRP values. This is important because other studies (Why Adding Vitamin D May Not Help IBD | gutsandgrowth)
have shown improvement in Vitamin D levels without vitamin D supplementation when underlying inflammation has been treated.

My take: This study shows that supplementation with Vitamin D is associated with improved levels –one can ‘get here’ with either regimen the authors studied. In those with low levels (not due to inflammation), it is likely that maintenance Vitamin D supplementation will be needed.

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Michigan Union, Ann Arbor

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Should Medical Marijuana Get a Free Pass?

Posted on May 6, 2016 by gutsandgrowth

In many states, including Georgia, medical marijuana has bypassed the rigorous Food and Drug Administration (FDA) approval process via state laws permitting its usage. A recent editorial (J Koliani-Pace, CA Siegel. Am J Gastroenterol 2016; 111: 161-62 -thx to Ben Gold for this reference) highlights the dilemma facing physicians with medical marijuana with regard to providing advice/approval for this treatment.

Key points:

12% of people aged 12 years or older report using cannabis in the past year.
For gastrointestinal illnesses, there is scant evidence effectiveness. There is some data indicating that it makes you feel better, but no data proving that there is objective improvement in conditions like Crohn’s disease.
Adverse effects require more research. “Approximately 9% of people who experiment with marijuana will become addicted.” Other concerns: increased car accidents, altered memory/judgment, hyperemesis syndrome, and respiratory effects. With increasing availability and increasing THC concentrations, there have been in an increase in emergency department visits related to usage.
Lack of quality control: various concentrations of THC and cannabinoids, different administration routes, contaminants.

My take: At least with GI illnesses, more studies are needed to determine whether medical marijuana should be recommended.

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Gibbs Gardens

Here’s Why Biologic Therapy for Crohn’s Helps Adolescents Grow

Posted on May 5, 2016 by gutsandgrowth

It is well-recognized that Crohn’s disease is associated with delays in the onset and progression of puberty with the potential for stunted growth, impaired bone accrual, and diminished quality of life.

Now, a study (MD DeBoer et al. J Pediatr 2016; 171: 146-52) shows that initiation of anti-tumor necrosis factor α (anti-TNFα) treatment results in a rapid increase in sex hormone and gonadotropin levels.

In 72 adolescents, this observational study followed levels of sex hormones, gonadotropin levels, dual-energy x-ray absorptiometry, along with cytokine/inflammatory markers at initiation of anti-TNFα therapy, at 10 weeks and at 12 months.

Key findings:

By week 10 , testosterone z scores in males increased from a median of -0.36 to 0.40 (P<0.05)
By week 10 , estradiol z scores in females increased from a median of -0.35 to -0.02 (P<0.01)

My take (from the authors): This study suggests that “systemic inflammation suppresses gonadotropin-stimulated production of sex hormones” and that treatment of this inflammation with anti-TNFα agents allows rapid resumption normal production.

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Law Quad, Univeristy of Michigan