Chapter XX.7. Gender Dysphoria in Children, Adolescents, and Young Adults
Pia H. Francisco-Natanauan, MD
April 2023

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Case 1: An 8-year-old assigned female at birth is brought to the Adolescent Medicine clinic by the father. The patient is referred by the pediatrician for male gender identity affirmation. The patient’s family, school, and community have known that the patient is a boy since age 2 as said by the patient and based on the patient’s physical expression in the manner of hairstyle and clothing. The patient has also chosen a masculine name and pronouns since age 3.

Case 2: A 13-year-old assigned male at birth is brought in by the mother for gender-affirming treatment. The patient’s family was surprised by the patient’s revelation of the female identity, the chosen name, and chosen female pronouns 4 months prior although the patient has known her identity since the first grade. The family, despite feeling surprised, supported the patient and worked with the school accordingly to ensure the patient’s safety. The patient expressed interest in affirming the female gender identity with cross-hormone treatment as she desires breast development and curves in her hips and thighs. She is unsure about the male genitalia although the early morning erections have been a constant reminder of her male body.

Case 3: A 16-year-old assigned male at birth is brought in by both parents for non-binary gender identity. The patient told the parents about this 6 months before the visit and asked them to use a different set of pronouns: they, them, theirs, xey, xem, xyrs. The patient kept their name given its unisex nature. The parents have a difficult time using the pronouns, but they would like to help their teen with gender affirmation. The patient does not want facial or body hair and acne. They desire a smoother jawline, soft facial features, and smooth skin.

Case 4: A 17-year-old assigned female at birth with a male gender identity, who has been on hormone replacement treatment with testosterone since age 16 and who has had puberty blocker treatment from age 12 to 15, is now returning to the clinic for surgery referral. He wants breast reconstruction to a male chest.


Children, adolescents, and young adults (CAYA) can present with gender non-conforming (GNC) behaviors in a variety of clinical settings. GNC can show as early as age 3 and throughout adolescence (1). Gender role behavior and GNC in young children mean that they prefer clothing, hairstyles, toys, activities, and playmates that are typically associated with the opposite sex. This behavior is common and normal in children. Cross-gender preferences and play are also a normal part of gender development and exploration regardless of future gender identity (1). For CAYA with GNC behaviors, parental inquiry typically starts at primary care offices (2).

GNC behaviors occurring early in childhood are not always predictive of their adolescent gender identity. It is GNC behaviors persisting from childhood through pre-puberty and puberty that can predict one’s gender identity (2). The innate sense of self is also known to an individual as early as age 3. At the pubertal onset, the body changes can yield the incongruence between the body and the innate self. To CAYA, this may be called transgender. If there is distress developing from the incongruence of the body and the innate self, this is, in the Diagnostic and Statistical Manual 5th edition (DSM-5), known as gender dysphoria (GD). The incongruent experience of being transgender is not pathological in and of itself; however, the resulting functional problems can become very distressing to the child especially when going through the psychosocial development of adolescence during puberty. GD should be addressed by a team of medical and mental health professionals. Gender-affirming treatment includes medication management with puberty blockers and gender-affirming hormones by the medical team. Gender-affirming treatment decreases the distress of a transgender individual, thereby decreasing the mental health issues arising from GD. Providers are instrumental in giving support and affirming services to CAYA with GD. Barriers to health care include limited access to providers who are sufficiently trained in care and treatment of CAYA with GD, provider bias, and/or misinformation (4,5). While adults with GD have had an established approach to treatment for GD, treatment for GD in CAYA remains elusive (6). Table 1 describes terms that are commonly used.

