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.

Slim Pickings: Data for 2nd-Line Autoimmune Hepatitis Pediatric Therapy

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A recent study (AN Zizzo et al. JPGN 2017; 65: 6-15) performed a systematic review and meta-analysis of pediatric autoimmune hepatitis (AIH) studies.

The most remarkable finding was that there were only 76 patients from 15 qualifying studies.

Other findings:

  • Response to mycophenolate mofetil (MMF) with 34 patients was 36% (according to abstract) at 6 months  (discrepancy in article –results state 38% response)
  • Response to cyclosporine with 15 patients was 83% (discrepancy in article –results state 86% response)
  • Response to tacrolimus with 4 patients was 50%
  • Adverse effects were very common, particularly with cyclosporine (64% noted at least 1 adverse effect)

The article has an associated editorial (N Kerkar, pg 2-3).  “The adverse event profile of cyclosporine with gingival hyperplasia, hypertrichosis, nephrotoxicity, and neurotoxicity made it challenging for long-term use in children.”  Besides the small number of patients, “the studies that were included were largely “observational”‘ which limits their findings as well.  The study authors recommend MMF as the preferred option for 2nd-line therapy.

My take: Fortunately, most patients with autoimmune hepatitis respond to first line therapy with azathioprine/steroids.  It is unclear what is the optimal 2nd-line treatment for refractory patients.

Related blog entries:

Egret, Shem Creek

Will Emerging Therapies for Fatty Liver Disease Be Affordable?

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With non-alcoholic steatohepatitis (NASH), there are currently no established medical therapies.  However, several candidate medications look promising. However in recent years, many new medications have come with an impressive price tag and this has led to questions about whether emerging therapies for NASH will be affordable.

A recent article looked at the medication Obeticholic Acid, which was approved for treating primary biliary cholangitis.  It is possible that it will be helpful for NASH.  Yet, its cost , currently, is about $70,000 per year

GIHepNews: Despite clinical promise, obeticholic acid may be too expensive for treating NASH

Here’s an excerpt:

In the 72-week Phase II trial, called FLINT, 273 men and women with NASH were randomly assigned to receive OCA or placebo (Lancet 2015;385:956-965). Liver histology improved in 45% of those receiving OCA versus 21% in those receiving sham therapy (P=0.002). An increased risk for pruritus was the most notable adverse event among patients taking OCA (23% vs. 6% for placebo), according to the researchers. Based on the favorable benefit–risk results of the Phase II study, a Phase III trial is ongoing…

The expected benefit of OCA over lifestyle modifications for all the major long-term outcomes, such as decompensated cirrhosis (10% vs. 9.4%), liver-related mortality (9% vs. 8.1%) and transplant-free survival (72.2% vs. 71.5%), were relatively modest, the researchers reported. Those differences resulted in a cost per quality-adjusted life-year saved of $5.2 million with the assumption that 16% of patients would relapse…

 “If the efficacy compared to placebo is of the same order found in the FLINT trial, the current cost of the drug would be prohibitive in a population-based context,” said Dr. Lavine, who was a co-investigator on the trial.

My take: Given the growing burden of NASH, new effective treatments are needed.  In my view, though, cost-effectiveness has to be a consideration.

Prague Castle

NASH: What Helps Beyond Weight Loss?

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Full text from ACG article: NASH: What Helps Beyond Weight Loss?

The article reinforces the value of weight loss and exercise for nonalcoholic steatohepatitis (NASH).  It suggests that Vitamin E and/or pioglitazone may be helpful. Many more medications are being evaluated.

My take: As of now, losing weight and exercise remain the cornerstone for NASH treatment.

Long Distance (Medical) Relationships Don’t Always Work

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Another study (NZ Borren et al Inflamm Bowel Dis 2017; 23: 1234-9) has shown detrimental outcomes due to distance from the health care team.

In this study with 2136 patients with IBD (1197 Crohn’s disease, 9393 ulcerative colitis) with mean age of 41 years, the distance from the hospital (Massachusetts General) was compared with need for IBD-related surgery and secondary outcomes of needing biological and immunomodulator therapy.

