Pediatric Capsule Endoscopy Curriculum Study

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UP Phatak et al. JPGN Reports 2022. 3: e130. Open Access: Pediatric Web-based Video Capsule Endoscopy Curriculum: A Pilot Study to Determine the Ability to Implement a Standardized Educational Curriculum

In this pilot study, 12 individuals completed a web-based curriculum for VCE proficiency.

Key finding:

  • Participants showed significant improvement in knowledge (P = 0.041) and photo recognition posttests (P = 0.015). All participants who completed the curriculum found it helpful and reported that they would recommend it to their colleagues

The discussion notes that “Studies have demonstrated that competence with VCE develops in an endoscopist after reading 10–15 VCE studies (6,10). There are some newer guidelines that suggest that this number may be higher…[and] it requires continuous practice. Pediatric gastroenterologists may feel their skills are not adequate when VCEs are not performed on a consistent basis at their institution”

Website for VCE Training: Pediatric Capsule Endoscopy Curriculum Study

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Early Antibiotics -Minimal Risk for Crohn’s Disease

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Previous studies have shown an association between the early use of antibiotics and an increased risk of inflammatory bowel disease. A recent study examined all the children born in Denmark from 1995-2009 and followed them up to 2013 via a prospectively maintained database.

A Mark-Christensen et al. Inflamm Bowel Dis 2022; 28: 415-422. Early-Life Exposure to Antibiotics and Risk for Crohn’s Disease: A Nationwide Danish Birth Cohort Study 

During a median 9.5 years (9.3 million total person-years), CD was diagnosed in 208 of 979,039 children.

Key findings:

  • Antibiotic use in the first year of life was associated with a higher risk of CD (adjusted hazard ratio, 1.4)…with the highest risk with ≥6 courses of antibiotics (adjusted hazard ratio, 4.1)
  • The cumulative risk of CD at the 11th birthday for children exposed to antibiotics in their first year of life was 0.16% compared to 0.11% for children unexposed to antibiotics in their first year of life. 

My take: This study indicates that antibiotics (and/or serious infections) are associated with an increased the risk of pediatric Crohn’s disease but the absolute risk is very low. We still have a lot to learn about how environmental exposures, including diet, infections, antibiotics, and pollution, contribute to the increasing prevalence of inflammatory bowel disease.

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From Atlanta Botanical Gardens -Thanks to Jennifer for this picture

Health Benefit from Disease State: Sucrase-Isomaltase Deficiency

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It is well-recognized that genetic mutations that persist often confer some advantages. For example, sickle cell trait (but not disease) provides protection against malaria.

A recent study shows potential health benefits in those with sucrase-isomaltase deficiency: MK Andersen, L Skotte, E Jorsboe et al. Gastroenterol 2022; 162: 1171-1182. Open Access: Loss of Sucrase-Isomaltase Function Increases Acetate Levels and Improves Metabolic Health in Greenlandic Cohorts

Methods: “The association between c.273_274delAG and phenotypes related to metabolic health was assessed in 2 cohorts of Greenlandic adults (n = 4922 and n = 1629). A sucrase-isomaltase knockout (Sis-KO) mouse model was used to further elucidate the findings”

Key findings:

  • Homozygous carriers of the variant had a markedly healthier metabolic profile than the remaining population, including lower body mass index ( –2.0 kg/m2; P = 3.1 × 10–5), body weight (–4.8 kg; P = 5.1 × 10–4), fat percentage (–3.3%; P = 3.7 × 10–4), fasting triglyceride (–0.27 mmol/L; P = 2.3 × 10–6), and remnant cholesterol (–0.11 mmol/L; P = 4.2 × 10–5).
  • The metabolic profile “was likely mediated partly by higher circulating levels of acetate observed in homozygous carriers” (0.056 mmol/L; P = 2.1 × 10–26), and partly by reduced sucrose uptake, but not lower caloric intake.
  • “These findings were verified in Sis-KO mice, which, compared with wild-type mice, were leaner on a sucrose-containing diet, despite similar caloric intake, had significantly higher plasma acetate levels in response to a sucrose gavage, and had lower plasma glucose level in response to a sucrose-tolerance test.” 

