Top Papers Of The Month

3 Top Papers You May Have Missed in June 2021

AUTHOR:
Scott T. Vergano, MD
Department of Pediatrics, Children’s Hospital of The King’s Daughters, Norfolk, VA

CITATION:
Vergano ST. 3 top papers you may have missed in June 2021. Consultant360. Published online July 14, 2021.

Hi, everyone. I am happy to share with you my choice of important publications from the past month. One requires immediate action to change screening for adolescents, one discusses a shift in thinking regarding obesity surgery, and the last reports on a systematic review of the effectiveness of single-enantiomer medications. As always, please discuss them with your colleagues and share your thoughts with us: editor@consultant360.com.

Sudden Death in the Young: Information for the Primary Care Provider1

This American Academy of Pediatrics (AAP) policy statement from the Section on Cardiology and Cardiac Surgery updates recommendations on the prevention of sudden cardiac arrest (SCA) and sudden cardiac death (SCD) in patients younger than age 25 years. The conditions responsible for SCA and SCD are reviewed, including cardiomyopathies, channelopathies like long-QT syndrome (LQTS) and Brugada syndrome (BrS), congenital heart disease, Wolff-Parkinson-White syndrome, commotio cordis, anomalous coronary arteries, and aortopathies like Marfan syndrome.

It is recommended that primary care physicians screen for these conditions, refer to a specialist when a risk factor is identified, assist in the evaluation of patients and family members after an SCA or SCD event, and advocate for secondary prevention methods like cardiopulmonary resuscitation training and availability of automated external defibrillators.

The following questions are recommended to be asked of all adolescents, athletes, and nonathletes at least every 3 years or at entry into middle school and high school:

  • Have you ever fainted, passed out, or had an unexplained seizure without warning, especially during exercise or in response to sudden loud noises, such as doorbells, alarm clocks, and ringing telephones?
  • Have you ever had exercise-related chest pain or shortness of breath?
  • Has anyone in your immediate family (parents, grandparents, siblings) or other, more distant relatives (aunts, uncles, cousins) died of heart problems or had an unexpected sudden death before age 50 years? This would include unexpected drownings, unexplained auto crashes in which the relative was driving, or sudden infant death syndrome.
  • Are you related to anyone with hypertrophic cardiomyopathy, Marfan syndrome, arrhythmogenic cardiomyopathy, LQTS, short-QT syndrome, BrS, or catecholaminergic polymorphic ventricular tachycardia, or anyone younger than 50 years with a pacemaker or implantable defibrillator?


The screening questions identified are a bit more extensive and specific than the ones that I typically have used on my annual sports preparticipation physical examination forms. In addition, the authors point out that SCA and SCD are not limited to athletes, and the questions need to be asked of nonathletes as well. For me, it makes the most sense to update the screening questionnaires that my office uses for the pre-adolescent and adolescent wellness visits to include the 4 questions above.

I have been lucky to have never dealt with the trauma of an SCA or SCD in any of my patients. I imagine that, given the statistic cited in the article, that SCD occurs in approximately 2000 children and young adults younger than age 25 years in the United States annually, some of you will have had that most unfortunate experience. Each such death is a tragedy and trauma, not just for the family but for the school and community as a whole. Please feel free to share your experiences and perspectives with us.

The Push for Earlier Bariatric Surgery for Adolescents With Severe Obesity2,3

This recent piece from JAMA2 and the report on the National Institutes of Health-Funded Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study from Pediatrics3 discuss expanding the use of bariatric surgery to include adolescents. The JAMA article quotes experts in the fields of obesity and bariatric surgery who recommend extending the option for surgery to younger and less morbidly obese adolescents. The Teen-LABS study, including 242 adolescents from US bariatric surgery centers, found equal responses to surgical intervention in younger (aged 13-15 years) and older (aged 16-19 years) adolescents. Experts recommend that adolescents be considered for bariatric surgery, regardless of age, if they meet criteria of the American Society for Metabolic and Bariatric Surgery: class 3 obesity, defined as a body mass index (BMI) of at least 40 kg/m2 or 140% of the 95th percentile for their age and sex, or class 2 obesity, defined as a BMI of 35 to 39 kg/m2 or at least 120% to less than 140% of the 95th percentile with a comorbidity, including hypertension, type 2 diabetes, obstructive sleep apnea, severe fatty liver disease, or idiopathic intracranial hypertension.

