The results of a phase 2 clinical trial of durvalumab with add-on therapies oleclumab or monalizumab, suggest this novel combination may prove beneficial in patients with unresectable stage 3 non–small-cell lung cancer.

Combinations of the PD-L1 inhibitor durvalumab (Imfinzi, AstraZeneca) with the anti-CD73 monoclonal antibody oleclumab or the anti-NKG2A monoclonal antibody monalizumab led to improved overall response rate and progression-free survival compared to durvalumab alone.

The findings support further study in a phase 3 clinical trial, according to the authors of the study recently published in the Journal of Clinical Oncology.

Durvalumab is the standard treatment following consolidation therapy of chemoradiotherapy in unresectable stage 3 non–small-cell lung cancer (NSCLC). Although it extended progression-free survival (PFS) and overall survival in the PACIFIC phase 3 study, some patients experience a recurrence, which has led to exploration of immunotherapy combinations.

Oleclumab inhibits the enzyme CD73, found on the surfaces of both tumor and immune cells. Its activity leads to an immunosuppressive effect in the tumor microenvironment, and preclinical studies have shown that it can have an additive antitumor effect when combined with PD-1 or PD-L1 inhibitors. A phase 1 study also suggested efficacy. Monalizumab blocks interactions between major histocompatibility complex-E (HLA-E) and an inhibitor receptor. A number of tumors overexpress HLA-E, triggering inhibitor signals that inhibit natural killer and CD8+ T cells.

“COAST was an interesting study that, although not definitive, suggested that the combination of durvalumab with oleclumab or with monalizumab was more effective than durvalumab alone in the consolidation setting after definitive concurrent chemoradiation for patients with stage 3 unresectable NSCLC,” said Nathan Pennell, MD, PhD, who wrote an accompanying editorial.

Despite the positive signal, Dr. Pennell expressed some skepticism that the combinations would pass a phase 3 test. He questioned the choice of response rate as the primary endpoint of the phase 2 study, and noted that the durvalumab arm had worse progression-free survival (PFS) than the previous PACIFIC trial. It could be that the clinical characteristics of the study population differed between the two trials, in which case the improved objective response rate (ORR) and PFS results should be encouraging. It’s also possible the COAST trial’s small sample size led to a mismatch between the control and treatment group despite randomization, in which case the findings may not be valid.

“These are the kinds of issues that keep drug developers up at night. There really is no way to know which scenario is correct without doing the larger trial. I do hope though that the phase 3 trials have robust biomarker analysis including PDL1 to make sure the arms are as well matched for known prognostic and predictive markers as possible,” said Dr. Pennell, who is vice chair of clinical research at Taussig Cancer Institute.
 

The study details

The researchers randomized 189 patients to durvalumab, durvalumab plus oleclumab, or durvalumab plus monalizumab between January 2019 and July 2020. After a median follow-up of 11.5 months, there was a higher confirmed objective response rate in the durvalumab plus oleclumab group (30.0%; 95% confidence interval, 18.8%-43.2%) and the durvalumab plus monalizumab group (35.5%; 95% CI, 23.7%-48.7%) versus durvalumab alone (17.9%; 95% CI, 9.6%-29.2%).

Compared to durvalumab alone, there was improved PFS in both durvalumab plus oleclumab (stratified hazard ratio, 0.44; 95% CI, 0.26-0.75) and durvalumab plus monalizumab (HR, 0.42; 95% CI, 0.24-0.72). At 12 months, PFS was 62.6% (95% CI, 48.1-74.2%) for durvalumab plus oleclumab, 72.7% (95% CI, 58.8-82.6%) for durvalumab plus monalizumab, and 33.9% (95% CI, 21.2-47.1%) for durvalumab alone.

The study was funded by AstraZeneca.

The results of a phase 2 clinical trial of durvalumab with add-on therapies oleclumab or monalizumab, suggest this novel combination may prove beneficial in patients with unresectable stage 3 non–small-cell lung cancer.

Combinations of the PD-L1 inhibitor durvalumab (Imfinzi, AstraZeneca) with the anti-CD73 monoclonal antibody oleclumab or the anti-NKG2A monoclonal antibody monalizumab led to improved overall response rate and progression-free survival compared to durvalumab alone.

