JOM - April 2021

426 Rehman et al.: Dropout after OMT for chronic pain in randomized trials

in future studies to build the strength and confidence in Clinical implications and future directions
OMTh research.
There was moderate quality evidence that OMTh in man-
Strengths and limitations aging CNCP is associated with low ACD and dropouts due to
AE. For this review, we extracted tolerability outcomes from
A key strength of our review was that we focused on spe- studies that were included in our previous systematic review
cific outcomes, which are often underreported and over- [22]. Making multiple publications using the same data
looked: tolerability outcomes of ACD, dropout rates due to set can be acceptable, provided the goals are explained
AE, and inefficacy. Our search strategy was broad, and our explicitly and the research question and rationale are adding
review was methodologically rigorous because we reported significant contribution to the scientific community [51, 52].
our results clearly and transparently, allowing for more As mentioned, most systematic reviews and metaanalyses
precise interpretation of our results. focus on beneficial outcomes of an intervention with little to
no emphasis on tolerability outcomes [17–19]. For any
Our review also had several limitations. First, we intervention and especially within osteopathic practice,
inherited limitations from the primary studies having high treatment philosophy is based on safety, equitability, effec-
ROB, which we downrated for major bias components such tiveness, and orientation to patients [53–55]. As OMTh is
as random sequence generation and blinding. Although increasingly utilized and is considered a safe and effective
none of the included studies met all criteria of ROB, this is a method of treatment, it is imperative to fully understand
common limitation to all procedure-based clinical trials both the benefits and potential harms. Understanding the
since it is nearly impossible to blind both patients and risks of treatment is important for both the healthcare pro-
practitioner(s). Second, the eligible studies were not suffi- vider and patients, as having an understanding of OMTh-
ciently powered and the dropout rate in the eligible studies associated ACD and dropouts due to AE will allow clinicians
was very high. Third, due to the nature and reporting of to create a safe practice and patients to establish realistic
current evidence, we were unable to pool the dropout rates expectations, give adequate consent, and make an informed
for many important comparisons. choice among all available interventions. Our goal was to
emphasize the importance of exploring the tolerability of
In the context of existing literature exploring the OMTh in the management of CNCP patients in osteopathic
tolerability outcomes of OMTh in CNCP, our review is research. We hope that future studies reporting on the
unique in its study design. In a survey of 884 patients by effectiveness of OMTh will also report reasons for dropouts,
Degenhardt et al. [26], the incidence of AE due to OMTh was ACD rates, and any AE experienced during the study.
2.5% (95% CI, 1.3–4.7%). Women (n=44; 97.8%) reportedly
experienced more AE than men (n=1; 2.23) (OR, 13.9; Conclusions
95% CI, 1.7–115.6; p=0.01), with pain/discomfort the most
commonly identified type of AE at 0.9% (95% CI, 0.5– In this systematic review with meta-analysis, we criti-
1.6%). Vogel et al. [50] reported AE from OMTh in 2039 cally appraised the existing literature to explore OMTh in
patients, of which 4% (n=82) patients reported mild CNCP patients with a focus on tolerability and drop out
disability and 10% (n=130) sought attention from other effects. The current evidence is based on studies with high
health care providers during treatment [50]. However, risk of bias and small sample sizes. Like any other inter-
Degenhardt et al. [26] and Vogel et al. [50] explored dropout vention and manipulation therapy, OMTh is not exempt
rates in observational studies and did not compare the from AE and dropouts, and was not significantly different
dropout rates to other interventions. Our review is unique than comparators such as physiotherapy and standard
in that we explored the ACD and AE of OMTh compared care (e.g., drug intervention). Moderate quality evidence
with controls in CNCP reported in previously published showed that ACD from OMTh were not significantly
RCT. RCTs are a more suitable study design to explore the different than the control interventions; however, data on
effectiveness and tolerability of a treatment compared with reporting AE and dropout rates with osteopathic treat-
observational studies due to an increase in control as well ment in RCTs were sparse and not explicitly reported in
as being able to more critically assess variables and bias, the included trials. Information about tolerability and AE
and it is important to compare the AE of OMTh to other is important for patients to make informed decisions and
recommended treatment modalities. Therefore, our review establish realistic expectations of treatment. Therefore,
provides better evidence for the safety of OMTh compared
with previous studies.

Rehman et al.: Dropout after OMT for chronic pain in randomized trials 427

more pragmatic RCTs comparing the effectiveness of 9. Burke SR, Myers R, Zhang AL. A profile of osteopathic practice in
OMTh with other treatment modalities such as pharma- Australia 2010-2011: a cross sectional survey. BMC Muscoskel
cological agents and physical therapies are required to Disord 2013;14:227.
determine the overall effectiveness of OMTh in the man-
agement of CNCP while trying to keep data transparent so 10. Carnes D, Mars TS, Mullinger B, Froud R, Underwood M. Adverse
that it can be compared with other studies. It is also events and manual therapy: a systematic review. Man Ther 2010;
imperative that future research should focus on OMTh in 15:355–63.
the management of specific CNCP conditions and include
general and visceral treatments to determine the relative 11. Licciardone JC, Schultz MJ, Amen B. Osteopathic manipulation in
effectiveness of various OMTh approaches. the management of chronic pain: current perspectives. J Pain Res
2020;13:1839–47.
Research funding: None declared.
Author contributions: Dr Rehman, Ms Ferguson, Mr Blair, 12. Saracutu M, Rance J, Davies H, Edwards DJ. The effects of
Ms Bozek, and Ms Alison provided substantial contributions osteopathic treatment on psychosocial factors in people with
to conception and design, acquisition of data, or analysis persistent pain: a systematic review. Int J Osteopath Med 2018;
and interpretation of data; Dr Rehman, Ms Ferguson, and Mr 27:23–33.
Blair drafted the article or revised it critically for important
intellectual content; Dr Rehman and Mr Johnston authors 13. Busse JW, Craigie S, Juurlink DN, Buckley Norman, Wang Li,
gave final approval of the version of the article to be Couban Rachel, et al. Guideline for opioid therapy and chronic
published; and all authors agree to be accountable for all noncancer pain. Can Med Assoc J 2017;189:E659–66.
aspects of the work in ensuring that questions related to
the accuracy or integrity of any part of the work are 14. Steel A, Peng W, Sibbritt D, Adams J. Introducing national
appropriately investigated and resolved. osteopathy practice-based research networks in Australia and
Competing interests: None declared. New Zealand: an overview to inform future osteopathic research.
Ethical approval: A previous systematic review from which Sci Rep 2020;10:846.
the data in this review was taken was registered with
Prospero (#CRD42019125659). 15. Carnes D, Mullinger B, Underwood M. Defining adverse events in
manual therapies: a modified Delphi consensus study. Man Ther
References 2010;15:2–6.

1. Reid KJ, Harker J, Bala MM, Truyers C, Kellen E, Bekkering GE, et al. 16. Carlesso LC, Cairney J, Dolovich L, Hoogenes J. Defining adverse
Epidemiology of chronic non-cancer pain in Europe: narrative events in manual therapy: an exploratory qualitative analysis of
review of prevalence, pain treatments and pain impact. Curr Med the patient perspective. Man Ther 2011;16:440–6.
Res Opin 2011;27:449–62.
17. McIntosh HM, Woolacott NF, Bagnall AM. Assessing harmful
2. Blyth FM, Briggs AM, Schneider CH, Hoy DG, March LM. The global effects in systematic reviews. BMC Med Res Methodol 2004;4:19.
burden of musculoskeletal pain-where to from here? Am J Publ
Health 2019;109:35–40. 18. Ernst E, Pittler MH. Assessment of therapeutic safety in
systematic reviews: literature review. BMJ 2001;323:546.
3. Schopflocher D, Taenzer P, Jovey R. The prevalence of chronic pain
in Canada. Pain Res Manag 2011;16:445–50. 19. Zorzela L, Golder S, Liu Y, Pilkington K, Hartling L, Joffe A, et al.
Quality of reporting in systematic reviews of adverse events:
4. Dahlhamer J, Lucas J, Zelaya C, Nahin R, Mackey S, Debar L, et al. systematic review. BMJ (Clin Res Ed) 2014;348:f7668.
Prevalence of chronic pain and high-impact chronic pain among
adults – United States, 2016. MMWR Morb Mortal Wkly Rep 2018; 20. Julian PTH, Sally G. Cochrane handbook for systematic reviews of
67:1001–6. interventions. Chichester, West Sussex, Hoboken NJ: John Wiley
& Sons; 2008.
5. Turk DC, Wilson HD, Cahana A. Treatment of chronic non-cancer
pain. Lancet 2011;377:2226–35. 21. Schmucker CM, Blümle A, Schell LK, Schwarzer G, Oeller P, Cabrera
L, et al. Systematic review finds that study data not published in full
6. Bogduk N. Management of chronic low back pain. Med J Aust 2004; text articles have unclear impact on meta-analyses results in
180:79–83. medical research. PloS One 2017;12:e0176210.

7. Giusti R. Glossary of osteopathy terminology. 3rd ed. USA: AACOM; 22. Rehman Y, Ferguson H, Blair J, Bozek A, Allison A, Johnston R. The
2017. effectiveness of osteopathic manual treatment in the reduction of
pain severity, functional improvement and return to work in
8. Fawkes CA, Leach CMJ, Mathias S, Moore AP. A profile of chronic non-cancer pain patients: meta-analysis and systematic
osteopathic care in private practices in the United Kingdom: a review. J Am Osteopath Assoc 2020;120:888–906.
national pilot using standardised data collection. Man Ther 2014;
19:125–30. 23. Licciardone JC, Herron KM. Characteristics, satisfaction, and
perceptions of patients receiving ambulatory healthcare from
osteopathic physicians: a comparative national survey. J Am
Osteopath Assoc 2001;101:374–85.

24. Adams J, Sibbritt D, Steel A, Peng W. A workforce survey of
Australian osteopathy: analysis of a nationally-representative
sample of osteopaths from the Osteopathy Research and Innovation
Network (ORION) project. BMC Health Serv Res 2018;18:352–52.

25. Alvarez Bustins G, López Plaza P-V, Carvajal SR. Profile of
osteopathic practice in Spain: results from a standardized data
collection study. BMC Compl Alternative Med 2018;18:129.

26. Degenhardt BF, Johnson JC, Brooks WJ, Norman L. Characterizing
adverse events reported immediately after osteopathic
manipulative treatment. J Am Osteopath Assoc 2018;118:
141–9.

428 Rehman et al.: Dropout after OMT for chronic pain in randomized trials

27. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche P, Ioannidis 42. Altinbilek T, Murat S, Yumusakhuylu Y, Icagasioglu A.
J, et al. The PRISMA statement for reporting systematic reviews Osteopathic manipulative treatment improves function and
and meta-analyses of studies that evaluate healthcare relieves pain in knee osteoarthritis: a single-blind, randomized-
interventions: explanation and elaboration. BMJ 2009;339: controlled trial. Turk J Phys Med Rehabil 2018;64:114–20.
b2700.
43. Chown M, Whittamore L, Rush M, Allan S, Stott D, Archer M. A
28. Moore RA, Derry, S, Wiffen, PJ. Challenges in design and prospective study of patients with chronic back pain randomised
interpretation of chronic pain trials. Br J Anaesth 2013;111: to group exercise, physiotherapy or osteopathy. Physiotherapy
38–45. 2008;94:21–8.

29. Licciardone JC, Brimhall AK, King LN. Osteopathic manipulative 44. Licciardone JC, Minotti DE, Gatchel RJ, Kearns CM, Singh KP.
treatment for low back pain: a systematic review and meta- Osteopathic manual treatment and ultrasound therapy for
analysis of randomized controlled trials. BMC Muscoskel Disord chronic low back pain: a randomized controlled trial. Ann Fam
2005;6:43. Med 2013;11:122–9.

30. Roose SP. Tolerability and patient compliance. J Clin Psychiatr 45. Marske C, Bernard N, Palacios A, Wheeler C, Preiss B, Brown M,
1999;60(17 Suppl):14–7; discussion 46–8. et al. Fibromyalgia with gabapentin and osteopathic
manipulative medicine: a pilot study. J Alternative Compl Med
31. Kluetz PG, Chingos DT, Basch EM, Mitchell SA. Patient-reported 2018;24:395–402.
outcomes in cancer clinical trials: measuring symptomatic
adverse events with the national cancer institute’s patient- 46. Marti-Salvador M, Hidalgo-Moreno L, Domenech-Fernandez J,
reported outcomes version of the common terminology criteria Lison JF, Arguisuelas MD. Osteopathic manipulative treatment
for adverse events (PRO-CTCAE). Am Soc Clin Oncol Educ Book including specific diaphragm techniques improves pain and
2016;35:67–73. disability in chronic nonspecific low back pain: a randomized
trial. Arch Phys Med Rehabil 2018;99:1720–9.
32. Atkinson TM, Ryan SJ, Bennett AV, Stover A, Saracino R, Rogak L,
et al. The association between clinician-based common 47. Papa L, Mandara A, Bottali M, Gulisano V, Orfei S. A randomised
terminology criteria for adverse events (CTCAE) and patient- control trial on the effectiveness of osteopathic manipulative
reported outcomes (PRO): a systematic review. Support Care treatment in reducing pain and improving the quality of life in
Canc 2016;24:3669–76. elderly patients affected by osteoporosis. Clin Cases Miner Bone
Metabol: Off J Ital Soc Osteoporos Miner Metabol Skeletal Dis
33. Gutie´rrez-Espinoza H, Araya-Quintanilla F, Cereceda-Muriel C, 2012;9:179–83.
Álvarez-Bueno C, Martínez-Vizcaíno V, Cavero-Redondo I. Effect
of supervised physiotherapy versus home exercise program in 48. Schwerla F, Bischoff A, Nurnberger A, Genter P, Guillaume JP,
patients with subacromial impingement syndrome: a Resch KL. Osteopathic treatment of patients with chronic non-
systematic review and meta-analysis. Phys Ther Sport 2020;41: specific neck pain: a randomised controlled trial of efficacy.
34–42. Forsch Komplementmed 2008;15:138–45.

