Blaming Reflux for BRUEs -Not Changing Despite Guideline Recommendations

Briefly noted: DR Duncan et al. J Pediatr 2019; 211: 112-9.

In this retrospective cohort study of infants with brief resolved unexplained events (BRUEs) at Boston Children’s Hospital, the authors examined guideline implementation among 359 subjects in the year before and the year after AAP guidelines.

Key findings:

  • There were no significant changes in practice after guideline publication
  • Only 13% had videofluoroscopic swallow study performed; 72% of these showed aspiration/penetration
  • No subject had reflux testing, “yet reflux was implicated as the cause” for BRUE in 40%. Children continued to be “discharged on acid suppression despite lack of efficacy”

My take: The pendulum is (slowly) starting to swing back from blaming everything (including BRUEs) on reflux but this change is not evident in this study.

Related blog posts:

Vaccine Injury Claims Are Rare

NY Times: Vaccine Injury Claims Are Few and Far Between

An excerpt:

The data comes from the National Vaccine Injury Compensation Program, a no-fault system begun in 1988 after federal law established it as the place where claims of harm from vaccines must be filed and evaluated. It currently covers claims related to 15 childhood vaccines and the seasonal flu shot.

Over the past three decades, when billions of doses of vaccines have been given to hundreds of millions of Americans, the program has compensated about 6,600 people for harm they claimed was caused by vaccines. About 70 percent of the awards have been settlements in cases in which program officials did not find sufficient evidence that vaccines were at fault…

The Centers for Disease Control and Prevention has estimated that vaccines prevented more than 21 million hospitalizations and 732,000 deaths among children over a 20-year period….

There were about two claims of injury for every one million doses of all vaccines distributed in the United States from 2006 through 2017, the period for which the injury compensation program has dosage data. It says more than 3.4 billion vaccine doses were distributed during that time.

The rarity of claims is especially notable because the program aims to make it easy to file a petition…

A growing proportion of recent claims, about half of all petitions since 2017, do not involve the content of vaccines themselves. Instead, they refer to shoulder injuries, usually in adults, that occurred because a health provider injected a vaccine too high on the shoulder, or into the joint space instead of into muscle tissue. That may cause an inflammatory response leading to shoulder pain and limited motion.

My take (from Paul Offit, MD): “The most dangerous aspect of giving your child vaccines is driving to the office to get them.”

Related blog posts:

Early Psychosocial Environment and Cardiometabolic Risk

“It is easier to build strong children that to repair broken men”

-Frederick Douglass

This quote comes from a previous lecture on adverse childhood experiences (ACEs) and comes to mind after reading a recent study: JR Doom et al. J Pediatr 2019; 209; 85-91.

This study examined 588 adolescents (16-18 yrs) from a longitudinal cohort that began in infancy (in Chile).

Methods: Psychosocial environmental factors including depressive symptoms, stressful life events, poor support for child development, father absence, and socioeconomic status was reported by mothers at 6-12 months of age.  These factors were analyzed to determine association with adolescent cardiometabolic parameters including BMI, higher blood pressure, anthropometric risk factors for cardiovascular disease, biomarkers for cardiovascular disease (e.g. triglycerides, HOMA, cholesterol) and metabolic syndrome

Key findings:

  • Infants with poor psychosocial environments had higher BMIs at 10 years and in adolescence, higher blood pressures, greater anthropometric risk, worsened cardiovascular biomarkers, and higher likelihood of metabolic syndrome (aOR 1.5)
  • The Figure in the article shows sequential worsening by quartiles -those with the highest risk based on psychosocial stress composite were worse on these outcomes compared to the 2nd highest risk factor quartile group. And in turn, the 2nd highest risk group >3rd highest risk group >lowest quartile.
  • “It is unknown whether these associations may be reversible.”

My take: While these results show a clear association of early life factors and worsened cardiovascular/metabolic outcomes, the mechanism for this is unclear.  Is this related to diet, less physical activity, stress hormones, a combination or other factors?

Related blog post:

How Often is Arthritis a Presenting Feature of Pediatric IBD & How to Make the Right Diagnosis

A recent retrospective study (R Levy et al. J Pediatr 2019; 209: 233-5) analyzed the musculoskeletal presenting manifestations of pediatric inflammatory bowel disease (IBD).

In their cohort of 715 patients with IBD, 137 had arthritis and/or arthralgia.  28 of these 137 patients (3.9% of total cohort) had arthritis preceding the diagnosis of IBD and were eligible for this study.  Only 23 had complete data and were compared with 46 children with arthritis due to JIA (n=21), FMF (n=7), and postinfectious arthritis (n=18).