Table 1. Terminology (7,8,9,10,11,12)
AgenderA gender identity characterized by feeling no identification with being a boy or man, girl or woman, or any other gender
AsexualA person with no sexual attraction to others or one who lacks interest in sexual orientation
Biologic sexThe genetic, anatomic, and hormonal determinants of sex classified as male or female, or indeterminate due to a disorder of sex development
BisexualAn individual who has a sexual or romantic, physical or spiritual attraction to more than one gender
CisgenderHaving a gender identity that is congruent with one’s biological sex
Coming OutDisclosure of one’s trans identity to loved ones/family, friends
GayA man with a romantic or sexual attraction to men
Gender attributionHow an observer decides which sex or gender they believe another person to be
Gender dysphoriaA DSM-5 defined diagnosis describing distress caused by incongruence between gender identity and biological
Gender fluidA gender identity that varies over time
Gender identityAn internal feeling of one’s gender as a boy or man, girl or woman, no gender, or a non-binary understanding of one’s gender
Gender non-conformingDescribes a person whose behaviors, actions, or interests do not conform to societal expectations based on their biological sex
Gender roleThe stereotypical role which members of each biological sex are expected to play based on societal norms or expectations
GenderqueerA term used by people who do not classify themselves using conventional gender distinctions
IntersexA person born with any variation in sex characteristics including chromosomes, gonads, sex hormones, or genitals.
LesbianA woman with a romantic or sexual attraction toward women
LGBTQi+Stands for Lesbian, Gay, Bisexual, Transgender, Queer/Questioning, Intersex. The Plus sign denotes the diversity of sexual orientation and gender identities that will include all.
MāhūA term and a cultural role that can be used to describe kanaka (or Native Hawaiian) people a third or middle gender other than male or female, with characteristics of both sexes.
MuxeFrom the Spanish word for woman, mujer. A Mexican who is assigned male at birth who identifies as different genders
Non-binaryRefers to a gender identity that does not fall within binary genders
PansexualA person with sexual or romantic, physical or spiritual attraction for members of all gender identities
QueerRefers to mostly non-heterosexual people
QuestioningA person exploring their gender identity and /or sexual orientation
Sexual attractionRefers to whom one is romantically or sexually attracted
Sexual behaviorDescribes the kind of sex one is having and with whom
Sexual identity Self-identification of one’s sexual orientation
Sexual OrientationComprised of sexual identity, sexual behavior, sexual attraction
TransgenderHaving a gender identity that is not congruent with one’s biological sex
TranssexualA term most often used to describe a transgender person who is or has transitioned using hormones and/or surgical procedures
Two-SpiritNative American term that refers to third gender, refers to non-heterosexual self-identification

The website genderbread.org provides information on the Genderbread Person, which is a model that depicts the ways society constructs gender and its different components. The components are Identity, Attraction, Expression, and Anatomic Sex which are independent of each other. The Identity is a spectrum of male-ness or female-ness and is not binary (13). It is about a person interpreting oneself and forming one’s identity as affected by hormones and the environment. Attraction is the physical, spiritual, emotional connectedness to another person. Expression is how one presents oneself to the world through clothing, behavior and interaction. Anatomic sex is the biological basis of hormones, chromosomes that one has. The components are independent of one another, which means, one does not determine the other, but they affect one another. The Genderbread Person is not a diagnostic tool or a model of sexuality or sexual orientation.

The true prevalence of GD is not known even though the number of transgender youths seeking gender-affirming care has increased over the past decade (11). In DSM-5, the prevalence of GD is 0.0005-0.014% in adults who were assigned males at birth and 0.002-0.003% for adults assigned females at birth (14). In the US, 0.5% or 1.3 million adults identify as transgender, 38.5% are transgender women, 36% are transgender men and 26% are gender non-conforming. Adolescents age 13 to 17 who identify as transgender make up 1.4% or 300,000 (15). In Hawaii, in 2018, 3% of public high school students (roughly 1,260 students) identify as transgender. 57% of these transgender youth identify as lesbian, gay, or bisexual. Hawaiian, Filipino, and Caucasian ethnicities each make up about a quarter of the transgender youth population. 1 in 5 (20%) Native Hawaiian/Pacific Islanders identify as māhū (12).

Several theories on the etiology and gender identify development have tried to explain the causes of GD but there is no clear etiology to provide a causal relationship for being transgender. The development of gender identity, however, happens early. At ages 1 to 2, a child becomes aware of the physical differences between genders. At age 3, one can identify themselves as a boy or a girl. At age 4, a child’s gender identity is established (2). The recognition of gender identity happens early, but the initial awareness of gender incongruence can also occur at different times in a child’s life. Some children can tell their parents/caregivers about their identity early in life, but most cannot. Given the inadequate information from parents/caregivers and some clinicians, a child that is aware of one’s gender identity but without the ability to express the gender incongruence may resort to the internet for information on feeling different or questioning. At the onset of puberty, when the body begins to develop permanent secondary sexual characteristics that are not congruent to one’s identity, GD is expressed and is often exacerbated.