34. Albers J, Jakel A, Wellmann K, von Hehn U, Schmidt T. 49. Knebl J, Shores J, Gamber R, Gray W, Herron K. Improving
Effectiveness of 2 osteopathic treatment approaches on pain, functional ability in the elderly via the Spencer technique,
pressure-pain threshold, and disease severity in patients with an osteopathic manipulative treatment: a randomized, controlled
fibromyalgia: a randomized controlled trial. Complement Med trial. J Am Osteopath Assoc 2002;102:387–96.
Res 2018;25:122–8.
50. Vogel T, Keeping S, Barton T, Marlin N, Froud R, Eldridge S, et al.
35. Licciardone JC, Stoll ST, Fulda KG, Russo D, Winn W, Swift J. Clinical risk osteopathy and management scientific report.
Osteopathic manipulative treatment for chronic low back pain: a London: The CROaM Study; 2013.
randomized controlled trial. Spine 2003;28:1355–62.
51. Kirkman BL, Chen G. Maximizing your data or data slicing?
36. Atkins D, Best D, Briss PA, Eccles M, Dalck-Ytter Y, Flottorp S, et al. Recommendations for managing multiple submissions from the
Grading quality of evidence and strength of recommendations. BMJ same dataset. Manag Organ Rev 2011;7:433–46.
(Clinical Res Ed) 2004;328:1490.
52. Fine MA, Kurdek LA. Publishing multiple journal articles from a
37. Balshem H, Helfand M, Schünemann HJ, et al. GRADE guidelines: single data set: issues and recommendations. J Fam Psychol
3. Rating the quality of evidence. J Clin Epidemiol 2011;64:401–6. 1994;8:371–9.

38. Guyatt GH, Oxman AD, Kunz R, Vist GE, Falck-Ytter Y, Schünemann 53. Mitchell PH. Chapter 1, defining patient safety and quality care.
HJ. What is “quality of evidence” and why is it important to In: Hughes RG, editor. Patient safety and quality: an evidence-
clinicians? BMJ 2008;336:995. based handbook for nurses. Rockville (MD): Agency for
Healthcare Research and Quality (US); 2008.
39. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello
P, et al. GRADE: an emerging consensus on rating quality of 54. Steel A, Blaich R, Sundberg T, Adams J. The role of osteopathy in
evidence and strength of recommendations. BMJ 2008;336:924. clinical care: broadening the evidence-base. Int J Osteopath Med
2017;24:32–6.
40. Higgins JPT, Altman DG, JAC S. Cochrane handbook for systematic
reviews of interventions; [Chapter 8]: assessing risk of bias in 55. Carnes D. What can osteopaths learn from concerns and
included studies. The Cochrane Collaboration; 2011. complaints raised against them? A review of insurance and
regulator reports. Int J Osteopath Med 2016;22:3–10.
41. Burton AK, Tillotson K, Cleary J. Single-blind randomised
controlled trial of chemonucleolysis and manipulation in the Supplementary Material: The online version of this article offers
treatment of symptomatic lumbar disc herniation. Eur Spine J: Off supplementary material (https://doi.org/10.1515/jom-2020-0240).
Publ Eur Spine Soc Eur Spinal Deformity Soc Eur Section Cervical
Spine Res Soc 2000;9:202–7.

J Osteopath Med 2021; 121(4): 429–430

Public Health and Primary Care Commentary

Kenneth H. Johnson*, DO

Joining forces to administer COVID-19 vaccines

https://doi.org/10.1515/jom-2021-0034 support afforded to the region by the university in partner-
Received January 28, 2021; accepted February 25, 2021; ship with the Athens City-County Health Department
published online March 5, 2021 (ACCHD) and OhioHealth, the predominate healthcare
provider in our area.
Abstract: The national vaccination effort for novel coro-
navirus 2019 (COVID-19) is among the greatest operational Through health education, screenings, and immuni-
challenges America has ever faced, the success of which zations, the college’s institutes and community health
depends upon reaching communities across the United programs have long bolstered the efforts of our local
States. In this Commentary, the Executive Dean of Ohio healthcare teams, most notably in service to southeast
University’s Heritage College of Osteopathic Medicine Ohio’s medically underserved populations – but COVID-19
(OUHCOM) describes the logistics and processes of vaccine raised the bar.
delivery at OUHCOM, both on campus and beyond. Among
those logistical considerations is a partnership with the It quickly became apparent that a coordinated
local health department and hospital system, as well as pandemic response – particularly immunizing people in
student involvement in vaccination efforts. the county against COVID-19 – would require an unprece-
dented synthesis of public health, education, private
Keywords: COM; coronavirus; COVID-19; distribution; healthcare, and care provision efforts. Protecting our
logistics; vaccination. community became the highest priority, and the bright
lines that have traditionally defined the boundaries of our
The national vaccination effort for novel coronavirus 2019 respective organizations blurred, with each organization
(COVID-19) is one of the greatest operational challenges filling needs from logistics to personnel.
America has ever faced, the success of which depends
upon reaching communities across the United States, ac- Logistics
cording to the National Strategy for the COVID-19 Response
and Pandemic Preparedness document issued by President One distinct advantage that our team has at its disposal is
Biden in January 2021 [1]. As the federal government works the college’s newly constructed medical education center,
to expand vaccination supply, community healthcare or- Heritage Hall. Designed to enhance the health and well-
ganizations are facing a daunting logistical charge: getting being of occupants, the facility features a large and open
shots into patients’ arms as quickly as possible. atrium, state of the art ventilation systems, and full acces-
sibility. Three stories of glass conference spaces and class-
In small rural settings, where resources, staff, and rooms lend themselves to patient monitoring. Above all, the
venues may be limited, the task requires “all hands on building is not slated for occupancy for another seven
deck.” In Athens, Ohio, public health servants and local months, making it an ideal location for patient vaccinations.
providers found a valuable vaccination partner in Ohio
University’s Heritage College of Osteopathic Medicine. With the realization that we had capacity to administer
mass vaccinations at a single facility, ACCHD and Ohio-
The story of the Heritage College is a familiar one among Health O’Bleness Hospital agreed to pool their vaccines. A
colleges of osteopathic medicine. Situated in the rolling referral process from the health system to public health
Appalachian foothills, the university’s main campus is the was developed, and an electronic scheduling system was
county’s largest employer and major economic driver [2]. quickly put in place for patients – a great relief to the local
This economic support is paralleled by the healthcare health department, which fielded approximately 2,500
calls on the day it opened its phone lines for vaccination
*Corresponding author: Kenneth H. Johnson, DO, Chief Medical appointments.
Affairs Officer of Ohio University, Executive Dean of Ohio University
Heritage College of Osteopathic Medicine, Heritage Hall 383, 1 Ohio In close coordination with ACCHD, we worked to
University, Athens, Ohio, 45701-2979, USA, develop a circular pedestrian flow through Heritage Hall.
E-mail: [email protected] Our goal was to mitigate risks related to viral spread

Open Access. © 2021 Kenneth H. Johnson, published by De Gruyter. This work is licensed under the Creative Commons Attribution 4.0
International License.

430 Johnson: Joining forces to administer COVID-19 vaccines

without impeding the efficiency of our operations. Upon identify issues and plot logistics for the following week’s
entering the building, patients are funneled into a long clinics.
hallway, where separate stations are set up for registration
and completing paperwork. The hallway opens into a 2,500 The marriage of public health, education, private
square foot space, which serves as a socially distanced healthcare, and care provision has resulted in innovative
waiting room and our vaccination room. Multiple vacci- problem solving at every step. As of February 22, 2021, the
nation stations staffed with public health nurses are scat- clinic had administered first vaccine doses to 3,398 pa-
tered along the far side of the room. tients and second vaccine doses to 1,570 patients since the
clinic launched on January 7, 2021. We expect that our
After their shot is administered, patients make their singular, county wide vaccination clinic could administer
way to a postvaccination checkout table, then proceed over 1,000 vaccines per day in its current form. At this pace,
down a parallel hallway to our grand atrium. At 4,000 we could theoretically vaccinate our entire county [3] via
square feet, the atrium is currently set up to safely this collaborative effort in a period of two to three months,
accommodate observations of up to 60 people at a time, given adequate vaccine supply. Many colleges of osteo-
with capacity to nearly double that figure. A separate room pathic medicine, with their focus on primary care and
off the atrium serves as an emergency treatment center, in impacting communities, are well poised to have a similar
case of adverse reactions. impact in their communities and regions.

Communication via two-way radios (“walkie talkies”) Our efforts will not stop there. The Heritage College
helps staff to facilitate a steady, yet socially distanced, flow Community Health Programs was recently recognized as
of patients through the facility. The city police department an Ohio COVID-19 vaccine provider and is currently
handles traffic and vehicular flow with dedicated working with Ohio Department of Health and the Ohio
personnel. Emergency Management Agency to take vaccines on the
road to underserved communities throughout our service
Personnel region through the use of our two fully equipped mobile
health units. But my hope is that the most impactful
On clinic days, ACCHD’s 13 full time employees – including changes are yet to come, as local healthcare partners build
nurses, a physician director, and administrative staff – take upon these bonds forged during the pandemic to better
the lead. Each has a designated role to prepare for and serve our community in postpandemic times.
fulfill in the clinic. Staff assignments include logistics
management, check in, shot preparation, shot adminis- Research funding: None reported.
tration, check out and postvaccination monitoring. Author contributions: All authors have accepted responsibility
for the entire content of this manuscript and approved its
University personnel are tasked with organizing clinic submission.
volunteers. These include clinical faculty volunteers Competing interests: Authors state no conflict of interest.
(overseen by the Heritage College’s executive director for
Community Health Programs) and student volunteers References
(overseen by the senior director of community relations in
Ohio University’s College of Health Sciences and 1. Biden JR. National strategy for the COVID-19 response and
Professions). pandemic preparedness. Available from: https://www.
whitehouse.gov/wp-content/uploads/2021/01/National-Strategy-
Currently, student roles include assisting with check in, for-the-COVID-19-Response-and-Pandemic-Preparedness.pdf
guiding patients to the various stations, monitoring for [Accessed 18 Feb 2021].
adverse effects after vaccination, and disinfecting surfaces.
To date, only professional staff are assisting with vaccina- 2. Ohio University’s Office of Institutional Effectiveness and Analytics.
tions, but we are planning to integrate student vaccinators Ohio University 2020 fact book. Available from: https://www.ohio.
under supervision as clinic volume increases. edu/instres/FactBook.pdf [Accessed 18 Feb 2021].

Adaptability and perpetual communication have been 3. United States Census Bureau. Quick facts: Athens County, Ohio.
key to our collective success in this constantly shifting Available from: https://www.census.gov/quickfacts/
landscape. Each week, team leaders gathers virtually to athenscountyohio [Accessed 18 Feb 2021].

J Osteopath Med 2021; 121(4): 431–440

Public Health and Primary Care Review Article

Antonia M. Molinari, OMS III and Jay H. Shubrook*, DO

Treatment options and current guidelines of care
for pediatric type 2 diabetes patients: a narrative
review

https://doi.org/10.1515/jom-2020-0172 environmental, societal, and lifestyle factors – to help
Received July 3, 2020; accepted November 3, 2020; patients achieve their health and wellness goals.
published online February 19, 2021
Keywords: diabetes treatment; obesity; pediatrics; type 2
Abstract diabetes.