Obesity is a complex medical condition for which I have not found easy solutions. Enrollment in comprehensive educational and motivational programs can be helpful, but access is extremely limited and participation requires intensive commitment from families and significant motivation from children and adolescents. I have referred only 2​ adolescents who were obese for bariatric surgery throughout my career. Given the recommendations of the experts above, perhaps it would be appropriate for me to raise the possibility of bariatric surgery with patients different from those 2 teenagers—both of whom were older and morbidly obese, and lifestyle interventions over several years had proven unsuccessful.

It is clear that few adolescents are being referred at this point, as the JAMA article reports fewer than 1600 adolescent procedures are performed per year in the United States. I am interested in hearing your opinions. Is this direction misplaced? Do you have more hope for lifestyle interventions, comprehensive weight loss programs, or perhaps medications that have yet to be approved or widely used? Or do you feel that the emphasis on earlier bariatric surgery is appropriate?

​Evaluation of Trials Comparing Single-Enantiomer Drugs to Their Racemic Precursors4

The authors of this systematic review published in JAMA Network Open4 examine the pharmaceutical process of chiral switching, or separating the mirror-image enantiomers of a racemic medication and studying one of the enantiomers to determine if it has superior clinical efficacy or reduced adverse effects. Many of the racemic medications commonly used in pediatrics, as indicated in Table 1 of the article, have approved single-enantiomer formulations, including albuterol and levalbuterol, cetirizine and levocetirizine, methylphenidate and dexmethylphenidate, dextroamphetamine/amphetamine and amphetamine, citalopram and escitalopram, and omeprazole and esomeprazole.4

The authors point out that chiral switching and approval of a single-enantiomer medication would provide extended exclusivity and protection from generic competition to pharmaceutical companies. In addition, these companies are required by the US Food and Drug Administration only to demonstrate efficacy of their new formulation, and according to one study, only one-third of approvals of these medications were based on randomized controlled comparisons with their existing racemic medication.

The authors report that, in their systematic review of 15 pairs of such medications, they identified 185 randomized controlled trials comparing the efficacy and safety of pairs of these medications. Only 12.8% of the trials showed increased efficacy of the single-enantiomer medication, only 13.7% of the trials showed increased safety of the single-enantiomer medication, and for 9 of the 15 medications examined, no randomized trial showed either improved efficacy or improved safety.4

I have often been skeptical of the benefits of the single-enantiomer medications that I have used and anecdotally have usually not heard parents/guardians report improved efficacy or decreased adverse effects compared with the racemic parent medication. What have your experiences been with the pairs of medications listed above?

Just a reminder, for those of us involved in teaching residents and medical students: this is July. Take some time to think back to your introduction to clinical medicine. It is always such a privilege and honor for me to help yet another group of doctors and pediatricians pursue their own callings. For those of you involved in teaching, my congratulations and appreciation for your efforts to train the next generation of physicians and medical providers.

 References:

  1. Erickson CC, Salerno JC, Berger S, et al; Section on Cardiology and Cardiac Surgery, Pediatric and Congenital Electrophysiology Society (Paces) Task Force on Prevention of Sudden Death in the Young. Sudden death in the young: information for the primary care provider. Pediatrics. Published online June 21, 2021. https://doi.org/10.1542/peds.2021-052044
  2. Jaklevic MC. The push for earlier bariatric surgery for adolescents with severe obesity. JAMA. 2021;325(22):2241-2242. https://doi.org/10.1001/jama.2021.7912
  3. Ogle SB, Dewberry LC, Jenkins TM, et al. Outcomes of bariatric surgery in older versus younger adolescents. Pediatrics. 2021;147(3):e2020024182. https://doi.org/10.1542/peds.2020-024182
  4. Long AS, Zhang AD, Meyer CE, Egilman AC, Ross JS, Wallach JD. Evaluation of trials comparing single-enantiomer drugs to their racemic precursors: a systematic review. JAMA Netw Open. 2021;4(5):e215731. https://doi.org/10.1001/jamanetworkopen.2021.5731