Author Archives: gutsandgrowth

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About gutsandgrowth

I am a pediatric gastroenterologist at GI Care for Kids (previously called CCDHC) in Atlanta, Georgia. The goal of my blog is to share some of my reading in my field more broadly. In addition, I wanted to provide my voice to a wide range of topics that often have inaccurate or incomplete information. Before starting this blog in 2011, I would tear out articles from journals and/or keep notes in a palm pilot. This blog helps provide an updated source of information that is easy to access and search, along with links to useful multimedia sources. I was born and raised in Chattanooga. After graduating from the University of Virginia, I attended Baylor College of Medicine. I completed residency and fellowship training at the University of Cincinnati at the Children’s Hospital Medical Center. I received funding from the National Institutes of Health for molecular biology research of the gastrointestinal tract. During my fellowship, I had the opportunity to work with some of the most amazing pediatric gastroenterologists and mentors. Some of these individuals included Mitchell Cohen, William Balistreri, James Heubi, Jorge Bezerra, Colin Rudolph, John Bucuvalas, and Michael Farrell. I am grateful for their teaching and their friendship. During my training with their help, I received a nationwide award for the best research by a GI fellow. I have authored numerous publications/presentations including original research, case reports, review articles, and textbook chapters on various pediatric gastrointestinal problems. In addition, I have been recognized by Atlanta Magazine as a "Top Doctor" in my field multiple times. Currently, I am the vice chair of the section of nutrition for the Georgia Chapter of the American Academy of Pediatrics. In addition, I am an adjunct Associate Clinical Professor of Pediatrics at Emory University School of Medicine. Other society memberships have included the North American Society for Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN), American Academy of Pediatrics, the Food Allergy Network, the American Gastroenterology Association, the American Association for the Study of Liver Diseases, and the Crohn’s and Colitis Foundation. As part of a national pediatric GI organization called NASPGHAN (and its affiliated website GIKids), I have helped develop educational materials on a wide-range of gastrointestinal and liver diseases which are used across the country. Also, I have been an invited speaker for national campaigns to improve the evaluation and treatment of gastroesophageal reflux disease, celiac disease, eosinophilic esophagitis, hepatitis C, and inflammatory bowel disease (IBD). Some information on these topics has been posted at my work website, www.gicareforkids.com, which has links to multiple other useful resources. I am fortunate to work at GI Care For Kids. Our group has 17 terrific physicians with a wide range of subspecialization, including liver diseases, feeding disorders, eosinophilic diseases, inflammatory bowel disease, cystic fibrosis, DiGeorge/22q, celiac disease, and motility disorders. Many of our physicians are recognized nationally for their achievements. Our group of physicians have worked closely together for many years. None of the physicians in our group have ever left to join other groups. I have also worked with the same nurse (Bernadette) since I moved to Atlanta in 1997. For many families, more practical matters about our office include the following: – 14 office/satellite locations – physicians who speak Spanish – cutting edge research – on-site nutritionists – on-site psychology support for abdominal pain and feeding disorders – participation in ImproveCareNow to better the outcomes for children with inflammatory bowel disease – office endoscopy suite (lower costs and easier scheduling) – office infusion center (lower costs and easier for families) – easy access to nursing advice (each physician has at least one nurse) I am married and have two sons (both adults). I like to read, walk/hike, bike, swim, and play tennis with my free time. I do not have any financial relationships with pharmaceutical companies or other financial relationships to disclose. I have helped enroll patients in industry-sponsored research studies.

Positive Results for Probiotics in Latest Study of Colicy Infants

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While not all studies have demonstrated benefit of probiotics for infant colic, many have, particularly in breastfed infants.  The latest study (J Pediatr 2015; 166: 74-78) shows that “administration of L reuteri DSM 17938 significantly improved colic symptoms by reducing crying and fussing times in breastfed Canadian infants.”

This study was conducted between 2012-2014 and enrolled 52 infants.  These infants were randomized to either probiotics or placebo; the study was double-blind as well.

Key results:

  • For the 21 day study:  Total average crying and fussing times for probiotic group was 1719 ± 750 minutes compared with 2195 ± 764 minutes in the placebo group. (P=0.028)
  • At the end of the study, the probiotic group crying/fussing for 60 minutes per day compared with 102 minutes/day in the placebo group.  (P=0.045)

Take-home message: In breastfed infants, the probiotic L reuteri DSM 17938 reduced crying.

