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.

Budesonide for Ulcerative Colitis

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Budesonide (Uceris) has been formulated with the MMX delivery technology and now has been FDA approved for mild to moderate ulcerative colitis in adults.  The potential advantage of budesonide compared with conventional corticosteroids is for targeting anti-inflammatory activity to the colon with less systemic side effects.  The potential downside includes the high cost.  According to one website (see below), the average wholesale cost is just below $1500 per month.  In addition, only a minority of individuals responded to budesonide in published studies:

Induction of Remission in Studies 1 and 2 (reference below)

Treatment Group

Study 1 n/N (%)

Study 2 n/N (%)

UCERIS 9 mg

22/123 (17.9)

19/109 (17.4)

UCERIS 6 mg

16/121 (13.2)

9/109 (8.3)

Reference Arm*

15/124 (12.1)

13/103 (12.6)

Placebo

9/121 (7.4)

4/89 (4.5)

Treatment Difference between UCERIS 9 mg and Placebo (95% CI)†

10.4% (2.2%, 18.7%)

12.9% (4.6%, 21.3%)

Data for budesonide for pediatric patients with ulcerative colitis is not available.

Ultrasound Unreliable to Exclude Fatty Liver

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More information on the sensitivity of ultrasonography for detecting fatty liver is available in the setting of living-related liver transplantation (Transplantation 2013; 95: DOI: 10.1097/TP.0b013e31828d1588).

In this study the authors retrospectively examined the degree of steatosis from 492 living liver donors who had normal ultrasounds and normal aminotransferase levels. The median age of the donors was 30.1 year and the median BMI was 22.4 kg/meter-squared.

Background: According to the authors, if liver histology shows severe macrosteatosis (>60%), transplantation is canceled.  Furthermore, in cases of moderate macrosteatosis (30-59%), the risks/benefits need to be considered on an individual basis due to increased risk of mortality; Spitzer et al (reference below) demonstrated that macrovesicular steatosis >30% was an independent predictor of reduced 1-year graft survival.  In addition, a previous report has indicated that both macrosteatosis and microsteatosis had similar impacts on postoperative  liver function.

Results:

  • 3 (0.6%) had severe total steatosis, moderate or greater steatosis was diagnosed in 4 (0.8%) for macrosteatosis, in 26 (5.3%) for microsteatosis, and 56 (11.4%) for total steatosis.
  • There were two identified risk factors BMI >23 kg/meter-squared and triglycerides >88 mg/dL.  Individuals with both risk factors had a 28.6% prevalence of moderate or greater degree of total steatosis compared with 6.6% with no risk factors.  In these individuals, a liver biopsy may be worthwhile.

Why this study matters for the non-transplant physician:  This study provides additional data that ultrasonography is not adequate to exclude significant degrees of fatty liver.

Study limitations included the retrospective analysis which relied on medical record accuracy, degree of steatosis was not based on a single pathologist, ultrasonography was not based on not based on a single radiologist, both BMI and triglycerides may vary based on age, gender, ethnicity and other factors.

Related blog entries:

Related references:

  • -Spitzer AL et al. Liver Transpl 2010; 16: 874-84.
  • -Liver Transpl 2013; 19: 437-49. Difficulty with precisely determining steatosis
  • -Hepatology 2011; 54: 1082.  U/S w ~85% sensitivity in detecting fatty liver.
  • -Gastroenterol 2008; 135: 1961.  Liver biopsy (in pediatrics) still needed as surrogates not accurate for correlating degree of fibrosis/injury.
  • -J Pediatr 2009; 155: 469.  Review.  No evidence-based guidelines for treating in pediatrics –main Rx wt loss/exercise.  Consider obtaining ultrasound.

Treatment of Short Stature

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While gastroenterology focuses more on being skinny than being short, understanding the current treatment approach to short stature is important.  Certainly, this is a common condition in a pediatric gastroenterology practice.  An update is available: NEJM 2013; 368: 1220-8.

This article presents the case of an 11-year-old with probable constitutional delay of growth and puberty (CDGP) who is projected to achieve an adult height of 5 ft 5 in.  It asks the question of the optimal management but does not answer this definitively.

Background:  Most children with short stature have either CDGP or familial short stature and are generally healthy.  The FDA has approved human growth hormone therapy for children with idiopathic short stature and height below the 1st percentile.  In the U.S. this amounts to more that 500,000 children (1% of children 4-13 years).  However, growth hormone is expensive $10,000-60,000 per year and achieves modest results, 1.2-2.8 inches in added final stature.

