Article

In the uterus, coordinated myometrial cell contraction is not triggered by neural activation; instead, myometrial cells work together as a contractile syncytium through cell-to-cell gap junction connections permitting the intercellular sharing of small molecules, which in turn facilitates activation of the actin-myosin contractile apparatus and coordinated uterine contraction. In myometrial cells, connexin 43 (Cx43) is the main gap junction protein. Cx43 permits the passage of small hydrophilic molecules (ATP) and ions (calcium) cell to cell. Estradiol increases Cx43 synthesis in human myometrial cells.¹ Progesterone decreases Cx43 synthesis effectively isolating myometrial cells, reducing cell-to-cell sharing of chemicals that stimulate contraction, blocking coordinated uterine contraction.² Progesterone suppression of Cx43 synthesis helps to prevent premature uterine contraction during pregnancy. At term, decreases in progesterone levels result in an increase in Cx43 synthesis, facilitating the onset of effective labor. In myometrial cells, antiprogestins, including mifepristone, increase the number of gap junction connections, facilitating a coordinated contractile signal in response to misoprostol or oxytocin.^3,4

It takes time for antiprogestins to stimulate myometrial cell production of Cx43. In the rat myometrium the administration of mifepristone results in a 2.5-fold increase of Cx43 mRNA transcripts within 9 hours and a 5.6-fold increase in 24 hours.³ Hence, most mifepristone treatment protocols involve administering mifepristone and waiting 24 to 48 hours before administering an agent that stimulates myometrial contraction, such as misoprostol. Antiprogestins also increase the sensitivity of myometrial cells to oxytocin stimulation of uterine contractions by increasing Cx43 concentration.⁴

Progesterone also regulates other important biological processes in the cervix, decidua, placenta, and cervix. Antiprogestins can facilitate cervical ripening and disrupt decidual function, interfering with the attachment of pregnancy tissue.⁵ In the cervix, antiprogestins increase matrix metalloproteinase expression, disrupting collagen organization, decreasing cervical tensile strength and leading to cervical ripening.⁶

Pharmacology of mifepristone

Mifepristone is an antiprogestin and antiglucocorticoid with high-affinity binding to both the progesterone and glucocorticoid receptors (FIGURE 1). The phenylaminodimethyl group at C-11 of mifepristone changes the positional equilibrium of helix 12 of the progesterone receptor, reducing the ability of the receptor to bind required co-activators, limiting receptor binding to DNA, resulting in an antiprogesterone effect.⁷ At the low, single-dose used for treatment of miscarriage and fetal demise (200 mg one dose), mifepristone is an antiprogestin. At the high, daily dose used for the treatment of hyperglycemia caused by Cushing disease (≥ 300 mg daily), mifepristone is also an antiglucocorticoid.

Although mifepristone is a powerful antiglucocorticoid, in patients with an intact hypothalamic-pituitary-adrenal axis, mifepristone does not cause adrenal insufficiency. In people with an intact hypothalamic-pituitary-adrenal axis, daily administration of mifepristone (≥ 200 mg) for 7 days or longer results in an increase in pituitary secretion of ACTH and adrenal secretion of cortisol, largely overcoming the antiglucocorticoid action of mifepristone.^8-10 This compensatory increase in ACTH and cortisol is not possible in patients who have had a hypophysectomy or bilateral adrenalectomy or have adrenal suppression due to long-term treatment with high doses of glucocorticoids. Mifepristone is contraindicated for patients with these conditions because it may cause glucocorticoid insufficiency by blocking glucocorticoid receptors.

The terminal half-life of mifepristone is 18 hours.¹¹ Following oral administration of a single dose of mifepristone 200 mg the peak circulating concentration is reached in 90 minutes. Mifepristone is metabolized by CYP3A4 and is also a strong inhibitor of CYP3A4. Contraindications to the use of mifepristone include adrenal failure, porphyria, hemorrhagic diseases, anticoagulation, an IUD in the uterus, ectopic pregnancy, long-term glucocorticoid administration, and an undiagnosed adnexal mass.

Continue to: Mifepristone-misoprostol for the treatment of early missed miscarriage with a gestational sac...

Mifepristone-misoprostol for the treatment of early missed miscarriage with a gestational sac

For patients with a miscarriage, the treatment options to resolve the pregnancy loss are expectant management, medication, or surgery.¹² Joint decision-making is recommended to establish a management plan that supports the patient’s values. Expectant management is most likely to result in a multi-week process to achieve completion of the miscarriage. A surgical procedure is most likely to result in rapid resolution of the miscarriage with the greatest rate of success. Surgical evacuation of the uterus may be the preferred option for patients who have excessive uterine bleeding or concerning vital signs. Both medical and surgical management are more likely than expectant management to successfully resolve the miscarriage.¹³

In the past, the standard approach to medication management of a miscarriage was the administration of one or more doses of misoprostol, a synthetic prostaglandin E1. However, two large trials have reported that the dual-medication sequence of mifepristone followed 24 to 48 hours later by misoprostol is more effective than misoprostol alone for resolving a miscarriage.^14,15 This is probably due to mifepristone making the uterus more responsive to the effects of misoprostol.

Schreiber and colleagues¹⁴ reported a study of 300 patients with an anembryonic gestation or embryonic demise, between 5 and 12 completed weeks of gestation, who were randomly assigned to treatment with mifepristone (200 mg) followed in 24 to 48 hours with vaginal misoprostol (800 µg) or vaginal misoprostol (800 µg) alone. Ultrasonography was performed 1 to 4 days after misoprostol administration. Successful treatment was defined as expulsion of the gestational sac plus no additional surgical or medical intervention within 30 days after treatment. In this study, the dual-medication regimen of mifepristone-misoprostol was more successful than misoprostol alone in resolving the miscarriage, 84% and 67%, respectively (relative risk [RR], 1.25; 95% confidence interval [CI], 1.09–1.43).

Surgical evacuation of the uterus occurred less often with mifepristone-misoprostol treatment than with misoprostol monotherapy—9% and 24%, respectively (RR, 0.37; 95% CI, 0.21–0.68). Pelvic infection occurred in 2 patients (1.3%) in each group. Uterine bleeding managed with blood transfusion occurred in 3 patients who received mifepristone-misoprostol and 1 patient who received misoprostol alone. In this study, clinical factors including active bleeding, parity, and gestational age did not influence treatment success with the mifepristone-misoprostol regimen.¹⁶ The mifepristone-misoprostol regimen was reported to be more cost-effective than misoprostol alone.¹⁷

Chu and colleagues¹⁵ reported a study of medication treatment of missed miscarriage that included more than 700 patients randomly assigned to treatment with mifepristone-misoprostol or placebo-misoprostol. Missed miscarriage was diagnosed by an ultrasound demonstrating a gestational sac and a nonviable pregnancy. The doses of mifepristone and misoprostol were 200 mg and 800 µg, respectively. In this study the misoprostol was administered 48 hours following mifepristone or placebo using a vaginal, oral, or buccal route, but 90% of patients used the vaginal route. Treatment was considered successful if the patient passed the gestational sac as determined by an ultrasound performed 7 days after entry into the study. If the gestational sac was passed, the patients were asked to do a urine pregnancy test 3 weeks after entering the study to conclude their care episode. If patients did not pass the gestational sac, they were offered a second dose of misoprostol or surgical evacuation. In this study, mifepristone-misoprostol resulted in fewer patients who did not pass the gestational sac within 7 days after entry into the study than placebo (mifepristone-misoprostol, 17% vs placebo-misoprostol, 24% (P=.043). Surgical intervention was performed in 25% of patients treated with placebo-misoprostol and 17% of patients treated with mifepristone-misoprostol (RR, 0.73; 95% CI, 0.53–0.95; P=.021). A cost-effectiveness analysis of the trial results reported that the combination of mifepristone-misoprostol was less costly than misoprostol alone for the management of missed miscarriages.¹⁸

Misoprostol can be administered by an oral, buccal, rectal, or vaginal route.^19,20 Vaginal administration results in higher circulating concentrations of misoprostol than buccal administration, but both routes of administration produce similar mean uterine tone and mean uterine activity as measured by an intrauterine pressure transducer over 5 hours.²¹ Hence, at our institution, we most often use buccal administration of misoprostol. To assess effectiveness of mifepristone-misoprostol treatment, 1 week after treatment with a pelvic ultrasound to detect expulsion of the gestational sac. Alternatively, a urine pregnancy test can be performed 3 weeks following medication treatment. The mifepristone-misoprostol regimen is not approved by the US Food and Drug Administration for the treatment of miscarriage.

Continue to: Mifepristone-misoprostol for the treatment of fetal demise...

Mifepristone-misoprostol for the treatment of fetal demise

Fetal loss in the second or third trimesters is a devastating experience for most patients, painfully echoing in the heart and mind for years. Empathic and effective treatment of fetal loss may reduce the adverse impact of the event. Multiple studies have reported that combinations of mifepristone and misoprostol reduced the time from initiation of labor contractions to birth compared with misoprostol alone.^22-28 In addition, the combination of mifepristone-misoprostol reduced the amount of misoprostol needed to achieve delivery.^22,23

In one clinical trial, 66 patients with fetal demise between 14 and 28 weeks’ gestation were randomized to receive mifepristone 200 mg or placebo.²² Twenty-four to 48 hours later, misoprostol for induction of labor was initiated. Among the patients from 14 to 23 completed weeks of gestation, the misoprostol dose was 400 µg vaginally every 6 hours. For patients from 24 to 28 weeks gestation, the misoprostol dose was 200 µg vaginally every 4 hours. The median times from initiation of misoprostol to birth for the patients in the mifepristone and placebo groups were 6.8 hours and 10.5 hours (P=.002).

Compared with the patients in the placebo-misoprostol group, the patients in the mifepristone-misoprostol group required fewer doses of misoprostol (2.1 vs 3.4; P=.002) and a lower total dose of misoprostol (768 µg vs 1,182 µg; P=.003). All patients in the mifepristone group delivered within 24 hours. By contrast, 13% of the patients in the placebo group delivered more than 24 hours after the initiation of misoprostol treatment. Five patients were readmitted with retained products of conception needing suction curettage—4 in the placebo group and 1 in the mifepristone group.²²

In a second clinical trial, 110 patients with fetal demise after 20 weeks of gestation were randomized to receive mifepristone 200 mg or placebo.²³ Thirty-six to 48 hours later, misoprostol for induction of labor was initiated. Among the patients from 20 to 25 completed weeks of gestation, the misoprostol dose was 100 µg vaginally every 6 hours for a maximum of 4 doses. For patients ≥26 weeks gestation, the misoprostol dose was 50 µg vaginally every 4 hours for a maximum of 6 doses. The median times from initiation of misoprostol to birth for the patients in the mifepristone and placebo groups were 9.8 hours and 16.3 hours. (P=.001).

Compared with the patients in the placebo-misoprostol group, the patients in the mifepristone-misoprostol group required a lower total dose of misoprostol (110 µg vs 198 µg, P<.001).

Delivery within 24 hours following initiation of misoprostol occurred in 93% and 73% of the patients in the mifepristone and placebo groups, respectively (P<.001). Compared with patients in the mifepristone group, shivering occurred more frequently among the patients in the placebo group (7.5% vs 19.2%; P=.09), likely because they received greater doses of misoprostol.²³

Miscarriage and fetal demise frequently cause patients to experience a range of emotions including denial, numbness, grief, anger, guilt, and depression. It may take months or years for people to progress to a tentative acceptance of the loss, refocusing on future aspirations. Empathic care and timely and effective medical intervention to resolve the pregnancy loss optimize outcomes. For medication treatment of miscarriage and fetal demise, mifepristone is an important agent because it improves the success rate for resolution of miscarriage without surgery and it shortens the time of labor for inductions for fetal demise. Obstetrician-gynecologists are the specialists leading advances in treatment of miscarriage and fetal demise. I encourage you to use mifepristone in your care of appropriate patients with miscarriage and fetal demise. ●

In the uterus, coordinated myometrial cell contraction is not triggered by neural activation; instead, myometrial cells work together as a contractile syncytium through cell-to-cell gap junction connections permitting the intercellular sharing of small molecules, which in turn facilitates activation of the actin-myosin contractile apparatus and coordinated uterine contraction. In myometrial cells, connexin 43 (Cx43) is the main gap junction protein. Cx43 permits the passage of small hydrophilic molecules (ATP) and ions (calcium) cell to cell. Estradiol increases Cx43 synthesis in human myometrial cells.¹ Progesterone decreases Cx43 synthesis effectively isolating myometrial cells, reducing cell-to-cell sharing of chemicals that stimulate contraction, blocking coordinated uterine contraction.² Progesterone suppression of Cx43 synthesis helps to prevent premature uterine contraction during pregnancy. At term, decreases in progesterone levels result in an increase in Cx43 synthesis, facilitating the onset of effective labor. In myometrial cells, antiprogestins, including mifepristone, increase the number of gap junction connections, facilitating a coordinated contractile signal in response to misoprostol or oxytocin.^3,4

It takes time for antiprogestins to stimulate myometrial cell production of Cx43. In the rat myometrium the administration of mifepristone results in a 2.5-fold increase of Cx43 mRNA transcripts within 9 hours and a 5.6-fold increase in 24 hours.³ Hence, most mifepristone treatment protocols involve administering mifepristone and waiting 24 to 48 hours before administering an agent that stimulates myometrial contraction, such as misoprostol. Antiprogestins also increase the sensitivity of myometrial cells to oxytocin stimulation of uterine contractions by increasing Cx43 concentration.⁴

Progesterone also regulates other important biological processes in the cervix, decidua, placenta, and cervix. Antiprogestins can facilitate cervical ripening and disrupt decidual function, interfering with the attachment of pregnancy tissue.⁵ In the cervix, antiprogestins increase matrix metalloproteinase expression, disrupting collagen organization, decreasing cervical tensile strength and leading to cervical ripening.⁶

Pharmacology of mifepristone

Mifepristone is an antiprogestin and antiglucocorticoid with high-affinity binding to both the progesterone and glucocorticoid receptors (FIGURE 1). The phenylaminodimethyl group at C-11 of mifepristone changes the positional equilibrium of helix 12 of the progesterone receptor, reducing the ability of the receptor to bind required co-activators, limiting receptor binding to DNA, resulting in an antiprogesterone effect.⁷ At the low, single-dose used for treatment of miscarriage and fetal demise (200 mg one dose), mifepristone is an antiprogestin. At the high, daily dose used for the treatment of hyperglycemia caused by Cushing disease (≥ 300 mg daily), mifepristone is also an antiglucocorticoid.

Although mifepristone is a powerful antiglucocorticoid, in patients with an intact hypothalamic-pituitary-adrenal axis, mifepristone does not cause adrenal insufficiency. In people with an intact hypothalamic-pituitary-adrenal axis, daily administration of mifepristone (≥ 200 mg) for 7 days or longer results in an increase in pituitary secretion of ACTH and adrenal secretion of cortisol, largely overcoming the antiglucocorticoid action of mifepristone.^8-10 This compensatory increase in ACTH and cortisol is not possible in patients who have had a hypophysectomy or bilateral adrenalectomy or have adrenal suppression due to long-term treatment with high doses of glucocorticoids. Mifepristone is contraindicated for patients with these conditions because it may cause glucocorticoid insufficiency by blocking glucocorticoid receptors.

The terminal half-life of mifepristone is 18 hours.¹¹ Following oral administration of a single dose of mifepristone 200 mg the peak circulating concentration is reached in 90 minutes. Mifepristone is metabolized by CYP3A4 and is also a strong inhibitor of CYP3A4. Contraindications to the use of mifepristone include adrenal failure, porphyria, hemorrhagic diseases, anticoagulation, an IUD in the uterus, ectopic pregnancy, long-term glucocorticoid administration, and an undiagnosed adnexal mass.

Continue to: Mifepristone-misoprostol for the treatment of early missed miscarriage with a gestational sac...

Mifepristone-misoprostol for the treatment of early missed miscarriage with a gestational sac

For patients with a miscarriage, the treatment options to resolve the pregnancy loss are expectant management, medication, or surgery.¹² Joint decision-making is recommended to establish a management plan that supports the patient’s values. Expectant management is most likely to result in a multi-week process to achieve completion of the miscarriage. A surgical procedure is most likely to result in rapid resolution of the miscarriage with the greatest rate of success. Surgical evacuation of the uterus may be the preferred option for patients who have excessive uterine bleeding or concerning vital signs. Both medical and surgical management are more likely than expectant management to successfully resolve the miscarriage.¹³

In the past, the standard approach to medication management of a miscarriage was the administration of one or more doses of misoprostol, a synthetic prostaglandin E1. However, two large trials have reported that the dual-medication sequence of mifepristone followed 24 to 48 hours later by misoprostol is more effective than misoprostol alone for resolving a miscarriage.^14,15 This is probably due to mifepristone making the uterus more responsive to the effects of misoprostol.

Schreiber and colleagues¹⁴ reported a study of 300 patients with an anembryonic gestation or embryonic demise, between 5 and 12 completed weeks of gestation, who were randomly assigned to treatment with mifepristone (200 mg) followed in 24 to 48 hours with vaginal misoprostol (800 µg) or vaginal misoprostol (800 µg) alone. Ultrasonography was performed 1 to 4 days after misoprostol administration. Successful treatment was defined as expulsion of the gestational sac plus no additional surgical or medical intervention within 30 days after treatment. In this study, the dual-medication regimen of mifepristone-misoprostol was more successful than misoprostol alone in resolving the miscarriage, 84% and 67%, respectively (relative risk [RR], 1.25; 95% confidence interval [CI], 1.09–1.43).

Surgical evacuation of the uterus occurred less often with mifepristone-misoprostol treatment than with misoprostol monotherapy—9% and 24%, respectively (RR, 0.37; 95% CI, 0.21–0.68). Pelvic infection occurred in 2 patients (1.3%) in each group. Uterine bleeding managed with blood transfusion occurred in 3 patients who received mifepristone-misoprostol and 1 patient who received misoprostol alone. In this study, clinical factors including active bleeding, parity, and gestational age did not influence treatment success with the mifepristone-misoprostol regimen.¹⁶ The mifepristone-misoprostol regimen was reported to be more cost-effective than misoprostol alone.¹⁷

Chu and colleagues¹⁵ reported a study of medication treatment of missed miscarriage that included more than 700 patients randomly assigned to treatment with mifepristone-misoprostol or placebo-misoprostol. Missed miscarriage was diagnosed by an ultrasound demonstrating a gestational sac and a nonviable pregnancy. The doses of mifepristone and misoprostol were 200 mg and 800 µg, respectively. In this study the misoprostol was administered 48 hours following mifepristone or placebo using a vaginal, oral, or buccal route, but 90% of patients used the vaginal route. Treatment was considered successful if the patient passed the gestational sac as determined by an ultrasound performed 7 days after entry into the study. If the gestational sac was passed, the patients were asked to do a urine pregnancy test 3 weeks after entering the study to conclude their care episode. If patients did not pass the gestational sac, they were offered a second dose of misoprostol or surgical evacuation. In this study, mifepristone-misoprostol resulted in fewer patients who did not pass the gestational sac within 7 days after entry into the study than placebo (mifepristone-misoprostol, 17% vs placebo-misoprostol, 24% (P=.043). Surgical intervention was performed in 25% of patients treated with placebo-misoprostol and 17% of patients treated with mifepristone-misoprostol (RR, 0.73; 95% CI, 0.53–0.95; P=.021). A cost-effectiveness analysis of the trial results reported that the combination of mifepristone-misoprostol was less costly than misoprostol alone for the management of missed miscarriages.¹⁸

Misoprostol can be administered by an oral, buccal, rectal, or vaginal route.^19,20 Vaginal administration results in higher circulating concentrations of misoprostol than buccal administration, but both routes of administration produce similar mean uterine tone and mean uterine activity as measured by an intrauterine pressure transducer over 5 hours.²¹ Hence, at our institution, we most often use buccal administration of misoprostol. To assess effectiveness of mifepristone-misoprostol treatment, 1 week after treatment with a pelvic ultrasound to detect expulsion of the gestational sac. Alternatively, a urine pregnancy test can be performed 3 weeks following medication treatment. The mifepristone-misoprostol regimen is not approved by the US Food and Drug Administration for the treatment of miscarriage.

Continue to: Mifepristone-misoprostol for the treatment of fetal demise...

Mifepristone-misoprostol for the treatment of fetal demise

Fetal loss in the second or third trimesters is a devastating experience for most patients, painfully echoing in the heart and mind for years. Empathic and effective treatment of fetal loss may reduce the adverse impact of the event. Multiple studies have reported that combinations of mifepristone and misoprostol reduced the time from initiation of labor contractions to birth compared with misoprostol alone.^22-28 In addition, the combination of mifepristone-misoprostol reduced the amount of misoprostol needed to achieve delivery.^22,23

In one clinical trial, 66 patients with fetal demise between 14 and 28 weeks’ gestation were randomized to receive mifepristone 200 mg or placebo.²² Twenty-four to 48 hours later, misoprostol for induction of labor was initiated. Among the patients from 14 to 23 completed weeks of gestation, the misoprostol dose was 400 µg vaginally every 6 hours. For patients from 24 to 28 weeks gestation, the misoprostol dose was 200 µg vaginally every 4 hours. The median times from initiation of misoprostol to birth for the patients in the mifepristone and placebo groups were 6.8 hours and 10.5 hours (P=.002).

Compared with the patients in the placebo-misoprostol group, the patients in the mifepristone-misoprostol group required fewer doses of misoprostol (2.1 vs 3.4; P=.002) and a lower total dose of misoprostol (768 µg vs 1,182 µg; P=.003). All patients in the mifepristone group delivered within 24 hours. By contrast, 13% of the patients in the placebo group delivered more than 24 hours after the initiation of misoprostol treatment. Five patients were readmitted with retained products of conception needing suction curettage—4 in the placebo group and 1 in the mifepristone group.²²

In a second clinical trial, 110 patients with fetal demise after 20 weeks of gestation were randomized to receive mifepristone 200 mg or placebo.²³ Thirty-six to 48 hours later, misoprostol for induction of labor was initiated. Among the patients from 20 to 25 completed weeks of gestation, the misoprostol dose was 100 µg vaginally every 6 hours for a maximum of 4 doses. For patients ≥26 weeks gestation, the misoprostol dose was 50 µg vaginally every 4 hours for a maximum of 6 doses. The median times from initiation of misoprostol to birth for the patients in the mifepristone and placebo groups were 9.8 hours and 16.3 hours. (P=.001).

Compared with the patients in the placebo-misoprostol group, the patients in the mifepristone-misoprostol group required a lower total dose of misoprostol (110 µg vs 198 µg, P<.001).

Delivery within 24 hours following initiation of misoprostol occurred in 93% and 73% of the patients in the mifepristone and placebo groups, respectively (P<.001). Compared with patients in the mifepristone group, shivering occurred more frequently among the patients in the placebo group (7.5% vs 19.2%; P=.09), likely because they received greater doses of misoprostol.²³

Miscarriage and fetal demise frequently cause patients to experience a range of emotions including denial, numbness, grief, anger, guilt, and depression. It may take months or years for people to progress to a tentative acceptance of the loss, refocusing on future aspirations. Empathic care and timely and effective medical intervention to resolve the pregnancy loss optimize outcomes. For medication treatment of miscarriage and fetal demise, mifepristone is an important agent because it improves the success rate for resolution of miscarriage without surgery and it shortens the time of labor for inductions for fetal demise. Obstetrician-gynecologists are the specialists leading advances in treatment of miscarriage and fetal demise. I encourage you to use mifepristone in your care of appropriate patients with miscarriage and fetal demise. ●

In the uterus, coordinated myometrial cell contraction is not triggered by neural activation; instead, myometrial cells work together as a contractile syncytium through cell-to-cell gap junction connections permitting the intercellular sharing of small molecules, which in turn facilitates activation of the actin-myosin contractile apparatus and coordinated uterine contraction. In myometrial cells, connexin 43 (Cx43) is the main gap junction protein. Cx43 permits the passage of small hydrophilic molecules (ATP) and ions (calcium) cell to cell. Estradiol increases Cx43 synthesis in human myometrial cells.¹ Progesterone decreases Cx43 synthesis effectively isolating myometrial cells, reducing cell-to-cell sharing of chemicals that stimulate contraction, blocking coordinated uterine contraction.² Progesterone suppression of Cx43 synthesis helps to prevent premature uterine contraction during pregnancy. At term, decreases in progesterone levels result in an increase in Cx43 synthesis, facilitating the onset of effective labor. In myometrial cells, antiprogestins, including mifepristone, increase the number of gap junction connections, facilitating a coordinated contractile signal in response to misoprostol or oxytocin.^3,4

It takes time for antiprogestins to stimulate myometrial cell production of Cx43. In the rat myometrium the administration of mifepristone results in a 2.5-fold increase of Cx43 mRNA transcripts within 9 hours and a 5.6-fold increase in 24 hours.³ Hence, most mifepristone treatment protocols involve administering mifepristone and waiting 24 to 48 hours before administering an agent that stimulates myometrial contraction, such as misoprostol. Antiprogestins also increase the sensitivity of myometrial cells to oxytocin stimulation of uterine contractions by increasing Cx43 concentration.⁴

Progesterone also regulates other important biological processes in the cervix, decidua, placenta, and cervix. Antiprogestins can facilitate cervical ripening and disrupt decidual function, interfering with the attachment of pregnancy tissue.⁵ In the cervix, antiprogestins increase matrix metalloproteinase expression, disrupting collagen organization, decreasing cervical tensile strength and leading to cervical ripening.⁶

Pharmacology of mifepristone

Mifepristone is an antiprogestin and antiglucocorticoid with high-affinity binding to both the progesterone and glucocorticoid receptors (FIGURE 1). The phenylaminodimethyl group at C-11 of mifepristone changes the positional equilibrium of helix 12 of the progesterone receptor, reducing the ability of the receptor to bind required co-activators, limiting receptor binding to DNA, resulting in an antiprogesterone effect.⁷ At the low, single-dose used for treatment of miscarriage and fetal demise (200 mg one dose), mifepristone is an antiprogestin. At the high, daily dose used for the treatment of hyperglycemia caused by Cushing disease (≥ 300 mg daily), mifepristone is also an antiglucocorticoid.

Although mifepristone is a powerful antiglucocorticoid, in patients with an intact hypothalamic-pituitary-adrenal axis, mifepristone does not cause adrenal insufficiency. In people with an intact hypothalamic-pituitary-adrenal axis, daily administration of mifepristone (≥ 200 mg) for 7 days or longer results in an increase in pituitary secretion of ACTH and adrenal secretion of cortisol, largely overcoming the antiglucocorticoid action of mifepristone.^8-10 This compensatory increase in ACTH and cortisol is not possible in patients who have had a hypophysectomy or bilateral adrenalectomy or have adrenal suppression due to long-term treatment with high doses of glucocorticoids. Mifepristone is contraindicated for patients with these conditions because it may cause glucocorticoid insufficiency by blocking glucocorticoid receptors.

The terminal half-life of mifepristone is 18 hours.¹¹ Following oral administration of a single dose of mifepristone 200 mg the peak circulating concentration is reached in 90 minutes. Mifepristone is metabolized by CYP3A4 and is also a strong inhibitor of CYP3A4. Contraindications to the use of mifepristone include adrenal failure, porphyria, hemorrhagic diseases, anticoagulation, an IUD in the uterus, ectopic pregnancy, long-term glucocorticoid administration, and an undiagnosed adnexal mass.

Continue to: Mifepristone-misoprostol for the treatment of early missed miscarriage with a gestational sac...

Mifepristone-misoprostol for the treatment of early missed miscarriage with a gestational sac

For patients with a miscarriage, the treatment options to resolve the pregnancy loss are expectant management, medication, or surgery.¹² Joint decision-making is recommended to establish a management plan that supports the patient’s values. Expectant management is most likely to result in a multi-week process to achieve completion of the miscarriage. A surgical procedure is most likely to result in rapid resolution of the miscarriage with the greatest rate of success. Surgical evacuation of the uterus may be the preferred option for patients who have excessive uterine bleeding or concerning vital signs. Both medical and surgical management are more likely than expectant management to successfully resolve the miscarriage.¹³

In the past, the standard approach to medication management of a miscarriage was the administration of one or more doses of misoprostol, a synthetic prostaglandin E1. However, two large trials have reported that the dual-medication sequence of mifepristone followed 24 to 48 hours later by misoprostol is more effective than misoprostol alone for resolving a miscarriage.^14,15 This is probably due to mifepristone making the uterus more responsive to the effects of misoprostol.

Schreiber and colleagues¹⁴ reported a study of 300 patients with an anembryonic gestation or embryonic demise, between 5 and 12 completed weeks of gestation, who were randomly assigned to treatment with mifepristone (200 mg) followed in 24 to 48 hours with vaginal misoprostol (800 µg) or vaginal misoprostol (800 µg) alone. Ultrasonography was performed 1 to 4 days after misoprostol administration. Successful treatment was defined as expulsion of the gestational sac plus no additional surgical or medical intervention within 30 days after treatment. In this study, the dual-medication regimen of mifepristone-misoprostol was more successful than misoprostol alone in resolving the miscarriage, 84% and 67%, respectively (relative risk [RR], 1.25; 95% confidence interval [CI], 1.09–1.43).

Surgical evacuation of the uterus occurred less often with mifepristone-misoprostol treatment than with misoprostol monotherapy—9% and 24%, respectively (RR, 0.37; 95% CI, 0.21–0.68). Pelvic infection occurred in 2 patients (1.3%) in each group. Uterine bleeding managed with blood transfusion occurred in 3 patients who received mifepristone-misoprostol and 1 patient who received misoprostol alone. In this study, clinical factors including active bleeding, parity, and gestational age did not influence treatment success with the mifepristone-misoprostol regimen.¹⁶ The mifepristone-misoprostol regimen was reported to be more cost-effective than misoprostol alone.¹⁷

Chu and colleagues¹⁵ reported a study of medication treatment of missed miscarriage that included more than 700 patients randomly assigned to treatment with mifepristone-misoprostol or placebo-misoprostol. Missed miscarriage was diagnosed by an ultrasound demonstrating a gestational sac and a nonviable pregnancy. The doses of mifepristone and misoprostol were 200 mg and 800 µg, respectively. In this study the misoprostol was administered 48 hours following mifepristone or placebo using a vaginal, oral, or buccal route, but 90% of patients used the vaginal route. Treatment was considered successful if the patient passed the gestational sac as determined by an ultrasound performed 7 days after entry into the study. If the gestational sac was passed, the patients were asked to do a urine pregnancy test 3 weeks after entering the study to conclude their care episode. If patients did not pass the gestational sac, they were offered a second dose of misoprostol or surgical evacuation. In this study, mifepristone-misoprostol resulted in fewer patients who did not pass the gestational sac within 7 days after entry into the study than placebo (mifepristone-misoprostol, 17% vs placebo-misoprostol, 24% (P=.043). Surgical intervention was performed in 25% of patients treated with placebo-misoprostol and 17% of patients treated with mifepristone-misoprostol (RR, 0.73; 95% CI, 0.53–0.95; P=.021). A cost-effectiveness analysis of the trial results reported that the combination of mifepristone-misoprostol was less costly than misoprostol alone for the management of missed miscarriages.¹⁸

Misoprostol can be administered by an oral, buccal, rectal, or vaginal route.^19,20 Vaginal administration results in higher circulating concentrations of misoprostol than buccal administration, but both routes of administration produce similar mean uterine tone and mean uterine activity as measured by an intrauterine pressure transducer over 5 hours.²¹ Hence, at our institution, we most often use buccal administration of misoprostol. To assess effectiveness of mifepristone-misoprostol treatment, 1 week after treatment with a pelvic ultrasound to detect expulsion of the gestational sac. Alternatively, a urine pregnancy test can be performed 3 weeks following medication treatment. The mifepristone-misoprostol regimen is not approved by the US Food and Drug Administration for the treatment of miscarriage.

