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.

IBD Updates: Understanding Newest IBD Therapies for Kids- Bowel Sounds, Hispanic Patients with IBD, More on Intestinal Ultrasound

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Bowel Sounds Link: Joel Rosh talks small molecules and biologics

This is another good chat. Dr. Rosh provides a lot of information about the newest IBD agents. Overall, the episode indicates a very enthusiastic experience with IL-23 targeting agents like risankizumab (perhaps the ‘Michael Jordan’ of biologics) and with JAK agents like tofacitinib and upadacitinib. Dr. Rosh’s experience with regard to safety of these newer agents has been very positive. For tofacitinib, the typical dosing alluded to in the podcast was 10 mg twice a day (not three times a day). The potential adverse effects, though unlikely in the pediatric population, are carefully discussed with families and monitored.

So far, Dr. Rosh has not found a niche for ozanimod. In addition, he briefly discusses therapeutic drug monitoring. With regard to using vedolizumab as a first-line agent for ulcerative colitis, he often uses the VARSITY study (BE Sands et al NEJM 2019; 381: 1215-26) to justify this to payers. There is a sad element to the podcast though –Dr. Rosh admits to being a lifelong Mets fan!

Related blog posts:

NH Nguyen et al. Clin Gastroenterol Hepatol 2023; 21: 173-181. Open Access! Effectiveness and Safety of Biologic Therapy in Hispanic Vs Non-Hispanic Patients With Inflammatory Bowel Diseases: A CA-IBD Cohort Study

Key findings in this retrospective study with 240 Hispanic patients:

  • Within 1 year of biologic initiation, Hispanic patients had higher rates of hospitalizations (31% vs 23%; adjusted hazard ratio [aHR], 1.32; 95% CI, 1.01–1.74) and IBD-related surgery (7.1% vs 4.6%; aHR, 2.00; 95% CI, 1.07–3.72), with a trend toward higher risk of serious infections (8.8% vs 4.9%; aHR, 1.74; 95% CI, 0.99–3.05).
  • The authors state “these findings suggest that biologic agents may not be as effective or safe in Hispanic patients as they are in non-Hispanic Caucasians… Besides biological factors, socioeconomic factors related to costs and access to care, which contribute to delayed initiation of biologics, and/or limited postinitiation monitoring, leading to higher rates of unplanned health care utilization.”

T Kucharzik et al. Clin Gastroenterol Hepatol 2023; 21: 153-163. Open Access! Early Ultrasound Response and Progressive Transmural Remission After Treatment With Ustekinumab in Crohn’s Disease (STARDUST study)

Key findings:

  • IUS showed that ustekinumab-treated CD patients achieved progressive IUS response (46.3%) and transmural remission (24.1%) through week 48, with a more robust response in the colon and biologic-naive patients
  • Fair/moderate reliability (κ = 0.21–0.51) was observed between week 4 IUS response and week 48 overall endoscopic response and fecal calprotectin/complete biomarker outcomes.

What’s Wrong with Noncompete Clauses

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NY Times (1/9/23): Lina Khan: Noncompetes Depress Wages and Kill Innovation

This editorial provides a rationale for the FTC’s proposal to eliminate non-compete clauses.

Background: “When you’re subject to a noncompete clause, you lose your right to go work for a competing company or start your own, typically within a certain geographic area and for a certain period of time…In theory, noncompete clauses promote investment and innovation by assuring companies that their employees can’t run off with valuable secrets. And, again in theory, workers should be paid more in exchange for agreeing to sign a contract that restricts their autonomy. But the reality looks very different.”

Key points:

  • About 1 in 5 U.S. workers are subject to noncompete clauses.
  • “Noncompete clauses systemically drive down wages, even for workers who aren’t bound by one.”
  • Employees do not receive additional compensation for signing a noncompete clause. “Employers often spring them on workers after they’ve accepted a job, when their bargaining power is effectively zero.”
  • “Noncompetes reduce entrepreneurship and start-up formation…and keep innovative ideas from breaking into the market.”
  • “Noncompetes are the type of restriction that Section 5 of the F.T.C. Act, a federal law passed by Congress more than a century ago, is supposed to prevent.”
  • There are alternative ways to protect company secrets like nondisclosure agreements
  • California does not allow noncompete clauses (since 19th century) and this “hasn’t kept the California economy — the world’s fifth-largest — stuck in the Stone Age.”

My take: Elimination of noncompete clauses would be good for doctors (and other workers) and for the economy as well. Established business with market dominance will need to use other ways besides coercion to keep talented employees when noncompete clauses go away.