My take: It should not be surprising that a genetic condition that results in limited sucrose intake would have health benefits. Perhaps correcting this condition will result in unexpected health issues similar to health issues that can develop in those with celiac disease after institution of a gluten-free diet (Gastroenterol 2013; 144: 912-17).

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Graphical Abstract:

Expert Advice: De-Prescribing Proton Pump Inhibitors

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LE Targownik et al. Gastroenterol 2022; 162: 1334-1342. Open Access: AGA Clinical Practice Update on De-Prescribing of Proton Pump Inhibitors: Expert Review

Background: “Proton pump inhibitors (PPIs) are among the most commonly used medications in the United States, if not the world. Observational studies have demonstrated that PPI use has increased over time and that 7%–15% of patients use these medications at any time, with the prevalence increasing to 40% for patients 70 years or older…In a large observational study examining ambulatory visits of PPI users, nearly two-thirds had no clear indication for PPI use.”

Some of the best practice advice:

  • Best Practice Advice 2 All patients taking a PPI should have a regular review of the ongoing indications for use and documentation of that indication. This review should be the responsibility of the patient’s primary care provider.
  • Best Practice Advice 3 Most patients with an indication for chronic PPI use who take twice-daily dosing should be considered for step down to once-daily PPI.
  • Best Practice Advice 4 Patients with complicated gastroesophageal reflux disease, such as those with a history of severe erosive esophagitis, esophageal ulcer, or peptic stricture, should generally not be considered for PPI discontinuation.
  • Best Practice Advice 5 Patients with known Barrett’s esophagus, eosinophilic esophagitis, or idiopathic pulmonary fibrosis should generally not be considered for a trial of de-prescribing.
  • Best Practice Advice 7 Patients at high risk for upper gastrointestinal bleeding should not be considered for PPI de-prescribing.
  • Best Practice Advice 10 The decision to discontinue PPIs should be based solely on the lack of an indication for PPI use, and not because of concern for PAAEs (PPI-associated adverse events).

My take: There are a lot of individuals who could benefit from de-prescribing PPIs.

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Thanks to Susan for this picture which shows why our neighborhood is covered in a fine yellow dust.

Shiny New Object: Gene Therapy in Gastroenterology

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It’s hard not to be fascinated by the emerging treatments in gene therapy. A great summary of this topic as it relates to gastroenterology:

RL Kruse et al. Gastroenterol 2022; 162: 1019-1023. Open Access: How to Embrace Gene Therapy in Gastroenterology

Key points:

  • Researcher’s have utilized viruses to introduce exogenous DNA in efforts to correct defects in genetic diseases. Adeno-associated virus (AAV) vectors are the most common vectors used. In addition, AAV have a natural tropism to the liver following intravenous infusion
  • “Highlighting programs with the most advanced efficacy, hemophilia gene therapies in the liver have advanced into phase 2/3 and have shown promising efficacy based on factor VIII or IX levels achieved and reduction in bleeding events, with the main questions being long-term expression and safety of the approach”

Limitations:

  • “Integrated AAV have been associated with an increased incidence of hepatocellular carcinoma in mice”
  • Antibodies to AAV may be present or develop after infusion…” this factor has precluded any redosing in trials because antibodies would neutralize all incoming vectors”
  • In hemophilia trials, in the liver there has been a slow decrease in the levels of expression over time 6 which indicates that years into the future patients will need to be redosed to maintain efficacy
  • “Practically, AAV can only achieve delivery in a fraction of cells within an organ”

Newer Approaches for Gene Delivery:

  • mRNA delivery: mRNA is being explored as a tool for gene therapy, because mRNA only requires cytoplasmic delivery for expression.
  • “mRNA can also express gene-editing enzymes like Cas9….However, gene editing presents inherent risks of off-targeting cutting or base editing that would occur in millions of hepatocytes, potentially leading to cancer”
  • “Nonviral approaches of DNA delivery could drop the costs of vector production at least 100-fold versus AAV…delivery of DNA through LNPs [lipid nanoparticles] has largely yielded inefficient gene expression”
  • “Hydrodynamic injection is a process where fluid pressure is used to deliver naked DNA directly into cell…injection into the biliary system through endoscopic retrograde cholangiopancreatography”

The authors note that gene delivery could be important in modifying more common disorders including nonalcoholic steatohepatitis, diabetes and autoimmune diseases.