Key Recommendations:

  • Thorough evaluation of short stature especially if child’s height deficit is severe (<1st percentile for age), the growth rate is abnormal (<10% for bone age), predicted height is significantly different from midparental height, or body proportions are abnormal.
  • History of intrauterine growth retardation is important since 15% remain short throughout life.
  • Screening labs (according to the authors) include measurement of thyroid assays, checking for renal dysfunction (BUN, creatinine), assessing for inflammatory conditions (eg. sedimentation rate), checking tissue transglutaminase antibody, and assessing hematologic conditions (eg. complete blood count).  In addition, examination should look for evidence of Turner syndrome.
  • The authors discuss growth hormone testing.  IGF-1 serves as a screen but even provocative testing can miss mild cases of growth hormone deficiency.
  • Psychosocial well-being has not predictably improved with growth hormone treatment.
  • Treatment options: observation, growth hormone, or androgen use (eg. oxandrolone).  The latter will expedite growth but not significantly impact long-term height.

Are there risks to growth hormone therapy?

Yes.  There have been occurrences of intracranial hypertension, glucose intolerance, and slipped capital femoral epiphysis. The absolute risks are considered low.  Long-term risks are not entirely clear.  One study suggested a slight increased mortality rate with increased mortality from bone cancer and circulatory disorders.  A similar study did not confirm these findings.

What are the costs?

For idiopathic short stature, the cost has been estimated to be $35,000-50,000 per inch of height.

Who benefits the most?

Predictors of growth hormone response in idiopathic short stature include younger age at baseline, delay in skeletal maturation, and taller parents.  Also, daily administration achieves superior results to less frequent administration.

Related reference:

  • -J Clin Endocrinol Metab 2008; 93: 4210-7.  Consensus statement on the diagnosis and treatment of children with idiopathic short stature.

Hepatitis C Virus Sexual Transmission and Monogamy

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Numerous sources state that there is a low risk of transmitting Hepatitis C virus (HCV) among monogamous heterosexual couples.  More information on this subject has been published (Hepatology 2013; 57: 881-89).

In this study, 500 couples were studied; all were long-term heterosexual partners and all were HIV-negative.  The index partner was anti-HCV positive with a median age of 49 years and had a median of 15 years with their partner.  Condom use was infrequent among the study participants.

Key finding: HCV prevalence among partners was 4% (n=20) and ~2% (n=9) had concordant genotype/serotype.  The maximum prevalence of HCV transmission among these sexual partners was 1.2%.  Based on 8,377 person-years of follow-up, the maximum incidence rate of HCV transmission was reported as 0.07% per year or approximately one per 190,000 sexual contacts.

Some of the interesting aspects of the study included details of sexual activity and discussion of factors that may increase HCV transmission.  With regard to sexual activity, 30.4% of the couples reported prior anal intercourse and more than 90% reported oral sex (by both partners); however, both of these activities were reported as infrequent: typically 0 per month for anal intercourse and 3 contacts per month for oral sex.  With regard to HCV transmission, the authors did not identify any risk factors in the current study but did note that this may be influenced by viral titer, integrity of mucosal surfaces, and the presence of other infections.

Related blog posts:

Life Cut Short by Obesity

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When someone is too heavy, everyone knows that this is associated with numerous health risks.  A recent estimate on the amount of life lost due to obesity has been published (Obesity 2013; 21: 405-12).

Using data from the National Health and Nutrition Examination Survey (NHANES) I (1971-75), II (1976-80), and III (1988-94), the author was able to follow-up for 15 years and prospectively analyzed the data to calculate the relative risk of death and the “advancement period” of death due to obesity.  Stratification of death was adjusted for covariates including pre-existing illness, smoking, and older age.

The study focused on otherwise healthy nonsmokers to isolate the effects of obesity on mortality.  The averages of the cohorts was 46-48 years of age. While the author studied only 37,632 patients who had 8,791 deaths during the study, these results are relevant to about one-third of American adults.

Key finding: Compared to reference weight (BMI 23-25 kg/meter-squared), mortality was likely to occur 9.44 years earlier for those who were obese (BMI ≥ 30).

When the data was divided by weight, overweight (BMI 25-30 kg/meter-squared), mild obesity (BMI 30-35 kg/meter-squared), and obesity grades 2-3 (BMI >35 kg/meter-squared), the results were 4.40 years, 6.69 years, and 14.16 years respectively. The effect on advancement period mortality was less in older age groups (>55 years).

The main limitation of the study was its reliance on statistical analysis.  For those without a statistical background, Figure 2 which describes the mortality risk advancement period formula could as easily be written in Chinese.  Nevertheless, in the discussion the author underscores that these estimates are consistent with prior studies.

Related blog posts:

ADHD patients– not at increased risk for Celiac disease

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It seems that so many conditions have been linked to Celiac disease; perhaps, Celiac disease is to health problems as Kevin Bacon is to actors (Six Degrees of Kevin Bacon – Wikipedia, the free encyclopedia).  A notable exception may be ADHD (JPGN 2013; 56: 211-14).

