PAO-HNS Soundings Spring Newsletter

Soundings

President’s Message

current President of the AAO-HNS, Kathleen Yaremchuk, MD, will be the keynote speaker at the PAO-HNS Annual Meeting in June. Dr. Yaremchuk will speak as part of the general program and again at the Women in Otolaryngology event. You can find more details about the meeting in the summary provided by Program Chairs Drs. Nick Purdy and Karen Choi in this issue of Soundings. The program committee has done an amazing job and it is a meeting that you will not want to miss!

Welcome to Spring Soundings! This is always a wonderful time of year in Pennsylvania and an exciting time of year for the Pennsylvania Academy of Otolaryngology – Head and Neck Surgery (PAO-HNS). The weather is getting warmer, and we are getting closer to the PAO-HNS 2023 Annual Meeting. This year we will be holding the meeting on June 16 – 15 at a beautiful venue that is new to us, the Lancaster Marriott at Penn Square. We are thrilled to offer this new setting for what we anticipate being another high-quality conference for both science and socializing. I was recently an invited speaker at the Virginia Society of Otolaryngology (VSO) Annual Meeting. It was stellar and I enjoyed the opportunity to see the work of another state society. There were many parallels between the VSO and the PAO-HNS and the experience deeply confirmed for me the importance of state societies. The value of a strong state society is something that is repeatedly acknowledged by the leadership at the American Academy of Otolaryngology – Head and Neck Surgery, and we are honored that the

After limited activity during the COVID pandemic, things are picking up again in the state legislature. As such, it was timely that the PAO-HNS engaged a new lobbyist earlier this year. I am excited to introduce Philip Dunn, whose extensive background in the PA State Senate will help in keeping our interests prioritized. Please see his update in this issue of Soundings to learn more about his background and some of the bills being considered in 2023.

I am also excited to introduce a new award that will be presented at our Annual Meeting this year. The Ellie Goldenberg Award will be given in loving memory and honor of the daughter of Drs. David and Renee Goldenberg.

It will be awarded annually to a resident in one of our state’s training programs who embodies the way in which Ellie lived her life: with a strong work ethic, diligence, initiative, and kindness. A detailed description of the award is included in this issue of Soundings. I strongly encourage nominations.

This is my final Soundings message as President of PAO-HNS. It is remarkable how quickly the two years have passed, and I am proud of what the organization has accomplished. We have returned to inperson annual meetings which are essential to trainee development and member networking, two of the most important missions of the PAO-HNS. The success of the annual meetings has strengthened our financial status and the addition of our new lobbyist has enhanced our advocacy. Our committee structure has been re-designed to facilitate involvement of our newest members. All the above translate into a bright future for the PAO-HNS. I would like to thank our PAMED TEAM: Audrey Dean for her partnership, Ariel Jones for her leadership, Jessica Winger for her fantastic meeting coordination, and Cindy Warren for this beautiful newsletter. Thank you to Dr. Jessyka Lighthall, who will take over as president at the annual meeting, and Dr. Colin Huntley, who will become presidentelect, for their collaboration and support in their current roles. I am confident they will take the PAO-HNS to new heights. Thank you to the entire executive council whose volunteerism and commitment are recognized and are the reason why the PAO-HNS has excelled for so many years. Finally, thank you to the entire membership. It has been an honor to serve as your president and you inspire all of us to keep making the PAO-HNS better. The future is bright indeed!

PUBLISHED IN THE INTEREST OF OUR MEMBERS AND THEIR PATIENTS

David Cognetti, MD, FACS PAO-HNS President

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President David M. Cognetti, MD, FACS

Otolaryngology-Head & Neck Surgery

Thomas Jefferson University 925 Chestnut St Fl 6 Philadelphia PA 19107-4204

President-Elect Jessyka G. Lighthall, MD Penn State Hershey Otolaryngology-Head & Neck Surgery

500 University Dr., Ste. 400 UPC, H091 Hershey, PA 17033-2360

Secretary-Treasurer Colin T Huntley MD Otolaryngology-Head & Neck Surgery

Thomas Jefferson University 925 Chestnut St Fl 6

Philadelphia, PA 19107-4204

Administrative

400 Winding Creek Blvd. Mechanicsburg, PA 17050-1885

833-770-1544

855-918-3611 (fax)

Visit

Soundings accepts classified advertisements; however, there is no guarantee that they will be published. All submissions are subject to review. The advertisement should be of interest/ pertain to otolaryngologists, their practice, and health care in Pennsylvania. Submissions that are self-promotional or commercial in nature will not be accepted. Publication of advertising does not imply endorsement of the products advertised or the statements contained in such advertising by Soundings or the PAO-HNS. The opinions expressed in this newsletter do not necessarily reflect the opinion of PAO-HNS.

A resident’s perspective on the role of the sleep surgeon in the treatment of OSA

Dylan Bertoni, MD Resident, PGY-3 Otolaryngology— Head and Neck Surgery Thomas Jefferson University Hospital

I have been unknowingly surrounded by sleep apnea for my entire life. I’ve never quite understood how my mother could sleep given the volume of snoring that emanates from my father’s face at night. The sweet English Bulldog I grew up with almost certainly had the canine equivalent of OSA. My grandmother frequently forgot to pack her CPAP machine when traveling. My father-in-law complains about how irritated his nose gets from his nasal CPAP mask. Sleep apnea has become so ubiquitous in our lives, it has become easy to ignore or become blind to it and the effects it has on those around us. I certainly wasn’t thinking about sleep apnea when applying to residency. I became attracted to the field of ENT in the same manner as many other medical students; I knew I was interested in a surgical field, found myself in a neck dissection one day, and fell in love with the surgery. Free flap reconstructions of massive facial defects made an 18hour OR day feel like 20 minutes to an eager student. I loved the breadth of techniques and procedures, patient ages and backgrounds, and pathologies and problems encountered in this field. I wanted to cure cancer, restore someone’s hearing with a cochlear implant, and perform cosmetic surgery and sinus surgery in the same day. The more I explored and learned about this field, the more I knew I had found my place. It wasn’t until matching into residency at Thomas Jefferson that I considered the role of the Sleep Surgeon. With dedicated Sleep trained faculty serving as both residency program director and assistant program director, as well as having one of the busiest hypoglossal nerve implant

centers in the country, it was no longer possible to remain blind to the OSA surrounding me.

OSA is a relatively recently identified pathology, with Charles Dickens frequently credited as first describing a patient in the Pickwick Papers in 1836. Reports of OSA as a formal diagnosis were first made in the 1950s, but it would be decades before the development of effective treatments. At that time, divorce was an acceptable solution for snoring. Tracheostomy was the only medical treatment to cure Pickwickian syndrome, and even that wasn’t utilized until the 1970s. CPAP was introduced as a treatment in 1981—the same year the UPPP was first performed in the USA. Although the field of Sleep Surgery continued to slowly smolder, the advent and effectiveness of CPAP led to the explosion of medical sleep specialists, predominantly pulmonologists, managing these patients. The American obesity epidemic has only exacerbated this country’s snoring problem. Recent studies have shown that although effective, the discomfort and inconvenience of CPAP use leads to poor compliance and decreased overall efficacy. Although it remains the first line treatment for moderate to severe OSA, my grandma and father-inlaw were on to something—there has been a gap in our treatment of these patients. In recent years, this gap has been explored

by the Otolaryngologist. With the advent of the hypoglossal nerve stimulator in 2014, Sleep Surgery has become a sleek alternative to CPAP in the appropriate patient. The number of available surgical options continues to grow, further driving the market for a surgeon capable of managing patients who are dissatisfied with their masks and their tubes. The current job market is catching on as well, with both private and academic institutions looking to expand their reach with trained Sleep Surgeons.