Related blog posts:

Neonatal Nutrition Lecture -What We Know Right Now

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A recent terrific lecture at Northside Hospital’s neonatology conference by Reese Clark highlighted what we know about neonatal nutrition and what we should be striving to achieve.  This blog entry has abbreviated/summarized this presentation. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.

Dr. Clark was willing to share slides from his talk and a related talk on necrotizing enterocolitis:

Here are a couple of key points from his talk regarding postnatal growth and feedings:

  • Every baby needs good nutrition.  While this is an obvious point, a lot of effort is focused on aspects of care needed in only a small number of neonates.
  • New target for weight gain in premature infants should be 20 gm/kg/day.  This growth is associated with better outcomes (Pediatrics 2006; 117: 1253 Ehrenkranz RA).  In this study, which controlled for a large number of variables, those in the top quartile of growth had much lower rates of cerebral palsy and neurologic impairments.  These improvements were also significant when comparing those in the top quartile to those in the 2nd and 3rd quartiles who were not sicker than those in the top quartile.
  • Most premature neonates are not achieving adequate growth with z-scores for weight and height lower at discharge from the NICU than their z-scores at birth. That is, despite advances in enteral and parenteral nutrition, premature neonates are falling behind while in the NICU. (Clark RH, et al. Pediatrics 2003; 111: 986)
  • Recognizing the supremacy of human milk has been the most important advance and has lead to much lower rates of necrotizing enterocolitis.  There is now a great case for exclusive human milk (J Pediatr 2013; 163: 1592-95; BMC Res Notes 2013; 6: 459)
  • With parenteral nutrition, higher amounts of amino acid have been associated with less issues with hyperglycemia. (Pediatrics 2007; 120: 12: 86-96; Pediatrics 2013; 163: 1278-82)
  • Insulin for hyperglycemia has been associated with poorer outcomes.
  • Does carnitine help with lipid metabolism? No one really knows –no randomized trials.
  • Continuous NG feeds are not associated with fewer signs/symptoms (e.g.. apnea, bradycardia, arching) than NG bolus feeds.
  • Acid suppression in neonates is not effective and potentially harmful
  • We need to use the best growth curves for premature infants: Fenton and Olsen growth charts

Since there are not going to be any trials randomizing neonates into groups assigned to poor growth, we will not know with certainty the impact of good nutrition on long-term outcomes.  Issues with reverse causation and selection bias make it difficult to know whether those with poor growth had other factors besides their nutritional plan which contributed to their outcomes.

Bottomline: We need to continue to optimize nutrition in premature infants; this includes using human milk and preventing necrotizing enterocolitis (which includes avoid acid blockers).  Our goal should be to have infants leave the NICU better nourished than when they arrived.

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  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.

 

Infliximab -Low Response in Young Kids (7 years and younger) with IBD

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 JPGN 2014; 59: 758-62. The full abstract for this reference follows but the message from this retrospective study of 33 children is clear –a much smaller percentage of the youngest children respond to infliximab compared to older children, adolescents and adults. In the discussion, the authors note that younger children may need higher dosing to maintain good infliximab levels or the disease pathogenesis may be much different (eg. underlying immunodeficiency and different gene mutations).

Here’s the abstract (from JPGN twitter feed):

Background: Infliximab (IFX) is efficacious for induction and maintenance of remission in pediatric patients with moderate-to-severe inflammatory bowel disease (IBD). It has, however, not been studied in patients 7 years old and younger. Our aim was to characterize efficacy and safety of IFX therapy in this cohort.

Methods: This was a retrospective study of patients with IBD ages 7 years and younger, treated with IFX between 1999 and 2011. Medical records were reviewed for age of diagnosis, disease phenotype, therapy, surgery, IFX infusion dates, dose, and intervals. Outcome measures included physician global assessment, corticosteroid requirement, and adverse events.

Results: Thirty-three children (ages 2.4–7 years) were included. Twenty patients had Crohn disease, 4 had ulcerative colitis, and 9 had indeterminate colitis. Maintenance of IFX therapy at 1, 2, and 3 years was 36%, 18%, and 12%, respectively. Patients of age 5 years and younger had the lowest rates of maintenance of therapy at 25% at year 1, and 10% at years 2 and 3 combined. Nine percent of all of the patients demonstrated response measured by the physician global assessment and were steroid free at 1 year. There were 8 infusion reactions. There were no malignancies, serious infections, or deaths.