There are several negative mental health and social outcomes associated with the distress from the gender incongruence experienced in GD. The psychosocial development of adolescents makes one particularly vulnerable to a decreased sense of well-being and low self-esteem which may easily perpetuate the adolescent with GD. Combining this with the external factors of lack of family and community support, the adolescent experiences more distress possibly leading to mood disorders such as depression and anxiety, or high-risk-taking behaviors such as substance use and abuse, self-harm, and suicidality. An adolescent may experience social isolation, peer rejection, bullying, economic marginalization, homelessness, and incarceration. The medical issues are secondary to the mental health and social outcomes. They can include physical injuries from physical abuse or violence, sexually transmitted diseases, or high-risk pregnancy from sexual exploitation and human sex trafficking (16). The body dysphoria experience is very common with patients with GD making them vulnerable to eating disorders or obesity. The medical, mental, and social health problems should not prohibit gender-affirming treatment, but, rather, the problems are addressed simultaneously during the process of gender affirmation to ensure one’s optimal well-being.

LGBTQ youth are 4 times more likely to attempt suicide (17). In 2022, 45% of LGBTQ youth seriously considered attempting suicide, including more than half of transgender and non-binary youth, which increased by 3% from 2021. 12% of Caucasian youth attempted suicide compared to 21% of Native/Indigenous youth, 20% of Middle Eastern, 19% of African American youth, 17% of multiracial youth, 16% of Latinx youth, and 12% of Asian/Pacific Islander youth (18). In Hawaii, nearly half of transgender youth live in unstable housing situations compared to only 6% of cisgender youth. 41% of transgender youth leave the home of their parent or guardian, and 8% are unsheltered (17).

As with any adolescent patient, transgender youth should be treated with respect and dignity. Respect starts with asking for the name(s) and the pronoun(s) that the adolescent expressed to be used. The office staff, from the front desk to the clinical personnel to the providers, should be knowledgeable in interacting with patients with GD and their families. Some special additional pronouns include: xey (they), xem (them), and xyrs (theirs). The patient records, including electronic health records or paper charts, should bear the correct gender identity and names for proper identification and address. The rooms for waiting and the patient encounter should show inclusivity and support for patients and families with GD. Patients will come at different stages of transitioning and office staff and clinical providers should not assume the gender identity or name until the patient has declared it so. Clinical providers should model nonjudgmental and respectful communication with the adolescent in front of the family/loved ones during the visit. It is important to address the needs, desires, and concerns of the transgender adolescent accordingly. It is important to discuss the adversities and the harm that can happen if GD is untreated and if the adolescent is not supported. Parents, families, or loved ones who struggle to understand their child’s gender identity or the process of gender affirmation should be referred to support groups and provided with appropriate literature.

The Transgender Athlete, the Trans-athlete

In 2021, the International Olympics Committee (IOC) 10-item Framework was updated from its 2016 version to show its commitment to respecting human rights and promoting gender equality and inclusion. The IOC 2021 Framework emphasized the principles of inclusion, and non-discrimination, as well as fairness and no presumption of advantage, and its promotion at all levels of sport (19). In contrast, the 2016 framework emphasized fairness with the assumption that testosterone provides an advantage in performance in athletes with Disorders of Sex Development (DSD) receiving testosterone and in athletes transitioning with gender-affirming testosterone. With the 2021 update, several international sports associations followed. The International Association of Athletics Federation (IAAF) World Athletics 2021 and National College Athletic Association (NCAA) 2022 aligned with the Framework.

The purpose of sports and recreational activities in children, adolescents, and young adults is to provide physical health and wellness, leadership and teamwork skills, and time management as stated in the Centers for Disease Control and Prevention (CDC) Healthy Schools program. Local state health departments and state education departments should collectively promote sports participation with an emphasis on the benefits of play and recreation regardless of gender identity in elementary, middle, and high schools. There should be no presumption of unfairness based on transitioning or gender affirmation. Schools, athletic trainers, and coaches should respect one’s privacy by not singling out the youth for their gender identity.

