Article

Acupuncture is a very popular treatment strategy in some areas of the world and is extensively applied in Chinese practice. Though this is a regularly applied treatment, a direct comparison with first-line antispasmodics has not been previously completed. The study by Shi and colleagues sought to compare the treatment of IBS using an adjusted indirect treatment comparison meta-analysis. This study proves that cimetropium was the most effective for relieving abdominal pain, whereas drotaverine, acupuncture, and pinaverium remained superior to the placebo. That being said, acupuncture was shown to be superior in relieving global IBS symptoms and caused fewer side effects than did antispasmodics. This shows that acupuncture may have a role in the treatment algorithm for IBS even outside of China, where it is used broadly.

The study by Formica and colleagues provides new insights on the etiology and pathogenesis of IBS. These insights include the positive correlation between disgust sensitivity and IBS quality of life (QOL) scores. The relationship between IBS and the emotional intensity of the experience of disgust is discussed throughout this study and more severe IBS-QOL scores were linked to those with high levels of disgust sensitivity. This study had gender limitations because of the low number of male participants, so these correlations were patterned mostly in female participants. 

Acupuncture is a very popular treatment strategy in some areas of the world and is extensively applied in Chinese practice. Though this is a regularly applied treatment, a direct comparison with first-line antispasmodics has not been previously completed. The study by Shi and colleagues sought to compare the treatment of IBS using an adjusted indirect treatment comparison meta-analysis. This study proves that cimetropium was the most effective for relieving abdominal pain, whereas drotaverine, acupuncture, and pinaverium remained superior to the placebo. That being said, acupuncture was shown to be superior in relieving global IBS symptoms and caused fewer side effects than did antispasmodics. This shows that acupuncture may have a role in the treatment algorithm for IBS even outside of China, where it is used broadly.

The study by Formica and colleagues provides new insights on the etiology and pathogenesis of IBS. These insights include the positive correlation between disgust sensitivity and IBS quality of life (QOL) scores. The relationship between IBS and the emotional intensity of the experience of disgust is discussed throughout this study and more severe IBS-QOL scores were linked to those with high levels of disgust sensitivity. This study had gender limitations because of the low number of male participants, so these correlations were patterned mostly in female participants. 

Acupuncture is a very popular treatment strategy in some areas of the world and is extensively applied in Chinese practice. Though this is a regularly applied treatment, a direct comparison with first-line antispasmodics has not been previously completed. The study by Shi and colleagues sought to compare the treatment of IBS using an adjusted indirect treatment comparison meta-analysis. This study proves that cimetropium was the most effective for relieving abdominal pain, whereas drotaverine, acupuncture, and pinaverium remained superior to the placebo. That being said, acupuncture was shown to be superior in relieving global IBS symptoms and caused fewer side effects than did antispasmodics. This shows that acupuncture may have a role in the treatment algorithm for IBS even outside of China, where it is used broadly.

The study by Formica and colleagues provides new insights on the etiology and pathogenesis of IBS. These insights include the positive correlation between disgust sensitivity and IBS quality of life (QOL) scores. The relationship between IBS and the emotional intensity of the experience of disgust is discussed throughout this study and more severe IBS-QOL scores were linked to those with high levels of disgust sensitivity. This study had gender limitations because of the low number of male participants, so these correlations were patterned mostly in female participants. 

Orimo and colleagues addressed the use of liver resection in patients with more than one HCC in the liver. Patients with no or Child-Pugh A/B cirrhosis were included in this single-center retrospective study of 1088 patients who underwent hepatectomy for Barcelona Clinic Liver Cancer (BCLC) stage 0 (n = 88), A (n = 750), or B (n = 250) HCC, with stages A and B subcategorized into A1 (single nodule 2-5 cm or ≤ 3 nodules ≤ 3 cm), A2 (single nodule 5-10 cm), A3 (single nodule ≥ 10 cm), B1 (2-3 nodules > 3 cm), and B2 (≥ 4 nodules). The 5-year overall survival (OS) rates for stage 0, A1, A2, A3, B1, and B2 patients were 70.4%, 74.2%, 63.8%, 47.7%, 47.5%, and 31.9%, respectively (P < .0001). Significant differences in overall survival (OS) were found between stages A1 and A2 (P = .0118), A2 and A3 (P = .0013), and B1 and B2 (P = .0050), but not between stages A3 and B1 (P = .4742). In stage B1 patients, Child-Pugh B cirrhosis was the only independent prognostic factor for OS. The authors concluded that hepatectomy is beneficial in patients with three or fewer hepatocellular carcinomas and either no or Child-Pugh class A cirrhosis, with the long-term results being comparable to those in patients who underwent a resection of a single HCC. Therefore, resection of up to three HCC is safe and should be considered in clinically appropriate patients.

Many patients with multifocal HCC are not eligible for liver-directed therapies. The standard of care for first-line systemic therapy is the combination of atezolizumab and bevacizumab, as reported in the IMbrave150 clinical trial. Fulgenzi and colleagues published the results of a multicenter prospective observational study, AB-Real, that included 433 patients who received atezolizumab and bevacizumab in routine clinical practice. The investigators confirmed the efficacy of the combination and found that portal vein tumor thrombosis and worse albumin-bilirubin grade were independent prognostic factors for poor OS and were associated with an increased risk for hemorrhagic events. In addition, the authors reported that the overall response rate (ORR) predicted better outcomes, including longer OS. Therefore, atezolizumab and bevacizumab remains a safe and effective first-line treatment for many patients with unresectable HCC.

Finally, Finn and colleagues reported the results of an open-label, noncomparative cohort of the REACH-2 study of ramucirumab in 47 patients with advanced HCC and an alpha-fetoprotein (AFP) level ≥ 400 ng/mL. These patients had previously received one to two lines of systemic therapy, excluding sorafenib or chemotherapy. Lenvatinib was the most common prior systemic therapy (n = 20; 43%). Others included immune checkpoint inhibitor (CPI) monotherapies (n = 11), CPI/antiangiogenic therapy (n = 14), or dual CPI therapy (n = 5). The ORR was 10.6% (95% CI 1.8-19.5) and disease control rate was 46.8% (95% CI 32.5-61.1), with a median duration of response of 8.3 months [95% CI 2.4 to not reached). The grade 3 or more adverse event rate was 57%, with hypertension (11%) being the most common, allowing the authors to conclude that ramucirumab offers clinically significant efficacy with no new safety signals in this setting. Therefore, ramucirumab remains as a safe and effective later-line treatment option for patients with unresectable HCC and an AFP ≥ 400 ng/mL.

Orimo and colleagues addressed the use of liver resection in patients with more than one HCC in the liver. Patients with no or Child-Pugh A/B cirrhosis were included in this single-center retrospective study of 1088 patients who underwent hepatectomy for Barcelona Clinic Liver Cancer (BCLC) stage 0 (n = 88), A (n = 750), or B (n = 250) HCC, with stages A and B subcategorized into A1 (single nodule 2-5 cm or ≤ 3 nodules ≤ 3 cm), A2 (single nodule 5-10 cm), A3 (single nodule ≥ 10 cm), B1 (2-3 nodules > 3 cm), and B2 (≥ 4 nodules). The 5-year overall survival (OS) rates for stage 0, A1, A2, A3, B1, and B2 patients were 70.4%, 74.2%, 63.8%, 47.7%, 47.5%, and 31.9%, respectively (P < .0001). Significant differences in overall survival (OS) were found between stages A1 and A2 (P = .0118), A2 and A3 (P = .0013), and B1 and B2 (P = .0050), but not between stages A3 and B1 (P = .4742). In stage B1 patients, Child-Pugh B cirrhosis was the only independent prognostic factor for OS. The authors concluded that hepatectomy is beneficial in patients with three or fewer hepatocellular carcinomas and either no or Child-Pugh class A cirrhosis, with the long-term results being comparable to those in patients who underwent a resection of a single HCC. Therefore, resection of up to three HCC is safe and should be considered in clinically appropriate patients.

Many patients with multifocal HCC are not eligible for liver-directed therapies. The standard of care for first-line systemic therapy is the combination of atezolizumab and bevacizumab, as reported in the IMbrave150 clinical trial. Fulgenzi and colleagues published the results of a multicenter prospective observational study, AB-Real, that included 433 patients who received atezolizumab and bevacizumab in routine clinical practice. The investigators confirmed the efficacy of the combination and found that portal vein tumor thrombosis and worse albumin-bilirubin grade were independent prognostic factors for poor OS and were associated with an increased risk for hemorrhagic events. In addition, the authors reported that the overall response rate (ORR) predicted better outcomes, including longer OS. Therefore, atezolizumab and bevacizumab remains a safe and effective first-line treatment for many patients with unresectable HCC.

Finally, Finn and colleagues reported the results of an open-label, noncomparative cohort of the REACH-2 study of ramucirumab in 47 patients with advanced HCC and an alpha-fetoprotein (AFP) level ≥ 400 ng/mL. These patients had previously received one to two lines of systemic therapy, excluding sorafenib or chemotherapy. Lenvatinib was the most common prior systemic therapy (n = 20; 43%). Others included immune checkpoint inhibitor (CPI) monotherapies (n = 11), CPI/antiangiogenic therapy (n = 14), or dual CPI therapy (n = 5). The ORR was 10.6% (95% CI 1.8-19.5) and disease control rate was 46.8% (95% CI 32.5-61.1), with a median duration of response of 8.3 months [95% CI 2.4 to not reached). The grade 3 or more adverse event rate was 57%, with hypertension (11%) being the most common, allowing the authors to conclude that ramucirumab offers clinically significant efficacy with no new safety signals in this setting. Therefore, ramucirumab remains as a safe and effective later-line treatment option for patients with unresectable HCC and an AFP ≥ 400 ng/mL.

Orimo and colleagues addressed the use of liver resection in patients with more than one HCC in the liver. Patients with no or Child-Pugh A/B cirrhosis were included in this single-center retrospective study of 1088 patients who underwent hepatectomy for Barcelona Clinic Liver Cancer (BCLC) stage 0 (n = 88), A (n = 750), or B (n = 250) HCC, with stages A and B subcategorized into A1 (single nodule 2-5 cm or ≤ 3 nodules ≤ 3 cm), A2 (single nodule 5-10 cm), A3 (single nodule ≥ 10 cm), B1 (2-3 nodules > 3 cm), and B2 (≥ 4 nodules). The 5-year overall survival (OS) rates for stage 0, A1, A2, A3, B1, and B2 patients were 70.4%, 74.2%, 63.8%, 47.7%, 47.5%, and 31.9%, respectively (P < .0001). Significant differences in overall survival (OS) were found between stages A1 and A2 (P = .0118), A2 and A3 (P = .0013), and B1 and B2 (P = .0050), but not between stages A3 and B1 (P = .4742). In stage B1 patients, Child-Pugh B cirrhosis was the only independent prognostic factor for OS. The authors concluded that hepatectomy is beneficial in patients with three or fewer hepatocellular carcinomas and either no or Child-Pugh class A cirrhosis, with the long-term results being comparable to those in patients who underwent a resection of a single HCC. Therefore, resection of up to three HCC is safe and should be considered in clinically appropriate patients.

Many patients with multifocal HCC are not eligible for liver-directed therapies. The standard of care for first-line systemic therapy is the combination of atezolizumab and bevacizumab, as reported in the IMbrave150 clinical trial. Fulgenzi and colleagues published the results of a multicenter prospective observational study, AB-Real, that included 433 patients who received atezolizumab and bevacizumab in routine clinical practice. The investigators confirmed the efficacy of the combination and found that portal vein tumor thrombosis and worse albumin-bilirubin grade were independent prognostic factors for poor OS and were associated with an increased risk for hemorrhagic events. In addition, the authors reported that the overall response rate (ORR) predicted better outcomes, including longer OS. Therefore, atezolizumab and bevacizumab remains a safe and effective first-line treatment for many patients with unresectable HCC.

Finally, Finn and colleagues reported the results of an open-label, noncomparative cohort of the REACH-2 study of ramucirumab in 47 patients with advanced HCC and an alpha-fetoprotein (AFP) level ≥ 400 ng/mL. These patients had previously received one to two lines of systemic therapy, excluding sorafenib or chemotherapy. Lenvatinib was the most common prior systemic therapy (n = 20; 43%). Others included immune checkpoint inhibitor (CPI) monotherapies (n = 11), CPI/antiangiogenic therapy (n = 14), or dual CPI therapy (n = 5). The ORR was 10.6% (95% CI 1.8-19.5) and disease control rate was 46.8% (95% CI 32.5-61.1), with a median duration of response of 8.3 months [95% CI 2.4 to not reached). The grade 3 or more adverse event rate was 57%, with hypertension (11%) being the most common, allowing the authors to conclude that ramucirumab offers clinically significant efficacy with no new safety signals in this setting. Therefore, ramucirumab remains as a safe and effective later-line treatment option for patients with unresectable HCC and an AFP ≥ 400 ng/mL.