Conclusions: IFX demonstrated a modest response rate and a low steroid-sparing effect in patients with IBD 7 years old and younger. Although this is a limited study, there appears to be a trend for decreased sustained efficacy with IFX in this age group, particularly in children 5 years old and younger, when compared with the previously published literature in older children.

Arsenic in Rice –New Recommendations

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Over the last two years, there has been increased concern about arsenic in rice.  This has been addressed by consumer reports, the American Academy of Pediatrics (AAP), and is being looked into by the FDA.

Due to the concerns about arsenic in rice, the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) committee on nutrition has published a consensus statement (JPGN 2015; 60: 142-145).  Pediatric gastroenterologists and pediatricians need to familiarize themselves with the report and their recommendations.

Key points:

  • Inorganic arsenic is a carcinogen.
  • “Arsenic content in raw rice varies from 0.1 to 0.4 mg of inorganic arsenic/kg of dry mass.  Rice has a much higher arsenic level than that in other grains.”
  • “Brown rice contains higher concentrations of arsenic.”
  • There is increased inorganic arsenic in products made from rice bran such as rice drinks is much higher due to the concentration of arsenic in the bran layers.
  • “Traditionally in European adults, an average of 9g of rice is consumed daily compared with 300g/day in Asian diets.”
  • “In the US population, mean childhood (1-6 years of age) dietary intake of inorganic arsenic is 3.2 mcg per day”
  • Currently, in the UK, the Food Standards Agency recommends against substitution of breastmilk, formula, or cow’s milk formula by rice drinks up to 4.5 years of age;  in contrast, in Sweden, recommendations advise no rice-based drinks for children <6 years.

Committee Conclusions/Recommendations:

  • “Inorganic arsenic intake during childhood is likely to affect long-term health”
  • “There is a lack of published data on the amount of arsenic in rice protein-based infant formula”
  • Inorganic arsenic in childhood should be as low as possible and the content in dietary products needs to be regulated
  • Rice drinks should not be used in infants and young children
  • Inorganic arsenic exposure can be reduced by including a variety of grains such as oat, barley, wheat, and maize.
  • Rice protein-based infant formulas remain an option in those with cow’s milk protein allergy,,.”the potential risks should be considered”

This is a link to the full length article (available via JPGNonline twitter feed): JGPN “Arsenic in Rice: A Cause for Concern”

This topic has been addressed by Nutrition4Kids website as well. Nutrition4Kids FDA Studying Arsenic

Bottomline: If there is an impact of arsenic in rice on long-term health, it is unclear; the amounts of these exposures are tiny in most cases.  Yet, given the availability of alternatives to rice and rice-based drinks, some changes in practice (ie. adhering to these guidelines) may be worthwhile.

 

 

HCV: When to Spike the Ball

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When a team scores a touchdown in football, often one sees a player spike the ball in celebration.  The equivalent of spiking a ball rarely happens in medicine.  That being said, a recent study (Hepatology 2015; 61: 41-45) indicates that after treatment sofosbuvir regimens, you can celebrate if you have a sustained virological response (SVR) at 12 weeks (SVR12).

The authors conducted a retrospective review of five trials with 863 patients with HCV genotypes 1-6.  “Of the 779 patients with an SVR12, 777 (99.7%) also achieved an SVR24.” Of the patients who relapsed, most (77.6%) did so within 4 weeks of completing therapy.

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Top Physician Skill -Listening

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One physician I’ve worked with recalls a mother of a patient telling him, ‘I really wish my husband would listen the way you do.’  This particular physician replied, ‘Well, just pay him $100 every time you say something.’

While this mother had a good experience with her physician (despite the cost), not all physicians are listening enough.  Here’s a link to a NY Times article that discusses this problem: Doctor, Shut Up and Listen

Here’s an excerpt:

A doctor’s ability to explain, listen and empathize has a profound impact on a patient’s care. Yet, as one survey found, two out of every three patients are discharged from the hospital without even knowing their diagnosis. Another study discovered that in over 60 percent of cases, patients misunderstood directions after a visit to their doctor’s office. And on average, physicians wait just 18 seconds before interrupting patients’ narratives of their symptoms. Evidently, we have a long way to go….

Observation soon revealed that physicians introduced themselves on only about one in four occasions…

Brief, rushed physician encounters were common, with limited opportunity for questions. A lack of empathy was often apparent…

We developed a physician-training program, which involved mock patient interviews and assessment from the actor role-playing the patient. Over 250 physicians were trained using this technique. We also arranged for a “physician coach” to sit in on real patient interviews and provide feedback.