Context: Type 2 diabetes (T2D) mellitus, which was once Type 2 diabetes (T2D) mellitus has long been considered a
considered a disease affecting adults, is a growing problem disease affecting adults, but now about 24% of children
among youths. Research now shows that T2D in youths is diagnosed with diabetes have T2D [1]. The estimated annual
more progressive and associated with earlier onset of increase in incidence of T2D among youths was 4.8% based
complications than adult-onset T2D. on incident rates from 2002 to 2012 [2], and research suggests
Objectives: To update practicing clinical physicians on that prevalence continues to grow rapidly [1].
what is currently known about pediatric T2D and share
current guidelines to care for these patients. T2D diagnosed in youth is more progressive and aggres-
Methods: The authors conducted a literature review through sive than adult-onset T2D [3–5]. T2D among youths also ap-
the MEDLINE/PubMed, Google Scholar, and clinicaltrials.gov pears to be more resistant to the standard treatment options,
databases in July 2019 using the following search phrases: including therapeutic lifestyle changes, and complications
“youth-onset type 2 diabetes,” “pediatric type 2 diabetes,” develop more quickly in children than adults [6–8]. Further-
“diabetes in youth,” and “FDA-approved pediatric diabetes more, there are fewer FDA-approved pharmacologic options
medications.” Items published between 2010 and 2019 and for pediatric patients [6, 7]. Among other key risk factors,
written in English were included. childhood obesity predisposes youths to an insulin-resistant
Results: A total of 65 items were included after database state and, when compounded with insulin-resistance during
review, including 44 articles, 10 FDA product inserts, six puberty, places overweight pediatric patients at risk [9]. The
clinicaltrials.gov listings, three position statements/guide- best chance at slowing the epidemic is for physicians to
line documents, one website, and one FDA announcement. become familiar at identifying at-risk youths and providing
Conclusions: There are very limited treatment options early intervention that emphasizes family-based preventive
available to manage pediatric T2D. Prevention of pediatric lifestyle modifications within pediatric populations.
T2D is paramount, which requires a high index of suspi-
cion, routine screening of children and adolescents, and The purpose of this narrative review is to update
willingness to engage in family-based interventions for practicing clinical physicians on what is presently known
those at risk for prediabetes and T2D. Osteopathic physi- about pediatric patients with T2D and to educate clinicians
cians have a unique opportunity to help by applying the on the current guidelines of care for these patients.
osteopathic principles to the whole person – including
Methods

*Corresponding author: Jay H. Shubrook, DO, College of Osteopathic The authors conducted a literature review in July 2019 focused on
Medicine, Touro University California, 1310 Club Drive, Vallejo, CA pediatric T2D by searching PubMed, Google Scholar, and clinicaltrials.gov
94592-1187, USA, E-mail: [email protected] with the following phrases: “youth-onset type 2 diabetes,” “pediatric
Antonia M. Molinari, OMS III, College of Osteopathic Medicine, Touro type 2 diabetes,” “diabetes in youth,” and “FDA-approved pediatric
University California, Vallejo, CA, USA diabetes medications.” Resources published between 2010 and 2019
and written in English were eligible for inclusion. The reference lists of
the articles found in the initial search were reviewed for additional

Open Access. © 2020 Antonia M. Molinari and Jay H. Shubrook, published by De Gruyter. This work is licensed under the Creative Commons
Attribution 4.0 International License.

432 Molinari and Shubrook: Pediatric type 2 diabetes review

material and specific FDA medication package insert were also fact, more than 100 alleles are associated with T2D. In the
included. Both authors reviewed all resources and mutually deter- Treatment Options for Type 2 Diabetes in Adolescents and
mined which to include in the final review. Youth (TODAY) cohort [5], 89.4% of pediatric participants
had a first-degree relative or grandparent with T2D.
Results
Screening those at risk: who should we screen?
A total of 65 items were included and analyzed after the au-
thors collaboratively reviewed the search results, including The American Diabetes Association (ADA) recommends
44 articles, 10 FDA product inserts, six clinicaltrials.gov list- screening pediatric patients after they begin puberty or after
ings, three position statements/guideline documents, one they turn 10 years old if they have a body mass index (BMI)
website, and one FDA announcement. In the narrative review greater than or equal to the 85th percentile and at least one
presented in the Discussion, we summarize these findings in additional risk factor present [7]. Risk factors include [7]:
these resources in a detailed overview of pediatric T2D, – Maternal history of diabetes or gestational diabetes
including what makes it distinctive, how to diagnose it, and
what treatment options exist. during child’s gestation.
– Family history of T2D in a first- or second-degree relative.
Discussion – Racial/ethnic heritages such as Native American, African

Pathophysiology American, Latino, Asian American, and Pacific Islander.
– Signs of insulin resistance (including conditions
Pediatric patients are not metabolically identical to adults
with regard to T2D. The Restoring Insulin Secretion Study associated with): acanthosis nigricans, hypertension,
(RISE) [3, 4] found that youths, compared to adults, have dyslipidemia, polycystic ovary syndrome, or low-for-
lower insulin sensitivity, hyper-responsive β-cells, decreased gestational-age birth weight.
insulin clearance by the liver, and more rapid decline in β-cell
function. Puberty alone is associated with lower insulin In the TODAY cohort [5], 85.6% of participants exhibited
sensitivity, which the body adjusts for by increasing insulin signs at baseline of acanthosis nigricans on the neck. In the
secretion [9]. During puberty, peripheral insulin sensitivity same cohort, 80.5% of participants presented with dysli-
decreases due to an increase of hormonal changes like pidemia at baseline, 13.6% with hypertension, and 33.3%
testosterone, growth hormone, and estrogen [10]. with a maternal history of gestational diabetes during
child’s gestation [5]. The composition of the cohort also
Obesity has also been identified as an insulin-resistant included a higher proportion of minority groups, as
state [11]. The prevalence of childhood obesity was 18.5% in demonstrated in Table 1 [5].
2015–2016 and has continued to rise [12]. The increase in
visceral fat associated with obesity is hypothesized to in- Diagnosis
crease peripheral insulin resistance in various ways. Visceral
fat secretes adipokines that alter the responsiveness of target Current diagnosis guidelines are based on the adult
tissues to insulin, effecting the signaling cascasde [13]. laboratory values for prediabetes and T2D, as seen in
Obesity is also associated with increased free fatty acids and Table 2 [7, 14].
lipids circulating in the body that can accumulate and induce
lipotoxicity in tissues, resulting in insulin resistance [13]. In The ADA recommends repeat laboratory testing for
adolescents during puberty, there is the hormone-induced confirmation unless initial presentation involves hyper-
decrease in insulin sensitivity and the insulin resistance glycemic crisis, including obtaining laboratory results
associated with obesity that overload the dynamic response testing for pancreatic autoantibodies to rule out type 1
of β-cells. Together, these two major factors work synergisti-
cally to place peripubertal youth at an increased risk for T2D. Table : Ethnic distribution of type  diabetes in the TODAY cohort
(n=), as selected from a predetermined list [].

Self-reported ethnicity TODAY cohort participants n (%)

Role of genetics Hispanic  (.%)
Non-Hispanic Black  (.%)
A family history of T2D has long been identified as a Non-Hispanic White  (.%)
prominent risk factor for developing T2D in adults [7]. In American Indian
Asian  (.%)
 (.%)

Molinari and Shubrook: Pediatric type 2 diabetes review 433

Table : Laboratory range values for diagnosis of prediabetes and higher FPG shows more hepatic insulin resistance [16].
diabetes from the  ADA guidelines [, ]. Consequently, the ADA still recommends at least one lab-
oratory test (Table 2) and repeated labs in the absence of
Glycemic Prediabetes Diabetes rangea overt hyperglycemic crisis. When laboratory testing is not
measure/test range clear or if waiting for diagnostic results, treating patients as
if they have T1D instead of T2D remains the safer option.
Hemoglobin Ac% .% to <.% ≥.%
Socioeconomic and psychosocial factors
Fasting glucose ≥ to < mg/dL ≥ mg/dL
The ADA recommends that healthcare providers consider
OGTT –  h ≥ → < mg/dL ≥ mg/dL possible food insecurity, housing instability, and financial
limitations when developing a feasible and effective
postprandial treatment plan for families and patients with T2D,
including children [7].
glucose
Children with T2D are more likely to suffer from other
aCriteria for diagnosis diabetes Random plasma glucose mental health issues compared to children without
is confirmed with at least  > mg/dL, symptoms of chronic illness [18]. Stress, isolation, depression, anxiety,
of the following. classic hyperglycemia, or substance abuse, and eating disorders should be screened
hyperglycemic crisis for by providers regularly in youth with T2D. Chronic
exposure to stressors places these individuals at higher
diabetes (T1D) [7]. Genetic testing, if monogenic diabetes is risk for developing psychosocial problems [18, 19]. It can
suspected, may also be indicated [7]. In the TODAY study also interfere with how individuals manage their diabetes
group [15], 9.8% of participants tested positive for either care, leading to poorer glycemic control [19]. In the
glutamic acid decarboxylase antibodies (GAD-65), islet TODAY cohort, 14.8% [20] of the 704 participants reported
antigen (IA-2) antibodies or both, and 9.8% were clinically clinically significant symptoms associated with depres-
diagnosed with T2D based on clinical presentation. sive disorders compared to 11.3% [21] estimated in the
general adolescent population. Depressive symptoms
The validity of A1c, fasting glucose, and OGTT tests as were more prominent in older (age ≥16 years) female
diagnostic criteria in pediatric populations remain ques- participants, but generally consistent across the different
tionable [7]. As an indirect measure of glycemic control, races/ethnicities in that group [20]. In addition, 26% of the
hemoglobin A1c (HbA1c) values can be altered by certain TODAY cohort participants reported some form of binge
medications, hemoglobinopathies (such as thalassemia or eating [22]. These same participants had higher rates of
sickle cell), age, and variations in sensitivity between obesity and waist circumference, and reported lower
certain ethnic groups [16]. Benefits of using HbA1c to quality of life ratings [22]. Thus, ADA guidelines recom-
screen at-risk populations include not requiring fasting, mend regularly screening for diabetes distress and mental
having less variability, and being unaffected by external health issues in pediatric patients with T2D [7].
circumstances such as illness and stress at the time of
blood draw [16]. However, current research suggests HbA1c Prevention
alone is not a reliable tool to diagnosis prediabetes and T2D
in pediatric patients due to evidence that it underestimates Childhood obesity: how does this affect pediatric T2D?
prevalence of dysglycemia in obese youths due to low
sensitivity and specificity [17]. Preventing and treating childhood obesity is a powerful
step toward avoiding the development of pediatric T2D in
Fasting plasma glucose (FPG), 2-h postprandial at-risk youth [23]. Childhood obesity is a complex problem
glucose levels, and the post-oral glucose tolerance test that extends beyond the health behaviors of a child and
(OGTT) have also not been significantly studied in youths, should be considered a possible reflection of family, so-
leaving diagnostic criteria based on cut-off values studied cioeconomic, and environmental factors. Obesity is often
in adult-only populations, similar to HbA1c [16]. Other an insulin-resistant state and the most common comor-
weaknesses of these tests include the stress and feasibility bidity in pediatric T2D [11, 24]. Obesity is defined as an age
of children completing an 8-h fast overnight, meeting at
least a 2-h time requirement in-office for OGTT, and an
additional task for staff to properly administer in office [16].
In addition, FPG, OGTT, and HbA1c all look at different
parts of glycemic control, suggesting a value for each in the
role of diagnosis and why Barr in 2019 [16] recommended
using FPG, OGTT, and HbA1c together to screen for pedi-
atric T2D and prediabetes. For example, a higher OGTT
identifies more postprandial insulin resistance while a

434 Molinari and Shubrook: Pediatric type 2 diabetes review

and gender specific BMI in the 95th percentile (z-score, Treatment goals
1.645) or higher [25]. To put this into perspective, the mean
BMI z-score in the TODAY study was 2.15, indicating a high The ADA recommends initiating comprehensive lifestyle
prevalence of obesity in the cohort [20]. While there are programs and diabetes education for families, with a goal
many causes leading to both obesity and T2D, certain traits of 7–10% decrease in body weight [7, 14]. The glycemic
and habits can be useful in the early detection and pre- target for most pediatric populations with T2D, according
vention of childhood obesity. Specific risk factors providers to the ADA, is an HbA1c <7% for patients taking only oral
can use to identify potential at-risk youth include “parental medications [7]. Lower A1c goals can be considered for
obesity, poor nutrition, low levels of physical activity, individuals who have certain disease characteristics (e.g.,
inadequate sleep, sedentary behaviors, and low family if providers believe that a lower goal is achievable without
income” [25]. Weight loss improves insulin resistance and causing hypoglycemic episodes) [7]. Every three months,
is a key component of management of T2D. Providers pediatric patients with T2D should have their HbA1c
should begin to screen children early for the factors checked, and treatment should be intensified if the HbA1c
mentioned above. Further, when a child is found to have goal has not been achieved [14].
excessive weight, the physician should address it imme-
diately and work with the family to treat obesity and/or Lifestyle interventions
prevent development of obesity-related chronic disease.
Family-based interventions will need to account for According to ADA guidelines, newly diagnosed children
possible socioeconomic factors and food insecurities when with T2D and their families should be counseled on life-
developing treatment plans. style interventions and given diabetes education [14].
Recommendations focus on weight loss, exercise, behav-
Prediabetes ioral changes, and diet modification. Children should be
advised to get at least 30–60 min of moderate-to-vigorous
National Health and Nutrition Examination Survey physical activity at least five days per week and at least
(NHANES) cross-sectional studies published in 2018 three days of strength training per week, in addition to
[26] and 2020 [27] found that the rate of obesity in youth reducing prolonged sedentary behaviors. The American
was 18.5% and prediabetes was found in 18% of Academy of Pediatrics (AAP) recommends less than 2 h of
adolescents. screen time per day not related to school work [28].