Continue to: Mifepristone-misoprostol for the treatment of fetal demise...

Mifepristone-misoprostol for the treatment of fetal demise

Fetal loss in the second or third trimesters is a devastating experience for most patients, painfully echoing in the heart and mind for years. Empathic and effective treatment of fetal loss may reduce the adverse impact of the event. Multiple studies have reported that combinations of mifepristone and misoprostol reduced the time from initiation of labor contractions to birth compared with misoprostol alone.^22-28 In addition, the combination of mifepristone-misoprostol reduced the amount of misoprostol needed to achieve delivery.^22,23

In one clinical trial, 66 patients with fetal demise between 14 and 28 weeks’ gestation were randomized to receive mifepristone 200 mg or placebo.²² Twenty-four to 48 hours later, misoprostol for induction of labor was initiated. Among the patients from 14 to 23 completed weeks of gestation, the misoprostol dose was 400 µg vaginally every 6 hours. For patients from 24 to 28 weeks gestation, the misoprostol dose was 200 µg vaginally every 4 hours. The median times from initiation of misoprostol to birth for the patients in the mifepristone and placebo groups were 6.8 hours and 10.5 hours (P=.002).

Compared with the patients in the placebo-misoprostol group, the patients in the mifepristone-misoprostol group required fewer doses of misoprostol (2.1 vs 3.4; P=.002) and a lower total dose of misoprostol (768 µg vs 1,182 µg; P=.003). All patients in the mifepristone group delivered within 24 hours. By contrast, 13% of the patients in the placebo group delivered more than 24 hours after the initiation of misoprostol treatment. Five patients were readmitted with retained products of conception needing suction curettage—4 in the placebo group and 1 in the mifepristone group.²²

In a second clinical trial, 110 patients with fetal demise after 20 weeks of gestation were randomized to receive mifepristone 200 mg or placebo.²³ Thirty-six to 48 hours later, misoprostol for induction of labor was initiated. Among the patients from 20 to 25 completed weeks of gestation, the misoprostol dose was 100 µg vaginally every 6 hours for a maximum of 4 doses. For patients ≥26 weeks gestation, the misoprostol dose was 50 µg vaginally every 4 hours for a maximum of 6 doses. The median times from initiation of misoprostol to birth for the patients in the mifepristone and placebo groups were 9.8 hours and 16.3 hours. (P=.001).

Compared with the patients in the placebo-misoprostol group, the patients in the mifepristone-misoprostol group required a lower total dose of misoprostol (110 µg vs 198 µg, P<.001).

Delivery within 24 hours following initiation of misoprostol occurred in 93% and 73% of the patients in the mifepristone and placebo groups, respectively (P<.001). Compared with patients in the mifepristone group, shivering occurred more frequently among the patients in the placebo group (7.5% vs 19.2%; P=.09), likely because they received greater doses of misoprostol.²³

Miscarriage and fetal demise frequently cause patients to experience a range of emotions including denial, numbness, grief, anger, guilt, and depression. It may take months or years for people to progress to a tentative acceptance of the loss, refocusing on future aspirations. Empathic care and timely and effective medical intervention to resolve the pregnancy loss optimize outcomes. For medication treatment of miscarriage and fetal demise, mifepristone is an important agent because it improves the success rate for resolution of miscarriage without surgery and it shortens the time of labor for inductions for fetal demise. Obstetrician-gynecologists are the specialists leading advances in treatment of miscarriage and fetal demise. I encourage you to use mifepristone in your care of appropriate patients with miscarriage and fetal demise. ●

CASE Pregnant woman’s husband is ill after traveling

A 29-year-old primigravid woman at 18 weeks’ gestation just returned from a 10-day trip to Nigeria with her husband. While in Nigeria, the couple went on safari. On several occasions during the safari, they consumed bushmeat prepared by their guides. Her husband now has severe malaise, fever, chills, myalgias, cough, and prominent submandibular, cervical, and inguinal adenopathy. In addition, he has developed a diffuse papular-vesicular rash on his trunk and extremities.

• What is the most likely diagnosis?
• Does this condition pose a danger to his wife?
• What treatment is indicated for his wife?

What we know

In recent weeks, the specter of another poorly understood biological threat has emerged in the medical literature and lay press: monkeypox. This article will first review the epidemiology, clinical manifestations, and diagnosis of this infection, followed by a discussion of how to prevent and treat the condition, with special emphasis on the risks that this infection poses in pregnant women.

Virology

The monkeypox virus is a member of the orthopoxvirus genus. The variola (smallpox) virus and vaccinia virus are included in this genus. It is one of the largest of all viruses, measuring 200-250 nm. It is enveloped and contains double-stranded DNA. Its natural reservoir is probably African rodents. Two distinct strains of monkeypox exist in different geographical regions of Africa: the Central African clade and the West African clade. The Central African clade is significantly more virulent than the latter, with a mortality rate approaching 10%, versus 1% in the West African clade. The incubation period of the virus ranges from 4-20 days and averages 12 days.^1,2

Epidemiology

Monkeypox was first discovered in 1958 by Preben von Magnus in a colony of research monkeys in Copenhagen, Denmark. The first case of monkeypox in humans occurred in the Democratic Republic of Congo in 1970 in a 9-year-old boy. Subsequently, cases were reported in the Ivory Coast, Liberia, Nigeria, and Sierra Leone. The infection was limited to the rain forests of central and western Africa until 2003. At that time, the first cases in the United States were reported. The US cases occurred in the Midwest and were traced to exposure to pet prairie dogs. These animals all came from a single distributor, and they apparently were infected when they were housed in the same space with Gambian rats, which are well recognized reservoirs of monkeypox in their native habitat in Africa.^1-3

A limited outbreak of monkeypox occurred in the United Kingdom in 2018. Seventy-one cases, with no fatalities, were reported. In 2021 another US case of monkeypox was reported in Dallas, Texas, in an individual who had recently traveled to the United States from Nigeria. A second US case was reported in November 2021 from a patient in Maryland who had returned from a visit to Nigeria. Those were the only 2 reported cases of monkeypox in the United States in 2021.^1-3

Then in early May 2022, the United Kingdom reported 9 cases of monkeypox. The first infected patient had recently traveled to Nigeria and, subsequently, infected 2 members of his family.⁴ On May 18, the Massachusetts Department of Public Health confirmed a case of monkeypox in an adult man who had recently traveled to Canada. As of July 7, 6,027 cases have been reported from at least 39 countries.⁵ Eight states in the United States reported cases. To date, 73 deaths have occurred in this recent outbreak of infections (case fatality rate, 4.5%).^4-6

The current outbreak is unusual in that, previously, almost all cases occurred in western and central Africa in remote tropical rain forests. Infection usually resulted from close exposure to rats, rabbits, squirrels, monkeys, porcupines, and gazelles. Exposure occurred when persons captured, slaughtered, prepared, and then ate these animals for food without properly cooking the flesh.

The leading theory is that the present outbreak originated among men who had sex with men at 2 raves held in Spain and Belgium. The virus appears to have been spread by skin-to-skin contact, by respiratory droplets, by contact with contaminated bedding, and probably by sperm.^2,4,6

Continue to: Clinical manifestations...

Clinical manifestations

Monkeypox evolves through 2 stages: a pre-eruptive stage and an eruptive stage. Prodromal symptoms include malaise, severe headache, myalgias, fever, drenching sweats, backache, fatigue, sore throat, dyspnea, and cough. Within 2-3 days, the characteristic skin eruption develops. The lesions usually begin on the face and then spread in a centrifugal manner to the trunk and extremities, including the palms of the hands and soles of the feet. The lesions typically progress from macules to papules to vesicles to pustules. They then crust and scab over. An interesting additional finding is the presence of prominent lymphadenopathy behind the ear, beneath the mandible, in the neck, and in the groin.¹

Several different illnesses must be considered in the differential diagnosis of monkeypox infection. They include measles, scabies, secondary syphilis, and medication-associated allergic reactions. However, the 2 conditions most likely to be confused with monkeypox are chickenpox (varicella) and smallpox. Lymphadenopathy is much more prominent in monkeypox compared with chickenpox. Moreover, with monkeypox, all lesions tend to be at the same stage of evolution as opposed to appearing in crops as they do in chickenpox. Smallpox would be extremely unlikely in the absence of a recognized laboratory accident or a bioterrorism incident.⁷

Diagnosis

The presumptive diagnosis of monkeypox infection is made primarily based on clinical examination. However, laboratory testing is indicated to definitively differentiate monkeypox from other orthopoxvirus infections such as varicella and smallpox.

In specialized laboratories that employ highly trained personnel and maintain strict safety precautions, the virus can be isolated in mammalian cell cultures. Electron microscopy is a valuable tool for identifying the characteristic brick-shaped poxvirus virions. Routine histologic examination of a lesion will show ballooning degeneration of keratinocytes, prominent spongiosis, dermal edema, and acute inflammation, although these findings are not unique to monkeypox.¹

The Centers for Disease Control and Prevention (CDC) has developed serologic tests that detect immunoglobulin (Ig) M- and IgG-specific antibody. However, the most useful and practical diagnostic test is assessment of a skin scraping by polymerase chain reaction (PCR). This test is more sensitive than assessment of serum PCR.¹

When the diagnosis of monkeypox is being considered, the clinician should coordinate testing through the local and state public health departments and through the CDC. Effective communication with all agencies will ensure that laboratory specimens are processed in a timely and efficient manner. The CDC website presents information on specimen collection.⁸

How do we manage monkeypox?

Prevention

The first step in prevention of infection is to isolate infected individuals until all lesions have dried and crusted over. Susceptible people should avoid close contact with skin lesions, respiratory and genital secretions, and bedding of patients who are infected.

The ultimate preventive measure, however, is vaccination of susceptible people either immediately before exposure (eg, military personnel, first responders, infection control investigators, health care workers) or immediately after exposure (general population). Older individuals who received the original smallpox vaccine likely have immunity to monkeypox infection. Unfortunately, very few women who currently are of reproductive age received this vaccine because its use was discontinued in the United States in the early 1970s. Therefore, the vast majority of our patients are uniquely susceptible to this infection and should be vaccinated if there is an outbreak of monkeypox in their locality.^7,9

The current preferred vaccine for prevention of both smallpox and monkeypox is the Jynneos (Bavarian Nordic A/S) vaccine.¹⁰ This agent incorporates a replication-deficient live virus and does not pose the same risk for adverse events as the original versions of the smallpox vaccine. Jynneos is administered subcutaneously rather than by scarification. Two 0.5-mL doses, delivered 28 days apart, are required for optimal effect. The vaccine must be obtained from local and state health departments, in consultation with the CDC.^7,9

There is very little published information on the safety of the Jynneos vaccine in pregnant or lactating women, although animal data are reassuring. Moreover, the dangers of monkeypox infection are significant, and in the event of an outbreak, vaccination of susceptible individuals, including pregnant women, is indicated.

Continue to: Treatment...

Treatment

Infected pregnant women should receive acetaminophen 1,000 mg orally every 8 hours, to control fever and provide analgesia. An antihistamine such as diphenhydramine 25 mg orally every 6-8 hours, may be used to control pruritus and provide mild sedation. Adequate fluid intake and optimal nutrition should be encouraged. Skin lesions should be inspected regularly to detect signs of superimposed bacterial infections. Small, localized bacterial skin infections can be treated with topical application of mupirocin ointment 2%, 3 times daily for 7-14 days. For diffuse and more severe bacterial skin infections, a systemic antibiotic may be necessary. Reasonable choices include amoxicillin-clavulanate 875 mg/125 mg orally every 12 hours, or trimethoprim-sulfamethoxazole double strength 800 mg/160 mg orally every 12 hours.¹¹ The latter agent should be avoided in the first trimester of pregnancy because of potential teratogenic effects.

Several specific agents are available through the CDC for treatment of orthopoxvirus infections such as smallpox and monkeypox. Information about these agents is summarized in the TABLE.^12-16

Unique considerations in pregnancy

Because monkeypox is so rare, there is very little information about the effects of this infection in pregnant women. The report most commonly cited in the literature is that by Mbala et al, which was published in 2017.¹⁷ These authors described 4 pregnant patients in the Democratic Republic of Congo who contracted monkeypox infection over a 4-year period. All 4 women were hospitalized and treated with systemic antibiotics, antiparasitic medications, and analgesics. One patient delivered a healthy infant. Two women had spontaneous abortions in the first trimester. The fourth patient experienced a stillbirth at 22 weeks’ gestation. At postmortem examination, the fetus had diffuse cutaneous lesions, prominent hepatomegaly, and hydrops. No structural malformations were noted. The placenta demonstrated numerous punctate hemorrhages, and high concentrations of virus were recovered from the placenta and from fetal tissue.

Although the information on pregnancy outcome is quite limited, it seems clear that the virus can cross the placenta and cause adverse effects such as spontaneous abortion and fetal death. Accordingly, I think the following guidelines are a reasonable approach to a pregnant patient who has been exposed to monkeypox or who has developed manifestations of infection.^3,7,9

• In the event of a community outbreak, bioterrorism event, or exposure to a person with suspected or confirmed monkeypox infection, the pregnant patient should receive the Jynneos vaccine.
• The pregnant patient should be isolated from any individual with suspected or confirmed monkeypox.
• If infection develops despite these measures, the patient should be treated with either tecovirimat or vaccinia immune globulin IV. Hospitalization may be necessary for seriously ill individuals.

• Within 2 weeks of infection, a comprehensive ultrasound examination should be performed to assess for structural abnormalities in the fetus.

• Subsequently, serial ultrasound examinations should be performed at intervals of 4-6 weeks to assess fetal growth and re-evaluate fetal anatomy.
• Following delivery, a detailed neonatal examination should be performed to assess for evidence of viral injury. Neonatal skin lesions and neonatal serum can be assessed by PCR for monkeypox virus. The newborn should be isolated from the mother until all the mother’s lesions have dried and crusted over.

CASE Resolved

Given the husband’s recent travel to Nigeria and consumption of bushmeat, he most likely has monkeypox. The infection can be spread from person to person by close contact; thus, his wife is at risk. The couple should isolate until all of his lesions have dried and crusted over. The woman also should receive the Jynneos vaccine. If she becomes symptomatic, she should be treated with tecovirimat or vaccinia immune globulin IV. ●

CASE Pregnant woman’s husband is ill after traveling

A 29-year-old primigravid woman at 18 weeks’ gestation just returned from a 10-day trip to Nigeria with her husband. While in Nigeria, the couple went on safari. On several occasions during the safari, they consumed bushmeat prepared by their guides. Her husband now has severe malaise, fever, chills, myalgias, cough, and prominent submandibular, cervical, and inguinal adenopathy. In addition, he has developed a diffuse papular-vesicular rash on his trunk and extremities.

• What is the most likely diagnosis?
• Does this condition pose a danger to his wife?
• What treatment is indicated for his wife?

What we know

In recent weeks, the specter of another poorly understood biological threat has emerged in the medical literature and lay press: monkeypox. This article will first review the epidemiology, clinical manifestations, and diagnosis of this infection, followed by a discussion of how to prevent and treat the condition, with special emphasis on the risks that this infection poses in pregnant women.

Virology

The monkeypox virus is a member of the orthopoxvirus genus. The variola (smallpox) virus and vaccinia virus are included in this genus. It is one of the largest of all viruses, measuring 200-250 nm. It is enveloped and contains double-stranded DNA. Its natural reservoir is probably African rodents. Two distinct strains of monkeypox exist in different geographical regions of Africa: the Central African clade and the West African clade. The Central African clade is significantly more virulent than the latter, with a mortality rate approaching 10%, versus 1% in the West African clade. The incubation period of the virus ranges from 4-20 days and averages 12 days.^1,2

Epidemiology

Monkeypox was first discovered in 1958 by Preben von Magnus in a colony of research monkeys in Copenhagen, Denmark. The first case of monkeypox in humans occurred in the Democratic Republic of Congo in 1970 in a 9-year-old boy. Subsequently, cases were reported in the Ivory Coast, Liberia, Nigeria, and Sierra Leone. The infection was limited to the rain forests of central and western Africa until 2003. At that time, the first cases in the United States were reported. The US cases occurred in the Midwest and were traced to exposure to pet prairie dogs. These animals all came from a single distributor, and they apparently were infected when they were housed in the same space with Gambian rats, which are well recognized reservoirs of monkeypox in their native habitat in Africa.^1-3

A limited outbreak of monkeypox occurred in the United Kingdom in 2018. Seventy-one cases, with no fatalities, were reported. In 2021 another US case of monkeypox was reported in Dallas, Texas, in an individual who had recently traveled to the United States from Nigeria. A second US case was reported in November 2021 from a patient in Maryland who had returned from a visit to Nigeria. Those were the only 2 reported cases of monkeypox in the United States in 2021.^1-3

Then in early May 2022, the United Kingdom reported 9 cases of monkeypox. The first infected patient had recently traveled to Nigeria and, subsequently, infected 2 members of his family.⁴ On May 18, the Massachusetts Department of Public Health confirmed a case of monkeypox in an adult man who had recently traveled to Canada. As of July 7, 6,027 cases have been reported from at least 39 countries.⁵ Eight states in the United States reported cases. To date, 73 deaths have occurred in this recent outbreak of infections (case fatality rate, 4.5%).^4-6

The current outbreak is unusual in that, previously, almost all cases occurred in western and central Africa in remote tropical rain forests. Infection usually resulted from close exposure to rats, rabbits, squirrels, monkeys, porcupines, and gazelles. Exposure occurred when persons captured, slaughtered, prepared, and then ate these animals for food without properly cooking the flesh.

The leading theory is that the present outbreak originated among men who had sex with men at 2 raves held in Spain and Belgium. The virus appears to have been spread by skin-to-skin contact, by respiratory droplets, by contact with contaminated bedding, and probably by sperm.^2,4,6

Continue to: Clinical manifestations...

Clinical manifestations

Monkeypox evolves through 2 stages: a pre-eruptive stage and an eruptive stage. Prodromal symptoms include malaise, severe headache, myalgias, fever, drenching sweats, backache, fatigue, sore throat, dyspnea, and cough. Within 2-3 days, the characteristic skin eruption develops. The lesions usually begin on the face and then spread in a centrifugal manner to the trunk and extremities, including the palms of the hands and soles of the feet. The lesions typically progress from macules to papules to vesicles to pustules. They then crust and scab over. An interesting additional finding is the presence of prominent lymphadenopathy behind the ear, beneath the mandible, in the neck, and in the groin.¹

Several different illnesses must be considered in the differential diagnosis of monkeypox infection. They include measles, scabies, secondary syphilis, and medication-associated allergic reactions. However, the 2 conditions most likely to be confused with monkeypox are chickenpox (varicella) and smallpox. Lymphadenopathy is much more prominent in monkeypox compared with chickenpox. Moreover, with monkeypox, all lesions tend to be at the same stage of evolution as opposed to appearing in crops as they do in chickenpox. Smallpox would be extremely unlikely in the absence of a recognized laboratory accident or a bioterrorism incident.⁷

Diagnosis

The presumptive diagnosis of monkeypox infection is made primarily based on clinical examination. However, laboratory testing is indicated to definitively differentiate monkeypox from other orthopoxvirus infections such as varicella and smallpox.

In specialized laboratories that employ highly trained personnel and maintain strict safety precautions, the virus can be isolated in mammalian cell cultures. Electron microscopy is a valuable tool for identifying the characteristic brick-shaped poxvirus virions. Routine histologic examination of a lesion will show ballooning degeneration of keratinocytes, prominent spongiosis, dermal edema, and acute inflammation, although these findings are not unique to monkeypox.¹

The Centers for Disease Control and Prevention (CDC) has developed serologic tests that detect immunoglobulin (Ig) M- and IgG-specific antibody. However, the most useful and practical diagnostic test is assessment of a skin scraping by polymerase chain reaction (PCR). This test is more sensitive than assessment of serum PCR.¹

When the diagnosis of monkeypox is being considered, the clinician should coordinate testing through the local and state public health departments and through the CDC. Effective communication with all agencies will ensure that laboratory specimens are processed in a timely and efficient manner. The CDC website presents information on specimen collection.⁸

How do we manage monkeypox?

Prevention

The first step in prevention of infection is to isolate infected individuals until all lesions have dried and crusted over. Susceptible people should avoid close contact with skin lesions, respiratory and genital secretions, and bedding of patients who are infected.

The ultimate preventive measure, however, is vaccination of susceptible people either immediately before exposure (eg, military personnel, first responders, infection control investigators, health care workers) or immediately after exposure (general population). Older individuals who received the original smallpox vaccine likely have immunity to monkeypox infection. Unfortunately, very few women who currently are of reproductive age received this vaccine because its use was discontinued in the United States in the early 1970s. Therefore, the vast majority of our patients are uniquely susceptible to this infection and should be vaccinated if there is an outbreak of monkeypox in their locality.^7,9

The current preferred vaccine for prevention of both smallpox and monkeypox is the Jynneos (Bavarian Nordic A/S) vaccine.¹⁰ This agent incorporates a replication-deficient live virus and does not pose the same risk for adverse events as the original versions of the smallpox vaccine. Jynneos is administered subcutaneously rather than by scarification. Two 0.5-mL doses, delivered 28 days apart, are required for optimal effect. The vaccine must be obtained from local and state health departments, in consultation with the CDC.^7,9

There is very little published information on the safety of the Jynneos vaccine in pregnant or lactating women, although animal data are reassuring. Moreover, the dangers of monkeypox infection are significant, and in the event of an outbreak, vaccination of susceptible individuals, including pregnant women, is indicated.

Continue to: Treatment...

Treatment

Infected pregnant women should receive acetaminophen 1,000 mg orally every 8 hours, to control fever and provide analgesia. An antihistamine such as diphenhydramine 25 mg orally every 6-8 hours, may be used to control pruritus and provide mild sedation. Adequate fluid intake and optimal nutrition should be encouraged. Skin lesions should be inspected regularly to detect signs of superimposed bacterial infections. Small, localized bacterial skin infections can be treated with topical application of mupirocin ointment 2%, 3 times daily for 7-14 days. For diffuse and more severe bacterial skin infections, a systemic antibiotic may be necessary. Reasonable choices include amoxicillin-clavulanate 875 mg/125 mg orally every 12 hours, or trimethoprim-sulfamethoxazole double strength 800 mg/160 mg orally every 12 hours.¹¹ The latter agent should be avoided in the first trimester of pregnancy because of potential teratogenic effects.

Several specific agents are available through the CDC for treatment of orthopoxvirus infections such as smallpox and monkeypox. Information about these agents is summarized in the TABLE.^12-16

Unique considerations in pregnancy

Because monkeypox is so rare, there is very little information about the effects of this infection in pregnant women. The report most commonly cited in the literature is that by Mbala et al, which was published in 2017.¹⁷ These authors described 4 pregnant patients in the Democratic Republic of Congo who contracted monkeypox infection over a 4-year period. All 4 women were hospitalized and treated with systemic antibiotics, antiparasitic medications, and analgesics. One patient delivered a healthy infant. Two women had spontaneous abortions in the first trimester. The fourth patient experienced a stillbirth at 22 weeks’ gestation. At postmortem examination, the fetus had diffuse cutaneous lesions, prominent hepatomegaly, and hydrops. No structural malformations were noted. The placenta demonstrated numerous punctate hemorrhages, and high concentrations of virus were recovered from the placenta and from fetal tissue.

Although the information on pregnancy outcome is quite limited, it seems clear that the virus can cross the placenta and cause adverse effects such as spontaneous abortion and fetal death. Accordingly, I think the following guidelines are a reasonable approach to a pregnant patient who has been exposed to monkeypox or who has developed manifestations of infection.^3,7,9

• In the event of a community outbreak, bioterrorism event, or exposure to a person with suspected or confirmed monkeypox infection, the pregnant patient should receive the Jynneos vaccine.
• The pregnant patient should be isolated from any individual with suspected or confirmed monkeypox.
• If infection develops despite these measures, the patient should be treated with either tecovirimat or vaccinia immune globulin IV. Hospitalization may be necessary for seriously ill individuals.

• Within 2 weeks of infection, a comprehensive ultrasound examination should be performed to assess for structural abnormalities in the fetus.

• Subsequently, serial ultrasound examinations should be performed at intervals of 4-6 weeks to assess fetal growth and re-evaluate fetal anatomy.
• Following delivery, a detailed neonatal examination should be performed to assess for evidence of viral injury. Neonatal skin lesions and neonatal serum can be assessed by PCR for monkeypox virus. The newborn should be isolated from the mother until all the mother’s lesions have dried and crusted over.

CASE Resolved

Given the husband’s recent travel to Nigeria and consumption of bushmeat, he most likely has monkeypox. The infection can be spread from person to person by close contact; thus, his wife is at risk. The couple should isolate until all of his lesions have dried and crusted over. The woman also should receive the Jynneos vaccine. If she becomes symptomatic, she should be treated with tecovirimat or vaccinia immune globulin IV. ●

CASE Pregnant woman’s husband is ill after traveling

A 29-year-old primigravid woman at 18 weeks’ gestation just returned from a 10-day trip to Nigeria with her husband. While in Nigeria, the couple went on safari. On several occasions during the safari, they consumed bushmeat prepared by their guides. Her husband now has severe malaise, fever, chills, myalgias, cough, and prominent submandibular, cervical, and inguinal adenopathy. In addition, he has developed a diffuse papular-vesicular rash on his trunk and extremities.

• What is the most likely diagnosis?
• Does this condition pose a danger to his wife?
• What treatment is indicated for his wife?

What we know

In recent weeks, the specter of another poorly understood biological threat has emerged in the medical literature and lay press: monkeypox. This article will first review the epidemiology, clinical manifestations, and diagnosis of this infection, followed by a discussion of how to prevent and treat the condition, with special emphasis on the risks that this infection poses in pregnant women.

Virology

The monkeypox virus is a member of the orthopoxvirus genus. The variola (smallpox) virus and vaccinia virus are included in this genus. It is one of the largest of all viruses, measuring 200-250 nm. It is enveloped and contains double-stranded DNA. Its natural reservoir is probably African rodents. Two distinct strains of monkeypox exist in different geographical regions of Africa: the Central African clade and the West African clade. The Central African clade is significantly more virulent than the latter, with a mortality rate approaching 10%, versus 1% in the West African clade. The incubation period of the virus ranges from 4-20 days and averages 12 days.^1,2

Epidemiology

Monkeypox was first discovered in 1958 by Preben von Magnus in a colony of research monkeys in Copenhagen, Denmark. The first case of monkeypox in humans occurred in the Democratic Republic of Congo in 1970 in a 9-year-old boy. Subsequently, cases were reported in the Ivory Coast, Liberia, Nigeria, and Sierra Leone. The infection was limited to the rain forests of central and western Africa until 2003. At that time, the first cases in the United States were reported. The US cases occurred in the Midwest and were traced to exposure to pet prairie dogs. These animals all came from a single distributor, and they apparently were infected when they were housed in the same space with Gambian rats, which are well recognized reservoirs of monkeypox in their native habitat in Africa.^1-3

A limited outbreak of monkeypox occurred in the United Kingdom in 2018. Seventy-one cases, with no fatalities, were reported. In 2021 another US case of monkeypox was reported in Dallas, Texas, in an individual who had recently traveled to the United States from Nigeria. A second US case was reported in November 2021 from a patient in Maryland who had returned from a visit to Nigeria. Those were the only 2 reported cases of monkeypox in the United States in 2021.^1-3

Then in early May 2022, the United Kingdom reported 9 cases of monkeypox. The first infected patient had recently traveled to Nigeria and, subsequently, infected 2 members of his family.⁴ On May 18, the Massachusetts Department of Public Health confirmed a case of monkeypox in an adult man who had recently traveled to Canada. As of July 7, 6,027 cases have been reported from at least 39 countries.⁵ Eight states in the United States reported cases. To date, 73 deaths have occurred in this recent outbreak of infections (case fatality rate, 4.5%).^4-6

The current outbreak is unusual in that, previously, almost all cases occurred in western and central Africa in remote tropical rain forests. Infection usually resulted from close exposure to rats, rabbits, squirrels, monkeys, porcupines, and gazelles. Exposure occurred when persons captured, slaughtered, prepared, and then ate these animals for food without properly cooking the flesh.

The leading theory is that the present outbreak originated among men who had sex with men at 2 raves held in Spain and Belgium. The virus appears to have been spread by skin-to-skin contact, by respiratory droplets, by contact with contaminated bedding, and probably by sperm.^2,4,6

Continue to: Clinical manifestations...

Clinical manifestations

Monkeypox evolves through 2 stages: a pre-eruptive stage and an eruptive stage. Prodromal symptoms include malaise, severe headache, myalgias, fever, drenching sweats, backache, fatigue, sore throat, dyspnea, and cough. Within 2-3 days, the characteristic skin eruption develops. The lesions usually begin on the face and then spread in a centrifugal manner to the trunk and extremities, including the palms of the hands and soles of the feet. The lesions typically progress from macules to papules to vesicles to pustules. They then crust and scab over. An interesting additional finding is the presence of prominent lymphadenopathy behind the ear, beneath the mandible, in the neck, and in the groin.¹

Several different illnesses must be considered in the differential diagnosis of monkeypox infection. They include measles, scabies, secondary syphilis, and medication-associated allergic reactions. However, the 2 conditions most likely to be confused with monkeypox are chickenpox (varicella) and smallpox. Lymphadenopathy is much more prominent in monkeypox compared with chickenpox. Moreover, with monkeypox, all lesions tend to be at the same stage of evolution as opposed to appearing in crops as they do in chickenpox. Smallpox would be extremely unlikely in the absence of a recognized laboratory accident or a bioterrorism incident.⁷

Diagnosis

The presumptive diagnosis of monkeypox infection is made primarily based on clinical examination. However, laboratory testing is indicated to definitively differentiate monkeypox from other orthopoxvirus infections such as varicella and smallpox.

In specialized laboratories that employ highly trained personnel and maintain strict safety precautions, the virus can be isolated in mammalian cell cultures. Electron microscopy is a valuable tool for identifying the characteristic brick-shaped poxvirus virions. Routine histologic examination of a lesion will show ballooning degeneration of keratinocytes, prominent spongiosis, dermal edema, and acute inflammation, although these findings are not unique to monkeypox.¹

The Centers for Disease Control and Prevention (CDC) has developed serologic tests that detect immunoglobulin (Ig) M- and IgG-specific antibody. However, the most useful and practical diagnostic test is assessment of a skin scraping by polymerase chain reaction (PCR). This test is more sensitive than assessment of serum PCR.¹

When the diagnosis of monkeypox is being considered, the clinician should coordinate testing through the local and state public health departments and through the CDC. Effective communication with all agencies will ensure that laboratory specimens are processed in a timely and efficient manner. The CDC website presents information on specimen collection.⁸

How do we manage monkeypox?