Orimo and colleagues addressed the use of liver resection in patients with more than one HCC in the liver. Patients with no or Child-Pugh A/B cirrhosis were included in this single-center retrospective study of 1088 patients who underwent hepatectomy for Barcelona Clinic Liver Cancer (BCLC) stage 0 (n = 88), A (n = 750), or B (n = 250) HCC, with stages A and B subcategorized into A1 (single nodule 2-5 cm or ≤ 3 nodules ≤ 3 cm), A2 (single nodule 5-10 cm), A3 (single nodule ≥ 10 cm), B1 (2-3 nodules > 3 cm), and B2 (≥ 4 nodules). The 5-year overall survival (OS) rates for stage 0, A1, A2, A3, B1, and B2 patients were 70.4%, 74.2%, 63.8%, 47.7%, 47.5%, and 31.9%, respectively (P < .0001). Significant differences in overall survival (OS) were found between stages A1 and A2 (P = .0118), A2 and A3 (P = .0013), and B1 and B2 (P = .0050), but not between stages A3 and B1 (P = .4742). In stage B1 patients, Child-Pugh B cirrhosis was the only independent prognostic factor for OS. The authors concluded that hepatectomy is beneficial in patients with three or fewer hepatocellular carcinomas and either no or Child-Pugh class A cirrhosis, with the long-term results being comparable to those in patients who underwent a resection of a single HCC. Therefore, resection of up to three HCC is safe and should be considered in clinically appropriate patients.

Many patients with multifocal HCC are not eligible for liver-directed therapies. The standard of care for first-line systemic therapy is the combination of atezolizumab and bevacizumab, as reported in the IMbrave150 clinical trial. Fulgenzi and colleagues published the results of a multicenter prospective observational study, AB-Real, that included 433 patients who received atezolizumab and bevacizumab in routine clinical practice. The investigators confirmed the efficacy of the combination and found that portal vein tumor thrombosis and worse albumin-bilirubin grade were independent prognostic factors for poor OS and were associated with an increased risk for hemorrhagic events. In addition, the authors reported that the overall response rate (ORR) predicted better outcomes, including longer OS. Therefore, atezolizumab and bevacizumab remains a safe and effective first-line treatment for many patients with unresectable HCC.

Finally, Finn and colleagues reported the results of an open-label, noncomparative cohort of the REACH-2 study of ramucirumab in 47 patients with advanced HCC and an alpha-fetoprotein (AFP) level ≥ 400 ng/mL. These patients had previously received one to two lines of systemic therapy, excluding sorafenib or chemotherapy. Lenvatinib was the most common prior systemic therapy (n = 20; 43%). Others included immune checkpoint inhibitor (CPI) monotherapies (n = 11), CPI/antiangiogenic therapy (n = 14), or dual CPI therapy (n = 5). The ORR was 10.6% (95% CI 1.8-19.5) and disease control rate was 46.8% (95% CI 32.5-61.1), with a median duration of response of 8.3 months (95% CI 2.4 to not reached). The grade 3 or more adverse event rate was 57%, with hypertension (11%) being the most common, allowing the authors to conclude that ramucirumab offers clinically significant efficacy with no new safety signals in this setting. Therefore, ramucirumab remains as a safe and effective later-line treatment option for patients with unresectable HCC and an AFP ≥ 400 ng/mL.

Orimo and colleagues addressed the use of liver resection in patients with more than one HCC in the liver. Patients with no or Child-Pugh A/B cirrhosis were included in this single-center retrospective study of 1088 patients who underwent hepatectomy for Barcelona Clinic Liver Cancer (BCLC) stage 0 (n = 88), A (n = 750), or B (n = 250) HCC, with stages A and B subcategorized into A1 (single nodule 2-5 cm or ≤ 3 nodules ≤ 3 cm), A2 (single nodule 5-10 cm), A3 (single nodule ≥ 10 cm), B1 (2-3 nodules > 3 cm), and B2 (≥ 4 nodules). The 5-year overall survival (OS) rates for stage 0, A1, A2, A3, B1, and B2 patients were 70.4%, 74.2%, 63.8%, 47.7%, 47.5%, and 31.9%, respectively (P < .0001). Significant differences in overall survival (OS) were found between stages A1 and A2 (P = .0118), A2 and A3 (P = .0013), and B1 and B2 (P = .0050), but not between stages A3 and B1 (P = .4742). In stage B1 patients, Child-Pugh B cirrhosis was the only independent prognostic factor for OS. The authors concluded that hepatectomy is beneficial in patients with three or fewer hepatocellular carcinomas and either no or Child-Pugh class A cirrhosis, with the long-term results being comparable to those in patients who underwent a resection of a single HCC. Therefore, resection of up to three HCC is safe and should be considered in clinically appropriate patients.

Many patients with multifocal HCC are not eligible for liver-directed therapies. The standard of care for first-line systemic therapy is the combination of atezolizumab and bevacizumab, as reported in the IMbrave150 clinical trial. Fulgenzi and colleagues published the results of a multicenter prospective observational study, AB-Real, that included 433 patients who received atezolizumab and bevacizumab in routine clinical practice. The investigators confirmed the efficacy of the combination and found that portal vein tumor thrombosis and worse albumin-bilirubin grade were independent prognostic factors for poor OS and were associated with an increased risk for hemorrhagic events. In addition, the authors reported that the overall response rate (ORR) predicted better outcomes, including longer OS. Therefore, atezolizumab and bevacizumab remains a safe and effective first-line treatment for many patients with unresectable HCC.

Finally, Finn and colleagues reported the results of an open-label, noncomparative cohort of the REACH-2 study of ramucirumab in 47 patients with advanced HCC and an alpha-fetoprotein (AFP) level ≥ 400 ng/mL. These patients had previously received one to two lines of systemic therapy, excluding sorafenib or chemotherapy. Lenvatinib was the most common prior systemic therapy (n = 20; 43%). Others included immune checkpoint inhibitor (CPI) monotherapies (n = 11), CPI/antiangiogenic therapy (n = 14), or dual CPI therapy (n = 5). The ORR was 10.6% (95% CI 1.8-19.5) and disease control rate was 46.8% (95% CI 32.5-61.1), with a median duration of response of 8.3 months (95% CI 2.4 to not reached). The grade 3 or more adverse event rate was 57%, with hypertension (11%) being the most common, allowing the authors to conclude that ramucirumab offers clinically significant efficacy with no new safety signals in this setting. Therefore, ramucirumab remains as a safe and effective later-line treatment option for patients with unresectable HCC and an AFP ≥ 400 ng/mL.

Orimo and colleagues addressed the use of liver resection in patients with more than one HCC in the liver. Patients with no or Child-Pugh A/B cirrhosis were included in this single-center retrospective study of 1088 patients who underwent hepatectomy for Barcelona Clinic Liver Cancer (BCLC) stage 0 (n = 88), A (n = 750), or B (n = 250) HCC, with stages A and B subcategorized into A1 (single nodule 2-5 cm or ≤ 3 nodules ≤ 3 cm), A2 (single nodule 5-10 cm), A3 (single nodule ≥ 10 cm), B1 (2-3 nodules > 3 cm), and B2 (≥ 4 nodules). The 5-year overall survival (OS) rates for stage 0, A1, A2, A3, B1, and B2 patients were 70.4%, 74.2%, 63.8%, 47.7%, 47.5%, and 31.9%, respectively (P < .0001). Significant differences in overall survival (OS) were found between stages A1 and A2 (P = .0118), A2 and A3 (P = .0013), and B1 and B2 (P = .0050), but not between stages A3 and B1 (P = .4742). In stage B1 patients, Child-Pugh B cirrhosis was the only independent prognostic factor for OS. The authors concluded that hepatectomy is beneficial in patients with three or fewer hepatocellular carcinomas and either no or Child-Pugh class A cirrhosis, with the long-term results being comparable to those in patients who underwent a resection of a single HCC. Therefore, resection of up to three HCC is safe and should be considered in clinically appropriate patients.

Many patients with multifocal HCC are not eligible for liver-directed therapies. The standard of care for first-line systemic therapy is the combination of atezolizumab and bevacizumab, as reported in the IMbrave150 clinical trial. Fulgenzi and colleagues published the results of a multicenter prospective observational study, AB-Real, that included 433 patients who received atezolizumab and bevacizumab in routine clinical practice. The investigators confirmed the efficacy of the combination and found that portal vein tumor thrombosis and worse albumin-bilirubin grade were independent prognostic factors for poor OS and were associated with an increased risk for hemorrhagic events. In addition, the authors reported that the overall response rate (ORR) predicted better outcomes, including longer OS. Therefore, atezolizumab and bevacizumab remains a safe and effective first-line treatment for many patients with unresectable HCC.

Finally, Finn and colleagues reported the results of an open-label, noncomparative cohort of the REACH-2 study of ramucirumab in 47 patients with advanced HCC and an alpha-fetoprotein (AFP) level ≥ 400 ng/mL. These patients had previously received one to two lines of systemic therapy, excluding sorafenib or chemotherapy. Lenvatinib was the most common prior systemic therapy (n = 20; 43%). Others included immune checkpoint inhibitor (CPI) monotherapies (n = 11), CPI/antiangiogenic therapy (n = 14), or dual CPI therapy (n = 5). The ORR was 10.6% (95% CI 1.8-19.5) and disease control rate was 46.8% (95% CI 32.5-61.1), with a median duration of response of 8.3 months (95% CI 2.4 to not reached). The grade 3 or more adverse event rate was 57%, with hypertension (11%) being the most common, allowing the authors to conclude that ramucirumab offers clinically significant efficacy with no new safety signals in this setting. Therefore, ramucirumab remains as a safe and effective later-line treatment option for patients with unresectable HCC and an AFP ≥ 400 ng/mL.

Taking call is one of the more challenging - and annoying - aspects of the job for many physicians. Calls may wake them up in the middle of the night and can interfere with their at-home activities. In Medscape’s Employed Physicians Report, 37% of respondents said they have from 1 to 5 hours of call per month; 19% said they have 6 to 10 hours; and 12% have 11 hours or more.

“Even if you don’t have to come in to the ED, you can get calls in the middle of the night, and you may get paid very little, if anything,” said Robert Bitterman MD, JD, an emergency physician and attorney in Harbor Springs, Mich.

And responding to the calls is not optional. Dr. Bitterman said if on-call physicians don’t perform their duties, they could lose their hospital privileges, be fined by the federal government, or be sued for malpractice.

On-call activities are regulated by the federal Emergency Medical Treatment and Active Labor Act (EMTALA). Dr. Bitterman said it’s rare for the federal government to prosecute on-call physicians for violating EMTALA. Instead, it’s more likely that the hospital will be fined for EMTALA violations committed by on-call physicians.

However, the hospital passes the on-call obligation on to individual physicians through medical staff bylaws. Physicians who violate the bylaws may have their privileges restricted or removed, Dr. Bitterman said. Physicians could also be sued for malpractice, even if they never treated the patient, he added.
 

After-hours call duty in physicians’ practices

A very different type of call duty is having to respond to calls from one’s own patients after regular hours. Unlike doctors on ED call, who usually deal with patients they have never met, these physicians deal with their established patients or those of a colleague in their practice.

Courts have established that physicians have to provide an answering service or other means for their patients to contact them after hours, and the doctor must respond to these calls in a timely manner.

In a 2015 Louisiana ruling, a cardiologist was found liable for malpractice because he didn’t respond to an after-hours call from his patient. The patient tried several times to contact the cardiologist but got no reply.

Physicians may also be responsible if their answering service does not send critical messages to them immediately, if it fails to make appropriate documentation, or if it sends inaccurate data to the doctor.
 

Cases when on-call doctors didn’t respond

The Office of the Inspector General (OIG) of the U.S. Health and Human Services Administration oversees federal EMTALA violations and regularly reports them.

In 2018, the OIG fined a hospital in Waterloo, Iowa, $90,000 when an on-call cardiologist failed to implant a pacemaker for an ED patient. According to the OIG’s report, the patient arrived at the hospital with heart problems. Reached by phone, the cardiologist directed the ED physician to begin transcutaneous pacing but asked that the patient be transferred to another hospital for placement of the pacemaker. The patient died after transfer.

The OIG found that the original cardiologist could have placed the pacemaker, but, as often happens, it only fined the hospital, not the on-call physician for the EMTALA violation.

EMTALA requires that hospitals provide on-call specialists to assist emergency physicians with care of patients who arrive in the ED. In specialties for which there are few doctors to choose from, the on-call specialist may be on duty every third night and every third weekend. This can be daunting, especially for specialists who’ve had a grueling day of work.

Occasionally, on-call physicians, fearful they could make a medical error, request that the patient be transferred to another hospital for treatment. This is what a neurosurgeon who was on call at a Topeka, Kan., hospital did in 2001. Transferred to another hospital, the patient underwent an operation but lost sensation in his lower extremities. The patient sued the on-call neurosurgeon for negligence.

During the trial, the on-call neurosurgeon testified that he was “feeling run-down because he had been an on-call physician every third night for more than 10 years.” He also said this was the first time he had refused to see a patient because of fatigue, and he had decided that the patient “would be better off at a trauma center that had a trauma team and a fresher surgeon.”

