A 21-year-old man presented to the dermatology clinic with a 2-month history of painless genital and perianal lesions. The patient reported having unprotected sex in recent months, but had no prior history of oral, penile, or anal mucosal lesions or ulcers. He was not on any medications or immunosuppressive agents and noted that the lesions did not represent a recurrence. He also reported a nonspecific, asymptomatic rash on his trunk and extremities that had been present for an unknown period of time.

The patient indicated that his primary care physician had looked at the genital/perianal lesions and told him they were genital warts. Previous treatments included an over-the-counter wart medication, cryotherapy, and a course of imiquimod, but none had helped.

The physical examination revealed multiple soft, moist, beefy papules and plaques around the genital area (FIGURE 1) and perianal region. In addition, there were multiple hyper-pigmented macules on the patient’s palms and soles (FIGURE 2), and reticulated, patchy eruptions on his arms, chest (FIGURE 3), and back.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Diagnosis: Secondary syphilis

The appearance of the genital and perianal lesions was consistent with condylomata lata—a cutaneous sign of secondary syphilis—rather than genital warts. The presence of a rash on the patient’s trunk and extremities further supported this diagnosis. We did a rapid plasma reagin (RPR) test and a Treponema pallidum particle agglutination test; we also tested for human immunodeficiency virus (HIV). The patient’s RPR titer was 1:128, and the T pallidum antibody test came back positive. HIV-1 and HIV-2 serology were negative.

Appearance of the lesions was a giveaway. Condylomata lata are flat-topped, broad papules that are usually located on folds of moist skin (particularly the genitals and anus), and have a smooth, gray, moist surface. Although they can be lobulated, they do not have the classic digitate projections that are characteristic of genital warts. A nonpruritic, symmetric, “raw ham”-colored papular eruption on a patient’s trunk, palms, and soles is also characteristic of secondary syphilis.¹ In this case, the reticular pattern on the patient’s chest represented the commonly seen lenticular rash of secondary syphilis.

Cutaneous lesions of secondary syphilis contain numerous spirochetes (T pallidum) and are highly infectious. Systemic symptoms of secondary syphilis may include fatigue, generalized lymphadenopathy, arthralgia, myalgia, pharyngitis, and headache.

Although condylomata lata can be lobulated, they do not have the classic digitate projections characteristic of genital warts.

Some patients may report having a recent chancre—a painless, self-limiting ulcer in the genital area—which is characteristic of primary syphilis (see “Single nontender ulcer on the glans,” J Fam Pract. 2017;66:253-255). For more on the stages of syphilis, see the TABLE². Our patient did not remember ever having a chancre.

Increase in cases. Rates of primary and secondary syphilis have increased in the past decade. In 2014, approximately 20,000 syphilis cases were reported—a record high since 1994.³ Men who have sex with men are particularly affected; however, increases in infection rates have also been noted in women and across people of all ages and ethnicities.³

Rule out other causes of genital lesions

Condyloma acuminata, commonly called genital warts, are localized human papilloma virus (HPV) infections that appear as discrete, gray to pale pink, lobulated papules that may coalesce to form a large, cauliflower-like mass. They are sexually transmitted and commonly involve the genital and anal areas. While physicians may confuse condylomata lata with genital warts, diffuse skin rashes and constitutional symptoms are not usually seen with genital warts.⁴

Fordyce spots are small, whitish, raised papules on the glans or the shaft of the penis or the vulva of the vagina. They may also appear on the lips and oral mucosa. They are a result of prominent sebaceous glands and are harmless. They are not infectious or sexually transmitted.^5,6

Lymphogranuloma venereum is an uncommon sexually transmitted disease caused by Chlamydia trachomatis. It is characterized by genital papules or ulcers, followed by bilateral, suppurative, inguinal adenitis known as buboes. The buboes may breakdown, form multiple fistulous openings, and discharge purulent material.⁶

Acute HIV may present with flu-like symptoms and well-circumscribed maculopapular rashes on the face, neck, and upper trunk. The palms and soles may also be affected. Patients with HIV may also develop genital plaque-like lesions from herpes simplex virus-2, genital warts from HPV, molluscum contagiosum, and, not uncommonly, anogenital malignancies.^7,8

Confluent and reticulated papillomatosis (CARP) is a disorder that occurs predominantly in young adults and teenagers, with cosmetically displeasing brown scaling macules that may coalesce to form patches or plaques affecting the neck, chest, back, and axillae. It is often mistaken for tinea versicolor.⁹ In this case, the eruption on the chest closely resembled CARP, but a diagnosis of CARP would not have explained the genital lesions.

Confirm diagnosis with treponemal tests

Syphilis is often a clinical diagnosis with pathologic confirmation. Patients suspected of having syphilis should be screened with nontreponemal tests, such as the Venereal Disease Research Laboratory (VDRL) test or the RPR test, which become positive within 3 weeks of developing primary syphilis.

Diagnosis is confirmed with specific treponemal testing, such as with a fluorescent treponemal antibody absorption assay or the T pallidum particle agglutination test. HIV testing is recommended for all patients with syphilis.

Penicillin G is the mainstay of treatment

Proper selection of penicillin is paramount in the treatment of syphilis. Primary, secondary, and early latent syphilis are treated with an intramuscular injection of 2.4 million units of long-acting benzathine penicillin G. Patients with late latent or latent syphilis of unknown duration are treated with 3 doses of the same injection at weekly intervals, totaling 7.2 million units of benzathine penicillin G.¹⁰ Certain penicillin preparations (eg, combinations of benzathine penicillin and procaine penicillin) are not appropriate treatments because they do not provide adequate amounts of the antibiotic.

Watch for this reaction. Approximately 30% of patients following penicillin treatment for spirochete infection develop a Jarisch-Herxheimer reaction (JHR).¹¹ JHR is characterized by an abrupt onset of fever, chills, myalgia, tachycardia, vasodilatation with flushing, exacerbated maculopapular skin rash, or mild hypotension. Care for JHR is generally supportive.

Our patient received an intramuscular injection of 2.4 million units of long-acting benzathine penicillin G. His skin eruption and condylomata lata lesions were completely resolved at follow-up 6 months later.

As recommended by the Centers for Disease Control and Prevention,¹⁰ our patient’s RPR titers were repeated at 6 months and again at 12 months to verify a four-fold decline, indicating successful treatment.

CORRESPONDENCE
Anne Bartels, MD, General Medicine, Naval Hospital Camp Lejeune, 100 Brewster Blvd., Camp Lejeune, NC 28547; [email protected].

A 21-year-old man presented to the dermatology clinic with a 2-month history of painless genital and perianal lesions. The patient reported having unprotected sex in recent months, but had no prior history of oral, penile, or anal mucosal lesions or ulcers. He was not on any medications or immunosuppressive agents and noted that the lesions did not represent a recurrence. He also reported a nonspecific, asymptomatic rash on his trunk and extremities that had been present for an unknown period of time.

The patient indicated that his primary care physician had looked at the genital/perianal lesions and told him they were genital warts. Previous treatments included an over-the-counter wart medication, cryotherapy, and a course of imiquimod, but none had helped.

The physical examination revealed multiple soft, moist, beefy papules and plaques around the genital area (FIGURE 1) and perianal region. In addition, there were multiple hyper-pigmented macules on the patient’s palms and soles (FIGURE 2), and reticulated, patchy eruptions on his arms, chest (FIGURE 3), and back.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Diagnosis: Secondary syphilis

The appearance of the genital and perianal lesions was consistent with condylomata lata—a cutaneous sign of secondary syphilis—rather than genital warts. The presence of a rash on the patient’s trunk and extremities further supported this diagnosis. We did a rapid plasma reagin (RPR) test and a Treponema pallidum particle agglutination test; we also tested for human immunodeficiency virus (HIV). The patient’s RPR titer was 1:128, and the T pallidum antibody test came back positive. HIV-1 and HIV-2 serology were negative.

Appearance of the lesions was a giveaway. Condylomata lata are flat-topped, broad papules that are usually located on folds of moist skin (particularly the genitals and anus), and have a smooth, gray, moist surface. Although they can be lobulated, they do not have the classic digitate projections that are characteristic of genital warts. A nonpruritic, symmetric, “raw ham”-colored papular eruption on a patient’s trunk, palms, and soles is also characteristic of secondary syphilis.¹ In this case, the reticular pattern on the patient’s chest represented the commonly seen lenticular rash of secondary syphilis.

Cutaneous lesions of secondary syphilis contain numerous spirochetes (T pallidum) and are highly infectious. Systemic symptoms of secondary syphilis may include fatigue, generalized lymphadenopathy, arthralgia, myalgia, pharyngitis, and headache.

Although condylomata lata can be lobulated, they do not have the classic digitate projections characteristic of genital warts.

Some patients may report having a recent chancre—a painless, self-limiting ulcer in the genital area—which is characteristic of primary syphilis (see “Single nontender ulcer on the glans,” J Fam Pract. 2017;66:253-255). For more on the stages of syphilis, see the TABLE². Our patient did not remember ever having a chancre.

Increase in cases. Rates of primary and secondary syphilis have increased in the past decade. In 2014, approximately 20,000 syphilis cases were reported—a record high since 1994.³ Men who have sex with men are particularly affected; however, increases in infection rates have also been noted in women and across people of all ages and ethnicities.³

Rule out other causes of genital lesions

Condyloma acuminata, commonly called genital warts, are localized human papilloma virus (HPV) infections that appear as discrete, gray to pale pink, lobulated papules that may coalesce to form a large, cauliflower-like mass. They are sexually transmitted and commonly involve the genital and anal areas. While physicians may confuse condylomata lata with genital warts, diffuse skin rashes and constitutional symptoms are not usually seen with genital warts.⁴

Fordyce spots are small, whitish, raised papules on the glans or the shaft of the penis or the vulva of the vagina. They may also appear on the lips and oral mucosa. They are a result of prominent sebaceous glands and are harmless. They are not infectious or sexually transmitted.^5,6

Lymphogranuloma venereum is an uncommon sexually transmitted disease caused by Chlamydia trachomatis. It is characterized by genital papules or ulcers, followed by bilateral, suppurative, inguinal adenitis known as buboes. The buboes may breakdown, form multiple fistulous openings, and discharge purulent material.⁶

Acute HIV may present with flu-like symptoms and well-circumscribed maculopapular rashes on the face, neck, and upper trunk. The palms and soles may also be affected. Patients with HIV may also develop genital plaque-like lesions from herpes simplex virus-2, genital warts from HPV, molluscum contagiosum, and, not uncommonly, anogenital malignancies.^7,8

Confluent and reticulated papillomatosis (CARP) is a disorder that occurs predominantly in young adults and teenagers, with cosmetically displeasing brown scaling macules that may coalesce to form patches or plaques affecting the neck, chest, back, and axillae. It is often mistaken for tinea versicolor.⁹ In this case, the eruption on the chest closely resembled CARP, but a diagnosis of CARP would not have explained the genital lesions.

Confirm diagnosis with treponemal tests

Syphilis is often a clinical diagnosis with pathologic confirmation. Patients suspected of having syphilis should be screened with nontreponemal tests, such as the Venereal Disease Research Laboratory (VDRL) test or the RPR test, which become positive within 3 weeks of developing primary syphilis.

Diagnosis is confirmed with specific treponemal testing, such as with a fluorescent treponemal antibody absorption assay or the T pallidum particle agglutination test. HIV testing is recommended for all patients with syphilis.

Penicillin G is the mainstay of treatment

Proper selection of penicillin is paramount in the treatment of syphilis. Primary, secondary, and early latent syphilis are treated with an intramuscular injection of 2.4 million units of long-acting benzathine penicillin G. Patients with late latent or latent syphilis of unknown duration are treated with 3 doses of the same injection at weekly intervals, totaling 7.2 million units of benzathine penicillin G.¹⁰ Certain penicillin preparations (eg, combinations of benzathine penicillin and procaine penicillin) are not appropriate treatments because they do not provide adequate amounts of the antibiotic.

Watch for this reaction. Approximately 30% of patients following penicillin treatment for spirochete infection develop a Jarisch-Herxheimer reaction (JHR).¹¹ JHR is characterized by an abrupt onset of fever, chills, myalgia, tachycardia, vasodilatation with flushing, exacerbated maculopapular skin rash, or mild hypotension. Care for JHR is generally supportive.

Our patient received an intramuscular injection of 2.4 million units of long-acting benzathine penicillin G. His skin eruption and condylomata lata lesions were completely resolved at follow-up 6 months later.

As recommended by the Centers for Disease Control and Prevention,¹⁰ our patient’s RPR titers were repeated at 6 months and again at 12 months to verify a four-fold decline, indicating successful treatment.

CORRESPONDENCE
Anne Bartels, MD, General Medicine, Naval Hospital Camp Lejeune, 100 Brewster Blvd., Camp Lejeune, NC 28547; [email protected].

A 21-year-old man presented to the dermatology clinic with a 2-month history of painless genital and perianal lesions. The patient reported having unprotected sex in recent months, but had no prior history of oral, penile, or anal mucosal lesions or ulcers. He was not on any medications or immunosuppressive agents and noted that the lesions did not represent a recurrence. He also reported a nonspecific, asymptomatic rash on his trunk and extremities that had been present for an unknown period of time.

The patient indicated that his primary care physician had looked at the genital/perianal lesions and told him they were genital warts. Previous treatments included an over-the-counter wart medication, cryotherapy, and a course of imiquimod, but none had helped.

The physical examination revealed multiple soft, moist, beefy papules and plaques around the genital area (FIGURE 1) and perianal region. In addition, there were multiple hyper-pigmented macules on the patient’s palms and soles (FIGURE 2), and reticulated, patchy eruptions on his arms, chest (FIGURE 3), and back.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Diagnosis: Secondary syphilis

The appearance of the genital and perianal lesions was consistent with condylomata lata—a cutaneous sign of secondary syphilis—rather than genital warts. The presence of a rash on the patient’s trunk and extremities further supported this diagnosis. We did a rapid plasma reagin (RPR) test and a Treponema pallidum particle agglutination test; we also tested for human immunodeficiency virus (HIV). The patient’s RPR titer was 1:128, and the T pallidum antibody test came back positive. HIV-1 and HIV-2 serology were negative.

Appearance of the lesions was a giveaway. Condylomata lata are flat-topped, broad papules that are usually located on folds of moist skin (particularly the genitals and anus), and have a smooth, gray, moist surface. Although they can be lobulated, they do not have the classic digitate projections that are characteristic of genital warts. A nonpruritic, symmetric, “raw ham”-colored papular eruption on a patient’s trunk, palms, and soles is also characteristic of secondary syphilis.¹ In this case, the reticular pattern on the patient’s chest represented the commonly seen lenticular rash of secondary syphilis.

Cutaneous lesions of secondary syphilis contain numerous spirochetes (T pallidum) and are highly infectious. Systemic symptoms of secondary syphilis may include fatigue, generalized lymphadenopathy, arthralgia, myalgia, pharyngitis, and headache.

Although condylomata lata can be lobulated, they do not have the classic digitate projections characteristic of genital warts.

Some patients may report having a recent chancre—a painless, self-limiting ulcer in the genital area—which is characteristic of primary syphilis (see “Single nontender ulcer on the glans,” J Fam Pract. 2017;66:253-255). For more on the stages of syphilis, see the TABLE². Our patient did not remember ever having a chancre.

Increase in cases. Rates of primary and secondary syphilis have increased in the past decade. In 2014, approximately 20,000 syphilis cases were reported—a record high since 1994.³ Men who have sex with men are particularly affected; however, increases in infection rates have also been noted in women and across people of all ages and ethnicities.³

Rule out other causes of genital lesions

Condyloma acuminata, commonly called genital warts, are localized human papilloma virus (HPV) infections that appear as discrete, gray to pale pink, lobulated papules that may coalesce to form a large, cauliflower-like mass. They are sexually transmitted and commonly involve the genital and anal areas. While physicians may confuse condylomata lata with genital warts, diffuse skin rashes and constitutional symptoms are not usually seen with genital warts.⁴

Fordyce spots are small, whitish, raised papules on the glans or the shaft of the penis or the vulva of the vagina. They may also appear on the lips and oral mucosa. They are a result of prominent sebaceous glands and are harmless. They are not infectious or sexually transmitted.^5,6

Lymphogranuloma venereum is an uncommon sexually transmitted disease caused by Chlamydia trachomatis. It is characterized by genital papules or ulcers, followed by bilateral, suppurative, inguinal adenitis known as buboes. The buboes may breakdown, form multiple fistulous openings, and discharge purulent material.⁶

Acute HIV may present with flu-like symptoms and well-circumscribed maculopapular rashes on the face, neck, and upper trunk. The palms and soles may also be affected. Patients with HIV may also develop genital plaque-like lesions from herpes simplex virus-2, genital warts from HPV, molluscum contagiosum, and, not uncommonly, anogenital malignancies.^7,8

Confluent and reticulated papillomatosis (CARP) is a disorder that occurs predominantly in young adults and teenagers, with cosmetically displeasing brown scaling macules that may coalesce to form patches or plaques affecting the neck, chest, back, and axillae. It is often mistaken for tinea versicolor.⁹ In this case, the eruption on the chest closely resembled CARP, but a diagnosis of CARP would not have explained the genital lesions.

Confirm diagnosis with treponemal tests

Syphilis is often a clinical diagnosis with pathologic confirmation. Patients suspected of having syphilis should be screened with nontreponemal tests, such as the Venereal Disease Research Laboratory (VDRL) test or the RPR test, which become positive within 3 weeks of developing primary syphilis.

Diagnosis is confirmed with specific treponemal testing, such as with a fluorescent treponemal antibody absorption assay or the T pallidum particle agglutination test. HIV testing is recommended for all patients with syphilis.

Penicillin G is the mainstay of treatment

Proper selection of penicillin is paramount in the treatment of syphilis. Primary, secondary, and early latent syphilis are treated with an intramuscular injection of 2.4 million units of long-acting benzathine penicillin G. Patients with late latent or latent syphilis of unknown duration are treated with 3 doses of the same injection at weekly intervals, totaling 7.2 million units of benzathine penicillin G.¹⁰ Certain penicillin preparations (eg, combinations of benzathine penicillin and procaine penicillin) are not appropriate treatments because they do not provide adequate amounts of the antibiotic.

Watch for this reaction. Approximately 30% of patients following penicillin treatment for spirochete infection develop a Jarisch-Herxheimer reaction (JHR).¹¹ JHR is characterized by an abrupt onset of fever, chills, myalgia, tachycardia, vasodilatation with flushing, exacerbated maculopapular skin rash, or mild hypotension. Care for JHR is generally supportive.

Our patient received an intramuscular injection of 2.4 million units of long-acting benzathine penicillin G. His skin eruption and condylomata lata lesions were completely resolved at follow-up 6 months later.

As recommended by the Centers for Disease Control and Prevention,¹⁰ our patient’s RPR titers were repeated at 6 months and again at 12 months to verify a four-fold decline, indicating successful treatment.

CORRESPONDENCE
Anne Bartels, MD, General Medicine, Naval Hospital Camp Lejeune, 100 Brewster Blvd., Camp Lejeune, NC 28547; [email protected].

Herpes zoster infection raised the risk of stroke by 35% and of myocardial infarction by 59%, in a South Korean nationwide study.

In addition, the risks of stroke and MI were highest in the first year following herpes zoster infection and decreased over time, said Min-Chul Kim, MD, the University of Ulsan, Seoul, South Korea, and associates.

Asvmdrn/Wikimedia Commons /CCA-SA 3.0

Herpes zoster infection raised the risk of stroke by 35% and of myocardial infarction by 59%, in a South Korean nationwide study.

In addition, the risks of stroke and MI were highest in the first year following herpes zoster infection and decreased over time, said Min-Chul Kim, MD, the University of Ulsan, Seoul, South Korea, and associates.

Asvmdrn/Wikimedia Commons /CCA-SA 3.0

Herpes zoster infection raised the risk of stroke by 35% and of myocardial infarction by 59%, in a South Korean nationwide study.

In addition, the risks of stroke and MI were highest in the first year following herpes zoster infection and decreased over time, said Min-Chul Kim, MD, the University of Ulsan, Seoul, South Korea, and associates.

Asvmdrn/Wikimedia Commons /CCA-SA 3.0

ILLUSTRATIVE CASE

A 28-year-old woman presents to your office for a routine health maintenance examination. She is currently using an oral contraceptive containing desogestrel and ethinyl estradiol for contraception and is inquiring about a refill for the coming year. What would you recommend?

When choosing a combined oral contraceptive (COC) for a patient, physicians often have “go-to” favorites—tried and true agents that are easy to prescribe on a busy clinic day. However, some of these may be placing patients at increased risk for venous thromboembolic events.

In general, when compared with nonusers, women who use COCs have a 2- to 4-fold increase in risk of venous thromboembolism (VTE) and an increased risk of myocardial infarction (MI) and stroke.^2,3 More specifically, higher doses of estrogen combined with the progesterones gestodene, desogestrel, and levonorgestrel, are associated with a higher risk of VTE.^2-6

In 2012, the European Medicines Agency warned that COCs containing drospirenone were associated with a higher risk of VTE than other preparations, despite similar estrogen content.⁷ The US Food and Drug Administration (FDA) produced a similar statement that same year, recommending that physicians carefully consider the risks and benefits before prescribing contraceptives containing drospirenone.⁸

The risks of ischemic stroke and MI have not been clearly established for varying doses of estrogen and different progesterones. This large observational study fills that informational gap by providing risk estimates for the various COC options.

STUDY SUMMARY

One combined oral contraceptive comes out ahead

The authors used an observational cohort model to determine the effects of different doses of estrogen combined with different progesterones in COCs on the risks of pulmonary embolism (PE), ischemic stroke, and MI.¹ Data were collected from the French national health insurance database and the French national hospital discharge database.^9,10 The study included just under 5 million women 15 to 49 years of age, living in France, with at least one prescription filled for COCs between July 2010 and September 2012.

The investigators calculated the absolute and relative risks of first PE, ischemic stroke, and MI in women using COC formulations containing either low-dose estrogen (20 mcg) or high-dose estrogen (30-40 mcg) combined with one of 5 progesterones (norethisterone, norgestrel, levonorgestrel, desogestrel, gestodene). The relative risk (RR) was adjusted for confounding factors, including age, complimentary universal health insurance, socioeconomic status, hypertension, diabetes, and consultation with a gynecologist in the previous year.

The absolute risk per 100,000 woman-years for all COC use was 33 for PE, 19 for ischemic stroke, and 7 for MI with a composite risk of 60. The RRs for low-dose estrogen vs high-dose estrogen were 0.75 (95% confidence interval [CI], 0.67-0.85) for PE, 0.82 (95% CI, 0.7-0.96) for ischemic stroke, and 0.56 (95% CI, 0.39-0.79) for MI. The absolute risk reduction (ARR) with low-dose estrogen vs high-dose estrogen was 14/100,000 person-years of use; the number needed to harm (NNH) was 7143.

Oral contraceptives containing levonorgestrel and low-dose estrogen resulted in the lowest overall risks of PE and arterial thromboembolism.

Compared with levonorgestrel, desogestrel and gestodene were associated with higher RRs of PE but not arterial events (2.16; 95% CI, 1.93-2.41 for desogestrel and 1.63; 95% CI, 1.34-1.97 for gestodene). The ARR with levonorgestrel use as opposed to desogestrel for PE was 19/100,000 person-years of use (NNH=5263); the ARR with levonorgestrel use as opposed to gestodene was 12/100,000 person-years of use (NNH=8333). The authors concluded that for the same progesterone, using a lower dose of estrogen decreases risk of PE, ischemic stroke, and MI, and that oral contraceptives containing levonorgestrel and low-dose estrogen resulted in the lowest overall risks of PE and arterial thromboembolism.

WHAT’S NEW?

Low-dose estrogen and levonorgestrel confer lowest risk of 3 CV conditions

Prior studies have shown that COCs increase the risk of PE and may also increase the risks of ischemic stroke and MI.^3,11 Studies have also suggested that a higher dose of estrogen in COCs is associated with an increased risk of VTE.^11,12 This study shows that 20 mcg of estrogen combined with levonorgestrel is associated with the lowest risks of PE, MI, and ischemic stroke.

CAVEATS

A cohort study, no contraceptive start date, and incomplete tobacco use data

This is an observational cohort study, so it is subject to confounding factors and biases. It does, however, include a very large population, which improves validity. The study did not account for COC start date, which may be confounding because the risk of VTE is highest in the first 3 months to one year of COC use.¹² Data on tobacco use, a significant independent risk factor for arterial but not VTE, was incomplete, but in other studies has only marginally affected outcomes.^3,13

CHALLENGES TO IMPLEMENTATION

Low-dose estrogen is associated with increased vaginal spotting

One potential challenge to implementing this practice changer may be the increased rate of vaginal spotting associated with low-dose estrogen. COCs containing 20 mcg of estrogen are associated with spotting in approximately two-thirds of menstrual cycles over the course of a year.¹⁴ That said, women may prefer to endure the spotting in light of the improved safety profile of a lower-dose estrogen pill.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 28-year-old woman presents to your office for a routine health maintenance examination. She is currently using an oral contraceptive containing desogestrel and ethinyl estradiol for contraception and is inquiring about a refill for the coming year. What would you recommend?

When choosing a combined oral contraceptive (COC) for a patient, physicians often have “go-to” favorites—tried and true agents that are easy to prescribe on a busy clinic day. However, some of these may be placing patients at increased risk for venous thromboembolic events.

In general, when compared with nonusers, women who use COCs have a 2- to 4-fold increase in risk of venous thromboembolism (VTE) and an increased risk of myocardial infarction (MI) and stroke.^2,3 More specifically, higher doses of estrogen combined with the progesterones gestodene, desogestrel, and levonorgestrel, are associated with a higher risk of VTE.^2-6

In 2012, the European Medicines Agency warned that COCs containing drospirenone were associated with a higher risk of VTE than other preparations, despite similar estrogen content.⁷ The US Food and Drug Administration (FDA) produced a similar statement that same year, recommending that physicians carefully consider the risks and benefits before prescribing contraceptives containing drospirenone.⁸

The risks of ischemic stroke and MI have not been clearly established for varying doses of estrogen and different progesterones. This large observational study fills that informational gap by providing risk estimates for the various COC options.

STUDY SUMMARY

One combined oral contraceptive comes out ahead

The authors used an observational cohort model to determine the effects of different doses of estrogen combined with different progesterones in COCs on the risks of pulmonary embolism (PE), ischemic stroke, and MI.¹ Data were collected from the French national health insurance database and the French national hospital discharge database.^9,10 The study included just under 5 million women 15 to 49 years of age, living in France, with at least one prescription filled for COCs between July 2010 and September 2012.

The investigators calculated the absolute and relative risks of first PE, ischemic stroke, and MI in women using COC formulations containing either low-dose estrogen (20 mcg) or high-dose estrogen (30-40 mcg) combined with one of 5 progesterones (norethisterone, norgestrel, levonorgestrel, desogestrel, gestodene). The relative risk (RR) was adjusted for confounding factors, including age, complimentary universal health insurance, socioeconomic status, hypertension, diabetes, and consultation with a gynecologist in the previous year.

The absolute risk per 100,000 woman-years for all COC use was 33 for PE, 19 for ischemic stroke, and 7 for MI with a composite risk of 60. The RRs for low-dose estrogen vs high-dose estrogen were 0.75 (95% confidence interval [CI], 0.67-0.85) for PE, 0.82 (95% CI, 0.7-0.96) for ischemic stroke, and 0.56 (95% CI, 0.39-0.79) for MI. The absolute risk reduction (ARR) with low-dose estrogen vs high-dose estrogen was 14/100,000 person-years of use; the number needed to harm (NNH) was 7143.

Oral contraceptives containing levonorgestrel and low-dose estrogen resulted in the lowest overall risks of PE and arterial thromboembolism.

Compared with levonorgestrel, desogestrel and gestodene were associated with higher RRs of PE but not arterial events (2.16; 95% CI, 1.93-2.41 for desogestrel and 1.63; 95% CI, 1.34-1.97 for gestodene). The ARR with levonorgestrel use as opposed to desogestrel for PE was 19/100,000 person-years of use (NNH=5263); the ARR with levonorgestrel use as opposed to gestodene was 12/100,000 person-years of use (NNH=8333). The authors concluded that for the same progesterone, using a lower dose of estrogen decreases risk of PE, ischemic stroke, and MI, and that oral contraceptives containing levonorgestrel and low-dose estrogen resulted in the lowest overall risks of PE and arterial thromboembolism.

WHAT’S NEW?

Low-dose estrogen and levonorgestrel confer lowest risk of 3 CV conditions

Prior studies have shown that COCs increase the risk of PE and may also increase the risks of ischemic stroke and MI.^3,11 Studies have also suggested that a higher dose of estrogen in COCs is associated with an increased risk of VTE.^11,12 This study shows that 20 mcg of estrogen combined with levonorgestrel is associated with the lowest risks of PE, MI, and ischemic stroke.

CAVEATS

A cohort study, no contraceptive start date, and incomplete tobacco use data

This is an observational cohort study, so it is subject to confounding factors and biases. It does, however, include a very large population, which improves validity. The study did not account for COC start date, which may be confounding because the risk of VTE is highest in the first 3 months to one year of COC use.¹² Data on tobacco use, a significant independent risk factor for arterial but not VTE, was incomplete, but in other studies has only marginally affected outcomes.^3,13

CHALLENGES TO IMPLEMENTATION

Low-dose estrogen is associated with increased vaginal spotting

One potential challenge to implementing this practice changer may be the increased rate of vaginal spotting associated with low-dose estrogen. COCs containing 20 mcg of estrogen are associated with spotting in approximately two-thirds of menstrual cycles over the course of a year.¹⁴ That said, women may prefer to endure the spotting in light of the improved safety profile of a lower-dose estrogen pill.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 28-year-old woman presents to your office for a routine health maintenance examination. She is currently using an oral contraceptive containing desogestrel and ethinyl estradiol for contraception and is inquiring about a refill for the coming year. What would you recommend?

When choosing a combined oral contraceptive (COC) for a patient, physicians often have “go-to” favorites—tried and true agents that are easy to prescribe on a busy clinic day. However, some of these may be placing patients at increased risk for venous thromboembolic events.

In general, when compared with nonusers, women who use COCs have a 2- to 4-fold increase in risk of venous thromboembolism (VTE) and an increased risk of myocardial infarction (MI) and stroke.^2,3 More specifically, higher doses of estrogen combined with the progesterones gestodene, desogestrel, and levonorgestrel, are associated with a higher risk of VTE.^2-6

In 2012, the European Medicines Agency warned that COCs containing drospirenone were associated with a higher risk of VTE than other preparations, despite similar estrogen content.⁷ The US Food and Drug Administration (FDA) produced a similar statement that same year, recommending that physicians carefully consider the risks and benefits before prescribing contraceptives containing drospirenone.⁸

The risks of ischemic stroke and MI have not been clearly established for varying doses of estrogen and different progesterones. This large observational study fills that informational gap by providing risk estimates for the various COC options.

STUDY SUMMARY

One combined oral contraceptive comes out ahead

The authors used an observational cohort model to determine the effects of different doses of estrogen combined with different progesterones in COCs on the risks of pulmonary embolism (PE), ischemic stroke, and MI.¹ Data were collected from the French national health insurance database and the French national hospital discharge database.^9,10 The study included just under 5 million women 15 to 49 years of age, living in France, with at least one prescription filled for COCs between July 2010 and September 2012.

The investigators calculated the absolute and relative risks of first PE, ischemic stroke, and MI in women using COC formulations containing either low-dose estrogen (20 mcg) or high-dose estrogen (30-40 mcg) combined with one of 5 progesterones (norethisterone, norgestrel, levonorgestrel, desogestrel, gestodene). The relative risk (RR) was adjusted for confounding factors, including age, complimentary universal health insurance, socioeconomic status, hypertension, diabetes, and consultation with a gynecologist in the previous year.

The absolute risk per 100,000 woman-years for all COC use was 33 for PE, 19 for ischemic stroke, and 7 for MI with a composite risk of 60. The RRs for low-dose estrogen vs high-dose estrogen were 0.75 (95% confidence interval [CI], 0.67-0.85) for PE, 0.82 (95% CI, 0.7-0.96) for ischemic stroke, and 0.56 (95% CI, 0.39-0.79) for MI. The absolute risk reduction (ARR) with low-dose estrogen vs high-dose estrogen was 14/100,000 person-years of use; the number needed to harm (NNH) was 7143.

Oral contraceptives containing levonorgestrel and low-dose estrogen resulted in the lowest overall risks of PE and arterial thromboembolism.

Compared with levonorgestrel, desogestrel and gestodene were associated with higher RRs of PE but not arterial events (2.16; 95% CI, 1.93-2.41 for desogestrel and 1.63; 95% CI, 1.34-1.97 for gestodene). The ARR with levonorgestrel use as opposed to desogestrel for PE was 19/100,000 person-years of use (NNH=5263); the ARR with levonorgestrel use as opposed to gestodene was 12/100,000 person-years of use (NNH=8333). The authors concluded that for the same progesterone, using a lower dose of estrogen decreases risk of PE, ischemic stroke, and MI, and that oral contraceptives containing levonorgestrel and low-dose estrogen resulted in the lowest overall risks of PE and arterial thromboembolism.

WHAT’S NEW?

Low-dose estrogen and levonorgestrel confer lowest risk of 3 CV conditions

Prior studies have shown that COCs increase the risk of PE and may also increase the risks of ischemic stroke and MI.^3,11 Studies have also suggested that a higher dose of estrogen in COCs is associated with an increased risk of VTE.^11,12 This study shows that 20 mcg of estrogen combined with levonorgestrel is associated with the lowest risks of PE, MI, and ischemic stroke.

CAVEATS

A cohort study, no contraceptive start date, and incomplete tobacco use data

This is an observational cohort study, so it is subject to confounding factors and biases. It does, however, include a very large population, which improves validity. The study did not account for COC start date, which may be confounding because the risk of VTE is highest in the first 3 months to one year of COC use.¹² Data on tobacco use, a significant independent risk factor for arterial but not VTE, was incomplete, but in other studies has only marginally affected outcomes.^3,13

CHALLENGES TO IMPLEMENTATION

Low-dose estrogen is associated with increased vaginal spotting

One potential challenge to implementing this practice changer may be the increased rate of vaginal spotting associated with low-dose estrogen. COCs containing 20 mcg of estrogen are associated with spotting in approximately two-thirds of menstrual cycles over the course of a year.¹⁴ That said, women may prefer to endure the spotting in light of the improved safety profile of a lower-dose estrogen pill.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

In April of this year, 3 counties in Minnesota reported a measles outbreak, illustrating the danger of vaccine hesitancy that exists in some communities, resulting in low rates of childhood immunization. Fifty people—mostly children under the age of 5 and almost all unimmunized—have been diagnosed with measles since this outbreak began. As of early May, 11 had been hospitalized. Most of those infected have been American-born children of Somali immigrants.^1,2

At the time of the outbreak, only 42% of the Somali children had been immunized against measles, compared with 88.5% of non-Somalis in Minnesota.² Because of concern about the number of Somali children being diagnosed with autism, a condition apparently not recognized in Somalia, Somali parents living in Minnesota began questioning why this was occurring.

If measles is suspected, care for patients in an isolation room or one that can be kept unused afterwards.

High profile anti-vaccine advocates reportedly visited the community and advised these parents that the measles-mumps-rubella (MMR) vaccine was the cause of this rise in autism incidence and encouraged them to avoid the vaccine.² This series of events led to low vaccination rates in what was once a well-vaccinated community. The outbreak appears to have started with a Somali child who visited Africa and then returned to his community while incubating measles.

The clinical course of measles. Measles is an acute viral respiratory illness, which, after an incubation period of 10 to 12 days, starts with a fever (as high as 105° F), malaise, and at least one of the 3 “C”s—cough, coryza, and conjunctivitis.^3,4 A maculopapular rash then starts on the face and spreads to the trunk and the extremities (FIGURE 1). Koplik spots (FIGURE 2) can be seen on the oral mucosa. Children with measles look very ill. Patients are contagious for approximately 8 days, starting 4 days before the rash appears. Complications can include otitis media, bronchopneumonia, encephalitis, and diarrhea.

Measles is not a benign childhood illness. Before the licensure of live measles vaccine in 1963, an average of 549,000 measles cases were reported in the United States each year.³ That number is likely an underestimate due to inconsistent reporting, with a more plausible number of infections annually being 3 to 4 million.³ These regular epidemics led each year to about 48,000 people being hospitalized from complications, 1000 developing chronic disability from acute measles encephalitis, and about 500 dying from measles-related complications. Today, worldwide, an estimated 134,200 individuals die from measles each year.³

Where the risk is greatest. In the year 2000, measles was declared eliminated from the United States, meaning that endemic transmission was no longer occurring. Since then, the annual number of cases has ranged from a low of 37 in 2004 to a high of 667 in 2014.³ Most measles cases have occurred in unvaccinated individuals and primarily through importation by people infected in other countries who then transmit the infection upon entry or reentry to this country. In the United States, measles is more likely to spread and cause outbreaks in communities where large groups of people are unvaccinated.

Laboratory confirmation of measles is important to establish a correct clinical diagnosis, as well as to verify the infection for public health purposes. Confirmation is achieved by detecting in a patient’s blood sample the measles-specific IgM antibody or measles RNA by real-time polymerase chain reaction (RT-PCR). Obtain both a serum sample and a throat swab (or nasopharyngeal swab) from patients you suspect may have measles. Urine samples may also contain virus, and can be useful. The local health department can offer advice on how to collect and process these laboratory specimens.

Measles is a preventable infection

The Centers for Disease Control and Prevention (CDC) recommends routine childhood immunization with MMR vaccine, with the first dose given at age 12 through 15 months, and the second dose at 4 through 6 years of age (or at least 28 days following the first dose).^3,5 Others for whom the vaccine is recommended are included in the TABLE.³

Because the MMR vaccine is a modified live-virus vaccine, it is contraindicated for pregnant women and those with severe immune deficiencies. It is also contraindicated for individuals who have ever had a life-threatening allergic reaction to the antibiotic neomycin or to any other MMR vaccine component.⁴ That these high-risk groups cannot receive protection from the vaccine underscores the importance of maintaining community herd immunity at a high level to prevent the spread of infection.

In response to this latest outbreak, the Minnesota Department of Health (MDH) has augmented its routine recommendations regarding measles vaccine,¹ including advising that:

• All children 12 months and older who have not received the MMR vaccine and all adults born in 1957 (or later) who have not received the vaccine or ever had the measles should get the first dose as soon as possible.
• Children who live in counties where measles cases have occurred and who have received their first dose of the MMR vaccine at least 28 days ago should get their second dose as soon as possible.
• All Somali Minnesotan children statewide who received their first dose of the vaccine at least 28 days ago should get their second as soon as possible.
• Health care providers statewide may recommend an early (before age 4 years) second dose of the vaccine during routine appointments for children.

Preventing measles outbreaks and minimizing community impact

Measures family physicians can take to protect their staff, patients, and community from measles (and other infectious diseases) include ensuring that all staff are fully immunized as recommended by the CDC,⁶ vaccinating all patients according to the recommended immunization schedules, implementing and enforcing good infection control practices in the clinical setting, and taking appropriate measures to diagnose and manage individuals with suspected measles. These measures are described on the CDC Web site.⁷

Measles virus, commonly believed to be the most infectious agent known, is often transmitted in medical facilities. An individual can become infected simply by entering a closed space that had been occupied by someone with measles several hours earlier. In your facility, physically separate those with fever and rash from other patients as soon as possible and, if measles is suspected, care for them in an isolation room or one that can be kept unused afterwards.

Any time you suspect that a patient has measles, immediately inform the local public health department. The health department should conduct an investigation to find susceptible individuals, provide immunizations for case contacts (and immune globulin for unvaccinated pregnant women and those who are severely immunosuppressed), and implement isolation and quarantine measures as indica­ted by the situation.

There is no antiviral medication for measles. Aim treatment at controlling symptoms and addressing any complicating bacterial infections. Children who have severe illness should receive vitamin A at recommended doses.³

Outbreaks such as the one in Minnesota demonstrate the importance of family physicians working in collaboration with public health officials to minimize the effect of infectious illnesses on the community.

In April of this year, 3 counties in Minnesota reported a measles outbreak, illustrating the danger of vaccine hesitancy that exists in some communities, resulting in low rates of childhood immunization. Fifty people—mostly children under the age of 5 and almost all unimmunized—have been diagnosed with measles since this outbreak began. As of early May, 11 had been hospitalized. Most of those infected have been American-born children of Somali immigrants.^1,2

At the time of the outbreak, only 42% of the Somali children had been immunized against measles, compared with 88.5% of non-Somalis in Minnesota.² Because of concern about the number of Somali children being diagnosed with autism, a condition apparently not recognized in Somalia, Somali parents living in Minnesota began questioning why this was occurring.

If measles is suspected, care for patients in an isolation room or one that can be kept unused afterwards.

High profile anti-vaccine advocates reportedly visited the community and advised these parents that the measles-mumps-rubella (MMR) vaccine was the cause of this rise in autism incidence and encouraged them to avoid the vaccine.² This series of events led to low vaccination rates in what was once a well-vaccinated community. The outbreak appears to have started with a Somali child who visited Africa and then returned to his community while incubating measles.

The clinical course of measles. Measles is an acute viral respiratory illness, which, after an incubation period of 10 to 12 days, starts with a fever (as high as 105° F), malaise, and at least one of the 3 “C”s—cough, coryza, and conjunctivitis.^3,4 A maculopapular rash then starts on the face and spreads to the trunk and the extremities (FIGURE 1). Koplik spots (FIGURE 2) can be seen on the oral mucosa. Children with measles look very ill. Patients are contagious for approximately 8 days, starting 4 days before the rash appears. Complications can include otitis media, bronchopneumonia, encephalitis, and diarrhea.

Measles is not a benign childhood illness. Before the licensure of live measles vaccine in 1963, an average of 549,000 measles cases were reported in the United States each year.³ That number is likely an underestimate due to inconsistent reporting, with a more plausible number of infections annually being 3 to 4 million.³ These regular epidemics led each year to about 48,000 people being hospitalized from complications, 1000 developing chronic disability from acute measles encephalitis, and about 500 dying from measles-related complications. Today, worldwide, an estimated 134,200 individuals die from measles each year.³

Where the risk is greatest. In the year 2000, measles was declared eliminated from the United States, meaning that endemic transmission was no longer occurring. Since then, the annual number of cases has ranged from a low of 37 in 2004 to a high of 667 in 2014.³ Most measles cases have occurred in unvaccinated individuals and primarily through importation by people infected in other countries who then transmit the infection upon entry or reentry to this country. In the United States, measles is more likely to spread and cause outbreaks in communities where large groups of people are unvaccinated.

Laboratory confirmation of measles is important to establish a correct clinical diagnosis, as well as to verify the infection for public health purposes. Confirmation is achieved by detecting in a patient’s blood sample the measles-specific IgM antibody or measles RNA by real-time polymerase chain reaction (RT-PCR). Obtain both a serum sample and a throat swab (or nasopharyngeal swab) from patients you suspect may have measles. Urine samples may also contain virus, and can be useful. The local health department can offer advice on how to collect and process these laboratory specimens.

Measles is a preventable infection

The Centers for Disease Control and Prevention (CDC) recommends routine childhood immunization with MMR vaccine, with the first dose given at age 12 through 15 months, and the second dose at 4 through 6 years of age (or at least 28 days following the first dose).^3,5 Others for whom the vaccine is recommended are included in the TABLE.³

Because the MMR vaccine is a modified live-virus vaccine, it is contraindicated for pregnant women and those with severe immune deficiencies. It is also contraindicated for individuals who have ever had a life-threatening allergic reaction to the antibiotic neomycin or to any other MMR vaccine component.⁴ That these high-risk groups cannot receive protection from the vaccine underscores the importance of maintaining community herd immunity at a high level to prevent the spread of infection.

In response to this latest outbreak, the Minnesota Department of Health (MDH) has augmented its routine recommendations regarding measles vaccine,¹ including advising that:

• All children 12 months and older who have not received the MMR vaccine and all adults born in 1957 (or later) who have not received the vaccine or ever had the measles should get the first dose as soon as possible.
• Children who live in counties where measles cases have occurred and who have received their first dose of the MMR vaccine at least 28 days ago should get their second dose as soon as possible.
• All Somali Minnesotan children statewide who received their first dose of the vaccine at least 28 days ago should get their second as soon as possible.
• Health care providers statewide may recommend an early (before age 4 years) second dose of the vaccine during routine appointments for children.

Preventing measles outbreaks and minimizing community impact

Measures family physicians can take to protect their staff, patients, and community from measles (and other infectious diseases) include ensuring that all staff are fully immunized as recommended by the CDC,⁶ vaccinating all patients according to the recommended immunization schedules, implementing and enforcing good infection control practices in the clinical setting, and taking appropriate measures to diagnose and manage individuals with suspected measles. These measures are described on the CDC Web site.⁷

Measles virus, commonly believed to be the most infectious agent known, is often transmitted in medical facilities. An individual can become infected simply by entering a closed space that had been occupied by someone with measles several hours earlier. In your facility, physically separate those with fever and rash from other patients as soon as possible and, if measles is suspected, care for them in an isolation room or one that can be kept unused afterwards.

Any time you suspect that a patient has measles, immediately inform the local public health department. The health department should conduct an investigation to find susceptible individuals, provide immunizations for case contacts (and immune globulin for unvaccinated pregnant women and those who are severely immunosuppressed), and implement isolation and quarantine measures as indica­ted by the situation.

There is no antiviral medication for measles. Aim treatment at controlling symptoms and addressing any complicating bacterial infections. Children who have severe illness should receive vitamin A at recommended doses.³

Outbreaks such as the one in Minnesota demonstrate the importance of family physicians working in collaboration with public health officials to minimize the effect of infectious illnesses on the community.

In April of this year, 3 counties in Minnesota reported a measles outbreak, illustrating the danger of vaccine hesitancy that exists in some communities, resulting in low rates of childhood immunization. Fifty people—mostly children under the age of 5 and almost all unimmunized—have been diagnosed with measles since this outbreak began. As of early May, 11 had been hospitalized. Most of those infected have been American-born children of Somali immigrants.^1,2

At the time of the outbreak, only 42% of the Somali children had been immunized against measles, compared with 88.5% of non-Somalis in Minnesota.² Because of concern about the number of Somali children being diagnosed with autism, a condition apparently not recognized in Somalia, Somali parents living in Minnesota began questioning why this was occurring.

If measles is suspected, care for patients in an isolation room or one that can be kept unused afterwards.

High profile anti-vaccine advocates reportedly visited the community and advised these parents that the measles-mumps-rubella (MMR) vaccine was the cause of this rise in autism incidence and encouraged them to avoid the vaccine.² This series of events led to low vaccination rates in what was once a well-vaccinated community. The outbreak appears to have started with a Somali child who visited Africa and then returned to his community while incubating measles.

The clinical course of measles. Measles is an acute viral respiratory illness, which, after an incubation period of 10 to 12 days, starts with a fever (as high as 105° F), malaise, and at least one of the 3 “C”s—cough, coryza, and conjunctivitis.^3,4 A maculopapular rash then starts on the face and spreads to the trunk and the extremities (FIGURE 1). Koplik spots (FIGURE 2) can be seen on the oral mucosa. Children with measles look very ill. Patients are contagious for approximately 8 days, starting 4 days before the rash appears. Complications can include otitis media, bronchopneumonia, encephalitis, and diarrhea.

Measles is not a benign childhood illness. Before the licensure of live measles vaccine in 1963, an average of 549,000 measles cases were reported in the United States each year.³ That number is likely an underestimate due to inconsistent reporting, with a more plausible number of infections annually being 3 to 4 million.³ These regular epidemics led each year to about 48,000 people being hospitalized from complications, 1000 developing chronic disability from acute measles encephalitis, and about 500 dying from measles-related complications. Today, worldwide, an estimated 134,200 individuals die from measles each year.³

Where the risk is greatest. In the year 2000, measles was declared eliminated from the United States, meaning that endemic transmission was no longer occurring. Since then, the annual number of cases has ranged from a low of 37 in 2004 to a high of 667 in 2014.³ Most measles cases have occurred in unvaccinated individuals and primarily through importation by people infected in other countries who then transmit the infection upon entry or reentry to this country. In the United States, measles is more likely to spread and cause outbreaks in communities where large groups of people are unvaccinated.

Laboratory confirmation of measles is important to establish a correct clinical diagnosis, as well as to verify the infection for public health purposes. Confirmation is achieved by detecting in a patient’s blood sample the measles-specific IgM antibody or measles RNA by real-time polymerase chain reaction (RT-PCR). Obtain both a serum sample and a throat swab (or nasopharyngeal swab) from patients you suspect may have measles. Urine samples may also contain virus, and can be useful. The local health department can offer advice on how to collect and process these laboratory specimens.

Measles is a preventable infection

The Centers for Disease Control and Prevention (CDC) recommends routine childhood immunization with MMR vaccine, with the first dose given at age 12 through 15 months, and the second dose at 4 through 6 years of age (or at least 28 days following the first dose).^3,5 Others for whom the vaccine is recommended are included in the TABLE.³

Because the MMR vaccine is a modified live-virus vaccine, it is contraindicated for pregnant women and those with severe immune deficiencies. It is also contraindicated for individuals who have ever had a life-threatening allergic reaction to the antibiotic neomycin or to any other MMR vaccine component.⁴ That these high-risk groups cannot receive protection from the vaccine underscores the importance of maintaining community herd immunity at a high level to prevent the spread of infection.

In response to this latest outbreak, the Minnesota Department of Health (MDH) has augmented its routine recommendations regarding measles vaccine,¹ including advising that:

• All children 12 months and older who have not received the MMR vaccine and all adults born in 1957 (or later) who have not received the vaccine or ever had the measles should get the first dose as soon as possible.
• Children who live in counties where measles cases have occurred and who have received their first dose of the MMR vaccine at least 28 days ago should get their second dose as soon as possible.
• All Somali Minnesotan children statewide who received their first dose of the vaccine at least 28 days ago should get their second as soon as possible.
• Health care providers statewide may recommend an early (before age 4 years) second dose of the vaccine during routine appointments for children.

Preventing measles outbreaks and minimizing community impact

Measures family physicians can take to protect their staff, patients, and community from measles (and other infectious diseases) include ensuring that all staff are fully immunized as recommended by the CDC,⁶ vaccinating all patients according to the recommended immunization schedules, implementing and enforcing good infection control practices in the clinical setting, and taking appropriate measures to diagnose and manage individuals with suspected measles. These measures are described on the CDC Web site.⁷

Measles virus, commonly believed to be the most infectious agent known, is often transmitted in medical facilities. An individual can become infected simply by entering a closed space that had been occupied by someone with measles several hours earlier. In your facility, physically separate those with fever and rash from other patients as soon as possible and, if measles is suspected, care for them in an isolation room or one that can be kept unused afterwards.

Any time you suspect that a patient has measles, immediately inform the local public health department. The health department should conduct an investigation to find susceptible individuals, provide immunizations for case contacts (and immune globulin for unvaccinated pregnant women and those who are severely immunosuppressed), and implement isolation and quarantine measures as indica­ted by the situation.

There is no antiviral medication for measles. Aim treatment at controlling symptoms and addressing any complicating bacterial infections. Children who have severe illness should receive vitamin A at recommended doses.³

Outbreaks such as the one in Minnesota demonstrate the importance of family physicians working in collaboration with public health officials to minimize the effect of infectious illnesses on the community.

Insulin degludec decreased both the rate and the severity of hypoglycemic episodes in adults with type 1 and type 2 diabetes, compared with insulin glargine, in two head-to-head trials sponsored by the maker of insulin degludec and reported online July 3 in JAMA.

The two trials had identical randomized double-blind crossover designs. The first involved 501 adults with type 1 diabetes treated at 84 sites in the United States and 6 sites in Poland, and the second involved 721 adults with type 2 diabetes treated at 152 sites in the United States. All the study participants were at risk for hypoglycemia by virtue of experiencing one or more severe hypoglycemic episodes within the preceding year, having moderate chronic renal failure, having a 15-year or longer duration of diabetes, being unaware of their hypoglycemic symptoms, or experiencing severe hypoglycemia within the 3 months preceding baseline.

In both trials, patients were randomized to one type of once-daily insulin for 32 weeks (a 16-week titration period followed by a 16-week maintenance period) and then crossed over to the other type of insulin for 32 weeks. The primary end point in both studies was the rate of overall severe hypoglycemia during the maintenance period. This was defined as either an episode requiring the assistance of another person to administer aid or an episode in which blood glucose measured less than 56 mg/dL.

In the first trial, rates of hypoglycemia were significantly lower with insulin degludec (2,201 episodes per 100 person-years of exposure) than with insulin glargine (2,463 episodes per 100 PYE), demonstrating not just the noninferiority but also the superiority of insulin degludec. In addition, a significantly lower proportion of patients had hypoglycemia with insulin degludec (32.8%) than with insulin glargine (43.1%), said Wendy Lane, MD, of Mountain Diabetes and Endocrine Center, Asheville NC, and her associates.

Regarding the severity of hypoglycemia, the rate of severe episodes was significantly lower with insulin degludec (69 episodes per 100 PYE) than with insulin glargine (92 episodes per 100 PYE). In addition, the proportion of patients who experienced a severe hypoglycemic episode was significantly lower with insulin degludec (10.3%) than with insulin glargine (17.1%).

Both types of insulin reduced hemoglobin A_1c levels to 7% or below. Rates of adverse events and serious adverse events were similar between the two study groups, and there were no differences between them in weight change, blood pressure, pulse rate, or laboratory findings, the investigators said (JAMA.2017;318[1]:33-44).

In the second trial, rates of hypoglycemia again were significantly lower with insulin degludec than with insulin glargine (186 vs. 265 episodes per 100 PYE). In addition, the proportion of patients who experienced a severe hypoglycemic episode was 1.6% vs. 2.4%, respectively, said Carol Wysham, MD, of Rockwood Clinic University of Washington, Spokane, and her associates.

As in the first trial, both types of insulin reduced HbA_1c levels to the same degree, and rates of adverse events and of serious adverse events were comparable, Dr. Wysham and her associates said (JAMA. 2017;318[1]:45-56).

The dropout rates were similar and higher than expected in both trials, at approximately 20%. Dr. Lane and her associates noted that this may have resulted from “the demanding nature” of the studies, including their 64-week duration; demand for close monitoring of blood glucose; and the requirement of using vials and syringes to maintain treatment blinding, instead of more convenient injector devices.

Both trials were funded by Novo Nordisk, maker of insulin degludec. Dr. Lane reported ties to Novo Nordisk, Insulet Corporation, and Eli Lilly, and her associates reported ties to numerous industry sources. Dr. Wysham reported ties to Novo Nordisk, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, and Sanofi, and her associates reported ties to numerous industry sources.

Insulin degludec decreased both the rate and the severity of hypoglycemic episodes in adults with type 1 and type 2 diabetes, compared with insulin glargine, in two head-to-head trials sponsored by the maker of insulin degludec and reported online July 3 in JAMA.

The two trials had identical randomized double-blind crossover designs. The first involved 501 adults with type 1 diabetes treated at 84 sites in the United States and 6 sites in Poland, and the second involved 721 adults with type 2 diabetes treated at 152 sites in the United States. All the study participants were at risk for hypoglycemia by virtue of experiencing one or more severe hypoglycemic episodes within the preceding year, having moderate chronic renal failure, having a 15-year or longer duration of diabetes, being unaware of their hypoglycemic symptoms, or experiencing severe hypoglycemia within the 3 months preceding baseline.

In both trials, patients were randomized to one type of once-daily insulin for 32 weeks (a 16-week titration period followed by a 16-week maintenance period) and then crossed over to the other type of insulin for 32 weeks. The primary end point in both studies was the rate of overall severe hypoglycemia during the maintenance period. This was defined as either an episode requiring the assistance of another person to administer aid or an episode in which blood glucose measured less than 56 mg/dL.

In the first trial, rates of hypoglycemia were significantly lower with insulin degludec (2,201 episodes per 100 person-years of exposure) than with insulin glargine (2,463 episodes per 100 PYE), demonstrating not just the noninferiority but also the superiority of insulin degludec. In addition, a significantly lower proportion of patients had hypoglycemia with insulin degludec (32.8%) than with insulin glargine (43.1%), said Wendy Lane, MD, of Mountain Diabetes and Endocrine Center, Asheville NC, and her associates.

Regarding the severity of hypoglycemia, the rate of severe episodes was significantly lower with insulin degludec (69 episodes per 100 PYE) than with insulin glargine (92 episodes per 100 PYE). In addition, the proportion of patients who experienced a severe hypoglycemic episode was significantly lower with insulin degludec (10.3%) than with insulin glargine (17.1%).

Both types of insulin reduced hemoglobin A_1c levels to 7% or below. Rates of adverse events and serious adverse events were similar between the two study groups, and there were no differences between them in weight change, blood pressure, pulse rate, or laboratory findings, the investigators said (JAMA.2017;318[1]:33-44).

In the second trial, rates of hypoglycemia again were significantly lower with insulin degludec than with insulin glargine (186 vs. 265 episodes per 100 PYE). In addition, the proportion of patients who experienced a severe hypoglycemic episode was 1.6% vs. 2.4%, respectively, said Carol Wysham, MD, of Rockwood Clinic University of Washington, Spokane, and her associates.

As in the first trial, both types of insulin reduced HbA_1c levels to the same degree, and rates of adverse events and of serious adverse events were comparable, Dr. Wysham and her associates said (JAMA. 2017;318[1]:45-56).

The dropout rates were similar and higher than expected in both trials, at approximately 20%. Dr. Lane and her associates noted that this may have resulted from “the demanding nature” of the studies, including their 64-week duration; demand for close monitoring of blood glucose; and the requirement of using vials and syringes to maintain treatment blinding, instead of more convenient injector devices.

Both trials were funded by Novo Nordisk, maker of insulin degludec. Dr. Lane reported ties to Novo Nordisk, Insulet Corporation, and Eli Lilly, and her associates reported ties to numerous industry sources. Dr. Wysham reported ties to Novo Nordisk, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, and Sanofi, and her associates reported ties to numerous industry sources.

Insulin degludec decreased both the rate and the severity of hypoglycemic episodes in adults with type 1 and type 2 diabetes, compared with insulin glargine, in two head-to-head trials sponsored by the maker of insulin degludec and reported online July 3 in JAMA.

The two trials had identical randomized double-blind crossover designs. The first involved 501 adults with type 1 diabetes treated at 84 sites in the United States and 6 sites in Poland, and the second involved 721 adults with type 2 diabetes treated at 152 sites in the United States. All the study participants were at risk for hypoglycemia by virtue of experiencing one or more severe hypoglycemic episodes within the preceding year, having moderate chronic renal failure, having a 15-year or longer duration of diabetes, being unaware of their hypoglycemic symptoms, or experiencing severe hypoglycemia within the 3 months preceding baseline.

In both trials, patients were randomized to one type of once-daily insulin for 32 weeks (a 16-week titration period followed by a 16-week maintenance period) and then crossed over to the other type of insulin for 32 weeks. The primary end point in both studies was the rate of overall severe hypoglycemia during the maintenance period. This was defined as either an episode requiring the assistance of another person to administer aid or an episode in which blood glucose measured less than 56 mg/dL.

In the first trial, rates of hypoglycemia were significantly lower with insulin degludec (2,201 episodes per 100 person-years of exposure) than with insulin glargine (2,463 episodes per 100 PYE), demonstrating not just the noninferiority but also the superiority of insulin degludec. In addition, a significantly lower proportion of patients had hypoglycemia with insulin degludec (32.8%) than with insulin glargine (43.1%), said Wendy Lane, MD, of Mountain Diabetes and Endocrine Center, Asheville NC, and her associates.

Regarding the severity of hypoglycemia, the rate of severe episodes was significantly lower with insulin degludec (69 episodes per 100 PYE) than with insulin glargine (92 episodes per 100 PYE). In addition, the proportion of patients who experienced a severe hypoglycemic episode was significantly lower with insulin degludec (10.3%) than with insulin glargine (17.1%).

Both types of insulin reduced hemoglobin A_1c levels to 7% or below. Rates of adverse events and serious adverse events were similar between the two study groups, and there were no differences between them in weight change, blood pressure, pulse rate, or laboratory findings, the investigators said (JAMA.2017;318[1]:33-44).

In the second trial, rates of hypoglycemia again were significantly lower with insulin degludec than with insulin glargine (186 vs. 265 episodes per 100 PYE). In addition, the proportion of patients who experienced a severe hypoglycemic episode was 1.6% vs. 2.4%, respectively, said Carol Wysham, MD, of Rockwood Clinic University of Washington, Spokane, and her associates.

As in the first trial, both types of insulin reduced HbA_1c levels to the same degree, and rates of adverse events and of serious adverse events were comparable, Dr. Wysham and her associates said (JAMA. 2017;318[1]:45-56).

The dropout rates were similar and higher than expected in both trials, at approximately 20%. Dr. Lane and her associates noted that this may have resulted from “the demanding nature” of the studies, including their 64-week duration; demand for close monitoring of blood glucose; and the requirement of using vials and syringes to maintain treatment blinding, instead of more convenient injector devices.

Both trials were funded by Novo Nordisk, maker of insulin degludec. Dr. Lane reported ties to Novo Nordisk, Insulet Corporation, and Eli Lilly, and her associates reported ties to numerous industry sources. Dr. Wysham reported ties to Novo Nordisk, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, and Sanofi, and her associates reported ties to numerous industry sources.

Click Here to Read Supplement. 

Topics Include:

• The Role of Cord Blood Stem Cells
• Impact of DCC in Cord Blood Collection
• Combining DCC and Cord Blood Collection
• When to Clamp the Umbilical Cord

Faculty/Faculty Disclosure:

Fung Lam, MD
Chair-GYN Quality, Director of Medical Education (OB-GYN), California-Pacific Medical Center
Senior Partner, Golden Gate Obstetrics & Gynecology
Clinical Professor-Department of Obstetrics, Gynecology and Reproductive Sciences
University of California, San Francisco
San Francisco, California

Click Here to Read the Supplement. 

Click Here to Read Supplement. 

Topics Include:

• The Role of Cord Blood Stem Cells
• Impact of DCC in Cord Blood Collection
• Combining DCC and Cord Blood Collection
• When to Clamp the Umbilical Cord

Faculty/Faculty Disclosure:

Fung Lam, MD
Chair-GYN Quality, Director of Medical Education (OB-GYN), California-Pacific Medical Center
Senior Partner, Golden Gate Obstetrics & Gynecology
Clinical Professor-Department of Obstetrics, Gynecology and Reproductive Sciences
University of California, San Francisco
San Francisco, California

Click Here to Read the Supplement. 

Click Here to Read Supplement. 

Topics Include:

• The Role of Cord Blood Stem Cells
• Impact of DCC in Cord Blood Collection
• Combining DCC and Cord Blood Collection
• When to Clamp the Umbilical Cord

Faculty/Faculty Disclosure:

Fung Lam, MD
Chair-GYN Quality, Director of Medical Education (OB-GYN), California-Pacific Medical Center
Senior Partner, Golden Gate Obstetrics & Gynecology
Clinical Professor-Department of Obstetrics, Gynecology and Reproductive Sciences
University of California, San Francisco
San Francisco, California

Click Here to Read the Supplement. 

Osteoporosis is defined by a clinically diagnosed fragility fracture or a bone mineral density (BMD) of at least 2.5 SD below the mean for young female adults, usually measured by dual-energy x-ray absorptiometry. Risk factors include age, female sex, post-menopause, hypogonadism or premature ovarian failure, history of cigarette smoking or alcohol consumption (3 or more drinks daily), rheumatoid arthritis, or medications including glucocorticoids, anticoagulants, anticonvulsants, and aromatase inhibitors.

This guideline update focuses on treatment with bisphosphonates (alendronate, risedronate, ibandronate, zoledronic acid) and denosumab. Denosumab, a human monoclonal antibody against RANK-ligand, approved by the Food and Drug Administration for treatment of osteoporosis, has been added to the list of allowed medications since publication of the 2008 guideline. Several therapies have been excluded from the update, including calcitonin, which is no longer widely used for osteoporosis treatment, and etidronate and pamidronate, neither of which are FDA-approved for the prevention of fractures or treatment of osteoporosis. It should be noted that the evidence continues to be insufficient regarding the effectiveness of therapies to prevent fractures or to treat osteoporosis in men.

Bottom line:

Clinicians should offer pharmacologic treatment with alendronate, risedronate, zoledronic acid, or denosumab to reduce the risk of hip and vertebral fractures in women who have known osteoporosis diagnosed as a T score less than –2.5 or those with a fragility fracture. Pharmacologic therapy should be used for 5 years; however, high risk patients may benefit from longer treatment. There is no benefit to bone density monitoring during the 5-year pharmacologic treatment period. In addition, bisphosphonates should be considered in men who have clinically recognized osteoporosis.

Reference:

Qaseem, A, Forciea, MA, McLean RM, Denberg TD. Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update From the American College of Physicians. Ann Int Med. 2017;166(11):818-39.
 

Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Meizinger is a second year resident in the Family Medicine Residency Program at Abington Jefferson Health.

Osteoporosis is defined by a clinically diagnosed fragility fracture or a bone mineral density (BMD) of at least 2.5 SD below the mean for young female adults, usually measured by dual-energy x-ray absorptiometry. Risk factors include age, female sex, post-menopause, hypogonadism or premature ovarian failure, history of cigarette smoking or alcohol consumption (3 or more drinks daily), rheumatoid arthritis, or medications including glucocorticoids, anticoagulants, anticonvulsants, and aromatase inhibitors.

This guideline update focuses on treatment with bisphosphonates (alendronate, risedronate, ibandronate, zoledronic acid) and denosumab. Denosumab, a human monoclonal antibody against RANK-ligand, approved by the Food and Drug Administration for treatment of osteoporosis, has been added to the list of allowed medications since publication of the 2008 guideline. Several therapies have been excluded from the update, including calcitonin, which is no longer widely used for osteoporosis treatment, and etidronate and pamidronate, neither of which are FDA-approved for the prevention of fractures or treatment of osteoporosis. It should be noted that the evidence continues to be insufficient regarding the effectiveness of therapies to prevent fractures or to treat osteoporosis in men.

Bottom line:

Clinicians should offer pharmacologic treatment with alendronate, risedronate, zoledronic acid, or denosumab to reduce the risk of hip and vertebral fractures in women who have known osteoporosis diagnosed as a T score less than –2.5 or those with a fragility fracture. Pharmacologic therapy should be used for 5 years; however, high risk patients may benefit from longer treatment. There is no benefit to bone density monitoring during the 5-year pharmacologic treatment period. In addition, bisphosphonates should be considered in men who have clinically recognized osteoporosis.

Reference:

Qaseem, A, Forciea, MA, McLean RM, Denberg TD. Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update From the American College of Physicians. Ann Int Med. 2017;166(11):818-39.
 

Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Meizinger is a second year resident in the Family Medicine Residency Program at Abington Jefferson Health.

Osteoporosis is defined by a clinically diagnosed fragility fracture or a bone mineral density (BMD) of at least 2.5 SD below the mean for young female adults, usually measured by dual-energy x-ray absorptiometry. Risk factors include age, female sex, post-menopause, hypogonadism or premature ovarian failure, history of cigarette smoking or alcohol consumption (3 or more drinks daily), rheumatoid arthritis, or medications including glucocorticoids, anticoagulants, anticonvulsants, and aromatase inhibitors.

This guideline update focuses on treatment with bisphosphonates (alendronate, risedronate, ibandronate, zoledronic acid) and denosumab. Denosumab, a human monoclonal antibody against RANK-ligand, approved by the Food and Drug Administration for treatment of osteoporosis, has been added to the list of allowed medications since publication of the 2008 guideline. Several therapies have been excluded from the update, including calcitonin, which is no longer widely used for osteoporosis treatment, and etidronate and pamidronate, neither of which are FDA-approved for the prevention of fractures or treatment of osteoporosis. It should be noted that the evidence continues to be insufficient regarding the effectiveness of therapies to prevent fractures or to treat osteoporosis in men.

Bottom line:

Clinicians should offer pharmacologic treatment with alendronate, risedronate, zoledronic acid, or denosumab to reduce the risk of hip and vertebral fractures in women who have known osteoporosis diagnosed as a T score less than –2.5 or those with a fragility fracture. Pharmacologic therapy should be used for 5 years; however, high risk patients may benefit from longer treatment. There is no benefit to bone density monitoring during the 5-year pharmacologic treatment period. In addition, bisphosphonates should be considered in men who have clinically recognized osteoporosis.

Reference:

Qaseem, A, Forciea, MA, McLean RM, Denberg TD. Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update From the American College of Physicians. Ann Int Med. 2017;166(11):818-39.
 

Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Meizinger is a second year resident in the Family Medicine Residency Program at Abington Jefferson Health.

CHICAGO – Patients with advanced breast cancer whose aromatase inhibitor therapy was supplemented with a cycline-dependent kinase inhibitor had better progression-free survival with no drop in quality of life. Health-related quality of life for patients on the combination therapy was equivalent to that of patients on monotherapy in most aspects, but patients receiving both therapies had a sustained and clinically meaningful decrease in pain.

Also, the time to definitive deterioration by 10% or more of the global health status/quality of life scale score was similar between treatment arms (hazard ratio [HR] 0.944; 95% confidence interval [CI] 0.720-1.237).

The MONALEESA-2 trial had previously shown that the CDK 4/6 inhibitor ribociclib, when added to the aromatase inhibitor letrozole, significantly improved progression-free survival for postmenopausal patients with hormone receptor-positive, HER2 negative advanced breast cancer, when compared to letrozole in combination with placebo.

Sunil Verma, MD, reported on health-related quality of life and symptoms in the two arms of MONALEESA-2, reporting change from baseline, time to a definitive 10% deterioration, and the mean scores for on-treatment time compared to end of treatment on the global health status/quality of life subscale of the European Organization for Research and Treatment of Cancer 30-item core quality of life questionnaire (EORTC QLQ-30).

“During treatment, overall health-related quality of life was maintained from baseline and was similar in both arms,” said Dr. Verma, the study’s first author. Changes during treatment were not statistically significant, and did not reach the predetermined threshold for a clinically meaningful difference. The effect of such key symptoms as fatigue, nausea, and vomiting on quality of life was similar regardless of whether patients received ribociclib or placebo, he said; though symptom scores were slightly higher for patients in the active arm of the study, the results were not clinically significant.

Reporting validated, cancer-specific patient-reported outcomes from the trial, Dr. Verma, professor and head of the department of oncology at the University of Calgary, (Alta.), sought to “highlight the patient experience with a focus on health-related quality of life and symptoms,” he said during his presentation at the annual meeting of the American Society of Clinical Oncology.

“A clinically meaningful – more than 5-point – improvement from baseline in pain score was maintained up to and including cycle 15 in the ribociclib plus letrozole arm,” said Dr. Verma. The placebo arm had a mild, clinically insignificant improvement at most assessment points. For both treatment arms, pain scores increased a bit above baseline levels at the time of disease progression or end of therapy, he said.

Patients completed the EORTC 30-item core quality of life questionnaire at their screening visit, and then every 8 weeks for the first 18 months. Then, they completed the questionnaires every 12 weeks until they experienced disease progression, died, were lost to follow-up or withdrew from the study, or stopped treatment.

Statistical analysis of the questionnaire results took into account the patients’ baseline scores, treatments received, and how they were stratified. Investigators assessed both statistical significance and the clinical meaningfulness of changes, defined as a change of 5-10 points.

In MONALEESA-2, 334 patients each were allocated to the ribociclib + letrozole arm and the placebo + letrozole arm. Patients in both arms, said Dr. Verma, were very compliant with questionnaire completion. Over 90% of patients who were eligible completed questionnaire through cycle 19 of ribociclib or placebo. He explained that the overall numbers completing the questionnaire declined with time, as more patients had disease progression.

It’s important to include these measures, he said, because patients and their families care about “the quality of the time gained,” so patient-reported outcomes should be a part of risk-benefit assessments for new cancer therapies. “While delaying disease progression may help to maintain patient quality of life, the addition of novel treatments to existing therapies can add toxicities, which may diminish quality of life,” said Dr. Verma.

Dr. Verma reported financial relationships with multiple pharmaceutical companies, including Novartis, which funded the study.
 

[email protected]

On Twitter @karioakes

CHICAGO – Patients with advanced breast cancer whose aromatase inhibitor therapy was supplemented with a cycline-dependent kinase inhibitor had better progression-free survival with no drop in quality of life. Health-related quality of life for patients on the combination therapy was equivalent to that of patients on monotherapy in most aspects, but patients receiving both therapies had a sustained and clinically meaningful decrease in pain.

Also, the time to definitive deterioration by 10% or more of the global health status/quality of life scale score was similar between treatment arms (hazard ratio [HR] 0.944; 95% confidence interval [CI] 0.720-1.237).

The MONALEESA-2 trial had previously shown that the CDK 4/6 inhibitor ribociclib, when added to the aromatase inhibitor letrozole, significantly improved progression-free survival for postmenopausal patients with hormone receptor-positive, HER2 negative advanced breast cancer, when compared to letrozole in combination with placebo.

Sunil Verma, MD, reported on health-related quality of life and symptoms in the two arms of MONALEESA-2, reporting change from baseline, time to a definitive 10% deterioration, and the mean scores for on-treatment time compared to end of treatment on the global health status/quality of life subscale of the European Organization for Research and Treatment of Cancer 30-item core quality of life questionnaire (EORTC QLQ-30).

“During treatment, overall health-related quality of life was maintained from baseline and was similar in both arms,” said Dr. Verma, the study’s first author. Changes during treatment were not statistically significant, and did not reach the predetermined threshold for a clinically meaningful difference. The effect of such key symptoms as fatigue, nausea, and vomiting on quality of life was similar regardless of whether patients received ribociclib or placebo, he said; though symptom scores were slightly higher for patients in the active arm of the study, the results were not clinically significant.

Reporting validated, cancer-specific patient-reported outcomes from the trial, Dr. Verma, professor and head of the department of oncology at the University of Calgary, (Alta.), sought to “highlight the patient experience with a focus on health-related quality of life and symptoms,” he said during his presentation at the annual meeting of the American Society of Clinical Oncology.

“A clinically meaningful – more than 5-point – improvement from baseline in pain score was maintained up to and including cycle 15 in the ribociclib plus letrozole arm,” said Dr. Verma. The placebo arm had a mild, clinically insignificant improvement at most assessment points. For both treatment arms, pain scores increased a bit above baseline levels at the time of disease progression or end of therapy, he said.

Patients completed the EORTC 30-item core quality of life questionnaire at their screening visit, and then every 8 weeks for the first 18 months. Then, they completed the questionnaires every 12 weeks until they experienced disease progression, died, were lost to follow-up or withdrew from the study, or stopped treatment.

Statistical analysis of the questionnaire results took into account the patients’ baseline scores, treatments received, and how they were stratified. Investigators assessed both statistical significance and the clinical meaningfulness of changes, defined as a change of 5-10 points.

In MONALEESA-2, 334 patients each were allocated to the ribociclib + letrozole arm and the placebo + letrozole arm. Patients in both arms, said Dr. Verma, were very compliant with questionnaire completion. Over 90% of patients who were eligible completed questionnaire through cycle 19 of ribociclib or placebo. He explained that the overall numbers completing the questionnaire declined with time, as more patients had disease progression.

It’s important to include these measures, he said, because patients and their families care about “the quality of the time gained,” so patient-reported outcomes should be a part of risk-benefit assessments for new cancer therapies. “While delaying disease progression may help to maintain patient quality of life, the addition of novel treatments to existing therapies can add toxicities, which may diminish quality of life,” said Dr. Verma.

Dr. Verma reported financial relationships with multiple pharmaceutical companies, including Novartis, which funded the study.
 

[email protected]

On Twitter @karioakes

CHICAGO – Patients with advanced breast cancer whose aromatase inhibitor therapy was supplemented with a cycline-dependent kinase inhibitor had better progression-free survival with no drop in quality of life. Health-related quality of life for patients on the combination therapy was equivalent to that of patients on monotherapy in most aspects, but patients receiving both therapies had a sustained and clinically meaningful decrease in pain.

Also, the time to definitive deterioration by 10% or more of the global health status/quality of life scale score was similar between treatment arms (hazard ratio [HR] 0.944; 95% confidence interval [CI] 0.720-1.237).

The MONALEESA-2 trial had previously shown that the CDK 4/6 inhibitor ribociclib, when added to the aromatase inhibitor letrozole, significantly improved progression-free survival for postmenopausal patients with hormone receptor-positive, HER2 negative advanced breast cancer, when compared to letrozole in combination with placebo.

Sunil Verma, MD, reported on health-related quality of life and symptoms in the two arms of MONALEESA-2, reporting change from baseline, time to a definitive 10% deterioration, and the mean scores for on-treatment time compared to end of treatment on the global health status/quality of life subscale of the European Organization for Research and Treatment of Cancer 30-item core quality of life questionnaire (EORTC QLQ-30).

“During treatment, overall health-related quality of life was maintained from baseline and was similar in both arms,” said Dr. Verma, the study’s first author. Changes during treatment were not statistically significant, and did not reach the predetermined threshold for a clinically meaningful difference. The effect of such key symptoms as fatigue, nausea, and vomiting on quality of life was similar regardless of whether patients received ribociclib or placebo, he said; though symptom scores were slightly higher for patients in the active arm of the study, the results were not clinically significant.

Reporting validated, cancer-specific patient-reported outcomes from the trial, Dr. Verma, professor and head of the department of oncology at the University of Calgary, (Alta.), sought to “highlight the patient experience with a focus on health-related quality of life and symptoms,” he said during his presentation at the annual meeting of the American Society of Clinical Oncology.

“A clinically meaningful – more than 5-point – improvement from baseline in pain score was maintained up to and including cycle 15 in the ribociclib plus letrozole arm,” said Dr. Verma. The placebo arm had a mild, clinically insignificant improvement at most assessment points. For both treatment arms, pain scores increased a bit above baseline levels at the time of disease progression or end of therapy, he said.

Patients completed the EORTC 30-item core quality of life questionnaire at their screening visit, and then every 8 weeks for the first 18 months. Then, they completed the questionnaires every 12 weeks until they experienced disease progression, died, were lost to follow-up or withdrew from the study, or stopped treatment.

Statistical analysis of the questionnaire results took into account the patients’ baseline scores, treatments received, and how they were stratified. Investigators assessed both statistical significance and the clinical meaningfulness of changes, defined as a change of 5-10 points.

In MONALEESA-2, 334 patients each were allocated to the ribociclib + letrozole arm and the placebo + letrozole arm. Patients in both arms, said Dr. Verma, were very compliant with questionnaire completion. Over 90% of patients who were eligible completed questionnaire through cycle 19 of ribociclib or placebo. He explained that the overall numbers completing the questionnaire declined with time, as more patients had disease progression.

It’s important to include these measures, he said, because patients and their families care about “the quality of the time gained,” so patient-reported outcomes should be a part of risk-benefit assessments for new cancer therapies. “While delaying disease progression may help to maintain patient quality of life, the addition of novel treatments to existing therapies can add toxicities, which may diminish quality of life,” said Dr. Verma.

Dr. Verma reported financial relationships with multiple pharmaceutical companies, including Novartis, which funded the study.
 

[email protected]

On Twitter @karioakes

THE CASE

A 26-year-old healthy male veteran with bipolar disorder and post-traumatic stress disorder was referred for a gastroenterology consultation after a routine laboratory evaluation revealed elevated levels of aspartate aminotransferase (AST), 1040 IU/L (normal range, 10-40 IU/L), and alanine aminotransferase (ALT), 334 IU/L (normal range, 7-56 IU/L). He had been taking divalproex and ziprasidone for the previous 2 years, during which time liver test results had been normal.

The patient reported no symptoms in the course of a detailed history. He had no family history of liver disease, drank alcohol infrequently, and didn’t use tobacco. He hadn’t received any blood transfusions and didn’t have tattoos.

The patient indicated that he had recently returned from military deployment and that a week before his laboratory tests, he’d resumed weight training. To boost his workout, he’d begun taking a nutritional supplement supplied by a friend. Further questioning revealed that the supplement was MuscleMeds’ Code Red, which contains 1,3-dimethylamylamine (DMAA). He denied using any other dietary supplements.

The physical examination was unremarkable and additional lab work was unrevealing. Lab results included normal levels of ceruloplasmin, alpha-1 antitrypsin, ferritin, iron, and transferrin. Viral hepatitis serologies revealed immunity to the hepatitis A and B virus. The patient tested negative for Epstein-Barr virus, cytomegalovirus, herpes simplex virus, human immunodeficiency virus, antinuclear antibody, anti-smooth muscle antibody, and antimitochondrial antibody. A toxicology screen was remarkable for cannabinoids. The remainder of the basic metabolic panel and complete blood count were within normal limits.

THE DIAGNOSIS

The patient’s AST and ALT levels prompted measurement of creatine phosphokinase (CPK), which was elevated at 34,270 IU/L (normal range, 22-198 IU/L). We diagnosed rhabdomyolysis in this patient, which can be associated with elevated levels of AST and ALT. When we contacted the patient about the diagnosis, he reported no muscle aches or pains, or other symptoms.

We instructed the patient to increase his fluid intake and refrain from further use of Code Red. Repeat liver tests one month after the initial consultation revealed significant improvement in AST (29 IU/L) and ALT (68 IU/L), as well as a decline in CPK to 743 IU/L.

DISCUSSION

Much debate has surrounded the safety and use of DMAA, also known as methylhexamine or Geranamine, in dietary supplements such as Code Red. Eli Lilly and Company developed and patented DMAA in the 1940s, then trademarked it under the name Forthane as an inhaled nasal decongestant in 1971.^1-3 United States Food and Drug Administration (FDA) approval for Forthane was withdrawn in 1983 at Lilly’s request.⁴ DMAA was reintroduced as a dietary supplement more than a decade ago after the FDA, in 2004, banned supplements containing ephedrine alkaloids, which have effects similar to DMAA.⁵

DMAA has been used to increase muscle mass, promote weight loss, and improve physical performance; it’s also been used as a recreational drug.^6-8 Several case reports have described poor outcomes in patients who consumed DMAA products. In 2012, the deaths of 2 military personnel who used DMAA prompted the FDA to warn manufacturers of DMAA-containing supplements to stop production, but such supplements remain easily available in the United States.⁶

DMAA’s validity as a dietary supplement is controversial. The claim that DMAA is naturally present in geraniums hasn’t been verified, leading some to question whether an inaccurate description of DMAA as a natural substance was employed to justify its use as a nutritional supplement.⁹ No published evidence exists to establish DMAA as a dietary ingredient.^10,11

A long list of potential adverse effects

DMAA is an indirect sympathomimetic with vasoconstricting and cardiovascular effects.¹² Animal studies have shown effects similar to ephedrine and amphetamines.^12-15 Marsh and colleagues reported that a single oral dose of 3 mg/kg in a human (210 mg/70 kg) moderately increases heart rate and blood pressure and can lead to confusion and concentration problems.¹⁶

Supplements containing DMAA are still readily available, despite a 2012 FDA warning to discontinue production.

Oral intake of DMAA affects the lungs at doses above 4 to 15 mg, the heart after 50 to 75 mg, and blood pressure after 100 mg.¹⁷ Because of the drug’s long half-life—24 hours based on urinary excretion rates—Venhuis and Kaste reported that there is a risk from repeated doses within 24 to 36 hours that can lead to steadily stronger pharmacologic effects.¹⁷

The use of DMAA has been cited in 5 cases of hemorrhagic stroke, a case of acute heart failure, and the deaths of 2 military personnel who experienced asystole during aerobic exercise.^7,8,18-20 These individuals ranged in age from 22 to 41 years.

Initial symptoms included severe headaches, palpitations, dizziness, twitching of extremities, nausea, vomiting, confusion, agitation, and chest pain. The 2 military personnel suffered leg cramps and dyspnea followed by loss of consciousness. Several individuals were hypertensive on presentation to the emergency department with blood pressures as high as 240/120 mm Hg.

THE TAKEAWAY

Our patient presented with transaminitis and was found to have rhabdomyolysis after using DMAA. A few case reports have associated rhabdomyolysis with elevated liver function tests.^21,22 We suspect that DMAA use, which has been linked to adverse effects such as hypertension, tachycardia, and muscle aches, may also cause leakage of muscle enzymes and the development of rhabdomyolysis.

Although a single instance can’t prove causation, this case may illustrate additional adverse effects of DMAA beyond the already long list of risks, including hypertension, seizures, cerebral hemorrhage, arrhythmias, myocardial infarction, cardiomyopathy, and death.^7,8,18-20,23 It’s important for physicians to recognize that their patients may be using dietary supplements to increase strength, energy, or weight loss and to be aware of the potential adverse effects.

THE CASE

A 26-year-old healthy male veteran with bipolar disorder and post-traumatic stress disorder was referred for a gastroenterology consultation after a routine laboratory evaluation revealed elevated levels of aspartate aminotransferase (AST), 1040 IU/L (normal range, 10-40 IU/L), and alanine aminotransferase (ALT), 334 IU/L (normal range, 7-56 IU/L). He had been taking divalproex and ziprasidone for the previous 2 years, during which time liver test results had been normal.

The patient reported no symptoms in the course of a detailed history. He had no family history of liver disease, drank alcohol infrequently, and didn’t use tobacco. He hadn’t received any blood transfusions and didn’t have tattoos.

The patient indicated that he had recently returned from military deployment and that a week before his laboratory tests, he’d resumed weight training. To boost his workout, he’d begun taking a nutritional supplement supplied by a friend. Further questioning revealed that the supplement was MuscleMeds’ Code Red, which contains 1,3-dimethylamylamine (DMAA). He denied using any other dietary supplements.

The physical examination was unremarkable and additional lab work was unrevealing. Lab results included normal levels of ceruloplasmin, alpha-1 antitrypsin, ferritin, iron, and transferrin. Viral hepatitis serologies revealed immunity to the hepatitis A and B virus. The patient tested negative for Epstein-Barr virus, cytomegalovirus, herpes simplex virus, human immunodeficiency virus, antinuclear antibody, anti-smooth muscle antibody, and antimitochondrial antibody. A toxicology screen was remarkable for cannabinoids. The remainder of the basic metabolic panel and complete blood count were within normal limits.

THE DIAGNOSIS

The patient’s AST and ALT levels prompted measurement of creatine phosphokinase (CPK), which was elevated at 34,270 IU/L (normal range, 22-198 IU/L). We diagnosed rhabdomyolysis in this patient, which can be associated with elevated levels of AST and ALT. When we contacted the patient about the diagnosis, he reported no muscle aches or pains, or other symptoms.

We instructed the patient to increase his fluid intake and refrain from further use of Code Red. Repeat liver tests one month after the initial consultation revealed significant improvement in AST (29 IU/L) and ALT (68 IU/L), as well as a decline in CPK to 743 IU/L.

DISCUSSION

Much debate has surrounded the safety and use of DMAA, also known as methylhexamine or Geranamine, in dietary supplements such as Code Red. Eli Lilly and Company developed and patented DMAA in the 1940s, then trademarked it under the name Forthane as an inhaled nasal decongestant in 1971.^1-3 United States Food and Drug Administration (FDA) approval for Forthane was withdrawn in 1983 at Lilly’s request.⁴ DMAA was reintroduced as a dietary supplement more than a decade ago after the FDA, in 2004, banned supplements containing ephedrine alkaloids, which have effects similar to DMAA.⁵

DMAA has been used to increase muscle mass, promote weight loss, and improve physical performance; it’s also been used as a recreational drug.^6-8 Several case reports have described poor outcomes in patients who consumed DMAA products. In 2012, the deaths of 2 military personnel who used DMAA prompted the FDA to warn manufacturers of DMAA-containing supplements to stop production, but such supplements remain easily available in the United States.⁶

DMAA’s validity as a dietary supplement is controversial. The claim that DMAA is naturally present in geraniums hasn’t been verified, leading some to question whether an inaccurate description of DMAA as a natural substance was employed to justify its use as a nutritional supplement.⁹ No published evidence exists to establish DMAA as a dietary ingredient.^10,11

A long list of potential adverse effects

DMAA is an indirect sympathomimetic with vasoconstricting and cardiovascular effects.¹² Animal studies have shown effects similar to ephedrine and amphetamines.^12-15 Marsh and colleagues reported that a single oral dose of 3 mg/kg in a human (210 mg/70 kg) moderately increases heart rate and blood pressure and can lead to confusion and concentration problems.¹⁶

Supplements containing DMAA are still readily available, despite a 2012 FDA warning to discontinue production.

Oral intake of DMAA affects the lungs at doses above 4 to 15 mg, the heart after 50 to 75 mg, and blood pressure after 100 mg.¹⁷ Because of the drug’s long half-life—24 hours based on urinary excretion rates—Venhuis and Kaste reported that there is a risk from repeated doses within 24 to 36 hours that can lead to steadily stronger pharmacologic effects.¹⁷

The use of DMAA has been cited in 5 cases of hemorrhagic stroke, a case of acute heart failure, and the deaths of 2 military personnel who experienced asystole during aerobic exercise.^7,8,18-20 These individuals ranged in age from 22 to 41 years.

Initial symptoms included severe headaches, palpitations, dizziness, twitching of extremities, nausea, vomiting, confusion, agitation, and chest pain. The 2 military personnel suffered leg cramps and dyspnea followed by loss of consciousness. Several individuals were hypertensive on presentation to the emergency department with blood pressures as high as 240/120 mm Hg.

THE TAKEAWAY

Our patient presented with transaminitis and was found to have rhabdomyolysis after using DMAA. A few case reports have associated rhabdomyolysis with elevated liver function tests.^21,22 We suspect that DMAA use, which has been linked to adverse effects such as hypertension, tachycardia, and muscle aches, may also cause leakage of muscle enzymes and the development of rhabdomyolysis.

Although a single instance can’t prove causation, this case may illustrate additional adverse effects of DMAA beyond the already long list of risks, including hypertension, seizures, cerebral hemorrhage, arrhythmias, myocardial infarction, cardiomyopathy, and death.^7,8,18-20,23 It’s important for physicians to recognize that their patients may be using dietary supplements to increase strength, energy, or weight loss and to be aware of the potential adverse effects.

THE CASE

A 26-year-old healthy male veteran with bipolar disorder and post-traumatic stress disorder was referred for a gastroenterology consultation after a routine laboratory evaluation revealed elevated levels of aspartate aminotransferase (AST), 1040 IU/L (normal range, 10-40 IU/L), and alanine aminotransferase (ALT), 334 IU/L (normal range, 7-56 IU/L). He had been taking divalproex and ziprasidone for the previous 2 years, during which time liver test results had been normal.

The patient reported no symptoms in the course of a detailed history. He had no family history of liver disease, drank alcohol infrequently, and didn’t use tobacco. He hadn’t received any blood transfusions and didn’t have tattoos.

The patient indicated that he had recently returned from military deployment and that a week before his laboratory tests, he’d resumed weight training. To boost his workout, he’d begun taking a nutritional supplement supplied by a friend. Further questioning revealed that the supplement was MuscleMeds’ Code Red, which contains 1,3-dimethylamylamine (DMAA). He denied using any other dietary supplements.

The physical examination was unremarkable and additional lab work was unrevealing. Lab results included normal levels of ceruloplasmin, alpha-1 antitrypsin, ferritin, iron, and transferrin. Viral hepatitis serologies revealed immunity to the hepatitis A and B virus. The patient tested negative for Epstein-Barr virus, cytomegalovirus, herpes simplex virus, human immunodeficiency virus, antinuclear antibody, anti-smooth muscle antibody, and antimitochondrial antibody. A toxicology screen was remarkable for cannabinoids. The remainder of the basic metabolic panel and complete blood count were within normal limits.

THE DIAGNOSIS

The patient’s AST and ALT levels prompted measurement of creatine phosphokinase (CPK), which was elevated at 34,270 IU/L (normal range, 22-198 IU/L). We diagnosed rhabdomyolysis in this patient, which can be associated with elevated levels of AST and ALT. When we contacted the patient about the diagnosis, he reported no muscle aches or pains, or other symptoms.

We instructed the patient to increase his fluid intake and refrain from further use of Code Red. Repeat liver tests one month after the initial consultation revealed significant improvement in AST (29 IU/L) and ALT (68 IU/L), as well as a decline in CPK to 743 IU/L.

DISCUSSION

Much debate has surrounded the safety and use of DMAA, also known as methylhexamine or Geranamine, in dietary supplements such as Code Red. Eli Lilly and Company developed and patented DMAA in the 1940s, then trademarked it under the name Forthane as an inhaled nasal decongestant in 1971.^1-3 United States Food and Drug Administration (FDA) approval for Forthane was withdrawn in 1983 at Lilly’s request.⁴ DMAA was reintroduced as a dietary supplement more than a decade ago after the FDA, in 2004, banned supplements containing ephedrine alkaloids, which have effects similar to DMAA.⁵

DMAA has been used to increase muscle mass, promote weight loss, and improve physical performance; it’s also been used as a recreational drug.^6-8 Several case reports have described poor outcomes in patients who consumed DMAA products. In 2012, the deaths of 2 military personnel who used DMAA prompted the FDA to warn manufacturers of DMAA-containing supplements to stop production, but such supplements remain easily available in the United States.⁶

DMAA’s validity as a dietary supplement is controversial. The claim that DMAA is naturally present in geraniums hasn’t been verified, leading some to question whether an inaccurate description of DMAA as a natural substance was employed to justify its use as a nutritional supplement.⁹ No published evidence exists to establish DMAA as a dietary ingredient.^10,11

A long list of potential adverse effects

DMAA is an indirect sympathomimetic with vasoconstricting and cardiovascular effects.¹² Animal studies have shown effects similar to ephedrine and amphetamines.^12-15 Marsh and colleagues reported that a single oral dose of 3 mg/kg in a human (210 mg/70 kg) moderately increases heart rate and blood pressure and can lead to confusion and concentration problems.¹⁶

Supplements containing DMAA are still readily available, despite a 2012 FDA warning to discontinue production.

Oral intake of DMAA affects the lungs at doses above 4 to 15 mg, the heart after 50 to 75 mg, and blood pressure after 100 mg.¹⁷ Because of the drug’s long half-life—24 hours based on urinary excretion rates—Venhuis and Kaste reported that there is a risk from repeated doses within 24 to 36 hours that can lead to steadily stronger pharmacologic effects.¹⁷

The use of DMAA has been cited in 5 cases of hemorrhagic stroke, a case of acute heart failure, and the deaths of 2 military personnel who experienced asystole during aerobic exercise.^7,8,18-20 These individuals ranged in age from 22 to 41 years.

Initial symptoms included severe headaches, palpitations, dizziness, twitching of extremities, nausea, vomiting, confusion, agitation, and chest pain. The 2 military personnel suffered leg cramps and dyspnea followed by loss of consciousness. Several individuals were hypertensive on presentation to the emergency department with blood pressures as high as 240/120 mm Hg.

THE TAKEAWAY

Our patient presented with transaminitis and was found to have rhabdomyolysis after using DMAA. A few case reports have associated rhabdomyolysis with elevated liver function tests.^21,22 We suspect that DMAA use, which has been linked to adverse effects such as hypertension, tachycardia, and muscle aches, may also cause leakage of muscle enzymes and the development of rhabdomyolysis.

Although a single instance can’t prove causation, this case may illustrate additional adverse effects of DMAA beyond the already long list of risks, including hypertension, seizures, cerebral hemorrhage, arrhythmias, myocardial infarction, cardiomyopathy, and death.^7,8,18-20,23 It’s important for physicians to recognize that their patients may be using dietary supplements to increase strength, energy, or weight loss and to be aware of the potential adverse effects.

Updated Clinical Documentation & Coding resources now available

SHM’s Clinical Documentation & Coding for Hospitalists, formerly CODE-H, has been updated for 2017.

“[It’s] an exciting program that offers valuable insight into the coding and billing challenges of hospitalist services. Whether you are a new or seasoned physician, SHM’s Clinical Documentation & Coding for Hospitalists provides you with a solid foundation for documentation, identifies common problems, and offers strategies for success.” – Carol Pohlig, BSN, RN, CPC, ASC Senior Coding and Compliance Specialist

For more information, visit hospitalmedicine.org/codeh.

Registration now open for NP/PA Bootcamp

Whether you’re new to hospital medicine or need a refresher on the latest topics, this course from the AAPA and SHM is perfect for you and offers up to 34.75 AAPA Category 1 CME credits.

At the Adult Hospital Medicine Bootcamp, you will cover commonly encountered diagnoses and diseases of adult hospitalized patients while networking with other hospital-based practitioners. Plus, attend optional pre-courses on reimbursement, hands-on ultrasound or hospital medicine basics.

Join us at the ninth annual Adult Hospital Medicine Boot Camp, September 27 – October 1, 2017, in San Diego. To register and learn more visit: aapa.org/bootcamp.

Learn how your HMG stacks up with the State of Hospital Medicine report

Did you know that hospitalist compensation typically consists of 80% base pay and 20% supplemental income based on production and performance? SHM’s State of Hospital Medicine Report continues to be your best source of information about how hospital medicine groups (HMGs) operate.

