Surgery

When an ovarian mass is anticipated or known, following evaluation of a patient’s history and physician examination, imaging via transvaginal and often abdominal ultrasound is the very next step. This evaluation likely will include both gray-scale and color Doppler examination. The initial concern always must be to identify ovarian malignancy.

Despite morphological scoring systems as well as the use of Doppler ultrasonography, there remains a lack of agreement and acceptance. In a 2008 multicenter study, Timmerman and colleagues evaluated 1,066 patients with 1,233 persistent adnexal tumors via transvaginal grayscale and Doppler ultrasound; 73% were benign tumors, and 27% were malignant tumors. Information on 42 gray-scale ultrasound variables and 6 Doppler variables was collected and evaluated to determine which variables had the highest positive predictive value for a malignant tumor and for a benign mass (Ultrasound Obstet Gynecol. 2008 Jun. doi: 10.1002/uog.5365).

Five simple rules were selected that best predict malignancy (M-rules), as follows:

• Irregular solid tumor.
• Ascites.
• At least four papillary projections.
• Irregular multilocular-solid tumor with a greatest diameter greater than or equal to 10 cm.
• Very high color content on Doppler exam.

The following five simple rules suggested that a mass is benign (B-rules):

• Unilocular cyst.
• Largest solid component less than 7 mm.
• Acoustic shadows.
• Smooth multilocular tumor less than 10 cm.
• No detectable blood flow with Doppler exam.

Unfortunately, despite a sensitivity of 93% and specificity of 90%, and a positive and negative predictive value of 80% and 97%, these 10 simple rules were applicable to only 76% of tumors.

To assist those of us who are not gynecologic oncologists and who are often faced with having to determine whether surgery is recommended, I have elicited the expertise of Jubilee Brown, MD, professor and associate director of gynecologic oncology at the Levine Cancer Institute, Carolinas HealthCare System, in Charlotte, N.C., and the current president of the AAGL, to lead us in a review of evaluating an ovarian mass.
 

Dr. Miller is professor of obstetrics & gynecology in the department of clinical sciences, Rosalind Franklin University, North Chicago, Ill., and director of minimally invasive gynecologic surgery at Advocate Lutheran General Hospital, Park Ridge, both in Illinois. Email him at [email protected].

When an ovarian mass is anticipated or known, following evaluation of a patient’s history and physician examination, imaging via transvaginal and often abdominal ultrasound is the very next step. This evaluation likely will include both gray-scale and color Doppler examination. The initial concern always must be to identify ovarian malignancy.

Despite morphological scoring systems as well as the use of Doppler ultrasonography, there remains a lack of agreement and acceptance. In a 2008 multicenter study, Timmerman and colleagues evaluated 1,066 patients with 1,233 persistent adnexal tumors via transvaginal grayscale and Doppler ultrasound; 73% were benign tumors, and 27% were malignant tumors. Information on 42 gray-scale ultrasound variables and 6 Doppler variables was collected and evaluated to determine which variables had the highest positive predictive value for a malignant tumor and for a benign mass (Ultrasound Obstet Gynecol. 2008 Jun. doi: 10.1002/uog.5365).

Five simple rules were selected that best predict malignancy (M-rules), as follows:

• Irregular solid tumor.
• Ascites.
• At least four papillary projections.
• Irregular multilocular-solid tumor with a greatest diameter greater than or equal to 10 cm.
• Very high color content on Doppler exam.

The following five simple rules suggested that a mass is benign (B-rules):

• Unilocular cyst.
• Largest solid component less than 7 mm.
• Acoustic shadows.
• Smooth multilocular tumor less than 10 cm.
• No detectable blood flow with Doppler exam.

Unfortunately, despite a sensitivity of 93% and specificity of 90%, and a positive and negative predictive value of 80% and 97%, these 10 simple rules were applicable to only 76% of tumors.

To assist those of us who are not gynecologic oncologists and who are often faced with having to determine whether surgery is recommended, I have elicited the expertise of Jubilee Brown, MD, professor and associate director of gynecologic oncology at the Levine Cancer Institute, Carolinas HealthCare System, in Charlotte, N.C., and the current president of the AAGL, to lead us in a review of evaluating an ovarian mass.
 

Dr. Miller is professor of obstetrics & gynecology in the department of clinical sciences, Rosalind Franklin University, North Chicago, Ill., and director of minimally invasive gynecologic surgery at Advocate Lutheran General Hospital, Park Ridge, both in Illinois. Email him at [email protected].

When an ovarian mass is anticipated or known, following evaluation of a patient’s history and physician examination, imaging via transvaginal and often abdominal ultrasound is the very next step. This evaluation likely will include both gray-scale and color Doppler examination. The initial concern always must be to identify ovarian malignancy.

Despite morphological scoring systems as well as the use of Doppler ultrasonography, there remains a lack of agreement and acceptance. In a 2008 multicenter study, Timmerman and colleagues evaluated 1,066 patients with 1,233 persistent adnexal tumors via transvaginal grayscale and Doppler ultrasound; 73% were benign tumors, and 27% were malignant tumors. Information on 42 gray-scale ultrasound variables and 6 Doppler variables was collected and evaluated to determine which variables had the highest positive predictive value for a malignant tumor and for a benign mass (Ultrasound Obstet Gynecol. 2008 Jun. doi: 10.1002/uog.5365).

Five simple rules were selected that best predict malignancy (M-rules), as follows:

• Irregular solid tumor.
• Ascites.
• At least four papillary projections.
• Irregular multilocular-solid tumor with a greatest diameter greater than or equal to 10 cm.
• Very high color content on Doppler exam.

The following five simple rules suggested that a mass is benign (B-rules):

• Unilocular cyst.
• Largest solid component less than 7 mm.
• Acoustic shadows.
• Smooth multilocular tumor less than 10 cm.
• No detectable blood flow with Doppler exam.

Unfortunately, despite a sensitivity of 93% and specificity of 90%, and a positive and negative predictive value of 80% and 97%, these 10 simple rules were applicable to only 76% of tumors.

To assist those of us who are not gynecologic oncologists and who are often faced with having to determine whether surgery is recommended, I have elicited the expertise of Jubilee Brown, MD, professor and associate director of gynecologic oncology at the Levine Cancer Institute, Carolinas HealthCare System, in Charlotte, N.C., and the current president of the AAGL, to lead us in a review of evaluating an ovarian mass.
 

Dr. Miller is professor of obstetrics & gynecology in the department of clinical sciences, Rosalind Franklin University, North Chicago, Ill., and director of minimally invasive gynecologic surgery at Advocate Lutheran General Hospital, Park Ridge, both in Illinois. Email him at [email protected].

Ovarian masses are common in women of all ages. It is important not to miss even one ovarian cancer, but we must also identify masses that will resolve on their own over time to avoid overtreatment. These concurrent goals of excluding malignancy while not overtreating patients are the basis for management of the pelvic mass. Additionally, fertility preservation is important when surgery is performed in a reproductive-aged woman.

An ovarian mass may be anything from a simple functional or physiologic cyst to an endometrioma to an epithelial carcinoma, a germ-cell tumor, or a stromal tumor (the latter three of which may metastasize). Across the general population, women have a 5%-10% lifetime risk of needing surgery for a suspected ovarian mass and a 1.4% (1 in 70) risk that this mass is cancerous. The majority of ovarian cysts or masses therefore are benign.

A thorough history – including family history – and physical examination with appropriate laboratory testing and directed imaging are important first steps for the ob.gyn. Fortunately, we have guidelines and criteria governing not only when observation or surgery is warranted but also when patients should be referred to a gynecologic oncologist. By following these guidelines,¹ we are able to achieve the best outcomes.
 

Transvaginal ultrasound

A 2007 groundbreaking study led by Barbara Goff, MD, demonstrated that there are warning signs for ovarian cancer – symptoms that are significantly associated with malignancy. Dr. Goff and her coinvestigators evaluated the charts of hundreds of patients, including about 150 with ovarian cancer, and found that pelvic/abdominal pressure or pain, bloating, increase in abdominal size, and difficulty eating or feeling full were significantly and independently associated with cancer if these symptoms were present for less than a year and occurred at least 12 times per month.²

A pelvic examination is an integral part of evaluating every patient who has such concerns. That said, pelvic exams have limited ability to identify adnexal masses, especially in women who are obese – and that’s where imaging becomes especially important.

Masses generally can be considered simple or complex based on their appearance. A simple cyst is fluid-filled with thin, smooth walls and the absence of solid components or septations; it is significantly more likely to resolve on its own and is less likely to imply malignancy than a complex cyst, especially in a premenopausal woman. A complex cyst is multiseptated and/or solid – possibly with papillary projections – and is more concerning, especially if there is increased, new vascularity. Making this distinction helps us determine the risk of malignancy.

Transvaginal ultrasound (TVUS) is the preferred method for imaging, and our threshold for obtaining a TVUS should be very low. Women who have symptoms or concerns that can’t be attributed to a particular condition, and women in whom a mass can be palpated (even if asymptomatic) should have a TVUS. The imaging modality is cost effective and well tolerated by patients, does not expose the patient to ionizing radiation, and should generally be considered first-line imaging.^3,4

Size is not predictive of malignancy, but it is important for determining whether surgery is warranted. In our experience, a mass of 8-10 cm or larger on TVUS is at risk of torsion and is unlikely to resolve on its own, even in a premenopausal woman. While large masses generally require surgery, patients of any age who have simple cysts smaller than 8-10 cm generally can be followed with serial exams and ultrasound; spontaneous regression is common.

Doppler ultrasonography is useful for evaluating blood flow in and around an ovarian mass and can be helpful for confirming suspected characteristics of a mass.

Recent studies from the radiology community have looked at the utility of the resistive index – a measure of the impedance and velocity of blood flow – as a predictor of ovarian malignancy. However, we caution against using Doppler to determine whether a mass is benign or malignant, or to determine the necessity of surgery. An abnormal ovary may have what is considered to be a normal resistive index, and the resistive index of a normal ovary may fall within the abnormal range. Doppler flow can be helpful, but it must be combined with other predictive features, like solid components with flow or papillary projections within a cyst, to define a decision about surgery.^4,5

Magnetic resonance imaging can be useful in differentiating a fibroid from an ovarian mass, and a CT scan can be helpful in looking for disseminated disease when ovarian cancer is suspected based on ultrasound imaging, physical and history, and serum markers. A CT is useful, for instance, in a patient whose ovary is distended with ascites or who has upper abdominal complaints and a complex cyst. CT, PET, and MRI are not recommended in the initial evaluation of an ovarian mass.

The utility of serum biomarkers

Cancer antigen 125 (CA-125) testing may be helpful – in combination with other findings – for decision-making regarding the likelihood of malignancy and the need to refer patients. CA-125 is like Doppler in that a normal CA-125 cannot eliminate the possibility of cancer, and an abnormal CA-125 does not in and of itself imply malignancy. It’s far from a perfect cancer screening test.

CA-125 is a protein associated with epithelial ovarian malignancies, the type of ovarian cancer most commonly seen in postmenopausal women with genetic predispositions. Its specificity and positive predictive value are much higher in postmenopausal women than in average-risk premenopausal women (those without a family history or a known mutation that predisposes them to ovarian cancer). Levels of the marker are elevated in association with many nonmalignant conditions in premenopausal women – endometriosis, fibroids, and various inflammatory conditions, for instance – so the marker’s utility in this population is limited.

For women who have a family history of ovarian cancer or a known breast cancer gene 1 (BRCA1) or BRCA2 mutation, there are some data that suggest that monitoring with CA-125 measurements and TVUS may be a good approach to following patients prior to the age at which risk-reducing surgery can best be performed.

In an adolescent girl or a woman of reproductive age, we think less about epithelial cancer and more about germ-cell and stromal tumors. When a solid mass is palpated or visualized on imaging, we therefore will utilize a different set of markers; alpha-fetoprotein, L-lactate dehydrogenase, and beta-HCG, for instance, have much higher specificity than CA-125 does for germ-cell tumors in this age group and may be helpful in the evaluation. Similarly, in cases of a very large mass resembling a mucinous tumor, a carcinoembryonic antigen may be helpful.

A number of proprietary profiling technologies have been developed to determine the risk of a diagnosed mass being malignant. For instance, the OVA1 assay looks at five serum markers and scores the results, and the Risk of Ovarian Malignancy Algorithm (ROMA) combines the results of three serum markers with menopausal status into a numerical score. Both have Food and Drug Administration approval for use in women in whom surgery has been deemed necessary. These panels can be fairly predictive of risk and may be helpful – especially in rural areas – in determining which women should be referred to a gynecologic oncologist for surgery.

It is important to appreciate that an ovarian cyst or mass should never be biopsied or aspirated lest a malignant tumor confined to one ovary be potentially spread to the peritoneum.
 

Referral to a gynecologic oncologist

Postmenopausal women with a CA-125 greater than 35 U/mL should be referred, as should postmenopausal women with ascites, those with a nodular or fixed pelvic mass, and those with suspected abdominal or distant metastases (per a CT scan, for instance).

In premenopausal women, ascites, a nodular or fixed mass, and evidence of metastases also are reasons for referral to a gynecologic oncologist. CA-125, again, is much more likely to be elevated for reasons other than malignancy and therefore is not as strong a driver for referral as in postmenopausal women. Patients with markedly elevated levels, however, should probably be referred – particularly when other clinical factors also suggest the need for consultation. While there is no evidence-based threshold for CA-125 in premenopausal women, a CA-125 greater than 200 U/mL is a good cutoff for referral.

For any patient, family history of breast and/or ovarian cancer – especially in a first-degree relative – raises the risk of malignancy and should figure prominently into decision-making regarding referral. Criteria for referral are among the points discussed in the ACOG 2016 Practice Bulletin on Evaluation and Management of Adnexal Masses.¹

A note on BRCA mutations

As the American College of Obstetricians and Gynecologists says in its practice bulletin, the most important personal risk factor for ovarian cancer is a strong family history of breast or ovarian cancer. Women with such a family history can undergo genetic testing for BRCA mutations and have the opportunity to prevent ovarian cancers when mutations are detected. This simple blood test can save lives.

A modeling study we recently completed – not yet published – shows that it actually would be cost effective to do population screening with BRCA testing performed on every woman at age 30 years.

According to the National Cancer Institute website (last review: 2018), it is estimated that about 44% of women who inherit a BRCA1 mutation, and about 17% of those who inherit a BRAC2 mutation, will develop ovarian cancer by the age of 80 years. By identifying those mutations, women may undergo risk-reducing surgery at designated ages after childbearing is complete and bring their risk down to under 5%.

An international take on managing adnexal masses

• Pelvic ultrasound should include the transvaginal approach. Use Doppler imaging as indicated.
• Although simple ovarian cysts are not precursor lesions to a malignant ovarian cancer, perform a high-quality examination to make sure there are no solid/papillary structures before classifying a cyst as a simple cyst. The risk of progression to malignancy is extremely low, but some follow-up is prudent.
• The most accurate method of characterizing an ovarian mass currently is real-time pattern recognition sonography in the hands of an experienced imager.
• Pattern recognition sonography or a risk model such as the International Ovarian Tumor Analysis (IOTA) Simple Rules can be used to initially characterize an ovarian mass.
• When an ovarian lesion is classified as benign, the patient may be followed conservatively, or if indicated, surgery can be performed by a general gynecologist.
• Serial sonography can be beneficial, but there are limited prospective data to support an exact interval and duration.
• Fewer surgical interventions may result in an increase in sonographic surveillance.
• When an ovarian lesion is considered indeterminate on initial sonography, and after appropriate clinical evaluation, a “second-step” evaluation may include referral to an expert sonologist, serial sonography, application of established risk-prediction models, correlation with serum biomarkers, correlation with MRI, or referral to a gynecologic oncologist for further evaluation.

From the First International Consensus Report on Adnexal Masses: Management Recommendations

Source: Glanc P et al. J Ultrasound Med. 2017 May;36(5):849-63.

Dr. Brown reported that she had received an earlier grant from Aspira Labs, the company that developed the OVA1 assay. Dr. Miller reported that he has no relevant financial disclosures.

References

1. Obstet Gynecol. 2016 Nov. doi: 10.1097/AOG.0000000000001768.

2. Cancer. 2007 Jan 15. doi: 10.1002/cncr.22371.

3. Clin Obstet Gynecol. 2015 Mar. doi: 10.1097/GRF.0000000000000083.

4. Ultrasound Q. 2013 Mar. doi: 10.1097/RUQ.0b013e3182814d9b.

5. Ultrasound Obstet Gynecol. 2008 Jun. doi: 10.1002/uog.5365.

Ovarian masses are common in women of all ages. It is important not to miss even one ovarian cancer, but we must also identify masses that will resolve on their own over time to avoid overtreatment. These concurrent goals of excluding malignancy while not overtreating patients are the basis for management of the pelvic mass. Additionally, fertility preservation is important when surgery is performed in a reproductive-aged woman.

An ovarian mass may be anything from a simple functional or physiologic cyst to an endometrioma to an epithelial carcinoma, a germ-cell tumor, or a stromal tumor (the latter three of which may metastasize). Across the general population, women have a 5%-10% lifetime risk of needing surgery for a suspected ovarian mass and a 1.4% (1 in 70) risk that this mass is cancerous. The majority of ovarian cysts or masses therefore are benign.

A thorough history – including family history – and physical examination with appropriate laboratory testing and directed imaging are important first steps for the ob.gyn. Fortunately, we have guidelines and criteria governing not only when observation or surgery is warranted but also when patients should be referred to a gynecologic oncologist. By following these guidelines,¹ we are able to achieve the best outcomes.
 

Transvaginal ultrasound

A 2007 groundbreaking study led by Barbara Goff, MD, demonstrated that there are warning signs for ovarian cancer – symptoms that are significantly associated with malignancy. Dr. Goff and her coinvestigators evaluated the charts of hundreds of patients, including about 150 with ovarian cancer, and found that pelvic/abdominal pressure or pain, bloating, increase in abdominal size, and difficulty eating or feeling full were significantly and independently associated with cancer if these symptoms were present for less than a year and occurred at least 12 times per month.²

A pelvic examination is an integral part of evaluating every patient who has such concerns. That said, pelvic exams have limited ability to identify adnexal masses, especially in women who are obese – and that’s where imaging becomes especially important.

Masses generally can be considered simple or complex based on their appearance. A simple cyst is fluid-filled with thin, smooth walls and the absence of solid components or septations; it is significantly more likely to resolve on its own and is less likely to imply malignancy than a complex cyst, especially in a premenopausal woman. A complex cyst is multiseptated and/or solid – possibly with papillary projections – and is more concerning, especially if there is increased, new vascularity. Making this distinction helps us determine the risk of malignancy.

Transvaginal ultrasound (TVUS) is the preferred method for imaging, and our threshold for obtaining a TVUS should be very low. Women who have symptoms or concerns that can’t be attributed to a particular condition, and women in whom a mass can be palpated (even if asymptomatic) should have a TVUS. The imaging modality is cost effective and well tolerated by patients, does not expose the patient to ionizing radiation, and should generally be considered first-line imaging.^3,4

Size is not predictive of malignancy, but it is important for determining whether surgery is warranted. In our experience, a mass of 8-10 cm or larger on TVUS is at risk of torsion and is unlikely to resolve on its own, even in a premenopausal woman. While large masses generally require surgery, patients of any age who have simple cysts smaller than 8-10 cm generally can be followed with serial exams and ultrasound; spontaneous regression is common.

Doppler ultrasonography is useful for evaluating blood flow in and around an ovarian mass and can be helpful for confirming suspected characteristics of a mass.

Recent studies from the radiology community have looked at the utility of the resistive index – a measure of the impedance and velocity of blood flow – as a predictor of ovarian malignancy. However, we caution against using Doppler to determine whether a mass is benign or malignant, or to determine the necessity of surgery. An abnormal ovary may have what is considered to be a normal resistive index, and the resistive index of a normal ovary may fall within the abnormal range. Doppler flow can be helpful, but it must be combined with other predictive features, like solid components with flow or papillary projections within a cyst, to define a decision about surgery.^4,5

Magnetic resonance imaging can be useful in differentiating a fibroid from an ovarian mass, and a CT scan can be helpful in looking for disseminated disease when ovarian cancer is suspected based on ultrasound imaging, physical and history, and serum markers. A CT is useful, for instance, in a patient whose ovary is distended with ascites or who has upper abdominal complaints and a complex cyst. CT, PET, and MRI are not recommended in the initial evaluation of an ovarian mass.

The utility of serum biomarkers

Cancer antigen 125 (CA-125) testing may be helpful – in combination with other findings – for decision-making regarding the likelihood of malignancy and the need to refer patients. CA-125 is like Doppler in that a normal CA-125 cannot eliminate the possibility of cancer, and an abnormal CA-125 does not in and of itself imply malignancy. It’s far from a perfect cancer screening test.

CA-125 is a protein associated with epithelial ovarian malignancies, the type of ovarian cancer most commonly seen in postmenopausal women with genetic predispositions. Its specificity and positive predictive value are much higher in postmenopausal women than in average-risk premenopausal women (those without a family history or a known mutation that predisposes them to ovarian cancer). Levels of the marker are elevated in association with many nonmalignant conditions in premenopausal women – endometriosis, fibroids, and various inflammatory conditions, for instance – so the marker’s utility in this population is limited.

For women who have a family history of ovarian cancer or a known breast cancer gene 1 (BRCA1) or BRCA2 mutation, there are some data that suggest that monitoring with CA-125 measurements and TVUS may be a good approach to following patients prior to the age at which risk-reducing surgery can best be performed.

In an adolescent girl or a woman of reproductive age, we think less about epithelial cancer and more about germ-cell and stromal tumors. When a solid mass is palpated or visualized on imaging, we therefore will utilize a different set of markers; alpha-fetoprotein, L-lactate dehydrogenase, and beta-HCG, for instance, have much higher specificity than CA-125 does for germ-cell tumors in this age group and may be helpful in the evaluation. Similarly, in cases of a very large mass resembling a mucinous tumor, a carcinoembryonic antigen may be helpful.

A number of proprietary profiling technologies have been developed to determine the risk of a diagnosed mass being malignant. For instance, the OVA1 assay looks at five serum markers and scores the results, and the Risk of Ovarian Malignancy Algorithm (ROMA) combines the results of three serum markers with menopausal status into a numerical score. Both have Food and Drug Administration approval for use in women in whom surgery has been deemed necessary. These panels can be fairly predictive of risk and may be helpful – especially in rural areas – in determining which women should be referred to a gynecologic oncologist for surgery.

It is important to appreciate that an ovarian cyst or mass should never be biopsied or aspirated lest a malignant tumor confined to one ovary be potentially spread to the peritoneum.
 

Referral to a gynecologic oncologist

Postmenopausal women with a CA-125 greater than 35 U/mL should be referred, as should postmenopausal women with ascites, those with a nodular or fixed pelvic mass, and those with suspected abdominal or distant metastases (per a CT scan, for instance).