Key findings:

  • In the four quartiles, mean distance was 2.5, 8.8, 22.0, and 50.8 miles.
  • Need for surgery was increased with distance from hospital: closest with odds ratio of 1.0, quartile 2 had OR of 1.68, quartile 3 had OR of 1.94, and quartile 4 had OR of 2.44

According to the authors, with other indications besides IBD, “over three-quarters of the examined studies demonstrated a distance-decay association with worse outcomes in individuals living further away from health care facilities.  Limitation: it is possible that patients who travel a greater distance have more disease severity and that those who have milder diseases are more likely to receive care closer to home.

My take: When highly qualified subspecialists are far away, the associated reduced access likely counters this potential benefit.  Early effective therapy is important in reducing complications.

Related blog posts:

Shem Creek, SC

Distance from Transplant Center -Not a Good Thing for Chronic Liver Disease

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It is said that “absence makes the heart grow fonder.”  This expression certainly cannot be extrapolated to the liver.  A recent study (DS Goldberg et al. Clin Gastroenterol Hepatol 2017; 15: 958-60) showed that increased distance to a liver transplant center was associated with higher mortality for patients with chronic liver failure (CLF).

This study examined 16,824 patients with CLF.  In the cohort (879, 5.2%) who lived  >150 miles from the closest LT center there was a 20% higher mortality rate (Hazard ratio of 1.20; P <.001).  According to the authors, mortality with distance “modeled as a continuous variable per unit increase in 50 miles.”

From the discussion:

  • “For patients with CLF, transplant remains the only option for long-term survival. Yet for the 11 out of 12 who are never transplanted, access to specialized care may still prolong life.”
  • Limitations: This study could not account for socioeconomic factors or control for geographical variation in care.  With regard to the later, death rates from liver disease are lowest in New York, where the entire population is within 150 miles of a transplant center.  In contrast, in New Mexico and Wyoming, which have the highest age-adjusted death rates, more than 95% of patients live >150 miles from a transplant center. However, there may be many other differences in care besides distance in these regions.

My take: This study, though with some limitations, bolsters the view that patients with chronic liver disease (and probably other chronic diseases) live longer if in proximity to specialized care.

Related blog posts:

Exquisite windows in St. Vitus Cathedral, Prague

 

PPI and Poor Outcomes

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A large observation study provides some bad publicity for proton pump inhibitors (PPI):

BMJ Open Access: Risk of death among users of Proton Pump Inhibitors: a longitudinal
observational cohort study of United States veterans (Y Xie et al BMJ Open
2017;7:e015735. doi:10.1136/bmjopen-2016-01573) Thanks to Ben Enav for this reference.

This study selected ~350,000 patients from a database which identified more than 1.7 million PPI users. These patients were ‘new’ PPI users.

Key finding:  Over a median follow-up of 5.71 years, PPI use was associated with increased risk of death compared with H2 blockers use (HR 1.25, CI 1.23 to 1.28).

The authors note the limitations of this observational study; however, they suggest that the findings cannot be fully explained by residual confounders.  They recommend limiting PPI use to “instances and durations where it is medically indicated.”

My take: As noted in a recent post (see below), some risks attributed to PPIs in observational studies do not pan out.  Yet, PPI therapies need to be better-targeted to those who will truly benefit from them.

Related blog posts:

The Battery, Charleston, SC

 

Understanding the Health Care Fight

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From Axios: This is what Washington has been fighting about

An excerpt:

Every time you hear the Trump administration or Congress fight about rising Affordable Care Act premiums, or what will happen to people with pre-existing conditions, just remember — we’re talking about issues that affect 7 percent of the population. That’s how many people are in the individual health insurance market, or the “non-group” market…

But when you hear about those sky-high rate hikes because of “Obamacare,” chances are, they’re not your sky-high rate hikes — unless you happen to be in that market…

The spending limits that have been proposed for Medicaid really do matter, and they affect a larger group — 20 percent of the population. 

Use of Antidepressant Medications to Treat Recurrent Abdominal Pain

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A recent study (C AM Zar-Kessler et al. JPGN 2017; 65: 16-21) retrospectively reviewed a single center’s 8 year experience (2005-2013) using antidepressant medications to treat nonorganic abdominal pain. Of 531 cases, 192 initiated treatment with either a selective serotonin reuptake inhibitor (SSRI) or a tricyclic antidepressant (TCA).