For those identified with impaired glucose tolerance It is important to note a unique aspect regarding the
or prediabetes (Table 2; see also the Diagnosis section of implementation of lifestyle modifications for pediatric
this review), the best recommended initial treatment plan patients. These patients are usually not responsible for
is intensive lifestyle interventions [28]. Currently, met- determining which foods are brought into the home or
formin and insulin are not recommended for youths with prepared, highlighting the need to engage the entire
prediabetes based on evidence from the Restoring Insulin family when attempting to implement lifestyle changes.
Secretion (RISE) trial [29]. In summary, physicians should It is important to emphasize healthy eating habits with
identify those at risk, especially patients with obesity nutrient-rich, high-quality food and reduction of high-
and/or prediabetes, and initiate integrative family-based calorie, low-nutrient foods, especially sugar-added
lifestyle interventions early. beverages [7, 14]. Interventions should be based on a
chronic care model with a goal of 7–10% decrease in body
weight [14].

Treatment Standard pharmacotherapy

Youth-onset T2D is more virulent and more progressive than Metformin therapy has been used as a comparison therapy
adult-onset T2D [6], meaning that a gentle and progressive- in previous trials, including TODAY [30] and RISE [4, 31]. In
intensity approach is less likely to be successful. Instead, one of the first studies of metformin in pediatric T2D
treatment should start immediately upon diagnosis. Titra- patients, metformin was determined to improve glycemic
tion of treatment may need to be more aggressive and of control in youths, with an average reduction in fasting
shorter duration than in adults. All children should receive blood glucose levels of 42.9 mg/dL. While this trial had a
team-based family care and require close supervision and small sample size (82 total subjects in metformin and pla-
follow up. cebo groups), the adverse events related to the metformin

Molinari and Shubrook: Pediatric type 2 diabetes review 435

were similar to those seen in adults, including gastroin- According to ADA guidelines, patients presenting with
testinal symptoms (like diarrhea and abdominal pain) in ketosis or diabetic ketoacidosis should be treated with
25% of participants [31]. No safety concerns were discov- subcutaneous or IV insulin immediately [7]. These patients
ered regarding use of metformin in pediatric T2D patients. should have their type of diabetes confirmed by lab testing
(c-peptide, glucose, and auto-antibodies—after the glucose
In the TODAY study [30], only 48.3% of metformin- has been stabilized). If the patient has T2D, start metformin
only treatment group were able to maintain glycemic while overlapping with outpatient subcutaneous insulin
control on the oral medication alone, supporting the [7]. Insulin may not be needed after the patient reaches
notion that pediatric patients with T2D are more likely to stable glycemia [7, 14]. If a patient presents with a blood
require more pharmacologic therapies than adults [7]. glucose greater than or equal to 600 mg/dL, check for
Initial pharmacologic therapy should include metformin hyperglycemic hypertonic non-ketotic (HHNK) syndrome
and/or insulin. For generally asymptomatic children over [7, 14].
the age of 10 with an HbA1c of less than 8.5%, providers
should prescribe metformin twice a day (BID) [32]. Pa- If patients are unable to reach glycemic targets with
tients should begin on 500–1,000 mg metformin BID with metformin and basal insulin, the ADA recommends
food and titrate dosage by 500 mg, up to maximum addressing medication adherence with the patient and
dosage of 2,000 mg per day (as tolerated by the patient) [7, family [7]. If still unable to reach targets, the ADA recom-
14]. Insulin therapy should be started for patients unable mends providers consider “higher doses of long-acting
to reach glycemic targets with oral metformin alone or insulin or initiation of multiple daily injections of basal and
who are unable to continue metformin treatment [14]. premeal rapid-acting insulin” [7]. Newly approved medi-
Adult doses of metformin are approved for use and are cations — not yet FDA-approved in children and not
efficacious in youths over the age of 10 years. Metformin currently in ADA Standards of Care — may be useful for this
acts to increase peripheral insulin sensitivity and glucose patient population (Table 3) [35].
uptake while decreasing glucose production in liver and
gastrointestinal (GI) absorption [7]. Possible side effects of As of June 2019, a new subcutaneous agent, Liraglu-
metformin therapy for children include GI disturbances, tide (Victoza®), was approved for use in pediatric patients
weight gain, anemia, elevated liver enzymes, and hypo- 10 years of age or older with T2D [45]. The 2020, ADA
glycemic episodes [33]. Standards of Care recommended that physicians consider
adding Liraglutide if the patients has been unable to reach
Initial treatment for symptomatic pediatric patients target glycemic control on initial pharmacologic agents
with an HbA1c greater than or equal to 8.5% or with blood [14]. Liraglutide is a GLP-1 receptor agonist (GLP-1RA) that
glucose greater than or equal to 250 mg/dL should include functions to slow gastric emptying, decrease appetite,
metformin and basal insulin [14]. Recommended dosing for enhance postmeal insulin production, suppress glucagon
basal insulin is 0.5 units/kg/day and can be increased secretion (and hence hepatic glucose production), and
every few days based on measured blood glucose levels improve existing β-cell function to make more insulin [7].
[14]. The most common side effect of insulin is hypogly- Tamborlane et al. [46] reported that the one-year estimated
cemia and weight gain [34]. treatment difference in hemoglobin A1c from liraglutide

Table : FDA-approved treatment for TD in children.

Medication class Drugs Minimum age for use

Biguanides Metformin  years
Glucagon-like peptide- agonist  years
Insulins: Basal Liraglutide (Victoza®) []  years
Glargine (Lantus) []a  years
Insulin: Bolus/prandial Detemir (Levemir) []a  year
Degludec (Tresiba®) []a Not specified (< years not studied)
Insulin NPH (Novolin N) []a  years
Insulin (Novolin R) []a  years
Insulin Aspart (NovoLog®) []a  years
Insulin Lispro (Humalog) []a  years
Insulin Glulisine (Apidra) []a

Data taken from ADA Position Statement, FDA, and FDA Drug Labels [, , ]. Most of the insulin therapies have not been studied for safety and
efficacy in pediatric patients with TD but use is derived from pediatric TD populations []. aNot studied in pediatric TD patients.

436 Molinari and Shubrook: Pediatric type 2 diabetes review

is −1.30%. The most common side effects include nausea, significantly increased BMIs [33]. In addition, there are
vomiting, and diarrhea; minor hypoglycemia is a less some clinical trials registered through clinicaltrials.gov
common side effect. Mean weight loss of 1.91 kg was also investigating other pharmacologic options in pediatric
seen in the Liraglutide group at the end of the 52 weeks, patients with T2D, but the results on the effectiveness of the
whereas an average weight gain of 0.87 kg was measured in medication on glycemic control have not been published
the placebo group [46]. Given the effectiveness of this [49–54].
medication, it may prove beneficial for pediatric patients
unable to reach glycemic targets on metformin and insulin There are a number of ongoing clinical trials registered
therapy alone. with clinicaltrials.gov that are evaluating the safety and
efficacy of other adult FDA-approved T2D therapies in pe-
It is important to note that most anti-diabetes medi- diatric patients. Such studies include investigation of the
cations approved for the management of T2D in adults are safety and efficacy of Ertugliflozin (SGLT-2 inhibitor)
not FDA-approved for use in pediatric patients. Thus, their (NCT04029480) [49], Dulaglutide (GLP-1RA) (NCT02963766)
use cannot be recommended on a routine basis. The FDA [50], and Dapagliflozin (SGLT-2 inhibitor) and Saxagliptin
notes many unique barriers to pediatric drug trials. Some of (DPP-4 inhibitor) (NCT03199053) [51]. Another study [52] is
the more pronounced barriers include the ethical consid- in phase 3 as of the writing of this review, researching
eration of consent in children and the high potential for the use of Alogliptin (DPP-4 inhibitor) (NCT02856113) in
risks given possible differences in metabolism between pediatric populations. Most notable of ongoing recruiting
adults and children [47]. In addition, safety concerns for pediatric studies involving T2D are the Surgical or Medical
pediatric participants have led the FDA to instill stricter Treatment (ST2OMP) trial [53] further investigating the effi-
guidelines for pediatric studies [47]. cacy of bariatric surgery in management of T2D in pediatric
populations (NCT04128995) and the study [54] investigating
In terms of general classes of adult-approved medica- effects bariatric surgery on T2D pancreatic, renal, and car-
tions for diabetes, sulfonylureas and meglitinides act by diovascular comorbidities in pediatric patients with T2D
stimulating the patient’s own pancreatic beta cells to secrete (NCT03620773). Future studies should be geared toward
insulin. Sulfonylureas such as glimepiride have been stud- other promising diabetic medications not yet approved in
ied in a small pediatric population and shown to lower the pediatric population.
HbA1c safely in children with T2D [48]. The most notable
side effect compared to metformin in the trial was weight While the 2020 American Diabetes Association Stan-
gain [48]. Other anti-diabetes medications available for the dards of Care [14] still recommended metformin and insulin
treatment of T2D in adults include alpha-glucosidase in- as first line treatment of T2D, it is likely that the newer
hibitors, GLP-1RA, and DPP-4 inhibitors. Only the GLP-1RA classes including GLP-1RA, DPP-4 inhibitors, and SGLT-2
class of medications has an FDA-approved medication inhibitors will be indicated for pediatric patients with T2D
(liraglutide) to be used in pediatric patients. Other options in the future.
are amylin analogs that effect gastric emptying and
glucagon secretion and SGLT-2 inhibitors that work in the Metabolic surgery
kidneys to reduce reabsorption of glucose, both of which are
not approved for use in the pediatric population. ADA guidelines support metabolic surgery as a treatment
option in some adolescent patients with T2D. Specifically,
Lastly, there are the thiazolidinediones, which metabolic surgery may be beneficial in patients with a BMI
perhaps have the most research available surrounding >35 kg/m2 and comorbidities who are unable to reach gly-
their use in pediatric patients with T2D based on the TODAY cemic stability with lifestyle and medications alone [7]. In
study [30] with rosiglitazone, but there are still no thiazo- order to ensure the safety of the patient and efficacy of the
lidinediones FDA approved for use in pediatric patients. In surgery, a full multidisciplinary team is required [7, 14].
the TODAY study [30], metformin plus rosiglitazone treat-
ment was compared to metformin alone and metformin Metabolic surgery is a relatively new treatment option
with lifestyle interventions to see which had more durable for pediatric patients with T2D. In 2018, a secondary anal-
glycemic control. That study found that rosiglitazone ysis [55] compared data from the 30 (out of 242) pediatric
combined with metformin therapy lead to a larger per- patients with T2D who underwent metabolic surgery as
centage of participants maintaining glycemic control part of the Teen Longitudinal Assessment of Bariatric
compared with the other two groups [30]. In terms of safety Surgery (Teen-LABS) study to 63 patients that were
and tolerability, the study found comparable side effects matched by similar baseline characteristics from the
and adverse effects between the three groups; however, TODAY study (pharmacologic and lifestyle therapy in
subjects in the metformin plus rosiglitazone group did see youths with T2D). Mean A1c decreased from 6.8% at

Molinari and Shubrook: Pediatric type 2 diabetes review 437

baseline to 5.5% at two years post-surgery in the Teen- for hypertension and dyslipidemia, further exacerbating
LABS cohort, whereas in the TODAY cohort, there was a the severity of complications [57].
mean A1c increase from 6.4% at baseline to 7.8% at two
years postsurgery [55]. Other notable results post- In another study [59] looking at the prevalence of
metabolic surgery included decreases in waist circumfer- impaired glucose tolerance (prediabetes or T2D) in youth
ence (−19.2% Teen-LABS cohort; +3.55% TODAY cohort), with nonalcoholic fatty liver disease (NAFLD), an esti-
an overall decrease in BMI (−29.2% Teen-LABS cohort; mated 23.4% of participants had prediabetes and 6.5%
+3.5% TODAY cohort), and reduction in triglyceride levels T2D. NAFLD associated with the pediatric population ap-
(−19% Teen-LABS cohort; +15.3% TODAY cohort) at the pears more aggressive compared to adult NAFLD with more
2-year follow up compared to starting baseline levels, severe histologic changes. This increase in severity is
demonstrated in Table 4 [55]. More research is still needed associated with a higher risk of progressing to liver com-
to determine long-term effects of metabolic surgery [7]; plications including fibrosis, cirrhosis, and hepatic failure
however, a 2019 study [56] reported that metabolic surgery [7, 59].
is as safe and effective in adolescents as in adult-based
populations, further supporting its validity as a treatment Luckily, screening and management for T2DM
option. complications/comorbidities in pediatric populations is
very similar to screening methods in adults. The
Complications ADA-recommended screening modalities and primary
treatment options are summarized in Table 5 [7]. More
research is still needed into many of the complications
associated with pediatric-specific populations.

