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.

Implementing High-Value Care

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A recent commentary (NEJM 2014; 371: 2145-47) describes some early successes and failures with efforts at “getting more performance from performance measurement.”

The authors note that “the current measurement paradigm..does not live up to its potential.”  There have been a proliferation of measurements “without commensurate results.”

Areas of progress:

Reducing hospital readmissions: “national readmission rates, which hovered around 19% between 2007 and 2011, had dropped to approximately 17.5% by 2013…recent research suggests that the measured decrease resulted from actual changes in care and not simply greater use of observation units or emergency department care.”

Rates of early elective deliveries: “the rate of early elective deliveries had stayed fixed for many years, even though there was evidence that the practice led to a greater need for neonatal intensive care, higher risks of maternal and neonatal complications, and health problems later in the children’s lives…the rates of early deliveries fell from 17% in 2010 to 4.6% in 2013 (www.leapfroggroup.org/tooearlydeliveries)”  This change happened due metrics in pay-for-performance or not paying for such deliveries along with educational efforts.

Areas Were Not Helpful (aka The Road Paved with Good Intentions)

“Unfortunately, for every instance in which performance initiatives improved care, there were cases …[that] simply enraged colleagues or inspired expenditures that produced no care improvements.”

Early Antibiotics for Community-Acquired Pneumonia:  Due to data suggesting that antibiotics within 6 hours of presentation positively influenced the outcome of community-acquired pneumonia (i.e. lower in-hospital mortality), this became a Centers for Medicare and Medicaid Services (CMS) metric.  “The measure led to inappropriate antibiotic use in patients without community-acquired pneumonia, had adverse consequences such as Clostridium difficile colitis, and did not reduce mortality.”

Bottomline: More work is needed to avoid needless busy work and improve patient outcomes.

As quoted in a previous blog entry:

“Not everything that counts can be counted, and not everything that can be counted counts.” –Albert Einstein

2015 Wish List

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A recent policy article (JAMA Pediatr 2014; 168: 1155-63 –thanks to Ben Gold for this reference) outlines “10 urgent priorities for the health and health care of US children.”  These priorities and some of the action steps are as follows:

  1. Poverty: “16.1 million children (22%) live in poverty. ” Action steps include enacting measures to improve employment in families and extending child tax credits.
  2. Food Insufficiency: “>16 million children live in food-insecure homes.” Actions could include investing rather than cutting children’s nutrition programs.
  3. Lack of health insurance: affects “7 million children (9%)” though two-thirds are eligible for coverage by Medicaid and CHIP. Actions could include fully funding CHOP and Medicaid and abolishing ACA family glitch along with improving outreach to enroll eligible children.
  4. Child abuse/neglect (maltreatment): “In 2011, 681,000 children experienced maltreatment and 1570 died” as a consequence.  Everyday, a child is abused or neglected every 47 seconds.  Action steps included focusing on domestic violence and treatment and funding more screening and preventative treatment research.
  5. Obesity: “32% of children are overweight and 17% are obese.”  Actions could include passing FIT kids Act (HR 2178) and maximizing funding for USDA’s Farmers market promotion program and the Fresh fruit and vegetable program.
  6. Firearms deaths/injuries: 5 children die daily by firearms.  Actions could include better background checks, along with regulations to require safer storage and safety classes.  Other options include higher taxation on weaponry and ammunition to “better represent societal costs.”
  7. Racial disparities: Action steps include monitoring and disclosing disparities and working to ensure all children have a medical home.
  8. Mental Health: up to 20% of children experience a mental health disorder annually.  Actions could include increasing the number of qualified mental-health providers (by enhancing reimbursement).
  9. Immigration: “children living in immigrant families are the fastest growing group of US children.” Action could include obtain health insurance for all children.
  10. Research: Increase funding for children.  Overall NIH pediatric funding is 12% of total budget whereas children represent 24% of US population.

The problems faced by this nation’s children will reverberate for a long time.  For example, with childhood poverty, it is “associated with substantially higher mortality rates in adults, regardless of adult socioeconomic status (i.e., even affluent adults who were poor as children have elevated death rates), and this increased mortality risk extends across 2 generations.”

Bottomline: Children receive a disproportionately low share of federal expenditures and this extends to healthcare.  In addition, federal spending on children in 2014 has decreased by more than $20 billion (14%) since 2010.