Reproductive Health (20,21)

There is a need to discuss future childbearing and/or family planning with the adolescent patient with GD. It is not surprising to hear that an adolescent is not thinking about future fertility or current family planning intent. This is again based on normal psychosocial and developmental adolescent thinking. Menstrual management, contraception, and fertility preservation are topics that are particularly addressed in gender-affirming treatment for patients with GD, especially when preparing for gender-affirming medications such as puberty blockers and hormones. Although the medications for menstrual management and contraception are the same birth control methods, the indication may differ based on the distress experienced and the desires of the individual. One may be distressed by menstrual bleeding as a constant reminder of the physical incongruence to one’s gender identity. The contraceptive methods of choice for a patient preparing for gender-affirming medications are the ones that do not contain hormones or only contain the hormone, progestin. Non-hormonal contraceptives include barrier methods like condoms, cervical caps, or diaphragms, which are not as efficient as hormonal birth control methods and will also not induce cessation of menses. Progestin-only contraceptives are available as once-daily oral pills, once-every-12-week injections, an implant, or an intrauterine device (IUD). The secondary amenorrhea induced provides relief to the patient with GD. All progestin-only contraceptives are effective although the implant and the IUD give the advantage of being very efficient and reliable contraceptives benefitting patients engaging in vaginal-penile sexual activity while on gender-affirming testosterone. Testosterone causes amenorrhea which may give the impression that ovulation is suppressed although this is not guaranteed. Patients on gender-affirming testosterone treatment are duly advised of the teratogenic effect of the hormone and, therefore, are recommended to be on a reliable form of progestin-only contraceptive.

Although ovulation may still occur while on gender-affirming testosterone, fertility is also not guaranteed. Fertility preservation with egg harvesting may be discussed before puberty blockade, and, definitely, before gender-affirming testosterone. Egg cryopreservation is difficult and expensive, and is not an option for patients at a pubertal developmental stage of Sexual Maturity Rating (SMR) 2 for breast. Patients on gender-affirming estradiol and androgen blocker medications ought to be counseled on the potential loss of fertility while on treatment. At pubertal stage SMR 3 for genitalia, sperm cryopreservation is an option that can be explored and discussed with a fertility preservation specialist. At a lower SMR level, sperm preservation may not be attainable. For both gender-affirming treatment situations, it is prudent for the patient and the family to be advised of the importance of fertility preservation before starting gender-affirming medications.

Medical Management in Gender Affirmation (22,23)

Starting gender-affirming medications depends on the age and sexual development of the adolescent, co-existing medical conditions, support system, and individual intent and desire. Puberty blockade is accomplished with gonadotropin-releasing hormone (GnRH) analogs which can be started at SMR 2 to 4 for pubertal development and continued until age 16 according to the Endocrine Society Clinical Care Guidelines. GnRH analogs are available as an intramuscular medication, leuprolide acetate (Lupron), given at regular intervals of once monthly, or every 3-month intervals; or as an implant, histrelin, once a year. Puberty blockers suppress sex hormones which makes bone mineral density accrual concerning. Another common side effect complaint is hot flashes. Before puberty blockade, baseline biometrics of weight, height, blood pressure, and SMR staging, as well as baseline blood work consisting of levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, free and total testosterone, and 25-hydroxy-vitamin D, and baseline imaging studies consisting of bone age x-ray and bone mineral density scan are completed. Regular monitoring of biometrics, blood work, and imaging are indicated while on pubertal suppression. The decreased bone mineral density accrual is reversible after stopping the GnRH analog.

Estrogen is available in pill, patch, and injectable forms. Androgen blockers include spironolactone, 5-alpha reductase inhibitors such as finasteride and dutasteride, and less common anti-androgens such as bicalutamide and cyproterone acetate, a synthetic progestogen. Baseline work-up includes a complete metabolic panel to check for electrolytes as well as kidney and liver function; a complete blood count; a fasting lipid panel; levels of glycosylated hemoglobin A1c, LH, FSH, estradiol, free and total testosterone, and 25-hydroxy-vitamin D; and a bone age x-ray.