Prevention

The first step in prevention of infection is to isolate infected individuals until all lesions have dried and crusted over. Susceptible people should avoid close contact with skin lesions, respiratory and genital secretions, and bedding of patients who are infected.

The ultimate preventive measure, however, is vaccination of susceptible people either immediately before exposure (eg, military personnel, first responders, infection control investigators, health care workers) or immediately after exposure (general population). Older individuals who received the original smallpox vaccine likely have immunity to monkeypox infection. Unfortunately, very few women who currently are of reproductive age received this vaccine because its use was discontinued in the United States in the early 1970s. Therefore, the vast majority of our patients are uniquely susceptible to this infection and should be vaccinated if there is an outbreak of monkeypox in their locality.^7,9

The current preferred vaccine for prevention of both smallpox and monkeypox is the Jynneos (Bavarian Nordic A/S) vaccine.¹⁰ This agent incorporates a replication-deficient live virus and does not pose the same risk for adverse events as the original versions of the smallpox vaccine. Jynneos is administered subcutaneously rather than by scarification. Two 0.5-mL doses, delivered 28 days apart, are required for optimal effect. The vaccine must be obtained from local and state health departments, in consultation with the CDC.^7,9

There is very little published information on the safety of the Jynneos vaccine in pregnant or lactating women, although animal data are reassuring. Moreover, the dangers of monkeypox infection are significant, and in the event of an outbreak, vaccination of susceptible individuals, including pregnant women, is indicated.

Continue to: Treatment...

Treatment

Infected pregnant women should receive acetaminophen 1,000 mg orally every 8 hours, to control fever and provide analgesia. An antihistamine such as diphenhydramine 25 mg orally every 6-8 hours, may be used to control pruritus and provide mild sedation. Adequate fluid intake and optimal nutrition should be encouraged. Skin lesions should be inspected regularly to detect signs of superimposed bacterial infections. Small, localized bacterial skin infections can be treated with topical application of mupirocin ointment 2%, 3 times daily for 7-14 days. For diffuse and more severe bacterial skin infections, a systemic antibiotic may be necessary. Reasonable choices include amoxicillin-clavulanate 875 mg/125 mg orally every 12 hours, or trimethoprim-sulfamethoxazole double strength 800 mg/160 mg orally every 12 hours.¹¹ The latter agent should be avoided in the first trimester of pregnancy because of potential teratogenic effects.

Several specific agents are available through the CDC for treatment of orthopoxvirus infections such as smallpox and monkeypox. Information about these agents is summarized in the TABLE.^12-16

Unique considerations in pregnancy

Because monkeypox is so rare, there is very little information about the effects of this infection in pregnant women. The report most commonly cited in the literature is that by Mbala et al, which was published in 2017.¹⁷ These authors described 4 pregnant patients in the Democratic Republic of Congo who contracted monkeypox infection over a 4-year period. All 4 women were hospitalized and treated with systemic antibiotics, antiparasitic medications, and analgesics. One patient delivered a healthy infant. Two women had spontaneous abortions in the first trimester. The fourth patient experienced a stillbirth at 22 weeks’ gestation. At postmortem examination, the fetus had diffuse cutaneous lesions, prominent hepatomegaly, and hydrops. No structural malformations were noted. The placenta demonstrated numerous punctate hemorrhages, and high concentrations of virus were recovered from the placenta and from fetal tissue.

Although the information on pregnancy outcome is quite limited, it seems clear that the virus can cross the placenta and cause adverse effects such as spontaneous abortion and fetal death. Accordingly, I think the following guidelines are a reasonable approach to a pregnant patient who has been exposed to monkeypox or who has developed manifestations of infection.^3,7,9

• In the event of a community outbreak, bioterrorism event, or exposure to a person with suspected or confirmed monkeypox infection, the pregnant patient should receive the Jynneos vaccine.
• The pregnant patient should be isolated from any individual with suspected or confirmed monkeypox.
• If infection develops despite these measures, the patient should be treated with either tecovirimat or vaccinia immune globulin IV. Hospitalization may be necessary for seriously ill individuals.

• Within 2 weeks of infection, a comprehensive ultrasound examination should be performed to assess for structural abnormalities in the fetus.

• Subsequently, serial ultrasound examinations should be performed at intervals of 4-6 weeks to assess fetal growth and re-evaluate fetal anatomy.
• Following delivery, a detailed neonatal examination should be performed to assess for evidence of viral injury. Neonatal skin lesions and neonatal serum can be assessed by PCR for monkeypox virus. The newborn should be isolated from the mother until all the mother’s lesions have dried and crusted over.

CASE Resolved

Given the husband’s recent travel to Nigeria and consumption of bushmeat, he most likely has monkeypox. The infection can be spread from person to person by close contact; thus, his wife is at risk. The couple should isolate until all of his lesions have dried and crusted over. The woman also should receive the Jynneos vaccine. If she becomes symptomatic, she should be treated with tecovirimat or vaccinia immune globulin IV. ●

In October 2020, Medicare released an updated guidance to reduce Mohs micrographic surgery (MMS) reimbursement issues,¹ which initially was released in 2013. This guidance defines the latest performance and documentation requirements that Medicare requires for MMS. Understanding these requirements and making sure that your Mohs surgical reports have all the needed documentation details are critical because auditors from not only Medicare Administrative Contractors (MACs) but also private insurers and Medicare Advantage plans have adopted these standards and will deny payment for Mohs surgical codes if they are not met. This article provides a review of the updated Medicare requirements to make sure your MMS procedure notes are audit proof.

Notes Must Indicate Mohs Is the Most Appropriate Treatment

I review many of my colleagues’ Mohs notes and can tell you that some of the requirements laid out in the updated guidance typically are already reported by Mohs surgeons in their notes, including the location, number, and size of the lesion or lesions treated and the number of stages performed. However, there are some new requirements that often are not reported by Mohs surgeons that now need to be included. The guidance indicates the following:

The majority of skin cancers can be managed by simple excision or destruction techniques. The medical record of a patient undergoing MMS should clearly show that this procedure was chosen because of the complexity (eg, poorly defined clinical borders, possible deep invasion, prior irradiation), size or location (eg, maximum conservation of tumor-free tissue is important). Medicare will consider reimbursement for MMS for accepted diagnoses and indications, which you must document in the patient’s medical record as being appropriate for MMS and that MMS is the most appropriate choice for the treatment of a particular lesion.¹

In my experience, most Mohs notes include some statement that the skin cancer treated is appropriate based on the Mohs appropriate use criteria (AUC) or the AUC score. However, notes should make clear not just that the lesion treated is “appropriate” for MMS but also that it is the most appropriate treatment (eg, why the lesion was not managed by standard excision or destruction technique).

Mohs Surgeon Must Perform the Surgery and Interpret Slides

The updated guidance clearly indicates that MMS may only be performed by a physician who is specifically trained and highly skilled in Mohs techniques and pathologic identification: “Medicare will only reimburse for MMS services when the Mohs surgeon acts as both surgeon and pathologist.”¹ Mohs micrographic surgery codes may not be billed if preparation or interpretation of the pathology slides is performed by a physician other than the Mohs surgeon. Operative notes and pathology documentation in the patient’s medical record should clearly show that MMS was performed using an accepted MMS technique in which the physician acts in 2 integrated and distinct capacities—surgeon and pathologist—thereby confirming that the procedure meets the definition of the Current Procedural Terminology code(s).

Furthermore, the Mohs operative report should detail “the number of specimens per stage.”¹ I interpret this statement to indicate that the Mohs surgeon should document the number of tissue blocks examined in each stage of Mohs surgery. For example, a statement in the notes such as “the specimen from the first Mohs stage was oriented, mapped, and divided into 4 blocks” should suffice to meet this requirement.

Histologic Description Must Be Included in Mohs Notes

Medicare will require the Mohs surgeon to document “the histology of the specimens taken. That description should include depth of invasion, pathological pattern, cell morphology, and, if present, perineural invasion or presence of scar tissue.”¹ Although this histologic description requirement appears daunting, it is common for Mohs surgeons to indicate their pathologic findings on their Mohs map such as “NBCC” next to a red area to indicate “nodular basal cell carcinoma visualized.” A template-based system to translate typical pathologic findings can be employed to rapidly and accurately populate a Mohs note with histologic description such as “NBBC=nodular aggregates of palisaded basaloid epithelial tumor arising from the epidermis forming a palisade with a cleft forming from the adjacent mucinous stroma extending to the mid dermis. Centrally the nuclei become crowded with scattered mitotic figures and necrotic bodies evident.”

Recent Improvement for 1-Stage Mohs Surgeries

The most notable improvement in the 2020 MMS reimbursement requirements vs the prior version is that, “If tumor is visualized on stage one, you must describe the histology of the specimens taken.”¹ This indicates that if no tumor is visualized in the first stage, then no description of the tumor is possible or necessary. This is a much-needed improvement, as I have observed that some auditors have denied 1-stage Mohs surgeries due to lack of tumor histology description.

Final Thoughts

Overall, the updated Medicare guidance provides important details in the requirements for performance and documentation of Mohs surgery cases. However, additional critical information will be found in Mohs coverage policies and local coverage determinations (LCDs) from MACs and private insurers.^2-4 Each LCD and insurer Mohs payment policy has unique wording and requirements. Coverage of MMS for specific malignant diagnoses, histologic subtypes, locations, and clinical scenarios varies between LCDs; most are based directly on the Mohs AUC, while others have a less specific coverage criteria. To understand the specific documentation and coverage requirements of the MAC for a particular region or private insurer, Mohs surgeons are encouraged to familiarize themselves with the Mohs surgery LCD of their local MAC and coverage policies of their insurers and to ensure their documentation substantiates these requirements. Making sure that your MMS documentation is accurate and complies with Medicare and insurer requirements will keep you out of hot water with auditors and allow reimbursement for this critical skin cancer procedure.

In October 2020, Medicare released an updated guidance to reduce Mohs micrographic surgery (MMS) reimbursement issues,¹ which initially was released in 2013. This guidance defines the latest performance and documentation requirements that Medicare requires for MMS. Understanding these requirements and making sure that your Mohs surgical reports have all the needed documentation details are critical because auditors from not only Medicare Administrative Contractors (MACs) but also private insurers and Medicare Advantage plans have adopted these standards and will deny payment for Mohs surgical codes if they are not met. This article provides a review of the updated Medicare requirements to make sure your MMS procedure notes are audit proof.

Notes Must Indicate Mohs Is the Most Appropriate Treatment

I review many of my colleagues’ Mohs notes and can tell you that some of the requirements laid out in the updated guidance typically are already reported by Mohs surgeons in their notes, including the location, number, and size of the lesion or lesions treated and the number of stages performed. However, there are some new requirements that often are not reported by Mohs surgeons that now need to be included. The guidance indicates the following:

The majority of skin cancers can be managed by simple excision or destruction techniques. The medical record of a patient undergoing MMS should clearly show that this procedure was chosen because of the complexity (eg, poorly defined clinical borders, possible deep invasion, prior irradiation), size or location (eg, maximum conservation of tumor-free tissue is important). Medicare will consider reimbursement for MMS for accepted diagnoses and indications, which you must document in the patient’s medical record as being appropriate for MMS and that MMS is the most appropriate choice for the treatment of a particular lesion.¹

In my experience, most Mohs notes include some statement that the skin cancer treated is appropriate based on the Mohs appropriate use criteria (AUC) or the AUC score. However, notes should make clear not just that the lesion treated is “appropriate” for MMS but also that it is the most appropriate treatment (eg, why the lesion was not managed by standard excision or destruction technique).

Mohs Surgeon Must Perform the Surgery and Interpret Slides

The updated guidance clearly indicates that MMS may only be performed by a physician who is specifically trained and highly skilled in Mohs techniques and pathologic identification: “Medicare will only reimburse for MMS services when the Mohs surgeon acts as both surgeon and pathologist.”¹ Mohs micrographic surgery codes may not be billed if preparation or interpretation of the pathology slides is performed by a physician other than the Mohs surgeon. Operative notes and pathology documentation in the patient’s medical record should clearly show that MMS was performed using an accepted MMS technique in which the physician acts in 2 integrated and distinct capacities—surgeon and pathologist—thereby confirming that the procedure meets the definition of the Current Procedural Terminology code(s).

Furthermore, the Mohs operative report should detail “the number of specimens per stage.”¹ I interpret this statement to indicate that the Mohs surgeon should document the number of tissue blocks examined in each stage of Mohs surgery. For example, a statement in the notes such as “the specimen from the first Mohs stage was oriented, mapped, and divided into 4 blocks” should suffice to meet this requirement.

Histologic Description Must Be Included in Mohs Notes

Medicare will require the Mohs surgeon to document “the histology of the specimens taken. That description should include depth of invasion, pathological pattern, cell morphology, and, if present, perineural invasion or presence of scar tissue.”¹ Although this histologic description requirement appears daunting, it is common for Mohs surgeons to indicate their pathologic findings on their Mohs map such as “NBCC” next to a red area to indicate “nodular basal cell carcinoma visualized.” A template-based system to translate typical pathologic findings can be employed to rapidly and accurately populate a Mohs note with histologic description such as “NBBC=nodular aggregates of palisaded basaloid epithelial tumor arising from the epidermis forming a palisade with a cleft forming from the adjacent mucinous stroma extending to the mid dermis. Centrally the nuclei become crowded with scattered mitotic figures and necrotic bodies evident.”

Recent Improvement for 1-Stage Mohs Surgeries

The most notable improvement in the 2020 MMS reimbursement requirements vs the prior version is that, “If tumor is visualized on stage one, you must describe the histology of the specimens taken.”¹ This indicates that if no tumor is visualized in the first stage, then no description of the tumor is possible or necessary. This is a much-needed improvement, as I have observed that some auditors have denied 1-stage Mohs surgeries due to lack of tumor histology description.

Final Thoughts

Overall, the updated Medicare guidance provides important details in the requirements for performance and documentation of Mohs surgery cases. However, additional critical information will be found in Mohs coverage policies and local coverage determinations (LCDs) from MACs and private insurers.^2-4 Each LCD and insurer Mohs payment policy has unique wording and requirements. Coverage of MMS for specific malignant diagnoses, histologic subtypes, locations, and clinical scenarios varies between LCDs; most are based directly on the Mohs AUC, while others have a less specific coverage criteria. To understand the specific documentation and coverage requirements of the MAC for a particular region or private insurer, Mohs surgeons are encouraged to familiarize themselves with the Mohs surgery LCD of their local MAC and coverage policies of their insurers and to ensure their documentation substantiates these requirements. Making sure that your MMS documentation is accurate and complies with Medicare and insurer requirements will keep you out of hot water with auditors and allow reimbursement for this critical skin cancer procedure.

In October 2020, Medicare released an updated guidance to reduce Mohs micrographic surgery (MMS) reimbursement issues,¹ which initially was released in 2013. This guidance defines the latest performance and documentation requirements that Medicare requires for MMS. Understanding these requirements and making sure that your Mohs surgical reports have all the needed documentation details are critical because auditors from not only Medicare Administrative Contractors (MACs) but also private insurers and Medicare Advantage plans have adopted these standards and will deny payment for Mohs surgical codes if they are not met. This article provides a review of the updated Medicare requirements to make sure your MMS procedure notes are audit proof.

Notes Must Indicate Mohs Is the Most Appropriate Treatment

I review many of my colleagues’ Mohs notes and can tell you that some of the requirements laid out in the updated guidance typically are already reported by Mohs surgeons in their notes, including the location, number, and size of the lesion or lesions treated and the number of stages performed. However, there are some new requirements that often are not reported by Mohs surgeons that now need to be included. The guidance indicates the following:

The majority of skin cancers can be managed by simple excision or destruction techniques. The medical record of a patient undergoing MMS should clearly show that this procedure was chosen because of the complexity (eg, poorly defined clinical borders, possible deep invasion, prior irradiation), size or location (eg, maximum conservation of tumor-free tissue is important). Medicare will consider reimbursement for MMS for accepted diagnoses and indications, which you must document in the patient’s medical record as being appropriate for MMS and that MMS is the most appropriate choice for the treatment of a particular lesion.¹

In my experience, most Mohs notes include some statement that the skin cancer treated is appropriate based on the Mohs appropriate use criteria (AUC) or the AUC score. However, notes should make clear not just that the lesion treated is “appropriate” for MMS but also that it is the most appropriate treatment (eg, why the lesion was not managed by standard excision or destruction technique).

Mohs Surgeon Must Perform the Surgery and Interpret Slides

The updated guidance clearly indicates that MMS may only be performed by a physician who is specifically trained and highly skilled in Mohs techniques and pathologic identification: “Medicare will only reimburse for MMS services when the Mohs surgeon acts as both surgeon and pathologist.”¹ Mohs micrographic surgery codes may not be billed if preparation or interpretation of the pathology slides is performed by a physician other than the Mohs surgeon. Operative notes and pathology documentation in the patient’s medical record should clearly show that MMS was performed using an accepted MMS technique in which the physician acts in 2 integrated and distinct capacities—surgeon and pathologist—thereby confirming that the procedure meets the definition of the Current Procedural Terminology code(s).

Furthermore, the Mohs operative report should detail “the number of specimens per stage.”¹ I interpret this statement to indicate that the Mohs surgeon should document the number of tissue blocks examined in each stage of Mohs surgery. For example, a statement in the notes such as “the specimen from the first Mohs stage was oriented, mapped, and divided into 4 blocks” should suffice to meet this requirement.

Histologic Description Must Be Included in Mohs Notes

Medicare will require the Mohs surgeon to document “the histology of the specimens taken. That description should include depth of invasion, pathological pattern, cell morphology, and, if present, perineural invasion or presence of scar tissue.”¹ Although this histologic description requirement appears daunting, it is common for Mohs surgeons to indicate their pathologic findings on their Mohs map such as “NBCC” next to a red area to indicate “nodular basal cell carcinoma visualized.” A template-based system to translate typical pathologic findings can be employed to rapidly and accurately populate a Mohs note with histologic description such as “NBBC=nodular aggregates of palisaded basaloid epithelial tumor arising from the epidermis forming a palisade with a cleft forming from the adjacent mucinous stroma extending to the mid dermis. Centrally the nuclei become crowded with scattered mitotic figures and necrotic bodies evident.”

Recent Improvement for 1-Stage Mohs Surgeries

The most notable improvement in the 2020 MMS reimbursement requirements vs the prior version is that, “If tumor is visualized on stage one, you must describe the histology of the specimens taken.”¹ This indicates that if no tumor is visualized in the first stage, then no description of the tumor is possible or necessary. This is a much-needed improvement, as I have observed that some auditors have denied 1-stage Mohs surgeries due to lack of tumor histology description.

Final Thoughts

Overall, the updated Medicare guidance provides important details in the requirements for performance and documentation of Mohs surgery cases. However, additional critical information will be found in Mohs coverage policies and local coverage determinations (LCDs) from MACs and private insurers.^2-4 Each LCD and insurer Mohs payment policy has unique wording and requirements. Coverage of MMS for specific malignant diagnoses, histologic subtypes, locations, and clinical scenarios varies between LCDs; most are based directly on the Mohs AUC, while others have a less specific coverage criteria. To understand the specific documentation and coverage requirements of the MAC for a particular region or private insurer, Mohs surgeons are encouraged to familiarize themselves with the Mohs surgery LCD of their local MAC and coverage policies of their insurers and to ensure their documentation substantiates these requirements. Making sure that your MMS documentation is accurate and complies with Medicare and insurer requirements will keep you out of hot water with auditors and allow reimbursement for this critical skin cancer procedure.

Keratinocyte carcinoma (KC), or nonmelanoma skin cancer, is the most commonly diagnosed cancer in the United States.¹ Basal cell carcinoma comprises the majority of all KCs.^2,3 Squamous cell carcinoma is the second most common skin cancer, representing approximately 20% of KCs and accounting for the majority of KC-related deaths.^4-7 Malignant melanoma represents the majority of all skin cancer–related deaths.⁸ The incidence of basal cell carcinoma, squamous cell carcinoma, and malignant melanoma in the United States is on the rise and carries substantial morbidity and mortality with notable social and economic burdens.^1,8-10

Prevention is necessary to reduce skin cancer morbidity and mortality as well as rising treatment costs. The most commonly used skin cancer screening method among dermatologists is the visual full-body skin examination (FBSE), which is a noninvasive, safe, quick, and cost-effective method of early detection and prevention.¹¹ To effectively confront the growing incidence and health care burden of skin cancer, primary care providers (PCPs) must join dermatologists in conducting FBSEs.^12,13

Despite being the predominant means of secondary skin cancer prevention, the US Preventive Services Task Force (USPSTF) issued an I rating for insufficient evidence to assess the benefits vs harms of screening the adult general population by PCPs.^14,15 A major barrier to studying screening is the lack of a standardized method for conducting and reporting FBSEs.¹³ Systematic thorough skin examination generally is not performed in the primary care setting.^16-18

We aimed to investigate what occurs during an FBSE in the primary care setting and how often they are performed. We examined whether there was potential variation in the execution of the examination, what was perceived by the patient vs reported by the physician, and what was ultimately included in the medical record. Miscommunication between patient and provider regarding performance of FBSEs has previously been noted,^17-19 and we sought to characterize and quantify that miscommunication. We hypothesized that there would be lower patient-reported FBSEs compared to physicians and patient medical records. We also hypothesized that there would be variability in how physicians screened for skin cancer.

METHODS

This study was cross-sectional and was conducted based on interviews and a review of medical records at secondary- and tertiary-level units (clinics and hospitals) across the United States. We examined baseline data from a randomized controlled trial of a Web-based skin cancer early detection continuing education course—the Basic Skin Cancer Triage curriculum. Complete details have been described elsewhere.¹² This study was approved by the institutional review boards of the Providence Veterans Affairs Medical Center, Rhode Island Hospital, and Brown University (all in Providence, Rhode Island), as well as those of all recruitment sites.

Data were collected from 2005 to 2008 and included physician online surveys, patient telephone interviews, and patient medical record data abstracted by research assistants. Primary care providers included in the study were general internists, family physicians, or medicine-pediatrics practitioners who were recruited from 4 collaborating centers across the United States in the mid-Atlantic region, Ohio, Kansas, and southern California, and who had been in practice for at least a year. Patients were recruited from participating physician practices and selected by research assistants who traveled to each clinic for coordination, recruitment, and performance of medical record reviews. Patients were selected as having minimal risk of melanoma (eg, no signs of severe photodamage to the skin). Patients completed structured telephone surveys within 1 to 2 weeks of the office visit regarding the practices observed and clinical questions asked during their recent clinical encounter with their PCP.

Measures

Demographics—Demographic variables asked of physicians included age, sex, ethnicity, academic degree (MD vs DO), years in practice, training, and prior dermatology training. Demographic information asked of patients included age, sex, ethnicity, education, and household income.

Physician-Reported Examination and Counseling Variables—Physicians were asked to characterize their clinical practices, prompted by questions regarding performance of FBSEs: “Please think of a typical month and using the scale below, indicate how frequently you perform a total body skin exam during an annual exam (eg, periodic follow-up exam).” Physicians responded to 3 questions on a 5-point scale (1=never, 2=sometimes, 3=about half, 4=often, 5=almost always).

Patient-Reported Examination Variables—Patients also were asked to characterize the skin examination experienced in their clinical encounter with their PCP, including: “During your last visit, as far as you could tell, did your physician: (1) look at the skin on your back? (2) look at the skin on your belly area? (3) look at the skin on the back of your legs?” Patient responses were coded as yes, no, don’t know, or refused. Participants who refused were excluded from analysis; participants who responded are detailed in Table 1. In addition, patients also reported the level of undress with their physician by answering the following question: “During your last medical exam, did you: 1=keep your clothes on; 2=partially undress; 3=totally undress except for undergarments; 4=totally undress, including all undergarments?”

Patient Medical Record–Extracted Data—Research assistants used a structured abstract form to extract the information from the patient’s medical record and graded it as 0 (absence) or 1 (presence) from the medical record.

Statistical Analysis

Descriptive statistics included mean and standard deviation (SD) for continuous variables as well as frequency and percentage for categorical variables. Logit/logistic regression analysis was used to predict the odds of patient-reported outcomes that were binary with physician-reported variables as the predictor. Linear regression analysis was used to assess the association between 2 continuous variables. All analyses were conducted using SPSS version 24 (IBM).²⁰ Significance criterion was set at α of .05.

RESULTS Demographics

The final sample included data from 53 physicians and 3343 patients. The study sample mean age (SD) was 50.3 (9.9) years for PCPs (n=53) and 59.8 (16.9) years for patients (n=3343). The physician sample was 36% female and predominantly White (83%). Ninety-one percent of the PCPs had an MD (the remaining had a DO degree), and the mean (SD) years practicing was 21.8 (10.6) years. Seventeen percent of PCPs were trained in internal medicine, 4% in internal medicine and pediatrics, and 79% family medicine; 79% of PCPs had received prior training in dermatology. The patient sample was 58% female, predominantly White (84%), non-Hispanic/Latinx (95%), had completed high school (94%), and earned more than $40,000 annually (66%).

Physician- and Patient-Reported FBSEs

Physicians reported performing FBSEs with variable frequency. Among PCPs who conducted FBSEs with greater frequency, there was a modest increase in the odds that patients reported a particular body part was examined (back: odds ratio [OR], 24.5% [95% CI, 1.18-1.31; P<.001]; abdomen: OR, 23.3% [95% CI, 1.17-1.30; P<.001]; backs of legs: OR, 20.4% [95% CI, 1.13-1.28; P<.001])(Table 1). The patient-reported level of undress during examination was significantly associated with physician-reported FBSE (β=0.16 [95% CI, 0.13-0.18; P<.001])(Table 2).

Because of the bimodal distribution of scores in the physician-reported frequency of FBSEs, particularly pertaining to the extreme points of the scale, we further repeated analysis with only the never and almost always groups (Table 1). Primary care providers who reported almost always for FBSE had 29.6% increased odds of patient-reported back examination (95% CI, 1.00-1.68; P=.048) and 59.3% increased odds of patient-reported abdomen examination (95% CI, 1.23-2.06; P<.001). The raw percentages of patients who reported having their back, abdomen, and backs of legs examined when the PCP reported having never conducted an FBSE were 56%, 40%, and 26%, respectively. The raw percentages of patients who reported having their back, abdomen, and backs of legs examined when the PCP reported having almost always conducted an FBSE were 52%, 51%, and 30%, respectively. Raw percentages were calculated by dividing the number of "yes" responses by participants for each body part examined by thetotal number of participant responses (“yes” and “no”) for each respective body part. There was no significant change in odds of patient-reported backs of legs examined with PCP-reported never vs almost always conducting an FBSE. In addition, a greater patient-reported level of undress was associated with 20.2% increased odds of PCPs reporting almost always conducting an FBSE (95% CI, 1.08-1.34; P=.001).

When comparing PCP-reported FBSE and report of FBSE in patient medical records, there was a 39.0% increased odds of the patient medical record indicating FBSE when physicians reported conducting an FBSE with greater frequency (95% CI, 1.30-1.48; P<.001)(eTable 1). When examining PCP-reported never vs almost always conducting an FBSE, a report of almost always was associated with 79.0% increased odds of the patient medical record indicating that an FBSE was conducted (95% CI, 1.28-2.49; P=.001). The raw percentage of the patient medical record indicating an FBSE was conducted when the PCP reported having never conducted an FBSE was 17% and 26% when the PCP reported having almost always conducted an FBSE.

When comparing the patient-reported body part examined with patient FBSE medical record documentation, an indication of yes for FBSE on the patient medical record was associated with a considerable increase in odds that patients reported a particular body part was examined (back: 91.4% [95% CI, 1.59-2.31; P<.001]; abdomen: 75.0% [95% CI, 1.45-2.11; P<.001]; backs of legs: 91.6% [95% CI, 1.56-2.36; P<.001])(eTable 2). The raw percentages of patients who reported having their back, abdomen, and backs of legs examined vs not examined when the patient medical record indicated an FBSE was completed were 24% vs 14%, 23% vs 15%, and 26% vs 16%, respectively. An increase in patient-reported level of undress was associated with a 57.0% increased odds of their medical record indicating an FBSE was conducted (95% CI, 1.45-1.70; P<.001).

COMMENT How PCPs Perform FBSEs Varies

We found that PCPs performed FBSEs with variable frequency, and among those who did, the patient report of their examination varied considerably (Table 1). There appears to be considerable ambiguity in each of these means of determining the extent to which the skin was inspected for skin cancer, which may render the task of improving such inspection more difficult. We asked patients whether their back, abdomen, and backs of legs were examined as an assessment of some of the variety of areas inspected during an FBSE. During a general well-visit appointment, a patient’s back and abdomen may be examined for multiple reasons. Patients may have misinterpreted elements of the pulmonary, cardiac, abdominal, or musculoskeletal examinations as being part of the FBSE. The back and abdomen—the least specific features of the FBSE—were reported by patients to be the most often examined. Conversely, the backs of the legs—the most specific feature of the FBSE—had the lowest odds of being examined (Table 1).

In addition to the potential limitations of patient awareness of physician activity, our results also could be explained by differences among PCPs in how they performed FBSEs. There is no standardized method of conducting an FBSE. Furthermore, not all medical students and residents are exposed to dermatology training. In our sample of 53 physicians, 79% had reported receiving dermatology training; however, we did not assess the extent to which they had been trained in conducting an FBSE and/or identifying malignant lesions. In an American survey of 659 medical students, more than two-thirds of students had never been trained or never examined a patient for skin cancer.²¹ In another American survey of 342 internal medicine, family medicine, pediatrics, and obstetrics/gynecology residents across 7 medical schools and 4 residency programs, more than three-quarters of residents had never been trained in skin cancer screening.²² Our findings reflect insufficient and inconsistent training in skin cancer screening and underscore the need for mandatory education to ensure quality FBSEs are performed in the primary care setting.

Frequency of PCPs Performing FBSEs

Similar to prior studies analyzing the frequency of FBSE performance in the primary care setting,^16,19,23,24 more than half of our PCP sample reported sometimes to never conducting FBSEs. The percentage of physicians who reported conducting FBSEs in our sample was greater than the proportion reported by the National Health Interview Survey, in which only 8% of patients received an FBSE in the prior year by a PCP or obstetrician/gynecologist,¹⁶ but similar to a smaller patient study.¹⁹ In that study, 87% of patients, regardless of their skin cancer history, also reported that they would like their PCP to perform an FBSE regularly.¹⁹ Although some of our patient participants may have declined an FBSE, it is unlikely that that would have entirely accounted for the relatively low number of PCPs who reported frequently performing FBSEs.

Documentation in Medical Records of FBSEs

Compared to PCP self-reported performance of FBSEs, considerably fewer PCPs marked the patient medical record as having completed an FBSE. Among patients with medical records that indicated an FBSE had been conducted, they reported higher odds of all 3 body parts being examined, the highest being the backs of the legs. Also, when the patient medical record indicated an FBSE had been completed, the odds that the PCP reported an FBSE also were higher. The relatively low medical record documentation of FBSEs highlights the need for more rigorous enforcement of accurate documentation. However, among the cases that were recorded, it appeared that the content of the examinations was more consistent.