As a resident, I am still fascinated by those 18-hour free flaps, but as a father to a 7-month-old baby, they have started to feel a lot more like 18-hour cases. I find myself drawn towards a field that can still have profound impact on patients but allows me the freedom to make it home for bath time. My exposure to the surgical treatments for OSA has opened my eyes to the prevalence and impact that sleep apnea can have, and has influenced how I see and speak to those in my life afflicted by it. Daisy the bulldog might not have been a candidate for sleep surgery, but other members of my family, or yours, just might be. My hope is that I, along with my fellow ENT residents across the country, can continue to learn from our Sleep Surgeons, so we can further address this growing need.

Investigating the Amoxicillin Shortage in Pennsylvania in the Era of Supply Chain Challenges: A Cross-Sectional Study

Harleen K. Sethi, DO; Timothy Fan, MD; Dan Eichorn, DO; Hye Rhee Chi, DO; Laura McDavid, DO; Keith Conti, MD; Pamela Roehm, MD, PhD St. Luke's University Health

Amoxicillin is the most common antibiotic prescribed for pediatric patients and the first line treatment for many Otolaryngologic conditions (Figure 1)1

of a “medically necessary” drug, there are no statutory definition of “medical necessity” nor penalty for failure to provide advanced notice.4,5 Thus, healthcare entities, physicians, and patients alike are often caught off guard by medication shortages.

Drug shortages have been a persistent problem in the US for many years, despite preventative efforts endeavored by public and private sectors involved in all parts of the drug supply chain.6 Common reasons for medication shortage include imbalances in supply and demand and supply chain disruptions, including raw material shortages, limited manufacturing workforce, recalls, transportation delays, lack of manufacturing incentives, and natural disasters. 7 The amoxicillin shortage at the end of 2022 coincided with the annual resurgence of influenza and respiratory

syncytial virus (RSV) infections, as well as COVID-19 interference with manufacturing workflow, making the causes of the shortage unclear. In this study, we have investigated the driving force(s) behind the amoxicillin shortage in Pennsylvania.

Our cross-sectional phone/email survey study consisted of 7 pharmacies in eastern Pennsylvania, 4 amoxicillin distributors, and the only amoxicillin manufacturer located in the US (USAntibiotics, Bristol Tennessee). Companies were first contacted by phone numbers identified during google searches for company names. Follow-up calls or emails were made based on contact information given during initial contact phone interviews. Interview questions focused on inquiring as to the subjective presence of a shortage, when the shortage noticed, and reasons for the shortage (Table 1)

In October of 2022, the United States (US) Food and Drug Administration (FDA) announced a shortage of numerous amoxicillin formulations.2 Per the American Academy of Pediatrics, the shortage was anticipated to last several months, requiring the usage of alternative antibiotics to fill in the therapeutic gaps.3

Medication shortages have multifaceted impacts on healthcare leading to undermining of therapy, delaying or compromising care, and/or increasing medical error, complications, and expenditures.4 While manufacturers are required to provide FDA advanced notice in anticipation of decreased production

Table 1: Survey results from pharmacies in Pennsylvania and amoxicillin manufacturer and distributors regarding the amoxicillin shortage at the end of 2022. Y- yes; N- no; LVHN- Lehigh Valley Health Network; SCHC- St. Christopher’s Hospital for Children; SLUHN- St. Luke’s University Health Network

Investigating the Amoxicillin Shortage in Pennsylvania in the Era of Supply Chain Challenges: A Cross-Sectional Study

All hospital affiliated pharmacies (3/3, 100%) and most of the commercial pharmacies (3/4, 75.0%) experienced an ongoing amoxicillin shortage beginning between August 2022 and October 2022. At the time of manuscript writing, the shortage was ongoing according to the FDA’s Drug Shortages list. USAntibiotics, the sole manufacturer of amoxicillin in the US, reported an amoxicillin shortage, which was similarly ascribed to demand increase in response to infections. Teva Pharmaceuticals, the only distributor of amoxicillin that answered the survey, did not experience a shortage of amoxicillin. The amoxicillin shortage primarily impacted the suspension formulas. All respondents who had experienced amoxicillin shortages also experienced deficiencies of amoxicillin capsule/chew tab/tablet and other antibiotics, presenting three to four weeks after the onset of the suspension formula shortage.

When asked to report on possible cause of the scarcity, 83.3% (5/6) of pharmacies with amoxicillin shortage attributed the crisis to rise in demand due to increase in infection rate, and 16.7% (1/6) to insufficient manufacturing capability. No significant shortage was experienced from Teva Pharmaceutical’s perspective, the only amoxicillin distributor company that could be reached for comment. Questions regarding USAntibiotics’ current manufacturing status and ability to produce at the maximal capacity they are licensed for were not answered. No medication recalls regarding amoxicillin were announced from August 2022 to December 2022. Lastly, in an analysis conducted by the American Society of Health-System Pharmacists (ASHP), amongst the top reasons for drug shortages in 2022, 56% were unknown/ undisclosed, followed by 19% supply and demand imbalance and 18% manufacturing difficulty, indicating much of the true cause remains unknown.6 In recent years, the frequency of drug shortages have steadily increased, from 113.8 medication deficiencies/ year (2001-2010) to 171.9 medication deficiencies/year (2011-2020).6

Antibiotics are the second most common drug class facing shortages, with 38 different antibiotics lacking in supply as of 12/31/2022. An October 2022 survey performed by the National Community Pharmacists Association revealed 98% of respondents experience drug shortages with 66% facing amoxicillin backorders. 7 Similarly, 85.7% responding pharmacies in eastern Pennsylvania contacted in this investigation reported deficiencies in amoxicillin supply.

Several reasonable deductions may be drawn from our findings regarding the cause of amoxicillin shortage. The diminished amoxicillin supply coincided with the seasonal resurgence of influenza and RSV, which is exacerbated by new COVID-19 infections.8 Not only are antibiotics commonly prescribed for patients presenting with viral illnesses, but amoxicillin is also the first line therapy for secondary bacterial diseases that can follow viral infection.9 With 83.3% of responding pharmacies reporting increases in amoxicillin prescriptions, it is reasonable to attribute the shortage to an increase in demand. The shortage appears to have mainly impacted amoxicillin suspension. Shortage of this formulation, coupled with the disproportionate effects of seasonal viral epidemics on children, disproportionately impacts pediatric patients and the timing of viral infection surges were disrupted by pandemic-related decreased infection for two years. Although only 1/6 (16.7%) of the pharmacies we surveyed attributed the low amoxicillin inventory to manufacturing deficiency, the COVID-19 pandemic likely contributed to the shortage directly or indirectly. COVID-19 contributed to shortages of many essential medications.10 Early on, measures to prevent COVID-19 spread led to closure of many pharmaceutical factories.11 With prolonged lockdown policies in China, several major sources of raw and active ingredients for amoxicillin were limited in quantity, further diminishing the pharmaceutical output in the US.11,12

Shortages were also observed for amoxicillin in capsule/chew tab/tablet, amoxicillin-clavulanic acid, and other antibiotic classes; however, these shortages

were found weeks after depletion of amoxicillin suspension formulas. Due to the unique temporal relationship, most respondents attributed the other amoxicillin formation shortages to trickle-down demand for substitutes.