Youth-onset T2D is associated with a higher risk of com- Technology to support children with type 2
plications and mortality than adult-onset T2D [57]. Similar diabetes
complications are seen, but youths with T2D develop
complications earlier than those with adult-onset T2D [6]. There were substantial advances during the decade
In addition, a study [6] comparing onset of complications covered in this review in the measurement of glucose and
in youths with T2D vs those with T1D showed complica- insulin delivery [61]. While tools such as continuous
tions occurring sooner in pediatric patients diagnosed with glucose monitoring, insulin pumps, and hybrid closed loop
T2D. Specifically, earlier renal and neurologic complica- systems have improved time in range, reduced hypogly-
tions were reported, but no significant change in time cemia rates, and improved patients’ quality of life, their
course for retinopathy was observed [6]. use in T2D is less common due to a lack of insurance
coverage [62].
For perspective, in the TODAY study, the prevalence of
hypertension was 11.6% at baseline (where mean age was Children who are on three or more insulin injections
14 years) and rose to 33.8% by the study’s end [58]. In per day and doing four or more fingerstick glucose checks
addition, high-risk LDL levels rose from 4.5 (baseline) to per day are most likely to benefit from a continuous glucose
10.7% (study’s end), evidence of microalbuminuria rose monitor or an insulin pump. However, it is likely that these
from 6.3 (baseline) to 16.6% (study’s end), and 6.3% had tools will be used more widely in the future and may benefit
microalbuminuria at baseline compared to 16.6% at the children with T2D as well. Excellent resources are available
end of the study [58]. The prevalence of diabetic retinop- online to demonstrate the range of technology to support
athy at the end of the TODAY study was 13.9% [58]. Studies diabetes care [63].
also found that young patients were less likely to be treated

Table : Significant comparisons between Teen-LABS and TODAY Osteopathic considerations
cohorts.
The benefits of an osteopathic approach to T2D in adults
Outcomes Teen-LABS TODAY has been well established and can readily be applied to
pediatric patients [64]. The first tenet of osteopathy states
HbAc% −.% (. → .) +.% (. → .) that the body is a unit, and the person is a unit of body,
mind, and spirit [65]. Osteopathic physicians should
Average body mass index −.% +.% readily account for full spectrum of factors, including the

Waist circumference −.% +.%

Triglyceride levels −% +.%

Values are shown as percent difference in least-squares means after
two years as a percentage of the baseline value [].

438 Molinari and Shubrook: Pediatric type 2 diabetes review

Table : Summary of complication screening with modality and primary treatment options based on ADA recommendations [, ].

Complication Management
Nephropathy
Monitor with regular blood pressure screenings at each visit. If high, treat with lifestyle interventions, if still
Neuropathy high after six months then start ACE inhibitor/ARB therapy [].
Retinopathy Obtain spot UACR, eGFR (calculated from serum creatinine and height with Schwartz equation), and serum
Non-alcoholic fatty liver disease potassium levels. If high, begin ACE inhibitor/ARB therapy (confirm elevated UACR on  of  samples) [].
Obstructive sleep apnea Inspect feet, pulses, -g monofilament test, vibration sensations, and ankle reflexes [].
Dilated eye exam at optometrist or ophthmalogist [].
Polycystic ovarian syndrome Screen with AST and ALT levels. If high, treat with weight loss regimen and consider referral to gastro-
Cardiovascular disease enterology unable to control [].
Dyslipidemia Screen for symptoms and refer to specialist for sleep study if needed []. Possible signs and symptoms
include audible pauses in breathing while sleeping, snoring, restless sleep, inattentiveness at school, and
behavioral abnormities. Excessive sleepiness is not common as is typical in adults [].
Screen for signs and symptoms and possible laboratory evaluation. Treat with metformin and lifestyle
modifications, can consider oral contraceptives [].
Testing not recommended without symptoms, focus on lifestyle modifications and obtaining glycemic
control [].
Lipid panel after initial glycemic control. If abnormal lipid levels, encourage/support diet modifications and
glycemic control for  months, if unable to improve, consider statin therapy. If severe hypertriglyceridemia,
consider fibrates + controlling blood sugar to due pancreatitis risk, noting use of fibrates in this population
has not been studied and use is extrapolated from adults [].

psychosocial factors discussed in this review, to allow for a there are additional studies that were not reported in this
holistic approach to pediatric patients with T2D [64]. manuscript. In our review, we only included studies found
in the databases used for our search, or those referenced in
The second tenet of osteopathy – the body is capable of our current sources.
self-regulation, self-healing, and health maintenance – is
applicable toward treatment plans in this population [65]. Conclusions
Physicians have a unique opportunity to empower and
educate patients and families on the importance of self- The prevalence of T2D is increasing among children.
care involved in diabetes management [64]. Importantly, Further, this condition is more virulent, progresses more
the barriers and circumstances of the parents/caregivers rapidly, and is less responsive to treatment than when
should be considered in terms of ability to teach and it is diagnosed in adults. To address these challenges,
encourage self-care in their children. physicians should screen those at risk, diagnose early, and
use a comprehensive family-based approach to address
The third tenet of osteopathy states that structure and these serious chronic and progressive condition.
function are reciprocally interrelated [65]. The recommen-
dations that physicians can give regarding physical activity Research funding: None reported.
will improve insulin sensitivity in muscles, which can Author contributions: Ms. Molinari provided substantial
improve glycemic control [64]. contributions to conception and design, acquisition of
data, or analysis and interpretation of data; Ms. Molinari
The fourth tenet of osteopathy states that rational drafted the article and Dr. Shubrook revised it critically for
treatment is based upon an understanding of the basic important intellectual content; both authors gave final
principles of body unity, self-regulation, and the interrela- approval of the version of the article to be published; and
tionship of structure and function [65]. Providers should use both authors agree to be accountable for all aspects of the
their knowledge of osteopathy to provide patient-centered work in ensuring that questions related to the accuracy or
care and promote health in youth presenting with T2D. integrity of any part of the work are appropriately
investigated and resolved.
Study limitations Competing interests: Dr. Shubrook has served on advisory
boards for Sanofi, NovoNordisk, EliLilly, MannKind, and
This study has a number of limitations. This review is Bayer.
intended to be a clinically-focused narrative review; it is
not intended to be comprehensive of all literature sources
or a systematic review and meta-analysis. It is possible that

Molinari and Shubrook: Pediatric type 2 diabetes review 439

Disclaimer: Dr. Shubrook, a former JAOA Associate Editor, 16. Brar PC. Update on the current modalities used to screen high risk
was not involved in the editorial review or decision to youth for prediabetes and/or type 2 diabetes mellitus. Ann
publish this article. Pediatr Endocrinol Metab 2019;24:71–7.

References 17. Nowicka P, Santoro N, Liu H, Lartaud D, Shaw M, Goldberg R, et al.
Utility of Hemoglobin A1c for diagnosing prediabetes and
1. National Diabetes Statistics Report. Estimates of diabetes and its diabetes in obese children and adolescents. Diabetes Care 2011;
burden in the United States. Centers for Disease Control and 34:1306–11.
Prevention Website; 2020. https://www.cdc.gov/diabetes/pdfs/
data/statistics/national-diabetes-statistics-report.pdf 18. Compas BE, Jaser SS, Dunn MJ, Rodriguez EM. Coping with
[Accessed 7 May 2020]. chronic illness in childhood and adolescence. Annu Rev Clin
Psychol 2012;8:455–80.
2. Mayer-Davis EJ, Lawrence JM, Dabelea D, Divers J, Isom S, Dolan L,
et al. Incidence trends of type 1 and type 2 diabetes among 19. Peters A, Laffel L, The American Diabetes Association Transitions
youths, 2002–2012. N Engl J Med 2017;376:1419–29. Working Group. Diabetes care for emerging adults:
recommendations for transition from pediatric to adult diabetes
3. The RISE Consortium. Metabolic contrasts between youth and care systems: a position statement of the American diabetes
adults with impaired glucose tolerance or recently diagnosed association. Diabetes Care 2011;34:2477–85.
type 2 diabetes: I. Observations using the hyperglycemic clamp.
Diabetes Care 2018;41:1696–706. 20. Anderson BJ, Edelstein S, Abramson NW, Levitt Katz LE, Yasuda
PM, Lavietes SJ, et al. Depressive symptoms and quality of life in
4. The RISE Consortium. Metabolic contrasts between youth and adolescents with type 2 diabetes: baseline data from the TODAY
adults with impaired glucose tolerance or recently diagnosed study. Diabetes Care 2011;34:2205–7.
type 2 diabetes: II. Observations using the oral glucose tolerance
test. Diabetes Care 2018;41:1707–16. 21. Mojtabai R, Olfson M, Han B. National trends in the prevalence
and treatment of depression in adolescents and young adults.
5. Copeland KC, Zeitler P, Geffner M, Guandalini C, Higgins J, Hirst K, Pediatrics 2016;138:e20161878.
et al. Characteristics of adolescents and youth with recent-onset
type 2 diabetes: the TODAY cohort at baseline. J Clin Endocrinol 22. The TODAY Study Group. Binge eating, mood, and quality of life in
Metab 2011;96:159–67. youth with type 2 diabetes: baseline data from the TODAY study.
Diabetes Care 2011;34:858–60.
6. Dart AB, Martens PJ, Rigatto C, Brownell MD, Dean HJ, Sellers EA.
Earlier onset of complications in youth with type 2 diabetes. 23. Galuska DA, Gunn JP, O’Connor AE, Petersen R. Addressing
Diabetes Care 2014;37:436–43. childhood obesity for type 2 diabetes prevention: challenges and
opportunities. Diabetes Spectr 2018;31:330–5.
7. Arslanian S, Bacha F, Grey M, Marcus MD, White NH, Zeitler P.
Evaluation and management of youth-onset type 2 diabetes: a 24. Pulgaron ER, Delamater AM. Obesity and type 2 diabetes in
position statement by the American Diabetes Association. Diabetes children: epidemiology and treatment. Curr Diabetes Rep 2014;
Care 2018;41:2648–68. 14:508.

8. The TODAY Study Group. Treatment options for type 2 diabetes in 25. Grossman DC, Bibbins-Domingo K, Curry SJ, Barry MJ, Davidson KW,
adolescents and youth: a study of the comparative efficacy of Doubeni CA, et al. US Preventive Services Task Force. Screening for
metformin alone or in combination with rosiglitazone or lifestyle obesity in children and adolescents: US preventive services task
intervention in adolescents with type 2 diabetes. Pediatr force recommendation statement. JAMA 2017;317:2417.
Diabetes 2007;8:74–87.
26. Hales CM, Fryar CD, Carroll MD, Freedman DS, Ogden CL. Trends
9. Goran MI, Gower BA. Longitudinal study on Pubertal insulin in obesity and severe obesity prevalence in us youth and adults
resistance. Diabetes 2001;50:2444–50. by sex and age, 2007–2008 to 2015–2016. JAMA 2018;319:1723.

10. Cree-Green M, Triolo TM, Nadeau KJ. Etiology of insulin 27. Andes LJ, Cheng YJ, Rolka DB, Gregg EW, Imperatore G. Prevalence
resistance in youth with type 2 diabetes. Curr Diabetes Rep of prediabetes among adolescents and young adults in the
2013;13:81–8. United States, 2005–2016. JAMA Pediatr 2020;174:e194498.

11. DeFronzo RA. From the triumvirate to the ominous octet: a new 28. Magge SN, Silverstein J, Elder D, Nadeau K, Hannon TS.
paradigm for the treatment of type 2 diabetes mellitus. Diabetes Evaluation and treatment of prediabetes in youth. J Pediatr 2020;
2009;58:773–95. 219:11–22.

12. Hales CM. Prevalence of obesity among adults and youth: United 29. The RISE Consortium. Impact of insulin and metformin versus
States, 2015–2016. NCHS Data Brief 2017;288:8. metformin alone on β-cell function in youth with impaired
glucose tolerance or recently diagnosed type 2 diabetes.
13. Hardy OT, Czech MP, Corvera S. What causes the insulin Diabetes Care 2018;41:1717–25.
resistance underlying obesity? Curr Opin Endocrinol Diabetes
Obes 2012;19:81–7. 30. TODAY Study Group. A clinical trial to maintain glycemic control in
youth with type 2 diabetes. N Engl J Med 2012;366:2247–56.
14. American Diabetes Association. Standards of medical Care in
Diabetes—2020. Diabetes Care 2020;43:S77–88. 31. Jones KL, Arslanian S, Peterokova VA, Park J-S, Tomlinson MJ.
Effect of metformin in pediatric patients with type 2 diabetes: a
15. Klingensmith GJ, Pyle L, Arslanian S, Copeland K, Cuttler L, randomized controlled trial. Diabetes Care 2002;25:89–94.
Kaufman F. The presence of GAD and IA-2 antibodies in youth with
a type 2 diabetes phenotype: results from the TODAY study. 32. Riomet ER (metformin) [package insert]. U.S. Food and Drug
Diabetes Care 2010;33:1970–5. Administration website; Revised August 2019. Available from:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/
212595s000lbl.pdf. [Accessed 1 June 2020].