My take: While this field of study is quite exciting, to me it is definitely a shiny object, like all of precision medicine, in that it may distract researchers and physicians away from more pressing common problems.

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For Policy Wonks: Bayh-Dole Act and Reducing Pharmaceutical Costs

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AB Engelberg et al. NEJM 2022; 386: 1104-1106 (Commentary). A New Way to Contain Unaffordable Medication Costs — Exercising the Government’s Existing Rights

This commentary notes that the National Institutes of Health (NIH) spends more than $40 billion each year to fund biomedical research. “We believe that medicines discovered at public expense should be affordable.”

A Few Excerpts:

  • “Existing laws provide two paths for achieving this result. First, the Bayh–Dole Act of 1980 gives the government a royalty-free license to use patented inventions that were discovered using federal funding. The government has never exercised its Bayh–Dole license”
  • “Second, 28 U.S. Code §1498, which dates to 1910, gives the government immunity from being sued for patent infringement in federal courts, while giving patent owners the right to receive reasonable compensation when the government makes or uses a patent-protected product”
  • Case in point: “Recently, the government signed a contract with Merck to purchase molnupiravir (Lagevrio), an oral antiviral drug that reduces the severity of Covid-19. The contract price of $712 per treatment is estimated to be more than 35 times the cost of producing the drug at a reasonable profit. Molnupiravir was discovered at Emory University using government funding, and Emory’s patent applications acknowledge the government’s Bayh–Dole license.5 Molnupiravir payments for Medicare, Medicaid, and VHA patients could cost the government billions in 2022. This amount could be reduced by more than 90% if the government exercised its license and allowed a generic manufacturer to supply the drug for patients in government-supported programs.”

My take: U.S. taxpayers should get a return on their investment when new medications are developed with government funding rather than paying more for these medications than any other country.

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Ravenel Bridge, Charleston SC (blue skies -no filter)

Digital Health Care Inclusion

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JA Rodriguez, et al. NEJM 2022; 386: 1101-1103 (commentary). Digital Inclusion as Health Care — Supporting Health Care Equity with Digital-Infrastructure Initiatives

Key points:

  • “With digital health tools such as telehealth and patient portals becoming prominent components of care delivery, the barriers to digital inclusion have grown increasingly apparent.1 For example, more than 100 studies have revealed disparities in portal use based on age, race, socioeconomic status, English-language proficiency, and other factors”
  • Barriers: digital redlining (discrimination by internet providers), limited broadband infrastructure/access, costs, and knowledge
  • “The recently enacted Infrastructure Investment and Jobs Act (IIJA) makes investments that could foster sustainable digital inclusion”
  • “The IIJA takes much of the responsibility for building digital infrastructure away from individual health care organizations and makes digital inclusion a public concern. The law includes $65 billion for digital-inclusion initiatives. It earmarks $42.5 billion for investment in broadband infrastructure by means of state deployment grants, promotes broadband affordability by providing $14.2 billion for $30-per-month subsidies for Internet costs for underserved people, and allocates $2.8 billion for the creation of digital-literacy programs. It also includes funds to support connectivity in tribal communities and broadband deployment in rural areas”
  • “The law charges the FCC with adopting rules to prevent “digital discrimination of access based on income level, race, ethnicity, color, religion, or national origin.” These policies are an attempt to overcome structural barriers to digital inclusion, such as redlining”
  • “By capitalizing on new policies, health care organizations could become a critical part of an environment of community-based players working toward digital inclusion”

Issues Not Addressed by Infrastructure Investment and Jobs Act (IIJA):

  • “Law doesn’t address changes that are needed to the design of digital health platforms (e.g., language translation) or to make workflows more inclusive (e.g., integration of interpreters into telehealth visits)”
  • “Simplification of interstate licensing laws for clinicians would also enable digital tools to increase access to care for marginalized populations”
  • Assuring adequate reimbursement for digital care

My take: Digital health literacy/availability is needed to improve outcomes.