Blog post:

Can an Altered Microbiome Explain Persistent Symptoms in Treated Celiac Disease?

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A recent study (Am J Gastroenterol dii:10.1038/ajg.2014.355) from Helsinki examined 177 patients with celiac disease.  Their goal was to investigate whether altered intestinal microbiota may be associated with persisting gastrointestinal symptoms in celiac patients who had been following a strict gluten-free diet (GFD) for at least 3 years.

After administering a questionnaire (Gastrointestinal Symptom Rating Scale or GSRS) to those with negative celiac antibodies and normal small bowel mucosa (n=164), the researchers identified the 18 subjects with the highest total score (persistent symptom group) and compared them to the 18 subjects with the lowest total score.  Three duodenal biopsies during endoscopy had been frozen and were subsequently analyzed for their microbial DNA.  In each group, one microbial profile was unsuccessful.

Key findings:

  • In the persistent symptom group, there was lower relative abundance of Bacteroidetes (15% vs. 25%, P=0.01), lower Firmicutes (33% vs 46%, P=0.05) and higher relative abundance of Proteobacteria (40% vs 21%, P=0.04).
  • The “microbial richness,” measured as a number of detected genera or operational taxonomic units (OTUs), was reduced in patients with persistent symptoms.  On average, patients with persistent symptoms had 32 genera and 72 OTUs per sample; in contrast, those without symptoms, on average had 37 genera and 106 OTUs.

Some of the strengths of this study include the normal villous architecture for all of the patients; this helps exclude refractory celiac disease as an etiology for the persistent symptoms.  In the discussion, the authors note that the “intestinal microbiota composition in healthy adults is relatively stable and can tolerate normal stress in the intestine caused by, e.g. daily changes in diet.” The speculate that long-term untreated celiac disease “may disrupt a stable intestinal microbiota community that, in some patients, could then reform in a dysbiotic state.”

The limitations of this study include the difficulty of excluding small intestinal bacterial overgrowth which could be related and the difficulty of excluding coexisting irritable bowel syndrome.  Like most studies regarding the micro biome, this study cannot “show causality or distinguish the effects of different bacteria to the persistent symptoms.”

Bottomline: Treated celiac patients with persistent symptoms have a different duodenal microbiome compared to treated celiac patients whose symptoms resolved with a gluten-free diet.

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Moving to MRE

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A recent review (JPGN 2014; 59: 429-39) regarding imaging for inflammatory bowel disease reiterates the accepted view that magnetic resonance enterography (MRE) is typically the most useful imaging test for children with inflammatory bowel disease; in Table 5, MRE is listed for each indication, though CT scan is recommended “if emergent or after hours.”  The review reviews prior pediatric publications, radiation risks (with non-MRE studies), and alternative imaging.  The discussion on costs is minimized, though the authors note that MRE is the most expensive and can be compromised by motion artifact. As a practical matter, I think giving a typical charge (or range) for each of the imaging techniques would be helpful.  Also, another important issue is assuring that radiologists have the technical expertise to obtain quality imaging.

Another study (Clin Gastroenterol Hepatol 2014; 12: 1702-07) retrospectively looked at 1095 emergency room visits by 613 individuals (average age ~40 years) to determine if they could develop a model to limit unnecessary CT scans.  Of the 1095 CT scans, 24.8% were normal; 10.9% had either perforation or non-perianal abscess.  In their discussion, they note that the equation “no scan for ESR (mm/h) + 5*CRP (mg/dL) ≤10” would avoid 18.5% of CT scans.  Implementation of a more complex model could eliminate up to 43% of the CT scans.  The algorithm (Figure 2) suggested by the authors:

  • Assess for obstruction.  If suggestive symptoms, obtain abdominal X-rays.  If concerns for obstruction remain, consider CT scan.
  • If not concerned about obstruction, is there a high likelihood of perforation or abscess? If yes proceed with CT scan.  If not, consider anti-inflammatory therapy if CD symptoms present (without imaging).

Here’s the link to the abstract –supplementary materials can be obtained by those who log in.   http://dx.doi.org/10.1016/j.cgh.2014.02.036

Bottomline: Cross-sectional imaging is particularly helpful at determining whether complications are developing in patients with inflammatory bowel disease.  Increasing use of MRE will reduce radiation risks.