33. TODAY Study Group. Safety and tolerability of the treatment of
youth-onset type 2 diabetes: the TODAY experience. Diabetes
Care 2013;36:1765–71.

440 Molinari and Shubrook: Pediatric type 2 diabetes review

34. Diabetes.org. Hypoglycemia (low blood glucose). American 49. Ertugliflozin type 2 diabetes mellitus (T2DM) pediatric study (MK-
Diabetes Association. Available from: http://www.diabetes.org/ 8835/PF-04971729) (MK-8835-059). ClinicalTrials.gov. Available
living-with-diabetes/treatment-and-care/blood-glucose- from: https://clinicaltrials.gov/ct2/show/NCT04029480
control/hypoglycemia-low-blood.html [Accessed 3 Aug 2019]. [Accessed 2 Aug 2020].

35. Gourgari E, Wilhelm EE, Hassanzadeh H, Aroda VR, Shoulson I. A 50. A study of dulaglutide (LY2189265) in children and adolescents
comprehensive review of the FDA-approved labels of diabetes with type 2 diabetes. Clinicaltrials.gov; 2020. Available from:
drugs: indications, safety, and emerging cardiovascular safety https://clinicaltrials.gov/ct2/show/NCT02963766 [Accessed 31
data. J Diabet Complicat 2017;31:1719–27. July 2020].

36. Victoza® (Liraglutide) [package insert]. Novo Nordisk, Plainsboro, 51. Study to evaluate safety and efficacy of dapagliflozin and
NJ; Revised June 2019. Available from: https://www.novo-pi. saxagliptin in patients with type 2 diabetes mellitus aged 10 to
com/victoza.pdf [Accessed 20 May 2020]. below 18 years old. Clinicaltrials.gov; 2020. Available from:
https://clinicaltrials.gov/ct2/show/NCT03199053 [Accessed 31
37. Lantus (glargine) [package insert]. U.S. Food and Drug July 2020].
Administration Website; Revised June 2009. Available from:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/ 52. Phase 3 alogliptin pediatric study. Clinicaltrials.gov. Available
021081s034lbl.pdf [Accessed 20 May 2020]. from: https://clinicaltrials.gov/ct2/show/NCT0285611
[Accessed 2 Aug 2020].
38. Levemir® (detemir) [package insert]. U.S. Food and Drug
Administration Website. Revised January 2019. Available from: 53. Surgical or medical treatment. Clinicaltrials.gov. Available from: https://
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/ clinicaltrials.gov/ct2/show/NCT04128995 [Accessed 2 Aug 2020].
021536s054lbl.pdf [Accessed 1 June 2020].
54. Bjornstad P. Impact of metabolic surgery on pancreatic, renal and
39. Tresiba® (insulin degludec) [package insert]. Novo Nordisk, cardiovascular health in youth with type 2 diabetes.
Plainsboro, NJ; Revised November 2019. Available from: https:// Clinicaltrials.gov; 2020. Available from: https://clinicaltrials.
www.novo-pi.com/tresiba.pdf [Accessed 20 May 2020]. gov/ct2/show/NCT03620773 [Accessed 31 July 2020].

40. Novolin® N (insulin NPH) [package insert]. U.S. Food and Drug 55. Inge TH, Laffel LM, Jenkins TM, Marcus MD, Leibel NI, Brandt ML, et al.
Administration Website; Revised November 2019. Available from: Comparison of surgical and medical therapy for type 2 diabetes in
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/ severely obese adolescents. JAMA Pediatr 2018;172:452.
019959s082lbl.pdf [Accessed 1 June 2020].
56. Bolling CF, Armstrong SC, Reichard KW, Michalsky MP. Metabolic
41. Novolin® R (regular, human insulin USP) [package insert]. U.S. Food and bariatric surgery for pediatric patients with severe obesity.
and Drug Administration Website, Princeton, NJ; Revised February Pediatrics 2019;144:e20193224.
2012. Available from: https://www.accessdata.fda.gov/drugsatfda_
docs/label/2012/019938s066lbl.pdf [Accessed 1 June 2020]. 57. Al-Saeed AH, Constantino MI, Molyneaux L, D’Souza M,
Limacher-Gisler F, Luo C, et al. An inverse relationship between
42. NovoLog® (insulin aspart) [package insert]. U.S. Food and age of type 2 diabetes onset and complication risk and
Drug Administration Website, Plainsboro, NJ; Revised February mortality: the impact of youth-onset type 2 diabetes. Diabetes
2015. Available from. https://www.accessdata.fda.gov/ Care 2016;39:823–9.
drugsatfda_docs/label/2015/020986s082lbl.pdf
[Accessed 1 June 2020]. 58. Tryggestad JB, Willi SM. Complications and comorbidities of
T2DM in adolescents: findings from the TODAY clinical trial. J
43. Humalog (insulin lispro) [package insert]. U.S. Food and Drug Diabet Complicat 2015;29:307–12.
Administration Website, Indianapolis, IN; Revised March 2013.
Available from: https://www.accessdata.fda.gov/drugsatfda_ 59. Newton KP, Hou J, Crimmins NA, Lavine JE, Barlow SE, Xanthakos
docs/label/2013/020563s115lbl.pdf [Accessed 1 June 2020]. SA, et al. Prevalence of prediabetes and type 2 diabetes in
children with nonalcoholic fatty liver disease. JAMA Pediatr 2016;
44. Apidra (insulin glulisine) [package insert]. U.S. Food and Drug 170:e161971.
Administration Website, Bridgewater, NJ; Revised October 2008.
Available from: https://www.accessdata.fda.gov/drugsatfda_ 60. Kansagra S, Vaughn B. Pediatric sleep apnea: five things you
docs/label/2008/021629s015lbl.pdf [Accessed 1 June 2020]. might not know. Neurol Clin Pract 2013;3:321–5.

45. FDA approves new treatment for pediatric patients with type 2 61. Sherr JL. Closing the loop on managing youth with type 1
diabetes. FDA; 2019. Available from: http://www.fda.gov/news- diabetes: children are not just small adults. Diabetes Care 2018;
events/press-announcements/fda-approves-new-treatment- 41:1572–8.
pediatric-patients-type-2-diabetes [Accessed 22 July 2019].
62. Juvenile Diabetes Research Foundation Continuous Glucose
46. Tamborlane WV, Barrientos-Pe´rez M, Fainberg U, Frimer-Larsen Monitoring Study Group. Effectiveness of continuous glucose
H, Hafez M, Hale PM, et al. Liraglutide in children and adolescents monitoring in a clinical care environment: evidence from the
with type 2 diabetes. N Engl J Med 2019;381:637–46. juvenile diabetes research foundation continuous glucose
monitoring (JDRF-CGM) trial. Diabetes Care 2010;33:17–22.
47. Center for DrugEvaluation and Research. Drug research and
children. U.S. Food and Drug Administration. Available from: 63. Diabetes Wise. Diabetes wise. Available from: https://
https://www.fda.gov/drugs/drug-information-consumers/drug- diabeteswise.org [Accessed 25 Oct 2020].
research-and-children [Accessed 29 July 2020].
64. Shubrook JH, Jr, Johnson AW. An osteopathic approach to type 2
48. Gottschalk M, Danne T, Vlajnic A, Cara JF. Glimepiride versus diabetes mellitus. J Am Osteopath Assoc 2011;111:531–7.
metformin as monotherapy in pediatric patients with type 2
diabetes: a randomized, single-blind comparative study. 65. Tenets of Osteopathic Medicine. American Osteopathic
Diabetes Care 2007;30:790–4. Association. Available from: https://osteopathic.org/about/
leadership/aoa-governance-documents/tenets-of-osteopathic-
medicine/ [Accessed 1 Sept 2019].

J Osteopath Med 2021; 121(4): 441–442

Clinical Image

Oluwadamilola A. Adeyemi*, MD and Craig A. Backous, DO

Giant cell arteritis of the uterus

https://doi.org/10.1515/jom-2020-0259 improvement was noted postoperatively, with complete
Received October 4, 2020; accepted December 22, 2020; resolution of the patient’s fever and associated symp-
published online February 17, 2021 toms following a course of prednisone. She remained

A 76-year-old woman was admitted to our hospital via Image A: Computed tomography of the abdomen and pelvis in this
the emergency room in June 2008 for persistent fever 76-year-old woman who presented to the emergency room with
(temperature on admission, 102 °F; maximum tempera- persistent fever showed a 3.8 cm collection of complex fluid or soft
ture, 102.8 °F). She was ill-appearing without concerns of tissue (arrows) within the uterine endometrium.
clinical instability. Her physical examination was
normal except for abdominal tenderness with no
rebound or guarding, and infection work-up was unre-
vealing. Her erythrocyte sedimentation rate was 110 mm/
h and her c-reactive protein level was 302 mg/L. A chest
radiograph was negative, but computed tomography of
the abdomen and pelvis showed a 3.8 cm collection of
complex fluid within the uterine endometrium (Image A).
She remained febrile despite treatment with vancomy-
cin, imipenem, and fluconazole. Examination under
anesthesia with dilation and curettage yielded negative
pathology and cultures including bacterial, fungal, and
acid-fast bacilli. Given the patient’s lack of improvement
with medical therapy and a presumed uterine source of
infection, the decision was made in collaboration with
the patient to pursue surgical management with total
abdominal hysterectomy and bilateral salpingo-
oophorectomy. Hematoxylin and eosin stain of the
uterus showed obliterated blood vessels with giant cells,
and elastic tissue stain showed loss of interna elastic
lamina (Image B) and inflammation of intima (Image B)
consistent with giant cell arteritis (GCA). Clinical

*Corresponding author: Oluwadamilola A. Adeyemi, MD, Image B: Elastic tissue stain of the uterus of this 76-year-old woman
Department of Medicine, Section of Infectious Diseases, Swedish showed loss of interna elastic lamina (arrows) and inflammation of
Hospital NorthShore University HealthSystem, Swedish Hospital intima (star).
Professional Plaza Building, 2740 W. Foster Avenue, Suite 401,
Chicago, IL 60625-3532, USA; and Department of Medicine, Section of
Infectious Diseases, Northwestern Medicine Lake Forest Hospital,
Lake Forest, IL, USA, E-mail: [email protected].
https://orcid.org/0000-0002-6460-364X
Craig A. Backous, DO, Department of Medicine, Section of Pulmonary
and Critical Care, Swedish Hospital NorthShore University
HealthSystem, Chicago, IL, USA, E-mail: [email protected]

Open Access. © 2020 Oluwadamilola A. Adeyemi and Craig A. Backous, published by De Gruyter. This work is licensed under the Creative
Commons Attribution 4.0 International License.

442 Adeyemi and Backous: Giant cell arteritis of the uterus

afebrile postoperatively during multiple gynecologic Research funding: None declared.
oncology follow-up appointments; she was last seen in Author contributions: All authors have accepted
our hospital in October 2012. responsibility for the entire content of this manuscript
and approved its submission.
GCA has been associated with extracranial involve- Competing interests: Authors state no conflict of interest.
ment in up to 15% of patients, usually affecting large- and
medium-sized vessels [1, 2]. Involvement of the uterus is References
uncommon, although it has been speculated that many
cases are unrecognized [3]. Histopathologic involvement 1. Lhote F, Mainguene C, Griselle-Wiseler V, Fior R, Feintuch MJ,
has been demonstrated in most genital organs [2]. GCA of Royer I, et al. Giant cell arteritis of the female genital tract with
the male genitourinary tract has also been reported [3]. In temporal arteritis. Ann Rheum Dis 1992;51:900–3.
most published cases, diagnosis of GCA involving the
uterus or other reproductive organs was made inciden- 2. Bajocchi G, Zamora G, Cavazza A, Bajocchi G, Pipitone N, Versari A,
tally [2, 3]. Our case highlights the need to consider sur- Boiardi L, et al. Giant-cell arteritis of the female genital tract
gical management as a means of source control in the associated with occult temporal arteritis and FDG-PET evidence of
setting of clinical infection uncontrolled by antimicrobial large-vessel vasculitis. Clin Exp Rheumatol 2007;25(1 Suppl 44):
therapy; it also highlights need for consideration of the S36–39.
pelvic viscera as the source of infection rather than an
incidental finding. 3. Butendieck RR Jr, Abril A, Cortese C. Unusual presentation of giant
cell arteritis in 2 patients: uterine involvement. J Rheumatol 2018;
45:1201–2.