Benefits of PCP-Led FBSEs

Although the USPSTF issued an I rating for PCP-led FBSEs,¹⁴ multiple national medical societies, including the American Cancer Society,²⁵ American Academy of Dermatology,²⁶ and Skin Cancer Foundation,²⁷ as well as international guidelines in Germany,²⁸ Australia,^29,30 and New Zealand,³¹ recommend regular FBSEs among the general or at-risk population; New Zealand and Australia have the highest incidence and prevalence of melanoma in the world.⁸ The benefits of physician-led FBSEs on detection of early-stage skin cancer, and in particular, melanoma detection, have been documented in numerous studies.^30,32-38 However, the variability and often poor quality of skin screening may contribute in part to the just as numerous null results from prior skin screening studies,¹⁵ perpetuating the insufficient status of skin examinations by USPSTF standards.¹⁴ Our study underscores both the variability in frequency and content of PCP-administered FBSEs. It also highlights the need for standardization of screening examinations at the medical student, trainee, and physician level.

The present study has several limitations. First, there was an unknown time lag between the FBSEs and physician self-reported surveys. Similarly, there was a variable time lag between the patient examination encounter and subsequent telephone survey. Both the physician and patient survey data may have been affected by recall bias. Second, patients were not asked directly whether an FBSE had been conducted. Furthermore, patients may not have appreciated whether the body part examined was part of the FBSE or another examination. Also, screenings often were not recorded in the medical record, assuming that the patient report and/or physician report was more accurate than the medical record.

Our study also was limited by demographics; our patient sample was largely comprised of White, educated, US adults, potentially limiting the generalizability of our findings. Conversely, a notable strength of our study was that our participants were recruited from 4 geographically diverse centers. Furthermore, we had a comparatively large sample size of patients and physicians. Also, the independent assessment of provider-reported examinations, objective assessment of medical records, and patient reports of their encounters provides a strong foundation for assessing the independent contributions of each data source.

CONCLUSION

Our study highlights the challenges future studies face in promoting skin cancer screening in the primary care setting. Our findings underscore the need for a standardized FBSE as well as clear clinical expectations regarding skin cancer screening that is expected of PCPs.

As long as skin cancer screening rates remain low in the United States, patients will be subject to potential delays and missed diagnoses, impacting morbidity and mortality.⁸ There are burgeoning resources and efforts in place to increase skin cancer screening. For example, free validated online training is available for early detection of melanoma and other skin cancers (https://www.visualdx.com/skin-cancer-education/).^39-42 Future directions for bolstering screening numbers must focus on educating PCPs about skin cancer prevention and perhaps narrowing the screening population by age-appropriate risk assessments.

Keratinocyte carcinoma (KC), or nonmelanoma skin cancer, is the most commonly diagnosed cancer in the United States.¹ Basal cell carcinoma comprises the majority of all KCs.^2,3 Squamous cell carcinoma is the second most common skin cancer, representing approximately 20% of KCs and accounting for the majority of KC-related deaths.^4-7 Malignant melanoma represents the majority of all skin cancer–related deaths.⁸ The incidence of basal cell carcinoma, squamous cell carcinoma, and malignant melanoma in the United States is on the rise and carries substantial morbidity and mortality with notable social and economic burdens.^1,8-10

Prevention is necessary to reduce skin cancer morbidity and mortality as well as rising treatment costs. The most commonly used skin cancer screening method among dermatologists is the visual full-body skin examination (FBSE), which is a noninvasive, safe, quick, and cost-effective method of early detection and prevention.¹¹ To effectively confront the growing incidence and health care burden of skin cancer, primary care providers (PCPs) must join dermatologists in conducting FBSEs.^12,13

Despite being the predominant means of secondary skin cancer prevention, the US Preventive Services Task Force (USPSTF) issued an I rating for insufficient evidence to assess the benefits vs harms of screening the adult general population by PCPs.^14,15 A major barrier to studying screening is the lack of a standardized method for conducting and reporting FBSEs.¹³ Systematic thorough skin examination generally is not performed in the primary care setting.^16-18

We aimed to investigate what occurs during an FBSE in the primary care setting and how often they are performed. We examined whether there was potential variation in the execution of the examination, what was perceived by the patient vs reported by the physician, and what was ultimately included in the medical record. Miscommunication between patient and provider regarding performance of FBSEs has previously been noted,^17-19 and we sought to characterize and quantify that miscommunication. We hypothesized that there would be lower patient-reported FBSEs compared to physicians and patient medical records. We also hypothesized that there would be variability in how physicians screened for skin cancer.

METHODS

This study was cross-sectional and was conducted based on interviews and a review of medical records at secondary- and tertiary-level units (clinics and hospitals) across the United States. We examined baseline data from a randomized controlled trial of a Web-based skin cancer early detection continuing education course—the Basic Skin Cancer Triage curriculum. Complete details have been described elsewhere.¹² This study was approved by the institutional review boards of the Providence Veterans Affairs Medical Center, Rhode Island Hospital, and Brown University (all in Providence, Rhode Island), as well as those of all recruitment sites.

Data were collected from 2005 to 2008 and included physician online surveys, patient telephone interviews, and patient medical record data abstracted by research assistants. Primary care providers included in the study were general internists, family physicians, or medicine-pediatrics practitioners who were recruited from 4 collaborating centers across the United States in the mid-Atlantic region, Ohio, Kansas, and southern California, and who had been in practice for at least a year. Patients were recruited from participating physician practices and selected by research assistants who traveled to each clinic for coordination, recruitment, and performance of medical record reviews. Patients were selected as having minimal risk of melanoma (eg, no signs of severe photodamage to the skin). Patients completed structured telephone surveys within 1 to 2 weeks of the office visit regarding the practices observed and clinical questions asked during their recent clinical encounter with their PCP.

Measures

Demographics—Demographic variables asked of physicians included age, sex, ethnicity, academic degree (MD vs DO), years in practice, training, and prior dermatology training. Demographic information asked of patients included age, sex, ethnicity, education, and household income.

Physician-Reported Examination and Counseling Variables—Physicians were asked to characterize their clinical practices, prompted by questions regarding performance of FBSEs: “Please think of a typical month and using the scale below, indicate how frequently you perform a total body skin exam during an annual exam (eg, periodic follow-up exam).” Physicians responded to 3 questions on a 5-point scale (1=never, 2=sometimes, 3=about half, 4=often, 5=almost always).

Patient-Reported Examination Variables—Patients also were asked to characterize the skin examination experienced in their clinical encounter with their PCP, including: “During your last visit, as far as you could tell, did your physician: (1) look at the skin on your back? (2) look at the skin on your belly area? (3) look at the skin on the back of your legs?” Patient responses were coded as yes, no, don’t know, or refused. Participants who refused were excluded from analysis; participants who responded are detailed in Table 1. In addition, patients also reported the level of undress with their physician by answering the following question: “During your last medical exam, did you: 1=keep your clothes on; 2=partially undress; 3=totally undress except for undergarments; 4=totally undress, including all undergarments?”

Patient Medical Record–Extracted Data—Research assistants used a structured abstract form to extract the information from the patient’s medical record and graded it as 0 (absence) or 1 (presence) from the medical record.

Statistical Analysis

Descriptive statistics included mean and standard deviation (SD) for continuous variables as well as frequency and percentage for categorical variables. Logit/logistic regression analysis was used to predict the odds of patient-reported outcomes that were binary with physician-reported variables as the predictor. Linear regression analysis was used to assess the association between 2 continuous variables. All analyses were conducted using SPSS version 24 (IBM).²⁰ Significance criterion was set at α of .05.

RESULTS Demographics

The final sample included data from 53 physicians and 3343 patients. The study sample mean age (SD) was 50.3 (9.9) years for PCPs (n=53) and 59.8 (16.9) years for patients (n=3343). The physician sample was 36% female and predominantly White (83%). Ninety-one percent of the PCPs had an MD (the remaining had a DO degree), and the mean (SD) years practicing was 21.8 (10.6) years. Seventeen percent of PCPs were trained in internal medicine, 4% in internal medicine and pediatrics, and 79% family medicine; 79% of PCPs had received prior training in dermatology. The patient sample was 58% female, predominantly White (84%), non-Hispanic/Latinx (95%), had completed high school (94%), and earned more than $40,000 annually (66%).

Physician- and Patient-Reported FBSEs

Physicians reported performing FBSEs with variable frequency. Among PCPs who conducted FBSEs with greater frequency, there was a modest increase in the odds that patients reported a particular body part was examined (back: odds ratio [OR], 24.5% [95% CI, 1.18-1.31; P<.001]; abdomen: OR, 23.3% [95% CI, 1.17-1.30; P<.001]; backs of legs: OR, 20.4% [95% CI, 1.13-1.28; P<.001])(Table 1). The patient-reported level of undress during examination was significantly associated with physician-reported FBSE (β=0.16 [95% CI, 0.13-0.18; P<.001])(Table 2).

Because of the bimodal distribution of scores in the physician-reported frequency of FBSEs, particularly pertaining to the extreme points of the scale, we further repeated analysis with only the never and almost always groups (Table 1). Primary care providers who reported almost always for FBSE had 29.6% increased odds of patient-reported back examination (95% CI, 1.00-1.68; P=.048) and 59.3% increased odds of patient-reported abdomen examination (95% CI, 1.23-2.06; P<.001). The raw percentages of patients who reported having their back, abdomen, and backs of legs examined when the PCP reported having never conducted an FBSE were 56%, 40%, and 26%, respectively. The raw percentages of patients who reported having their back, abdomen, and backs of legs examined when the PCP reported having almost always conducted an FBSE were 52%, 51%, and 30%, respectively. Raw percentages were calculated by dividing the number of "yes" responses by participants for each body part examined by thetotal number of participant responses (“yes” and “no”) for each respective body part. There was no significant change in odds of patient-reported backs of legs examined with PCP-reported never vs almost always conducting an FBSE. In addition, a greater patient-reported level of undress was associated with 20.2% increased odds of PCPs reporting almost always conducting an FBSE (95% CI, 1.08-1.34; P=.001).

When comparing PCP-reported FBSE and report of FBSE in patient medical records, there was a 39.0% increased odds of the patient medical record indicating FBSE when physicians reported conducting an FBSE with greater frequency (95% CI, 1.30-1.48; P<.001)(eTable 1). When examining PCP-reported never vs almost always conducting an FBSE, a report of almost always was associated with 79.0% increased odds of the patient medical record indicating that an FBSE was conducted (95% CI, 1.28-2.49; P=.001). The raw percentage of the patient medical record indicating an FBSE was conducted when the PCP reported having never conducted an FBSE was 17% and 26% when the PCP reported having almost always conducted an FBSE.

When comparing the patient-reported body part examined with patient FBSE medical record documentation, an indication of yes for FBSE on the patient medical record was associated with a considerable increase in odds that patients reported a particular body part was examined (back: 91.4% [95% CI, 1.59-2.31; P<.001]; abdomen: 75.0% [95% CI, 1.45-2.11; P<.001]; backs of legs: 91.6% [95% CI, 1.56-2.36; P<.001])(eTable 2). The raw percentages of patients who reported having their back, abdomen, and backs of legs examined vs not examined when the patient medical record indicated an FBSE was completed were 24% vs 14%, 23% vs 15%, and 26% vs 16%, respectively. An increase in patient-reported level of undress was associated with a 57.0% increased odds of their medical record indicating an FBSE was conducted (95% CI, 1.45-1.70; P<.001).

COMMENT How PCPs Perform FBSEs Varies

We found that PCPs performed FBSEs with variable frequency, and among those who did, the patient report of their examination varied considerably (Table 1). There appears to be considerable ambiguity in each of these means of determining the extent to which the skin was inspected for skin cancer, which may render the task of improving such inspection more difficult. We asked patients whether their back, abdomen, and backs of legs were examined as an assessment of some of the variety of areas inspected during an FBSE. During a general well-visit appointment, a patient’s back and abdomen may be examined for multiple reasons. Patients may have misinterpreted elements of the pulmonary, cardiac, abdominal, or musculoskeletal examinations as being part of the FBSE. The back and abdomen—the least specific features of the FBSE—were reported by patients to be the most often examined. Conversely, the backs of the legs—the most specific feature of the FBSE—had the lowest odds of being examined (Table 1).

In addition to the potential limitations of patient awareness of physician activity, our results also could be explained by differences among PCPs in how they performed FBSEs. There is no standardized method of conducting an FBSE. Furthermore, not all medical students and residents are exposed to dermatology training. In our sample of 53 physicians, 79% had reported receiving dermatology training; however, we did not assess the extent to which they had been trained in conducting an FBSE and/or identifying malignant lesions. In an American survey of 659 medical students, more than two-thirds of students had never been trained or never examined a patient for skin cancer.²¹ In another American survey of 342 internal medicine, family medicine, pediatrics, and obstetrics/gynecology residents across 7 medical schools and 4 residency programs, more than three-quarters of residents had never been trained in skin cancer screening.²² Our findings reflect insufficient and inconsistent training in skin cancer screening and underscore the need for mandatory education to ensure quality FBSEs are performed in the primary care setting.

Frequency of PCPs Performing FBSEs

Similar to prior studies analyzing the frequency of FBSE performance in the primary care setting,^16,19,23,24 more than half of our PCP sample reported sometimes to never conducting FBSEs. The percentage of physicians who reported conducting FBSEs in our sample was greater than the proportion reported by the National Health Interview Survey, in which only 8% of patients received an FBSE in the prior year by a PCP or obstetrician/gynecologist,¹⁶ but similar to a smaller patient study.¹⁹ In that study, 87% of patients, regardless of their skin cancer history, also reported that they would like their PCP to perform an FBSE regularly.¹⁹ Although some of our patient participants may have declined an FBSE, it is unlikely that that would have entirely accounted for the relatively low number of PCPs who reported frequently performing FBSEs.

Documentation in Medical Records of FBSEs

Compared to PCP self-reported performance of FBSEs, considerably fewer PCPs marked the patient medical record as having completed an FBSE. Among patients with medical records that indicated an FBSE had been conducted, they reported higher odds of all 3 body parts being examined, the highest being the backs of the legs. Also, when the patient medical record indicated an FBSE had been completed, the odds that the PCP reported an FBSE also were higher. The relatively low medical record documentation of FBSEs highlights the need for more rigorous enforcement of accurate documentation. However, among the cases that were recorded, it appeared that the content of the examinations was more consistent.

Benefits of PCP-Led FBSEs

Although the USPSTF issued an I rating for PCP-led FBSEs,¹⁴ multiple national medical societies, including the American Cancer Society,²⁵ American Academy of Dermatology,²⁶ and Skin Cancer Foundation,²⁷ as well as international guidelines in Germany,²⁸ Australia,^29,30 and New Zealand,³¹ recommend regular FBSEs among the general or at-risk population; New Zealand and Australia have the highest incidence and prevalence of melanoma in the world.⁸ The benefits of physician-led FBSEs on detection of early-stage skin cancer, and in particular, melanoma detection, have been documented in numerous studies.^30,32-38 However, the variability and often poor quality of skin screening may contribute in part to the just as numerous null results from prior skin screening studies,¹⁵ perpetuating the insufficient status of skin examinations by USPSTF standards.¹⁴ Our study underscores both the variability in frequency and content of PCP-administered FBSEs. It also highlights the need for standardization of screening examinations at the medical student, trainee, and physician level.

The present study has several limitations. First, there was an unknown time lag between the FBSEs and physician self-reported surveys. Similarly, there was a variable time lag between the patient examination encounter and subsequent telephone survey. Both the physician and patient survey data may have been affected by recall bias. Second, patients were not asked directly whether an FBSE had been conducted. Furthermore, patients may not have appreciated whether the body part examined was part of the FBSE or another examination. Also, screenings often were not recorded in the medical record, assuming that the patient report and/or physician report was more accurate than the medical record.

Our study also was limited by demographics; our patient sample was largely comprised of White, educated, US adults, potentially limiting the generalizability of our findings. Conversely, a notable strength of our study was that our participants were recruited from 4 geographically diverse centers. Furthermore, we had a comparatively large sample size of patients and physicians. Also, the independent assessment of provider-reported examinations, objective assessment of medical records, and patient reports of their encounters provides a strong foundation for assessing the independent contributions of each data source.

CONCLUSION

Our study highlights the challenges future studies face in promoting skin cancer screening in the primary care setting. Our findings underscore the need for a standardized FBSE as well as clear clinical expectations regarding skin cancer screening that is expected of PCPs.

As long as skin cancer screening rates remain low in the United States, patients will be subject to potential delays and missed diagnoses, impacting morbidity and mortality.⁸ There are burgeoning resources and efforts in place to increase skin cancer screening. For example, free validated online training is available for early detection of melanoma and other skin cancers (https://www.visualdx.com/skin-cancer-education/).^39-42 Future directions for bolstering screening numbers must focus on educating PCPs about skin cancer prevention and perhaps narrowing the screening population by age-appropriate risk assessments.

Keratinocyte carcinoma (KC), or nonmelanoma skin cancer, is the most commonly diagnosed cancer in the United States.¹ Basal cell carcinoma comprises the majority of all KCs.^2,3 Squamous cell carcinoma is the second most common skin cancer, representing approximately 20% of KCs and accounting for the majority of KC-related deaths.^4-7 Malignant melanoma represents the majority of all skin cancer–related deaths.⁸ The incidence of basal cell carcinoma, squamous cell carcinoma, and malignant melanoma in the United States is on the rise and carries substantial morbidity and mortality with notable social and economic burdens.^1,8-10

Prevention is necessary to reduce skin cancer morbidity and mortality as well as rising treatment costs. The most commonly used skin cancer screening method among dermatologists is the visual full-body skin examination (FBSE), which is a noninvasive, safe, quick, and cost-effective method of early detection and prevention.¹¹ To effectively confront the growing incidence and health care burden of skin cancer, primary care providers (PCPs) must join dermatologists in conducting FBSEs.^12,13

Despite being the predominant means of secondary skin cancer prevention, the US Preventive Services Task Force (USPSTF) issued an I rating for insufficient evidence to assess the benefits vs harms of screening the adult general population by PCPs.^14,15 A major barrier to studying screening is the lack of a standardized method for conducting and reporting FBSEs.¹³ Systematic thorough skin examination generally is not performed in the primary care setting.^16-18

We aimed to investigate what occurs during an FBSE in the primary care setting and how often they are performed. We examined whether there was potential variation in the execution of the examination, what was perceived by the patient vs reported by the physician, and what was ultimately included in the medical record. Miscommunication between patient and provider regarding performance of FBSEs has previously been noted,^17-19 and we sought to characterize and quantify that miscommunication. We hypothesized that there would be lower patient-reported FBSEs compared to physicians and patient medical records. We also hypothesized that there would be variability in how physicians screened for skin cancer.

METHODS

This study was cross-sectional and was conducted based on interviews and a review of medical records at secondary- and tertiary-level units (clinics and hospitals) across the United States. We examined baseline data from a randomized controlled trial of a Web-based skin cancer early detection continuing education course—the Basic Skin Cancer Triage curriculum. Complete details have been described elsewhere.¹² This study was approved by the institutional review boards of the Providence Veterans Affairs Medical Center, Rhode Island Hospital, and Brown University (all in Providence, Rhode Island), as well as those of all recruitment sites.

Data were collected from 2005 to 2008 and included physician online surveys, patient telephone interviews, and patient medical record data abstracted by research assistants. Primary care providers included in the study were general internists, family physicians, or medicine-pediatrics practitioners who were recruited from 4 collaborating centers across the United States in the mid-Atlantic region, Ohio, Kansas, and southern California, and who had been in practice for at least a year. Patients were recruited from participating physician practices and selected by research assistants who traveled to each clinic for coordination, recruitment, and performance of medical record reviews. Patients were selected as having minimal risk of melanoma (eg, no signs of severe photodamage to the skin). Patients completed structured telephone surveys within 1 to 2 weeks of the office visit regarding the practices observed and clinical questions asked during their recent clinical encounter with their PCP.

Measures

Demographics—Demographic variables asked of physicians included age, sex, ethnicity, academic degree (MD vs DO), years in practice, training, and prior dermatology training. Demographic information asked of patients included age, sex, ethnicity, education, and household income.

Physician-Reported Examination and Counseling Variables—Physicians were asked to characterize their clinical practices, prompted by questions regarding performance of FBSEs: “Please think of a typical month and using the scale below, indicate how frequently you perform a total body skin exam during an annual exam (eg, periodic follow-up exam).” Physicians responded to 3 questions on a 5-point scale (1=never, 2=sometimes, 3=about half, 4=often, 5=almost always).

Patient-Reported Examination Variables—Patients also were asked to characterize the skin examination experienced in their clinical encounter with their PCP, including: “During your last visit, as far as you could tell, did your physician: (1) look at the skin on your back? (2) look at the skin on your belly area? (3) look at the skin on the back of your legs?” Patient responses were coded as yes, no, don’t know, or refused. Participants who refused were excluded from analysis; participants who responded are detailed in Table 1. In addition, patients also reported the level of undress with their physician by answering the following question: “During your last medical exam, did you: 1=keep your clothes on; 2=partially undress; 3=totally undress except for undergarments; 4=totally undress, including all undergarments?”

Patient Medical Record–Extracted Data—Research assistants used a structured abstract form to extract the information from the patient’s medical record and graded it as 0 (absence) or 1 (presence) from the medical record.

Statistical Analysis

Descriptive statistics included mean and standard deviation (SD) for continuous variables as well as frequency and percentage for categorical variables. Logit/logistic regression analysis was used to predict the odds of patient-reported outcomes that were binary with physician-reported variables as the predictor. Linear regression analysis was used to assess the association between 2 continuous variables. All analyses were conducted using SPSS version 24 (IBM).²⁰ Significance criterion was set at α of .05.

RESULTS Demographics

The final sample included data from 53 physicians and 3343 patients. The study sample mean age (SD) was 50.3 (9.9) years for PCPs (n=53) and 59.8 (16.9) years for patients (n=3343). The physician sample was 36% female and predominantly White (83%). Ninety-one percent of the PCPs had an MD (the remaining had a DO degree), and the mean (SD) years practicing was 21.8 (10.6) years. Seventeen percent of PCPs were trained in internal medicine, 4% in internal medicine and pediatrics, and 79% family medicine; 79% of PCPs had received prior training in dermatology. The patient sample was 58% female, predominantly White (84%), non-Hispanic/Latinx (95%), had completed high school (94%), and earned more than $40,000 annually (66%).

Physician- and Patient-Reported FBSEs

Physicians reported performing FBSEs with variable frequency. Among PCPs who conducted FBSEs with greater frequency, there was a modest increase in the odds that patients reported a particular body part was examined (back: odds ratio [OR], 24.5% [95% CI, 1.18-1.31; P<.001]; abdomen: OR, 23.3% [95% CI, 1.17-1.30; P<.001]; backs of legs: OR, 20.4% [95% CI, 1.13-1.28; P<.001])(Table 1). The patient-reported level of undress during examination was significantly associated with physician-reported FBSE (β=0.16 [95% CI, 0.13-0.18; P<.001])(Table 2).

Because of the bimodal distribution of scores in the physician-reported frequency of FBSEs, particularly pertaining to the extreme points of the scale, we further repeated analysis with only the never and almost always groups (Table 1). Primary care providers who reported almost always for FBSE had 29.6% increased odds of patient-reported back examination (95% CI, 1.00-1.68; P=.048) and 59.3% increased odds of patient-reported abdomen examination (95% CI, 1.23-2.06; P<.001). The raw percentages of patients who reported having their back, abdomen, and backs of legs examined when the PCP reported having never conducted an FBSE were 56%, 40%, and 26%, respectively. The raw percentages of patients who reported having their back, abdomen, and backs of legs examined when the PCP reported having almost always conducted an FBSE were 52%, 51%, and 30%, respectively. Raw percentages were calculated by dividing the number of "yes" responses by participants for each body part examined by thetotal number of participant responses (“yes” and “no”) for each respective body part. There was no significant change in odds of patient-reported backs of legs examined with PCP-reported never vs almost always conducting an FBSE. In addition, a greater patient-reported level of undress was associated with 20.2% increased odds of PCPs reporting almost always conducting an FBSE (95% CI, 1.08-1.34; P=.001).

When comparing PCP-reported FBSE and report of FBSE in patient medical records, there was a 39.0% increased odds of the patient medical record indicating FBSE when physicians reported conducting an FBSE with greater frequency (95% CI, 1.30-1.48; P<.001)(eTable 1). When examining PCP-reported never vs almost always conducting an FBSE, a report of almost always was associated with 79.0% increased odds of the patient medical record indicating that an FBSE was conducted (95% CI, 1.28-2.49; P=.001). The raw percentage of the patient medical record indicating an FBSE was conducted when the PCP reported having never conducted an FBSE was 17% and 26% when the PCP reported having almost always conducted an FBSE.

When comparing the patient-reported body part examined with patient FBSE medical record documentation, an indication of yes for FBSE on the patient medical record was associated with a considerable increase in odds that patients reported a particular body part was examined (back: 91.4% [95% CI, 1.59-2.31; P<.001]; abdomen: 75.0% [95% CI, 1.45-2.11; P<.001]; backs of legs: 91.6% [95% CI, 1.56-2.36; P<.001])(eTable 2). The raw percentages of patients who reported having their back, abdomen, and backs of legs examined vs not examined when the patient medical record indicated an FBSE was completed were 24% vs 14%, 23% vs 15%, and 26% vs 16%, respectively. An increase in patient-reported level of undress was associated with a 57.0% increased odds of their medical record indicating an FBSE was conducted (95% CI, 1.45-1.70; P<.001).

COMMENT How PCPs Perform FBSEs Varies

We found that PCPs performed FBSEs with variable frequency, and among those who did, the patient report of their examination varied considerably (Table 1). There appears to be considerable ambiguity in each of these means of determining the extent to which the skin was inspected for skin cancer, which may render the task of improving such inspection more difficult. We asked patients whether their back, abdomen, and backs of legs were examined as an assessment of some of the variety of areas inspected during an FBSE. During a general well-visit appointment, a patient’s back and abdomen may be examined for multiple reasons. Patients may have misinterpreted elements of the pulmonary, cardiac, abdominal, or musculoskeletal examinations as being part of the FBSE. The back and abdomen—the least specific features of the FBSE—were reported by patients to be the most often examined. Conversely, the backs of the legs—the most specific feature of the FBSE—had the lowest odds of being examined (Table 1).

In addition to the potential limitations of patient awareness of physician activity, our results also could be explained by differences among PCPs in how they performed FBSEs. There is no standardized method of conducting an FBSE. Furthermore, not all medical students and residents are exposed to dermatology training. In our sample of 53 physicians, 79% had reported receiving dermatology training; however, we did not assess the extent to which they had been trained in conducting an FBSE and/or identifying malignant lesions. In an American survey of 659 medical students, more than two-thirds of students had never been trained or never examined a patient for skin cancer.²¹ In another American survey of 342 internal medicine, family medicine, pediatrics, and obstetrics/gynecology residents across 7 medical schools and 4 residency programs, more than three-quarters of residents had never been trained in skin cancer screening.²² Our findings reflect insufficient and inconsistent training in skin cancer screening and underscore the need for mandatory education to ensure quality FBSEs are performed in the primary care setting.

Frequency of PCPs Performing FBSEs

Similar to prior studies analyzing the frequency of FBSE performance in the primary care setting,^16,19,23,24 more than half of our PCP sample reported sometimes to never conducting FBSEs. The percentage of physicians who reported conducting FBSEs in our sample was greater than the proportion reported by the National Health Interview Survey, in which only 8% of patients received an FBSE in the prior year by a PCP or obstetrician/gynecologist,¹⁶ but similar to a smaller patient study.¹⁹ In that study, 87% of patients, regardless of their skin cancer history, also reported that they would like their PCP to perform an FBSE regularly.¹⁹ Although some of our patient participants may have declined an FBSE, it is unlikely that that would have entirely accounted for the relatively low number of PCPs who reported frequently performing FBSEs.

Documentation in Medical Records of FBSEs

Compared to PCP self-reported performance of FBSEs, considerably fewer PCPs marked the patient medical record as having completed an FBSE. Among patients with medical records that indicated an FBSE had been conducted, they reported higher odds of all 3 body parts being examined, the highest being the backs of the legs. Also, when the patient medical record indicated an FBSE had been completed, the odds that the PCP reported an FBSE also were higher. The relatively low medical record documentation of FBSEs highlights the need for more rigorous enforcement of accurate documentation. However, among the cases that were recorded, it appeared that the content of the examinations was more consistent.

Benefits of PCP-Led FBSEs

Although the USPSTF issued an I rating for PCP-led FBSEs,¹⁴ multiple national medical societies, including the American Cancer Society,²⁵ American Academy of Dermatology,²⁶ and Skin Cancer Foundation,²⁷ as well as international guidelines in Germany,²⁸ Australia,^29,30 and New Zealand,³¹ recommend regular FBSEs among the general or at-risk population; New Zealand and Australia have the highest incidence and prevalence of melanoma in the world.⁸ The benefits of physician-led FBSEs on detection of early-stage skin cancer, and in particular, melanoma detection, have been documented in numerous studies.^30,32-38 However, the variability and often poor quality of skin screening may contribute in part to the just as numerous null results from prior skin screening studies,¹⁵ perpetuating the insufficient status of skin examinations by USPSTF standards.¹⁴ Our study underscores both the variability in frequency and content of PCP-administered FBSEs. It also highlights the need for standardization of screening examinations at the medical student, trainee, and physician level.

The present study has several limitations. First, there was an unknown time lag between the FBSEs and physician self-reported surveys. Similarly, there was a variable time lag between the patient examination encounter and subsequent telephone survey. Both the physician and patient survey data may have been affected by recall bias. Second, patients were not asked directly whether an FBSE had been conducted. Furthermore, patients may not have appreciated whether the body part examined was part of the FBSE or another examination. Also, screenings often were not recorded in the medical record, assuming that the patient report and/or physician report was more accurate than the medical record.

Our study also was limited by demographics; our patient sample was largely comprised of White, educated, US adults, potentially limiting the generalizability of our findings. Conversely, a notable strength of our study was that our participants were recruited from 4 geographically diverse centers. Furthermore, we had a comparatively large sample size of patients and physicians. Also, the independent assessment of provider-reported examinations, objective assessment of medical records, and patient reports of their encounters provides a strong foundation for assessing the independent contributions of each data source.

CONCLUSION

Our study highlights the challenges future studies face in promoting skin cancer screening in the primary care setting. Our findings underscore the need for a standardized FBSE as well as clear clinical expectations regarding skin cancer screening that is expected of PCPs.

As long as skin cancer screening rates remain low in the United States, patients will be subject to potential delays and missed diagnoses, impacting morbidity and mortality.⁸ There are burgeoning resources and efforts in place to increase skin cancer screening. For example, free validated online training is available for early detection of melanoma and other skin cancers (https://www.visualdx.com/skin-cancer-education/).^39-42 Future directions for bolstering screening numbers must focus on educating PCPs about skin cancer prevention and perhaps narrowing the screening population by age-appropriate risk assessments.

Practice Gap

Nonmelanoma skin cancer is the most common cancer, typically growing in sun-exposed areas. As such, the nasal area is a common site of onset, constituting approximately 25% of cases. Surgical excision of these cancers generally has a high cure rate.¹

Although complete excision of the tumor is the primary goal of the dermatologic surgeon, achieving a cosmetically satisfactory scar also is important. As a prominent feature of the face, any irregularities to the nose are easily noticeable.² The subsequent scar may exhibit features that are less than ideal and cause notable stress to the patient.

When a scar presents with several complications, using a single surgical technique may not sufficiently address all defects. As a result, it can be challenging for the surgeon to decide which combination of methods among the myriad of nonsurgical and surgical options for scar revision will produce the best cosmetic outcome.