Gender-affirming hormones with estrogen and an androgen-blocker give the following permanent effects: breast growth and development, a decrease in testicular size and mass, and a decrease in sperm production. Other changes that are not permanent include loss of muscle mass, decreased strength, weight gain concentrating on the lower abdomen, hips, buttocks, and thighs, loss of facial and body hair, and slowing down of male-pattern scalp baldness (however the hair will not regrow if male-pattern scalp baldness had already occurred before starting gender-affirming estrogen and androgen blocker), decreased sexual function (decreased libido, decreased penile erection or inability to get an erection, decreased ejaculate from less sperm production), and changes in mood symptoms either positively with improvement, or negatively, as in mood swings and irritability. Loss of fertility is a risk and should be discussed before starting gender-affirming hormones. Other side effects include nausea, vomiting, mood swings, venous thromboembolism, elevated transaminases, prolactinoma, gallstones, and hyperkalemia (specific to androgen blocker, spironolactone).

Testosterone is available as an injection, intramuscularly or subcutaneously, and as a topical medication. Before starting testosterone, a baseline work-up would include a complete metabolic panel to check for electrolytes as well as kidney and liver function; a complete blood count particularly for baseline hemoglobin and hematocrit values; a fasting lipid panel; levels of glycosylated hemoglobin A1c, LH, FSH, estradiol, free and total testosterone, and 25-hydroxy-vitamin D; and a bone age x-ray.

Testosterone has the following permanent effects: deepening of the voice, growth of thick, coarse facial and body hair, scalp hair loss, and increased clitoral size. Other effects that are reversible include menstrual cessation, weight gain, increased strength, acne, increased libido, and mood changes either positively, as in mood improvement, or negatively, such as anger or aggression. Serious side effects include elevation of transaminases, insulin resistance, hyperlipidemia, and polycythemia.

Phases of Transitioning (24)

The guidelines for transgender healthcare in the US include the University of California-San Francisco HealthCare for Transgender Persons and the Endocrine Society Clinical Practice Guideline for Gender-Dysphoric/Gender-Incongruent Persons, and, internationally, the World Professional Association for Transgender Health (WPATH). Gender-affirming treatment and management is accomplished with a multidisciplinary team consisting typically of mental health, medical, and surgical specialists. The mental health provider can be a psychologist or psychiatrist, the medical provider/s can be the primary care provider, an adolescent specialist, a pediatric or adult endocrinologist, and a fertility preservation specialist. The surgical team can include plastic surgery, breast surgery, urology, urogynecology, and gynecology.

The phases of transitioning can be grouped into the following:

1. Reversible. This includes the changes that are physically non-permanent and may be started at any age, except for puberty blocker which is started based on sexual development (SMR 2 to 4). This phase may include the following:
   a. social transitioning and affirmation with the assertion of name and pronoun
     i. Legal affirmation of the name changes and gender identity on civil documents
   b. physical transitioning
     i. with makeup, hairstyle, clothing, and manner of speaking
     ii. binding/taping breast; wearing a padded bra; tucking the male genitalia which is done by placing the testicles into the inguinal canal, held in place with
     tight underwear or a garment called a gaff, to give a feminine genital contour
     iii. voice modulation with voice training which can be accomplished with a voice coach
     iv. hair removal treatment for assigned male at birth which may include shaving, depilatory products, androgen blocker
   c. menstrual management for assigned females at birth and androgen blocker for assigned males at birth
   d. puberty blocker at SMR 2 to 4
     i. Medication with puberty blockers requires parental consent and child assent

2. Partially reversible. This includes the changes secondary to gender-affirming hormone use some of which are permanent. The Endocrine Society Clinical Practice Guidelines for Gender-Dysphoric/Gender-Incongruent Persons recommend age 16 to start gender-affirming hormones. If puberty blockade is started, it can be continued while on gender-affirming hormones.
   a. Gender-affirming hormones include estradiol, anti-androgen, and testosterone

3. Irreversible. This includes changes that are physically and physiologically permanent. Any surgical procedure falls under this phase. The Endocrine Society Clinical Practice Guidelines for Gender-Dysphoric/Gender-Incongruent Persons and UCSF HealthCare for Transgender Persons recommend the age of 18 for surgery. The legal age of consent can differ in every state, province, or country. Surgical procedures may include the following
   a. Laser hair removal treatment
   b. Male chest reconstruction for ones who have had female breast development before medication intervention. Breast augmentation for assigned male at birth
   c. Facial contouring, tracheal shaving
   d. Genital surgery for genital affirmation

Mental health support is an important element in all phases and should be established early in the transition. Guidance from a mental health provider is necessary for the patient and the family and is substantial to the gender-affirming process particularly given an adolescent’s active psychosocial development. Mental health providers provide the necessary coping skills for the patient and the family as one affirms one’s gender identity. A letter of support from the mental health provider indicating the patient’s readiness for the gender affirmation process and responsibility in taking medications and following through with medical recommendations is helpful for the clinician managing the medications and has been instrumental in the continuum of multi-disciplinary care.