With regard to costs, a recent NPR story discussed “How Much Is That MRI, Really? Massachusetts Shines A Light.” While this story discussed costs related to a Massachusetts law which mandates that insurers reveal the costs of various tests, it did not relate any information regarding quality.  The study implied that an MRI at one institution would be equivalent to an MRI at another.  This is not the case.

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Sorting Out Discrepancies in Hepatitis B Testing

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A recent study (J Pediatrics 2014; 165: 773-8) highlighted the clinical problem of discrepant hepatitis B virus (HBV) testing in pregnant women.

Design: The Centers for Disease Control and Prevention analyzed a nonrandom sample of discordant cases of HBV reported by US Perinatal Hepatitis B Prevention Program.  Discordant cases indicated that there were differences between an initial HBsAg result and a subsequent test.  Among 142 cases, 89 had sufficient information to determine accuracy of the initial test.

Key finding: 14 (15.7%) of these cases were true positives, the remainders were false-positives.

How did authors sort out cases?

Negative testing for “total anti-HBc or no detectable HBV DNA result indicating no HBV infection…A positive total anti-HBc indicates current or past HBV infection, is not elicited by vaccination, and usually persists for life.”

Pointers regarding serology:

  • IgM anti-HBc -acute or recent infection and can persist for more than 6 months.
  • HBV DNA confirms active infection and can detect infection at levels below those of HBsAg assays.  This can occur either due to “occult HBV infection” or due to a mutant HBV strain that results in non-reactive test for HBsAg.
  • There were at least 11 HBsAg assays that have been FDA-approved –most but not all of them will confirm results before reporting.

It is important to sort out patients with discrepant HBV serology.  In infants who are not identified with HBV testing (false-negatives), this results in suboptimal post exposure prophylaxis and increased likelihood of chronic HBV.  Whereas, infants with false-positive results, incur unnecessary prophylaxis and costs.  The authors note that “total anti-HBc was the most useful single test to resolve HBsAg discrepancies.

Also noted: J Pediatr 2014; 165: 767-72.  “Factors Affecting the Natural Decay of Hepatitis B Surface Antigen in Children with Chronic Hepatitis B Virus Infection during Long-Term Followup”  This study followed 349 Taiwanese children over 20 years and noted annual HBsAg clearance of 0.58% (42 cleared HBsAg).  Spontaneous clearance was more common in HBeAg-seroconverters, infants with low initial HBsAg level <1000 IU/mL, and to those born to non-HBsAg-carrier mothers.

What is Panayiotopoulos Syndrome?

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Recently, Panayiotopoulos syndrome was mentioned on the GI Listserv as a possible explanation for a child with seizures following vomiting and gagging.  I hope that I was not the only one to wonder what that was.

According to Pediatrics Review Article:

Panayiotopoulos syndrome is a common idiopathic childhood-specific seizure disorder formally recognized by the International League Against Epilepsy. An expert consensus has defined Panayiotopoulos syndrome as “a benign age-related focal seizure disorder occurring in early and mid-childhood. It is characterized by seizures, often prolonged, with predominantly autonomic symptoms, and by an EEG [electroencephalogram] that shows shifting and/or multiple foci, often with occipital predominance.”

Autonomic epileptic seizures and autonomic status epilepticus are the cardinal manifestations of Panayiotopoulos syndrome. Autonomic seizures in Panayiotopoulos syndrome consist of episodes of disturbed autonomic function with emesis as the predominant symptom. Other autonomic manifestations include pallor (or, less often, flushing or cyanosis), mydriasis (or, less often, miosis), cardiorespiratory and thermoregulatory alterations, incontinence of urine and/or feces, hypersalivation, and modifications of intestinal motility.

Bottomline: If a parent is convinced that vomiting or retching is triggering seizures, the child’s neurologist needs to consider this disorder.

Magnetic Resonance Elastography in Nonalcoholic Fatty Liver Disease

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A recent study (Hepatolology 2014; 60: 1920-8) shows that magnetic resonance (MR) elastography can be an accurate noninvasive tool to assess liver fibrosis.

Background: Assessing severity of liver fibrosis provides important prognostic information in patients with nonalcoholic fatty liver disease (NAFLD); however, these patients are often obese which decreases the success of transient elastography.  In addition, high hepatic fat content may alter the results of transient elastography.  Hence, an alternative noninvasive technique is desirable.

