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.

Source Article: Methotrexate Safety

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A recent post (Monotherapy or Combination Therapy with Adalimumab) referenced an article indicating some potential concern for malignancy potential with methotrexate (Semin Arthritis Rheum 2014; 43: 489-97). Here’s a link to the source article/abstract:  Comparative cancer risk associated with methotrexate, other…

The authors conducted a comparative effectiveness study with cancer as an outcome in patients with rheumatoid arthritis (RA).  The final sample size was 6806 patients.  The most common drugs examined included methotrexate (n=1566) and TNF antagonists (n=3761). Other disease-modifying anti-rheumatic drugs (DMARDs) included other non-biologics (n=904), rituximab (n=167), and abatacept (n=408).

The authors note that with “the advent of newer DMARDs and combination therapy (this) has allowed more RA patients to lead more functional lives.  With this improvement in therapy, more attention is focused on the comparative risks and benefits of treatment.”

Key findings/discussion:

  • TNF antagonists were associated “with a reduced overall cancer risk versus methotrexate.” (HR 0.29).  Figure 2B, shows a plot with specific HR for various malignancies.  TNF antagonists had a HR of 0.15 for lymphoma.
  • Oncogenic potential of methotrexate was described almost 20 years ago, however, “its obvious clinical benefits have overshadowed malignancy concerns.”
  • “Our findings suggest that when examining the cancer risk associated with other DMARDs, combined methotrexate use must be factor into adjusted analyses.”

How does this translate to inflammatory bowel disease (IBD)?  While RA and IBD patients may have different risks for malignancy, this study suggests that patients receiving methotrexate therapy may have a low risk of malignancy.  The potential benefits of methotrexate therapy along with alternatives need to be weighed against this possible risk. Perhaps, this article may help reduce the concerns regarding anti-TNF therapy with regard to relative risk.

Related post:

A Lack of $2.17 Can Cost Thousands More

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An interesting article in the NY Times explains a couple situations in which patients reluctantly admit their lack of financial resources and how this impacts their care.  The article underscores the message that doctors need to find a careful way to find out if patients can afford their medications.

Here’s the link: http://nyti.ms/1fVPzDx  and here’s an excerpt:

His protuberant belly was actually a sign of serious liver disease that had quickly worsened…

“I know how to take the pills, but I can’t buy them,” he said, his eyes refusing to meet mine as he stared at a spot on the hospital’s beige floor…The medicines were crucial to helping him avoid landing in the hospital again, so I went down to the pharmacy to see what the problem might be. “The co-pay is $2.17,” the pharmacist told me matter-of-factly, referring to a white paper bag with a few pill-filled bottles inside…The medications cost less than a subway ticket, but were still more than my patient could afford. If he ended up in the hospital again because he couldn’t take them, the medical costs would be thousands of times greater than $2.17…

A recent report in The American Journal of Medicine that found that one-third of Americans suffering from a chronic illness such as diabetes or high blood pressure said they had trouble affording medications, food or both…

The standard co-payment was $20, the doctor told her, and then gently asked if it would be a problem to pay.  The mother shook her head, but tears were welling up in her eyes. “But we can’t come back in a few months,” she blurted out. “It’s just too expensive.”

Tears rolled down her cheeks, and she looked away as her cheeks flushed. Her daughters sat silently on the exam table, their thin legs swinging back and forth.

I felt the family’s shame and embarrassment, and in retrospect, it seems obvious they lacked enough to eat. Yet we wouldn’t have known they were pressed for funds if our patient hadn’t brought up the issue at the last minute. The pediatrician was able to waive the co-payment, but it was just another short-term fix to a longer-term problem.

Neither doctors nor medical students can solve a patient’s financial problems on the spot. Yet any one of us can be the first to detect a problem. If we’ve done the research, we can help patients get the assistance they need, or at least direct them to social workers, pharmacists and other members of the health care team who can. What we cannot do is fail to ask.

Marriage, Divorce and Separation with Anti-TNF Therapy

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This review article (Inflamm Bowel Dis 2014; 20: 757-66) examines the question of whether and when anti-tumor necrosis factor (anti-TNF) agents can be stopped in Crohn’s disease (CD) patients in remission.  This topic is particularly helpful since this comes up frequently in clinical practice.

As recently as a few years ago, one expert advised me that starting an anti-TNF agent (like infliximab or adalimumab) was like getting married.  Once you committed, you stayed in that relationship indefinitely.  Of course, it is well-known that individuals get divorced.  In medical terms, I guess that would be the equivalent of developing antibodies to the anti-TNF agent or other adverse reactions.  Switching from one anti-TNF to another would be equivalent to marital infidelity.