In a prospective study from Turkey, a total 362 children between 5 and 15 years who were diagnosed with ADHD at a child psychiatry clinic (2007-2010) were evaluated.  Serum levels of tissue transglutaminase (TTG) IgA and IgG antibodies were obtained; serum IgA levels were determined in those with isolated TTG IgG positivity.  In addition, the authors identified a matched control group of 390 children.

Results:

  • TTG IgA seropositivity was noted in 4 patients with ADHD (1.1%) compared with 3 controls (0.8%).  Only one of the four ADHD patients had histologic evidence of celiac disease (0.27%).
  • There was a higher incidence of TTG IgG in the ADHD group, 3.9% compared with 0.5% in controls. However, serum IgA was normal in all of these patients (indicating that TTG IgA was likely reliable).  Followup TTG IgG testing was negative consistent with false positivity.

Perhaps this result is not surprising to those who have seen a ‘classic’ celiac disease presentation.  In these children who often had physical signs of malnutrition including a bloated abdomen, the effect of a gluten-free diet changed a “perfectly-behaved” (=listless) child into a very active toddler.  So, in these children, a gluten-free diet but not celiac disease triggered hyperactivity.

Related blog posts:

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Why Social Media is Important for Doctors

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The following link is to a NY Times article and below are a few excerpts:

http://well.blogs.nytimes.com/2013/03/21/doctors-and-their-online-reputation/?smid=tw-nytimeshealth&seid=auto

 “While most doctors have come to terms with the fact that their patients routinely go online for information about what ails them, they remain uneasy about a more recent trend: the Internet is quickly becoming the resource of choice for patients to connect with, learn more about and even rate their doctors. And while many have used Facebook, Twitter, LinkedIn or online medical community sites like Sermo to engage with friends and colleagues, few have communicated with patients as, well, doctors. Most abstain for one simple reason: they aren’t sure how to be a doctor online.”
The link discusses a new book by Kevin Pho (KevinMD) and Susan Gay.  “In“Establishing, Managing and Protecting Your Online Reputation: A Social Media Guide for Physicians and Medical Practices,” “Dr. Pho and Ms. Gay offer highly organized key points, useful statistics and exuberant testimonials from doctors who have successfully leapt over the digital divide. There is plenty of practical advice, too, on topics ranging from what to post and when to engage, confer or rebuff, to how to decide what might be unethical or T.M.I. (Answer: ‘Can you say it aloud in a full hospital elevator?”)The book is an excellent and helpful resource. But what elevates it beyond the category of valuable how-to manual is the passionate call to arms that resonates from all those well-enumerated directions and clearly labeled diagrams. Like it or not, the authors warn, the Internet has profoundly changed the patient-doctor relationship, and doctors must embrace its effects on patient care — or risk losing their own influence.'”The article also notes that on the internet many individuals without any scientific background may have equal footing with recognized experts.  Another subject broached in this article is the issue of ranking physicians.”The biggest risk of social media in health care,” they conclude, “is not using it at all.”
Related website resources:

The Difficulty with Drug Development

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Recent statistics from the pharmaceutical industry provide information about why it costs so much (1.2 billion dollars) to develop new medications.

  • Average time for experimental drug to go from lab to patients: 10-15 years
  • Only 5 in 5,000 compounds that enter preclinical testing make it to human testing
  • Only one of those five is approved for use in humans
  • Of approved drugs, only one in five makes more than the costs of development
  • FDA applications typically run more than 100,000 pages

Source: PhRMA Report 2012: Medicines in Development for Cancer

“I want a new drug …
One that don’t cost too much…
I want a new drug
One that does what it should
One that won’t make me feel too bad
One that won’t make me feel too good”

–Huey Lewis and the News: “I want a new drug”

Clostridium difficile in IBD

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A useful review of Clostridium difficile infection (CDI) in the inflammatory bowel disease population has been published and makes several useful points (Inflamm Bowel Dis 2013; 19: 194-204). (Thanks to Ben Gold for suggesting this reference.)

Key points:

  • The incidence of CDI in IBD patients is increasing (faster than general population).  The prevalence of CDI in IBD was nearly eight times greater than non-iBD gastrointestinal patients in a recent population-based study (37.3 cases vs. 4.8 cases per 1000 discharges).
  • Though there is some conflicting data, CDI appears to worsen both short- and long-term outcomes in IBD patients.
  • Carriage (asymptomatic) rates in outpatient IBD patients is higher than the general population (8.2% vs. 1%) according to a recent study.
  • Endoscopic appearance of CDI is rarely classic in the setting of IBD.  Only 13% of hospitalized IBD patients with CDI had pseudomembranes (J Crohns Colitis 2010; 4: 194-98).  Thus, endoscopy has little utility in helping to distinguish IBD flare from superimposed infection.
  • Unique IBD risk factors for CDI: colonic disease and steroid use.
  • The review has a thorough discussion of the available testing and recommends testing only patients with unformed stools unless an ileus is present.
  • For recurrent disease, the authors suggest prolonged tapered vancomycin in adults: 125 mg QID for 10-14 days, then 125 mg BID x 1 week, then 125 mg QD x 1 week, then 125 mg QOD for 2-8 weeks.  Alternative approaches could included fidaxomicin, IVIG/antibody therapy, and fecal transplantation.