The findings support further study in a phase 3 clinical trial, according to the authors of the study recently published in the Journal of Clinical Oncology.

Durvalumab is the standard treatment following consolidation therapy of chemoradiotherapy in unresectable stage 3 non–small-cell lung cancer (NSCLC). Although it extended progression-free survival (PFS) and overall survival in the PACIFIC phase 3 study, some patients experience a recurrence, which has led to exploration of immunotherapy combinations.

Oleclumab inhibits the enzyme CD73, found on the surfaces of both tumor and immune cells. Its activity leads to an immunosuppressive effect in the tumor microenvironment, and preclinical studies have shown that it can have an additive antitumor effect when combined with PD-1 or PD-L1 inhibitors. A phase 1 study also suggested efficacy. Monalizumab blocks interactions between major histocompatibility complex-E (HLA-E) and an inhibitor receptor. A number of tumors overexpress HLA-E, triggering inhibitor signals that inhibit natural killer and CD8+ T cells.

“COAST was an interesting study that, although not definitive, suggested that the combination of durvalumab with oleclumab or with monalizumab was more effective than durvalumab alone in the consolidation setting after definitive concurrent chemoradiation for patients with stage 3 unresectable NSCLC,” said Nathan Pennell, MD, PhD, who wrote an accompanying editorial.

Despite the positive signal, Dr. Pennell expressed some skepticism that the combinations would pass a phase 3 test. He questioned the choice of response rate as the primary endpoint of the phase 2 study, and noted that the durvalumab arm had worse progression-free survival (PFS) than the previous PACIFIC trial. It could be that the clinical characteristics of the study population differed between the two trials, in which case the improved objective response rate (ORR) and PFS results should be encouraging. It’s also possible the COAST trial’s small sample size led to a mismatch between the control and treatment group despite randomization, in which case the findings may not be valid.

“These are the kinds of issues that keep drug developers up at night. There really is no way to know which scenario is correct without doing the larger trial. I do hope though that the phase 3 trials have robust biomarker analysis including PDL1 to make sure the arms are as well matched for known prognostic and predictive markers as possible,” said Dr. Pennell, who is vice chair of clinical research at Taussig Cancer Institute.
 

The study details

The researchers randomized 189 patients to durvalumab, durvalumab plus oleclumab, or durvalumab plus monalizumab between January 2019 and July 2020. After a median follow-up of 11.5 months, there was a higher confirmed objective response rate in the durvalumab plus oleclumab group (30.0%; 95% confidence interval, 18.8%-43.2%) and the durvalumab plus monalizumab group (35.5%; 95% CI, 23.7%-48.7%) versus durvalumab alone (17.9%; 95% CI, 9.6%-29.2%).

Compared to durvalumab alone, there was improved PFS in both durvalumab plus oleclumab (stratified hazard ratio, 0.44; 95% CI, 0.26-0.75) and durvalumab plus monalizumab (HR, 0.42; 95% CI, 0.24-0.72). At 12 months, PFS was 62.6% (95% CI, 48.1-74.2%) for durvalumab plus oleclumab, 72.7% (95% CI, 58.8-82.6%) for durvalumab plus monalizumab, and 33.9% (95% CI, 21.2-47.1%) for durvalumab alone.

The study was funded by AstraZeneca.

The results of a phase 2 clinical trial of durvalumab with add-on therapies oleclumab or monalizumab, suggest this novel combination may prove beneficial in patients with unresectable stage 3 non–small-cell lung cancer.

Combinations of the PD-L1 inhibitor durvalumab (Imfinzi, AstraZeneca) with the anti-CD73 monoclonal antibody oleclumab or the anti-NKG2A monoclonal antibody monalizumab led to improved overall response rate and progression-free survival compared to durvalumab alone.

The findings support further study in a phase 3 clinical trial, according to the authors of the study recently published in the Journal of Clinical Oncology.

Durvalumab is the standard treatment following consolidation therapy of chemoradiotherapy in unresectable stage 3 non–small-cell lung cancer (NSCLC). Although it extended progression-free survival (PFS) and overall survival in the PACIFIC phase 3 study, some patients experience a recurrence, which has led to exploration of immunotherapy combinations.

