Category Archives: Uncategorized

Why Is There Low Adherence to H pylori Guidelines?

Posted on by

S Bonilla et al. JPGN 2021; 73: 178-183. Low Adherence to Society Guidelines for the Management of Helicobacter Pylori Among Pediatric Gastroenterologists

This retrospective study with 250 patients determined that clinicians at this large center (Boston Children’s) have a low rate of adherence to the NASPGHAN/ESPGHAN H pylori guidelines (JPGN 2017; 64: 991-1003).

Key findings:

  • Patient outcomes: 107/186 (58%) had resolution of symptoms after treatment; abdominal pain was the most common presenting symptom (67%)
  • 131 (62%) had documented followup visit and an eradication test
  • First-line treatment was most commonly amoxicillin, clarithromycin, and PPI (69%) (in those without sensitivity information, amoxicillin, metronidazole, and PPI are recommended in the guidelines)
  • Biopsy culture was sent in 3% of patients

In their discussion, the authors make a number of points:

  • Both pediatricians and gastroenterologists “are utilizing a ‘test and treat’ strategy rather than endoscopy-based diagnostic testing.” This along with low followup and low biopsy culture deviate from NASPGHAN guideline.
  • 77 of 256 patients had non-invasive testing prior to referral and in this subset, more than two-thirds of patients received a clarithromycin-based triple therapy before being referred; “this has a high likelihood of failure.”
  • The authors advocate endoscopy over empiric treatment but acknowledge some reasons why families may want to avoid endoscopy (interestingly the authors do not mention the cost of the procedure). They also note that H pylori culture is not widely available.

My take: There are several reasons why there is low adherence to NASPGHAN/ESPGHAN guidelines

  1. Treatment recommendations for initial triple therapy does not align with adult guidelines for quadruple therapy. Even the “rescue” therapies (Table 5), these pediatric guidelines do not recommend quadruple therapy. Yet, there is no indication that H pylori is more susceptible to treatment in children.
  2. Recommendations for susceptibility/antibiotic resistance testing (Table 1, #11) makes no sense if susceptibility testing is not available. Fortunately, PCR-based assays are making this easier recently.
  3. The absence of susceptibility testing and cost would favor empiric treatment over endoscopy as a first-line approach in those who have a reliable non-invasive test indicating infection along with symptoms suggestive of H pylori infection.

Related blog posts:

Adult Guidelines:

Other related posts

This is the treatment approach per pediatric guidelines; these recommendations
do NOT align with treatment recommendations in adults

Sugary Diet and Colonic Adenomas

Posted on by

H-K Joh et al. Gastroenterol 2021; 161: 128-142. Full text: Simple Sugar and Sugar-Sweetened Beverage Intake During Adolescence and Risk of Colorectal Cancer Precursors

Methods: We prospectively investigated the association of adolescent simple sugar (fructose, glucose, added sugar, total sugar) and sugar-sweetened beverage (SSB) intake with CRC precursor risk in 33,106 participants of the Nurses’ Health Study II who provided adolescent dietary information in 1998 and subsequently underwent lower gastrointestinal endoscopy between 1999 and 2015.

Key Findings:

  • High sugar and SSB intake during adolescence was positively associated with risk of adenoma, but not serrated lesions.
  • Per each increment of 5% of calories from total fructose intake, multivariable ORs were 1.17 (95% CI, 1.05–1.31) for total and 1.30 (95% CI, 1.06–1.60) for high-risk adenoma

Full text (editorial, pg 27): JK Lee et al: Sugary Truth of Early-Onset Colorectal Neoplasia—Not So Sweet After All

Key points:

  • “In the United States, SSB [sugar-sweetened beverage] consumption has increased by nearly 5-fold over time, from 10.8 gallons per person in 1950 to 49.3 gallons per person in 2000.8 In adolescents, SSB consumption has more than doubled since the 1960s and comprises the largest source of simple sugar and calories in their diets”
  • “Recent studies, including several from the Nurses’ Health Study, have identified lifestyle factors from early adulthood, including Western diet,13,14 alcohol,15 tobacco,16 sedentary television viewing,11 diabetes,17 and obesity12 as risk factors for early-onset CRC or adenoma. Other studies report no association between sugar, fruit juice, and SSB consumption during adulthood and risk of CRC in older adults”

My take (borrowed from editorial): “Increasing fructose and SSB consumption, particularly among adolescents and young adults, is troublesome because substantial evidence links consumption to various health outcomes, including obesity, type 2 diabetes, cardiovascular disease, some cancers, all-cause mortality, and now early-onset high-risk adenoma…. clinicians should continue to support public health policies discouraging or reducing consumption of simple sugars and SSBs in adolescents, for whom exposure might have lifelong consequences.”