These abruptly occurring scarcities of essential medications lead to practice changes that can lead to multiple adverse events, including inadequate or improper treatment of medical conditions, delay in definitive treatment, and adverse drug reactions or interactions. Time spent visiting multiple pharmacies in search of a supply-limited medication may also negatively impact quality of life.13,14 Additionally, the amoxicillin shortage exposes patients to second-line therapies at increased price points.15,16

Different strategies were employed by the private and public sectors in response to the worsening drug shortages. Multiple pharmacies participating in this study increased usage of networkwide real-time monitoring of inventories to supplement and adjust stockpile as necessary to maximize prescription fulfillment without compromising optimal choices. Additionally, recent shortages sparked public interest in legislation to address the growing scarcity. In 2021, the PASTEUR Act was introduced to the US Congress to stimulate the development of new antibiotics with government backing.17 In reality, the drug shortage problem is multifactorial and likely requires a comprehensive action plan to anticipate and adapt to future drug supply deficiencies.

The amoxicillin shortage at the end of 2022 coincided with increased viral infections in the fall, a time characterized by heightened demand for antibiotic prescriptions. Suspension formulas were primarily impacted by the scarcity, with trickle-down shortages impacting other formulations and antibiotic classes weeks later. Concerted efforts from individual entities, supply chain, and legislature may be necessary to combat the complex causes behind increasingly frequent medication shortages.

Continued on page 6

Investigating the Amoxicillin Shortage in Pennsylvania in the Era of Supply Chain Challenges: A Cross-Sectional Study

References

1. Abrams EM, Ben-Shoshan M. Should testing be initiated prior to amoxicillin challenge in children? Clin Exp Allergy. 2019;49(8):1060-1066. doi:10.1111/ CEA.13443

2. U.S. Food & Drug Administration. Current and Resolved Drug Shortages and Discontinuations Reported to FDA. Published 2022. Accessed December 18, 2022. https://www.accessdata. fda.gov/scripts/drugshortages/default. cfm

3. American Academy of Pediatrics. Amoxicillin Shortage: Antibiotic Options for Common Pediatric Conditions. Accessed December 16, 2022. https:// www.aap.org/en/pages/amoxicillinshortage-antibiotic-options-forcommon-pediatric-conditions/

4. Nonzee NJ, Luu TH. The Drug Shortage Crisis in the United States: Impact on Cancer Pharmaceutical Safety. Cancer Treat Res. 2019;171:75-92. doi:10.1007/978-3-319-43896-2_6

5. U.S. Food & Drug Administration. Title II of the Drug Quality and Security Act | FDA. Accessed December 14, 2022. https://www.fda.gov/drugs/drugsupply-chain-security-act-dscsa/title-iidrug-quality-and-security-act

6. American Society of Health-System Pharmacists. Drug Shortages Statistics - ASHP. Accessed December 18, 2022. https://www.ashp.org/drugshortages/shortage-resources/drugshortages-statistics?loginreturnUrl=SSO CheckOnly

7. National Community Pharmacists Association. National Community Pharmacists Association Nov. 2022 Report on Drug Shortages. Accessed December 18, 2022. https://ncpa.org/ sites/default/files/2022-11/NCPAExecSummary_DrugShortage_NOV22. pdf

8. Centers for Disease Control and Prevention. Respiratory Syncytial Virus Hospitalization Surveillance Network (RSV-NET) | CDC. Published 2022. Accessed January 18, 2023. https:// www.cdc.gov/rsv/research/rsv-net/ dashboard.html

9. Sande CJ, Njunge JM, Mwongeli Ngoi J, et al. Airway response to respiratory syncytial virus has incidental antibacterial effects. Nature Communications 2019 10:1. 2019;10(1):1-11. doi:10.1038/ s41467-019-10222-z

10. Bookwalter CM (2021). Drug shortages amid the COVID-19 pandemic. US Pharmacist, 46(2), 25-8. 2021;46(2):25-28. Accessed December 20, 2022. https://www. uspharmacist.com/article/drugshortages-amid-the-covid19-pandemic

11. Arnum V. API Sourcing: The Supply Side for US-Marketed Drugs - DCAT Value Chain Insights. Published 2019. Accessed March 10, 2023. https:// www.dcatvci.org/features/global-apisourcing-which-countries-lead/

12. Schondelmeyer SW, Seifert J, Margraf DJ, et al. COVID-19: The CIDRAP Viewpoint. Published online 2020. Accessed March 18, 2023. www. waltonfamilyfoundation.org.

13. MacDonald E, Fox E, Tyler L. Drug Shortages: Process for Evaluating Impact on Patient Safety. http:// dx.doi.org/101310/hpj4612-943. 2011;46(12):943-951. doi:10.1310/ HPJ4612-943

14. Moss JD, Schwenk HT, Chen M, Gaskari S. Drug Shortage and Critical Medication Inventory Management at a Children’s Hospital During the COVID-19 Pandemic. J Pediatr Pharmacol Ther. 2021;26(1):21-25. doi:10.5863/1551-6776-26.1.21

15. Holcombe B, Mattox TW, Plogsted S. Drug Shortages: Effect on Parenteral Nutrition Therapy. Nutr Clin Pract. 2018;33(1):53-61. doi:10.1002/ NCP.10052

16. Gundlapalli A V., Beekmann SE, Graham DR, Polgreen PM. Antimicrobial Agent Shortages: The New Norm for Infectious Diseases Physicians. Open Forum Infect Dis. 2018;5(4). doi:10.1093/OFID/ OFY068

17. Doyle MF. PASTEUR Act of 2021: H.R.3932 - 117th Congress (20212022). Library of Congress, Congress. gov. Published 2021. Accessed March 18, 2023. https://www.congress.gov/ bill/117th-congress/house-bill/3932/ text

The Board of Governors for the American Academy of Otolaryngology Head and Neck Surgery held its Spring meeting on April 29th 2023 as a live virtual event promoting legislative advocacy, candidate’s forum, and practice management session. Registration was free to all members of the Academy. Participants could earn 2.50 AMA PPRA Category 1 credits. The program did focus on legislative advocacy with updates on health care bills and the 118th Congress, the academy's legislative priorities for 2023, and the AMA advocacy plan. The AMA recovery plan focuses on fixing prior authorization, reforming Medicare payment, fighting scope creep, supporting telehealth, and strategies for reducing physician burnout. Dr. Bobby Mukkamala, otolaryngologist and immediate past chair of the AMA Board of Trustees gave an informative presentation on those topics.

The meeting also included a candidates forum including a question and answer session involving the two presidentelect candidates in this year's upcoming elections, Dr. Troy Woodard (Rhinologist at Cleveland Clinic) and Dr. Mark Wax (Head and Neck Surgeon at Oregon University). This gave grassroot

members the opportunity to learn more about both candidates and hear their vision for the future of the specialty. The third component of the program involved practice management pearls. Learning about successful payer contract negotiation strategies that a practice could immediately implement and understanding how insurance companies approach practices in all regions of the country were addressed. Providers must learn to navigate future reimbursement models, contract language, payer policies, and their relationship with payers. Providers must continually oversee billing and collections to optimize reimbursement. Participants did learn from experts in healthcare management from the Lighthouse Healthcare Advisors Company based in Maryland on how to evaluate your current reimbursement, understand potential pain points within contract language, and best practices for A/R and Denial management.

In addition, an update on coding was provided by Dr. Peter Manes and a discussion on the importance of quality metrics by Dr. Willard Harrill.