Over the next two years, patient satisfaction with doctors, as measured by a standard questionnaire, moved the hospital’s predicted score up in national rankings by a remarkable 40 percentile points.

My take: I wonder about the accuracy of the information presented in this article.  Despite this, the message is clear that patients want to make sure that physicians are listening to them.

Another NY Times article worth a glance: The Drugs That Companies Promote to Doctors Are Rarely Breakthroughs  One quote: If a drug is either the first to treat a disease or is much better than existing drugs, said Dr. Sidney Wolfe, the founder and now senior adviser to Public Citizen’s Health Research Group, “they ‘sell themselves’ on the merits of their unique benefits.”

Heavy Heart due to Obesity

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A recent study (J Pediatr 2014; 165: 1184-9) documents a “cardiometabolic phenotype” which indicates that obesity and metabolic disease exert effects at a young age.

Design: A cohort of 281 white children from Italy were carefully studied with antropometrics, lipids profiles, blood pressure, glucose, and echocardiography. Of these children, 105 were obese (mean age 11 years) and 105 were morbidly obese (mean age 12 years); 31 had normal weight and 40 were overweight.

Key findings:

  • Heart disease: 53 had eccentric left ventricular hypertrophy (LVH), 36 had concentric LV remodeling, 44 had concentric LVH, 148 had normal echocardiograms.
  • Children with concentric LVH exhibited the most severe metabolic disturbances (graphically demonstrated in Figure 1)

Bottomline: The authors conclude that “we have identified a “cardiometabolic phenotype” occurring early in life, characterized by concentric LVH, visceral obesity, high BP, high Tg/HDL-C, and high-normal FPG [fasting plasma glucose].  This result may be clinically relevant because, in adulthood, a concentric LV geometric pattern is associated with a greater risk of CV events.”

Yosemite

Yosemite

IBD Update January 2015 (Part 2)

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1. A retrospective study (Inflamm Bowel Dis 2014; 20: 2292-98) of 217 patients with inflammatory bowel disease(108 infliximab-treated, 109 adalimumab-treated) provides data which indicates that combination therapy (mainly with thiopurines) resulted in higher trough levels and lower antibodies to infliximab (ATI) than monotherapy in patients treated with infliximab (IFX).  This was not evident in the adalimumab (ADA)-treated patients. Overall, approximately 90% of study population had Crohn’s disease.

Key points from this study:

  • The majority of trough level/antidrug antibody levels were drawn due to loss of response.  This is a major limitation of this study.
  • Among IFX-treated patients, those with combination therapy had trough level of 7.5 mcg/mL compared with 4.6 mcg/mL.  In combination therapy patients, the incidence of ATIs was 5.7% compared with 29.8% in monotherapy patients.
  • According to this study, the dose of the immunomodulator (IM) did not significantly influence the infliximab trough level or antibody formation; that is, more than half of patients were receiving “suboptimal dosed IM” and their infliximab levels/ATIs were similar to those who were optimally-dosed.
  • Among those who were receiving combination therapy, the incidence of antibody formation was lower in IFX-treated patients who started IM concurrently with IFX compared with those in which IM was added subsequently.
  • There were many other limitations in this study, including the finding that 94% of monotherapy patients had received previous immunomodulator therapy.

Bottomline: This study suggests that combination therapy is beneficial for patients receiving infliximab (in agreement with the previous SONIC study) and may not be beneficial for patients receiving adalimumab; however, only a well-designed prospective study

2. Inflamm Bowel Dis 2014; 20: 2266-70.  This study with 749 patients from Sweden showed that a large number of inflammatory bowel disease patients did not receive with iron supplementation: “Only 46% of patients with anemia were treated with iron supplementation or blood transfusion.”  This study showed frequent persistence of anemia one year after diagnosis, especially in children. At time of diagnosis, 55% of children and 27% of adults had anemia and 28% and 16% at one year followup, respectively.

My take: Treatment of the underlying IBD, often helps anemia.  However, in some patients treating the anemia with iron may help improve symptoms as much or more than other aspects of treatment.

3. Inflamm Bowel Dis 2014; 20: 2433-49.  Reviews pain management approaches for patients with IBD. The article emphasizes how pain can be multifactoral and that opiod-induced hyperalgesia may worsen pain.