J Osteopath Med 2021; 121(4): 443–445

Letter to the Editor

David Hohenschurz-Schmidt*, MSc, MOst, Jan Vollert, Dr sc hum MSc, Steven Vogel, DO,
Andrew S.C. Rice, MD, PhD and Jerry Draper-Rodi, D.Prof.(Ost) DO

Performing and interpreting randomized clinical
trials

https://doi.org/10.1515/jom-2020-0320 Tramontano and colleagues [5] published a pilot ran-
Received December 20, 2020; accepted December 29, 2020;
published online March 3, 2021 domized, placebo-controlled trial reporting on management

To the Editor, of patients with patellofemoral pain syndrome (PFPS) based
on an assessment of “somatic dysfunction”. Notably, the
The quality of clinical trials determines their usefulness in authors assessed osteopathic interventions in a disorder
evaluating a therapy’s effectiveness [1]. Initiatives such as the
Enhancing the Quality and Transparency of Health Research other than low back pain, and there are several commend-
(EQUATOR) Network have aimed at improving trial methods,
mainly by connecting important stakeholders and by pro- able aspects of their placebo control design, which is noto-
ducing guidelines for reporting. For randomized controlled riously difficult for nonpharmacological interventions [6–8].
trials, the Consolidated Standards of Reporting Trials (CON- In particular, the researchers specifically trained practi-
SORT) Statement [2, 3] provides researchers with checklists to tioners in the application of the “sham” therapy and only
guide trial design, analysis, and reporting in scientific jour- enrolled therapy-naïve participants, possibly improving
nals [2, 3]. Such initiatives can help ensure that basic methods
are employed, thus enhancing trial rigor and reducing bias, blinding.
and that key information is reported, allowing readers to The placebo intervention in that trial consisted of “pas-
critically appraise trials. Many academic journals have made
it mandatory to use reporting guidelines and to register trial sive touching without joint mobilization in a protocolled or-
protocols prior to recruitment to assure research integrity [4]. der. First, the osteopath […] touched the patient’s lumbar
In this letter, we discuss a trial published in the Journal of the spine for 10 min and dorsal spine for 10 min, [then] the pa-
American Osteopathic Association in 2020 [5] to illustrate tient’s shoulders for 10 min, hips for 10 min, and neck, ster-
some major considerations in designing, interpreting, and num, and chest for 5 min” [5]. We congratulate the authors on
reporting a randomized, placebo-controlled trial of osteo- using an approach that controlled for nonspecific effects of
pathic manipulative therapy (OMTh) and highlight some touch and the therapeutic encounter, but we are concerned
possible sources of confusion regarding the interpretation of that the placebo intervention may lack credibility, as it did not
pilot trials. address the symptomatic area, which the authors acknowl-
edged [5]. Further, providing touch for 45 min with apparently
*Corresponding author: David Hohenschurz-Schmidt, MSc, MOst, no movement may have caused patients and practitioners in
Dept. of Surgery and Cancer, Faculty of Medicine, Imperial College the control group to lose interest, possibly undermining
London, Chelsea & Westminster Hospital, 4th Floor, 369 Fulham Road, blinding and leading to attrition (in fact, five of 40 partici-
London SW10 9NH, UK, E-mail: d.hohenschurz- pants (12.5%) were lost, but the authors did not report from
[email protected] which group). Termed “frustrebo effect,” [9] this may be an
Jan Vollert, Dr sc hum MSc and Andrew S.C. Rice, MD, PhD, Dept. of explanation for the lack of change seen in the control group
Surgery and Cancer, Faculty of Medicine, Imperial College London, over time, whereas in most trials, placebo groups improve
London, UK somewhat [10]. This study’s design would have been
Steven Vogel, DO and Jerry Draper-Rodi, D.Prof.(Ost) DO, Research enhanced by assessing the placebo intervention’s credibility,
Centre, University College of Osteopathy, London, UK blinding effectiveness, and acceptability to patients and
practitioners. Indeed, a pilot trial such as this would have
been ideal to ask those questions. With more trust in the
placebo control intervention, the trustworthiness of trial
results would increase.

We suggest that the authors further consider what they
assume to be the “active” (or “specific”) component of their
therapy and then design the placebo intervention to match

Open Access. © 2020 David Hohenschurz-chmidt et al., published by De Gruyter. This work is licensed under the Creative Commons Attribution
4.0 International License.

444 Hohenschurz-Schmidt et al.: Performing and interpreting randomized clinical trials

all the nonspecific factors [11–15]. According to the authors, planned trial. If so, the focus should have been on report-
the active component was the manual diagnosis and treat- ing the success of the pilot and lessons learned rather than
ment of “somatic dysfunction” by means of osteopathic premature judgements about efficacy or effectiveness. If
techniques [5]. Based on a mechanistic understanding of the taken to be a full-scale trial, it would have to withstand a
intervention, it would have been possible to provide simple formal risk of bias assessment. Without going into detail
touch to the symptomatic area or some form of tissue regarding further methodological shortcomings, but to
movement, possibly enhancing the potential of the placebo illustrate that our concerns reflect current research prac-
intervention to be considered by patients as a true treatment. tice, we offer an assessment of the study by Tramontano
We recognize, however, that there are currently no clear et al. [5] trial using the Cochrane risk-of-bias tool [23] and a
guidelines on the design of a sham intervention in manual risk-of-bias visualization tool [24] (Figure 1).
therapies, which is why feasibility testing is so important
and why pilot studies have a crucial role in the development In summary, the work by Tramontano et al. [5] has the
of good-quality trials. potential to be developed into a valuable contribution to
osteopathic research, especially regarding placebo control
According to the authors, their study was a pilot methods for a long-term trial of multimodal treatment. In its
trial, defined as a future study conducted on a smaller current form, however, we are concerned that readers unfa-
scale, distinctly aimed at preparing a larger trial [16–18]. miliar with the required methodological standards of clinical
Pilot trials are also valuable for hypothesis-generation trials are misled to believe that the described osteopathic
and the development and assessment of complex inter- interventions have been demonstrated as effective treatment
vention programmes [16] – all of which are important for patellofemoral syndrome – a conclusion which, as we
objectives in osteopathy. However, such small trials hold have shown, cannot be drawn from the present trial. Study
an inherently larger risk of bias, which is why many authors must clearly describe methodological limitations and
authors recommend not drawing conclusions regarding report that the focus of pilot and feasibility studies is to
efficacy or clinical effectiveness [19, 20]. In doing so, enhance the design of appropriately powered and designed
small trials also introduce bias into literature reviews studies, which may then make claims about effectiveness and
and metaanalyses [21] – a problem endemic to the efficacy of interventions. For dedicated research colleagues,
manual therapy field [22]. we kindly suggest that pilot work and larger scale trials be
planned and reported with more attention to accepted
Despite calling their study a pilot, there is no indica- research guidance. We further suggest that only trials with
tion in their report that Tramontano et al. [5] are planning to preregistered protocols be published to improve the trust-
conduct such a main study. Instead, the results are inter- worthiness of the analysis [25]. We need a concerted effort to
preted as if they were based on a sufficiently powered and enhance the quality of research and research dissemination
well-designed trial to draw implications regarding the to support clinicians and policy makers when considering
intervention effectiveness: “Significant differences in VAS published evidence.
scores [pain intensity] were found between the […] groups.
These findings emphasize that [osteopathy] can lead to Editor’s Note: Journal of Osteopathic Medicine now
reduced pain in patients with PFPS.” [5] Given these cir- only accepts for publication prospective human subject
cumstances, we suggest that the authors should clarify the studies that have been submitted to a clinical trial registry,
aims of the trial, including whether it was in fact a pilot of a in accordance with the Declaration of Helsinki.

Figure 1: Risk of bias for the outcome “general pain” as measured per patient self-report on a visual analogue scale (VAS) in Tramontano et al
[5]. The data was rated by three independent reviewers (D.H.S., J.D.R., J.V.) and reconciled by discussion. Ratings were based on the risk-of-
bias tool 2 [23], and the figure was created with the risk-of-bias visualization tool [24].

Hohenschurz-Schmidt et al.: Performing and interpreting randomized clinical trials 445

Research funding: According to your style guide, Research 11. Baskin TW, Tierney SC, Minami T, Wampold BE. Establishing
funding appears above Author contributions. specificity in psychotherapy: a meta-analysis of structural
Author contributions: All authors provided substantial equivalence of placebo controls. J Consult 2003;71:973–9.
contributions to conception and design, acquisition of data,
or analysis and interpretation of data; all authors drafted the 12. Hart T, Bagiella E. Design and implementation of clinical trials in
article or all authors revised it critically for important rehabilitation research. Arch Phys Med Rehabil 2012;93:
intellectual content; all authors gave final approval of the S117–26.
version of the article to be published; and all authors agree to
be accountable for all aspects of the work in ensuring that 13. Felson DT, Redmond AC, Chapman GJ, Smith TO, Hamilton DF,
questions related to the accuracy or integrity of any part of the Jones RK, et al. Recommendations for the conduct of efficacy
work are appropriately investigated and resolved. trials of treatment devices for osteoarthritis: a report from a
Competing interests: Dr. Vogel is Editor-in-Chief of the working group of the Arthritis Research UK Osteoarthritis and
International Journal of Osteopathic Medicine. The other Crystal Diseases Clinical Studies Group. Rheumatology (Oxford)
authors have nothing to report. 2016;55:320–6.

References 14. Puhl AA, Reinhart CJ, Doan JB, Vernon H. The quality of placebos
used in randomized, controlled trials of lumbar and pelvic joint
1. Schwartz D, Lellouch J. Explanatory and pragmatic attitudes in thrust manipulation–a systematic review. Spine J 2017;17:
therapeutical trials. J Clin Epidemiol 2009;62:499–505. 445–56.

2. Schulz KF, Altman DG, Moher D. CONSORT 2010 Statement: 15. Aycock DM, Hayat MJ, Helvig A, Dunbar SB, Clark PC. Essential
updated guidelines for reporting parallel group randomised considerations in developing attention control groups in
trials. BMJ 2010;340:c332. behavioral research. Res Nurs Health 2018;41:320–8.

3. Boutron I, Altman DG, Moher D, Schulz KF, Ravaud P, For the 16. Craig P, Dieppe P, Macintyre S, Michie S, Nazareth I, Petticrew M.
CONSORT NPT Group. CONSORT statement for randomized trials Developing and evaluating complex interventions: the new
of nonpharmacologic treatments: a 2017 update and a CONSORT Medical Research Council guidance. BMJ 2008;337:a1655.
extension for nonpharmacologic trial abstracts. Ann Intern Med
2017;167:40. 17. Eldridge SM, Lancaster GA, Campbell MJ, Thabane L, Hopewell S,
Coleman CL, et al. Defining feasibility and pilot studies in
4. Chan L, Heinemann AW, Roberts J. Elevating the quality of preparation for randomised controlled trials: development of a
disability and rehabilitation research: mandatory use of the conceptual framework. PLoS One 2016;11:e0150205.
reporting guidelines. Can J Occup Ther 2014;81:72–7.
18. NIHR. National Institute for Health Research glossary. https://
5. Tramontano M, Pagnotta S, Lunghi C, Manzo C, Manzo F, Consolo www.nihr.ac.uk/glossary [Accessed 4 Nov 2019].
S, et al. Assessment and management of somatic dysfunctions in
patients with patellofemoral pain syndrome. J Am Osteopath 19. Arnold DM, Burns KEA, Adhikari NKJ, Kho ME, Meade MO, Cook DJ.
Assoc 2020;120:165–73. The design and interpretation of pilot trials in clinical research in
critical care. Crit Care Med 2009;37:S69.
6. Boutron I, Tubach F, Giraudeau B, Ravaud P. Blinding was judged
more difficult to achieve and maintain in nonpharmacologic than 20. Teare MD, Dimairo M, Shephard N, Hayman A, Whitehead A,
pharmacologic trials. J Clin Epidemiol 2004;57:543–50. Walters SJ. Sample size requirements to estimate key design
parameters from external pilot randomised controlled trials: a
7. Boutron I, Moher D, Altman DG, Schulz KF, Ravaud P, For the simulation study. Trials 2014;15:264.
CONSORT Group. Extending the CONSORT statement to
randomized trials of nonpharmacologic treatment: explanation 21. Riley S, Swanson BT, Sawyer SF, Brisme´e J-M, Staysniak G. Should
and elaboration. Ann Intern Med 2008;148:295. low-quality evidence dominate high-level evidence? A systematic
review and meta-analysis of systematic reviews of
8. Cerritelli F, Verzella M, Cicchitti L, D’Alessandro G, Vanacore N. musculoskeletal physical therapy interventions. J Man Manip Ther
The paradox of sham therapy and placebo effect in osteopathy. 2020:1–13. https://doi.org/10.1080/10669817.2020.1839728.
Medicine (Baltim) 2016;95:e4728.
22. Alvarez G, Núñez-Corte´s R, Solà I, Sitjà-Rabert M, Fort-
9. Power M, Hopayian K. Exposing the evidence gap for Vanmeerhaeghe A, Fernández C, et al. Sample size, study length
complementary and alternative medicine to be integrated into and inadequate controls were the most common self-
science-based medicine. J R Soc Med 2011;104:155–61. acknowledged limitations in manual therapy trials: a
methodological review. J Clin Epidemiol 2020;130:96–106.
10. Hróbjartsson A, Miller F. Chapter 2: Blinding in
nonpharmacological randomized controlled trials. In: Boutron I, 23. Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I,
Ravaud P, Moher D, editors. Randomized clinical trials of et al. RoB 2: a revised tool for assessing risk of bias in randomised
nonpharmacologic treatments, 1 ed. London: Chapman and trials. BMJ 2019;366:l4898.
Hall/CRC; 2011.
24. McGuinness L, Higgins J. Risk-of-bias VISualization (robvis): an R
package and Shiny web app for visualizing risk-of-bias
assessments. Res Syn Meth 2020;1. https://doi.org/10.1002/
jrsm.1411.