COVID Booster Advice for IBD from Dr. David Rubin (@IBDMD)

Posted on by

On Friday, our office started fielding questions regarding COVID-19 booster shots in our IBD population. Currently, I agree with the advice for patients as detailed by Dr. Rubin in the screenshots that follow. Key points:

  • Studies have shown that IBD patients are not at increased risk of COVID-19 infections compared to the general population. 
  • Except for those on high-dose prednisone, it appears that our patient population with IBD does mount an adequate response to vaccination.  That is, they are not considered severely immunocompromised. 
  • In short, it is reasonable, but not a clear recommendation, to give a booster mRNA vaccine dose to patients who are receiving anti-TNF agents and those receiving immunomodulators; this is a patient choice.

Also, from CDC 8/13/21:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  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.

“What is Biden Waiting For?” & COVID-19 Vaccine Effectiveness for Delta Variant

Posted on by

A good read by Don McNeil Jr: What is Biden Waiting For?

He argues that the federal government needs to do a lot more, including the use of vaccine mandates to control this pandemic.

Some excerpts:

  • Why is this administration so hesitant about saving American lives? And the American economy?….
  • The key to saving lives is vaccine. The key to reopening offices and factories is vaccine. The key to reopening schools is vaccine. The key to keeping bars and restaurants open in cold weather is vaccine. The key to travel and shopping is vaccine. Vaccine in everybody….
  • mRNA vaccines start waning after six months. Israel is already offering booster shots to everyone over 60. We must do the same….We are too fearful of very rare side effects…
  • Why in the world do we not yet have federal vaccine passports? In a land of block-chain currencies, QR code menus, encrypted texts and microchip credit cards, those little CDC-logo flashcards are just pathetic…
  • It’s also time to drop “religious exemptions.” No major religion — not one, from Confucianism to Catholicism — opposes vaccination…
  • We need to treat deliberate disinformation for what it is: a betrayal of the American public.

My take: With the emergence of the Delta variant, it will take a much higher level of vaccination/natural immunity (>95%) to control this pandemic. Vaccination is a much safer strategy than natural immunity (after infections).

Also, NEJM Quick take: Effectiveness of COVID-19 Vaccines (1:29 min). Pfizer-(BNT162b2) vaccine had 88% effectiveness against Delta variant in England after 2 doses compared to 94% for alpha variant..

Zantac 360 is Not Zantac

Posted on by

Recently the FDA has allowed Zantac to be relaunched as Zantac 360. This is well-described in a recent blog post on GoodRx: Zantac Returns to Market With a New Ingredient

While famotidine (the new ingredient in Zantac 360) acts similar to ranitidine (the old ingredient), there is no longer N-nitrosodimethylamine (NDMA) detectable which was a concern as a potential cancer risk. It comes in two different strengths (10 mg and 20 mg).

My take: In my view, it is a bad decision to allow Zantac to be relaunched with this new ingredient; this is like allowing some hot dogs to be sold as hamburgers.

Related blog posts:

Engineering New Treatments for Celiac Disease

Posted on by

This month’s Gastroenterology featured two new approaches for the treatment of celiac disease.

CP Kelly et al. Gastroenterol 2021; 161: 66-80. Full text: TAK-101 Nanoparticles Induce Gluten-Specific Tolerance in Celiac Disease: A Randomized, Double-Blind, Placebo-Controlled Study

IS Pultz et al. Gastroenterol 2021; 161: 81-93. Full text: Gluten Degradation, Pharmacokinetics, Safety, and Tolerability of TAK-062, an Engineered Enzyme to Treat Celiac Disease

In the first study, Kelly et al used TAK-101 nanoparticles in Phase 1 and Phase 2a trials. In the Phase 2a trial with 33 patients, TAK-101 induced an 88% reduction in change from baseline in interferon-γ spot-forming units vs placebo (2.01 vs 17.58, P = .006). Vh:Cd deteriorated in the placebo group (−0.63, P = .002), but not in the TAK-101 group (−0.18, P = .110) Overall, TAK-101 was well tolerated and prevented gluten-induced immune activation.

Graphical abstract from CP Kelly et al. Gastroenterol 2021; 161: 66-80.

In the second study, Pultz et al developed TAK-062 which is a novel, computationally designed endopeptidase to break down gluten under simulated gastric conditions in vitro and in healthy participants in the phase I study.  Residual gluten (collected through gastric aspiration in the phase I study) was quantified using R5 and G12 monoclonal antibody enzyme-linked immunosorbent assays. Key finding: In vitro, TAK-062 degraded more than 99% of gluten (3 g and 9 g) within 10 minutes. In the phase I study, administration of TAK-062 was well tolerated and resulted in a median gluten degradation ranging from 97% to more than 99% in complex meals containing 1–6 g gluten at 20–65 minutes postdose.