The Board of Governors will also be sponsoring on June 21 a webinar on the otolaryngology workforce as it currently stands in our country. Dr Andrew Tompkins will be the lead presenter on this topic and has worked extensively on accumulating this data and analyzing it for the Academy. The discussion will take a comprehensive look at where the workforce currently stands, where it may be headed, patient access needs, market forces affecting the workforce, and evaluation of the 2022 otolaryngology workforce survey. The BOG will be highlighting this presentation in the next few months.

Efforts to continue to improve communication between the Board of Governors and state specialty societies and grassroot members of the Academy continue to grow. The importance of sharing information and enhancing communication amongst all members of the Academy continues to be of vital importance. Please continue to participate in the many webinars and podcasts that are being promoted by the BOG and AAO and stay involved. Don’t forget to vote in the upcoming election for Academy leaders as well!

Karen A. Rizzo, MD FACS Chair BOG PA Governor/BOG

Karen A. Rizzo, MD, FACS Chair BOG PA Governor/BOG

Sana Siddiqui MD

Joseph Spiegel, MD

Thomas Jefferson University

Dr. Spiegel, would you consider doing something that I found about on Reddit?” With this question, I was introduced to the on-line “no burp” community and became one of the physicians on their “list.” Our first patient with retrograde cricopharyngeal dysfunction (RCPD) came to us for what she described as a “swallowing problem.” She didn’t realize that her lifelong inability to burp was a related symptom until she started searching the internet. There, on Reddit, she found a community of people that all had a similar array of symptoms. Those that had sought medical evaluation were frustrated that they had undergone many tests yet received no answers or effective treatment.

Our colleague, Dr. Robert Bastian, in the Chicago area, was the first to identify the syndrome and establish a protocol for treatment. His patients also were self-diagnosed from internet blogs. His paper detailing treatment of 51 patients was published in early 2019, just as our first patient presented to our clinic. Based on Dr. Bastian’s report, we proceeded to treat our patient with a Botox injection to the UES which resulted in complete resolution of her symptoms and she proceeded to let the blog know that there was now another doctor that could care for them. We have now treated more that 150 patients with RCPD at Jefferson.

RCPD is a syndrome with four symptoms:

1) the lifelong inability to burp, 2) abdominal bloating, 3) throat and chest noises (“squeaks” or “croaks”), and, 4) excessive flatulence, and the absence of dysphagia as a fifth “negative symptom.” Some patients’ families report occasional burps in early childhood and some patients can produce a burp with great effort. Many patients also

report difficulty vomiting or a severe fear of vomiting. Those patients that present for medical evaluation are often treated for gastroesophageal reflux and worked up for GERD and inflammatory bowel disease. These patients routinely come in with files full of normal test results.

Two things stand out that make RCPD unique. First, the condition was defined via “crowd sourcing” on internet blogs where multiple patients with similar symptoms came together. These bloggers brought the definition of the syndrome to the healthcare system and that process continues currently. In our published study of the first 85 patients treated at Jefferson, only one was seen as a result of physician referral and all of the others were self-referred after internet research. This pattern has mostly continued. But, we are starting to see some awareness of the condition in our local GI and Pediatric communities so we are slowly, beginning to see more direct medical referrals. The second unique issue with RCPD is that we have chosen to treat this cohort of patients based exclusively on their symptom complex without further testing or workup. While choosing a subgroup to study with videofluoroscopy and high-resolution esophageal manometry may help define the pathophysiology of RCPD, it has not been necessary to perform these tests to proceed to safe and effective treatment. As a result, this additional testing, outside of a study, may well represent a waste of healthcare resources when the symptombased syndrome is so consistent.

When patients present with the RCPD symptom complex, they are offered treatment with Botox injection to the UES. Most initial injections are performed in the OR, under general anesthesia and esophagoscopy is done at that time as well. The injections can also be performed in the office under local anesthesia with EMG guidance, using either a lateral or trans-tracheal approach and are well

tolerated. We are currently looking across multiple institutions to assess if there is a difference in response depending on approach.

In our initial cohort at Jefferson, 88.2% of patients had a successful response to their initial UES Botox treatment. Many in the group that failed to have a good response went on to have a response to a second injection. Most of the responders have maintained good symptom control well beyond the expected three month lifespan of the Botox effect. 30% of patients complain of transient dysphagia for 3-4 weeks after injection and a few patients have had heartburn, regurgitation or mild dyspnea during this interval. Otherwise, there have been no significant side effects or complications of treatment.

There are patients out there with RCPD that have been suffering a restricted quality of life but could not find a solution in the healthcare community. They first found each other, defined their own problem and have now broken through the barriers to be recognized and treated. Listen to your patients, especially when they can’t burp!

Bastian RW, Smithson ML, Inability to Belch and Associated Symptoms Due to Retrograde Cricopharyngeus Dysfunction: Diagnosis and Treatment, Diagn Treat OTO Open, 2019; 3:2473974X19834553.

Siddiqui SH, Sagalow ES, Fiorella MA, Jain N, Spiegel JR, Retrograde Cricopharyngeal Dysfunction: The Jefferson Experience, Laryngoscope, 00:1-5:2022

Impact of Circulating Cell Free Tumor Tissue Modified Viral-HPV DNA Testing on Post-Treatment Imaging Surveillance Protocol in Oropharyngeal Carcinoma

Harleen K. Sethi, DO

Nayel Khan, MD

Varsha Jain, MD, PhD

Melanie Nordlinger, MD

Leila J. Mady, MD, PhD, MPH

Christopher E. Fundakowski, MD Thomas Jefferson University

Post-treatment surveillance imaging recommendations for oropharyngeal squamous cell carcinoma (OPSCC) lack level I evidence, with significant variability in protocols by institution and providers. In addition to cross-sectional imaging (CSI), peripheral blood testing is available to detect circulating, cell free tumor tissue modified viral (TTMV)-HPV DNA in >90% of OPSSC. Given the paucity of data regarding radiologic surveillance with circulating tumor DNA (ctDNA) blood testing,1 our study aims to evaluate a novel post-treatment serologic surveillance pathway.

We performed a retrospective review of post-treatment imaging in HPV-associated OPSCC over 2-years at a single site. Institutional review board approval was obtained. Frequency of CSI was compared between 2 groups: 1-year prior to ctDNA (control) versus 1-year after ctDNA (experimental) integration (Table 1, Table 2). Eligible participants

Figures/Tables

included patients treated for primary HPVassociated OPSCC with no evidence of disease on 3-month, post-treatment PET/ CT following the completion of definitive treatment. In-office exam and point of care ultrasound (POCUS) was used at each surveillance visit for all participants to assess for regional recurrence. The control group received CT neck with contrast every 6-months and CT chest at 6-12

Abbreviations: BOT, base of tongue; GT, glossotonsillar

a US Preventative Services Task Force (USPSTF) defines high-risk smokers as adults aged 50 to 80 years who have a 20 pack-year smoking history and currently smoke or have quit within the past 15 years and recommends annual low dose computed tomography (CT) scans.

b Low risk smokers were defined as patients whose tobacco history fell below USPSTF recommendations for annual CT surveillance

c Stages are based on the American Joint Committee on Cancer staging manual, 8th edition

Table 1. Summary of patient characteristics: Experimental Group

Impact of Circulating Cell Free Tumor Tissue Modified Viral-HPV DNA Testing on Post-Treatment Imaging Surveillance Protocol in Oropharyngeal Carcinoma

Continued from page 9

Abbreviations: BOT, base of tongue; GT, glossotonsillar

a US Preventative Services Task Force (USPSTF) defines high-risk smokers as adults aged 50 to 80 years who have a 20 pack-year smoking history and currently smoke or have quit within the past 15 years and recommends annual low dose computed tomography (CT) scans.

b Low risk smokers were defined as patients whose tobacco history fell below USPSTF recommendations for annual CT surveillance

c Stages are based on the American Joint Committee on Cancer staging manual, 8th edition

months based on smoking history. The experimental group received ctDNA testing (NavDx, Naveris, Inc.) every 3-months: no additional imaging was obtained 1) unless there was concern for recurrence based on exam/ POCUS/blood testing or, 2) deemed high-risk for metachronous lung primary per US Preventative Services Task Force (USPSTF) recommendations.2

Among 81 participants, 25 controls (31%) underwent routine surveillance imaging and 56 (69%) received serologic surveillance. Over 12-months, all controls (100%) obtained at least 1 CT neck and chest. In the experimental group, 3 patients (5.4%) obtained a CT neck, yielding a 95% reduction in neck CSI (Figure 1).