Key findings:

  • 63 of 84 (75%) of SSRI-treated patients improved; 56 of 92 (61%) of TCA-treated patients improved.  The higher response rate to SSRIs persisted after control for psychiatric factors.
  • A much higher percentage of SSRI-treated patients, compared to TCA-treated patients, had anxiety (49% vs 22%); an additional 15% and 5%, respectively, had combined anxiety/depression.
  • The most common SSRI in this study was citalopram with median dose of 10 mg (range 5-60 mg).
  • The most common TCA in this study was nortriptyline with median dose of 20 mg (range 10-50).
  • Similar numbers of patients in each group had adverse effects, include 21 (25%) of SSRI-treated patients and 20 (22%) of TCA-treated patients.  14% of SRRI-treated patients discontinue medication due to adverse effects, compared with 17% of TCA-treated patients.
  • Mood disturbances were higher in this study among TCA-treated patients: 14% compared with 6% of SSRI-treated patients
  • TCAs were prescribed by gastroenterologists in 88% of cases; with SSRIs, only 39% of prescriptions were from gastroenterologists.

In the discussion, the authors note that “all patients who experienced GI adverse effect were prescribed medications that would worsen their underlying bowel complaint…these issues may have been mitigated if more attention was paid” to this.  “Specifically, TCAs should be used cautiously in those with constipation, whereas SSRIs should be avoided in those with diarrhea.”

My take: This study shows that both classes of antidepressants were associated with improvement.  The conclusions about effectiveness are limited as this is a retrospective study and could not control/evaluate many variables. That being said, particularly if there is coexisting anxiety, as was frequent in this study population, a SSRI may be more effective.

Related blog posts:

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.

Tynn Church, Prague

 

Afraid to Eat -Could be “Avoidant Restrictive Food Intake Disorder”

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A recent case report (JJ Thomas et al. NEJM 2017; 376: 2377-86) provides insight into something I’ve seen a lot but did not have a good label for previously: Avoidant Restrictive Food Intake Disorder (ARFID).

This report highlights an 11 year old who after a having a piece of meat briefly lodged into an orthodontic palate expander, stopped eating solid foods because she was “afraid I can’t chew it up enough to swallow it so I don’t choke.”  Even before this event, she had been a highly selective eater since infancy.  “Similar to many patients with ARFID, this patient had a long-term failure to gain weight appropriately and now had more acute weight loss.”  She did desired to gain weight and did not have any body distortion typical for anorexia nervosa.

This report provides a good list of etiologies which could trigger acute food refusal as well as conditions that could cause chronic poor weight gain.

  • For acute food refusal, etiologies included acute oromotor dysfunction, foreign body ingestion, gastrointestinal ulceration, anorexia nervosa/other psychiatric reasons (including globus hystericus).
  • For chronic failure to gain weight: chronic oromotor dysfunction (numerous neurologic causes), achalasia, inflammatory bowel disease, celiac disease, endocrine etiologies (eg. Addison’s, hyperthyroidism, type 1 diabetes mellitus), infections (eg. tuberculosis, HIV), insufficient food/abuse & neglect, stimulant use, cancers, and other chronic diseases (pulmonary, cardiac, or renal)

Definition of ARFID:

  • “The presence of avoidant or restrictive eating that results in persistent failure to meet nutritional needs; evidence of ARFID includes low weight or failure to have expected gains or growth, nutritional deficiencies, reliance on nutritional supplements or enteral feeding, psychosocial impairment, or a combination of these features. Restrictive eating may be motivated by low appetite or lack of interest in eating, sensitivities to certain sensory aspects of foods, or fear of adverse consequences of eating, such as choking or vomiting.”
  • It is noted that coexisting psychiatric conditions “appear to be common among patients with ARFID. Concurrent anxiety disorders are the most prevalent; they occur in more than 70% of patients in some clinical samples.”

Treatment of ARFID:

There is little data to guide treatment.  Treatment of coexisting psychiatric conditions is recommended and behavioral interventions to improve eating.  In this patient with a choking phobia, the treatment included a gradual stepwise progression in food textures:

  • Liquids–>Purees (eg yogurt, applesauce)–>Textured purees (eg. oatmeal, mashed potatoes) –>Soft solids (eg. rice, mac & cheese, pasta, bread, potatoes, pizza) –>Crunchy solids (eg. chips, pretzels, crackers) –>Hard-to-chew solids (eg. meats)

My take: I think being able to use this relatively new term of Avoidant Restrictive Food Intake Disorder will improve disease classification and ultimately help promote better treatments.

I thought this candy store icon was funny due to the missing tooth