Oleclumab inhibits the enzyme CD73, found on the surfaces of both tumor and immune cells. Its activity leads to an immunosuppressive effect in the tumor microenvironment, and preclinical studies have shown that it can have an additive antitumor effect when combined with PD-1 or PD-L1 inhibitors. A phase 1 study also suggested efficacy. Monalizumab blocks interactions between major histocompatibility complex-E (HLA-E) and an inhibitor receptor. A number of tumors overexpress HLA-E, triggering inhibitor signals that inhibit natural killer and CD8+ T cells.

“COAST was an interesting study that, although not definitive, suggested that the combination of durvalumab with oleclumab or with monalizumab was more effective than durvalumab alone in the consolidation setting after definitive concurrent chemoradiation for patients with stage 3 unresectable NSCLC,” said Nathan Pennell, MD, PhD, who wrote an accompanying editorial.

Despite the positive signal, Dr. Pennell expressed some skepticism that the combinations would pass a phase 3 test. He questioned the choice of response rate as the primary endpoint of the phase 2 study, and noted that the durvalumab arm had worse progression-free survival (PFS) than the previous PACIFIC trial. It could be that the clinical characteristics of the study population differed between the two trials, in which case the improved objective response rate (ORR) and PFS results should be encouraging. It’s also possible the COAST trial’s small sample size led to a mismatch between the control and treatment group despite randomization, in which case the findings may not be valid.

“These are the kinds of issues that keep drug developers up at night. There really is no way to know which scenario is correct without doing the larger trial. I do hope though that the phase 3 trials have robust biomarker analysis including PDL1 to make sure the arms are as well matched for known prognostic and predictive markers as possible,” said Dr. Pennell, who is vice chair of clinical research at Taussig Cancer Institute.
 

The study details

The researchers randomized 189 patients to durvalumab, durvalumab plus oleclumab, or durvalumab plus monalizumab between January 2019 and July 2020. After a median follow-up of 11.5 months, there was a higher confirmed objective response rate in the durvalumab plus oleclumab group (30.0%; 95% confidence interval, 18.8%-43.2%) and the durvalumab plus monalizumab group (35.5%; 95% CI, 23.7%-48.7%) versus durvalumab alone (17.9%; 95% CI, 9.6%-29.2%).

Compared to durvalumab alone, there was improved PFS in both durvalumab plus oleclumab (stratified hazard ratio, 0.44; 95% CI, 0.26-0.75) and durvalumab plus monalizumab (HR, 0.42; 95% CI, 0.24-0.72). At 12 months, PFS was 62.6% (95% CI, 48.1-74.2%) for durvalumab plus oleclumab, 72.7% (95% CI, 58.8-82.6%) for durvalumab plus monalizumab, and 33.9% (95% CI, 21.2-47.1%) for durvalumab alone.

The study was funded by AstraZeneca.

Pancreatic cancer screening appears to be safe and effective for certain patients with high-risk indications due to genetic susceptibility, according to a prospective multicenter study presented at the annual meeting of the American College of Gastroenterology.

Screening in high-risk patients detected high-risk lesions in 0.8% of patients, which was lower than the typical range found in the literature, at 3%, said Andy Silva-Santisteban, MD, a research fellow at Beth Israel Deaconess Medical Center at Harvard Medical School in Boston.

Pancreatic cancer is the third leading cause of cancer death in the U.S., which is estimated to become the second leading cause by 2030. About 15%-20% of patients are candidates for surgical resection at the time of diagnosis, with survival rates below 10%.

“These statistics have led pancreatic cancer screening to be studied with the goal of detecting earlier stages of the disease to improve survival,” Dr. Silva-Santisteban said. “However, pancreatic cancer screening is not recommended for the general population.”

Pancreatic cancer screening is recommended for patients with increased risk due to genetic susceptibility, yet recent studies have found that screening studies face limitations from factors like small sample sizes, single-center focus, retrospective nature, nonconsecutive accrual of patients, varied inclusion criteria, and use of nonstandardized screening protocols.

To overcome these limitations, Dr. Silva-Santisteban and colleagues conducted a prospective multicenter study of pancreatic cancer screening in consecutive high-risk patients at five centers in the United States between 2020 and 2022, also called the Pancreas Scan Study. Dr. Silva-Santisteban presented results from the first round of enrollment, which was awarded the Outstanding Research Award in the Biliary/Pancreas Category for Trainee.