So what does this review article say about all of this?  The article examines nine studies with a little more than 500 patients.  “Current evidence suggests that a group of CD patients, possibly 30% to 40% in clinical remission while on IM (immunomodulators) and infliximab can stop the latter and maintain clinical remission for a relatively long interval.  It seems that, if followed long enough, virtually all patients (including those on IM) will eventually develop clinical recurrence.”

If tempted to separate but not divorce anti-TNF therapy, the authors recommend, in addition to clinical remission, “normal colonoscopy (and/or normal surrogate markers of disease activity) should be adopted as a criterion when stopping therapy and during follow-up….As of today, many authors do not recommend to routinely stop anti-TNF agents in patients responding to this therapy and in the absence of other issues.  Others propose to stop them after a minimum of 2 years of clinical and endoscopic remission or longer if only clinical remission can be documented…

If costs or other issues are present, we suggest to cautiously stop anti-TNF agents only in patients on combination therapy with profound (clinical, biochemical, and endoscopic) and long lasting (>1 year) remission and continuing the IM.  Such patients should be closely followed by serial determinations of fecal calprotectin and inflammatory indices, and the medication immediately restarted in the presence of a flare. When in doubt, colonoscopy should be performed.”

Take-home message: Most patients are better off staying married to their anti-TNF therapy.

Also noted: Inflamm Bowel Dis 2014; 20: 742-56.  Clinical Utility of Fecal Biomarkers for the Diagnosis and Management of Inflammatory Bowel Disease.  This is a useful review with 103 references.

After I Passed The Test

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After I passed my maintenance exam (American Board of Pediatrics -Pediatric Gastroenterology Subspecialty), I thought I would publish a few criticisms.

1. The test has not kept up with the digital age. In daily practice, it is a good idea to look up information and research difficult cases.  Knowing how to use these resources is more important than memorizing a lot of rare facts for an exam.

2. Why should any of the questions ask me to interpret radiographs or histology slides?  In daily practice, I would rely on my colleagues in radiology and pathology.  One of my surgical colleagues years ago used to say, “when I order a CT it should be like ordering a pizza.  Don’t ask me why I want it.  Ask me what I want on it.”  In the case of the maintenance exam, ask which test I want.  There are excellent radiologists and pathologists who are the experts at interpreting the results.

3. How is the MOC evidence-based? The popular buzz word of quality care is “evidence-based.”  Where is the data that taking the test & keeping up with the MOC (maintenance of certification) process improves physician performance?   From my discussions, it is apparent that physicians do not believe that the test “weeds” out underperforming physicians.

4. If the MOC process is so important, how come there are so many physicians who were “grandfathered” out of the requirements?  While the official line to this question is that the “diplomates” at that time who were board-certified were not time-limited, an honest answer is that it was the only politically feasible way to get enough physician support.

As a whole, these criticisms indicate the difficulty in designing a test to assess whether a physician has the necessary competencies.  As alluded to in a previous post (Training Not Meeting Procedure Thresholds for Fellows …), it is crucial that physicians gain the necessary experience/knnowledge in their training.

The MOC has lofty goals of assuring that physicians acquire and maintain their skills.  Yet, the current approach does not meet these goals.  Ultimately, the burden on a physician, like in other career pathways, on keeping up his knowledge and clinical skills relies mainly on the conscientious individual.  Those interested in taking shortcuts will do this and the current system is merely a nuisance.

Superiority of Anti-TNF Therapy (Part 2)

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A recent blog (Superiority of Anti-TNF Therapy in Children | gutsandgrowth) described a recent article showing that kids treated with anti-TNF therapy at the time of diagnosis had improved outcomes compared to children who were treated with other medications.  In this day of multimedia, there is a video explaining the study which may be helpful for families and clinicians alike –here’s the link:  Dr. Michael Stephens discusses the research findings: .

An excerpt from the explanation with the video:

The current research study looks at outcomes and compares three different types of treatments. The first group receives anti-TNF therapy. The second group received immune modulating therapy. The third group received no treatment within the first three months. This study was an observational study and the choice of treatment was at the discretion of the physician. In order to correct for this factor, a statistical technique was used. Patients with similar characteristics were paired within the three groups . The results showed that patients who received the anti-TNF therapy had an improved outcome, such as a higher remission rate and some indications of improved growth, at one year. All three groups had improvements in weight and body mass index but only the anti-TNF group had improvements in linear growth.

Just the Beginning: Mutations in Very Early Onset Inflammatory Bowel Disease

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A recent study (Gastroenterol 2014; 146: 1028-39) indicates that mutations in tetratricopeptide repeat domain 7A (TTC7A) can result in a severe form of very early onset inflammatory bowel disease (VEOIBD).