Design: Prospective study with 117 consecutive patients with biopsy-proven NAFLD who also underwent 2D-MR elastography between 2011-2013.

Results:

  • Fibrosis stage: stage 0 n=43, stage 1 n=39, stage 2 n=13, stage 3 n=12, stage 4 n=10.
  • MR elastography identified stage 3-4 with an accuracy of 0.92, with little overlap between advanced (F3-4) and non-advanced (F0-2) values.  The specificity, sensitivity, positive/negative predictive values, and cutoff values are detailed in Table 2.
  • Figure 3 provides a cool picture demonstrating the different MR elastography stiffness heat maps correlated with liver fibrosis. Link to similar web-based image from Siemens.

Bottomline: This technology allows a noninvasive measure of liver fibrosis in NAFLD patients and will probably be of use in other liver conditions.  Given the fact that a liver biopsy is more risky and often expensive, this technology and other noninvasive markers of advanced liver disease will be important tools.

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Lack of Meaningful Improvement in Crohn’s Patients with Tofacitinib

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As noted in a previous blog (see below for link), tofacitinib, an oral Janus Kinase Inhibitor has shown promise as an agent for ulcerative colitis. However, its results thus far for Crohn’s disease (CD) have been discouraging.  Another study (Clin Gastroenterol Hepatol 2014; 12: 1485-93) reiterates that message.

In brief, 139 patients with moderate-to-severe active CD were randomly assigned to 3 dosage groups of tofacitinib (1-, 5-, and 15-mg) and compared with placebo.  There were no significant differences in response or remission between tofacitinib and the placebo group, though there were reductions in both C-reactive protein and fecal calprotectin among patients given the 15-mg dose.

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Do Oral Nutrition Supplements Help Hospitalized Patients?

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A recent retrospective study suggests that oral nutrition supplements may shorten hospital stays and lower costs when matched against similar patients.

Here’s a link to the abstract: JPEN Oral Nutrition Supplement Study

Some of the details:

  • Retrospective analysis of 557,348 hospitalizations of children aged 2–8 years in the Premier Research Database
  • ONS were prescribed in 6066 of 557,348 inpatient episodes (1.09%).
  • ONS use was associated with a 2.9-day increase (95% confidence interval [CI], 2.32–3.39), or 51.6% increase in LOS, from 5.5 to 8.4 days. ONS use was also associated with increased episode cost of $8568
  • Using a matched sample of 11,031 episodes, hospitalizations with ONS use had 14.8% shorter LOS (6.4 vs 7.5 days). Hospitalizations with ONS use had 9.7% lower cost ($16,552 vs $18,320)

Bottomline: Despite the large numbers of patients, the retrospective nature of the study makes it difficult to determine whether these supplements are effective.  Only a randomized study can answer this blog’s title question.

What is the Role of Ursodeoxycholic Acid in Primary Sclerosing Cholangitis?

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While previous studies of ursodeoxycholic acid (UDCA) at high doses (28-30 mg/kg/day) have been shown to have detrimental effects, a number of randomized controlled trials (RCTs) have shown that low-dose UDCA has been associated with biochemical improvements but no differences in endpoints like death, liver transplantation or cholangiocarcinoma.  Given this conflicting information, a new study (Hepatology 2014; 60: 931-40, editorial 785-88) has examined the effects of withdrawal of low-dose UDCA.

In this cohort, the median age was 34 years, “62% were male, 69% had IBD, 19% had cirrhosis, and the baseline UDCA dose was 10-15 mg/kg/day.”

Key findings:

  • “At 3 months, discontinuation of UDCA in patients with PSC causes significant deterioration in liver biochemistry and influences concentrations of bile acid metabolites.”
  • Alkaline phosphatase increased 75.6%, GGT increased 117.9%, bilirubin increased by 50%, aspartate aminotransferase increased by 45.0%, and alanine amiontransferase increased by 63.9%
  • The Mayo Risk Score for PSC (associated with PSC prognosis) also increased 0.5 points from baseline.

Conclusion (from editorial): “there may still be a role for judicious use of UDCA in patients with well-compensated disease.”  A suggested “yet unproven” algorithm for use of UDCA is noted in Figure 1 pg 787 and considers UDCA for patients with alkaline phosphatase >1.5x ULN and/or PSC-associated symptoms like pruritus.  If no clinical improvement within 6 months, then stopping UDCA is recommended.

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