Of the experimental group, 26 (46%) were non-smokers (USPSTF low-risk); 30 (54%) were former/current smokers, of which 7 (23%) were considered USPSTF high-risk and received annual screening chest CT. Utilizing serologic surveillance, chest CSI was avoided in 100% of patients considered low-risk for metachronous lung primary (n=49, 88%) (Figure 2).

Table 2. Summary of patient characteristics: Control Group

Impact of Circulating Cell Free Tumor Tissue Modified Viral-HPV DNA Testing on Post-Treatment Imaging Surveillance Protocol in Oropharyngeal Carcinoma

References

1. Berger BM, Hanna GJ, Posner MR, et al. Detection of Occult Recurrence Using Circulating Tumor Tissue Modified Viral HPV DNA among Patients Treated for HPV-Driven Oropharyngeal Carcinoma. doi:10.1158/1078-0432.CCR-22-0562

2. Krist AH, Davidson KW, Mangione CM, et al. Screening for Lung Cancer: US Preventive Services Task Force Recommendation Statement. JAMA - Journal of the American Medical Association. 2021;325(10):962-970. doi:10.1001/JAMA.2021.1117

3. Haddad RI, Hicks WL, Hitchcock YJ, et al. NCCN Guidelines Version 1.2023 Head and Neck Cancers Continue NCCN Guidelines Panel Disclosures. Published online 2022. Accessed March 13, 2023. https://www.nccn. org/home/member-

Current National Comprehensive Cancer Network (NCCN) recommended surveillance intervals lack head and neck cancer subsite specificity and risk stratified recommendations. Additionally, NCCN includes a wide range of variability with the current schedule of every 1 to 3 months for the first year, every 2 to 6 months for the second year, every 4 to 8 months for years 3 to 5, and annually thereafter.3 Limited benefit of PET/CT and a low positive predictive value in detecting local and regional recurrence have been demonstrated following a negative three month post definitive treatment scan.4 Recurrences are also more likely to be detected clinically two years after definitive treatment.5 These observations suggests a multimodal approach to HPV-associated OPSCC surveillance may be warranted.

In conclusion, ctDNA testing for OPSCC surveillance can decrease CSI of the neck and chest by 95% and 100%, respectively, in patients with low-risk smoking history. The impact of imaging reductions on health-system and individual-level costs, including patient financial toxicity, presents an area for future investigation. The potential to integrate surveillance ctDNA protocols may improve patient adherence to follow-ups and presents opportunities for novel remote tele-surveillance paradigms.

4. Ho AS, Tsao GJ, Chen FW, et al. Impact of positron emission tomography/ computed tomography surveillance at 12 and 24 months for detecting head and neck cancer recurrence. Cancer.

Figure 2: Chest CT Imaging Before and After ctDNA Surveillance Protocol

Figure 2 The non-smoker and low risk smoker group experienced a 100% reduction in chest CT imaging. Overall, an 88% reduction in chest imaging was observed. Seven patients were in the high risk smoker group with chest CT

Manan H. Parekh, BA

Nithin Adappa, MD Robert M. Brody, MD University of Pennsylvania

Noncompete agreements are a form of restrictive covenant aimed at protecting employer investments and reducing the risk for unfair advantages amongst competitors.1 Among physicians, noncompete agreements are varied in scope and enforceability, leading to frustration and sometimes exploitation of physicians. A 2021 Medscape survey of 558 physicians showed greater than 90% of physicians had or have a noncompete agreement, indicating the commonplace nature of these restrictive clauses.2 On January 5, 2023, the Federal Trade Commission (FTC) announced an initiative to ban noncompete agreements almost unilaterally, prompting speculation about how this may impact physicians in various locations.3 The banning of noncompete agreements may empower physicians, increase wages, improve working environments, and improve patient care. However, the potential benefits of this ruling hinge on court rulings and legal definitions.

“The freedom to change jobs is core to economic liberty,” said FTC chair Lina M. Khan regarding the initial proposal launch in January. Noncompete agreements have limited physician bargaining power against their employers. While physicians benefit from hospital systems/corporate entities by being able to collaborate with other providers, improve standard of care, and develop a varied patient base, these noncompete agreements can limit their mobility in the job market.4 For physicians with established families, moving may not be feasible, making contract negotiations difficult. In Pennsylvania, noncompete clauses are enforceable, severely limiting local alternative prospects for physicians. Due to the possibility of termination without alternatives, physicians are unable or hesitant to bargain for better working conditions or pay, as they have little

leverage against their employers. The banning of noncompete agreements would change this.

Noncompete agreements put the physician-patient relationship in the hands of the employer. The physician-patient relationship is particularly important in otolaryngology, where clinicians have a longitudinal relationship with patients treating conditions ranging from sinus complaints to hearing loss to voice complaints to head and neck cancer. Thus, patients should be able to see physicians with whom they have developed a trusting relationship. Noncompete agreements minimize choices for patients should the physician leave or be terminated. While the employer is focused on protecting their investments and business assets (i.e. the physician-patient relationship), patients are left out of the conversation which harms care and trust in physicians overall.

Pennsylvania has lofted the idea of banning noncompete agreements in recent history, and this FTC ruling is part of a nationwide employee-rights initiative.5 If enacted, this ruling prevents the signing of new noncompete agreements and makes existing ones non-enforceable. Private practice otolaryngologists can gain significant mobility; however, this may create turbulence within private practices at both the partner and associate levels. Whether this FTC ban permeates into the many hospital systems of Pennsylvania depends on key definitions. The new proposed rule states an entity not “organized to carry on business for its own profit or that of its members” is exempt. Academic and non-academic centers spanning the state fall into this classification of nonprofit entities (tax code 501c3). However, questions remain regarding the actual jurisdictional limitations of the FTC and the behavior of large nonprofit hospital systems which seek to maximize profits.6,7 To determine whether this FTC ruling will apply to nonprofit health systems, court examination of each system’s behavior and determination of whether its behavior matches its nonprofit classification will be needed. Thus, there may be a broad variation in how this

FTC ruling impacts otolaryngologists in Pennsylvania, particularly depending on their employment structure and rulings on FTC jurisdiction.

The public comment period for this ruling regarding noncompete agreements is open until April 19th. Following this comment period, there is a mandatory 180-day notice before the ruling goes into effect.

References

1. Harris SM. How reasonable non-compete clauses can protect your practice. ENTtoday. https:// www.enttoday.org/article/reasonable-noncompete-clauses-can-protect-practice/. Published October 18, 2016. Accessed March 26, 2023.

