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.

Vonoprazan versus Lansoprazole for Initial Heartburn Relief

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A recent study (T Oshima et al. Aliment Pharmacol Ther 2019; 49: 140-6) showed that a new potassium-competitive acid blocker (P-CAB) can more rapidly improve symptoms than lansoprazole. Thanks to Ben Gold for this reference.

This small study with 32 adult patients with endoscopically-confirmed erosive esophagitis with frequent heartburn were randomized in a double-blind study and received either lansoprazole 30 mg or vonoprazan 20 mg before breakfast.  The authors note that with PPIs, there is a slow onset of action, such that ‘half of all patients remain symptomatic even after 3 days of treatment.” In contrast, vonoprazan can increase intragastric pH to almost 7 within 4 hours.

Key finding:

  • Heartburn relief occurred quicker with vonoprazan.  Complete relief was noted in 31.3% at day 1 compared with only 12.5% in the lansoprazole group.

My take: Vonoprazan is currently approved in Japan.

Related article: Update on the Use of Vonoprazan DY Graham, MP Dore; Gastroenterol 2018; Volume 154, Issue 3, Pages 462–466

Mesquite Flat Sand Dunes, Death Valley

Vedolizumab Drug Levels –Are They Needed?

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A recent retrospective study (E Dreesen et al Clin Gastroenterol Hepatol 2018; 16: 1937-46) with 179 consecutive patients (66 with ulcerative colitis, and 113 with Crohn’s disease) found that vedolizumab (VDZ) trough concentrations were correlated with response.

Key findings:

  • VDZ trough >30 mcg/mL at week 2, >24 mcg/mL at week 6, and >14 mcg/mL during maintenance were associated with effectiveness endpoints including endoscopic healing, physician global assessment and biochemical response (based on CRP).
  • Median VDZ trough levels during induction were 27.7 mcg/mL at week 2, 27.4 mcg/mL at week 6. With standard dosing, the maintenance VDZ trough was 13.5 mcg/mL at week 14
  • Higher BMI and more severe disease, based on CRP, albumin, and/or hemoglobin, were associated with lower VDZ trough levels and lower probability of mucosal healing (P<.05).

Interestingly, in the discussion the authors note that VDZ troughs above  3 mcg/mL completely saturate α4β7 intergrin.  This physiologic phenomenon is hard to reconcile with data showing better response with higher VDZ levels.  The authors note that “at present, there are not enough data in our study to support the role for TDM to guide clinical decision-making on dose escalation for vedolizumab.”

My take: This study implies that VDZ levels may help predict response but are not necessarily helpful in determining whether dose escalation is warranted.

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Riverwalk, Chattanooga

Blood Test is Better Than a Liver Biopsy for Biliary Atresia

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A recent study (L Yang et al. Hepatology 2018; 68: 2069-72) confirms the utility of Serum Matrix Metalloproteinase-7 (MMP-7) as a biomarker for biliary atresia (BA). The authors studied MMP-7 among healthy controls (n=72 with 54 <6 months) and among 135 with cholestasis (75 with BA, 60 with non-BA).  BA samples were taken at a median age of 54 days.

Key findings:

  • Median concentration for MMP-7 was 2.86 ng/mL in healthy controls, 11.47 ng/mL for non-BA cholestasis, and 121.1 ng/mL for BA.
  • Using a cutoff value of 52.85 ng/mL, the diagnostic sensitivity and specificity were 98.67% and 95.0% respectively.
  • The AUC for MMP-7 in BA was 0.99 compared for AUC for GGT of 0.72.  The sensitivity and specificity for GGT was much lower at 64% and 72% respectively with a cutoff of 314 U/L.
  • The predictive value for MMP-7 was particularly impressive, 74 of 75 BA  subjects were correctly identified as having BA.  Only 3 non-BA patients were incorrectly assigned a BA diagnosis based on MMP-7 values.
  • The authors noted that MMP-7 testing indicates that there are no substantial changes in its values for normal subjects extending to 54 years of age.
  • One limitation the authors note is the relatively small number of patients with non-BA syndromatic intrahepatic cholestasis which made up less than 30% of their non-BA cohort.  Thus, more testing in specific populations is needed.

My take: The diagnostic performance of MMP-7** appears to be superior to that of a liver biopsy (though this was not directly compared in this study) in predicting BA and could obviate the need for most liver biopsies in infants with cholestasis.  Those with high MMP-7 values would proceed directly to intraoperative cholangiogram with possible hepatoportojejunostomy. Those with non-BA MMP-7 values and persistent cholestasis could undergo additional investigation with genetic panels and/or other metabolic/infectious testing.

**This assay is likely to be commercially-available in the coming weeks according to a colleague at Cincnnati Children’s Hospital.  The expectation is an approximagely 2-day turnaround.

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Moon over Zabriskie Point, Death Valley before Sunrise

Resolution: Eradication of Hepatitis C

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Eradication of hepatitis C virus (HCV) is going to be difficult despite the huge improvements in treatment.  One obstacle that has been highlighted previously has been the increase in HCV transmission associated with the opioid epidemic.  Another basic problem is establishing a ‘cascade of care’ that makes sure that those with HCV receive appropriate treatment and followup.

In a recent study (RL Epstein et al. J Pediatr 2018; 203: 34-40, editoria by KB Schwarz, W Karnsakul 7-8) describe the deficiencies in the followup of women in an obstetric clinic serving women with substance use disorders. The authors reviewed electronic records of 879 women over a 10 year period.  Key findings:

  • 85% of women were screened for HCV.  Of the 68% who were seropositive, only 72% had HCV RNA testing and 71% were viremic.
  • There were 404 infants born to women who were HCVB seropositive.  Only 45% of these infants completed AAP-recommended perinatal HCV screening.