In premenopausal women, ascites, a nodular or fixed mass, and evidence of metastases also are reasons for referral to a gynecologic oncologist. CA-125, again, is much more likely to be elevated for reasons other than malignancy and therefore is not as strong a driver for referral as in postmenopausal women. Patients with markedly elevated levels, however, should probably be referred – particularly when other clinical factors also suggest the need for consultation. While there is no evidence-based threshold for CA-125 in premenopausal women, a CA-125 greater than 200 U/mL is a good cutoff for referral.

For any patient, family history of breast and/or ovarian cancer – especially in a first-degree relative – raises the risk of malignancy and should figure prominently into decision-making regarding referral. Criteria for referral are among the points discussed in the ACOG 2016 Practice Bulletin on Evaluation and Management of Adnexal Masses.¹

A note on BRCA mutations

As the American College of Obstetricians and Gynecologists says in its practice bulletin, the most important personal risk factor for ovarian cancer is a strong family history of breast or ovarian cancer. Women with such a family history can undergo genetic testing for BRCA mutations and have the opportunity to prevent ovarian cancers when mutations are detected. This simple blood test can save lives.

A modeling study we recently completed – not yet published – shows that it actually would be cost effective to do population screening with BRCA testing performed on every woman at age 30 years.

According to the National Cancer Institute website (last review: 2018), it is estimated that about 44% of women who inherit a BRCA1 mutation, and about 17% of those who inherit a BRAC2 mutation, will develop ovarian cancer by the age of 80 years. By identifying those mutations, women may undergo risk-reducing surgery at designated ages after childbearing is complete and bring their risk down to under 5%.

An international take on managing adnexal masses

• Pelvic ultrasound should include the transvaginal approach. Use Doppler imaging as indicated.
• Although simple ovarian cysts are not precursor lesions to a malignant ovarian cancer, perform a high-quality examination to make sure there are no solid/papillary structures before classifying a cyst as a simple cyst. The risk of progression to malignancy is extremely low, but some follow-up is prudent.
• The most accurate method of characterizing an ovarian mass currently is real-time pattern recognition sonography in the hands of an experienced imager.
• Pattern recognition sonography or a risk model such as the International Ovarian Tumor Analysis (IOTA) Simple Rules can be used to initially characterize an ovarian mass.
• When an ovarian lesion is classified as benign, the patient may be followed conservatively, or if indicated, surgery can be performed by a general gynecologist.
• Serial sonography can be beneficial, but there are limited prospective data to support an exact interval and duration.
• Fewer surgical interventions may result in an increase in sonographic surveillance.
• When an ovarian lesion is considered indeterminate on initial sonography, and after appropriate clinical evaluation, a “second-step” evaluation may include referral to an expert sonologist, serial sonography, application of established risk-prediction models, correlation with serum biomarkers, correlation with MRI, or referral to a gynecologic oncologist for further evaluation.

From the First International Consensus Report on Adnexal Masses: Management Recommendations

Source: Glanc P et al. J Ultrasound Med. 2017 May;36(5):849-63.

Dr. Brown reported that she had received an earlier grant from Aspira Labs, the company that developed the OVA1 assay. Dr. Miller reported that he has no relevant financial disclosures.

References

1. Obstet Gynecol. 2016 Nov. doi: 10.1097/AOG.0000000000001768.

2. Cancer. 2007 Jan 15. doi: 10.1002/cncr.22371.

3. Clin Obstet Gynecol. 2015 Mar. doi: 10.1097/GRF.0000000000000083.

4. Ultrasound Q. 2013 Mar. doi: 10.1097/RUQ.0b013e3182814d9b.

5. Ultrasound Obstet Gynecol. 2008 Jun. doi: 10.1002/uog.5365.

Ovarian masses are common in women of all ages. It is important not to miss even one ovarian cancer, but we must also identify masses that will resolve on their own over time to avoid overtreatment. These concurrent goals of excluding malignancy while not overtreating patients are the basis for management of the pelvic mass. Additionally, fertility preservation is important when surgery is performed in a reproductive-aged woman.

An ovarian mass may be anything from a simple functional or physiologic cyst to an endometrioma to an epithelial carcinoma, a germ-cell tumor, or a stromal tumor (the latter three of which may metastasize). Across the general population, women have a 5%-10% lifetime risk of needing surgery for a suspected ovarian mass and a 1.4% (1 in 70) risk that this mass is cancerous. The majority of ovarian cysts or masses therefore are benign.

A thorough history – including family history – and physical examination with appropriate laboratory testing and directed imaging are important first steps for the ob.gyn. Fortunately, we have guidelines and criteria governing not only when observation or surgery is warranted but also when patients should be referred to a gynecologic oncologist. By following these guidelines,¹ we are able to achieve the best outcomes.
 

Transvaginal ultrasound

A 2007 groundbreaking study led by Barbara Goff, MD, demonstrated that there are warning signs for ovarian cancer – symptoms that are significantly associated with malignancy. Dr. Goff and her coinvestigators evaluated the charts of hundreds of patients, including about 150 with ovarian cancer, and found that pelvic/abdominal pressure or pain, bloating, increase in abdominal size, and difficulty eating or feeling full were significantly and independently associated with cancer if these symptoms were present for less than a year and occurred at least 12 times per month.²

A pelvic examination is an integral part of evaluating every patient who has such concerns. That said, pelvic exams have limited ability to identify adnexal masses, especially in women who are obese – and that’s where imaging becomes especially important.

Masses generally can be considered simple or complex based on their appearance. A simple cyst is fluid-filled with thin, smooth walls and the absence of solid components or septations; it is significantly more likely to resolve on its own and is less likely to imply malignancy than a complex cyst, especially in a premenopausal woman. A complex cyst is multiseptated and/or solid – possibly with papillary projections – and is more concerning, especially if there is increased, new vascularity. Making this distinction helps us determine the risk of malignancy.

Transvaginal ultrasound (TVUS) is the preferred method for imaging, and our threshold for obtaining a TVUS should be very low. Women who have symptoms or concerns that can’t be attributed to a particular condition, and women in whom a mass can be palpated (even if asymptomatic) should have a TVUS. The imaging modality is cost effective and well tolerated by patients, does not expose the patient to ionizing radiation, and should generally be considered first-line imaging.^3,4

Size is not predictive of malignancy, but it is important for determining whether surgery is warranted. In our experience, a mass of 8-10 cm or larger on TVUS is at risk of torsion and is unlikely to resolve on its own, even in a premenopausal woman. While large masses generally require surgery, patients of any age who have simple cysts smaller than 8-10 cm generally can be followed with serial exams and ultrasound; spontaneous regression is common.

Doppler ultrasonography is useful for evaluating blood flow in and around an ovarian mass and can be helpful for confirming suspected characteristics of a mass.

Recent studies from the radiology community have looked at the utility of the resistive index – a measure of the impedance and velocity of blood flow – as a predictor of ovarian malignancy. However, we caution against using Doppler to determine whether a mass is benign or malignant, or to determine the necessity of surgery. An abnormal ovary may have what is considered to be a normal resistive index, and the resistive index of a normal ovary may fall within the abnormal range. Doppler flow can be helpful, but it must be combined with other predictive features, like solid components with flow or papillary projections within a cyst, to define a decision about surgery.^4,5

Magnetic resonance imaging can be useful in differentiating a fibroid from an ovarian mass, and a CT scan can be helpful in looking for disseminated disease when ovarian cancer is suspected based on ultrasound imaging, physical and history, and serum markers. A CT is useful, for instance, in a patient whose ovary is distended with ascites or who has upper abdominal complaints and a complex cyst. CT, PET, and MRI are not recommended in the initial evaluation of an ovarian mass.

The utility of serum biomarkers

Cancer antigen 125 (CA-125) testing may be helpful – in combination with other findings – for decision-making regarding the likelihood of malignancy and the need to refer patients. CA-125 is like Doppler in that a normal CA-125 cannot eliminate the possibility of cancer, and an abnormal CA-125 does not in and of itself imply malignancy. It’s far from a perfect cancer screening test.

CA-125 is a protein associated with epithelial ovarian malignancies, the type of ovarian cancer most commonly seen in postmenopausal women with genetic predispositions. Its specificity and positive predictive value are much higher in postmenopausal women than in average-risk premenopausal women (those without a family history or a known mutation that predisposes them to ovarian cancer). Levels of the marker are elevated in association with many nonmalignant conditions in premenopausal women – endometriosis, fibroids, and various inflammatory conditions, for instance – so the marker’s utility in this population is limited.

For women who have a family history of ovarian cancer or a known breast cancer gene 1 (BRCA1) or BRCA2 mutation, there are some data that suggest that monitoring with CA-125 measurements and TVUS may be a good approach to following patients prior to the age at which risk-reducing surgery can best be performed.

In an adolescent girl or a woman of reproductive age, we think less about epithelial cancer and more about germ-cell and stromal tumors. When a solid mass is palpated or visualized on imaging, we therefore will utilize a different set of markers; alpha-fetoprotein, L-lactate dehydrogenase, and beta-HCG, for instance, have much higher specificity than CA-125 does for germ-cell tumors in this age group and may be helpful in the evaluation. Similarly, in cases of a very large mass resembling a mucinous tumor, a carcinoembryonic antigen may be helpful.

A number of proprietary profiling technologies have been developed to determine the risk of a diagnosed mass being malignant. For instance, the OVA1 assay looks at five serum markers and scores the results, and the Risk of Ovarian Malignancy Algorithm (ROMA) combines the results of three serum markers with menopausal status into a numerical score. Both have Food and Drug Administration approval for use in women in whom surgery has been deemed necessary. These panels can be fairly predictive of risk and may be helpful – especially in rural areas – in determining which women should be referred to a gynecologic oncologist for surgery.

It is important to appreciate that an ovarian cyst or mass should never be biopsied or aspirated lest a malignant tumor confined to one ovary be potentially spread to the peritoneum.
 

Referral to a gynecologic oncologist

Postmenopausal women with a CA-125 greater than 35 U/mL should be referred, as should postmenopausal women with ascites, those with a nodular or fixed pelvic mass, and those with suspected abdominal or distant metastases (per a CT scan, for instance).

In premenopausal women, ascites, a nodular or fixed mass, and evidence of metastases also are reasons for referral to a gynecologic oncologist. CA-125, again, is much more likely to be elevated for reasons other than malignancy and therefore is not as strong a driver for referral as in postmenopausal women. Patients with markedly elevated levels, however, should probably be referred – particularly when other clinical factors also suggest the need for consultation. While there is no evidence-based threshold for CA-125 in premenopausal women, a CA-125 greater than 200 U/mL is a good cutoff for referral.

For any patient, family history of breast and/or ovarian cancer – especially in a first-degree relative – raises the risk of malignancy and should figure prominently into decision-making regarding referral. Criteria for referral are among the points discussed in the ACOG 2016 Practice Bulletin on Evaluation and Management of Adnexal Masses.¹

A note on BRCA mutations

As the American College of Obstetricians and Gynecologists says in its practice bulletin, the most important personal risk factor for ovarian cancer is a strong family history of breast or ovarian cancer. Women with such a family history can undergo genetic testing for BRCA mutations and have the opportunity to prevent ovarian cancers when mutations are detected. This simple blood test can save lives.

A modeling study we recently completed – not yet published – shows that it actually would be cost effective to do population screening with BRCA testing performed on every woman at age 30 years.

According to the National Cancer Institute website (last review: 2018), it is estimated that about 44% of women who inherit a BRCA1 mutation, and about 17% of those who inherit a BRAC2 mutation, will develop ovarian cancer by the age of 80 years. By identifying those mutations, women may undergo risk-reducing surgery at designated ages after childbearing is complete and bring their risk down to under 5%.

An international take on managing adnexal masses

• Pelvic ultrasound should include the transvaginal approach. Use Doppler imaging as indicated.
• Although simple ovarian cysts are not precursor lesions to a malignant ovarian cancer, perform a high-quality examination to make sure there are no solid/papillary structures before classifying a cyst as a simple cyst. The risk of progression to malignancy is extremely low, but some follow-up is prudent.
• The most accurate method of characterizing an ovarian mass currently is real-time pattern recognition sonography in the hands of an experienced imager.
• Pattern recognition sonography or a risk model such as the International Ovarian Tumor Analysis (IOTA) Simple Rules can be used to initially characterize an ovarian mass.
• When an ovarian lesion is classified as benign, the patient may be followed conservatively, or if indicated, surgery can be performed by a general gynecologist.
• Serial sonography can be beneficial, but there are limited prospective data to support an exact interval and duration.
• Fewer surgical interventions may result in an increase in sonographic surveillance.
• When an ovarian lesion is considered indeterminate on initial sonography, and after appropriate clinical evaluation, a “second-step” evaluation may include referral to an expert sonologist, serial sonography, application of established risk-prediction models, correlation with serum biomarkers, correlation with MRI, or referral to a gynecologic oncologist for further evaluation.

From the First International Consensus Report on Adnexal Masses: Management Recommendations

Source: Glanc P et al. J Ultrasound Med. 2017 May;36(5):849-63.

Dr. Brown reported that she had received an earlier grant from Aspira Labs, the company that developed the OVA1 assay. Dr. Miller reported that he has no relevant financial disclosures.

References

1. Obstet Gynecol. 2016 Nov. doi: 10.1097/AOG.0000000000001768.

2. Cancer. 2007 Jan 15. doi: 10.1002/cncr.22371.

3. Clin Obstet Gynecol. 2015 Mar. doi: 10.1097/GRF.0000000000000083.

4. Ultrasound Q. 2013 Mar. doi: 10.1097/RUQ.0b013e3182814d9b.

5. Ultrasound Obstet Gynecol. 2008 Jun. doi: 10.1002/uog.5365.

About 22% of children with COVID-19 infections were asymptomatic, and 66% of the symptomatic children had unrecognized symptoms at the time of diagnosis, based on data from a case series of 91 confirmed cases.

South_agency/Getty Images

Although recent reports suggest that COVID-19 infections in children are generally mild, data on the full spectrum of illness and duration of viral RNA in children are limited, wrote Mi Seon Han, MD, PhD, of Seoul (South Korea) Metropolitan Government–Seoul National University Boramae Medical Center, and colleagues.

To examine the full clinical course and duration of COVID-19 RNA detectability in children with confirmed infections, the researchers reviewed data from 91 individuals with confirmed infections. The children ranged in age from 27 days to 18 years, and 58% were male. The children were monitored at 20 hospitals and 2 isolation facilities for a mean 21.9 days. The findings were published in JAMA Pediatrics.

Overall, COVID-19 viral RNA was present in the study population for a mean 17.6 days, with testing done at a median interval of 3 days. A total of 20 children (22%) were asymptomatic throughout the study period. In these children, viral RNA was detected for a mean 14 days.

“The major hurdle implicated in this study in diagnosing and treating children with COVID-19 is that a considerable number of children are asymptomatic, and even if symptoms are present, they are unrecognized and overlooked before COVID-19 is diagnosed,” the researchers noted.

Of the 71 symptomatic children, 47 (66%) had unrecognized symptoms prior to diagnosis, 18 (25%) developed symptoms after diagnosis, and 6 (9%) were diagnosed at the time of symptom onset. The symptomatic children were symptomatic for a median of 11 days; 43 (61%) remained symptomatic at 7 days’ follow-up after the study period, 27 (38%) were symptomatic at 14 days, and 7 (10%) were symptomatic at 21 days.

A total of 41 children had upper respiratory infections (58%) and 22 children (24%) had lower respiratory tract infections. No difference in the duration of virus RNA was detected between children with upper respiratory tract infections and lower respiratory tract infections (average, 18.7 days vs. 19.9 days).

Among the symptomatic children, 46 (65%) had mild cases and 20 (28%) had moderate cases.

For treatment, 14 children (15%) received lopinavir-ritonavir and/or hydroxychloroquine. Two patients had severe illness and received oxygen via nasal prong, without the need for mechanical ventilation. All the children in the case series recovered from their infections with no fatalities.

The study’s main limitation was the inability to analyze the transmission potential of the children because of the quarantine and isolation policies in Korea, the researchers noted. In addition, the researchers did not perform follow-up testing at consistent intervals, so the duration of COVID-19 RNA detection may be inexact.

However, the results suggest “that suspecting and diagnosing COVID-19 in children based on their symptoms without epidemiologic information and virus testing is very challenging,” the researchers emphasized.

“Most of the children with COVID-19 have silent disease, but SARS-CoV-2 RNA can still be detected in the respiratory tract for a prolonged period,” they wrote. More research is needed to explore the potential for disease transmission by children in the community, and increased surveillance with laboratory screening can help identify children with unrecognized infections.

The study is the first known to focus on the frequency of asymptomatic infection in children and the duration of symptoms in both asymptomatic and symptomatic children, Roberta L. DeBiasi, MD, and Meghan Delaney, DO, both affiliated with Children’s National Hospital and Research Institute, Washington, and George Washington University, Washington, wrote in an accompanying editorial. The structure of the Korean public health system “allowed for the sequential observation, testing (median testing interval of every 3 days), and comparison of 91 asymptomatic, presymptomatic, and symptomatic children with mild to moderate upper and lower respiratory tract infection, identified primarily by contact tracing from laboratory-proven cases.”

Two take-home points from the study are that not all infected children are symptomatic, and the duration of symptoms in those who are varies widely, they noted. “Interestingly, this study aligns with adult data in which up to 40% of adults may remain asymptomatic in the face of infection.”

However, “The third and most important take-home point from this study relates to the duration of viral shedding in infected pediatric patients,” Dr. DeBiasi and Dr. Delaney said (JAMA Pediatr. 2020 Aug 28. doi: 10.1001/jamapediatrics.2020.3996).

“Fully half of symptomatic children with both upper and lower tract disease were still shedding virus at 21 days. These are striking data, particularly since 86 of 88 diagnosed children (98%) either had no symptoms or mild or moderate disease,” they explained. The results highlight the need for improvements in qualitative molecular testing and formal studies to identify differences in results from different testing scenarios, such as hospital entry, preprocedure screening, and symptomatic testing. In addition, “these findings are highly relevant to the development of public health strategies to mitigate and contain spread within communities, particularly as affected communities begin their recovery phases.”

The study is important because “schools are opening, and we don’t know what is going to happen,” Michael E. Pichichero, MD, of Rochester General Hospital, N.Y., said in an interview.

“Clinicians, parents, students, school administrators and politicians are worried,” he said. “This study adds to others recently published, bringing into focus the challenges to several suppositions that existed when the COVID-19 pandemic began and over the summer.”

“This study of 91 Korean children tells us that taking a child’s temperature as a screening tool to decide if they may enter school will not be a highly successful strategy,” he said. “Many children are without fever and asymptomatic when infected and contagious. The notion that children shed less virus or shed it for shorter lengths of time we keep learning from this type of research is not true. In another recent study the authors found that children shed as much of the SARS-CoV-2 virus as an adult in the ICU on a ventilator.”

Dr. Pichichero said he was not surprised by the study findings. “A similar paper was published last week in the Journal of Pediatrics from Massachusetts General Hospital, so the findings in the JAMA paper are similar to what has been reported in the United States.”

“Availability of testing will continue to be a challenge in some communities,” said Dr. Pichichero. “Here in the Rochester, New York, area we will use a screening questionnaire based on the CDC [Centers for Disease Control and Prevention] symptom criteria of SARS-CoV-2 infections to decide whom to test.”

As for additional research, “We have so much more to learn about SARS-CoV-2 in children,” he emphasized. “The focus has been on adults because the morbidity and mortality has been greatest in adults, especially the elderly and those with compromised health.”

“The National Institutes of Health has issued a call for more research in children to characterize the spectrum of SARS-CoV-2 illness, including the multisystem inflammatory syndrome in children [MIS-C] and try to identify biomarkers and/or biosignatures for a prognostic algorithm to predict the longitudinal risk of disease severity after a child is exposed to and may be infected with SARS-CoV-2,” said Dr. Pichichero. “NIH has asked researchers to answer the following questions.”

• Why do children have milder illness?
• Are there differences in childhood biology (e.g., gender, puberty, etc.) that contribute to illness severity?
• Are there genetic host differences associated with different disease severity phenotypes, including MIS-C?
• Are there innate mucosal, humoral, cellular and other adaptive immune profiles that are associated with reduced or increased risk of progressive disease, including previous coronavirus infections?
• Will SARS-CoV-2 reinfection cause worse disease as seen with antibody-dependent enhancement (ADE) in other viral infections (e.g., dengue)? Will future vaccines carry a risk of the ADE phenomenon?
• Does substance use (e.g., nicotine, marijuana) exacerbate or trigger MIS-C through immune activation?

“We have no knowledge yet about SARS-CoV-2 vaccination of children, especially young children,” Dr. Pichichero emphasized. “There are different types of vaccines – messenger RNA, adenovirus vector and purified spike proteins of the virus – among others, but questions remain: Will the vaccines work in children? What about side effects? Will the antibodies and cellular immunity protect partially or completely?”

The researchers and editorialists had no financial conflicts to disclose. Dr. Pichichero had no financial conflicts to disclose.

SOURCE: Han MS et al. JAMA Pediatr. 2020 Aug 28. doi:10.1001/jamapediatrics.2020.3988.

About 22% of children with COVID-19 infections were asymptomatic, and 66% of the symptomatic children had unrecognized symptoms at the time of diagnosis, based on data from a case series of 91 confirmed cases.

South_agency/Getty Images

Although recent reports suggest that COVID-19 infections in children are generally mild, data on the full spectrum of illness and duration of viral RNA in children are limited, wrote Mi Seon Han, MD, PhD, of Seoul (South Korea) Metropolitan Government–Seoul National University Boramae Medical Center, and colleagues.

To examine the full clinical course and duration of COVID-19 RNA detectability in children with confirmed infections, the researchers reviewed data from 91 individuals with confirmed infections. The children ranged in age from 27 days to 18 years, and 58% were male. The children were monitored at 20 hospitals and 2 isolation facilities for a mean 21.9 days. The findings were published in JAMA Pediatrics.

Overall, COVID-19 viral RNA was present in the study population for a mean 17.6 days, with testing done at a median interval of 3 days. A total of 20 children (22%) were asymptomatic throughout the study period. In these children, viral RNA was detected for a mean 14 days.

“The major hurdle implicated in this study in diagnosing and treating children with COVID-19 is that a considerable number of children are asymptomatic, and even if symptoms are present, they are unrecognized and overlooked before COVID-19 is diagnosed,” the researchers noted.

Of the 71 symptomatic children, 47 (66%) had unrecognized symptoms prior to diagnosis, 18 (25%) developed symptoms after diagnosis, and 6 (9%) were diagnosed at the time of symptom onset. The symptomatic children were symptomatic for a median of 11 days; 43 (61%) remained symptomatic at 7 days’ follow-up after the study period, 27 (38%) were symptomatic at 14 days, and 7 (10%) were symptomatic at 21 days.