The associated editorial highlights these studies and reviews their limitations; in addition, the authors review the current non-dietary strategies (see below), pg 21-24: Full text: The Promise of Novel Therapies to Abolish Gluten Immunogenicity in Celiac Disease

From editorial, Gastroenterol 2021; 161: 21-24.

My take: These studies indicate that non-dietary treatments may be effective at some point, but not in the near future.

Related blog posts:

Paternal Exposure to IBD Medications and Neonatal Outcomes

Posted on by

COVID-19 Vaccine Effectiveness (8/10/21):

————————————————————————————————————-

J Meserve et al. Gastroenterol 2021; 161: 107-115. Full text: Paternal Exposure to Immunosuppressive and/or Biologic Agents and Birth Outcomes in Patients With Immune-Mediated Inflammatory Diseases

Methods: The investigators used a deidentified administrative claims database (OptumLabs Data Warehouse) with a total of 7453 expectant fathers with immune-mediated diseases.

Key findings:

  • As compared to unexposed fathers (3.4% prevalence of major congenital malformations), exposure to immunosuppressives/biologics were not associated with increased risk of major congenital malformations: thiopurines (relative risk [RR], 1.12; 95% confidence interval [CI], 0.66–1.76), methotrexate (RR, 0.67; 95% CI, 0.21–1.55), TNF-α antagonists (RR, 1.14; 95% CI, 0.81-1.57), and non–TNF-targeting biologic agents (RR, 1.75; 95% CI, 0.80–3.24).
  • No association was observed between paternal medication exposure and risk of preterm birth or low birth weight.

Editorial, pg 24-27: S Friedman et al. Full text: Does Fatherhood Matter? Preconception Use of Biologics and Immunomodulators by Fathers With Immune-Mediated Diseases and Birth Outcomes of Their Offspring

“Regarding major congenital malformations, we believe that the results should be interpreted with caution. The numbers of these outcomes are relatively low and the statistical precision of the risk estimates should be taken into consideration.”

My take: Overall, this study is reassuring. Though it is difficult to prove these medications do not have impacts on newborns, if these effects were frequent, it would likely be evident in this type of study.

Hepatitis B: Natural History and Difficulty Treating Immunotolerant Children

Posted on by

S Mo et al. JPGN 2021; 73: 150-155. Natural History of Chronic Hepatitis B Infection Among Chinese Children and Young Adults: A Single-Center Experience

Key findings:

  • Of the 353 patients, there were immune-tolerant 112 (34%), HBeAg-positive immune-active 47 (14%), and inactive carrier 82 (25%). The remaining 88 patients (27%) did not fit into a particular category with 26 of 88 patients meeting the criteria for inactive carrier except for mildly elevated alanine aminotransferase
  • Among 179 patients followed for ≥5 years, the spontaneous seroconversion rate was 38% (from HBeAg-positive to HBeAg-negative along with anti-HBeAb positivity)

In their discussion, the authors make two key points:

  1. “No substantial benefit from anti-viral therapy” has been evident in children in the immuno-tolerant phase (MM Jonas et al. Hepatology 2016; 63: 307-318.)
  2. The updated AASLD guidelines “strongly recommend anti-viral therapy for HBeAg-positive pregnant women with a serum HBV DNA >200,000 IU/mL”

G Mieli-Vergani et al. JPGN 2021; 73: 156-160. Peginterferon Alfa-2a (40KD) Plus Lamivudine or Entecavir in Children With Immune-Tolerant Chronic Hepatitis B

As noted above, antiviral therapy has not been shown to be effective in children who are in the immuno-tolerant phase; however, the authors of this study explored whether combination therapy could be effective in a randomized, controlled, multicenter study (n=59).

  • Key finding: At 24 weeks post-treatment, 1 of 26 patients in the antiviral treatment group experienced HBsAg loss (vs none of 33 patients in the control group)

My take: These studies reinforce the notion that children in the immuno-tolerant phase of HBV infection do not benefit from antiviral therapy. Prevention of infection is the most promising strategy.

Related blog posts:

Confirmation Bias diagram. From Steve Stewart-Williams

Jim Heubi

Posted on by

So sad to hear that Jim Heubi has passed away. Jim Heubi was the person I interviewed with when I was considering where to do my pediatric residency and he helped convince me to come to Cincinnati. During my fellowship, I came to admire how he was so good at everything though it was always unassuming. He was such a kind person in addition to being a mentor and role model.

Here is a link from Cincinnati Children’s: In Memoriam: James E. Heubi, MD 1948-2021