Top Papers of the Month

4 Top Papers You May Have Missed in February 2022

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

Vergano ST. 4 top papers you may have missed in February 2022. Consultant360. Published online March 16, 2022.


I am hoping that life is starting to return to a degree of normalcy for many of you after the severe surge of COVID-19 at the beginning of the year. This is my curated list of key papers from February that you may have missed.

Please feel free to share with your colleagues, discuss in your offices, and write to with your thoughts and opinions.

An Addition to the Adult Vaccine Schedule1

A January 28 publication of Morbidity and Mortality Weekly Report (MMWR) disseminated the new Advisory Committee on Immunization Practices (ACIP) recommendations for adult pneumococcal vaccination. Previous recommendations included 23-valent polysaccharide vaccine and 13-valent conjugate vaccine in adults aged 65 years or older and those with high-risk conditions. The new guidance recommends that all previously unvaccinated adults aged 65 years or older, or younger adults susceptible to pneumococcal infections, receive one of the new expanded pneumococcal vaccines. All such patients should receive either 20-valent pneumococcal conjugate vaccine (PCV20) once or 15-valent pneumococcal conjugate vaccine (PCV15) once followed by 23-valent pneumococcal polysaccharide vaccine. In the latter case, the interval between the 2 vaccines should be greater than 1 year, with a minimum interval of 8 weeks in adults at highest risk.

It has been gratifying to witness the severe decline in invasive pneumococcal infections in children since the introduction of the first conjugate vaccine in 2000, as well as the less dramatic decrease in episodes of otitis media caused by this organism. Efforts to overcome serotype switching led to the introduction of 13-valent vaccine in US children in 2010. In order to continue to prevent pneumococcal infections, the expansion to newer vaccines with efficacy against more pneumococcal serotypes seems prudent. An application for approval for PCV15 (Vaxneuvance) in children aged 6 weeks through 17 years was submitted to the US Food and Drug Administration (FDA) in December 2021, with a decision anticipated by April 2022. Pediatric trials of PCV20 (Prevnar 20) are expected to be completed by the end of 2022.

Neonates and Vitamin K2

To complement the policy statement highlighted last month regarding alternative perinatal practices, the American Academy of Pediatrics (AAP) in March 2022 released its updated statement regarding prevention of vitamin K-deficient bleeding (VKDB) in the neonate. The policy statement documents the history of hemorrhagic disease of the newborn and its prevention with the introduction of a single dose of parenteral vitamin K to all neonates in the United States in 1961. It reiterates the strong recommendation that all neonates receive a vitamin K injection. The report also calls attention to a recent increase in refusal of parenteral vitamin K and a subsequent increase in the incidence of VKDB among babies.

Reasons for parental refusal include concerns about safety, belief systems about “natural birth,” and outside influences of friends, celebrities, and other health care personnel. The statement refutes prior concerns about associations with cancer or leukemia, and provides data regarding the decreased efficacy of oral administration compared with parenteral vitamin K. It discusses the importance of understanding reasons for parental refusal, while restating the important role of parental vitamin K in prevention of VKDB in neonates. 

While I am gratified to read that the AAP has reaffirmed its support for this intervention and the avoidance of preventable cases of intracranial hemorrhage, I wish that more information had been included in the statement. I will definitely cite the justification for parenteral vitamin K and will use the discussion of reasons for refusal in my dialogue with families. However, I found the statement lacking in definitive data regarding the incidence of VKDB in neonates. This information would be helpful in discussing the magnitude and severity of risk with families who are refusing to administer a vitamin K injection to their neonate.

Group A Streptococcal Infections and Onset of Tics3

This prospective cohort study published in Neurology this month is about the new onset of tics in children aged 3 to 10 years with a first-degree relative with chronic tic disorder. The study included 259 children from 16 European centers and found that over an average follow-up period of 1 year, 61 participants (23.6%) developed a tic disorder. In order to investigate the potential relationship between streptococcal infections and new-onset tics, the authors looked at several definitions of exposure to group A Streptococcus (GAS) in these children. Regardless of the definition used, they found no association between exposure to GAS and new onset of tics in this cohort of children with first-degree relatives with chronic tic disorders.