A total of 41 children had upper respiratory infections (58%) and 22 children (24%) had lower respiratory tract infections. No difference in the duration of virus RNA was detected between children with upper respiratory tract infections and lower respiratory tract infections (average, 18.7 days vs. 19.9 days).

Among the symptomatic children, 46 (65%) had mild cases and 20 (28%) had moderate cases.

For treatment, 14 children (15%) received lopinavir-ritonavir and/or hydroxychloroquine. Two patients had severe illness and received oxygen via nasal prong, without the need for mechanical ventilation. All the children in the case series recovered from their infections with no fatalities.

The study’s main limitation was the inability to analyze the transmission potential of the children because of the quarantine and isolation policies in Korea, the researchers noted. In addition, the researchers did not perform follow-up testing at consistent intervals, so the duration of COVID-19 RNA detection may be inexact.

However, the results suggest “that suspecting and diagnosing COVID-19 in children based on their symptoms without epidemiologic information and virus testing is very challenging,” the researchers emphasized.

“Most of the children with COVID-19 have silent disease, but SARS-CoV-2 RNA can still be detected in the respiratory tract for a prolonged period,” they wrote. More research is needed to explore the potential for disease transmission by children in the community, and increased surveillance with laboratory screening can help identify children with unrecognized infections.

The study is the first known to focus on the frequency of asymptomatic infection in children and the duration of symptoms in both asymptomatic and symptomatic children, Roberta L. DeBiasi, MD, and Meghan Delaney, DO, both affiliated with Children’s National Hospital and Research Institute, Washington, and George Washington University, Washington, wrote in an accompanying editorial. The structure of the Korean public health system “allowed for the sequential observation, testing (median testing interval of every 3 days), and comparison of 91 asymptomatic, presymptomatic, and symptomatic children with mild to moderate upper and lower respiratory tract infection, identified primarily by contact tracing from laboratory-proven cases.”

Two take-home points from the study are that not all infected children are symptomatic, and the duration of symptoms in those who are varies widely, they noted. “Interestingly, this study aligns with adult data in which up to 40% of adults may remain asymptomatic in the face of infection.”

However, “The third and most important take-home point from this study relates to the duration of viral shedding in infected pediatric patients,” Dr. DeBiasi and Dr. Delaney said (JAMA Pediatr. 2020 Aug 28. doi: 10.1001/jamapediatrics.2020.3996).

“Fully half of symptomatic children with both upper and lower tract disease were still shedding virus at 21 days. These are striking data, particularly since 86 of 88 diagnosed children (98%) either had no symptoms or mild or moderate disease,” they explained. The results highlight the need for improvements in qualitative molecular testing and formal studies to identify differences in results from different testing scenarios, such as hospital entry, preprocedure screening, and symptomatic testing. In addition, “these findings are highly relevant to the development of public health strategies to mitigate and contain spread within communities, particularly as affected communities begin their recovery phases.”

The study is important because “schools are opening, and we don’t know what is going to happen,” Michael E. Pichichero, MD, of Rochester General Hospital, N.Y., said in an interview.

“Clinicians, parents, students, school administrators and politicians are worried,” he said. “This study adds to others recently published, bringing into focus the challenges to several suppositions that existed when the COVID-19 pandemic began and over the summer.”

“This study of 91 Korean children tells us that taking a child’s temperature as a screening tool to decide if they may enter school will not be a highly successful strategy,” he said. “Many children are without fever and asymptomatic when infected and contagious. The notion that children shed less virus or shed it for shorter lengths of time we keep learning from this type of research is not true. In another recent study the authors found that children shed as much of the SARS-CoV-2 virus as an adult in the ICU on a ventilator.”

Dr. Pichichero said he was not surprised by the study findings. “A similar paper was published last week in the Journal of Pediatrics from Massachusetts General Hospital, so the findings in the JAMA paper are similar to what has been reported in the United States.”

“Availability of testing will continue to be a challenge in some communities,” said Dr. Pichichero. “Here in the Rochester, New York, area we will use a screening questionnaire based on the CDC [Centers for Disease Control and Prevention] symptom criteria of SARS-CoV-2 infections to decide whom to test.”

As for additional research, “We have so much more to learn about SARS-CoV-2 in children,” he emphasized. “The focus has been on adults because the morbidity and mortality has been greatest in adults, especially the elderly and those with compromised health.”

“The National Institutes of Health has issued a call for more research in children to characterize the spectrum of SARS-CoV-2 illness, including the multisystem inflammatory syndrome in children [MIS-C] and try to identify biomarkers and/or biosignatures for a prognostic algorithm to predict the longitudinal risk of disease severity after a child is exposed to and may be infected with SARS-CoV-2,” said Dr. Pichichero. “NIH has asked researchers to answer the following questions.”

• Why do children have milder illness?
• Are there differences in childhood biology (e.g., gender, puberty, etc.) that contribute to illness severity?
• Are there genetic host differences associated with different disease severity phenotypes, including MIS-C?
• Are there innate mucosal, humoral, cellular and other adaptive immune profiles that are associated with reduced or increased risk of progressive disease, including previous coronavirus infections?
• Will SARS-CoV-2 reinfection cause worse disease as seen with antibody-dependent enhancement (ADE) in other viral infections (e.g., dengue)? Will future vaccines carry a risk of the ADE phenomenon?
• Does substance use (e.g., nicotine, marijuana) exacerbate or trigger MIS-C through immune activation?

“We have no knowledge yet about SARS-CoV-2 vaccination of children, especially young children,” Dr. Pichichero emphasized. “There are different types of vaccines – messenger RNA, adenovirus vector and purified spike proteins of the virus – among others, but questions remain: Will the vaccines work in children? What about side effects? Will the antibodies and cellular immunity protect partially or completely?”

The researchers and editorialists had no financial conflicts to disclose. Dr. Pichichero had no financial conflicts to disclose.

SOURCE: Han MS et al. JAMA Pediatr. 2020 Aug 28. doi:10.1001/jamapediatrics.2020.3988.

About 22% of children with COVID-19 infections were asymptomatic, and 66% of the symptomatic children had unrecognized symptoms at the time of diagnosis, based on data from a case series of 91 confirmed cases.

South_agency/Getty Images

Although recent reports suggest that COVID-19 infections in children are generally mild, data on the full spectrum of illness and duration of viral RNA in children are limited, wrote Mi Seon Han, MD, PhD, of Seoul (South Korea) Metropolitan Government–Seoul National University Boramae Medical Center, and colleagues.

To examine the full clinical course and duration of COVID-19 RNA detectability in children with confirmed infections, the researchers reviewed data from 91 individuals with confirmed infections. The children ranged in age from 27 days to 18 years, and 58% were male. The children were monitored at 20 hospitals and 2 isolation facilities for a mean 21.9 days. The findings were published in JAMA Pediatrics.

Overall, COVID-19 viral RNA was present in the study population for a mean 17.6 days, with testing done at a median interval of 3 days. A total of 20 children (22%) were asymptomatic throughout the study period. In these children, viral RNA was detected for a mean 14 days.

“The major hurdle implicated in this study in diagnosing and treating children with COVID-19 is that a considerable number of children are asymptomatic, and even if symptoms are present, they are unrecognized and overlooked before COVID-19 is diagnosed,” the researchers noted.

Of the 71 symptomatic children, 47 (66%) had unrecognized symptoms prior to diagnosis, 18 (25%) developed symptoms after diagnosis, and 6 (9%) were diagnosed at the time of symptom onset. The symptomatic children were symptomatic for a median of 11 days; 43 (61%) remained symptomatic at 7 days’ follow-up after the study period, 27 (38%) were symptomatic at 14 days, and 7 (10%) were symptomatic at 21 days.

A total of 41 children had upper respiratory infections (58%) and 22 children (24%) had lower respiratory tract infections. No difference in the duration of virus RNA was detected between children with upper respiratory tract infections and lower respiratory tract infections (average, 18.7 days vs. 19.9 days).

Among the symptomatic children, 46 (65%) had mild cases and 20 (28%) had moderate cases.

For treatment, 14 children (15%) received lopinavir-ritonavir and/or hydroxychloroquine. Two patients had severe illness and received oxygen via nasal prong, without the need for mechanical ventilation. All the children in the case series recovered from their infections with no fatalities.

The study’s main limitation was the inability to analyze the transmission potential of the children because of the quarantine and isolation policies in Korea, the researchers noted. In addition, the researchers did not perform follow-up testing at consistent intervals, so the duration of COVID-19 RNA detection may be inexact.

However, the results suggest “that suspecting and diagnosing COVID-19 in children based on their symptoms without epidemiologic information and virus testing is very challenging,” the researchers emphasized.

“Most of the children with COVID-19 have silent disease, but SARS-CoV-2 RNA can still be detected in the respiratory tract for a prolonged period,” they wrote. More research is needed to explore the potential for disease transmission by children in the community, and increased surveillance with laboratory screening can help identify children with unrecognized infections.

The study is the first known to focus on the frequency of asymptomatic infection in children and the duration of symptoms in both asymptomatic and symptomatic children, Roberta L. DeBiasi, MD, and Meghan Delaney, DO, both affiliated with Children’s National Hospital and Research Institute, Washington, and George Washington University, Washington, wrote in an accompanying editorial. The structure of the Korean public health system “allowed for the sequential observation, testing (median testing interval of every 3 days), and comparison of 91 asymptomatic, presymptomatic, and symptomatic children with mild to moderate upper and lower respiratory tract infection, identified primarily by contact tracing from laboratory-proven cases.”

Two take-home points from the study are that not all infected children are symptomatic, and the duration of symptoms in those who are varies widely, they noted. “Interestingly, this study aligns with adult data in which up to 40% of adults may remain asymptomatic in the face of infection.”

However, “The third and most important take-home point from this study relates to the duration of viral shedding in infected pediatric patients,” Dr. DeBiasi and Dr. Delaney said (JAMA Pediatr. 2020 Aug 28. doi: 10.1001/jamapediatrics.2020.3996).

“Fully half of symptomatic children with both upper and lower tract disease were still shedding virus at 21 days. These are striking data, particularly since 86 of 88 diagnosed children (98%) either had no symptoms or mild or moderate disease,” they explained. The results highlight the need for improvements in qualitative molecular testing and formal studies to identify differences in results from different testing scenarios, such as hospital entry, preprocedure screening, and symptomatic testing. In addition, “these findings are highly relevant to the development of public health strategies to mitigate and contain spread within communities, particularly as affected communities begin their recovery phases.”

The study is important because “schools are opening, and we don’t know what is going to happen,” Michael E. Pichichero, MD, of Rochester General Hospital, N.Y., said in an interview.

“Clinicians, parents, students, school administrators and politicians are worried,” he said. “This study adds to others recently published, bringing into focus the challenges to several suppositions that existed when the COVID-19 pandemic began and over the summer.”

“This study of 91 Korean children tells us that taking a child’s temperature as a screening tool to decide if they may enter school will not be a highly successful strategy,” he said. “Many children are without fever and asymptomatic when infected and contagious. The notion that children shed less virus or shed it for shorter lengths of time we keep learning from this type of research is not true. In another recent study the authors found that children shed as much of the SARS-CoV-2 virus as an adult in the ICU on a ventilator.”

Dr. Pichichero said he was not surprised by the study findings. “A similar paper was published last week in the Journal of Pediatrics from Massachusetts General Hospital, so the findings in the JAMA paper are similar to what has been reported in the United States.”

“Availability of testing will continue to be a challenge in some communities,” said Dr. Pichichero. “Here in the Rochester, New York, area we will use a screening questionnaire based on the CDC [Centers for Disease Control and Prevention] symptom criteria of SARS-CoV-2 infections to decide whom to test.”

As for additional research, “We have so much more to learn about SARS-CoV-2 in children,” he emphasized. “The focus has been on adults because the morbidity and mortality has been greatest in adults, especially the elderly and those with compromised health.”

“The National Institutes of Health has issued a call for more research in children to characterize the spectrum of SARS-CoV-2 illness, including the multisystem inflammatory syndrome in children [MIS-C] and try to identify biomarkers and/or biosignatures for a prognostic algorithm to predict the longitudinal risk of disease severity after a child is exposed to and may be infected with SARS-CoV-2,” said Dr. Pichichero. “NIH has asked researchers to answer the following questions.”

• Why do children have milder illness?
• Are there differences in childhood biology (e.g., gender, puberty, etc.) that contribute to illness severity?
• Are there genetic host differences associated with different disease severity phenotypes, including MIS-C?
• Are there innate mucosal, humoral, cellular and other adaptive immune profiles that are associated with reduced or increased risk of progressive disease, including previous coronavirus infections?
• Will SARS-CoV-2 reinfection cause worse disease as seen with antibody-dependent enhancement (ADE) in other viral infections (e.g., dengue)? Will future vaccines carry a risk of the ADE phenomenon?
• Does substance use (e.g., nicotine, marijuana) exacerbate or trigger MIS-C through immune activation?

“We have no knowledge yet about SARS-CoV-2 vaccination of children, especially young children,” Dr. Pichichero emphasized. “There are different types of vaccines – messenger RNA, adenovirus vector and purified spike proteins of the virus – among others, but questions remain: Will the vaccines work in children? What about side effects? Will the antibodies and cellular immunity protect partially or completely?”

The researchers and editorialists had no financial conflicts to disclose. Dr. Pichichero had no financial conflicts to disclose.

SOURCE: Han MS et al. JAMA Pediatr. 2020 Aug 28. doi:10.1001/jamapediatrics.2020.3988.

Voiding trials after female pelvic floor surgery may detect similar rates of voiding dysfunction regardless of whether voiding occurs spontaneously or after the bladder is retrograde-filled with saline, according to a randomized study.

Nevertheless, patients may prefer the more common retrograde-fill approach.

In the study of 109 patients, those who underwent retrograde fill reported significantly greater satisfaction with their method of voiding evaluation, compared with patients whose voiding trials occurred spontaneously. The increased satisfaction could relate to the fact that retrograde-fill trials take less time, study investigator Patrick Popiel, MD, of Yale University, New Haven, Conn., suggested at the virtual annual scientific meeting of the Society of Gynecologic Surgeons. The exact reasons are unclear, however.

Voiding trials help identify patients who cannot sufficiently empty their bladder after surgery. Prior research has indicated that the incidence of voiding dysfunction after pelvic floor surgery is about 25%-35%. “Patients with voiding dysfunction are generally managed with an indwelling Foley catheter or clean intermittent self-catheterization,” Dr. Popiel said. “Catheterization increases the risk of urinary tract infection, increases anxiety, and decreases patient satisfaction. A large proportion of patients who are discharged home with a Foley catheter state that the catheter was the worst aspect of their experience.”

Dr. Popiel and colleagues conducted a randomized, prospective study to examine the rate of failed voiding trials that necessitate discharge home with an indwelling Foley catheter using spontaneous and retrograde-fill approaches. The study included women who required a voiding trial after surgery for pelvic organ prolapse or urinary incontinence. Patients who required prolonged catheterization after surgery, such as those with a urinary tract infection, bowel injury, or large amount of blood loss, were excluded.

Researchers analyzed data from 55 patients who were randomly assigned to the retrograde-fill group and 54 patients who were randomly assigned to the spontaneous trial group.

In the spontaneous group, patients were required to void at least 150 mL at one time within 6 hours of catheter removal to successfully complete the voiding trial.

In the retrograde-fill group, the bladder was filled in the postanesthesia care unit with 300 mL of saline or until the maximum volume tolerated by the patient (not exceeding 300 mL ) was reached. Patients in this group had to void at least 150 mL or 50% of the instilled volume at one time within 60 minutes of catheter removal to pass the trial.

The researchers documented postvoid residual (PVR) but did not use this measure to determine voiding function.

The baseline demographics of the two groups were similar, although prior hysterectomy was more common in the retrograde-fill group than in the spontaneous group (32.7% vs. 14.8%). The average age was 58.5 years in the retrograde-fill group and 61 years in the spontaneous group.

“There was no significant difference in our primary outcome,” Dr. Popiel said. “There was a 12.7% rate of failed voiding trial in the retrograde group versus 7.7% in the spontaneous group.”

No patients had urinary retention after initially passing their voiding trial. Force of stream did not differ between groups, and about 15% in each group had a postoperative urinary tract infection.

The study demonstrates that voiding assessment based on a spontaneous minimum void of 150 mL is safe and has similar pass rates, compared with the more commonly performed retrograde void trial, Dr. Popiel said. “If the voided amount is at least 150 mL, PVR is not critical to obtain. The study adds to the body of literature that supports less stringent criteria for evaluating voiding function and can limit postoperative urinary recatheterization.”

The investigators allowed patients with PVRs as high as 575 mL to return home without an alternative way to empty the bladder, C. Sage Claydon, MD, a urogynecologist who was not involved in the study, noted during a discussion after the presentation. In all, 6 patients who met the passing criteria for the spontaneous voiding trial had a PVR greater than 200 mL, with volumes ranging from 205-575 mL.

The patients received standardized counseling about postoperative voiding problems, said Dr. Popiel. “This is similar to the work done by Ingber et al. from 2011, where patients who reached a certain force of stream, greater than 5 out of 10, were discharged home regardless of PVR.”

Dr. Popiel had no relevant disclosures. Two coinvestigators disclosed ties to BlossomMed, Renovia, and ArmadaHealth.

[email protected]

SOURCE: Popiel P et al. SGS 2020, Abstract 14.

Voiding trials after female pelvic floor surgery may detect similar rates of voiding dysfunction regardless of whether voiding occurs spontaneously or after the bladder is retrograde-filled with saline, according to a randomized study.

Nevertheless, patients may prefer the more common retrograde-fill approach.

In the study of 109 patients, those who underwent retrograde fill reported significantly greater satisfaction with their method of voiding evaluation, compared with patients whose voiding trials occurred spontaneously. The increased satisfaction could relate to the fact that retrograde-fill trials take less time, study investigator Patrick Popiel, MD, of Yale University, New Haven, Conn., suggested at the virtual annual scientific meeting of the Society of Gynecologic Surgeons. The exact reasons are unclear, however.

Voiding trials help identify patients who cannot sufficiently empty their bladder after surgery. Prior research has indicated that the incidence of voiding dysfunction after pelvic floor surgery is about 25%-35%. “Patients with voiding dysfunction are generally managed with an indwelling Foley catheter or clean intermittent self-catheterization,” Dr. Popiel said. “Catheterization increases the risk of urinary tract infection, increases anxiety, and decreases patient satisfaction. A large proportion of patients who are discharged home with a Foley catheter state that the catheter was the worst aspect of their experience.”

Dr. Popiel and colleagues conducted a randomized, prospective study to examine the rate of failed voiding trials that necessitate discharge home with an indwelling Foley catheter using spontaneous and retrograde-fill approaches. The study included women who required a voiding trial after surgery for pelvic organ prolapse or urinary incontinence. Patients who required prolonged catheterization after surgery, such as those with a urinary tract infection, bowel injury, or large amount of blood loss, were excluded.

Researchers analyzed data from 55 patients who were randomly assigned to the retrograde-fill group and 54 patients who were randomly assigned to the spontaneous trial group.

In the spontaneous group, patients were required to void at least 150 mL at one time within 6 hours of catheter removal to successfully complete the voiding trial.

In the retrograde-fill group, the bladder was filled in the postanesthesia care unit with 300 mL of saline or until the maximum volume tolerated by the patient (not exceeding 300 mL ) was reached. Patients in this group had to void at least 150 mL or 50% of the instilled volume at one time within 60 minutes of catheter removal to pass the trial.

The researchers documented postvoid residual (PVR) but did not use this measure to determine voiding function.

The baseline demographics of the two groups were similar, although prior hysterectomy was more common in the retrograde-fill group than in the spontaneous group (32.7% vs. 14.8%). The average age was 58.5 years in the retrograde-fill group and 61 years in the spontaneous group.

“There was no significant difference in our primary outcome,” Dr. Popiel said. “There was a 12.7% rate of failed voiding trial in the retrograde group versus 7.7% in the spontaneous group.”

No patients had urinary retention after initially passing their voiding trial. Force of stream did not differ between groups, and about 15% in each group had a postoperative urinary tract infection.

The study demonstrates that voiding assessment based on a spontaneous minimum void of 150 mL is safe and has similar pass rates, compared with the more commonly performed retrograde void trial, Dr. Popiel said. “If the voided amount is at least 150 mL, PVR is not critical to obtain. The study adds to the body of literature that supports less stringent criteria for evaluating voiding function and can limit postoperative urinary recatheterization.”

The investigators allowed patients with PVRs as high as 575 mL to return home without an alternative way to empty the bladder, C. Sage Claydon, MD, a urogynecologist who was not involved in the study, noted during a discussion after the presentation. In all, 6 patients who met the passing criteria for the spontaneous voiding trial had a PVR greater than 200 mL, with volumes ranging from 205-575 mL.

The patients received standardized counseling about postoperative voiding problems, said Dr. Popiel. “This is similar to the work done by Ingber et al. from 2011, where patients who reached a certain force of stream, greater than 5 out of 10, were discharged home regardless of PVR.”

Dr. Popiel had no relevant disclosures. Two coinvestigators disclosed ties to BlossomMed, Renovia, and ArmadaHealth.

[email protected]

SOURCE: Popiel P et al. SGS 2020, Abstract 14.

Voiding trials after female pelvic floor surgery may detect similar rates of voiding dysfunction regardless of whether voiding occurs spontaneously or after the bladder is retrograde-filled with saline, according to a randomized study.

Nevertheless, patients may prefer the more common retrograde-fill approach.

In the study of 109 patients, those who underwent retrograde fill reported significantly greater satisfaction with their method of voiding evaluation, compared with patients whose voiding trials occurred spontaneously. The increased satisfaction could relate to the fact that retrograde-fill trials take less time, study investigator Patrick Popiel, MD, of Yale University, New Haven, Conn., suggested at the virtual annual scientific meeting of the Society of Gynecologic Surgeons. The exact reasons are unclear, however.

Voiding trials help identify patients who cannot sufficiently empty their bladder after surgery. Prior research has indicated that the incidence of voiding dysfunction after pelvic floor surgery is about 25%-35%. “Patients with voiding dysfunction are generally managed with an indwelling Foley catheter or clean intermittent self-catheterization,” Dr. Popiel said. “Catheterization increases the risk of urinary tract infection, increases anxiety, and decreases patient satisfaction. A large proportion of patients who are discharged home with a Foley catheter state that the catheter was the worst aspect of their experience.”

Dr. Popiel and colleagues conducted a randomized, prospective study to examine the rate of failed voiding trials that necessitate discharge home with an indwelling Foley catheter using spontaneous and retrograde-fill approaches. The study included women who required a voiding trial after surgery for pelvic organ prolapse or urinary incontinence. Patients who required prolonged catheterization after surgery, such as those with a urinary tract infection, bowel injury, or large amount of blood loss, were excluded.

Researchers analyzed data from 55 patients who were randomly assigned to the retrograde-fill group and 54 patients who were randomly assigned to the spontaneous trial group.

In the spontaneous group, patients were required to void at least 150 mL at one time within 6 hours of catheter removal to successfully complete the voiding trial.

In the retrograde-fill group, the bladder was filled in the postanesthesia care unit with 300 mL of saline or until the maximum volume tolerated by the patient (not exceeding 300 mL ) was reached. Patients in this group had to void at least 150 mL or 50% of the instilled volume at one time within 60 minutes of catheter removal to pass the trial.

The researchers documented postvoid residual (PVR) but did not use this measure to determine voiding function.

The baseline demographics of the two groups were similar, although prior hysterectomy was more common in the retrograde-fill group than in the spontaneous group (32.7% vs. 14.8%). The average age was 58.5 years in the retrograde-fill group and 61 years in the spontaneous group.

“There was no significant difference in our primary outcome,” Dr. Popiel said. “There was a 12.7% rate of failed voiding trial in the retrograde group versus 7.7% in the spontaneous group.”

No patients had urinary retention after initially passing their voiding trial. Force of stream did not differ between groups, and about 15% in each group had a postoperative urinary tract infection.

The study demonstrates that voiding assessment based on a spontaneous minimum void of 150 mL is safe and has similar pass rates, compared with the more commonly performed retrograde void trial, Dr. Popiel said. “If the voided amount is at least 150 mL, PVR is not critical to obtain. The study adds to the body of literature that supports less stringent criteria for evaluating voiding function and can limit postoperative urinary recatheterization.”

The investigators allowed patients with PVRs as high as 575 mL to return home without an alternative way to empty the bladder, C. Sage Claydon, MD, a urogynecologist who was not involved in the study, noted during a discussion after the presentation. In all, 6 patients who met the passing criteria for the spontaneous voiding trial had a PVR greater than 200 mL, with volumes ranging from 205-575 mL.

The patients received standardized counseling about postoperative voiding problems, said Dr. Popiel. “This is similar to the work done by Ingber et al. from 2011, where patients who reached a certain force of stream, greater than 5 out of 10, were discharged home regardless of PVR.”

Dr. Popiel had no relevant disclosures. Two coinvestigators disclosed ties to BlossomMed, Renovia, and ArmadaHealth.

[email protected]

SOURCE: Popiel P et al. SGS 2020, Abstract 14.

Uterine papillary serous carcinoma (UPSC) is an infrequent but deadly form of endometrial cancer comprising 10% of cases but contributing 40% of deaths from the disease. Recurrence rates are high for this disease. Five-year survival is 55% for all patients and only 70% for stage I disease.¹ Patterns of recurrence tend to be distant (extrapelvic and extraabdominal) as frequently as they are localized to the pelvis, and metastases and recurrences are unrelated to the extent of uterine disease (such as myometrial invasion). It is for these reasons that the recommended course of adjuvant therapy for this disease is systemic therapy (typically six doses of carboplatin and paclitaxel chemotherapy) with consideration for radiation to the vagina or pelvis to consolidate pelvic and vaginal control.² This differs from early-stage high/intermediate–risk endometrioid adenocarcinomas, for which adjuvant chemotherapy has not been found to be helpful.

Dr Joshua Kish

Because of the lower incidence of UPSC, it frequently has been studied alongside endometrioid cell types in clinical trials which explore novel adjuvant therapies. However, UPSC is biologically distinct from endometrioid endometrial cancers, which likely results in inferior clinical responses to conventional interventions. Fortunately we are beginning to better understand UPSC at a molecular level, and advancements are being made in the targeted therapies for these patients that are unique, compared with those applied to other cancer subtypes.

As discussed above, UPSC is a particularly aggressive form of uterine cancer. Histologically it is characterized by a precursor lesion of endometrial glandular dysplasia progressing to endometrial intraepithelial neoplasia (EIC). Histologically it presents with a highly atypical slit-like glandular configuration, which appears similar to serous carcinomas of the fallopian tube and ovary. Molecularly these tumors commonly manifest mutations in tumor protein p53 (TP53) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), which are both genes associated with oncogenic potential.¹ While most UPSC tumors have loss of expression in hormone receptors such as estrogen and progesterone, 25%-30% of cases overexpress the tyrosine kinase receptor human epidermal growth factor receptor 2 (HER2).^3-5 This has proven to provide an exciting target for therapeutic interventions.
 

A target for therapeutic intervention

HER2 is a transmembrane receptor which, when activated, signals complex downstream pathways responsible for cellular proliferation, dedifferentiation, and metastasis. In a recent multi-institutional analysis of early-stage UPSC, HER2 overexpression was identified among 25% of cases.⁴ Approximately 30% of cases of advanced disease manifest overexpression of this biomarker.⁵ HER2 overexpression (HER2-positive status) is significantly associated with higher rates of recurrence and mortality, even among patients treated with conventional therapies.³ Thus HER2-positive status is obviously an indicator of particularly aggressive disease.

Fortunately this particular biomarker is one for which we have established and developing therapeutics. The humanized monoclonal antibody, trastuzumab, has been highly effective in improving survival for HER2-positive breast cancer.⁶ More recently, it was studied in a phase 2 trial with carboplatin and paclitaxel chemotherapy for advanced or recurrent HER2-positive UPSC.⁵ This trial showed that the addition of this targeted therapy to conventional chemotherapy improved recurrence-free survival from 8 months to 12 months, and improved overall survival from 24.4 months to 29.6 months.⁵
 

^{One discovery leads to another treatment}

This discovery led to the approval of trastuzumab to be used in addition to chemotherapy for advanced or recurrent disease.² The most significant effects appear to be among those who have not received prior therapies, with a doubling of progression-free survival among these patients, and a more modest response among patients treated for recurrent, mostly pretreated disease.

Work currently is underway to explore an array of antibody or small-molecule blockades of HER2 in addition to vaccines against the protein or treatment with conjugate compounds in which an antibody to HER2 is paired with a cytotoxic drug able to be internalized into HER2-expressing cells.⁷ This represents a form of personalized medicine referred to as biomarker-driven targeted therapy, in which therapies are prescribed based on the expression of specific molecular markers (such as HER2 expression) typically in combination with other clinical markers such as surgical staging results, race, age, etc. These approaches can be very effective strategies in rare tumor subtypes with distinct molecular and clinical behaviors.

As previously mentioned, the targeting of HER2 overexpression with trastuzumab has been shown to be highly effective in the treatment of HER2-positive breast cancers where even patients with early-stage disease receive a multimodal therapy approach including antibody, chemotherapy, surgical, and often radiation treatments.⁶ We are moving towards a similar multimodal comprehensive treatment strategy for UPSC. If it is as successful as it is in breast cancer, it will be long overdue, and desperately necessary given the poor prognosis of this disease for all stages because of the inadequacies of current treatments strategies.

Routine testing of UPSC for HER2 expression is now a part of routine molecular substaging of uterine cancers in the same way we have embraced testing for microsatellite instability and hormone-receptor status. While a diagnosis of HER2 overexpression in UPSC portends a poor prognosis, patients can be reassured that treatment strategies exist that can target this malignant mechanism in advanced disease and more are under further development for early-stage disease.
 

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no relevant financial disclosures. Email her at [email protected].

References

1. Curr Opin Obstet Gynecol. 2010 Feb. doi: 10.1097/GCO.0b013e328334d8a3.

2. National Comprehensive Cancer Network. Uterine Neoplasms (version 2.2020).

3. Cancer 2005 Oct 1. doi: 10.1002/cncr.21308.

4. Gynecol Oncol 2020 doi: 10.1016/j.ygyno.2020.07.016.

5. J Clin Oncol 2018. doi: 10.1200/JCO.2017.76.5966.

6. N Engl J Med 2011. doi: 10.1056/NEJMoa0910383.

7. Discov Med. 2016 Apr;21(116):293-303.

Uterine papillary serous carcinoma (UPSC) is an infrequent but deadly form of endometrial cancer comprising 10% of cases but contributing 40% of deaths from the disease. Recurrence rates are high for this disease. Five-year survival is 55% for all patients and only 70% for stage I disease.¹ Patterns of recurrence tend to be distant (extrapelvic and extraabdominal) as frequently as they are localized to the pelvis, and metastases and recurrences are unrelated to the extent of uterine disease (such as myometrial invasion). It is for these reasons that the recommended course of adjuvant therapy for this disease is systemic therapy (typically six doses of carboplatin and paclitaxel chemotherapy) with consideration for radiation to the vagina or pelvis to consolidate pelvic and vaginal control.² This differs from early-stage high/intermediate–risk endometrioid adenocarcinomas, for which adjuvant chemotherapy has not been found to be helpful.

Dr Joshua Kish

Because of the lower incidence of UPSC, it frequently has been studied alongside endometrioid cell types in clinical trials which explore novel adjuvant therapies. However, UPSC is biologically distinct from endometrioid endometrial cancers, which likely results in inferior clinical responses to conventional interventions. Fortunately we are beginning to better understand UPSC at a molecular level, and advancements are being made in the targeted therapies for these patients that are unique, compared with those applied to other cancer subtypes.

As discussed above, UPSC is a particularly aggressive form of uterine cancer. Histologically it is characterized by a precursor lesion of endometrial glandular dysplasia progressing to endometrial intraepithelial neoplasia (EIC). Histologically it presents with a highly atypical slit-like glandular configuration, which appears similar to serous carcinomas of the fallopian tube and ovary. Molecularly these tumors commonly manifest mutations in tumor protein p53 (TP53) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), which are both genes associated with oncogenic potential.¹ While most UPSC tumors have loss of expression in hormone receptors such as estrogen and progesterone, 25%-30% of cases overexpress the tyrosine kinase receptor human epidermal growth factor receptor 2 (HER2).^3-5 This has proven to provide an exciting target for therapeutic interventions.
 

A target for therapeutic intervention

HER2 is a transmembrane receptor which, when activated, signals complex downstream pathways responsible for cellular proliferation, dedifferentiation, and metastasis. In a recent multi-institutional analysis of early-stage UPSC, HER2 overexpression was identified among 25% of cases.⁴ Approximately 30% of cases of advanced disease manifest overexpression of this biomarker.⁵ HER2 overexpression (HER2-positive status) is significantly associated with higher rates of recurrence and mortality, even among patients treated with conventional therapies.³ Thus HER2-positive status is obviously an indicator of particularly aggressive disease.

Fortunately this particular biomarker is one for which we have established and developing therapeutics. The humanized monoclonal antibody, trastuzumab, has been highly effective in improving survival for HER2-positive breast cancer.⁶ More recently, it was studied in a phase 2 trial with carboplatin and paclitaxel chemotherapy for advanced or recurrent HER2-positive UPSC.⁵ This trial showed that the addition of this targeted therapy to conventional chemotherapy improved recurrence-free survival from 8 months to 12 months, and improved overall survival from 24.4 months to 29.6 months.⁵
 

^{One discovery leads to another treatment}

This discovery led to the approval of trastuzumab to be used in addition to chemotherapy for advanced or recurrent disease.² The most significant effects appear to be among those who have not received prior therapies, with a doubling of progression-free survival among these patients, and a more modest response among patients treated for recurrent, mostly pretreated disease.

Work currently is underway to explore an array of antibody or small-molecule blockades of HER2 in addition to vaccines against the protein or treatment with conjugate compounds in which an antibody to HER2 is paired with a cytotoxic drug able to be internalized into HER2-expressing cells.⁷ This represents a form of personalized medicine referred to as biomarker-driven targeted therapy, in which therapies are prescribed based on the expression of specific molecular markers (such as HER2 expression) typically in combination with other clinical markers such as surgical staging results, race, age, etc. These approaches can be very effective strategies in rare tumor subtypes with distinct molecular and clinical behaviors.

As previously mentioned, the targeting of HER2 overexpression with trastuzumab has been shown to be highly effective in the treatment of HER2-positive breast cancers where even patients with early-stage disease receive a multimodal therapy approach including antibody, chemotherapy, surgical, and often radiation treatments.⁶ We are moving towards a similar multimodal comprehensive treatment strategy for UPSC. If it is as successful as it is in breast cancer, it will be long overdue, and desperately necessary given the poor prognosis of this disease for all stages because of the inadequacies of current treatments strategies.

Routine testing of UPSC for HER2 expression is now a part of routine molecular substaging of uterine cancers in the same way we have embraced testing for microsatellite instability and hormone-receptor status. While a diagnosis of HER2 overexpression in UPSC portends a poor prognosis, patients can be reassured that treatment strategies exist that can target this malignant mechanism in advanced disease and more are under further development for early-stage disease.
 

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no relevant financial disclosures. Email her at [email protected].

References

1. Curr Opin Obstet Gynecol. 2010 Feb. doi: 10.1097/GCO.0b013e328334d8a3.

2. National Comprehensive Cancer Network. Uterine Neoplasms (version 2.2020).

3. Cancer 2005 Oct 1. doi: 10.1002/cncr.21308.

4. Gynecol Oncol 2020 doi: 10.1016/j.ygyno.2020.07.016.

5. J Clin Oncol 2018. doi: 10.1200/JCO.2017.76.5966.

6. N Engl J Med 2011. doi: 10.1056/NEJMoa0910383.

7. Discov Med. 2016 Apr;21(116):293-303.

Uterine papillary serous carcinoma (UPSC) is an infrequent but deadly form of endometrial cancer comprising 10% of cases but contributing 40% of deaths from the disease. Recurrence rates are high for this disease. Five-year survival is 55% for all patients and only 70% for stage I disease.¹ Patterns of recurrence tend to be distant (extrapelvic and extraabdominal) as frequently as they are localized to the pelvis, and metastases and recurrences are unrelated to the extent of uterine disease (such as myometrial invasion). It is for these reasons that the recommended course of adjuvant therapy for this disease is systemic therapy (typically six doses of carboplatin and paclitaxel chemotherapy) with consideration for radiation to the vagina or pelvis to consolidate pelvic and vaginal control.² This differs from early-stage high/intermediate–risk endometrioid adenocarcinomas, for which adjuvant chemotherapy has not been found to be helpful.

Dr Joshua Kish

Because of the lower incidence of UPSC, it frequently has been studied alongside endometrioid cell types in clinical trials which explore novel adjuvant therapies. However, UPSC is biologically distinct from endometrioid endometrial cancers, which likely results in inferior clinical responses to conventional interventions. Fortunately we are beginning to better understand UPSC at a molecular level, and advancements are being made in the targeted therapies for these patients that are unique, compared with those applied to other cancer subtypes.

As discussed above, UPSC is a particularly aggressive form of uterine cancer. Histologically it is characterized by a precursor lesion of endometrial glandular dysplasia progressing to endometrial intraepithelial neoplasia (EIC). Histologically it presents with a highly atypical slit-like glandular configuration, which appears similar to serous carcinomas of the fallopian tube and ovary. Molecularly these tumors commonly manifest mutations in tumor protein p53 (TP53) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), which are both genes associated with oncogenic potential.¹ While most UPSC tumors have loss of expression in hormone receptors such as estrogen and progesterone, 25%-30% of cases overexpress the tyrosine kinase receptor human epidermal growth factor receptor 2 (HER2).^3-5 This has proven to provide an exciting target for therapeutic interventions.
 

A target for therapeutic intervention

HER2 is a transmembrane receptor which, when activated, signals complex downstream pathways responsible for cellular proliferation, dedifferentiation, and metastasis. In a recent multi-institutional analysis of early-stage UPSC, HER2 overexpression was identified among 25% of cases.⁴ Approximately 30% of cases of advanced disease manifest overexpression of this biomarker.⁵ HER2 overexpression (HER2-positive status) is significantly associated with higher rates of recurrence and mortality, even among patients treated with conventional therapies.³ Thus HER2-positive status is obviously an indicator of particularly aggressive disease.

Fortunately this particular biomarker is one for which we have established and developing therapeutics. The humanized monoclonal antibody, trastuzumab, has been highly effective in improving survival for HER2-positive breast cancer.⁶ More recently, it was studied in a phase 2 trial with carboplatin and paclitaxel chemotherapy for advanced or recurrent HER2-positive UPSC.⁵ This trial showed that the addition of this targeted therapy to conventional chemotherapy improved recurrence-free survival from 8 months to 12 months, and improved overall survival from 24.4 months to 29.6 months.⁵
 

^{One discovery leads to another treatment}

This discovery led to the approval of trastuzumab to be used in addition to chemotherapy for advanced or recurrent disease.² The most significant effects appear to be among those who have not received prior therapies, with a doubling of progression-free survival among these patients, and a more modest response among patients treated for recurrent, mostly pretreated disease.

Work currently is underway to explore an array of antibody or small-molecule blockades of HER2 in addition to vaccines against the protein or treatment with conjugate compounds in which an antibody to HER2 is paired with a cytotoxic drug able to be internalized into HER2-expressing cells.⁷ This represents a form of personalized medicine referred to as biomarker-driven targeted therapy, in which therapies are prescribed based on the expression of specific molecular markers (such as HER2 expression) typically in combination with other clinical markers such as surgical staging results, race, age, etc. These approaches can be very effective strategies in rare tumor subtypes with distinct molecular and clinical behaviors.

As previously mentioned, the targeting of HER2 overexpression with trastuzumab has been shown to be highly effective in the treatment of HER2-positive breast cancers where even patients with early-stage disease receive a multimodal therapy approach including antibody, chemotherapy, surgical, and often radiation treatments.⁶ We are moving towards a similar multimodal comprehensive treatment strategy for UPSC. If it is as successful as it is in breast cancer, it will be long overdue, and desperately necessary given the poor prognosis of this disease for all stages because of the inadequacies of current treatments strategies.

Routine testing of UPSC for HER2 expression is now a part of routine molecular substaging of uterine cancers in the same way we have embraced testing for microsatellite instability and hormone-receptor status. While a diagnosis of HER2 overexpression in UPSC portends a poor prognosis, patients can be reassured that treatment strategies exist that can target this malignant mechanism in advanced disease and more are under further development for early-stage disease.
 

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no relevant financial disclosures. Email her at [email protected].

References

1. Curr Opin Obstet Gynecol. 2010 Feb. doi: 10.1097/GCO.0b013e328334d8a3.

2. National Comprehensive Cancer Network. Uterine Neoplasms (version 2.2020).

3. Cancer 2005 Oct 1. doi: 10.1002/cncr.21308.

4. Gynecol Oncol 2020 doi: 10.1016/j.ygyno.2020.07.016.

5. J Clin Oncol 2018. doi: 10.1200/JCO.2017.76.5966.

6. N Engl J Med 2011. doi: 10.1056/NEJMoa0910383.

7. Discov Med. 2016 Apr;21(116):293-303.

As communities wrestle with the decision to send children back to school or opt for distance learning, a key question is how many children are likely to have asymptomatic SARS-CoV-2 infections. Researchers have now found that the prevalence of asymptomatic infections in children correlates with the overall incidence of COVID-19 in the local population, according to an analysis of data from 28 U.S. children’s hospitals.

Courtesy NIAID

“The strong association between prevalence of SARS-CoV-2 in children who are asymptomatic and contemporaneous weekly incidence of COVID-19 in the general population ... provides a simple means for institutions to estimate local pediatric asymptomatic prevalence from the publicly available Johns Hopkins University database,” researchers say in an article published online August 25 in JAMA Pediatrics.

Ana Marija Sola, BS, a researcher at the University of California, San Francisco, and colleagues examined the prevalence of SARS-CoV-2 infection among 33,041 children who underwent routine testing in April and May when hospitals resumed elective medical and surgical care. The hospitals performed reverse transcription–polymerase chain reaction tests for SARS-CoV-2 RNA before surgery, clinic visits, or hospital admissions. Pediatric otolaryngologists reported the prevalence data through May 29 as part of a quality improvement project.

In all, 250 patients tested positive for the virus, for an overall prevalence of 0.65%. Across 25 geographic areas, the prevalence ranged from 0% to 2.2%. By region, prevalence was highest in the Northeast, at 0.90%, and the Midwest, at 0.87%; prevalence was lower in the West, at 0.59%, and the South, at 0.52%.

To get a sense of how those rates compared with overall rates in the same geographic areas, the researchers used the Johns Hopkins University confirmed cases database to calculate the average weekly incidence of COVID-19 for the entire population for each geographic area.

“Asymptomatic pediatric prevalence was significantly associated with weekly incidence of COVID-19 in the general population during the 6-week period over which most testing of individuals without symptoms occurred,” Ms. Sola and colleagues reported. An analysis using additional data from 11 geographic areas demonstrated that this association persisted at a later time point.

The study provides “another window on the question of how likely is it that an asymptomatic child will be carrying coronavirus,” said Susan E. Coffin, MD, MPH, an attending physician for the division of infectious diseases at Children’s Hospital of Philadelphia. However, important related questions remain, said Dr. Coffin, who was not involved with the study.

For one, it is unclear how many children remain asymptomatic in comparison with those who were in a presymptomatic phase at the time of testing. And importantly, “what proportion of these children are infectious?” said Dr. Coffin. “There is some data to suggest that children with asymptomatic infection may be less infectious than children with symptomatic infection.”

It also could be that patients seen at children’s hospitals differ from the general pediatric population. “What does this look like if you do the exact same study in a group of randomly selected children, not children who are queueing up to have a procedure? ... And what do these numbers look like now that stay-at-home orders have been lifted?” Dr. Coffin asked.

Further studies are needed to establish that detection of COVID-19 in the general population is predictive of the prevalence of SARS-CoV-2 infection in asymptomatic children, Dr. Coffin said.

The authors have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

As communities wrestle with the decision to send children back to school or opt for distance learning, a key question is how many children are likely to have asymptomatic SARS-CoV-2 infections. Researchers have now found that the prevalence of asymptomatic infections in children correlates with the overall incidence of COVID-19 in the local population, according to an analysis of data from 28 U.S. children’s hospitals.

Courtesy NIAID

“The strong association between prevalence of SARS-CoV-2 in children who are asymptomatic and contemporaneous weekly incidence of COVID-19 in the general population ... provides a simple means for institutions to estimate local pediatric asymptomatic prevalence from the publicly available Johns Hopkins University database,” researchers say in an article published online August 25 in JAMA Pediatrics.

Ana Marija Sola, BS, a researcher at the University of California, San Francisco, and colleagues examined the prevalence of SARS-CoV-2 infection among 33,041 children who underwent routine testing in April and May when hospitals resumed elective medical and surgical care. The hospitals performed reverse transcription–polymerase chain reaction tests for SARS-CoV-2 RNA before surgery, clinic visits, or hospital admissions. Pediatric otolaryngologists reported the prevalence data through May 29 as part of a quality improvement project.

In all, 250 patients tested positive for the virus, for an overall prevalence of 0.65%. Across 25 geographic areas, the prevalence ranged from 0% to 2.2%. By region, prevalence was highest in the Northeast, at 0.90%, and the Midwest, at 0.87%; prevalence was lower in the West, at 0.59%, and the South, at 0.52%.

To get a sense of how those rates compared with overall rates in the same geographic areas, the researchers used the Johns Hopkins University confirmed cases database to calculate the average weekly incidence of COVID-19 for the entire population for each geographic area.

“Asymptomatic pediatric prevalence was significantly associated with weekly incidence of COVID-19 in the general population during the 6-week period over which most testing of individuals without symptoms occurred,” Ms. Sola and colleagues reported. An analysis using additional data from 11 geographic areas demonstrated that this association persisted at a later time point.

The study provides “another window on the question of how likely is it that an asymptomatic child will be carrying coronavirus,” said Susan E. Coffin, MD, MPH, an attending physician for the division of infectious diseases at Children’s Hospital of Philadelphia. However, important related questions remain, said Dr. Coffin, who was not involved with the study.

For one, it is unclear how many children remain asymptomatic in comparison with those who were in a presymptomatic phase at the time of testing. And importantly, “what proportion of these children are infectious?” said Dr. Coffin. “There is some data to suggest that children with asymptomatic infection may be less infectious than children with symptomatic infection.”

It also could be that patients seen at children’s hospitals differ from the general pediatric population. “What does this look like if you do the exact same study in a group of randomly selected children, not children who are queueing up to have a procedure? ... And what do these numbers look like now that stay-at-home orders have been lifted?” Dr. Coffin asked.

Further studies are needed to establish that detection of COVID-19 in the general population is predictive of the prevalence of SARS-CoV-2 infection in asymptomatic children, Dr. Coffin said.

The authors have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

As communities wrestle with the decision to send children back to school or opt for distance learning, a key question is how many children are likely to have asymptomatic SARS-CoV-2 infections. Researchers have now found that the prevalence of asymptomatic infections in children correlates with the overall incidence of COVID-19 in the local population, according to an analysis of data from 28 U.S. children’s hospitals.

Courtesy NIAID

“The strong association between prevalence of SARS-CoV-2 in children who are asymptomatic and contemporaneous weekly incidence of COVID-19 in the general population ... provides a simple means for institutions to estimate local pediatric asymptomatic prevalence from the publicly available Johns Hopkins University database,” researchers say in an article published online August 25 in JAMA Pediatrics.

Ana Marija Sola, BS, a researcher at the University of California, San Francisco, and colleagues examined the prevalence of SARS-CoV-2 infection among 33,041 children who underwent routine testing in April and May when hospitals resumed elective medical and surgical care. The hospitals performed reverse transcription–polymerase chain reaction tests for SARS-CoV-2 RNA before surgery, clinic visits, or hospital admissions. Pediatric otolaryngologists reported the prevalence data through May 29 as part of a quality improvement project.

In all, 250 patients tested positive for the virus, for an overall prevalence of 0.65%. Across 25 geographic areas, the prevalence ranged from 0% to 2.2%. By region, prevalence was highest in the Northeast, at 0.90%, and the Midwest, at 0.87%; prevalence was lower in the West, at 0.59%, and the South, at 0.52%.

To get a sense of how those rates compared with overall rates in the same geographic areas, the researchers used the Johns Hopkins University confirmed cases database to calculate the average weekly incidence of COVID-19 for the entire population for each geographic area.

“Asymptomatic pediatric prevalence was significantly associated with weekly incidence of COVID-19 in the general population during the 6-week period over which most testing of individuals without symptoms occurred,” Ms. Sola and colleagues reported. An analysis using additional data from 11 geographic areas demonstrated that this association persisted at a later time point.

The study provides “another window on the question of how likely is it that an asymptomatic child will be carrying coronavirus,” said Susan E. Coffin, MD, MPH, an attending physician for the division of infectious diseases at Children’s Hospital of Philadelphia. However, important related questions remain, said Dr. Coffin, who was not involved with the study.

For one, it is unclear how many children remain asymptomatic in comparison with those who were in a presymptomatic phase at the time of testing. And importantly, “what proportion of these children are infectious?” said Dr. Coffin. “There is some data to suggest that children with asymptomatic infection may be less infectious than children with symptomatic infection.”

It also could be that patients seen at children’s hospitals differ from the general pediatric population. “What does this look like if you do the exact same study in a group of randomly selected children, not children who are queueing up to have a procedure? ... And what do these numbers look like now that stay-at-home orders have been lifted?” Dr. Coffin asked.

Further studies are needed to establish that detection of COVID-19 in the general population is predictive of the prevalence of SARS-CoV-2 infection in asymptomatic children, Dr. Coffin said.

The authors have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

A newly described uterine compression technique that uses simple supplies and does not require hysterotomy was successful in controlling postpartum hemorrhage in 16 of 18 (89%) women in two teaching hospitals in Nigeria, averting the need for hysterectomy in these women.

Each of the women had severe postpartum hemorrhage attributable to uterine atony and had undergone local protocols for medical management “to no avail,” Chidi Ochu Uzoma Esike, MD, who developed the technique, wrote in a report published in Obstetrics and Gynecology.

The technique involves placing six polyglactin (Vicryl) #2 or chromic #2 sutures in the lower uterine segment – three anteriorly and three posteriorly – and could be particularly useful in developing countries, where many women die from postpartum hemorrhage “because most of the medical officers who attend the majority of births in health facilities can perform cesarean delivery but cannot perform hysterectomy and find existing compression suture techniques too complex to perform,” Dr. Esike wrote in the case series report.

In addition, “specialized sutures and needles required for some of the known compression techniques are not readily available,” said Dr. Esike of the department of obstetrics and gynecology at Alex Ekwueme Federal University Hospital and Ebyonyi State University in Abakaliki, Nigeria.

Angela Martin, MD, a maternal-fetal medicine specialist at the University of Kansas Medical Center in Kansas City, said that “having a quick and effective surgical technique [for uncontrollable postpartum hemorrhage] is essential.”

“I love that Esike’s technique uses polyglactin (Vicryl) or chromic sutures. These are familiar to most surgeons, cheap, and typically available even in most resource-deficient settings,” said Dr. Martin, who was asked to comment on the report, adding that several of the known surgical techniques for uterine atony require a skilled operator and are indeed not universally feasible.

“If successful,” Dr. Martin said in an interview, “compression sutures can be lifesaving and fertility preserving.”

The technique involves tying the two middle sutures (one placed anteriorly and one posteriorly) at the fundus as an assistant slowly and continuously compresses the uterus. The more laterally placed sutures are tied similarly, with each pair tied at about 4 cm from the lateral edge of the uterus. “As the uterus is compressed, the slack should be taken up by the sutures before tying,” said Dr. Esike, whose report features both diagrammatic and photographic representations of suture insertion and tying.

For patients who delivered vaginally – nine in this case series – the technique involves performing a laparotomy and exteriorizing the uterus. The technique’s “suture placement,” Dr. Esike wrote, “took 11-25 minutes from the onset of laparotomy to completion.” There were no short or long-term complications in any of the 18 patients.

B-Lynch compression sutures are more complex to perform and require a larger curved needle, Dr. Esike wrote, and the Hayman technique similarly requires a longer needle that may not be available in resource-constrained countries. The hysterotomy required in the B-Lynch technique, Dr. Esike added, “leads to the uterus not contracting maximally until it is repaired,” which increases blood loss from the procedure.

Dr. Martin said the small size of the case series is not discouraging. “The B-Lynch suture was widely adopted after it was described in five cases in 1997,” she said. There are no randomized controlled trials to suggest that one method of uterine compression sutures is better than another. “Ultimately,” she said, “the technique chosen will depend on the surgeon’s training and available supplies.”

Dr. Esike had no relevant financial disclosures. Dr. Martin had no relevant financial disclosures.

SOURCE: Esike COU. Obstet Gynecol. 2020. doi: 10.1097/AOG.0000000000003947.

A newly described uterine compression technique that uses simple supplies and does not require hysterotomy was successful in controlling postpartum hemorrhage in 16 of 18 (89%) women in two teaching hospitals in Nigeria, averting the need for hysterectomy in these women.

Each of the women had severe postpartum hemorrhage attributable to uterine atony and had undergone local protocols for medical management “to no avail,” Chidi Ochu Uzoma Esike, MD, who developed the technique, wrote in a report published in Obstetrics and Gynecology.

The technique involves placing six polyglactin (Vicryl) #2 or chromic #2 sutures in the lower uterine segment – three anteriorly and three posteriorly – and could be particularly useful in developing countries, where many women die from postpartum hemorrhage “because most of the medical officers who attend the majority of births in health facilities can perform cesarean delivery but cannot perform hysterectomy and find existing compression suture techniques too complex to perform,” Dr. Esike wrote in the case series report.

In addition, “specialized sutures and needles required for some of the known compression techniques are not readily available,” said Dr. Esike of the department of obstetrics and gynecology at Alex Ekwueme Federal University Hospital and Ebyonyi State University in Abakaliki, Nigeria.

Angela Martin, MD, a maternal-fetal medicine specialist at the University of Kansas Medical Center in Kansas City, said that “having a quick and effective surgical technique [for uncontrollable postpartum hemorrhage] is essential.”

“I love that Esike’s technique uses polyglactin (Vicryl) or chromic sutures. These are familiar to most surgeons, cheap, and typically available even in most resource-deficient settings,” said Dr. Martin, who was asked to comment on the report, adding that several of the known surgical techniques for uterine atony require a skilled operator and are indeed not universally feasible.

“If successful,” Dr. Martin said in an interview, “compression sutures can be lifesaving and fertility preserving.”

The technique involves tying the two middle sutures (one placed anteriorly and one posteriorly) at the fundus as an assistant slowly and continuously compresses the uterus. The more laterally placed sutures are tied similarly, with each pair tied at about 4 cm from the lateral edge of the uterus. “As the uterus is compressed, the slack should be taken up by the sutures before tying,” said Dr. Esike, whose report features both diagrammatic and photographic representations of suture insertion and tying.

For patients who delivered vaginally – nine in this case series – the technique involves performing a laparotomy and exteriorizing the uterus. The technique’s “suture placement,” Dr. Esike wrote, “took 11-25 minutes from the onset of laparotomy to completion.” There were no short or long-term complications in any of the 18 patients.

B-Lynch compression sutures are more complex to perform and require a larger curved needle, Dr. Esike wrote, and the Hayman technique similarly requires a longer needle that may not be available in resource-constrained countries. The hysterotomy required in the B-Lynch technique, Dr. Esike added, “leads to the uterus not contracting maximally until it is repaired,” which increases blood loss from the procedure.

Dr. Martin said the small size of the case series is not discouraging. “The B-Lynch suture was widely adopted after it was described in five cases in 1997,” she said. There are no randomized controlled trials to suggest that one method of uterine compression sutures is better than another. “Ultimately,” she said, “the technique chosen will depend on the surgeon’s training and available supplies.”

Dr. Esike had no relevant financial disclosures. Dr. Martin had no relevant financial disclosures.

SOURCE: Esike COU. Obstet Gynecol. 2020. doi: 10.1097/AOG.0000000000003947.

A newly described uterine compression technique that uses simple supplies and does not require hysterotomy was successful in controlling postpartum hemorrhage in 16 of 18 (89%) women in two teaching hospitals in Nigeria, averting the need for hysterectomy in these women.

Each of the women had severe postpartum hemorrhage attributable to uterine atony and had undergone local protocols for medical management “to no avail,” Chidi Ochu Uzoma Esike, MD, who developed the technique, wrote in a report published in Obstetrics and Gynecology.

The technique involves placing six polyglactin (Vicryl) #2 or chromic #2 sutures in the lower uterine segment – three anteriorly and three posteriorly – and could be particularly useful in developing countries, where many women die from postpartum hemorrhage “because most of the medical officers who attend the majority of births in health facilities can perform cesarean delivery but cannot perform hysterectomy and find existing compression suture techniques too complex to perform,” Dr. Esike wrote in the case series report.

In addition, “specialized sutures and needles required for some of the known compression techniques are not readily available,” said Dr. Esike of the department of obstetrics and gynecology at Alex Ekwueme Federal University Hospital and Ebyonyi State University in Abakaliki, Nigeria.

Angela Martin, MD, a maternal-fetal medicine specialist at the University of Kansas Medical Center in Kansas City, said that “having a quick and effective surgical technique [for uncontrollable postpartum hemorrhage] is essential.”

“I love that Esike’s technique uses polyglactin (Vicryl) or chromic sutures. These are familiar to most surgeons, cheap, and typically available even in most resource-deficient settings,” said Dr. Martin, who was asked to comment on the report, adding that several of the known surgical techniques for uterine atony require a skilled operator and are indeed not universally feasible.

“If successful,” Dr. Martin said in an interview, “compression sutures can be lifesaving and fertility preserving.”

The technique involves tying the two middle sutures (one placed anteriorly and one posteriorly) at the fundus as an assistant slowly and continuously compresses the uterus. The more laterally placed sutures are tied similarly, with each pair tied at about 4 cm from the lateral edge of the uterus. “As the uterus is compressed, the slack should be taken up by the sutures before tying,” said Dr. Esike, whose report features both diagrammatic and photographic representations of suture insertion and tying.

For patients who delivered vaginally – nine in this case series – the technique involves performing a laparotomy and exteriorizing the uterus. The technique’s “suture placement,” Dr. Esike wrote, “took 11-25 minutes from the onset of laparotomy to completion.” There were no short or long-term complications in any of the 18 patients.

B-Lynch compression sutures are more complex to perform and require a larger curved needle, Dr. Esike wrote, and the Hayman technique similarly requires a longer needle that may not be available in resource-constrained countries. The hysterotomy required in the B-Lynch technique, Dr. Esike added, “leads to the uterus not contracting maximally until it is repaired,” which increases blood loss from the procedure.

Dr. Martin said the small size of the case series is not discouraging. “The B-Lynch suture was widely adopted after it was described in five cases in 1997,” she said. There are no randomized controlled trials to suggest that one method of uterine compression sutures is better than another. “Ultimately,” she said, “the technique chosen will depend on the surgeon’s training and available supplies.”

Dr. Esike had no relevant financial disclosures. Dr. Martin had no relevant financial disclosures.

SOURCE: Esike COU. Obstet Gynecol. 2020. doi: 10.1097/AOG.0000000000003947.

The abrupt transition to online learning for American children in kindergarten through 12th grade has left educators and parents unprepared, but virtual learning can be a successful part of education going forward, according to a viewpoint published in JAMA Pediatrics. However, schools also can reopen safely if precautions are taken, and students would benefit in many ways, according to a second viewpoint.

monkeybusinessimages/Thinkstock

“As policy makers, health care professionals, and parents prepare for the fall semester and as public and private schools grapple with how to make that possible, a better understanding of K-12 virtual learning options and outcomes may facilitate those difficult decisions,” wrote Erik Black, PhD, of the University of Florida, Gainesville; Richard Ferdig, PhD, of Kent State University, Ohio; and Lindsay A. Thompson, MD, of the University of Florida, Gainesville.

“Importantly, K-12 virtual schooling is not suited for all students or all families.”

In a viewpoint published in JAMA Pediatrics, the authors noted that virtual schooling has existed in the United States in various forms for some time. “Just like the myriad options that are available for face-to-face schooling in the U.S., virtual schooling exists in a complex landscape of for-profit, charter, and public options.”
 

Not all virtual schools are equal

Consequently, not all virtual schools are created equal, they emphasized. Virtual education can be successful for many students when presented by trained online instructors using a curriculum designed to be effective in an online venue.

“Parents need to seek reviews and ask for educational outcomes from each virtual school system to assess the quality of the provided education,” Dr. Black, Dr. Ferdig, and Dr. Thompson emphasized.

Key questions for parents to consider when faced with online learning include the type of technology needed to participate; whether their child can maintain a study schedule and complete assignments with limited supervision; whether their child could ask for help and communicate with teachers through technology including phone, text, email, or video; and whether their child has the basic reading, math, and computer literacy skills to engage in online learning, the authors said. Other questions include the school’s expectations for parents and caregivers, how student information may be shared, and how the virtual school lines up with state standards for K-12 educators (in the case of options outside the public school system).

“The COVID-19 pandemic offers a unique challenge for educators, policymakers, and health care professionals to partner with parents to make the best local and individual decisions for children,” Dr. Black, Dr. Ferdig, and Dr. Thompson concluded.
 

Schools may be able to open safely

Children continue to make up a low percentage of COVID-19 cases and appear less likely to experience illness, wrote C. Jason Wang, MD, PhD, and Henry Bair, BS, of Stanford (Calif.) University in a second viewpoint also published in JAMA Pediatrics. The impact of long-term school closures extends beyond education and can “exacerbate socioeconomic disparities, amplify existing educational inequalities, and aggravate food insecurity, domestic violence, and mental health disorders,” they wrote.

Dr. Wang and Mr. Bair proposed that school districts “engage key stakeholders to establish a COVID-19 task force, composed of the superintendent, members of the school board, teachers, parents, and health care professionals to develop policies and procedures,” that would allow schools to open safely.

The authors outlined strategies including adapting teaching spaces to accommodate physical distance, with the addition of temporary modular buildings if needed. They advised assigned seating on school buses, and acknowledged the need for the availability of protective equipment, including hand sanitizer and masks, as well as the possible use of transparent barriers on the sides of student desks.

“As the AAP [American Academy of Pediatrics] guidance suggests, teachers who must work closely with students with special needs or with students who are unable to wear masks should wear N95 masks if possible or wear face shields in addition to surgical masks,” Dr. Wang and Mr. Bair noted. Other elements of the AAP guidance include the creation of fixed cohorts of students and teachers to limit virus exposure.

“Even with all the precautions in place, COVID-19 outbreaks within schools are still likely,” they said. “Therefore, schools will need to remain flexible and consider temporary closures if there is an outbreak involving multiple students and/or staff and be ready to transition to online education.”

The AAP guidance does not address operational approaches to identifying signs and symptoms of COVID-19, the authors noted. “To address this, we recommend that schools implement multilevel screening for students and staff.”

“In summary, to maximize health and educational outcomes, school districts should adopt some or all of the measures of the AAP guidance and prioritize them after considering local COVID-19 incidence, key stakeholder input, and budgetary constraints,” Dr. Wang and Mr. Bair concluded.
 

Schools opening is a regional decision

“The mission of the AAP is to attain optimal physical, mental, and social health and well-being for all infants, children, adolescents, and young adults,” Howard Smart, MD, said in an interview. The question of school reopening “is of national importance, and the AAP has a national role in making recommendations regarding national policy affecting the health of the children.”

“The decision to open schools will be made regionally, but it is important for a nonpolitical national voice to make expert recommendations,” he emphasized.

“Many of the recommendations are ideal goals,” noted Dr. Smart, chairman of the department of pediatrics at the Sharp Rees-Stealy Medical Group in San Diego. “It will be difficult, for example, to implement symptom screening every day before school, no matter where it is performed. Some of the measures may be quite costly, and take time to implement, or require expansion of school staff, for which there may be no budget.”

In addition, “[n]ot all students are likely to comply with masking, distance, and hand-washing recommendations. One student who is noncompliant will be able to infect many other students and staff, as has been seen in other countries.” Also, parental attitudes toward control measures are likely to affect student attitudes, he noted.

“I have interviewed many families at recent checkups, and most have felt that the rush to remote learning that occurred at the end of the last school year resulted in fairly disorganized instruction,” Dr. Smart said. “They are hoping that, having had the summer to plan ahead, the remote teaching will be handled better. Remote learning will certainly work best for self-motivated, organized students with good family support, as noted in the Black, Ferdig, and Thompson article,” he said.

Pediatricians can support the schools by being a source of evidence-based information for parents, Dr. Smart said. “Pediatricians with time and energy might want to volunteer to hold informational video conferences for parents and/or school personnel if they feel they are up to date on current COVID-19 science and want to handle potentially contentious questions.”

The decision parents make to send their children back to school comes down to a risk-benefit calculation. “In some communities this may be left to parents, while in other communities this will a public health decision,” he said. “It is still not clear whether having students attend school in person will result in increased spread of COVID-19 among the students, or in their communities. Although some evidence from early in the pandemic suggests that children may not spread the virus as much as adults, more recent evidence suggests that children 10 years and older do transmit the virus at least as much as adults.”

“The risk to the students and the community, therefore, is unknown,” and difficult to compare with the benefit of in-person schooling, Dr. Smart noted.

“We will learn quite a bit from communities where students do go back to in-person class, as we follow the progression of COVID-19 over the weeks following the resumption of instruction.” Ultimately, advice to parents will need to be tailored to the current conditions of COVID-19 transmission in the community, he concluded.
 

It’s not just about education

“The AAP released its guidance to ensure that as school districts were contemplating reopening they were considering the full array of risks for children and adolescents. These risks included not only those related to COVID-19, but also those related to the impact of not reopening in-person,” Nathaniel Beers, MD, president of the HSC Health Care System in Washington, said in an interview.

“Students and families are dependent on schools for much more than just an education, and those [elements] need to be factored into the decisions to reopen,” the pediatrician said.

However, “[t]he major barrier for schools is resources to safely reopen,” said Dr. Beers. “The additional staffing and supplies will require additional funding. There are increased demands regardless of whether students are learning in-person or virtually or through hybrid models.”

“Another significant barrier is ensuring that parents and staff are actively engaged in planning for the type of model being used,” he said.

“All of the models require buy-in by staff and parents. This will require significant outreach and strong communication plans. Schools also need to ensure they are planning not just for how to return students to schools, but what will happen when staff or students test positive for COVID-19. Students, families, and staff all will need to know what these plans are up front to feel confident in returning to school,” he emphasized.

“There are students who can thrive in a virtual learning environment,” Dr. Beers said. “There are also students who benefit from the virtual learning environment because of their own risk, or because of a family member’s risk for COVID-19 or the complications from it.”

“However, many children with disabilities have struggled in a virtual environment,” he said. “These students struggle to access the educational services without the adequate supports at home. They often receive additional services in school, such as speech, occupational therapy or physical therapy, or nursing services, that may not have transitioned to home but are critical for their health and development. Many students with disabilities are dependent on family members to successfully access the educational services they need.”

“Pediatricians can play a role in providing feedback on recommendations related to physical distancing and face coverings in particular,” said Dr. Beers. “In addition, they can be helpful in developing plans for children with disabilities as well as what the response plan should be for students who become sick during the school day.”

The Centers for Disease Control and Prevention released a decision tool for parents who are considering whether to send their child to in-person school, and pediatricians can help parents walk through these questions, Dr. Beers noted. “In addition, pediatricians play an important role in helping patients and families think about the risks of COVID for the patient and other family members, and this can be helpful in addressing the anxiety that parents and patients may be experiencing.”

Further information can be found in Return to School During COVID-19, which can be located at HealthyChildren.org, by the American Academy of Pediatrics.

The authors of the viewpoints had no relevant financial disclosures. Dr. Smart, a member of the Pediatric News editorial advisory board, had no relevant financial disclosures. Dr. Beers has served on the editorial advisory board of Pediatric News in the past, but had no relevant financial disclosures.

SOURCES: Black E, Ferdig R, Thompson LA. JAMA Pediatr. 2020 Aug 11. doi: 10.1001/jamapediatrics.2020.3800. Wang CJ and Bair H. JAMA Pediatr. Aug 11. doi: 10.1001/jamapediatrics.2020.3871.
 

The abrupt transition to online learning for American children in kindergarten through 12th grade has left educators and parents unprepared, but virtual learning can be a successful part of education going forward, according to a viewpoint published in JAMA Pediatrics. However, schools also can reopen safely if precautions are taken, and students would benefit in many ways, according to a second viewpoint.

monkeybusinessimages/Thinkstock

“As policy makers, health care professionals, and parents prepare for the fall semester and as public and private schools grapple with how to make that possible, a better understanding of K-12 virtual learning options and outcomes may facilitate those difficult decisions,” wrote Erik Black, PhD, of the University of Florida, Gainesville; Richard Ferdig, PhD, of Kent State University, Ohio; and Lindsay A. Thompson, MD, of the University of Florida, Gainesville.

“Importantly, K-12 virtual schooling is not suited for all students or all families.”

In a viewpoint published in JAMA Pediatrics, the authors noted that virtual schooling has existed in the United States in various forms for some time. “Just like the myriad options that are available for face-to-face schooling in the U.S., virtual schooling exists in a complex landscape of for-profit, charter, and public options.”
 

Not all virtual schools are equal

Consequently, not all virtual schools are created equal, they emphasized. Virtual education can be successful for many students when presented by trained online instructors using a curriculum designed to be effective in an online venue.

“Parents need to seek reviews and ask for educational outcomes from each virtual school system to assess the quality of the provided education,” Dr. Black, Dr. Ferdig, and Dr. Thompson emphasized.

Key questions for parents to consider when faced with online learning include the type of technology needed to participate; whether their child can maintain a study schedule and complete assignments with limited supervision; whether their child could ask for help and communicate with teachers through technology including phone, text, email, or video; and whether their child has the basic reading, math, and computer literacy skills to engage in online learning, the authors said. Other questions include the school’s expectations for parents and caregivers, how student information may be shared, and how the virtual school lines up with state standards for K-12 educators (in the case of options outside the public school system).

“The COVID-19 pandemic offers a unique challenge for educators, policymakers, and health care professionals to partner with parents to make the best local and individual decisions for children,” Dr. Black, Dr. Ferdig, and Dr. Thompson concluded.
 

Schools may be able to open safely

Children continue to make up a low percentage of COVID-19 cases and appear less likely to experience illness, wrote C. Jason Wang, MD, PhD, and Henry Bair, BS, of Stanford (Calif.) University in a second viewpoint also published in JAMA Pediatrics. The impact of long-term school closures extends beyond education and can “exacerbate socioeconomic disparities, amplify existing educational inequalities, and aggravate food insecurity, domestic violence, and mental health disorders,” they wrote.

Dr. Wang and Mr. Bair proposed that school districts “engage key stakeholders to establish a COVID-19 task force, composed of the superintendent, members of the school board, teachers, parents, and health care professionals to develop policies and procedures,” that would allow schools to open safely.

The authors outlined strategies including adapting teaching spaces to accommodate physical distance, with the addition of temporary modular buildings if needed. They advised assigned seating on school buses, and acknowledged the need for the availability of protective equipment, including hand sanitizer and masks, as well as the possible use of transparent barriers on the sides of student desks.

“As the AAP [American Academy of Pediatrics] guidance suggests, teachers who must work closely with students with special needs or with students who are unable to wear masks should wear N95 masks if possible or wear face shields in addition to surgical masks,” Dr. Wang and Mr. Bair noted. Other elements of the AAP guidance include the creation of fixed cohorts of students and teachers to limit virus exposure.

“Even with all the precautions in place, COVID-19 outbreaks within schools are still likely,” they said. “Therefore, schools will need to remain flexible and consider temporary closures if there is an outbreak involving multiple students and/or staff and be ready to transition to online education.”

The AAP guidance does not address operational approaches to identifying signs and symptoms of COVID-19, the authors noted. “To address this, we recommend that schools implement multilevel screening for students and staff.”

“In summary, to maximize health and educational outcomes, school districts should adopt some or all of the measures of the AAP guidance and prioritize them after considering local COVID-19 incidence, key stakeholder input, and budgetary constraints,” Dr. Wang and Mr. Bair concluded.
 

Schools opening is a regional decision

“The mission of the AAP is to attain optimal physical, mental, and social health and well-being for all infants, children, adolescents, and young adults,” Howard Smart, MD, said in an interview. The question of school reopening “is of national importance, and the AAP has a national role in making recommendations regarding national policy affecting the health of the children.”

“The decision to open schools will be made regionally, but it is important for a nonpolitical national voice to make expert recommendations,” he emphasized.

“Many of the recommendations are ideal goals,” noted Dr. Smart, chairman of the department of pediatrics at the Sharp Rees-Stealy Medical Group in San Diego. “It will be difficult, for example, to implement symptom screening every day before school, no matter where it is performed. Some of the measures may be quite costly, and take time to implement, or require expansion of school staff, for which there may be no budget.”

In addition, “[n]ot all students are likely to comply with masking, distance, and hand-washing recommendations. One student who is noncompliant will be able to infect many other students and staff, as has been seen in other countries.” Also, parental attitudes toward control measures are likely to affect student attitudes, he noted.

“I have interviewed many families at recent checkups, and most have felt that the rush to remote learning that occurred at the end of the last school year resulted in fairly disorganized instruction,” Dr. Smart said. “They are hoping that, having had the summer to plan ahead, the remote teaching will be handled better. Remote learning will certainly work best for self-motivated, organized students with good family support, as noted in the Black, Ferdig, and Thompson article,” he said.

Pediatricians can support the schools by being a source of evidence-based information for parents, Dr. Smart said. “Pediatricians with time and energy might want to volunteer to hold informational video conferences for parents and/or school personnel if they feel they are up to date on current COVID-19 science and want to handle potentially contentious questions.”

The decision parents make to send their children back to school comes down to a risk-benefit calculation. “In some communities this may be left to parents, while in other communities this will a public health decision,” he said. “It is still not clear whether having students attend school in person will result in increased spread of COVID-19 among the students, or in their communities. Although some evidence from early in the pandemic suggests that children may not spread the virus as much as adults, more recent evidence suggests that children 10 years and older do transmit the virus at least as much as adults.”

“The risk to the students and the community, therefore, is unknown,” and difficult to compare with the benefit of in-person schooling, Dr. Smart noted.

“We will learn quite a bit from communities where students do go back to in-person class, as we follow the progression of COVID-19 over the weeks following the resumption of instruction.” Ultimately, advice to parents will need to be tailored to the current conditions of COVID-19 transmission in the community, he concluded.
 

It’s not just about education

“The AAP released its guidance to ensure that as school districts were contemplating reopening they were considering the full array of risks for children and adolescents. These risks included not only those related to COVID-19, but also those related to the impact of not reopening in-person,” Nathaniel Beers, MD, president of the HSC Health Care System in Washington, said in an interview.

“Students and families are dependent on schools for much more than just an education, and those [elements] need to be factored into the decisions to reopen,” the pediatrician said.

However, “[t]he major barrier for schools is resources to safely reopen,” said Dr. Beers. “The additional staffing and supplies will require additional funding. There are increased demands regardless of whether students are learning in-person or virtually or through hybrid models.”

“Another significant barrier is ensuring that parents and staff are actively engaged in planning for the type of model being used,” he said.

“All of the models require buy-in by staff and parents. This will require significant outreach and strong communication plans. Schools also need to ensure they are planning not just for how to return students to schools, but what will happen when staff or students test positive for COVID-19. Students, families, and staff all will need to know what these plans are up front to feel confident in returning to school,” he emphasized.

“There are students who can thrive in a virtual learning environment,” Dr. Beers said. “There are also students who benefit from the virtual learning environment because of their own risk, or because of a family member’s risk for COVID-19 or the complications from it.”

“However, many children with disabilities have struggled in a virtual environment,” he said. “These students struggle to access the educational services without the adequate supports at home. They often receive additional services in school, such as speech, occupational therapy or physical therapy, or nursing services, that may not have transitioned to home but are critical for their health and development. Many students with disabilities are dependent on family members to successfully access the educational services they need.”

“Pediatricians can play a role in providing feedback on recommendations related to physical distancing and face coverings in particular,” said Dr. Beers. “In addition, they can be helpful in developing plans for children with disabilities as well as what the response plan should be for students who become sick during the school day.”

The Centers for Disease Control and Prevention released a decision tool for parents who are considering whether to send their child to in-person school, and pediatricians can help parents walk through these questions, Dr. Beers noted. “In addition, pediatricians play an important role in helping patients and families think about the risks of COVID for the patient and other family members, and this can be helpful in addressing the anxiety that parents and patients may be experiencing.”

Further information can be found in Return to School During COVID-19, which can be located at HealthyChildren.org, by the American Academy of Pediatrics.

The authors of the viewpoints had no relevant financial disclosures. Dr. Smart, a member of the Pediatric News editorial advisory board, had no relevant financial disclosures. Dr. Beers has served on the editorial advisory board of Pediatric News in the past, but had no relevant financial disclosures.

SOURCES: Black E, Ferdig R, Thompson LA. JAMA Pediatr. 2020 Aug 11. doi: 10.1001/jamapediatrics.2020.3800. Wang CJ and Bair H. JAMA Pediatr. Aug 11. doi: 10.1001/jamapediatrics.2020.3871.
 

The abrupt transition to online learning for American children in kindergarten through 12th grade has left educators and parents unprepared, but virtual learning can be a successful part of education going forward, according to a viewpoint published in JAMA Pediatrics. However, schools also can reopen safely if precautions are taken, and students would benefit in many ways, according to a second viewpoint.

monkeybusinessimages/Thinkstock

“As policy makers, health care professionals, and parents prepare for the fall semester and as public and private schools grapple with how to make that possible, a better understanding of K-12 virtual learning options and outcomes may facilitate those difficult decisions,” wrote Erik Black, PhD, of the University of Florida, Gainesville; Richard Ferdig, PhD, of Kent State University, Ohio; and Lindsay A. Thompson, MD, of the University of Florida, Gainesville.

“Importantly, K-12 virtual schooling is not suited for all students or all families.”

In a viewpoint published in JAMA Pediatrics, the authors noted that virtual schooling has existed in the United States in various forms for some time. “Just like the myriad options that are available for face-to-face schooling in the U.S., virtual schooling exists in a complex landscape of for-profit, charter, and public options.”
 

Not all virtual schools are equal

Consequently, not all virtual schools are created equal, they emphasized. Virtual education can be successful for many students when presented by trained online instructors using a curriculum designed to be effective in an online venue.

“Parents need to seek reviews and ask for educational outcomes from each virtual school system to assess the quality of the provided education,” Dr. Black, Dr. Ferdig, and Dr. Thompson emphasized.

Key questions for parents to consider when faced with online learning include the type of technology needed to participate; whether their child can maintain a study schedule and complete assignments with limited supervision; whether their child could ask for help and communicate with teachers through technology including phone, text, email, or video; and whether their child has the basic reading, math, and computer literacy skills to engage in online learning, the authors said. Other questions include the school’s expectations for parents and caregivers, how student information may be shared, and how the virtual school lines up with state standards for K-12 educators (in the case of options outside the public school system).

“The COVID-19 pandemic offers a unique challenge for educators, policymakers, and health care professionals to partner with parents to make the best local and individual decisions for children,” Dr. Black, Dr. Ferdig, and Dr. Thompson concluded.
 

Schools may be able to open safely

Children continue to make up a low percentage of COVID-19 cases and appear less likely to experience illness, wrote C. Jason Wang, MD, PhD, and Henry Bair, BS, of Stanford (Calif.) University in a second viewpoint also published in JAMA Pediatrics. The impact of long-term school closures extends beyond education and can “exacerbate socioeconomic disparities, amplify existing educational inequalities, and aggravate food insecurity, domestic violence, and mental health disorders,” they wrote.

Dr. Wang and Mr. Bair proposed that school districts “engage key stakeholders to establish a COVID-19 task force, composed of the superintendent, members of the school board, teachers, parents, and health care professionals to develop policies and procedures,” that would allow schools to open safely.

The authors outlined strategies including adapting teaching spaces to accommodate physical distance, with the addition of temporary modular buildings if needed. They advised assigned seating on school buses, and acknowledged the need for the availability of protective equipment, including hand sanitizer and masks, as well as the possible use of transparent barriers on the sides of student desks.

“As the AAP [American Academy of Pediatrics] guidance suggests, teachers who must work closely with students with special needs or with students who are unable to wear masks should wear N95 masks if possible or wear face shields in addition to surgical masks,” Dr. Wang and Mr. Bair noted. Other elements of the AAP guidance include the creation of fixed cohorts of students and teachers to limit virus exposure.

“Even with all the precautions in place, COVID-19 outbreaks within schools are still likely,” they said. “Therefore, schools will need to remain flexible and consider temporary closures if there is an outbreak involving multiple students and/or staff and be ready to transition to online education.”

The AAP guidance does not address operational approaches to identifying signs and symptoms of COVID-19, the authors noted. “To address this, we recommend that schools implement multilevel screening for students and staff.”

“In summary, to maximize health and educational outcomes, school districts should adopt some or all of the measures of the AAP guidance and prioritize them after considering local COVID-19 incidence, key stakeholder input, and budgetary constraints,” Dr. Wang and Mr. Bair concluded.
 

Schools opening is a regional decision

“The mission of the AAP is to attain optimal physical, mental, and social health and well-being for all infants, children, adolescents, and young adults,” Howard Smart, MD, said in an interview. The question of school reopening “is of national importance, and the AAP has a national role in making recommendations regarding national policy affecting the health of the children.”

“The decision to open schools will be made regionally, but it is important for a nonpolitical national voice to make expert recommendations,” he emphasized.

“Many of the recommendations are ideal goals,” noted Dr. Smart, chairman of the department of pediatrics at the Sharp Rees-Stealy Medical Group in San Diego. “It will be difficult, for example, to implement symptom screening every day before school, no matter where it is performed. Some of the measures may be quite costly, and take time to implement, or require expansion of school staff, for which there may be no budget.”

In addition, “[n]ot all students are likely to comply with masking, distance, and hand-washing recommendations. One student who is noncompliant will be able to infect many other students and staff, as has been seen in other countries.” Also, parental attitudes toward control measures are likely to affect student attitudes, he noted.

“I have interviewed many families at recent checkups, and most have felt that the rush to remote learning that occurred at the end of the last school year resulted in fairly disorganized instruction,” Dr. Smart said. “They are hoping that, having had the summer to plan ahead, the remote teaching will be handled better. Remote learning will certainly work best for self-motivated, organized students with good family support, as noted in the Black, Ferdig, and Thompson article,” he said.

Pediatricians can support the schools by being a source of evidence-based information for parents, Dr. Smart said. “Pediatricians with time and energy might want to volunteer to hold informational video conferences for parents and/or school personnel if they feel they are up to date on current COVID-19 science and want to handle potentially contentious questions.”

The decision parents make to send their children back to school comes down to a risk-benefit calculation. “In some communities this may be left to parents, while in other communities this will a public health decision,” he said. “It is still not clear whether having students attend school in person will result in increased spread of COVID-19 among the students, or in their communities. Although some evidence from early in the pandemic suggests that children may not spread the virus as much as adults, more recent evidence suggests that children 10 years and older do transmit the virus at least as much as adults.”

“The risk to the students and the community, therefore, is unknown,” and difficult to compare with the benefit of in-person schooling, Dr. Smart noted.

“We will learn quite a bit from communities where students do go back to in-person class, as we follow the progression of COVID-19 over the weeks following the resumption of instruction.” Ultimately, advice to parents will need to be tailored to the current conditions of COVID-19 transmission in the community, he concluded.
 

It’s not just about education

“The AAP released its guidance to ensure that as school districts were contemplating reopening they were considering the full array of risks for children and adolescents. These risks included not only those related to COVID-19, but also those related to the impact of not reopening in-person,” Nathaniel Beers, MD, president of the HSC Health Care System in Washington, said in an interview.

“Students and families are dependent on schools for much more than just an education, and those [elements] need to be factored into the decisions to reopen,” the pediatrician said.

However, “[t]he major barrier for schools is resources to safely reopen,” said Dr. Beers. “The additional staffing and supplies will require additional funding. There are increased demands regardless of whether students are learning in-person or virtually or through hybrid models.”

“Another significant barrier is ensuring that parents and staff are actively engaged in planning for the type of model being used,” he said.

“All of the models require buy-in by staff and parents. This will require significant outreach and strong communication plans. Schools also need to ensure they are planning not just for how to return students to schools, but what will happen when staff or students test positive for COVID-19. Students, families, and staff all will need to know what these plans are up front to feel confident in returning to school,” he emphasized.

“There are students who can thrive in a virtual learning environment,” Dr. Beers said. “There are also students who benefit from the virtual learning environment because of their own risk, or because of a family member’s risk for COVID-19 or the complications from it.”

“However, many children with disabilities have struggled in a virtual environment,” he said. “These students struggle to access the educational services without the adequate supports at home. They often receive additional services in school, such as speech, occupational therapy or physical therapy, or nursing services, that may not have transitioned to home but are critical for their health and development. Many students with disabilities are dependent on family members to successfully access the educational services they need.”

“Pediatricians can play a role in providing feedback on recommendations related to physical distancing and face coverings in particular,” said Dr. Beers. “In addition, they can be helpful in developing plans for children with disabilities as well as what the response plan should be for students who become sick during the school day.”

The Centers for Disease Control and Prevention released a decision tool for parents who are considering whether to send their child to in-person school, and pediatricians can help parents walk through these questions, Dr. Beers noted. “In addition, pediatricians play an important role in helping patients and families think about the risks of COVID for the patient and other family members, and this can be helpful in addressing the anxiety that parents and patients may be experiencing.”

Further information can be found in Return to School During COVID-19, which can be located at HealthyChildren.org, by the American Academy of Pediatrics.

The authors of the viewpoints had no relevant financial disclosures. Dr. Smart, a member of the Pediatric News editorial advisory board, had no relevant financial disclosures. Dr. Beers has served on the editorial advisory board of Pediatric News in the past, but had no relevant financial disclosures.

SOURCES: Black E, Ferdig R, Thompson LA. JAMA Pediatr. 2020 Aug 11. doi: 10.1001/jamapediatrics.2020.3800. Wang CJ and Bair H. JAMA Pediatr. Aug 11. doi: 10.1001/jamapediatrics.2020.3871.
 

Uterine leiomyomata (fibroids) are the most common pelvic tumor diagnosed in women.¹ Women with symptomatic fibroids often report abnormal uterine bleeding (AUB) and pelvic cramping, fullness, or pain. Fibroids also may cause frequency of urination and contribute to fertility and pregnancy problems. Treatment options for the AUB caused by fibroids include, but are not limited to, hysterectomy, myomectomy, uterine artery embolization, endometrial ablation, insertion of a levonorgestrel intrauterine device, focused ultrasound surgery, radiofrequency ablation, leuprolide acetate, and elagolix plus low-dose hormone add-back (Oriahnn; AbbVie, North Chicago, Illinois).¹ Oriahnn is the most recent addition to our treatment armamentarium for fibroids and represents the first US Food and Drug Administration (FDA)-approved long-term hormonal option for AUB caused by fibroids.

Gene dysregulation contributes to fibroid development

Most uterine fibroids are clonal tumors, which develop following a somatic mutation in a precursor uterine myocyte. The somatic mutation causes gene dysregulation that stimulates cell growth resulting in a benign tumor mass. The majority of fibroids contain a mutation in one of the following 6 genes: mediator complex subunit 12 (MED12), high mobility group AT-hook (HMGA2 or HMGA1), RAD51B, fumarate hydratase (FH), collagen type IV, alpha 5 chain (COL4A5), or collagen type IV alpha 6 chain (COL4A6).²

Gene dysregulation in fibroids may arise following chromothripsis of the uterine myocyte genome

Chromothripsis is a catastrophic intracellular genetic event in which one or more chromosomes are broken and reassemble in a new nucleic acid sequence, producing a derivative chromosome that contains complex genetic rearrangements.³ Chromothripsis is believed to occur frequently in uterine myocytes. It is unknown why uterine myocytes are susceptible to chromothripsis,³ or why a catastrophic intracellular event such as chromothripsis results in preferential mutations in the 6 genes that are associated with myoma formation.

Estrogen and progesterone influence fibroid size and cell activity

Although uterine fibroids are clonal tumors containing broken genes, they are also exquisitely responsive to estradiol and progesterone. Estradiol and progesterone play an important role in regulating fibroid size and function.⁴ Estrogen stimulates uterine fibroids to increase in size. In a hypoestrogenic state, uterine fibroids decrease in size. In addition, a hypoestrogenic state results in an atrophic endometrium and thereby reduces AUB. For women with uterine fibroids and AUB, a reversible hypoestrogenic state can be induced either with a parenteral GnRH-agonist analogue (leuprolide) or an oral GnRH-antagonist (elagolix). Both leuprolide and elagolix are approved for the treatment of uterine fibroids (see below).

Surprisingly, progesterone stimulates cell division in normal uterine myocytes and fibroid cells.⁵ In the luteal phase of the menstrual cycle, uterine myocyte mitoses are more frequent than in the follicular phase. In addition, synthetic progestins appear to maintain fibroid size in a hypoestrogenic environment. In one randomized trial, women with uterine fibroids treated with leuprolide acetate plus a placebo pill for 24 weeks had a 51% reduction in uterine volume as measured by ultrasound.⁶ Women with uterine fibroids treated with leuprolide acetate plus the synthetic progestin, oral medroxyprogesterone acetate 20 mg daily, had only a 15% reduction in uterine volume.⁶ This finding suggests that synthetic progestins partially block the decrease in uterine volume that occurs in a hypoestrogenic state.

Further evidence that progesterone plays a role in fibroid biology is the observation that treatment of women with uterine fibroids with the antiprogestin ulipristal decreases fibroid size and reduces AUB.^7-9 Ulipristal was approved for the treatment of fibroids in many countries but not the United States. Reports of severe, life-threatening liver injury—some necessitating liver transplantation—among women using ulipristal prompted the European Medicines Agency (EMA) in 2020 to recommend that women stop taking ulipristal. In addition, the EMA recommended that no woman should initiate ulipristal treatment at this time.¹⁰

Continue to: Leuprolide acetate...