Case and Technique

A 76-year-old man presented 1 year after he underwent Mohs micrographic surgery for squamous cell carcinoma on the nasal dorsum. The tumor cleared after 1 stage and was repaired using a bilateral V-Y advancement flap. Postoperatively, the patient developed pincushioning of the flap, atrophic scarring inferior to the flap, and webbing of the pivotal restraint point at the nasal root (Figures 1A and 1B). We opted to address the pincushioning and nasal root webbing by defatting the flap and performing Z-plasty, respectively.

Pincushioning—Pincushioning of a flap arises due to contraction and lymphedema at the edge of the repair. It is seen more often in nasal repairs due to the limited availability of surrounding skin and changes in skin texture from rhinion to tip.³ To combat this in our patient, an incision was made around the site of the original flap, surrounding tissue was undermined, and the flap was reflected back. Subcutaneous tissue was removed with scissors. The flap was then laid back into the defect, and the subcutaneous tissue and dermis were closed with interrupted buried vertical mattress sutures. The epidermis was closed in a simple running fashion.

Webbing—Webbing of a scar also may develop from the contractile wound-healing process.⁴ Z-plasty commonly is used to camouflage a linear or contracted scar, increase skin availability in an area, or alter scar direction to better align with skin-tension lines.^5,6 In our patient, we incised the webbing of the nasal root along the vertical scar. Two arms were drawn at each end of the scar at a 60° angle (Figure 2); the side arms were drawn equal in length and incised vertically. Full-thickness skin flaps were then undermined at the level of subcutaneous fat, creating 2 triangular flaps. Adequate undermining of the surrounding subcutaneous tissue was performed to achieve proper mobilization of the flaps, which allowed for flap transposition to occur without tension and therefore for proper redirection of the scar.⁶ The flaps were secured using buried vertical mattress sutures and simple running sutures. Using too many buried interrupted sutures can cause vascular compromise of the fragile tips of the Z and should be avoided.³

At 4-month postoperative follow-up, the cosmetic outcome was judged satisfactory (Figure 1C).

Practice Implications

In our patient, pincushioning of the flap was easily addressed by defatting the area. However, doing just this would not have sufficed and necessitated another surgical technique—the Z-plasty—which needed to be designed carefully. The larger the angle between the side arms and central limb, the greater directional change and scar length that is gained (Figure 3). As a result, longer limbs and a greater angle could advantageously break up the scar line but consequently would lengthen the scar considerably. Therefore, if the scar was longer or the skin was inelastic, multiple Z-plasty procedures may have been preferred.

Additionally, for each central limb, both mirror-image options for peripheral arms were considered, with the optimal choice being the one that allowed for final scar lines to mimic relaxed skin-tension lines. Accuracy of the incisions was critical and was assessed by drawing a line between the free ends of the lateral limbs of the Z; this line should pass perpendicularly through the midpoint of the central limb. Last, as with other transposition flap options, Z-plasty has the potential to create a trapdoor or pincushion effect; we reduced this risk by wide undermining to establish an even contraction plate.⁶

When planning the revision, we considered multiple approaches to achieve the best aesthetic outcome in 1 stage. Had there been notable depression in the scar, we may have used a full-thickness skin graft. If the skin surface was lumpy and uneven, dermabrasion or a laser may have been utilized. Another consideration was to avoid using intralesional steroids, which could have made the already atrophied portions of the scar worse.

Overall, the surgical plan that we chose took into consideration the patient’s nasal anatomic structure, the combination of scar defects, the patient’s desires, and the tools available.

Final Thoughts

The ideal scar is inconspicuous, does not impair the function of surrounding structures, and blends well with adjacent skin.⁵ Consequently, the combination of pincushioning and webbing of a scar, especially in the nasal area, can pose a surgical challenge to the surgeon and can cause severe anxiety in the patient. In those circumstances, a single surgical technique is not likely to produce the revision with the best cosmetic outcome. Therefore, the synergy of 2 or more surgical techniques with proper planning and meticulous selection may be necessary. A broad knowledge of various scar revision techniques increases the surgeon’s capability to create the ideal scar.

Acknowledgment—The authors thank the case patient for granting permission to publish this information.

Practice Gap

Nonmelanoma skin cancer is the most common cancer, typically growing in sun-exposed areas. As such, the nasal area is a common site of onset, constituting approximately 25% of cases. Surgical excision of these cancers generally has a high cure rate.¹

Although complete excision of the tumor is the primary goal of the dermatologic surgeon, achieving a cosmetically satisfactory scar also is important. As a prominent feature of the face, any irregularities to the nose are easily noticeable.² The subsequent scar may exhibit features that are less than ideal and cause notable stress to the patient.

When a scar presents with several complications, using a single surgical technique may not sufficiently address all defects. As a result, it can be challenging for the surgeon to decide which combination of methods among the myriad of nonsurgical and surgical options for scar revision will produce the best cosmetic outcome.

Case and Technique

A 76-year-old man presented 1 year after he underwent Mohs micrographic surgery for squamous cell carcinoma on the nasal dorsum. The tumor cleared after 1 stage and was repaired using a bilateral V-Y advancement flap. Postoperatively, the patient developed pincushioning of the flap, atrophic scarring inferior to the flap, and webbing of the pivotal restraint point at the nasal root (Figures 1A and 1B). We opted to address the pincushioning and nasal root webbing by defatting the flap and performing Z-plasty, respectively.

Pincushioning—Pincushioning of a flap arises due to contraction and lymphedema at the edge of the repair. It is seen more often in nasal repairs due to the limited availability of surrounding skin and changes in skin texture from rhinion to tip.³ To combat this in our patient, an incision was made around the site of the original flap, surrounding tissue was undermined, and the flap was reflected back. Subcutaneous tissue was removed with scissors. The flap was then laid back into the defect, and the subcutaneous tissue and dermis were closed with interrupted buried vertical mattress sutures. The epidermis was closed in a simple running fashion.

Webbing—Webbing of a scar also may develop from the contractile wound-healing process.⁴ Z-plasty commonly is used to camouflage a linear or contracted scar, increase skin availability in an area, or alter scar direction to better align with skin-tension lines.^5,6 In our patient, we incised the webbing of the nasal root along the vertical scar. Two arms were drawn at each end of the scar at a 60° angle (Figure 2); the side arms were drawn equal in length and incised vertically. Full-thickness skin flaps were then undermined at the level of subcutaneous fat, creating 2 triangular flaps. Adequate undermining of the surrounding subcutaneous tissue was performed to achieve proper mobilization of the flaps, which allowed for flap transposition to occur without tension and therefore for proper redirection of the scar.⁶ The flaps were secured using buried vertical mattress sutures and simple running sutures. Using too many buried interrupted sutures can cause vascular compromise of the fragile tips of the Z and should be avoided.³

At 4-month postoperative follow-up, the cosmetic outcome was judged satisfactory (Figure 1C).

Practice Implications

In our patient, pincushioning of the flap was easily addressed by defatting the area. However, doing just this would not have sufficed and necessitated another surgical technique—the Z-plasty—which needed to be designed carefully. The larger the angle between the side arms and central limb, the greater directional change and scar length that is gained (Figure 3). As a result, longer limbs and a greater angle could advantageously break up the scar line but consequently would lengthen the scar considerably. Therefore, if the scar was longer or the skin was inelastic, multiple Z-plasty procedures may have been preferred.

Additionally, for each central limb, both mirror-image options for peripheral arms were considered, with the optimal choice being the one that allowed for final scar lines to mimic relaxed skin-tension lines. Accuracy of the incisions was critical and was assessed by drawing a line between the free ends of the lateral limbs of the Z; this line should pass perpendicularly through the midpoint of the central limb. Last, as with other transposition flap options, Z-plasty has the potential to create a trapdoor or pincushion effect; we reduced this risk by wide undermining to establish an even contraction plate.⁶

When planning the revision, we considered multiple approaches to achieve the best aesthetic outcome in 1 stage. Had there been notable depression in the scar, we may have used a full-thickness skin graft. If the skin surface was lumpy and uneven, dermabrasion or a laser may have been utilized. Another consideration was to avoid using intralesional steroids, which could have made the already atrophied portions of the scar worse.

Overall, the surgical plan that we chose took into consideration the patient’s nasal anatomic structure, the combination of scar defects, the patient’s desires, and the tools available.

Final Thoughts

The ideal scar is inconspicuous, does not impair the function of surrounding structures, and blends well with adjacent skin.⁵ Consequently, the combination of pincushioning and webbing of a scar, especially in the nasal area, can pose a surgical challenge to the surgeon and can cause severe anxiety in the patient. In those circumstances, a single surgical technique is not likely to produce the revision with the best cosmetic outcome. Therefore, the synergy of 2 or more surgical techniques with proper planning and meticulous selection may be necessary. A broad knowledge of various scar revision techniques increases the surgeon’s capability to create the ideal scar.

Acknowledgment—The authors thank the case patient for granting permission to publish this information.

Practice Gap

Nonmelanoma skin cancer is the most common cancer, typically growing in sun-exposed areas. As such, the nasal area is a common site of onset, constituting approximately 25% of cases. Surgical excision of these cancers generally has a high cure rate.¹

Although complete excision of the tumor is the primary goal of the dermatologic surgeon, achieving a cosmetically satisfactory scar also is important. As a prominent feature of the face, any irregularities to the nose are easily noticeable.² The subsequent scar may exhibit features that are less than ideal and cause notable stress to the patient.

When a scar presents with several complications, using a single surgical technique may not sufficiently address all defects. As a result, it can be challenging for the surgeon to decide which combination of methods among the myriad of nonsurgical and surgical options for scar revision will produce the best cosmetic outcome.

Case and Technique

A 76-year-old man presented 1 year after he underwent Mohs micrographic surgery for squamous cell carcinoma on the nasal dorsum. The tumor cleared after 1 stage and was repaired using a bilateral V-Y advancement flap. Postoperatively, the patient developed pincushioning of the flap, atrophic scarring inferior to the flap, and webbing of the pivotal restraint point at the nasal root (Figures 1A and 1B). We opted to address the pincushioning and nasal root webbing by defatting the flap and performing Z-plasty, respectively.

Pincushioning—Pincushioning of a flap arises due to contraction and lymphedema at the edge of the repair. It is seen more often in nasal repairs due to the limited availability of surrounding skin and changes in skin texture from rhinion to tip.³ To combat this in our patient, an incision was made around the site of the original flap, surrounding tissue was undermined, and the flap was reflected back. Subcutaneous tissue was removed with scissors. The flap was then laid back into the defect, and the subcutaneous tissue and dermis were closed with interrupted buried vertical mattress sutures. The epidermis was closed in a simple running fashion.

Webbing—Webbing of a scar also may develop from the contractile wound-healing process.⁴ Z-plasty commonly is used to camouflage a linear or contracted scar, increase skin availability in an area, or alter scar direction to better align with skin-tension lines.^5,6 In our patient, we incised the webbing of the nasal root along the vertical scar. Two arms were drawn at each end of the scar at a 60° angle (Figure 2); the side arms were drawn equal in length and incised vertically. Full-thickness skin flaps were then undermined at the level of subcutaneous fat, creating 2 triangular flaps. Adequate undermining of the surrounding subcutaneous tissue was performed to achieve proper mobilization of the flaps, which allowed for flap transposition to occur without tension and therefore for proper redirection of the scar.⁶ The flaps were secured using buried vertical mattress sutures and simple running sutures. Using too many buried interrupted sutures can cause vascular compromise of the fragile tips of the Z and should be avoided.³

At 4-month postoperative follow-up, the cosmetic outcome was judged satisfactory (Figure 1C).

Practice Implications

In our patient, pincushioning of the flap was easily addressed by defatting the area. However, doing just this would not have sufficed and necessitated another surgical technique—the Z-plasty—which needed to be designed carefully. The larger the angle between the side arms and central limb, the greater directional change and scar length that is gained (Figure 3). As a result, longer limbs and a greater angle could advantageously break up the scar line but consequently would lengthen the scar considerably. Therefore, if the scar was longer or the skin was inelastic, multiple Z-plasty procedures may have been preferred.

Additionally, for each central limb, both mirror-image options for peripheral arms were considered, with the optimal choice being the one that allowed for final scar lines to mimic relaxed skin-tension lines. Accuracy of the incisions was critical and was assessed by drawing a line between the free ends of the lateral limbs of the Z; this line should pass perpendicularly through the midpoint of the central limb. Last, as with other transposition flap options, Z-plasty has the potential to create a trapdoor or pincushion effect; we reduced this risk by wide undermining to establish an even contraction plate.⁶

When planning the revision, we considered multiple approaches to achieve the best aesthetic outcome in 1 stage. Had there been notable depression in the scar, we may have used a full-thickness skin graft. If the skin surface was lumpy and uneven, dermabrasion or a laser may have been utilized. Another consideration was to avoid using intralesional steroids, which could have made the already atrophied portions of the scar worse.

Overall, the surgical plan that we chose took into consideration the patient’s nasal anatomic structure, the combination of scar defects, the patient’s desires, and the tools available.

Final Thoughts

The ideal scar is inconspicuous, does not impair the function of surrounding structures, and blends well with adjacent skin.⁵ Consequently, the combination of pincushioning and webbing of a scar, especially in the nasal area, can pose a surgical challenge to the surgeon and can cause severe anxiety in the patient. In those circumstances, a single surgical technique is not likely to produce the revision with the best cosmetic outcome. Therefore, the synergy of 2 or more surgical techniques with proper planning and meticulous selection may be necessary. A broad knowledge of various scar revision techniques increases the surgeon’s capability to create the ideal scar.

Acknowledgment—The authors thank the case patient for granting permission to publish this information.

The impacts of anthropogenic climate change on human health are numerous and growing. The evidence that climate change is occurring due to the burning of fossil fuels is substantial, with a 2019 report elevating the data supporting anthropogenic climate change to a gold standard 5-sigma level of significance.¹ In the peer-reviewed scientific literature, the consensus that humans are causing climate change is greater than 99%.² Both the American Medical Association and the American College of Physicians have acknowledged the health impacts of climate change and importance for action. They encourage physicians to engage in environmentally sustainable practices and to advocate for effective climate change mitigation strategies.^3,4 A survey of dermatologists also found that 99.3% (n=148) recognize climate change is occurring, and similarly high numbers are concerned about its health impacts.⁵

Notably, the health care industry must grapple not only with the health impacts of climate change but with the fact that the health care sector itself is responsible for a large amount of carbon emissions.⁶ The global health care industry as a whole produces enough carbon emissions to be ranked as the fifth largest emitting nation in the world.⁷ A quarter of these emissions are attributed to the US health care system.^8,9 Climate science has shown we must limit CO₂ emissions to avoid catastrophic climate change, with the sixth assessment report of the United Nations’ Intergovernmental Panel on Climate Change and the Paris Agreement targeting large emission reductions within the next decade.¹⁰ In August 2021, the US Department of Health and Human Services created the Office of Climate Change and Health Equity. Assistant Secretary for Health ADM Rachel L. Levine, MD, has committed to reducing the carbon emissions from the health care sector by 25% in the next decade, in line with scientific consensus regarding necessary changes.¹¹

The dermatologic impacts of climate change are myriad. Rising temperatures, increasing air and water pollution, and stratospheric ozone depletion will lead to expanded geographic ranges of vector-borne diseases, worsening of chronic skin conditions such as atopic dermatitis/eczema and pemphigus, and increasing rates of skin cancer.¹² For instance, warmer temperatures have allowed mosquitoes of the Aedes genus to infest new areas, leading to outbreaks of viral illnesses with cutaneous manifestations such as dengue, chikungunya, and Zika virus in previously nonindigenous regions.¹³ Rising temperatures also have been associated with an expanding geographic range of tick- and sandfly-borne illnesses such as Lyme disease, Rocky Mountain spotted fever, and cutaneous leishmaniasis.^13,14 Additionally, short-term exposure to air pollution from wildfire smoke has been associated with an increased use of health care services by patients with atopic dermatitis.¹⁵ Increased levels of air pollutants also have been found to be associated with psoriasis flares as well as hyperpigmentation and wrinkle formation.^16,17 Skin cancer incidence is predicted to rise due to increased UV radiation exposure secondary to stratospheric ozone depletion.¹⁸

Although the effects of climate change are significant and the magnitude of the climate crisis may feel overwhelming, it is essential to avoid doomerism and focus on meaningful impactful actions. Current CO₂ emissions will remain in the atmosphere for hundreds to thousands of years, and the choices we make now commit future generations to live in a world shaped by our decisions. Importantly, there are impactful and low-cost, cost-effective, or cost-saving changes that can be made to mitigate the climate crisis. Herein, we provide 10 practical actionable interventions for dermatologists to help combat climate change.

10 Interventions for Dermatologists to Combat Climate Change

1. Consider switching to renewable sources of energy. Making this switch often is the most impactful decision a dermatologist can make to address climate change. The electricity sector is the largest source of greenhouse gas emissions in the US health care system, and dermatology outpatient practices in particular have been observed to have a higher peak energy consumption than most other specialties studied.^19,20 Many dermatology practices—both privately owned and academic—can switch to renewable energy seamlessly through power purchase agreements (PPAs), which are contracts between power providers and private entities to install renewable energy equipment or source renewable energy from offsite sources at a fixed rate. Using PPAs instead of traditional fossil fuel energy can provide cost savings as well as protect buyers from electrical price volatility. Numerous health care systems utilize PPAs such as Kaiser Permanente, Cleveland Clinic, and Rochester Regional Health. Additionally, dermatologists can directly purchase renewable energy equipment and eventually receive a return on investment from substantially lowered electric bills. It is important to note that the cost of commercial solar energy systems has decreased 69% since 2010 with further cost reductions predicted.^21,22

2. Reduce standby power consumption. This refers to the use of electricity by a device when it appears to be off or is not in use, which can lead to considerable energy consumption and subsequently a larger carbon footprint for your practice. Ensuring electronics such as phone chargers, light fixtures, television screens, and computers are switched off prior to the end of the workday can make a large difference; for instance, a single radiology department at the University of Maryland (College Park, Maryland) found that if clinical workstations were shut down when not in use after an 8-hour workday, it would save 83,866 kWh of energy and $9225.33 per year.²³ Additionally, using power strips with an automatic shutoff feature to shut off power to devices not in use provides a more convenient way to reduce standby power.

3. Optimize thermostat settings. An analysis of energy consumption in 157,000 US health care facilities found that space heating and cooling accounted for 40% of their total energy consumption.²⁴ Thus, ensuring your thermostat and heating/cooling systems are working efficiently can conserve a substantial amount of energy. For maximum efficiency, it is recommended to set air conditioners to 74 °F (24 °C) and heaters to 68 °F (20 °C) or employ smart thermostats to optimally adjust temperatures when the office is not in use.²⁵ In addition, routinely replacing or cleaning air conditioner filters can lower energy consumption by 5% to 15%.²⁶ Similarly, improving insulation and ruggedization of both homes and offices may reduce heating and cooling waste and limit costs and emissions as a result.

4. Offer bicycle racks and charging ports for electric vehicles. In the United States, transportation generates more greenhouse gas emissions than any other source, primarily due to the burning of fossil fuels to power automobiles, trains, and planes. Because bicycles do not consume any fossil fuels and the use of electric vehicles has been found to result in substantial air pollution health benefits, encouraging the use of both can make a considerable positive impact on our climate.²⁷ Providing these resources not only allows those who already travel sustainably to continue to do so but also serves as a reminder to your patients that sustainability is important to you as their health care provider. As electric vehicle sales continue to climb, infrastructure to support their use, including charging stations, will grow in importance. A physician’s office that offers a car-charging station may soon have a competitive advantage over others in the area.

5. Ensure properly regulated medical waste management. Regulated medical waste (also known as infectious medical waste or red bag waste) refers to health care–generated waste unsuitable for disposal in municipal solid waste systems due to concern for the spread of infectious or pathogenic materials. This waste largely is disposed via incineration, which harms the environment in a multitude of ways—both through harmful byproducts and from the CO₂ emissions required to ship the waste to special processing facilities.²⁸ Incineration of regulated medical waste emits potent toxins such as dioxins and furans as well as particulate matter, which contribute to air pollution. Ensuring only materials with infectious potential (as defined by each state’s Environmental Protection Agency) are disposed in regulated medical waste containers can dramatically reduce the harmful effects of incineration. Additionally, limiting regulated medical waste can be very cost-effective, as its disposal is 5- to 10-times more expensive than that of unregulated medical waste.²⁹ Simple nudge measures such as educating staff about what waste goes in which receptacle, placing signage over the red bag waste to prompt staff to pause to consider if use of that bin is required before utilizing, using weights or clasps to make opening red bag waste containers slightly harder, and positioning different trash receptacles in different parts of examination rooms may help reduce inappropriate use of red bag waste.

6. Consider virtual platforms when possible. Due to the COVID-19 pandemic, virtual meeting platforms saw a considerable increase in usage by dermatologists. Teledermatology for patient care became much more widely adopted, and traditionally in-person meetings turned virtual.³⁰ The reduction in emissions from these changes was remarkable. A recent study looking at the environmental impact of 3 months of teledermatology visits early during the COVID-19 pandemic found that 1476 teledermatology appointments saved 55,737 miles of car travel, equivalent to 15.37 metric tons of CO₂.³¹ Whether for patient care when appropriate, academic conferences and continuing medical education credit, or for interviews (eg, medical students, residents, other staff), use of virtual platforms can reduce unnecessary travel and therefore substantially reduce travel-related emissions. When travel is unavoidable, consider exploring validated vetted companies that offer carbon offsets to reduce the harmful environmental impact of high-emission flights.

7. Limit use of single-use disposable items. Although single-use items such as examination gloves or needles are necessary in a dermatology practice, there are many opportunities to incorporate reusable items in your workplace. For instance, you can replace plastic cutlery and single-use plates in kitchen or dining areas with reusable alternatives. Additionally, using reusable isolation gowns instead of their single-use counterparts can help reduce waste; a reusable isolation gown system for providers including laundering services was found to consume 28% less energy and emit 30% fewer greenhouse gases than a single-use isolation gown system.³² Similarly, opting for reusable instruments instead of single-use instruments when possible also can help reduce your practice’s carbon footprint. Carefully evaluating each part of your “dermatology visit supply chain” may offer opportunities to utilize additional cost-saving, environmentally friendly options; for example, an individually plastic-wrapped Dermablade vs a bulk-packaged blade for shave biopsies has a higher cost and worse environmental impact. A single gauze often is sufficient for shave biopsies, but many practices open a plastic container of bulk gauze, much of which results in waste that too often is inappropriately disposed of as regulated medical waste despite not being saturated in blood/body fluids.

8. Educate on the effects of climate change. Dermatologists and other physicians have the unique opportunity to teach members of their community every day through patient care. Physicians are trusted messengers, and appropriately counseling patients regarding the risks of climate change and its effects on their dermatologic health is in line with both American Medical Association and American College of Physicians guidelines.^3,4 For instance, patients with Lyme disease in Canada or Maine were unheard of a few decades ago, but now they are common; flares of atopic dermatitis in regions adjacent to recent wildfires may be attributable to harmful particulate matter resulting from fossil-fueled climate change and record droughts. Educating medical trainees on the impacts of climate change is just as vital, as it is a topic that often is neglected in medical school and residency curricula.³³

9. Install water-efficient toilets and faucets. Anthropogenic climate change has been shown to increase the duration and intensity of droughts throughout the world.³⁴ Much of the western United States also is experiencing record droughts. One way in which dermatology practices can work to combat droughts is through the use of water-conserving toilets, faucets, and urinals. Using water fixtures with the US Environmental Protection Agency’s WaterSense label is a convenient way to do so. The WaterSense label helps identify water fixtures certified to use at least 20% less water as well as save energy and decrease water costs.

10. Advocate through local and national organizations. There are numerous ways in which dermatologists can advocate for action against climate change. Joining professional organizations focused on addressing the climate crisis can help you connect with fellow dermatologists and physicians. The Expert Resource Group on Climate Change and Environmental Issues affiliated with the American Academy of Dermatology (AAD) is one such organization with many opportunities to raise awareness within the field of dermatology. The AAD recently joined the Medical Society Consortium on Climate and Health, an organization providing opportunities for policy and media outreach as well as research on climate change. Advocacy also can mean joining your local chapter of Physicians for Social Responsibility or encouraging divestment from fossil fuel companies within your institution. Voicing support for climate change–focused lectures at events such as grand rounds and society meetings at the local, regional, and state-wide levels can help raise awareness. As the dermatologic effects of climate change grow, being knowledgeable of the views of future leaders in our specialty and country on this issue will become increasingly important.

Final Thoughts

In addition to the climate-friendly decisions one can make as a dermatologist, there are many personal lifestyle choices to consider. Small dietary changes such as limiting consumption of beef and minimizing food waste can have large downstream effects. Opting for transportation via train and limiting air travel are both impactful decisions in reducing CO₂ emissions. Similarly, switching to an electric vehicle or vehicle with minimal emissions can work to reduce greenhouse gas accumulation. For additional resources, note the AAD has partnered with My Green Doctor, a nonprofit service for health care practices that includes practical cost-saving suggestions to support sustainability in physician practices.

A recent joint publication in more than 200 medical journals described climate change as the greatest threat to global public health.³⁵ Climate change is having devastating effects on dermatologic health and will only continue to do so if not addressed now. Dermatologists have the opportunity to join with our colleagues in the house of medicine and to take action to fight climate change and mitigate the health impacts on our patients, the population, and future generations.

The impacts of anthropogenic climate change on human health are numerous and growing. The evidence that climate change is occurring due to the burning of fossil fuels is substantial, with a 2019 report elevating the data supporting anthropogenic climate change to a gold standard 5-sigma level of significance.¹ In the peer-reviewed scientific literature, the consensus that humans are causing climate change is greater than 99%.² Both the American Medical Association and the American College of Physicians have acknowledged the health impacts of climate change and importance for action. They encourage physicians to engage in environmentally sustainable practices and to advocate for effective climate change mitigation strategies.^3,4 A survey of dermatologists also found that 99.3% (n=148) recognize climate change is occurring, and similarly high numbers are concerned about its health impacts.⁵

Notably, the health care industry must grapple not only with the health impacts of climate change but with the fact that the health care sector itself is responsible for a large amount of carbon emissions.⁶ The global health care industry as a whole produces enough carbon emissions to be ranked as the fifth largest emitting nation in the world.⁷ A quarter of these emissions are attributed to the US health care system.^8,9 Climate science has shown we must limit CO₂ emissions to avoid catastrophic climate change, with the sixth assessment report of the United Nations’ Intergovernmental Panel on Climate Change and the Paris Agreement targeting large emission reductions within the next decade.¹⁰ In August 2021, the US Department of Health and Human Services created the Office of Climate Change and Health Equity. Assistant Secretary for Health ADM Rachel L. Levine, MD, has committed to reducing the carbon emissions from the health care sector by 25% in the next decade, in line with scientific consensus regarding necessary changes.¹¹

The dermatologic impacts of climate change are myriad. Rising temperatures, increasing air and water pollution, and stratospheric ozone depletion will lead to expanded geographic ranges of vector-borne diseases, worsening of chronic skin conditions such as atopic dermatitis/eczema and pemphigus, and increasing rates of skin cancer.¹² For instance, warmer temperatures have allowed mosquitoes of the Aedes genus to infest new areas, leading to outbreaks of viral illnesses with cutaneous manifestations such as dengue, chikungunya, and Zika virus in previously nonindigenous regions.¹³ Rising temperatures also have been associated with an expanding geographic range of tick- and sandfly-borne illnesses such as Lyme disease, Rocky Mountain spotted fever, and cutaneous leishmaniasis.^13,14 Additionally, short-term exposure to air pollution from wildfire smoke has been associated with an increased use of health care services by patients with atopic dermatitis.¹⁵ Increased levels of air pollutants also have been found to be associated with psoriasis flares as well as hyperpigmentation and wrinkle formation.^16,17 Skin cancer incidence is predicted to rise due to increased UV radiation exposure secondary to stratospheric ozone depletion.¹⁸

Although the effects of climate change are significant and the magnitude of the climate crisis may feel overwhelming, it is essential to avoid doomerism and focus on meaningful impactful actions. Current CO₂ emissions will remain in the atmosphere for hundreds to thousands of years, and the choices we make now commit future generations to live in a world shaped by our decisions. Importantly, there are impactful and low-cost, cost-effective, or cost-saving changes that can be made to mitigate the climate crisis. Herein, we provide 10 practical actionable interventions for dermatologists to help combat climate change.

10 Interventions for Dermatologists to Combat Climate Change

1. Consider switching to renewable sources of energy. Making this switch often is the most impactful decision a dermatologist can make to address climate change. The electricity sector is the largest source of greenhouse gas emissions in the US health care system, and dermatology outpatient practices in particular have been observed to have a higher peak energy consumption than most other specialties studied.^19,20 Many dermatology practices—both privately owned and academic—can switch to renewable energy seamlessly through power purchase agreements (PPAs), which are contracts between power providers and private entities to install renewable energy equipment or source renewable energy from offsite sources at a fixed rate. Using PPAs instead of traditional fossil fuel energy can provide cost savings as well as protect buyers from electrical price volatility. Numerous health care systems utilize PPAs such as Kaiser Permanente, Cleveland Clinic, and Rochester Regional Health. Additionally, dermatologists can directly purchase renewable energy equipment and eventually receive a return on investment from substantially lowered electric bills. It is important to note that the cost of commercial solar energy systems has decreased 69% since 2010 with further cost reductions predicted.^21,22

2. Reduce standby power consumption. This refers to the use of electricity by a device when it appears to be off or is not in use, which can lead to considerable energy consumption and subsequently a larger carbon footprint for your practice. Ensuring electronics such as phone chargers, light fixtures, television screens, and computers are switched off prior to the end of the workday can make a large difference; for instance, a single radiology department at the University of Maryland (College Park, Maryland) found that if clinical workstations were shut down when not in use after an 8-hour workday, it would save 83,866 kWh of energy and $9225.33 per year.²³ Additionally, using power strips with an automatic shutoff feature to shut off power to devices not in use provides a more convenient way to reduce standby power.

3. Optimize thermostat settings. An analysis of energy consumption in 157,000 US health care facilities found that space heating and cooling accounted for 40% of their total energy consumption.²⁴ Thus, ensuring your thermostat and heating/cooling systems are working efficiently can conserve a substantial amount of energy. For maximum efficiency, it is recommended to set air conditioners to 74 °F (24 °C) and heaters to 68 °F (20 °C) or employ smart thermostats to optimally adjust temperatures when the office is not in use.²⁵ In addition, routinely replacing or cleaning air conditioner filters can lower energy consumption by 5% to 15%.²⁶ Similarly, improving insulation and ruggedization of both homes and offices may reduce heating and cooling waste and limit costs and emissions as a result.

4. Offer bicycle racks and charging ports for electric vehicles. In the United States, transportation generates more greenhouse gas emissions than any other source, primarily due to the burning of fossil fuels to power automobiles, trains, and planes. Because bicycles do not consume any fossil fuels and the use of electric vehicles has been found to result in substantial air pollution health benefits, encouraging the use of both can make a considerable positive impact on our climate.²⁷ Providing these resources not only allows those who already travel sustainably to continue to do so but also serves as a reminder to your patients that sustainability is important to you as their health care provider. As electric vehicle sales continue to climb, infrastructure to support their use, including charging stations, will grow in importance. A physician’s office that offers a car-charging station may soon have a competitive advantage over others in the area.