2. Reese SM. Docs suffer from noncompete clauses: Any hope for change? Medscape. https://www. medscape.com/viewarticle/948871. Published April 21, 2021. Accessed March 26, 2023.

3. Vedova H, Technology TFTCOof. FTC proposes rule to ban noncompete clauses, which Hurt Workers and Harm Competition. Federal Trade Commission. https://www.ftc.gov/news-events/ news/press-releases/2023/01/ftc-proposesrule-ban-noncompete-clauses-which-hurt-workersharm-competition. Published March 7, 2023. Accessed March 26, 2023.

4. Skerrett P. FTC's proposed ban on noncompete agreements could be a game changer for some physicians. STAT. https://www.statnews. com/2023/01/11/ftc-proposed-bannoncompete-agreements-game-changersome-physicians/. Published January 11, 2023. Accessed March 26, 2023.

5. Hollinger S. PA legislators propose to ban noncompete agreements in health care practitioners' employment contracts. Lamb McErlane PC. https://www.lambmcerlane.com/articles/ pa-legislators-propose-to-ban-non-competeagreements-in-health-care-practitionersemployment-contracts-2/. Published June 1, 2021. Accessed March 26, 2023.

6. Boden S. The FTC wants to end noncompete agreements. here's how it'll impact PittsburghArea Physicians. 90.5 WESA. https://www. wesa.fm/health-science-tech/2023-03-06/ the-ftc-wants-to-end-noncompete-agreementsheres-how-itll-impact-pittsburgh-area-physicians. Published March 7, 2023. Accessed March 27, 2023.

7. Bookman T. With $185 million in earnings, Hup is nation's seventh most profitable hospital. WHYY. https://whyy.org/articles/with-185-million-inearnings-hup-is-nations-seventh-most-profitablehospital/. Published May 3, 2016. Accessed March 27, 2023.

NOW HIRING

Pediatric Otolaryngologist

Facial Plastic Surgeon General Otolaryngologists

Penn State Health is seeking Otolaryngologists to join our growing team in either academic or community-based settings. Penn State is a multi-hospital health system serving patients and communities across 29 counties in central Pennsylvania. It employs more than 16,500 people system-wide. For more information, please contact: Ashley Nippert, Physician Recruiter anippert@pennstatehealth.psu.edu.

Penn State Health is fundamentally committed to the diversity of our faculty and staff. We believe diversity is unapologetically expressing itself through every person’s perspectives and lived experiences. We are an equal opportunity and affirmative action employer. All qualified applicants will receive consideration for employment without regard to age, color, disability, gender identity or expression, marital status, national or ethnic origin, political affiliation, race, religion, sex (including pregnancy), sexual orientation, veteran status, and family medical or genetic information.

Philip Dunn PAO HNS Lobbyist

As of January 1, 2023, I became the lobbyist for the Pennsylvania Academy of Otolaryngology. Previously, I spent 35 years employed by the Pennsylvania State Senate, retiring as Chief of Staff to the Senate Majority Whip; Senator John Gordner. Senator Gordner was an 18 year member of the Senate Consumer Protection and Professional Licensure Committee. Due to this assignment, I reviewed all Professional Licensure bills that were considered by this committee. I personally rewrote the Audiology and Speech Language Pathology Practice Act and was the principal architect of updates to the Professional Psychology Practice Act.

Pennsylvania General Assembly

Also in January of this year, the Pennsylvania General Assembly commenced the 2023-2024 legislative session. The Senate has reorganized with new leadership in place and a new majority chairperson of the Senate Consumer Protection and Professional Committee; Senator Pat Stefano. Senator Lisa Boscola continues as the Minority Chairperson of this committee.

The House, due to uncertainties over the majority status, has not been able to function normally as committee assignments have yet to be made. Once finished, the legislative process should begin in earnest.

It should be noted that all legislation introduced in the previous session that was not enacted into law will need to be reintroduced for renewed consideration.

Legislation in the 2023-2024 Session

A co-sponsorship memo has been circulating to all Senate members for the reintroduction of SB 25 from the last session. SB 25 provides independent practice for Certified Registered Nurse Practitioners. This measure has been around for some time and has even passed the Senate, most recently in the 2019-2020 session. Last session it never received full Senate consideration due to the opposition of the House Committee Chairman at the time, who has since retired. This changing political landscape in the House of Representatives will have to be watched carefully in regards to his bill.

After speaking with Dr. Cognetti, one of the duties I have been tasked to ensure that quarterly updates on relevant legislation are posted to the PAO website.

In the meantime, should you have any questions on legislation or become aware of proposals that should be brought to my attention, please email me at pfdunn444@gmail.com.

Annual Scientific Meeting Information

Friday, June 16, 2023

6:30-7:00 am

7:00-7:30 am

7:30-9:15 am

7:30-7:45 am

7:45-8:00 am

8:00-815 am

8:15-8:30 am

8:30-8:35 am

8:35-9:15 am

9:15-10:00 am

10:00-10:30 am

10:30 am-12:15 pm

10:30-10:55 am

10:55-11:20 am

11:20-11:45 am

11:45-12:10 pm

12:10-12:15 pm

12:30-1:15 pm

Registration & Continental Breakfast with Exhibitors

Welcome and Annual Business Meeting

David Cognetti, MD, President

Pediatric Otolaryngology

Session Chairs: Reema Padia, MD and Kavita Dedhia, MD

Chronic Sinusitis Beyond Adenoidecomy

Meghan Wilson, MD

Management of Residual Sleep Apnea Post T&A

Rachel Whelan, MD

The Noisy Breather

Jenna Briddell, MD

Peds Neck Mass

Conor Devine, MD

Q & A

Panel Discussion

20 23 ANNUAL SCIENTIFIC MEETING

June 16-17, 2023

Lancaster Marriott at Penn Square

Lancaster, PA

Panelists: Meghan Wilson, MD, Rachel Whelan, MD, Jenna Briddell, MD, Conor Devine, MD

Keynote Presentation: If We Knew Then, What We Know Now About Sleep

Kathleen Yaremchuk, MD

Break with Exhibitors

Procedural ENT

Session Chairs: JP Gniady, MD and Kevin Kovatch, MD

Office-Based Rhinology Procedures

David Yen, MD

Superior Laryngeal Nerve Block: Indications and Outcomes

Kathleen Tibbetts, MD

The Stones and Groans of Sialendoscopy

David Cognetti, MD

Making an Impact: Evaluation and Treatment of Patients with Post-Paralysis Facial Synkinesis

Jessyka Lighthall, MD and Cathy Henry, MD

Open Discussion

PAO-HNS Committee Meetings

Sleep Medicine

Patient Safety & Quality Improvement

Facial Plastic & Reconstructive Surgery

Head & Neck Surgery

Allergy & Rhinology

Pediatrics

Otology

Voice & Swallowing

1:15-2:15 pm

2:15-5:00 pm

5:00-6:00 pm

6:00-9:00 pm

Saturday, June 17, 2023

7:00-7:30 am

7:30-8:30 am

Industry Sponsored Lunch Symposium—Regeneron (non-CME)

Free Time

PAO-HNS Women in Otolaryngology Event at the Lancaster Marriott at Penn SquareThat Day

Session Chair/Host: Karen Rizzo, MD

Speaker: Kathleen Yaremchuk, MD

Sponsor: Stryker

Reception and Dinner Event at the Lancaster Marriott at Penn Square

Registration & Continental Breakfast with Exhibitors

Business Practice

Use of Physician Extenders in Otolaryngology

Session Chairs: Karen Rizzo, MD and Sandra Stinett, MD

Panelists: Lindsey Eisler, MD and Tiffany Heikel, PA-C, Brian Woodhead, Danielle DeMaio-DeAngelis