After identifying a TTC7A heterozygote mutation in an infant by using whole exome sequencing of DNA, the authors subsequently identified 4 additional patients (2 siblings from 2 families) who also had loss of function mutations in VEOIBD.  Thus far, four of the five identified infants have died.

The manuscript has some terrific figures describing endoscopic/histologic characteristics, TTC7A genetic analysis, functional TTC7A enterocyte studies with immunofluorescence, impaired cell adhesion figure, tandem mass spectrometry, and a summary mechanistic figure (figure 6).  Hematopoietic stem cell transplantation has not been effective and might not work due to the enterocyte defect.

This study adds another VEOIBD gene mutation.  Previous mutations have involved in VEOIBD have included IL10RA/B, XIAP, ADAM17, NCF4, and NCF2/RAC2. The specific subtype matters as some defects may respond to stem cell transplantation.

Take-home message: there are a diverse number of pathways that can lead to VEOIBD.  Given the recent availability of whole exome sequencing, more mutations are sure to be identified soon.

Related blog post/link:

IL-10 and early onset IBD | gutsandgrowth In addition to the Toronto group (noted in this blog), a group in Boston with Harland Winter/CJ Moran is also interested in whole exome sequencing for VEOIBD patients.

Causes and Treatment of Very-Early Onset IBD –-this link is to the AGA Journals blog post on the same subject.

How Long Will Infliximab Work?

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Given the limited therapeutic options, the question of infliximab (IFX) durability in pediatrics is quite important.  One center has published its 10-year retrospective experience (Inflamm Bowel Dis 2014; 20: 606-13).

Inclusion criteria for the 188 patients included initiating IFX prior to age 21 years and patients who had a minimum of 1-year followup.

Demographics: Median age at diagnosis was 11 years for Crohn’s disease (CD) and 12 years for ulcerative colitis (UC). Indication for IFX due to steroid refractory disease was present in 42% of UC patients compared with 14% of CD patients.  Monotherapy was more common in UC patients, 65%, compared to 35% of CD patients.

Methotrexate was administered in 69 (44%) of CD patients at time of IFX with the majority (n=56) as oral treatment (low-dose <10 mg every week).  In addition, MTX was initiated after IFX induction in another 38 (24%).  Only 36 (23%) remained on IFX mono therapy throughout the duration of treatment in CD patients.

Key findings:

  • 88% of CD patients remained on IFX at 1 year, 80% at 2 years, and 72% at 5 years.
  • Only 7 of 157 CD patients were primary nonresponders.
  • 65 of 89 CD patients who did not achieve a sustained durable remission underwent dose escalation. 40 of 65 responded to dose escalation.
  • Of those who lost response to IFX, the majority were transitioned to adalimumab (ADA) and among this group, 82% remained on ADA treatment at last followup.
  • Among UC patients (n=31), 9 were primary nonresponders. At last followup, 41% (9) remained in a durable sustained response at last followup.
  • While the authors used MTX due to favorable effects on IFX pharmacokinetics (Arthritis Rheum 1998; 41: 1552-63), there was “not a significant difference in IFX durability or efficacy between this group and patients with CD on IFX monotherapy”
  • Availability of antibodies to infliximab (ATIs) and IFX trough levels were only assessed in a subset.  However, “we did see a significant difference in those that responded to dose intensification when ATIs were undetectable.”

Bottomline: The majority of CD patients can remain on IFX for >5 years.  Among those who lose response, adalimumab was a durable alternative.  A much lower durable response was evident with the subset of patients with UC.

Related blog post:

Also noted:

Inflamm Bowel Dis 2014; 20: 614-21. In this study of 78 youth with IBD, depressive symptoms warranting additional evaluation were present in 13% which was lower than in the community comparison group.  Disease severity was noted to be inactive in 63% and mild in another 18%.

Inflamm Bowel Dis 2014; 20: 495-501. This study showed that 25 children exposed to anti-TNFs prenatally for maternal IBD seemed to show good safety.  Immunologic investigation undertaken in 17 of the children was normal.  No control group limited the ability to determine if increased infections were present.

And, here’s a link to Mar-April Circle Newsletter from ImproveCareNow -topics include group medical appointments, parent working group, dieting with IBD, and includes link to self management handbook.