The discussion of fertility preservation can be completed during the reversible phase. Harvesting eggs is possible at SMR 3 to 4 when one is post-menarchal, and sperm banking is an option for assigned males at birth at SMR 3 to 4. Specimen collection is optimal before starting gender-affirming hormones.

Anatomical Inventory, also known as Organ Inventory, is the anatomical inventory form of documentation to track the presence or absence of specific organs with any surgical procedure(s) (25). This is particularly beneficial to guide preventive health screenings and post-operative care plans. This inventory is important for all patients regardless of gender identity or transition phase as clinicians may be unaware of a patient’s past procedures. The inventory can be a structured form in the chart as a checklist or in an electronic health record. A review of systems may be like the anatomical inventory, but the latter is more specific to the absence or presence of organs and the surgeries related to the organs as well as prostheses. A clinician asks and completes the anatomical inventory within history taking. Organs for inventory may include breasts, ovaries, uterus, cervix, vagina, penis, testes, and prostate, with their corresponding procedures. Anatomical inventories ought to be updated regularly and accordingly. See Table 2. To take such a history, an introductory statement could something such as: To provide you with the best medical clinical care, it is important for me to know if you have certain body parts...

Table 2. Sample list of anatomical inventory
OrganPresentAbsentTreatment and procedure
BreastChest reconstruction / bilateral mammoplasty/mastectomy, bilateral
OvariesOophorectomy, bilateral/unilateral
Fallopian tubesSalpingectomy, bilateral/unilateral
UterusHysterectomy
Cervix
VaginaColpocleisis / Vaginoplasty, penile inversion
PenisPenectomy / Phalloplasty / penile implant / erectile device
TestesOrchiectomy, bilateral/unilateral, testicular implant
Urethralengthening
Prostateprostatectomy
Others:
LipsSoft tissue filler
ScalpForehead reconstruction, hair implant
VoiceReduction thyroid chondroplasty (tracheal cartilage shave)

Gender Dysphoria in CAYA addressed with gender-affirming treatment with the support of family and their loved ones are valuable determinants of one’s overall health outcomes. As more evidence in the medical literature unfolds, clinicians can continue to care for and treat our CAYA with gender dysphoria as they would their peers.


Questions

1. Having a gender identity is no longer binary. Based on the terminology and the Genderbread person, the following are the gender identities reported
   a. Boy, girl, all, pan
   b. Attraction to boys, girls, all, both
   c. Male, female, both, neither, all
   d. Attraction to none

2. There are several adversities in the LGBTQ youth. Which of the following conditions is 4 times higher in occurrence than their peers?
   a. Suicide
   b. Depression
   c. Anxiety
   d. Substance use

3. What is the most common cause of acute unilateral cervical lymphadenitis?
   a. Partially reversible
   b. Reversible
   c. Irreversible
   d. Social


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23. Deutsch MB. Initiating Hormone Therapy. Feminizing Therapy. Masculinizing Therapy. The University of California-San Francisco Transgender Care and Treatment Guidelines. June 2016. https://transcare.ucsf.edu/guidelines Accessed 5/13/23.

24. Rafferty J, Committee in Psychosocial Aspects of Child and Family Health, Committee on Adolescence, Section on Lesbian, Gay, Bisexual, and Transgender Health and Wellness. Ensuring Comprehensive Care and Support for Transgender and Gender-Diverse Children and Adolescents. Pediatrics. 2018;142(4):e20182162. doi: 10.1542/peds.2018-2162

25. Grasso C, Goldhammer H, Thompson J, Keuroghlian AS. Optimizing gender-affirming medical care through anatomical inventories, clinical decision support, and population health management in electronic health record systems. J Am Med Inform Assoc. 2021;28(11):2531-2535. doi: 10.1093/jamia/ocab080


Answers to questions

1. C

2. A

3. B


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