The research team evaluated the yield (low-, moderate-, and high-risk pancreatic pathology), safety, and outcomes of screening. Low-risk pancreas pathology was categorized as fatty pancreas and chronic pancreatitis-like changes. Intermediate-risk was categorized as branch duct–intraductal papillary mucinous neoplasm or neuroendocrine tumor under 2 cm. High-risk was categorized as main duct–intraductal papillary mucinous neoplasm (MD-IPMN), pancreatic intraepithelial neoplasia grade III (PanIN-III)/dysplasia, neuroendocrine tumor over 2 cm, or pancreatic cancer.

Patients were included if they were 18 years or older and had at least one of the following: BRCA1, BRCA2, or PALB2 plus a family history of pancreatic cancer; Lynch syndrome plus a family history of pancreatic cancer; Peutz-Jeghers syndrome; familial atypical multiple mole melanoma (FAMMM); ataxia telangiectasia mutated plus family history of pancreatic cancer; hereditary pancreatitis; or familial pancreatic cancer (FPC) syndrome.

Pancreatic cancer screening appears to be safe and effective for certain patients with high-risk indications due to genetic susceptibility, according to a prospective multicenter study presented at the annual meeting of the American College of Gastroenterology.

Screening in high-risk patients detected high-risk lesions in 0.8% of patients, which was lower than the typical range found in the literature, at 3%, said Andy Silva-Santisteban, MD, a research fellow at Beth Israel Deaconess Medical Center at Harvard Medical School in Boston.

Pancreatic cancer is the third leading cause of cancer death in the U.S., which is estimated to become the second leading cause by 2030. About 15%-20% of patients are candidates for surgical resection at the time of diagnosis, with survival rates below 10%.

“These statistics have led pancreatic cancer screening to be studied with the goal of detecting earlier stages of the disease to improve survival,” Dr. Silva-Santisteban said. “However, pancreatic cancer screening is not recommended for the general population.”

Pancreatic cancer screening is recommended for patients with increased risk due to genetic susceptibility, yet recent studies have found that screening studies face limitations from factors like small sample sizes, single-center focus, retrospective nature, nonconsecutive accrual of patients, varied inclusion criteria, and use of nonstandardized screening protocols.

To overcome these limitations, Dr. Silva-Santisteban and colleagues conducted a prospective multicenter study of pancreatic cancer screening in consecutive high-risk patients at five centers in the United States between 2020 and 2022, also called the Pancreas Scan Study. Dr. Silva-Santisteban presented results from the first round of enrollment, which was awarded the Outstanding Research Award in the Biliary/Pancreas Category for Trainee.

The research team evaluated the yield (low-, moderate-, and high-risk pancreatic pathology), safety, and outcomes of screening. Low-risk pancreas pathology was categorized as fatty pancreas and chronic pancreatitis-like changes. Intermediate-risk was categorized as branch duct–intraductal papillary mucinous neoplasm or neuroendocrine tumor under 2 cm. High-risk was categorized as main duct–intraductal papillary mucinous neoplasm (MD-IPMN), pancreatic intraepithelial neoplasia grade III (PanIN-III)/dysplasia, neuroendocrine tumor over 2 cm, or pancreatic cancer.

Patients were included if they were 18 years or older and had at least one of the following: BRCA1, BRCA2, or PALB2 plus a family history of pancreatic cancer; Lynch syndrome plus a family history of pancreatic cancer; Peutz-Jeghers syndrome; familial atypical multiple mole melanoma (FAMMM); ataxia telangiectasia mutated plus family history of pancreatic cancer; hereditary pancreatitis; or familial pancreatic cancer (FPC) syndrome.

Pancreatic cancer screening appears to be safe and effective for certain patients with high-risk indications due to genetic susceptibility, according to a prospective multicenter study presented at the annual meeting of the American College of Gastroenterology.

Screening in high-risk patients detected high-risk lesions in 0.8% of patients, which was lower than the typical range found in the literature, at 3%, said Andy Silva-Santisteban, MD, a research fellow at Beth Israel Deaconess Medical Center at Harvard Medical School in Boston.

Pancreatic cancer is the third leading cause of cancer death in the U.S., which is estimated to become the second leading cause by 2030. About 15%-20% of patients are candidates for surgical resection at the time of diagnosis, with survival rates below 10%.