25. World Medical Association. World Medical Association
Declaration of Helsinki: ethical principles for medical
research involving human subjects. J Am Med Assoc 2013;310:
2191–4.



J Osteopath Med 2021; 121(4): 447–448

Letter to the Editor

Marco Tramontano*, DO, Christian Lunghi, DO, Simone Pagnotta, DO, Camilla Manzo, DO,
Francesca Manzo, DO, Stefano Consolo, MSc and Vincenzo Manzo, MD, DO

Response to a letter to editor from Hohenschurz-
Schmidt et al

https://doi.org/10.1515/jom-2021-0037 undermined the credibility of both. In our previous work
Received February 1, 2021; accepted February 10, 2021; [3, 4], we designed another manual-placebo intervention
published online March 1, 2021 and introduced a “deblinding” questionnaire. This survey,
delivered posttreatment after patients were “deblinded,”
To the Editor, demonstrated that a fair percentage of participants who
received the placebo intervention found it effective, thus
We are grateful to Hohenschurz-Schmidt and colleagues suggesting that the “sham” (the very same adopted in the
[1] for their interest in our brief report on the potential present brief report) was actually credible.
effects of osteopathic manipulative therapy (OMTh) in
patients with patellofemoral pain syndrome (PFPS) [2] Interestingly, Hohenschurz-Schmidt et al. [1] attributed
and for their valuable effort to enhance the rigor of
research in osteopathic medicine. the lack of change seen in our control group over time to a
“frustrebo effect.” The fact that five patients who dropped out
In what we perceived as an absence of shared guide- of our pilot study were from the placebo group might suggest
lines for performing placebo-controlled trials in manual
therapy, we took particular care in designing the methods that the passive nature of the sham intervention may have
for this brief report (pilot study) and specifically trained
practitioners in the application of the “sham” therapy we determined such attrition. However, from a clinical point of
selected for therapy-naïve participants. Hohenschurz-
Schmidt et al. [1] acknowledged the effort made in control- view, the lack of change in the control group cannot be strictly
ling for “non-specific effects of touch and the therapeutic considered a null effect, as PFPS is characterized in 70–90%
encounter,” but suggested further improvements to the of individuals by recurrent or chronic pain [5]. Therefore, the
manual-placebo intervention. Since the use of a placebo
arm is crucial to disentangle the bottom-up and top-down fact that self-reported pain did not change in the placebo
effects of a specific touch, we particularly appreciated the
clinical suggestion. While the idea to “provide simple touch group during the assessment period would suggest a positive
to the symptomatic area or some form of tissue movement”
to enhance “the potential of the placebo intervention to be effect of sham on recurrence of symptoms, at least.
considered as a true treatment” is interesting, we believe it is Aside from the academic discussion on the best way to
still insubstantial, as the effect of OMTh also was observed in
the pilot trial after treatment was delivered to areas remote design a placebo-control intervention, we believe results
from the pain site. Thus, treatment that was indirect to the from a pilot study like ours can be discussed in terms of
symptomatic area was a factor shared by the active and the efficacy or clinical effectiveness. As Hohenschurz-Schmidt
sham intervention groups and would have theoretically correctly pointed out, a pilot is “a future study conducted on
a smaller scale,” and including some consideration of the
*Corresponding author: Marco Tramontano, DO, Fondazione Santa clinical importance of these preliminary findings will, in
Lucia IRCCS, Via Ardeatina 306, 00179 Rome, Italy, fact, justify the development and assessment of more com-
E-mail: [email protected] plex intervention programs [1]. Regarding their concern that
Christian Lunghi, DO, Malta Icom Educational, San Gilijan, Malta readers unfamiliar with the “required methodological
Simone Pagnotta, DO, Camilla Manzo, DO, Francesca Manzo, DO, standards of clinical trials” [1] might assume that the
Stefano Consolo, MSc and Vincenzo Manzo, MD, DO, Centre Pour described osteopathic intervention resulted in a high level of
l’Etude, la Recherche et la Diffusion Osteopathiques, Rome, Italy evidence or a recommendation for the treatment of the
patellofemoral syndrome, we are confident enough that
limitations we acknowledged in the appropriate section of
our article and our fairly cautious conclusions [2] will guide
readers’ understanding. Our report might, at most, com-
plement recent evidence [6] demonstrating a positive effect
of osteopathic treatment (when compared with exercise
protocol) for reducing knee pain in runners with PFPS [6].

Open Access. © 2021 Marco Tramontano et al., published by De Gruyter. This work is licensed under the Creative Commons Attribution 4.0
International License.

448 Tramontano et al.: Letter to the editor response

Moreover, as the the Cochrane tool for assessing risk of the accuracy or integrity of any part of the work are
bias (RoB) in randomized trials (RoB2) [7] is intended “to appropriately investigated and resolved.
evaluate the risk of bias in each study included in a systematic Competing interests: Authors state no conflict of interest.
review” to document “potential flaws in the evidence
summarized,” [1] we are puzzled by the RoB assessment References
offered by the authors of the letter – which should, at least,
include the same evaluation conducted on evidence similar 1. Hohenschurz-Schmidt D, Vollert J, Vogel S, Rice A, Draper-Rodi J.
to the one presented in our brief report [7], while the “high” Performing and interpreting randomised Clinical Trials – an
concerns in domains two, three, and five are not particular- illustrated commentary on Tramontano et al. J Osteopath Med
ized in the letter. 2020;121:447–49.

We would also like to underline that we submitted the 2. Tramontano M, Pagnotta S, Lunghi C, Manzo C, Manzo F, Consolo S,
manuscript as a brief report. Although the study design is et al. Assessment and management of somatic dysfunctions in
not flawless (which is why you perform a pilot), our paper patients with patellofemoral pain syndrome. J Am Osteopath Assoc
aimed at sharing our preliminary clinical experience on 2020;120:165–73.
this new osteopathic topic. We hope that we have provided
helpful feedback and clarification. 3. Tramontano M, Cerritelli F, Piras F, Spanò B, Tamburella F, Piras F,
et al. Brain connectivity changes after osteopathic manipulative
Editor’s Note: Journal of Osteopathic Medicine now treatment: a randomized manual placebo-controlled trial. Brain Sci
only accepts for publication prospective human subject 2020;10:969.
studies that have been submitted to a clinical trial registry,
in accordance with the Declaration of Helsinki. 4. Tamburella F, Piras F, Piras F, Spanò B, Tramontano M, Gili T.
Cerebral perfusion changes after osteopathic manipulative
Research funding: None reported. treatment: a randomized manual placebo-controlled trial. Front
Author contributions: All authors provided substantial Physiol 2019;10:403.
contributions to conception, design, and interpretation of
data; Drs Tramontano and Lunghi drafted the article and 5. Willy RW, Hoglund LT, Barton CJ, Bolgla LA, Scalzitti DA,
all authors revised it critically for important intellectual Logerstedt DS, et al. Patellofemoral pain. J Orthop Sports Phys
content; all authors gave final approval of the article to be Ther 2019;49:CPG1–95.
published; and all authors agree to be accountable for all
aspects of the work in ensuring that questions related to 6. Zago J, Amatuzzi F, Rondinel T, Matheus JP. Osteopathic
manipulative treatment versus exercise program in runners with
patellofemoral pain syndrome: a randomized controlled trial. J
Sport Rehabil 2020:1–10. https://doi.org/10.1123/jsr.2020-
0108.

7. Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I,
et al. RoB2: a revised tool for assessing risk of bias in randomised
trials. BMJ 2019;366:l4898.

J Osteopath Med 2021; 121(4): 449–450

Letter to the Editor

Jason D. Vadhan*, OMS IV, Lauren J. Crispino, OMS IV and James B. Carmody, MD

Teleclerkships? The role of telemedicine in
medical student education during COVID-19 and
beyond

https://doi.org/10.1515/jom-2021-0051 clinical experience and does not improve medical knowl-
Received February 13, 2021; accepted February 16, 2021; edge or clinical reasoning. It is only after students “grad-
published online March 3, 2021 uated” to Stage 3 that they witnessed patient-physician
interactions. This stands in stark contrast to traditional
To the Editor, clerkships, in which observing and conducting clinical
patient encounters is the cornerstone of most clerkships
We read with interest the article by Bhatia et al. [1] from the from the outset.
January 2021 issue of Journal of Osteopathic Medicine, in
which the authors described the replacement of a tradi- Although Table 2 [1] demonstrated the similarities
tional family medicine clerkship with a telehealth model at between traditional and telehealth clerkships, some of the
Rowan University School of Osteopathic Medicine. The most critical educational opportunities in a traditional
implementation of a virtual clerkship was necessary given clerkship occur through casual observations and faculty
the novel coronavirus 2019 (COVID-19) pandemic, and the interactions. These interactions likely play an essential role
authors deserve credit for creating a workable alternative in developing a student’s professional identity, but are
so quickly. Yet, speaking as current osteopathic medical subjective and difficult to quantify, making it very chal-
students and a medical educator, we would have serious lenging to recreate them virtually [2].
concerns if these alternatives were to persist or expand
after the pandemic. Despite the limitations of virtual clerkships, many
schools could find the possibility of expanding them to
Although the telehealth clerkship described by be appealing. Even before the COVID-19 pandemic, 87%
Bhati et al. [1] was thoughtfully designed, neither short- of allopathic schools reported difficulty finding enough
nor long-term educational outcomes were assessed. primary care preceptors for students [3]. These chal-
Without systematic evaluation of clinical evaluations, lenges may be felt even more acutely at osteopathic
student feedback, residency preparedness, and/or medical schools, which are less likely to have an affili-
Comprehensive Osteopathic Medical Achievement Test ated hospital on-campus and face increasing competi-
performance, we wonder whether telehealth students tion at many training sites from students from foreign
achieved the same competencies as their traditional medical schools and nurse practitioner/physician as-
counterparts. sistant programs [4].

Such concerns are heightened by the clerkship’s A telemedicine clerkship like the one described by
structure, which decreased the time that students spent Bhatia et al. [1] was necessary during the pandemic.
with patients and preceptors. Students spent much of the However, that approach’s limitations must be studied and
initial portion of the clerkship helping patients download mitigated, and decisions by other institutions to emulate
telemedicine software – a task that provides minimal the authors’ approach should be based on similar public
health necessity or the desire to teach telehealth as a
*Corresponding author: Jason D. Vadhan, OMS IV, Kiran C. Patel specific competency, not convenience or financial
College of Osteopathic Medicine, Nova Southeastern University, 3200 expediency.
S University Dr, Davie, Ft. Lauderdale, FL 33328, USA,
E-mail: [email protected] Research funding: None reported.
Lauren J. Crispino, OMS IV, College of Osteopathic Medicine, Rowan Author contributions: All authors provided substantial
University, Rowan, NJ, USA contributions to conception and design, acquisition of
James B. Carmody, MD, Department of Pediatrics, Eastern Virginia data, or analysis and interpretation of data; all authors
Medical School, Norfolk, VA, USA drafted the article or all authors revised it critically for

Open Access. © 2021 Jason D. Vadhan et al., published by De Gruyter. This work is licensed under the Creative Commons Attribution 4.0
International License.

450 Vadhan et al.: The role of telemedicine in medical student education

important intellectual content; all authors gave final References
approval of the version of the article to be published; and
all authors agree to be accountable for all aspects of the 1. Bhatia RK, Cooley D, Collins PB, Caudle J, Coren J. Transforming a
work in ensuring that questions related to the accuracy clerkship with telemedicine. J Am Osteopath Assoc 2021;121:43–7.
or integrity of any part of the work are appropriately
investigated and resolved. 2. Akers A, Blough C, Iyer MS. COVID-19 implications on clinical
Competing interests: Ms. Crispino is a student at Rowan clerkships and the residency application process for medical
University College of Osteopathic Medicine, the institution students. Cureus 2020;12:e7800.
where the study to which the authors refer in this letter was
conducted. 3. Colleges AoAM. AAMC medical school enrollment survey: 2019
results. Washington D.C.: AAMC; 2020.

4. Sarzynski E, Barry H. Current evidence and controversies: advanced
practice providers in healthcare. Am J Manag Care 2019;25:366–8.