Siesta Key Beach, FL

Meds for Obesity: AAP Guidelines

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Selected recommendations:

  • In children 10 y and older, pediatricians and other PHCPs should evaluate for lipid abnormalities, abnormal glucose metabolism, and abnormal liver function in children and adolescents with obesity (BMI ≥95th percentile) and for lipid abnormalities in children and adolescents with overweight (BMI ≥85th percentile to <95th percentile). 
  • Pediatricians and other PHCPs should provide or refer children 6 y and older (Grade B) and may provide or refer children 2 through 5 y of age (Grade C) with overweight (BMI ≥85th percentile to <95th percentile) and obesity (BMI ≥95th percentile) to intensive health behavior and lifestyle treatment.
  • Pediatricians and other PHCPs should offer adolescents 12 y and older with obesity (BMI ≥95th percentile) wt loss pharmacotherapy, according to medication indications, risks, and benefits, as an adjunct to health behavior and lifestyle treatment. 
  • Pediatricians and other PHCPs should offer referral for adolescents 13 y and older with severe obesity (BMI ≥120% of the 95th percentile for age and sex) for evaluation for metabolic and bariatric surgery to local or regional comprehensive multidisciplinary pediatric metabolic and bariatric surgery centers. 

My take: As with the AGA, the AAP has now recommended the widespread adoption of pharmacologic therapy for use in patients with obesity. It appears that treatment would be required indefinitely, though, given the likelihood of weight gain when treatment is stopped (reviewed on a future post).

Related blot posts:

 Garden Lights, Holiday Lights at Atlanta Botanical Gardens

The Onion’s Take on the New AAP Guidelines:

“A Smarter Way to Reduce Gun Deaths” Plus Two

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N Kristof, NY Times (1/24/23): A Smarter Way to Reduce Gun Deaths

Some excerpts:

In 2021 a record 48,000 Americans were killed by firearms, including suicides, homicides and accidents. So let’s try to bypass the culture wars and try a harm-reduction model familiar from public health efforts to reduce deaths from other dangerous products such as cars and cigarettes.

Harm reduction for guns would start by acknowledging the blunt reality that we’re not going to eliminate guns any more than we have eliminated vehicles or tobacco, not in a country that already has more guns than people. 

Recommendations from article:

  • We can try to keep firearms from people who are under 21 or who have a record of violent misdemeanors, alcohol abuse, domestic violence or some red flag that they may be a threat to themselves or others
  • To keep ineligible people from buying firearms, we need universal background checks
  • A pillar of harm reduction involving motor vehicles is the requirement of a license to drive a car. So why not a license to buy a gun?… In Massachusetts, which has one of the lowest gun mortality rates in the country, an applicant who wants to buy a gun must pay $100 for a license, be fingerprinted, undergo a background check and explain why he or she wants a gun. If the permit is granted, as it typically is after a few weeks, the bearer can then go to a gun store and buy the firearm. There is then an obligation to store it safely and report if it is stolen.
  • Smoking and alcohol cause more deaths in U.S. –both are regulated, not banned. “Because we’ve worked to reduce vehicle deaths and haven’t seriously attempted to curb gun violence, firearms now kill more people than cars.”
  • Background checks to purchase ammunition… this should be possible without creating burdens for gun owners who have already gone through background checks to buy weapons
  • Waiting periods and limits on how many guns one can purchase at a time may also help. We also need to crack down on untraceable ghost guns and on firearms made by 3-D printers; ghost guns are already a growing source of weapons for criminals
  • Warning labels: One proposed ammunition label has a photo of a bloody face and states that a gun increases the risk of someone in a home being killed
  • Increase costs of ownership to cover the damage associated with weapons: raise cost of guns through taxes/fees

This article proposes a lot of practical interventions that if implemented would likely reduce gun violence.

Related article: NPR Jan 24, 2023: Gun violence deaths: How the U.S. compares with the rest of the world The chart below shows how the U.S compares to gun violence in countries with low levels of gun violence. The U.S. compares favorably with Mexico, El Salvador, Guatemala, Venezuela, The Phillipines and Iraq. However, many violent places have lower gun violence than U.S. including Syria, Somalia, Afganistan, Iran, Pakistan, Yemen, and Libya.

Related blog posts:

Atlanta Botanical Gardens

From NPR article.

Aslo, gun violence is widespread and is more common in ‘red’ states than ‘blue’ states despite the widely-held notion that gun violence occurs mainly in large urban centers.

Axios 1/27/23: Not an anomaly: 2020’s red states have higher murder rates Murder rates in red states have outpaced blue states by an average of 23% over the past two decades.