 

 

Imaging in NAFLD -Don’t Rely on Ultrasound

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A recent article (Clin Gastroenterol Hepatol 2014; 12: 765-73) notes that ultrasound is not accurate for diagnosing NAFLD:

The link to the article: http://goo.gl/R1GdAG, video abstract: http://youtu.be/spnlSPTS-SE (from Jeff Schwimmer’s twitter feed) ,and an excerpt from the article’s abstract:

Results

We analyzed 9 studies comprising 610 children; 4 studies assessed ultrasonography and 5 studies assessed magnetic resonance imaging (MRI). Ultrasonography was used in the diagnosis of fatty liver with positive predictive values of 47% to 62%. There was not a consistent relationship between ultrasound steatosis score and the reference measurement of hepatic steatosis. Liver fat as measurements by MRI or by spectroscopy varied with the methodologies used. Liver fat measurements by MRI correlated with results from histologic analyses, but sample size did not allow for an assessment of diagnostic accuracy.

Conclusions

Available evidence does not support the use of ultrasonography for the diagnosis or grading of fatty liver in children. Although MRI is a promising approach, the data are insufficient to make evidence-based recommendations regarding its use in children for the assessment of hepatic steatosis.

Related blog posts:

“Low quality of evidence; strong recommendation” for Probiotics in Gastroenteritis

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Recently a position paper on “Use of probiotics for management of acute gastroenteritis: a position paper by the ESPGHAN working group for probiotics and prebiotics” was published (JPGN 2014; 58: 531-39).

Two specific probiotics were recommended “strongly” but the working group describes the evidence for both as “low quality.”  This strikes me as odd.  The authors extensively reviewed previous studies and used the “GRADE” system to classify the quality of evidence and the category of recommendation.  There were 4 categories of quality of evidence: high, moderate, low and very low.  There were 2 possible recommendation categories: strong or weak.

The summary recommendations included the following:

  • Rehydration is the key treatment for AGE
  • Probiotics, overall, reduce diarrhea by approximately 1 day
  • However, probiotic effects are strain specific; findings from one probiotic cannot be extrapolated to another
  • The group recommends choosing probiotics with efficacy confirmed in well-conducted RCTs from a reputable manufacturer
  • Two specific recommended probiotics: Lactobacillus GG and Saccromyces boulardii

Take-home message: This article summarizes the available evidence for the use of probiotics in acute gastroenteritis.  Despite their classification as  “low quality of evidence,” the authors provide a strong recommendation for two probiotics (Lactobacillus GG and Saccromyces boulardii) as adjunctive therapy.

Related blog posts:

 

 

 

Why Rich Kids Get Measles More Often in the U.S.

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Most of the time, having more wealth and education translates into better health care outcomes.  One exception has been with some vaccine-preventable illnesses like the measles, according to a recent article in USA Today which reported on the CDC’s efforts to counter anti-vaccination misinformation.

Here’s an excerpt:

Vaccines given to infants and young children over the past two decades will prevent 322 million illnesses, 21 million hospitalizations and 732,000 deaths over the course of their lifetimes, according to a new report from the Centers for Disease Control and Prevention.

Vaccines also will have saved $295 billion in direct costs, such as medical expenses, and a total of more than $1.3 trillion in societal costs over that time, because children who were spared from sometimes-devastating illnesses will be able to contribute to society, the report shows. These calculations may underestimate the full impact of vaccines, the study notes, because authors considered only the early 14 routine childhood immunizations typically required for school entry. Authors didn’t include flu shots or adolescent vaccines given at ages 11 or 12…

Before the measles vaccine became available in 1963, the virus infected about 500,000 Americans a year, causing 500 deaths and 48,000 hospitalizations. In recent years, the number of diagnoses fell to around 60 to 65, mostly in isolated travelers arriving in the USA.

Doubts about vaccines safety – and fading memories of vaccine-preventable diseases — have contributed to a resurgence of nearly forgotten diseases such as measles, which was officially declared eradicated in the USA in 2000. Numerous studies have debunked the notion that vaccines cause autism or other chronic diseases, says William Schaffner , an infectious disease specialist and professor at the Vanderbilt University School of Medicine in Nashville….

Congress created the entitlement program in 1994, responding to a measles outbreak in 1989 to 1991 that sickened 55,000 people and killed more than 100. At the time, measles outbreaks were fueled by viruses circulating among low-income, inner-city residents.

The picture has completely changed today, Schaffner says. The federal program has eliminated racial and ethnic disparities among vaccines. Today, the bulk of the unvaccinated children come from wealthy, educated families where parents intentionally choose not to immunize them, due to concerns about vaccine safety. These relatively wealthy children can then spread measles after returning from vacations in Europe, which has had large outbreaks for several years, Schaffner says.

“Borders can’t stop measles, but vaccination can,” says CDC Director Tom Frieden.