8:30-9:30 am

9:30-10:00 am

10:00-11:00 am

11:00-11:15 am

11:15 am-12:15 pm

12:15-12:45 pm

12:45-12:50 pm

12:50 pm

Patient Safety

ERAS/Pain Management After Surgery

Session Chairs: Neerav Goyal, MD

Panelists: Sanjib Adhikary, MD, Robert Brody, MD, Monika Holbein, MD

Break with Exhibitors

Resident Research Session

Session Chairs: Kevin Stavrides, MD and Craig Bollig, MD

Resident Conchal Bowl Setup and Introductions

Resident Conchal Bowl

Session Chairs: Kevin Stavrides, MD and Craig Bolig, MD

Jeopardy & Abstract Award Presentations

Closing Remarks

Nicholas Purdy, DO, Program Chair

Meeting Adjourned

Ellie Goldenberg Legacy Award

Ellie Goldenberg (z"l) was one of the most genuine, loyal, talented, kind-hearted, and passionate people you could ever hope to know.

Ellie cared about those she loved like no other; she did all she could for you when you were sad, cheered you on when you succeeded, and, most importantly, pushed you to be your very best self. Her love was unconditional and so very deep. She would go to the ends of the earth for her friends and family.

And then, there was that voice. Ellie was always singing; in the shower, in the kitchen, and in the bathroom. She would sing when she was happy, when she was

sad, and when she was angry. When Ellie sang, we would stop whatever we were doing to listen. Her voice melted our hearts. We still hear her voice in our dreams.

Ellie was the hardest-working person you could ever know. We used to joke with her that in a family of doctors and future doctors, she got off easy majoring in "jazz hands and accents," but nothing was farther from the truth. When studying a playwright or preparing for a show by a specific author, Ellie bought all their plays and read them cover to cover until she could predict every right acting choice and understand the intention of each of the author's words. Then, she would stand in the shower singing the same note or line of a song repeatedly until she was sure it was perfect. That was Ellie.

But of all of these things, most importantly, Ellie was genuine and passionate. She did everything with purpose, determination, and with all of her heart. In establishing this resident award at the Pennsylvania Academy of Otolaryngology, we, her family, wanted her legacy of hard work, dedication, and kindness to be commemorated and perpetuated. The Ellie Goldenberg Award will recognize an Otolaryngology resident within the Commonwealth of Pennsylvania who demonstrates a strong work ethic, diligence, initiative, and kindness. The award will be presented at the annual PAO meeting.

Jennifer E. Douglas, MD University of Pennsylvania

With the development of the COVID-19 pandemic, smell loss has emerged as a particularly common symptom among patients recently infected by SARS-CoV-2. Current literature indicates that around 40% of patients experience some form of smell or taste dysfunction following SARS-CoV-2 infection. Anosmia poses a variety of safety concerns, such as the loss of odor recognition of fires, gas leaks, and spoiled food. Given the safety concerns and long-term quality of life issues associated with this condition, knowledge of current treatments addressing COVID-related anosmia is critical. In the past several years, a number of investigations have occurred regarding effective treatment methods, and we have sought to highlight these findings.

COVID 19 Pathophysiology

While further research is necessary to better understand the mechanisms through which SARS-CoV-2 is able to cause infection, relatively high rates of angiotensin converting enzyme 2 (ACE2) expression among cells infected with SARS-CoV-2 point towards ACE2 involvement in viral infection. Current studies highlight the role of ACE2 as a receptor that permits SARS-CoV-2 entry into cells and subsequent initiation of viral replication. Transmembrane serine protease 2 (TMPRSS2), which is involved in priming of the spike protein in SARS-CoV-2 through cleavage at the S1/S2 and S2 site, is also associated with COVID-19 infection. Given the much broader spread of TMPRSS2 across various organs and tissues, a focus on ACE2 provides a more tailored approach to addressing the mechanisms through which SARS-CoV-2 is able to affect various systems. Some studies indicate that SARS-CoV-2 can utilize ACE2 and TMPRSS2 to facilitate viral infection without inducing a local

inflammatory response, providing an explanation for the relatively large body of patients who experience anosmia as the only symptom of COVID-19 infection and illustrating the importance of educating patients about anosmia as an indicator of viral infection. In addition to determining the role of ACE2 and TRMPSS2 in SARS-CoV-2 infection, a recent multiancestry genome-wide association study involving self-reported data from 69,841 23andMe participants identified a genetic locus at chr4q13.3 linked to COVID-associated anosmia. Two of the genes identified within 150 kb of this locus, UGT2A1 and UGT2A2, are uridine diphosphate glycosyltransferases present in the olfactory epithelium and have been shown to be involved in olfactory signal termination in animal studies.

A number of other theories have been presented regarding the mechanisms through which SARS-CoV-2 is able to induce anosmia among patients who have been recently affected. The sustentacular cells of the olfactory epithelium have been a particular point of focus given their role in the maintenance of the olfactory epithelium and the relatively high rates of ACE2 and TMPRSS2 expressed among these cells. Damage to the sustentacular cells and the release of tumor necrosis factor-(TNF-) can directly cause dysfunction of the olfactory epithelium via local inflammation and indirectly limit the activity of olfactory sensory neurons through destruction of the cilia layer involved in olfactory transduction. Despite the relatively low levels of ACE2 expressed in OSNs, studies continue to examine mechanisms through which SARSCoV-2 is able gain entrance to the central nervous system in light of the presence of neuronal infection via the olfactory nerve in SARS-CoV-1. As research progresses, more recent studies have begun to incorporate multi-modal MRI analysis to assess alterations to the function of cortical structures involved in olfactory function among patients suffering from long-term COVID-induced anosmia. Treatments aim at addressing the particular mechanisms through which SARS-CoV-2 infects cells via olfactory pathways and results in

an increased prevalence of anosmia among infected patients.

Treatment Options

Olfactory Training

Olfactory training, which involves repeated, brief exposure to a series of odorants over a period of months, remains one of the most common methods for addressing COVID-induced anosmia. Following an extensive review of 107 articles addressing management of postinfectious olfactory dysfunction, the Clinical Olfactory Working Group highly endorsed olfactory training to address postinfectious olfactory dysfunction. One study reported a significant increase in olfactory function following repeated twice-daily exposure to rose, eucalyptus, lemon, and cloves over the course of 12 weeks compared to a control group that showed no improvement without olfactory training.

Additional research has been completed regarding the effectiveness of olfactory testing in combination with other odorants or treatment methods. Among three groups of patients completing either a modified olfactory training, standard olfactory training, or no olfactory training over the course of 36 weeks, the group completing modified olfactory training showed significant improvement in olfactory function compared to the groups completing standard olfactory training or no olfactory training. The modified olfactory training utilized three sets of four different odorants administered for 12 weeks at a time in comparison to the standard olfactory training, which utilized the same four odorants (rose, eucalyptol, lemon, cloves) over the 36-week period. Additional odorants utilized in modified olfactory training included menthol, thyme, tangerine, jasmine, green tea, bergamot, rosemary, gardenia. Considering the promising results of recent studies, as well as the accessibility of smell training to many patients experiencing postinfectious olfactory dysfunction, more research is warranted on this method of treatment.