The neurosurgeon successfully defended the malpractice suit, but Dr. Bitterman said he might have lost had there not been some unusual circumstances in the case. The court ruled that the hospital had not clearly defined the duties of on-call physicians, and the lawsuit didn’t cite the neurosurgeon’s EMTALA duty.
 

On-call duties defined by EMTALA

EMTALA sets the overall rules for on-call duties, which each hospital is expected to fine-tune on the basis of its own particular circumstances. Here are some of those rules, issued by the Centers for Medicare & Medicaid Services and the OIG.

Only an individual physician can be on call. The hospital’s on-call schedule cannot name a physician practice.

Call applies to all ED patients. Physicians cannot limit their on-call responsibilities to their own patients, to patients in their insurance network, or to paying patients.

There may be some gaps in the call schedule. The OIG is not specific as to how many gaps are allowed, said Nick Healey, an attorney in Cheyenne, Wyo., who has written about on-call duties. Among other things, adequate coverage depends on the number of available physicians and the demand for their services. Mr. Healey added that states may require more extensive availability of on-call physicians at high-level trauma centers.

Hospitals must have made arrangements for transfer. Whenever there is a gap in the schedule, hospitals need to have a designated hospital to send the patient to. Hospitals that unnecessarily transfer patients will be penalized.

The ED physician calls the shots. The emergency physician handling the case decides if the on-call doctor has to come in and treat the patient firsthand.

The on-call physician may delegate the work to others. On-call physicians may designate a nurse practitioner or physician assistant, but the on-call physician is ultimately responsible. The ED doctor may require the physician to come in anyway, according to Todd B. Taylor, MD, an emergency physician in Phoenix, who has written about on-call duties. Dr. Bitterman noted that the physician may designate a colleague to take their call, but the substitute has to have privileges at the hospital.

Physicians may do their own work while on call. Physicians can perform elective surgery while on call, provided they have made arrangements if they then become unavailable for duty, Dr. Taylor said. He added that physicians can also have simultaneous call at other hospitals, provided they make arrangements.
 

The hospital fine-tunes call obligations

The hospital is expected to further define the federal rules. For instance, the CMS says physicians should respond to calls within a “reasonable period of time” and requires hospitals to specify response times, which may be 15-30 minutes for responding to phone calls and traveling to the ED, Dr. Bitterman said.

The CMS says older physicians can be exempted from call. The hospital determines the age at which physicians can be exempted. “Hospitals typically exempt physicians over age 65 or 70, or when they have certain medical conditions,” said Lowell Brown, a Los Angeles attorney who deals with on-call duties.

The hospital also sets the call schedule, which may result in uncovered periods in specialties in which there are few physicians to draw from, according to Mr. Healey. He said many hospitals still use a simple rule of thumb, even though it has been dismissed by the CMS. Under this so-called “rule of three,” hospitals that have three doctors or fewer in a specialty do not have to provide constant call coverage.

On-call rules are part of the medical staff bylaws, and they have to be approved by the medical staff. This may require delicate negotiations between the staff’s leadership and administrators, Dr. Bitterman said.

It is often up to the emergency physician on duty to enforce the hospital’s on-call rules, Dr. Taylor said. “If the ED physician is having trouble, he or she may contact the on-call physician’s department chairman or, if necessary, the chief of the medical staff and ask that person to deal with the physician,” Dr. Taylor said.

The ED physician has to determine whether the patient needs to be transferred to another hospital. Dr. Taylor said the ED physician must fill out a transfer form and obtain consent from the receiving hospital.

If a patient has to be transferred because an on-call physician failed to appear, the originating hospital has to report this to the CMS, and the physician and the hospital can be cited for an inappropriate transfer and fined, Mr. Brown said. “The possibility of being identified in this way should be a powerful incentive to accept call duty,” he added.
 

Malpractice exposure of on-call physicians

When on-call doctors provide medical advice regarding an ED patient, that advice may be subject to malpractice litigation, Dr. Taylor said. “Even if you only give the ED doctor advice over the phone, that may establish a patient-physician relationship and a duty that patient can cite in a malpractice case,” he noted.

Refusing to take call may also be grounds for a malpractice lawsuit, Dr. Bitterman said. Refusing to see a patient would not be considered medical negligence, he continued, because no medical decision is made. Rather, it involves general negligence, which occurs when physicians fail to carry out duties expected of them.

Dr. Bitterman cited a 2006 malpractice judgment in which an on-call neurosurgeon in Missouri was found to be generally negligent. The neurosurgeon had arranged for a colleague in his practice to take his call, but the colleague did not have privileges at the hospital.

A patient with a brain bleed came in and the substitute was on duty. The patient had to be transferred to another hospital, where the patient died. The court ordered that the on-call doctor and the originating hospital had to split a fine of $400,800.
 

On-call physicians can be charged with abandonment

Dr. Bitterman said that if on-call physicians do not provide expected follow-up treatment for an ED patient, they could be charged with abandonment, which is a matter of state law and involves filing a malpractice lawsuit.

Abandonment involves unilaterally terminating the patient relationship without providing notice. There must be an established relationship, which, in the case of call, is formed when the doctor comes to the ED to examine or admit the patient, Dr. Bitterman said. He added that the on-call doctor’s obligation applies only to the medical condition the patient came in for.

Even when an on-call doctor does not see a patient, a relationship can be established if the hospital requires its on-call doctors to make follow-up visits for ED patients, Dr. Taylor said. At some hospitals, he said, on-call doctors have blanket agreements to provide follow-up care in return for not having to arrive in the middle of the night during the ED visit.

Dr. Taylor gave an example of the on-call doctor’s obligation: “The ED doctor puts a splint on the patient’s ankle fracture, and the orthopedic surgeon on call agrees to follow up with the patient within the next few days. If the orthopedic surgeon refuses to follow up without making a reasonable accommodation, it may become an issue of patient abandonment.”
 

Now everyone has a good grasp of the rules

Fifteen years ago, many doctors were in open revolt against on-call duties, but they are more accepting now and understand the rules better, Mr. Healey said.

“Many hospitals have begun paying some specialists for call and designating hospitalists and surgicalists to do at least some of the work that used to be expected of on-call doctors,” he said.

According to Dr. Taylor, today’s on-call doctors often have less to do than in the past. “For example,” he said, “the hospitalist may admit an orthopedic patient at night, and then the orthopedic surgeon does the operation the next day. We’ve had EMTALA for 36 years now, and hospitals and doctors know how call works.”

A version of this article first appeared on Medscape.com.

Taking call is one of the more challenging - and annoying - aspects of the job for many physicians. Calls may wake them up in the middle of the night and can interfere with their at-home activities. In Medscape’s Employed Physicians Report, 37% of respondents said they have from 1 to 5 hours of call per month; 19% said they have 6 to 10 hours; and 12% have 11 hours or more.

“Even if you don’t have to come in to the ED, you can get calls in the middle of the night, and you may get paid very little, if anything,” said Robert Bitterman MD, JD, an emergency physician and attorney in Harbor Springs, Mich.

And responding to the calls is not optional. Dr. Bitterman said if on-call physicians don’t perform their duties, they could lose their hospital privileges, be fined by the federal government, or be sued for malpractice.

On-call activities are regulated by the federal Emergency Medical Treatment and Active Labor Act (EMTALA). Dr. Bitterman said it’s rare for the federal government to prosecute on-call physicians for violating EMTALA. Instead, it’s more likely that the hospital will be fined for EMTALA violations committed by on-call physicians.

However, the hospital passes the on-call obligation on to individual physicians through medical staff bylaws. Physicians who violate the bylaws may have their privileges restricted or removed, Dr. Bitterman said. Physicians could also be sued for malpractice, even if they never treated the patient, he added.
 

After-hours call duty in physicians’ practices

A very different type of call duty is having to respond to calls from one’s own patients after regular hours. Unlike doctors on ED call, who usually deal with patients they have never met, these physicians deal with their established patients or those of a colleague in their practice.

Courts have established that physicians have to provide an answering service or other means for their patients to contact them after hours, and the doctor must respond to these calls in a timely manner.

In a 2015 Louisiana ruling, a cardiologist was found liable for malpractice because he didn’t respond to an after-hours call from his patient. The patient tried several times to contact the cardiologist but got no reply.

Physicians may also be responsible if their answering service does not send critical messages to them immediately, if it fails to make appropriate documentation, or if it sends inaccurate data to the doctor.
 

Cases when on-call doctors didn’t respond

The Office of the Inspector General (OIG) of the U.S. Health and Human Services Administration oversees federal EMTALA violations and regularly reports them.

In 2018, the OIG fined a hospital in Waterloo, Iowa, $90,000 when an on-call cardiologist failed to implant a pacemaker for an ED patient. According to the OIG’s report, the patient arrived at the hospital with heart problems. Reached by phone, the cardiologist directed the ED physician to begin transcutaneous pacing but asked that the patient be transferred to another hospital for placement of the pacemaker. The patient died after transfer.

The OIG found that the original cardiologist could have placed the pacemaker, but, as often happens, it only fined the hospital, not the on-call physician for the EMTALA violation.

EMTALA requires that hospitals provide on-call specialists to assist emergency physicians with care of patients who arrive in the ED. In specialties for which there are few doctors to choose from, the on-call specialist may be on duty every third night and every third weekend. This can be daunting, especially for specialists who’ve had a grueling day of work.

Occasionally, on-call physicians, fearful they could make a medical error, request that the patient be transferred to another hospital for treatment. This is what a neurosurgeon who was on call at a Topeka, Kan., hospital did in 2001. Transferred to another hospital, the patient underwent an operation but lost sensation in his lower extremities. The patient sued the on-call neurosurgeon for negligence.

During the trial, the on-call neurosurgeon testified that he was “feeling run-down because he had been an on-call physician every third night for more than 10 years.” He also said this was the first time he had refused to see a patient because of fatigue, and he had decided that the patient “would be better off at a trauma center that had a trauma team and a fresher surgeon.”

The neurosurgeon successfully defended the malpractice suit, but Dr. Bitterman said he might have lost had there not been some unusual circumstances in the case. The court ruled that the hospital had not clearly defined the duties of on-call physicians, and the lawsuit didn’t cite the neurosurgeon’s EMTALA duty.
 

On-call duties defined by EMTALA

EMTALA sets the overall rules for on-call duties, which each hospital is expected to fine-tune on the basis of its own particular circumstances. Here are some of those rules, issued by the Centers for Medicare & Medicaid Services and the OIG.

Only an individual physician can be on call. The hospital’s on-call schedule cannot name a physician practice.

Call applies to all ED patients. Physicians cannot limit their on-call responsibilities to their own patients, to patients in their insurance network, or to paying patients.

There may be some gaps in the call schedule. The OIG is not specific as to how many gaps are allowed, said Nick Healey, an attorney in Cheyenne, Wyo., who has written about on-call duties. Among other things, adequate coverage depends on the number of available physicians and the demand for their services. Mr. Healey added that states may require more extensive availability of on-call physicians at high-level trauma centers.

Hospitals must have made arrangements for transfer. Whenever there is a gap in the schedule, hospitals need to have a designated hospital to send the patient to. Hospitals that unnecessarily transfer patients will be penalized.

The ED physician calls the shots. The emergency physician handling the case decides if the on-call doctor has to come in and treat the patient firsthand.

The on-call physician may delegate the work to others. On-call physicians may designate a nurse practitioner or physician assistant, but the on-call physician is ultimately responsible. The ED doctor may require the physician to come in anyway, according to Todd B. Taylor, MD, an emergency physician in Phoenix, who has written about on-call duties. Dr. Bitterman noted that the physician may designate a colleague to take their call, but the substitute has to have privileges at the hospital.

Physicians may do their own work while on call. Physicians can perform elective surgery while on call, provided they have made arrangements if they then become unavailable for duty, Dr. Taylor said. He added that physicians can also have simultaneous call at other hospitals, provided they make arrangements.
 

The hospital fine-tunes call obligations

The hospital is expected to further define the federal rules. For instance, the CMS says physicians should respond to calls within a “reasonable period of time” and requires hospitals to specify response times, which may be 15-30 minutes for responding to phone calls and traveling to the ED, Dr. Bitterman said.

The CMS says older physicians can be exempted from call. The hospital determines the age at which physicians can be exempted. “Hospitals typically exempt physicians over age 65 or 70, or when they have certain medical conditions,” said Lowell Brown, a Los Angeles attorney who deals with on-call duties.

The hospital also sets the call schedule, which may result in uncovered periods in specialties in which there are few physicians to draw from, according to Mr. Healey. He said many hospitals still use a simple rule of thumb, even though it has been dismissed by the CMS. Under this so-called “rule of three,” hospitals that have three doctors or fewer in a specialty do not have to provide constant call coverage.

On-call rules are part of the medical staff bylaws, and they have to be approved by the medical staff. This may require delicate negotiations between the staff’s leadership and administrators, Dr. Bitterman said.

It is often up to the emergency physician on duty to enforce the hospital’s on-call rules, Dr. Taylor said. “If the ED physician is having trouble, he or she may contact the on-call physician’s department chairman or, if necessary, the chief of the medical staff and ask that person to deal with the physician,” Dr. Taylor said.

The ED physician has to determine whether the patient needs to be transferred to another hospital. Dr. Taylor said the ED physician must fill out a transfer form and obtain consent from the receiving hospital.

If a patient has to be transferred because an on-call physician failed to appear, the originating hospital has to report this to the CMS, and the physician and the hospital can be cited for an inappropriate transfer and fined, Mr. Brown said. “The possibility of being identified in this way should be a powerful incentive to accept call duty,” he added.
 

Malpractice exposure of on-call physicians

When on-call doctors provide medical advice regarding an ED patient, that advice may be subject to malpractice litigation, Dr. Taylor said. “Even if you only give the ED doctor advice over the phone, that may establish a patient-physician relationship and a duty that patient can cite in a malpractice case,” he noted.

Refusing to take call may also be grounds for a malpractice lawsuit, Dr. Bitterman said. Refusing to see a patient would not be considered medical negligence, he continued, because no medical decision is made. Rather, it involves general negligence, which occurs when physicians fail to carry out duties expected of them.

Dr. Bitterman cited a 2006 malpractice judgment in which an on-call neurosurgeon in Missouri was found to be generally negligent. The neurosurgeon had arranged for a colleague in his practice to take his call, but the colleague did not have privileges at the hospital.

A patient with a brain bleed came in and the substitute was on duty. The patient had to be transferred to another hospital, where the patient died. The court ordered that the on-call doctor and the originating hospital had to split a fine of $400,800.
 

On-call physicians can be charged with abandonment

Dr. Bitterman said that if on-call physicians do not provide expected follow-up treatment for an ED patient, they could be charged with abandonment, which is a matter of state law and involves filing a malpractice lawsuit.

Abandonment involves unilaterally terminating the patient relationship without providing notice. There must be an established relationship, which, in the case of call, is formed when the doctor comes to the ED to examine or admit the patient, Dr. Bitterman said. He added that the on-call doctor’s obligation applies only to the medical condition the patient came in for.

Even when an on-call doctor does not see a patient, a relationship can be established if the hospital requires its on-call doctors to make follow-up visits for ED patients, Dr. Taylor said. At some hospitals, he said, on-call doctors have blanket agreements to provide follow-up care in return for not having to arrive in the middle of the night during the ED visit.

Dr. Taylor gave an example of the on-call doctor’s obligation: “The ED doctor puts a splint on the patient’s ankle fracture, and the orthopedic surgeon on call agrees to follow up with the patient within the next few days. If the orthopedic surgeon refuses to follow up without making a reasonable accommodation, it may become an issue of patient abandonment.”
 

Now everyone has a good grasp of the rules

Fifteen years ago, many doctors were in open revolt against on-call duties, but they are more accepting now and understand the rules better, Mr. Healey said.

“Many hospitals have begun paying some specialists for call and designating hospitalists and surgicalists to do at least some of the work that used to be expected of on-call doctors,” he said.

According to Dr. Taylor, today’s on-call doctors often have less to do than in the past. “For example,” he said, “the hospitalist may admit an orthopedic patient at night, and then the orthopedic surgeon does the operation the next day. We’ve had EMTALA for 36 years now, and hospitals and doctors know how call works.”

A version of this article first appeared on Medscape.com.

Taking call is one of the more challenging - and annoying - aspects of the job for many physicians. Calls may wake them up in the middle of the night and can interfere with their at-home activities. In Medscape’s Employed Physicians Report, 37% of respondents said they have from 1 to 5 hours of call per month; 19% said they have 6 to 10 hours; and 12% have 11 hours or more.

“Even if you don’t have to come in to the ED, you can get calls in the middle of the night, and you may get paid very little, if anything,” said Robert Bitterman MD, JD, an emergency physician and attorney in Harbor Springs, Mich.

And responding to the calls is not optional. Dr. Bitterman said if on-call physicians don’t perform their duties, they could lose their hospital privileges, be fined by the federal government, or be sued for malpractice.

On-call activities are regulated by the federal Emergency Medical Treatment and Active Labor Act (EMTALA). Dr. Bitterman said it’s rare for the federal government to prosecute on-call physicians for violating EMTALA. Instead, it’s more likely that the hospital will be fined for EMTALA violations committed by on-call physicians.

However, the hospital passes the on-call obligation on to individual physicians through medical staff bylaws. Physicians who violate the bylaws may have their privileges restricted or removed, Dr. Bitterman said. Physicians could also be sued for malpractice, even if they never treated the patient, he added.
 

After-hours call duty in physicians’ practices

A very different type of call duty is having to respond to calls from one’s own patients after regular hours. Unlike doctors on ED call, who usually deal with patients they have never met, these physicians deal with their established patients or those of a colleague in their practice.

Courts have established that physicians have to provide an answering service or other means for their patients to contact them after hours, and the doctor must respond to these calls in a timely manner.

In a 2015 Louisiana ruling, a cardiologist was found liable for malpractice because he didn’t respond to an after-hours call from his patient. The patient tried several times to contact the cardiologist but got no reply.

Physicians may also be responsible if their answering service does not send critical messages to them immediately, if it fails to make appropriate documentation, or if it sends inaccurate data to the doctor.
 

Cases when on-call doctors didn’t respond

The Office of the Inspector General (OIG) of the U.S. Health and Human Services Administration oversees federal EMTALA violations and regularly reports them.

In 2018, the OIG fined a hospital in Waterloo, Iowa, $90,000 when an on-call cardiologist failed to implant a pacemaker for an ED patient. According to the OIG’s report, the patient arrived at the hospital with heart problems. Reached by phone, the cardiologist directed the ED physician to begin transcutaneous pacing but asked that the patient be transferred to another hospital for placement of the pacemaker. The patient died after transfer.

The OIG found that the original cardiologist could have placed the pacemaker, but, as often happens, it only fined the hospital, not the on-call physician for the EMTALA violation.

EMTALA requires that hospitals provide on-call specialists to assist emergency physicians with care of patients who arrive in the ED. In specialties for which there are few doctors to choose from, the on-call specialist may be on duty every third night and every third weekend. This can be daunting, especially for specialists who’ve had a grueling day of work.

Occasionally, on-call physicians, fearful they could make a medical error, request that the patient be transferred to another hospital for treatment. This is what a neurosurgeon who was on call at a Topeka, Kan., hospital did in 2001. Transferred to another hospital, the patient underwent an operation but lost sensation in his lower extremities. The patient sued the on-call neurosurgeon for negligence.

During the trial, the on-call neurosurgeon testified that he was “feeling run-down because he had been an on-call physician every third night for more than 10 years.” He also said this was the first time he had refused to see a patient because of fatigue, and he had decided that the patient “would be better off at a trauma center that had a trauma team and a fresher surgeon.”

The neurosurgeon successfully defended the malpractice suit, but Dr. Bitterman said he might have lost had there not been some unusual circumstances in the case. The court ruled that the hospital had not clearly defined the duties of on-call physicians, and the lawsuit didn’t cite the neurosurgeon’s EMTALA duty.
 

On-call duties defined by EMTALA

EMTALA sets the overall rules for on-call duties, which each hospital is expected to fine-tune on the basis of its own particular circumstances. Here are some of those rules, issued by the Centers for Medicare & Medicaid Services and the OIG.

Only an individual physician can be on call. The hospital’s on-call schedule cannot name a physician practice.

Call applies to all ED patients. Physicians cannot limit their on-call responsibilities to their own patients, to patients in their insurance network, or to paying patients.

There may be some gaps in the call schedule. The OIG is not specific as to how many gaps are allowed, said Nick Healey, an attorney in Cheyenne, Wyo., who has written about on-call duties. Among other things, adequate coverage depends on the number of available physicians and the demand for their services. Mr. Healey added that states may require more extensive availability of on-call physicians at high-level trauma centers.

Hospitals must have made arrangements for transfer. Whenever there is a gap in the schedule, hospitals need to have a designated hospital to send the patient to. Hospitals that unnecessarily transfer patients will be penalized.

The ED physician calls the shots. The emergency physician handling the case decides if the on-call doctor has to come in and treat the patient firsthand.

The on-call physician may delegate the work to others. On-call physicians may designate a nurse practitioner or physician assistant, but the on-call physician is ultimately responsible. The ED doctor may require the physician to come in anyway, according to Todd B. Taylor, MD, an emergency physician in Phoenix, who has written about on-call duties. Dr. Bitterman noted that the physician may designate a colleague to take their call, but the substitute has to have privileges at the hospital.

Physicians may do their own work while on call. Physicians can perform elective surgery while on call, provided they have made arrangements if they then become unavailable for duty, Dr. Taylor said. He added that physicians can also have simultaneous call at other hospitals, provided they make arrangements.
 

The hospital fine-tunes call obligations

The hospital is expected to further define the federal rules. For instance, the CMS says physicians should respond to calls within a “reasonable period of time” and requires hospitals to specify response times, which may be 15-30 minutes for responding to phone calls and traveling to the ED, Dr. Bitterman said.

The CMS says older physicians can be exempted from call. The hospital determines the age at which physicians can be exempted. “Hospitals typically exempt physicians over age 65 or 70, or when they have certain medical conditions,” said Lowell Brown, a Los Angeles attorney who deals with on-call duties.

The hospital also sets the call schedule, which may result in uncovered periods in specialties in which there are few physicians to draw from, according to Mr. Healey. He said many hospitals still use a simple rule of thumb, even though it has been dismissed by the CMS. Under this so-called “rule of three,” hospitals that have three doctors or fewer in a specialty do not have to provide constant call coverage.

On-call rules are part of the medical staff bylaws, and they have to be approved by the medical staff. This may require delicate negotiations between the staff’s leadership and administrators, Dr. Bitterman said.

It is often up to the emergency physician on duty to enforce the hospital’s on-call rules, Dr. Taylor said. “If the ED physician is having trouble, he or she may contact the on-call physician’s department chairman or, if necessary, the chief of the medical staff and ask that person to deal with the physician,” Dr. Taylor said.

The ED physician has to determine whether the patient needs to be transferred to another hospital. Dr. Taylor said the ED physician must fill out a transfer form and obtain consent from the receiving hospital.

If a patient has to be transferred because an on-call physician failed to appear, the originating hospital has to report this to the CMS, and the physician and the hospital can be cited for an inappropriate transfer and fined, Mr. Brown said. “The possibility of being identified in this way should be a powerful incentive to accept call duty,” he added.
 

Malpractice exposure of on-call physicians

When on-call doctors provide medical advice regarding an ED patient, that advice may be subject to malpractice litigation, Dr. Taylor said. “Even if you only give the ED doctor advice over the phone, that may establish a patient-physician relationship and a duty that patient can cite in a malpractice case,” he noted.

Refusing to take call may also be grounds for a malpractice lawsuit, Dr. Bitterman said. Refusing to see a patient would not be considered medical negligence, he continued, because no medical decision is made. Rather, it involves general negligence, which occurs when physicians fail to carry out duties expected of them.

Dr. Bitterman cited a 2006 malpractice judgment in which an on-call neurosurgeon in Missouri was found to be generally negligent. The neurosurgeon had arranged for a colleague in his practice to take his call, but the colleague did not have privileges at the hospital.

A patient with a brain bleed came in and the substitute was on duty. The patient had to be transferred to another hospital, where the patient died. The court ordered that the on-call doctor and the originating hospital had to split a fine of $400,800.
 

On-call physicians can be charged with abandonment

Dr. Bitterman said that if on-call physicians do not provide expected follow-up treatment for an ED patient, they could be charged with abandonment, which is a matter of state law and involves filing a malpractice lawsuit.

Abandonment involves unilaterally terminating the patient relationship without providing notice. There must be an established relationship, which, in the case of call, is formed when the doctor comes to the ED to examine or admit the patient, Dr. Bitterman said. He added that the on-call doctor’s obligation applies only to the medical condition the patient came in for.

Even when an on-call doctor does not see a patient, a relationship can be established if the hospital requires its on-call doctors to make follow-up visits for ED patients, Dr. Taylor said. At some hospitals, he said, on-call doctors have blanket agreements to provide follow-up care in return for not having to arrive in the middle of the night during the ED visit.

Dr. Taylor gave an example of the on-call doctor’s obligation: “The ED doctor puts a splint on the patient’s ankle fracture, and the orthopedic surgeon on call agrees to follow up with the patient within the next few days. If the orthopedic surgeon refuses to follow up without making a reasonable accommodation, it may become an issue of patient abandonment.”
 

Now everyone has a good grasp of the rules

Fifteen years ago, many doctors were in open revolt against on-call duties, but they are more accepting now and understand the rules better, Mr. Healey said.

“Many hospitals have begun paying some specialists for call and designating hospitalists and surgicalists to do at least some of the work that used to be expected of on-call doctors,” he said.

According to Dr. Taylor, today’s on-call doctors often have less to do than in the past. “For example,” he said, “the hospitalist may admit an orthopedic patient at night, and then the orthopedic surgeon does the operation the next day. We’ve had EMTALA for 36 years now, and hospitals and doctors know how call works.”

A version of this article first appeared on Medscape.com.

The US Preventive Services Task Force (USPSTF) published updated recommendations on screening for syphilis on September 27.¹ The Task Force continues to recommend screening for all adolescents and adults who are at increased risk for infection. (As part of previous recommendations, the USPSTF also advocates screening all pregnant women for syphilis early in their pregnancy to prevent congenital syphilis.²)

Who is at increased risk? Men who have sex with men (MSM), those with HIV or other sexually transmitted infections (STIs), those who use illicit drugs, and those with a history of incarceration, sex work, or military service are considered to be at increased risk for syphilis. Additionally, since state and local health departments collect and publish STI incidence data, it’s important to stay up to date on how common syphilis is in one’s community and tailor screening practices accordingly.

Men account for more than 80% of all primary and secondary syphilis infections, and MSM account for 53% of cases in men.³ The highest rates of syphilis are in men ages 25-29 years and 30-34 years (58.1 and 55.7 cases per 100,000, respectively).³

Why screening is important. Primary and secondary syphilis rates have increased steadily from an all-time low of 2.1 per 100,000 in 2000 to 12.7 per 100,000 in 2020.⁴ There were 171,074 cases reported in 2021.⁵

If not detected and treated, syphilis will progress from the primary and secondary stages to a latent form. About one-third of those with latent syphilis will develop tertiary syphilis, which can affect every organ system and cause multiple neurologic disorders.

How to screen. Syphilis screening typically involves a 2-step process. The first test that should be performed is a Venereal Disease Research Laboratory (VDRL) or rapid plasma reagin (RPR) test. This is followed by a treponemal antibody test if the initial test is positive. While the VDRL and RPR tests have high sensitivity, many other conditions can cause a false-positive result, necessitating confirmation with the more specific antibody test.

As far as frequency, the Task Force suggests screening annually for those at continued risk and more frequently (every 3 or 6 months) for those at highest risk.

Treatment for primary, secondary, and early latent syphilis (< 1 year’s duration) is a single intramuscular (IM) injection of benzathine penicillin, 2.4 million units. For late latent syphilis or syphilis of unknown duration, treatment is benzathine penicillin, 2.4 million units, administered in 3 weekly IM doses.

Treatment for those with penicillin allergies depends on the stage of syphilis and whether or not the patient is pregnant. Refer to the STD treatment guidelines for guidance.⁶

The CDC recommends presumptive treatment for anyone who has had sexual contact in the past 90 days with a person who’s been given a diagnosis of primary, secondary, or early latent syphilis.⁶

And finally, remember that all STIs are reportable to your local health department, which can assist with contract tracing and treatment follow-up.

The US Preventive Services Task Force (USPSTF) published updated recommendations on screening for syphilis on September 27.¹ The Task Force continues to recommend screening for all adolescents and adults who are at increased risk for infection. (As part of previous recommendations, the USPSTF also advocates screening all pregnant women for syphilis early in their pregnancy to prevent congenital syphilis.²)

Who is at increased risk? Men who have sex with men (MSM), those with HIV or other sexually transmitted infections (STIs), those who use illicit drugs, and those with a history of incarceration, sex work, or military service are considered to be at increased risk for syphilis. Additionally, since state and local health departments collect and publish STI incidence data, it’s important to stay up to date on how common syphilis is in one’s community and tailor screening practices accordingly.

Men account for more than 80% of all primary and secondary syphilis infections, and MSM account for 53% of cases in men.³ The highest rates of syphilis are in men ages 25-29 years and 30-34 years (58.1 and 55.7 cases per 100,000, respectively).³

Why screening is important. Primary and secondary syphilis rates have increased steadily from an all-time low of 2.1 per 100,000 in 2000 to 12.7 per 100,000 in 2020.⁴ There were 171,074 cases reported in 2021.⁵

If not detected and treated, syphilis will progress from the primary and secondary stages to a latent form. About one-third of those with latent syphilis will develop tertiary syphilis, which can affect every organ system and cause multiple neurologic disorders.

How to screen. Syphilis screening typically involves a 2-step process. The first test that should be performed is a Venereal Disease Research Laboratory (VDRL) or rapid plasma reagin (RPR) test. This is followed by a treponemal antibody test if the initial test is positive. While the VDRL and RPR tests have high sensitivity, many other conditions can cause a false-positive result, necessitating confirmation with the more specific antibody test.

As far as frequency, the Task Force suggests screening annually for those at continued risk and more frequently (every 3 or 6 months) for those at highest risk.

Treatment for primary, secondary, and early latent syphilis (< 1 year’s duration) is a single intramuscular (IM) injection of benzathine penicillin, 2.4 million units. For late latent syphilis or syphilis of unknown duration, treatment is benzathine penicillin, 2.4 million units, administered in 3 weekly IM doses.

Treatment for those with penicillin allergies depends on the stage of syphilis and whether or not the patient is pregnant. Refer to the STD treatment guidelines for guidance.⁶

The CDC recommends presumptive treatment for anyone who has had sexual contact in the past 90 days with a person who’s been given a diagnosis of primary, secondary, or early latent syphilis.⁶

And finally, remember that all STIs are reportable to your local health department, which can assist with contract tracing and treatment follow-up.

The US Preventive Services Task Force (USPSTF) published updated recommendations on screening for syphilis on September 27.¹ The Task Force continues to recommend screening for all adolescents and adults who are at increased risk for infection. (As part of previous recommendations, the USPSTF also advocates screening all pregnant women for syphilis early in their pregnancy to prevent congenital syphilis.²)

Who is at increased risk? Men who have sex with men (MSM), those with HIV or other sexually transmitted infections (STIs), those who use illicit drugs, and those with a history of incarceration, sex work, or military service are considered to be at increased risk for syphilis. Additionally, since state and local health departments collect and publish STI incidence data, it’s important to stay up to date on how common syphilis is in one’s community and tailor screening practices accordingly.

Men account for more than 80% of all primary and secondary syphilis infections, and MSM account for 53% of cases in men.³ The highest rates of syphilis are in men ages 25-29 years and 30-34 years (58.1 and 55.7 cases per 100,000, respectively).³

Why screening is important. Primary and secondary syphilis rates have increased steadily from an all-time low of 2.1 per 100,000 in 2000 to 12.7 per 100,000 in 2020.⁴ There were 171,074 cases reported in 2021.⁵

If not detected and treated, syphilis will progress from the primary and secondary stages to a latent form. About one-third of those with latent syphilis will develop tertiary syphilis, which can affect every organ system and cause multiple neurologic disorders.

How to screen. Syphilis screening typically involves a 2-step process. The first test that should be performed is a Venereal Disease Research Laboratory (VDRL) or rapid plasma reagin (RPR) test. This is followed by a treponemal antibody test if the initial test is positive. While the VDRL and RPR tests have high sensitivity, many other conditions can cause a false-positive result, necessitating confirmation with the more specific antibody test.

As far as frequency, the Task Force suggests screening annually for those at continued risk and more frequently (every 3 or 6 months) for those at highest risk.

Treatment for primary, secondary, and early latent syphilis (< 1 year’s duration) is a single intramuscular (IM) injection of benzathine penicillin, 2.4 million units. For late latent syphilis or syphilis of unknown duration, treatment is benzathine penicillin, 2.4 million units, administered in 3 weekly IM doses.

Treatment for those with penicillin allergies depends on the stage of syphilis and whether or not the patient is pregnant. Refer to the STD treatment guidelines for guidance.⁶

The CDC recommends presumptive treatment for anyone who has had sexual contact in the past 90 days with a person who’s been given a diagnosis of primary, secondary, or early latent syphilis.⁶

And finally, remember that all STIs are reportable to your local health department, which can assist with contract tracing and treatment follow-up.

The effectiveness and safety of advanced therapies for psoriatic arthritis (PsA) was a focus of many published studies last month. Janus kinase inhibitors (JAKi) are a recent class of drugs made available to treat PsA and related diseases, and several clinical trials have been published. Sarabia and colleagues reported the results of a meta-analysis of 15 randomized controlled trials including 6757 patients with psoriasis or PsA who received treatment with a JAKi or placebo. Their analyses revealed that treatment with JAKi vs placebo was associated with higher odds of achieving American College of Rheumatology 20 (ACR20) response (odds ratio [OR] 4.45; 95% CI 3.64-5.44), with similar outcomes observed with tofacitinib vs placebo (OR 2.96; 95% CI 2.01-4.35) and non-tofacitinib JAKi vs placebo (OR 5.41; 95% CI 3.95-7.40). Serious adverse event rates were low (1%-7% in the maximum-dose intervention group).

Interleukin-23i (guselkumab, tildrakizumab, or risankizumab) are another class of biologics recently approved for the treatment of PsA. Preliminary results from a real-world study demonstrate the efficacy of these drugs for PsA. In a retrospective observational study including 80 patients with psoriasis (22 with PsA) who received guselkumab, tildrakizumab, or risankizumab, Elgaard and colleagues demonstrated that 40.9% or 36.4% of the PsA patients achieved complete or partial remission, respectively, compared with only 18.2% of patients with no improvement.

Regarding drug safety, a recent study demonstrated low rates of opportunistic infections with biologic disease-modifying antirheumatic drugs (bDMARD) and targeted synthetic DMARD (tsDMARD). Vassilopoulos and colleagues conducted a meta-analysis of 47 randomized controlled trials and 26 follow-up extension studies that included patients with PsA who received at least one dose of a bDMARD or a tsDMARD (n = 11,790) or placebo (n = 6425) during the placebo-controlled period, and 17,197 patients who received at least one dose of a bDMARD or a tsDMARD in the long-term extension period.

The cumulative incidence of opportunistic infections was < 3% when stratified by the mechanism of action: JAKi (2.72%; 95% CI 1.05%-5.04%), anti-interleukin (IL)-17i (1.18%; 95% CI 0.60%-1.90%), anti-IL-23i (0.24%; 95% CI 0.04%-0.54%), and TNFi (0.01%; 95% CI 0.00%-0.21%). These results are consistent with my own observations in my clinic. Thus, currently available advanced therapies, including JAKi and IL-23i, are effective and safe for the management of patients with PsA when used as monotherapy with or without conventional synthetic DMARD (csDMARD). Ongoing studies on combination therapy will provide us with guidance on the efficacy and safety of combining these drugs for the treatment of resistant disease.

Many patients do not respond to treatment, however. Actionable risk factors for lack of response are of clinical interest. One such factor is obesity. In an observational study of 774 adult PsA patients who started their first b/tsDMARD, Vallejo-Yague and colleagues reported that the odds of achieving minimal disease activity (adjusted OR [aOR] 0.45; 95% CI 0.24-0.82) and Disease Activity Index for Psoriatic Arthritis (DAPSA)-remission (aOR 0.42; 95% CI 0.21-0.85) were lower in the obese vs normal-weight group within the first year. Thus, obese patients had ~50% lower likelihood of achieving a state of low disease activity. Comprehensive management of PsA must include management of obesity and other comorbid conditions to achieve optimal outcomes.

Finally, an interesting study by Freuer and colleagues used bidirectional two-sample Mendelian randomization in 12,882 patients with inflammatory bowel disease (IBD), 21,770 matched controls, 5621 patients with psoriasis, 2063 patients with PsA, and 252,323 controls. The study found that genetically predicted IBD was associated with a higher risk for PsA (pooled OR 1.11; P = .003) with the risk being majorly mediated by Crohn's disease (OR 1.12; P = .002) and not ulcerative colitis (P = .70). Thus, patients with Crohn's disease need to be carefully evaluated for the development of PsA.

The effectiveness and safety of advanced therapies for psoriatic arthritis (PsA) was a focus of many published studies last month. Janus kinase inhibitors (JAKi) are a recent class of drugs made available to treat PsA and related diseases, and several clinical trials have been published. Sarabia and colleagues reported the results of a meta-analysis of 15 randomized controlled trials including 6757 patients with psoriasis or PsA who received treatment with a JAKi or placebo. Their analyses revealed that treatment with JAKi vs placebo was associated with higher odds of achieving American College of Rheumatology 20 (ACR20) response (odds ratio [OR] 4.45; 95% CI 3.64-5.44), with similar outcomes observed with tofacitinib vs placebo (OR 2.96; 95% CI 2.01-4.35) and non-tofacitinib JAKi vs placebo (OR 5.41; 95% CI 3.95-7.40). Serious adverse event rates were low (1%-7% in the maximum-dose intervention group).

Interleukin-23i (guselkumab, tildrakizumab, or risankizumab) are another class of biologics recently approved for the treatment of PsA. Preliminary results from a real-world study demonstrate the efficacy of these drugs for PsA. In a retrospective observational study including 80 patients with psoriasis (22 with PsA) who received guselkumab, tildrakizumab, or risankizumab, Elgaard and colleagues demonstrated that 40.9% or 36.4% of the PsA patients achieved complete or partial remission, respectively, compared with only 18.2% of patients with no improvement.