Leuprolide acetate

Leuprolide acetate is a peptide GnRH-agonist analogue. Initiation of leuprolide treatment stimulates gonadotropin release, but with chronic administration pituitary secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) decreases, resulting in reduced ovarian follicular activity, anovulation, and low serum concentration of estradiol and progesterone. Leuprolide treatment concomitant with iron therapy is approved by the FDA for improving red blood cell volume prior to surgery in women with fibroids, AUB, and anemia.¹¹ Among women with fibroids, AUB, and anemia, after 12 weeks of treatment, the hemoglobin concentration was ≥12 g/dL in 79% treated with leuprolide plus iron and 56% treated with iron alone.¹¹ The FDA recommends limiting preoperative leuprolide treatment to no more than 3 months. The approved leuprolide regimens are a maximum of 3 monthly injections of leuprolide 3.75 mg or a single injection of leuprolide 11.25 mg. Leuprolide treatment prior to hysterectomy surgery for uterine fibroids usually will result in a decrease in uterine size and may facilitate vaginal hysterectomy.

Elagolix plus estradiol plus norethindrone acetate (Oriahnn)

GnRH analogues cause a hypoestrogenic state resulting in adverse effects, including moderate to severe hot flashes and a reduction in bone mineral density. One approach to reducing the unwanted effects of hot flashes and decreased bone density is to combine a GnRH analogue with low-dose steroid hormone add-back therapy. Combining a GnRH analogue with low-dose steroid hormone add-back permits long-term treatment of AUB caused by fibroids, with few hot flashes and a minimal decrease in bone mineral density. The FDA recently has approved the combination of elagolix plus low-dose estradiol and norethindrone acetate (Oriahnn) for the long-term treatment of AUB caused by fibroids.

Elagolix is a nonpeptide oral GnRH antagonist that reduces pituitary secretion of LH and FSH, resulting in a decrease in ovarian follicular activity, anovulation, and low serum concentration of estradiol and progesterone. Unlike leuprolide, which causes an initial increase in LH and FSH secretion, the initiation of elagolix treatment causes an immediate and sustained reduction in LH and FSH secretion. Combining elagolix with a low dose of estradiol and norethindrone acetate reduces the side effects of hot flashes and decreased bone density. Clinical trials have reported that the combination of elagolix (300 mg) twice daily plus estradiol (1 mg) and norethindrone acetate (0.5 mg) once daily is an effective long-term treatment of AUB caused by uterine fibroids.

To study the efficacy of elagolix (alone or with estrogen-progestin add-back therapy) for the treatment of AUB caused by uterine fibroids, two identical trials were performed,¹² in which 790 women participated. The participants had a mean age of 42 years and were documented to have heavy menstrual bleeding (>80 mL blood loss per cycle) and ultrasound-diagnosed uterine fibroids. The participants were randomized to one of 3 groups:

• elagolix (300 mg twice daily) plus low-dose steroid add-back (1 mg estradiol and 0.5 mg norethindrone acetate once daily),
• elagolix 300 mg twice daily with no steroid add-back (elagolix alone), or
• placebo for 6 months.¹²

Menstrual blood loss was quantified using the alkaline hematin method on collected sanitary products. The primary endpoint was menstrual blood loss <80 mL per cycle as well as a ≥50% reduction in quantified blood loss from baseline during the final month of treatment. At 6 months, the percentage of women achieving the primary endpoint in the first trial was 84% (elagolix alone), 69% (elagolix plus add-back), and 9% (placebo). Mean changes from baseline in lumbar spine bone density were −2.95% (elagolix alone), −0.76% (elagolix plus add-back), and −0.21% (placebo). The percentage of women reporting hot flashes was 64% in the elagolix group, 20% in the elagolix plus low-dose steroid add-back group, and 9% in the placebo group. Results were similar in the second trial.¹²

The initial trials were extended to 12 months with two groups: elagolix 300 mg twice daily plus low-dose hormone add-back with 1 mg estradiol and 0.5 mg norethindrone acetate once daily (n = 218) or elagolix 300 mg twice daily (elagolix alone) (n = 98).¹³ Following 12 months of treatment, heavy menstrual bleeding was controlled in 88% and 89% of women treated with elagolix plus add-back and elagolix alone, respectively. Amenorrhea was reported by 65% of the women in the elagolix plus add-back group. Compared with baseline bone density, at the end of 12 months of treatment, bone mineral density in the lumbar spine was reduced by -1.5% and -4.8% in the women treated with elagolix plus add-back and elagolix alone, respectively. Compared with baseline bone density, at 1 year following completion of treatment, bone mineral density in the lumbar spine was reduced by -0.6% and -2.0% in the women treated with elagolix plus add-back and elagolix alone, respectively. Similar trends were observed in total hip and femoral neck bone density. During treatment with elagolix plus add-back, adverse effects were modest, including hot flushes (6%), night sweats (3.2%), headache (5.5%), and nausea (4.1%). Two women developed liver transaminase levels >3 times the upper limit of normal, resulting in one woman discontinuing treatment.¹³

Continue to: Contraindications to Oriahnn include known allergies...

Contraindications to Oriahnn include known allergies to the components of the medication (including the yellow dye tartrazine); high risk of arterial, venous thrombotic or thromboembolic disorders; pregnancy; known osteoporosis; current breast cancer or other hormonally-sensitive malignancies; known liver disease; and concurrent use of organic anion transporting polypeptide 1B1 inhibitors, which includes many HIV antiviral medications.¹⁴ Undiagnosed AUB is a contraindication, and all women prescribed Oriahnn should have endometrial sampling before initiating treatment. Oriahnn should not be used for more than 24 months due to the risk of irreversible bone loss.¹⁴ Systemic estrogen and progestin combinations, a component of Oriahnn, increases the risk for pulmonary embolism, deep vein thrombosis, stroke, and myocardial infarction, especially in women at increased risk for these events (such as women >35 years who smoke cigarettes and women with uncontrolled hypertension).¹⁴ In two studies there was a higher incidence of depression, depressed mood, and/or tearfulness in women taking Oriahnn (3%) compared with those taking a placebo (1%).¹⁴ The FDA recommends promptly evaluating women with depressive symptoms to determine the risks of initiating and continuing Oriahnn therapy. In two studies there was a higher risk of reported alopecia among women taking Oriahnn (3.5%) compared with placebo (1%).¹⁴

It should be noted that elagolix is approved for the treatment of pelvic pain caused by endometriosis at a dose of 150 mg daily for 24 months or 200 mg twice daily for 6 months. The elagolix dose for the treatment of AUB caused by fibroids is 300 mg twice daily for up to 24 months, necessitating the addition of low-dose estradiol-norethindrone add-back to reduce the frequency and severity of hot flashes and minimize the loss of bone density. Norethindrone acetate also protects the endometrium from the stimulatory effect of estradiol, reducing the risk of developing endometrial hyperplasia and cancer. Oriahnn is formulated as two different capsules. A yellow and white capsule contains elagolix 300 mg plus estradiol 1 mg and norethindrone acetate 0.5 mg to be taken in the morning, and a blue and white capsule contains elagolix 300 mg to be taken in the evening.

AUB caused by fibroids is a common problem in gyn practice

There are many procedural interventions that are effective in reducing AUB caused by fibroids. However, prior to the approval of Oriahnn there were no hormonal medications that were FDA approved for the long-term treatment of AUB caused by fibroids. Hence, Oriahnn represents an important advance in the hormonal treatment of AUB caused by fibroids and expands the treatment options available to our patients. ●

Uterine leiomyomata (fibroids) are the most common pelvic tumor diagnosed in women.¹ Women with symptomatic fibroids often report abnormal uterine bleeding (AUB) and pelvic cramping, fullness, or pain. Fibroids also may cause frequency of urination and contribute to fertility and pregnancy problems. Treatment options for the AUB caused by fibroids include, but are not limited to, hysterectomy, myomectomy, uterine artery embolization, endometrial ablation, insertion of a levonorgestrel intrauterine device, focused ultrasound surgery, radiofrequency ablation, leuprolide acetate, and elagolix plus low-dose hormone add-back (Oriahnn; AbbVie, North Chicago, Illinois).¹ Oriahnn is the most recent addition to our treatment armamentarium for fibroids and represents the first US Food and Drug Administration (FDA)-approved long-term hormonal option for AUB caused by fibroids.

Gene dysregulation contributes to fibroid development

Most uterine fibroids are clonal tumors, which develop following a somatic mutation in a precursor uterine myocyte. The somatic mutation causes gene dysregulation that stimulates cell growth resulting in a benign tumor mass. The majority of fibroids contain a mutation in one of the following 6 genes: mediator complex subunit 12 (MED12), high mobility group AT-hook (HMGA2 or HMGA1), RAD51B, fumarate hydratase (FH), collagen type IV, alpha 5 chain (COL4A5), or collagen type IV alpha 6 chain (COL4A6).²

Gene dysregulation in fibroids may arise following chromothripsis of the uterine myocyte genome

Chromothripsis is a catastrophic intracellular genetic event in which one or more chromosomes are broken and reassemble in a new nucleic acid sequence, producing a derivative chromosome that contains complex genetic rearrangements.³ Chromothripsis is believed to occur frequently in uterine myocytes. It is unknown why uterine myocytes are susceptible to chromothripsis,³ or why a catastrophic intracellular event such as chromothripsis results in preferential mutations in the 6 genes that are associated with myoma formation.

Estrogen and progesterone influence fibroid size and cell activity

Although uterine fibroids are clonal tumors containing broken genes, they are also exquisitely responsive to estradiol and progesterone. Estradiol and progesterone play an important role in regulating fibroid size and function.⁴ Estrogen stimulates uterine fibroids to increase in size. In a hypoestrogenic state, uterine fibroids decrease in size. In addition, a hypoestrogenic state results in an atrophic endometrium and thereby reduces AUB. For women with uterine fibroids and AUB, a reversible hypoestrogenic state can be induced either with a parenteral GnRH-agonist analogue (leuprolide) or an oral GnRH-antagonist (elagolix). Both leuprolide and elagolix are approved for the treatment of uterine fibroids (see below).

Surprisingly, progesterone stimulates cell division in normal uterine myocytes and fibroid cells.⁵ In the luteal phase of the menstrual cycle, uterine myocyte mitoses are more frequent than in the follicular phase. In addition, synthetic progestins appear to maintain fibroid size in a hypoestrogenic environment. In one randomized trial, women with uterine fibroids treated with leuprolide acetate plus a placebo pill for 24 weeks had a 51% reduction in uterine volume as measured by ultrasound.⁶ Women with uterine fibroids treated with leuprolide acetate plus the synthetic progestin, oral medroxyprogesterone acetate 20 mg daily, had only a 15% reduction in uterine volume.⁶ This finding suggests that synthetic progestins partially block the decrease in uterine volume that occurs in a hypoestrogenic state.

Further evidence that progesterone plays a role in fibroid biology is the observation that treatment of women with uterine fibroids with the antiprogestin ulipristal decreases fibroid size and reduces AUB.^7-9 Ulipristal was approved for the treatment of fibroids in many countries but not the United States. Reports of severe, life-threatening liver injury—some necessitating liver transplantation—among women using ulipristal prompted the European Medicines Agency (EMA) in 2020 to recommend that women stop taking ulipristal. In addition, the EMA recommended that no woman should initiate ulipristal treatment at this time.¹⁰

Continue to: Leuprolide acetate...

Leuprolide acetate

Leuprolide acetate is a peptide GnRH-agonist analogue. Initiation of leuprolide treatment stimulates gonadotropin release, but with chronic administration pituitary secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) decreases, resulting in reduced ovarian follicular activity, anovulation, and low serum concentration of estradiol and progesterone. Leuprolide treatment concomitant with iron therapy is approved by the FDA for improving red blood cell volume prior to surgery in women with fibroids, AUB, and anemia.¹¹ Among women with fibroids, AUB, and anemia, after 12 weeks of treatment, the hemoglobin concentration was ≥12 g/dL in 79% treated with leuprolide plus iron and 56% treated with iron alone.¹¹ The FDA recommends limiting preoperative leuprolide treatment to no more than 3 months. The approved leuprolide regimens are a maximum of 3 monthly injections of leuprolide 3.75 mg or a single injection of leuprolide 11.25 mg. Leuprolide treatment prior to hysterectomy surgery for uterine fibroids usually will result in a decrease in uterine size and may facilitate vaginal hysterectomy.

Elagolix plus estradiol plus norethindrone acetate (Oriahnn)

GnRH analogues cause a hypoestrogenic state resulting in adverse effects, including moderate to severe hot flashes and a reduction in bone mineral density. One approach to reducing the unwanted effects of hot flashes and decreased bone density is to combine a GnRH analogue with low-dose steroid hormone add-back therapy. Combining a GnRH analogue with low-dose steroid hormone add-back permits long-term treatment of AUB caused by fibroids, with few hot flashes and a minimal decrease in bone mineral density. The FDA recently has approved the combination of elagolix plus low-dose estradiol and norethindrone acetate (Oriahnn) for the long-term treatment of AUB caused by fibroids.

Elagolix is a nonpeptide oral GnRH antagonist that reduces pituitary secretion of LH and FSH, resulting in a decrease in ovarian follicular activity, anovulation, and low serum concentration of estradiol and progesterone. Unlike leuprolide, which causes an initial increase in LH and FSH secretion, the initiation of elagolix treatment causes an immediate and sustained reduction in LH and FSH secretion. Combining elagolix with a low dose of estradiol and norethindrone acetate reduces the side effects of hot flashes and decreased bone density. Clinical trials have reported that the combination of elagolix (300 mg) twice daily plus estradiol (1 mg) and norethindrone acetate (0.5 mg) once daily is an effective long-term treatment of AUB caused by uterine fibroids.

To study the efficacy of elagolix (alone or with estrogen-progestin add-back therapy) for the treatment of AUB caused by uterine fibroids, two identical trials were performed,¹² in which 790 women participated. The participants had a mean age of 42 years and were documented to have heavy menstrual bleeding (>80 mL blood loss per cycle) and ultrasound-diagnosed uterine fibroids. The participants were randomized to one of 3 groups:

• elagolix (300 mg twice daily) plus low-dose steroid add-back (1 mg estradiol and 0.5 mg norethindrone acetate once daily),
• elagolix 300 mg twice daily with no steroid add-back (elagolix alone), or
• placebo for 6 months.¹²

Menstrual blood loss was quantified using the alkaline hematin method on collected sanitary products. The primary endpoint was menstrual blood loss <80 mL per cycle as well as a ≥50% reduction in quantified blood loss from baseline during the final month of treatment. At 6 months, the percentage of women achieving the primary endpoint in the first trial was 84% (elagolix alone), 69% (elagolix plus add-back), and 9% (placebo). Mean changes from baseline in lumbar spine bone density were −2.95% (elagolix alone), −0.76% (elagolix plus add-back), and −0.21% (placebo). The percentage of women reporting hot flashes was 64% in the elagolix group, 20% in the elagolix plus low-dose steroid add-back group, and 9% in the placebo group. Results were similar in the second trial.¹²

The initial trials were extended to 12 months with two groups: elagolix 300 mg twice daily plus low-dose hormone add-back with 1 mg estradiol and 0.5 mg norethindrone acetate once daily (n = 218) or elagolix 300 mg twice daily (elagolix alone) (n = 98).¹³ Following 12 months of treatment, heavy menstrual bleeding was controlled in 88% and 89% of women treated with elagolix plus add-back and elagolix alone, respectively. Amenorrhea was reported by 65% of the women in the elagolix plus add-back group. Compared with baseline bone density, at the end of 12 months of treatment, bone mineral density in the lumbar spine was reduced by -1.5% and -4.8% in the women treated with elagolix plus add-back and elagolix alone, respectively. Compared with baseline bone density, at 1 year following completion of treatment, bone mineral density in the lumbar spine was reduced by -0.6% and -2.0% in the women treated with elagolix plus add-back and elagolix alone, respectively. Similar trends were observed in total hip and femoral neck bone density. During treatment with elagolix plus add-back, adverse effects were modest, including hot flushes (6%), night sweats (3.2%), headache (5.5%), and nausea (4.1%). Two women developed liver transaminase levels >3 times the upper limit of normal, resulting in one woman discontinuing treatment.¹³

Continue to: Contraindications to Oriahnn include known allergies...

Contraindications to Oriahnn include known allergies to the components of the medication (including the yellow dye tartrazine); high risk of arterial, venous thrombotic or thromboembolic disorders; pregnancy; known osteoporosis; current breast cancer or other hormonally-sensitive malignancies; known liver disease; and concurrent use of organic anion transporting polypeptide 1B1 inhibitors, which includes many HIV antiviral medications.¹⁴ Undiagnosed AUB is a contraindication, and all women prescribed Oriahnn should have endometrial sampling before initiating treatment. Oriahnn should not be used for more than 24 months due to the risk of irreversible bone loss.¹⁴ Systemic estrogen and progestin combinations, a component of Oriahnn, increases the risk for pulmonary embolism, deep vein thrombosis, stroke, and myocardial infarction, especially in women at increased risk for these events (such as women >35 years who smoke cigarettes and women with uncontrolled hypertension).¹⁴ In two studies there was a higher incidence of depression, depressed mood, and/or tearfulness in women taking Oriahnn (3%) compared with those taking a placebo (1%).¹⁴ The FDA recommends promptly evaluating women with depressive symptoms to determine the risks of initiating and continuing Oriahnn therapy. In two studies there was a higher risk of reported alopecia among women taking Oriahnn (3.5%) compared with placebo (1%).¹⁴

It should be noted that elagolix is approved for the treatment of pelvic pain caused by endometriosis at a dose of 150 mg daily for 24 months or 200 mg twice daily for 6 months. The elagolix dose for the treatment of AUB caused by fibroids is 300 mg twice daily for up to 24 months, necessitating the addition of low-dose estradiol-norethindrone add-back to reduce the frequency and severity of hot flashes and minimize the loss of bone density. Norethindrone acetate also protects the endometrium from the stimulatory effect of estradiol, reducing the risk of developing endometrial hyperplasia and cancer. Oriahnn is formulated as two different capsules. A yellow and white capsule contains elagolix 300 mg plus estradiol 1 mg and norethindrone acetate 0.5 mg to be taken in the morning, and a blue and white capsule contains elagolix 300 mg to be taken in the evening.

AUB caused by fibroids is a common problem in gyn practice

There are many procedural interventions that are effective in reducing AUB caused by fibroids. However, prior to the approval of Oriahnn there were no hormonal medications that were FDA approved for the long-term treatment of AUB caused by fibroids. Hence, Oriahnn represents an important advance in the hormonal treatment of AUB caused by fibroids and expands the treatment options available to our patients. ●

Uterine leiomyomata (fibroids) are the most common pelvic tumor diagnosed in women.¹ Women with symptomatic fibroids often report abnormal uterine bleeding (AUB) and pelvic cramping, fullness, or pain. Fibroids also may cause frequency of urination and contribute to fertility and pregnancy problems. Treatment options for the AUB caused by fibroids include, but are not limited to, hysterectomy, myomectomy, uterine artery embolization, endometrial ablation, insertion of a levonorgestrel intrauterine device, focused ultrasound surgery, radiofrequency ablation, leuprolide acetate, and elagolix plus low-dose hormone add-back (Oriahnn; AbbVie, North Chicago, Illinois).¹ Oriahnn is the most recent addition to our treatment armamentarium for fibroids and represents the first US Food and Drug Administration (FDA)-approved long-term hormonal option for AUB caused by fibroids.

Gene dysregulation contributes to fibroid development

Most uterine fibroids are clonal tumors, which develop following a somatic mutation in a precursor uterine myocyte. The somatic mutation causes gene dysregulation that stimulates cell growth resulting in a benign tumor mass. The majority of fibroids contain a mutation in one of the following 6 genes: mediator complex subunit 12 (MED12), high mobility group AT-hook (HMGA2 or HMGA1), RAD51B, fumarate hydratase (FH), collagen type IV, alpha 5 chain (COL4A5), or collagen type IV alpha 6 chain (COL4A6).²

Gene dysregulation in fibroids may arise following chromothripsis of the uterine myocyte genome

Chromothripsis is a catastrophic intracellular genetic event in which one or more chromosomes are broken and reassemble in a new nucleic acid sequence, producing a derivative chromosome that contains complex genetic rearrangements.³ Chromothripsis is believed to occur frequently in uterine myocytes. It is unknown why uterine myocytes are susceptible to chromothripsis,³ or why a catastrophic intracellular event such as chromothripsis results in preferential mutations in the 6 genes that are associated with myoma formation.

Estrogen and progesterone influence fibroid size and cell activity

Although uterine fibroids are clonal tumors containing broken genes, they are also exquisitely responsive to estradiol and progesterone. Estradiol and progesterone play an important role in regulating fibroid size and function.⁴ Estrogen stimulates uterine fibroids to increase in size. In a hypoestrogenic state, uterine fibroids decrease in size. In addition, a hypoestrogenic state results in an atrophic endometrium and thereby reduces AUB. For women with uterine fibroids and AUB, a reversible hypoestrogenic state can be induced either with a parenteral GnRH-agonist analogue (leuprolide) or an oral GnRH-antagonist (elagolix). Both leuprolide and elagolix are approved for the treatment of uterine fibroids (see below).

Surprisingly, progesterone stimulates cell division in normal uterine myocytes and fibroid cells.⁵ In the luteal phase of the menstrual cycle, uterine myocyte mitoses are more frequent than in the follicular phase. In addition, synthetic progestins appear to maintain fibroid size in a hypoestrogenic environment. In one randomized trial, women with uterine fibroids treated with leuprolide acetate plus a placebo pill for 24 weeks had a 51% reduction in uterine volume as measured by ultrasound.⁶ Women with uterine fibroids treated with leuprolide acetate plus the synthetic progestin, oral medroxyprogesterone acetate 20 mg daily, had only a 15% reduction in uterine volume.⁶ This finding suggests that synthetic progestins partially block the decrease in uterine volume that occurs in a hypoestrogenic state.

Further evidence that progesterone plays a role in fibroid biology is the observation that treatment of women with uterine fibroids with the antiprogestin ulipristal decreases fibroid size and reduces AUB.^7-9 Ulipristal was approved for the treatment of fibroids in many countries but not the United States. Reports of severe, life-threatening liver injury—some necessitating liver transplantation—among women using ulipristal prompted the European Medicines Agency (EMA) in 2020 to recommend that women stop taking ulipristal. In addition, the EMA recommended that no woman should initiate ulipristal treatment at this time.¹⁰

Continue to: Leuprolide acetate...