Don’t miss the new additions to the report for the 2016 version, including:

• Percentage of the hospital’s total patient volume the HMG was responsible for caring for.

• Presence of medical hospitalists within the HMG focusing their practice in a specific medical subspecialty.

• Value of CME allowances for hospitalists.

• Utilization of prolonged service codes by hospitalists.

• Charge capture methodologies being used by HMGs.

• For academic HMGs, the dollar amount of financial support provided for non-clinical work.

Order your print or digital copy at hospitalmedicine.org/sohm.

Enhance your leadership skills at SHM’s Leadership Academy

SHM’s Leadership Academy is the only leadership program designed specifically for hospitalists. The 2017 meeting will be held October 23 – 26 at the JW Marriott Camelback Inn in Scottsdale, Ariz.

Course highlight: Leadership mastering teamwork

Developed in response to high demand from previous Leadership Academy attendees, this course focuses on strengthening teams and institutions. Participants learn how to critically assess program growth opportunities and develop operational plans; utilize the principles of SWARM intelligence; lead, manage, and motivate teams in complex hospital environments; and develop effective communication strategies.

Upon completion of this course, participants will be able to apply communication strategies that allow others to fully experience their message, lead teams in complex environments to achieve the best results, invest in themselves as leaders to optimize their professional growth and career path, and critically assess program growth opportunities and implement the necessary infrastructure for success.

To view the course schedule, faculty and more visit shmleadershipacademy.org/masteringteamwork.

Improve glycemic control efforts in your hospital with online resources & mentorship

SHM offers a variety of resources to improve glycemic control in your hospital. Glycemic Control Electronic Quality Improvement Programs (eQUIPS) are designed to enhance the efficiency and reliability of your quality improvement efforts to close the gap between best practices and methods for caring for the inpatient with hyperglycemia.

Benefits of SHM’s eQUIPS include:

• Data and performance tracking tools.

• Step-by-step instructions for improving glycemic control, preventing hypoglycemia, and optimizing care of inpatients with hyperglycemia and diabetes.

• An online community and library of tools and documents, including sample order sets and protocols, awareness campaigns, patient educational materials, and supplemental articles.

• Toolkit of clinical tools and interventions, research materials, literature reviews, case studies, teaching slide sets, and more.

SHM’s Glycemic Control Mentored Implementation program sites receive 1 year of individualized mentoring including:

• On-site mentoring and training for the entire care team to help members interpret needs and resource assessments, map system processes, and develop site-specific action and intervention plans.

• Monthly coaching calls with the mentor to develop, modify, and implement interventions, establish evaluation processes, and monitor performance over time.

• SHM-facilitated calls with live webinars with other sites in the collaborative to share success stories and experiences.

• Access to the online community to share ideas, documents, and other resources.

• Data collection and analysis tools to generate on-demand reports and benchmark against other program participants.

Learn more about all of SHM’s Glycemic Control offerings by watching the recorded webinar from June 28, 2017, at hospitalmedicine.org/gc.

Earn CME with SHM’s Learning Portal

SHM’s Learning Portal is the online learning destination for hospitalists, featuring all of SHM’s eLearning initiatives in one place. Members can access over 85 CME credits for free in the Learning Portal.

Featured topics currently include perioperative medicine, anticoagulation, quality improvement, cardiac arrhythmia, and antimicrobial stewardship.

Try out the most popular modules:

• The Role of the Medical Consultant.

• Pulmonary Risk Management in the Perioperative Setting.

• Perioperative Medication Management.

• Venous Thromboembolism Prophylaxis in Surgical Patients.

• Perioperative Cardiac Risk Assessment.

Not a member? Join today or pay a small fee per module. Visit shmlearningportal.org to learn more and earn CME credits today.
 

Brett Radler is communications specialist at the Society of Hospital Medicine.

Updated Clinical Documentation & Coding resources now available

SHM’s Clinical Documentation & Coding for Hospitalists, formerly CODE-H, has been updated for 2017.

“[It’s] an exciting program that offers valuable insight into the coding and billing challenges of hospitalist services. Whether you are a new or seasoned physician, SHM’s Clinical Documentation & Coding for Hospitalists provides you with a solid foundation for documentation, identifies common problems, and offers strategies for success.” – Carol Pohlig, BSN, RN, CPC, ASC Senior Coding and Compliance Specialist

For more information, visit hospitalmedicine.org/codeh.

Registration now open for NP/PA Bootcamp

Whether you’re new to hospital medicine or need a refresher on the latest topics, this course from the AAPA and SHM is perfect for you and offers up to 34.75 AAPA Category 1 CME credits.

At the Adult Hospital Medicine Bootcamp, you will cover commonly encountered diagnoses and diseases of adult hospitalized patients while networking with other hospital-based practitioners. Plus, attend optional pre-courses on reimbursement, hands-on ultrasound or hospital medicine basics.

Join us at the ninth annual Adult Hospital Medicine Boot Camp, September 27 – October 1, 2017, in San Diego. To register and learn more visit: aapa.org/bootcamp.

Learn how your HMG stacks up with the State of Hospital Medicine report

Did you know that hospitalist compensation typically consists of 80% base pay and 20% supplemental income based on production and performance? SHM’s State of Hospital Medicine Report continues to be your best source of information about how hospital medicine groups (HMGs) operate.

Don’t miss the new additions to the report for the 2016 version, including:

• Percentage of the hospital’s total patient volume the HMG was responsible for caring for.

• Presence of medical hospitalists within the HMG focusing their practice in a specific medical subspecialty.

• Value of CME allowances for hospitalists.

• Utilization of prolonged service codes by hospitalists.

• Charge capture methodologies being used by HMGs.

• For academic HMGs, the dollar amount of financial support provided for non-clinical work.

Order your print or digital copy at hospitalmedicine.org/sohm.

Enhance your leadership skills at SHM’s Leadership Academy

SHM’s Leadership Academy is the only leadership program designed specifically for hospitalists. The 2017 meeting will be held October 23 – 26 at the JW Marriott Camelback Inn in Scottsdale, Ariz.

Course highlight: Leadership mastering teamwork

Developed in response to high demand from previous Leadership Academy attendees, this course focuses on strengthening teams and institutions. Participants learn how to critically assess program growth opportunities and develop operational plans; utilize the principles of SWARM intelligence; lead, manage, and motivate teams in complex hospital environments; and develop effective communication strategies.

Upon completion of this course, participants will be able to apply communication strategies that allow others to fully experience their message, lead teams in complex environments to achieve the best results, invest in themselves as leaders to optimize their professional growth and career path, and critically assess program growth opportunities and implement the necessary infrastructure for success.

To view the course schedule, faculty and more visit shmleadershipacademy.org/masteringteamwork.

Improve glycemic control efforts in your hospital with online resources & mentorship

SHM offers a variety of resources to improve glycemic control in your hospital. Glycemic Control Electronic Quality Improvement Programs (eQUIPS) are designed to enhance the efficiency and reliability of your quality improvement efforts to close the gap between best practices and methods for caring for the inpatient with hyperglycemia.

Benefits of SHM’s eQUIPS include:

• Data and performance tracking tools.

• Step-by-step instructions for improving glycemic control, preventing hypoglycemia, and optimizing care of inpatients with hyperglycemia and diabetes.

• An online community and library of tools and documents, including sample order sets and protocols, awareness campaigns, patient educational materials, and supplemental articles.

• Toolkit of clinical tools and interventions, research materials, literature reviews, case studies, teaching slide sets, and more.

SHM’s Glycemic Control Mentored Implementation program sites receive 1 year of individualized mentoring including:

• On-site mentoring and training for the entire care team to help members interpret needs and resource assessments, map system processes, and develop site-specific action and intervention plans.

• Monthly coaching calls with the mentor to develop, modify, and implement interventions, establish evaluation processes, and monitor performance over time.

• SHM-facilitated calls with live webinars with other sites in the collaborative to share success stories and experiences.

• Access to the online community to share ideas, documents, and other resources.

• Data collection and analysis tools to generate on-demand reports and benchmark against other program participants.

Learn more about all of SHM’s Glycemic Control offerings by watching the recorded webinar from June 28, 2017, at hospitalmedicine.org/gc.

Earn CME with SHM’s Learning Portal

SHM’s Learning Portal is the online learning destination for hospitalists, featuring all of SHM’s eLearning initiatives in one place. Members can access over 85 CME credits for free in the Learning Portal.

Featured topics currently include perioperative medicine, anticoagulation, quality improvement, cardiac arrhythmia, and antimicrobial stewardship.

Try out the most popular modules:

• The Role of the Medical Consultant.

• Pulmonary Risk Management in the Perioperative Setting.

• Perioperative Medication Management.

• Venous Thromboembolism Prophylaxis in Surgical Patients.

• Perioperative Cardiac Risk Assessment.

Not a member? Join today or pay a small fee per module. Visit shmlearningportal.org to learn more and earn CME credits today.
 

Brett Radler is communications specialist at the Society of Hospital Medicine.

Updated Clinical Documentation & Coding resources now available

SHM’s Clinical Documentation & Coding for Hospitalists, formerly CODE-H, has been updated for 2017.

“[It’s] an exciting program that offers valuable insight into the coding and billing challenges of hospitalist services. Whether you are a new or seasoned physician, SHM’s Clinical Documentation & Coding for Hospitalists provides you with a solid foundation for documentation, identifies common problems, and offers strategies for success.” – Carol Pohlig, BSN, RN, CPC, ASC Senior Coding and Compliance Specialist

For more information, visit hospitalmedicine.org/codeh.

Registration now open for NP/PA Bootcamp

Whether you’re new to hospital medicine or need a refresher on the latest topics, this course from the AAPA and SHM is perfect for you and offers up to 34.75 AAPA Category 1 CME credits.

At the Adult Hospital Medicine Bootcamp, you will cover commonly encountered diagnoses and diseases of adult hospitalized patients while networking with other hospital-based practitioners. Plus, attend optional pre-courses on reimbursement, hands-on ultrasound or hospital medicine basics.

Join us at the ninth annual Adult Hospital Medicine Boot Camp, September 27 – October 1, 2017, in San Diego. To register and learn more visit: aapa.org/bootcamp.

Learn how your HMG stacks up with the State of Hospital Medicine report

Did you know that hospitalist compensation typically consists of 80% base pay and 20% supplemental income based on production and performance? SHM’s State of Hospital Medicine Report continues to be your best source of information about how hospital medicine groups (HMGs) operate.

Don’t miss the new additions to the report for the 2016 version, including:

• Percentage of the hospital’s total patient volume the HMG was responsible for caring for.

• Presence of medical hospitalists within the HMG focusing their practice in a specific medical subspecialty.

• Value of CME allowances for hospitalists.

• Utilization of prolonged service codes by hospitalists.

• Charge capture methodologies being used by HMGs.

• For academic HMGs, the dollar amount of financial support provided for non-clinical work.

Order your print or digital copy at hospitalmedicine.org/sohm.

Enhance your leadership skills at SHM’s Leadership Academy

SHM’s Leadership Academy is the only leadership program designed specifically for hospitalists. The 2017 meeting will be held October 23 – 26 at the JW Marriott Camelback Inn in Scottsdale, Ariz.

Course highlight: Leadership mastering teamwork

Developed in response to high demand from previous Leadership Academy attendees, this course focuses on strengthening teams and institutions. Participants learn how to critically assess program growth opportunities and develop operational plans; utilize the principles of SWARM intelligence; lead, manage, and motivate teams in complex hospital environments; and develop effective communication strategies.

Upon completion of this course, participants will be able to apply communication strategies that allow others to fully experience their message, lead teams in complex environments to achieve the best results, invest in themselves as leaders to optimize their professional growth and career path, and critically assess program growth opportunities and implement the necessary infrastructure for success.

To view the course schedule, faculty and more visit shmleadershipacademy.org/masteringteamwork.

Improve glycemic control efforts in your hospital with online resources & mentorship

SHM offers a variety of resources to improve glycemic control in your hospital. Glycemic Control Electronic Quality Improvement Programs (eQUIPS) are designed to enhance the efficiency and reliability of your quality improvement efforts to close the gap between best practices and methods for caring for the inpatient with hyperglycemia.

Benefits of SHM’s eQUIPS include:

• Data and performance tracking tools.

• Step-by-step instructions for improving glycemic control, preventing hypoglycemia, and optimizing care of inpatients with hyperglycemia and diabetes.

• An online community and library of tools and documents, including sample order sets and protocols, awareness campaigns, patient educational materials, and supplemental articles.

• Toolkit of clinical tools and interventions, research materials, literature reviews, case studies, teaching slide sets, and more.

SHM’s Glycemic Control Mentored Implementation program sites receive 1 year of individualized mentoring including:

• On-site mentoring and training for the entire care team to help members interpret needs and resource assessments, map system processes, and develop site-specific action and intervention plans.

• Monthly coaching calls with the mentor to develop, modify, and implement interventions, establish evaluation processes, and monitor performance over time.

• SHM-facilitated calls with live webinars with other sites in the collaborative to share success stories and experiences.

• Access to the online community to share ideas, documents, and other resources.

• Data collection and analysis tools to generate on-demand reports and benchmark against other program participants.

Learn more about all of SHM’s Glycemic Control offerings by watching the recorded webinar from June 28, 2017, at hospitalmedicine.org/gc.

Earn CME with SHM’s Learning Portal

SHM’s Learning Portal is the online learning destination for hospitalists, featuring all of SHM’s eLearning initiatives in one place. Members can access over 85 CME credits for free in the Learning Portal.

Featured topics currently include perioperative medicine, anticoagulation, quality improvement, cardiac arrhythmia, and antimicrobial stewardship.

Try out the most popular modules:

• The Role of the Medical Consultant.

• Pulmonary Risk Management in the Perioperative Setting.

• Perioperative Medication Management.

• Venous Thromboembolism Prophylaxis in Surgical Patients.

• Perioperative Cardiac Risk Assessment.

Not a member? Join today or pay a small fee per module. Visit shmlearningportal.org to learn more and earn CME credits today.
 

Brett Radler is communications specialist at the Society of Hospital Medicine.