Regarding drug safety, a recent study demonstrated low rates of opportunistic infections with biologic disease-modifying antirheumatic drugs (bDMARD) and targeted synthetic DMARD (tsDMARD). Vassilopoulos and colleagues conducted a meta-analysis of 47 randomized controlled trials and 26 follow-up extension studies that included patients with PsA who received at least one dose of a bDMARD or a tsDMARD (n = 11,790) or placebo (n = 6425) during the placebo-controlled period, and 17,197 patients who received at least one dose of a bDMARD or a tsDMARD in the long-term extension period.

The cumulative incidence of opportunistic infections was < 3% when stratified by the mechanism of action: JAKi (2.72%; 95% CI 1.05%-5.04%), anti-interleukin (IL)-17i (1.18%; 95% CI 0.60%-1.90%), anti-IL-23i (0.24%; 95% CI 0.04%-0.54%), and TNFi (0.01%; 95% CI 0.00%-0.21%). These results are consistent with my own observations in my clinic. Thus, currently available advanced therapies, including JAKi and IL-23i, are effective and safe for the management of patients with PsA when used as monotherapy with or without conventional synthetic DMARD (csDMARD). Ongoing studies on combination therapy will provide us with guidance on the efficacy and safety of combining these drugs for the treatment of resistant disease.

Many patients do not respond to treatment, however. Actionable risk factors for lack of response are of clinical interest. One such factor is obesity. In an observational study of 774 adult PsA patients who started their first b/tsDMARD, Vallejo-Yague and colleagues reported that the odds of achieving minimal disease activity (adjusted OR [aOR] 0.45; 95% CI 0.24-0.82) and Disease Activity Index for Psoriatic Arthritis (DAPSA)-remission (aOR 0.42; 95% CI 0.21-0.85) were lower in the obese vs normal-weight group within the first year. Thus, obese patients had ~50% lower likelihood of achieving a state of low disease activity. Comprehensive management of PsA must include management of obesity and other comorbid conditions to achieve optimal outcomes.

Finally, an interesting study by Freuer and colleagues used bidirectional two-sample Mendelian randomization in 12,882 patients with inflammatory bowel disease (IBD), 21,770 matched controls, 5621 patients with psoriasis, 2063 patients with PsA, and 252,323 controls. The study found that genetically predicted IBD was associated with a higher risk for PsA (pooled OR 1.11; P = .003) with the risk being majorly mediated by Crohn's disease (OR 1.12; P = .002) and not ulcerative colitis (P = .70). Thus, patients with Crohn's disease need to be carefully evaluated for the development of PsA.

The effectiveness and safety of advanced therapies for psoriatic arthritis (PsA) was a focus of many published studies last month. Janus kinase inhibitors (JAKi) are a recent class of drugs made available to treat PsA and related diseases, and several clinical trials have been published. Sarabia and colleagues reported the results of a meta-analysis of 15 randomized controlled trials including 6757 patients with psoriasis or PsA who received treatment with a JAKi or placebo. Their analyses revealed that treatment with JAKi vs placebo was associated with higher odds of achieving American College of Rheumatology 20 (ACR20) response (odds ratio [OR] 4.45; 95% CI 3.64-5.44), with similar outcomes observed with tofacitinib vs placebo (OR 2.96; 95% CI 2.01-4.35) and non-tofacitinib JAKi vs placebo (OR 5.41; 95% CI 3.95-7.40). Serious adverse event rates were low (1%-7% in the maximum-dose intervention group).

Interleukin-23i (guselkumab, tildrakizumab, or risankizumab) are another class of biologics recently approved for the treatment of PsA. Preliminary results from a real-world study demonstrate the efficacy of these drugs for PsA. In a retrospective observational study including 80 patients with psoriasis (22 with PsA) who received guselkumab, tildrakizumab, or risankizumab, Elgaard and colleagues demonstrated that 40.9% or 36.4% of the PsA patients achieved complete or partial remission, respectively, compared with only 18.2% of patients with no improvement.

Regarding drug safety, a recent study demonstrated low rates of opportunistic infections with biologic disease-modifying antirheumatic drugs (bDMARD) and targeted synthetic DMARD (tsDMARD). Vassilopoulos and colleagues conducted a meta-analysis of 47 randomized controlled trials and 26 follow-up extension studies that included patients with PsA who received at least one dose of a bDMARD or a tsDMARD (n = 11,790) or placebo (n = 6425) during the placebo-controlled period, and 17,197 patients who received at least one dose of a bDMARD or a tsDMARD in the long-term extension period.

The cumulative incidence of opportunistic infections was < 3% when stratified by the mechanism of action: JAKi (2.72%; 95% CI 1.05%-5.04%), anti-interleukin (IL)-17i (1.18%; 95% CI 0.60%-1.90%), anti-IL-23i (0.24%; 95% CI 0.04%-0.54%), and TNFi (0.01%; 95% CI 0.00%-0.21%). These results are consistent with my own observations in my clinic. Thus, currently available advanced therapies, including JAKi and IL-23i, are effective and safe for the management of patients with PsA when used as monotherapy with or without conventional synthetic DMARD (csDMARD). Ongoing studies on combination therapy will provide us with guidance on the efficacy and safety of combining these drugs for the treatment of resistant disease.

Many patients do not respond to treatment, however. Actionable risk factors for lack of response are of clinical interest. One such factor is obesity. In an observational study of 774 adult PsA patients who started their first b/tsDMARD, Vallejo-Yague and colleagues reported that the odds of achieving minimal disease activity (adjusted OR [aOR] 0.45; 95% CI 0.24-0.82) and Disease Activity Index for Psoriatic Arthritis (DAPSA)-remission (aOR 0.42; 95% CI 0.21-0.85) were lower in the obese vs normal-weight group within the first year. Thus, obese patients had ~50% lower likelihood of achieving a state of low disease activity. Comprehensive management of PsA must include management of obesity and other comorbid conditions to achieve optimal outcomes.

Finally, an interesting study by Freuer and colleagues used bidirectional two-sample Mendelian randomization in 12,882 patients with inflammatory bowel disease (IBD), 21,770 matched controls, 5621 patients with psoriasis, 2063 patients with PsA, and 252,323 controls. The study found that genetically predicted IBD was associated with a higher risk for PsA (pooled OR 1.11; P = .003) with the risk being majorly mediated by Crohn's disease (OR 1.12; P = .002) and not ulcerative colitis (P = .70). Thus, patients with Crohn's disease need to be carefully evaluated for the development of PsA.

Agents proven to reduce major kidney issues in type 2 diabetes include renin-angiotensin system blockers, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and nonsteroidal mineralocorticoid inhibitors, but there are few data on the renal effects of the glucagon-like peptide-1 (GLP-1)/glucose-dependent insulinotropic polypeptide (GIP) receptor agonist tirzepatide. In a post-hoc analysis of the SURPASS-4 trial, Heerspink and colleagues reported that tirzepatide slowed the rate of estimated glomerular filtration rate (eGFR) decline and reduced urine albumin-to-creatinine ratio (ACR) compared with insulin glargine U100. There was also a reduction (≥ 40% decline) in the composite kidney outcome of eGFR, end-stage kidney disease (ESKD), death due to kidney failure, and new-onset macroalbuminuria, and this was driven by the reduction in new-onset macroalbuminuria. Although this was a post-hoc, exploratory analysis, the benefit of tirzepatide on kidney effects suggests that this agent should be studied in type 2 diabetes patients at high risk for kidney disease progression to determine whether indeed there will be a kidney protective effect.

Diabetes is the leading cause of ESKD, and recognizing patients at high risk for progression to ESKD is paramount. Abnormal glycolipid metabolism contributes to the development and progression of diabetic kidney disease (DKD). Bile acids, by regulating glycolipid metabolism, may indirectly provide renoprotective effects. Xiao and colleagues have published a retrospective cohort study of 184 Chinese patients with type 2 diabetes and biopsy-proven DKD. They found that low levels of bile acids (≤2.8 mmol/L) were associated with an over fivefold risk for ESKD after adjusting for known factors associated with ESKD. This is the first study suggesting a link between low bile acid levels and adverse kidney outcomes in DKD, and it provides a rationale for studying bile acid analogs as therapeutic agents for the treatment of DKD.

SGLT2 inhibitors and GLP-1 receptor agonists have proven cardiorenal benefits in type 2 diabetes, and each is recommended in guidelines for patients at higher risk for cardiorenal complications. There are no head-to-head randomized trials of SGLT2 inhibitors vs GLP-1 receptor agonists, and studies suggesting an increased risk for lower-extremity amputation with SGLT2 inhibitors have shown inconsistent results. Lee and colleagues conducted a retrospective cohort study in Taiwan, and, after propensity score-matching patients with type 2 diabetes treated with SGLT inhibitors or GLP-1 receptor agonists, they found no significant difference in major adverse limb events between the two groups. Although limited by retrospective design, short follow-up, and a low number of events, this study suggests that SGLT2 inhibitors and GLP-1 receptor agonists should continue to be used as indicated and according to diabetes guidelines, with no difference in amputation rates between these two classes of antihyperglycemic agents.

Gastrointestinal adverse events are the most common side effects related to metformin use. Many clinicians choose an extended-release metformin preparation over immediate-release, believing that there may be better tolerability, but studies have shown inconsistent results. In a systematic review, meta-analysis, and meta-regression of randomized controlled trials, Nabrdalik and colleagues demonstrated an increased risk for abdominal pain, nausea, and diarrhea with metformin compared with other antidiabetic drugs or placebo, as well as a reduced risk for bloating and diarrhea with extended-release metformin compared with immediate-release formulations. These findings reinforce the practice for considering metformin extended-release over immediate-release formulations to reduce the chance of gastrointestinal side effects.

Agents proven to reduce major kidney issues in type 2 diabetes include renin-angiotensin system blockers, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and nonsteroidal mineralocorticoid inhibitors, but there are few data on the renal effects of the glucagon-like peptide-1 (GLP-1)/glucose-dependent insulinotropic polypeptide (GIP) receptor agonist tirzepatide. In a post-hoc analysis of the SURPASS-4 trial, Heerspink and colleagues reported that tirzepatide slowed the rate of estimated glomerular filtration rate (eGFR) decline and reduced urine albumin-to-creatinine ratio (ACR) compared with insulin glargine U100. There was also a reduction (≥ 40% decline) in the composite kidney outcome of eGFR, end-stage kidney disease (ESKD), death due to kidney failure, and new-onset macroalbuminuria, and this was driven by the reduction in new-onset macroalbuminuria. Although this was a post-hoc, exploratory analysis, the benefit of tirzepatide on kidney effects suggests that this agent should be studied in type 2 diabetes patients at high risk for kidney disease progression to determine whether indeed there will be a kidney protective effect.

Diabetes is the leading cause of ESKD, and recognizing patients at high risk for progression to ESKD is paramount. Abnormal glycolipid metabolism contributes to the development and progression of diabetic kidney disease (DKD). Bile acids, by regulating glycolipid metabolism, may indirectly provide renoprotective effects. Xiao and colleagues have published a retrospective cohort study of 184 Chinese patients with type 2 diabetes and biopsy-proven DKD. They found that low levels of bile acids (≤2.8 mmol/L) were associated with an over fivefold risk for ESKD after adjusting for known factors associated with ESKD. This is the first study suggesting a link between low bile acid levels and adverse kidney outcomes in DKD, and it provides a rationale for studying bile acid analogs as therapeutic agents for the treatment of DKD.

SGLT2 inhibitors and GLP-1 receptor agonists have proven cardiorenal benefits in type 2 diabetes, and each is recommended in guidelines for patients at higher risk for cardiorenal complications. There are no head-to-head randomized trials of SGLT2 inhibitors vs GLP-1 receptor agonists, and studies suggesting an increased risk for lower-extremity amputation with SGLT2 inhibitors have shown inconsistent results. Lee and colleagues conducted a retrospective cohort study in Taiwan, and, after propensity score-matching patients with type 2 diabetes treated with SGLT inhibitors or GLP-1 receptor agonists, they found no significant difference in major adverse limb events between the two groups. Although limited by retrospective design, short follow-up, and a low number of events, this study suggests that SGLT2 inhibitors and GLP-1 receptor agonists should continue to be used as indicated and according to diabetes guidelines, with no difference in amputation rates between these two classes of antihyperglycemic agents.

Gastrointestinal adverse events are the most common side effects related to metformin use. Many clinicians choose an extended-release metformin preparation over immediate-release, believing that there may be better tolerability, but studies have shown inconsistent results. In a systematic review, meta-analysis, and meta-regression of randomized controlled trials, Nabrdalik and colleagues demonstrated an increased risk for abdominal pain, nausea, and diarrhea with metformin compared with other antidiabetic drugs or placebo, as well as a reduced risk for bloating and diarrhea with extended-release metformin compared with immediate-release formulations. These findings reinforce the practice for considering metformin extended-release over immediate-release formulations to reduce the chance of gastrointestinal side effects.

Agents proven to reduce major kidney issues in type 2 diabetes include renin-angiotensin system blockers, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and nonsteroidal mineralocorticoid inhibitors, but there are few data on the renal effects of the glucagon-like peptide-1 (GLP-1)/glucose-dependent insulinotropic polypeptide (GIP) receptor agonist tirzepatide. In a post-hoc analysis of the SURPASS-4 trial, Heerspink and colleagues reported that tirzepatide slowed the rate of estimated glomerular filtration rate (eGFR) decline and reduced urine albumin-to-creatinine ratio (ACR) compared with insulin glargine U100. There was also a reduction (≥ 40% decline) in the composite kidney outcome of eGFR, end-stage kidney disease (ESKD), death due to kidney failure, and new-onset macroalbuminuria, and this was driven by the reduction in new-onset macroalbuminuria. Although this was a post-hoc, exploratory analysis, the benefit of tirzepatide on kidney effects suggests that this agent should be studied in type 2 diabetes patients at high risk for kidney disease progression to determine whether indeed there will be a kidney protective effect.

Diabetes is the leading cause of ESKD, and recognizing patients at high risk for progression to ESKD is paramount. Abnormal glycolipid metabolism contributes to the development and progression of diabetic kidney disease (DKD). Bile acids, by regulating glycolipid metabolism, may indirectly provide renoprotective effects. Xiao and colleagues have published a retrospective cohort study of 184 Chinese patients with type 2 diabetes and biopsy-proven DKD. They found that low levels of bile acids (≤2.8 mmol/L) were associated with an over fivefold risk for ESKD after adjusting for known factors associated with ESKD. This is the first study suggesting a link between low bile acid levels and adverse kidney outcomes in DKD, and it provides a rationale for studying bile acid analogs as therapeutic agents for the treatment of DKD.

SGLT2 inhibitors and GLP-1 receptor agonists have proven cardiorenal benefits in type 2 diabetes, and each is recommended in guidelines for patients at higher risk for cardiorenal complications. There are no head-to-head randomized trials of SGLT2 inhibitors vs GLP-1 receptor agonists, and studies suggesting an increased risk for lower-extremity amputation with SGLT2 inhibitors have shown inconsistent results. Lee and colleagues conducted a retrospective cohort study in Taiwan, and, after propensity score-matching patients with type 2 diabetes treated with SGLT inhibitors or GLP-1 receptor agonists, they found no significant difference in major adverse limb events between the two groups. Although limited by retrospective design, short follow-up, and a low number of events, this study suggests that SGLT2 inhibitors and GLP-1 receptor agonists should continue to be used as indicated and according to diabetes guidelines, with no difference in amputation rates between these two classes of antihyperglycemic agents.

Gastrointestinal adverse events are the most common side effects related to metformin use. Many clinicians choose an extended-release metformin preparation over immediate-release, believing that there may be better tolerability, but studies have shown inconsistent results. In a systematic review, meta-analysis, and meta-regression of randomized controlled trials, Nabrdalik and colleagues demonstrated an increased risk for abdominal pain, nausea, and diarrhea with metformin compared with other antidiabetic drugs or placebo, as well as a reduced risk for bloating and diarrhea with extended-release metformin compared with immediate-release formulations. These findings reinforce the practice for considering metformin extended-release over immediate-release formulations to reduce the chance of gastrointestinal side effects.

Richards and colleagues explored the effects of aspirin prophylaxis in women with chronic hypertension. They did not detect a lowered risk for preeclampsia but did note a significantly decreased risk for preterm birth in the aspirin group. This was a systematic review and meta-analysis of nine studies (including retrospective cohort and randomized controlled trials). The mixed quality of the source data did limit the meta-analysis. However, this finding suggests that further research is warranted, and we may have a new role for aspirin in helping to decrease preterm birth in women with chronic hypertension.

Cleary and colleagues investigated the use of 30 mg oral nifedipine ER given every 24 hours until delivery in patients with preE with SF. In this randomized, triple-blinded, placebo-controlled trial, 110 patients were randomly assigned to nifedipine treatment or placebo. The results suggest a role for this medication early in the treatment of preE with SF, as the treated patients were much less likely to require acute therapy for severe-range blood pressure. The researchers also noted a trend toward fewer cesarean deliveries (20.8% vs 34.7%) and lower neonatal intensive care unit admissions (29.1% vs 47.1%) in the nifedipine ER group. This favors the use of nifedipine ER in patients with preE with SF.

Stewart and colleagues examined the more common morbidities associated with MTOP after 20 weeks estimated gestational age using a 10-year retrospective cohort study involving 407 patients. They found that 99% of the women had a successful vaginal delivery; however, 25% had some morbidity. Additionally, 16% of the women needed manual removal of placental tissue, 11% had postpartum hemorrhage, and 1.3% experienced severe maternal morbidity (including amniotic fluid embolism), but no maternal deaths occurred. Increased surveillance for postpartum hemorrhage in this patient population should be considered.

Righini and colleagues provide reassurance regarding a commonly used test to rule out pulmonary embolism in pregnant women. They present ancillary data from a prospective management outcome study of 149 women who underwent CT pulmonary angiography testing in pregnancy. There have been concerns raised regarding potential harmful effects related to intravenous iodinated contrast agents on thyroid function. None of the infants born to these patients had evidence of neonatal hypothyroidism (assessed via thyroid-stimulating hormone measurements). This gives reassurance that the use of CT pulmonary angiography testing for pulmonary embolism in pregnancy is safe.

Richards and colleagues explored the effects of aspirin prophylaxis in women with chronic hypertension. They did not detect a lowered risk for preeclampsia but did note a significantly decreased risk for preterm birth in the aspirin group. This was a systematic review and meta-analysis of nine studies (including retrospective cohort and randomized controlled trials). The mixed quality of the source data did limit the meta-analysis. However, this finding suggests that further research is warranted, and we may have a new role for aspirin in helping to decrease preterm birth in women with chronic hypertension.

Cleary and colleagues investigated the use of 30 mg oral nifedipine ER given every 24 hours until delivery in patients with preE with SF. In this randomized, triple-blinded, placebo-controlled trial, 110 patients were randomly assigned to nifedipine treatment or placebo. The results suggest a role for this medication early in the treatment of preE with SF, as the treated patients were much less likely to require acute therapy for severe-range blood pressure. The researchers also noted a trend toward fewer cesarean deliveries (20.8% vs 34.7%) and lower neonatal intensive care unit admissions (29.1% vs 47.1%) in the nifedipine ER group. This favors the use of nifedipine ER in patients with preE with SF.

Stewart and colleagues examined the more common morbidities associated with MTOP after 20 weeks estimated gestational age using a 10-year retrospective cohort study involving 407 patients. They found that 99% of the women had a successful vaginal delivery; however, 25% had some morbidity. Additionally, 16% of the women needed manual removal of placental tissue, 11% had postpartum hemorrhage, and 1.3% experienced severe maternal morbidity (including amniotic fluid embolism), but no maternal deaths occurred. Increased surveillance for postpartum hemorrhage in this patient population should be considered.

Righini and colleagues provide reassurance regarding a commonly used test to rule out pulmonary embolism in pregnant women. They present ancillary data from a prospective management outcome study of 149 women who underwent CT pulmonary angiography testing in pregnancy. There have been concerns raised regarding potential harmful effects related to intravenous iodinated contrast agents on thyroid function. None of the infants born to these patients had evidence of neonatal hypothyroidism (assessed via thyroid-stimulating hormone measurements). This gives reassurance that the use of CT pulmonary angiography testing for pulmonary embolism in pregnancy is safe.

Richards and colleagues explored the effects of aspirin prophylaxis in women with chronic hypertension. They did not detect a lowered risk for preeclampsia but did note a significantly decreased risk for preterm birth in the aspirin group. This was a systematic review and meta-analysis of nine studies (including retrospective cohort and randomized controlled trials). The mixed quality of the source data did limit the meta-analysis. However, this finding suggests that further research is warranted, and we may have a new role for aspirin in helping to decrease preterm birth in women with chronic hypertension.

Cleary and colleagues investigated the use of 30 mg oral nifedipine ER given every 24 hours until delivery in patients with preE with SF. In this randomized, triple-blinded, placebo-controlled trial, 110 patients were randomly assigned to nifedipine treatment or placebo. The results suggest a role for this medication early in the treatment of preE with SF, as the treated patients were much less likely to require acute therapy for severe-range blood pressure. The researchers also noted a trend toward fewer cesarean deliveries (20.8% vs 34.7%) and lower neonatal intensive care unit admissions (29.1% vs 47.1%) in the nifedipine ER group. This favors the use of nifedipine ER in patients with preE with SF.

Stewart and colleagues examined the more common morbidities associated with MTOP after 20 weeks estimated gestational age using a 10-year retrospective cohort study involving 407 patients. They found that 99% of the women had a successful vaginal delivery; however, 25% had some morbidity. Additionally, 16% of the women needed manual removal of placental tissue, 11% had postpartum hemorrhage, and 1.3% experienced severe maternal morbidity (including amniotic fluid embolism), but no maternal deaths occurred. Increased surveillance for postpartum hemorrhage in this patient population should be considered.

Righini and colleagues provide reassurance regarding a commonly used test to rule out pulmonary embolism in pregnant women. They present ancillary data from a prospective management outcome study of 149 women who underwent CT pulmonary angiography testing in pregnancy. There have been concerns raised regarding potential harmful effects related to intravenous iodinated contrast agents on thyroid function. None of the infants born to these patients had evidence of neonatal hypothyroidism (assessed via thyroid-stimulating hormone measurements). This gives reassurance that the use of CT pulmonary angiography testing for pulmonary embolism in pregnancy is safe.

A total of 126 patients were included in the full analysis set; median progression-free survival (PFS) was 18.8 months, overall response rate was 64.3%, and the safety profile was similar to prior studies. The median PFS in this observational study was comparable to a median PFS of 16.9 months in the CLEOPTRA study among 88 patients with prior (neo)adjuvant trastuzumab. HELENA also demonstrated similar PFS results for the hormone receptor (HR)-negative and HR-positive (HR+) subgroups (19.4 months vs 18.2 months), as well as for patients with nonvisceral and visceral metastases (20.5 months vs 18.0 months). These findings provide further support for use of the THP regimen as first-line treatment in the real-world setting for patients with HER2+ MBC and prior receipt of trastuzumab.

Adjuvant endocrine therapy (ET) is associated with a survival benefit for early-stage HR+ breast cancer; however, the absolute degree of benefit depends on various clinicopathologic features.² Although it generally has a manageable toxicity profile, some side effects carry more significant consequences (thromboembolism, endometrial carcinoma, osteoporosis), and some of the more common ones can affect routine quality of life (hot flashes, vaginal dryness, arthralgia).

A retrospective observational study including 5545 patients with pT1a-b estrogen receptor-positive (ER+) breast cancer demonstrated improvements in disease-free survival (DFS) and recurrence-free survival (RFS) among those who received ET vs those who did not receive ET after 5 and 7 years of follow-up (DFS: increases of 2.5% and 3.3%; RFS: increases of 1.9% and 4.3%) (Houvenaeghel et al). Among all patients, absence of ET was associated with decreased DFS (hazard ratio [HR] 1.275; P = .047) but no difference in RFS or OS. Patients with pT1a-b ER+ grade 2-3 tumors (n = 2363) experienced decreased DFS (HR 1.502, P = .049) without ET; however, those with pT1a-b ER+ grade 1 tumors did not experience a negative effect on DFS without ET.

These results provide further support for the survival improvements seen with adjuvant ET — although the relative benefit may be fairly modest — and that ET omission is a relevant consideration in patients with comorbidities or tolerance issues, particularly those with pT1a-b grade 1 tumors.

Advancements in breast cancer therapies have led to improvements in survival outcomes, and it is therefore increasingly essential to recognize risks for other cancer types in breast cancer survivors. Male breast cancer is rare, and although clinical management for the most part mirrors that of female breast cancer, it is important to be aware of potential differences in this population, including risks for subsequent non-breast primary cancers.³

A meta-analysis including eight retrospective cohort studies with male breast cancer survivors reported the standardized incidence ratio (SIR), which compares the incidence of non-breast second primary cancers (SPC) among men with first primary breast cancer vs the expected incidence of non-breast primary cancers in the general male population. The summary SIR estimate was 1.27 (95% CI 1.03-1.56), with increased risk for certain SPCs: colorectal (SIR 1.29; 95% CI 1.03-1.61), pancreatic (SIR 1.64; 95% CI 1.05-2.55), and thyroid (SIR 5.58; 95% CI 1.04-30.05) (Allen et al). Additionally, men diagnosed with breast cancer before 50 years of age were observed to have increased SPC risk compared with men who were older than 50 years at breast cancer onset (SIR 1.50 vs 1.14; P = .040).