2023 ACG Celiac Guidelines for Adult and Children

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A Rubio-Tapia et al. Am J Gastroenterol 2023;118:59–76. Open Access! American College of Gastroenterology Guidelines Update: Diagnosis and Management of Celiac Disease Thanks to Ben Gold for this reference.

Here are some of the recommendations from updated ACG Celiac Guidelines:

Comments: The authors favor a non-biopsy approach for Celiac diagnosis in children with very elevated serology but not in adults. In adults, they cite a paucity of literature. “One multicenter international study of adults found that a 10-fold elevation of TTG IgA had a positive predictive value of 95% for CD (50). Given the life-long treatment implications of a GFD, this may be unacceptably low.”

The authors suggest assessing for mucosal healing after 2 years of treatment in all patients though they indicate a low quality of evidence for this recommendation. In those undergoing endoscopy, biopsies of the duodenal bulb along with at least 4 post-bulbar biopsies are recommended.

Figure 3 provides an algorithm for non-responsive celiac disease.

Related blog posts:

Liver Briefs: HLH in Infancy, Maralixibat for Alagille Syndrome, Liver Disease Due to Inborn Errors of Immunity

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N Hadzic et al. J Pediatr 2022; 250: 67-74. High Prevalence of Hemophagocytic Lymphohistiocytosis in Acute Liver Failure of Infancy In this retrospective study of pediatric acute liver failure (PALF, n=78) in children <24 months of age: Thirty of the 78 children had the HLH phenotype and underwent genetic assessment, which demonstrated positive findings in 19 (63.3%), including 9 (30%) with biallelic primary HLH mutations and 10 (33.3%) with heterozygous mutations and/or polymorphisms. The mortality in this group was 33% (n=10). The authors conclude that targeted genetic analysis (ie perforin, SIAP, XIAP, and GRA) or whole exome sequencing should become a standard part of PALF workup.

Related blog posts:

BM Kamath et al. J Pediaatr 2023; 252: 68-75. Open Access! Maralixibat Treatment Response in Alagille Syndrome is Associated with Improved Health-Related Quality of Life. Twenty of the 27 patients (74%), all with moderate-to-severe pruritus at enrollment, achieved an Itch-Reported Outcome (Observer) treatment response at week 48. “The significant improvements in pruritus seen with maralixibat at week 48 of the ICONIC study are clinically meaningful and are associated with improved HRQoL.”

Related blog posts:

D Sharma et al. Hepatology 2022; 76: 1845-1861. Tip of the iceberg: A comprehensive review of liver disease in Inborn errors of immunity This articles reviews inborn errors of immunity (IEI) and their liver manifestations. This includes the following:

  • T-cell/B-cell deficiency: SCID, CD40 ligand deficiency, DOCK8 deficiency, IL-21R deficiency, and Activated P13K delta syndrome
  • Antibody deficiency: CVID, X-linked aggamoglobulinemia
  • Phagocytic disorders: CGD
  • Primary Immune Regulatory Disorders: STAT1 GOF, STAT3 GOF, IPEX, APECED
  • Others: Wiskott-Aldrich syndrome, Immunodeficiency-centromeric instability-facial anomalies syndrome, Hepatic veno-occlusive disease with immunodeficiency, STAT3-deficient hyper IgE syndrome

In patients with IEIs with liver abnormalities, one needs to consider infectious etiologies (eg. HAV, HBV, HCV, HEV, CMV, EBV, HSV, cryptosporidium, liver abscess), autoimmune disorders (eg. AIH), drug-induced liver disease, and sclerosing cholangitis

Royal Terns at Siesta Key, FL

Poster Child for Gaming Pharmaceutical Regulations: Humira

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NY Times 1/29/23): How a Drug Company Made $114 Billion by Gaming the U.S. Patent System “AbbVie for years delayed competition for its blockbuster drug Humira, at the expense of patients and taxpayers. The monopoly is about to end.”

This article details how AbbVie has perfected the use of patent protections to extend its monopoly over adalimumab; this has been to the detriment of many patients , employers and taxpayers who bear the additional costs. Key points:

  • In 2016, a blockbuster drug called Humira was poised to become a lot less valuable. The key patent on the best-selling anti-inflammatory medication, used to treat conditions like arthritis, was expiring at the end of the year…Through its savvy but legal exploitation of the U.S. patent system, Humira’s manufacturer, AbbVie, blocked competitors from entering the market.
  • Since the end of 2016, the drug’s list price has gone up 60 percent to over $80,000 a year, according to SSR Health, a research firm.
  • Patents are good for 20 years after an application is filed. Because they protect patent holders’ right to profit off their inventions, they are supposed to incentivize the expensive risk-taking that sometimes yields breakthrough innovations. But drug companies have turned patents into weapons to thwart competition. AbbVie and its affiliates have applied for 311 patents, of which 165 have been granted, related to Humira, according to the Initiative for Medicines, Access and Knowledge, which tracks drug patents. A vast majority were filed after Humira was on the market.
  • The article notes that one employer has been flying a patient receiving Humira to the Bahamas to pick up her medication.
  • AbbVie … will have a new way to make more money from the drug. Under the terms of the legal settlements… AbbVie will earn royalties from the knockoff products that it delayed.
  • In the longer run, though, AbbVie’s success with Humira may boomerang on the drug industry. Last year, the company’s tactics became a rallying cry for federal lawmakers as they successfully pushed for Medicare to have greater control over the price of widely used drugs that, like Humira, have been on the market for many years but still lack competition.

My take: It makes me mad when I read this article. First of all, there are a lot of patients harmed by this gaming. Second, it is outrageous that the cost of this expensive medication was raised 60% over the last 6 years (and going up 8% more in 2023). Third, I am disappointed to learn that AbbVie will still make money off biosimilars because I am looking forward to NOT using Humira because of these tactics. Lastly, I hope that this does prompt legislative/regulatory changes to limit this practice going forward.

Related article: USA Today (1/30/23) Why drugmakers have raised prices on nearly 1,000 drugs so far this year Average medication increase for 2023 is 5%. “Nearly half of new drugs cost $150 000 per year in 2020 and 2021. Fewer than 10% of new drugs launched at that price in 2008.”

Related blog posts:

Picking Apart the SERENE-CD Study & Constipation Vibrating Capsule FDA Approved

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Several recent letters to the editor provide some insight into some of the shortcomings of the SERENE-CD study which reported that higher adalimumab induction dosing and proactive therapeutic drug monitoring (TDM) were not associated with improved outcomes.

“The rerandomization design of SERENE CD, which selectively enrolled patients with clinical response at week 12 to the TDM vs CA part of the study, may have resulted in the exclusion of those who would have benefited the most from early adjustment of their anti-tumor necrosis factor (TNF) dose. The rerandomization design and the late adaptation of the proactive strategy at week 12 were 2 significant aspects of the design that may have led to the negative results. On the other hand, PAILOT, which showed beneficial effects of proactive TDM, randomized patients as early as week 4 and assessed the outcome at week 72. This is distinct from the 1-year time frame used in most other studies, including SERENE CD.8 A properly designed, adequately powered clinical trial is needed before we can make a judgement on the use of proactive TDM in patients with inflammatory bowel disease. Until then, the jury remains out.”

“The study design only allowed patients in the TDM group with adalimumab concentrations of ≥5 and ≤10 μg/mL to be escalated to 40 mg every week if their CD activity index was ≥220 or their high-sensitivity C-reactive protein level was ≥10 mg/L.. The goal of proactive TDM is to attain a threshold concentration regardless of disease activity. This design probably led the 2 groups to have similar drug concentrations at week 56…

Second, a rather low targeted drug concentration of 5 μg/mL was used, although previous studies have suggested that higher concentrations are more appropriate.5, 6, 7, 8 A study from Ungar et al5 showed that adalimumab concentrations of 8–12 μg/mL are required to achieve mucosal healing in 80%–90% of patients with IBD, and the prospective PANTS (The Personalised Anti-TNF Therapy in Crohn’s Disease Study) study identified an adalimumab concentration of 12 μg/mL at week 14 associated with remission at both week 14 and week 54.8..

Third, dose escalation for the TDM group could only happen at weeks 14, 28, or 42 (and not earlier and more often). In the PAILOT RCT, proactive TDM based on adalimumab concentration evaluations started as early as week 4 followed by week 8 and every 8 weeks thereafter until the end of the follow-up at week 72.3 Fourth, there was a rather short follow-up of the patients (44 weeks).”

” Even with the assumption of a 30% benefit of proactive TDM and that 20% of patients would have low drug levels in the absence of symptoms, the sample size for 80% power would range from 1228 to 2170. Thus, although SERENE CD1 and other clinical trials3,4 have suggested a lack of benefit of proactive TDM in adults with inflammatory bowel disease, all were likely substantially underpowered to do so.”

My take: While the SERENE-CD results have suggested that a strategy of proactive TDM may not be helpful, there are a lot of reasons to disregard these findings. Achieving a therapeutic level is a fundamental principle and proactive TDM, particularly in pediatrics, is well-supported by other studies.

Related blog posts:

Also noted: