CASE A patient experiences unnessary inconvenience, distress, and cost following IUD placement

Ms. J had a levonorgestrel intrauterine device (IUD) placed at her postpartum visit. Her physician asked her to return for a string check in 4 to 6 weeks. She was dismayed at the prospect of re-presenting for care, as she is losing the Medicaid coverage that paid for her pregnancy care. One month later, she arranged for a babysitter so she could obtain the recommended string check. The physician told her the strings seemed longer than expected and ordered ultrasonography. Ms. J is distressed because of the mounting cost of care but is anxious to ensure that the IUD will prevent future pregnancy.

Should the routine IUD string check be reconsidered?

The string check dissension

Intrauterine devices offer reliable contraception with a high rate of satisfaction and a remarkably low rate of complications.^1-3 With the increased uptake of IUDs, the value of “string checks” is being debated, with myriad responses from professional groups, manufacturers, and individual clinicians. For many practicing ObGyns, the question remains: Should patients be counseled about presenting for or doing their own IUD string checks?

Indeed, all IUD manufacturers recommend monthly self-examination to evaluate string presence.^4-8 Manufacturers’ websites prominently display this information in material directed toward current or potential users, so many patients may be familiar already with this recommendation before their clinician visit. Yet, the Centers for Disease Control and Prevention state that no routine follow-up or monitoring is needed.⁹

In our case scenario, follow-up is clearly burdensome and ultimately costly. Instead, clinicians can advise patients to return with rare but important to recognize complications (such as perforation, expulsion, infection), adverse effects, or desire for change. While no data are available to support in-office or at-home string checks, data do show that women reliably present when intervention is needed.

Here, we explore 5 questions relevant to IUD string checks and discuss why it is time to rethink this practice habit.

What is the purpose of a string check?

String checks serve as a surrogate for assessing an IUD’s position and function. A string check can be performed by a clinician, who observes the IUD strings on speculum exam or palpates the strings on bimanual exam, or by the patient doing a self-exam. A positive string check purportedly assures both the IUD user and the health care provider that an IUD remains in a fundal, intrauterine position, thus providing an ongoing reliable contraceptive effect.

However, string check reliability in detecting contraceptive effectiveness is uncertain. Strings that subjectively feel or appear longer than anticipated can lead to unnecessary additional evaluation and emotional distress: These are harms. By contrast, when an expulsion occurs, it often is a partial expulsion or displacement, with unclear effect on patient or physician perception of the strings on examination. One retrospective review identified women with a history of IUD placement and a positive pregnancy test; those with an intrauterine pregnancy (74%) frequently also had a malpositioned IUD (55%) and rarely identifiable string issues (16%).¹⁰ Before asking patients and clinicians to use resources for performing string evaluations, the association between this action and outcomes of interest must be elucidated.

If not for assessing risk of expulsion, IUD follow-up allows the clinician to evaluate for other complications or adverse effects and to address patient concerns. This practice often is performed when the patient is starting a new medication or medical intervention. However, a systematic review involving 4 studies of IUD follow-up visits or phone calls after contraceptive initiation generated limited data, with no notable impact on contraceptive continuation or indicated use.¹¹

Most important, data show that patients present to their clinician when issues arise with IUD use. One prospective study of 280 women compared multiple follow-up visits with a single 6-week follow-up visit after IUD placement; 10 expulsions were identified, and 8 of these were noted at unscheduled visits when patients presented with symptoms.¹² This study suggests that there is little benefit in scheduled follow-up or set self-checks.

Furthermore, in a study in Finland of more than 17,000 IUD users, the rare participants who became pregnant during IUD use promptly presented for care because of a change in menses, pain, or symptoms of pregnancy.¹³ While IUDs are touted as user independent, this overlooks the reality: Data show that device failure, although rare, is rapidly and appropriately addressed by the user.

Continue to: Does the risk of IUD expulsion warrant string checks?...

Does the risk of IUD expulsion warrant string checks?

The risk of IUD expulsion is estimated to be 1% at 1 month and 4% at 1 year, with a contraceptive failure rate of 0.4% at 1 year. The risk of expulsion does not differ by age group, including adolescents, or parity, but it is higher with use of the copper IUD (2% at 1 month, 6% at 1 year) and with prior expulsion (14%, limited by small numbers).¹ Furthermore, risk of expulsion is higher with postplacental placement and second trimester abortion.^14,15 Despite this risk, the contraceptive failure rate of all types of IUDs remains consistently lower than all other reversible methods besides the contraceptive implant.¹⁶

Furthermore, while IUD expulsion is rare, unnoticed expulsion is even more rare. In one study with more than 58,000 person-years of use, 132 pregnancies were noted, and 7 of these occurred in the setting of an unnoticed expulsion.¹³ Notably, a higher risk threshold is held for other medications. For example, statins are associated with a 3% risk of irreversible hepatic injury, yet serial liver function tests are not performed in patients without baseline liver dysfunction.¹⁷ A less than 0.1% risk of a non–life-threatening complication—unnoticed expulsion—does not warrant routine follow-up. Instead, the patient gauges the tolerability of that risk in making a follow-up plan, particularly given the varied individual preferences in patients’ management of the associated outcome of unintended pregnancy.

Are women interested in and able to perform their own string checks?

Recommendations to perform IUD string self-checks should consider whether women are willing and able to do so. In a study of 126 IUD users, 59% of women had attempted to check their IUD strings at home, and one-third were unable to do so successfully; all participants had visible strings on subsequent speculum exam.¹⁸ The women also were given the opportunity to perform a string self-check at the study visit. Overall, only 46% of participants found the exercise acceptable and were able to palpate the IUD strings.¹⁸ The authors aptly stated, “A universal recommendation for practice that is meant to identify a rare complication has no clinical utility if at least half of the women are unable to follow it.”

In which scenarios might a string check have clear utility?

The most important reason for follow-up after IUD placement or for patients to perform string self-checks is patient preference. At least anecdotally, some patients take comfort, particularly in the absence of menses, in palpating IUD strings regularly; these individuals should know that there is no necessity for but also no harm in this practice. In addition, patients may desire a string check or follow-up visit to discuss their new contraceptive’s goodness-of-fit.

While limited data show that routinely scheduling such visits does not improve contraceptive continuation, it is difficult to extrapolate these data to the select individuals who independently desire follow-up. (In addition, contraceptive continuance is hardly a metric of success, as clinicians and patients can agree that discontinuation in the setting of patient dissatisfaction is always appropriate.)

Clinicians should share with patients differing risks of IUD expulsion, and this may prompt more nuanced decisions about string checks and/or follow-up. Patients with postplacental or postabortion (second trimester) IUD placement or placement following prior expulsion may opt to perform string checks given the relatively higher risk of expulsion despite the maintained, absolutely low risk that such an event is unnoticed.

If a patient does present for a string check and strings are not visualized on exam, reasonable attempts should be made to identify the strings at that time. A cytobrush can be used to liberate and identify strings within the cervical canal. If the clinician cannot identify the strings or the patient is unable to tolerate such attempts, ultrasonography should be performed to localize the IUD. The ultrasound scan can be done in the office, if available, which is more cost-effective for women than a referral to radiology. If ultrasonography does not identify an intrauterine IUD, an x-ray is the next step to determine if the IUD has expulsed or perforated.

Continue to: Is a string check worth the cost?...

Is a string check worth the cost?

Health care providers may not be aware of the cost of care from the patient perspective. While the Affordable Care Act of 2010 mandates contraceptive coverage for women with insurance, a string check often is coded as a problem-based visit and thus may require a significant copay or out-of-pocket cost for high-deductible plans—without a proven benefit.¹⁹ Women who lack insurance coverage may forgo even necessary care due to the cost.²⁰

The bottom line

The medical community and ObGyns specifically are familiar with a practice of patient self-examination falling by the wayside, as has been the case with breast self-examination.²¹ While counseling on string checks can complement conversations about risks and patients’ personal preferences regarding follow-up, no data support routine string checks in the clinic or at home. One of the great benefits of IUD use is its lack of barriers and resources for ongoing use. Physicians need not reintroduce burdens without benefits to those who desire this contraceptive method.

CASE A patient experiences unnessary inconvenience, distress, and cost following IUD placement

Ms. J had a levonorgestrel intrauterine device (IUD) placed at her postpartum visit. Her physician asked her to return for a string check in 4 to 6 weeks. She was dismayed at the prospect of re-presenting for care, as she is losing the Medicaid coverage that paid for her pregnancy care. One month later, she arranged for a babysitter so she could obtain the recommended string check. The physician told her the strings seemed longer than expected and ordered ultrasonography. Ms. J is distressed because of the mounting cost of care but is anxious to ensure that the IUD will prevent future pregnancy.

Should the routine IUD string check be reconsidered?

The string check dissension

Intrauterine devices offer reliable contraception with a high rate of satisfaction and a remarkably low rate of complications.^1-3 With the increased uptake of IUDs, the value of “string checks” is being debated, with myriad responses from professional groups, manufacturers, and individual clinicians. For many practicing ObGyns, the question remains: Should patients be counseled about presenting for or doing their own IUD string checks?

Indeed, all IUD manufacturers recommend monthly self-examination to evaluate string presence.^4-8 Manufacturers’ websites prominently display this information in material directed toward current or potential users, so many patients may be familiar already with this recommendation before their clinician visit. Yet, the Centers for Disease Control and Prevention state that no routine follow-up or monitoring is needed.⁹

In our case scenario, follow-up is clearly burdensome and ultimately costly. Instead, clinicians can advise patients to return with rare but important to recognize complications (such as perforation, expulsion, infection), adverse effects, or desire for change. While no data are available to support in-office or at-home string checks, data do show that women reliably present when intervention is needed.

Here, we explore 5 questions relevant to IUD string checks and discuss why it is time to rethink this practice habit.

What is the purpose of a string check?

String checks serve as a surrogate for assessing an IUD’s position and function. A string check can be performed by a clinician, who observes the IUD strings on speculum exam or palpates the strings on bimanual exam, or by the patient doing a self-exam. A positive string check purportedly assures both the IUD user and the health care provider that an IUD remains in a fundal, intrauterine position, thus providing an ongoing reliable contraceptive effect.

However, string check reliability in detecting contraceptive effectiveness is uncertain. Strings that subjectively feel or appear longer than anticipated can lead to unnecessary additional evaluation and emotional distress: These are harms. By contrast, when an expulsion occurs, it often is a partial expulsion or displacement, with unclear effect on patient or physician perception of the strings on examination. One retrospective review identified women with a history of IUD placement and a positive pregnancy test; those with an intrauterine pregnancy (74%) frequently also had a malpositioned IUD (55%) and rarely identifiable string issues (16%).¹⁰ Before asking patients and clinicians to use resources for performing string evaluations, the association between this action and outcomes of interest must be elucidated.

If not for assessing risk of expulsion, IUD follow-up allows the clinician to evaluate for other complications or adverse effects and to address patient concerns. This practice often is performed when the patient is starting a new medication or medical intervention. However, a systematic review involving 4 studies of IUD follow-up visits or phone calls after contraceptive initiation generated limited data, with no notable impact on contraceptive continuation or indicated use.¹¹

Most important, data show that patients present to their clinician when issues arise with IUD use. One prospective study of 280 women compared multiple follow-up visits with a single 6-week follow-up visit after IUD placement; 10 expulsions were identified, and 8 of these were noted at unscheduled visits when patients presented with symptoms.¹² This study suggests that there is little benefit in scheduled follow-up or set self-checks.

Furthermore, in a study in Finland of more than 17,000 IUD users, the rare participants who became pregnant during IUD use promptly presented for care because of a change in menses, pain, or symptoms of pregnancy.¹³ While IUDs are touted as user independent, this overlooks the reality: Data show that device failure, although rare, is rapidly and appropriately addressed by the user.

Continue to: Does the risk of IUD expulsion warrant string checks?...

Does the risk of IUD expulsion warrant string checks?

The risk of IUD expulsion is estimated to be 1% at 1 month and 4% at 1 year, with a contraceptive failure rate of 0.4% at 1 year. The risk of expulsion does not differ by age group, including adolescents, or parity, but it is higher with use of the copper IUD (2% at 1 month, 6% at 1 year) and with prior expulsion (14%, limited by small numbers).¹ Furthermore, risk of expulsion is higher with postplacental placement and second trimester abortion.^14,15 Despite this risk, the contraceptive failure rate of all types of IUDs remains consistently lower than all other reversible methods besides the contraceptive implant.¹⁶

Furthermore, while IUD expulsion is rare, unnoticed expulsion is even more rare. In one study with more than 58,000 person-years of use, 132 pregnancies were noted, and 7 of these occurred in the setting of an unnoticed expulsion.¹³ Notably, a higher risk threshold is held for other medications. For example, statins are associated with a 3% risk of irreversible hepatic injury, yet serial liver function tests are not performed in patients without baseline liver dysfunction.¹⁷ A less than 0.1% risk of a non–life-threatening complication—unnoticed expulsion—does not warrant routine follow-up. Instead, the patient gauges the tolerability of that risk in making a follow-up plan, particularly given the varied individual preferences in patients’ management of the associated outcome of unintended pregnancy.

Are women interested in and able to perform their own string checks?

Recommendations to perform IUD string self-checks should consider whether women are willing and able to do so. In a study of 126 IUD users, 59% of women had attempted to check their IUD strings at home, and one-third were unable to do so successfully; all participants had visible strings on subsequent speculum exam.¹⁸ The women also were given the opportunity to perform a string self-check at the study visit. Overall, only 46% of participants found the exercise acceptable and were able to palpate the IUD strings.¹⁸ The authors aptly stated, “A universal recommendation for practice that is meant to identify a rare complication has no clinical utility if at least half of the women are unable to follow it.”

In which scenarios might a string check have clear utility?

The most important reason for follow-up after IUD placement or for patients to perform string self-checks is patient preference. At least anecdotally, some patients take comfort, particularly in the absence of menses, in palpating IUD strings regularly; these individuals should know that there is no necessity for but also no harm in this practice. In addition, patients may desire a string check or follow-up visit to discuss their new contraceptive’s goodness-of-fit.

While limited data show that routinely scheduling such visits does not improve contraceptive continuation, it is difficult to extrapolate these data to the select individuals who independently desire follow-up. (In addition, contraceptive continuance is hardly a metric of success, as clinicians and patients can agree that discontinuation in the setting of patient dissatisfaction is always appropriate.)

Clinicians should share with patients differing risks of IUD expulsion, and this may prompt more nuanced decisions about string checks and/or follow-up. Patients with postplacental or postabortion (second trimester) IUD placement or placement following prior expulsion may opt to perform string checks given the relatively higher risk of expulsion despite the maintained, absolutely low risk that such an event is unnoticed.

If a patient does present for a string check and strings are not visualized on exam, reasonable attempts should be made to identify the strings at that time. A cytobrush can be used to liberate and identify strings within the cervical canal. If the clinician cannot identify the strings or the patient is unable to tolerate such attempts, ultrasonography should be performed to localize the IUD. The ultrasound scan can be done in the office, if available, which is more cost-effective for women than a referral to radiology. If ultrasonography does not identify an intrauterine IUD, an x-ray is the next step to determine if the IUD has expulsed or perforated.

Continue to: Is a string check worth the cost?...

Is a string check worth the cost?

Health care providers may not be aware of the cost of care from the patient perspective. While the Affordable Care Act of 2010 mandates contraceptive coverage for women with insurance, a string check often is coded as a problem-based visit and thus may require a significant copay or out-of-pocket cost for high-deductible plans—without a proven benefit.¹⁹ Women who lack insurance coverage may forgo even necessary care due to the cost.²⁰

The bottom line

The medical community and ObGyns specifically are familiar with a practice of patient self-examination falling by the wayside, as has been the case with breast self-examination.²¹ While counseling on string checks can complement conversations about risks and patients’ personal preferences regarding follow-up, no data support routine string checks in the clinic or at home. One of the great benefits of IUD use is its lack of barriers and resources for ongoing use. Physicians need not reintroduce burdens without benefits to those who desire this contraceptive method.

CASE A patient experiences unnessary inconvenience, distress, and cost following IUD placement

Ms. J had a levonorgestrel intrauterine device (IUD) placed at her postpartum visit. Her physician asked her to return for a string check in 4 to 6 weeks. She was dismayed at the prospect of re-presenting for care, as she is losing the Medicaid coverage that paid for her pregnancy care. One month later, she arranged for a babysitter so she could obtain the recommended string check. The physician told her the strings seemed longer than expected and ordered ultrasonography. Ms. J is distressed because of the mounting cost of care but is anxious to ensure that the IUD will prevent future pregnancy.

Should the routine IUD string check be reconsidered?

The string check dissension

Intrauterine devices offer reliable contraception with a high rate of satisfaction and a remarkably low rate of complications.^1-3 With the increased uptake of IUDs, the value of “string checks” is being debated, with myriad responses from professional groups, manufacturers, and individual clinicians. For many practicing ObGyns, the question remains: Should patients be counseled about presenting for or doing their own IUD string checks?

Indeed, all IUD manufacturers recommend monthly self-examination to evaluate string presence.^4-8 Manufacturers’ websites prominently display this information in material directed toward current or potential users, so many patients may be familiar already with this recommendation before their clinician visit. Yet, the Centers for Disease Control and Prevention state that no routine follow-up or monitoring is needed.⁹

In our case scenario, follow-up is clearly burdensome and ultimately costly. Instead, clinicians can advise patients to return with rare but important to recognize complications (such as perforation, expulsion, infection), adverse effects, or desire for change. While no data are available to support in-office or at-home string checks, data do show that women reliably present when intervention is needed.

Here, we explore 5 questions relevant to IUD string checks and discuss why it is time to rethink this practice habit.

What is the purpose of a string check?

String checks serve as a surrogate for assessing an IUD’s position and function. A string check can be performed by a clinician, who observes the IUD strings on speculum exam or palpates the strings on bimanual exam, or by the patient doing a self-exam. A positive string check purportedly assures both the IUD user and the health care provider that an IUD remains in a fundal, intrauterine position, thus providing an ongoing reliable contraceptive effect.

However, string check reliability in detecting contraceptive effectiveness is uncertain. Strings that subjectively feel or appear longer than anticipated can lead to unnecessary additional evaluation and emotional distress: These are harms. By contrast, when an expulsion occurs, it often is a partial expulsion or displacement, with unclear effect on patient or physician perception of the strings on examination. One retrospective review identified women with a history of IUD placement and a positive pregnancy test; those with an intrauterine pregnancy (74%) frequently also had a malpositioned IUD (55%) and rarely identifiable string issues (16%).¹⁰ Before asking patients and clinicians to use resources for performing string evaluations, the association between this action and outcomes of interest must be elucidated.

If not for assessing risk of expulsion, IUD follow-up allows the clinician to evaluate for other complications or adverse effects and to address patient concerns. This practice often is performed when the patient is starting a new medication or medical intervention. However, a systematic review involving 4 studies of IUD follow-up visits or phone calls after contraceptive initiation generated limited data, with no notable impact on contraceptive continuation or indicated use.¹¹

Most important, data show that patients present to their clinician when issues arise with IUD use. One prospective study of 280 women compared multiple follow-up visits with a single 6-week follow-up visit after IUD placement; 10 expulsions were identified, and 8 of these were noted at unscheduled visits when patients presented with symptoms.¹² This study suggests that there is little benefit in scheduled follow-up or set self-checks.

Furthermore, in a study in Finland of more than 17,000 IUD users, the rare participants who became pregnant during IUD use promptly presented for care because of a change in menses, pain, or symptoms of pregnancy.¹³ While IUDs are touted as user independent, this overlooks the reality: Data show that device failure, although rare, is rapidly and appropriately addressed by the user.

Continue to: Does the risk of IUD expulsion warrant string checks?...

Does the risk of IUD expulsion warrant string checks?

The risk of IUD expulsion is estimated to be 1% at 1 month and 4% at 1 year, with a contraceptive failure rate of 0.4% at 1 year. The risk of expulsion does not differ by age group, including adolescents, or parity, but it is higher with use of the copper IUD (2% at 1 month, 6% at 1 year) and with prior expulsion (14%, limited by small numbers).¹ Furthermore, risk of expulsion is higher with postplacental placement and second trimester abortion.^14,15 Despite this risk, the contraceptive failure rate of all types of IUDs remains consistently lower than all other reversible methods besides the contraceptive implant.¹⁶

Furthermore, while IUD expulsion is rare, unnoticed expulsion is even more rare. In one study with more than 58,000 person-years of use, 132 pregnancies were noted, and 7 of these occurred in the setting of an unnoticed expulsion.¹³ Notably, a higher risk threshold is held for other medications. For example, statins are associated with a 3% risk of irreversible hepatic injury, yet serial liver function tests are not performed in patients without baseline liver dysfunction.¹⁷ A less than 0.1% risk of a non–life-threatening complication—unnoticed expulsion—does not warrant routine follow-up. Instead, the patient gauges the tolerability of that risk in making a follow-up plan, particularly given the varied individual preferences in patients’ management of the associated outcome of unintended pregnancy.

Are women interested in and able to perform their own string checks?

Recommendations to perform IUD string self-checks should consider whether women are willing and able to do so. In a study of 126 IUD users, 59% of women had attempted to check their IUD strings at home, and one-third were unable to do so successfully; all participants had visible strings on subsequent speculum exam.¹⁸ The women also were given the opportunity to perform a string self-check at the study visit. Overall, only 46% of participants found the exercise acceptable and were able to palpate the IUD strings.¹⁸ The authors aptly stated, “A universal recommendation for practice that is meant to identify a rare complication has no clinical utility if at least half of the women are unable to follow it.”

In which scenarios might a string check have clear utility?

The most important reason for follow-up after IUD placement or for patients to perform string self-checks is patient preference. At least anecdotally, some patients take comfort, particularly in the absence of menses, in palpating IUD strings regularly; these individuals should know that there is no necessity for but also no harm in this practice. In addition, patients may desire a string check or follow-up visit to discuss their new contraceptive’s goodness-of-fit.

While limited data show that routinely scheduling such visits does not improve contraceptive continuation, it is difficult to extrapolate these data to the select individuals who independently desire follow-up. (In addition, contraceptive continuance is hardly a metric of success, as clinicians and patients can agree that discontinuation in the setting of patient dissatisfaction is always appropriate.)

Clinicians should share with patients differing risks of IUD expulsion, and this may prompt more nuanced decisions about string checks and/or follow-up. Patients with postplacental or postabortion (second trimester) IUD placement or placement following prior expulsion may opt to perform string checks given the relatively higher risk of expulsion despite the maintained, absolutely low risk that such an event is unnoticed.

If a patient does present for a string check and strings are not visualized on exam, reasonable attempts should be made to identify the strings at that time. A cytobrush can be used to liberate and identify strings within the cervical canal. If the clinician cannot identify the strings or the patient is unable to tolerate such attempts, ultrasonography should be performed to localize the IUD. The ultrasound scan can be done in the office, if available, which is more cost-effective for women than a referral to radiology. If ultrasonography does not identify an intrauterine IUD, an x-ray is the next step to determine if the IUD has expulsed or perforated.

Continue to: Is a string check worth the cost?...

Is a string check worth the cost?

Health care providers may not be aware of the cost of care from the patient perspective. While the Affordable Care Act of 2010 mandates contraceptive coverage for women with insurance, a string check often is coded as a problem-based visit and thus may require a significant copay or out-of-pocket cost for high-deductible plans—without a proven benefit.¹⁹ Women who lack insurance coverage may forgo even necessary care due to the cost.²⁰

The bottom line

The medical community and ObGyns specifically are familiar with a practice of patient self-examination falling by the wayside, as has been the case with breast self-examination.²¹ While counseling on string checks can complement conversations about risks and patients’ personal preferences regarding follow-up, no data support routine string checks in the clinic or at home. One of the great benefits of IUD use is its lack of barriers and resources for ongoing use. Physicians need not reintroduce burdens without benefits to those who desire this contraceptive method.

For more than 45 years, gynecologists have used hysteroscopy to diagnose endometrial carcinoma and to associate morphologic descriptive terms with visual findings.¹ Today, considerably more clinical evidence supports visual pattern recognition to assess the risk for and presence of endometrial carcinoma, improving observer-dependent biopsy of the most suspect lesions (VIDEO 1).

In this article, I discuss the clinical evolution of hysteroscopic pattern recognition of endometrial disease and review the visual findings that correlate with the likelihood of endometrial carcinoma. In addition, I have provided 9 short videos that show hysteroscopic views of various endometrial pathologies in the online version of this article at https://www.mdedge.com/obgyn.

Video 1. Endometrial carcinoma and visually directed biopsy

Vidyard Video

The negative hysteroscopic view defined

In 1989, Dr. Frank Loffer confirmed the diagnostic superiority of visually directed biopsy. He demonstrated the advantages of using hysteroscopy and directed biopsy in the evaluation of abnormal uterine bleeding (AUB) to obtain a more accurate diagnosis compared with dilation and curettage (D&C) alone (sensitivity, 98% vs 65%, respectively).²

Also derived from this work is the clinical application of the “negative hysteroscopic view” (NHV). Loffer used the following criteria to define the NHV: good visualization of the entire uterine cavity, no structural abnormalities of the cavity, and a uniformly thin, homogeneous-appearing endometrium without variations in thickness (TABLE 1). The last criterion can be expected to occur only in the early proliferative phase or in postmenopausal women.

Use of hysteroscopy therefore can predict accurately the absence of intrauterine and endometrial pathology when visual findings are negative and tissue sampling is not warranted (FIGURE 1, VIDEO 2).

Video 2. Negative hysteroscopic view 

Vidyard Video

 

Efforts in hysteroscopic classification of endometrial carcinoma

Lesion morphologic characteristics. Sugimoto was among the first to describe the hysteroscopic identification of visual morphologic features that are most likely to be associated with endometrial carcinoma.¹ Patients with AUB were evaluated with hysteroscopy as first-line management to describe lesion morphology and confirm biopsy with histopathology. Sugimoto classified endometrial carcinoma as circumscribed or exophytic with distinct forms, such as polypoid, nodular, papillary, and ulcerated (FIGURE 2). Diffuse or endophytic carcinoma is defined by an ulcerated type of lesion that indicates necrosis; this is most likely to represent an undifferentiated tumor. Sugimoto also described abnormal vascularity that often is associated with carcinoma.¹

Endometrial features. Valli and Zupi created a nomenclature and classification for hysteroscopic endometrial lesions by prospectively grading 4 features: thickness, surface, vascularization, and color.³ Features were scored based on the degree of abnormality and could be considered to be of low or high risk for the presence of carcinoma. High-risk hysteroscopic features included endometrial thickness greater than 10 mm, polymorphous surface, irregular vascularization, and white-grayish color. The sensitivity for accurately diagnosing endometrial lesions was 86.9% for mild lesions and 96% for severe lesions.³ Also, these investigators confirmed the clinical value of the NHV and associated overall risk of precancer or cancer of the endometrium.

Continue to: Amount of endometrial involvement...

 

 

Amount of endometrial involvement. A few years later, Garuti and colleagues retrospectively related the hysteroscopic tumor features of known endometrial adenocarcinoma to stage, grade, and overall survival.⁴ In this system, they focused on classification of tumor morphology as nodular (bulging), polypoid (thin pedicles), or papillary (numerous dendritic projections), as well as whether the amount of abnormal tissue present was less than or more than half of the endometrium and if the lesion involved the cervix.

Several important findings associated with this system may improve visual diagnosis. First, hysteroscopic evaluation had a 100% negative predictive value for the cervical spread of disease (FIGURE 3, VIDEO 3). Second, the hysteroscopic morphologic tumor type did not relate to surgical stage or pathologic grade. Third, when less than half of the endometrium was involved, stage I disease was found (97%, 33 of 34). Last, when more than half of the endometrium was involved, advanced disease beyond stage I was found (9 of 26, 6 of whom had poorly differentiated disease).⁴

Video 3. Cervical spread of adenocarcinoma and visually directed biopsy

Vidyard Video

Structured pattern analysis. Recently, Dueholm and co-investigators published a prospective evaluation of women with postmenopausal bleeding and an endometrial thickness of 5 mm or greater.⁵ They used a structured system of visual pattern analysis during hysteroscopy that they termed the hysteroscopic cancer (HYCA) scoring system. The HYCA scoring system is based on surface outline (uneven, polypoid, and papillary projections), necrosis (cotton candy endometrium [FIGURE 4], whitish-grayish areas without vessels on the surface), and vessel pattern (tortuous S-shaped, loops, irregular caliber, irregular branching, and irregular distribution [FIGURE 5]). Structured pattern analysis predicted cancer with higher accuracy than subjective evaluation.⁵

Morphologic variables as indicators. In 2016, Ianieri and colleagues published a retrospective study on a risk scoring system for diagnosing endometrial hyperplasia and adenocarcinoma via hysteroscopy.⁶ They created a statistical risk model for development of the scoring system. A number of morphologic variables were prognostic indicators of atypical endometrial hyperplasia (AEH) and adenocarcinoma. These included widespread and irregular endometrial thickness, presence of multiple polyps with irregular aspects, dilated glandular orifices, irregular endometrial color (grey, white, or hyperemic), atypical vessels, crumbling of the endometrial neoplasms, and growth of cerebroid and arborescent aspects (VIDEO 4).

Video 4. Endometrial adenocarcinoma 

 

 

Vidyard Video

The scoring system for endometrial adenocarcinoma correctly classified 42 of 44 cancers (sensitivity, 95.4%; specificity, 98.2%), and AEH had a sensitivity of 63.3% and a specificity of 90.4%.⁶ These investigators also showed a high negative predictive value of 99.5% for endometrial adenocarcinoma associated with a negative view at hysteroscopy. Similar to the Dueholm data, Ianieri and colleagues’ morphologic pattern analysis predicted cancer with high accuracy.

Glomerular pattern association. Su and colleagues also showed that pattern recognition could aid in the accurate hysteroscopic diagnosis of endometrial adenocarcinoma.⁷ They used the hysteroscopic presence of a glomerular pattern to predict the association with endometrial adenocarcinoma. A glomerular pattern was described as polypoid endometrium with a papillary-like feature, containing an abnormal neovascularization feature with “intertwined neovascular vessels covered by a thin layer of endometrial tissue” (FIGURE 6). The presence of a glomerular pattern indicated grade 2 or grade 3 disease in 25 of 26 women (96%; sensitivity, 84.6%, specificity, 81.8%)⁷ (see video 4).

TABLE 2 summarizes significant morphologic findings relating to the presences of endometrial carcinoma.

Continue to: Atypical endometrial hyperplasia: A difficult diagnosis...

 

 

Atypical endometrial hyperplasia: A difficult diagnosis

The most common type of endometrial cancer is endometrioid adenocarcinoma (type 1 endometrial carcinoma), and it accounts for approximately 75% to 80% of endometrial cancer diagnoses.⁸ Risk factors include prolonged unopposed estrogen exposure, obesity, diabetes, and age. Type 1 endometrial carcinoma follows a progressive continuum of histopathologic change: from endometrial hyperplasia without atypia to endometrial hyperplasia with atypia (AEH) to well-differentiated endometrial cancer. Therefore, it is possible for endometrial carcinoma to be present simultaneously with AEH. The reported prevalence of concurrent endometrial carcinoma among patients with AEH on biopsy is between 17% and 52%.⁸ Thus, the clinical consideration is for hysterectomy, especially in the postmenopausal patient with a diagnosis of AEH.

Hysteroscopic diagnosis of AEH, however, is more difficult than identification of endometrial carcinoma because a range of morphologic characteristics exist that resemble normal endometrium as well as more progressive disease (VIDEO 5). De Franciscis and colleagues based a hysteroscopic diagnosis of hyperplasia on one or more of the following findings: focal or diffuse, papillary or polypoid, endometrial thickening; abnormal vascular patterns; evidence of glandular cysts; and abnormal architecture features of the glandular outlets (thickening, irregular gland density, or dilatation)⁹ (VIDEO 6).

Video 5. Endometrial polyp and atypical hyperplasia 

Vidyard Video

Additional studies, including that from Ianieri and colleagues, also have determined that AEH is difficult to discern visually from normal endometrium and other endometrial pathologies.⁶ In another investigation, Lasmar and coauthors reported a retrospective analysis of 4,054 hysteroscopic procedures with directed biopsies evaluating for concordance between the hysteroscopic view and histopathology.¹⁰ Agreement was 56.3% for AEH versus 94% for endometrial carcinoma. Among those with a histologic diagnosis of AEH, in 35.4% benign disease was suspected; in 2.1%, endometrial carcinoma was suspected; and in 6%, normal findings were presumed.¹⁰

Video 6. Nodular, polypoid atypical hyperplasia 

Vidyard Video

Because of the similarities in morphologic features between AEH and endometrial carcinoma, tissue biopsy under direct visualization is warranted to assure sampling of the most significantly abnormal tissue and to confirm visual interpretation of findings.

Techniques for hysteroscopic-directed biopsy

Using a visual assessment of endometrial abnormalities allows the surgeon to examine the entire uterine cavity and to biopsy the most suspicious and concerning lesions. The directed biopsy technique can involve a simple grasping maneuver: With the jaws of a small grasper open, push slightly forward to accumulate tissue within the jaw, close the jaw, and remove the tissue carefully through the cervix (VIDEO 7). The size of the sample may be limited, and multiple samples may be needed, depending on the quantity of the tissue retrieved.

Video 7. Visually directed endometrial biopsy

Vidyard Video

Another technique involves first creating a plane of tissue to be removed with scissors and subsequently grasping and removing the tissue (see video 1 and video 3). This particular technique will yield more tissue with one pass of the hysteroscope into the cavity. Careful removal of tissue through the cervix is facilitated by withdrawing the sample in the grasper and the hysteroscope together at the same time, without pulling the sample through the operative channel of the hysteroscope. Also, by turning off the inflow port, the stream of saline does not wash the sample off the grasper at hysteroscope removal from the cervix.

Blind biopsy. If visual inspection reveals a diffuse process within the uterine cavity such that no normal endometrium is noted and the abnormality is of equal degree throughout the endometrial surface, a decision can be made to replace directed biopsy with a blind biopsy. In this scenario, the blind biopsy is certain to sample the representative disease process and not potentially miss significant lesions (see video 4 and video 6). Otherwise, the hysteroscope-directed biopsy would be preferable.

Continue to: Potential for intraperitoneal dissemination of endometrial cancer...

 

 

Potential for intraperitoneal dissemination of endometrial cancer

There is some concern about intraperitoneal dissemination of endometrial carcinoma at the time of hysteroscopy and effect on disease prognosis. Chang and colleagues conducted a large meta-analysis and found that hysteroscopy performed in the presence of type 1 endometrial carcinoma statistically significantly increased the likelihood of positive intraperitoneal cytology.¹¹ In the included studies that reported survival rates (6 of 19), positive cytology did not alter the clinical outcome. The investigators recommended that hysteroscopy not be avoided for this reason, as it helps in the diagnosis of endometrial carcinoma, especially in the early stages of disease.¹¹

In a recent retrospective analysis, Namazov and colleagues included only stage I endometrial carcinoma (to exclude the adverse effect of advanced stage on survival) and evaluated the assumed isolated effect of hysteroscopy on survival.¹² They compared women in whom stage I endometrial carcinoma was diagnosed: 355 by hysteroscopy and 969 by a nonhysteroscopy method (D&C or office endometrial biopsy). Tumors were classified and grouped as low grade (endometrioid grade 1-2 and villoglandular) and high grade, consisting of endometrioid grade 3 and type 2 endometrial carcinoma (serous carcinoma, clear cell carcinoma, and carcinosarcoma) (VIDEOS 8 and 9). Positive intraperitoneal cytology at the time of surgery was 2.3% and 2.1% (P = .832), with an average interval from diagnosis to surgery of 34.6 days (range, 7–43 days).

Video 8. Carcinosarcoma 

Vidyard Video

The authors proposed several explanations for the low rate of intraperitoneal cytology with hysteroscopy. One possibility is having lower mean intrauterine pressure below 100 mm Hg for saline uterine distension, although this was not standardized for all surgeons in the study but rather was a custom of the institution. In addition, the length of time between hysteroscopy and surgery may allow the immune-reactive peritoneum to respond to the cellular insult, thus decreasing the biologic burden at the time of surgery. The median follow-up was 52 months (range, 12–120 months), and there were no differences between the hysteroscopy and the nonhysteroscopy groups in the 5-year recurrence-free survival (90.2% vs 88.2%; P = .53), disease-specific survival (93.4% vs 91.7%; P = .5), and overall survival (86.2% vs 80.6%; P = .22). The authors concluded that hysteroscopy does not compromise the survival of patients with early-stage endometrial cancer.¹²

Video 9. Carcinosarcoma 

Vidyard Video

Retrospective data from Chen and colleagues regarding type 2 endometrial carcinoma indicated a statistically significant increase in positive intraperitoneal cytology for carcinomas evaluated by hysteroscopy versus D&C (30% vs 12%; P = .008).¹³ Among the patients who died, there was no difference in disease-specific survival (53 months for hysteroscopy and 63.5 months for D&C; P = .34), and there was no difference in overall recurrence rates.¹³ Compared with type 1 endometrial carcinoma, type 2 endometrial carcinoma behaves more aggressively, with a higher incidence of extrauterine disease and an increased propensity for recurrence and poor outcome even in the early stages of the disease. This makes it difficult to determine the role of hysteroscopy in the prognosis of these carcinomas, especially in this study where most patients were diagnosed at a later stage.

Key takeaways

Hysteroscopy and directed biopsy are highly effective for visual and histopathologic diagnosis of atypical endometrial hyperplasia and endometrial carcinoma, and they are recommended in the evaluation of AUB, especially in the postmenopausal woman. When the hysteroscopic view is negative, there is a high correlation with the absence of uterine cavity and endometrial pathology. Hysteroscopic diagnostic accuracy is improved with structured use of visual grading scales, well-defined descriptors of endometrial pathology, and hysteroscopist experience.

Low operating intrauterine pressure may decrease the intraperitoneal spread of carcinoma cells during hysteroscopy, and current evidence suggests that there is no change in type 1 endometrial carcinoma prognosis and overall outcomes. Type 2 endometrial carcinoma is more aggressive and is associated with poor outcomes even in early stages, and the effect on disease progression by intraperitoneal spread of carcinoma cells at hysteroscopy is not yet known. Hysteroscopic evaluation of the uterine cavity and directed biopsy is easily and safely performed in the office and adds significantly to the evaluation and management of endometrial carcinoma.

Don’t miss the videos that accompany this article

---

Access them in the article online at mdedge.com/obgyn

Video 1. Endometrial carcinoma and visually directed biopsy

Nodular endometrioid adenocarcinoma grade 1 (type 1 endometrial carcinoma), benign endometrial polyps, and endometrial atrophy in a postmenopausal woman with bleeding. This video demonstrates visually directed biopsy to assure sampling of the most significant lesion.

Video 2. Negative hysteroscopic view

Digital flexible diagnostic hysteroscopy showing a negative hysteroscopic view in a premenopausal woman.

Video 3. Cervical spread of adenocarcinoma and visually directed biopsy 

Diffuse endometrioid adenocarcinoma spread to the upper cervical canal near the internal cervical os. Hysteroscopic directed biopsy is performed.

Video 4. Endometrial adenocarcinoma

Fiberoptic flexible diagnostic hysteroscopy demonstrating diffuse endometrioid adenocarcinoma grade 3 with multiple morphologic features: polypoid, nodular, papillary, and glomerular with areas of necrosis.

Video 5. Endometrial polyp and atypical hyperplasia

Large benign endometrial polyp in an asymptomatic postmenopausal woman with enlarged endometrial stripe on pelvic ultrasound. The endometrium is atrophic except for a small whitish area on the anterior wall, which is atypical hyperplasia. This video highlights the need for visually directed biopsy to assure sampling of the most significant lesion.

Video 6. Nodular, polypoid atypical hyperplasia

Fiberoptic flexible diagnostic hysteroscopy showing diffuse nodular and polypoid atypical hyperplasia with abnormal glandular openings in a postmenopausal woman. Hysterectomy was performed secondary to the significant likelihood of concomitant endometrial carcinoma.

Video 7. Visually directed endometrial biopsy

Hysteroscopic-directed biopsy showing the technique of grasping and removing tissue of a benign adenomyosis cyst and proliferative endometrium.

Video 8. Carcinosarcoma

Carcinosarcoma (type 2 endometrial carcinoma) presents as a large intracavitary mass with soft, polypoid-like tissue in a symptomatic postmenopausal woman with bleeding.

Video 9. Carcinosarcoma

Carcinosarcoma (type 2 endometrial carcinoma) presents as a dense mass in a symptomatic postmenopausal woman with bleeding. This video shows the mass is nodular. These cancers typically grow into a spherical mass within the cavity

 

For more than 45 years, gynecologists have used hysteroscopy to diagnose endometrial carcinoma and to associate morphologic descriptive terms with visual findings.¹ Today, considerably more clinical evidence supports visual pattern recognition to assess the risk for and presence of endometrial carcinoma, improving observer-dependent biopsy of the most suspect lesions (VIDEO 1).

In this article, I discuss the clinical evolution of hysteroscopic pattern recognition of endometrial disease and review the visual findings that correlate with the likelihood of endometrial carcinoma. In addition, I have provided 9 short videos that show hysteroscopic views of various endometrial pathologies in the online version of this article at https://www.mdedge.com/obgyn.

Video 1. Endometrial carcinoma and visually directed biopsy

Vidyard Video

The negative hysteroscopic view defined

In 1989, Dr. Frank Loffer confirmed the diagnostic superiority of visually directed biopsy. He demonstrated the advantages of using hysteroscopy and directed biopsy in the evaluation of abnormal uterine bleeding (AUB) to obtain a more accurate diagnosis compared with dilation and curettage (D&C) alone (sensitivity, 98% vs 65%, respectively).²

Also derived from this work is the clinical application of the “negative hysteroscopic view” (NHV). Loffer used the following criteria to define the NHV: good visualization of the entire uterine cavity, no structural abnormalities of the cavity, and a uniformly thin, homogeneous-appearing endometrium without variations in thickness (TABLE 1). The last criterion can be expected to occur only in the early proliferative phase or in postmenopausal women.

Use of hysteroscopy therefore can predict accurately the absence of intrauterine and endometrial pathology when visual findings are negative and tissue sampling is not warranted (FIGURE 1, VIDEO 2).

Video 2. Negative hysteroscopic view 

Vidyard Video

 

Efforts in hysteroscopic classification of endometrial carcinoma

Lesion morphologic characteristics. Sugimoto was among the first to describe the hysteroscopic identification of visual morphologic features that are most likely to be associated with endometrial carcinoma.¹ Patients with AUB were evaluated with hysteroscopy as first-line management to describe lesion morphology and confirm biopsy with histopathology. Sugimoto classified endometrial carcinoma as circumscribed or exophytic with distinct forms, such as polypoid, nodular, papillary, and ulcerated (FIGURE 2). Diffuse or endophytic carcinoma is defined by an ulcerated type of lesion that indicates necrosis; this is most likely to represent an undifferentiated tumor. Sugimoto also described abnormal vascularity that often is associated with carcinoma.¹

Endometrial features. Valli and Zupi created a nomenclature and classification for hysteroscopic endometrial lesions by prospectively grading 4 features: thickness, surface, vascularization, and color.³ Features were scored based on the degree of abnormality and could be considered to be of low or high risk for the presence of carcinoma. High-risk hysteroscopic features included endometrial thickness greater than 10 mm, polymorphous surface, irregular vascularization, and white-grayish color. The sensitivity for accurately diagnosing endometrial lesions was 86.9% for mild lesions and 96% for severe lesions.³ Also, these investigators confirmed the clinical value of the NHV and associated overall risk of precancer or cancer of the endometrium.

Continue to: Amount of endometrial involvement...

 

 

Amount of endometrial involvement. A few years later, Garuti and colleagues retrospectively related the hysteroscopic tumor features of known endometrial adenocarcinoma to stage, grade, and overall survival.⁴ In this system, they focused on classification of tumor morphology as nodular (bulging), polypoid (thin pedicles), or papillary (numerous dendritic projections), as well as whether the amount of abnormal tissue present was less than or more than half of the endometrium and if the lesion involved the cervix.

Several important findings associated with this system may improve visual diagnosis. First, hysteroscopic evaluation had a 100% negative predictive value for the cervical spread of disease (FIGURE 3, VIDEO 3). Second, the hysteroscopic morphologic tumor type did not relate to surgical stage or pathologic grade. Third, when less than half of the endometrium was involved, stage I disease was found (97%, 33 of 34). Last, when more than half of the endometrium was involved, advanced disease beyond stage I was found (9 of 26, 6 of whom had poorly differentiated disease).⁴

Video 3. Cervical spread of adenocarcinoma and visually directed biopsy

Vidyard Video

Structured pattern analysis. Recently, Dueholm and co-investigators published a prospective evaluation of women with postmenopausal bleeding and an endometrial thickness of 5 mm or greater.⁵ They used a structured system of visual pattern analysis during hysteroscopy that they termed the hysteroscopic cancer (HYCA) scoring system. The HYCA scoring system is based on surface outline (uneven, polypoid, and papillary projections), necrosis (cotton candy endometrium [FIGURE 4], whitish-grayish areas without vessels on the surface), and vessel pattern (tortuous S-shaped, loops, irregular caliber, irregular branching, and irregular distribution [FIGURE 5]). Structured pattern analysis predicted cancer with higher accuracy than subjective evaluation.⁵

Morphologic variables as indicators. In 2016, Ianieri and colleagues published a retrospective study on a risk scoring system for diagnosing endometrial hyperplasia and adenocarcinoma via hysteroscopy.⁶ They created a statistical risk model for development of the scoring system. A number of morphologic variables were prognostic indicators of atypical endometrial hyperplasia (AEH) and adenocarcinoma. These included widespread and irregular endometrial thickness, presence of multiple polyps with irregular aspects, dilated glandular orifices, irregular endometrial color (grey, white, or hyperemic), atypical vessels, crumbling of the endometrial neoplasms, and growth of cerebroid and arborescent aspects (VIDEO 4).

Video 4. Endometrial adenocarcinoma 

 

 

Vidyard Video

The scoring system for endometrial adenocarcinoma correctly classified 42 of 44 cancers (sensitivity, 95.4%; specificity, 98.2%), and AEH had a sensitivity of 63.3% and a specificity of 90.4%.⁶ These investigators also showed a high negative predictive value of 99.5% for endometrial adenocarcinoma associated with a negative view at hysteroscopy. Similar to the Dueholm data, Ianieri and colleagues’ morphologic pattern analysis predicted cancer with high accuracy.

Glomerular pattern association. Su and colleagues also showed that pattern recognition could aid in the accurate hysteroscopic diagnosis of endometrial adenocarcinoma.⁷ They used the hysteroscopic presence of a glomerular pattern to predict the association with endometrial adenocarcinoma. A glomerular pattern was described as polypoid endometrium with a papillary-like feature, containing an abnormal neovascularization feature with “intertwined neovascular vessels covered by a thin layer of endometrial tissue” (FIGURE 6). The presence of a glomerular pattern indicated grade 2 or grade 3 disease in 25 of 26 women (96%; sensitivity, 84.6%, specificity, 81.8%)⁷ (see video 4).

TABLE 2 summarizes significant morphologic findings relating to the presences of endometrial carcinoma.

Continue to: Atypical endometrial hyperplasia: A difficult diagnosis...

 

 

Atypical endometrial hyperplasia: A difficult diagnosis

The most common type of endometrial cancer is endometrioid adenocarcinoma (type 1 endometrial carcinoma), and it accounts for approximately 75% to 80% of endometrial cancer diagnoses.⁸ Risk factors include prolonged unopposed estrogen exposure, obesity, diabetes, and age. Type 1 endometrial carcinoma follows a progressive continuum of histopathologic change: from endometrial hyperplasia without atypia to endometrial hyperplasia with atypia (AEH) to well-differentiated endometrial cancer. Therefore, it is possible for endometrial carcinoma to be present simultaneously with AEH. The reported prevalence of concurrent endometrial carcinoma among patients with AEH on biopsy is between 17% and 52%.⁸ Thus, the clinical consideration is for hysterectomy, especially in the postmenopausal patient with a diagnosis of AEH.

Hysteroscopic diagnosis of AEH, however, is more difficult than identification of endometrial carcinoma because a range of morphologic characteristics exist that resemble normal endometrium as well as more progressive disease (VIDEO 5). De Franciscis and colleagues based a hysteroscopic diagnosis of hyperplasia on one or more of the following findings: focal or diffuse, papillary or polypoid, endometrial thickening; abnormal vascular patterns; evidence of glandular cysts; and abnormal architecture features of the glandular outlets (thickening, irregular gland density, or dilatation)⁹ (VIDEO 6).

Video 5. Endometrial polyp and atypical hyperplasia 

Vidyard Video

Additional studies, including that from Ianieri and colleagues, also have determined that AEH is difficult to discern visually from normal endometrium and other endometrial pathologies.⁶ In another investigation, Lasmar and coauthors reported a retrospective analysis of 4,054 hysteroscopic procedures with directed biopsies evaluating for concordance between the hysteroscopic view and histopathology.¹⁰ Agreement was 56.3% for AEH versus 94% for endometrial carcinoma. Among those with a histologic diagnosis of AEH, in 35.4% benign disease was suspected; in 2.1%, endometrial carcinoma was suspected; and in 6%, normal findings were presumed.¹⁰

Video 6. Nodular, polypoid atypical hyperplasia 

Vidyard Video

Because of the similarities in morphologic features between AEH and endometrial carcinoma, tissue biopsy under direct visualization is warranted to assure sampling of the most significantly abnormal tissue and to confirm visual interpretation of findings.

Techniques for hysteroscopic-directed biopsy

Using a visual assessment of endometrial abnormalities allows the surgeon to examine the entire uterine cavity and to biopsy the most suspicious and concerning lesions. The directed biopsy technique can involve a simple grasping maneuver: With the jaws of a small grasper open, push slightly forward to accumulate tissue within the jaw, close the jaw, and remove the tissue carefully through the cervix (VIDEO 7). The size of the sample may be limited, and multiple samples may be needed, depending on the quantity of the tissue retrieved.

Video 7. Visually directed endometrial biopsy

Vidyard Video

Another technique involves first creating a plane of tissue to be removed with scissors and subsequently grasping and removing the tissue (see video 1 and video 3). This particular technique will yield more tissue with one pass of the hysteroscope into the cavity. Careful removal of tissue through the cervix is facilitated by withdrawing the sample in the grasper and the hysteroscope together at the same time, without pulling the sample through the operative channel of the hysteroscope. Also, by turning off the inflow port, the stream of saline does not wash the sample off the grasper at hysteroscope removal from the cervix.

Blind biopsy. If visual inspection reveals a diffuse process within the uterine cavity such that no normal endometrium is noted and the abnormality is of equal degree throughout the endometrial surface, a decision can be made to replace directed biopsy with a blind biopsy. In this scenario, the blind biopsy is certain to sample the representative disease process and not potentially miss significant lesions (see video 4 and video 6). Otherwise, the hysteroscope-directed biopsy would be preferable.

Continue to: Potential for intraperitoneal dissemination of endometrial cancer...

 

 

Potential for intraperitoneal dissemination of endometrial cancer

There is some concern about intraperitoneal dissemination of endometrial carcinoma at the time of hysteroscopy and effect on disease prognosis. Chang and colleagues conducted a large meta-analysis and found that hysteroscopy performed in the presence of type 1 endometrial carcinoma statistically significantly increased the likelihood of positive intraperitoneal cytology.¹¹ In the included studies that reported survival rates (6 of 19), positive cytology did not alter the clinical outcome. The investigators recommended that hysteroscopy not be avoided for this reason, as it helps in the diagnosis of endometrial carcinoma, especially in the early stages of disease.¹¹

In a recent retrospective analysis, Namazov and colleagues included only stage I endometrial carcinoma (to exclude the adverse effect of advanced stage on survival) and evaluated the assumed isolated effect of hysteroscopy on survival.¹² They compared women in whom stage I endometrial carcinoma was diagnosed: 355 by hysteroscopy and 969 by a nonhysteroscopy method (D&C or office endometrial biopsy). Tumors were classified and grouped as low grade (endometrioid grade 1-2 and villoglandular) and high grade, consisting of endometrioid grade 3 and type 2 endometrial carcinoma (serous carcinoma, clear cell carcinoma, and carcinosarcoma) (VIDEOS 8 and 9). Positive intraperitoneal cytology at the time of surgery was 2.3% and 2.1% (P = .832), with an average interval from diagnosis to surgery of 34.6 days (range, 7–43 days).

Video 8. Carcinosarcoma 

Vidyard Video

The authors proposed several explanations for the low rate of intraperitoneal cytology with hysteroscopy. One possibility is having lower mean intrauterine pressure below 100 mm Hg for saline uterine distension, although this was not standardized for all surgeons in the study but rather was a custom of the institution. In addition, the length of time between hysteroscopy and surgery may allow the immune-reactive peritoneum to respond to the cellular insult, thus decreasing the biologic burden at the time of surgery. The median follow-up was 52 months (range, 12–120 months), and there were no differences between the hysteroscopy and the nonhysteroscopy groups in the 5-year recurrence-free survival (90.2% vs 88.2%; P = .53), disease-specific survival (93.4% vs 91.7%; P = .5), and overall survival (86.2% vs 80.6%; P = .22). The authors concluded that hysteroscopy does not compromise the survival of patients with early-stage endometrial cancer.¹²

Video 9. Carcinosarcoma 

Vidyard Video

Retrospective data from Chen and colleagues regarding type 2 endometrial carcinoma indicated a statistically significant increase in positive intraperitoneal cytology for carcinomas evaluated by hysteroscopy versus D&C (30% vs 12%; P = .008).¹³ Among the patients who died, there was no difference in disease-specific survival (53 months for hysteroscopy and 63.5 months for D&C; P = .34), and there was no difference in overall recurrence rates.¹³ Compared with type 1 endometrial carcinoma, type 2 endometrial carcinoma behaves more aggressively, with a higher incidence of extrauterine disease and an increased propensity for recurrence and poor outcome even in the early stages of the disease. This makes it difficult to determine the role of hysteroscopy in the prognosis of these carcinomas, especially in this study where most patients were diagnosed at a later stage.

Key takeaways

Hysteroscopy and directed biopsy are highly effective for visual and histopathologic diagnosis of atypical endometrial hyperplasia and endometrial carcinoma, and they are recommended in the evaluation of AUB, especially in the postmenopausal woman. When the hysteroscopic view is negative, there is a high correlation with the absence of uterine cavity and endometrial pathology. Hysteroscopic diagnostic accuracy is improved with structured use of visual grading scales, well-defined descriptors of endometrial pathology, and hysteroscopist experience.

Low operating intrauterine pressure may decrease the intraperitoneal spread of carcinoma cells during hysteroscopy, and current evidence suggests that there is no change in type 1 endometrial carcinoma prognosis and overall outcomes. Type 2 endometrial carcinoma is more aggressive and is associated with poor outcomes even in early stages, and the effect on disease progression by intraperitoneal spread of carcinoma cells at hysteroscopy is not yet known. Hysteroscopic evaluation of the uterine cavity and directed biopsy is easily and safely performed in the office and adds significantly to the evaluation and management of endometrial carcinoma.

Don’t miss the videos that accompany this article

---

Access them in the article online at mdedge.com/obgyn

Video 1. Endometrial carcinoma and visually directed biopsy

Nodular endometrioid adenocarcinoma grade 1 (type 1 endometrial carcinoma), benign endometrial polyps, and endometrial atrophy in a postmenopausal woman with bleeding. This video demonstrates visually directed biopsy to assure sampling of the most significant lesion.

Video 2. Negative hysteroscopic view

Digital flexible diagnostic hysteroscopy showing a negative hysteroscopic view in a premenopausal woman.

Video 3. Cervical spread of adenocarcinoma and visually directed biopsy 

Diffuse endometrioid adenocarcinoma spread to the upper cervical canal near the internal cervical os. Hysteroscopic directed biopsy is performed.

Video 4. Endometrial adenocarcinoma

Fiberoptic flexible diagnostic hysteroscopy demonstrating diffuse endometrioid adenocarcinoma grade 3 with multiple morphologic features: polypoid, nodular, papillary, and glomerular with areas of necrosis.

Video 5. Endometrial polyp and atypical hyperplasia

Large benign endometrial polyp in an asymptomatic postmenopausal woman with enlarged endometrial stripe on pelvic ultrasound. The endometrium is atrophic except for a small whitish area on the anterior wall, which is atypical hyperplasia. This video highlights the need for visually directed biopsy to assure sampling of the most significant lesion.

Video 6. Nodular, polypoid atypical hyperplasia

Fiberoptic flexible diagnostic hysteroscopy showing diffuse nodular and polypoid atypical hyperplasia with abnormal glandular openings in a postmenopausal woman. Hysterectomy was performed secondary to the significant likelihood of concomitant endometrial carcinoma.

Video 7. Visually directed endometrial biopsy

Hysteroscopic-directed biopsy showing the technique of grasping and removing tissue of a benign adenomyosis cyst and proliferative endometrium.

Video 8. Carcinosarcoma

Carcinosarcoma (type 2 endometrial carcinoma) presents as a large intracavitary mass with soft, polypoid-like tissue in a symptomatic postmenopausal woman with bleeding.

Video 9. Carcinosarcoma

Carcinosarcoma (type 2 endometrial carcinoma) presents as a dense mass in a symptomatic postmenopausal woman with bleeding. This video shows the mass is nodular. These cancers typically grow into a spherical mass within the cavity

 

For more than 45 years, gynecologists have used hysteroscopy to diagnose endometrial carcinoma and to associate morphologic descriptive terms with visual findings.¹ Today, considerably more clinical evidence supports visual pattern recognition to assess the risk for and presence of endometrial carcinoma, improving observer-dependent biopsy of the most suspect lesions (VIDEO 1).

In this article, I discuss the clinical evolution of hysteroscopic pattern recognition of endometrial disease and review the visual findings that correlate with the likelihood of endometrial carcinoma. In addition, I have provided 9 short videos that show hysteroscopic views of various endometrial pathologies in the online version of this article at https://www.mdedge.com/obgyn.

Video 1. Endometrial carcinoma and visually directed biopsy

Vidyard Video

The negative hysteroscopic view defined

In 1989, Dr. Frank Loffer confirmed the diagnostic superiority of visually directed biopsy. He demonstrated the advantages of using hysteroscopy and directed biopsy in the evaluation of abnormal uterine bleeding (AUB) to obtain a more accurate diagnosis compared with dilation and curettage (D&C) alone (sensitivity, 98% vs 65%, respectively).²

Also derived from this work is the clinical application of the “negative hysteroscopic view” (NHV). Loffer used the following criteria to define the NHV: good visualization of the entire uterine cavity, no structural abnormalities of the cavity, and a uniformly thin, homogeneous-appearing endometrium without variations in thickness (TABLE 1). The last criterion can be expected to occur only in the early proliferative phase or in postmenopausal women.

Use of hysteroscopy therefore can predict accurately the absence of intrauterine and endometrial pathology when visual findings are negative and tissue sampling is not warranted (FIGURE 1, VIDEO 2).

Video 2. Negative hysteroscopic view 

Vidyard Video

 

Efforts in hysteroscopic classification of endometrial carcinoma

Lesion morphologic characteristics. Sugimoto was among the first to describe the hysteroscopic identification of visual morphologic features that are most likely to be associated with endometrial carcinoma.¹ Patients with AUB were evaluated with hysteroscopy as first-line management to describe lesion morphology and confirm biopsy with histopathology. Sugimoto classified endometrial carcinoma as circumscribed or exophytic with distinct forms, such as polypoid, nodular, papillary, and ulcerated (FIGURE 2). Diffuse or endophytic carcinoma is defined by an ulcerated type of lesion that indicates necrosis; this is most likely to represent an undifferentiated tumor. Sugimoto also described abnormal vascularity that often is associated with carcinoma.¹

Endometrial features. Valli and Zupi created a nomenclature and classification for hysteroscopic endometrial lesions by prospectively grading 4 features: thickness, surface, vascularization, and color.³ Features were scored based on the degree of abnormality and could be considered to be of low or high risk for the presence of carcinoma. High-risk hysteroscopic features included endometrial thickness greater than 10 mm, polymorphous surface, irregular vascularization, and white-grayish color. The sensitivity for accurately diagnosing endometrial lesions was 86.9% for mild lesions and 96% for severe lesions.³ Also, these investigators confirmed the clinical value of the NHV and associated overall risk of precancer or cancer of the endometrium.

Continue to: Amount of endometrial involvement...

 

 

Amount of endometrial involvement. A few years later, Garuti and colleagues retrospectively related the hysteroscopic tumor features of known endometrial adenocarcinoma to stage, grade, and overall survival.⁴ In this system, they focused on classification of tumor morphology as nodular (bulging), polypoid (thin pedicles), or papillary (numerous dendritic projections), as well as whether the amount of abnormal tissue present was less than or more than half of the endometrium and if the lesion involved the cervix.

Several important findings associated with this system may improve visual diagnosis. First, hysteroscopic evaluation had a 100% negative predictive value for the cervical spread of disease (FIGURE 3, VIDEO 3). Second, the hysteroscopic morphologic tumor type did not relate to surgical stage or pathologic grade. Third, when less than half of the endometrium was involved, stage I disease was found (97%, 33 of 34). Last, when more than half of the endometrium was involved, advanced disease beyond stage I was found (9 of 26, 6 of whom had poorly differentiated disease).⁴

Video 3. Cervical spread of adenocarcinoma and visually directed biopsy

Vidyard Video

Structured pattern analysis. Recently, Dueholm and co-investigators published a prospective evaluation of women with postmenopausal bleeding and an endometrial thickness of 5 mm or greater.⁵ They used a structured system of visual pattern analysis during hysteroscopy that they termed the hysteroscopic cancer (HYCA) scoring system. The HYCA scoring system is based on surface outline (uneven, polypoid, and papillary projections), necrosis (cotton candy endometrium [FIGURE 4], whitish-grayish areas without vessels on the surface), and vessel pattern (tortuous S-shaped, loops, irregular caliber, irregular branching, and irregular distribution [FIGURE 5]). Structured pattern analysis predicted cancer with higher accuracy than subjective evaluation.⁵

Morphologic variables as indicators. In 2016, Ianieri and colleagues published a retrospective study on a risk scoring system for diagnosing endometrial hyperplasia and adenocarcinoma via hysteroscopy.⁶ They created a statistical risk model for development of the scoring system. A number of morphologic variables were prognostic indicators of atypical endometrial hyperplasia (AEH) and adenocarcinoma. These included widespread and irregular endometrial thickness, presence of multiple polyps with irregular aspects, dilated glandular orifices, irregular endometrial color (grey, white, or hyperemic), atypical vessels, crumbling of the endometrial neoplasms, and growth of cerebroid and arborescent aspects (VIDEO 4).

Video 4. Endometrial adenocarcinoma 

 

 

Vidyard Video

The scoring system for endometrial adenocarcinoma correctly classified 42 of 44 cancers (sensitivity, 95.4%; specificity, 98.2%), and AEH had a sensitivity of 63.3% and a specificity of 90.4%.⁶ These investigators also showed a high negative predictive value of 99.5% for endometrial adenocarcinoma associated with a negative view at hysteroscopy. Similar to the Dueholm data, Ianieri and colleagues’ morphologic pattern analysis predicted cancer with high accuracy.

Glomerular pattern association. Su and colleagues also showed that pattern recognition could aid in the accurate hysteroscopic diagnosis of endometrial adenocarcinoma.⁷ They used the hysteroscopic presence of a glomerular pattern to predict the association with endometrial adenocarcinoma. A glomerular pattern was described as polypoid endometrium with a papillary-like feature, containing an abnormal neovascularization feature with “intertwined neovascular vessels covered by a thin layer of endometrial tissue” (FIGURE 6). The presence of a glomerular pattern indicated grade 2 or grade 3 disease in 25 of 26 women (96%; sensitivity, 84.6%, specificity, 81.8%)⁷ (see video 4).

TABLE 2 summarizes significant morphologic findings relating to the presences of endometrial carcinoma.

Continue to: Atypical endometrial hyperplasia: A difficult diagnosis...

 

 

Atypical endometrial hyperplasia: A difficult diagnosis

The most common type of endometrial cancer is endometrioid adenocarcinoma (type 1 endometrial carcinoma), and it accounts for approximately 75% to 80% of endometrial cancer diagnoses.⁸ Risk factors include prolonged unopposed estrogen exposure, obesity, diabetes, and age. Type 1 endometrial carcinoma follows a progressive continuum of histopathologic change: from endometrial hyperplasia without atypia to endometrial hyperplasia with atypia (AEH) to well-differentiated endometrial cancer. Therefore, it is possible for endometrial carcinoma to be present simultaneously with AEH. The reported prevalence of concurrent endometrial carcinoma among patients with AEH on biopsy is between 17% and 52%.⁸ Thus, the clinical consideration is for hysterectomy, especially in the postmenopausal patient with a diagnosis of AEH.

Hysteroscopic diagnosis of AEH, however, is more difficult than identification of endometrial carcinoma because a range of morphologic characteristics exist that resemble normal endometrium as well as more progressive disease (VIDEO 5). De Franciscis and colleagues based a hysteroscopic diagnosis of hyperplasia on one or more of the following findings: focal or diffuse, papillary or polypoid, endometrial thickening; abnormal vascular patterns; evidence of glandular cysts; and abnormal architecture features of the glandular outlets (thickening, irregular gland density, or dilatation)⁹ (VIDEO 6).

Video 5. Endometrial polyp and atypical hyperplasia 

Vidyard Video

Additional studies, including that from Ianieri and colleagues, also have determined that AEH is difficult to discern visually from normal endometrium and other endometrial pathologies.⁶ In another investigation, Lasmar and coauthors reported a retrospective analysis of 4,054 hysteroscopic procedures with directed biopsies evaluating for concordance between the hysteroscopic view and histopathology.¹⁰ Agreement was 56.3% for AEH versus 94% for endometrial carcinoma. Among those with a histologic diagnosis of AEH, in 35.4% benign disease was suspected; in 2.1%, endometrial carcinoma was suspected; and in 6%, normal findings were presumed.¹⁰

Video 6. Nodular, polypoid atypical hyperplasia 

Vidyard Video

Because of the similarities in morphologic features between AEH and endometrial carcinoma, tissue biopsy under direct visualization is warranted to assure sampling of the most significantly abnormal tissue and to confirm visual interpretation of findings.

Techniques for hysteroscopic-directed biopsy

Using a visual assessment of endometrial abnormalities allows the surgeon to examine the entire uterine cavity and to biopsy the most suspicious and concerning lesions. The directed biopsy technique can involve a simple grasping maneuver: With the jaws of a small grasper open, push slightly forward to accumulate tissue within the jaw, close the jaw, and remove the tissue carefully through the cervix (VIDEO 7). The size of the sample may be limited, and multiple samples may be needed, depending on the quantity of the tissue retrieved.

Video 7. Visually directed endometrial biopsy

Vidyard Video

Another technique involves first creating a plane of tissue to be removed with scissors and subsequently grasping and removing the tissue (see video 1 and video 3). This particular technique will yield more tissue with one pass of the hysteroscope into the cavity. Careful removal of tissue through the cervix is facilitated by withdrawing the sample in the grasper and the hysteroscope together at the same time, without pulling the sample through the operative channel of the hysteroscope. Also, by turning off the inflow port, the stream of saline does not wash the sample off the grasper at hysteroscope removal from the cervix.

Blind biopsy. If visual inspection reveals a diffuse process within the uterine cavity such that no normal endometrium is noted and the abnormality is of equal degree throughout the endometrial surface, a decision can be made to replace directed biopsy with a blind biopsy. In this scenario, the blind biopsy is certain to sample the representative disease process and not potentially miss significant lesions (see video 4 and video 6). Otherwise, the hysteroscope-directed biopsy would be preferable.

Continue to: Potential for intraperitoneal dissemination of endometrial cancer...

 

 

Potential for intraperitoneal dissemination of endometrial cancer

There is some concern about intraperitoneal dissemination of endometrial carcinoma at the time of hysteroscopy and effect on disease prognosis. Chang and colleagues conducted a large meta-analysis and found that hysteroscopy performed in the presence of type 1 endometrial carcinoma statistically significantly increased the likelihood of positive intraperitoneal cytology.¹¹ In the included studies that reported survival rates (6 of 19), positive cytology did not alter the clinical outcome. The investigators recommended that hysteroscopy not be avoided for this reason, as it helps in the diagnosis of endometrial carcinoma, especially in the early stages of disease.¹¹

In a recent retrospective analysis, Namazov and colleagues included only stage I endometrial carcinoma (to exclude the adverse effect of advanced stage on survival) and evaluated the assumed isolated effect of hysteroscopy on survival.¹² They compared women in whom stage I endometrial carcinoma was diagnosed: 355 by hysteroscopy and 969 by a nonhysteroscopy method (D&C or office endometrial biopsy). Tumors were classified and grouped as low grade (endometrioid grade 1-2 and villoglandular) and high grade, consisting of endometrioid grade 3 and type 2 endometrial carcinoma (serous carcinoma, clear cell carcinoma, and carcinosarcoma) (VIDEOS 8 and 9). Positive intraperitoneal cytology at the time of surgery was 2.3% and 2.1% (P = .832), with an average interval from diagnosis to surgery of 34.6 days (range, 7–43 days).

Video 8. Carcinosarcoma 

Vidyard Video

The authors proposed several explanations for the low rate of intraperitoneal cytology with hysteroscopy. One possibility is having lower mean intrauterine pressure below 100 mm Hg for saline uterine distension, although this was not standardized for all surgeons in the study but rather was a custom of the institution. In addition, the length of time between hysteroscopy and surgery may allow the immune-reactive peritoneum to respond to the cellular insult, thus decreasing the biologic burden at the time of surgery. The median follow-up was 52 months (range, 12–120 months), and there were no differences between the hysteroscopy and the nonhysteroscopy groups in the 5-year recurrence-free survival (90.2% vs 88.2%; P = .53), disease-specific survival (93.4% vs 91.7%; P = .5), and overall survival (86.2% vs 80.6%; P = .22). The authors concluded that hysteroscopy does not compromise the survival of patients with early-stage endometrial cancer.¹²

Video 9. Carcinosarcoma 

Vidyard Video

Retrospective data from Chen and colleagues regarding type 2 endometrial carcinoma indicated a statistically significant increase in positive intraperitoneal cytology for carcinomas evaluated by hysteroscopy versus D&C (30% vs 12%; P = .008).¹³ Among the patients who died, there was no difference in disease-specific survival (53 months for hysteroscopy and 63.5 months for D&C; P = .34), and there was no difference in overall recurrence rates.¹³ Compared with type 1 endometrial carcinoma, type 2 endometrial carcinoma behaves more aggressively, with a higher incidence of extrauterine disease and an increased propensity for recurrence and poor outcome even in the early stages of the disease. This makes it difficult to determine the role of hysteroscopy in the prognosis of these carcinomas, especially in this study where most patients were diagnosed at a later stage.

Key takeaways

Hysteroscopy and directed biopsy are highly effective for visual and histopathologic diagnosis of atypical endometrial hyperplasia and endometrial carcinoma, and they are recommended in the evaluation of AUB, especially in the postmenopausal woman. When the hysteroscopic view is negative, there is a high correlation with the absence of uterine cavity and endometrial pathology. Hysteroscopic diagnostic accuracy is improved with structured use of visual grading scales, well-defined descriptors of endometrial pathology, and hysteroscopist experience.

Low operating intrauterine pressure may decrease the intraperitoneal spread of carcinoma cells during hysteroscopy, and current evidence suggests that there is no change in type 1 endometrial carcinoma prognosis and overall outcomes. Type 2 endometrial carcinoma is more aggressive and is associated with poor outcomes even in early stages, and the effect on disease progression by intraperitoneal spread of carcinoma cells at hysteroscopy is not yet known. Hysteroscopic evaluation of the uterine cavity and directed biopsy is easily and safely performed in the office and adds significantly to the evaluation and management of endometrial carcinoma.

Don’t miss the videos that accompany this article

---

Access them in the article online at mdedge.com/obgyn

Video 1. Endometrial carcinoma and visually directed biopsy

Nodular endometrioid adenocarcinoma grade 1 (type 1 endometrial carcinoma), benign endometrial polyps, and endometrial atrophy in a postmenopausal woman with bleeding. This video demonstrates visually directed biopsy to assure sampling of the most significant lesion.

Video 2. Negative hysteroscopic view

Digital flexible diagnostic hysteroscopy showing a negative hysteroscopic view in a premenopausal woman.

Video 3. Cervical spread of adenocarcinoma and visually directed biopsy 

Diffuse endometrioid adenocarcinoma spread to the upper cervical canal near the internal cervical os. Hysteroscopic directed biopsy is performed.

Video 4. Endometrial adenocarcinoma

Fiberoptic flexible diagnostic hysteroscopy demonstrating diffuse endometrioid adenocarcinoma grade 3 with multiple morphologic features: polypoid, nodular, papillary, and glomerular with areas of necrosis.

Video 5. Endometrial polyp and atypical hyperplasia

Large benign endometrial polyp in an asymptomatic postmenopausal woman with enlarged endometrial stripe on pelvic ultrasound. The endometrium is atrophic except for a small whitish area on the anterior wall, which is atypical hyperplasia. This video highlights the need for visually directed biopsy to assure sampling of the most significant lesion.

Video 6. Nodular, polypoid atypical hyperplasia

Fiberoptic flexible diagnostic hysteroscopy showing diffuse nodular and polypoid atypical hyperplasia with abnormal glandular openings in a postmenopausal woman. Hysterectomy was performed secondary to the significant likelihood of concomitant endometrial carcinoma.

Video 7. Visually directed endometrial biopsy

Hysteroscopic-directed biopsy showing the technique of grasping and removing tissue of a benign adenomyosis cyst and proliferative endometrium.

Video 8. Carcinosarcoma

Carcinosarcoma (type 2 endometrial carcinoma) presents as a large intracavitary mass with soft, polypoid-like tissue in a symptomatic postmenopausal woman with bleeding.

Video 9. Carcinosarcoma

Carcinosarcoma (type 2 endometrial carcinoma) presents as a dense mass in a symptomatic postmenopausal woman with bleeding. This video shows the mass is nodular. These cancers typically grow into a spherical mass within the cavity

 

This is the third and final article in a series focusing on malpractice, liability, and reform. In the first article, we looked at the background on malpractice and reasons malpractice rates have been so high—including large verdicts and lawsuit-prone physicians. In the second article we considered recent experience and developments in malpractice exposure, who is sued and why. Finally, in this third article, we focus on apologies, apology laws, and liability.

“I’m sorry”

In childhood we are all taught the basic courtesies: “please” and “thank you,” and “I’m sorry,” when harm has occurred. Should we as adult health care providers fear the consequences of apologizing? Apologies are a way for clinicians to express empathy; they also serve as a tool to reduce medical malpractice claims.¹

Apologies, ethics, and care

The American Medical Association takes the position that a physician has an ethical duty to disclose a harmful error to a patient.^2,3 Indeed this approach has been an impetus for states to enact apology laws, which we discuss below. As pointed out in this 2013 article title, “Dealing with a medical mistake: Should physicians apologize to patients?”,⁴ the legal benefits of any apology are an issue. It is a controversial area in medicine still today, including in obstetrics and gynecology.

“Ethical codes for both M.D.s and D.O.s suggest providers should display honesty and empathy following adverse events and errors.”^1,3,5 In addition, the American Medical Association states, “a physician should at all times deal honestly and openly with patients.”² Concerns about liability that may result from truthful disclosure should not affect the physician’s honesty (TABLE). Increasingly, the law has sided with that principle through apology laws.

Continue to: Legal issues and medical apologies...

Legal issues and medical apologies

From a legal standpoint, traditionally, an apology from a physician to a patient could be used against a physician in a medical liability (malpractice) case as proof of negligence.

Statements of interest. Such out-of-court statements ordinarily would be “hearsay” and excluded from evidence; there is, however, an exception to this hearsay rule that allows “confessions” or “statements against interest” to be admissible against the party making the statement. The theory is that when a statement is harmful to the person making it, the person likely thought that it was true, and the statement should be admissible at trial. We do not generally go around confessing to things that are not true. Following an auto crash, if one driver jumps out of the car saying, “I am so sorry I hit you. I was using my cell phone and did not see you stop,” the statement is against the interest of the driver and could be used in court.

As a matter of general legal principle, the same issue can arise in medical practice. Suppose a physician says, “I am so sorry for your injury. We made a mistake in interpreting the data from the monitors.” That sounds a lot like not just an apology but a statement against interest. Malpractice cases generally are based on the claim that a “doctor failed to do what a reasonable provider in the same specialty would have done in a similar situation.”¹³ An apology may be little more than general sympathy (“I’m sorry to tell you that we have not cured the infection. Unfortunately, that will mean more time in the hospital.”), but it can include a confession of error (“I’m sorry we got the x-ray backward and removed the wrong kidney.”). In the latter kind of apology, courts traditionally have found a “statement against interest.”

The legal consequence of a statement against interest is that the statement may be admitted in court. Such statements do not automatically establish negligence, but they can be powerful evidence when presented to a jury.

Courts have struggled with medical apologies. General sympathy or feelings of regret or compassion do not generally rise to the level of an admission that the physician did not use reasonable care under the circumstances and ordinarily are not admissible. (For further details, we refer you to the case of Cobbs v. Grant.¹⁴ Even if a physician said to the patient that he “blamed himself for [the patient] being back in the hospital for a second time,…the statement signifies compassion, or at most, a feeling of remorse, for plaintiff’s ordeal.”) On the other hand, in cases in which a physician in an apology referred to a “careless” mistake or even a “negligent” mistake, courts have allowed it admitted at trial as a statement against interest. (A 1946 case, Woronka v. Sewall, is an example.¹⁵ In that case, the physician said to the patient, “My God, what a mess…she had a very hard delivery, and it was a burning shame to get [an injury] on top of it, and it was because of negligence when they were upstairs.”) Some of these cases come down to the provider’s use of a single word: fault, careless, or negligence.

The ambiguity over the legal place of medical apologies in medicine led attorneys to urge medical providers to avoid statements that might even remotely be taken as statements against interest, including real apologies. The confusion over the admissibility of medical apologies led state legislatures to adopt apology laws. These laws essentially limit what statements against interest may be introduced in professional liability cases when a provider has issued a responsibility or apologized.

Continue to: Apology statutes...

Apology statutes

Massachusetts was the first state to enact an apology law—in 1986.¹ As of 2019, a clear majority of states have some form of apology statute. “Apology laws are gaining traction,” was the first sentence in a 2012 review on the subject by Saitta and colleagues.³ Only a few (5 states) have “strong” statutes that have broad protection for statements of fault, error, and negligence, as well as sympathy. The other 33 states have statutes that only protect against statements of sympathy.^4,16 FIGURE 1 is a US map showing the apology laws by state.¹

Do apology statutes and apologies reduce liability?

The positive aspects of apology include personal, psychological, and emotional benefits to both the one apologizing and the one receiving the apology. It also may have financial benefits to health care providers.⁴ The assumption has been, and there has been some evidence for the proposition, that apologies reduce the possibility of malpractice claims. That is one of the reasons that institutions may have formal apology policies. Indeed, there is evidence that apologies reduce financial awards to patients, as manifest in the states of Pennsylvania and Kentucky.⁴ Apologies appear to reduce patient anger and can open the door to better communication with the provider. There is evidence that some kinds of apologies tend to diminish blame and make the injured patient less likely to pursue litigation.¹⁰ The conclusion from these studies might be that honest and open communication serves to decrease the incidence of medical malpractice lawsuit initiation and that honesty is the best policy.

It is important to note the difference, however, between apologies (or institutional apology policies) and apology laws. There is some evidence that apology and institutional apology policies may reduce malpractice claims or losses.^17,18 On the other hand, the studies of apology laws have not found that these laws have much impact on malpractice rates. An especially good and thorough study of the effect of apology laws nationwide, using insurance claims data, essentially found little net effect of the apology laws.^19,20 One other study could find no evidence that apology statutes reduce defensive medicine (so no reduction in provider concerns over liability).²¹

It should be noted that most studies on medical apology and its effects on malpractice claims generally have looked at the narrow or limited apology statutes (that do not cover expressions of fault or negligence). Few states have the broader statutes, and it is possible that those broader statutes would be more effective in reducing liability. Removing the disincentives to medical apologies is a good thing, but in and of itself it is probably not a liability game changer.

Continue to: Institutional policy and apology...

Institutional policy and apology

Some institutions have established an “inclusion of apology” strategy for medical errors. These policies appear to have a meaningful effect on reducing medical malpractice costs. These programs commonly include a proactive investigation, disclosure of error, and apologies. Such policies have been studied at the University of Michigan and the Veterans Affairs (VA) Hospital in Lexington, Kentucky. The University of Michigan program resulted in a 60% reduction in compensation costs for medical errors.²² It also cut litigation costs by half.²³ The review of the Kentucky VA program also was positive.¹⁷ FIGURE 2 illustrates the key features of the Michigan program.²⁴

Conclusions: Effective apologies

Our conclusions, first, are that apologies are important from all perspectives: ethical, medical, and legal. On the other hand, all of the attention given in recent years to apology statutes may have been misplaced, at least if they were intended to be malpractice reform.¹⁷

Institutional apology and response programs are likely successful because they are thoughtfully put together, generally based on the best understanding of how injured patients respond to apologies and what it takes to be sincere, and communicate that sincerity, in the apology. What is an effective apology?, “The acceptance of responsibility for having caused harm.” It may, for example, mean accepting some financial responsibility for the harm. It is also important that the apology is conveyed in such a way that it includes an element of self-critical expression.²⁵ Although there are many formulations of the elements of an effective apology, one example is, “(1) acknowledging and accepting responsibility for the offense; (2) expressing remorse with forbearance, sincerity, and honesty; (3) explaining the understanding of the offense; and (4) willingness to make reparations.”²⁶

At the other extreme is a medical professional, after a bad event, trying to engage in a half-hearted, awkward, or insincere apology on an ad hoc and poorly planned basis. Worse still, “when victims perceive apologies to be insincere and designed simply to cool them off, they react with more rather than less indignation.”²⁷ Of course, the “forced apology” may be the worst of all. An instance of this was addressed in a New Zealand study in which providers were “forced” to provide a written apology to a couple (Mr. and Mrs. B) and a separate written apology to Baby B when there was failure to discuss vitamin K administration during the antenatal period when it was indicated.²⁸ Rather than emphasizing required apology in such a case, which can seem hollow and disingenuous, emphasis was placed on the apology providing a “positive-physiological” effect for those harmed, and on strategies that “nurture the development of the moral maturity required for authentic apology.”

The great advantage of institutional or practice-wide policies is that they can be developed in the calm of planning, with good foresight and careful consideration. This is much different from having to come up with some approach in the heat of something having gone wrong. Ultimately, however, apologies are not about liability. They are about caring for, respecting, and communicating with those who are harmed. Apologizing is often the right and professional thing to do.

This is the third and final article in a series focusing on malpractice, liability, and reform. In the first article, we looked at the background on malpractice and reasons malpractice rates have been so high—including large verdicts and lawsuit-prone physicians. In the second article we considered recent experience and developments in malpractice exposure, who is sued and why. Finally, in this third article, we focus on apologies, apology laws, and liability.

“I’m sorry”

In childhood we are all taught the basic courtesies: “please” and “thank you,” and “I’m sorry,” when harm has occurred. Should we as adult health care providers fear the consequences of apologizing? Apologies are a way for clinicians to express empathy; they also serve as a tool to reduce medical malpractice claims.¹

Apologies, ethics, and care

The American Medical Association takes the position that a physician has an ethical duty to disclose a harmful error to a patient.^2,3 Indeed this approach has been an impetus for states to enact apology laws, which we discuss below. As pointed out in this 2013 article title, “Dealing with a medical mistake: Should physicians apologize to patients?”,⁴ the legal benefits of any apology are an issue. It is a controversial area in medicine still today, including in obstetrics and gynecology.

“Ethical codes for both M.D.s and D.O.s suggest providers should display honesty and empathy following adverse events and errors.”^1,3,5 In addition, the American Medical Association states, “a physician should at all times deal honestly and openly with patients.”² Concerns about liability that may result from truthful disclosure should not affect the physician’s honesty (TABLE). Increasingly, the law has sided with that principle through apology laws.

Continue to: Legal issues and medical apologies...

Legal issues and medical apologies

From a legal standpoint, traditionally, an apology from a physician to a patient could be used against a physician in a medical liability (malpractice) case as proof of negligence.

Statements of interest. Such out-of-court statements ordinarily would be “hearsay” and excluded from evidence; there is, however, an exception to this hearsay rule that allows “confessions” or “statements against interest” to be admissible against the party making the statement. The theory is that when a statement is harmful to the person making it, the person likely thought that it was true, and the statement should be admissible at trial. We do not generally go around confessing to things that are not true. Following an auto crash, if one driver jumps out of the car saying, “I am so sorry I hit you. I was using my cell phone and did not see you stop,” the statement is against the interest of the driver and could be used in court.

As a matter of general legal principle, the same issue can arise in medical practice. Suppose a physician says, “I am so sorry for your injury. We made a mistake in interpreting the data from the monitors.” That sounds a lot like not just an apology but a statement against interest. Malpractice cases generally are based on the claim that a “doctor failed to do what a reasonable provider in the same specialty would have done in a similar situation.”¹³ An apology may be little more than general sympathy (“I’m sorry to tell you that we have not cured the infection. Unfortunately, that will mean more time in the hospital.”), but it can include a confession of error (“I’m sorry we got the x-ray backward and removed the wrong kidney.”). In the latter kind of apology, courts traditionally have found a “statement against interest.”

The legal consequence of a statement against interest is that the statement may be admitted in court. Such statements do not automatically establish negligence, but they can be powerful evidence when presented to a jury.

Courts have struggled with medical apologies. General sympathy or feelings of regret or compassion do not generally rise to the level of an admission that the physician did not use reasonable care under the circumstances and ordinarily are not admissible. (For further details, we refer you to the case of Cobbs v. Grant.¹⁴ Even if a physician said to the patient that he “blamed himself for [the patient] being back in the hospital for a second time,…the statement signifies compassion, or at most, a feeling of remorse, for plaintiff’s ordeal.”) On the other hand, in cases in which a physician in an apology referred to a “careless” mistake or even a “negligent” mistake, courts have allowed it admitted at trial as a statement against interest. (A 1946 case, Woronka v. Sewall, is an example.¹⁵ In that case, the physician said to the patient, “My God, what a mess…she had a very hard delivery, and it was a burning shame to get [an injury] on top of it, and it was because of negligence when they were upstairs.”) Some of these cases come down to the provider’s use of a single word: fault, careless, or negligence.

The ambiguity over the legal place of medical apologies in medicine led attorneys to urge medical providers to avoid statements that might even remotely be taken as statements against interest, including real apologies. The confusion over the admissibility of medical apologies led state legislatures to adopt apology laws. These laws essentially limit what statements against interest may be introduced in professional liability cases when a provider has issued a responsibility or apologized.

Continue to: Apology statutes...

Apology statutes

Massachusetts was the first state to enact an apology law—in 1986.¹ As of 2019, a clear majority of states have some form of apology statute. “Apology laws are gaining traction,” was the first sentence in a 2012 review on the subject by Saitta and colleagues.³ Only a few (5 states) have “strong” statutes that have broad protection for statements of fault, error, and negligence, as well as sympathy. The other 33 states have statutes that only protect against statements of sympathy.^4,16 FIGURE 1 is a US map showing the apology laws by state.¹

Do apology statutes and apologies reduce liability?

The positive aspects of apology include personal, psychological, and emotional benefits to both the one apologizing and the one receiving the apology. It also may have financial benefits to health care providers.⁴ The assumption has been, and there has been some evidence for the proposition, that apologies reduce the possibility of malpractice claims. That is one of the reasons that institutions may have formal apology policies. Indeed, there is evidence that apologies reduce financial awards to patients, as manifest in the states of Pennsylvania and Kentucky.⁴ Apologies appear to reduce patient anger and can open the door to better communication with the provider. There is evidence that some kinds of apologies tend to diminish blame and make the injured patient less likely to pursue litigation.¹⁰ The conclusion from these studies might be that honest and open communication serves to decrease the incidence of medical malpractice lawsuit initiation and that honesty is the best policy.

It is important to note the difference, however, between apologies (or institutional apology policies) and apology laws. There is some evidence that apology and institutional apology policies may reduce malpractice claims or losses.^17,18 On the other hand, the studies of apology laws have not found that these laws have much impact on malpractice rates. An especially good and thorough study of the effect of apology laws nationwide, using insurance claims data, essentially found little net effect of the apology laws.^19,20 One other study could find no evidence that apology statutes reduce defensive medicine (so no reduction in provider concerns over liability).²¹

It should be noted that most studies on medical apology and its effects on malpractice claims generally have looked at the narrow or limited apology statutes (that do not cover expressions of fault or negligence). Few states have the broader statutes, and it is possible that those broader statutes would be more effective in reducing liability. Removing the disincentives to medical apologies is a good thing, but in and of itself it is probably not a liability game changer.

Continue to: Institutional policy and apology...

Institutional policy and apology

Some institutions have established an “inclusion of apology” strategy for medical errors. These policies appear to have a meaningful effect on reducing medical malpractice costs. These programs commonly include a proactive investigation, disclosure of error, and apologies. Such policies have been studied at the University of Michigan and the Veterans Affairs (VA) Hospital in Lexington, Kentucky. The University of Michigan program resulted in a 60% reduction in compensation costs for medical errors.²² It also cut litigation costs by half.²³ The review of the Kentucky VA program also was positive.¹⁷ FIGURE 2 illustrates the key features of the Michigan program.²⁴

Conclusions: Effective apologies

Our conclusions, first, are that apologies are important from all perspectives: ethical, medical, and legal. On the other hand, all of the attention given in recent years to apology statutes may have been misplaced, at least if they were intended to be malpractice reform.¹⁷

Institutional apology and response programs are likely successful because they are thoughtfully put together, generally based on the best understanding of how injured patients respond to apologies and what it takes to be sincere, and communicate that sincerity, in the apology. What is an effective apology?, “The acceptance of responsibility for having caused harm.” It may, for example, mean accepting some financial responsibility for the harm. It is also important that the apology is conveyed in such a way that it includes an element of self-critical expression.²⁵ Although there are many formulations of the elements of an effective apology, one example is, “(1) acknowledging and accepting responsibility for the offense; (2) expressing remorse with forbearance, sincerity, and honesty; (3) explaining the understanding of the offense; and (4) willingness to make reparations.”²⁶

At the other extreme is a medical professional, after a bad event, trying to engage in a half-hearted, awkward, or insincere apology on an ad hoc and poorly planned basis. Worse still, “when victims perceive apologies to be insincere and designed simply to cool them off, they react with more rather than less indignation.”²⁷ Of course, the “forced apology” may be the worst of all. An instance of this was addressed in a New Zealand study in which providers were “forced” to provide a written apology to a couple (Mr. and Mrs. B) and a separate written apology to Baby B when there was failure to discuss vitamin K administration during the antenatal period when it was indicated.²⁸ Rather than emphasizing required apology in such a case, which can seem hollow and disingenuous, emphasis was placed on the apology providing a “positive-physiological” effect for those harmed, and on strategies that “nurture the development of the moral maturity required for authentic apology.”

The great advantage of institutional or practice-wide policies is that they can be developed in the calm of planning, with good foresight and careful consideration. This is much different from having to come up with some approach in the heat of something having gone wrong. Ultimately, however, apologies are not about liability. They are about caring for, respecting, and communicating with those who are harmed. Apologizing is often the right and professional thing to do.

This is the third and final article in a series focusing on malpractice, liability, and reform. In the first article, we looked at the background on malpractice and reasons malpractice rates have been so high—including large verdicts and lawsuit-prone physicians. In the second article we considered recent experience and developments in malpractice exposure, who is sued and why. Finally, in this third article, we focus on apologies, apology laws, and liability.

“I’m sorry”

In childhood we are all taught the basic courtesies: “please” and “thank you,” and “I’m sorry,” when harm has occurred. Should we as adult health care providers fear the consequences of apologizing? Apologies are a way for clinicians to express empathy; they also serve as a tool to reduce medical malpractice claims.¹

Apologies, ethics, and care

The American Medical Association takes the position that a physician has an ethical duty to disclose a harmful error to a patient.^2,3 Indeed this approach has been an impetus for states to enact apology laws, which we discuss below. As pointed out in this 2013 article title, “Dealing with a medical mistake: Should physicians apologize to patients?”,⁴ the legal benefits of any apology are an issue. It is a controversial area in medicine still today, including in obstetrics and gynecology.

“Ethical codes for both M.D.s and D.O.s suggest providers should display honesty and empathy following adverse events and errors.”^1,3,5 In addition, the American Medical Association states, “a physician should at all times deal honestly and openly with patients.”² Concerns about liability that may result from truthful disclosure should not affect the physician’s honesty (TABLE). Increasingly, the law has sided with that principle through apology laws.

Continue to: Legal issues and medical apologies...

Legal issues and medical apologies

From a legal standpoint, traditionally, an apology from a physician to a patient could be used against a physician in a medical liability (malpractice) case as proof of negligence.

Statements of interest. Such out-of-court statements ordinarily would be “hearsay” and excluded from evidence; there is, however, an exception to this hearsay rule that allows “confessions” or “statements against interest” to be admissible against the party making the statement. The theory is that when a statement is harmful to the person making it, the person likely thought that it was true, and the statement should be admissible at trial. We do not generally go around confessing to things that are not true. Following an auto crash, if one driver jumps out of the car saying, “I am so sorry I hit you. I was using my cell phone and did not see you stop,” the statement is against the interest of the driver and could be used in court.

As a matter of general legal principle, the same issue can arise in medical practice. Suppose a physician says, “I am so sorry for your injury. We made a mistake in interpreting the data from the monitors.” That sounds a lot like not just an apology but a statement against interest. Malpractice cases generally are based on the claim that a “doctor failed to do what a reasonable provider in the same specialty would have done in a similar situation.”¹³ An apology may be little more than general sympathy (“I’m sorry to tell you that we have not cured the infection. Unfortunately, that will mean more time in the hospital.”), but it can include a confession of error (“I’m sorry we got the x-ray backward and removed the wrong kidney.”). In the latter kind of apology, courts traditionally have found a “statement against interest.”

The legal consequence of a statement against interest is that the statement may be admitted in court. Such statements do not automatically establish negligence, but they can be powerful evidence when presented to a jury.

Courts have struggled with medical apologies. General sympathy or feelings of regret or compassion do not generally rise to the level of an admission that the physician did not use reasonable care under the circumstances and ordinarily are not admissible. (For further details, we refer you to the case of Cobbs v. Grant.¹⁴ Even if a physician said to the patient that he “blamed himself for [the patient] being back in the hospital for a second time,…the statement signifies compassion, or at most, a feeling of remorse, for plaintiff’s ordeal.”) On the other hand, in cases in which a physician in an apology referred to a “careless” mistake or even a “negligent” mistake, courts have allowed it admitted at trial as a statement against interest. (A 1946 case, Woronka v. Sewall, is an example.¹⁵ In that case, the physician said to the patient, “My God, what a mess…she had a very hard delivery, and it was a burning shame to get [an injury] on top of it, and it was because of negligence when they were upstairs.”) Some of these cases come down to the provider’s use of a single word: fault, careless, or negligence.

The ambiguity over the legal place of medical apologies in medicine led attorneys to urge medical providers to avoid statements that might even remotely be taken as statements against interest, including real apologies. The confusion over the admissibility of medical apologies led state legislatures to adopt apology laws. These laws essentially limit what statements against interest may be introduced in professional liability cases when a provider has issued a responsibility or apologized.

Continue to: Apology statutes...

Apology statutes

Massachusetts was the first state to enact an apology law—in 1986.¹ As of 2019, a clear majority of states have some form of apology statute. “Apology laws are gaining traction,” was the first sentence in a 2012 review on the subject by Saitta and colleagues.³ Only a few (5 states) have “strong” statutes that have broad protection for statements of fault, error, and negligence, as well as sympathy. The other 33 states have statutes that only protect against statements of sympathy.^4,16 FIGURE 1 is a US map showing the apology laws by state.¹

Do apology statutes and apologies reduce liability?

The positive aspects of apology include personal, psychological, and emotional benefits to both the one apologizing and the one receiving the apology. It also may have financial benefits to health care providers.⁴ The assumption has been, and there has been some evidence for the proposition, that apologies reduce the possibility of malpractice claims. That is one of the reasons that institutions may have formal apology policies. Indeed, there is evidence that apologies reduce financial awards to patients, as manifest in the states of Pennsylvania and Kentucky.⁴ Apologies appear to reduce patient anger and can open the door to better communication with the provider. There is evidence that some kinds of apologies tend to diminish blame and make the injured patient less likely to pursue litigation.¹⁰ The conclusion from these studies might be that honest and open communication serves to decrease the incidence of medical malpractice lawsuit initiation and that honesty is the best policy.

It is important to note the difference, however, between apologies (or institutional apology policies) and apology laws. There is some evidence that apology and institutional apology policies may reduce malpractice claims or losses.^17,18 On the other hand, the studies of apology laws have not found that these laws have much impact on malpractice rates. An especially good and thorough study of the effect of apology laws nationwide, using insurance claims data, essentially found little net effect of the apology laws.^19,20 One other study could find no evidence that apology statutes reduce defensive medicine (so no reduction in provider concerns over liability).²¹

It should be noted that most studies on medical apology and its effects on malpractice claims generally have looked at the narrow or limited apology statutes (that do not cover expressions of fault or negligence). Few states have the broader statutes, and it is possible that those broader statutes would be more effective in reducing liability. Removing the disincentives to medical apologies is a good thing, but in and of itself it is probably not a liability game changer.

Continue to: Institutional policy and apology...

Institutional policy and apology

Some institutions have established an “inclusion of apology” strategy for medical errors. These policies appear to have a meaningful effect on reducing medical malpractice costs. These programs commonly include a proactive investigation, disclosure of error, and apologies. Such policies have been studied at the University of Michigan and the Veterans Affairs (VA) Hospital in Lexington, Kentucky. The University of Michigan program resulted in a 60% reduction in compensation costs for medical errors.²² It also cut litigation costs by half.²³ The review of the Kentucky VA program also was positive.¹⁷ FIGURE 2 illustrates the key features of the Michigan program.²⁴

Conclusions: Effective apologies

Our conclusions, first, are that apologies are important from all perspectives: ethical, medical, and legal. On the other hand, all of the attention given in recent years to apology statutes may have been misplaced, at least if they were intended to be malpractice reform.¹⁷

Institutional apology and response programs are likely successful because they are thoughtfully put together, generally based on the best understanding of how injured patients respond to apologies and what it takes to be sincere, and communicate that sincerity, in the apology. What is an effective apology?, “The acceptance of responsibility for having caused harm.” It may, for example, mean accepting some financial responsibility for the harm. It is also important that the apology is conveyed in such a way that it includes an element of self-critical expression.²⁵ Although there are many formulations of the elements of an effective apology, one example is, “(1) acknowledging and accepting responsibility for the offense; (2) expressing remorse with forbearance, sincerity, and honesty; (3) explaining the understanding of the offense; and (4) willingness to make reparations.”²⁶

At the other extreme is a medical professional, after a bad event, trying to engage in a half-hearted, awkward, or insincere apology on an ad hoc and poorly planned basis. Worse still, “when victims perceive apologies to be insincere and designed simply to cool them off, they react with more rather than less indignation.”²⁷ Of course, the “forced apology” may be the worst of all. An instance of this was addressed in a New Zealand study in which providers were “forced” to provide a written apology to a couple (Mr. and Mrs. B) and a separate written apology to Baby B when there was failure to discuss vitamin K administration during the antenatal period when it was indicated.²⁸ Rather than emphasizing required apology in such a case, which can seem hollow and disingenuous, emphasis was placed on the apology providing a “positive-physiological” effect for those harmed, and on strategies that “nurture the development of the moral maturity required for authentic apology.”

The great advantage of institutional or practice-wide policies is that they can be developed in the calm of planning, with good foresight and careful consideration. This is much different from having to come up with some approach in the heat of something having gone wrong. Ultimately, however, apologies are not about liability. They are about caring for, respecting, and communicating with those who are harmed. Apologizing is often the right and professional thing to do.

Obesity is a disease causing a public health crisis. In the United States, tobacco use and obesity are the two most important causes of preventable premature death. They result in an estimated 480,000¹ and 300,000² premature deaths per year, respectively. Obesity is a major contributor to diabetes mellitus, hypertension, dyslipidemia, and coronary heart disease. Obesity is also associated with increased rates of colon, breast, and endometrial cancer. Experts predict that in 2030, 50% of adults in the United States will have a body mass index (BMI) ≥ 30 kg/m², and 25% will have a BMI ≥ 35 kg/m².³ More women than men are predicted to be severely obese (FIGURE).³

As clinicians we need to increase our efforts to reduce the epidemic of obesity. ObGyns can play an important role in preventing and managing obesity, by recommending primary-care weight management practices, prescribing medications that influence central metabolism, and referring appropriate patients to bariatric surgery centers of excellence.

Primary-care weight management

Measuring BMI and recommending interventions to prevent and treat obesity are important components of a health maintenance encounter. For women who are overweight or obese, dietary changes and exercise are important recommendations. The American Heart Association recommends the following lifestyle interventions⁴:

• Eat a high-quality diet that includes vegetables, fruit, whole grains, beans, legumes, nuts, plant-based protein, lean animal protein, and fish.
• Limit intake of sugary drinks and foods, fatty or processed meats, full-fat dairy products, eggs, highly processed foods, and tropical oils.
• Exercise at least 150 minutes weekly at a moderate activity level, including muscle-strengthening activity.
• Reduce prolonged intervals of sitting.
• Consider using an activity tracker to monitor activity level.

Clinicians should consider referring overweight and obese patients to a nutritionist for a consultation to plan how to consume a high-quality, low-calorie diet. A nutritionist can spend time with patients explaining options for implementing a calorie-restricted diet. In addition, some health insurers will require patients to participate in a supervised calorie-restricted diet plan for at least 6 months before authorizing coverage of expensive weight loss medications or bariatric surgery. In addition to recommending diet and exercise, ObGyns may consider prescribing metformin for their obese patients.

Continue to: Metformin...

Metformin

Metformin is approved for the treatment of type 2 diabetes mellitus. Unlike insulin therapy, which is associated with weight gain, metformin is associated with modest weight loss. The Diabetes Prevention Program (DPP) randomly assigned 3,234 nondiabetic participants with a fasting glucose level between 95 and 125 mg/dL and impaired glucose tolerance (140 to 199 mg/dL) after a 75-g oral glucose load to intensive lifestyle changes (calorie-restricted diet to achieve 7% weight loss plus 150 minutes of exercise weekly), metformin (850 mg twice daily), or placebo.^5,6 The mean age of the participants was 51 years, with a mean BMI of 34 kg/m². Most (68%) of the participants were women.

After 12 months of follow-up, mean weight loss in the intensive lifestyle change, metformin, and placebo groups was 6.5%, 2.7%, and 0.4%, respectively. After 2 years of treatment, weight loss among those who reliably took their metformin pills was approximately 4%, while participants in the placebo group had a 1% weight gain. Among those who continued to reliably take their metformin pills, the weight loss persisted through 9 years of follow up.

The mechanisms by which metformin causes weight loss are not clear. Metformin stimulates phosphorylation of adenosine monophosphate (AMP)-activated protein kinase, which regulates mitochondrial function, hepatic and muscle fatty acid oxidation, glucose transport, insulin secretion, and lipogenesis.⁷

Many ObGyns have experience in using metformin for the treatment of polycystic ovary syndrome or gestational diabetes. Hence, the dosing and adverse effects of metformin are familiar to many obstetricians-gynecologists. Metformin is contraindicated in individuals with creatinine clearance less than 30 mL/min. Rarely, metformin can cause lactic acidosis. According to Lexicomp,⁸ the most common adverse effects of metformin extended release (metformin ER) are diarrhea (17%), nausea and vomiting (7%), and decreased vitamin B12 concentration (7%) due to malabsorption in the terminal ileum. Of note, in the DPP study, hemoglobin concentration was slightly lower over time in the metformin compared with the placebo group (13.6 mg/dL vs 13.8 mg/dL, respectively; P<.001).⁶ Some experts recommend annual vitamin B12 measurement in individuals taking metformin.

In my practice, I only prescribe metformin ER. I usually start metformin treatment with one 750 mg ER tablet with dinner. If the patient tolerates that dose, I increase the dose to two 750 mg ER tablets with dinner. Metformin-induced adverse effects include diarrhea (17%) and nausea and vomiting (7%). Metformin ER is inexpensive. A one-month supply of metformin (sixty 750 mg tablets) costs between $4 and $21 at major pharmacies.⁹ Health insurance companies generally do not require preauthorization to cover metformin prescriptions.

Weight loss medications

US Food and Drug Administration (FDA)-approved weight loss medications include: liraglutide (Victoza), orlistat (Xenical, Alli), combination phentermine-extended release topiramate (Qsymia), and combination extended release naltrexone-bupropion (Contrave). All FDA-approved weight loss medications result in mean weight loss in the range of 6% to 10%. Many of these medications are very expensive (more than $200 per month).¹⁰ Insurance preauthorization is commonly required for these medications. For ObGyns, it may be best to refer patients who would like to use a weight loss medication to a specialist or specialty center with expertise in using these medications.

Sleeve gastrectomy

Two children are playing in a school yard. One child proudly states, “My mother is an endocrinologist. She treats diabetes.” Not to be outdone, the other child replies, “My mother is a bariatric surgeon. She cures diabetes.”

The dialogue reflects the reality that bariatric surgery results in more reliable and significant weight loss than diet, exercise, or weight loss medications. Diet, exercise, and weight loss medications often result in a 5% to 10% decrease in weight, but bariatric surgery typically results in a 25% decrease in weight. Until recently, 3 bariatric surgical procedures were commonly performed: Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and adjustable gastric banding (AGB). AGB is now seldom performed because it is less effective than RYGB and SG. Two recently published randomized trials compared the long-term outcomes associated with RYGB and SG. The studies found that SG and RYGB result in a similar degree of weight loss. RYGB resulted in slightly more weight loss than SG, but SG was associated with a lower rate of major complications, such as internal hernias. SG takes much less time to perform than RYGB. SG has become the most commonly performed bariatric surgery in premenopausal women considering pregnancy because of the low risk of internal hernias.

In the Swiss Multicenter Bypass or Sleeve Study (SM-BOSS), 217 participants with a mean BMI of 44 kg/m² and mean age of 45.5 years were randomly assigned to RYGB or SG and followed for 5 years.¹¹ The majority (72%) of the participants were women. At 5 years of follow-up, in the RYGB and SG groups, mean weight loss was 37 kg and 33 kg, respectively (P=.19). In both groups, weight loss nadir was reached 12 to 24 months after surgery. Expressed as a percentage of original weight, weight loss in the RYGB and SG groups was -29% and -25%, respectively (P=.02). Gastric reflux worsened in both the RYGB and SG groups (6% vs 32%, respectively). The number of reoperations in the RYGB and SG groups was 22% and 16%. Of note, among individuals with prevalent diabetes, RYGB and SG resulted in remission of the diabetes in 68% and 62% of participants, respectively.

In the Sleeve vs Bypass study (SLEEVEPASS), 240 participants, with mean BMI of 46 kg/m² and mean age of 48 years, were randomly assigned to RYGB or SG and followed for 5 years.¹² Most (70%) of the participants were women. Following bariatric surgery, BMI decreased significantly in both groups. In the RYGB group, BMI decreased from 48 kg/m² preoperatively to 35.4 kg/m² at 5 years of follow up. In the SG group, BMI decreased from 47 kg/m² preoperatively to 36.5 kg/m² at 5 years of follow up. Late major complications (defined as complications occurring from 30 days to 5 years postoperatively) occurred more frequently in the RYGB group (15%) versus the SG group (8%). All the late major complications required reoperation. In the SG group, 7 of 10 reoperations were for severe gastric reflux disease. In the RYGB group 17 of 18 reoperations were for suspected internal hernia, requiring closure of a mesenteric defect at reoperation. There was no treatment-related mortality during the 5-year follow up.

Guidelines for bariatric surgery are BMI ≥ 40 kg/m² without a comorbid illness or BMI ≥ 35 kg/m² with at least one serious comorbid disease, such as diabetes.¹³ ObGyns can build a synergistic relationship with bariatric surgeons by referring eligible patients for surgical consultation and, in return, accepting referrals. A paradox and challenge is that many health insurers require patients to complete a supervised medical weight loss management program prior to being approved for bariatric surgery. However, the medical weight loss program might result in the patient no longer being eligible for insurance coverage of their surgery. For example, a patient who had a BMI of 42 kg/m² prior to a medical weight loss management program who then lost enough weight to achieve a BMI of 38 kg/m² might no longer be eligible for insurance coverage of a bariatric operation.¹⁴

Continue to: ObGyns need to prioritize treatment for obesity...

ObGyns need to prioritize treatment for obesity

Between 1959 and 2014, US life expectancy increased from 69.9 years to 79.1 years. However, in 2015 and 2016 life expectancy in the United States decreased slightly to 78.9 years, while continuing to improve in other countries.¹⁵ What could cause such an unexpected trend? Some experts believe that excess overweight and obesity in the US population, resulting in increased rates of diabetes, hypertension, and heart disease, accounts for a significant proportion of the life expectancy gap between US citizens and those who reside in Australia, Finland, Japan, and Sweden.^16,17 All frontline clinicians play an important role in reversing the decades-long trend of increasing rates of overweight and obesity. Interventions that ObGyns could prioritize in their practices for treating overweight and obese patients include: a calorie-restricted diet, exercise, metformin, and SG.

Obesity is a disease causing a public health crisis. In the United States, tobacco use and obesity are the two most important causes of preventable premature death. They result in an estimated 480,000¹ and 300,000² premature deaths per year, respectively. Obesity is a major contributor to diabetes mellitus, hypertension, dyslipidemia, and coronary heart disease. Obesity is also associated with increased rates of colon, breast, and endometrial cancer. Experts predict that in 2030, 50% of adults in the United States will have a body mass index (BMI) ≥ 30 kg/m², and 25% will have a BMI ≥ 35 kg/m².³ More women than men are predicted to be severely obese (FIGURE).³

As clinicians we need to increase our efforts to reduce the epidemic of obesity. ObGyns can play an important role in preventing and managing obesity, by recommending primary-care weight management practices, prescribing medications that influence central metabolism, and referring appropriate patients to bariatric surgery centers of excellence.

Primary-care weight management

Measuring BMI and recommending interventions to prevent and treat obesity are important components of a health maintenance encounter. For women who are overweight or obese, dietary changes and exercise are important recommendations. The American Heart Association recommends the following lifestyle interventions⁴:

• Eat a high-quality diet that includes vegetables, fruit, whole grains, beans, legumes, nuts, plant-based protein, lean animal protein, and fish.
• Limit intake of sugary drinks and foods, fatty or processed meats, full-fat dairy products, eggs, highly processed foods, and tropical oils.
• Exercise at least 150 minutes weekly at a moderate activity level, including muscle-strengthening activity.
• Reduce prolonged intervals of sitting.
• Consider using an activity tracker to monitor activity level.

Clinicians should consider referring overweight and obese patients to a nutritionist for a consultation to plan how to consume a high-quality, low-calorie diet. A nutritionist can spend time with patients explaining options for implementing a calorie-restricted diet. In addition, some health insurers will require patients to participate in a supervised calorie-restricted diet plan for at least 6 months before authorizing coverage of expensive weight loss medications or bariatric surgery. In addition to recommending diet and exercise, ObGyns may consider prescribing metformin for their obese patients.

Continue to: Metformin...

Metformin

Metformin is approved for the treatment of type 2 diabetes mellitus. Unlike insulin therapy, which is associated with weight gain, metformin is associated with modest weight loss. The Diabetes Prevention Program (DPP) randomly assigned 3,234 nondiabetic participants with a fasting glucose level between 95 and 125 mg/dL and impaired glucose tolerance (140 to 199 mg/dL) after a 75-g oral glucose load to intensive lifestyle changes (calorie-restricted diet to achieve 7% weight loss plus 150 minutes of exercise weekly), metformin (850 mg twice daily), or placebo.^5,6 The mean age of the participants was 51 years, with a mean BMI of 34 kg/m². Most (68%) of the participants were women.

After 12 months of follow-up, mean weight loss in the intensive lifestyle change, metformin, and placebo groups was 6.5%, 2.7%, and 0.4%, respectively. After 2 years of treatment, weight loss among those who reliably took their metformin pills was approximately 4%, while participants in the placebo group had a 1% weight gain. Among those who continued to reliably take their metformin pills, the weight loss persisted through 9 years of follow up.

The mechanisms by which metformin causes weight loss are not clear. Metformin stimulates phosphorylation of adenosine monophosphate (AMP)-activated protein kinase, which regulates mitochondrial function, hepatic and muscle fatty acid oxidation, glucose transport, insulin secretion, and lipogenesis.⁷

Many ObGyns have experience in using metformin for the treatment of polycystic ovary syndrome or gestational diabetes. Hence, the dosing and adverse effects of metformin are familiar to many obstetricians-gynecologists. Metformin is contraindicated in individuals with creatinine clearance less than 30 mL/min. Rarely, metformin can cause lactic acidosis. According to Lexicomp,⁸ the most common adverse effects of metformin extended release (metformin ER) are diarrhea (17%), nausea and vomiting (7%), and decreased vitamin B12 concentration (7%) due to malabsorption in the terminal ileum. Of note, in the DPP study, hemoglobin concentration was slightly lower over time in the metformin compared with the placebo group (13.6 mg/dL vs 13.8 mg/dL, respectively; P<.001).⁶ Some experts recommend annual vitamin B12 measurement in individuals taking metformin.

In my practice, I only prescribe metformin ER. I usually start metformin treatment with one 750 mg ER tablet with dinner. If the patient tolerates that dose, I increase the dose to two 750 mg ER tablets with dinner. Metformin-induced adverse effects include diarrhea (17%) and nausea and vomiting (7%). Metformin ER is inexpensive. A one-month supply of metformin (sixty 750 mg tablets) costs between $4 and $21 at major pharmacies.⁹ Health insurance companies generally do not require preauthorization to cover metformin prescriptions.

Weight loss medications

US Food and Drug Administration (FDA)-approved weight loss medications include: liraglutide (Victoza), orlistat (Xenical, Alli), combination phentermine-extended release topiramate (Qsymia), and combination extended release naltrexone-bupropion (Contrave). All FDA-approved weight loss medications result in mean weight loss in the range of 6% to 10%. Many of these medications are very expensive (more than $200 per month).¹⁰ Insurance preauthorization is commonly required for these medications. For ObGyns, it may be best to refer patients who would like to use a weight loss medication to a specialist or specialty center with expertise in using these medications.

Sleeve gastrectomy

Two children are playing in a school yard. One child proudly states, “My mother is an endocrinologist. She treats diabetes.” Not to be outdone, the other child replies, “My mother is a bariatric surgeon. She cures diabetes.”

The dialogue reflects the reality that bariatric surgery results in more reliable and significant weight loss than diet, exercise, or weight loss medications. Diet, exercise, and weight loss medications often result in a 5% to 10% decrease in weight, but bariatric surgery typically results in a 25% decrease in weight. Until recently, 3 bariatric surgical procedures were commonly performed: Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and adjustable gastric banding (AGB). AGB is now seldom performed because it is less effective than RYGB and SG. Two recently published randomized trials compared the long-term outcomes associated with RYGB and SG. The studies found that SG and RYGB result in a similar degree of weight loss. RYGB resulted in slightly more weight loss than SG, but SG was associated with a lower rate of major complications, such as internal hernias. SG takes much less time to perform than RYGB. SG has become the most commonly performed bariatric surgery in premenopausal women considering pregnancy because of the low risk of internal hernias.

In the Swiss Multicenter Bypass or Sleeve Study (SM-BOSS), 217 participants with a mean BMI of 44 kg/m² and mean age of 45.5 years were randomly assigned to RYGB or SG and followed for 5 years.¹¹ The majority (72%) of the participants were women. At 5 years of follow-up, in the RYGB and SG groups, mean weight loss was 37 kg and 33 kg, respectively (P=.19). In both groups, weight loss nadir was reached 12 to 24 months after surgery. Expressed as a percentage of original weight, weight loss in the RYGB and SG groups was -29% and -25%, respectively (P=.02). Gastric reflux worsened in both the RYGB and SG groups (6% vs 32%, respectively). The number of reoperations in the RYGB and SG groups was 22% and 16%. Of note, among individuals with prevalent diabetes, RYGB and SG resulted in remission of the diabetes in 68% and 62% of participants, respectively.

In the Sleeve vs Bypass study (SLEEVEPASS), 240 participants, with mean BMI of 46 kg/m² and mean age of 48 years, were randomly assigned to RYGB or SG and followed for 5 years.¹² Most (70%) of the participants were women. Following bariatric surgery, BMI decreased significantly in both groups. In the RYGB group, BMI decreased from 48 kg/m² preoperatively to 35.4 kg/m² at 5 years of follow up. In the SG group, BMI decreased from 47 kg/m² preoperatively to 36.5 kg/m² at 5 years of follow up. Late major complications (defined as complications occurring from 30 days to 5 years postoperatively) occurred more frequently in the RYGB group (15%) versus the SG group (8%). All the late major complications required reoperation. In the SG group, 7 of 10 reoperations were for severe gastric reflux disease. In the RYGB group 17 of 18 reoperations were for suspected internal hernia, requiring closure of a mesenteric defect at reoperation. There was no treatment-related mortality during the 5-year follow up.

Guidelines for bariatric surgery are BMI ≥ 40 kg/m² without a comorbid illness or BMI ≥ 35 kg/m² with at least one serious comorbid disease, such as diabetes.¹³ ObGyns can build a synergistic relationship with bariatric surgeons by referring eligible patients for surgical consultation and, in return, accepting referrals. A paradox and challenge is that many health insurers require patients to complete a supervised medical weight loss management program prior to being approved for bariatric surgery. However, the medical weight loss program might result in the patient no longer being eligible for insurance coverage of their surgery. For example, a patient who had a BMI of 42 kg/m² prior to a medical weight loss management program who then lost enough weight to achieve a BMI of 38 kg/m² might no longer be eligible for insurance coverage of a bariatric operation.¹⁴

Continue to: ObGyns need to prioritize treatment for obesity...

ObGyns need to prioritize treatment for obesity

Between 1959 and 2014, US life expectancy increased from 69.9 years to 79.1 years. However, in 2015 and 2016 life expectancy in the United States decreased slightly to 78.9 years, while continuing to improve in other countries.¹⁵ What could cause such an unexpected trend? Some experts believe that excess overweight and obesity in the US population, resulting in increased rates of diabetes, hypertension, and heart disease, accounts for a significant proportion of the life expectancy gap between US citizens and those who reside in Australia, Finland, Japan, and Sweden.^16,17 All frontline clinicians play an important role in reversing the decades-long trend of increasing rates of overweight and obesity. Interventions that ObGyns could prioritize in their practices for treating overweight and obese patients include: a calorie-restricted diet, exercise, metformin, and SG.

Obesity is a disease causing a public health crisis. In the United States, tobacco use and obesity are the two most important causes of preventable premature death. They result in an estimated 480,000¹ and 300,000² premature deaths per year, respectively. Obesity is a major contributor to diabetes mellitus, hypertension, dyslipidemia, and coronary heart disease. Obesity is also associated with increased rates of colon, breast, and endometrial cancer. Experts predict that in 2030, 50% of adults in the United States will have a body mass index (BMI) ≥ 30 kg/m², and 25% will have a BMI ≥ 35 kg/m².³ More women than men are predicted to be severely obese (FIGURE).³

As clinicians we need to increase our efforts to reduce the epidemic of obesity. ObGyns can play an important role in preventing and managing obesity, by recommending primary-care weight management practices, prescribing medications that influence central metabolism, and referring appropriate patients to bariatric surgery centers of excellence.

Primary-care weight management

Measuring BMI and recommending interventions to prevent and treat obesity are important components of a health maintenance encounter. For women who are overweight or obese, dietary changes and exercise are important recommendations. The American Heart Association recommends the following lifestyle interventions⁴:

• Eat a high-quality diet that includes vegetables, fruit, whole grains, beans, legumes, nuts, plant-based protein, lean animal protein, and fish.
• Limit intake of sugary drinks and foods, fatty or processed meats, full-fat dairy products, eggs, highly processed foods, and tropical oils.
• Exercise at least 150 minutes weekly at a moderate activity level, including muscle-strengthening activity.
• Reduce prolonged intervals of sitting.
• Consider using an activity tracker to monitor activity level.

Clinicians should consider referring overweight and obese patients to a nutritionist for a consultation to plan how to consume a high-quality, low-calorie diet. A nutritionist can spend time with patients explaining options for implementing a calorie-restricted diet. In addition, some health insurers will require patients to participate in a supervised calorie-restricted diet plan for at least 6 months before authorizing coverage of expensive weight loss medications or bariatric surgery. In addition to recommending diet and exercise, ObGyns may consider prescribing metformin for their obese patients.

Continue to: Metformin...

Metformin

Metformin is approved for the treatment of type 2 diabetes mellitus. Unlike insulin therapy, which is associated with weight gain, metformin is associated with modest weight loss. The Diabetes Prevention Program (DPP) randomly assigned 3,234 nondiabetic participants with a fasting glucose level between 95 and 125 mg/dL and impaired glucose tolerance (140 to 199 mg/dL) after a 75-g oral glucose load to intensive lifestyle changes (calorie-restricted diet to achieve 7% weight loss plus 150 minutes of exercise weekly), metformin (850 mg twice daily), or placebo.^5,6 The mean age of the participants was 51 years, with a mean BMI of 34 kg/m². Most (68%) of the participants were women.

After 12 months of follow-up, mean weight loss in the intensive lifestyle change, metformin, and placebo groups was 6.5%, 2.7%, and 0.4%, respectively. After 2 years of treatment, weight loss among those who reliably took their metformin pills was approximately 4%, while participants in the placebo group had a 1% weight gain. Among those who continued to reliably take their metformin pills, the weight loss persisted through 9 years of follow up.

The mechanisms by which metformin causes weight loss are not clear. Metformin stimulates phosphorylation of adenosine monophosphate (AMP)-activated protein kinase, which regulates mitochondrial function, hepatic and muscle fatty acid oxidation, glucose transport, insulin secretion, and lipogenesis.⁷

Many ObGyns have experience in using metformin for the treatment of polycystic ovary syndrome or gestational diabetes. Hence, the dosing and adverse effects of metformin are familiar to many obstetricians-gynecologists. Metformin is contraindicated in individuals with creatinine clearance less than 30 mL/min. Rarely, metformin can cause lactic acidosis. According to Lexicomp,⁸ the most common adverse effects of metformin extended release (metformin ER) are diarrhea (17%), nausea and vomiting (7%), and decreased vitamin B12 concentration (7%) due to malabsorption in the terminal ileum. Of note, in the DPP study, hemoglobin concentration was slightly lower over time in the metformin compared with the placebo group (13.6 mg/dL vs 13.8 mg/dL, respectively; P<.001).⁶ Some experts recommend annual vitamin B12 measurement in individuals taking metformin.

In my practice, I only prescribe metformin ER. I usually start metformin treatment with one 750 mg ER tablet with dinner. If the patient tolerates that dose, I increase the dose to two 750 mg ER tablets with dinner. Metformin-induced adverse effects include diarrhea (17%) and nausea and vomiting (7%). Metformin ER is inexpensive. A one-month supply of metformin (sixty 750 mg tablets) costs between $4 and $21 at major pharmacies.⁹ Health insurance companies generally do not require preauthorization to cover metformin prescriptions.

Weight loss medications

US Food and Drug Administration (FDA)-approved weight loss medications include: liraglutide (Victoza), orlistat (Xenical, Alli), combination phentermine-extended release topiramate (Qsymia), and combination extended release naltrexone-bupropion (Contrave). All FDA-approved weight loss medications result in mean weight loss in the range of 6% to 10%. Many of these medications are very expensive (more than $200 per month).¹⁰ Insurance preauthorization is commonly required for these medications. For ObGyns, it may be best to refer patients who would like to use a weight loss medication to a specialist or specialty center with expertise in using these medications.

Sleeve gastrectomy

Two children are playing in a school yard. One child proudly states, “My mother is an endocrinologist. She treats diabetes.” Not to be outdone, the other child replies, “My mother is a bariatric surgeon. She cures diabetes.”

The dialogue reflects the reality that bariatric surgery results in more reliable and significant weight loss than diet, exercise, or weight loss medications. Diet, exercise, and weight loss medications often result in a 5% to 10% decrease in weight, but bariatric surgery typically results in a 25% decrease in weight. Until recently, 3 bariatric surgical procedures were commonly performed: Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and adjustable gastric banding (AGB). AGB is now seldom performed because it is less effective than RYGB and SG. Two recently published randomized trials compared the long-term outcomes associated with RYGB and SG. The studies found that SG and RYGB result in a similar degree of weight loss. RYGB resulted in slightly more weight loss than SG, but SG was associated with a lower rate of major complications, such as internal hernias. SG takes much less time to perform than RYGB. SG has become the most commonly performed bariatric surgery in premenopausal women considering pregnancy because of the low risk of internal hernias.

In the Swiss Multicenter Bypass or Sleeve Study (SM-BOSS), 217 participants with a mean BMI of 44 kg/m² and mean age of 45.5 years were randomly assigned to RYGB or SG and followed for 5 years.¹¹ The majority (72%) of the participants were women. At 5 years of follow-up, in the RYGB and SG groups, mean weight loss was 37 kg and 33 kg, respectively (P=.19). In both groups, weight loss nadir was reached 12 to 24 months after surgery. Expressed as a percentage of original weight, weight loss in the RYGB and SG groups was -29% and -25%, respectively (P=.02). Gastric reflux worsened in both the RYGB and SG groups (6% vs 32%, respectively). The number of reoperations in the RYGB and SG groups was 22% and 16%. Of note, among individuals with prevalent diabetes, RYGB and SG resulted in remission of the diabetes in 68% and 62% of participants, respectively.

In the Sleeve vs Bypass study (SLEEVEPASS), 240 participants, with mean BMI of 46 kg/m² and mean age of 48 years, were randomly assigned to RYGB or SG and followed for 5 years.¹² Most (70%) of the participants were women. Following bariatric surgery, BMI decreased significantly in both groups. In the RYGB group, BMI decreased from 48 kg/m² preoperatively to 35.4 kg/m² at 5 years of follow up. In the SG group, BMI decreased from 47 kg/m² preoperatively to 36.5 kg/m² at 5 years of follow up. Late major complications (defined as complications occurring from 30 days to 5 years postoperatively) occurred more frequently in the RYGB group (15%) versus the SG group (8%). All the late major complications required reoperation. In the SG group, 7 of 10 reoperations were for severe gastric reflux disease. In the RYGB group 17 of 18 reoperations were for suspected internal hernia, requiring closure of a mesenteric defect at reoperation. There was no treatment-related mortality during the 5-year follow up.

Guidelines for bariatric surgery are BMI ≥ 40 kg/m² without a comorbid illness or BMI ≥ 35 kg/m² with at least one serious comorbid disease, such as diabetes.¹³ ObGyns can build a synergistic relationship with bariatric surgeons by referring eligible patients for surgical consultation and, in return, accepting referrals. A paradox and challenge is that many health insurers require patients to complete a supervised medical weight loss management program prior to being approved for bariatric surgery. However, the medical weight loss program might result in the patient no longer being eligible for insurance coverage of their surgery. For example, a patient who had a BMI of 42 kg/m² prior to a medical weight loss management program who then lost enough weight to achieve a BMI of 38 kg/m² might no longer be eligible for insurance coverage of a bariatric operation.¹⁴

Continue to: ObGyns need to prioritize treatment for obesity...

ObGyns need to prioritize treatment for obesity

Between 1959 and 2014, US life expectancy increased from 69.9 years to 79.1 years. However, in 2015 and 2016 life expectancy in the United States decreased slightly to 78.9 years, while continuing to improve in other countries.¹⁵ What could cause such an unexpected trend? Some experts believe that excess overweight and obesity in the US population, resulting in increased rates of diabetes, hypertension, and heart disease, accounts for a significant proportion of the life expectancy gap between US citizens and those who reside in Australia, Finland, Japan, and Sweden.^16,17 All frontline clinicians play an important role in reversing the decades-long trend of increasing rates of overweight and obesity. Interventions that ObGyns could prioritize in their practices for treating overweight and obese patients include: a calorie-restricted diet, exercise, metformin, and SG.

The toilet bowl, sink, and bathroom door handle of an isolation room housing a patient with the novel coronavirus tested positive for the virus, raising the possibility that viral shedding in the stool could represent another route of transmission, investigators reported.

CDC/ Dr. Fred Murphy; Sylvia Whitfield

Air outlet fans and other room sites also tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), though an anteroom, a corridor, and most personal protective equipment (PPE) worn by health care providers tested negative, according to the researchers, led by Sean Wei Xiang Ong, MBBS, of the National Centre for Infectious Diseases, Singapore.

Taken together, these findings suggest a “need for strict adherence to environmental and hand hygiene” to combat significant environmental contamination through respiratory droplets and fecal shedding, Dr. Ong and colleagues wrote in JAMA.

Aaron Eli Glatt, MD, chair of medicine at Mount Sinai South Nassau in New York, said these results demonstrate that SARS-CoV-2 is “clearly capable” of contaminating bathroom sinks and toilets.

“That wouldn’t have been the first place I would have thought of, before this study,” he said in an interview. “You need to pay attention to cleaning the bathrooms, which we obviously do, but that’s an important reminder.”

The report by Dr. Ong and coauthors included a total of three patients housed in airborne infection isolation rooms in a dedicated SARS-CoV-2 outbreak center in Singapore. For each patient, surface samples were taken from 26 sites in the isolation room, an anteroom, and a bathroom. Samples were also taken from PPE on physicians as they left the patient rooms.

Samples for the first patient, taken right after routine cleaning, were all negative, according to researchers. That room was sampled twice, on days 4 and 10 of the illness, while the patient was still symptomatic. Likewise, for the second patient, postcleaning samples were negative; those samples were taken 2 days after cleaning.

However, for the third patient, samples were taken before routine cleaning. In this case, Dr. Ong and colleagues said 13 of 15 room sites (87%) were positive, including air outlet fans, while 3 of 5 toilet sites (60%) were positive as well, though no contamination was found in the anteroom, corridor, or in air samples.

That patient had two stool samples that were positive for SARS-CoV-2, but no diarrhea, authors said, and had upper respiratory tract involvement without pneumonia.

The fact that swabs of the air exhaust outlets tested positive suggests that virus-laden droplets could be “displaced by airflows” and end up on vents or other equipment, Dr. Ong and coauthors reported.

All PPE samples tested negative, except for the front of one shoe.

“The risk of transmission from contaminated footwear is likely low, as evidenced by negative results in the anteroom and corridor,” they wrote.

While this study included only a small number of patients, Dr. Glatt said the findings represent an important and useful contribution to the literature on coronavirus disease 2019 (COVID-19).

“Every day we’re getting more information, and each little piece of the puzzle helps us in the overall management of individuals with COVID-19,” he said in the interview. “They’re adding to our ability to manage, control, and mitigate further spread of the disease.”

Funding for the study came from the National Medical Research Council in Singapore and DSO National Laboratories. Dr. Ong and colleagues reported no conflicts of interest.

SOURCE: Ong SWX et al. JAMA. 2020 Mar 4. doi: 10.1001/jama.2020.3227.

The toilet bowl, sink, and bathroom door handle of an isolation room housing a patient with the novel coronavirus tested positive for the virus, raising the possibility that viral shedding in the stool could represent another route of transmission, investigators reported.

CDC/ Dr. Fred Murphy; Sylvia Whitfield

Air outlet fans and other room sites also tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), though an anteroom, a corridor, and most personal protective equipment (PPE) worn by health care providers tested negative, according to the researchers, led by Sean Wei Xiang Ong, MBBS, of the National Centre for Infectious Diseases, Singapore.

Taken together, these findings suggest a “need for strict adherence to environmental and hand hygiene” to combat significant environmental contamination through respiratory droplets and fecal shedding, Dr. Ong and colleagues wrote in JAMA.

Aaron Eli Glatt, MD, chair of medicine at Mount Sinai South Nassau in New York, said these results demonstrate that SARS-CoV-2 is “clearly capable” of contaminating bathroom sinks and toilets.

“That wouldn’t have been the first place I would have thought of, before this study,” he said in an interview. “You need to pay attention to cleaning the bathrooms, which we obviously do, but that’s an important reminder.”

The report by Dr. Ong and coauthors included a total of three patients housed in airborne infection isolation rooms in a dedicated SARS-CoV-2 outbreak center in Singapore. For each patient, surface samples were taken from 26 sites in the isolation room, an anteroom, and a bathroom. Samples were also taken from PPE on physicians as they left the patient rooms.

Samples for the first patient, taken right after routine cleaning, were all negative, according to researchers. That room was sampled twice, on days 4 and 10 of the illness, while the patient was still symptomatic. Likewise, for the second patient, postcleaning samples were negative; those samples were taken 2 days after cleaning.

However, for the third patient, samples were taken before routine cleaning. In this case, Dr. Ong and colleagues said 13 of 15 room sites (87%) were positive, including air outlet fans, while 3 of 5 toilet sites (60%) were positive as well, though no contamination was found in the anteroom, corridor, or in air samples.

That patient had two stool samples that were positive for SARS-CoV-2, but no diarrhea, authors said, and had upper respiratory tract involvement without pneumonia.

The fact that swabs of the air exhaust outlets tested positive suggests that virus-laden droplets could be “displaced by airflows” and end up on vents or other equipment, Dr. Ong and coauthors reported.

All PPE samples tested negative, except for the front of one shoe.

“The risk of transmission from contaminated footwear is likely low, as evidenced by negative results in the anteroom and corridor,” they wrote.

While this study included only a small number of patients, Dr. Glatt said the findings represent an important and useful contribution to the literature on coronavirus disease 2019 (COVID-19).

“Every day we’re getting more information, and each little piece of the puzzle helps us in the overall management of individuals with COVID-19,” he said in the interview. “They’re adding to our ability to manage, control, and mitigate further spread of the disease.”

Funding for the study came from the National Medical Research Council in Singapore and DSO National Laboratories. Dr. Ong and colleagues reported no conflicts of interest.

SOURCE: Ong SWX et al. JAMA. 2020 Mar 4. doi: 10.1001/jama.2020.3227.

The toilet bowl, sink, and bathroom door handle of an isolation room housing a patient with the novel coronavirus tested positive for the virus, raising the possibility that viral shedding in the stool could represent another route of transmission, investigators reported.

CDC/ Dr. Fred Murphy; Sylvia Whitfield

Air outlet fans and other room sites also tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), though an anteroom, a corridor, and most personal protective equipment (PPE) worn by health care providers tested negative, according to the researchers, led by Sean Wei Xiang Ong, MBBS, of the National Centre for Infectious Diseases, Singapore.

Taken together, these findings suggest a “need for strict adherence to environmental and hand hygiene” to combat significant environmental contamination through respiratory droplets and fecal shedding, Dr. Ong and colleagues wrote in JAMA.

Aaron Eli Glatt, MD, chair of medicine at Mount Sinai South Nassau in New York, said these results demonstrate that SARS-CoV-2 is “clearly capable” of contaminating bathroom sinks and toilets.

“That wouldn’t have been the first place I would have thought of, before this study,” he said in an interview. “You need to pay attention to cleaning the bathrooms, which we obviously do, but that’s an important reminder.”

The report by Dr. Ong and coauthors included a total of three patients housed in airborne infection isolation rooms in a dedicated SARS-CoV-2 outbreak center in Singapore. For each patient, surface samples were taken from 26 sites in the isolation room, an anteroom, and a bathroom. Samples were also taken from PPE on physicians as they left the patient rooms.

Samples for the first patient, taken right after routine cleaning, were all negative, according to researchers. That room was sampled twice, on days 4 and 10 of the illness, while the patient was still symptomatic. Likewise, for the second patient, postcleaning samples were negative; those samples were taken 2 days after cleaning.

However, for the third patient, samples were taken before routine cleaning. In this case, Dr. Ong and colleagues said 13 of 15 room sites (87%) were positive, including air outlet fans, while 3 of 5 toilet sites (60%) were positive as well, though no contamination was found in the anteroom, corridor, or in air samples.

That patient had two stool samples that were positive for SARS-CoV-2, but no diarrhea, authors said, and had upper respiratory tract involvement without pneumonia.

The fact that swabs of the air exhaust outlets tested positive suggests that virus-laden droplets could be “displaced by airflows” and end up on vents or other equipment, Dr. Ong and coauthors reported.

All PPE samples tested negative, except for the front of one shoe.

“The risk of transmission from contaminated footwear is likely low, as evidenced by negative results in the anteroom and corridor,” they wrote.

While this study included only a small number of patients, Dr. Glatt said the findings represent an important and useful contribution to the literature on coronavirus disease 2019 (COVID-19).

“Every day we’re getting more information, and each little piece of the puzzle helps us in the overall management of individuals with COVID-19,” he said in the interview. “They’re adding to our ability to manage, control, and mitigate further spread of the disease.”

Funding for the study came from the National Medical Research Council in Singapore and DSO National Laboratories. Dr. Ong and colleagues reported no conflicts of interest.

SOURCE: Ong SWX et al. JAMA. 2020 Mar 4. doi: 10.1001/jama.2020.3227.

NATIONAL HARBOR, MD. – Stimulation of the infrapatellar branch of the saphenous nerve with an implantable electrical device is a potentially effective treatment for chronic, intractable knee pain.

In a small case series consisting of five patients with chronic knee pain, pain intensity scores on the visual analog scale (VAS) dropped from an average of 8 out of 10 before the implant to 1.4 out of 10 when measured 6 months afterward.

Pain relief was also long lasting, with an average score at 2 years still significantly reduced from baseline, at 3 out of 10 on the VAS.

“We have a lot of patients with chronic knee pain, and unfortunately, our hands are tied in terms of what we can do for them,” lead author Kwo Wei David Ho, MD, PhD, Stanford University, California, told Medscape Medical News.

“They can use NSAIDs, physical therapy, some get steroid injections, or genicular nerve blocks, but they don’t work that well. Some have knee replacement surgery, and can still have persistent knee pain after the operation, so here we are using an alternative therapy called peripheral nerve stimulation of the saphenous nerve. This provides a way to relieve pain without nerve destruction or motor dysfunction,” Ho said.

The findings were presented here at the American Academy of Pain Medicine (AAPM) 2020 Annual Meeting.

Patient Controlled

For the study, the investigators surgically implanted five patients with intractable knee pain with the StimRouter™ (Bioness, Inc).

The device takes about 15 to 30 minutes to implant, much like a pacemaker, and reduces pain by delivering gentle electrical stimulation directly to a target peripheral nerve, in this case the saphenous nerve, to interrupt the pain signal, Ho said.

“A thin, threadlike lead, or noodle, is implanted below the skin next to the target peripheral nerve responsible for the pain signal under ultrasound guidance, and then a patch or external pulse transmitter (EPT) is worn on top of the skin. This sends electric stimulation through the skin to the lead,” he explained.

The patient can then control the EPT and adjust stimulation with a wireless handheld programmer.

“Some patients turn it on at night for a couple of hours and then turn it off, some leave it on for the entire night, or the whole day if they prefer. What we’ve been noticing in our series is that after a while, patients are using less and less, and the pain gets better and better, and eventually they stop using it entirely because the pain completely resolves,” Ho said.

Good candidates for this treatment are post-knee replacement patients with residual pain, he added.

Durable Effect

Of the five patients in the case series, four had previous knee arthroplasty.

To determine the chances of a good response to the implant, study participants underwent a diagnostic saphenous nerve block, with the rationale that if the block successfully reduced knee pain by 50% or more in the short term, patients would likely respond well to the implant.

Before the peripheral nerve stimulation implant, the average pain intensity was 7.8 out of 10 on the VAS. After stimulator implantation, the average pain intensity was 1.4 at 6 months (P = .019, in 5 patients). At 1 year, the average pain intensity score was virtually the same, at 1.5 on the VAS, (P = .0032, in 4 patients). At 2 years, the average pain intensity score was 2.75 (P = .12, in 2 patients).

“This study provides preliminary evidence that stimulation at the saphenous nerve may be effective for selected patients with chronic knee pain,” Ho said.

Commenting on the findings for Medscape Medical News, Patrick Tighe, MD, MS, University of Florida, Gainesville, said that chronic knee pain continues to present “numerous diagnostic and therapeutic challenges for many patients.”

“It may be surprising, but there is still so much we don’t know about the innervation of the knee, and we are still learning about different ways to alter the behavior of those nerves,” said Tighe, who was not involved with the current study.

“This work points to some exciting opportunities to help patients suffering from chronic knee pain. We certainly need more research in this area to figure out the optimal approach to applying these findings more widely,” he said.

Ho and Tighe have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

NATIONAL HARBOR, MD. – Stimulation of the infrapatellar branch of the saphenous nerve with an implantable electrical device is a potentially effective treatment for chronic, intractable knee pain.

In a small case series consisting of five patients with chronic knee pain, pain intensity scores on the visual analog scale (VAS) dropped from an average of 8 out of 10 before the implant to 1.4 out of 10 when measured 6 months afterward.

Pain relief was also long lasting, with an average score at 2 years still significantly reduced from baseline, at 3 out of 10 on the VAS.

“We have a lot of patients with chronic knee pain, and unfortunately, our hands are tied in terms of what we can do for them,” lead author Kwo Wei David Ho, MD, PhD, Stanford University, California, told Medscape Medical News.

“They can use NSAIDs, physical therapy, some get steroid injections, or genicular nerve blocks, but they don’t work that well. Some have knee replacement surgery, and can still have persistent knee pain after the operation, so here we are using an alternative therapy called peripheral nerve stimulation of the saphenous nerve. This provides a way to relieve pain without nerve destruction or motor dysfunction,” Ho said.

The findings were presented here at the American Academy of Pain Medicine (AAPM) 2020 Annual Meeting.

Patient Controlled

For the study, the investigators surgically implanted five patients with intractable knee pain with the StimRouter™ (Bioness, Inc).

The device takes about 15 to 30 minutes to implant, much like a pacemaker, and reduces pain by delivering gentle electrical stimulation directly to a target peripheral nerve, in this case the saphenous nerve, to interrupt the pain signal, Ho said.

“A thin, threadlike lead, or noodle, is implanted below the skin next to the target peripheral nerve responsible for the pain signal under ultrasound guidance, and then a patch or external pulse transmitter (EPT) is worn on top of the skin. This sends electric stimulation through the skin to the lead,” he explained.

The patient can then control the EPT and adjust stimulation with a wireless handheld programmer.

“Some patients turn it on at night for a couple of hours and then turn it off, some leave it on for the entire night, or the whole day if they prefer. What we’ve been noticing in our series is that after a while, patients are using less and less, and the pain gets better and better, and eventually they stop using it entirely because the pain completely resolves,” Ho said.

Good candidates for this treatment are post-knee replacement patients with residual pain, he added.

Durable Effect

Of the five patients in the case series, four had previous knee arthroplasty.

To determine the chances of a good response to the implant, study participants underwent a diagnostic saphenous nerve block, with the rationale that if the block successfully reduced knee pain by 50% or more in the short term, patients would likely respond well to the implant.

Before the peripheral nerve stimulation implant, the average pain intensity was 7.8 out of 10 on the VAS. After stimulator implantation, the average pain intensity was 1.4 at 6 months (P = .019, in 5 patients). At 1 year, the average pain intensity score was virtually the same, at 1.5 on the VAS, (P = .0032, in 4 patients). At 2 years, the average pain intensity score was 2.75 (P = .12, in 2 patients).

“This study provides preliminary evidence that stimulation at the saphenous nerve may be effective for selected patients with chronic knee pain,” Ho said.

Commenting on the findings for Medscape Medical News, Patrick Tighe, MD, MS, University of Florida, Gainesville, said that chronic knee pain continues to present “numerous diagnostic and therapeutic challenges for many patients.”

“It may be surprising, but there is still so much we don’t know about the innervation of the knee, and we are still learning about different ways to alter the behavior of those nerves,” said Tighe, who was not involved with the current study.

“This work points to some exciting opportunities to help patients suffering from chronic knee pain. We certainly need more research in this area to figure out the optimal approach to applying these findings more widely,” he said.

Ho and Tighe have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

NATIONAL HARBOR, MD. – Stimulation of the infrapatellar branch of the saphenous nerve with an implantable electrical device is a potentially effective treatment for chronic, intractable knee pain.

In a small case series consisting of five patients with chronic knee pain, pain intensity scores on the visual analog scale (VAS) dropped from an average of 8 out of 10 before the implant to 1.4 out of 10 when measured 6 months afterward.

Pain relief was also long lasting, with an average score at 2 years still significantly reduced from baseline, at 3 out of 10 on the VAS.

“We have a lot of patients with chronic knee pain, and unfortunately, our hands are tied in terms of what we can do for them,” lead author Kwo Wei David Ho, MD, PhD, Stanford University, California, told Medscape Medical News.

“They can use NSAIDs, physical therapy, some get steroid injections, or genicular nerve blocks, but they don’t work that well. Some have knee replacement surgery, and can still have persistent knee pain after the operation, so here we are using an alternative therapy called peripheral nerve stimulation of the saphenous nerve. This provides a way to relieve pain without nerve destruction or motor dysfunction,” Ho said.

The findings were presented here at the American Academy of Pain Medicine (AAPM) 2020 Annual Meeting.

Patient Controlled

For the study, the investigators surgically implanted five patients with intractable knee pain with the StimRouter™ (Bioness, Inc).

The device takes about 15 to 30 minutes to implant, much like a pacemaker, and reduces pain by delivering gentle electrical stimulation directly to a target peripheral nerve, in this case the saphenous nerve, to interrupt the pain signal, Ho said.

“A thin, threadlike lead, or noodle, is implanted below the skin next to the target peripheral nerve responsible for the pain signal under ultrasound guidance, and then a patch or external pulse transmitter (EPT) is worn on top of the skin. This sends electric stimulation through the skin to the lead,” he explained.

The patient can then control the EPT and adjust stimulation with a wireless handheld programmer.

“Some patients turn it on at night for a couple of hours and then turn it off, some leave it on for the entire night, or the whole day if they prefer. What we’ve been noticing in our series is that after a while, patients are using less and less, and the pain gets better and better, and eventually they stop using it entirely because the pain completely resolves,” Ho said.

Good candidates for this treatment are post-knee replacement patients with residual pain, he added.

Durable Effect

Of the five patients in the case series, four had previous knee arthroplasty.

To determine the chances of a good response to the implant, study participants underwent a diagnostic saphenous nerve block, with the rationale that if the block successfully reduced knee pain by 50% or more in the short term, patients would likely respond well to the implant.

Before the peripheral nerve stimulation implant, the average pain intensity was 7.8 out of 10 on the VAS. After stimulator implantation, the average pain intensity was 1.4 at 6 months (P = .019, in 5 patients). At 1 year, the average pain intensity score was virtually the same, at 1.5 on the VAS, (P = .0032, in 4 patients). At 2 years, the average pain intensity score was 2.75 (P = .12, in 2 patients).

“This study provides preliminary evidence that stimulation at the saphenous nerve may be effective for selected patients with chronic knee pain,” Ho said.

Commenting on the findings for Medscape Medical News, Patrick Tighe, MD, MS, University of Florida, Gainesville, said that chronic knee pain continues to present “numerous diagnostic and therapeutic challenges for many patients.”

“It may be surprising, but there is still so much we don’t know about the innervation of the knee, and we are still learning about different ways to alter the behavior of those nerves,” said Tighe, who was not involved with the current study.

“This work points to some exciting opportunities to help patients suffering from chronic knee pain. We certainly need more research in this area to figure out the optimal approach to applying these findings more widely,” he said.

Ho and Tighe have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

For patients undergoing major oncologic surgery, the best definition of malnutrition used to assess postoperative risk varies by cancer type, results of a retrospective study suggest.

The current, one-size-fits-all approach to nutritional status leads to both undertreatment and overtreatment of malnutrition, as well as inaccurate estimations of postoperative risk, reported lead study author Nicholas P. McKenna, MD, of the Mayo Clinic in Rochester, Minn., and colleagues.

“Assessing nutritional status is important because it impacts preoperative planning, particularly with respect to the use of prehabilitation,” the investigators wrote. Their report is in the Journal of the American College of Surgeons. They noted that while prehabilitation has been shown to reduce postoperative risk among those who need it, identification of these patients is an area that needs improvement.

With this in mind, Dr. McKenna and colleagues analyzed 205,840 major oncologic operations, with data drawn from the American College of Surgeons National Surgical Quality Improvement (NSQIP) database.

The researchers evaluated patients’ nutritional status using three techniques: the NSQIP method, the European Society for Clinical Nutrition and Metabolism (ESPEN) definitions, and the World Health Organization body mass index (BMI) classification system.

Combining these three assessments led to seven hierarchical nutritional status categories:

• Severe malnutrition – BMI less than 18.5 kg/m² and greater than 10% weight loss
• ESPEN 1 – BMI 18.5-20 kg/m² (if younger than 70 years) or less than 22 kg/m² (if 70 years or older) plus greater than 10% weight loss
• ESPEN 2 – BMI less than 18.5 kg/m²
• NSQIP – BMI greater than 20 kg/m² (if younger than 70 years) or 22 kg/m² (if 70 years or older) plus greater than 10% weight loss
• Mild malnutrition – BMI 18.5-20 kg/m² (if younger than 70 years) or less than 22 kg/m² (if 70 years or older)
• Obese – BMI at least 30 kg/m²
• No malnutrition.

The study’s primary outcomes were 30-day mortality and 30-day morbidity. The latter included a variety of complications, such as deep incisional surgical site infection, septic shock, and acute renal failure. Demographic and clinical factors were included in multivariate analyses.
 

Results

Most of the operations involved patients with colorectal cancer (74%), followed by pancreatic (10%), lung (9%), gastric (3%), esophageal (3%), and liver (2%) cancer.

Across all patients, 16% fell into one of five malnutrition categories: mild malnutrition (6%), NSQIP (6%), ESPEN 2 (2%), ESPEN 1 (1%), or severe malnutrition (0.6%). The remainder of patients were either obese (31%) or had normal nutritional status (54%).

Malnutrition was most common among patients with pancreatic cancer (28%) and least common among those with colorectal cancer (14%).

Aligning with previous research, this study showed that nutritional status was associated with postoperative risk. Mortality risk was highest among patients with severe malnutrition, and morbidity was most common in the severe and ESPEN 1 groups (P less than .0001 for both).

While the spectrum of classifications appeared accurate across the population, multivariable models for mortality and morbidity revealed an interaction between cancer type and malnutrition definition (P less than .0001 for both), which suggested the most accurate definition of malnutrition differed from one type of cancer to another.

Specifically, a classification of severe malnutrition was most predictive of mortality among patients with esophageal or colorectal cancer. ESPEN 1 was most predictive of mortality for patients with gastric or lung cancer, and NSQIP was most predictive for those with liver cancer.

For predicting morbidity, severe malnutrition was most accurate among patients with colorectal cancer, whereas ESPEN 1 was better suited for gastric and lung cancer.
 

Interpreting and applying the results

“The biggest takeaway is that the optimal definition of malnutrition varies by cancer type,” Dr. McKenna said in an interview.

He went on to explain that weight loss is a particularly important indicator of malnutrition for patients with esophageal or gastric cancer. “These are the cancers that more commonly undergo neoadjuvant chemotherapy,” he noted.

The other major finding, Dr. McKenna said, offers some perspective on short-term versus long-term risk.

“Most people consider obesity a negative prognostic factor,” he said. “But in terms of operative risk, it’s kind of a neutral effect. It doesn’t really affect the short-term outcomes of an operation.”

Still, Dr. McKenna warned that a visual assessment of patient body condition is not enough to predict postoperative risk. Instead, he recommended accurate height and weight measurements during annual and preoperative exams. He also noted that more patients are at risk than clinicians may suspect.

“Even definitions that didn’t previously exist, such as mild malnutrition, had a somewhat negative effect within colorectal cancer and esophageal cancer,” Dr. McKenna said. “So these are patients who previously probably would be considered pretty healthy, but there is probably some room to improve their nutritional status.”

While the study revealed that different types of cancer should have unique tools for measuring nutritional status, development of these systems will require more research concerning prehabilitation outcomes, according to Dr. McKenna. In the meantime, he highlighted a point of action in the clinic.

“We think, overall, especially with the rise of neoadjuvant chemotherapy upfront, before surgery, that identifying patients at risk before they start neoadjuvant chemotherapy is going to be important,” he said. “They are the ones who really need to be targeted.”

There was no external funding for this study, and the investigators reported no conflicts of interest.
 

SOURCE: McKenna NP et al. J Am Coll Surg. 2020 Feb 26. doi: 10.1016/j.jamcollsurg.2019.12.034.

For patients undergoing major oncologic surgery, the best definition of malnutrition used to assess postoperative risk varies by cancer type, results of a retrospective study suggest.

The current, one-size-fits-all approach to nutritional status leads to both undertreatment and overtreatment of malnutrition, as well as inaccurate estimations of postoperative risk, reported lead study author Nicholas P. McKenna, MD, of the Mayo Clinic in Rochester, Minn., and colleagues.

“Assessing nutritional status is important because it impacts preoperative planning, particularly with respect to the use of prehabilitation,” the investigators wrote. Their report is in the Journal of the American College of Surgeons. They noted that while prehabilitation has been shown to reduce postoperative risk among those who need it, identification of these patients is an area that needs improvement.

With this in mind, Dr. McKenna and colleagues analyzed 205,840 major oncologic operations, with data drawn from the American College of Surgeons National Surgical Quality Improvement (NSQIP) database.

The researchers evaluated patients’ nutritional status using three techniques: the NSQIP method, the European Society for Clinical Nutrition and Metabolism (ESPEN) definitions, and the World Health Organization body mass index (BMI) classification system.

Combining these three assessments led to seven hierarchical nutritional status categories:

• Severe malnutrition – BMI less than 18.5 kg/m² and greater than 10% weight loss
• ESPEN 1 – BMI 18.5-20 kg/m² (if younger than 70 years) or less than 22 kg/m² (if 70 years or older) plus greater than 10% weight loss
• ESPEN 2 – BMI less than 18.5 kg/m²
• NSQIP – BMI greater than 20 kg/m² (if younger than 70 years) or 22 kg/m² (if 70 years or older) plus greater than 10% weight loss
• Mild malnutrition – BMI 18.5-20 kg/m² (if younger than 70 years) or less than 22 kg/m² (if 70 years or older)
• Obese – BMI at least 30 kg/m²
• No malnutrition.

The study’s primary outcomes were 30-day mortality and 30-day morbidity. The latter included a variety of complications, such as deep incisional surgical site infection, septic shock, and acute renal failure. Demographic and clinical factors were included in multivariate analyses.
 

Results

Most of the operations involved patients with colorectal cancer (74%), followed by pancreatic (10%), lung (9%), gastric (3%), esophageal (3%), and liver (2%) cancer.

Across all patients, 16% fell into one of five malnutrition categories: mild malnutrition (6%), NSQIP (6%), ESPEN 2 (2%), ESPEN 1 (1%), or severe malnutrition (0.6%). The remainder of patients were either obese (31%) or had normal nutritional status (54%).

Malnutrition was most common among patients with pancreatic cancer (28%) and least common among those with colorectal cancer (14%).

Aligning with previous research, this study showed that nutritional status was associated with postoperative risk. Mortality risk was highest among patients with severe malnutrition, and morbidity was most common in the severe and ESPEN 1 groups (P less than .0001 for both).

While the spectrum of classifications appeared accurate across the population, multivariable models for mortality and morbidity revealed an interaction between cancer type and malnutrition definition (P less than .0001 for both), which suggested the most accurate definition of malnutrition differed from one type of cancer to another.

Specifically, a classification of severe malnutrition was most predictive of mortality among patients with esophageal or colorectal cancer. ESPEN 1 was most predictive of mortality for patients with gastric or lung cancer, and NSQIP was most predictive for those with liver cancer.

For predicting morbidity, severe malnutrition was most accurate among patients with colorectal cancer, whereas ESPEN 1 was better suited for gastric and lung cancer.
 

Interpreting and applying the results

“The biggest takeaway is that the optimal definition of malnutrition varies by cancer type,” Dr. McKenna said in an interview.

He went on to explain that weight loss is a particularly important indicator of malnutrition for patients with esophageal or gastric cancer. “These are the cancers that more commonly undergo neoadjuvant chemotherapy,” he noted.

The other major finding, Dr. McKenna said, offers some perspective on short-term versus long-term risk.

“Most people consider obesity a negative prognostic factor,” he said. “But in terms of operative risk, it’s kind of a neutral effect. It doesn’t really affect the short-term outcomes of an operation.”

Still, Dr. McKenna warned that a visual assessment of patient body condition is not enough to predict postoperative risk. Instead, he recommended accurate height and weight measurements during annual and preoperative exams. He also noted that more patients are at risk than clinicians may suspect.

“Even definitions that didn’t previously exist, such as mild malnutrition, had a somewhat negative effect within colorectal cancer and esophageal cancer,” Dr. McKenna said. “So these are patients who previously probably would be considered pretty healthy, but there is probably some room to improve their nutritional status.”

While the study revealed that different types of cancer should have unique tools for measuring nutritional status, development of these systems will require more research concerning prehabilitation outcomes, according to Dr. McKenna. In the meantime, he highlighted a point of action in the clinic.

“We think, overall, especially with the rise of neoadjuvant chemotherapy upfront, before surgery, that identifying patients at risk before they start neoadjuvant chemotherapy is going to be important,” he said. “They are the ones who really need to be targeted.”

There was no external funding for this study, and the investigators reported no conflicts of interest.
 

SOURCE: McKenna NP et al. J Am Coll Surg. 2020 Feb 26. doi: 10.1016/j.jamcollsurg.2019.12.034.

For patients undergoing major oncologic surgery, the best definition of malnutrition used to assess postoperative risk varies by cancer type, results of a retrospective study suggest.

The current, one-size-fits-all approach to nutritional status leads to both undertreatment and overtreatment of malnutrition, as well as inaccurate estimations of postoperative risk, reported lead study author Nicholas P. McKenna, MD, of the Mayo Clinic in Rochester, Minn., and colleagues.

“Assessing nutritional status is important because it impacts preoperative planning, particularly with respect to the use of prehabilitation,” the investigators wrote. Their report is in the Journal of the American College of Surgeons. They noted that while prehabilitation has been shown to reduce postoperative risk among those who need it, identification of these patients is an area that needs improvement.

With this in mind, Dr. McKenna and colleagues analyzed 205,840 major oncologic operations, with data drawn from the American College of Surgeons National Surgical Quality Improvement (NSQIP) database.

The researchers evaluated patients’ nutritional status using three techniques: the NSQIP method, the European Society for Clinical Nutrition and Metabolism (ESPEN) definitions, and the World Health Organization body mass index (BMI) classification system.

Combining these three assessments led to seven hierarchical nutritional status categories:

• Severe malnutrition – BMI less than 18.5 kg/m² and greater than 10% weight loss
• ESPEN 1 – BMI 18.5-20 kg/m² (if younger than 70 years) or less than 22 kg/m² (if 70 years or older) plus greater than 10% weight loss
• ESPEN 2 – BMI less than 18.5 kg/m²
• NSQIP – BMI greater than 20 kg/m² (if younger than 70 years) or 22 kg/m² (if 70 years or older) plus greater than 10% weight loss
• Mild malnutrition – BMI 18.5-20 kg/m² (if younger than 70 years) or less than 22 kg/m² (if 70 years or older)
• Obese – BMI at least 30 kg/m²
• No malnutrition.

The study’s primary outcomes were 30-day mortality and 30-day morbidity. The latter included a variety of complications, such as deep incisional surgical site infection, septic shock, and acute renal failure. Demographic and clinical factors were included in multivariate analyses.
 

Results

Most of the operations involved patients with colorectal cancer (74%), followed by pancreatic (10%), lung (9%), gastric (3%), esophageal (3%), and liver (2%) cancer.

Across all patients, 16% fell into one of five malnutrition categories: mild malnutrition (6%), NSQIP (6%), ESPEN 2 (2%), ESPEN 1 (1%), or severe malnutrition (0.6%). The remainder of patients were either obese (31%) or had normal nutritional status (54%).

Malnutrition was most common among patients with pancreatic cancer (28%) and least common among those with colorectal cancer (14%).

Aligning with previous research, this study showed that nutritional status was associated with postoperative risk. Mortality risk was highest among patients with severe malnutrition, and morbidity was most common in the severe and ESPEN 1 groups (P less than .0001 for both).

While the spectrum of classifications appeared accurate across the population, multivariable models for mortality and morbidity revealed an interaction between cancer type and malnutrition definition (P less than .0001 for both), which suggested the most accurate definition of malnutrition differed from one type of cancer to another.

Specifically, a classification of severe malnutrition was most predictive of mortality among patients with esophageal or colorectal cancer. ESPEN 1 was most predictive of mortality for patients with gastric or lung cancer, and NSQIP was most predictive for those with liver cancer.

For predicting morbidity, severe malnutrition was most accurate among patients with colorectal cancer, whereas ESPEN 1 was better suited for gastric and lung cancer.
 

Interpreting and applying the results

“The biggest takeaway is that the optimal definition of malnutrition varies by cancer type,” Dr. McKenna said in an interview.

He went on to explain that weight loss is a particularly important indicator of malnutrition for patients with esophageal or gastric cancer. “These are the cancers that more commonly undergo neoadjuvant chemotherapy,” he noted.

The other major finding, Dr. McKenna said, offers some perspective on short-term versus long-term risk.

“Most people consider obesity a negative prognostic factor,” he said. “But in terms of operative risk, it’s kind of a neutral effect. It doesn’t really affect the short-term outcomes of an operation.”

Still, Dr. McKenna warned that a visual assessment of patient body condition is not enough to predict postoperative risk. Instead, he recommended accurate height and weight measurements during annual and preoperative exams. He also noted that more patients are at risk than clinicians may suspect.

“Even definitions that didn’t previously exist, such as mild malnutrition, had a somewhat negative effect within colorectal cancer and esophageal cancer,” Dr. McKenna said. “So these are patients who previously probably would be considered pretty healthy, but there is probably some room to improve their nutritional status.”

While the study revealed that different types of cancer should have unique tools for measuring nutritional status, development of these systems will require more research concerning prehabilitation outcomes, according to Dr. McKenna. In the meantime, he highlighted a point of action in the clinic.

“We think, overall, especially with the rise of neoadjuvant chemotherapy upfront, before surgery, that identifying patients at risk before they start neoadjuvant chemotherapy is going to be important,” he said. “They are the ones who really need to be targeted.”

There was no external funding for this study, and the investigators reported no conflicts of interest.
 

SOURCE: McKenna NP et al. J Am Coll Surg. 2020 Feb 26. doi: 10.1016/j.jamcollsurg.2019.12.034.

Telehealth is increasingly being viewed as a key way to help fight the COVID-19 outbreak in the United States. Recognizing the potential of this technology to slow the spread of the disease, the House of Representatives included a provision in an $8.3 billion emergency response bill it approved today that would temporarily lift restrictions on Medicare telehealth coverage to assist in the efforts to contain the virus.

Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention (CDC), said that hospitals should be prepared to use telehealth as one of their tools in fighting the outbreak, according to a recent news release from the American Hospital Association (AHA).

Congress is responding to that need by including the service in the new coronavirus legislation now headed to the Senate, after the funding bill was approved in a 415-2 vote by the House.

The bill empowers the Secretary of Health and Human Services (HHS) to “waive or modify application of certain Medicare requirements with respect to telehealth services furnished during certain emergency periods.”

While the measure adds telehealth to the waiver authority that the HHS secretary currently has during national emergencies, it’s only for the coronavirus crisis in this case, Krista Drobac, executive director of the Alliance for Connected Care, told Medscape Medical News.

The waiver would apply to originating sites of telehealth visits, she noted. Thus Medicare coverage of telemedicine would be expanded beyond rural areas.

In addition, the waiver would allow coverage of virtual visits conducted on smartphones with audio and video capabilities. A “qualified provider,” as defined by the legislation, would be a practitioner who has an established relationship with the patient or who is in the same practice as the provider who has that relationship.

An advantage of telehealth, proponents say, is that it can enable people who believe they have COVID-19 to be seen at home rather than visit offices or emergency departments (EDs) where they might spread the disease or be in proximity to others who have it.

In an editorial published March 2 in Modern Healthcare, medical directors from Stanford Medicine, MedStar Health, and Intermountain Healthcare also noted that telehealth can give patients 24/7 access to care, allow surveillance of patients at risk while keeping them at home, ensure that treatment in hospitals is reserved for high-need patients, and enable providers to triage and screen more patients than can be handled in brick-and-mortar care settings.

However, telehealth screening would allow physicians only to judge whether a patient’s symptoms might be indicative of COVID-19, the Alliance for Connected Care, a telehealth advocacy group, noted in a letter to Congressional leaders. Patients would still have to be seen in person to be tested for the disease.

The group, which represents technology companies, health insurers, pharmacies, and other healthcare players, has been lobbying Congress to include telehealth in federal funds to combat the outbreak.

The American Telemedicine Association (ATA) also supports this goal, ATA President Joseph Kvedar, MD, told Medscape Medical News. And the authors of the Modern Healthcare editorial also advocated for this legislative solution. Because the fatality rate for COVID-19 is significantly higher for older people than for other age groups, they noted, telehealth should be an economically viable option for all seniors.

The Centers for Medicare and Medicaid Services (CMS) long covered telemedicine only in rural areas and only when initiated in healthcare settings. Recently, however, CMS loosened its approach to some extent. Virtual “check-in visits” can now be initiated from any location, including home, to determine whether a Medicare patient needs to be seen in the office. In addition, CMS allows Medicare Advantage plans to offer telemedicine as a core benefit.

Are healthcare systems prepared?

Some large healthcare systems such as Stanford, MedStar, and Intermountain are already using telehealth to diagnose and treat patients who have traditional influenza. Telehealth providers at Stanford estimate that almost 50% of these patients are being prescribed the antiviral drug Tamiflu.

It’s unclear whether other healthcare systems are this well prepared to offer telehealth on a large scale. But, according to an AHA survey, Kvedar noted, three quarters of AHA members are engaged in some form of telehealth.

Drobac said “it wouldn’t require too much effort” to ramp up a wide-scale telehealth program that could help reduce the impact of the outbreak. “The technology is there,” she noted. “You need a HIPAA-compliant telehealth platform, but there are so many out there.”

Kvedar agreed. To begin with, he said, hospitals might sequester patients who visit the ED with COVID-19 symptoms in a video-equipped “isolation room.” Staff members could then do the patient intake from a different location in the hospital.

He admitted that this approach would be infeasible if a lot of patients arrived in EDs with coronavirus symptoms. However, Kvedar noted, “All the tools are in place to go well beyond that. American Well, Teladoc, and others are all offering ways to get out in front of this. There are plenty of vendors out there, and most people have a connected cell phone that you can do a video call on.”

Hospital leaders would have to decide whether to embrace telehealth, which would mean less use of services in their institutions, he said. “But it would be for the greater good of the public.”

Kvedar recalled that there was some use of telehealth in the New York area after 9/11. Telehealth was also used in the aftermath of Hurricane Katrina in 2005. But the ATA president, who is also vice president of connected health at Partners HealthCare in Boston, noted that the COVID-19 outbreak is the first public health emergency to occur in the era of Skype and smartphones.

If Congress does ultimately authorize CMS to cover telehealth across the board during this emergency, might that lead to a permanent change in Medicare coverage policy? Kvedar wouldn’t venture an opinion. “However, the current CMS leadership has been incredibly telehealth friendly,” he said. “So it’s possible they would [embrace a lifting of restrictions]. As patients get a sense of this modality of care and how convenient it is for them, they’ll start asking for more.”

Meanwhile, he said, the telehealth opportunity goes beyond video visits with doctors to mitigate the outbreak. Telehealth data could also be used to track disease spread, similar to how researchers have studied Google searches to predict the spread of the flu, he noted.

Teladoc, a major telehealth vendor, recently told stock analysts it’s already working with the CDC on disease surveillance, according to a report in FierceHealthcare.

This article first appeared on Medscape.com.

Telehealth is increasingly being viewed as a key way to help fight the COVID-19 outbreak in the United States. Recognizing the potential of this technology to slow the spread of the disease, the House of Representatives included a provision in an $8.3 billion emergency response bill it approved today that would temporarily lift restrictions on Medicare telehealth coverage to assist in the efforts to contain the virus.

Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention (CDC), said that hospitals should be prepared to use telehealth as one of their tools in fighting the outbreak, according to a recent news release from the American Hospital Association (AHA).

Congress is responding to that need by including the service in the new coronavirus legislation now headed to the Senate, after the funding bill was approved in a 415-2 vote by the House.

The bill empowers the Secretary of Health and Human Services (HHS) to “waive or modify application of certain Medicare requirements with respect to telehealth services furnished during certain emergency periods.”

While the measure adds telehealth to the waiver authority that the HHS secretary currently has during national emergencies, it’s only for the coronavirus crisis in this case, Krista Drobac, executive director of the Alliance for Connected Care, told Medscape Medical News.

The waiver would apply to originating sites of telehealth visits, she noted. Thus Medicare coverage of telemedicine would be expanded beyond rural areas.

In addition, the waiver would allow coverage of virtual visits conducted on smartphones with audio and video capabilities. A “qualified provider,” as defined by the legislation, would be a practitioner who has an established relationship with the patient or who is in the same practice as the provider who has that relationship.

An advantage of telehealth, proponents say, is that it can enable people who believe they have COVID-19 to be seen at home rather than visit offices or emergency departments (EDs) where they might spread the disease or be in proximity to others who have it.

In an editorial published March 2 in Modern Healthcare, medical directors from Stanford Medicine, MedStar Health, and Intermountain Healthcare also noted that telehealth can give patients 24/7 access to care, allow surveillance of patients at risk while keeping them at home, ensure that treatment in hospitals is reserved for high-need patients, and enable providers to triage and screen more patients than can be handled in brick-and-mortar care settings.

However, telehealth screening would allow physicians only to judge whether a patient’s symptoms might be indicative of COVID-19, the Alliance for Connected Care, a telehealth advocacy group, noted in a letter to Congressional leaders. Patients would still have to be seen in person to be tested for the disease.

The group, which represents technology companies, health insurers, pharmacies, and other healthcare players, has been lobbying Congress to include telehealth in federal funds to combat the outbreak.

The American Telemedicine Association (ATA) also supports this goal, ATA President Joseph Kvedar, MD, told Medscape Medical News. And the authors of the Modern Healthcare editorial also advocated for this legislative solution. Because the fatality rate for COVID-19 is significantly higher for older people than for other age groups, they noted, telehealth should be an economically viable option for all seniors.

The Centers for Medicare and Medicaid Services (CMS) long covered telemedicine only in rural areas and only when initiated in healthcare settings. Recently, however, CMS loosened its approach to some extent. Virtual “check-in visits” can now be initiated from any location, including home, to determine whether a Medicare patient needs to be seen in the office. In addition, CMS allows Medicare Advantage plans to offer telemedicine as a core benefit.

Are healthcare systems prepared?

Some large healthcare systems such as Stanford, MedStar, and Intermountain are already using telehealth to diagnose and treat patients who have traditional influenza. Telehealth providers at Stanford estimate that almost 50% of these patients are being prescribed the antiviral drug Tamiflu.

It’s unclear whether other healthcare systems are this well prepared to offer telehealth on a large scale. But, according to an AHA survey, Kvedar noted, three quarters of AHA members are engaged in some form of telehealth.

Drobac said “it wouldn’t require too much effort” to ramp up a wide-scale telehealth program that could help reduce the impact of the outbreak. “The technology is there,” she noted. “You need a HIPAA-compliant telehealth platform, but there are so many out there.”

Kvedar agreed. To begin with, he said, hospitals might sequester patients who visit the ED with COVID-19 symptoms in a video-equipped “isolation room.” Staff members could then do the patient intake from a different location in the hospital.

He admitted that this approach would be infeasible if a lot of patients arrived in EDs with coronavirus symptoms. However, Kvedar noted, “All the tools are in place to go well beyond that. American Well, Teladoc, and others are all offering ways to get out in front of this. There are plenty of vendors out there, and most people have a connected cell phone that you can do a video call on.”

Hospital leaders would have to decide whether to embrace telehealth, which would mean less use of services in their institutions, he said. “But it would be for the greater good of the public.”

Kvedar recalled that there was some use of telehealth in the New York area after 9/11. Telehealth was also used in the aftermath of Hurricane Katrina in 2005. But the ATA president, who is also vice president of connected health at Partners HealthCare in Boston, noted that the COVID-19 outbreak is the first public health emergency to occur in the era of Skype and smartphones.

If Congress does ultimately authorize CMS to cover telehealth across the board during this emergency, might that lead to a permanent change in Medicare coverage policy? Kvedar wouldn’t venture an opinion. “However, the current CMS leadership has been incredibly telehealth friendly,” he said. “So it’s possible they would [embrace a lifting of restrictions]. As patients get a sense of this modality of care and how convenient it is for them, they’ll start asking for more.”

Meanwhile, he said, the telehealth opportunity goes beyond video visits with doctors to mitigate the outbreak. Telehealth data could also be used to track disease spread, similar to how researchers have studied Google searches to predict the spread of the flu, he noted.

Teladoc, a major telehealth vendor, recently told stock analysts it’s already working with the CDC on disease surveillance, according to a report in FierceHealthcare.

This article first appeared on Medscape.com.

Telehealth is increasingly being viewed as a key way to help fight the COVID-19 outbreak in the United States. Recognizing the potential of this technology to slow the spread of the disease, the House of Representatives included a provision in an $8.3 billion emergency response bill it approved today that would temporarily lift restrictions on Medicare telehealth coverage to assist in the efforts to contain the virus.

Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention (CDC), said that hospitals should be prepared to use telehealth as one of their tools in fighting the outbreak, according to a recent news release from the American Hospital Association (AHA).

Congress is responding to that need by including the service in the new coronavirus legislation now headed to the Senate, after the funding bill was approved in a 415-2 vote by the House.

The bill empowers the Secretary of Health and Human Services (HHS) to “waive or modify application of certain Medicare requirements with respect to telehealth services furnished during certain emergency periods.”

While the measure adds telehealth to the waiver authority that the HHS secretary currently has during national emergencies, it’s only for the coronavirus crisis in this case, Krista Drobac, executive director of the Alliance for Connected Care, told Medscape Medical News.

The waiver would apply to originating sites of telehealth visits, she noted. Thus Medicare coverage of telemedicine would be expanded beyond rural areas.

In addition, the waiver would allow coverage of virtual visits conducted on smartphones with audio and video capabilities. A “qualified provider,” as defined by the legislation, would be a practitioner who has an established relationship with the patient or who is in the same practice as the provider who has that relationship.

An advantage of telehealth, proponents say, is that it can enable people who believe they have COVID-19 to be seen at home rather than visit offices or emergency departments (EDs) where they might spread the disease or be in proximity to others who have it.

In an editorial published March 2 in Modern Healthcare, medical directors from Stanford Medicine, MedStar Health, and Intermountain Healthcare also noted that telehealth can give patients 24/7 access to care, allow surveillance of patients at risk while keeping them at home, ensure that treatment in hospitals is reserved for high-need patients, and enable providers to triage and screen more patients than can be handled in brick-and-mortar care settings.

However, telehealth screening would allow physicians only to judge whether a patient’s symptoms might be indicative of COVID-19, the Alliance for Connected Care, a telehealth advocacy group, noted in a letter to Congressional leaders. Patients would still have to be seen in person to be tested for the disease.

The group, which represents technology companies, health insurers, pharmacies, and other healthcare players, has been lobbying Congress to include telehealth in federal funds to combat the outbreak.

The American Telemedicine Association (ATA) also supports this goal, ATA President Joseph Kvedar, MD, told Medscape Medical News. And the authors of the Modern Healthcare editorial also advocated for this legislative solution. Because the fatality rate for COVID-19 is significantly higher for older people than for other age groups, they noted, telehealth should be an economically viable option for all seniors.

The Centers for Medicare and Medicaid Services (CMS) long covered telemedicine only in rural areas and only when initiated in healthcare settings. Recently, however, CMS loosened its approach to some extent. Virtual “check-in visits” can now be initiated from any location, including home, to determine whether a Medicare patient needs to be seen in the office. In addition, CMS allows Medicare Advantage plans to offer telemedicine as a core benefit.

Are healthcare systems prepared?

Some large healthcare systems such as Stanford, MedStar, and Intermountain are already using telehealth to diagnose and treat patients who have traditional influenza. Telehealth providers at Stanford estimate that almost 50% of these patients are being prescribed the antiviral drug Tamiflu.

It’s unclear whether other healthcare systems are this well prepared to offer telehealth on a large scale. But, according to an AHA survey, Kvedar noted, three quarters of AHA members are engaged in some form of telehealth.

Drobac said “it wouldn’t require too much effort” to ramp up a wide-scale telehealth program that could help reduce the impact of the outbreak. “The technology is there,” she noted. “You need a HIPAA-compliant telehealth platform, but there are so many out there.”

Kvedar agreed. To begin with, he said, hospitals might sequester patients who visit the ED with COVID-19 symptoms in a video-equipped “isolation room.” Staff members could then do the patient intake from a different location in the hospital.

He admitted that this approach would be infeasible if a lot of patients arrived in EDs with coronavirus symptoms. However, Kvedar noted, “All the tools are in place to go well beyond that. American Well, Teladoc, and others are all offering ways to get out in front of this. There are plenty of vendors out there, and most people have a connected cell phone that you can do a video call on.”

Hospital leaders would have to decide whether to embrace telehealth, which would mean less use of services in their institutions, he said. “But it would be for the greater good of the public.”

Kvedar recalled that there was some use of telehealth in the New York area after 9/11. Telehealth was also used in the aftermath of Hurricane Katrina in 2005. But the ATA president, who is also vice president of connected health at Partners HealthCare in Boston, noted that the COVID-19 outbreak is the first public health emergency to occur in the era of Skype and smartphones.

If Congress does ultimately authorize CMS to cover telehealth across the board during this emergency, might that lead to a permanent change in Medicare coverage policy? Kvedar wouldn’t venture an opinion. “However, the current CMS leadership has been incredibly telehealth friendly,” he said. “So it’s possible they would [embrace a lifting of restrictions]. As patients get a sense of this modality of care and how convenient it is for them, they’ll start asking for more.”

Meanwhile, he said, the telehealth opportunity goes beyond video visits with doctors to mitigate the outbreak. Telehealth data could also be used to track disease spread, similar to how researchers have studied Google searches to predict the spread of the flu, he noted.

Teladoc, a major telehealth vendor, recently told stock analysts it’s already working with the CDC on disease surveillance, according to a report in FierceHealthcare.

This article first appeared on Medscape.com.

In this edition of “Applying research to practice,” I highlight I-SPY2 and other studies of pembrolizumab plus chemotherapy in breast cancer patients.

Pathologic complete response (pCR) rates up to 60% were reported for patients with high-risk, stage II/III breast cancer who received pembrolizumab plus standard neoadjuvant chemotherapy (NAC) in I-SPY2, an ongoing platform trial designed to screen multiple agents and pinpoint those with a high probability of success (JAMA Oncol. 2020 Feb 13. doi: 10.1001/jamaoncol.2019.6650).

The addition of pembrolizumab to NAC doubled pCR rates in all three biomarker signatures studied, including ERBB2 (HER2)-negative, hormone receptor (HR)-positive/ERBB2-negative, and triple-negative breast cancer (TNBC).

As a result, pembrolizumab “graduated” from I-SPY2, with a more than 99% predictive probability that the pembrolizumab-plus-NAC approach would be superior to NAC alone in a phase 3 trial. In the HR-positive/ERBB2-negative signature, pembrolizumab is the first agent to graduate among the 10 agents studied since I-SPY2 opened in 2010.

The control arm in I-SPY2 had 181 patients randomized to standard NAC (paclitaxel followed by doxorubicin plus cyclophosphamide). The pembrolizumab arm included 69 patients who received the same NAC regimen plus pembrolizumab, given concurrently with paclitaxel.

The estimated pCR rates in all ERBB2-negative patients were 44% in the pembrolizumab arm and 17% in the control arm. Among the 40 HR-positive/ERBB2-negative patients, the estimated pCR rates were 30% and 13%, respectively. In the 29 TNBC patients, the estimated pCR rates were 60% and 22%, respectively.

Extensive residual cancer burden was less often seen in the pembrolizumab-treated patients than in the comparison group. At a median follow-up of 2.8 years in the pembrolizumab arm and 3.5 years in the NAC arm, 3-year event-free survival was similar between the arms. However, the investigators cautioned against drawing conclusions from this exploratory analysis in a small number of patients. Testifying to the importance of the primary endpoint of pCR rate, patients who achieved pCR had excellent outcomes regardless of their assigned study arms.

Immune-related adverse events in the pembrolizumab-treated patients were generally grade 1 or 2 and were managed with dose interruption or corticosteroid therapy. Most commonly seen was thyroid dysfunction in 13% of patients, as in previously published reports. Adrenal insufficiency occurred more often than expected (8.7%), for unclear reasons, with five of the six reported cases occurring more than 30 days after the last dose of pembrolizumab.

The bigger picture: Putting I-SPY2 results into context

It is well known that responses to pembrolizumab monotherapy in patients with advanced, refractory breast cancer are infrequent. In contrast, in previously untreated patients with PD-L1 positive TNBC, pembrolizumab monotherapy produced a response rate of 21% in KEYNOTE-086 (Ann Oncol. 2019 Mar 1;30(3):405-11). This response rate is similar to that observed with standard chemotherapy, but responses with pembrolizumab were more durable.

In the phase 3 KEYNOTE-355 trial (NCT02819518), researchers are comparing pembrolizumab plus chemotherapy to placebo plus chemotherapy in patients with previously untreated, stage IV TNBC with high PD-L1 expression. Researchers saw a significant and clinically meaningful improvement in progression-free survival in the pembrolizumab arm, according to a recent announcement from Merck. These results lend credence to the I-SPY2 authors’ hypothesis that immune-targeted agents would show their greatest benefit in early-stage breast cancer patients.

In fact, results from I-SPY2 have been confirmed by results from the phase 3 KEYNOTE-522 trial, which were recently published (N Engl J Med 2020;382:810-21) and presented at the San Antonio Breast Cancer Symposium. I-SPY2 predicted that pembrolizumab would be superior to standard NAC in TNBC patients in a phase 3 trial, and it was.

In KEYNOTE-522, the pCR rate was significantly higher in early-stage TNBC patients who received pembrolizumab plus NAC than in early-stage TNBC patients who received placebo plus NAC. The pCR rate was 64.8% in the pembrolizumab-NAC arm and 51.2% in the placebo–NAC arm (estimated treatment difference, 13.6 percentage points; 95% CI, 5.4 to 21.8; P less than .001).

These results are exciting. Results from I-SPY2 and KEYNOTE-522 whet the appetite for results of KEYNOTE-756, an ongoing trial of pembrolizumab plus NAC in HR-positive/ERBB2-negative patients (NCT03725059). Hopefully, the efficacy and toxicity results of KEYNOTE-756 will be as exciting as the I-SPY2 results predict they will be. Among patients with early stage breast cancer whose tumor characteristics are adverse enough to require NAC, better regimens are needed to attain pCR, a validated surrogate for long-term freedom from recurrence.


Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations.

In this edition of “Applying research to practice,” I highlight I-SPY2 and other studies of pembrolizumab plus chemotherapy in breast cancer patients.

Pathologic complete response (pCR) rates up to 60% were reported for patients with high-risk, stage II/III breast cancer who received pembrolizumab plus standard neoadjuvant chemotherapy (NAC) in I-SPY2, an ongoing platform trial designed to screen multiple agents and pinpoint those with a high probability of success (JAMA Oncol. 2020 Feb 13. doi: 10.1001/jamaoncol.2019.6650).

The addition of pembrolizumab to NAC doubled pCR rates in all three biomarker signatures studied, including ERBB2 (HER2)-negative, hormone receptor (HR)-positive/ERBB2-negative, and triple-negative breast cancer (TNBC).

As a result, pembrolizumab “graduated” from I-SPY2, with a more than 99% predictive probability that the pembrolizumab-plus-NAC approach would be superior to NAC alone in a phase 3 trial. In the HR-positive/ERBB2-negative signature, pembrolizumab is the first agent to graduate among the 10 agents studied since I-SPY2 opened in 2010.

The control arm in I-SPY2 had 181 patients randomized to standard NAC (paclitaxel followed by doxorubicin plus cyclophosphamide). The pembrolizumab arm included 69 patients who received the same NAC regimen plus pembrolizumab, given concurrently with paclitaxel.

The estimated pCR rates in all ERBB2-negative patients were 44% in the pembrolizumab arm and 17% in the control arm. Among the 40 HR-positive/ERBB2-negative patients, the estimated pCR rates were 30% and 13%, respectively. In the 29 TNBC patients, the estimated pCR rates were 60% and 22%, respectively.

Extensive residual cancer burden was less often seen in the pembrolizumab-treated patients than in the comparison group. At a median follow-up of 2.8 years in the pembrolizumab arm and 3.5 years in the NAC arm, 3-year event-free survival was similar between the arms. However, the investigators cautioned against drawing conclusions from this exploratory analysis in a small number of patients. Testifying to the importance of the primary endpoint of pCR rate, patients who achieved pCR had excellent outcomes regardless of their assigned study arms.

Immune-related adverse events in the pembrolizumab-treated patients were generally grade 1 or 2 and were managed with dose interruption or corticosteroid therapy. Most commonly seen was thyroid dysfunction in 13% of patients, as in previously published reports. Adrenal insufficiency occurred more often than expected (8.7%), for unclear reasons, with five of the six reported cases occurring more than 30 days after the last dose of pembrolizumab.

The bigger picture: Putting I-SPY2 results into context

It is well known that responses to pembrolizumab monotherapy in patients with advanced, refractory breast cancer are infrequent. In contrast, in previously untreated patients with PD-L1 positive TNBC, pembrolizumab monotherapy produced a response rate of 21% in KEYNOTE-086 (Ann Oncol. 2019 Mar 1;30(3):405-11). This response rate is similar to that observed with standard chemotherapy, but responses with pembrolizumab were more durable.

In the phase 3 KEYNOTE-355 trial (NCT02819518), researchers are comparing pembrolizumab plus chemotherapy to placebo plus chemotherapy in patients with previously untreated, stage IV TNBC with high PD-L1 expression. Researchers saw a significant and clinically meaningful improvement in progression-free survival in the pembrolizumab arm, according to a recent announcement from Merck. These results lend credence to the I-SPY2 authors’ hypothesis that immune-targeted agents would show their greatest benefit in early-stage breast cancer patients.

In fact, results from I-SPY2 have been confirmed by results from the phase 3 KEYNOTE-522 trial, which were recently published (N Engl J Med 2020;382:810-21) and presented at the San Antonio Breast Cancer Symposium. I-SPY2 predicted that pembrolizumab would be superior to standard NAC in TNBC patients in a phase 3 trial, and it was.

In KEYNOTE-522, the pCR rate was significantly higher in early-stage TNBC patients who received pembrolizumab plus NAC than in early-stage TNBC patients who received placebo plus NAC. The pCR rate was 64.8% in the pembrolizumab-NAC arm and 51.2% in the placebo–NAC arm (estimated treatment difference, 13.6 percentage points; 95% CI, 5.4 to 21.8; P less than .001).

These results are exciting. Results from I-SPY2 and KEYNOTE-522 whet the appetite for results of KEYNOTE-756, an ongoing trial of pembrolizumab plus NAC in HR-positive/ERBB2-negative patients (NCT03725059). Hopefully, the efficacy and toxicity results of KEYNOTE-756 will be as exciting as the I-SPY2 results predict they will be. Among patients with early stage breast cancer whose tumor characteristics are adverse enough to require NAC, better regimens are needed to attain pCR, a validated surrogate for long-term freedom from recurrence.


Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations.

In this edition of “Applying research to practice,” I highlight I-SPY2 and other studies of pembrolizumab plus chemotherapy in breast cancer patients.

Pathologic complete response (pCR) rates up to 60% were reported for patients with high-risk, stage II/III breast cancer who received pembrolizumab plus standard neoadjuvant chemotherapy (NAC) in I-SPY2, an ongoing platform trial designed to screen multiple agents and pinpoint those with a high probability of success (JAMA Oncol. 2020 Feb 13. doi: 10.1001/jamaoncol.2019.6650).

The addition of pembrolizumab to NAC doubled pCR rates in all three biomarker signatures studied, including ERBB2 (HER2)-negative, hormone receptor (HR)-positive/ERBB2-negative, and triple-negative breast cancer (TNBC).

As a result, pembrolizumab “graduated” from I-SPY2, with a more than 99% predictive probability that the pembrolizumab-plus-NAC approach would be superior to NAC alone in a phase 3 trial. In the HR-positive/ERBB2-negative signature, pembrolizumab is the first agent to graduate among the 10 agents studied since I-SPY2 opened in 2010.

The control arm in I-SPY2 had 181 patients randomized to standard NAC (paclitaxel followed by doxorubicin plus cyclophosphamide). The pembrolizumab arm included 69 patients who received the same NAC regimen plus pembrolizumab, given concurrently with paclitaxel.

The estimated pCR rates in all ERBB2-negative patients were 44% in the pembrolizumab arm and 17% in the control arm. Among the 40 HR-positive/ERBB2-negative patients, the estimated pCR rates were 30% and 13%, respectively. In the 29 TNBC patients, the estimated pCR rates were 60% and 22%, respectively.

Extensive residual cancer burden was less often seen in the pembrolizumab-treated patients than in the comparison group. At a median follow-up of 2.8 years in the pembrolizumab arm and 3.5 years in the NAC arm, 3-year event-free survival was similar between the arms. However, the investigators cautioned against drawing conclusions from this exploratory analysis in a small number of patients. Testifying to the importance of the primary endpoint of pCR rate, patients who achieved pCR had excellent outcomes regardless of their assigned study arms.

Immune-related adverse events in the pembrolizumab-treated patients were generally grade 1 or 2 and were managed with dose interruption or corticosteroid therapy. Most commonly seen was thyroid dysfunction in 13% of patients, as in previously published reports. Adrenal insufficiency occurred more often than expected (8.7%), for unclear reasons, with five of the six reported cases occurring more than 30 days after the last dose of pembrolizumab.

The bigger picture: Putting I-SPY2 results into context

It is well known that responses to pembrolizumab monotherapy in patients with advanced, refractory breast cancer are infrequent. In contrast, in previously untreated patients with PD-L1 positive TNBC, pembrolizumab monotherapy produced a response rate of 21% in KEYNOTE-086 (Ann Oncol. 2019 Mar 1;30(3):405-11). This response rate is similar to that observed with standard chemotherapy, but responses with pembrolizumab were more durable.

In the phase 3 KEYNOTE-355 trial (NCT02819518), researchers are comparing pembrolizumab plus chemotherapy to placebo plus chemotherapy in patients with previously untreated, stage IV TNBC with high PD-L1 expression. Researchers saw a significant and clinically meaningful improvement in progression-free survival in the pembrolizumab arm, according to a recent announcement from Merck. These results lend credence to the I-SPY2 authors’ hypothesis that immune-targeted agents would show their greatest benefit in early-stage breast cancer patients.

In fact, results from I-SPY2 have been confirmed by results from the phase 3 KEYNOTE-522 trial, which were recently published (N Engl J Med 2020;382:810-21) and presented at the San Antonio Breast Cancer Symposium. I-SPY2 predicted that pembrolizumab would be superior to standard NAC in TNBC patients in a phase 3 trial, and it was.

In KEYNOTE-522, the pCR rate was significantly higher in early-stage TNBC patients who received pembrolizumab plus NAC than in early-stage TNBC patients who received placebo plus NAC. The pCR rate was 64.8% in the pembrolizumab-NAC arm and 51.2% in the placebo–NAC arm (estimated treatment difference, 13.6 percentage points; 95% CI, 5.4 to 21.8; P less than .001).

These results are exciting. Results from I-SPY2 and KEYNOTE-522 whet the appetite for results of KEYNOTE-756, an ongoing trial of pembrolizumab plus NAC in HR-positive/ERBB2-negative patients (NCT03725059). Hopefully, the efficacy and toxicity results of KEYNOTE-756 will be as exciting as the I-SPY2 results predict they will be. Among patients with early stage breast cancer whose tumor characteristics are adverse enough to require NAC, better regimens are needed to attain pCR, a validated surrogate for long-term freedom from recurrence.


Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations.

Background

On Dec. 31, 2019, the Chinese city of Wuhan reported an outbreak of pneumonia from an unknown cause. The outbreak was found to be linked to the Hunan seafood market because of a shared history of exposure by many patients. After a full-scale investigation, China’s Center for Disease Control activated a level 2 emergency response on Jan. 4, 2020. A novel coronavirus was officially identified as a causative pathogen for the outbreak.¹

Coronavirus, first discovered in the 1960s, is a respiratory RNA virus, most commonly associated with the “common cold.” However, we have had two highly pathogenic forms of coronavirus that originated from animal reservoirs, leading to global epidemics. This includes SARS-CoV in 2002-2004 and MERS-CoV in 2012 with more than 10,000 combined cases. The primary host has been bats, but mammals like camels, cattle, cats, and palm civets have been intermediate hosts in previous epidemics.²

The International Committee on Taxonomy of Viruses named the 2019-nCoV officially as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease, COVID-19, on Feb. 11, 2020.³ Currently, the presentation includes fever, cough, trouble breathing, fatigue, and, rarely, watery diarrhea. More severe presentations include respiratory failure and death. Based on the incubation period of illness for Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) coronaviruses, as well as observational data from reports of travel-related COVID-19, CDC estimates that symptoms of COVID-19 occur within 2-14 days after exposure. Asymptomatic transmission is also documented in some cases.⁴

On Jan. 13, the first case of COVID-19 outside of China was identified in Thailand. On Jan. 21, the first case of COVID-19 was identified in the United States. On Jan. 23, Chinese authorities suspended travel in and out of Wuhan, followed by other cities in the Hubei Province, leading to a quarantine of 50 million people. By Jan. 30, the World Health Organization had identified COVID-19 as the highest level of an epidemic alert referred to as a PHEIC: Public Health Emergency of International Concern. On Feb. 2, the first death outside China from coronavirus was reported in the Philippines. As of March 4 there have been 95,000 confirmed cases and 3,246 deaths globally. Within China, there have been 80,200 cases with 2,981 deaths.⁵

Cases have now been diagnosed in increasing numbers in Italy, Japan, South Korea, Iran, and 76 countries. Of note, the fatalities were of patients already in critical condition, who were typically older (more than 60 years old, especially more than 80) and immunocompromised with comorbid conditions (cardiovascular disease, diabetes, chronic respiratory disease, cancer).⁶ To put this in perspective, since 2010, CDC reports 140,000-810,000 hospitalizations and 12,000-61,000 deaths from the influenza virus annually in the US.⁷
 

The current situation in the United States

In the United States, as of March 4, 2020, there are currently 152 confirmed cases in 16 states. The first U.S. case of coronavirus without any of the travel-related and exposure risk factors was identified on Feb. 27 in California, indicating the first instance of community spread.⁸ The first death was reported in Washington state on Feb. 28, after which the state’s governor declared a state of emergency.⁹ On March 1, Washington state health officials investigated an outbreak of coronavirus at a long-term nursing facility in which two people tested positive for the disease, heralding the probable first nosocomial transmission of the virus in the United States. Since then, there have been 10 deaths in Washington state related to the coronavirus.

Current interventions in the United States

The U.S. Centers for Disease Control and Prevention is leading a multiagency effort to combat the COVID-19 potential pandemic. A Feb. 24 report in Morbidity and Mortality Weekly Report revealed that 1,336 CDC staff members have been involved in the COVID-19 response.¹⁰ CDC staff members have been deployed to 39 locations in the United States and internationally. CDC staff members are working with state and local health departments and other public health authorities to assist with case identification, contact tracing, evaluation of persons under investigation (PUI) for COVID-19, and medical management of cases, as well as with research and academic institutions to understand the virulence, risk for transmission, and other characteristics of this novel virus. The CDC is also working with other agencies of the U.S. government including the U.S. Department of Defense, Department of Health & Human Services and the U.S. Department of State to safely evacuate U.S. citizens, residents, and their families from international locations with high incidence and transmission of COVID-19.

Specific real-time updated guidance has been developed and posted online for health care settings for patient management, infection control and prevention, laboratory testing, environmental cleaning, worker safety, and international travel. The CDC has developed communications materials in English and Spanish for communities and guidance for health care settings, public health, laboratories, schools, and businesses to prepare for a potential pandemic. Travel advisories to countries affected by the epidemic are regularly updated to inform travelers and clinicians about current health issues that need to be considered before travel.¹¹ A level 3 travel notice (avoid all nonessential travel) for China has been in effect since Jan. 27, and on Feb. 29 this was upgraded to a level 4 travel notice.¹² Airport screening has been implemented in the 11 U.S. international airports to which flights from China have been diverted, and a total of 46,016 air travelers had been screened by Feb. 23. Incoming passengers are screened for fever, cough, and shortness of breath.

Currently, the CDC has a comprehensive algorithm for further investigation of a PUI – fever, cough, shortness of breath, and a history of travel to areas with increased coronavirus circulation within 14 days of onset of symptoms, OR a close household contact of a confirmed case. When there is a PUI, the current protocol indicates health care providers should alert a local or state health department official. After the health department completes a case investigation, the CDC will help transport specimens (upper respiratory and lower respiratory specimens, and sometimes stool or urine) as soon as possible to the centralized lab for polymerase chain reaction (PCR) testing.¹³ CDC laboratories are currently using real-time reverse transcription–PCR (RT-PCR). The CDC is also developing a serologic test to assist with surveillance for SARS-CoV-2 circulation in the U.S. population. There is also a safe repository of viral isolates set up to help with sharing of isolates with academic institutions for research purposes.¹⁴

At hospitals and outpatient offices in the United States, we are preparing for potential cases by reminding frontline health care workers to routinely ask about travel history in addition to relevant symptoms. By eliciting the history early, they should be able to identify and isolate PUIs, appropriately minimizing exposure. Some facilities are displaying signage in waiting rooms to alert patients to provide relevant history, helping to improve triage. COVID-19 symptoms are like those of influenza (e.g., fever, cough, and shortness of breath), and the current outbreak is occurring during a time of year when respiratory illnesses from influenza and other viruses are highly prevalent. To prevent influenza and possible unnecessary evaluation for COVID-19, all persons aged 6 months and older are strongly encouraged to receive an annual influenza vaccine.

To decrease the risk for respiratory disease, persons can practice recommended preventive measures. Persons ill with symptoms of COVID-19 who have had contact with a person with COVID-19, or recent travel to countries with apparent community spread, should proactively communicate with their health care provider before showing up at the health care facility to help make arrangements to prevent possible transmission in the health care setting. In a medical emergency, they should inform emergency medical personnel about possible COVID-19 exposure. If found positive, the current recommendation is to place patients on airborne isolation. N95 masks are being recommended for health care professionals. Hospitals are reinforcing effective infection control procedures, updating pandemic preparedness protocols, and ensuring adequate supplies in the case of an enormous influx of patients.¹⁵

Challenges and opportunities

Many challenges present in the process of getting prepared for a potential outbreak. Personal protective equipment such as N-95 masks are in short supply, as they are in high demand in the general public.¹⁶ The CDC currently does not recommend that members of the general public use face masks, given low levels of circulation of SARS-CoV-2 currently in the United States. The CDC has developed several documents regarding infection control, hospital preparedness assessments, personal protective equipment (PPE) supply planning, clinical evaluation and management, and respirator conservation strategies.

The RT-PCR test developed by the CDC has had some setbacks, with recent testing kits showing “inconclusive results.” The testing was initially available only through the CDC lab in Atlanta, with a 48-hour turnaround. This led to potential delays in diagnosis and the timely isolation and treatment of infected patients. On March 3, the CDC broadened the guidelines for coronavirus testing, allowing clinicians to order a test for any patients who have symptoms of COVID-19 infection. The greatest need is for decentralized testing in local and state labs, as well as validated testing in local hospitals and commercial labs. The ability to develop and scale-up diagnostic abilities is critically important.

There is also concern about overwhelming hospitals with a strain on the availability of beds, ventilators, and airborne isolation rooms. The CDC is recommending leveraging telehealth tools to direct people to the right level of health care for their medical needs. Hospitalization should only be for the sickest patients.¹⁷

Funding for a pandemic response is of paramount importance. Proposed 2021 federal budget cuts include $2.9 billion in cuts to the National Institutes of Health, and $708 million in cuts to the CDC, which makes the situation look especially worrisome as we face a potentially severe pandemic. The Infectious Diseases Society of America identifies antimicrobial resistance, NIH research, global health security, global HIV epidemic, and CDC vaccine programs as five “deeply underfunded” areas in the federal budget.¹⁸

The NIH has recently begun the first randomized clinical trial, treating patients at the University of Nebraska with laboratory-confirmed SARS-CoV-2 with a broad-spectrum antiviral drug called remdesivir. Patients from the Diamond Princess Cruise ship are also participating in this clinical trial. This study will hopefully shed light on potential treatments for coronavirus to stop or alleviate the consequences in real time. Similar clinical trials are also occurring in China.¹⁹

Vaccine development is underway in many public and private research facilities, but it will take approximately 6-18 months before they will be available for use. In the absence of a vaccine or therapeutic, community mitigation measures are the primary method to respond to the widespread transmission, and supportive care is the current medical treatment. In the case of a pandemic, the mitigation measures might include school dismissals and social distancing in other settings, like suspension of mass gatherings, telework and remote-meeting options in workplaces.

Many respected medical journals in the United States have made access to SARS-CoV-2 articles and literature readily and freely available, which is a remarkable step. Multiple societies and journals have made information available in real time and have used media effectively (e.g., podcasts, e-learning) to disseminate information to the general public. Articles have been made available in other languages, including Chinese.
 

Conclusions

In summary, there have been 3,280 total deaths attributable to SARS-CoV-2 to date globally, mostly among geriatric patients with comorbidities. To provide some perspective on the statistics, influenza has killed almost 14,000 patients this season alone (much more than coronavirus). COVID-19 is undoubtedly a global public health threat. We in the U.S. health care system are taking swift public health actions, including isolation of patients and contacts to prevent secondary spread, but it is unclear if this is enough to stop an outbreak from becoming a pandemic.

The CDC is warning of significant social and economic disruption in the coming weeks, with more expected community spread and confirmed cases. It is challenging to prepare for a pandemic when the transmission dynamics are not clearly known, the duration of infectiousness is not well defined, and asymptomatic transmission is a possibility. It is time for the public to be informed from trusted sources and avoid unverified information, especially on social media which can lead to confusion and panic. The spread of COVID-19 infection in the United States is inevitable, and there must be sufficient, well-coordinated planning that can curtail the spread and reduce the impact.
 

Dr. Tirupathi is the medical director of Keystone Infectious Diseases/HIV in Chambersburg, Pa., and currently chair of infection prevention at Wellspan Chambersburg and Waynesboro (Pa.) Hospitals. He also is the lead physician for antibiotic stewardship at these hospitals. Dr. Palabindala is hospital medicine division chief at the University of Mississippi Medical Center, Jackson. Ms. Sathya Areti is a 3rd-year medical student at the Virginia Commonwealth University School of Medicine (class of 2021), planning to apply into Internal Medicine-Pediatrics. Dr. Swetha Areti is currently working as a hospitalist at Wellspan Chambersburg Hospital and is also a member of the Wellspan Pharmacy and Therapeutics committee.

References

1. Phelan AL et al. The novel coronavirus originating in Wuhan, China: Challenges for global health governance. JAMA. 2020;323(8):709-10. doi: 10.1001/jama.2020.1097.

2. del Rio C, Malani PN. 2019 Novel coronavirus – Important information for clinicians. JAMA. Published online Feb. 5, 2020. doi: 10.1001/jama.2020.1490.

3. Gorbalenya AE et al. Severe acute respiratory syndrome-related coronavirus: The species and its viruses – a statement of the Coronavirus Study Group. bioRxiv. Published Jan. 1, 2020. doi: 10.1101/2020.02.07.937862.

4. Jernigan DB. CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020;69:216-19. doi: 10.15585/mmwr.mm6908e1.

5. Coronavirus disease 2019 (COVID-19). Situation Report – 40. Published Feb. 29, 2020.

6. Kaiyuan Sun, et al. Early epidemiological analysis of the coronavirus disease 2019 outbreak based on crowdsourced data: a population level observational study, Feb. 20, 2020. Lancet Digital Health 2020. doi: 10.1016/S2589-7500(20)30026-1.

7. Rolfes MA et al. Annual estimates of the burden of seasonal influenza in the United States: A tool for strengthening influenza surveillance and preparedness. Influenza Other Respir Viruses. 2018;12(1):132-7. doi: 10.1111/irv.12486.

8. Jernigan DB. CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb. 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020;69:216-19. doi: 10.15585/mmwr.mm6908e1.

9. Jablon R, Baumann L. Washington governor declares state of emergency over virus. AP News. Published Feb. 29, 2020.

10. Jernigan DB, CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb. 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020; 69:216-219. doi: 10.15585/mmwr.mm6908e1.

11. Information for health departments on reporting a person under investigation (PUI) or laboratory-confirmed case for COVID-19. Centers for Disease Control and Prevention. Published Feb 24, 2020.

12. Hines M. Coronavirus: Travel advisory for Italy, South Korea raised to level 4, ‘Do Not Travel’. USA Today. Published Feb. 29, 2020.

13. Information for health departments on reporting a person under investigation (PUI) or laboratory-confirmed case for COVID-19. Centers for Disease Control and Prevention. Published Feb. 24, 2020.

14. CDC Tests for COVID-19. Centers for Disease Control and Prevention. Published Feb. 25, 2020.

15. Jernigan DB. CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb. 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020; 69:216-19. doi: 10.15585/mmwr.mm6908e1.

16. Gunia A. The global shortage of medical masks won’t be easing soon. Time. Published Feb. 27, 2020.

17. CDC in action: Preparing communities for potential spread of COVID-19. Centers for Disease Control and Prevention. Published Feb. 23, 2020.

18. Kadets L. White House budget cuts vital domestic and global public health programs. IDSA Home. Published 2020.

19. NIH clinical trial of remdesivir to treat COVID-19 begins. National Institutes of Health. Feb. 25, 2020.

Background

On Dec. 31, 2019, the Chinese city of Wuhan reported an outbreak of pneumonia from an unknown cause. The outbreak was found to be linked to the Hunan seafood market because of a shared history of exposure by many patients. After a full-scale investigation, China’s Center for Disease Control activated a level 2 emergency response on Jan. 4, 2020. A novel coronavirus was officially identified as a causative pathogen for the outbreak.¹

Coronavirus, first discovered in the 1960s, is a respiratory RNA virus, most commonly associated with the “common cold.” However, we have had two highly pathogenic forms of coronavirus that originated from animal reservoirs, leading to global epidemics. This includes SARS-CoV in 2002-2004 and MERS-CoV in 2012 with more than 10,000 combined cases. The primary host has been bats, but mammals like camels, cattle, cats, and palm civets have been intermediate hosts in previous epidemics.²

The International Committee on Taxonomy of Viruses named the 2019-nCoV officially as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease, COVID-19, on Feb. 11, 2020.³ Currently, the presentation includes fever, cough, trouble breathing, fatigue, and, rarely, watery diarrhea. More severe presentations include respiratory failure and death. Based on the incubation period of illness for Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) coronaviruses, as well as observational data from reports of travel-related COVID-19, CDC estimates that symptoms of COVID-19 occur within 2-14 days after exposure. Asymptomatic transmission is also documented in some cases.⁴

On Jan. 13, the first case of COVID-19 outside of China was identified in Thailand. On Jan. 21, the first case of COVID-19 was identified in the United States. On Jan. 23, Chinese authorities suspended travel in and out of Wuhan, followed by other cities in the Hubei Province, leading to a quarantine of 50 million people. By Jan. 30, the World Health Organization had identified COVID-19 as the highest level of an epidemic alert referred to as a PHEIC: Public Health Emergency of International Concern. On Feb. 2, the first death outside China from coronavirus was reported in the Philippines. As of March 4 there have been 95,000 confirmed cases and 3,246 deaths globally. Within China, there have been 80,200 cases with 2,981 deaths.⁵

Cases have now been diagnosed in increasing numbers in Italy, Japan, South Korea, Iran, and 76 countries. Of note, the fatalities were of patients already in critical condition, who were typically older (more than 60 years old, especially more than 80) and immunocompromised with comorbid conditions (cardiovascular disease, diabetes, chronic respiratory disease, cancer).⁶ To put this in perspective, since 2010, CDC reports 140,000-810,000 hospitalizations and 12,000-61,000 deaths from the influenza virus annually in the US.⁷
 

The current situation in the United States

In the United States, as of March 4, 2020, there are currently 152 confirmed cases in 16 states. The first U.S. case of coronavirus without any of the travel-related and exposure risk factors was identified on Feb. 27 in California, indicating the first instance of community spread.⁸ The first death was reported in Washington state on Feb. 28, after which the state’s governor declared a state of emergency.⁹ On March 1, Washington state health officials investigated an outbreak of coronavirus at a long-term nursing facility in which two people tested positive for the disease, heralding the probable first nosocomial transmission of the virus in the United States. Since then, there have been 10 deaths in Washington state related to the coronavirus.

Current interventions in the United States

The U.S. Centers for Disease Control and Prevention is leading a multiagency effort to combat the COVID-19 potential pandemic. A Feb. 24 report in Morbidity and Mortality Weekly Report revealed that 1,336 CDC staff members have been involved in the COVID-19 response.¹⁰ CDC staff members have been deployed to 39 locations in the United States and internationally. CDC staff members are working with state and local health departments and other public health authorities to assist with case identification, contact tracing, evaluation of persons under investigation (PUI) for COVID-19, and medical management of cases, as well as with research and academic institutions to understand the virulence, risk for transmission, and other characteristics of this novel virus. The CDC is also working with other agencies of the U.S. government including the U.S. Department of Defense, Department of Health & Human Services and the U.S. Department of State to safely evacuate U.S. citizens, residents, and their families from international locations with high incidence and transmission of COVID-19.

Specific real-time updated guidance has been developed and posted online for health care settings for patient management, infection control and prevention, laboratory testing, environmental cleaning, worker safety, and international travel. The CDC has developed communications materials in English and Spanish for communities and guidance for health care settings, public health, laboratories, schools, and businesses to prepare for a potential pandemic. Travel advisories to countries affected by the epidemic are regularly updated to inform travelers and clinicians about current health issues that need to be considered before travel.¹¹ A level 3 travel notice (avoid all nonessential travel) for China has been in effect since Jan. 27, and on Feb. 29 this was upgraded to a level 4 travel notice.¹² Airport screening has been implemented in the 11 U.S. international airports to which flights from China have been diverted, and a total of 46,016 air travelers had been screened by Feb. 23. Incoming passengers are screened for fever, cough, and shortness of breath.

Currently, the CDC has a comprehensive algorithm for further investigation of a PUI – fever, cough, shortness of breath, and a history of travel to areas with increased coronavirus circulation within 14 days of onset of symptoms, OR a close household contact of a confirmed case. When there is a PUI, the current protocol indicates health care providers should alert a local or state health department official. After the health department completes a case investigation, the CDC will help transport specimens (upper respiratory and lower respiratory specimens, and sometimes stool or urine) as soon as possible to the centralized lab for polymerase chain reaction (PCR) testing.¹³ CDC laboratories are currently using real-time reverse transcription–PCR (RT-PCR). The CDC is also developing a serologic test to assist with surveillance for SARS-CoV-2 circulation in the U.S. population. There is also a safe repository of viral isolates set up to help with sharing of isolates with academic institutions for research purposes.¹⁴

At hospitals and outpatient offices in the United States, we are preparing for potential cases by reminding frontline health care workers to routinely ask about travel history in addition to relevant symptoms. By eliciting the history early, they should be able to identify and isolate PUIs, appropriately minimizing exposure. Some facilities are displaying signage in waiting rooms to alert patients to provide relevant history, helping to improve triage. COVID-19 symptoms are like those of influenza (e.g., fever, cough, and shortness of breath), and the current outbreak is occurring during a time of year when respiratory illnesses from influenza and other viruses are highly prevalent. To prevent influenza and possible unnecessary evaluation for COVID-19, all persons aged 6 months and older are strongly encouraged to receive an annual influenza vaccine.

To decrease the risk for respiratory disease, persons can practice recommended preventive measures. Persons ill with symptoms of COVID-19 who have had contact with a person with COVID-19, or recent travel to countries with apparent community spread, should proactively communicate with their health care provider before showing up at the health care facility to help make arrangements to prevent possible transmission in the health care setting. In a medical emergency, they should inform emergency medical personnel about possible COVID-19 exposure. If found positive, the current recommendation is to place patients on airborne isolation. N95 masks are being recommended for health care professionals. Hospitals are reinforcing effective infection control procedures, updating pandemic preparedness protocols, and ensuring adequate supplies in the case of an enormous influx of patients.¹⁵

Challenges and opportunities

Many challenges present in the process of getting prepared for a potential outbreak. Personal protective equipment such as N-95 masks are in short supply, as they are in high demand in the general public.¹⁶ The CDC currently does not recommend that members of the general public use face masks, given low levels of circulation of SARS-CoV-2 currently in the United States. The CDC has developed several documents regarding infection control, hospital preparedness assessments, personal protective equipment (PPE) supply planning, clinical evaluation and management, and respirator conservation strategies.

The RT-PCR test developed by the CDC has had some setbacks, with recent testing kits showing “inconclusive results.” The testing was initially available only through the CDC lab in Atlanta, with a 48-hour turnaround. This led to potential delays in diagnosis and the timely isolation and treatment of infected patients. On March 3, the CDC broadened the guidelines for coronavirus testing, allowing clinicians to order a test for any patients who have symptoms of COVID-19 infection. The greatest need is for decentralized testing in local and state labs, as well as validated testing in local hospitals and commercial labs. The ability to develop and scale-up diagnostic abilities is critically important.

There is also concern about overwhelming hospitals with a strain on the availability of beds, ventilators, and airborne isolation rooms. The CDC is recommending leveraging telehealth tools to direct people to the right level of health care for their medical needs. Hospitalization should only be for the sickest patients.¹⁷

Funding for a pandemic response is of paramount importance. Proposed 2021 federal budget cuts include $2.9 billion in cuts to the National Institutes of Health, and $708 million in cuts to the CDC, which makes the situation look especially worrisome as we face a potentially severe pandemic. The Infectious Diseases Society of America identifies antimicrobial resistance, NIH research, global health security, global HIV epidemic, and CDC vaccine programs as five “deeply underfunded” areas in the federal budget.¹⁸

The NIH has recently begun the first randomized clinical trial, treating patients at the University of Nebraska with laboratory-confirmed SARS-CoV-2 with a broad-spectrum antiviral drug called remdesivir. Patients from the Diamond Princess Cruise ship are also participating in this clinical trial. This study will hopefully shed light on potential treatments for coronavirus to stop or alleviate the consequences in real time. Similar clinical trials are also occurring in China.¹⁹

Vaccine development is underway in many public and private research facilities, but it will take approximately 6-18 months before they will be available for use. In the absence of a vaccine or therapeutic, community mitigation measures are the primary method to respond to the widespread transmission, and supportive care is the current medical treatment. In the case of a pandemic, the mitigation measures might include school dismissals and social distancing in other settings, like suspension of mass gatherings, telework and remote-meeting options in workplaces.

Many respected medical journals in the United States have made access to SARS-CoV-2 articles and literature readily and freely available, which is a remarkable step. Multiple societies and journals have made information available in real time and have used media effectively (e.g., podcasts, e-learning) to disseminate information to the general public. Articles have been made available in other languages, including Chinese.
 

Conclusions

In summary, there have been 3,280 total deaths attributable to SARS-CoV-2 to date globally, mostly among geriatric patients with comorbidities. To provide some perspective on the statistics, influenza has killed almost 14,000 patients this season alone (much more than coronavirus). COVID-19 is undoubtedly a global public health threat. We in the U.S. health care system are taking swift public health actions, including isolation of patients and contacts to prevent secondary spread, but it is unclear if this is enough to stop an outbreak from becoming a pandemic.

The CDC is warning of significant social and economic disruption in the coming weeks, with more expected community spread and confirmed cases. It is challenging to prepare for a pandemic when the transmission dynamics are not clearly known, the duration of infectiousness is not well defined, and asymptomatic transmission is a possibility. It is time for the public to be informed from trusted sources and avoid unverified information, especially on social media which can lead to confusion and panic. The spread of COVID-19 infection in the United States is inevitable, and there must be sufficient, well-coordinated planning that can curtail the spread and reduce the impact.
 

Dr. Tirupathi is the medical director of Keystone Infectious Diseases/HIV in Chambersburg, Pa., and currently chair of infection prevention at Wellspan Chambersburg and Waynesboro (Pa.) Hospitals. He also is the lead physician for antibiotic stewardship at these hospitals. Dr. Palabindala is hospital medicine division chief at the University of Mississippi Medical Center, Jackson. Ms. Sathya Areti is a 3rd-year medical student at the Virginia Commonwealth University School of Medicine (class of 2021), planning to apply into Internal Medicine-Pediatrics. Dr. Swetha Areti is currently working as a hospitalist at Wellspan Chambersburg Hospital and is also a member of the Wellspan Pharmacy and Therapeutics committee.

References

1. Phelan AL et al. The novel coronavirus originating in Wuhan, China: Challenges for global health governance. JAMA. 2020;323(8):709-10. doi: 10.1001/jama.2020.1097.

2. del Rio C, Malani PN. 2019 Novel coronavirus – Important information for clinicians. JAMA. Published online Feb. 5, 2020. doi: 10.1001/jama.2020.1490.

3. Gorbalenya AE et al. Severe acute respiratory syndrome-related coronavirus: The species and its viruses – a statement of the Coronavirus Study Group. bioRxiv. Published Jan. 1, 2020. doi: 10.1101/2020.02.07.937862.

4. Jernigan DB. CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020;69:216-19. doi: 10.15585/mmwr.mm6908e1.

5. Coronavirus disease 2019 (COVID-19). Situation Report – 40. Published Feb. 29, 2020.

6. Kaiyuan Sun, et al. Early epidemiological analysis of the coronavirus disease 2019 outbreak based on crowdsourced data: a population level observational study, Feb. 20, 2020. Lancet Digital Health 2020. doi: 10.1016/S2589-7500(20)30026-1.

7. Rolfes MA et al. Annual estimates of the burden of seasonal influenza in the United States: A tool for strengthening influenza surveillance and preparedness. Influenza Other Respir Viruses. 2018;12(1):132-7. doi: 10.1111/irv.12486.

8. Jernigan DB. CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb. 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020;69:216-19. doi: 10.15585/mmwr.mm6908e1.

9. Jablon R, Baumann L. Washington governor declares state of emergency over virus. AP News. Published Feb. 29, 2020.

10. Jernigan DB, CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb. 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020; 69:216-219. doi: 10.15585/mmwr.mm6908e1.

11. Information for health departments on reporting a person under investigation (PUI) or laboratory-confirmed case for COVID-19. Centers for Disease Control and Prevention. Published Feb 24, 2020.

12. Hines M. Coronavirus: Travel advisory for Italy, South Korea raised to level 4, ‘Do Not Travel’. USA Today. Published Feb. 29, 2020.

13. Information for health departments on reporting a person under investigation (PUI) or laboratory-confirmed case for COVID-19. Centers for Disease Control and Prevention. Published Feb. 24, 2020.

14. CDC Tests for COVID-19. Centers for Disease Control and Prevention. Published Feb. 25, 2020.

15. Jernigan DB. CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb. 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020; 69:216-19. doi: 10.15585/mmwr.mm6908e1.

16. Gunia A. The global shortage of medical masks won’t be easing soon. Time. Published Feb. 27, 2020.

17. CDC in action: Preparing communities for potential spread of COVID-19. Centers for Disease Control and Prevention. Published Feb. 23, 2020.

18. Kadets L. White House budget cuts vital domestic and global public health programs. IDSA Home. Published 2020.

19. NIH clinical trial of remdesivir to treat COVID-19 begins. National Institutes of Health. Feb. 25, 2020.

Background

On Dec. 31, 2019, the Chinese city of Wuhan reported an outbreak of pneumonia from an unknown cause. The outbreak was found to be linked to the Hunan seafood market because of a shared history of exposure by many patients. After a full-scale investigation, China’s Center for Disease Control activated a level 2 emergency response on Jan. 4, 2020. A novel coronavirus was officially identified as a causative pathogen for the outbreak.¹

Coronavirus, first discovered in the 1960s, is a respiratory RNA virus, most commonly associated with the “common cold.” However, we have had two highly pathogenic forms of coronavirus that originated from animal reservoirs, leading to global epidemics. This includes SARS-CoV in 2002-2004 and MERS-CoV in 2012 with more than 10,000 combined cases. The primary host has been bats, but mammals like camels, cattle, cats, and palm civets have been intermediate hosts in previous epidemics.²

The International Committee on Taxonomy of Viruses named the 2019-nCoV officially as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease, COVID-19, on Feb. 11, 2020.³ Currently, the presentation includes fever, cough, trouble breathing, fatigue, and, rarely, watery diarrhea. More severe presentations include respiratory failure and death. Based on the incubation period of illness for Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) coronaviruses, as well as observational data from reports of travel-related COVID-19, CDC estimates that symptoms of COVID-19 occur within 2-14 days after exposure. Asymptomatic transmission is also documented in some cases.⁴

On Jan. 13, the first case of COVID-19 outside of China was identified in Thailand. On Jan. 21, the first case of COVID-19 was identified in the United States. On Jan. 23, Chinese authorities suspended travel in and out of Wuhan, followed by other cities in the Hubei Province, leading to a quarantine of 50 million people. By Jan. 30, the World Health Organization had identified COVID-19 as the highest level of an epidemic alert referred to as a PHEIC: Public Health Emergency of International Concern. On Feb. 2, the first death outside China from coronavirus was reported in the Philippines. As of March 4 there have been 95,000 confirmed cases and 3,246 deaths globally. Within China, there have been 80,200 cases with 2,981 deaths.⁵

Cases have now been diagnosed in increasing numbers in Italy, Japan, South Korea, Iran, and 76 countries. Of note, the fatalities were of patients already in critical condition, who were typically older (more than 60 years old, especially more than 80) and immunocompromised with comorbid conditions (cardiovascular disease, diabetes, chronic respiratory disease, cancer).⁶ To put this in perspective, since 2010, CDC reports 140,000-810,000 hospitalizations and 12,000-61,000 deaths from the influenza virus annually in the US.⁷
 

The current situation in the United States

In the United States, as of March 4, 2020, there are currently 152 confirmed cases in 16 states. The first U.S. case of coronavirus without any of the travel-related and exposure risk factors was identified on Feb. 27 in California, indicating the first instance of community spread.⁸ The first death was reported in Washington state on Feb. 28, after which the state’s governor declared a state of emergency.⁹ On March 1, Washington state health officials investigated an outbreak of coronavirus at a long-term nursing facility in which two people tested positive for the disease, heralding the probable first nosocomial transmission of the virus in the United States. Since then, there have been 10 deaths in Washington state related to the coronavirus.

Current interventions in the United States

The U.S. Centers for Disease Control and Prevention is leading a multiagency effort to combat the COVID-19 potential pandemic. A Feb. 24 report in Morbidity and Mortality Weekly Report revealed that 1,336 CDC staff members have been involved in the COVID-19 response.¹⁰ CDC staff members have been deployed to 39 locations in the United States and internationally. CDC staff members are working with state and local health departments and other public health authorities to assist with case identification, contact tracing, evaluation of persons under investigation (PUI) for COVID-19, and medical management of cases, as well as with research and academic institutions to understand the virulence, risk for transmission, and other characteristics of this novel virus. The CDC is also working with other agencies of the U.S. government including the U.S. Department of Defense, Department of Health & Human Services and the U.S. Department of State to safely evacuate U.S. citizens, residents, and their families from international locations with high incidence and transmission of COVID-19.

Specific real-time updated guidance has been developed and posted online for health care settings for patient management, infection control and prevention, laboratory testing, environmental cleaning, worker safety, and international travel. The CDC has developed communications materials in English and Spanish for communities and guidance for health care settings, public health, laboratories, schools, and businesses to prepare for a potential pandemic. Travel advisories to countries affected by the epidemic are regularly updated to inform travelers and clinicians about current health issues that need to be considered before travel.¹¹ A level 3 travel notice (avoid all nonessential travel) for China has been in effect since Jan. 27, and on Feb. 29 this was upgraded to a level 4 travel notice.¹² Airport screening has been implemented in the 11 U.S. international airports to which flights from China have been diverted, and a total of 46,016 air travelers had been screened by Feb. 23. Incoming passengers are screened for fever, cough, and shortness of breath.

Currently, the CDC has a comprehensive algorithm for further investigation of a PUI – fever, cough, shortness of breath, and a history of travel to areas with increased coronavirus circulation within 14 days of onset of symptoms, OR a close household contact of a confirmed case. When there is a PUI, the current protocol indicates health care providers should alert a local or state health department official. After the health department completes a case investigation, the CDC will help transport specimens (upper respiratory and lower respiratory specimens, and sometimes stool or urine) as soon as possible to the centralized lab for polymerase chain reaction (PCR) testing.¹³ CDC laboratories are currently using real-time reverse transcription–PCR (RT-PCR). The CDC is also developing a serologic test to assist with surveillance for SARS-CoV-2 circulation in the U.S. population. There is also a safe repository of viral isolates set up to help with sharing of isolates with academic institutions for research purposes.¹⁴

At hospitals and outpatient offices in the United States, we are preparing for potential cases by reminding frontline health care workers to routinely ask about travel history in addition to relevant symptoms. By eliciting the history early, they should be able to identify and isolate PUIs, appropriately minimizing exposure. Some facilities are displaying signage in waiting rooms to alert patients to provide relevant history, helping to improve triage. COVID-19 symptoms are like those of influenza (e.g., fever, cough, and shortness of breath), and the current outbreak is occurring during a time of year when respiratory illnesses from influenza and other viruses are highly prevalent. To prevent influenza and possible unnecessary evaluation for COVID-19, all persons aged 6 months and older are strongly encouraged to receive an annual influenza vaccine.

To decrease the risk for respiratory disease, persons can practice recommended preventive measures. Persons ill with symptoms of COVID-19 who have had contact with a person with COVID-19, or recent travel to countries with apparent community spread, should proactively communicate with their health care provider before showing up at the health care facility to help make arrangements to prevent possible transmission in the health care setting. In a medical emergency, they should inform emergency medical personnel about possible COVID-19 exposure. If found positive, the current recommendation is to place patients on airborne isolation. N95 masks are being recommended for health care professionals. Hospitals are reinforcing effective infection control procedures, updating pandemic preparedness protocols, and ensuring adequate supplies in the case of an enormous influx of patients.¹⁵

Challenges and opportunities

Many challenges present in the process of getting prepared for a potential outbreak. Personal protective equipment such as N-95 masks are in short supply, as they are in high demand in the general public.¹⁶ The CDC currently does not recommend that members of the general public use face masks, given low levels of circulation of SARS-CoV-2 currently in the United States. The CDC has developed several documents regarding infection control, hospital preparedness assessments, personal protective equipment (PPE) supply planning, clinical evaluation and management, and respirator conservation strategies.

The RT-PCR test developed by the CDC has had some setbacks, with recent testing kits showing “inconclusive results.” The testing was initially available only through the CDC lab in Atlanta, with a 48-hour turnaround. This led to potential delays in diagnosis and the timely isolation and treatment of infected patients. On March 3, the CDC broadened the guidelines for coronavirus testing, allowing clinicians to order a test for any patients who have symptoms of COVID-19 infection. The greatest need is for decentralized testing in local and state labs, as well as validated testing in local hospitals and commercial labs. The ability to develop and scale-up diagnostic abilities is critically important.

There is also concern about overwhelming hospitals with a strain on the availability of beds, ventilators, and airborne isolation rooms. The CDC is recommending leveraging telehealth tools to direct people to the right level of health care for their medical needs. Hospitalization should only be for the sickest patients.¹⁷

Funding for a pandemic response is of paramount importance. Proposed 2021 federal budget cuts include $2.9 billion in cuts to the National Institutes of Health, and $708 million in cuts to the CDC, which makes the situation look especially worrisome as we face a potentially severe pandemic. The Infectious Diseases Society of America identifies antimicrobial resistance, NIH research, global health security, global HIV epidemic, and CDC vaccine programs as five “deeply underfunded” areas in the federal budget.¹⁸

The NIH has recently begun the first randomized clinical trial, treating patients at the University of Nebraska with laboratory-confirmed SARS-CoV-2 with a broad-spectrum antiviral drug called remdesivir. Patients from the Diamond Princess Cruise ship are also participating in this clinical trial. This study will hopefully shed light on potential treatments for coronavirus to stop or alleviate the consequences in real time. Similar clinical trials are also occurring in China.¹⁹

Vaccine development is underway in many public and private research facilities, but it will take approximately 6-18 months before they will be available for use. In the absence of a vaccine or therapeutic, community mitigation measures are the primary method to respond to the widespread transmission, and supportive care is the current medical treatment. In the case of a pandemic, the mitigation measures might include school dismissals and social distancing in other settings, like suspension of mass gatherings, telework and remote-meeting options in workplaces.

Many respected medical journals in the United States have made access to SARS-CoV-2 articles and literature readily and freely available, which is a remarkable step. Multiple societies and journals have made information available in real time and have used media effectively (e.g., podcasts, e-learning) to disseminate information to the general public. Articles have been made available in other languages, including Chinese.
 

Conclusions

In summary, there have been 3,280 total deaths attributable to SARS-CoV-2 to date globally, mostly among geriatric patients with comorbidities. To provide some perspective on the statistics, influenza has killed almost 14,000 patients this season alone (much more than coronavirus). COVID-19 is undoubtedly a global public health threat. We in the U.S. health care system are taking swift public health actions, including isolation of patients and contacts to prevent secondary spread, but it is unclear if this is enough to stop an outbreak from becoming a pandemic.

The CDC is warning of significant social and economic disruption in the coming weeks, with more expected community spread and confirmed cases. It is challenging to prepare for a pandemic when the transmission dynamics are not clearly known, the duration of infectiousness is not well defined, and asymptomatic transmission is a possibility. It is time for the public to be informed from trusted sources and avoid unverified information, especially on social media which can lead to confusion and panic. The spread of COVID-19 infection in the United States is inevitable, and there must be sufficient, well-coordinated planning that can curtail the spread and reduce the impact.
 

Dr. Tirupathi is the medical director of Keystone Infectious Diseases/HIV in Chambersburg, Pa., and currently chair of infection prevention at Wellspan Chambersburg and Waynesboro (Pa.) Hospitals. He also is the lead physician for antibiotic stewardship at these hospitals. Dr. Palabindala is hospital medicine division chief at the University of Mississippi Medical Center, Jackson. Ms. Sathya Areti is a 3rd-year medical student at the Virginia Commonwealth University School of Medicine (class of 2021), planning to apply into Internal Medicine-Pediatrics. Dr. Swetha Areti is currently working as a hospitalist at Wellspan Chambersburg Hospital and is also a member of the Wellspan Pharmacy and Therapeutics committee.

References

1. Phelan AL et al. The novel coronavirus originating in Wuhan, China: Challenges for global health governance. JAMA. 2020;323(8):709-10. doi: 10.1001/jama.2020.1097.

2. del Rio C, Malani PN. 2019 Novel coronavirus – Important information for clinicians. JAMA. Published online Feb. 5, 2020. doi: 10.1001/jama.2020.1490.

3. Gorbalenya AE et al. Severe acute respiratory syndrome-related coronavirus: The species and its viruses – a statement of the Coronavirus Study Group. bioRxiv. Published Jan. 1, 2020. doi: 10.1101/2020.02.07.937862.

4. Jernigan DB. CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020;69:216-19. doi: 10.15585/mmwr.mm6908e1.

5. Coronavirus disease 2019 (COVID-19). Situation Report – 40. Published Feb. 29, 2020.

6. Kaiyuan Sun, et al. Early epidemiological analysis of the coronavirus disease 2019 outbreak based on crowdsourced data: a population level observational study, Feb. 20, 2020. Lancet Digital Health 2020. doi: 10.1016/S2589-7500(20)30026-1.

7. Rolfes MA et al. Annual estimates of the burden of seasonal influenza in the United States: A tool for strengthening influenza surveillance and preparedness. Influenza Other Respir Viruses. 2018;12(1):132-7. doi: 10.1111/irv.12486.

8. Jernigan DB. CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb. 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020;69:216-19. doi: 10.15585/mmwr.mm6908e1.

9. Jablon R, Baumann L. Washington governor declares state of emergency over virus. AP News. Published Feb. 29, 2020.

10. Jernigan DB, CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb. 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020; 69:216-219. doi: 10.15585/mmwr.mm6908e1.

11. Information for health departments on reporting a person under investigation (PUI) or laboratory-confirmed case for COVID-19. Centers for Disease Control and Prevention. Published Feb 24, 2020.

12. Hines M. Coronavirus: Travel advisory for Italy, South Korea raised to level 4, ‘Do Not Travel’. USA Today. Published Feb. 29, 2020.

13. Information for health departments on reporting a person under investigation (PUI) or laboratory-confirmed case for COVID-19. Centers for Disease Control and Prevention. Published Feb. 24, 2020.

14. CDC Tests for COVID-19. Centers for Disease Control and Prevention. Published Feb. 25, 2020.

15. Jernigan DB. CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb. 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020; 69:216-19. doi: 10.15585/mmwr.mm6908e1.

16. Gunia A. The global shortage of medical masks won’t be easing soon. Time. Published Feb. 27, 2020.

17. CDC in action: Preparing communities for potential spread of COVID-19. Centers for Disease Control and Prevention. Published Feb. 23, 2020.

18. Kadets L. White House budget cuts vital domestic and global public health programs. IDSA Home. Published 2020.

19. NIH clinical trial of remdesivir to treat COVID-19 begins. National Institutes of Health. Feb. 25, 2020.