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Fundoplication effects on esophageal motility

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Trying to decide whether a child should undergo a fundoplication is often quite difficult.  The best candidates with gastroesophageal reflux disease (GERD) don’t need surgery because medical treatment is usually effective.  Typical patients who fail medical treatments may have numerous comorbidities that could cause a complicated postoperative course or failure of the procedure.

One aspect about the surgery that has been questioned has been whether surgery causes dysmotility of the esophagus.  A recent article describes a study, which enrolled only ten children who had surgery; however, these patients underwent extensive preoperative and postoperative evaluations to try to provide more information about the motility effects of fundoplication (J Pediatr 2013; 162: 566-73).

Patients were considered for surgery if they had failed medical therapy. Four of the ten patients were neurologically-impaired. Testing included automated impedance manometry, 24-hour pH-impedance, gastric emptying breath test, and GERD questionnaires (though the authors note that GERD questionnaires are not validated in children aged 1-12 years).  Median patient age was 6.4 years, with a range of 1-17 years.

Surgery: laparascopic anterior partial fundoplication

Results:

  • 4 patients developed postoperative dysphagia, two patients had redo fundoplications (one due to dysphagia and one due to persistent emesis).
  • Postsurgery, GER measures were reduced.  Total number of acid reflux episodes dropped from an average of 37 to an average of 10.  Total GER (acid and nonacid) episodes dropped from an average of 97 to an average of 66.  The percentage of time with pH<4 dropped as well from an average of 12.5% to an average of 3.1%.
  • Average gastric emptying time was unchanged: 64 minutes pre surgery and 63 minutes post surgery.
  • Conventional esophageal motility measures/peristaltic contractions were unaltered.  However, patients with postoperative dysphagia had longer gastric emptying times compared with those who did not develop postoperative dysphagia.

Related blog posts:

The Medical Pendulum and Gastroesophageal Reflux | gutsandgrowth

Gastroesophageal Reflux: I know it when I see it | gutsandgrowth

Related references:

  • -Gastroenterology 2011; 141: 1938 LOTUS study in JAMA summarized. JAMA 2011; 305: 1969. Medical rx outperformed surgery. 92% under control (remission) with long-term medical Rx vs 85% with surgery & fewer side effects of medical Rx.
  • -Clin Gastro & Hepatology 2009; 7: 1292, 1264 (editorial). 12 yr outcomes for surgery vs PPI. n=154 omeprazole, n=144 surgery. Similar long-term outcome ~50% with long-term remission.
  • -JPGN 2010; 50: 25. Reflux detected by impedance does NOT determine fundoplication outcome. n=34.
  • -JPGN 2006; 43: 185.  Effect of fundo: no change in  gastric motor activity & increased discomfort with distention
  • -Pediatrics 2006; 118: 2326. n=1142. Fundoplication decreased hospitalization rates for children <4yrs; in older children with developmental delay, there were increased hospitalization rates after fundoplication. (47% had no hospitalizations prior to fundoplication.)
  • -Clin Gastro & Hep 2004; 2: 978-984. Gilger et al. n=198. 63% required p-op medical treatment for recurrent GERD -retrospective review 1996-99.
  • -J Pediatrics 2011; 159: 597. Hypoglycemia (likely due to dumping) was common post-op. n=285. 24% of screened children with low glucose (only 1.3%of those without formal screening). 2/3rds with hypoglycemia had preceding hyperglycemia. Only 53% had dumping symptoms.  Many in this cohort were NICU pts -~1/3rd of pts had mean age of 3months & another ~1/3rd with mean age of 6months.Rx often was continuous feeds.
  • -Pediatrics 2006; 118:1828. 48,665 antireflux surgeries done from 1996-2003 (~7000/yr) in US
  • -Clin Gastro & Hep 2006; 4: 299. Frequent complications p-op and frequent need for GERD meds. dysphagia in 19%, dilation in 6%, repeat surgery in 2%, mortality in 0.8% (n=3145). 50% required GERD meds.
  • -Gastroenterology 2001; 121: 5-14 & 214.  Dysmotility with GER reflects severe disease & is present ~30%. According to this study, dysmotility does not affect postoperative outcome, is not corrected by fundoplication, may occur p-op, and requires no tailoring of surgical mgt.