5. Ensure properly regulated medical waste management. Regulated medical waste (also known as infectious medical waste or red bag waste) refers to health care–generated waste unsuitable for disposal in municipal solid waste systems due to concern for the spread of infectious or pathogenic materials. This waste largely is disposed via incineration, which harms the environment in a multitude of ways—both through harmful byproducts and from the CO₂ emissions required to ship the waste to special processing facilities.²⁸ Incineration of regulated medical waste emits potent toxins such as dioxins and furans as well as particulate matter, which contribute to air pollution. Ensuring only materials with infectious potential (as defined by each state’s Environmental Protection Agency) are disposed in regulated medical waste containers can dramatically reduce the harmful effects of incineration. Additionally, limiting regulated medical waste can be very cost-effective, as its disposal is 5- to 10-times more expensive than that of unregulated medical waste.²⁹ Simple nudge measures such as educating staff about what waste goes in which receptacle, placing signage over the red bag waste to prompt staff to pause to consider if use of that bin is required before utilizing, using weights or clasps to make opening red bag waste containers slightly harder, and positioning different trash receptacles in different parts of examination rooms may help reduce inappropriate use of red bag waste.

6. Consider virtual platforms when possible. Due to the COVID-19 pandemic, virtual meeting platforms saw a considerable increase in usage by dermatologists. Teledermatology for patient care became much more widely adopted, and traditionally in-person meetings turned virtual.³⁰ The reduction in emissions from these changes was remarkable. A recent study looking at the environmental impact of 3 months of teledermatology visits early during the COVID-19 pandemic found that 1476 teledermatology appointments saved 55,737 miles of car travel, equivalent to 15.37 metric tons of CO₂.³¹ Whether for patient care when appropriate, academic conferences and continuing medical education credit, or for interviews (eg, medical students, residents, other staff), use of virtual platforms can reduce unnecessary travel and therefore substantially reduce travel-related emissions. When travel is unavoidable, consider exploring validated vetted companies that offer carbon offsets to reduce the harmful environmental impact of high-emission flights.

7. Limit use of single-use disposable items. Although single-use items such as examination gloves or needles are necessary in a dermatology practice, there are many opportunities to incorporate reusable items in your workplace. For instance, you can replace plastic cutlery and single-use plates in kitchen or dining areas with reusable alternatives. Additionally, using reusable isolation gowns instead of their single-use counterparts can help reduce waste; a reusable isolation gown system for providers including laundering services was found to consume 28% less energy and emit 30% fewer greenhouse gases than a single-use isolation gown system.³² Similarly, opting for reusable instruments instead of single-use instruments when possible also can help reduce your practice’s carbon footprint. Carefully evaluating each part of your “dermatology visit supply chain” may offer opportunities to utilize additional cost-saving, environmentally friendly options; for example, an individually plastic-wrapped Dermablade vs a bulk-packaged blade for shave biopsies has a higher cost and worse environmental impact. A single gauze often is sufficient for shave biopsies, but many practices open a plastic container of bulk gauze, much of which results in waste that too often is inappropriately disposed of as regulated medical waste despite not being saturated in blood/body fluids.

8. Educate on the effects of climate change. Dermatologists and other physicians have the unique opportunity to teach members of their community every day through patient care. Physicians are trusted messengers, and appropriately counseling patients regarding the risks of climate change and its effects on their dermatologic health is in line with both American Medical Association and American College of Physicians guidelines.^3,4 For instance, patients with Lyme disease in Canada or Maine were unheard of a few decades ago, but now they are common; flares of atopic dermatitis in regions adjacent to recent wildfires may be attributable to harmful particulate matter resulting from fossil-fueled climate change and record droughts. Educating medical trainees on the impacts of climate change is just as vital, as it is a topic that often is neglected in medical school and residency curricula.³³

9. Install water-efficient toilets and faucets. Anthropogenic climate change has been shown to increase the duration and intensity of droughts throughout the world.³⁴ Much of the western United States also is experiencing record droughts. One way in which dermatology practices can work to combat droughts is through the use of water-conserving toilets, faucets, and urinals. Using water fixtures with the US Environmental Protection Agency’s WaterSense label is a convenient way to do so. The WaterSense label helps identify water fixtures certified to use at least 20% less water as well as save energy and decrease water costs.

10. Advocate through local and national organizations. There are numerous ways in which dermatologists can advocate for action against climate change. Joining professional organizations focused on addressing the climate crisis can help you connect with fellow dermatologists and physicians. The Expert Resource Group on Climate Change and Environmental Issues affiliated with the American Academy of Dermatology (AAD) is one such organization with many opportunities to raise awareness within the field of dermatology. The AAD recently joined the Medical Society Consortium on Climate and Health, an organization providing opportunities for policy and media outreach as well as research on climate change. Advocacy also can mean joining your local chapter of Physicians for Social Responsibility or encouraging divestment from fossil fuel companies within your institution. Voicing support for climate change–focused lectures at events such as grand rounds and society meetings at the local, regional, and state-wide levels can help raise awareness. As the dermatologic effects of climate change grow, being knowledgeable of the views of future leaders in our specialty and country on this issue will become increasingly important.

Final Thoughts

In addition to the climate-friendly decisions one can make as a dermatologist, there are many personal lifestyle choices to consider. Small dietary changes such as limiting consumption of beef and minimizing food waste can have large downstream effects. Opting for transportation via train and limiting air travel are both impactful decisions in reducing CO₂ emissions. Similarly, switching to an electric vehicle or vehicle with minimal emissions can work to reduce greenhouse gas accumulation. For additional resources, note the AAD has partnered with My Green Doctor, a nonprofit service for health care practices that includes practical cost-saving suggestions to support sustainability in physician practices.

A recent joint publication in more than 200 medical journals described climate change as the greatest threat to global public health.³⁵ Climate change is having devastating effects on dermatologic health and will only continue to do so if not addressed now. Dermatologists have the opportunity to join with our colleagues in the house of medicine and to take action to fight climate change and mitigate the health impacts on our patients, the population, and future generations.

The impacts of anthropogenic climate change on human health are numerous and growing. The evidence that climate change is occurring due to the burning of fossil fuels is substantial, with a 2019 report elevating the data supporting anthropogenic climate change to a gold standard 5-sigma level of significance.¹ In the peer-reviewed scientific literature, the consensus that humans are causing climate change is greater than 99%.² Both the American Medical Association and the American College of Physicians have acknowledged the health impacts of climate change and importance for action. They encourage physicians to engage in environmentally sustainable practices and to advocate for effective climate change mitigation strategies.^3,4 A survey of dermatologists also found that 99.3% (n=148) recognize climate change is occurring, and similarly high numbers are concerned about its health impacts.⁵

Notably, the health care industry must grapple not only with the health impacts of climate change but with the fact that the health care sector itself is responsible for a large amount of carbon emissions.⁶ The global health care industry as a whole produces enough carbon emissions to be ranked as the fifth largest emitting nation in the world.⁷ A quarter of these emissions are attributed to the US health care system.^8,9 Climate science has shown we must limit CO₂ emissions to avoid catastrophic climate change, with the sixth assessment report of the United Nations’ Intergovernmental Panel on Climate Change and the Paris Agreement targeting large emission reductions within the next decade.¹⁰ In August 2021, the US Department of Health and Human Services created the Office of Climate Change and Health Equity. Assistant Secretary for Health ADM Rachel L. Levine, MD, has committed to reducing the carbon emissions from the health care sector by 25% in the next decade, in line with scientific consensus regarding necessary changes.¹¹

The dermatologic impacts of climate change are myriad. Rising temperatures, increasing air and water pollution, and stratospheric ozone depletion will lead to expanded geographic ranges of vector-borne diseases, worsening of chronic skin conditions such as atopic dermatitis/eczema and pemphigus, and increasing rates of skin cancer.¹² For instance, warmer temperatures have allowed mosquitoes of the Aedes genus to infest new areas, leading to outbreaks of viral illnesses with cutaneous manifestations such as dengue, chikungunya, and Zika virus in previously nonindigenous regions.¹³ Rising temperatures also have been associated with an expanding geographic range of tick- and sandfly-borne illnesses such as Lyme disease, Rocky Mountain spotted fever, and cutaneous leishmaniasis.^13,14 Additionally, short-term exposure to air pollution from wildfire smoke has been associated with an increased use of health care services by patients with atopic dermatitis.¹⁵ Increased levels of air pollutants also have been found to be associated with psoriasis flares as well as hyperpigmentation and wrinkle formation.^16,17 Skin cancer incidence is predicted to rise due to increased UV radiation exposure secondary to stratospheric ozone depletion.¹⁸

Although the effects of climate change are significant and the magnitude of the climate crisis may feel overwhelming, it is essential to avoid doomerism and focus on meaningful impactful actions. Current CO₂ emissions will remain in the atmosphere for hundreds to thousands of years, and the choices we make now commit future generations to live in a world shaped by our decisions. Importantly, there are impactful and low-cost, cost-effective, or cost-saving changes that can be made to mitigate the climate crisis. Herein, we provide 10 practical actionable interventions for dermatologists to help combat climate change.

10 Interventions for Dermatologists to Combat Climate Change

1. Consider switching to renewable sources of energy. Making this switch often is the most impactful decision a dermatologist can make to address climate change. The electricity sector is the largest source of greenhouse gas emissions in the US health care system, and dermatology outpatient practices in particular have been observed to have a higher peak energy consumption than most other specialties studied.^19,20 Many dermatology practices—both privately owned and academic—can switch to renewable energy seamlessly through power purchase agreements (PPAs), which are contracts between power providers and private entities to install renewable energy equipment or source renewable energy from offsite sources at a fixed rate. Using PPAs instead of traditional fossil fuel energy can provide cost savings as well as protect buyers from electrical price volatility. Numerous health care systems utilize PPAs such as Kaiser Permanente, Cleveland Clinic, and Rochester Regional Health. Additionally, dermatologists can directly purchase renewable energy equipment and eventually receive a return on investment from substantially lowered electric bills. It is important to note that the cost of commercial solar energy systems has decreased 69% since 2010 with further cost reductions predicted.^21,22

2. Reduce standby power consumption. This refers to the use of electricity by a device when it appears to be off or is not in use, which can lead to considerable energy consumption and subsequently a larger carbon footprint for your practice. Ensuring electronics such as phone chargers, light fixtures, television screens, and computers are switched off prior to the end of the workday can make a large difference; for instance, a single radiology department at the University of Maryland (College Park, Maryland) found that if clinical workstations were shut down when not in use after an 8-hour workday, it would save 83,866 kWh of energy and $9225.33 per year.²³ Additionally, using power strips with an automatic shutoff feature to shut off power to devices not in use provides a more convenient way to reduce standby power.

3. Optimize thermostat settings. An analysis of energy consumption in 157,000 US health care facilities found that space heating and cooling accounted for 40% of their total energy consumption.²⁴ Thus, ensuring your thermostat and heating/cooling systems are working efficiently can conserve a substantial amount of energy. For maximum efficiency, it is recommended to set air conditioners to 74 °F (24 °C) and heaters to 68 °F (20 °C) or employ smart thermostats to optimally adjust temperatures when the office is not in use.²⁵ In addition, routinely replacing or cleaning air conditioner filters can lower energy consumption by 5% to 15%.²⁶ Similarly, improving insulation and ruggedization of both homes and offices may reduce heating and cooling waste and limit costs and emissions as a result.

4. Offer bicycle racks and charging ports for electric vehicles. In the United States, transportation generates more greenhouse gas emissions than any other source, primarily due to the burning of fossil fuels to power automobiles, trains, and planes. Because bicycles do not consume any fossil fuels and the use of electric vehicles has been found to result in substantial air pollution health benefits, encouraging the use of both can make a considerable positive impact on our climate.²⁷ Providing these resources not only allows those who already travel sustainably to continue to do so but also serves as a reminder to your patients that sustainability is important to you as their health care provider. As electric vehicle sales continue to climb, infrastructure to support their use, including charging stations, will grow in importance. A physician’s office that offers a car-charging station may soon have a competitive advantage over others in the area.

5. Ensure properly regulated medical waste management. Regulated medical waste (also known as infectious medical waste or red bag waste) refers to health care–generated waste unsuitable for disposal in municipal solid waste systems due to concern for the spread of infectious or pathogenic materials. This waste largely is disposed via incineration, which harms the environment in a multitude of ways—both through harmful byproducts and from the CO₂ emissions required to ship the waste to special processing facilities.²⁸ Incineration of regulated medical waste emits potent toxins such as dioxins and furans as well as particulate matter, which contribute to air pollution. Ensuring only materials with infectious potential (as defined by each state’s Environmental Protection Agency) are disposed in regulated medical waste containers can dramatically reduce the harmful effects of incineration. Additionally, limiting regulated medical waste can be very cost-effective, as its disposal is 5- to 10-times more expensive than that of unregulated medical waste.²⁹ Simple nudge measures such as educating staff about what waste goes in which receptacle, placing signage over the red bag waste to prompt staff to pause to consider if use of that bin is required before utilizing, using weights or clasps to make opening red bag waste containers slightly harder, and positioning different trash receptacles in different parts of examination rooms may help reduce inappropriate use of red bag waste.

6. Consider virtual platforms when possible. Due to the COVID-19 pandemic, virtual meeting platforms saw a considerable increase in usage by dermatologists. Teledermatology for patient care became much more widely adopted, and traditionally in-person meetings turned virtual.³⁰ The reduction in emissions from these changes was remarkable. A recent study looking at the environmental impact of 3 months of teledermatology visits early during the COVID-19 pandemic found that 1476 teledermatology appointments saved 55,737 miles of car travel, equivalent to 15.37 metric tons of CO₂.³¹ Whether for patient care when appropriate, academic conferences and continuing medical education credit, or for interviews (eg, medical students, residents, other staff), use of virtual platforms can reduce unnecessary travel and therefore substantially reduce travel-related emissions. When travel is unavoidable, consider exploring validated vetted companies that offer carbon offsets to reduce the harmful environmental impact of high-emission flights.

7. Limit use of single-use disposable items. Although single-use items such as examination gloves or needles are necessary in a dermatology practice, there are many opportunities to incorporate reusable items in your workplace. For instance, you can replace plastic cutlery and single-use plates in kitchen or dining areas with reusable alternatives. Additionally, using reusable isolation gowns instead of their single-use counterparts can help reduce waste; a reusable isolation gown system for providers including laundering services was found to consume 28% less energy and emit 30% fewer greenhouse gases than a single-use isolation gown system.³² Similarly, opting for reusable instruments instead of single-use instruments when possible also can help reduce your practice’s carbon footprint. Carefully evaluating each part of your “dermatology visit supply chain” may offer opportunities to utilize additional cost-saving, environmentally friendly options; for example, an individually plastic-wrapped Dermablade vs a bulk-packaged blade for shave biopsies has a higher cost and worse environmental impact. A single gauze often is sufficient for shave biopsies, but many practices open a plastic container of bulk gauze, much of which results in waste that too often is inappropriately disposed of as regulated medical waste despite not being saturated in blood/body fluids.

8. Educate on the effects of climate change. Dermatologists and other physicians have the unique opportunity to teach members of their community every day through patient care. Physicians are trusted messengers, and appropriately counseling patients regarding the risks of climate change and its effects on their dermatologic health is in line with both American Medical Association and American College of Physicians guidelines.^3,4 For instance, patients with Lyme disease in Canada or Maine were unheard of a few decades ago, but now they are common; flares of atopic dermatitis in regions adjacent to recent wildfires may be attributable to harmful particulate matter resulting from fossil-fueled climate change and record droughts. Educating medical trainees on the impacts of climate change is just as vital, as it is a topic that often is neglected in medical school and residency curricula.³³

9. Install water-efficient toilets and faucets. Anthropogenic climate change has been shown to increase the duration and intensity of droughts throughout the world.³⁴ Much of the western United States also is experiencing record droughts. One way in which dermatology practices can work to combat droughts is through the use of water-conserving toilets, faucets, and urinals. Using water fixtures with the US Environmental Protection Agency’s WaterSense label is a convenient way to do so. The WaterSense label helps identify water fixtures certified to use at least 20% less water as well as save energy and decrease water costs.

10. Advocate through local and national organizations. There are numerous ways in which dermatologists can advocate for action against climate change. Joining professional organizations focused on addressing the climate crisis can help you connect with fellow dermatologists and physicians. The Expert Resource Group on Climate Change and Environmental Issues affiliated with the American Academy of Dermatology (AAD) is one such organization with many opportunities to raise awareness within the field of dermatology. The AAD recently joined the Medical Society Consortium on Climate and Health, an organization providing opportunities for policy and media outreach as well as research on climate change. Advocacy also can mean joining your local chapter of Physicians for Social Responsibility or encouraging divestment from fossil fuel companies within your institution. Voicing support for climate change–focused lectures at events such as grand rounds and society meetings at the local, regional, and state-wide levels can help raise awareness. As the dermatologic effects of climate change grow, being knowledgeable of the views of future leaders in our specialty and country on this issue will become increasingly important.

Final Thoughts

In addition to the climate-friendly decisions one can make as a dermatologist, there are many personal lifestyle choices to consider. Small dietary changes such as limiting consumption of beef and minimizing food waste can have large downstream effects. Opting for transportation via train and limiting air travel are both impactful decisions in reducing CO₂ emissions. Similarly, switching to an electric vehicle or vehicle with minimal emissions can work to reduce greenhouse gas accumulation. For additional resources, note the AAD has partnered with My Green Doctor, a nonprofit service for health care practices that includes practical cost-saving suggestions to support sustainability in physician practices.

A recent joint publication in more than 200 medical journals described climate change as the greatest threat to global public health.³⁵ Climate change is having devastating effects on dermatologic health and will only continue to do so if not addressed now. Dermatologists have the opportunity to join with our colleagues in the house of medicine and to take action to fight climate change and mitigate the health impacts on our patients, the population, and future generations.

The Diagnosis: Syringoma

Syringomas are benign adnexal tumors with distinct histopathologic features, including the characteristic comma- or tadpole-shaped tail comprised of dilated cystic eccrine ducts. Clinically, syringomas typically present predominantly in the periorbital region in adolescent girls. They may present as solitary or multiple lesions, and sites such as the genital area, palms, scalp, and chest rarely can be involved.¹ Eruptive syringoma is a clinical subtype of syringoma that is seen on the face, neck, chest, and axillae that predominantly occurs in females with skin of color in countries such as Asia and Africa before or during puberty.^2,3 Lesions appear as small, flesh-colored or slightly pigmented, flat-topped papules.³ The condition can be cosmetically disfiguring and difficult to treat, especially in patients with darker skin.

In our patient, dermoscopic evaluation revealed reticular light brown lines, structureless light brown areas, clustered brown dots, globules, and reticular vessels on a faint background (Figure 1A). Glittering yellow-whitish round structures over a fading pink-brown background also were seen at some sites (Figure 1B). Histologic examination of a neck lesion revealed an epidermis with focal acanthosis; the upper dermis had tumor islands and ducts with cells with round to vesicular nuclei and eosinophilic cytoplasm. A well-circumscribed tumor in the dermis composed of tubules of varying sizes lined by cuboidal cells was seen, consistent with syringoma (Figure 2).

Dermoscopic features of syringomas have not been widely studied. Hayashi et al⁴ reported the dermoscopic features of unilateral linear syringomas as a delicate and faint reticular pigmentation network and multiple hypopigmented areas. Sakiyama et al⁵ also defined an incomplete pigment network with faint erythema in 2 eruptive syringoma cases.

Treatment of this condition is for cosmetic reasons only, and there are no reports of long-term morbidity associated with the disease.^6,7 Multiple therapeutic options are available but are associated with complications such as hyperpigmentation and sclerosis in patients with skin of color due to the dermal location of these syringomas. Management of syringomas includes topical and surgical methods, including topical retinoids such as tretinoin and atropine solution 1%; surgical methods include dermabrasion, excision, cryotherapy, electrocautery, electrofulguration, laser therapy, and chemical cautery. However, there is a substantial risk for recurrence with these treatment options. In a case series of 5 patients with periorbital syringomas, treatment using radiofrequency and a CO₂ laser was performed with favorable outcomes, highlighting the use of combination therapies for treatment.8 Seo et al⁹ reported a retrospective case series of 92 patients with periorbital syringomas in which they treated one group with CO₂ laser and the other with botulinum toxin A injection; CO₂ laser combined with botulinum toxin A showed a greater effect than laser treatment alone. The differential diagnosis includes pigmented plane warts, sebaceous hyperplasia, eruptive xanthomas, and hidrocystomas. Pigmented plane warts characteristically present as flat-topped papules with small hemorrhagic dots or tiny pinpoint vessels on dermoscopy. In sebaceous hyperplasia, yellowish umbilicated papular lesions are seen with crown vessels on dermoscopy. Eruptive xanthomas usually are erythematous to yellow, dome-shaped papules that appear mainly over the extensor aspects of the extremities. Hidrocystoma presents as a solitary translucent larger syringomalike lesion commonly seen in the periorbital region and/or on the cheeks.

We report a case of widespread syringomas with multiple close mimickers such as pigmented plane warts; however, dermoscopy of the lesions helped to arrive at the diagnosis. Dermatologists should be aware of this condition and its benign nature to ensure correct diagnosis and appropriate treatment.

The Diagnosis: Syringoma

Syringomas are benign adnexal tumors with distinct histopathologic features, including the characteristic comma- or tadpole-shaped tail comprised of dilated cystic eccrine ducts. Clinically, syringomas typically present predominantly in the periorbital region in adolescent girls. They may present as solitary or multiple lesions, and sites such as the genital area, palms, scalp, and chest rarely can be involved.¹ Eruptive syringoma is a clinical subtype of syringoma that is seen on the face, neck, chest, and axillae that predominantly occurs in females with skin of color in countries such as Asia and Africa before or during puberty.^2,3 Lesions appear as small, flesh-colored or slightly pigmented, flat-topped papules.³ The condition can be cosmetically disfiguring and difficult to treat, especially in patients with darker skin.

In our patient, dermoscopic evaluation revealed reticular light brown lines, structureless light brown areas, clustered brown dots, globules, and reticular vessels on a faint background (Figure 1A). Glittering yellow-whitish round structures over a fading pink-brown background also were seen at some sites (Figure 1B). Histologic examination of a neck lesion revealed an epidermis with focal acanthosis; the upper dermis had tumor islands and ducts with cells with round to vesicular nuclei and eosinophilic cytoplasm. A well-circumscribed tumor in the dermis composed of tubules of varying sizes lined by cuboidal cells was seen, consistent with syringoma (Figure 2).

Dermoscopic features of syringomas have not been widely studied. Hayashi et al⁴ reported the dermoscopic features of unilateral linear syringomas as a delicate and faint reticular pigmentation network and multiple hypopigmented areas. Sakiyama et al⁵ also defined an incomplete pigment network with faint erythema in 2 eruptive syringoma cases.

Treatment of this condition is for cosmetic reasons only, and there are no reports of long-term morbidity associated with the disease.^6,7 Multiple therapeutic options are available but are associated with complications such as hyperpigmentation and sclerosis in patients with skin of color due to the dermal location of these syringomas. Management of syringomas includes topical and surgical methods, including topical retinoids such as tretinoin and atropine solution 1%; surgical methods include dermabrasion, excision, cryotherapy, electrocautery, electrofulguration, laser therapy, and chemical cautery. However, there is a substantial risk for recurrence with these treatment options. In a case series of 5 patients with periorbital syringomas, treatment using radiofrequency and a CO₂ laser was performed with favorable outcomes, highlighting the use of combination therapies for treatment.8 Seo et al⁹ reported a retrospective case series of 92 patients with periorbital syringomas in which they treated one group with CO₂ laser and the other with botulinum toxin A injection; CO₂ laser combined with botulinum toxin A showed a greater effect than laser treatment alone. The differential diagnosis includes pigmented plane warts, sebaceous hyperplasia, eruptive xanthomas, and hidrocystomas. Pigmented plane warts characteristically present as flat-topped papules with small hemorrhagic dots or tiny pinpoint vessels on dermoscopy. In sebaceous hyperplasia, yellowish umbilicated papular lesions are seen with crown vessels on dermoscopy. Eruptive xanthomas usually are erythematous to yellow, dome-shaped papules that appear mainly over the extensor aspects of the extremities. Hidrocystoma presents as a solitary translucent larger syringomalike lesion commonly seen in the periorbital region and/or on the cheeks.

We report a case of widespread syringomas with multiple close mimickers such as pigmented plane warts; however, dermoscopy of the lesions helped to arrive at the diagnosis. Dermatologists should be aware of this condition and its benign nature to ensure correct diagnosis and appropriate treatment.

The Diagnosis: Syringoma

Syringomas are benign adnexal tumors with distinct histopathologic features, including the characteristic comma- or tadpole-shaped tail comprised of dilated cystic eccrine ducts. Clinically, syringomas typically present predominantly in the periorbital region in adolescent girls. They may present as solitary or multiple lesions, and sites such as the genital area, palms, scalp, and chest rarely can be involved.¹ Eruptive syringoma is a clinical subtype of syringoma that is seen on the face, neck, chest, and axillae that predominantly occurs in females with skin of color in countries such as Asia and Africa before or during puberty.^2,3 Lesions appear as small, flesh-colored or slightly pigmented, flat-topped papules.³ The condition can be cosmetically disfiguring and difficult to treat, especially in patients with darker skin.

In our patient, dermoscopic evaluation revealed reticular light brown lines, structureless light brown areas, clustered brown dots, globules, and reticular vessels on a faint background (Figure 1A). Glittering yellow-whitish round structures over a fading pink-brown background also were seen at some sites (Figure 1B). Histologic examination of a neck lesion revealed an epidermis with focal acanthosis; the upper dermis had tumor islands and ducts with cells with round to vesicular nuclei and eosinophilic cytoplasm. A well-circumscribed tumor in the dermis composed of tubules of varying sizes lined by cuboidal cells was seen, consistent with syringoma (Figure 2).

Dermoscopic features of syringomas have not been widely studied. Hayashi et al⁴ reported the dermoscopic features of unilateral linear syringomas as a delicate and faint reticular pigmentation network and multiple hypopigmented areas. Sakiyama et al⁵ also defined an incomplete pigment network with faint erythema in 2 eruptive syringoma cases.

Treatment of this condition is for cosmetic reasons only, and there are no reports of long-term morbidity associated with the disease.^6,7 Multiple therapeutic options are available but are associated with complications such as hyperpigmentation and sclerosis in patients with skin of color due to the dermal location of these syringomas. Management of syringomas includes topical and surgical methods, including topical retinoids such as tretinoin and atropine solution 1%; surgical methods include dermabrasion, excision, cryotherapy, electrocautery, electrofulguration, laser therapy, and chemical cautery. However, there is a substantial risk for recurrence with these treatment options. In a case series of 5 patients with periorbital syringomas, treatment using radiofrequency and a CO₂ laser was performed with favorable outcomes, highlighting the use of combination therapies for treatment.8 Seo et al⁹ reported a retrospective case series of 92 patients with periorbital syringomas in which they treated one group with CO₂ laser and the other with botulinum toxin A injection; CO₂ laser combined with botulinum toxin A showed a greater effect than laser treatment alone. The differential diagnosis includes pigmented plane warts, sebaceous hyperplasia, eruptive xanthomas, and hidrocystomas. Pigmented plane warts characteristically present as flat-topped papules with small hemorrhagic dots or tiny pinpoint vessels on dermoscopy. In sebaceous hyperplasia, yellowish umbilicated papular lesions are seen with crown vessels on dermoscopy. Eruptive xanthomas usually are erythematous to yellow, dome-shaped papules that appear mainly over the extensor aspects of the extremities. Hidrocystoma presents as a solitary translucent larger syringomalike lesion commonly seen in the periorbital region and/or on the cheeks.

We report a case of widespread syringomas with multiple close mimickers such as pigmented plane warts; however, dermoscopy of the lesions helped to arrive at the diagnosis. Dermatologists should be aware of this condition and its benign nature to ensure correct diagnosis and appropriate treatment.

Radiation therapy, along with surgery and systemic therapy, is a primary therapeutic modality for cancer management. At least half of cancer patients receive radiation as part of their treatment regimen.¹ Multiple studies demonstrate that radiotherapy is underutilized worldwide.² One reason for underutilization of radiotherapy globally is poor access to this treatment modality. Factors that contribute to poor access include long wait times for consultation, delays in treatment initiation, distance to a treatment facility, and poor coordination of care.

Taskforce Findings

The presence of onsite radiation oncology and its impact on utilization of radiotherapy is poorly studied. The Veterans Health Administration (VHA) Palliative Radiotherapy Taskforce recently conducted a survey to determine the barriers to referral and timeliness of treatment for palliative radiotherapy within the VHA.³ Key findings of this study comparing centers with onsite radiation departments with centers without onsite radiation departments include:

a. Radiation consults are more likely to be completed within 1 week of consult request at centers with onsite radiation therapy (68% vs 31%, respectively; P = .01).

b. Centers with onsite radiation therapy more frequently deliver emergent treatment within 24 hours for patients with spinal cord compression, an emergency condition in which prompt radiation can prevent or minimize long-term neurologic disability (94% vs 70%, respectively; P = .01).

c. Referring practitioners with onsite radiation departments are less likely to report difficulty contacting a radiation oncologist as a barrier to referral for palliative radiotherapy (0% vs 20%, respectively; P = .006).

d. Referring practitioners with onsite radiotherapy report patient travel as a barrier to referral for palliative radiotherapy less frequently (28% vs 71%, respectively; P < .001).

e. Practitioners with onsite radiation oncology departments are more likely to have multidisciplinary tumor boards (31% vs 3%, respectively; P = .01) and are more likely to be influenced by radiation oncology recommendations at tumor boards (69% vs 44%, respectively; P = .02).

Based on the findings of this study, the VHA Palliative Radiotherapy Taskforce has prepared this consensus statement regarding the importance of onsite radiation oncology departments at VHA medical centers. More information regarding our 5 key findings and their implications for patient care are as follows:

Timeliness of Radiation Oncology Consultation

Delays in radiation oncology consultation, which can also delay treatment initiation, are associated with poor satisfaction among both patients and referring clinicians.⁴ Wait times have been identified as a barrier to utilization of radiotherapy by both patients and clinicians.^5,6 Furthermore, delays in initiation of definitive therapy have been associated with worse outcomes, including worse overall survival.^7,8 Our survey study demonstrates that consults for palliative radiotherapy are occurring in a more timely manner at centers with onsite radiation departments. Radiation oncology consults are more frequently completed within 1 week at centers with onsite radiation oncology departments compared with centers without onsite radiation oncology departments (68% vs 31%, P = .01). This trend would likely be seen for nonpalliative, definitive cases as well. The presence of radiation oncology departments onsite at VHA medical centers is an important component of timely care for veterans to optimize outcomes of cancer treatment.

Timely Delivery of Radiotherapy for Oncologic Emergencies

There are a few scenarios in which emergent radiation treatment, within 24 hours, is indicated. These include malignant spinal cord compression, uncal herniation from brain metastasis, superior vena cava syndrome, and tumor hemorrhage.⁹ Studies on management of metastatic spinal cord compression demonstrate that delays in treatment are associated with reduced ambulation¹⁰ as well as loss of sphincter function and incontinence.¹¹

Our study demonstrates that VHA medical centers with onsite radiotherapy more frequently deliver radiotherapy within 24 hours for patients with metastatic spinal cord compression. This timely delivery of treatment is critical to optimizing functional status and quality of life in patients requiring treatment for oncologic emergencies. Revisiting treatment pathways for such situations at regular intervals is crucial given that residents and staff may rotate and be unfamiliar with emergency protocols.