In the commentary, the authors point to the suboptimal rates of followup.  They note that there is a “huge gap between infected women and the linkage of their infected progency to care.” Furthermore, the AASLD has recommended that “all children with HCV infection in age groups for which direct-acting antiviral agents are approved should be treated.”

My take: this study identifies gaps in followup and treatment that need to be addressed systematically if we are to realize the goal of HCV eradication.

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NASPGHAN Toolbox App -Review

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To all my colleagues and to others who follow this blog, I wish you a happy new year.  Thank you to all of you, especially to those who provide feedback to help improve the content and usefulness.

Recently NASPGHAN released an App, titled NASPGHAN Toolbox.  There are some very useful features but also some areas where more work is needed.

Work in progress: Many of the algorithms that are listed are dated and no longer accurate.  To list a few examples:

  • The UC Algorithm suggests holding off on anti-TNF therapy in severe disease for 7-14 days
  • The EoE Algorithm lists only diet treatments and topical steroids and does not list PPIs as a treatment option
  • The GERD guidelines are from 2001 rather than more recent recommendations

Also, this ‘algorithms’ section should probably be renamed into ‘algorithms and tables’ as a large amount of the information is not algorithmic.

What I Like:

  • Scores and Calculators for items like MELD score, PUCAI score, Mayo score
  • Extensive patient education handouts and image atlas -this could facilitate “airdrop”ing or messaging of these items to families.  (To be picky –the normal esophagus image could be better)
  • Formula charts –though the lists for infants and older children could be more comprehensive
  • Bristol charts (especially children version) -listed in algorithm section

My take: This is a very good start and a very helpful toolbox for pediatric gastroenterologists but I would not rely on the algorithms.

 

Late-Night Pages –Are they a Conspiracy?

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A few thoughts while I’m still in a post-call daze:

One of my biggest gripes is that there must be a hidden camera in my bedroom.  Someone must monitor this camera whenever I am on call.  Because everytime, every single time it seems, someone calls me 15-20 minutes after I get in bed.  As soon as I get nice and cozy and start to doze off, it is a guarantee that I will get a page.  In addition, it is usually something that could have been called hours earlier.  Last night, at 11:22 pm, a nurse from the hospital called me to say that a 12 year old girl (who was well-nourished) had not been eating all evening and wanted to know if we should put in an NG tube.

Despite my antipathy for late-night calls, particularly some pointless ones, I try to always project a pleasant demeanor on the phone.  I might grumble after a call but not during.  There have been so many times when I have received timely information from nurses which have made important changes in a patient’s care.

Unwanted phone calls remind me of an anecdote that I heard in fellowship.  My mentor said he had received a pointless call from a family at 4 am about their young son.  So, he decided to set his alarm clock for 4 am the next morning and asked the parents how the son had been doing.  Later that morning, the family called the GI division to report the phone call.  They said, ‘When he called us at 4 am, we realized that he could not sleep because he was so worried about our child.  He is an amazing doctor.’

On another topic, can someone explain to me why it seems that whenever I am retrieving a foreign body that the forceps always line up parallel to the object rather than in the optimal perpendicular?

I sometimes tell colleagues that when I am post-call that I don’t realize how it has affected me.  Sometimes I am ‘punch-drunk’ and think everything is funny.  Sometimes I am irritable –but in my view –always justified.  The next day is sometimes like the difference portrayed in the snickers bar commercial where Betty White is transformed into a young adult.

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How Parents Feel After Tracheostomy Decision

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A recent study (S Nageswaran et al. J Pediatr 2018; 203; 354-60) examined parents’ perceptions about their decision to proceed with a tracheostomy.  As a GI doctor, I am not directly involved in the discussions about tracheostomy; however, we interact closely with many complex patients whose families have reached this decision.  Many times I have wondered whether families regret this decision and whether a more palliative approach may have been appropriate in some children.

In this study with interviews from 56 caregivers of 41 children, their was very high satisfaction with the decision to proceed with a tracheostomy.  All children in this study had a tracheostomy for 5 years or less.

The parents reported the following reasons:

  • Extending the life of their children.  In fact, many parents reported there were no other options available to ensure their children’s survival; thus, many caregivers felt they did not have a choice other than a tracheostomy.
  • Being able to provide care at home
  • Improvement in respiratory symptoms
  • Improved quality of life
  • Physical and developmental health

Key finding: Among 38 interviews, 38 out of 41 explicitly expressed satisfaction with their decision to pursue a tracheostomy.  In none of the interviews did any caregiver express clear regrets about their decision.

At the same time, the parents acknowledged difficulties like mucus plugs, accidental decannulation, and difficulty of home care with a tracheostomy..

Big Biosimilar Study

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Briefly noted: A Meyer et al. Ann Intern Med. 2018. DOI: 10.7326/M18-1512

Abstract link: Effectiveness and Safety of Reference Infliximab and Biosimilar in Crohn Disease: A French Equivalence Study

In this study with 5050 patients, based on review of an administration database, the authors found the following:

  • In multivariable analysis of the primary outcome, CT-P13 (biosimilar) was equivalent to infliximab reference product (RP) (HR, 0.92 [95% CI, 0.85 to 0.99]). 1147 patients in the RP group and 952 patients in the CT-P13 group met the composite end point (including 838 and 719 hospitalizations, respectively).
  • No differences in safety outcomes were observed between the 2 groups: serious infections (HR, 0.82 [CI, 0.61 to 1.11]), tuberculosis (HR, 1.10 [CI, 0.36 to 3.34]), and solid or hematologic cancer (HR, 0.66 [CI, 0.33 to 1.32]).

The authors conclude that “real-world data indicates that the effectiveness of CT-P13 is equivalent to that of RP for infliximab-naive patients with CD.”

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