There are extensive debates as to the existence of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). It should be reassuring from this study that if these disorders exist, they are uncommon. Nonetheless, a 1-year follow-up study of 260 susceptible children does not disprove the possibility of this condition. Personally, I am a proponent of the, albeit rare, association that defines PANDAS, though I would love to hear your thoughts and experiences with this condition.

Reliever-Triggered Inhaled Glucocorticoid in Black and Latinx Adults with Asthma4

This pragmatic, open-label trial released ahead of print in the NEJM included 1201 Black and Latinx adults with moderate- to severe-asthma, and randomly assigned them to 2 groups: those directed to use as-needed inhaled corticosteroid, and those assigned to received usual care. At a one-time office visit, the intervention group was instructed to use 1 puff of 80 mcg fluticasone with each quick-relief inhaler use and 5 puffs with each quick-relief nebulizer use. The participants were followed for 15 months; outcome measures included number of severe exacerbations, Asthma Control Test scores, and other measures of monthly asthma control. The investigators found fewer severe exacerbations and improved asthma control in the reliever-triggered fluticasone group.

Recently, there has been much interest in the use of inhaled corticosteroids as needed for asthma exacerbations. This approach was included in the most recent Expert Panel Working Group asthma guideline update released in 2020.5 The guidelines recommend use of as-needed inhaled corticosteroids in children aged 0 to 4 years with recurrent wheezing at the onset of upper respiratory infections. They also recommend single maintenance and rescue therapy (SMART) with a steroid-formoterol combination inhaler for patients aged 4 years or older with moderate- to severe-persistent asthma. The approach taken by the authors of the current study, dubbed patient-activated, reliever-triggered inhaled corticosteroid (PARTICS), seems an easier and more natural transition for many patients than SMART. If confirmed to be effective, it might prove a more practical approach than SMART, which requires daily use of a combined inhaler, plus as-needed use of the same inhaler during exacerbations and removal of rescue short-acting beta-agonist inhalers and nebulizers.

This study raises several important concerns. The authors’ approach of PARTICS is compared with usual care, not with the current standard of care SMART therapy, and the authors have chosen to focus on Black and Latinx patients who have traditionally had higher rates of asthma complications. How does PARTICS compare with SMART? How does it work in patients who are not Black or Latinx? If it is less effective than SMART, are we doing these Black and Latinx patients a disservice by advocating for a simpler but less effective therapy? Although intriguing, this study leads to more questions than answers. Before implementing this approach with my patients, I will need to see results of other studies that address some of these important issues.

 What do you think? As always, I am eager to hear your opinion!


1. Kobayashi M, Farrar JL, Gierke R, et al. Use of 15-valent pneumococcal conjugate vaccine and 20-valent pneumococcal conjugate vaccine among U.S. adults: updated recommendations of the advisory committee on immunization practices - United States, 2022. MMWR Morb Mortal Wkly Rep. 2022;71(4):109-117. doi:10.15585/mmwr.mm7104a1

2. Hand I, Noble L, Abrams SA, Committee on Fetus and Newborn, Section on Breastfeeding, Committee on Nutrition. Vitamin K and the newborn infant. Pediatrics. 2022;149(3):e2021056036. doi:10.1542/peds.2021.056036

3. Schrag AE, Martino D, Wang H, et al; European Multicentre Tics in Children Study (EMTICS). Lack of association of group A Streptococcal infections and onset of tics: European multicenter tics in children study. Neurology. 2022;98(11):e1175-e1183. doi:10.1212/WNL.0000000000013298

4. Israel E, Cardet JC, Carroll JK, et al. Reliever-triggered inhaled glucocorticoid in Black and Latinx adults with asthma. N Engl J Med. Preview published online February 26, 2022. doi:10.1056/NEJMoa2118813

5. Cloutier MM, Baptist AP, Blake KV, et al; Expert Panel Working Group of the National Heart, Lung, and Blood Institute (NHLBI); National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC). 2020 focused updates to the asthma management guidelines: a report from the national asthma education and prevention program coordinating committee expert panel working group. J Allergy Clin Immunol. 2020;146(6):1217-1270. doi:10.1016/j.jaci.2020.10.003