Leuprolide acetate

Leuprolide acetate is a peptide GnRH-agonist analogue. Initiation of leuprolide treatment stimulates gonadotropin release, but with chronic administration pituitary secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) decreases, resulting in reduced ovarian follicular activity, anovulation, and low serum concentration of estradiol and progesterone. Leuprolide treatment concomitant with iron therapy is approved by the FDA for improving red blood cell volume prior to surgery in women with fibroids, AUB, and anemia.¹¹ Among women with fibroids, AUB, and anemia, after 12 weeks of treatment, the hemoglobin concentration was ≥12 g/dL in 79% treated with leuprolide plus iron and 56% treated with iron alone.¹¹ The FDA recommends limiting preoperative leuprolide treatment to no more than 3 months. The approved leuprolide regimens are a maximum of 3 monthly injections of leuprolide 3.75 mg or a single injection of leuprolide 11.25 mg. Leuprolide treatment prior to hysterectomy surgery for uterine fibroids usually will result in a decrease in uterine size and may facilitate vaginal hysterectomy.

Elagolix plus estradiol plus norethindrone acetate (Oriahnn)

GnRH analogues cause a hypoestrogenic state resulting in adverse effects, including moderate to severe hot flashes and a reduction in bone mineral density. One approach to reducing the unwanted effects of hot flashes and decreased bone density is to combine a GnRH analogue with low-dose steroid hormone add-back therapy. Combining a GnRH analogue with low-dose steroid hormone add-back permits long-term treatment of AUB caused by fibroids, with few hot flashes and a minimal decrease in bone mineral density. The FDA recently has approved the combination of elagolix plus low-dose estradiol and norethindrone acetate (Oriahnn) for the long-term treatment of AUB caused by fibroids.

Elagolix is a nonpeptide oral GnRH antagonist that reduces pituitary secretion of LH and FSH, resulting in a decrease in ovarian follicular activity, anovulation, and low serum concentration of estradiol and progesterone. Unlike leuprolide, which causes an initial increase in LH and FSH secretion, the initiation of elagolix treatment causes an immediate and sustained reduction in LH and FSH secretion. Combining elagolix with a low dose of estradiol and norethindrone acetate reduces the side effects of hot flashes and decreased bone density. Clinical trials have reported that the combination of elagolix (300 mg) twice daily plus estradiol (1 mg) and norethindrone acetate (0.5 mg) once daily is an effective long-term treatment of AUB caused by uterine fibroids.

To study the efficacy of elagolix (alone or with estrogen-progestin add-back therapy) for the treatment of AUB caused by uterine fibroids, two identical trials were performed,¹² in which 790 women participated. The participants had a mean age of 42 years and were documented to have heavy menstrual bleeding (>80 mL blood loss per cycle) and ultrasound-diagnosed uterine fibroids. The participants were randomized to one of 3 groups:

• elagolix (300 mg twice daily) plus low-dose steroid add-back (1 mg estradiol and 0.5 mg norethindrone acetate once daily),
• elagolix 300 mg twice daily with no steroid add-back (elagolix alone), or
• placebo for 6 months.¹²

Menstrual blood loss was quantified using the alkaline hematin method on collected sanitary products. The primary endpoint was menstrual blood loss <80 mL per cycle as well as a ≥50% reduction in quantified blood loss from baseline during the final month of treatment. At 6 months, the percentage of women achieving the primary endpoint in the first trial was 84% (elagolix alone), 69% (elagolix plus add-back), and 9% (placebo). Mean changes from baseline in lumbar spine bone density were −2.95% (elagolix alone), −0.76% (elagolix plus add-back), and −0.21% (placebo). The percentage of women reporting hot flashes was 64% in the elagolix group, 20% in the elagolix plus low-dose steroid add-back group, and 9% in the placebo group. Results were similar in the second trial.¹²

The initial trials were extended to 12 months with two groups: elagolix 300 mg twice daily plus low-dose hormone add-back with 1 mg estradiol and 0.5 mg norethindrone acetate once daily (n = 218) or elagolix 300 mg twice daily (elagolix alone) (n = 98).¹³ Following 12 months of treatment, heavy menstrual bleeding was controlled in 88% and 89% of women treated with elagolix plus add-back and elagolix alone, respectively. Amenorrhea was reported by 65% of the women in the elagolix plus add-back group. Compared with baseline bone density, at the end of 12 months of treatment, bone mineral density in the lumbar spine was reduced by -1.5% and -4.8% in the women treated with elagolix plus add-back and elagolix alone, respectively. Compared with baseline bone density, at 1 year following completion of treatment, bone mineral density in the lumbar spine was reduced by -0.6% and -2.0% in the women treated with elagolix plus add-back and elagolix alone, respectively. Similar trends were observed in total hip and femoral neck bone density. During treatment with elagolix plus add-back, adverse effects were modest, including hot flushes (6%), night sweats (3.2%), headache (5.5%), and nausea (4.1%). Two women developed liver transaminase levels >3 times the upper limit of normal, resulting in one woman discontinuing treatment.¹³

Continue to: Contraindications to Oriahnn include known allergies...

Contraindications to Oriahnn include known allergies to the components of the medication (including the yellow dye tartrazine); high risk of arterial, venous thrombotic or thromboembolic disorders; pregnancy; known osteoporosis; current breast cancer or other hormonally-sensitive malignancies; known liver disease; and concurrent use of organic anion transporting polypeptide 1B1 inhibitors, which includes many HIV antiviral medications.¹⁴ Undiagnosed AUB is a contraindication, and all women prescribed Oriahnn should have endometrial sampling before initiating treatment. Oriahnn should not be used for more than 24 months due to the risk of irreversible bone loss.¹⁴ Systemic estrogen and progestin combinations, a component of Oriahnn, increases the risk for pulmonary embolism, deep vein thrombosis, stroke, and myocardial infarction, especially in women at increased risk for these events (such as women >35 years who smoke cigarettes and women with uncontrolled hypertension).¹⁴ In two studies there was a higher incidence of depression, depressed mood, and/or tearfulness in women taking Oriahnn (3%) compared with those taking a placebo (1%).¹⁴ The FDA recommends promptly evaluating women with depressive symptoms to determine the risks of initiating and continuing Oriahnn therapy. In two studies there was a higher risk of reported alopecia among women taking Oriahnn (3.5%) compared with placebo (1%).¹⁴

It should be noted that elagolix is approved for the treatment of pelvic pain caused by endometriosis at a dose of 150 mg daily for 24 months or 200 mg twice daily for 6 months. The elagolix dose for the treatment of AUB caused by fibroids is 300 mg twice daily for up to 24 months, necessitating the addition of low-dose estradiol-norethindrone add-back to reduce the frequency and severity of hot flashes and minimize the loss of bone density. Norethindrone acetate also protects the endometrium from the stimulatory effect of estradiol, reducing the risk of developing endometrial hyperplasia and cancer. Oriahnn is formulated as two different capsules. A yellow and white capsule contains elagolix 300 mg plus estradiol 1 mg and norethindrone acetate 0.5 mg to be taken in the morning, and a blue and white capsule contains elagolix 300 mg to be taken in the evening.

AUB caused by fibroids is a common problem in gyn practice

There are many procedural interventions that are effective in reducing AUB caused by fibroids. However, prior to the approval of Oriahnn there were no hormonal medications that were FDA approved for the long-term treatment of AUB caused by fibroids. Hence, Oriahnn represents an important advance in the hormonal treatment of AUB caused by fibroids and expands the treatment options available to our patients. ●

August was National Immunization Awareness Month. ... just in time to address the precipitous drop in immunization delivered during the early months of the pandemic.

FatCamera/Getty Images

In May, the Centers for Disease Control and Prevention reported substantial reductions in vaccine doses ordered through the Vaccines for Children program after the declaration of national emergency because of COVID-19 on March 13. Approximately 2.5 million fewer doses of routine, noninfluenza vaccines were administered between Jan. 6 and April 2020, compared with a similar period last year (MMWR Morb Mortal Wkly Rep. 2020 May 15;69[19]:591-3). Declines in immunization rates were echoed by states and municipalities across the United States. Last month, the health system in which I work reported 40,000 children behind on at least one vaccine.

We all know that, when immunization rates drop, outbreaks of vaccine-preventable diseases follow. In order to avert another public health crisis, we need action as well as awareness to catch up with childhood immunizations, and that is going to take more than a single month.
 

Identify patients who’ve missed vaccinations

Simply being open and ready to vaccinate is not enough. The Centers for Disease Control and Prevention urges providers to identify patients who have missed vaccines, and call them to schedule in-person visits. Proactively let parents know about strategies implemented in your office to ensure a safe environment.

Pediatricians are accustomed to an influx of patients in the summer, as parents make sure their children have all of the vaccines required for school attendance. As noted in a Washington Post article from Aug. 4, 2020, schools have traditionally served as a backstop for immunization rates. But as many school districts opt to take education online this fall, the implications for vaccine requirements are unclear. District of Columbia public schools continue to require immunization for virtual school attendance, but it is not clear how easily this can be enforced. To read about how other school districts have chosen to address – or not address – immunization requirements for school, visit the the Immunization Action Coalition’s Repository of Resources for Maintaining Immunization during the COVID-19 Pandemic. The repository links to international, national, and state-level policies and guidance and advocacy materials, including talking points, webinars, press releases, media articles from around the United States and social media posts, as well as telehealth resources.
 

Get some inspiration to talk about vaccination

Need a little inspiration for talking to parents about vaccines? Check out the CDC’s #HowIRecommend video series. These are short videos, most under a minute in length, that explain the importance of vaccination, how to effectively address questions from parents about vaccine safety, and how clinicians routinely recommend same day vaccination to their patients. These videos are part of the CDC’s National Immunization Awareness Month (NIAM) toolkit for communication with health care professionals. A companion toolkit for communicating with parents and patients contains sample social media messages with graphics, along with educational resources to share with parents.

The “Comprehensive Vaccine Education Program – From Training to Practice,” a free online program offered by the Pediatric Infectious Diseases Society, takes a deeper dive into strategies to combat vaccine misinformation and address vaccine hesitancy. Available modules cover vaccine fundamentals, vaccine safety, clinical manifestations of vaccine-preventable diseases, and communication skills that lead to more effective conversations with patients and parents. The curriculum also includes the newest edition of The Vaccine Handbook app, a comprehensive source of practical information for vaccine providers.
 

Educate young children about vaccines

Don’t leave young children out of the conversation. Vax-Force is a children’s book that explores how vaccination works inside the human body. Dr. Vaxson the pediatrician explains how trusted doctors and scientists made Vicky the Vaccine. Her mission is to tell Willy the White Blood Cell and his Antibuddies how to find and fight bad-guy germs like measles, tetanus, and polio. The book was written by Kelsey Rowe, MD, while she was a medical student at Saint Louis University School of Medicine. Dr. Rowe, now a pediatric resident, notes, “In a world where anti-vaccination rhetoric threatens the health of our global community, this book’s mission is to teach children and adults alike that getting vaccinations is a safe, effective, and even exciting thing to do.” The book is available for purchase at https://www.vax-force.com/, and a small part of every sale is donated to Unicef USA.
 

Consider vaccination advocacy in your communities

Vaccinate Your Family, a national, nonprofit organization dedicated to protecting people of all ages from vaccine-preventable diseases, suggests that health care providers need to take an active role in raising immunization rates, not just in their own practices, but in their communities. One way to do this is to submit an opinion piece or letter to the editor to a local newspaper describing why it’s important for parents to make sure their child’s immunizations are current. Those who have never written an opinion-editorial should look at the guidance developed by Voices for Vaccines.
 

How are we doing?

Early data suggest a rebound in immunization rates in May and June, but that is unlikely to close the gap created by disruptions in health care delivery earlier in the year. Collectively, we need to set ambitious goals. Are we just trying to reach prepandemic immunization levels? In Kentucky, where I practice, only 71% of kids aged 19-45 months had received all doses of seven routinely recommended vaccines (≥4 DTaP doses, ≥3 polio doses, ≥1 MMR dose, Hib full series, ≥3 HepB doses, ≥1 varicella dose, and ≥4 PCV doses) based on 2017 National Immunization Survey data. The Healthy People 2020 target goal is 80%. Only 55% of Kentucky girls aged 13-17 years received at least one dose of HPV vaccine, and rates in boys were even lower. Flu vaccine coverage in children 6 months to 17 years also was 55%. The status quo sets the bar too low. To see how your state is doing, check out the interactive map developed by the American Academy of Pediatrics.

Are we attempting to avoid disaster or can we seize the opportunity to protect more children than ever from vaccine-preventable diseases? The latter would really be something to celebrate.
 

Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at [email protected].

August was National Immunization Awareness Month. ... just in time to address the precipitous drop in immunization delivered during the early months of the pandemic.

FatCamera/Getty Images

In May, the Centers for Disease Control and Prevention reported substantial reductions in vaccine doses ordered through the Vaccines for Children program after the declaration of national emergency because of COVID-19 on March 13. Approximately 2.5 million fewer doses of routine, noninfluenza vaccines were administered between Jan. 6 and April 2020, compared with a similar period last year (MMWR Morb Mortal Wkly Rep. 2020 May 15;69[19]:591-3). Declines in immunization rates were echoed by states and municipalities across the United States. Last month, the health system in which I work reported 40,000 children behind on at least one vaccine.

We all know that, when immunization rates drop, outbreaks of vaccine-preventable diseases follow. In order to avert another public health crisis, we need action as well as awareness to catch up with childhood immunizations, and that is going to take more than a single month.
 

Identify patients who’ve missed vaccinations

Simply being open and ready to vaccinate is not enough. The Centers for Disease Control and Prevention urges providers to identify patients who have missed vaccines, and call them to schedule in-person visits. Proactively let parents know about strategies implemented in your office to ensure a safe environment.

Pediatricians are accustomed to an influx of patients in the summer, as parents make sure their children have all of the vaccines required for school attendance. As noted in a Washington Post article from Aug. 4, 2020, schools have traditionally served as a backstop for immunization rates. But as many school districts opt to take education online this fall, the implications for vaccine requirements are unclear. District of Columbia public schools continue to require immunization for virtual school attendance, but it is not clear how easily this can be enforced. To read about how other school districts have chosen to address – or not address – immunization requirements for school, visit the the Immunization Action Coalition’s Repository of Resources for Maintaining Immunization during the COVID-19 Pandemic. The repository links to international, national, and state-level policies and guidance and advocacy materials, including talking points, webinars, press releases, media articles from around the United States and social media posts, as well as telehealth resources.
 

Get some inspiration to talk about vaccination

Need a little inspiration for talking to parents about vaccines? Check out the CDC’s #HowIRecommend video series. These are short videos, most under a minute in length, that explain the importance of vaccination, how to effectively address questions from parents about vaccine safety, and how clinicians routinely recommend same day vaccination to their patients. These videos are part of the CDC’s National Immunization Awareness Month (NIAM) toolkit for communication with health care professionals. A companion toolkit for communicating with parents and patients contains sample social media messages with graphics, along with educational resources to share with parents.

The “Comprehensive Vaccine Education Program – From Training to Practice,” a free online program offered by the Pediatric Infectious Diseases Society, takes a deeper dive into strategies to combat vaccine misinformation and address vaccine hesitancy. Available modules cover vaccine fundamentals, vaccine safety, clinical manifestations of vaccine-preventable diseases, and communication skills that lead to more effective conversations with patients and parents. The curriculum also includes the newest edition of The Vaccine Handbook app, a comprehensive source of practical information for vaccine providers.
 

Educate young children about vaccines

Don’t leave young children out of the conversation. Vax-Force is a children’s book that explores how vaccination works inside the human body. Dr. Vaxson the pediatrician explains how trusted doctors and scientists made Vicky the Vaccine. Her mission is to tell Willy the White Blood Cell and his Antibuddies how to find and fight bad-guy germs like measles, tetanus, and polio. The book was written by Kelsey Rowe, MD, while she was a medical student at Saint Louis University School of Medicine. Dr. Rowe, now a pediatric resident, notes, “In a world where anti-vaccination rhetoric threatens the health of our global community, this book’s mission is to teach children and adults alike that getting vaccinations is a safe, effective, and even exciting thing to do.” The book is available for purchase at https://www.vax-force.com/, and a small part of every sale is donated to Unicef USA.
 

Consider vaccination advocacy in your communities

Vaccinate Your Family, a national, nonprofit organization dedicated to protecting people of all ages from vaccine-preventable diseases, suggests that health care providers need to take an active role in raising immunization rates, not just in their own practices, but in their communities. One way to do this is to submit an opinion piece or letter to the editor to a local newspaper describing why it’s important for parents to make sure their child’s immunizations are current. Those who have never written an opinion-editorial should look at the guidance developed by Voices for Vaccines.
 

How are we doing?

Early data suggest a rebound in immunization rates in May and June, but that is unlikely to close the gap created by disruptions in health care delivery earlier in the year. Collectively, we need to set ambitious goals. Are we just trying to reach prepandemic immunization levels? In Kentucky, where I practice, only 71% of kids aged 19-45 months had received all doses of seven routinely recommended vaccines (≥4 DTaP doses, ≥3 polio doses, ≥1 MMR dose, Hib full series, ≥3 HepB doses, ≥1 varicella dose, and ≥4 PCV doses) based on 2017 National Immunization Survey data. The Healthy People 2020 target goal is 80%. Only 55% of Kentucky girls aged 13-17 years received at least one dose of HPV vaccine, and rates in boys were even lower. Flu vaccine coverage in children 6 months to 17 years also was 55%. The status quo sets the bar too low. To see how your state is doing, check out the interactive map developed by the American Academy of Pediatrics.

Are we attempting to avoid disaster or can we seize the opportunity to protect more children than ever from vaccine-preventable diseases? The latter would really be something to celebrate.
 

Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at [email protected].

August was National Immunization Awareness Month. ... just in time to address the precipitous drop in immunization delivered during the early months of the pandemic.

FatCamera/Getty Images

In May, the Centers for Disease Control and Prevention reported substantial reductions in vaccine doses ordered through the Vaccines for Children program after the declaration of national emergency because of COVID-19 on March 13. Approximately 2.5 million fewer doses of routine, noninfluenza vaccines were administered between Jan. 6 and April 2020, compared with a similar period last year (MMWR Morb Mortal Wkly Rep. 2020 May 15;69[19]:591-3). Declines in immunization rates were echoed by states and municipalities across the United States. Last month, the health system in which I work reported 40,000 children behind on at least one vaccine.

We all know that, when immunization rates drop, outbreaks of vaccine-preventable diseases follow. In order to avert another public health crisis, we need action as well as awareness to catch up with childhood immunizations, and that is going to take more than a single month.
 

Identify patients who’ve missed vaccinations

Simply being open and ready to vaccinate is not enough. The Centers for Disease Control and Prevention urges providers to identify patients who have missed vaccines, and call them to schedule in-person visits. Proactively let parents know about strategies implemented in your office to ensure a safe environment.

Pediatricians are accustomed to an influx of patients in the summer, as parents make sure their children have all of the vaccines required for school attendance. As noted in a Washington Post article from Aug. 4, 2020, schools have traditionally served as a backstop for immunization rates. But as many school districts opt to take education online this fall, the implications for vaccine requirements are unclear. District of Columbia public schools continue to require immunization for virtual school attendance, but it is not clear how easily this can be enforced. To read about how other school districts have chosen to address – or not address – immunization requirements for school, visit the the Immunization Action Coalition’s Repository of Resources for Maintaining Immunization during the COVID-19 Pandemic. The repository links to international, national, and state-level policies and guidance and advocacy materials, including talking points, webinars, press releases, media articles from around the United States and social media posts, as well as telehealth resources.
 

Get some inspiration to talk about vaccination

Need a little inspiration for talking to parents about vaccines? Check out the CDC’s #HowIRecommend video series. These are short videos, most under a minute in length, that explain the importance of vaccination, how to effectively address questions from parents about vaccine safety, and how clinicians routinely recommend same day vaccination to their patients. These videos are part of the CDC’s National Immunization Awareness Month (NIAM) toolkit for communication with health care professionals. A companion toolkit for communicating with parents and patients contains sample social media messages with graphics, along with educational resources to share with parents.

The “Comprehensive Vaccine Education Program – From Training to Practice,” a free online program offered by the Pediatric Infectious Diseases Society, takes a deeper dive into strategies to combat vaccine misinformation and address vaccine hesitancy. Available modules cover vaccine fundamentals, vaccine safety, clinical manifestations of vaccine-preventable diseases, and communication skills that lead to more effective conversations with patients and parents. The curriculum also includes the newest edition of The Vaccine Handbook app, a comprehensive source of practical information for vaccine providers.
 

Educate young children about vaccines

Don’t leave young children out of the conversation. Vax-Force is a children’s book that explores how vaccination works inside the human body. Dr. Vaxson the pediatrician explains how trusted doctors and scientists made Vicky the Vaccine. Her mission is to tell Willy the White Blood Cell and his Antibuddies how to find and fight bad-guy germs like measles, tetanus, and polio. The book was written by Kelsey Rowe, MD, while she was a medical student at Saint Louis University School of Medicine. Dr. Rowe, now a pediatric resident, notes, “In a world where anti-vaccination rhetoric threatens the health of our global community, this book’s mission is to teach children and adults alike that getting vaccinations is a safe, effective, and even exciting thing to do.” The book is available for purchase at https://www.vax-force.com/, and a small part of every sale is donated to Unicef USA.
 

Consider vaccination advocacy in your communities

Vaccinate Your Family, a national, nonprofit organization dedicated to protecting people of all ages from vaccine-preventable diseases, suggests that health care providers need to take an active role in raising immunization rates, not just in their own practices, but in their communities. One way to do this is to submit an opinion piece or letter to the editor to a local newspaper describing why it’s important for parents to make sure their child’s immunizations are current. Those who have never written an opinion-editorial should look at the guidance developed by Voices for Vaccines.
 

How are we doing?

Early data suggest a rebound in immunization rates in May and June, but that is unlikely to close the gap created by disruptions in health care delivery earlier in the year. Collectively, we need to set ambitious goals. Are we just trying to reach prepandemic immunization levels? In Kentucky, where I practice, only 71% of kids aged 19-45 months had received all doses of seven routinely recommended vaccines (≥4 DTaP doses, ≥3 polio doses, ≥1 MMR dose, Hib full series, ≥3 HepB doses, ≥1 varicella dose, and ≥4 PCV doses) based on 2017 National Immunization Survey data. The Healthy People 2020 target goal is 80%. Only 55% of Kentucky girls aged 13-17 years received at least one dose of HPV vaccine, and rates in boys were even lower. Flu vaccine coverage in children 6 months to 17 years also was 55%. The status quo sets the bar too low. To see how your state is doing, check out the interactive map developed by the American Academy of Pediatrics.

Are we attempting to avoid disaster or can we seize the opportunity to protect more children than ever from vaccine-preventable diseases? The latter would really be something to celebrate.
 

Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at [email protected].