It’s becoming clear that COVID-19 infection can involve the cardiovascular system in many different ways, and this has “evolving” potential implications for treatment, say a team of cardiologists on the frontlines of the COVID-19 battle in New York City.

In an article published online April 3 in Circulation, Justin Fried, MD, Division of Cardiology, Columbia University, New York City, and colleagues present four case studies of COVID-19 patients with various cardiovascular presentations.

Case 1 is a 64-year-old woman whose predominant symptoms on admission were cardiac in nature, including chest pain and ST elevation, but without fever, cough, or other symptoms suggestive of COVID-19.

“In patients presenting with what appears to be a typical cardiac syndrome, COVID-19 infection should be in the differential during the current pandemic, even in the absence of fever or cough,” the clinicians advise.

Case 2 is a 38-year-old man with cardiogenic shock and acute respiratory distress with profound hypoxia who was rescued with veno-arterial-venous extracorporeal membrane oxygenation (VV ECMO).

The initial presentation of this patient was more characteristic of severe COVID-19 disease, and cardiac involvement only became apparent after the initiation of ECMO, Fried and colleagues report.

Based on this case, they advise a “low threshold” to assess for cardiogenic shock in patients with acute systolic heart failure related to COVID-19. If inotropic support fails in these patients, intra-aortic balloon pump should be considered first for mechanical circulatory support because it requires the least maintenance from medical support staff.

In addition, in their experience, when a patient on VV ECMO develops superimposed cardiogenic shock, adding an arterial conduit at a relatively low blood flow rate may provide the necessary circulatory support without inducing left ventricular distension, they note.

“Our experience confirms that rescue of patients even with profound cardiogenic or mixed shock may be possible with temporary hemodynamic support at centers with availability of such devices,” Fried and colleagues report.

Case 3 is a 64-year-old woman with underlying cardiac disease who developed profound decompensation with COVID-19 infection.

This case demonstrates that the infection can cause decompensation of underlying heart failure and may lead to mixed shock, the clinicians say.

“Invasive hemodynamic monitoring, if feasible, may be helpful to manage the cardiac component of shock in such cases. Medications that prolong the QT interval are being considered for COVID-19 patients and may require closer monitoring in patients with underlying structural heart disease,” they note.

Case 4 is a 51-year-old man who underwent a heart transplant in 2007 and a kidney transplant in 2010. He had COVID-19 symptoms akin to those seen in nonimmunosuppressed patients with COVID-19.

The COVID-19 pandemic presents a “unique challenge” for solid organ transplant recipients, with only “limited” data on how to adjust immunosuppression during COVID-19 infection, Fried and colleagues say.

The pandemic also creates a challenge for the management of heart failure patients on the heart transplant wait list; the risks of delaying a transplant need to be balanced against the risks of donor infection and uncertainty regarding the impact of post-transplant immunosuppression protocols, they note.

As reported by Medscape Medical News, the American Heart Association has developed a COVID-19 patient registry to collect data on cardiovascular conditions and outcomes related to COVID-19 infection.

To participate in the registry, contact qualityresearch@heart.org.

This article first appeared on Medscape.com.

It’s becoming clear that COVID-19 infection can involve the cardiovascular system in many different ways, and this has “evolving” potential implications for treatment, say a team of cardiologists on the frontlines of the COVID-19 battle in New York City.

In an article published online April 3 in Circulation, Justin Fried, MD, Division of Cardiology, Columbia University, New York City, and colleagues present four case studies of COVID-19 patients with various cardiovascular presentations.

Case 1 is a 64-year-old woman whose predominant symptoms on admission were cardiac in nature, including chest pain and ST elevation, but without fever, cough, or other symptoms suggestive of COVID-19.

“In patients presenting with what appears to be a typical cardiac syndrome, COVID-19 infection should be in the differential during the current pandemic, even in the absence of fever or cough,” the clinicians advise.

Case 2 is a 38-year-old man with cardiogenic shock and acute respiratory distress with profound hypoxia who was rescued with veno-arterial-venous extracorporeal membrane oxygenation (VV ECMO).

The initial presentation of this patient was more characteristic of severe COVID-19 disease, and cardiac involvement only became apparent after the initiation of ECMO, Fried and colleagues report.

Based on this case, they advise a “low threshold” to assess for cardiogenic shock in patients with acute systolic heart failure related to COVID-19. If inotropic support fails in these patients, intra-aortic balloon pump should be considered first for mechanical circulatory support because it requires the least maintenance from medical support staff.

In addition, in their experience, when a patient on VV ECMO develops superimposed cardiogenic shock, adding an arterial conduit at a relatively low blood flow rate may provide the necessary circulatory support without inducing left ventricular distension, they note.

“Our experience confirms that rescue of patients even with profound cardiogenic or mixed shock may be possible with temporary hemodynamic support at centers with availability of such devices,” Fried and colleagues report.

Case 3 is a 64-year-old woman with underlying cardiac disease who developed profound decompensation with COVID-19 infection.

This case demonstrates that the infection can cause decompensation of underlying heart failure and may lead to mixed shock, the clinicians say.

“Invasive hemodynamic monitoring, if feasible, may be helpful to manage the cardiac component of shock in such cases. Medications that prolong the QT interval are being considered for COVID-19 patients and may require closer monitoring in patients with underlying structural heart disease,” they note.

Case 4 is a 51-year-old man who underwent a heart transplant in 2007 and a kidney transplant in 2010. He had COVID-19 symptoms akin to those seen in nonimmunosuppressed patients with COVID-19.

The COVID-19 pandemic presents a “unique challenge” for solid organ transplant recipients, with only “limited” data on how to adjust immunosuppression during COVID-19 infection, Fried and colleagues say.

The pandemic also creates a challenge for the management of heart failure patients on the heart transplant wait list; the risks of delaying a transplant need to be balanced against the risks of donor infection and uncertainty regarding the impact of post-transplant immunosuppression protocols, they note.

As reported by Medscape Medical News, the American Heart Association has developed a COVID-19 patient registry to collect data on cardiovascular conditions and outcomes related to COVID-19 infection.

To participate in the registry, contact qualityresearch@heart.org.

This article first appeared on Medscape.com.

It’s becoming clear that COVID-19 infection can involve the cardiovascular system in many different ways, and this has “evolving” potential implications for treatment, say a team of cardiologists on the frontlines of the COVID-19 battle in New York City.

In an article published online April 3 in Circulation, Justin Fried, MD, Division of Cardiology, Columbia University, New York City, and colleagues present four case studies of COVID-19 patients with various cardiovascular presentations.

Case 1 is a 64-year-old woman whose predominant symptoms on admission were cardiac in nature, including chest pain and ST elevation, but without fever, cough, or other symptoms suggestive of COVID-19.

“In patients presenting with what appears to be a typical cardiac syndrome, COVID-19 infection should be in the differential during the current pandemic, even in the absence of fever or cough,” the clinicians advise.

Case 2 is a 38-year-old man with cardiogenic shock and acute respiratory distress with profound hypoxia who was rescued with veno-arterial-venous extracorporeal membrane oxygenation (VV ECMO).

The initial presentation of this patient was more characteristic of severe COVID-19 disease, and cardiac involvement only became apparent after the initiation of ECMO, Fried and colleagues report.

Based on this case, they advise a “low threshold” to assess for cardiogenic shock in patients with acute systolic heart failure related to COVID-19. If inotropic support fails in these patients, intra-aortic balloon pump should be considered first for mechanical circulatory support because it requires the least maintenance from medical support staff.

In addition, in their experience, when a patient on VV ECMO develops superimposed cardiogenic shock, adding an arterial conduit at a relatively low blood flow rate may provide the necessary circulatory support without inducing left ventricular distension, they note.

“Our experience confirms that rescue of patients even with profound cardiogenic or mixed shock may be possible with temporary hemodynamic support at centers with availability of such devices,” Fried and colleagues report.

Case 3 is a 64-year-old woman with underlying cardiac disease who developed profound decompensation with COVID-19 infection.

This case demonstrates that the infection can cause decompensation of underlying heart failure and may lead to mixed shock, the clinicians say.

“Invasive hemodynamic monitoring, if feasible, may be helpful to manage the cardiac component of shock in such cases. Medications that prolong the QT interval are being considered for COVID-19 patients and may require closer monitoring in patients with underlying structural heart disease,” they note.

Case 4 is a 51-year-old man who underwent a heart transplant in 2007 and a kidney transplant in 2010. He had COVID-19 symptoms akin to those seen in nonimmunosuppressed patients with COVID-19.

The COVID-19 pandemic presents a “unique challenge” for solid organ transplant recipients, with only “limited” data on how to adjust immunosuppression during COVID-19 infection, Fried and colleagues say.

The pandemic also creates a challenge for the management of heart failure patients on the heart transplant wait list; the risks of delaying a transplant need to be balanced against the risks of donor infection and uncertainty regarding the impact of post-transplant immunosuppression protocols, they note.

As reported by Medscape Medical News, the American Heart Association has developed a COVID-19 patient registry to collect data on cardiovascular conditions and outcomes related to COVID-19 infection.

To participate in the registry, contact qualityresearch@heart.org.

This article first appeared on Medscape.com.

Authors of a recent Cochrane review concluded that low-dose aspirin treatment of 1,000 pregnant women at risk of developing preeclampsia resulted in 16 fewer cases of preeclampsia, 16 fewer preterm births, 7 fewer cases of small-for-gestational age newborns, and 5 fewer fetal or neonatal deaths.¹

The American College of Obstetricians and Gynecologists (ACOG) and the US Preventive Services Task Force (USPSTF) recommend treatment with 81 mg of aspirin daily, initiated before 16 weeks of pregnancy to prevent preeclampsia in women with one major risk factor (personal history of preeclampsia, multifetal gestation, chronic hypertension, type 1 or 2 diabetes, renal or autoimmune disease) or at least two moderate risk factors (nulliparity; obesity; mother or sister with preeclampsia; a sociodemographic characteristic such as African American race or low socioeconomic status; age ≥35 years; personal history factors such as prior low birth weight infant, previous adverse pregnancy outcome, or >10-year interpregnancy interval).^2,3 Healthy pregnant women with a previous uncomplicated full-term delivery do not need treatment with low-dose aspirin.^2,3

However, evolving data and expert opinion suggest that expanding the indications for aspirin treatment and increasing the recommended dose of aspirin may be warranted. 

Nulliparity

Nulliparity is the single clinical characteristic that is associated with the greatest number of cases of preeclampsia.⁴ Hence, from a public health perspective, reducing the rate of preeclampsia among nulliparous women is a top priority.

ACOG and USPSTF do not recommend aspirin treatment for all nulliparous women because risk factors help to identify those nulliparous women who benefit from aspirin treatment.

However, a recent cost-effectiveness analysis compared the health care costs and rates of preeclampsia for 4 prevention strategies among all pregnant women in the United States (nulliparous and parous)⁵:

1. no aspirin use
2. use of aspirin based on biomarker and ultrasound measurements
3. use of aspirin based on USPSTF guidelines for identifying women at risk
4. prescription of aspirin to all pregnant women.

Health care costs and rates of preeclampsia were lowest with the universal prescription of aspirin to all pregnant women in the United States. Compared with universal prescription of aspirin, the USPSTF approach, the biomarker-ultrasound approach, and the no aspirin approach were associated with 346, 308, and 762 additional cases of preeclampsia per 100,000 women. In sensitivity analyses, universal aspirin was the optimal strategy under most assumptions.

Another cost effectiveness analysis concluded that among nulliparous pregnant women, universal aspirin treatment was superior to aspirin treatment based on biomarker-ultrasound identification of women at high risk.⁶ 

In a recent clinical trial performed in India, Guatemala, Pakistan, Democratic Republic of Congo, Kenya, and Zambia, 14,361 nulliparous women were randomly assigned to placebo or 81 mg of aspirin daily between 6 and 14 weeks of gestation.⁷ Preterm birth (<37 weeks’ gestation) occurred in 13.1% and 11.6% of women treated with placebo or aspirin (relative risk [RR], 0.89; 95% confidence interval [CI], 0.81 to 0.98, P = .012). Most of the decrease in preterm birth appeared to be due to a decrease in the rate of preeclampsia in the aspirin-treated nulliparous women. The investigators also noted that aspirin treatment of nulliparous women resulted in a statistically significant decrease in perinatal mortality (RR, 0.86) and early preterm delivery, <34 weeks’ gestation (RR, 0.75). 

Universal prescription of low-dose aspirin to nulliparous women in order to prevent preeclampsia and preterm birth may become recognized as an optimal public health strategy. As a step toward universal prescription of aspirin to nulliparous women, an opt-out rather than a screen-in strategy might be considered.⁸

Continue to: Booking systolic blood pressure, 120 to 134 mm Hg...

Booking systolic blood pressure, 120 to 134 mm Hg

All obstetricians recognize that women with chronic hypertension should be treated with low-dose aspirin because they are at high risk for preeclampsia. However, there is evidence that nulliparous women with a booking systolic pressure ≥120 mm Hg might also benefit from low-dose aspirin treatment. In one US trial, 3,135 nulliparous normotensive women (booking blood pressure [BP] <135/85 mm Hg) were randomly assigned to treatment with aspirin (60 mg daily) or placebo initiated between 13 and 26 weeks’ gestation. Preeclampsia occurred in 6.3% and 4.6% of the women treated with placebo or aspirin, respectively (RR, 0.7; 95% CI, 0.6–1.0; P = .05).⁹ A secondary analysis showed that, among 519 nulliparous women with a booking systolic BP from 120 to 134 mm Hg, compared with placebo, low-dose aspirin treatment reduced the rate of preeclampsia from 11.9% to 5.6%.⁹ Aspirin did not reduce the rate of preeclampsia among nulliparous women with a booking systolic BP <120 mm Hg.⁹ A systematic review of risk factors for developing preeclampsia reported that a booking diastolic BP of ≥80 mm Hg was associated with an increased risk of developing preeclampsia (RR, 1.38).¹⁰ 

The American Heart Association (AHA) and the American College of Cardiology (ACC) recently updated the definition of hypertension.¹¹ Normal BP is now defined as a systolic pressure <120 mm Hg and diastolic pressure <80 mm Hg. Elevated BP is a systolic pressure of 120 to 129 mm Hg and diastolic pressure of <80 mm Hg. Stage I hypertension is a systolic BP from 130 to 139 mm Hg or diastolic blood pressure from 80 to 89 mm Hg. Stage II hypertension is a systolic BP of ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg.¹¹ 

A recent study reported that 90% of women at 12 weeks’ gestation have a BP of ≤130 mm Hg systolic and ≤80 mm Hg diastolic, suggesting that the AHA-ACC criteria for stage I hypertension are reasonable.¹² Obstetricians have not yet fully adopted the AHA-ACC criteria for defining stage I hypertension in pregnant women. Future research may demonstrate that a booking systolic BP 
 ≥130 mm Hg or a diastolic BP ≥80 mm Hg are major risk factors for developing preeclampsia and warrant treatment with low-dose aspirin.

Continue to: Pregnancy resulting from fertility therapy...

Pregnancy resulting from fertility therapy

Current ACOG and USPSTF guidelines do not specifically identify pregnancies resulting from assisted reproductive technology as a major or moderate risk factor for preeclampsia.^2,3 In a study comparing 83,582 births resulting from in vitro fertilization (IVF) and 1,382,311 births to fertile women, treatment with autologous cryopreserved embryos (adjusted odds ratio [aOR], 1.30), fresh donor embryos (aOR, 1.92), and cryopreserved donor embryos (aOR, 1.70) significantly increased the risk of preeclampsia.¹³ However, use of fresh autologous embryos did not increase the risk of preeclampsia (aOR, 1.04). These associations persisted after controlling for diabetes, hypertension, body mass index, and cause of infertility.¹³

Other studies also have reported that use of cryopreserved embryos is associated with a higher rate of preeclampsia than use of fresh autologous embryos. In a study of 825 infertile women undergoing IVF and randomly assigned to single embryo cryopreserved or fresh cycles, the rate of preeclampsia was 3.1% and 1.0% in the pregnancies that resulted from cryopreserved versus fresh cycles.¹⁴ 

What is the optimal dose of aspirin?

ACOG and the USPSTF recommend aspirin 81 mg daily for the prevention of preeclampsia.^2,3 The International Federation of Gynecology and Obstetrics (FIGO) recommends aspirin 150 mg daily for the prevention of preeclampsia.¹⁵ The FIGO recommendation is based, in part, on the results of a large international clinical trial that randomly assigned 1,776 women at high risk for preeclampsia as determined by clinical factors plus biomarker and ultrasound screening to receive aspirin 150 mg daily or placebo daily initiated at 11 to 14 weeks’ gestation and continued until 36 weeks’ gestation.¹⁶ Preeclampsia before 37 weeks’ gestation occurred in 4.3% and 1.6% of women in the placebo and aspirin groups (OR, 0.38; 95% CI, 0.20–0.74; P = .004).¹⁶ FIGO recommends that women at risk for preeclampsia with a body mass <40 kg take aspirin 100 mg daily and women with a body mass ≥40 kg take aspirin at a dose of 150 mg daily. For women who live in a country where aspirin is not available in a pill containing 150 mg, FIGO recommends taking two 81 mg tablets.¹⁵ FIGO recommends initiating aspirin between 11 and 14 weeks and 6 days of gestation and continuing aspirin therapy until 36 weeks of gestation.¹⁵

Aspirin is an inexpensive intervention with many possible benefits

For many nulliparous women and some parous women aspirin treatment initiated early in pregnancy will improve maternal and newborn outcomes, including reducing the risk of preeclampsia, preterm birth, and intrauterine growth restriction.¹ Obstetricians may want to begin to expand the indications for offering aspirin to prevent preeclampsia from those recommended by ACOG and the USPSTF to include nulliparous women with a booking systolic pressure of 120 to 134 mm Hg and women whose pregnancy was the result of an assisted reproduction treatment that used cryopreserved embryos. In addition, obstetricians who currently prescribe 81 mg of aspirin daily might want to consider increasing the prescribed dose to 162 mg of aspirin daily (two 81 mg tablets daily or one-half of a 325 mg tablet). Aspirin costs about less than 5 cents per 81 mg tablet (according to GoodRx website). It is an inexpensive intervention that could benefit many mothers and newborns. ●

Authors of a recent Cochrane review concluded that low-dose aspirin treatment of 1,000 pregnant women at risk of developing preeclampsia resulted in 16 fewer cases of preeclampsia, 16 fewer preterm births, 7 fewer cases of small-for-gestational age newborns, and 5 fewer fetal or neonatal deaths.¹

The American College of Obstetricians and Gynecologists (ACOG) and the US Preventive Services Task Force (USPSTF) recommend treatment with 81 mg of aspirin daily, initiated before 16 weeks of pregnancy to prevent preeclampsia in women with one major risk factor (personal history of preeclampsia, multifetal gestation, chronic hypertension, type 1 or 2 diabetes, renal or autoimmune disease) or at least two moderate risk factors (nulliparity; obesity; mother or sister with preeclampsia; a sociodemographic characteristic such as African American race or low socioeconomic status; age ≥35 years; personal history factors such as prior low birth weight infant, previous adverse pregnancy outcome, or >10-year interpregnancy interval).^2,3 Healthy pregnant women with a previous uncomplicated full-term delivery do not need treatment with low-dose aspirin.^2,3

However, evolving data and expert opinion suggest that expanding the indications for aspirin treatment and increasing the recommended dose of aspirin may be warranted. 

Nulliparity

Nulliparity is the single clinical characteristic that is associated with the greatest number of cases of preeclampsia.⁴ Hence, from a public health perspective, reducing the rate of preeclampsia among nulliparous women is a top priority.

ACOG and USPSTF do not recommend aspirin treatment for all nulliparous women because risk factors help to identify those nulliparous women who benefit from aspirin treatment.

However, a recent cost-effectiveness analysis compared the health care costs and rates of preeclampsia for 4 prevention strategies among all pregnant women in the United States (nulliparous and parous)⁵:

1. no aspirin use
2. use of aspirin based on biomarker and ultrasound measurements
3. use of aspirin based on USPSTF guidelines for identifying women at risk
4. prescription of aspirin to all pregnant women.

Health care costs and rates of preeclampsia were lowest with the universal prescription of aspirin to all pregnant women in the United States. Compared with universal prescription of aspirin, the USPSTF approach, the biomarker-ultrasound approach, and the no aspirin approach were associated with 346, 308, and 762 additional cases of preeclampsia per 100,000 women. In sensitivity analyses, universal aspirin was the optimal strategy under most assumptions.

Another cost effectiveness analysis concluded that among nulliparous pregnant women, universal aspirin treatment was superior to aspirin treatment based on biomarker-ultrasound identification of women at high risk.⁶ 

In a recent clinical trial performed in India, Guatemala, Pakistan, Democratic Republic of Congo, Kenya, and Zambia, 14,361 nulliparous women were randomly assigned to placebo or 81 mg of aspirin daily between 6 and 14 weeks of gestation.⁷ Preterm birth (<37 weeks’ gestation) occurred in 13.1% and 11.6% of women treated with placebo or aspirin (relative risk [RR], 0.89; 95% confidence interval [CI], 0.81 to 0.98, P = .012). Most of the decrease in preterm birth appeared to be due to a decrease in the rate of preeclampsia in the aspirin-treated nulliparous women. The investigators also noted that aspirin treatment of nulliparous women resulted in a statistically significant decrease in perinatal mortality (RR, 0.86) and early preterm delivery, <34 weeks’ gestation (RR, 0.75). 

Universal prescription of low-dose aspirin to nulliparous women in order to prevent preeclampsia and preterm birth may become recognized as an optimal public health strategy. As a step toward universal prescription of aspirin to nulliparous women, an opt-out rather than a screen-in strategy might be considered.⁸

Continue to: Booking systolic blood pressure, 120 to 134 mm Hg...

Booking systolic blood pressure, 120 to 134 mm Hg

All obstetricians recognize that women with chronic hypertension should be treated with low-dose aspirin because they are at high risk for preeclampsia. However, there is evidence that nulliparous women with a booking systolic pressure ≥120 mm Hg might also benefit from low-dose aspirin treatment. In one US trial, 3,135 nulliparous normotensive women (booking blood pressure [BP] <135/85 mm Hg) were randomly assigned to treatment with aspirin (60 mg daily) or placebo initiated between 13 and 26 weeks’ gestation. Preeclampsia occurred in 6.3% and 4.6% of the women treated with placebo or aspirin, respectively (RR, 0.7; 95% CI, 0.6–1.0; P = .05).⁹ A secondary analysis showed that, among 519 nulliparous women with a booking systolic BP from 120 to 134 mm Hg, compared with placebo, low-dose aspirin treatment reduced the rate of preeclampsia from 11.9% to 5.6%.⁹ Aspirin did not reduce the rate of preeclampsia among nulliparous women with a booking systolic BP <120 mm Hg.⁹ A systematic review of risk factors for developing preeclampsia reported that a booking diastolic BP of ≥80 mm Hg was associated with an increased risk of developing preeclampsia (RR, 1.38).¹⁰ 

The American Heart Association (AHA) and the American College of Cardiology (ACC) recently updated the definition of hypertension.¹¹ Normal BP is now defined as a systolic pressure <120 mm Hg and diastolic pressure <80 mm Hg. Elevated BP is a systolic pressure of 120 to 129 mm Hg and diastolic pressure of <80 mm Hg. Stage I hypertension is a systolic BP from 130 to 139 mm Hg or diastolic blood pressure from 80 to 89 mm Hg. Stage II hypertension is a systolic BP of ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg.¹¹ 

A recent study reported that 90% of women at 12 weeks’ gestation have a BP of ≤130 mm Hg systolic and ≤80 mm Hg diastolic, suggesting that the AHA-ACC criteria for stage I hypertension are reasonable.¹² Obstetricians have not yet fully adopted the AHA-ACC criteria for defining stage I hypertension in pregnant women. Future research may demonstrate that a booking systolic BP 
 ≥130 mm Hg or a diastolic BP ≥80 mm Hg are major risk factors for developing preeclampsia and warrant treatment with low-dose aspirin.

Continue to: Pregnancy resulting from fertility therapy...

Pregnancy resulting from fertility therapy

Current ACOG and USPSTF guidelines do not specifically identify pregnancies resulting from assisted reproductive technology as a major or moderate risk factor for preeclampsia.^2,3 In a study comparing 83,582 births resulting from in vitro fertilization (IVF) and 1,382,311 births to fertile women, treatment with autologous cryopreserved embryos (adjusted odds ratio [aOR], 1.30), fresh donor embryos (aOR, 1.92), and cryopreserved donor embryos (aOR, 1.70) significantly increased the risk of preeclampsia.¹³ However, use of fresh autologous embryos did not increase the risk of preeclampsia (aOR, 1.04). These associations persisted after controlling for diabetes, hypertension, body mass index, and cause of infertility.¹³

Other studies also have reported that use of cryopreserved embryos is associated with a higher rate of preeclampsia than use of fresh autologous embryos. In a study of 825 infertile women undergoing IVF and randomly assigned to single embryo cryopreserved or fresh cycles, the rate of preeclampsia was 3.1% and 1.0% in the pregnancies that resulted from cryopreserved versus fresh cycles.¹⁴ 

What is the optimal dose of aspirin?

ACOG and the USPSTF recommend aspirin 81 mg daily for the prevention of preeclampsia.^2,3 The International Federation of Gynecology and Obstetrics (FIGO) recommends aspirin 150 mg daily for the prevention of preeclampsia.¹⁵ The FIGO recommendation is based, in part, on the results of a large international clinical trial that randomly assigned 1,776 women at high risk for preeclampsia as determined by clinical factors plus biomarker and ultrasound screening to receive aspirin 150 mg daily or placebo daily initiated at 11 to 14 weeks’ gestation and continued until 36 weeks’ gestation.¹⁶ Preeclampsia before 37 weeks’ gestation occurred in 4.3% and 1.6% of women in the placebo and aspirin groups (OR, 0.38; 95% CI, 0.20–0.74; P = .004).¹⁶ FIGO recommends that women at risk for preeclampsia with a body mass <40 kg take aspirin 100 mg daily and women with a body mass ≥40 kg take aspirin at a dose of 150 mg daily. For women who live in a country where aspirin is not available in a pill containing 150 mg, FIGO recommends taking two 81 mg tablets.¹⁵ FIGO recommends initiating aspirin between 11 and 14 weeks and 6 days of gestation and continuing aspirin therapy until 36 weeks of gestation.¹⁵

Aspirin is an inexpensive intervention with many possible benefits

For many nulliparous women and some parous women aspirin treatment initiated early in pregnancy will improve maternal and newborn outcomes, including reducing the risk of preeclampsia, preterm birth, and intrauterine growth restriction.¹ Obstetricians may want to begin to expand the indications for offering aspirin to prevent preeclampsia from those recommended by ACOG and the USPSTF to include nulliparous women with a booking systolic pressure of 120 to 134 mm Hg and women whose pregnancy was the result of an assisted reproduction treatment that used cryopreserved embryos. In addition, obstetricians who currently prescribe 81 mg of aspirin daily might want to consider increasing the prescribed dose to 162 mg of aspirin daily (two 81 mg tablets daily or one-half of a 325 mg tablet). Aspirin costs about less than 5 cents per 81 mg tablet (according to GoodRx website). It is an inexpensive intervention that could benefit many mothers and newborns. ●

Authors of a recent Cochrane review concluded that low-dose aspirin treatment of 1,000 pregnant women at risk of developing preeclampsia resulted in 16 fewer cases of preeclampsia, 16 fewer preterm births, 7 fewer cases of small-for-gestational age newborns, and 5 fewer fetal or neonatal deaths.¹

The American College of Obstetricians and Gynecologists (ACOG) and the US Preventive Services Task Force (USPSTF) recommend treatment with 81 mg of aspirin daily, initiated before 16 weeks of pregnancy to prevent preeclampsia in women with one major risk factor (personal history of preeclampsia, multifetal gestation, chronic hypertension, type 1 or 2 diabetes, renal or autoimmune disease) or at least two moderate risk factors (nulliparity; obesity; mother or sister with preeclampsia; a sociodemographic characteristic such as African American race or low socioeconomic status; age ≥35 years; personal history factors such as prior low birth weight infant, previous adverse pregnancy outcome, or >10-year interpregnancy interval).^2,3 Healthy pregnant women with a previous uncomplicated full-term delivery do not need treatment with low-dose aspirin.^2,3

However, evolving data and expert opinion suggest that expanding the indications for aspirin treatment and increasing the recommended dose of aspirin may be warranted. 

Nulliparity

Nulliparity is the single clinical characteristic that is associated with the greatest number of cases of preeclampsia.⁴ Hence, from a public health perspective, reducing the rate of preeclampsia among nulliparous women is a top priority.

ACOG and USPSTF do not recommend aspirin treatment for all nulliparous women because risk factors help to identify those nulliparous women who benefit from aspirin treatment.

However, a recent cost-effectiveness analysis compared the health care costs and rates of preeclampsia for 4 prevention strategies among all pregnant women in the United States (nulliparous and parous)⁵:

1. no aspirin use
2. use of aspirin based on biomarker and ultrasound measurements
3. use of aspirin based on USPSTF guidelines for identifying women at risk
4. prescription of aspirin to all pregnant women.

Health care costs and rates of preeclampsia were lowest with the universal prescription of aspirin to all pregnant women in the United States. Compared with universal prescription of aspirin, the USPSTF approach, the biomarker-ultrasound approach, and the no aspirin approach were associated with 346, 308, and 762 additional cases of preeclampsia per 100,000 women. In sensitivity analyses, universal aspirin was the optimal strategy under most assumptions.

Another cost effectiveness analysis concluded that among nulliparous pregnant women, universal aspirin treatment was superior to aspirin treatment based on biomarker-ultrasound identification of women at high risk.⁶ 

In a recent clinical trial performed in India, Guatemala, Pakistan, Democratic Republic of Congo, Kenya, and Zambia, 14,361 nulliparous women were randomly assigned to placebo or 81 mg of aspirin daily between 6 and 14 weeks of gestation.⁷ Preterm birth (<37 weeks’ gestation) occurred in 13.1% and 11.6% of women treated with placebo or aspirin (relative risk [RR], 0.89; 95% confidence interval [CI], 0.81 to 0.98, P = .012). Most of the decrease in preterm birth appeared to be due to a decrease in the rate of preeclampsia in the aspirin-treated nulliparous women. The investigators also noted that aspirin treatment of nulliparous women resulted in a statistically significant decrease in perinatal mortality (RR, 0.86) and early preterm delivery, <34 weeks’ gestation (RR, 0.75). 

Universal prescription of low-dose aspirin to nulliparous women in order to prevent preeclampsia and preterm birth may become recognized as an optimal public health strategy. As a step toward universal prescription of aspirin to nulliparous women, an opt-out rather than a screen-in strategy might be considered.⁸

Continue to: Booking systolic blood pressure, 120 to 134 mm Hg...

Booking systolic blood pressure, 120 to 134 mm Hg

All obstetricians recognize that women with chronic hypertension should be treated with low-dose aspirin because they are at high risk for preeclampsia. However, there is evidence that nulliparous women with a booking systolic pressure ≥120 mm Hg might also benefit from low-dose aspirin treatment. In one US trial, 3,135 nulliparous normotensive women (booking blood pressure [BP] <135/85 mm Hg) were randomly assigned to treatment with aspirin (60 mg daily) or placebo initiated between 13 and 26 weeks’ gestation. Preeclampsia occurred in 6.3% and 4.6% of the women treated with placebo or aspirin, respectively (RR, 0.7; 95% CI, 0.6–1.0; P = .05).⁹ A secondary analysis showed that, among 519 nulliparous women with a booking systolic BP from 120 to 134 mm Hg, compared with placebo, low-dose aspirin treatment reduced the rate of preeclampsia from 11.9% to 5.6%.⁹ Aspirin did not reduce the rate of preeclampsia among nulliparous women with a booking systolic BP <120 mm Hg.⁹ A systematic review of risk factors for developing preeclampsia reported that a booking diastolic BP of ≥80 mm Hg was associated with an increased risk of developing preeclampsia (RR, 1.38).¹⁰ 

The American Heart Association (AHA) and the American College of Cardiology (ACC) recently updated the definition of hypertension.¹¹ Normal BP is now defined as a systolic pressure <120 mm Hg and diastolic pressure <80 mm Hg. Elevated BP is a systolic pressure of 120 to 129 mm Hg and diastolic pressure of <80 mm Hg. Stage I hypertension is a systolic BP from 130 to 139 mm Hg or diastolic blood pressure from 80 to 89 mm Hg. Stage II hypertension is a systolic BP of ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg.¹¹ 

A recent study reported that 90% of women at 12 weeks’ gestation have a BP of ≤130 mm Hg systolic and ≤80 mm Hg diastolic, suggesting that the AHA-ACC criteria for stage I hypertension are reasonable.¹² Obstetricians have not yet fully adopted the AHA-ACC criteria for defining stage I hypertension in pregnant women. Future research may demonstrate that a booking systolic BP 
 ≥130 mm Hg or a diastolic BP ≥80 mm Hg are major risk factors for developing preeclampsia and warrant treatment with low-dose aspirin.

Continue to: Pregnancy resulting from fertility therapy...

Pregnancy resulting from fertility therapy

Current ACOG and USPSTF guidelines do not specifically identify pregnancies resulting from assisted reproductive technology as a major or moderate risk factor for preeclampsia.^2,3 In a study comparing 83,582 births resulting from in vitro fertilization (IVF) and 1,382,311 births to fertile women, treatment with autologous cryopreserved embryos (adjusted odds ratio [aOR], 1.30), fresh donor embryos (aOR, 1.92), and cryopreserved donor embryos (aOR, 1.70) significantly increased the risk of preeclampsia.¹³ However, use of fresh autologous embryos did not increase the risk of preeclampsia (aOR, 1.04). These associations persisted after controlling for diabetes, hypertension, body mass index, and cause of infertility.¹³

Other studies also have reported that use of cryopreserved embryos is associated with a higher rate of preeclampsia than use of fresh autologous embryos. In a study of 825 infertile women undergoing IVF and randomly assigned to single embryo cryopreserved or fresh cycles, the rate of preeclampsia was 3.1% and 1.0% in the pregnancies that resulted from cryopreserved versus fresh cycles.¹⁴ 

What is the optimal dose of aspirin?

ACOG and the USPSTF recommend aspirin 81 mg daily for the prevention of preeclampsia.^2,3 The International Federation of Gynecology and Obstetrics (FIGO) recommends aspirin 150 mg daily for the prevention of preeclampsia.¹⁵ The FIGO recommendation is based, in part, on the results of a large international clinical trial that randomly assigned 1,776 women at high risk for preeclampsia as determined by clinical factors plus biomarker and ultrasound screening to receive aspirin 150 mg daily or placebo daily initiated at 11 to 14 weeks’ gestation and continued until 36 weeks’ gestation.¹⁶ Preeclampsia before 37 weeks’ gestation occurred in 4.3% and 1.6% of women in the placebo and aspirin groups (OR, 0.38; 95% CI, 0.20–0.74; P = .004).¹⁶ FIGO recommends that women at risk for preeclampsia with a body mass <40 kg take aspirin 100 mg daily and women with a body mass ≥40 kg take aspirin at a dose of 150 mg daily. For women who live in a country where aspirin is not available in a pill containing 150 mg, FIGO recommends taking two 81 mg tablets.¹⁵ FIGO recommends initiating aspirin between 11 and 14 weeks and 6 days of gestation and continuing aspirin therapy until 36 weeks of gestation.¹⁵

Aspirin is an inexpensive intervention with many possible benefits

For many nulliparous women and some parous women aspirin treatment initiated early in pregnancy will improve maternal and newborn outcomes, including reducing the risk of preeclampsia, preterm birth, and intrauterine growth restriction.¹ Obstetricians may want to begin to expand the indications for offering aspirin to prevent preeclampsia from those recommended by ACOG and the USPSTF to include nulliparous women with a booking systolic pressure of 120 to 134 mm Hg and women whose pregnancy was the result of an assisted reproduction treatment that used cryopreserved embryos. In addition, obstetricians who currently prescribe 81 mg of aspirin daily might want to consider increasing the prescribed dose to 162 mg of aspirin daily (two 81 mg tablets daily or one-half of a 325 mg tablet). Aspirin costs about less than 5 cents per 81 mg tablet (according to GoodRx website). It is an inexpensive intervention that could benefit many mothers and newborns. ●

I think it’s fair to say, none of us have seen anything like this before. Yet here we are, and we must lead. We are many weeks into the COVID-19 crisis. We moved our offices home and tried not to miss a beat. Our patients need us more than ever – and in different ways.

Lest we become like the shoemaker’s daughter who has no shoes, let’s make sure we take care of ourselves. The shock waves from this pandemic are going to be massive and long lasting. I am already witnessing massive psychological growth on the part of my patients, and I hope, myself and my family. We must be strong as individuals and as a group of professionals.

Now more than ever, we need to set boundaries. So many are suffering. We must take stock of our own lives. Many of us are extremely fortunate. We have homes, families, and plenty of food. We are doctors performing essential services, and we can do so without risking our lives.

The priority is to make sure you are safe, and keeping your family and loved ones safe. As physicians, we have learned to distance ourselves from illness, but the coronavirus has affected us in disproportionate numbers. As a group, we must be risk averse as we will be called upon to heal a very traumatized nation.

To be physically and mentally strong, we must get enough sleep. This is exhausting for some and energizing for others. It is definitely a marathon not a sprint, so pace yourself. Eat well. This is no time for empty calories, and that goes for alcohol as well.

Create new routines. Exercise at the same time each day or perhaps twice a day. Try to be productive during certain hours, and relax at other times. Eat at similar times each day. We must strive to quickly create a “new normal” as we spend our days at home.

Find safe alternatives to your usual workout routine. Use YouTube and Instagram to help you find ways to stay fit in your own home. Ask friends for tips and consider sharing workout time with them via Zoom or FaceTime. New options are coming on line daily.

Make sure you are getting enough information to stay safe, and follow the advice of experts. Then turn off the news. I offer the same advice for financial worries. Try not to stress too much about finances right now. Most of us are feeling the pain of lost income and lost savings. Many of us have spouses or partners who suddenly found themselves out of work. Most likely, we will have ample ability to recover financially as we move forward and find ourselves with more work than ever.

Meditate. This may be advice you have been telling your patients for years but never found the time to try yourself. You can begin very simply with an app called Headspace or Calm. Google “5-minute meditation” on YouTube or find a meditation of any length you desire. If not now, when?

Reach out to one another. We can all use a caring word, or some humor or advice about how to move our practices online.

You may find your concentration is decreased, so be realistic in your expectations of yourself. I am finding shorter sessions more often are providing more comfort to some patients. Other patients are digging deeper than ever emotionally, and the work is becoming more rewarding.

Make sure you take a break to engage in positive activities. Read a book. Listen to soft music. Dim the lights. Watch the sunset, or be in nature if you can do so safely. Watch a TedTalk. Brush up on a foreign language. Take a deep breath. Journal. Puzzles, games, cooking, magazines, and humor all provide much needed respite from the stress. If you are lucky enough to be with family, try to take advantage of this unique time.

Try to avoid or minimize conflict with others. We need one another now more than ever. If you lose your cool, forgive yourself and make amends.

Even in these most challenging times, we must focus on what we are grateful for. Express gratitude to those around you as it will lift their mood as well. I know I am extremely grateful to be able to continue meaningful work when so many are unable to do so.

The next waves of this virus will be hitting our specialty directly so be strong and be prepared. It is an honor to serve, and we must rise to the occasion.
 

Dr. Ritvo, a psychiatrist with more than 25 years’ experience, practices in Miami Beach, Fla. She is the author of “Bekindr – The Transformative Power of Kindness” (Hellertown, Pa.: Momosa Publishing, 2018), and is the founder of the Bekindr Global Initiative, a movement aimed at cultivating kindness in the world. Dr. Ritvo also is the cofounder of the Bold Beauty Project, a nonprofit group that pairs women with disabilities with photographers who create art exhibitions to raise awareness.

I think it’s fair to say, none of us have seen anything like this before. Yet here we are, and we must lead. We are many weeks into the COVID-19 crisis. We moved our offices home and tried not to miss a beat. Our patients need us more than ever – and in different ways.

Lest we become like the shoemaker’s daughter who has no shoes, let’s make sure we take care of ourselves. The shock waves from this pandemic are going to be massive and long lasting. I am already witnessing massive psychological growth on the part of my patients, and I hope, myself and my family. We must be strong as individuals and as a group of professionals.

Now more than ever, we need to set boundaries. So many are suffering. We must take stock of our own lives. Many of us are extremely fortunate. We have homes, families, and plenty of food. We are doctors performing essential services, and we can do so without risking our lives.

The priority is to make sure you are safe, and keeping your family and loved ones safe. As physicians, we have learned to distance ourselves from illness, but the coronavirus has affected us in disproportionate numbers. As a group, we must be risk averse as we will be called upon to heal a very traumatized nation.

To be physically and mentally strong, we must get enough sleep. This is exhausting for some and energizing for others. It is definitely a marathon not a sprint, so pace yourself. Eat well. This is no time for empty calories, and that goes for alcohol as well.

Create new routines. Exercise at the same time each day or perhaps twice a day. Try to be productive during certain hours, and relax at other times. Eat at similar times each day. We must strive to quickly create a “new normal” as we spend our days at home.

Find safe alternatives to your usual workout routine. Use YouTube and Instagram to help you find ways to stay fit in your own home. Ask friends for tips and consider sharing workout time with them via Zoom or FaceTime. New options are coming on line daily.

Make sure you are getting enough information to stay safe, and follow the advice of experts. Then turn off the news. I offer the same advice for financial worries. Try not to stress too much about finances right now. Most of us are feeling the pain of lost income and lost savings. Many of us have spouses or partners who suddenly found themselves out of work. Most likely, we will have ample ability to recover financially as we move forward and find ourselves with more work than ever.

Meditate. This may be advice you have been telling your patients for years but never found the time to try yourself. You can begin very simply with an app called Headspace or Calm. Google “5-minute meditation” on YouTube or find a meditation of any length you desire. If not now, when?

Reach out to one another. We can all use a caring word, or some humor or advice about how to move our practices online.

You may find your concentration is decreased, so be realistic in your expectations of yourself. I am finding shorter sessions more often are providing more comfort to some patients. Other patients are digging deeper than ever emotionally, and the work is becoming more rewarding.

Make sure you take a break to engage in positive activities. Read a book. Listen to soft music. Dim the lights. Watch the sunset, or be in nature if you can do so safely. Watch a TedTalk. Brush up on a foreign language. Take a deep breath. Journal. Puzzles, games, cooking, magazines, and humor all provide much needed respite from the stress. If you are lucky enough to be with family, try to take advantage of this unique time.

Try to avoid or minimize conflict with others. We need one another now more than ever. If you lose your cool, forgive yourself and make amends.

Even in these most challenging times, we must focus on what we are grateful for. Express gratitude to those around you as it will lift their mood as well. I know I am extremely grateful to be able to continue meaningful work when so many are unable to do so.

The next waves of this virus will be hitting our specialty directly so be strong and be prepared. It is an honor to serve, and we must rise to the occasion.
 

Dr. Ritvo, a psychiatrist with more than 25 years’ experience, practices in Miami Beach, Fla. She is the author of “Bekindr – The Transformative Power of Kindness” (Hellertown, Pa.: Momosa Publishing, 2018), and is the founder of the Bekindr Global Initiative, a movement aimed at cultivating kindness in the world. Dr. Ritvo also is the cofounder of the Bold Beauty Project, a nonprofit group that pairs women with disabilities with photographers who create art exhibitions to raise awareness.

I think it’s fair to say, none of us have seen anything like this before. Yet here we are, and we must lead. We are many weeks into the COVID-19 crisis. We moved our offices home and tried not to miss a beat. Our patients need us more than ever – and in different ways.

Lest we become like the shoemaker’s daughter who has no shoes, let’s make sure we take care of ourselves. The shock waves from this pandemic are going to be massive and long lasting. I am already witnessing massive psychological growth on the part of my patients, and I hope, myself and my family. We must be strong as individuals and as a group of professionals.

Now more than ever, we need to set boundaries. So many are suffering. We must take stock of our own lives. Many of us are extremely fortunate. We have homes, families, and plenty of food. We are doctors performing essential services, and we can do so without risking our lives.

The priority is to make sure you are safe, and keeping your family and loved ones safe. As physicians, we have learned to distance ourselves from illness, but the coronavirus has affected us in disproportionate numbers. As a group, we must be risk averse as we will be called upon to heal a very traumatized nation.

To be physically and mentally strong, we must get enough sleep. This is exhausting for some and energizing for others. It is definitely a marathon not a sprint, so pace yourself. Eat well. This is no time for empty calories, and that goes for alcohol as well.

Create new routines. Exercise at the same time each day or perhaps twice a day. Try to be productive during certain hours, and relax at other times. Eat at similar times each day. We must strive to quickly create a “new normal” as we spend our days at home.

Find safe alternatives to your usual workout routine. Use YouTube and Instagram to help you find ways to stay fit in your own home. Ask friends for tips and consider sharing workout time with them via Zoom or FaceTime. New options are coming on line daily.

Make sure you are getting enough information to stay safe, and follow the advice of experts. Then turn off the news. I offer the same advice for financial worries. Try not to stress too much about finances right now. Most of us are feeling the pain of lost income and lost savings. Many of us have spouses or partners who suddenly found themselves out of work. Most likely, we will have ample ability to recover financially as we move forward and find ourselves with more work than ever.

Meditate. This may be advice you have been telling your patients for years but never found the time to try yourself. You can begin very simply with an app called Headspace or Calm. Google “5-minute meditation” on YouTube or find a meditation of any length you desire. If not now, when?

Reach out to one another. We can all use a caring word, or some humor or advice about how to move our practices online.

You may find your concentration is decreased, so be realistic in your expectations of yourself. I am finding shorter sessions more often are providing more comfort to some patients. Other patients are digging deeper than ever emotionally, and the work is becoming more rewarding.

Make sure you take a break to engage in positive activities. Read a book. Listen to soft music. Dim the lights. Watch the sunset, or be in nature if you can do so safely. Watch a TedTalk. Brush up on a foreign language. Take a deep breath. Journal. Puzzles, games, cooking, magazines, and humor all provide much needed respite from the stress. If you are lucky enough to be with family, try to take advantage of this unique time.

Try to avoid or minimize conflict with others. We need one another now more than ever. If you lose your cool, forgive yourself and make amends.

Even in these most challenging times, we must focus on what we are grateful for. Express gratitude to those around you as it will lift their mood as well. I know I am extremely grateful to be able to continue meaningful work when so many are unable to do so.

The next waves of this virus will be hitting our specialty directly so be strong and be prepared. It is an honor to serve, and we must rise to the occasion.
 

Dr. Ritvo, a psychiatrist with more than 25 years’ experience, practices in Miami Beach, Fla. She is the author of “Bekindr – The Transformative Power of Kindness” (Hellertown, Pa.: Momosa Publishing, 2018), and is the founder of the Bekindr Global Initiative, a movement aimed at cultivating kindness in the world. Dr. Ritvo also is the cofounder of the Bold Beauty Project, a nonprofit group that pairs women with disabilities with photographers who create art exhibitions to raise awareness.

The president of the American Medical Association is calling on politicians and the media to rely on science and evidence to help the public through the COVID-19 pandemic.

“We live in a time when misinformation, falsehoods, and outright lies spread like viruses online, through social media and even, at times, in the media at large,” Patrice A. Harris, MD, said during an April 7 address. “We have witnessed a concerning shift over the last several decades where policy decisions seem to be driven by ideology and politics instead of facts and evidence. The result is a growing mistrust in American institutions, in science, and in the counsel of leading experts whose lives are dedicated to the pursuit of evidence and reason.”

To that end, she called on everyone – from politicians to the general public – to trust the scientific evidence.

Dr. Harris noted that the scientific data on COVID-19 have already yielded important lessons about who is more likely to be affected and how easily the virus can spread. The data also point to the effectiveness of stay-at-home and shelter-in-place orders. “This is our best chance to slow the spread of the virus,” she said, adding that the enhanced emphasis on hand washing and other hygiene practices “may seem ‘simplistic,’ but they are, in fact, based in science and evidence.”

And, as the pandemic continues, Dr. Harris said that now is the time to rely on science. She said the AMA “calls on all elected officials to affirm science, evidence, and fact in their words and actions,” and she urged that the government’s scientific institutions be led by experts who are “protected from political influence.”

It is incumbent upon everyone to actively work to contain and stop the spread of misinformation related to COVID-19, she said. “We must ensure the war is against the virus and not against science,” Dr. Harris said.

gtwachtman@mdedge.com

The president of the American Medical Association is calling on politicians and the media to rely on science and evidence to help the public through the COVID-19 pandemic.

“We live in a time when misinformation, falsehoods, and outright lies spread like viruses online, through social media and even, at times, in the media at large,” Patrice A. Harris, MD, said during an April 7 address. “We have witnessed a concerning shift over the last several decades where policy decisions seem to be driven by ideology and politics instead of facts and evidence. The result is a growing mistrust in American institutions, in science, and in the counsel of leading experts whose lives are dedicated to the pursuit of evidence and reason.”

To that end, she called on everyone – from politicians to the general public – to trust the scientific evidence.

Dr. Harris noted that the scientific data on COVID-19 have already yielded important lessons about who is more likely to be affected and how easily the virus can spread. The data also point to the effectiveness of stay-at-home and shelter-in-place orders. “This is our best chance to slow the spread of the virus,” she said, adding that the enhanced emphasis on hand washing and other hygiene practices “may seem ‘simplistic,’ but they are, in fact, based in science and evidence.”

And, as the pandemic continues, Dr. Harris said that now is the time to rely on science. She said the AMA “calls on all elected officials to affirm science, evidence, and fact in their words and actions,” and she urged that the government’s scientific institutions be led by experts who are “protected from political influence.”

It is incumbent upon everyone to actively work to contain and stop the spread of misinformation related to COVID-19, she said. “We must ensure the war is against the virus and not against science,” Dr. Harris said.

gtwachtman@mdedge.com

The president of the American Medical Association is calling on politicians and the media to rely on science and evidence to help the public through the COVID-19 pandemic.

“We live in a time when misinformation, falsehoods, and outright lies spread like viruses online, through social media and even, at times, in the media at large,” Patrice A. Harris, MD, said during an April 7 address. “We have witnessed a concerning shift over the last several decades where policy decisions seem to be driven by ideology and politics instead of facts and evidence. The result is a growing mistrust in American institutions, in science, and in the counsel of leading experts whose lives are dedicated to the pursuit of evidence and reason.”

To that end, she called on everyone – from politicians to the general public – to trust the scientific evidence.

Dr. Harris noted that the scientific data on COVID-19 have already yielded important lessons about who is more likely to be affected and how easily the virus can spread. The data also point to the effectiveness of stay-at-home and shelter-in-place orders. “This is our best chance to slow the spread of the virus,” she said, adding that the enhanced emphasis on hand washing and other hygiene practices “may seem ‘simplistic,’ but they are, in fact, based in science and evidence.”

And, as the pandemic continues, Dr. Harris said that now is the time to rely on science. She said the AMA “calls on all elected officials to affirm science, evidence, and fact in their words and actions,” and she urged that the government’s scientific institutions be led by experts who are “protected from political influence.”

It is incumbent upon everyone to actively work to contain and stop the spread of misinformation related to COVID-19, she said. “We must ensure the war is against the virus and not against science,” Dr. Harris said.

gtwachtman@mdedge.com

To the early trainee, often the goal of performing a colonoscopy is to reach the cecum using whatever technique necessary. Although the recommended amount of colonoscopies for safe independent practice is 140 (with some sources stating more than 500), this only relates to the safety of the patient.¹ We receive scant education on how to form good procedural habits to preserve our own safety and efficiency over the course of our career. Here are some tips on how to prevent injury:

Maintain an appropriate stance. The optimal stance during endoscopy is an athletic stance: chest out, shoulders back to facilitate ease of neck movements, and a slight bend in the knees to facilitate good blood return and distribute weight. Feet should be hip width apart with toes pointed at the endoscopy screen to allow for easy pivoting of the hips and torque of upper body if needed. Ideally, this stance is complemented by the use of proper footwear and a cushioned mat to facilitate weight distribution while standing. An athletic stance facilitates a fluidity for movements from head to toe and an ability to use larger muscles groups to accomplish fine movements.

Handle the endoscope properly. Preserve energy by understanding your equipment and how to manipulate it. Orienting the endoscope directly in front of the endoscopist for upper endoscopy, and at a 45-degree angle for colonoscopy, places the instrument at optimal location to complete the procedure.⁵ Reviewing how to perform common techniques such as retroflexion, scope reduction, and instrumentation can also facilitate improved ergonomics and adjustment of incorrect techniques at an early stage of endoscopic training. An area of particular concern for most early trainees is the amount of rotational force placed on the right wrist with administration of torque to the endoscope. This is a foreign movement for most endoscopists and requires use of smaller muscle groups of the forearms. We suggest attempting torque with internal and external rotation of the left shoulder to utilize larger muscle groups. We can also combat fatigue during the procedure with the use of microrests intermittently to reduce prolonged muscle contraction. A common way to utilize microrests is by pinning the scope to the patient’s bed with the endoscopist’s hip to provide stability of endoscope and allow removal and relaxation of the right hand. This can be done periodically throughout the procedure to provide the ability to regroup mentally and physically.

Seek feedback. Because it is difficult to focus on ergonomics while performing a diagnostic procedure, utilize your team of observers to facilitate proper form during procedure. This includes your attending gastroenterologists, nurses, and technicians who can observe posture and technique to help detect incorrect positioning early and make corrections. A common practice is to discuss areas of desired improvement before procedures to facilitate a more vigilant observation of areas for improvement.

Assess and adjust often. As early trainees, these endoscopists perform all endoscopies under the direct supervision and often with significant assistance from a supervising gastroenterologist. This can lead to a sharp differential in psychological size; it can be hard to adjust a room to your needs when you have an intimidating and demanding attending physician who has different needs. Despite this disparity, we strongly encourage all trainees to be vigilant about adjusting the room (monitors and beds) to their own needs rather than their attendings’. A great way to head off potential conflict is to discuss the ergonomic positioning of the room before you start endoscopy with your attending, nurse, and technicians so that everyone is in agreement.
 

Conclusion

We offer this article as a guide for the novice endoscopist to make small changes early to prevent injuries later. Reaching competency with our skills is difficult, and we hope it can be achieved safely with our health in mind.

Dr. Magee, first-year fellow, NCC Gastroenterology; Dr. Singla, associate program director, NCC Gastroenterology, and gastroenterology service, department of internal medicine, Walter Reed National Military Medical Center, Bethesda, Md.

References

1. Spier B et al. Colonoscopy training in gastroenterology fellowships: determining competence. Gastrointest Endosc. 2010 Feb;71(2):319-24G.

2. Malmström EM et al. A slouched body posture decreases arm mobility and changes muscle recruitment in the neck and shoulder region. Eur J Appl Physiol. 2015;115(12):2491-503.

3. Singla M et al. Training the endo-athlete: an update in ergonomics in endoscopy. Clin Gastroenterol Hepatol. 2018 Jul;16(7):1003-6.

4. Bexander CS, et al. Effect of gaze direction on neck muscle activity during cervical rotation. Exp Brain Res. 2005 Dec;167(3):422-32.

5. Soetikno R et al. Holding and manipulating the endoscope: A user’s guide. Techn Gastrointest Endosc. 2019;21:124-32.

To the early trainee, often the goal of performing a colonoscopy is to reach the cecum using whatever technique necessary. Although the recommended amount of colonoscopies for safe independent practice is 140 (with some sources stating more than 500), this only relates to the safety of the patient.¹ We receive scant education on how to form good procedural habits to preserve our own safety and efficiency over the course of our career. Here are some tips on how to prevent injury:

Maintain an appropriate stance. The optimal stance during endoscopy is an athletic stance: chest out, shoulders back to facilitate ease of neck movements, and a slight bend in the knees to facilitate good blood return and distribute weight. Feet should be hip width apart with toes pointed at the endoscopy screen to allow for easy pivoting of the hips and torque of upper body if needed. Ideally, this stance is complemented by the use of proper footwear and a cushioned mat to facilitate weight distribution while standing. An athletic stance facilitates a fluidity for movements from head to toe and an ability to use larger muscles groups to accomplish fine movements.

Handle the endoscope properly. Preserve energy by understanding your equipment and how to manipulate it. Orienting the endoscope directly in front of the endoscopist for upper endoscopy, and at a 45-degree angle for colonoscopy, places the instrument at optimal location to complete the procedure.⁵ Reviewing how to perform common techniques such as retroflexion, scope reduction, and instrumentation can also facilitate improved ergonomics and adjustment of incorrect techniques at an early stage of endoscopic training. An area of particular concern for most early trainees is the amount of rotational force placed on the right wrist with administration of torque to the endoscope. This is a foreign movement for most endoscopists and requires use of smaller muscle groups of the forearms. We suggest attempting torque with internal and external rotation of the left shoulder to utilize larger muscle groups. We can also combat fatigue during the procedure with the use of microrests intermittently to reduce prolonged muscle contraction. A common way to utilize microrests is by pinning the scope to the patient’s bed with the endoscopist’s hip to provide stability of endoscope and allow removal and relaxation of the right hand. This can be done periodically throughout the procedure to provide the ability to regroup mentally and physically.

Seek feedback. Because it is difficult to focus on ergonomics while performing a diagnostic procedure, utilize your team of observers to facilitate proper form during procedure. This includes your attending gastroenterologists, nurses, and technicians who can observe posture and technique to help detect incorrect positioning early and make corrections. A common practice is to discuss areas of desired improvement before procedures to facilitate a more vigilant observation of areas for improvement.

Assess and adjust often. As early trainees, these endoscopists perform all endoscopies under the direct supervision and often with significant assistance from a supervising gastroenterologist. This can lead to a sharp differential in psychological size; it can be hard to adjust a room to your needs when you have an intimidating and demanding attending physician who has different needs. Despite this disparity, we strongly encourage all trainees to be vigilant about adjusting the room (monitors and beds) to their own needs rather than their attendings’. A great way to head off potential conflict is to discuss the ergonomic positioning of the room before you start endoscopy with your attending, nurse, and technicians so that everyone is in agreement.
 

Conclusion

We offer this article as a guide for the novice endoscopist to make small changes early to prevent injuries later. Reaching competency with our skills is difficult, and we hope it can be achieved safely with our health in mind.

Dr. Magee, first-year fellow, NCC Gastroenterology; Dr. Singla, associate program director, NCC Gastroenterology, and gastroenterology service, department of internal medicine, Walter Reed National Military Medical Center, Bethesda, Md.

References

1. Spier B et al. Colonoscopy training in gastroenterology fellowships: determining competence. Gastrointest Endosc. 2010 Feb;71(2):319-24G.

2. Malmström EM et al. A slouched body posture decreases arm mobility and changes muscle recruitment in the neck and shoulder region. Eur J Appl Physiol. 2015;115(12):2491-503.

3. Singla M et al. Training the endo-athlete: an update in ergonomics in endoscopy. Clin Gastroenterol Hepatol. 2018 Jul;16(7):1003-6.

4. Bexander CS, et al. Effect of gaze direction on neck muscle activity during cervical rotation. Exp Brain Res. 2005 Dec;167(3):422-32.

5. Soetikno R et al. Holding and manipulating the endoscope: A user’s guide. Techn Gastrointest Endosc. 2019;21:124-32.

To the early trainee, often the goal of performing a colonoscopy is to reach the cecum using whatever technique necessary. Although the recommended amount of colonoscopies for safe independent practice is 140 (with some sources stating more than 500), this only relates to the safety of the patient.¹ We receive scant education on how to form good procedural habits to preserve our own safety and efficiency over the course of our career. Here are some tips on how to prevent injury:

Maintain an appropriate stance. The optimal stance during endoscopy is an athletic stance: chest out, shoulders back to facilitate ease of neck movements, and a slight bend in the knees to facilitate good blood return and distribute weight. Feet should be hip width apart with toes pointed at the endoscopy screen to allow for easy pivoting of the hips and torque of upper body if needed. Ideally, this stance is complemented by the use of proper footwear and a cushioned mat to facilitate weight distribution while standing. An athletic stance facilitates a fluidity for movements from head to toe and an ability to use larger muscles groups to accomplish fine movements.

Handle the endoscope properly. Preserve energy by understanding your equipment and how to manipulate it. Orienting the endoscope directly in front of the endoscopist for upper endoscopy, and at a 45-degree angle for colonoscopy, places the instrument at optimal location to complete the procedure.⁵ Reviewing how to perform common techniques such as retroflexion, scope reduction, and instrumentation can also facilitate improved ergonomics and adjustment of incorrect techniques at an early stage of endoscopic training. An area of particular concern for most early trainees is the amount of rotational force placed on the right wrist with administration of torque to the endoscope. This is a foreign movement for most endoscopists and requires use of smaller muscle groups of the forearms. We suggest attempting torque with internal and external rotation of the left shoulder to utilize larger muscle groups. We can also combat fatigue during the procedure with the use of microrests intermittently to reduce prolonged muscle contraction. A common way to utilize microrests is by pinning the scope to the patient’s bed with the endoscopist’s hip to provide stability of endoscope and allow removal and relaxation of the right hand. This can be done periodically throughout the procedure to provide the ability to regroup mentally and physically.

Seek feedback. Because it is difficult to focus on ergonomics while performing a diagnostic procedure, utilize your team of observers to facilitate proper form during procedure. This includes your attending gastroenterologists, nurses, and technicians who can observe posture and technique to help detect incorrect positioning early and make corrections. A common practice is to discuss areas of desired improvement before procedures to facilitate a more vigilant observation of areas for improvement.

Assess and adjust often. As early trainees, these endoscopists perform all endoscopies under the direct supervision and often with significant assistance from a supervising gastroenterologist. This can lead to a sharp differential in psychological size; it can be hard to adjust a room to your needs when you have an intimidating and demanding attending physician who has different needs. Despite this disparity, we strongly encourage all trainees to be vigilant about adjusting the room (monitors and beds) to their own needs rather than their attendings’. A great way to head off potential conflict is to discuss the ergonomic positioning of the room before you start endoscopy with your attending, nurse, and technicians so that everyone is in agreement.
 

Conclusion

We offer this article as a guide for the novice endoscopist to make small changes early to prevent injuries later. Reaching competency with our skills is difficult, and we hope it can be achieved safely with our health in mind.

Dr. Magee, first-year fellow, NCC Gastroenterology; Dr. Singla, associate program director, NCC Gastroenterology, and gastroenterology service, department of internal medicine, Walter Reed National Military Medical Center, Bethesda, Md.

References

1. Spier B et al. Colonoscopy training in gastroenterology fellowships: determining competence. Gastrointest Endosc. 2010 Feb;71(2):319-24G.

2. Malmström EM et al. A slouched body posture decreases arm mobility and changes muscle recruitment in the neck and shoulder region. Eur J Appl Physiol. 2015;115(12):2491-503.

3. Singla M et al. Training the endo-athlete: an update in ergonomics in endoscopy. Clin Gastroenterol Hepatol. 2018 Jul;16(7):1003-6.

4. Bexander CS, et al. Effect of gaze direction on neck muscle activity during cervical rotation. Exp Brain Res. 2005 Dec;167(3):422-32.

5. Soetikno R et al. Holding and manipulating the endoscope: A user’s guide. Techn Gastrointest Endosc. 2019;21:124-32.

Synbiotics can alter gut microbiota in patients with nonalcoholic fatty liver disease (NAFLD), but associated liver benefits remain unseen, according to a recent phase II study.

NAFLD patients who received a year-long regimen of fructo-oligosaccharides and Bifidobacterium animalis had no significant changes in liver fat content or fibrosis, compared with those who received placebo, reported lead author Eleonora Scorletti, MD, of the University of Pennsylvania, Philadelphia, and colleagues.

“There is recent growing interest in the role of gut microbiota in NAFLD pathogenesis, and there are several metaorganismal pathways linking altered gut microbiota ... and NAFLD,” the investigators wrote in Gastroenterology.According to the investigators, previous studies have shown that patients with NAFLD may have some characteristic alterations to their microbiota, such as increased Gram-negative bacteria or more abundant Ruminococcus species, the latter of which were associated with worse fibrosis.

“However, there is currently a lack of consistency in these findings due to the marked variance in the population studied, with differing ages, diets, and geographic locations,” the investigators wrote. “Nonetheless, despite these inconsistencies, there is the possibility that manipulation of the gut microbiota to a more favorable profile could provide a beneficial effect on liver disease in patients with NAFLD.”

To evaluate this possibility, the investigators enrolled 104 patients with NAFLD in the United Kingdom. Patients were randomly divided into a placebo (n = 49) and synbiotic group (n = 55), with the latter receiving 4 grams of fructo-oligosaccharides twice per day plus 10 billion colony-forming units of Bifidobacterium animalis subspecies lactis BB-12 on a daily basis. Treatments were given for 10-14 months.

Diagnostics were conducted across all participants at the beginning and end of the study. These included fecal microbiota analysis by 16s ribosomal DNA sequencing, liver fat measurement by proton magnetic resonance spectroscopy, biomarker-based liver fibrosis scoring, and liver stiffness assessment by vibration-controlled transient elastography.

At the end of the study, patients in the synbiotic group had increased abundance of Bifidobacterium and Faecalibacterium species and reduced proportions of Oscillibacter and Alistipes species, compared with baseline. These changes were not observed in the placebo group.

But changes in microbiota had no apparent impact on liver pathology. Although mean liver fat percentages dropped from 32.3% to 28.5% in the synbiotic group (approximately 4%), they also dropped in the placebo group, from 31.3% to 25.2% (approximately 6%), with differences between groups lacking statistical significance. Using multivariate analysis, the investigators linked these liver fat improvements, which occurred in 65% of participants, with weight loss.

“The fact that most patients had an improvement in ... liver fat, regardless of treatment allocation, is consistent with the so-called clinical trial effect, whereby participants benefit from participating in clinical trials,” the investigators wrote.

Similarly to liver fat content, no significant intergroup differences were found for liver fibrosis or stiffness, whereas, again, weight loss was linked with improvements in both disease parameters.

“Our randomized clinical trial suggests that changing the gut microbiota with this synbiotic may occur without clinically significant effects on the liver in NAFLD,” the investigators concluded.

Still, they noted that the failure of one synbiotic regimen does not discount the possibility of microbiota-based NAFLD interventions as a whole.

“Previous studies that have tested the effects of synbiotic treatment in NAFLD have also used a combination of multiple strains of probiotics as a component of the synbiotic treatment,” the investigators wrote. “Therefore, it might be possible that, because the intestine harbors trillions of bacteria, adding 1 single type of bacterium in a synbiotic may not be as effective as adding 3 or 6 different types of bacteria with the potential to influence many more bacterial species.”

The study was supported by the National Institute of Health Research, the Parnell Diabetes Trust, and Chr. Hansen Holding. One author reported funding from Chr. Hansen unrelated to this trial.

SOURCE: Scorletti E et al. Gastro. 2020 Jan 24. doi: 10.1053/j.gastro.2020.01.031.

Synbiotics can alter gut microbiota in patients with nonalcoholic fatty liver disease (NAFLD), but associated liver benefits remain unseen, according to a recent phase II study.

NAFLD patients who received a year-long regimen of fructo-oligosaccharides and Bifidobacterium animalis had no significant changes in liver fat content or fibrosis, compared with those who received placebo, reported lead author Eleonora Scorletti, MD, of the University of Pennsylvania, Philadelphia, and colleagues.

“There is recent growing interest in the role of gut microbiota in NAFLD pathogenesis, and there are several metaorganismal pathways linking altered gut microbiota ... and NAFLD,” the investigators wrote in Gastroenterology.According to the investigators, previous studies have shown that patients with NAFLD may have some characteristic alterations to their microbiota, such as increased Gram-negative bacteria or more abundant Ruminococcus species, the latter of which were associated with worse fibrosis.

“However, there is currently a lack of consistency in these findings due to the marked variance in the population studied, with differing ages, diets, and geographic locations,” the investigators wrote. “Nonetheless, despite these inconsistencies, there is the possibility that manipulation of the gut microbiota to a more favorable profile could provide a beneficial effect on liver disease in patients with NAFLD.”

To evaluate this possibility, the investigators enrolled 104 patients with NAFLD in the United Kingdom. Patients were randomly divided into a placebo (n = 49) and synbiotic group (n = 55), with the latter receiving 4 grams of fructo-oligosaccharides twice per day plus 10 billion colony-forming units of Bifidobacterium animalis subspecies lactis BB-12 on a daily basis. Treatments were given for 10-14 months.

Diagnostics were conducted across all participants at the beginning and end of the study. These included fecal microbiota analysis by 16s ribosomal DNA sequencing, liver fat measurement by proton magnetic resonance spectroscopy, biomarker-based liver fibrosis scoring, and liver stiffness assessment by vibration-controlled transient elastography.

At the end of the study, patients in the synbiotic group had increased abundance of Bifidobacterium and Faecalibacterium species and reduced proportions of Oscillibacter and Alistipes species, compared with baseline. These changes were not observed in the placebo group.

But changes in microbiota had no apparent impact on liver pathology. Although mean liver fat percentages dropped from 32.3% to 28.5% in the synbiotic group (approximately 4%), they also dropped in the placebo group, from 31.3% to 25.2% (approximately 6%), with differences between groups lacking statistical significance. Using multivariate analysis, the investigators linked these liver fat improvements, which occurred in 65% of participants, with weight loss.

“The fact that most patients had an improvement in ... liver fat, regardless of treatment allocation, is consistent with the so-called clinical trial effect, whereby participants benefit from participating in clinical trials,” the investigators wrote.

Similarly to liver fat content, no significant intergroup differences were found for liver fibrosis or stiffness, whereas, again, weight loss was linked with improvements in both disease parameters.

“Our randomized clinical trial suggests that changing the gut microbiota with this synbiotic may occur without clinically significant effects on the liver in NAFLD,” the investigators concluded.

Still, they noted that the failure of one synbiotic regimen does not discount the possibility of microbiota-based NAFLD interventions as a whole.

“Previous studies that have tested the effects of synbiotic treatment in NAFLD have also used a combination of multiple strains of probiotics as a component of the synbiotic treatment,” the investigators wrote. “Therefore, it might be possible that, because the intestine harbors trillions of bacteria, adding 1 single type of bacterium in a synbiotic may not be as effective as adding 3 or 6 different types of bacteria with the potential to influence many more bacterial species.”

The study was supported by the National Institute of Health Research, the Parnell Diabetes Trust, and Chr. Hansen Holding. One author reported funding from Chr. Hansen unrelated to this trial.

SOURCE: Scorletti E et al. Gastro. 2020 Jan 24. doi: 10.1053/j.gastro.2020.01.031.

Synbiotics can alter gut microbiota in patients with nonalcoholic fatty liver disease (NAFLD), but associated liver benefits remain unseen, according to a recent phase II study.

NAFLD patients who received a year-long regimen of fructo-oligosaccharides and Bifidobacterium animalis had no significant changes in liver fat content or fibrosis, compared with those who received placebo, reported lead author Eleonora Scorletti, MD, of the University of Pennsylvania, Philadelphia, and colleagues.

“There is recent growing interest in the role of gut microbiota in NAFLD pathogenesis, and there are several metaorganismal pathways linking altered gut microbiota ... and NAFLD,” the investigators wrote in Gastroenterology.According to the investigators, previous studies have shown that patients with NAFLD may have some characteristic alterations to their microbiota, such as increased Gram-negative bacteria or more abundant Ruminococcus species, the latter of which were associated with worse fibrosis.

“However, there is currently a lack of consistency in these findings due to the marked variance in the population studied, with differing ages, diets, and geographic locations,” the investigators wrote. “Nonetheless, despite these inconsistencies, there is the possibility that manipulation of the gut microbiota to a more favorable profile could provide a beneficial effect on liver disease in patients with NAFLD.”

To evaluate this possibility, the investigators enrolled 104 patients with NAFLD in the United Kingdom. Patients were randomly divided into a placebo (n = 49) and synbiotic group (n = 55), with the latter receiving 4 grams of fructo-oligosaccharides twice per day plus 10 billion colony-forming units of Bifidobacterium animalis subspecies lactis BB-12 on a daily basis. Treatments were given for 10-14 months.

Diagnostics were conducted across all participants at the beginning and end of the study. These included fecal microbiota analysis by 16s ribosomal DNA sequencing, liver fat measurement by proton magnetic resonance spectroscopy, biomarker-based liver fibrosis scoring, and liver stiffness assessment by vibration-controlled transient elastography.

At the end of the study, patients in the synbiotic group had increased abundance of Bifidobacterium and Faecalibacterium species and reduced proportions of Oscillibacter and Alistipes species, compared with baseline. These changes were not observed in the placebo group.

But changes in microbiota had no apparent impact on liver pathology. Although mean liver fat percentages dropped from 32.3% to 28.5% in the synbiotic group (approximately 4%), they also dropped in the placebo group, from 31.3% to 25.2% (approximately 6%), with differences between groups lacking statistical significance. Using multivariate analysis, the investigators linked these liver fat improvements, which occurred in 65% of participants, with weight loss.

“The fact that most patients had an improvement in ... liver fat, regardless of treatment allocation, is consistent with the so-called clinical trial effect, whereby participants benefit from participating in clinical trials,” the investigators wrote.

Similarly to liver fat content, no significant intergroup differences were found for liver fibrosis or stiffness, whereas, again, weight loss was linked with improvements in both disease parameters.

“Our randomized clinical trial suggests that changing the gut microbiota with this synbiotic may occur without clinically significant effects on the liver in NAFLD,” the investigators concluded.

Still, they noted that the failure of one synbiotic regimen does not discount the possibility of microbiota-based NAFLD interventions as a whole.

“Previous studies that have tested the effects of synbiotic treatment in NAFLD have also used a combination of multiple strains of probiotics as a component of the synbiotic treatment,” the investigators wrote. “Therefore, it might be possible that, because the intestine harbors trillions of bacteria, adding 1 single type of bacterium in a synbiotic may not be as effective as adding 3 or 6 different types of bacteria with the potential to influence many more bacterial species.”

The study was supported by the National Institute of Health Research, the Parnell Diabetes Trust, and Chr. Hansen Holding. One author reported funding from Chr. Hansen unrelated to this trial.

SOURCE: Scorletti E et al. Gastro. 2020 Jan 24. doi: 10.1053/j.gastro.2020.01.031.

Stratifying diagnostic cut-off values of tumor markers based on genetic variants may improve detection of pancreatic cancer, according to investigators.

Stratification had the greatest positive impact on accuracy of carbohydrate antigen 19-9 (CA19-9), reported lead author Toshiya Abe, MD, PhD, of Johns Hopkins Hospital, Baltimore, and colleagues.

“Despite the evidence that genetic factors influence tumor marker levels, the potential utility of using a genetic test to improve the interpretation of tumor markers has drawn limited attention,” the investigators wrote in Clinical Gastroenterology and Hepatology.

And improvements are needed, the investigators noted, particularly for early cancer detection in high-risk individuals.

“[T]he toughest hurdle for a pancreatic cancer detection blood test is the detection of stage I disease,” the investigators wrote. “Cancers generally shed biomarkers in proportion to their size, and small stage I pancreatic cancers shed fewer diagnostic biomarkers into the circulation, making diagnosis more difficult.”

Although a 2016 study by Dr. Guopei Luo and colleagues demonstrated that diagnostic accuracy of CA19-9 could be improved via genotyping, tumor marker performance was not characterized by high-specificity cut-off values, which the present study aimed to do.

The control group included 504 high-risk individuals who were prospectively enrolled in the Cancer of the Pancreas Screening (CAPS) studies from 2002 to 2018, while the case group included 245 patients with pancreatic ductal adenocarcinoma (PDAC) who underwent resection at Johns Hopkins from 2010 to 2017.

The control group was randomly divided into discovery and validation sets in order to achieve 99% specificity cut-off values, which were used to measure sensitivity in the case group. According to the investigators, high-specificity cut-off values are necessary for surveillance of asymptomatic high-risk individuals in order to minimize false-positive results.

In all patients, tumor markers and genotype were analyzed. Tumor markers included carcinoembryonic antigen (CEA), CA19-9, and cancer antigen 125 (CA-125). Genotyping included 16 single-nucleotide polymorphisms (SNPs) in 9 genes, including FUT2 and FUT3, which are known to influence levels of CA19-9.

In contrast with previous findings, which identified three relevant subgroups of FUT2/FUT3, the present study found that four distinct subgroups were significantly associated with CA19-9 levels: FUT3-null, FUT3+/-, FUT3+/+, and FUT2-null.

When CA19-9 cut-off levels were stratified by these four subgroups and applied to the 245 patients with pancreatic cancer, the investigators achieved a sensitivity of 60.8%, compared with 52.7% without stratification. The new cut-off values led to reclassification of 28 (11.4%) patients with pancreatic cancer, including 24 who switched from negative to positive, and 4 who switched from positive to negative.

Sensitivity of the SNP-adjusted CA19-9 test was improved to 66.4% when used exclusively in patients with functional FUT3 genes. Conversely, sensitivity was markedly lower, at 36.7%, when the test was used for patients with stage I disease.

While CA19-9 testing was notably improved by SNP-based stratification, results from CEA and CA-125 testing were more modest. Standard CEA testing had a sensitivity of 13.8%, compared with 15.9% when cut-off values were stratified by FUT2 status and ABO blood group. Similarly, modifying CA-125 values based on SNPs in GAL3ST2 raised sensitivity from 15.5% to 17.6%.

Although combining SNP-modified tumor marker results did increase overall sensitivity to as high as 66.1%, this also reduced specificity to as low as 95.4%

Still, Dr. Abe and colleagues suggested that the findings demonstrate proof of concept.

“Our results show that a tumor marker SNP test can improve the diagnostic accuracy of CA19-9 and, to a lesser extent, CEA and CA-125, but further work is needed to improve the diagnostic accuracy of our panel for the detection of early-stage pancreatic cancer,” they concluded.

The investigators also suggested that the technique could have value for surveillance of ovarian cancer; however, again, they emphasized the need for more research.The study was funded by the National Institutes of Health, Susan Wojcicki and Dennis Troper, the Pancreatic Cancer Action Network, and others. The investigators reported no conflicts of interest.

SOURCE: Abe T et al. Clin Gastro Hepatol. 2019 Oct 29. doi: 10.1016/j.cgh.2019.10.036.

Stratifying diagnostic cut-off values of tumor markers based on genetic variants may improve detection of pancreatic cancer, according to investigators.

Stratification had the greatest positive impact on accuracy of carbohydrate antigen 19-9 (CA19-9), reported lead author Toshiya Abe, MD, PhD, of Johns Hopkins Hospital, Baltimore, and colleagues.

“Despite the evidence that genetic factors influence tumor marker levels, the potential utility of using a genetic test to improve the interpretation of tumor markers has drawn limited attention,” the investigators wrote in Clinical Gastroenterology and Hepatology.

And improvements are needed, the investigators noted, particularly for early cancer detection in high-risk individuals.

“[T]he toughest hurdle for a pancreatic cancer detection blood test is the detection of stage I disease,” the investigators wrote. “Cancers generally shed biomarkers in proportion to their size, and small stage I pancreatic cancers shed fewer diagnostic biomarkers into the circulation, making diagnosis more difficult.”

Although a 2016 study by Dr. Guopei Luo and colleagues demonstrated that diagnostic accuracy of CA19-9 could be improved via genotyping, tumor marker performance was not characterized by high-specificity cut-off values, which the present study aimed to do.

The control group included 504 high-risk individuals who were prospectively enrolled in the Cancer of the Pancreas Screening (CAPS) studies from 2002 to 2018, while the case group included 245 patients with pancreatic ductal adenocarcinoma (PDAC) who underwent resection at Johns Hopkins from 2010 to 2017.

The control group was randomly divided into discovery and validation sets in order to achieve 99% specificity cut-off values, which were used to measure sensitivity in the case group. According to the investigators, high-specificity cut-off values are necessary for surveillance of asymptomatic high-risk individuals in order to minimize false-positive results.

In all patients, tumor markers and genotype were analyzed. Tumor markers included carcinoembryonic antigen (CEA), CA19-9, and cancer antigen 125 (CA-125). Genotyping included 16 single-nucleotide polymorphisms (SNPs) in 9 genes, including FUT2 and FUT3, which are known to influence levels of CA19-9.

In contrast with previous findings, which identified three relevant subgroups of FUT2/FUT3, the present study found that four distinct subgroups were significantly associated with CA19-9 levels: FUT3-null, FUT3+/-, FUT3+/+, and FUT2-null.

When CA19-9 cut-off levels were stratified by these four subgroups and applied to the 245 patients with pancreatic cancer, the investigators achieved a sensitivity of 60.8%, compared with 52.7% without stratification. The new cut-off values led to reclassification of 28 (11.4%) patients with pancreatic cancer, including 24 who switched from negative to positive, and 4 who switched from positive to negative.

Sensitivity of the SNP-adjusted CA19-9 test was improved to 66.4% when used exclusively in patients with functional FUT3 genes. Conversely, sensitivity was markedly lower, at 36.7%, when the test was used for patients with stage I disease.

While CA19-9 testing was notably improved by SNP-based stratification, results from CEA and CA-125 testing were more modest. Standard CEA testing had a sensitivity of 13.8%, compared with 15.9% when cut-off values were stratified by FUT2 status and ABO blood group. Similarly, modifying CA-125 values based on SNPs in GAL3ST2 raised sensitivity from 15.5% to 17.6%.

Although combining SNP-modified tumor marker results did increase overall sensitivity to as high as 66.1%, this also reduced specificity to as low as 95.4%

Still, Dr. Abe and colleagues suggested that the findings demonstrate proof of concept.

“Our results show that a tumor marker SNP test can improve the diagnostic accuracy of CA19-9 and, to a lesser extent, CEA and CA-125, but further work is needed to improve the diagnostic accuracy of our panel for the detection of early-stage pancreatic cancer,” they concluded.

The investigators also suggested that the technique could have value for surveillance of ovarian cancer; however, again, they emphasized the need for more research.The study was funded by the National Institutes of Health, Susan Wojcicki and Dennis Troper, the Pancreatic Cancer Action Network, and others. The investigators reported no conflicts of interest.

SOURCE: Abe T et al. Clin Gastro Hepatol. 2019 Oct 29. doi: 10.1016/j.cgh.2019.10.036.

Stratifying diagnostic cut-off values of tumor markers based on genetic variants may improve detection of pancreatic cancer, according to investigators.

Stratification had the greatest positive impact on accuracy of carbohydrate antigen 19-9 (CA19-9), reported lead author Toshiya Abe, MD, PhD, of Johns Hopkins Hospital, Baltimore, and colleagues.

“Despite the evidence that genetic factors influence tumor marker levels, the potential utility of using a genetic test to improve the interpretation of tumor markers has drawn limited attention,” the investigators wrote in Clinical Gastroenterology and Hepatology.

And improvements are needed, the investigators noted, particularly for early cancer detection in high-risk individuals.

“[T]he toughest hurdle for a pancreatic cancer detection blood test is the detection of stage I disease,” the investigators wrote. “Cancers generally shed biomarkers in proportion to their size, and small stage I pancreatic cancers shed fewer diagnostic biomarkers into the circulation, making diagnosis more difficult.”

Although a 2016 study by Dr. Guopei Luo and colleagues demonstrated that diagnostic accuracy of CA19-9 could be improved via genotyping, tumor marker performance was not characterized by high-specificity cut-off values, which the present study aimed to do.

The control group included 504 high-risk individuals who were prospectively enrolled in the Cancer of the Pancreas Screening (CAPS) studies from 2002 to 2018, while the case group included 245 patients with pancreatic ductal adenocarcinoma (PDAC) who underwent resection at Johns Hopkins from 2010 to 2017.

The control group was randomly divided into discovery and validation sets in order to achieve 99% specificity cut-off values, which were used to measure sensitivity in the case group. According to the investigators, high-specificity cut-off values are necessary for surveillance of asymptomatic high-risk individuals in order to minimize false-positive results.

In all patients, tumor markers and genotype were analyzed. Tumor markers included carcinoembryonic antigen (CEA), CA19-9, and cancer antigen 125 (CA-125). Genotyping included 16 single-nucleotide polymorphisms (SNPs) in 9 genes, including FUT2 and FUT3, which are known to influence levels of CA19-9.

In contrast with previous findings, which identified three relevant subgroups of FUT2/FUT3, the present study found that four distinct subgroups were significantly associated with CA19-9 levels: FUT3-null, FUT3+/-, FUT3+/+, and FUT2-null.

When CA19-9 cut-off levels were stratified by these four subgroups and applied to the 245 patients with pancreatic cancer, the investigators achieved a sensitivity of 60.8%, compared with 52.7% without stratification. The new cut-off values led to reclassification of 28 (11.4%) patients with pancreatic cancer, including 24 who switched from negative to positive, and 4 who switched from positive to negative.

Sensitivity of the SNP-adjusted CA19-9 test was improved to 66.4% when used exclusively in patients with functional FUT3 genes. Conversely, sensitivity was markedly lower, at 36.7%, when the test was used for patients with stage I disease.

While CA19-9 testing was notably improved by SNP-based stratification, results from CEA and CA-125 testing were more modest. Standard CEA testing had a sensitivity of 13.8%, compared with 15.9% when cut-off values were stratified by FUT2 status and ABO blood group. Similarly, modifying CA-125 values based on SNPs in GAL3ST2 raised sensitivity from 15.5% to 17.6%.

Although combining SNP-modified tumor marker results did increase overall sensitivity to as high as 66.1%, this also reduced specificity to as low as 95.4%

Still, Dr. Abe and colleagues suggested that the findings demonstrate proof of concept.

“Our results show that a tumor marker SNP test can improve the diagnostic accuracy of CA19-9 and, to a lesser extent, CEA and CA-125, but further work is needed to improve the diagnostic accuracy of our panel for the detection of early-stage pancreatic cancer,” they concluded.

The investigators also suggested that the technique could have value for surveillance of ovarian cancer; however, again, they emphasized the need for more research.The study was funded by the National Institutes of Health, Susan Wojcicki and Dennis Troper, the Pancreatic Cancer Action Network, and others. The investigators reported no conflicts of interest.

SOURCE: Abe T et al. Clin Gastro Hepatol. 2019 Oct 29. doi: 10.1016/j.cgh.2019.10.036.

Obstructive sleep apnea (OSA) is a common disorder in the US and other industrialized countries. The Wisconsin Sleep Cohort Study reported prevalence rates as high as 20% to 30% in men and 10% to 15% in women.^1,2 Several studies have shown high prevalence of OSA among veterans. Ancoli-Israel and colleagues reported a OSA rate of 36% in a cohort of elderly patients at a US Department of Veterans Affairs (VA) medical center.³ A study by Kreis and colleagues showed that OSA was present in 27% of patients hospitalized on the medical ward at a VA hospital.⁴ Incidence of sleep apnea among veterans in the US will likely increase over time as obesity is becoming more prevalent. Rates of obesity have increased from 14% in 2000 to 18% in 2010 among both male and female veterans.⁵

Untreated OSA is associated with increased risk of coronary artery disease, cerebrovascular accidents, uncontrolled diabetes mellitus, and other complications. Patients with OSA are less productive, have increased health care utilization, and have a higher risk of motor vehicle accidents.⁶ Continuous positive airway pressure (CPAP) is the main form of treatment of OSA. However, despite the adverse outcomes of untreated sleep apnea, suboptimal CPAP adherence remains a major problem in clinical practice. When adherence is defined as > 4 hours of nightly use, 29% to 83% of patients with OSA have been reported to be nonadherent to treatment.⁷ Stepnowsky and colleagues estimated that 50% of patients with OSA for whom CPAP was recommended were no longer using it 1 year later.⁸ CPAP adherence among veterans also has been poor. Wallace and colleagues reported that about one-third of patients with OSA at a VA Miami Healthcare System had mean daily use ≥ 4 hours.⁹ Typical reasons for poor CPAP adherence include pressure intolerance, mask discomfort, nasal and oropharyngeal dryness and irritation.¹⁰ Development and implementation of alternate treatment strategies for OSA is important to reduce disease burden of this widespread and debilitating condition.

Upper airway stimulation (UAS) is a novel therapy for management of OSA that has been gaining popularity and acceptance within the sleep medicine community in the past few years. This treatment option involves implantation of a neurostimulator with a sensing lead and a stimulation lead. The device is similar to a pacemaker and is surgically implanted in chest wall. The sensing lead is placed close to the diaphragm for monitoring of pleural pressure to help assess ventilation. The stimulation lead is placed under the tongue in proximity to the hypoglossal nerve (cranial nerve XII). The neurostimulator delivers electrical pulses to the hypoglossal nerve through the stimulation lead. These stimulating pulses are synchronized with the ventilation detected by the sensing lead. This electrical stimulation results in anterior displacement of the tongue via action of the genioglossus and geniohyoid muscles. Mechanical coupling with the palate also is common and leads to additional airway opening within the oropharynx to prevent apneic episodes. The patient turns on the stimulation through the use of a portable remote control and is turned off in the morning. The patient is able to operate the UAS device by placing the remote control on the skin in proximity of the device. The patient also is able to adjust device voltage within a range set by their physician. The effective voltage range is determined via an overnight sleep study titration performed 1 month after device activation. UAS therapy is not considered first-line treatment for OSA as it requires surgical implantation under general anesthesia; however, it provides an alternative to patients with OSA who are unable to tolerate traditional therapy with CPAP.

The landmark Stimulation Therapy for Apnea Reduction (STAR) trial showed effectiveness of UAS therapy at 12 months postimplantation.¹¹ Follow-up of these participants has proven the sustainability of this effect at 18, 24, 36, and 48 months of therapy.^12-15 Inclusion criteria of the study was moderate-to-severe sleep apnea with predominantly obstructive events. Subjects were excluded if there were anatomical abnormalities of the upper airway or if the pattern of airway collapse was not conducive to UAS on sedated endoscopy evaluation. Participants in the trial were predominantly white males, the average age was 54.5 years, and the average body mass index (BMI) was 28.4. The outcomes measured included Functional Outcomes of Sleep Questionnaire, Epworth Sleepiness Scale (ESS), percentage of sleep time with oxygen saturation < 90%, and subjective snoring. All of these objective and subjective markers of sleep improved significantly with UAS therapy at 12 months and were maintained at improved levels at 48 months of therapy.

The adverse effects (AEs) associated with device implantation and subsequent UAS therapy have been infrequent and mostly transient. Out of 126 device implantations, there were 2 participants who had serious AEs due to implantation and required repositioning and fixation of the neurostimulator to resolve discomfort. Other AEs related to the procedure, including sore throat and muscle soreness, were considered nonserious and resolved with supportive care. AEs related to subsequent UAS therapy included temporary tongue weakness and tongue soreness/abrasion. These complications also have either resolved spontaneously or with use of supportive strategies such as a mouth guard. Due to the sustained clinical benefit and acceptable AE profile as demonstrated by the STAR trial, UAS has emerged as a realistic alternative for management of OSA.

Development of a successful program that provides and supports all aspects of UAS, including device implantation and follow-up, necessitates a multispecialty team approach. Ideally surgical and nonsurgical sleep physicians as well as clinical and administrative support staff should be part of this group.

This study is based on the experience of the development of the UAS program at the Clement J. Zablocki VA Medical Center (CJZ VAMC) in Milwaukee. Currently, there are 25 patients who are part of this UAS program. The inclusion and exclusion criteria were adopted from the STAR trial. The patient population is similar to the population in that trial. They are all white males with average age of 57.2 years and BMI of 31.3. The CJZVAMC UAS Program consists of multidisciplinary group of health care professionals. This article describes the role of a nonsurgical sleep medicine physician that was crucial in the development of this UAS program.

Process

Introduction of this novel alternative therapy has sparked much interest among health care providers (HCPs) at CJZVAMC. However, there has been much misunderstanding among patients and HCPs about what this treatment involves and how it is implemented. For example, many patients that called the sleep clinic to set up an evaluation for UAS did not realize that this is a surgical procedure that requires general anesthesia. One of the most important tasks for a nonsurgical sleep physician is to educate patients and HCPs about this therapy. Most of patient education at CJZVAMC has been done during individual clinic appointments; however, setting up group educational classes for patients is a more efficient strategy to deliver this information. Similarly, giving a lecture on UAS at medicine (or another specialty) grand rounds has been effective in the education of HCPs who refer patients to the sleep clinic. If possible, a combined lecture with a surgical colleague could provide a more balanced and complete depiction of UAS and help to answer a broader range of questions for the audience.

Screening

Screening and identification of appropriate candidates is an important first step in the patient pathway in the UAS therapy. Failure of CPAP therapy is a key starting point in this screening process. When patients present to the sleep clinic with difficulty tolerating CPAP therapy, an extensive and thorough troubleshooting process needs to take place to make sure that all CPAP options have been exhausted. This process would typically include trial of various masks, including different mask interfaces. A dedicated appointment with a registered polysomnographic technologist (RPSGT) or another clinic staff member with vast experience in PAP mask fitting is typically part of this effort.

Adjustment of CPAP pressure settings also may be helpful as high PAP pressure may be another obstacle. Patients frequently have trouble tolerating higher pressure settings especially when they are new to this therapy. Pressure restriction to 4-cm to 7-cm water pressure on auto CPAP has been a helpful technique to allow patients to become more comfortable with this therapy. Once patients are able to use PAP at lower pressures, these settings can be titrated up gradually for optimal effectiveness. Other desensitization techniques, such as use during daytime while distracted by other activities (such as watching TV) can be helpful in adjustment to PAP therapy. Addressing problems with nasal congestion can help improve PAP adherence. Finally, patients should be offered opportunities for education about their PAP machine on an ongoing basis. Lack of proficiency with humidifier use is a very common obstacle and frequently leads to PAP nonadherence. Teaching PAP operation should correspond to the patient’s level of education to be effective. PAP therapy remains the first-line treatment strategy for OSA as it is not invasive and highly effective. Nonsurgical sleep medicine physicians are uniquely positioned to implement and troubleshoot this therapy for sleep apnea patients before considering UAS.

As part of the screening process, it can be helpful to conduct routine multidisciplinary meetings to discuss patients who are being evaluated for UAS implantation. These meetings should include the otolaryngologist, nonsurgical sleep medicine physician, as well as additional staff (nurses, respiratory therapists, etc) who are involved in the UAS process. Having a mental health care provider as part of the multidisciplinary team during the screening process also could be a valuable addition as this specialist could evaluate and provide insight into a patient’s emotional status prior to implantation. This is common practice during evaluation for organ transplantation and would help to predict patient’s psychological well-being after this life-changing procedure.¹⁶ Having multidisciplinary agreement on patient’s candidacy for UAS therapy could improve long-term success of this treatment. Additionally, these multidisciplinary meetings as part of the UAS program can improve team camaraderie and prevent miscommunications during this therapy.

Drug-Induced Sedated Endoscopy

Patient pathway to neurostimulator implantation involves evaluation of the upper airway using drug-induced sedated endoscopy (DISE). This procedure helps determine whether the patient’s anatomy is appropriate for UAS. DISE also can evaluate the pattern of airway closure during an apneic episode. Anterior-posterior pattern of closure is associated with greater UAS effectiveness compared with concentric pattern of airway closure. DISE is typically performed by the otolaryngologist scheduled to implant the UAS. However, nonsurgical physicians who are part of the patient’s care team can be trained to perform this procedure especially if they have experience in performing endoscopy of the upper airway (such as a pulmonary specialist). This can make the evaluation process more efficient and dramatically improve access to care.

Coordination of Care

In order for the UAS program to be successful, the patient’s care team has to work closely with the device manufacturer throughout the implantation pathway and for ongoing patient care. The device manufacturer can assist with education of HCPs, surgical physicians, clinical support staff, and the patient. However, an even more essential role for industry support is during UAS device activation and subsequent titration of UAS via an overnight in-laboratory sleep study.

After surgical implantation, the UAS device activation can be performed in the nonsurgical sleep clinic and is done about 1 month later. This period allows for tissue healing after the surgery and for the patient to get accustomed to having this new device in their body. This activation can be done with assistance from an industry technician until the HCP is comfortable with this process. The multidisciplinary UAS team could choose to delegate device activation to a technician with specialized relevant training, such as RPSGT or respiratory therapist (RT).

This procedure involves determination of sensory and functional threshold for UAS. Sensory threshold is minimum voltage required for the patient to feel the stimulation. The functional threshold is the minimum voltage required to move the tongue past the lower front teeth during stimulation. After these thresholds are established, a voltage range is set on the device. The voltage at functional threshold is typically set at the lower level of this range, and the maximum level is set at 1 volt higher. Patients are able to adjust voltage within this range and are instructed to increase the voltage gradually (0.1-volt increments) while maintaining levels that are comfortable during sleep.

About a month after device activation, patients undergo another overnight polysomnogram for titration of UAS device. In order to educate and train the institutional RPSGT on how to perform this type of titration, an industry technician is required for the first few overnight titrations. The goal of this study is to establish appropriate voltage to resolve sleep-disordered breathing and insure patient comfort at this setting. Patients typically leave the study with a new voltage range. They are asked to keep effective voltage in mind and make appropriate adjustments to maintain comfortable therapy.

Successful UAS therapy includes multiple steps, such as implantation, activation, and titration. This protocol requires effective coordination of care that includes communication with surgical staff, patients, support staff, and industry liaison. Nonsurgical sleep medicine physicians can play a vital role by helping to coordinate care at the early stages of UAS therapy and facilitate effective communication among various providers involved in this process.

Follow-Up

After completion of the initial therapeutic pathway, patients continue to follow up regularly, monitoring for AEs from UAS therapy and sleep apnea symptoms. Patients can be followed in the nonsurgical sleep clinic after the initial postoperative appointment with the surgeon. Frequency of follow-up depends on the presence and severity of any AEs and residual symptoms of sleep apnea. Even though most AEs related to UAS therapy reported in the STAR trial were nonserious and transient, 2% of participants required surgical revision.³ Therefore, maintaining open channels of communication among the entire UAS patient care team even months and years after surgical implantation is important. The nonsurgical sleep medicine physician who will continue to monitor the patient’s progress may need to consult with the surgical colleague or industry liaison at any point during treatment.
 

Limitations

This review outlines the UAS therapy pathway and emphasizes the role of the nonsurgical sleep medicine provider. However, the experience describes a UAS program development at a single VA medical center. Since this UAS device and therapy have already been approved by the VA on a national level, we did not face any challenges with authorization and insurance compensation. Therefore, this review does not provide any guidance with these matters. These are certainly common concerns for sleep medicine providers who offer UAS therapy in medical practices outside the VA, and these would hopefully be addressed in the future.

Furthermore, this review is based on the pulmonary sleep medicine provider’s experience and perspective. Therefore, certain aspects of UAS therapy could be better addressed by nonsurgical sleep medicine providers in different fields of expertise. For example, a study by a psychiatrist or psychologist could provide insight into the emotional concerns of patients who are undergoing this novel and life-altering treatment that includes surgical implantation of hardware into the body. A neurologist could explore the long-term effects of recurrent electrical stimulation on the autonomic and somatic nervous system as well as the musculature of the upper airway.

Conclusion

Multidisciplinary perspectives are needed to provide guidance for practitioners and institutions looking to set up and improve established UAS programs. As the long-term outcomes of the STAR trial continue to be published and provide more validation for UAS, this novel therapy will likely continue to gain acceptance as a safe and effective treatment for OSA.¹¹

Obstructive sleep apnea (OSA) is a common disorder in the US and other industrialized countries. The Wisconsin Sleep Cohort Study reported prevalence rates as high as 20% to 30% in men and 10% to 15% in women.^1,2 Several studies have shown high prevalence of OSA among veterans. Ancoli-Israel and colleagues reported a OSA rate of 36% in a cohort of elderly patients at a US Department of Veterans Affairs (VA) medical center.³ A study by Kreis and colleagues showed that OSA was present in 27% of patients hospitalized on the medical ward at a VA hospital.⁴ Incidence of sleep apnea among veterans in the US will likely increase over time as obesity is becoming more prevalent. Rates of obesity have increased from 14% in 2000 to 18% in 2010 among both male and female veterans.⁵

Untreated OSA is associated with increased risk of coronary artery disease, cerebrovascular accidents, uncontrolled diabetes mellitus, and other complications. Patients with OSA are less productive, have increased health care utilization, and have a higher risk of motor vehicle accidents.⁶ Continuous positive airway pressure (CPAP) is the main form of treatment of OSA. However, despite the adverse outcomes of untreated sleep apnea, suboptimal CPAP adherence remains a major problem in clinical practice. When adherence is defined as > 4 hours of nightly use, 29% to 83% of patients with OSA have been reported to be nonadherent to treatment.⁷ Stepnowsky and colleagues estimated that 50% of patients with OSA for whom CPAP was recommended were no longer using it 1 year later.⁸ CPAP adherence among veterans also has been poor. Wallace and colleagues reported that about one-third of patients with OSA at a VA Miami Healthcare System had mean daily use ≥ 4 hours.⁹ Typical reasons for poor CPAP adherence include pressure intolerance, mask discomfort, nasal and oropharyngeal dryness and irritation.¹⁰ Development and implementation of alternate treatment strategies for OSA is important to reduce disease burden of this widespread and debilitating condition.

Upper airway stimulation (UAS) is a novel therapy for management of OSA that has been gaining popularity and acceptance within the sleep medicine community in the past few years. This treatment option involves implantation of a neurostimulator with a sensing lead and a stimulation lead. The device is similar to a pacemaker and is surgically implanted in chest wall. The sensing lead is placed close to the diaphragm for monitoring of pleural pressure to help assess ventilation. The stimulation lead is placed under the tongue in proximity to the hypoglossal nerve (cranial nerve XII). The neurostimulator delivers electrical pulses to the hypoglossal nerve through the stimulation lead. These stimulating pulses are synchronized with the ventilation detected by the sensing lead. This electrical stimulation results in anterior displacement of the tongue via action of the genioglossus and geniohyoid muscles. Mechanical coupling with the palate also is common and leads to additional airway opening within the oropharynx to prevent apneic episodes. The patient turns on the stimulation through the use of a portable remote control and is turned off in the morning. The patient is able to operate the UAS device by placing the remote control on the skin in proximity of the device. The patient also is able to adjust device voltage within a range set by their physician. The effective voltage range is determined via an overnight sleep study titration performed 1 month after device activation. UAS therapy is not considered first-line treatment for OSA as it requires surgical implantation under general anesthesia; however, it provides an alternative to patients with OSA who are unable to tolerate traditional therapy with CPAP.

The landmark Stimulation Therapy for Apnea Reduction (STAR) trial showed effectiveness of UAS therapy at 12 months postimplantation.¹¹ Follow-up of these participants has proven the sustainability of this effect at 18, 24, 36, and 48 months of therapy.^12-15 Inclusion criteria of the study was moderate-to-severe sleep apnea with predominantly obstructive events. Subjects were excluded if there were anatomical abnormalities of the upper airway or if the pattern of airway collapse was not conducive to UAS on sedated endoscopy evaluation. Participants in the trial were predominantly white males, the average age was 54.5 years, and the average body mass index (BMI) was 28.4. The outcomes measured included Functional Outcomes of Sleep Questionnaire, Epworth Sleepiness Scale (ESS), percentage of sleep time with oxygen saturation < 90%, and subjective snoring. All of these objective and subjective markers of sleep improved significantly with UAS therapy at 12 months and were maintained at improved levels at 48 months of therapy.

The adverse effects (AEs) associated with device implantation and subsequent UAS therapy have been infrequent and mostly transient. Out of 126 device implantations, there were 2 participants who had serious AEs due to implantation and required repositioning and fixation of the neurostimulator to resolve discomfort. Other AEs related to the procedure, including sore throat and muscle soreness, were considered nonserious and resolved with supportive care. AEs related to subsequent UAS therapy included temporary tongue weakness and tongue soreness/abrasion. These complications also have either resolved spontaneously or with use of supportive strategies such as a mouth guard. Due to the sustained clinical benefit and acceptable AE profile as demonstrated by the STAR trial, UAS has emerged as a realistic alternative for management of OSA.

Development of a successful program that provides and supports all aspects of UAS, including device implantation and follow-up, necessitates a multispecialty team approach. Ideally surgical and nonsurgical sleep physicians as well as clinical and administrative support staff should be part of this group.

This study is based on the experience of the development of the UAS program at the Clement J. Zablocki VA Medical Center (CJZ VAMC) in Milwaukee. Currently, there are 25 patients who are part of this UAS program. The inclusion and exclusion criteria were adopted from the STAR trial. The patient population is similar to the population in that trial. They are all white males with average age of 57.2 years and BMI of 31.3. The CJZVAMC UAS Program consists of multidisciplinary group of health care professionals. This article describes the role of a nonsurgical sleep medicine physician that was crucial in the development of this UAS program.

Process

Introduction of this novel alternative therapy has sparked much interest among health care providers (HCPs) at CJZVAMC. However, there has been much misunderstanding among patients and HCPs about what this treatment involves and how it is implemented. For example, many patients that called the sleep clinic to set up an evaluation for UAS did not realize that this is a surgical procedure that requires general anesthesia. One of the most important tasks for a nonsurgical sleep physician is to educate patients and HCPs about this therapy. Most of patient education at CJZVAMC has been done during individual clinic appointments; however, setting up group educational classes for patients is a more efficient strategy to deliver this information. Similarly, giving a lecture on UAS at medicine (or another specialty) grand rounds has been effective in the education of HCPs who refer patients to the sleep clinic. If possible, a combined lecture with a surgical colleague could provide a more balanced and complete depiction of UAS and help to answer a broader range of questions for the audience.

Screening

Screening and identification of appropriate candidates is an important first step in the patient pathway in the UAS therapy. Failure of CPAP therapy is a key starting point in this screening process. When patients present to the sleep clinic with difficulty tolerating CPAP therapy, an extensive and thorough troubleshooting process needs to take place to make sure that all CPAP options have been exhausted. This process would typically include trial of various masks, including different mask interfaces. A dedicated appointment with a registered polysomnographic technologist (RPSGT) or another clinic staff member with vast experience in PAP mask fitting is typically part of this effort.

Adjustment of CPAP pressure settings also may be helpful as high PAP pressure may be another obstacle. Patients frequently have trouble tolerating higher pressure settings especially when they are new to this therapy. Pressure restriction to 4-cm to 7-cm water pressure on auto CPAP has been a helpful technique to allow patients to become more comfortable with this therapy. Once patients are able to use PAP at lower pressures, these settings can be titrated up gradually for optimal effectiveness. Other desensitization techniques, such as use during daytime while distracted by other activities (such as watching TV) can be helpful in adjustment to PAP therapy. Addressing problems with nasal congestion can help improve PAP adherence. Finally, patients should be offered opportunities for education about their PAP machine on an ongoing basis. Lack of proficiency with humidifier use is a very common obstacle and frequently leads to PAP nonadherence. Teaching PAP operation should correspond to the patient’s level of education to be effective. PAP therapy remains the first-line treatment strategy for OSA as it is not invasive and highly effective. Nonsurgical sleep medicine physicians are uniquely positioned to implement and troubleshoot this therapy for sleep apnea patients before considering UAS.

As part of the screening process, it can be helpful to conduct routine multidisciplinary meetings to discuss patients who are being evaluated for UAS implantation. These meetings should include the otolaryngologist, nonsurgical sleep medicine physician, as well as additional staff (nurses, respiratory therapists, etc) who are involved in the UAS process. Having a mental health care provider as part of the multidisciplinary team during the screening process also could be a valuable addition as this specialist could evaluate and provide insight into a patient’s emotional status prior to implantation. This is common practice during evaluation for organ transplantation and would help to predict patient’s psychological well-being after this life-changing procedure.¹⁶ Having multidisciplinary agreement on patient’s candidacy for UAS therapy could improve long-term success of this treatment. Additionally, these multidisciplinary meetings as part of the UAS program can improve team camaraderie and prevent miscommunications during this therapy.

Drug-Induced Sedated Endoscopy

Patient pathway to neurostimulator implantation involves evaluation of the upper airway using drug-induced sedated endoscopy (DISE). This procedure helps determine whether the patient’s anatomy is appropriate for UAS. DISE also can evaluate the pattern of airway closure during an apneic episode. Anterior-posterior pattern of closure is associated with greater UAS effectiveness compared with concentric pattern of airway closure. DISE is typically performed by the otolaryngologist scheduled to implant the UAS. However, nonsurgical physicians who are part of the patient’s care team can be trained to perform this procedure especially if they have experience in performing endoscopy of the upper airway (such as a pulmonary specialist). This can make the evaluation process more efficient and dramatically improve access to care.

Coordination of Care

In order for the UAS program to be successful, the patient’s care team has to work closely with the device manufacturer throughout the implantation pathway and for ongoing patient care. The device manufacturer can assist with education of HCPs, surgical physicians, clinical support staff, and the patient. However, an even more essential role for industry support is during UAS device activation and subsequent titration of UAS via an overnight in-laboratory sleep study.

After surgical implantation, the UAS device activation can be performed in the nonsurgical sleep clinic and is done about 1 month later. This period allows for tissue healing after the surgery and for the patient to get accustomed to having this new device in their body. This activation can be done with assistance from an industry technician until the HCP is comfortable with this process. The multidisciplinary UAS team could choose to delegate device activation to a technician with specialized relevant training, such as RPSGT or respiratory therapist (RT).

This procedure involves determination of sensory and functional threshold for UAS. Sensory threshold is minimum voltage required for the patient to feel the stimulation. The functional threshold is the minimum voltage required to move the tongue past the lower front teeth during stimulation. After these thresholds are established, a voltage range is set on the device. The voltage at functional threshold is typically set at the lower level of this range, and the maximum level is set at 1 volt higher. Patients are able to adjust voltage within this range and are instructed to increase the voltage gradually (0.1-volt increments) while maintaining levels that are comfortable during sleep.

About a month after device activation, patients undergo another overnight polysomnogram for titration of UAS device. In order to educate and train the institutional RPSGT on how to perform this type of titration, an industry technician is required for the first few overnight titrations. The goal of this study is to establish appropriate voltage to resolve sleep-disordered breathing and insure patient comfort at this setting. Patients typically leave the study with a new voltage range. They are asked to keep effective voltage in mind and make appropriate adjustments to maintain comfortable therapy.

Successful UAS therapy includes multiple steps, such as implantation, activation, and titration. This protocol requires effective coordination of care that includes communication with surgical staff, patients, support staff, and industry liaison. Nonsurgical sleep medicine physicians can play a vital role by helping to coordinate care at the early stages of UAS therapy and facilitate effective communication among various providers involved in this process.

Follow-Up

After completion of the initial therapeutic pathway, patients continue to follow up regularly, monitoring for AEs from UAS therapy and sleep apnea symptoms. Patients can be followed in the nonsurgical sleep clinic after the initial postoperative appointment with the surgeon. Frequency of follow-up depends on the presence and severity of any AEs and residual symptoms of sleep apnea. Even though most AEs related to UAS therapy reported in the STAR trial were nonserious and transient, 2% of participants required surgical revision.³ Therefore, maintaining open channels of communication among the entire UAS patient care team even months and years after surgical implantation is important. The nonsurgical sleep medicine physician who will continue to monitor the patient’s progress may need to consult with the surgical colleague or industry liaison at any point during treatment.
 

Limitations

This review outlines the UAS therapy pathway and emphasizes the role of the nonsurgical sleep medicine provider. However, the experience describes a UAS program development at a single VA medical center. Since this UAS device and therapy have already been approved by the VA on a national level, we did not face any challenges with authorization and insurance compensation. Therefore, this review does not provide any guidance with these matters. These are certainly common concerns for sleep medicine providers who offer UAS therapy in medical practices outside the VA, and these would hopefully be addressed in the future.

Furthermore, this review is based on the pulmonary sleep medicine provider’s experience and perspective. Therefore, certain aspects of UAS therapy could be better addressed by nonsurgical sleep medicine providers in different fields of expertise. For example, a study by a psychiatrist or psychologist could provide insight into the emotional concerns of patients who are undergoing this novel and life-altering treatment that includes surgical implantation of hardware into the body. A neurologist could explore the long-term effects of recurrent electrical stimulation on the autonomic and somatic nervous system as well as the musculature of the upper airway.

Conclusion

Multidisciplinary perspectives are needed to provide guidance for practitioners and institutions looking to set up and improve established UAS programs. As the long-term outcomes of the STAR trial continue to be published and provide more validation for UAS, this novel therapy will likely continue to gain acceptance as a safe and effective treatment for OSA.¹¹

Obstructive sleep apnea (OSA) is a common disorder in the US and other industrialized countries. The Wisconsin Sleep Cohort Study reported prevalence rates as high as 20% to 30% in men and 10% to 15% in women.^1,2 Several studies have shown high prevalence of OSA among veterans. Ancoli-Israel and colleagues reported a OSA rate of 36% in a cohort of elderly patients at a US Department of Veterans Affairs (VA) medical center.³ A study by Kreis and colleagues showed that OSA was present in 27% of patients hospitalized on the medical ward at a VA hospital.⁴ Incidence of sleep apnea among veterans in the US will likely increase over time as obesity is becoming more prevalent. Rates of obesity have increased from 14% in 2000 to 18% in 2010 among both male and female veterans.⁵

Untreated OSA is associated with increased risk of coronary artery disease, cerebrovascular accidents, uncontrolled diabetes mellitus, and other complications. Patients with OSA are less productive, have increased health care utilization, and have a higher risk of motor vehicle accidents.⁶ Continuous positive airway pressure (CPAP) is the main form of treatment of OSA. However, despite the adverse outcomes of untreated sleep apnea, suboptimal CPAP adherence remains a major problem in clinical practice. When adherence is defined as > 4 hours of nightly use, 29% to 83% of patients with OSA have been reported to be nonadherent to treatment.⁷ Stepnowsky and colleagues estimated that 50% of patients with OSA for whom CPAP was recommended were no longer using it 1 year later.⁸ CPAP adherence among veterans also has been poor. Wallace and colleagues reported that about one-third of patients with OSA at a VA Miami Healthcare System had mean daily use ≥ 4 hours.⁹ Typical reasons for poor CPAP adherence include pressure intolerance, mask discomfort, nasal and oropharyngeal dryness and irritation.¹⁰ Development and implementation of alternate treatment strategies for OSA is important to reduce disease burden of this widespread and debilitating condition.

Upper airway stimulation (UAS) is a novel therapy for management of OSA that has been gaining popularity and acceptance within the sleep medicine community in the past few years. This treatment option involves implantation of a neurostimulator with a sensing lead and a stimulation lead. The device is similar to a pacemaker and is surgically implanted in chest wall. The sensing lead is placed close to the diaphragm for monitoring of pleural pressure to help assess ventilation. The stimulation lead is placed under the tongue in proximity to the hypoglossal nerve (cranial nerve XII). The neurostimulator delivers electrical pulses to the hypoglossal nerve through the stimulation lead. These stimulating pulses are synchronized with the ventilation detected by the sensing lead. This electrical stimulation results in anterior displacement of the tongue via action of the genioglossus and geniohyoid muscles. Mechanical coupling with the palate also is common and leads to additional airway opening within the oropharynx to prevent apneic episodes. The patient turns on the stimulation through the use of a portable remote control and is turned off in the morning. The patient is able to operate the UAS device by placing the remote control on the skin in proximity of the device. The patient also is able to adjust device voltage within a range set by their physician. The effective voltage range is determined via an overnight sleep study titration performed 1 month after device activation. UAS therapy is not considered first-line treatment for OSA as it requires surgical implantation under general anesthesia; however, it provides an alternative to patients with OSA who are unable to tolerate traditional therapy with CPAP.

The landmark Stimulation Therapy for Apnea Reduction (STAR) trial showed effectiveness of UAS therapy at 12 months postimplantation.¹¹ Follow-up of these participants has proven the sustainability of this effect at 18, 24, 36, and 48 months of therapy.^12-15 Inclusion criteria of the study was moderate-to-severe sleep apnea with predominantly obstructive events. Subjects were excluded if there were anatomical abnormalities of the upper airway or if the pattern of airway collapse was not conducive to UAS on sedated endoscopy evaluation. Participants in the trial were predominantly white males, the average age was 54.5 years, and the average body mass index (BMI) was 28.4. The outcomes measured included Functional Outcomes of Sleep Questionnaire, Epworth Sleepiness Scale (ESS), percentage of sleep time with oxygen saturation < 90%, and subjective snoring. All of these objective and subjective markers of sleep improved significantly with UAS therapy at 12 months and were maintained at improved levels at 48 months of therapy.

The adverse effects (AEs) associated with device implantation and subsequent UAS therapy have been infrequent and mostly transient. Out of 126 device implantations, there were 2 participants who had serious AEs due to implantation and required repositioning and fixation of the neurostimulator to resolve discomfort. Other AEs related to the procedure, including sore throat and muscle soreness, were considered nonserious and resolved with supportive care. AEs related to subsequent UAS therapy included temporary tongue weakness and tongue soreness/abrasion. These complications also have either resolved spontaneously or with use of supportive strategies such as a mouth guard. Due to the sustained clinical benefit and acceptable AE profile as demonstrated by the STAR trial, UAS has emerged as a realistic alternative for management of OSA.

Development of a successful program that provides and supports all aspects of UAS, including device implantation and follow-up, necessitates a multispecialty team approach. Ideally surgical and nonsurgical sleep physicians as well as clinical and administrative support staff should be part of this group.

This study is based on the experience of the development of the UAS program at the Clement J. Zablocki VA Medical Center (CJZ VAMC) in Milwaukee. Currently, there are 25 patients who are part of this UAS program. The inclusion and exclusion criteria were adopted from the STAR trial. The patient population is similar to the population in that trial. They are all white males with average age of 57.2 years and BMI of 31.3. The CJZVAMC UAS Program consists of multidisciplinary group of health care professionals. This article describes the role of a nonsurgical sleep medicine physician that was crucial in the development of this UAS program.

Process

Introduction of this novel alternative therapy has sparked much interest among health care providers (HCPs) at CJZVAMC. However, there has been much misunderstanding among patients and HCPs about what this treatment involves and how it is implemented. For example, many patients that called the sleep clinic to set up an evaluation for UAS did not realize that this is a surgical procedure that requires general anesthesia. One of the most important tasks for a nonsurgical sleep physician is to educate patients and HCPs about this therapy. Most of patient education at CJZVAMC has been done during individual clinic appointments; however, setting up group educational classes for patients is a more efficient strategy to deliver this information. Similarly, giving a lecture on UAS at medicine (or another specialty) grand rounds has been effective in the education of HCPs who refer patients to the sleep clinic. If possible, a combined lecture with a surgical colleague could provide a more balanced and complete depiction of UAS and help to answer a broader range of questions for the audience.

Screening

Screening and identification of appropriate candidates is an important first step in the patient pathway in the UAS therapy. Failure of CPAP therapy is a key starting point in this screening process. When patients present to the sleep clinic with difficulty tolerating CPAP therapy, an extensive and thorough troubleshooting process needs to take place to make sure that all CPAP options have been exhausted. This process would typically include trial of various masks, including different mask interfaces. A dedicated appointment with a registered polysomnographic technologist (RPSGT) or another clinic staff member with vast experience in PAP mask fitting is typically part of this effort.

Adjustment of CPAP pressure settings also may be helpful as high PAP pressure may be another obstacle. Patients frequently have trouble tolerating higher pressure settings especially when they are new to this therapy. Pressure restriction to 4-cm to 7-cm water pressure on auto CPAP has been a helpful technique to allow patients to become more comfortable with this therapy. Once patients are able to use PAP at lower pressures, these settings can be titrated up gradually for optimal effectiveness. Other desensitization techniques, such as use during daytime while distracted by other activities (such as watching TV) can be helpful in adjustment to PAP therapy. Addressing problems with nasal congestion can help improve PAP adherence. Finally, patients should be offered opportunities for education about their PAP machine on an ongoing basis. Lack of proficiency with humidifier use is a very common obstacle and frequently leads to PAP nonadherence. Teaching PAP operation should correspond to the patient’s level of education to be effective. PAP therapy remains the first-line treatment strategy for OSA as it is not invasive and highly effective. Nonsurgical sleep medicine physicians are uniquely positioned to implement and troubleshoot this therapy for sleep apnea patients before considering UAS.

As part of the screening process, it can be helpful to conduct routine multidisciplinary meetings to discuss patients who are being evaluated for UAS implantation. These meetings should include the otolaryngologist, nonsurgical sleep medicine physician, as well as additional staff (nurses, respiratory therapists, etc) who are involved in the UAS process. Having a mental health care provider as part of the multidisciplinary team during the screening process also could be a valuable addition as this specialist could evaluate and provide insight into a patient’s emotional status prior to implantation. This is common practice during evaluation for organ transplantation and would help to predict patient’s psychological well-being after this life-changing procedure.¹⁶ Having multidisciplinary agreement on patient’s candidacy for UAS therapy could improve long-term success of this treatment. Additionally, these multidisciplinary meetings as part of the UAS program can improve team camaraderie and prevent miscommunications during this therapy.

Drug-Induced Sedated Endoscopy

Patient pathway to neurostimulator implantation involves evaluation of the upper airway using drug-induced sedated endoscopy (DISE). This procedure helps determine whether the patient’s anatomy is appropriate for UAS. DISE also can evaluate the pattern of airway closure during an apneic episode. Anterior-posterior pattern of closure is associated with greater UAS effectiveness compared with concentric pattern of airway closure. DISE is typically performed by the otolaryngologist scheduled to implant the UAS. However, nonsurgical physicians who are part of the patient’s care team can be trained to perform this procedure especially if they have experience in performing endoscopy of the upper airway (such as a pulmonary specialist). This can make the evaluation process more efficient and dramatically improve access to care.

Coordination of Care

In order for the UAS program to be successful, the patient’s care team has to work closely with the device manufacturer throughout the implantation pathway and for ongoing patient care. The device manufacturer can assist with education of HCPs, surgical physicians, clinical support staff, and the patient. However, an even more essential role for industry support is during UAS device activation and subsequent titration of UAS via an overnight in-laboratory sleep study.

After surgical implantation, the UAS device activation can be performed in the nonsurgical sleep clinic and is done about 1 month later. This period allows for tissue healing after the surgery and for the patient to get accustomed to having this new device in their body. This activation can be done with assistance from an industry technician until the HCP is comfortable with this process. The multidisciplinary UAS team could choose to delegate device activation to a technician with specialized relevant training, such as RPSGT or respiratory therapist (RT).

This procedure involves determination of sensory and functional threshold for UAS. Sensory threshold is minimum voltage required for the patient to feel the stimulation. The functional threshold is the minimum voltage required to move the tongue past the lower front teeth during stimulation. After these thresholds are established, a voltage range is set on the device. The voltage at functional threshold is typically set at the lower level of this range, and the maximum level is set at 1 volt higher. Patients are able to adjust voltage within this range and are instructed to increase the voltage gradually (0.1-volt increments) while maintaining levels that are comfortable during sleep.

About a month after device activation, patients undergo another overnight polysomnogram for titration of UAS device. In order to educate and train the institutional RPSGT on how to perform this type of titration, an industry technician is required for the first few overnight titrations. The goal of this study is to establish appropriate voltage to resolve sleep-disordered breathing and insure patient comfort at this setting. Patients typically leave the study with a new voltage range. They are asked to keep effective voltage in mind and make appropriate adjustments to maintain comfortable therapy.

Successful UAS therapy includes multiple steps, such as implantation, activation, and titration. This protocol requires effective coordination of care that includes communication with surgical staff, patients, support staff, and industry liaison. Nonsurgical sleep medicine physicians can play a vital role by helping to coordinate care at the early stages of UAS therapy and facilitate effective communication among various providers involved in this process.

Follow-Up

After completion of the initial therapeutic pathway, patients continue to follow up regularly, monitoring for AEs from UAS therapy and sleep apnea symptoms. Patients can be followed in the nonsurgical sleep clinic after the initial postoperative appointment with the surgeon. Frequency of follow-up depends on the presence and severity of any AEs and residual symptoms of sleep apnea. Even though most AEs related to UAS therapy reported in the STAR trial were nonserious and transient, 2% of participants required surgical revision.³ Therefore, maintaining open channels of communication among the entire UAS patient care team even months and years after surgical implantation is important. The nonsurgical sleep medicine physician who will continue to monitor the patient’s progress may need to consult with the surgical colleague or industry liaison at any point during treatment.
 

Limitations

This review outlines the UAS therapy pathway and emphasizes the role of the nonsurgical sleep medicine provider. However, the experience describes a UAS program development at a single VA medical center. Since this UAS device and therapy have already been approved by the VA on a national level, we did not face any challenges with authorization and insurance compensation. Therefore, this review does not provide any guidance with these matters. These are certainly common concerns for sleep medicine providers who offer UAS therapy in medical practices outside the VA, and these would hopefully be addressed in the future.

Furthermore, this review is based on the pulmonary sleep medicine provider’s experience and perspective. Therefore, certain aspects of UAS therapy could be better addressed by nonsurgical sleep medicine providers in different fields of expertise. For example, a study by a psychiatrist or psychologist could provide insight into the emotional concerns of patients who are undergoing this novel and life-altering treatment that includes surgical implantation of hardware into the body. A neurologist could explore the long-term effects of recurrent electrical stimulation on the autonomic and somatic nervous system as well as the musculature of the upper airway.

Conclusion

Multidisciplinary perspectives are needed to provide guidance for practitioners and institutions looking to set up and improve established UAS programs. As the long-term outcomes of the STAR trial continue to be published and provide more validation for UAS, this novel therapy will likely continue to gain acceptance as a safe and effective treatment for OSA.¹¹

Adolescents who undergo metabolic bariatric surgery may require long-term nutrient monitoring and supplementation to prevent nutritional deficiencies, according to investigators.

In a 5-year prospective study, more than a quarter of the participants who underwent vertical sleeve gastrectomy (VSG) developed two or more nutritional deficiencies, reported lead author Stavra A. Xanthakos, MD, of the Cincinnati Children’s Hospital Medical Center, and colleagues.

“Although prevalence of nutritional deficiencies has been estimated largely from adult cohorts, bariatric surgery is an increasingly accepted treatment for severe obesity in youth,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Yet, lower adherence to supplementation and anticipated longer lifespan with altered gastrointestinal physiology may increase risk of adverse nutritional outcomes in these youth.”

Previous research has suggested that teens may be at higher risk for nutritional deficiencies, but these studies were largely retrospective, or when prospective, lacked sufficient long-term follow-up, analysis of comprehensive patient factors, or inclusion of VSG, which is now the predominant technique in the field, the investigators noted.

“Our study is the first to assess comparative nutritional outcomes in adolescents after both VSG and gastric bypass,” they wrote.

The study involved 226 participants aged 13-19 years who underwent either Roux-en-Y gastric bypass (n = 161) or VSG (n = 67) at five tertiary-care centers in the United States during 2007-2012.

Six months after surgery, at 12 months, and on an annual basis thereafter, the investigators gathered clinical data and measured participant serum levels of ferritin; transferrin; albumin; parathyroid hormone; C-reactive protein; and vitamins A, D, B₁, B₁₂, and folate. Analyses also included sex, age, ethnicity, race, household demographics, weight, height, comorbidities, and body mass index (BMI).

The majority of participants were female (75%) and white (72%). At baseline, mean BMI and age were 52.7 kg/m² and 16.5 years, respectively. After 5 years, mean body mass index decreased 23% without a significant difference between procedures.

Generally, nutritional deficiencies occurred earlier and were more common after gastric bypass, although both procedures were ultimately associated with increased risks.

In the gastric bypass group, 59% of participants had two or more nutritional deficiencies at 5 years, and 19% had three more deficiencies, which represented increased rates of fivefold and sixfold, respectively, which the investigators described as “striking.” In the VSG group, 27% of patients had two or more nutritional deficiencies at 5 years; while this fourfold increase was not statistically significant, the investigators suggested that it indicated “a lower, but not negligible, nutritional risk.”

Hypoferritinemia was particularly common in both groups, with rates at year 5 of 71% and 45% among patients who underwent gastric bypass and VSG, respectively.

“Our results now provide critical evidence that VSG does in fact carry significantly lower nutritional risk than Roux-en-Y gastric bypass, but can still worsen iron status,” the investigators wrote.

The investigators also highlighted a nonsignificant increase in the incidence of vitamin B₁₂ deficiency among patients who underwent gastric bypass, with rates increasing from 0.6% at baseline to 11.5% at 5 years.

“Vitamin B₁₂ status likewise worsened disproportionately after [gastric bypass], despite similar trajectories of weight loss after VSG,” the investigators wrote. “This suggests that the differential risk is caused by anatomic and physiological differences between procedures, rather than weight loss alone.”

Beyond surgery type, risk factors for nutritional deficiency included inadequate supplement intake, pregnancy, weight regain, and black race.

“Our findings underscore the importance of long-term nutritional monitoring in adolescents after bariatric surgery and the need to examine impact on health outcomes and quality of life as these youth advance into adulthood, including systematic assessment of anemia and bone health,” the investigators concluded.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Center for Advancing Translational Sciences of the National Institutes of Health. Dr. Courcoulas reported grant support from Allurion.

SOURCE: Xanthakos SA et al. Clin Gastro Hepatol. 2019 Nov 6. doi: 10.1016/j.cgh.2019.10.048.

Adolescents who undergo metabolic bariatric surgery may require long-term nutrient monitoring and supplementation to prevent nutritional deficiencies, according to investigators.

In a 5-year prospective study, more than a quarter of the participants who underwent vertical sleeve gastrectomy (VSG) developed two or more nutritional deficiencies, reported lead author Stavra A. Xanthakos, MD, of the Cincinnati Children’s Hospital Medical Center, and colleagues.

“Although prevalence of nutritional deficiencies has been estimated largely from adult cohorts, bariatric surgery is an increasingly accepted treatment for severe obesity in youth,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Yet, lower adherence to supplementation and anticipated longer lifespan with altered gastrointestinal physiology may increase risk of adverse nutritional outcomes in these youth.”

Previous research has suggested that teens may be at higher risk for nutritional deficiencies, but these studies were largely retrospective, or when prospective, lacked sufficient long-term follow-up, analysis of comprehensive patient factors, or inclusion of VSG, which is now the predominant technique in the field, the investigators noted.

“Our study is the first to assess comparative nutritional outcomes in adolescents after both VSG and gastric bypass,” they wrote.

The study involved 226 participants aged 13-19 years who underwent either Roux-en-Y gastric bypass (n = 161) or VSG (n = 67) at five tertiary-care centers in the United States during 2007-2012.

Six months after surgery, at 12 months, and on an annual basis thereafter, the investigators gathered clinical data and measured participant serum levels of ferritin; transferrin; albumin; parathyroid hormone; C-reactive protein; and vitamins A, D, B₁, B₁₂, and folate. Analyses also included sex, age, ethnicity, race, household demographics, weight, height, comorbidities, and body mass index (BMI).

The majority of participants were female (75%) and white (72%). At baseline, mean BMI and age were 52.7 kg/m² and 16.5 years, respectively. After 5 years, mean body mass index decreased 23% without a significant difference between procedures.

Generally, nutritional deficiencies occurred earlier and were more common after gastric bypass, although both procedures were ultimately associated with increased risks.

In the gastric bypass group, 59% of participants had two or more nutritional deficiencies at 5 years, and 19% had three more deficiencies, which represented increased rates of fivefold and sixfold, respectively, which the investigators described as “striking.” In the VSG group, 27% of patients had two or more nutritional deficiencies at 5 years; while this fourfold increase was not statistically significant, the investigators suggested that it indicated “a lower, but not negligible, nutritional risk.”

Hypoferritinemia was particularly common in both groups, with rates at year 5 of 71% and 45% among patients who underwent gastric bypass and VSG, respectively.

“Our results now provide critical evidence that VSG does in fact carry significantly lower nutritional risk than Roux-en-Y gastric bypass, but can still worsen iron status,” the investigators wrote.

The investigators also highlighted a nonsignificant increase in the incidence of vitamin B₁₂ deficiency among patients who underwent gastric bypass, with rates increasing from 0.6% at baseline to 11.5% at 5 years.

“Vitamin B₁₂ status likewise worsened disproportionately after [gastric bypass], despite similar trajectories of weight loss after VSG,” the investigators wrote. “This suggests that the differential risk is caused by anatomic and physiological differences between procedures, rather than weight loss alone.”

Beyond surgery type, risk factors for nutritional deficiency included inadequate supplement intake, pregnancy, weight regain, and black race.

“Our findings underscore the importance of long-term nutritional monitoring in adolescents after bariatric surgery and the need to examine impact on health outcomes and quality of life as these youth advance into adulthood, including systematic assessment of anemia and bone health,” the investigators concluded.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Center for Advancing Translational Sciences of the National Institutes of Health. Dr. Courcoulas reported grant support from Allurion.

SOURCE: Xanthakos SA et al. Clin Gastro Hepatol. 2019 Nov 6. doi: 10.1016/j.cgh.2019.10.048.

Adolescents who undergo metabolic bariatric surgery may require long-term nutrient monitoring and supplementation to prevent nutritional deficiencies, according to investigators.

In a 5-year prospective study, more than a quarter of the participants who underwent vertical sleeve gastrectomy (VSG) developed two or more nutritional deficiencies, reported lead author Stavra A. Xanthakos, MD, of the Cincinnati Children’s Hospital Medical Center, and colleagues.

“Although prevalence of nutritional deficiencies has been estimated largely from adult cohorts, bariatric surgery is an increasingly accepted treatment for severe obesity in youth,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Yet, lower adherence to supplementation and anticipated longer lifespan with altered gastrointestinal physiology may increase risk of adverse nutritional outcomes in these youth.”

Previous research has suggested that teens may be at higher risk for nutritional deficiencies, but these studies were largely retrospective, or when prospective, lacked sufficient long-term follow-up, analysis of comprehensive patient factors, or inclusion of VSG, which is now the predominant technique in the field, the investigators noted.

“Our study is the first to assess comparative nutritional outcomes in adolescents after both VSG and gastric bypass,” they wrote.

The study involved 226 participants aged 13-19 years who underwent either Roux-en-Y gastric bypass (n = 161) or VSG (n = 67) at five tertiary-care centers in the United States during 2007-2012.

Six months after surgery, at 12 months, and on an annual basis thereafter, the investigators gathered clinical data and measured participant serum levels of ferritin; transferrin; albumin; parathyroid hormone; C-reactive protein; and vitamins A, D, B₁, B₁₂, and folate. Analyses also included sex, age, ethnicity, race, household demographics, weight, height, comorbidities, and body mass index (BMI).

The majority of participants were female (75%) and white (72%). At baseline, mean BMI and age were 52.7 kg/m² and 16.5 years, respectively. After 5 years, mean body mass index decreased 23% without a significant difference between procedures.

Generally, nutritional deficiencies occurred earlier and were more common after gastric bypass, although both procedures were ultimately associated with increased risks.

In the gastric bypass group, 59% of participants had two or more nutritional deficiencies at 5 years, and 19% had three more deficiencies, which represented increased rates of fivefold and sixfold, respectively, which the investigators described as “striking.” In the VSG group, 27% of patients had two or more nutritional deficiencies at 5 years; while this fourfold increase was not statistically significant, the investigators suggested that it indicated “a lower, but not negligible, nutritional risk.”

Hypoferritinemia was particularly common in both groups, with rates at year 5 of 71% and 45% among patients who underwent gastric bypass and VSG, respectively.

“Our results now provide critical evidence that VSG does in fact carry significantly lower nutritional risk than Roux-en-Y gastric bypass, but can still worsen iron status,” the investigators wrote.

The investigators also highlighted a nonsignificant increase in the incidence of vitamin B₁₂ deficiency among patients who underwent gastric bypass, with rates increasing from 0.6% at baseline to 11.5% at 5 years.

“Vitamin B₁₂ status likewise worsened disproportionately after [gastric bypass], despite similar trajectories of weight loss after VSG,” the investigators wrote. “This suggests that the differential risk is caused by anatomic and physiological differences between procedures, rather than weight loss alone.”

Beyond surgery type, risk factors for nutritional deficiency included inadequate supplement intake, pregnancy, weight regain, and black race.

“Our findings underscore the importance of long-term nutritional monitoring in adolescents after bariatric surgery and the need to examine impact on health outcomes and quality of life as these youth advance into adulthood, including systematic assessment of anemia and bone health,” the investigators concluded.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Center for Advancing Translational Sciences of the National Institutes of Health. Dr. Courcoulas reported grant support from Allurion.

SOURCE: Xanthakos SA et al. Clin Gastro Hepatol. 2019 Nov 6. doi: 10.1016/j.cgh.2019.10.048.

Amid the COVID-19 pandemic, defer therapeutic lymphadenectomy for stage III melanoma and opt instead for treatment with checkpoint or BRAF/MEK inhibitors, except when metastatic nodes are threatening vital structures or neoadjuvant therapy is not possible or has already failed, the National Comprehensive Cancer Network said in a new document about managing melanoma during the pandemic.

“The NCCN Melanoma Panel does not consider neoadjuvant therapy as a superior option to surgery followed by systemic adjuvant therapy for stage III melanoma, but available data suggest this is a reasonable resource-conserving option during the COVID-19 outbreak,” according to the panel. Surgery should be performed 8-9 weeks after initiation, said the group, an alliance of physicians from 30 U.S. cancer centers.

Echoing pandemic advice from other medical fields, the group’s melanoma recommendations focused on deferring nonurgent care until after the pandemic passes, and in the meantime limiting patient contact with the medical system and preserving hospital resources by, for instance, using telemedicine and opting for treatment regimens that require fewer trips to the clinic.

In a separate document on nonmelanoma skin cancer (NMSC), the group said that, with the exception of Merkel cell carcinoma, excisions for NMSC – including basal and squamous cell carcinoma, dermatofibrosarcoma protuberans, and rare tumors – should also generally be postponed during the pandemic.

The exception is if there is a risk of metastases within 3 months, but “such estimations of risks ... should be weighed against risks of the patient contracting COVID-19 infection or asymptomatically transmitting COVID-19 to health care workers,” the panel said.

Along the same lines, adjuvant therapy after surgical clearance of localized NMSC “should generally not be undertaken given the multiple visits required,” except for more extensive disease.

For primary cutaneous melanoma , “most time-to-treat studies show no adverse patient outcomes following a 90-day treatment delay, even for thicker [cutaneous melanoma],” the group said, so it recommended delaying wide excisions for melanoma in situ, lesions no thicker than 1 mm (T1) so long as the biopsy removed most of the lesion, and invasive melanomas of any depth if the biopsy had clear margins or only peripheral transection of the in situ component. They said sentinel lymph node biopsy can also be delayed for up to 3 months.

Resections for metastatic stage III-IV disease should also be put on hold unless the patient is symptomatic; systemic treatments should instead be continued. However, “given hospital-intensive resources, the use of talimogene laherparepvec for cutaneous/nodal/in-transit metastasis should be cautiously considered and, if possible, deferred until the COVID-19 crisis abates. A single dose of palliative radiation therapy may be useful for larger/symptomatic metastasis, as appropriate,” the group said.

If resection is still a go, the group noted that adjuvant therapy “has not been shown to improve melanoma-specific survival and should be deferred during the COVID-19 pandemic for patients with [a less than] 50% chance of disease relapse.” Dabrafenib/trametinib is the evidence-based choice if adjuvant treatment is opted for, but “alternative BRAF/MEK inhibitor regimens (encorafenib/binimetinib or vemurafenib/cobimetinib) may be substituted if drug supply is limited” by the pandemic, the group said.

For stage IV melanoma, “single-agent anti-PD-1 [programmed cell death 1] is recommended over combination ipilimumab/nivolumab at present” because there’s less inflammation and possible exacerbation of COVID-19, less need for steroids to counter adverse events, and less need for follow up to check for toxicities.

The group said evidence supports that 400 mg pembrolizumab administered intravenously every 6 weeks would likely be as effective as 200 mg intravenously every 3 weeks and would help keep people out of the hospital.

However, for stage IV melanoma with brain metastasis, there’s a strong rate of response to ipilimumab/nivolumab, so it may still be an option. In that case, “a regimen of ipilimumab 1 mg/kg and nivolumab 3 mg/kg every 3 weeks for four infusions, with subsequent consideration for nivolumab monotherapy, is associated with lower rates of immune-mediated toxicity,” compared with standard dosing.

Regarding potential drug shortages, the group noted that encorafenib/binimetinib or vemurafenib/cobimetinib combinations can be substituted for dabrafenib/trametinib for adjuvant therapy, and single-agent BRAF inhibitors can be used in the event of MEK inhibitor shortages.

In hospice, the group said oral temozolomide is the preferred option for palliative chemotherapy since it would limit resource utilization and contact with the medical system.
 

aotto@mdedge.com

Amid the COVID-19 pandemic, defer therapeutic lymphadenectomy for stage III melanoma and opt instead for treatment with checkpoint or BRAF/MEK inhibitors, except when metastatic nodes are threatening vital structures or neoadjuvant therapy is not possible or has already failed, the National Comprehensive Cancer Network said in a new document about managing melanoma during the pandemic.

“The NCCN Melanoma Panel does not consider neoadjuvant therapy as a superior option to surgery followed by systemic adjuvant therapy for stage III melanoma, but available data suggest this is a reasonable resource-conserving option during the COVID-19 outbreak,” according to the panel. Surgery should be performed 8-9 weeks after initiation, said the group, an alliance of physicians from 30 U.S. cancer centers.

Echoing pandemic advice from other medical fields, the group’s melanoma recommendations focused on deferring nonurgent care until after the pandemic passes, and in the meantime limiting patient contact with the medical system and preserving hospital resources by, for instance, using telemedicine and opting for treatment regimens that require fewer trips to the clinic.

In a separate document on nonmelanoma skin cancer (NMSC), the group said that, with the exception of Merkel cell carcinoma, excisions for NMSC – including basal and squamous cell carcinoma, dermatofibrosarcoma protuberans, and rare tumors – should also generally be postponed during the pandemic.

The exception is if there is a risk of metastases within 3 months, but “such estimations of risks ... should be weighed against risks of the patient contracting COVID-19 infection or asymptomatically transmitting COVID-19 to health care workers,” the panel said.

Along the same lines, adjuvant therapy after surgical clearance of localized NMSC “should generally not be undertaken given the multiple visits required,” except for more extensive disease.

For primary cutaneous melanoma , “most time-to-treat studies show no adverse patient outcomes following a 90-day treatment delay, even for thicker [cutaneous melanoma],” the group said, so it recommended delaying wide excisions for melanoma in situ, lesions no thicker than 1 mm (T1) so long as the biopsy removed most of the lesion, and invasive melanomas of any depth if the biopsy had clear margins or only peripheral transection of the in situ component. They said sentinel lymph node biopsy can also be delayed for up to 3 months.

Resections for metastatic stage III-IV disease should also be put on hold unless the patient is symptomatic; systemic treatments should instead be continued. However, “given hospital-intensive resources, the use of talimogene laherparepvec for cutaneous/nodal/in-transit metastasis should be cautiously considered and, if possible, deferred until the COVID-19 crisis abates. A single dose of palliative radiation therapy may be useful for larger/symptomatic metastasis, as appropriate,” the group said.

If resection is still a go, the group noted that adjuvant therapy “has not been shown to improve melanoma-specific survival and should be deferred during the COVID-19 pandemic for patients with [a less than] 50% chance of disease relapse.” Dabrafenib/trametinib is the evidence-based choice if adjuvant treatment is opted for, but “alternative BRAF/MEK inhibitor regimens (encorafenib/binimetinib or vemurafenib/cobimetinib) may be substituted if drug supply is limited” by the pandemic, the group said.

For stage IV melanoma, “single-agent anti-PD-1 [programmed cell death 1] is recommended over combination ipilimumab/nivolumab at present” because there’s less inflammation and possible exacerbation of COVID-19, less need for steroids to counter adverse events, and less need for follow up to check for toxicities.

The group said evidence supports that 400 mg pembrolizumab administered intravenously every 6 weeks would likely be as effective as 200 mg intravenously every 3 weeks and would help keep people out of the hospital.

However, for stage IV melanoma with brain metastasis, there’s a strong rate of response to ipilimumab/nivolumab, so it may still be an option. In that case, “a regimen of ipilimumab 1 mg/kg and nivolumab 3 mg/kg every 3 weeks for four infusions, with subsequent consideration for nivolumab monotherapy, is associated with lower rates of immune-mediated toxicity,” compared with standard dosing.

Regarding potential drug shortages, the group noted that encorafenib/binimetinib or vemurafenib/cobimetinib combinations can be substituted for dabrafenib/trametinib for adjuvant therapy, and single-agent BRAF inhibitors can be used in the event of MEK inhibitor shortages.

In hospice, the group said oral temozolomide is the preferred option for palliative chemotherapy since it would limit resource utilization and contact with the medical system.
 

aotto@mdedge.com

Amid the COVID-19 pandemic, defer therapeutic lymphadenectomy for stage III melanoma and opt instead for treatment with checkpoint or BRAF/MEK inhibitors, except when metastatic nodes are threatening vital structures or neoadjuvant therapy is not possible or has already failed, the National Comprehensive Cancer Network said in a new document about managing melanoma during the pandemic.

“The NCCN Melanoma Panel does not consider neoadjuvant therapy as a superior option to surgery followed by systemic adjuvant therapy for stage III melanoma, but available data suggest this is a reasonable resource-conserving option during the COVID-19 outbreak,” according to the panel. Surgery should be performed 8-9 weeks after initiation, said the group, an alliance of physicians from 30 U.S. cancer centers.

Echoing pandemic advice from other medical fields, the group’s melanoma recommendations focused on deferring nonurgent care until after the pandemic passes, and in the meantime limiting patient contact with the medical system and preserving hospital resources by, for instance, using telemedicine and opting for treatment regimens that require fewer trips to the clinic.

In a separate document on nonmelanoma skin cancer (NMSC), the group said that, with the exception of Merkel cell carcinoma, excisions for NMSC – including basal and squamous cell carcinoma, dermatofibrosarcoma protuberans, and rare tumors – should also generally be postponed during the pandemic.

The exception is if there is a risk of metastases within 3 months, but “such estimations of risks ... should be weighed against risks of the patient contracting COVID-19 infection or asymptomatically transmitting COVID-19 to health care workers,” the panel said.

Along the same lines, adjuvant therapy after surgical clearance of localized NMSC “should generally not be undertaken given the multiple visits required,” except for more extensive disease.

For primary cutaneous melanoma , “most time-to-treat studies show no adverse patient outcomes following a 90-day treatment delay, even for thicker [cutaneous melanoma],” the group said, so it recommended delaying wide excisions for melanoma in situ, lesions no thicker than 1 mm (T1) so long as the biopsy removed most of the lesion, and invasive melanomas of any depth if the biopsy had clear margins or only peripheral transection of the in situ component. They said sentinel lymph node biopsy can also be delayed for up to 3 months.

Resections for metastatic stage III-IV disease should also be put on hold unless the patient is symptomatic; systemic treatments should instead be continued. However, “given hospital-intensive resources, the use of talimogene laherparepvec for cutaneous/nodal/in-transit metastasis should be cautiously considered and, if possible, deferred until the COVID-19 crisis abates. A single dose of palliative radiation therapy may be useful for larger/symptomatic metastasis, as appropriate,” the group said.

If resection is still a go, the group noted that adjuvant therapy “has not been shown to improve melanoma-specific survival and should be deferred during the COVID-19 pandemic for patients with [a less than] 50% chance of disease relapse.” Dabrafenib/trametinib is the evidence-based choice if adjuvant treatment is opted for, but “alternative BRAF/MEK inhibitor regimens (encorafenib/binimetinib or vemurafenib/cobimetinib) may be substituted if drug supply is limited” by the pandemic, the group said.

For stage IV melanoma, “single-agent anti-PD-1 [programmed cell death 1] is recommended over combination ipilimumab/nivolumab at present” because there’s less inflammation and possible exacerbation of COVID-19, less need for steroids to counter adverse events, and less need for follow up to check for toxicities.

The group said evidence supports that 400 mg pembrolizumab administered intravenously every 6 weeks would likely be as effective as 200 mg intravenously every 3 weeks and would help keep people out of the hospital.

However, for stage IV melanoma with brain metastasis, there’s a strong rate of response to ipilimumab/nivolumab, so it may still be an option. In that case, “a regimen of ipilimumab 1 mg/kg and nivolumab 3 mg/kg every 3 weeks for four infusions, with subsequent consideration for nivolumab monotherapy, is associated with lower rates of immune-mediated toxicity,” compared with standard dosing.

Regarding potential drug shortages, the group noted that encorafenib/binimetinib or vemurafenib/cobimetinib combinations can be substituted for dabrafenib/trametinib for adjuvant therapy, and single-agent BRAF inhibitors can be used in the event of MEK inhibitor shortages.

In hospice, the group said oral temozolomide is the preferred option for palliative chemotherapy since it would limit resource utilization and contact with the medical system.
 

aotto@mdedge.com