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Island in Charleston Harbor with Ravenel Bridge in the distant (near Shem Creek)

Predicting Intestinal Failure After Gastroschisis Repair

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N Vinit et al. J Pediatr 2022; DOI:https://doi.org/10.1016/j.jpeds.2021.11.004 (Ahead of print) Predicting Factors of Protracted Intestinal Failure in Children with Gastroschisis

Methods: Retrospective study. Among 180 patients, 35 required long-term parenteral nutrition (SBS-IF group) and 145 acquired full oral feeding within 6 months (oral feeding group) over mean f/u of 7.9 years.

Key findings:

  • Both bowel matting (OR, 14.2, P = .039) and secondarily diagnosed atresia or stenosis (OR, 17.78, P = .001) were independent postnatal predictors of SBS-IF.
  • An initial residual small bowel length of more than 50 cm was the best predictive cut-off for nutritional autonomy, with a sensitivity of 67% and a specificity of 100%

My take: This study identifies bowel matting and atresia/stenosis as additional factors in predicting nutritional autonomy.

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Tricky Article Title: IBD and Celiac

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M Alkhayyat et al. Inflamm Bowel Dis 2022; 28: 385-392. Patients With Inflammatory Bowel Disease on Treatment Have Lower Rates of Celiac Disease

When I first saw this title, I mistakenly thought the title indicated that celiac disease (CD) occurred less often in those with inflammatory bowel disease (IBD). This would have been surprising given previous studies have found the opposite. In fact, this study confirms the bidirectional associated risk between patients with CD and in patients with IBD but with a twist. Most IBD treatments were associated with a lower risk of developing CD than those who were not treated.

Database study: Of the 72,965,940 individuals in the database (1999-2020), 133,400 had celiac disease (CD) (0.18%), 191,570 (0.26%) had ulcerative colitis (UC), and 230,670 (0.32%) had Crohn disease.

Key findings:

  • Patients with IBD were more likely to have a diagnosis of celiac disease (odds ratio [OR], 13.680), with a greater association with Crohn disease (OR 24.473).
  • Treated patients with IBD with UC and with Crohn disease, respectively, had a lower risk association with CD compared to those not undergoing IBD treatment, specifically corticosteroids (OR, 0.407 and 0.585), 5-aminosalicylates (OR, 0.124 and 0.127), immunomodulators (OR, 0.385 and 0.425), and anti-tumor necrosis factor drugs (OR, 0.215 and 0.242)
  • A new diagnosis of CD after 1 year of IBD diagnosis, was 1.59% for Crohn disease and 0.90% for UC compared to 0.16% in patients without IBD (P<0.0001)
  • A new diagnosis of IBD, Crohn disease and UC respectively, in patients with celiac disease was 2.75% and 1.11% compared to 0.29% and 0.25% in the non-celiac population (P<0.0001)
  • A new diagnosis of IBD and celiac disease among patients with microscopic colitis was 10.5% and 2.6% respectively; a new diagnosis of microscopic colitis among patients with celiac disease was 0.01%

My take: This study confirms the bidirectional associated risk between IBD and celiac disease. The risk of developing celiac disease in those with IBD may be lower in those receiving some treatments; however, this assertion is limited by the nature of a database study.

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Pelicans at Shem Creek, SC (near Charleston)

Does Motivational Interviewing Help Long-Term Outcomes for Obesity?

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M Michalopoulou et al. Annals Int Med 2022; https://doi.org/10.7326/M21-3128. Effectiveness of Motivational Interviewing in Managing Overweight and Obesity

This review and meta-analysis examined forty-six studies involving 11 077 participants.

Key findings:

  • At 6 months, behavior weight management programs (BWMPs) using motivational interviewing (MI) were more effective than no/minimal intervention (−0.88) but were not statistically significantly more effective than lower-intensity (−0.88 ) or similar-intensity (−1.36 ) BWMPs.
  • “At 1 year, data were too sparse to pool comparisons with no/minimal intervention, but MI did not produce statistically significantly greater weight change compared with lower-intensity”

My take: Several years ago our hospital system strongly encouraged practitioners to learn motivation interviewing techniques. However, based on this review, “there is no evidence that MI increases effectiveness of BWMPs in controlling weight.”

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Isle of Palms, SC