To the Editor:

An 81-year-old man presented with a nodular polypoid lesion that developed on a flat lesion on the back of 2 years’ duration. The lesion grew progressively over the course of 3 months prior to presentation. The patient had a history of melanoma in situ on the forehead that was treated with conventional surgery with clear surgical margins 6 years prior to the current presentation.

On physical examination the patient had a 4×2-cm ulcerated polypoid lesion on the back. The lesion was pink with a pigmented base. Additionally, 2 pink papules with superficial telangiectases were observed around the main lesion (Figure 1).

The gross section showed an exophytic tumor largely growing above the skin surface (Figure 2). Histopathologic analysis revealed an ulcerated lesion consisting of confluent nest and sheets of epithelioid and spindle atypical cells with numerous mitotic figures and necrotic foci (Figure 3). The thickness of the lesion was 2200 µm, and the mitotic count was 28 mitoses/mm². There also was peritumoral vascular invasion and satellite metastasis within the perilesional hypodermis measuring 0.4 mm. Immunohistochemistry staining for S-100, human melanoma black 45 (HMB-45)(Figure 4), and Melan-A was positive in neoplastic cells.

The dissemination study revealed multiple mediastinal and axillary lymphadenopathies and lesions with metastatic appearance in the brain, liver, pancreas, and muscle, together with peritoneal carcinomatosis. The patient was lost to follow-up and did not follow coadjuvant therapy with interferon alfa.

Polypoid melanoma initially was described as a type of melanoma characterized by an exophytic growth in which most of the tumor is located on the cutaneous surface, together with ulceration.¹ It usually occurs in patients aged 20 to 39 years,² and the reported incidence ranges from 1.9% to 43.3%.¹ It more commonly affects mucosae, including the upper respiratory tract, esophagus, and vagina. Polypoid melanoma has a rapid progression and a poor prognosis.³ Polypoid melanoma involving the skin primarily affects the back and has a 5-year survival rate of 32% to 42%.⁴ Poor prognosis has been attributed to the high risk for vascular embolization under the lesion.⁵ Histologically, there is marked cell atypia with nuclear and cellular pleomorphism and a high mitotic count. The tumor rarely involves the reticular dermis.^1,2

Polypoid melanomas are rare; however, reported frequency rates cover a wide range. These frequency rates may be due to the definition of polypoid melanoma used by the pathologist issuing the report. One of the most accepted definitions at present is a pigmented macule that progresses in months with a rapid vertical growth, invading the epidermis and the papillary dermis.² The differential diagnosis includes pyogenic granuloma, squamous cell carcinoma, basal cell carcinoma, soft tissue sarcomas, and hemangioma.

Although our patient had a history of melanoma and the polypoid lesion developed from a flat lesion, he was late to seek medical care. The diagnosis of melanoma is made on increasingly smaller lesions with better prognosis, but there still are reports of larger melanomas. This case highlights the role dermatologists serve in the education of patients on their diagnoses and risk factors so that we may be able to diagnose non–life-threatening small lesions. It is important to remember this morphologic variety of melanoma and highlight its rapid progression and poor prognosis.

To the Editor:

An 81-year-old man presented with a nodular polypoid lesion that developed on a flat lesion on the back of 2 years’ duration. The lesion grew progressively over the course of 3 months prior to presentation. The patient had a history of melanoma in situ on the forehead that was treated with conventional surgery with clear surgical margins 6 years prior to the current presentation.

On physical examination the patient had a 4×2-cm ulcerated polypoid lesion on the back. The lesion was pink with a pigmented base. Additionally, 2 pink papules with superficial telangiectases were observed around the main lesion (Figure 1).

The gross section showed an exophytic tumor largely growing above the skin surface (Figure 2). Histopathologic analysis revealed an ulcerated lesion consisting of confluent nest and sheets of epithelioid and spindle atypical cells with numerous mitotic figures and necrotic foci (Figure 3). The thickness of the lesion was 2200 µm, and the mitotic count was 28 mitoses/mm². There also was peritumoral vascular invasion and satellite metastasis within the perilesional hypodermis measuring 0.4 mm. Immunohistochemistry staining for S-100, human melanoma black 45 (HMB-45)(Figure 4), and Melan-A was positive in neoplastic cells.

The dissemination study revealed multiple mediastinal and axillary lymphadenopathies and lesions with metastatic appearance in the brain, liver, pancreas, and muscle, together with peritoneal carcinomatosis. The patient was lost to follow-up and did not follow coadjuvant therapy with interferon alfa.

Polypoid melanoma initially was described as a type of melanoma characterized by an exophytic growth in which most of the tumor is located on the cutaneous surface, together with ulceration.¹ It usually occurs in patients aged 20 to 39 years,² and the reported incidence ranges from 1.9% to 43.3%.¹ It more commonly affects mucosae, including the upper respiratory tract, esophagus, and vagina. Polypoid melanoma has a rapid progression and a poor prognosis.³ Polypoid melanoma involving the skin primarily affects the back and has a 5-year survival rate of 32% to 42%.⁴ Poor prognosis has been attributed to the high risk for vascular embolization under the lesion.⁵ Histologically, there is marked cell atypia with nuclear and cellular pleomorphism and a high mitotic count. The tumor rarely involves the reticular dermis.^1,2

Polypoid melanomas are rare; however, reported frequency rates cover a wide range. These frequency rates may be due to the definition of polypoid melanoma used by the pathologist issuing the report. One of the most accepted definitions at present is a pigmented macule that progresses in months with a rapid vertical growth, invading the epidermis and the papillary dermis.² The differential diagnosis includes pyogenic granuloma, squamous cell carcinoma, basal cell carcinoma, soft tissue sarcomas, and hemangioma.

Although our patient had a history of melanoma and the polypoid lesion developed from a flat lesion, he was late to seek medical care. The diagnosis of melanoma is made on increasingly smaller lesions with better prognosis, but there still are reports of larger melanomas. This case highlights the role dermatologists serve in the education of patients on their diagnoses and risk factors so that we may be able to diagnose non–life-threatening small lesions. It is important to remember this morphologic variety of melanoma and highlight its rapid progression and poor prognosis.

To the Editor:

An 81-year-old man presented with a nodular polypoid lesion that developed on a flat lesion on the back of 2 years’ duration. The lesion grew progressively over the course of 3 months prior to presentation. The patient had a history of melanoma in situ on the forehead that was treated with conventional surgery with clear surgical margins 6 years prior to the current presentation.

On physical examination the patient had a 4×2-cm ulcerated polypoid lesion on the back. The lesion was pink with a pigmented base. Additionally, 2 pink papules with superficial telangiectases were observed around the main lesion (Figure 1).

The gross section showed an exophytic tumor largely growing above the skin surface (Figure 2). Histopathologic analysis revealed an ulcerated lesion consisting of confluent nest and sheets of epithelioid and spindle atypical cells with numerous mitotic figures and necrotic foci (Figure 3). The thickness of the lesion was 2200 µm, and the mitotic count was 28 mitoses/mm². There also was peritumoral vascular invasion and satellite metastasis within the perilesional hypodermis measuring 0.4 mm. Immunohistochemistry staining for S-100, human melanoma black 45 (HMB-45)(Figure 4), and Melan-A was positive in neoplastic cells.

The dissemination study revealed multiple mediastinal and axillary lymphadenopathies and lesions with metastatic appearance in the brain, liver, pancreas, and muscle, together with peritoneal carcinomatosis. The patient was lost to follow-up and did not follow coadjuvant therapy with interferon alfa.

Polypoid melanoma initially was described as a type of melanoma characterized by an exophytic growth in which most of the tumor is located on the cutaneous surface, together with ulceration.¹ It usually occurs in patients aged 20 to 39 years,² and the reported incidence ranges from 1.9% to 43.3%.¹ It more commonly affects mucosae, including the upper respiratory tract, esophagus, and vagina. Polypoid melanoma has a rapid progression and a poor prognosis.³ Polypoid melanoma involving the skin primarily affects the back and has a 5-year survival rate of 32% to 42%.⁴ Poor prognosis has been attributed to the high risk for vascular embolization under the lesion.⁵ Histologically, there is marked cell atypia with nuclear and cellular pleomorphism and a high mitotic count. The tumor rarely involves the reticular dermis.^1,2

Polypoid melanomas are rare; however, reported frequency rates cover a wide range. These frequency rates may be due to the definition of polypoid melanoma used by the pathologist issuing the report. One of the most accepted definitions at present is a pigmented macule that progresses in months with a rapid vertical growth, invading the epidermis and the papillary dermis.² The differential diagnosis includes pyogenic granuloma, squamous cell carcinoma, basal cell carcinoma, soft tissue sarcomas, and hemangioma.

Although our patient had a history of melanoma and the polypoid lesion developed from a flat lesion, he was late to seek medical care. The diagnosis of melanoma is made on increasingly smaller lesions with better prognosis, but there still are reports of larger melanomas. This case highlights the role dermatologists serve in the education of patients on their diagnoses and risk factors so that we may be able to diagnose non–life-threatening small lesions. It is important to remember this morphologic variety of melanoma and highlight its rapid progression and poor prognosis.

AMSTERDAM – A significantly higher proportion of patients with lupus experienced improvements in joint and skin symptoms if they were treated with baricitinib (Olumiant) than if they received placebo in a phase 2 trial.

The primary endpoint of arthritis or rash resolution as measured by the Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI-2K) was met by approximately 67% of patients who were treated with 4 mg baricitinib once daily and by around 53% of patients given a matching placebo (P less than .05).

SOURCE: Wallace DJ et al. Ann Rheum Dis. 2018;77(Suppl 2):59. Abstract OP0019.

AMSTERDAM – A significantly higher proportion of patients with lupus experienced improvements in joint and skin symptoms if they were treated with baricitinib (Olumiant) than if they received placebo in a phase 2 trial.

The primary endpoint of arthritis or rash resolution as measured by the Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI-2K) was met by approximately 67% of patients who were treated with 4 mg baricitinib once daily and by around 53% of patients given a matching placebo (P less than .05).

SOURCE: Wallace DJ et al. Ann Rheum Dis. 2018;77(Suppl 2):59. Abstract OP0019.

AMSTERDAM – A significantly higher proportion of patients with lupus experienced improvements in joint and skin symptoms if they were treated with baricitinib (Olumiant) than if they received placebo in a phase 2 trial.

The primary endpoint of arthritis or rash resolution as measured by the Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI-2K) was met by approximately 67% of patients who were treated with 4 mg baricitinib once daily and by around 53% of patients given a matching placebo (P less than .05).

SOURCE: Wallace DJ et al. Ann Rheum Dis. 2018;77(Suppl 2):59. Abstract OP0019.

The American College of Surgeons (ACS) Honors Committee is soliciting nominations for several prestigious awards and honors. These include the Distinguished Service Award; the Rodman E. and Thomas G. Sheen Award; the Jacobson Innovation Award; the Lifetime Achievement Award; candidates for Honorary Fellowship (from countries outside of the U.S. and Canada); and potential innovative speakers for the Martin Memorial Lecture, delivered at the Opening Ceremony of the annual ACS Clinical Congress.

Nominations are accepted all year long; however, Honorary Fellowship nominees are selected each October for induction at the following year’s Clinical Congress.

Visit the Honors Committee web page at www.facs.org/about-acs/governance/acs-committees/honors-committee for additional details about the criteria for nominations. Specific questions may be directed to Donna Coulombe, Honors Committee Staff Liaison, at [email protected] or 312-202-5203.
 

The American College of Surgeons (ACS) Honors Committee is soliciting nominations for several prestigious awards and honors. These include the Distinguished Service Award; the Rodman E. and Thomas G. Sheen Award; the Jacobson Innovation Award; the Lifetime Achievement Award; candidates for Honorary Fellowship (from countries outside of the U.S. and Canada); and potential innovative speakers for the Martin Memorial Lecture, delivered at the Opening Ceremony of the annual ACS Clinical Congress.

Nominations are accepted all year long; however, Honorary Fellowship nominees are selected each October for induction at the following year’s Clinical Congress.

Visit the Honors Committee web page at www.facs.org/about-acs/governance/acs-committees/honors-committee for additional details about the criteria for nominations. Specific questions may be directed to Donna Coulombe, Honors Committee Staff Liaison, at [email protected] or 312-202-5203.
 

The American College of Surgeons (ACS) Honors Committee is soliciting nominations for several prestigious awards and honors. These include the Distinguished Service Award; the Rodman E. and Thomas G. Sheen Award; the Jacobson Innovation Award; the Lifetime Achievement Award; candidates for Honorary Fellowship (from countries outside of the U.S. and Canada); and potential innovative speakers for the Martin Memorial Lecture, delivered at the Opening Ceremony of the annual ACS Clinical Congress.

Nominations are accepted all year long; however, Honorary Fellowship nominees are selected each October for induction at the following year’s Clinical Congress.

Visit the Honors Committee web page at www.facs.org/about-acs/governance/acs-committees/honors-committee for additional details about the criteria for nominations. Specific questions may be directed to Donna Coulombe, Honors Committee Staff Liaison, at [email protected] or 312-202-5203.
 

Micrograph showing myelofibrosis

The US Food and Drug Administration (FDA) has granted orphan drug designation to PU-H71 to treat patients with myelofibrosis.

The drug specifically targets the epichaperome, a network of high-molecular-weight complexes found in multiple diseases, including cancer and neurologic disorders. These complexes enhance cellular survival, irrespective of tissue of origin or genetic background.

According to research published in Nature Reviews Cancer, Pu-H71 interferes with the epichaperome function in diseases and does not affect normal cells.

PU-H71 is being evaluated in a phase 1b trial in myelofibrosis and advanced metastatic breast cancer.

“In myelofibrosis, the epichaperome plays a central role in optimizing the JAK-STAT pathway,” said Srdan Verstovsek, MD, PhD, “allowing JAK2 to form dimers that evade inhibition with a JAK2 inhibitor such as ruxolitinib.”

“By inhibiting epichaperome function and breaking this mechanism, we believe PU-H71 can increase anti-cancer activity of JAK2 inhibitors,” he said. Dr Verstovsek, of the MD Anderson Cancer Center in Houston, Texas, is lead clinical research advisor for the phase 1b myelofibrosis study.

Phase 1b Study (NCT01393509)

This is a multicenter study designed to assess the safety, tolerability, pharmacokinetic and preliminary efficacy of PU-H71 in patients taking concomitant ruxolitinib.

The safety expansion phase of the trial is open for accrual only to patients with myeloproliferative neoplasms (MPNs).

These patients must have been on ruxolitinib for at least 3 months, be on a stable dose for at least 1 month prior to enrollment and be taking at least 5 mg twice daily.

Patients must have persistent disease manifestations, despite ruxolitinib therapy. These include persistent splenomegaly, abnormal blood counts, persistent constitutional symptoms, residual fibrosis in bone marrow (2+ or greater), or measurable allele burden as evidenced by clonal JAK2 or MPL mutation.

Samus Therapeutics, the developer of PU-H71, announced, simultaneously with the orphan drug designation, the dosing of the first patient in the phase 1b myelofibrosis study.

“Targeting the epichaperome offers an exciting new avenue for treating myelofibrosis and related diseases,” Dr Verstovsek said.

“I look forward to seeing how the combination of these therapies can affect outcomes in patients for whom this resistance is associated with poor prognoses.” 

Micrograph showing myelofibrosis

The US Food and Drug Administration (FDA) has granted orphan drug designation to PU-H71 to treat patients with myelofibrosis.

The drug specifically targets the epichaperome, a network of high-molecular-weight complexes found in multiple diseases, including cancer and neurologic disorders. These complexes enhance cellular survival, irrespective of tissue of origin or genetic background.

According to research published in Nature Reviews Cancer, Pu-H71 interferes with the epichaperome function in diseases and does not affect normal cells.

PU-H71 is being evaluated in a phase 1b trial in myelofibrosis and advanced metastatic breast cancer.

“In myelofibrosis, the epichaperome plays a central role in optimizing the JAK-STAT pathway,” said Srdan Verstovsek, MD, PhD, “allowing JAK2 to form dimers that evade inhibition with a JAK2 inhibitor such as ruxolitinib.”

“By inhibiting epichaperome function and breaking this mechanism, we believe PU-H71 can increase anti-cancer activity of JAK2 inhibitors,” he said. Dr Verstovsek, of the MD Anderson Cancer Center in Houston, Texas, is lead clinical research advisor for the phase 1b myelofibrosis study.

Phase 1b Study (NCT01393509)

This is a multicenter study designed to assess the safety, tolerability, pharmacokinetic and preliminary efficacy of PU-H71 in patients taking concomitant ruxolitinib.

The safety expansion phase of the trial is open for accrual only to patients with myeloproliferative neoplasms (MPNs).

These patients must have been on ruxolitinib for at least 3 months, be on a stable dose for at least 1 month prior to enrollment and be taking at least 5 mg twice daily.

Patients must have persistent disease manifestations, despite ruxolitinib therapy. These include persistent splenomegaly, abnormal blood counts, persistent constitutional symptoms, residual fibrosis in bone marrow (2+ or greater), or measurable allele burden as evidenced by clonal JAK2 or MPL mutation.

Samus Therapeutics, the developer of PU-H71, announced, simultaneously with the orphan drug designation, the dosing of the first patient in the phase 1b myelofibrosis study.

“Targeting the epichaperome offers an exciting new avenue for treating myelofibrosis and related diseases,” Dr Verstovsek said.

“I look forward to seeing how the combination of these therapies can affect outcomes in patients for whom this resistance is associated with poor prognoses.” 

Micrograph showing myelofibrosis

The US Food and Drug Administration (FDA) has granted orphan drug designation to PU-H71 to treat patients with myelofibrosis.

The drug specifically targets the epichaperome, a network of high-molecular-weight complexes found in multiple diseases, including cancer and neurologic disorders. These complexes enhance cellular survival, irrespective of tissue of origin or genetic background.

According to research published in Nature Reviews Cancer, Pu-H71 interferes with the epichaperome function in diseases and does not affect normal cells.

PU-H71 is being evaluated in a phase 1b trial in myelofibrosis and advanced metastatic breast cancer.

“In myelofibrosis, the epichaperome plays a central role in optimizing the JAK-STAT pathway,” said Srdan Verstovsek, MD, PhD, “allowing JAK2 to form dimers that evade inhibition with a JAK2 inhibitor such as ruxolitinib.”

“By inhibiting epichaperome function and breaking this mechanism, we believe PU-H71 can increase anti-cancer activity of JAK2 inhibitors,” he said. Dr Verstovsek, of the MD Anderson Cancer Center in Houston, Texas, is lead clinical research advisor for the phase 1b myelofibrosis study.

Phase 1b Study (NCT01393509)

This is a multicenter study designed to assess the safety, tolerability, pharmacokinetic and preliminary efficacy of PU-H71 in patients taking concomitant ruxolitinib.

The safety expansion phase of the trial is open for accrual only to patients with myeloproliferative neoplasms (MPNs).

These patients must have been on ruxolitinib for at least 3 months, be on a stable dose for at least 1 month prior to enrollment and be taking at least 5 mg twice daily.

Patients must have persistent disease manifestations, despite ruxolitinib therapy. These include persistent splenomegaly, abnormal blood counts, persistent constitutional symptoms, residual fibrosis in bone marrow (2+ or greater), or measurable allele burden as evidenced by clonal JAK2 or MPL mutation.

Samus Therapeutics, the developer of PU-H71, announced, simultaneously with the orphan drug designation, the dosing of the first patient in the phase 1b myelofibrosis study.

“Targeting the epichaperome offers an exciting new avenue for treating myelofibrosis and related diseases,” Dr Verstovsek said.

“I look forward to seeing how the combination of these therapies can affect outcomes in patients for whom this resistance is associated with poor prognoses.” 

The National Accreditation Program for Rectal Cancer (NAPRC), recently launched by the American College of Surgeons (ACS), has awarded its first accreditation to the John Muir Health Rectal Cancer Program, Walnut Creek and Concord, CA. To earn the voluntary accreditation, the John Muir Health Rectal Cancer Program met 19 standards, including the establishment of a rectal cancer multidisciplinary team (RC-MDT) with clinical representatives from surgery, pathology, radiology, radiation oncology, and medical oncology.

Thirteen of those standards address clinical services that the program was required to provide, including carcinoembryonic antigen testing and magnetic resonance and computed tomography imaging for cancer staging, and ensuring a process whereby the patient starts treatment within a defined time frame. One of the most important clinical standards requires all rectal cancer patients to be present at both pre- and post-treatment RC-MDT meetings.

“When a cancer center achieves this type of specialized accreditation, it means that their rectal cancer patients will receive streamlined, modern evaluation and treatment for the disease. Compliance with our standards will assure optimal care for these patients,” said David P. Winchester, MD, FACS, Medical Director of ACS Cancer Programs.

The NAPRC was developed through a collaboration between the Optimizing the Surgical Treatment of Rectal Cancer Consortium and the ACS Commission on Cancer. It is based on successful international models that emphasize program structure, patient care processes, performance improvement, and performance measures. Its goal is to ensure that rectal cancer patients receive appropriate care using a multidisciplinary approach.

Read more in the ACS press release at www.facs.org/media/press-releases/2018/naprc052218. For more information about the program and instructions on how to apply for accreditation, visit the NAPRC website at www.facs.org/quality-programs/cancer/naprc, or contact [email protected].

The National Accreditation Program for Rectal Cancer (NAPRC), recently launched by the American College of Surgeons (ACS), has awarded its first accreditation to the John Muir Health Rectal Cancer Program, Walnut Creek and Concord, CA. To earn the voluntary accreditation, the John Muir Health Rectal Cancer Program met 19 standards, including the establishment of a rectal cancer multidisciplinary team (RC-MDT) with clinical representatives from surgery, pathology, radiology, radiation oncology, and medical oncology.

Thirteen of those standards address clinical services that the program was required to provide, including carcinoembryonic antigen testing and magnetic resonance and computed tomography imaging for cancer staging, and ensuring a process whereby the patient starts treatment within a defined time frame. One of the most important clinical standards requires all rectal cancer patients to be present at both pre- and post-treatment RC-MDT meetings.

“When a cancer center achieves this type of specialized accreditation, it means that their rectal cancer patients will receive streamlined, modern evaluation and treatment for the disease. Compliance with our standards will assure optimal care for these patients,” said David P. Winchester, MD, FACS, Medical Director of ACS Cancer Programs.

The NAPRC was developed through a collaboration between the Optimizing the Surgical Treatment of Rectal Cancer Consortium and the ACS Commission on Cancer. It is based on successful international models that emphasize program structure, patient care processes, performance improvement, and performance measures. Its goal is to ensure that rectal cancer patients receive appropriate care using a multidisciplinary approach.

Read more in the ACS press release at www.facs.org/media/press-releases/2018/naprc052218. For more information about the program and instructions on how to apply for accreditation, visit the NAPRC website at www.facs.org/quality-programs/cancer/naprc, or contact [email protected].

The National Accreditation Program for Rectal Cancer (NAPRC), recently launched by the American College of Surgeons (ACS), has awarded its first accreditation to the John Muir Health Rectal Cancer Program, Walnut Creek and Concord, CA. To earn the voluntary accreditation, the John Muir Health Rectal Cancer Program met 19 standards, including the establishment of a rectal cancer multidisciplinary team (RC-MDT) with clinical representatives from surgery, pathology, radiology, radiation oncology, and medical oncology.

Thirteen of those standards address clinical services that the program was required to provide, including carcinoembryonic antigen testing and magnetic resonance and computed tomography imaging for cancer staging, and ensuring a process whereby the patient starts treatment within a defined time frame. One of the most important clinical standards requires all rectal cancer patients to be present at both pre- and post-treatment RC-MDT meetings.

“When a cancer center achieves this type of specialized accreditation, it means that their rectal cancer patients will receive streamlined, modern evaluation and treatment for the disease. Compliance with our standards will assure optimal care for these patients,” said David P. Winchester, MD, FACS, Medical Director of ACS Cancer Programs.

The NAPRC was developed through a collaboration between the Optimizing the Surgical Treatment of Rectal Cancer Consortium and the ACS Commission on Cancer. It is based on successful international models that emphasize program structure, patient care processes, performance improvement, and performance measures. Its goal is to ensure that rectal cancer patients receive appropriate care using a multidisciplinary approach.

Read more in the ACS press release at www.facs.org/media/press-releases/2018/naprc052218. For more information about the program and instructions on how to apply for accreditation, visit the NAPRC website at www.facs.org/quality-programs/cancer/naprc, or contact [email protected].

The first findings from a collaborative study within the American College of Surgeons (ACS) Cancer Programs—and published earlier this week in the Journal of the American Medical Association (JAMA)—showed no significant association between frequency of surveillance testing and the time to detection of recurrence for colorectal cancer patients.

The study is an effort of the ACS Clinical Research Program and the Commission on Cancer and uses data from the National Cancer Database (NCDB), which is jointly sponsored by the ACS and the American Cancer Society. It focuses on post-treatment surveillance for breast, colon, and lung cancers and was funded by the Patient-Centered Outcomes Research Institute.

This portion of the study included more than 8,500 patients and was the first of eight manuscripts accepted for publication from a larger study conducted in 2015. The corresponding author is George J. Chang, MD, FACS, chief, section of colon and rectal surgery; professor of surgical oncology and health services research; and director of clinical operations, minimally invasive and new technologies in oncologic surgery program, University of Texas MD Anderson Cancer Center, Houston.

View the full text article on the JAMA website at https://jamanetwork.com/journals/jama/fullarticle/2681746/.

The first findings from a collaborative study within the American College of Surgeons (ACS) Cancer Programs—and published earlier this week in the Journal of the American Medical Association (JAMA)—showed no significant association between frequency of surveillance testing and the time to detection of recurrence for colorectal cancer patients.

The study is an effort of the ACS Clinical Research Program and the Commission on Cancer and uses data from the National Cancer Database (NCDB), which is jointly sponsored by the ACS and the American Cancer Society. It focuses on post-treatment surveillance for breast, colon, and lung cancers and was funded by the Patient-Centered Outcomes Research Institute.

This portion of the study included more than 8,500 patients and was the first of eight manuscripts accepted for publication from a larger study conducted in 2015. The corresponding author is George J. Chang, MD, FACS, chief, section of colon and rectal surgery; professor of surgical oncology and health services research; and director of clinical operations, minimally invasive and new technologies in oncologic surgery program, University of Texas MD Anderson Cancer Center, Houston.

View the full text article on the JAMA website at https://jamanetwork.com/journals/jama/fullarticle/2681746/.

The first findings from a collaborative study within the American College of Surgeons (ACS) Cancer Programs—and published earlier this week in the Journal of the American Medical Association (JAMA)—showed no significant association between frequency of surveillance testing and the time to detection of recurrence for colorectal cancer patients.

The study is an effort of the ACS Clinical Research Program and the Commission on Cancer and uses data from the National Cancer Database (NCDB), which is jointly sponsored by the ACS and the American Cancer Society. It focuses on post-treatment surveillance for breast, colon, and lung cancers and was funded by the Patient-Centered Outcomes Research Institute.

This portion of the study included more than 8,500 patients and was the first of eight manuscripts accepted for publication from a larger study conducted in 2015. The corresponding author is George J. Chang, MD, FACS, chief, section of colon and rectal surgery; professor of surgical oncology and health services research; and director of clinical operations, minimally invasive and new technologies in oncologic surgery program, University of Texas MD Anderson Cancer Center, Houston.

View the full text article on the JAMA website at https://jamanetwork.com/journals/jama/fullarticle/2681746/.

Deaths from abdominal aortic aneurysm among Swedish men are going down – but not because they’re being screened for the potentially fatal condition.

Although the death rate has decreased by 70% since the early 2000s, screening only saved 2 lives per 10,000 men screened. It did, however, increase by 59% the risk of unnecessary surgery, Minna Johansson, MD, and colleagues wrote in the June 16 issue of the Lancet.

James Hellman, MD/Wikimedia Commons

“Screening had only a minor effect on AAA mortality,” wrote Dr. Johansson of the University of Gothenburg (Sweden). “In absolute numbers, only 7% of the benefit estimated in the largest trial of AAA screening was observed. The observed large reductions in AAA mortality were present in both the screened and nonscreened cohorts and were thus mainly caused by other factors – probably reduced smoking. … Our results call the continued justification of AAA screening into question.”

In Sweden, all men aged 65 years are invited to a one-time ultrasound abdominal aorta screening. Most participate. Anyone with an aneurysm is followed up at a vascular surgery clinic, with surgery considered if the aortic diameter is 55 mm or larger.

Dr. Johansson and her colleagues plumbed national health records to estimate the risks and benefits of this routine screening. The study comprised 25,265 men invited to join the AAA screening program in Sweden from 2006 to 2009. Mortality data were compared with those from a contemporaneous cohort of 106,087 men of similar age who were not invited to screen. Finally, the mortality data were compared with national trends in AAA mortality in all Swedish men aged 40-99 years from 1987 to 2015.

A multivariate analysis adjusted for cohort year, marital status, educational level, income, and whether the patient already had an AAA diagnosis at baseline.

From the early 2000s to 2015, AAA mortality among men aged 65-74 years declined from 36 to10 deaths per 100,000. This 70% reduction was similar in both screened and unscreened populations; in fact, the decline began about a decade before population-based screening was introduced and continued to decrease at a steady rate afterward.

After 6 years of screening, there was a 30% reduction of AAA mortality in the screened population, compared with the unscreened, translating to an absolute mortality reduction of two deaths per 10,000 men offered screening.

Screening increased by 52% the number of AAAs detected. The absolute difference in incidence after 6 years of screening translated to an additional 49 overdiagnoses per 10,000 screened men.

Looking back into the mid-1990s, the investigators saw the numbers of elective AAA surgeries rise steadily. In the adjusted model, screened men were 59% more likely to have this procedure than unscreened. The increased risk didn’t come with an equally increased benefit, though. There was a 10% decrease in AAA ruptures, “rendering a risk of overtreatment of 19%, or 19 potentially avoidable elective surgeries per 10,000 men,” the team noted. “Sixty-three percent of all additional elective surgeries for AAA might therefore have constituted overtreat.”

The findings are at odds with large published studies that found a consistent benefit to screening.

“Compared with results at 7-year follow-up of the largest trial of screening for abdominal aortic aneurysm [Multicentre Aneurysm Screening Study (MASS)], we found about half of the benefit in terms of a relative effect and 7% of the estimated benefit in terms of absolute numbers [2 vs. 27 avoided deaths from AAA per 10,000 invited men]. Compared with previous estimates of overdiagnosis and overtreatment, we found a lower absolute number of over-diagnosed cases [49 vs.176 per 10,000 invited men] and fewer overtreated cases [19 vs. 37 per 10,000 invited men]. However, since the harms of screening decreased less than the benefit, the balance between benefits and harms seems much less appealing in today’s setting.”

None of the authors had any financial disclosures.

[email protected]

SOURCE: Johansson et al. Lancet 2018;391:2441-7.

Deaths from abdominal aortic aneurysm among Swedish men are going down – but not because they’re being screened for the potentially fatal condition.

Although the death rate has decreased by 70% since the early 2000s, screening only saved 2 lives per 10,000 men screened. It did, however, increase by 59% the risk of unnecessary surgery, Minna Johansson, MD, and colleagues wrote in the June 16 issue of the Lancet.

James Hellman, MD/Wikimedia Commons

“Screening had only a minor effect on AAA mortality,” wrote Dr. Johansson of the University of Gothenburg (Sweden). “In absolute numbers, only 7% of the benefit estimated in the largest trial of AAA screening was observed. The observed large reductions in AAA mortality were present in both the screened and nonscreened cohorts and were thus mainly caused by other factors – probably reduced smoking. … Our results call the continued justification of AAA screening into question.”

In Sweden, all men aged 65 years are invited to a one-time ultrasound abdominal aorta screening. Most participate. Anyone with an aneurysm is followed up at a vascular surgery clinic, with surgery considered if the aortic diameter is 55 mm or larger.

Dr. Johansson and her colleagues plumbed national health records to estimate the risks and benefits of this routine screening. The study comprised 25,265 men invited to join the AAA screening program in Sweden from 2006 to 2009. Mortality data were compared with those from a contemporaneous cohort of 106,087 men of similar age who were not invited to screen. Finally, the mortality data were compared with national trends in AAA mortality in all Swedish men aged 40-99 years from 1987 to 2015.

A multivariate analysis adjusted for cohort year, marital status, educational level, income, and whether the patient already had an AAA diagnosis at baseline.

From the early 2000s to 2015, AAA mortality among men aged 65-74 years declined from 36 to10 deaths per 100,000. This 70% reduction was similar in both screened and unscreened populations; in fact, the decline began about a decade before population-based screening was introduced and continued to decrease at a steady rate afterward.

After 6 years of screening, there was a 30% reduction of AAA mortality in the screened population, compared with the unscreened, translating to an absolute mortality reduction of two deaths per 10,000 men offered screening.

Screening increased by 52% the number of AAAs detected. The absolute difference in incidence after 6 years of screening translated to an additional 49 overdiagnoses per 10,000 screened men.

Looking back into the mid-1990s, the investigators saw the numbers of elective AAA surgeries rise steadily. In the adjusted model, screened men were 59% more likely to have this procedure than unscreened. The increased risk didn’t come with an equally increased benefit, though. There was a 10% decrease in AAA ruptures, “rendering a risk of overtreatment of 19%, or 19 potentially avoidable elective surgeries per 10,000 men,” the team noted. “Sixty-three percent of all additional elective surgeries for AAA might therefore have constituted overtreat.”

The findings are at odds with large published studies that found a consistent benefit to screening.

“Compared with results at 7-year follow-up of the largest trial of screening for abdominal aortic aneurysm [Multicentre Aneurysm Screening Study (MASS)], we found about half of the benefit in terms of a relative effect and 7% of the estimated benefit in terms of absolute numbers [2 vs. 27 avoided deaths from AAA per 10,000 invited men]. Compared with previous estimates of overdiagnosis and overtreatment, we found a lower absolute number of over-diagnosed cases [49 vs.176 per 10,000 invited men] and fewer overtreated cases [19 vs. 37 per 10,000 invited men]. However, since the harms of screening decreased less than the benefit, the balance between benefits and harms seems much less appealing in today’s setting.”

None of the authors had any financial disclosures.

[email protected]

SOURCE: Johansson et al. Lancet 2018;391:2441-7.

Deaths from abdominal aortic aneurysm among Swedish men are going down – but not because they’re being screened for the potentially fatal condition.

Although the death rate has decreased by 70% since the early 2000s, screening only saved 2 lives per 10,000 men screened. It did, however, increase by 59% the risk of unnecessary surgery, Minna Johansson, MD, and colleagues wrote in the June 16 issue of the Lancet.

James Hellman, MD/Wikimedia Commons

“Screening had only a minor effect on AAA mortality,” wrote Dr. Johansson of the University of Gothenburg (Sweden). “In absolute numbers, only 7% of the benefit estimated in the largest trial of AAA screening was observed. The observed large reductions in AAA mortality were present in both the screened and nonscreened cohorts and were thus mainly caused by other factors – probably reduced smoking. … Our results call the continued justification of AAA screening into question.”

In Sweden, all men aged 65 years are invited to a one-time ultrasound abdominal aorta screening. Most participate. Anyone with an aneurysm is followed up at a vascular surgery clinic, with surgery considered if the aortic diameter is 55 mm or larger.

Dr. Johansson and her colleagues plumbed national health records to estimate the risks and benefits of this routine screening. The study comprised 25,265 men invited to join the AAA screening program in Sweden from 2006 to 2009. Mortality data were compared with those from a contemporaneous cohort of 106,087 men of similar age who were not invited to screen. Finally, the mortality data were compared with national trends in AAA mortality in all Swedish men aged 40-99 years from 1987 to 2015.

A multivariate analysis adjusted for cohort year, marital status, educational level, income, and whether the patient already had an AAA diagnosis at baseline.

From the early 2000s to 2015, AAA mortality among men aged 65-74 years declined from 36 to10 deaths per 100,000. This 70% reduction was similar in both screened and unscreened populations; in fact, the decline began about a decade before population-based screening was introduced and continued to decrease at a steady rate afterward.

After 6 years of screening, there was a 30% reduction of AAA mortality in the screened population, compared with the unscreened, translating to an absolute mortality reduction of two deaths per 10,000 men offered screening.

Screening increased by 52% the number of AAAs detected. The absolute difference in incidence after 6 years of screening translated to an additional 49 overdiagnoses per 10,000 screened men.

Looking back into the mid-1990s, the investigators saw the numbers of elective AAA surgeries rise steadily. In the adjusted model, screened men were 59% more likely to have this procedure than unscreened. The increased risk didn’t come with an equally increased benefit, though. There was a 10% decrease in AAA ruptures, “rendering a risk of overtreatment of 19%, or 19 potentially avoidable elective surgeries per 10,000 men,” the team noted. “Sixty-three percent of all additional elective surgeries for AAA might therefore have constituted overtreat.”

The findings are at odds with large published studies that found a consistent benefit to screening.

“Compared with results at 7-year follow-up of the largest trial of screening for abdominal aortic aneurysm [Multicentre Aneurysm Screening Study (MASS)], we found about half of the benefit in terms of a relative effect and 7% of the estimated benefit in terms of absolute numbers [2 vs. 27 avoided deaths from AAA per 10,000 invited men]. Compared with previous estimates of overdiagnosis and overtreatment, we found a lower absolute number of over-diagnosed cases [49 vs.176 per 10,000 invited men] and fewer overtreated cases [19 vs. 37 per 10,000 invited men]. However, since the harms of screening decreased less than the benefit, the balance between benefits and harms seems much less appealing in today’s setting.”

None of the authors had any financial disclosures.

[email protected]

SOURCE: Johansson et al. Lancet 2018;391:2441-7.

The use of only one 2017 novel drug (Benznidazole) during breastfeeding has been reported. No reports describing the use of the other drugs while breastfeeding have been located. Nevertheless, exposure of a nursing infant should be considered if the mother is taking any of these drugs.

During the first 2 days after birth, nearly all drugs will be excreted into milk, but the amounts are very small and will probably have no effect on the nursing infant. After the second day, drugs with molecular weights of less than 1,000 g/mol will be excreted into milk. Some drugs with high molecular weights may also be excreted, but they may be digested in the infant’s gut. If a mother is receiving one of the drugs below and is breastfeeding, her infant should be monitored for the most common adverse effects, shown below, that were observed in nonpregnant adults.

Anti-infectives

Benznidazole (MW 260 g/mol). Abdominal pain, rash, decreased weight, headache, nausea, vomiting, neutropenia, urticaria, pruritus, eosinophilia, decreased appetite.

Delafloxacin (Baxdela) (MW 441 g/mol). Nausea, diarrhea, headache, transaminase elevations, vomiting.

Glecaprevir / Pibrentasvir (Mavyret) (MWs 839, 1,113 g/mol). Headache, fatigue.

Letermovir (Prevymis) (MW 573 g/mol). Nausea, vomiting, diarrhea, peripheral edema, cough, headache, fatigue, abdominal pain.

Meropenem / vaborbactam (Vabomere) (MWs 438, 297 g/mol). Headache, diarrhea.

Ozenoxacin cream (Xepi) (MW 363 g/mol). No relevant adverse reactions.

Sofosbuvir / Velpatasvir / Voxilaprevir (Vosevi) (MWs 529, 883, 869 g/mol). Headache, fatigue, diarrhea, nausea.

Secnidazole (Solosec) (MW 185 g/mol). Headache, nausea, dysgeusia, vomiting, diarrhea, abdominal pain. Manufacturer recommends discontinuing breastfeeding for 96 hours after administration of the drug.

Antineoplastics

[Note: All of the drugs in this category are best avoided, if possible, when breastfeeding.]

Abemaciclib (Verzenio) (MW 507 g/mol). Diarrhea, neutropenia, nausea, vomiting, abdominal pain, infections, fatigue, anemia, leukopenia, decreased appetite, headache, alopecia, thrombocytopenia.

Acalabrutinib (Calquence) (MW 466 g/mol). Anemia, thrombocytopenia, headache, neutropenia, diarrhea, myalgia, bruising.

Avelumab (Bavencio) (MW 147 kg/mol). Fatigue, musculoskeletal pain, diarrhea, nausea, rash, decreased appetite, peripheral edema, urinary tract infection.

Brigatinib (Alunbrig) (MW 584 g/mol). Nausea, fatigue, cough, headache.

Copanlisib (Aliqopa) (MW 480 g/mol). Hyperglycemia, diarrhea, decreased strength and energy, hypertension, leukopenia, neutropenia, nausea, lower respiratory infections, thrombocytopenia.

Durvalumab (Imfinzi) (MW 146 kg/mol). Fatigue, musculoskeletal pain, constipation, decreased appetite, nausea, peripheral edema, urinary tract infections, cough, upper respiratory tract infections, dyspnea, rash.

Enasidenib mesylate (Idhifa) (MW 569 g/mol). Nausea, vomiting, diarrhea, elevated bilirubin, decreased appetite.

Inotuzumab ozogamicin (Besponsa) (MW 160 kg/mol). Thrombocytopenia, neutropenia, anemia, leukopenia, fatigue, hemorrhage, pyrexia, nausea, headache, febrile neutropenia, transaminases increased, abdominal pain, increased gamma-glutamyltransferase, and hyperbilirubinemia.

Midostaurin (Rydapt) (MW 571 g/mol). Febrile neutropenia, nausea, mucositis, vomiting, headache, petechiae, musculoskeletal pain, epistaxis, hyperglycemia, vomiting, diarrhea, edema, pyrexia, dyspnea.

Neratinib (Nerlynx) (MW 557 g/mol). Diarrhea, nausea, vomiting, abdominal pain, fatigue, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, nail disorder, dry skin, abdominal distention, decreased weight, urinary tract infection.

Niraparib (Zejula) (MW 511 g/mol). Thrombocytopenia, anemia, neutropenia, leukopenia, palpitations, nausea, vomiting, constipation, abdominal pain/distention, mucositis/stomatitis, diarrhea, dry mouth, fatigue/asthenia, decreased appetite, urinary tract infection, myalgia, back pain, arthralgia, headache, dizziness, dysgeusia, insomnia, anxiety, nasopharyngitis, dyspnea, cough, rash, hypertension.

Ribociclib (Kisqali) (MW 553 g/mol). Neutropenia, nausea, fatigue, diarrhea, leukopenia, alopecia, vomiting, constipation, headache, back pain.

Cardiovascular

Angiotensin II (Giapreza) (MW 1,046 g/mol). Thromboembolic events.

Central nervous system

Deutetrabenazine (Austedo) (MW 324 g/mol). Somnolence, diarrhea, dry mouth, fatigue, nasopharyngitis.

Edaravone (Radicava) (MW 174 g/mol). Confusion, gait disturbance, headache.

Naldemedine (Symproic) (MW 743 g/mol). Abdominal pain, diarrhea, nausea, gastroenteritis.

Ocrelizumab (Ocrevus) (MW 145 kg/mol). Upper and lower respiratory tract infections.

Safinamide (Xadago) (MW 399 g/mol). Dyskinesia, fall, nausea, insomnia.

Valbenazine (Ingrezza) (MW 419 g/mol). Somnolence.

Dermatologic

Brodalumab (Siliq) (MW 144 kg/mol). Arthralgia, headache, fatigue, diarrhea, oropharyngeal pain, nausea, myalgia, influenza, neutropenia, tinea infections.

Dupilumab (Dupixent) (MW 146.9 kg/mol). Conjunctivitis, blepharitis, oral herpes, keratitis, eye pruritus, other herpes simplex virus infection, dry eye.

Guselkumab (Tremfya) (MW 143.6 kg/mol). Upper respiratory infections, headache, arthralgia, diarrhea, gastroenteritis, tinea infections, herpes simplex infections.

Endocrine / metabolic

Deflazacort (Emflaza) (MW 442 g/mol). Cushingoid appearance, weight increased, increased appetite, upper respiratory tract infection, cough, pollakiuria, hirsutism, central obesity, nasopharyngitis.

Ertugliflozin (Steglatro) (MW 566 g/mol). Female genital mycotic infections.

Etelcalcetide (Parsabiv) (MW 1,048 g/mol). Blood calcium decreased, muscle spasms, diarrhea, nausea, vomiting, headache, hypocalcemia, paresthesia.

Macimorelin (Macrilen) (MW 535 g/mol). Dysgeusia, dizziness, headache, fatigue, nausea, hunger, diarrhea, upper respiratory tract infection, feeling hot, hyperhidrosis, nasopharyngitis, sinus bradycardia.

Semaglutide (Ozempic) (MW 4,114 g/mol). Nausea, vomiting, diarrhea, abdominal pain, constipation.

Vestronidase alfa (Mepsevii) (MW 72.5 kg/mol). Diarrhea, rash, anaphylaxis, pruritus.

Gastrointestinal

Plecanatide (Trulance) (MW 1.7 kg/mol). Diarrhea.

Telotristat (Xermelo) (MW 574 g/mol). Nausea, headache, increased gamma-glutamyltransferase, depression, flatulence, decreased appetite, peripheral edema, pyrexia.

Hematologic

Betrixaban (Bevyxxa) (MW 568 g/mol). Bleeding.

Emicizumab (Hemlibra) (MW 145.6 kg/mol). Headache, arthralgia.

Immunologic

Sarilumab (Kevzara) (MW 150 kg/mol). Neutropenia, increased ALT, upper respiratory infections, urinary tract infections.

Ophthalmic

Latanoprostene bunod (Vyzulta) (MW 508 g/mol). All related to the eye.

Netarsudil (Rhopressa) (MW 454 g/mol). All related to the eye.

Parathyroid hormone

Abaloparatide (Tymlos) (MW 3.9 kg/mol). Hypercalciuria, dizziness, nausea, headache, palpitations, fatigue, upper abdominal pain, vertigo.

Respiratory

Benralizumab (Fasenra) (MW 150 kg/mol). Headache, pharyngitis.

The use of only one 2017 novel drug (Benznidazole) during breastfeeding has been reported. No reports describing the use of the other drugs while breastfeeding have been located. Nevertheless, exposure of a nursing infant should be considered if the mother is taking any of these drugs.

During the first 2 days after birth, nearly all drugs will be excreted into milk, but the amounts are very small and will probably have no effect on the nursing infant. After the second day, drugs with molecular weights of less than 1,000 g/mol will be excreted into milk. Some drugs with high molecular weights may also be excreted, but they may be digested in the infant’s gut. If a mother is receiving one of the drugs below and is breastfeeding, her infant should be monitored for the most common adverse effects, shown below, that were observed in nonpregnant adults.

Anti-infectives

Benznidazole (MW 260 g/mol). Abdominal pain, rash, decreased weight, headache, nausea, vomiting, neutropenia, urticaria, pruritus, eosinophilia, decreased appetite.

Delafloxacin (Baxdela) (MW 441 g/mol). Nausea, diarrhea, headache, transaminase elevations, vomiting.

Glecaprevir / Pibrentasvir (Mavyret) (MWs 839, 1,113 g/mol). Headache, fatigue.

Letermovir (Prevymis) (MW 573 g/mol). Nausea, vomiting, diarrhea, peripheral edema, cough, headache, fatigue, abdominal pain.

Meropenem / vaborbactam (Vabomere) (MWs 438, 297 g/mol). Headache, diarrhea.

Ozenoxacin cream (Xepi) (MW 363 g/mol). No relevant adverse reactions.

Sofosbuvir / Velpatasvir / Voxilaprevir (Vosevi) (MWs 529, 883, 869 g/mol). Headache, fatigue, diarrhea, nausea.

Secnidazole (Solosec) (MW 185 g/mol). Headache, nausea, dysgeusia, vomiting, diarrhea, abdominal pain. Manufacturer recommends discontinuing breastfeeding for 96 hours after administration of the drug.

Antineoplastics

[Note: All of the drugs in this category are best avoided, if possible, when breastfeeding.]

Abemaciclib (Verzenio) (MW 507 g/mol). Diarrhea, neutropenia, nausea, vomiting, abdominal pain, infections, fatigue, anemia, leukopenia, decreased appetite, headache, alopecia, thrombocytopenia.

Acalabrutinib (Calquence) (MW 466 g/mol). Anemia, thrombocytopenia, headache, neutropenia, diarrhea, myalgia, bruising.

Avelumab (Bavencio) (MW 147 kg/mol). Fatigue, musculoskeletal pain, diarrhea, nausea, rash, decreased appetite, peripheral edema, urinary tract infection.

Brigatinib (Alunbrig) (MW 584 g/mol). Nausea, fatigue, cough, headache.

Copanlisib (Aliqopa) (MW 480 g/mol). Hyperglycemia, diarrhea, decreased strength and energy, hypertension, leukopenia, neutropenia, nausea, lower respiratory infections, thrombocytopenia.

Durvalumab (Imfinzi) (MW 146 kg/mol). Fatigue, musculoskeletal pain, constipation, decreased appetite, nausea, peripheral edema, urinary tract infections, cough, upper respiratory tract infections, dyspnea, rash.

Enasidenib mesylate (Idhifa) (MW 569 g/mol). Nausea, vomiting, diarrhea, elevated bilirubin, decreased appetite.

Inotuzumab ozogamicin (Besponsa) (MW 160 kg/mol). Thrombocytopenia, neutropenia, anemia, leukopenia, fatigue, hemorrhage, pyrexia, nausea, headache, febrile neutropenia, transaminases increased, abdominal pain, increased gamma-glutamyltransferase, and hyperbilirubinemia.

Midostaurin (Rydapt) (MW 571 g/mol). Febrile neutropenia, nausea, mucositis, vomiting, headache, petechiae, musculoskeletal pain, epistaxis, hyperglycemia, vomiting, diarrhea, edema, pyrexia, dyspnea.

Neratinib (Nerlynx) (MW 557 g/mol). Diarrhea, nausea, vomiting, abdominal pain, fatigue, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, nail disorder, dry skin, abdominal distention, decreased weight, urinary tract infection.

Niraparib (Zejula) (MW 511 g/mol). Thrombocytopenia, anemia, neutropenia, leukopenia, palpitations, nausea, vomiting, constipation, abdominal pain/distention, mucositis/stomatitis, diarrhea, dry mouth, fatigue/asthenia, decreased appetite, urinary tract infection, myalgia, back pain, arthralgia, headache, dizziness, dysgeusia, insomnia, anxiety, nasopharyngitis, dyspnea, cough, rash, hypertension.

Ribociclib (Kisqali) (MW 553 g/mol). Neutropenia, nausea, fatigue, diarrhea, leukopenia, alopecia, vomiting, constipation, headache, back pain.

Cardiovascular

Angiotensin II (Giapreza) (MW 1,046 g/mol). Thromboembolic events.

Central nervous system

Deutetrabenazine (Austedo) (MW 324 g/mol). Somnolence, diarrhea, dry mouth, fatigue, nasopharyngitis.

Edaravone (Radicava) (MW 174 g/mol). Confusion, gait disturbance, headache.

Naldemedine (Symproic) (MW 743 g/mol). Abdominal pain, diarrhea, nausea, gastroenteritis.

Ocrelizumab (Ocrevus) (MW 145 kg/mol). Upper and lower respiratory tract infections.

Safinamide (Xadago) (MW 399 g/mol). Dyskinesia, fall, nausea, insomnia.

Valbenazine (Ingrezza) (MW 419 g/mol). Somnolence.

Dermatologic

Brodalumab (Siliq) (MW 144 kg/mol). Arthralgia, headache, fatigue, diarrhea, oropharyngeal pain, nausea, myalgia, influenza, neutropenia, tinea infections.

Dupilumab (Dupixent) (MW 146.9 kg/mol). Conjunctivitis, blepharitis, oral herpes, keratitis, eye pruritus, other herpes simplex virus infection, dry eye.

Guselkumab (Tremfya) (MW 143.6 kg/mol). Upper respiratory infections, headache, arthralgia, diarrhea, gastroenteritis, tinea infections, herpes simplex infections.

Endocrine / metabolic

Deflazacort (Emflaza) (MW 442 g/mol). Cushingoid appearance, weight increased, increased appetite, upper respiratory tract infection, cough, pollakiuria, hirsutism, central obesity, nasopharyngitis.

Ertugliflozin (Steglatro) (MW 566 g/mol). Female genital mycotic infections.

Etelcalcetide (Parsabiv) (MW 1,048 g/mol). Blood calcium decreased, muscle spasms, diarrhea, nausea, vomiting, headache, hypocalcemia, paresthesia.

Macimorelin (Macrilen) (MW 535 g/mol). Dysgeusia, dizziness, headache, fatigue, nausea, hunger, diarrhea, upper respiratory tract infection, feeling hot, hyperhidrosis, nasopharyngitis, sinus bradycardia.

Semaglutide (Ozempic) (MW 4,114 g/mol). Nausea, vomiting, diarrhea, abdominal pain, constipation.

Vestronidase alfa (Mepsevii) (MW 72.5 kg/mol). Diarrhea, rash, anaphylaxis, pruritus.

Gastrointestinal

Plecanatide (Trulance) (MW 1.7 kg/mol). Diarrhea.

Telotristat (Xermelo) (MW 574 g/mol). Nausea, headache, increased gamma-glutamyltransferase, depression, flatulence, decreased appetite, peripheral edema, pyrexia.

Hematologic

Betrixaban (Bevyxxa) (MW 568 g/mol). Bleeding.

Emicizumab (Hemlibra) (MW 145.6 kg/mol). Headache, arthralgia.

Immunologic

Sarilumab (Kevzara) (MW 150 kg/mol). Neutropenia, increased ALT, upper respiratory infections, urinary tract infections.

Ophthalmic

Latanoprostene bunod (Vyzulta) (MW 508 g/mol). All related to the eye.

Netarsudil (Rhopressa) (MW 454 g/mol). All related to the eye.

Parathyroid hormone

Abaloparatide (Tymlos) (MW 3.9 kg/mol). Hypercalciuria, dizziness, nausea, headache, palpitations, fatigue, upper abdominal pain, vertigo.

Respiratory

Benralizumab (Fasenra) (MW 150 kg/mol). Headache, pharyngitis.

The use of only one 2017 novel drug (Benznidazole) during breastfeeding has been reported. No reports describing the use of the other drugs while breastfeeding have been located. Nevertheless, exposure of a nursing infant should be considered if the mother is taking any of these drugs.

During the first 2 days after birth, nearly all drugs will be excreted into milk, but the amounts are very small and will probably have no effect on the nursing infant. After the second day, drugs with molecular weights of less than 1,000 g/mol will be excreted into milk. Some drugs with high molecular weights may also be excreted, but they may be digested in the infant’s gut. If a mother is receiving one of the drugs below and is breastfeeding, her infant should be monitored for the most common adverse effects, shown below, that were observed in nonpregnant adults.

Anti-infectives

Benznidazole (MW 260 g/mol). Abdominal pain, rash, decreased weight, headache, nausea, vomiting, neutropenia, urticaria, pruritus, eosinophilia, decreased appetite.

Delafloxacin (Baxdela) (MW 441 g/mol). Nausea, diarrhea, headache, transaminase elevations, vomiting.

Glecaprevir / Pibrentasvir (Mavyret) (MWs 839, 1,113 g/mol). Headache, fatigue.

Letermovir (Prevymis) (MW 573 g/mol). Nausea, vomiting, diarrhea, peripheral edema, cough, headache, fatigue, abdominal pain.

Meropenem / vaborbactam (Vabomere) (MWs 438, 297 g/mol). Headache, diarrhea.

Ozenoxacin cream (Xepi) (MW 363 g/mol). No relevant adverse reactions.

Sofosbuvir / Velpatasvir / Voxilaprevir (Vosevi) (MWs 529, 883, 869 g/mol). Headache, fatigue, diarrhea, nausea.

Secnidazole (Solosec) (MW 185 g/mol). Headache, nausea, dysgeusia, vomiting, diarrhea, abdominal pain. Manufacturer recommends discontinuing breastfeeding for 96 hours after administration of the drug.

Antineoplastics

[Note: All of the drugs in this category are best avoided, if possible, when breastfeeding.]

Abemaciclib (Verzenio) (MW 507 g/mol). Diarrhea, neutropenia, nausea, vomiting, abdominal pain, infections, fatigue, anemia, leukopenia, decreased appetite, headache, alopecia, thrombocytopenia.

Acalabrutinib (Calquence) (MW 466 g/mol). Anemia, thrombocytopenia, headache, neutropenia, diarrhea, myalgia, bruising.

Avelumab (Bavencio) (MW 147 kg/mol). Fatigue, musculoskeletal pain, diarrhea, nausea, rash, decreased appetite, peripheral edema, urinary tract infection.

Brigatinib (Alunbrig) (MW 584 g/mol). Nausea, fatigue, cough, headache.

Copanlisib (Aliqopa) (MW 480 g/mol). Hyperglycemia, diarrhea, decreased strength and energy, hypertension, leukopenia, neutropenia, nausea, lower respiratory infections, thrombocytopenia.

Durvalumab (Imfinzi) (MW 146 kg/mol). Fatigue, musculoskeletal pain, constipation, decreased appetite, nausea, peripheral edema, urinary tract infections, cough, upper respiratory tract infections, dyspnea, rash.

Enasidenib mesylate (Idhifa) (MW 569 g/mol). Nausea, vomiting, diarrhea, elevated bilirubin, decreased appetite.

Inotuzumab ozogamicin (Besponsa) (MW 160 kg/mol). Thrombocytopenia, neutropenia, anemia, leukopenia, fatigue, hemorrhage, pyrexia, nausea, headache, febrile neutropenia, transaminases increased, abdominal pain, increased gamma-glutamyltransferase, and hyperbilirubinemia.

Midostaurin (Rydapt) (MW 571 g/mol). Febrile neutropenia, nausea, mucositis, vomiting, headache, petechiae, musculoskeletal pain, epistaxis, hyperglycemia, vomiting, diarrhea, edema, pyrexia, dyspnea.

Neratinib (Nerlynx) (MW 557 g/mol). Diarrhea, nausea, vomiting, abdominal pain, fatigue, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, nail disorder, dry skin, abdominal distention, decreased weight, urinary tract infection.

Niraparib (Zejula) (MW 511 g/mol). Thrombocytopenia, anemia, neutropenia, leukopenia, palpitations, nausea, vomiting, constipation, abdominal pain/distention, mucositis/stomatitis, diarrhea, dry mouth, fatigue/asthenia, decreased appetite, urinary tract infection, myalgia, back pain, arthralgia, headache, dizziness, dysgeusia, insomnia, anxiety, nasopharyngitis, dyspnea, cough, rash, hypertension.

Ribociclib (Kisqali) (MW 553 g/mol). Neutropenia, nausea, fatigue, diarrhea, leukopenia, alopecia, vomiting, constipation, headache, back pain.

Cardiovascular

Angiotensin II (Giapreza) (MW 1,046 g/mol). Thromboembolic events.

Central nervous system

Deutetrabenazine (Austedo) (MW 324 g/mol). Somnolence, diarrhea, dry mouth, fatigue, nasopharyngitis.

Edaravone (Radicava) (MW 174 g/mol). Confusion, gait disturbance, headache.

Naldemedine (Symproic) (MW 743 g/mol). Abdominal pain, diarrhea, nausea, gastroenteritis.

Ocrelizumab (Ocrevus) (MW 145 kg/mol). Upper and lower respiratory tract infections.

Safinamide (Xadago) (MW 399 g/mol). Dyskinesia, fall, nausea, insomnia.

Valbenazine (Ingrezza) (MW 419 g/mol). Somnolence.

Dermatologic

Brodalumab (Siliq) (MW 144 kg/mol). Arthralgia, headache, fatigue, diarrhea, oropharyngeal pain, nausea, myalgia, influenza, neutropenia, tinea infections.

Dupilumab (Dupixent) (MW 146.9 kg/mol). Conjunctivitis, blepharitis, oral herpes, keratitis, eye pruritus, other herpes simplex virus infection, dry eye.

Guselkumab (Tremfya) (MW 143.6 kg/mol). Upper respiratory infections, headache, arthralgia, diarrhea, gastroenteritis, tinea infections, herpes simplex infections.

Endocrine / metabolic

Deflazacort (Emflaza) (MW 442 g/mol). Cushingoid appearance, weight increased, increased appetite, upper respiratory tract infection, cough, pollakiuria, hirsutism, central obesity, nasopharyngitis.

Ertugliflozin (Steglatro) (MW 566 g/mol). Female genital mycotic infections.

Etelcalcetide (Parsabiv) (MW 1,048 g/mol). Blood calcium decreased, muscle spasms, diarrhea, nausea, vomiting, headache, hypocalcemia, paresthesia.

Macimorelin (Macrilen) (MW 535 g/mol). Dysgeusia, dizziness, headache, fatigue, nausea, hunger, diarrhea, upper respiratory tract infection, feeling hot, hyperhidrosis, nasopharyngitis, sinus bradycardia.

Semaglutide (Ozempic) (MW 4,114 g/mol). Nausea, vomiting, diarrhea, abdominal pain, constipation.

Vestronidase alfa (Mepsevii) (MW 72.5 kg/mol). Diarrhea, rash, anaphylaxis, pruritus.

Gastrointestinal

Plecanatide (Trulance) (MW 1.7 kg/mol). Diarrhea.

Telotristat (Xermelo) (MW 574 g/mol). Nausea, headache, increased gamma-glutamyltransferase, depression, flatulence, decreased appetite, peripheral edema, pyrexia.

Hematologic

Betrixaban (Bevyxxa) (MW 568 g/mol). Bleeding.

Emicizumab (Hemlibra) (MW 145.6 kg/mol). Headache, arthralgia.

Immunologic

Sarilumab (Kevzara) (MW 150 kg/mol). Neutropenia, increased ALT, upper respiratory infections, urinary tract infections.

Ophthalmic

Latanoprostene bunod (Vyzulta) (MW 508 g/mol). All related to the eye.

Netarsudil (Rhopressa) (MW 454 g/mol). All related to the eye.

Parathyroid hormone

Abaloparatide (Tymlos) (MW 3.9 kg/mol). Hypercalciuria, dizziness, nausea, headache, palpitations, fatigue, upper abdominal pain, vertigo.

Respiratory

Benralizumab (Fasenra) (MW 150 kg/mol). Headache, pharyngitis.

Question: The “Captain of the Ship” doctrine:

A. Is a legal principle used mostly in maritime law.

B. Is applicable only to surgeons in the operating room.

C. Is good law in all jurisdictions.

D. May be used by plaintiffs in emergency department triage litigation.

E. Originated when hospitals lost their charitable immunity.


Answer: D. Historically, the Captain of the Ship doctrine imputes liability to the surgeon who has the authority and right to control the actions of his assistants in the operating room.

Pennsylvania famously saw the use of the phrase in a 1949 case: “In the course of an operation in the operating room of a hospital, and until the surgeon leaves that room at the conclusion of the operation … he is in the same complete charge of those who are present and assisting him as is the captain of a ship over all on board.”¹

Wavebreakmedia Ltd/Thinkstock

Dr. Tan is emeritus professor of medicine and former adjunct professor of law at the University of Hawaii, Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. For additional information, readers may contact the author at [email protected].

References

1. McConnell v. Williams, 361 Pa. 355, 65 A.2d 243 (1949).

2. ED Legal Letter, Feb 1, 2018.

3. Collins v. Hand, 246 A.2d 398 (Pa 1968).

4. AORN J. 2001 Oct;74(4):525-8.

5. Lewis v. Physicians Insurance Company et al., 627 NW2d 484 (Wis 2001).

6. Krane v. St. Anthony Hospital Systems, 738 P.2d 75 (Co 1987).

7. Fields v. Yusuf, 144 Cal.App.4th 1381 (2006).

Question: The “Captain of the Ship” doctrine:

A. Is a legal principle used mostly in maritime law.

B. Is applicable only to surgeons in the operating room.

C. Is good law in all jurisdictions.

D. May be used by plaintiffs in emergency department triage litigation.

E. Originated when hospitals lost their charitable immunity.


Answer: D. Historically, the Captain of the Ship doctrine imputes liability to the surgeon who has the authority and right to control the actions of his assistants in the operating room.

Pennsylvania famously saw the use of the phrase in a 1949 case: “In the course of an operation in the operating room of a hospital, and until the surgeon leaves that room at the conclusion of the operation … he is in the same complete charge of those who are present and assisting him as is the captain of a ship over all on board.”¹

Wavebreakmedia Ltd/Thinkstock

Dr. Tan is emeritus professor of medicine and former adjunct professor of law at the University of Hawaii, Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. For additional information, readers may contact the author at [email protected].

References

1. McConnell v. Williams, 361 Pa. 355, 65 A.2d 243 (1949).

2. ED Legal Letter, Feb 1, 2018.

3. Collins v. Hand, 246 A.2d 398 (Pa 1968).

4. AORN J. 2001 Oct;74(4):525-8.

5. Lewis v. Physicians Insurance Company et al., 627 NW2d 484 (Wis 2001).

6. Krane v. St. Anthony Hospital Systems, 738 P.2d 75 (Co 1987).

7. Fields v. Yusuf, 144 Cal.App.4th 1381 (2006).

Question: The “Captain of the Ship” doctrine:

A. Is a legal principle used mostly in maritime law.

B. Is applicable only to surgeons in the operating room.

C. Is good law in all jurisdictions.

D. May be used by plaintiffs in emergency department triage litigation.

E. Originated when hospitals lost their charitable immunity.


Answer: D. Historically, the Captain of the Ship doctrine imputes liability to the surgeon who has the authority and right to control the actions of his assistants in the operating room.

Pennsylvania famously saw the use of the phrase in a 1949 case: “In the course of an operation in the operating room of a hospital, and until the surgeon leaves that room at the conclusion of the operation … he is in the same complete charge of those who are present and assisting him as is the captain of a ship over all on board.”¹

Wavebreakmedia Ltd/Thinkstock

Dr. Tan is emeritus professor of medicine and former adjunct professor of law at the University of Hawaii, Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. For additional information, readers may contact the author at [email protected].

References

1. McConnell v. Williams, 361 Pa. 355, 65 A.2d 243 (1949).

2. ED Legal Letter, Feb 1, 2018.

3. Collins v. Hand, 246 A.2d 398 (Pa 1968).

4. AORN J. 2001 Oct;74(4):525-8.

5. Lewis v. Physicians Insurance Company et al., 627 NW2d 484 (Wis 2001).

6. Krane v. St. Anthony Hospital Systems, 738 P.2d 75 (Co 1987).

7. Fields v. Yusuf, 144 Cal.App.4th 1381 (2006).

A capsule containing a combination of 17-beta-estradiol and progesterone significantly improved vasomotor symptoms in menopausal women without causing a single case of endometrial hyperplasia.

The results of the 12-week REPLENISH study suggested that this preparation effectively treats vasomotor symptoms and could be a safe alternative to the popular, but unstudied, compounded bioidentical hormones that millions of women turned to after the Women’s Health Initiative study cast doubt on the safety of hormone therapy, Rogerio A. Lobo, MD, and his colleagues wrote in Obstetrics and Gynecology.

“17-beta-estradiol–progesterone may represent a new option, using natural hormones, for postmenopausal women, including the estimated millions currently using inadequately studied, non–FDA approved, compounded [hormone therapy],” wrote Dr. Lobo of Columbia University, New York.

REPLENISH randomized 1,845 postmenopausal women (mean age 55 years) to placebo or one of four active, daily, oral estradiol-progesterone doses (1 mg/100 mg, 0.5 mg/100 mg, 0.5 mg/50 mg, or 0.25 mg/50 mg). The primary safety outcome was endometrial hyperplasia. There were two primary efficacy endpoints: mean changes in frequency and severity of moderate to severe vasomotor symptoms from baseline at weeks 4 and 12.

There were no cases of endometrial hyperplasia with any estradiol-progesterone dose, nor were there any endometrial cancers. The rates of endometrial proliferation and endometrial polyps were low (about 3% each).

The frequency of vasomotor symptoms decreased significantly, compared with placebo, in all active groups. The severity of vasomotor symptoms also decreased significantly and in a dose-dependent manner. Onset of action was similarly dose-dependent, with the 1 mg/100 mg group experiencing a clinically meaningful benefit by week 3 and the 0.5 mg/50 mg group by week 6.

Adverse events were mild-moderate and included breast tenderness, headache, nausea, pelvic pain, vaginal bleeding, and vaginal discharge. Serious adverse events included acute pancreatitis, deep vein thrombosis (in a woman with prior left femoral popliteal bypass surgery and a family history of deep vein thrombosis), chronic obstructive pulmonary disease, infective cholecystitis, and breast cancer.

TherapeuticsMD sponsored the study; Dr. Lobo has received research grants from TherapeuticsMD and has served as a consultant for the company and several others. Some coauthors report additional research support from and consulting with TherapeuticsMD and other companies, and three coauthors are stock-holding employees of TherapeuticsMD.

[email protected]

SOURCE: Lobo RA et al. Obstet Gynecol. 2018 Jan;132(1):161-70.

A capsule containing a combination of 17-beta-estradiol and progesterone significantly improved vasomotor symptoms in menopausal women without causing a single case of endometrial hyperplasia.

The results of the 12-week REPLENISH study suggested that this preparation effectively treats vasomotor symptoms and could be a safe alternative to the popular, but unstudied, compounded bioidentical hormones that millions of women turned to after the Women’s Health Initiative study cast doubt on the safety of hormone therapy, Rogerio A. Lobo, MD, and his colleagues wrote in Obstetrics and Gynecology.

“17-beta-estradiol–progesterone may represent a new option, using natural hormones, for postmenopausal women, including the estimated millions currently using inadequately studied, non–FDA approved, compounded [hormone therapy],” wrote Dr. Lobo of Columbia University, New York.

REPLENISH randomized 1,845 postmenopausal women (mean age 55 years) to placebo or one of four active, daily, oral estradiol-progesterone doses (1 mg/100 mg, 0.5 mg/100 mg, 0.5 mg/50 mg, or 0.25 mg/50 mg). The primary safety outcome was endometrial hyperplasia. There were two primary efficacy endpoints: mean changes in frequency and severity of moderate to severe vasomotor symptoms from baseline at weeks 4 and 12.

There were no cases of endometrial hyperplasia with any estradiol-progesterone dose, nor were there any endometrial cancers. The rates of endometrial proliferation and endometrial polyps were low (about 3% each).

The frequency of vasomotor symptoms decreased significantly, compared with placebo, in all active groups. The severity of vasomotor symptoms also decreased significantly and in a dose-dependent manner. Onset of action was similarly dose-dependent, with the 1 mg/100 mg group experiencing a clinically meaningful benefit by week 3 and the 0.5 mg/50 mg group by week 6.

Adverse events were mild-moderate and included breast tenderness, headache, nausea, pelvic pain, vaginal bleeding, and vaginal discharge. Serious adverse events included acute pancreatitis, deep vein thrombosis (in a woman with prior left femoral popliteal bypass surgery and a family history of deep vein thrombosis), chronic obstructive pulmonary disease, infective cholecystitis, and breast cancer.

TherapeuticsMD sponsored the study; Dr. Lobo has received research grants from TherapeuticsMD and has served as a consultant for the company and several others. Some coauthors report additional research support from and consulting with TherapeuticsMD and other companies, and three coauthors are stock-holding employees of TherapeuticsMD.

[email protected]

SOURCE: Lobo RA et al. Obstet Gynecol. 2018 Jan;132(1):161-70.

A capsule containing a combination of 17-beta-estradiol and progesterone significantly improved vasomotor symptoms in menopausal women without causing a single case of endometrial hyperplasia.

The results of the 12-week REPLENISH study suggested that this preparation effectively treats vasomotor symptoms and could be a safe alternative to the popular, but unstudied, compounded bioidentical hormones that millions of women turned to after the Women’s Health Initiative study cast doubt on the safety of hormone therapy, Rogerio A. Lobo, MD, and his colleagues wrote in Obstetrics and Gynecology.

“17-beta-estradiol–progesterone may represent a new option, using natural hormones, for postmenopausal women, including the estimated millions currently using inadequately studied, non–FDA approved, compounded [hormone therapy],” wrote Dr. Lobo of Columbia University, New York.

REPLENISH randomized 1,845 postmenopausal women (mean age 55 years) to placebo or one of four active, daily, oral estradiol-progesterone doses (1 mg/100 mg, 0.5 mg/100 mg, 0.5 mg/50 mg, or 0.25 mg/50 mg). The primary safety outcome was endometrial hyperplasia. There were two primary efficacy endpoints: mean changes in frequency and severity of moderate to severe vasomotor symptoms from baseline at weeks 4 and 12.

There were no cases of endometrial hyperplasia with any estradiol-progesterone dose, nor were there any endometrial cancers. The rates of endometrial proliferation and endometrial polyps were low (about 3% each).

The frequency of vasomotor symptoms decreased significantly, compared with placebo, in all active groups. The severity of vasomotor symptoms also decreased significantly and in a dose-dependent manner. Onset of action was similarly dose-dependent, with the 1 mg/100 mg group experiencing a clinically meaningful benefit by week 3 and the 0.5 mg/50 mg group by week 6.

Adverse events were mild-moderate and included breast tenderness, headache, nausea, pelvic pain, vaginal bleeding, and vaginal discharge. Serious adverse events included acute pancreatitis, deep vein thrombosis (in a woman with prior left femoral popliteal bypass surgery and a family history of deep vein thrombosis), chronic obstructive pulmonary disease, infective cholecystitis, and breast cancer.

TherapeuticsMD sponsored the study; Dr. Lobo has received research grants from TherapeuticsMD and has served as a consultant for the company and several others. Some coauthors report additional research support from and consulting with TherapeuticsMD and other companies, and three coauthors are stock-holding employees of TherapeuticsMD.

[email protected]

SOURCE: Lobo RA et al. Obstet Gynecol. 2018 Jan;132(1):161-70.