This study highlights the importance of genetic assessment for men diagnosed with breast cancer, so they can be appropriately counseled on subsequent cancer risk. It also stimulates thinking regarding other potential contributing factors to the observed increased SPC risk among male breast cancer survivors, including the effect of various treatments, hormonal influences, and significant family history.

Studies have shown that older women derive a survival benefit with adjuvant chemotherapy; however, they may be at increased risk of experiencing toxicities owing to physical functioning and comorbidities.⁴ A comprehensive geriatric assessment is key, and it is also beneficial for identifying which patients have a higher likelihood of clinical decline after chemotherapy.

A prospective study including 295 robust women age ≥ 65 years with stage I-III breast cancer treated with chemotherapy showed that 26% had a chemotherapy-induced decline in frailty status; patients with high interleukin-6 (IL-6) and C-reactive protein (CRP) inflammatory markers before chemotherapy had a more than threefold odds of experiencing a chemotherapy-induced decline in frailty compared with those with low IL-6 and CRP (odds ratio 3.52; 95% CI 1.55-8.01; P = .003) (Ji et al).

These findings support the relationship between inflammation, aging, and chemotherapy-induced functional decline. Further research is warranted to identify whether there are specific drugs that are implicated, methods to enhance anti-inflammatory effects, and any downstream effect on breast cancer outcomes of these patients.

Additional References

1. Swain SM, Miles D, Kim SB, et al; CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): End-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21:519-530. Doi: 10.1016/S1470-2045(19)30863-0
2. Ma SJ, Oladeru OT, Singh AK. Association of endocrine therapy with overall survival in women with small, hormone receptor-positive, ERBB2-negative breast cancer. JAMA Netw Open. 2020;3:e2013973. Doi: 10.1001/jamanetworkopen.2020.13973
3. Pritzlaff M, Summerour P, McFarland R, et al. Male breast cancer in a multi-gene panel testing cohort: Insights and unexpected results. Breast Cancer Res Treat. 2017;161:575-586. Doi: 10.1007/s10549-016-4085-4
4. Tamirisa N, Lin H, Shen Y, et al. Association of chemotherapy with survival in elderly patients with multiple comorbidities and estrogen receptor-positive, node-positive breast cancer. JAMA Oncol. 2020;6:1548-155 Doi: 10.1001/jamaoncol.2020.2388

A total of 126 patients were included in the full analysis set; median progression-free survival (PFS) was 18.8 months, overall response rate was 64.3%, and the safety profile was similar to prior studies. The median PFS in this observational study was comparable to a median PFS of 16.9 months in the CLEOPTRA study among 88 patients with prior (neo)adjuvant trastuzumab. HELENA also demonstrated similar PFS results for the hormone receptor (HR)-negative and HR-positive (HR+) subgroups (19.4 months vs 18.2 months), as well as for patients with nonvisceral and visceral metastases (20.5 months vs 18.0 months). These findings provide further support for use of the THP regimen as first-line treatment in the real-world setting for patients with HER2+ MBC and prior receipt of trastuzumab.

Adjuvant endocrine therapy (ET) is associated with a survival benefit for early-stage HR+ breast cancer; however, the absolute degree of benefit depends on various clinicopathologic features.² Although it generally has a manageable toxicity profile, some side effects carry more significant consequences (thromboembolism, endometrial carcinoma, osteoporosis), and some of the more common ones can affect routine quality of life (hot flashes, vaginal dryness, arthralgia).

A retrospective observational study including 5545 patients with pT1a-b estrogen receptor-positive (ER+) breast cancer demonstrated improvements in disease-free survival (DFS) and recurrence-free survival (RFS) among those who received ET vs those who did not receive ET after 5 and 7 years of follow-up (DFS: increases of 2.5% and 3.3%; RFS: increases of 1.9% and 4.3%) (Houvenaeghel et al). Among all patients, absence of ET was associated with decreased DFS (hazard ratio [HR] 1.275; P = .047) but no difference in RFS or OS. Patients with pT1a-b ER+ grade 2-3 tumors (n = 2363) experienced decreased DFS (HR 1.502, P = .049) without ET; however, those with pT1a-b ER+ grade 1 tumors did not experience a negative effect on DFS without ET.

These results provide further support for the survival improvements seen with adjuvant ET — although the relative benefit may be fairly modest — and that ET omission is a relevant consideration in patients with comorbidities or tolerance issues, particularly those with pT1a-b grade 1 tumors.

Advancements in breast cancer therapies have led to improvements in survival outcomes, and it is therefore increasingly essential to recognize risks for other cancer types in breast cancer survivors. Male breast cancer is rare, and although clinical management for the most part mirrors that of female breast cancer, it is important to be aware of potential differences in this population, including risks for subsequent non-breast primary cancers.³

A meta-analysis including eight retrospective cohort studies with male breast cancer survivors reported the standardized incidence ratio (SIR), which compares the incidence of non-breast second primary cancers (SPC) among men with first primary breast cancer vs the expected incidence of non-breast primary cancers in the general male population. The summary SIR estimate was 1.27 (95% CI 1.03-1.56), with increased risk for certain SPCs: colorectal (SIR 1.29; 95% CI 1.03-1.61), pancreatic (SIR 1.64; 95% CI 1.05-2.55), and thyroid (SIR 5.58; 95% CI 1.04-30.05) (Allen et al). Additionally, men diagnosed with breast cancer before 50 years of age were observed to have increased SPC risk compared with men who were older than 50 years at breast cancer onset (SIR 1.50 vs 1.14; P = .040).

This study highlights the importance of genetic assessment for men diagnosed with breast cancer, so they can be appropriately counseled on subsequent cancer risk. It also stimulates thinking regarding other potential contributing factors to the observed increased SPC risk among male breast cancer survivors, including the effect of various treatments, hormonal influences, and significant family history.

Studies have shown that older women derive a survival benefit with adjuvant chemotherapy; however, they may be at increased risk of experiencing toxicities owing to physical functioning and comorbidities.⁴ A comprehensive geriatric assessment is key, and it is also beneficial for identifying which patients have a higher likelihood of clinical decline after chemotherapy.

A prospective study including 295 robust women age ≥ 65 years with stage I-III breast cancer treated with chemotherapy showed that 26% had a chemotherapy-induced decline in frailty status; patients with high interleukin-6 (IL-6) and C-reactive protein (CRP) inflammatory markers before chemotherapy had a more than threefold odds of experiencing a chemotherapy-induced decline in frailty compared with those with low IL-6 and CRP (odds ratio 3.52; 95% CI 1.55-8.01; P = .003) (Ji et al).

These findings support the relationship between inflammation, aging, and chemotherapy-induced functional decline. Further research is warranted to identify whether there are specific drugs that are implicated, methods to enhance anti-inflammatory effects, and any downstream effect on breast cancer outcomes of these patients.

Additional References

1. Swain SM, Miles D, Kim SB, et al; CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): End-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21:519-530. Doi: 10.1016/S1470-2045(19)30863-0
2. Ma SJ, Oladeru OT, Singh AK. Association of endocrine therapy with overall survival in women with small, hormone receptor-positive, ERBB2-negative breast cancer. JAMA Netw Open. 2020;3:e2013973. Doi: 10.1001/jamanetworkopen.2020.13973
3. Pritzlaff M, Summerour P, McFarland R, et al. Male breast cancer in a multi-gene panel testing cohort: Insights and unexpected results. Breast Cancer Res Treat. 2017;161:575-586. Doi: 10.1007/s10549-016-4085-4
4. Tamirisa N, Lin H, Shen Y, et al. Association of chemotherapy with survival in elderly patients with multiple comorbidities and estrogen receptor-positive, node-positive breast cancer. JAMA Oncol. 2020;6:1548-155 Doi: 10.1001/jamaoncol.2020.2388

A total of 126 patients were included in the full analysis set; median progression-free survival (PFS) was 18.8 months, overall response rate was 64.3%, and the safety profile was similar to prior studies. The median PFS in this observational study was comparable to a median PFS of 16.9 months in the CLEOPTRA study among 88 patients with prior (neo)adjuvant trastuzumab. HELENA also demonstrated similar PFS results for the hormone receptor (HR)-negative and HR-positive (HR+) subgroups (19.4 months vs 18.2 months), as well as for patients with nonvisceral and visceral metastases (20.5 months vs 18.0 months). These findings provide further support for use of the THP regimen as first-line treatment in the real-world setting for patients with HER2+ MBC and prior receipt of trastuzumab.

Adjuvant endocrine therapy (ET) is associated with a survival benefit for early-stage HR+ breast cancer; however, the absolute degree of benefit depends on various clinicopathologic features.² Although it generally has a manageable toxicity profile, some side effects carry more significant consequences (thromboembolism, endometrial carcinoma, osteoporosis), and some of the more common ones can affect routine quality of life (hot flashes, vaginal dryness, arthralgia).

A retrospective observational study including 5545 patients with pT1a-b estrogen receptor-positive (ER+) breast cancer demonstrated improvements in disease-free survival (DFS) and recurrence-free survival (RFS) among those who received ET vs those who did not receive ET after 5 and 7 years of follow-up (DFS: increases of 2.5% and 3.3%; RFS: increases of 1.9% and 4.3%) (Houvenaeghel et al). Among all patients, absence of ET was associated with decreased DFS (hazard ratio [HR] 1.275; P = .047) but no difference in RFS or OS. Patients with pT1a-b ER+ grade 2-3 tumors (n = 2363) experienced decreased DFS (HR 1.502, P = .049) without ET; however, those with pT1a-b ER+ grade 1 tumors did not experience a negative effect on DFS without ET.

These results provide further support for the survival improvements seen with adjuvant ET — although the relative benefit may be fairly modest — and that ET omission is a relevant consideration in patients with comorbidities or tolerance issues, particularly those with pT1a-b grade 1 tumors.

Advancements in breast cancer therapies have led to improvements in survival outcomes, and it is therefore increasingly essential to recognize risks for other cancer types in breast cancer survivors. Male breast cancer is rare, and although clinical management for the most part mirrors that of female breast cancer, it is important to be aware of potential differences in this population, including risks for subsequent non-breast primary cancers.³

A meta-analysis including eight retrospective cohort studies with male breast cancer survivors reported the standardized incidence ratio (SIR), which compares the incidence of non-breast second primary cancers (SPC) among men with first primary breast cancer vs the expected incidence of non-breast primary cancers in the general male population. The summary SIR estimate was 1.27 (95% CI 1.03-1.56), with increased risk for certain SPCs: colorectal (SIR 1.29; 95% CI 1.03-1.61), pancreatic (SIR 1.64; 95% CI 1.05-2.55), and thyroid (SIR 5.58; 95% CI 1.04-30.05) (Allen et al). Additionally, men diagnosed with breast cancer before 50 years of age were observed to have increased SPC risk compared with men who were older than 50 years at breast cancer onset (SIR 1.50 vs 1.14; P = .040).

This study highlights the importance of genetic assessment for men diagnosed with breast cancer, so they can be appropriately counseled on subsequent cancer risk. It also stimulates thinking regarding other potential contributing factors to the observed increased SPC risk among male breast cancer survivors, including the effect of various treatments, hormonal influences, and significant family history.

Studies have shown that older women derive a survival benefit with adjuvant chemotherapy; however, they may be at increased risk of experiencing toxicities owing to physical functioning and comorbidities.⁴ A comprehensive geriatric assessment is key, and it is also beneficial for identifying which patients have a higher likelihood of clinical decline after chemotherapy.

A prospective study including 295 robust women age ≥ 65 years with stage I-III breast cancer treated with chemotherapy showed that 26% had a chemotherapy-induced decline in frailty status; patients with high interleukin-6 (IL-6) and C-reactive protein (CRP) inflammatory markers before chemotherapy had a more than threefold odds of experiencing a chemotherapy-induced decline in frailty compared with those with low IL-6 and CRP (odds ratio 3.52; 95% CI 1.55-8.01; P = .003) (Ji et al).

These findings support the relationship between inflammation, aging, and chemotherapy-induced functional decline. Further research is warranted to identify whether there are specific drugs that are implicated, methods to enhance anti-inflammatory effects, and any downstream effect on breast cancer outcomes of these patients.

Additional References

1. Swain SM, Miles D, Kim SB, et al; CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): End-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21:519-530. Doi: 10.1016/S1470-2045(19)30863-0
2. Ma SJ, Oladeru OT, Singh AK. Association of endocrine therapy with overall survival in women with small, hormone receptor-positive, ERBB2-negative breast cancer. JAMA Netw Open. 2020;3:e2013973. Doi: 10.1001/jamanetworkopen.2020.13973
3. Pritzlaff M, Summerour P, McFarland R, et al. Male breast cancer in a multi-gene panel testing cohort: Insights and unexpected results. Breast Cancer Res Treat. 2017;161:575-586. Doi: 10.1007/s10549-016-4085-4
4. Tamirisa N, Lin H, Shen Y, et al. Association of chemotherapy with survival in elderly patients with multiple comorbidities and estrogen receptor-positive, node-positive breast cancer. JAMA Oncol. 2020;6:1548-155 Doi: 10.1001/jamaoncol.2020.2388