Related blog posts:

 

Bryce Canyon

Bryce Canyon

 

IBD Update January 2015 (Part 1)

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1. From the recent Advances in IBD Conference, Healio Gastroenterology reports on Dr. Baldassano’s update on PLEASE study which examined enteral nutrition in comparison to anti-TNF therapy.  Here’s the link: Enteral Nutrition Outcomes (Thanks to Kipp Ellsworth for this reference)

Here’s an excerpt:

Citing the findings from the Pediatric Longitudinal Study of Semi-Elemental Diet and Stool Microbiome (PLEASE), Baldassano demonstrated that greater mucosal healing was achieved in CD patients on exclusive enteral nutrition compared with partial enteral nutrition therapy. In this prospective cohort study, 38 children received enteral therapy with defined formula diet and 52 controls received anti-TNF-alpha therapy. The enteral nutrition group was further stratified to evaluate mucosal healing on a more restrictive diet; one subgroup received 80% to 90% of total caloric needs from enteral therapy, of which 14% achieved induction of remission at 8 weeks, the other subgroup received 90% to 100% of total caloric needs from enteral therapy, of which 45% achieved remission, and 62% of controls achieved remission.

2. NEJM 2014; 371: 2418-27. This is a case report of a 9-year-old with Crohn’s Disease and pulmonary nodules.  This report serves as a useful review.

3. Standardized use of fecal calprotectin (here’s the link -from KT Park’s Twitter feed):

Fecal calprotectin -use for identifying IBD and for identifying relapse risk

4. Inflamm Bowel Dis 2014; 20: 2247-59. Study examined factors associated with infliximab clearance.  Higher clearance noted with low albumin, high body weight, and the presence of antibodies to infliximab (ATI).  The authors note that higher concentrations with dose escalation are more likely when the dose interval was shortened than by increasing the administered dose.

5. Inflamm Bowel Dis 2014; 20: 2260-65. “Natural History of Perianal Crohn’s Disease After Fecal Diversion.”  Despite greater use of biologics, only 15 of 49 patients reestablished intestinal continuity between 2000-2011.  In this group of 15, only 5 remained reconnected and 3 of these 5 patients had procedures to control sepsis.  The likelihood of sustained intestinal continuity remains low in patients who have required a diverting procedure.

Related blog posts:

Sandy Springs, Georgia

Sandy Springs, Georgia

Miralax -More Scrutiny, Research Study

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A recent NY Times article is probably ‘required reading’ for all pediatric gastroenterologists, pediatricians, and family practitioners:

Here’s the link: Mirlax -Scrutiny for a Childhood Remedy

Here are some excerpts:

The [FDA] agency has asked a team of scientists in Philadelphia to look more closely at the active ingredient in Miralax and similar generic products, called polyethylene glycol 3350, or PEG 3350. While outlining the scope of the research, the agency also disclosed that its scientists had discovered trace amounts of two potential toxins in batches of Miralax tested six years ago.

The news is likely to surprise parents and some doctors.

“Every pediatric GI physician, I would guarantee you, has told a family this is a safe product,” said Dr. Kent C. Williams, a gastroenterologist at Nationwide Children’s Hospital in Columbus, Ohio. Now, he worries, “it may not be true.”

Doctors have long recommended these laxatives for their convenience and on the grounds that very little PEG 3350 is absorbed in the intestines. But the F.D.A. says there is little data on its absorption in children, especially the very young and chronically constipated. The agency never approved long-term daily use of the laxatives, even in adults….

Moreover, for years the F.D.A. has received occasional reports of tremors, tics and obsessive-compulsive behavior in children given laxatives containing PEG 3350. It is not known whether the laxatives are the cause….

The F.D.A. said that it had tested eight batches of Miralax and found tiny amounts of ethylene glycol (EG) and diethylene glycol (DEG), ingredients in antifreeze, in all of them. The agency said the toxins were impurities resulting from the manufacturing process.

Those tests were conducted in 2008..The agency again tested PEG 3350 laxatives from five makers in 2013, Mr. Ventura said. None had detectable amounts of EG or DEG. “The amounts were so low,” he added, and “complied with internationally recognized safety standards.”

Bottomline: The previous pediatric studies of Miralax that have been published have shown favorable benefits and not disclosed adverse effects.  It is difficult to exclude the possibility that there is a small subset of children in which Miralax results in adverse effects.  As with many medications, more pediatric data is needed.

Question: Will this or should this change how Miralax is discussed with families?

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