Key findings:

  • Patients with subsequent IBD diagnosis were more likely to have sacroiliac involvement (34.8% vs. 2.2%), more likely to have anemia (mean hgb 10.5 vs 12), more likely to have low albumin (mean 3.5 vs 4.3) and to have higher inflammatory markers (ESR 81 vs 46; CRP 6.6 vs 4.5 mg/dL)
  • In patients with calprotectin levels, 5 of 6 were >300 mg/kg and one was borderline
  • On direct questioning at time of IBD diagnosis, prolonged gastrointestinal symptoms (e.g. abdominal pain, diarrhea, weight loss, aphthous ulcers) were evident in 78%.
  • 4 of the 23 (17.3%) were diagnosed with IBD during the primary investigation. Ultimately, Crohn’s diagnosis was established in 87% of the IBD group.

My take: This study is important for pediatricians and rheumatologists. ~4% of children presenting with arthritis have IBD.  Careful interrogation for GI symptoms (and perianal exam) will avoid diagnostic delay in most patients as would a stool calprotectin. Features like sacroileitis, and abnormal labs should also increase the suspicion for IBD.

Briefly noted: In a study discussing pediatrician beliefs about JIA (MR Pavo, J de Inocencio, J Pediatr 2019; 209: 236-9) there is an important caveat for GI doctors:

“It is clear that booster vaccinations against measles, mumps, rubella, or varicella zoster virus, can be considered in patients receiving < 15 mg/m-squared/week of MTX [methotrexate]”  (Pediatr Rheumatol Online J 2018; 16: 46).

Related blog post:

  • IBD Update Feb 2019 -last entry shows study indicating that patients with IBD and arthritis were more likely to require biologics.

Calprotectin:

El Retiro Park, Madrid

 

Briefly noted: Can We Afford (Multi) Million Dollar New Therapies?

New Gene Therapy: NPR: Zolgensma From Novartis -Most Expensive Medication Ever Approved

An excerpt:

The federal Food and Drug Administration has approved a gene therapy for a rare childhood disorder that is now the most expensive drug on the market. It costs $2.125 million per patient….

Zolgensma’s price tag, he says, is just the most extreme example of how drug prices are draining resources from society. The first gene therapy for an inherited disease was approved in 2017 for a genetic form of blindness. It is also very expensive — $425,000 for each eye.

 

Psychosis with ADHD Treatments

While I do not prescribe treatments for ADHD, a recent study (LV Moran et al. NEJM 380: 1128-38) was interesting, indicating that amphetamine use was associated with a greater risk of new-onset psychosis than methylphenidate.

Key points:

  • Amphetamine is used for ADHD treatment in the U.S. but rarely in other developed countries. It releases dopamine four times as much as methylphenidate.  “The changes in neurotransmission observed in primary psychosis are more consistent with those induced by amphetamine than methylphenidate”
  • Using data from two commercial insurance databases, the authors compared 221,846 patients receiving either amphetamine or methylphenidate.  There were 343 episodes of new onset psychosis (defined by diagnosis code and prescription for antipsychotic).
  • The risk of psychosis was 0.10% (n=106) in the methylphenidate group compared to 0.21% (n=237) in the amphetamine group. Overall, 1 in 660 patients had new onset psychosis with a greater risk in the patients receiving amphetamine.

My take: Only a prospective study can eliminate confounding variables and determine conclusively whether amphetamine is more likely to increase the risk of psychosis; that said, this study indicates a potential for more risk with amphetamine compared to methylphenidate.

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  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

Briefly noted: Autism Spectrum Prevalence

A recent study (G Xu et al. JAMA Pediatr 2019; 173: 153-9) uses a nationwide, population-based, cross-sectional survey to provided updated estimates of autism spectrum disorder (ASD) prevalence. The authors include more than 43,000 children (3-17 yrs).

Key findings:

  • The weighted prevalence of ever-diagnosed and current ASD was 2.79% and 2.50% respectively
  • State-level prevalence varied considerably with ever-diagnosed ASD of 1.54% in Texas to 4.88% in Florida.
  • 29.5% of those with current ASD did not receive either behavioral or medication treatment.

My take: This study documents the high rates of ASD in the pediatric population and shows that many are not receiving potentially beneficial treatment.

Also, in the same issue, there are three unrelated commentaries regarding vaccine policy (thanks to Ben Gold for these references):

  • New York City Childcare Influenza Mandate (YT Yang, J Colgrove. JAMA Pediatr 2019; 173: 119-20)
  • Lessons from California’s Discipline of a Popular Physician for Vaccination Exemptions Without Medical Cause (RD Silverman, YT Yang. JAMA Pediatr 2019; 173: 121-2)
  • Requiring Human Papillomavirus Vaccination for School Entry  (MJ Bayefsky, LO Gastin. JAMA Pediatr 2019; 173: 123-4)

The first of these commentaries discusses the implications of NYC influenza 2013 mandate for infants/children 6 mo-59 months.  After implementation, there was an increase in vaccination rates by 11.4% which dropped back after a legal challenge. The second commentary discusses the California State Board’s discipline of a vaccine skeptic, Dr. ‘Bob’ Sears. The final commentary calls for mandating the HPV vaccine. (Related post: HPV Vaccine Eliminating Cervical Cancer)

View from Ryan Mountain, Joshua Tree National Park