Jadyn Wilensky, BA

Nithin D. Adappa, MD

Corticosteroids

While widely employed based on their anti-inflammatory abilities in treating CRS and respiratory distress, the use of corticosteroids in conjunction with olfactory training has also proven promising in treating COVID-related anosmia. In a randomized controlled trial with 138 patients experiencing olfactory loss and without signs of sinonasal inflammation, patients were asked to either complete olfactory training in conjunction with saline irrigation or olfactory training in conjunction with budesonide irrigations for 6 months. Subject outcomes were determined based on the results of the University of Pennsylvania Smell Identification Test (UPSIT). Of the 47 patients showing improvement in olfactory function, 43.9% of patients completing the budesonide irrigations and olfactory training and 26.9% of patients completing saline irrigations and olfactory training demonstrated improvement.

Another study examining the use of oral and intranasal corticosteroid use in conjunction with olfactory training among 152 patients experiencing COVID-related olfactory dysfunction found a significant improvement in patients using oral corticosteroids in early usage but found that any significant improvement in comparison to intranasal corticosteroid use or olfactory training alone diminished after two months. The study divided patients into three groups, who were instructed to use oral corticosteroids while completing olfactory training, intranasal corticosteroids while completing olfactory training, or olfactory training alone. Subject olfactory function was examined using Sniffin’ Sticks. No patients experienced a worsening of COVID symptoms. A similar outcome was observed in a study examining 100 subjects experiencing COVIDinduced anosmia who were instructed to administer mometasone furoate nasal spray in each nostril once daily for three

weeks while performing olfactory training or were instructed to complete olfactory training alone. While smell scores improved for both subject groups, there was no significant difference in outcome between the two groups.

Of note, some earlier studies have raised concern regarding delayed viral clearance and immunosuppression as a result of frequent or prolonged corticosteroid use. While current research is generally promising regarding the use of corticosteroids in managing postinfectious olfactory dysfunction, further discussion of the use of this treatment in patients recently infected with SARS-CoV-2 or the need for adjuvant therapies during treatment requires further examination.

Additional Treatments

A number of other treatments have shown promising results in improving symptoms of anosmia following COVID-19 infection, including theophylline, sodium citrate, fatty acids, and platelet-rich plasma (PRP). These treatments operate through a variety of methods. Parotid saliva levels of cAMP and cGMP have been shown to be decreased in patients experiencing smell loss, and theophylline is thought to improve olfactory sensitivity by inhibiting phosphodiesterase, thereby increasing neuronal levels of second messengers cAMP and cGMP. Sodium citrate operates via sequestering of calcium to reduce feedback inhibition in olfactory signaling transduction. Fatty acids utilize their anti-inflammatory, antioxidative, and protective functions in order to improve olfactory function.

The injection of PRP, an autologous blood product, into the olfactory cleft constitutes a new approach to addressing olfactory dysfunction following COVID-induced anosmia. The anti-inflammatory and regenerative capacity of PRP occurs via degranulation of platelets containing high concentrations of growth factors and other proteins involved in inflammation and tissue regeneration. Based on comparative analysis of TDI scores in a study involving 56 patients experiencing COVID-induced olfactory dysfunction, PRP injections led to a significant improvement in olfactory function

after 1 month compared to the control group. A single-blinded, randomized controlled study involving 29 patients extended the period in which subjects were followed from 1 to 3 months and employed a placebo injection. Results of this second study demonstrated a significant improvement in olfaction scores and smell discrimination among patients receiving a PRP injection at both the 1-month and 3-month mark compared to the placebo group, but no significant difference in smell identification, smell threshold, or subjective scores. No long-standing adverse effects were noted in either study.

Conclusion

Ongoing discussion is warranted regarding the best treatment methods for improving olfactory loss following SARS-CoV-2 infection. While olfactory training remains a highly regarded treatment method, recent studies indicate that combined therapies including corticosteroids may be a more appropriate form of treatment among patients experiencing persistent anosmia. As treatment methods continue to develop, organizations such as the Smell and Taste Association of North America (STANA), the Monell Chemical Senses Center Smell for Life Project, AbScent, and Anosmia Awareness Organization provide resources, opportunities, and other forms of support for patients experiencing anosmia.

References:

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2. Meng, X., & Pan, Y. (2021). COVID-19 and anosmia: The story so far. Ear, nose, & throat journal, 1455613211048998. Advance online publication. https://doi. org/10.1177/01455613211048998

3. Ahmed, A. K., Sayad, R., Mahmoud, I. A., ElMonem, A. M. A., Badry, S. H., Ibrahim, I. H., Hafez, M. H., El-Mokhtar, M. A., & Sayed, I. M. (2022). "Anosmia" the mysterious collateral damage of COVID-19. Journal of neurovirology, 28(2), 189–200. https://doi.org/10.1007/ s13365-022-01060-9

4. Torabi, A., Mohammadbagheri, E., Akbari Dilmaghani, N., Bayat, A. H., Fathi, M., Vakili, K., Alizadeh, R., Rezaeimirghaed, O., Hajiesmaeili, M., Ramezani, M., Simani, L., & Aliaghaei, A. (2020). Proinflammatory Cytokines in the Olfactory Mucosa Result in COVID-19 Induced Anosmia. ACS chemical neuroscience, 11(13), 1909–1913. https://doi.org/10.1021/ acschemneuro.0c00249

5. Hoffmann, M., Kleine-Weber, H., Schroeder, S., Krüger, N., Herrler, T., Erichsen, S., Schiergens, T. S., Herrler, G., Wu, N. H., Nitsche, A., Müller, M. A., Drosten, C., & Pöhlmann, S. (2020). SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell, 181(2), 271–280.e8. https://doi.org/10.1016/j.cell.2020.02.052

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7. Abdelalim, A. A., Mohamady, A. A., Elsayed, R. A., Elawady, M. A., & Ghallab, A. F. (2021). Corticosteroid nasal spray for recovery of smell sensation in COVID-19 patients: A randomized controlled trial. American journal of otolaryngology, 42(2), 102884. https://doi. org/10.1016/j.amjoto.2020.102884

8. Neta, F. I., Fernandes, A. C. L., Vale, A. J. M., Pinheiro, F. I., Cobucci, R. N., Azevedo, E. P., & Guzen, F. P. (2021). Pathophysiology and possible treatments for olfactory-gustatory disorders in patients affected by COVID-19. Current research in pharmacology and drug discovery, 2, 100035. https://doi. org/10.1016/j.crphar.2021.100035

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11. Addison, A. B., Wong, B., Ahmed, T., Macchi, A., Konstantinidis, I., Huart, C., Frasnelli, J., Fjaeldstad, A. W., Ramakrishnan, V. R., Rombaux, P., Whitcroft, K. L., Holbrook, E. H., Poletti, S. C., Hsieh, J. W., Landis, B. N., Boardman, J., Welge-Lüssen, A., Maru, D., Hummel, T., & Philpott, C. M. (2021). Clinical Olfactory Working Group consensus statement

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13. Altundag, A., Cayonu, M., Kayabasoglu, G., Salihoglu, M., Tekeli, H., Saglam, O., & Hummel, T. (2015). Modified olfactory training in patients with postinfectious olfactory loss. The Laryngoscope, 125(8), 1763–1766. https://doi. org/10.1002/lary.25245

14. Nguyen, T. P., & Patel, Z. M. (2018). Budesonide irrigation with olfactory training improves outcomes compared with olfactory training alone in patients with olfactory loss. International forum of allergy & rhinology, 8(9), 977–981. https:// doi.org/10.1002/alr.22140

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