Communication With Radiation Oncologists

Several studies have demonstrated that the inability to contact a radiation oncologist and poor communication result in decreased referrals for palliative radiotherapy.^12,13 Our study demonstrates that onsite radiation oncology is associated with improved ability to contact a radiation oncologist. About 20% of clinicians at facilities without onsite radiation oncology reported difficulty contacting a radiation oncologist, compared with 0% at facilities with onsite radiation departments (P = .006).

It is possible that increased radiation oncology presence at VHA medical centers, through attenuation of barriers related to contacting a radiation oncologist and improved communication, would lead to increased use of radiotherapy. Increased communication between referring clinicians and radiation oncologists also can help with education of those clinicians making the referral. Since knowledge gaps have been identified in multiple studies as a barrier to referral for radiotherapy, such communication and increased education on the role of radiotherapy could increase use.^12-14

Patient Travel

Patient ability to travel was the most commonly reported barrier (81%) to referral for palliative radiotherapy in our study. Travel time and transportation difficulties have been established in multiple studies as barriers to radiotherapy for both definitive and palliative management.^15-18 Travel for radiotherapy was much less frequently reported as a barrier among respondents with onsite radiation oncology departments compared with those without onsite radiation departments (28% vs 71%, respectively; P < .001).

It is therefore possible that expansion of VHA radiation oncology services, allowing for provision of onsite radiotherapy at more VHA facilities, would reduce travel burden. Increasing travel accommodations for patients and provision of patient lodging on hospital campuses, which is already offered at some VHA medical centers (ie, Fisher House Foundation), could also help attenuate this barrier.

Multidisciplinary Tumor Boards

Our study demonstrates that centers with onsite radiation departments more frequently hold multidisciplinary tumor boards compared with centers without radiation departments (31% vs 3%, respectively; P = .01). Multidisciplinary tumor boards allow subspecialties to meet regularly to communicate about patient care and can help mitigate barriers related to communication and education of the referring health care practitioners.

As cases are discussed in multidisciplinary tumor boards, health care practitioners have the opportunity to make recommendations and provide education on potential benefits and/or downsides of treatments offered by their respective specialties. Several studies have demonstrated that cases discussed at multidisciplinary tumor boards are more likely to be referred for radiation therapy.^19-21 Furthermore, multidisciplinary tumor boards have been associated with improved treatment outcomes.²²

Conclusions

In this consensus statement the VHA Palliative Radiotherapy Taskforce recommends the optimization of use of radiotherapy within the VHA. Radiation oncology services should be maintained where present in the VHA, with consideration for expansion of services to additional facilities. Telehealth should be used to expedite consults and treatment. Hypofractionation should be used, when appropriate, to ease travel burden. Options for transportation services and onsite housing, or hospitalization, should be understood by practitioners and offered to patients to mitigate barriers related to travel.

Radiation therapy, along with surgery and systemic therapy, is a primary therapeutic modality for cancer management. At least half of cancer patients receive radiation as part of their treatment regimen.¹ Multiple studies demonstrate that radiotherapy is underutilized worldwide.² One reason for underutilization of radiotherapy globally is poor access to this treatment modality. Factors that contribute to poor access include long wait times for consultation, delays in treatment initiation, distance to a treatment facility, and poor coordination of care.

Taskforce Findings

The presence of onsite radiation oncology and its impact on utilization of radiotherapy is poorly studied. The Veterans Health Administration (VHA) Palliative Radiotherapy Taskforce recently conducted a survey to determine the barriers to referral and timeliness of treatment for palliative radiotherapy within the VHA.³ Key findings of this study comparing centers with onsite radiation departments with centers without onsite radiation departments include:

a. Radiation consults are more likely to be completed within 1 week of consult request at centers with onsite radiation therapy (68% vs 31%, respectively; P = .01).

b. Centers with onsite radiation therapy more frequently deliver emergent treatment within 24 hours for patients with spinal cord compression, an emergency condition in which prompt radiation can prevent or minimize long-term neurologic disability (94% vs 70%, respectively; P = .01).

c. Referring practitioners with onsite radiation departments are less likely to report difficulty contacting a radiation oncologist as a barrier to referral for palliative radiotherapy (0% vs 20%, respectively; P = .006).

d. Referring practitioners with onsite radiotherapy report patient travel as a barrier to referral for palliative radiotherapy less frequently (28% vs 71%, respectively; P < .001).

e. Practitioners with onsite radiation oncology departments are more likely to have multidisciplinary tumor boards (31% vs 3%, respectively; P = .01) and are more likely to be influenced by radiation oncology recommendations at tumor boards (69% vs 44%, respectively; P = .02).

Based on the findings of this study, the VHA Palliative Radiotherapy Taskforce has prepared this consensus statement regarding the importance of onsite radiation oncology departments at VHA medical centers. More information regarding our 5 key findings and their implications for patient care are as follows:

Timeliness of Radiation Oncology Consultation

Delays in radiation oncology consultation, which can also delay treatment initiation, are associated with poor satisfaction among both patients and referring clinicians.⁴ Wait times have been identified as a barrier to utilization of radiotherapy by both patients and clinicians.^5,6 Furthermore, delays in initiation of definitive therapy have been associated with worse outcomes, including worse overall survival.^7,8 Our survey study demonstrates that consults for palliative radiotherapy are occurring in a more timely manner at centers with onsite radiation departments. Radiation oncology consults are more frequently completed within 1 week at centers with onsite radiation oncology departments compared with centers without onsite radiation oncology departments (68% vs 31%, P = .01). This trend would likely be seen for nonpalliative, definitive cases as well. The presence of radiation oncology departments onsite at VHA medical centers is an important component of timely care for veterans to optimize outcomes of cancer treatment.

Timely Delivery of Radiotherapy for Oncologic Emergencies

There are a few scenarios in which emergent radiation treatment, within 24 hours, is indicated. These include malignant spinal cord compression, uncal herniation from brain metastasis, superior vena cava syndrome, and tumor hemorrhage.⁹ Studies on management of metastatic spinal cord compression demonstrate that delays in treatment are associated with reduced ambulation¹⁰ as well as loss of sphincter function and incontinence.¹¹

Our study demonstrates that VHA medical centers with onsite radiotherapy more frequently deliver radiotherapy within 24 hours for patients with metastatic spinal cord compression. This timely delivery of treatment is critical to optimizing functional status and quality of life in patients requiring treatment for oncologic emergencies. Revisiting treatment pathways for such situations at regular intervals is crucial given that residents and staff may rotate and be unfamiliar with emergency protocols.

Communication With Radiation Oncologists

Several studies have demonstrated that the inability to contact a radiation oncologist and poor communication result in decreased referrals for palliative radiotherapy.^12,13 Our study demonstrates that onsite radiation oncology is associated with improved ability to contact a radiation oncologist. About 20% of clinicians at facilities without onsite radiation oncology reported difficulty contacting a radiation oncologist, compared with 0% at facilities with onsite radiation departments (P = .006).

It is possible that increased radiation oncology presence at VHA medical centers, through attenuation of barriers related to contacting a radiation oncologist and improved communication, would lead to increased use of radiotherapy. Increased communication between referring clinicians and radiation oncologists also can help with education of those clinicians making the referral. Since knowledge gaps have been identified in multiple studies as a barrier to referral for radiotherapy, such communication and increased education on the role of radiotherapy could increase use.^12-14

Patient Travel

Patient ability to travel was the most commonly reported barrier (81%) to referral for palliative radiotherapy in our study. Travel time and transportation difficulties have been established in multiple studies as barriers to radiotherapy for both definitive and palliative management.^15-18 Travel for radiotherapy was much less frequently reported as a barrier among respondents with onsite radiation oncology departments compared with those without onsite radiation departments (28% vs 71%, respectively; P < .001).

It is therefore possible that expansion of VHA radiation oncology services, allowing for provision of onsite radiotherapy at more VHA facilities, would reduce travel burden. Increasing travel accommodations for patients and provision of patient lodging on hospital campuses, which is already offered at some VHA medical centers (ie, Fisher House Foundation), could also help attenuate this barrier.

Multidisciplinary Tumor Boards

Our study demonstrates that centers with onsite radiation departments more frequently hold multidisciplinary tumor boards compared with centers without radiation departments (31% vs 3%, respectively; P = .01). Multidisciplinary tumor boards allow subspecialties to meet regularly to communicate about patient care and can help mitigate barriers related to communication and education of the referring health care practitioners.

As cases are discussed in multidisciplinary tumor boards, health care practitioners have the opportunity to make recommendations and provide education on potential benefits and/or downsides of treatments offered by their respective specialties. Several studies have demonstrated that cases discussed at multidisciplinary tumor boards are more likely to be referred for radiation therapy.^19-21 Furthermore, multidisciplinary tumor boards have been associated with improved treatment outcomes.²²

Conclusions

In this consensus statement the VHA Palliative Radiotherapy Taskforce recommends the optimization of use of radiotherapy within the VHA. Radiation oncology services should be maintained where present in the VHA, with consideration for expansion of services to additional facilities. Telehealth should be used to expedite consults and treatment. Hypofractionation should be used, when appropriate, to ease travel burden. Options for transportation services and onsite housing, or hospitalization, should be understood by practitioners and offered to patients to mitigate barriers related to travel.

Radiation therapy, along with surgery and systemic therapy, is a primary therapeutic modality for cancer management. At least half of cancer patients receive radiation as part of their treatment regimen.¹ Multiple studies demonstrate that radiotherapy is underutilized worldwide.² One reason for underutilization of radiotherapy globally is poor access to this treatment modality. Factors that contribute to poor access include long wait times for consultation, delays in treatment initiation, distance to a treatment facility, and poor coordination of care.

Taskforce Findings

The presence of onsite radiation oncology and its impact on utilization of radiotherapy is poorly studied. The Veterans Health Administration (VHA) Palliative Radiotherapy Taskforce recently conducted a survey to determine the barriers to referral and timeliness of treatment for palliative radiotherapy within the VHA.³ Key findings of this study comparing centers with onsite radiation departments with centers without onsite radiation departments include:

a. Radiation consults are more likely to be completed within 1 week of consult request at centers with onsite radiation therapy (68% vs 31%, respectively; P = .01).

b. Centers with onsite radiation therapy more frequently deliver emergent treatment within 24 hours for patients with spinal cord compression, an emergency condition in which prompt radiation can prevent or minimize long-term neurologic disability (94% vs 70%, respectively; P = .01).

c. Referring practitioners with onsite radiation departments are less likely to report difficulty contacting a radiation oncologist as a barrier to referral for palliative radiotherapy (0% vs 20%, respectively; P = .006).

d. Referring practitioners with onsite radiotherapy report patient travel as a barrier to referral for palliative radiotherapy less frequently (28% vs 71%, respectively; P < .001).

e. Practitioners with onsite radiation oncology departments are more likely to have multidisciplinary tumor boards (31% vs 3%, respectively; P = .01) and are more likely to be influenced by radiation oncology recommendations at tumor boards (69% vs 44%, respectively; P = .02).

Based on the findings of this study, the VHA Palliative Radiotherapy Taskforce has prepared this consensus statement regarding the importance of onsite radiation oncology departments at VHA medical centers. More information regarding our 5 key findings and their implications for patient care are as follows:

Timeliness of Radiation Oncology Consultation

Delays in radiation oncology consultation, which can also delay treatment initiation, are associated with poor satisfaction among both patients and referring clinicians.⁴ Wait times have been identified as a barrier to utilization of radiotherapy by both patients and clinicians.^5,6 Furthermore, delays in initiation of definitive therapy have been associated with worse outcomes, including worse overall survival.^7,8 Our survey study demonstrates that consults for palliative radiotherapy are occurring in a more timely manner at centers with onsite radiation departments. Radiation oncology consults are more frequently completed within 1 week at centers with onsite radiation oncology departments compared with centers without onsite radiation oncology departments (68% vs 31%, P = .01). This trend would likely be seen for nonpalliative, definitive cases as well. The presence of radiation oncology departments onsite at VHA medical centers is an important component of timely care for veterans to optimize outcomes of cancer treatment.

Timely Delivery of Radiotherapy for Oncologic Emergencies

There are a few scenarios in which emergent radiation treatment, within 24 hours, is indicated. These include malignant spinal cord compression, uncal herniation from brain metastasis, superior vena cava syndrome, and tumor hemorrhage.⁹ Studies on management of metastatic spinal cord compression demonstrate that delays in treatment are associated with reduced ambulation¹⁰ as well as loss of sphincter function and incontinence.¹¹

Our study demonstrates that VHA medical centers with onsite radiotherapy more frequently deliver radiotherapy within 24 hours for patients with metastatic spinal cord compression. This timely delivery of treatment is critical to optimizing functional status and quality of life in patients requiring treatment for oncologic emergencies. Revisiting treatment pathways for such situations at regular intervals is crucial given that residents and staff may rotate and be unfamiliar with emergency protocols.

Communication With Radiation Oncologists

Several studies have demonstrated that the inability to contact a radiation oncologist and poor communication result in decreased referrals for palliative radiotherapy.^12,13 Our study demonstrates that onsite radiation oncology is associated with improved ability to contact a radiation oncologist. About 20% of clinicians at facilities without onsite radiation oncology reported difficulty contacting a radiation oncologist, compared with 0% at facilities with onsite radiation departments (P = .006).

It is possible that increased radiation oncology presence at VHA medical centers, through attenuation of barriers related to contacting a radiation oncologist and improved communication, would lead to increased use of radiotherapy. Increased communication between referring clinicians and radiation oncologists also can help with education of those clinicians making the referral. Since knowledge gaps have been identified in multiple studies as a barrier to referral for radiotherapy, such communication and increased education on the role of radiotherapy could increase use.^12-14

Patient Travel

Patient ability to travel was the most commonly reported barrier (81%) to referral for palliative radiotherapy in our study. Travel time and transportation difficulties have been established in multiple studies as barriers to radiotherapy for both definitive and palliative management.^15-18 Travel for radiotherapy was much less frequently reported as a barrier among respondents with onsite radiation oncology departments compared with those without onsite radiation departments (28% vs 71%, respectively; P < .001).

It is therefore possible that expansion of VHA radiation oncology services, allowing for provision of onsite radiotherapy at more VHA facilities, would reduce travel burden. Increasing travel accommodations for patients and provision of patient lodging on hospital campuses, which is already offered at some VHA medical centers (ie, Fisher House Foundation), could also help attenuate this barrier.

Multidisciplinary Tumor Boards

Our study demonstrates that centers with onsite radiation departments more frequently hold multidisciplinary tumor boards compared with centers without radiation departments (31% vs 3%, respectively; P = .01). Multidisciplinary tumor boards allow subspecialties to meet regularly to communicate about patient care and can help mitigate barriers related to communication and education of the referring health care practitioners.

As cases are discussed in multidisciplinary tumor boards, health care practitioners have the opportunity to make recommendations and provide education on potential benefits and/or downsides of treatments offered by their respective specialties. Several studies have demonstrated that cases discussed at multidisciplinary tumor boards are more likely to be referred for radiation therapy.^19-21 Furthermore, multidisciplinary tumor boards have been associated with improved treatment outcomes.²²

Conclusions

In this consensus statement the VHA Palliative Radiotherapy Taskforce recommends the optimization of use of radiotherapy within the VHA. Radiation oncology services should be maintained where present in the VHA, with consideration for expansion of services to additional facilities. Telehealth should be used to expedite consults and treatment. Hypofractionation should be used, when appropriate, to ease travel burden. Options for transportation services and onsite housing, or hospitalization, should be understood by practitioners and offered to patients to mitigate barriers related to travel.

Multiple myeloma (MM) accounts for 1% to 2% of all cancers and slightly more than 17% of hematologic malignancies in the United States.¹ MM is characterized by the neoplastic proliferation of immunoglobulin (Ig)-producing plasma cells with ≥ 10% clonal plasma cells in the bone marrow or biopsy-proven bony or soft tissue plasmacytoma, plus presence of related organ or tissue impairment or presence of a biomarker associated with near-inevitable progression to end-organ damage.²

Background

Up to 97% of patients with MM will have a monoclonal (M) protein produced and secreted by the malignant plasma cells, which can be detected by protein electrophoresis of the serum and an aliquot of urine from a 24-hour collection combined with immunofixation of the serum and urine. The M protein in MM usually consists of IgG 50% of the time and light chains 16% of the time. Patients who lack detectable M protein are considered to have nonsecretory myeloma. MM presents with end-organ damage, which includes hypercalcemia, renal dysfunction, anemia, or lytic bone lesions. Patients with MM frequently present with renal insufficiency due to cast nephropathy or light chain deposition disease.³

MM is thought to evolve from monoclonal gammopathy of uncertain significance (MGUS), an asymptomatic premalignant stage of clonal plasma cell proliferation with a risk of progression to active myeloma at 1% per year.^4,5 Epidemiologic data suggest that people who develop MM have a genetic predisposition, but risk factors may develop or be acquired, such as age, immunosuppression, and environmental exposures. To better assess what causes transformation from MGUS to MM, it is important to identify agents that may cause this second hit.⁶

In November 1961, President John F. Kennedy authorized the start of Operation Ranch Hand, the US Air Force’s herbicide program during the Vietnam War. Twenty million gallons of various chemicals were sprayed in Vietnam, eastern Laos, and parts of Cambodia to defoliate rural land, depriving guerillas of their support base. Agent Orange (AO) was one of these chemicals; it is a mixed herbicide with traces of dioxin, a compound that has been associated with major health problems among exposed individuals.⁷ Several studies have evaluated exposure to AO and its potential harmful repercussions. Studies have assessed the link between AO and MGUS as well as AO to various leukemias, such as chronic lymphocytic leukemia.^8,9 Other studies have shown the relationship between AO exposure and worse outcomes in persons with MM.¹⁰ To date, only a single abstract from a US Department of Veterans Affairs (VA) medical center has investigated the relationships between AO exposure and MGUS, MM, and the rate of transformation. The VA study of patients seen from 2005 to 2015 in Detroit, Michigan, found that AO exposure led to an increase in cumulative incidence rate of MGUS/MM, suggesting possible changes in disease biology and genetics.¹¹

In this study, we aimed to determine the incidence of transformation of MGUS to MM in patients with and without exposure to AO. We then analyzed survival as a function of AO exposure, transformation, and clinical and sociodemographic variables. We also explored the impact of psychosocial variables and hematopoietic stem cell transplantation (HSCT), a standard of treatment for MM.

Methods

This retrospective cohort study assembled electronic health record (EHR) data from the Veterans Health Administration Corporate Data Warehouse (CDW). The VA Central Texas Veterans Healthcare System Institutional Review Board granted a waiver of consent for this record review. Eligible patients were Vietnam-era veterans who were in the military during the time that AO was used (1961-1971). Veterans were included if they were being cared for and received a diagnosis for MGUS or MM between October 1, 2009, and September 30, 2015 (all prevalent cases fiscal years 2010-2015). Cases were excluded if there was illogical death data or if age, race, ethnicity, body mass index (BMI), or prior-year diagnostic data were missing.

Measures

Patients were followed through April 2020. Presence of MGUS was defined by the International Classification of Diseases, Ninth Revision (ICD-9) diagnosis code 273.1. MM was identified by ICD-9 diagnosis codes 203.00, 203.01, and 203.02. The study index date was the earliest date of diagnosis of MGUS or MM in fiscal years 2010-2015. It was suspected that some patients with MM may have had a history of MGUS prior to this period. Therefore, for patients with MM, historical diagnosis of MGUS was extracted going back through the earliest data in the CDW (October 1999). Patients diagnosed with both MGUS and MM were considered transformation patients.

Other measures included age at index date, sex, race, ethnicity, VA priority status (a value 1 to 8 summarizing why the veteran qualified for VA care, such as military service-connected disability or very low income), and AO exposure authenticated per VA enrollment files and disability records. Service years were separated into 1961 to 1968 and 1969 to 1971 to match a change in the formulation of AO associated with decreased carcinogenic effect. Comorbidity data from the year prior to first MGUS/MM diagnosis in the observation period were extracted. Lifestyle factors associated with development of MGUS/MM were determined using the following codes: obesity per BMI calculation or diagnosis (ICD-9, 278.0), tobacco use per diagnosis (ICD-9, 305.1, V15.82), and survival from MGUS/MM diagnosis index date to date of death from any cause. Comorbidity was assessed using ICD-9 diagnosis codes to calculate the Charlson Comorbidity Index (CCI), which includes cardiovascular diseases, diabetes mellitus, liver and kidney diseases, cancers, and metastatic solid tumors. Cancers were omitted from our adapted CCI to avoid collinearity in the multivariable models. The theoretical maximum CCI score in this study was 25.^12,13 Additional conditions known to be associated with variation in outcomes among veterans using the VA were indicated, including major depressive disorder, posttraumatic stress disorder (PTSD), alcohol use disorder (AUD), substance use disorder (SUD), and common chronic disease (hypertension, lipid disorders).¹⁴

Statistical Analysis

Sample characteristics were represented by frequencies and percentages for categorical variables and means and SDs (or medians and ranges where appropriate) for continuous variables. A χ² test (or Fisher exact test when cell counts were low) assessed associations in bivariate comparisons. A 2-sample t test (or Wilcoxon rank sum test as appropriate) assessed differences in continuous variables between 2 groups. Kaplan-Meier curves depicted the unadjusted relationship of AO exposure to survival. Cox proportional hazards survival models examined an unadjusted model containing only the AO exposure indicator as a predictor and adjusted models were used for demographic and clinical factors for MGUS and patients with MM separately.

Predictors were age in decades, sex, Hispanic ethnicity, race, nicotine dependence, obesity, overweight, AUD, SUD, major depressive disorder, PTSD, and the adapted CCI. When modeling patients with MM, MGUS was added to the model to identify the transformation group. The interaction of AO with transformation was also analyzed for patients with MM. Results were reported as hazard ratios (HR) with their 95% CI.

Results

We identified 18,215 veterans diagnosed with either MGUS or MM during fiscal years 2010-2015 with 16,366 meeting inclusion criteria. Patients were excluded for missing data on exposure (n = 334), age (n = 12), race (n = 1058), ethnicity (n = 164), diagnosis (n = 47), treatment (n = 56), and BMI (n = 178). All were Vietnam War era veterans; 14 also served in other eras.

The cohort was 98.5% male (Table 1). Twenty-nine percent were Black veterans, 65% were White veterans, and 4% of individuals reported Hispanic ethnicity. Patients had a mean (SD) age of 66.7 (5.9) years (range, 52-96). Most patients were married (58%) or divorced/separated (27%). All were VA priority 1 to 5 (no 6, 7, or 8); 50% were priority 1 with 50% to 100% service-connected disability. Another 29% were eligible for VA care by reason of low income, 17% had 10% to 40% service-connected disability, and 4% were otherwise disabled.

Disscussion

Elucidating the pathophysiology and risk of transformation from MGUS to MM is an ongoing endeavor, even 35 years after the end of US involvement in the Vietnam War. Our study sought to understand a relationship between AO exposure, risk of MGUS transforming to MM, and associated mortality in US Vietnam War veterans. The rate of transformation (MGUS progressing to active MM) is well cited at 1% per year.¹⁵ Here, we found 12% of our cohort had undergone this transformation over 10 years.

Vietnam War era veterans who were exposed to AO during the Operation Ranch Hand period had 2.4 times greater risk of developing MGUS compared with veterans not exposed to AO.⁸ Our study was not designed to look at this association of AO exposure and MGUS/MM as this was a retrospective review to assess the difference in outcomes based on AO exposure. We found that AO exposure is associated with a decrease in mortality in contrast to a prior study showing worse survival with individuals with AO exposure.¹⁰ Another single center study found no association between AO exposure and overall survival, but it did identify an increased risk of progression from MGUS to MM.¹¹ Our study did not show increased risk of transformation but did show positive effect on survival.

Black individuals have twice the risk of developing MM compared with White individuals and are diagnosed at a younger age (66 vs 70 years, respectively).¹⁶ Interestingly, Black race was a protective factor in our study. Given the length of time (35 years) elapsed since the Vietnam War ended, it is likely that most vulnerable Black veterans did not survive until our observation period.

HSCT, as expected, was a protective factor for veterans undergoing this treatment modality, but it is unclear why such a small number (8%) underwent HSCT as this is a standard of care in the management of MM. Obesity was also found to be a protective factor in a prior study, which was also seen in our study cohort.⁸

Limitations

This study was limited by its retrospective review of survivors among the Vietnam-era cohort several decades after the exposure of concern. Clinician notes and full historical data, such as date of onset for any disorder, were unavailable. These data also relied on the practitioners caring for the veterans to make the correct diagnosis with the associated code so that the data could be captured. Neither AO exposure nor diagnoses codes were verified against other sources of data; however, validation studies over the years have supported the accuracy of the diagnosis codes recorded in the VA EHR.

Conclusions

Because AO exposure is a nonmodifiable risk factor, focus should be placed on modifiable risk factors (eg, nicotine dependence, alcohol and substance use disorders, underlying comorbid conditions) as these were associated with worse outcomes. Future studies will look at the correlation of AO exposure, cytogenetics, and clinical outcomes in these veterans to learn how best to identify their disease course and optimize their care in the latter part of their life.

Acknowledgments

This research was supported by the Central Texas Veterans Health Care System and Baylor Scott and White Health, both in Temple and Veterans Affairs Central Western Massachusetts Healthcare System, Leeds.

Multiple myeloma (MM) accounts for 1% to 2% of all cancers and slightly more than 17% of hematologic malignancies in the United States.¹ MM is characterized by the neoplastic proliferation of immunoglobulin (Ig)-producing plasma cells with ≥ 10% clonal plasma cells in the bone marrow or biopsy-proven bony or soft tissue plasmacytoma, plus presence of related organ or tissue impairment or presence of a biomarker associated with near-inevitable progression to end-organ damage.²

Background

Up to 97% of patients with MM will have a monoclonal (M) protein produced and secreted by the malignant plasma cells, which can be detected by protein electrophoresis of the serum and an aliquot of urine from a 24-hour collection combined with immunofixation of the serum and urine. The M protein in MM usually consists of IgG 50% of the time and light chains 16% of the time. Patients who lack detectable M protein are considered to have nonsecretory myeloma. MM presents with end-organ damage, which includes hypercalcemia, renal dysfunction, anemia, or lytic bone lesions. Patients with MM frequently present with renal insufficiency due to cast nephropathy or light chain deposition disease.³

MM is thought to evolve from monoclonal gammopathy of uncertain significance (MGUS), an asymptomatic premalignant stage of clonal plasma cell proliferation with a risk of progression to active myeloma at 1% per year.^4,5 Epidemiologic data suggest that people who develop MM have a genetic predisposition, but risk factors may develop or be acquired, such as age, immunosuppression, and environmental exposures. To better assess what causes transformation from MGUS to MM, it is important to identify agents that may cause this second hit.⁶

In November 1961, President John F. Kennedy authorized the start of Operation Ranch Hand, the US Air Force’s herbicide program during the Vietnam War. Twenty million gallons of various chemicals were sprayed in Vietnam, eastern Laos, and parts of Cambodia to defoliate rural land, depriving guerillas of their support base. Agent Orange (AO) was one of these chemicals; it is a mixed herbicide with traces of dioxin, a compound that has been associated with major health problems among exposed individuals.⁷ Several studies have evaluated exposure to AO and its potential harmful repercussions. Studies have assessed the link between AO and MGUS as well as AO to various leukemias, such as chronic lymphocytic leukemia.^8,9 Other studies have shown the relationship between AO exposure and worse outcomes in persons with MM.¹⁰ To date, only a single abstract from a US Department of Veterans Affairs (VA) medical center has investigated the relationships between AO exposure and MGUS, MM, and the rate of transformation. The VA study of patients seen from 2005 to 2015 in Detroit, Michigan, found that AO exposure led to an increase in cumulative incidence rate of MGUS/MM, suggesting possible changes in disease biology and genetics.¹¹

In this study, we aimed to determine the incidence of transformation of MGUS to MM in patients with and without exposure to AO. We then analyzed survival as a function of AO exposure, transformation, and clinical and sociodemographic variables. We also explored the impact of psychosocial variables and hematopoietic stem cell transplantation (HSCT), a standard of treatment for MM.

Methods

This retrospective cohort study assembled electronic health record (EHR) data from the Veterans Health Administration Corporate Data Warehouse (CDW). The VA Central Texas Veterans Healthcare System Institutional Review Board granted a waiver of consent for this record review. Eligible patients were Vietnam-era veterans who were in the military during the time that AO was used (1961-1971). Veterans were included if they were being cared for and received a diagnosis for MGUS or MM between October 1, 2009, and September 30, 2015 (all prevalent cases fiscal years 2010-2015). Cases were excluded if there was illogical death data or if age, race, ethnicity, body mass index (BMI), or prior-year diagnostic data were missing.

Measures

Patients were followed through April 2020. Presence of MGUS was defined by the International Classification of Diseases, Ninth Revision (ICD-9) diagnosis code 273.1. MM was identified by ICD-9 diagnosis codes 203.00, 203.01, and 203.02. The study index date was the earliest date of diagnosis of MGUS or MM in fiscal years 2010-2015. It was suspected that some patients with MM may have had a history of MGUS prior to this period. Therefore, for patients with MM, historical diagnosis of MGUS was extracted going back through the earliest data in the CDW (October 1999). Patients diagnosed with both MGUS and MM were considered transformation patients.

Other measures included age at index date, sex, race, ethnicity, VA priority status (a value 1 to 8 summarizing why the veteran qualified for VA care, such as military service-connected disability or very low income), and AO exposure authenticated per VA enrollment files and disability records. Service years were separated into 1961 to 1968 and 1969 to 1971 to match a change in the formulation of AO associated with decreased carcinogenic effect. Comorbidity data from the year prior to first MGUS/MM diagnosis in the observation period were extracted. Lifestyle factors associated with development of MGUS/MM were determined using the following codes: obesity per BMI calculation or diagnosis (ICD-9, 278.0), tobacco use per diagnosis (ICD-9, 305.1, V15.82), and survival from MGUS/MM diagnosis index date to date of death from any cause. Comorbidity was assessed using ICD-9 diagnosis codes to calculate the Charlson Comorbidity Index (CCI), which includes cardiovascular diseases, diabetes mellitus, liver and kidney diseases, cancers, and metastatic solid tumors. Cancers were omitted from our adapted CCI to avoid collinearity in the multivariable models. The theoretical maximum CCI score in this study was 25.^12,13 Additional conditions known to be associated with variation in outcomes among veterans using the VA were indicated, including major depressive disorder, posttraumatic stress disorder (PTSD), alcohol use disorder (AUD), substance use disorder (SUD), and common chronic disease (hypertension, lipid disorders).¹⁴

Statistical Analysis

Sample characteristics were represented by frequencies and percentages for categorical variables and means and SDs (or medians and ranges where appropriate) for continuous variables. A χ² test (or Fisher exact test when cell counts were low) assessed associations in bivariate comparisons. A 2-sample t test (or Wilcoxon rank sum test as appropriate) assessed differences in continuous variables between 2 groups. Kaplan-Meier curves depicted the unadjusted relationship of AO exposure to survival. Cox proportional hazards survival models examined an unadjusted model containing only the AO exposure indicator as a predictor and adjusted models were used for demographic and clinical factors for MGUS and patients with MM separately.

Predictors were age in decades, sex, Hispanic ethnicity, race, nicotine dependence, obesity, overweight, AUD, SUD, major depressive disorder, PTSD, and the adapted CCI. When modeling patients with MM, MGUS was added to the model to identify the transformation group. The interaction of AO with transformation was also analyzed for patients with MM. Results were reported as hazard ratios (HR) with their 95% CI.

Results

We identified 18,215 veterans diagnosed with either MGUS or MM during fiscal years 2010-2015 with 16,366 meeting inclusion criteria. Patients were excluded for missing data on exposure (n = 334), age (n = 12), race (n = 1058), ethnicity (n = 164), diagnosis (n = 47), treatment (n = 56), and BMI (n = 178). All were Vietnam War era veterans; 14 also served in other eras.

The cohort was 98.5% male (Table 1). Twenty-nine percent were Black veterans, 65% were White veterans, and 4% of individuals reported Hispanic ethnicity. Patients had a mean (SD) age of 66.7 (5.9) years (range, 52-96). Most patients were married (58%) or divorced/separated (27%). All were VA priority 1 to 5 (no 6, 7, or 8); 50% were priority 1 with 50% to 100% service-connected disability. Another 29% were eligible for VA care by reason of low income, 17% had 10% to 40% service-connected disability, and 4% were otherwise disabled.

Disscussion

Elucidating the pathophysiology and risk of transformation from MGUS to MM is an ongoing endeavor, even 35 years after the end of US involvement in the Vietnam War. Our study sought to understand a relationship between AO exposure, risk of MGUS transforming to MM, and associated mortality in US Vietnam War veterans. The rate of transformation (MGUS progressing to active MM) is well cited at 1% per year.¹⁵ Here, we found 12% of our cohort had undergone this transformation over 10 years.

Vietnam War era veterans who were exposed to AO during the Operation Ranch Hand period had 2.4 times greater risk of developing MGUS compared with veterans not exposed to AO.⁸ Our study was not designed to look at this association of AO exposure and MGUS/MM as this was a retrospective review to assess the difference in outcomes based on AO exposure. We found that AO exposure is associated with a decrease in mortality in contrast to a prior study showing worse survival with individuals with AO exposure.¹⁰ Another single center study found no association between AO exposure and overall survival, but it did identify an increased risk of progression from MGUS to MM.¹¹ Our study did not show increased risk of transformation but did show positive effect on survival.

Black individuals have twice the risk of developing MM compared with White individuals and are diagnosed at a younger age (66 vs 70 years, respectively).¹⁶ Interestingly, Black race was a protective factor in our study. Given the length of time (35 years) elapsed since the Vietnam War ended, it is likely that most vulnerable Black veterans did not survive until our observation period.

HSCT, as expected, was a protective factor for veterans undergoing this treatment modality, but it is unclear why such a small number (8%) underwent HSCT as this is a standard of care in the management of MM. Obesity was also found to be a protective factor in a prior study, which was also seen in our study cohort.⁸

Limitations

This study was limited by its retrospective review of survivors among the Vietnam-era cohort several decades after the exposure of concern. Clinician notes and full historical data, such as date of onset for any disorder, were unavailable. These data also relied on the practitioners caring for the veterans to make the correct diagnosis with the associated code so that the data could be captured. Neither AO exposure nor diagnoses codes were verified against other sources of data; however, validation studies over the years have supported the accuracy of the diagnosis codes recorded in the VA EHR.

Conclusions

Because AO exposure is a nonmodifiable risk factor, focus should be placed on modifiable risk factors (eg, nicotine dependence, alcohol and substance use disorders, underlying comorbid conditions) as these were associated with worse outcomes. Future studies will look at the correlation of AO exposure, cytogenetics, and clinical outcomes in these veterans to learn how best to identify their disease course and optimize their care in the latter part of their life.

Acknowledgments

This research was supported by the Central Texas Veterans Health Care System and Baylor Scott and White Health, both in Temple and Veterans Affairs Central Western Massachusetts Healthcare System, Leeds.

Multiple myeloma (MM) accounts for 1% to 2% of all cancers and slightly more than 17% of hematologic malignancies in the United States.¹ MM is characterized by the neoplastic proliferation of immunoglobulin (Ig)-producing plasma cells with ≥ 10% clonal plasma cells in the bone marrow or biopsy-proven bony or soft tissue plasmacytoma, plus presence of related organ or tissue impairment or presence of a biomarker associated with near-inevitable progression to end-organ damage.²

Background

Up to 97% of patients with MM will have a monoclonal (M) protein produced and secreted by the malignant plasma cells, which can be detected by protein electrophoresis of the serum and an aliquot of urine from a 24-hour collection combined with immunofixation of the serum and urine. The M protein in MM usually consists of IgG 50% of the time and light chains 16% of the time. Patients who lack detectable M protein are considered to have nonsecretory myeloma. MM presents with end-organ damage, which includes hypercalcemia, renal dysfunction, anemia, or lytic bone lesions. Patients with MM frequently present with renal insufficiency due to cast nephropathy or light chain deposition disease.³

MM is thought to evolve from monoclonal gammopathy of uncertain significance (MGUS), an asymptomatic premalignant stage of clonal plasma cell proliferation with a risk of progression to active myeloma at 1% per year.^4,5 Epidemiologic data suggest that people who develop MM have a genetic predisposition, but risk factors may develop or be acquired, such as age, immunosuppression, and environmental exposures. To better assess what causes transformation from MGUS to MM, it is important to identify agents that may cause this second hit.⁶

In November 1961, President John F. Kennedy authorized the start of Operation Ranch Hand, the US Air Force’s herbicide program during the Vietnam War. Twenty million gallons of various chemicals were sprayed in Vietnam, eastern Laos, and parts of Cambodia to defoliate rural land, depriving guerillas of their support base. Agent Orange (AO) was one of these chemicals; it is a mixed herbicide with traces of dioxin, a compound that has been associated with major health problems among exposed individuals.⁷ Several studies have evaluated exposure to AO and its potential harmful repercussions. Studies have assessed the link between AO and MGUS as well as AO to various leukemias, such as chronic lymphocytic leukemia.^8,9 Other studies have shown the relationship between AO exposure and worse outcomes in persons with MM.¹⁰ To date, only a single abstract from a US Department of Veterans Affairs (VA) medical center has investigated the relationships between AO exposure and MGUS, MM, and the rate of transformation. The VA study of patients seen from 2005 to 2015 in Detroit, Michigan, found that AO exposure led to an increase in cumulative incidence rate of MGUS/MM, suggesting possible changes in disease biology and genetics.¹¹

In this study, we aimed to determine the incidence of transformation of MGUS to MM in patients with and without exposure to AO. We then analyzed survival as a function of AO exposure, transformation, and clinical and sociodemographic variables. We also explored the impact of psychosocial variables and hematopoietic stem cell transplantation (HSCT), a standard of treatment for MM.

Methods

This retrospective cohort study assembled electronic health record (EHR) data from the Veterans Health Administration Corporate Data Warehouse (CDW). The VA Central Texas Veterans Healthcare System Institutional Review Board granted a waiver of consent for this record review. Eligible patients were Vietnam-era veterans who were in the military during the time that AO was used (1961-1971). Veterans were included if they were being cared for and received a diagnosis for MGUS or MM between October 1, 2009, and September 30, 2015 (all prevalent cases fiscal years 2010-2015). Cases were excluded if there was illogical death data or if age, race, ethnicity, body mass index (BMI), or prior-year diagnostic data were missing.

Measures

Patients were followed through April 2020. Presence of MGUS was defined by the International Classification of Diseases, Ninth Revision (ICD-9) diagnosis code 273.1. MM was identified by ICD-9 diagnosis codes 203.00, 203.01, and 203.02. The study index date was the earliest date of diagnosis of MGUS or MM in fiscal years 2010-2015. It was suspected that some patients with MM may have had a history of MGUS prior to this period. Therefore, for patients with MM, historical diagnosis of MGUS was extracted going back through the earliest data in the CDW (October 1999). Patients diagnosed with both MGUS and MM were considered transformation patients.

Other measures included age at index date, sex, race, ethnicity, VA priority status (a value 1 to 8 summarizing why the veteran qualified for VA care, such as military service-connected disability or very low income), and AO exposure authenticated per VA enrollment files and disability records. Service years were separated into 1961 to 1968 and 1969 to 1971 to match a change in the formulation of AO associated with decreased carcinogenic effect. Comorbidity data from the year prior to first MGUS/MM diagnosis in the observation period were extracted. Lifestyle factors associated with development of MGUS/MM were determined using the following codes: obesity per BMI calculation or diagnosis (ICD-9, 278.0), tobacco use per diagnosis (ICD-9, 305.1, V15.82), and survival from MGUS/MM diagnosis index date to date of death from any cause. Comorbidity was assessed using ICD-9 diagnosis codes to calculate the Charlson Comorbidity Index (CCI), which includes cardiovascular diseases, diabetes mellitus, liver and kidney diseases, cancers, and metastatic solid tumors. Cancers were omitted from our adapted CCI to avoid collinearity in the multivariable models. The theoretical maximum CCI score in this study was 25.^12,13 Additional conditions known to be associated with variation in outcomes among veterans using the VA were indicated, including major depressive disorder, posttraumatic stress disorder (PTSD), alcohol use disorder (AUD), substance use disorder (SUD), and common chronic disease (hypertension, lipid disorders).¹⁴

Statistical Analysis

Sample characteristics were represented by frequencies and percentages for categorical variables and means and SDs (or medians and ranges where appropriate) for continuous variables. A χ² test (or Fisher exact test when cell counts were low) assessed associations in bivariate comparisons. A 2-sample t test (or Wilcoxon rank sum test as appropriate) assessed differences in continuous variables between 2 groups. Kaplan-Meier curves depicted the unadjusted relationship of AO exposure to survival. Cox proportional hazards survival models examined an unadjusted model containing only the AO exposure indicator as a predictor and adjusted models were used for demographic and clinical factors for MGUS and patients with MM separately.

Predictors were age in decades, sex, Hispanic ethnicity, race, nicotine dependence, obesity, overweight, AUD, SUD, major depressive disorder, PTSD, and the adapted CCI. When modeling patients with MM, MGUS was added to the model to identify the transformation group. The interaction of AO with transformation was also analyzed for patients with MM. Results were reported as hazard ratios (HR) with their 95% CI.

Results

We identified 18,215 veterans diagnosed with either MGUS or MM during fiscal years 2010-2015 with 16,366 meeting inclusion criteria. Patients were excluded for missing data on exposure (n = 334), age (n = 12), race (n = 1058), ethnicity (n = 164), diagnosis (n = 47), treatment (n = 56), and BMI (n = 178). All were Vietnam War era veterans; 14 also served in other eras.

The cohort was 98.5% male (Table 1). Twenty-nine percent were Black veterans, 65% were White veterans, and 4% of individuals reported Hispanic ethnicity. Patients had a mean (SD) age of 66.7 (5.9) years (range, 52-96). Most patients were married (58%) or divorced/separated (27%). All were VA priority 1 to 5 (no 6, 7, or 8); 50% were priority 1 with 50% to 100% service-connected disability. Another 29% were eligible for VA care by reason of low income, 17% had 10% to 40% service-connected disability, and 4% were otherwise disabled.

Disscussion

Elucidating the pathophysiology and risk of transformation from MGUS to MM is an ongoing endeavor, even 35 years after the end of US involvement in the Vietnam War. Our study sought to understand a relationship between AO exposure, risk of MGUS transforming to MM, and associated mortality in US Vietnam War veterans. The rate of transformation (MGUS progressing to active MM) is well cited at 1% per year.¹⁵ Here, we found 12% of our cohort had undergone this transformation over 10 years.

Vietnam War era veterans who were exposed to AO during the Operation Ranch Hand period had 2.4 times greater risk of developing MGUS compared with veterans not exposed to AO.⁸ Our study was not designed to look at this association of AO exposure and MGUS/MM as this was a retrospective review to assess the difference in outcomes based on AO exposure. We found that AO exposure is associated with a decrease in mortality in contrast to a prior study showing worse survival with individuals with AO exposure.¹⁰ Another single center study found no association between AO exposure and overall survival, but it did identify an increased risk of progression from MGUS to MM.¹¹ Our study did not show increased risk of transformation but did show positive effect on survival.

Black individuals have twice the risk of developing MM compared with White individuals and are diagnosed at a younger age (66 vs 70 years, respectively).¹⁶ Interestingly, Black race was a protective factor in our study. Given the length of time (35 years) elapsed since the Vietnam War ended, it is likely that most vulnerable Black veterans did not survive until our observation period.

HSCT, as expected, was a protective factor for veterans undergoing this treatment modality, but it is unclear why such a small number (8%) underwent HSCT as this is a standard of care in the management of MM. Obesity was also found to be a protective factor in a prior study, which was also seen in our study cohort.⁸

Limitations

This study was limited by its retrospective review of survivors among the Vietnam-era cohort several decades after the exposure of concern. Clinician notes and full historical data, such as date of onset for any disorder, were unavailable. These data also relied on the practitioners caring for the veterans to make the correct diagnosis with the associated code so that the data could be captured. Neither AO exposure nor diagnoses codes were verified against other sources of data; however, validation studies over the years have supported the accuracy of the diagnosis codes recorded in the VA EHR.

Conclusions

Because AO exposure is a nonmodifiable risk factor, focus should be placed on modifiable risk factors (eg, nicotine dependence, alcohol and substance use disorders, underlying comorbid conditions) as these were associated with worse outcomes. Future studies will look at the correlation of AO exposure, cytogenetics, and clinical outcomes in these veterans to learn how best to identify their disease course and optimize their care in the latter part of their life.

Acknowledgments

This research was supported by the Central Texas Veterans Health Care System and Baylor Scott and White Health, both in Temple and Veterans Affairs Central Western Massachusetts Healthcare System, Leeds.

The negative impact of the unnecessary prescribing of antibiotic is well known. Consequences include exposing patients to antibiotic adverse effects, risk of overgrowth of pathogenetic organisms such as clostridial species, unnecessary cost of drugs, and development of selection of antibiotic-resistant organisms in the populace at large. Acute viral respiratory infections are among the leading causes of inappropriate antibiotic usage.¹ In a study of 1000 adults with respiratory tract infections in an outpatient setting, 77% of patients were prescribed antibiotics, and the treatment was inappropriate in 64% of those who received prescriptions.² Patient expectations and clinician perceptions of these expectations play a role. One study showed that 54% of clinicians felt their patients expected to receive antibiotics for a visit due to an acute respiratory infection (ARI), such as a cough or cold; 26% of patients did in fact have this expectation.³

The US Department of Veterans Affairs (VA) Central Ohio Health Care System is a large ambulatory care facility, with 4 associated community-based outpatient clinics, serving more than 43,000 central Ohio veterans and completing more than 500,000 medical appointments annually. An antimicrobial stewardship program has been in place since 2013. In May 2018, the clinical pharmacist assigned to the program alerted medical leadership that, of 67 patients seen in primary care for ARIs between April 16, 2018, and May 15, 2018, 42 (63%) had been prescribed an antibiotic. Based on this finding, clinical leadership designed a process improvement program aimed at reducing inappropriate antibiotic usage for the treatment of uncomplicated ARls likely due to viral pathogens. Key components were clinician and patient education and the substitution of a symptomatic treatment kit in place of an antibiotic prescription.

Methods

Facility clinical leadership, assisted by Volunteer Services, developed a Viral Illness Support Pack to be dispensed by primary care practitioners (PCPs) to patients presenting with symptoms of viral ARIs. The contents of this support pack are shown in the Figure. Patients were provided with tissues, throat lozenges, lip balm, acetaminophen, hand sanitizer, a surgical mask, patient instructions, and the Antibiotics Aren’t Always the Answer pamphlet.⁴ The contents of the viral support pack were purchased through Volunteer Services using donated funds. In total, 460 packs were distributed to the primary care patient aligned care teams (PACTs), including the community-based outpatient clinics.

Clinicians and care teams received academic detailing prior to distribution of the viral support packs, stressing the importance of avoiding antibiotics to treat viral illnesses. Viral illness support packs were available for distribution from December 1, 2018, through March 31, 2019. The frequency of antibiotic dispensing to patients coded for ARI during this period was compared with that of the same time period in the previous year. All charts were reviewed for coding accuracy. Patients with illnesses requiring antibiotic treatment, such as pneumonia, exacerbations of chronic obstructive pulmonary disease and chronic bronchitis, and streptococcal pharyngitis, were excluded from the study. Statistical significance was determined using the unpaired t test.

Results

From December 1, 2018, to March 31, 2019, 357 viral support packs were distributed to patients (Table). For the historical control period from December 1, 2017, through March 31, 2018, 508 patients were treated for ARIs. Of these, 295 (58%) received clinically inappropriate antibiotics. In contrast, of the 627 patients treated for ARIs during the study period from December 1, 2018, through March 31, 2019, 310 (49%) received clinically inappropriate antibiotics. The 9% decrease during the period when viral support packs were distributed, compared with the prior year, was statistically significant (P = .02).

Discussion

The decrease in antibiotic prescriptions for ARIs was statistically significant. The success of this project can be attributed to 3 factors: clinician education, patient education, and the option for PCPs to provide symptomatic treatment for these patients rather than prescribe an antibiotic.

The importance of antibiotic stewardship has been emphasized to all PCPs at the VA Central Ohio Health Care System. Antibiotic stewardship has been the subject of grand rounds. Prior to distribution of the viral support pack, the chief of specialty medicine, the project’s champion, spoke to all PCPs. Adequate numbers of viral support packs were distributed to all primary care teams.

In addition to direct clinician-to-patient education at the time of the patients’ visits, educational materials were included in the viral support pack. The Antibiotics Aren’t Always the Answer pamphlet is available from the Centers for Disease Control and Prevention. It covers the importance of antibiotic awareness, discusses what antibiotics do and do not treat, how to stay healthy, and causes of antibiotic resistance. The pamphlet contains the clear message that antibiotics are not only ineffective against viral illness, but also can cause significant undesirable outcomes.

The pamphlet Viral Illness Support Pack Traffic Light Card (eAppendix available online at doi:10.12788/fp.0302) provides important clinical information to the patients about their illness. Patients are instructed to contact their primary care team if they are worse after 3 days of illness; symptoms are not improving after 10 days; or they experience blood in respiratory secretions, chills or generalized aching, and localized pain that is one-sided or significantly worsening. Patients are clearly informed to seek further care if not improving with symptomatic treatment.

The ability to provide patients with symptomatic relief, including throat lozenges, lip balm, and acetaminophen, was felt to be important in the success of the project. Furthermore, this eliminated an extra step of the patient needing to visit the pharmacy.

Limitations

Limitations of the study included starting distribution of the support packs somewhat after the onset of the viral illness season, failure to reach all prescribers for academic detailing at the start of the program, and several instances of temporary unavailability of the support packs in some areas.

Conclusions

Patients with ARIs are often significantly symptomatic and frequently believe that they require an antibiotic for treatment. Clinicians may adjust their behavior in response to their patients’ expectations, stated or unstated. The results of this project demonstrate that the combination of patient education and the ready availability of a nonantibiotic symptomatic treatment option can significantly decrease the unnecessary prescribing of antibiotics for viral illnesses.

Acknowledgments

The authors are grateful to Ms. Traci Washington for assistance in sourcing materials; to Karen Corr, PhD, and Anthony Restuccio, MD, for advice on methods; to Mr. Daniel Pignatelli for assistance with data interpretation; and to Mr. Keith Skidmore, Ms. Crystal Conley, and Ms. Megan Harris for assistance with assembling the Viral Illness Support Packs.

The negative impact of the unnecessary prescribing of antibiotic is well known. Consequences include exposing patients to antibiotic adverse effects, risk of overgrowth of pathogenetic organisms such as clostridial species, unnecessary cost of drugs, and development of selection of antibiotic-resistant organisms in the populace at large. Acute viral respiratory infections are among the leading causes of inappropriate antibiotic usage.¹ In a study of 1000 adults with respiratory tract infections in an outpatient setting, 77% of patients were prescribed antibiotics, and the treatment was inappropriate in 64% of those who received prescriptions.² Patient expectations and clinician perceptions of these expectations play a role. One study showed that 54% of clinicians felt their patients expected to receive antibiotics for a visit due to an acute respiratory infection (ARI), such as a cough or cold; 26% of patients did in fact have this expectation.³

The US Department of Veterans Affairs (VA) Central Ohio Health Care System is a large ambulatory care facility, with 4 associated community-based outpatient clinics, serving more than 43,000 central Ohio veterans and completing more than 500,000 medical appointments annually. An antimicrobial stewardship program has been in place since 2013. In May 2018, the clinical pharmacist assigned to the program alerted medical leadership that, of 67 patients seen in primary care for ARIs between April 16, 2018, and May 15, 2018, 42 (63%) had been prescribed an antibiotic. Based on this finding, clinical leadership designed a process improvement program aimed at reducing inappropriate antibiotic usage for the treatment of uncomplicated ARls likely due to viral pathogens. Key components were clinician and patient education and the substitution of a symptomatic treatment kit in place of an antibiotic prescription.

Methods

Facility clinical leadership, assisted by Volunteer Services, developed a Viral Illness Support Pack to be dispensed by primary care practitioners (PCPs) to patients presenting with symptoms of viral ARIs. The contents of this support pack are shown in the Figure. Patients were provided with tissues, throat lozenges, lip balm, acetaminophen, hand sanitizer, a surgical mask, patient instructions, and the Antibiotics Aren’t Always the Answer pamphlet.⁴ The contents of the viral support pack were purchased through Volunteer Services using donated funds. In total, 460 packs were distributed to the primary care patient aligned care teams (PACTs), including the community-based outpatient clinics.

Clinicians and care teams received academic detailing prior to distribution of the viral support packs, stressing the importance of avoiding antibiotics to treat viral illnesses. Viral illness support packs were available for distribution from December 1, 2018, through March 31, 2019. The frequency of antibiotic dispensing to patients coded for ARI during this period was compared with that of the same time period in the previous year. All charts were reviewed for coding accuracy. Patients with illnesses requiring antibiotic treatment, such as pneumonia, exacerbations of chronic obstructive pulmonary disease and chronic bronchitis, and streptococcal pharyngitis, were excluded from the study. Statistical significance was determined using the unpaired t test.

Results

From December 1, 2018, to March 31, 2019, 357 viral support packs were distributed to patients (Table). For the historical control period from December 1, 2017, through March 31, 2018, 508 patients were treated for ARIs. Of these, 295 (58%) received clinically inappropriate antibiotics. In contrast, of the 627 patients treated for ARIs during the study period from December 1, 2018, through March 31, 2019, 310 (49%) received clinically inappropriate antibiotics. The 9% decrease during the period when viral support packs were distributed, compared with the prior year, was statistically significant (P = .02).

Discussion

The decrease in antibiotic prescriptions for ARIs was statistically significant. The success of this project can be attributed to 3 factors: clinician education, patient education, and the option for PCPs to provide symptomatic treatment for these patients rather than prescribe an antibiotic.

The importance of antibiotic stewardship has been emphasized to all PCPs at the VA Central Ohio Health Care System. Antibiotic stewardship has been the subject of grand rounds. Prior to distribution of the viral support pack, the chief of specialty medicine, the project’s champion, spoke to all PCPs. Adequate numbers of viral support packs were distributed to all primary care teams.

In addition to direct clinician-to-patient education at the time of the patients’ visits, educational materials were included in the viral support pack. The Antibiotics Aren’t Always the Answer pamphlet is available from the Centers for Disease Control and Prevention. It covers the importance of antibiotic awareness, discusses what antibiotics do and do not treat, how to stay healthy, and causes of antibiotic resistance. The pamphlet contains the clear message that antibiotics are not only ineffective against viral illness, but also can cause significant undesirable outcomes.

The pamphlet Viral Illness Support Pack Traffic Light Card (eAppendix available online at doi:10.12788/fp.0302) provides important clinical information to the patients about their illness. Patients are instructed to contact their primary care team if they are worse after 3 days of illness; symptoms are not improving after 10 days; or they experience blood in respiratory secretions, chills or generalized aching, and localized pain that is one-sided or significantly worsening. Patients are clearly informed to seek further care if not improving with symptomatic treatment.

The ability to provide patients with symptomatic relief, including throat lozenges, lip balm, and acetaminophen, was felt to be important in the success of the project. Furthermore, this eliminated an extra step of the patient needing to visit the pharmacy.

Limitations

Limitations of the study included starting distribution of the support packs somewhat after the onset of the viral illness season, failure to reach all prescribers for academic detailing at the start of the program, and several instances of temporary unavailability of the support packs in some areas.

Conclusions

Patients with ARIs are often significantly symptomatic and frequently believe that they require an antibiotic for treatment. Clinicians may adjust their behavior in response to their patients’ expectations, stated or unstated. The results of this project demonstrate that the combination of patient education and the ready availability of a nonantibiotic symptomatic treatment option can significantly decrease the unnecessary prescribing of antibiotics for viral illnesses.

Acknowledgments

The authors are grateful to Ms. Traci Washington for assistance in sourcing materials; to Karen Corr, PhD, and Anthony Restuccio, MD, for advice on methods; to Mr. Daniel Pignatelli for assistance with data interpretation; and to Mr. Keith Skidmore, Ms. Crystal Conley, and Ms. Megan Harris for assistance with assembling the Viral Illness Support Packs.

The negative impact of the unnecessary prescribing of antibiotic is well known. Consequences include exposing patients to antibiotic adverse effects, risk of overgrowth of pathogenetic organisms such as clostridial species, unnecessary cost of drugs, and development of selection of antibiotic-resistant organisms in the populace at large. Acute viral respiratory infections are among the leading causes of inappropriate antibiotic usage.¹ In a study of 1000 adults with respiratory tract infections in an outpatient setting, 77% of patients were prescribed antibiotics, and the treatment was inappropriate in 64% of those who received prescriptions.² Patient expectations and clinician perceptions of these expectations play a role. One study showed that 54% of clinicians felt their patients expected to receive antibiotics for a visit due to an acute respiratory infection (ARI), such as a cough or cold; 26% of patients did in fact have this expectation.³

The US Department of Veterans Affairs (VA) Central Ohio Health Care System is a large ambulatory care facility, with 4 associated community-based outpatient clinics, serving more than 43,000 central Ohio veterans and completing more than 500,000 medical appointments annually. An antimicrobial stewardship program has been in place since 2013. In May 2018, the clinical pharmacist assigned to the program alerted medical leadership that, of 67 patients seen in primary care for ARIs between April 16, 2018, and May 15, 2018, 42 (63%) had been prescribed an antibiotic. Based on this finding, clinical leadership designed a process improvement program aimed at reducing inappropriate antibiotic usage for the treatment of uncomplicated ARls likely due to viral pathogens. Key components were clinician and patient education and the substitution of a symptomatic treatment kit in place of an antibiotic prescription.

Methods

Facility clinical leadership, assisted by Volunteer Services, developed a Viral Illness Support Pack to be dispensed by primary care practitioners (PCPs) to patients presenting with symptoms of viral ARIs. The contents of this support pack are shown in the Figure. Patients were provided with tissues, throat lozenges, lip balm, acetaminophen, hand sanitizer, a surgical mask, patient instructions, and the Antibiotics Aren’t Always the Answer pamphlet.⁴ The contents of the viral support pack were purchased through Volunteer Services using donated funds. In total, 460 packs were distributed to the primary care patient aligned care teams (PACTs), including the community-based outpatient clinics.

Clinicians and care teams received academic detailing prior to distribution of the viral support packs, stressing the importance of avoiding antibiotics to treat viral illnesses. Viral illness support packs were available for distribution from December 1, 2018, through March 31, 2019. The frequency of antibiotic dispensing to patients coded for ARI during this period was compared with that of the same time period in the previous year. All charts were reviewed for coding accuracy. Patients with illnesses requiring antibiotic treatment, such as pneumonia, exacerbations of chronic obstructive pulmonary disease and chronic bronchitis, and streptococcal pharyngitis, were excluded from the study. Statistical significance was determined using the unpaired t test.

Results

From December 1, 2018, to March 31, 2019, 357 viral support packs were distributed to patients (Table). For the historical control period from December 1, 2017, through March 31, 2018, 508 patients were treated for ARIs. Of these, 295 (58%) received clinically inappropriate antibiotics. In contrast, of the 627 patients treated for ARIs during the study period from December 1, 2018, through March 31, 2019, 310 (49%) received clinically inappropriate antibiotics. The 9% decrease during the period when viral support packs were distributed, compared with the prior year, was statistically significant (P = .02).

Discussion

The decrease in antibiotic prescriptions for ARIs was statistically significant. The success of this project can be attributed to 3 factors: clinician education, patient education, and the option for PCPs to provide symptomatic treatment for these patients rather than prescribe an antibiotic.

The importance of antibiotic stewardship has been emphasized to all PCPs at the VA Central Ohio Health Care System. Antibiotic stewardship has been the subject of grand rounds. Prior to distribution of the viral support pack, the chief of specialty medicine, the project’s champion, spoke to all PCPs. Adequate numbers of viral support packs were distributed to all primary care teams.

In addition to direct clinician-to-patient education at the time of the patients’ visits, educational materials were included in the viral support pack. The Antibiotics Aren’t Always the Answer pamphlet is available from the Centers for Disease Control and Prevention. It covers the importance of antibiotic awareness, discusses what antibiotics do and do not treat, how to stay healthy, and causes of antibiotic resistance. The pamphlet contains the clear message that antibiotics are not only ineffective against viral illness, but also can cause significant undesirable outcomes.

The pamphlet Viral Illness Support Pack Traffic Light Card (eAppendix available online at doi:10.12788/fp.0302) provides important clinical information to the patients about their illness. Patients are instructed to contact their primary care team if they are worse after 3 days of illness; symptoms are not improving after 10 days; or they experience blood in respiratory secretions, chills or generalized aching, and localized pain that is one-sided or significantly worsening. Patients are clearly informed to seek further care if not improving with symptomatic treatment.

The ability to provide patients with symptomatic relief, including throat lozenges, lip balm, and acetaminophen, was felt to be important in the success of the project. Furthermore, this eliminated an extra step of the patient needing to visit the pharmacy.

Limitations

Limitations of the study included starting distribution of the support packs somewhat after the onset of the viral illness season, failure to reach all prescribers for academic detailing at the start of the program, and several instances of temporary unavailability of the support packs in some areas.

Conclusions

Patients with ARIs are often significantly symptomatic and frequently believe that they require an antibiotic for treatment. Clinicians may adjust their behavior in response to their patients’ expectations, stated or unstated. The results of this project demonstrate that the combination of patient education and the ready availability of a nonantibiotic symptomatic treatment option can significantly decrease the unnecessary prescribing of antibiotics for viral illnesses.

Acknowledgments

The authors are grateful to Ms. Traci Washington for assistance in sourcing materials; to Karen Corr, PhD, and Anthony Restuccio, MD, for advice on methods; to Mr. Daniel Pignatelli for assistance with data interpretation; and to Mr. Keith Skidmore, Ms. Crystal Conley, and Ms. Megan Harris for assistance with assembling the Viral Illness Support Packs.