“These statistics have led pancreatic cancer screening to be studied with the goal of detecting earlier stages of the disease to improve survival,” Dr. Silva-Santisteban said. “However, pancreatic cancer screening is not recommended for the general population.”

Pancreatic cancer screening is recommended for patients with increased risk due to genetic susceptibility, yet recent studies have found that screening studies face limitations from factors like small sample sizes, single-center focus, retrospective nature, nonconsecutive accrual of patients, varied inclusion criteria, and use of nonstandardized screening protocols.

To overcome these limitations, Dr. Silva-Santisteban and colleagues conducted a prospective multicenter study of pancreatic cancer screening in consecutive high-risk patients at five centers in the United States between 2020 and 2022, also called the Pancreas Scan Study. Dr. Silva-Santisteban presented results from the first round of enrollment, which was awarded the Outstanding Research Award in the Biliary/Pancreas Category for Trainee.

The research team evaluated the yield (low-, moderate-, and high-risk pancreatic pathology), safety, and outcomes of screening. Low-risk pancreas pathology was categorized as fatty pancreas and chronic pancreatitis-like changes. Intermediate-risk was categorized as branch duct–intraductal papillary mucinous neoplasm or neuroendocrine tumor under 2 cm. High-risk was categorized as main duct–intraductal papillary mucinous neoplasm (MD-IPMN), pancreatic intraepithelial neoplasia grade III (PanIN-III)/dysplasia, neuroendocrine tumor over 2 cm, or pancreatic cancer.

Patients were included if they were 18 years or older and had at least one of the following: BRCA1, BRCA2, or PALB2 plus a family history of pancreatic cancer; Lynch syndrome plus a family history of pancreatic cancer; Peutz-Jeghers syndrome; familial atypical multiple mole melanoma (FAMMM); ataxia telangiectasia mutated plus family history of pancreatic cancer; hereditary pancreatitis; or familial pancreatic cancer (FPC) syndrome.

This transcript has been edited for clarity.

Matthew F. Watto, MD: Welcome back to The Curbsiders. I’m Dr. Matthew Watto, here with my very good friend, Dr. Paul Williams. It’s time to talk about headaches. We did a great recent podcast on migraines, Headache Update: Making Migraines Less Painful with Dr. Kevin Weber. One of the quotes from that episode that stayed with me was when he said, “I tell my patients to think about migraine as an irritable old miser set in their ways, and your brain is set in its ways. It doesn’t like changes in routine. It doesn’t like lack of sleep, it doesn’t like being hungry, it doesn’t like being thirsty, and it doesn’t like changes in the weather.” That’s a reminder of the good, old-fashioned primary care tips for taking care of headache.

Paul N. Williams, MD: That’s right. Conservative supportive management goes by the wayside because we focus on the medications. But I thought that was a really nice way to start the episode.

Dr. Watto: I asked him about cervicogenic headaches, which I guess you have to diagnose by giving a cervical steroid injection and see if the patient feels better, but he said he doesn’t do this. This is expert opinion territory. He asks his patients with chronic headache about cervical neck pain, because if they have it, he goes after it with physical therapy, which can help with the headaches. I thought that was a great pearl that I hadn’t heard before.

Give the audience a pearl from this great episode.

Dr. Williams: We talked about foundational treatments. We reviewed some of the abortive therapies and over-the-counter products. Some patients do quite well with acetaminophen or NSAIDs. We also talked about triptans, which are the standard medicines that we all know about. You can use those in combination, by the way. Patients can take their triptan with the NSAID that works best for them. They don’t have to be used one at a time, trying one and then trying the other one if the first one doesn’t help. Dr. Weber gave us practical guides in terms of which triptans he favors. He mentioned rizatriptan and naratriptan, which is one that I had not used with any frequency. I’ve seen rizatriptan a fair amount and that one seems to be covered by most insurances. He favors those two triptans.

He also reminded us that even though there is theoretical concern for serotonin toxicity because these are serotonergic and you’ll see these scary pop-ups in your electronic health record, that concern is almost purely theoretical. It hasn’t been borne out. They are really safe medications to use. But do use caution if you have a patient with known cardiovascular disease or cerebrovascular disease. We spent a fair amount of time talking about chest pressure as a common side effect. We also talked about some of the newer agents.

Dr. Watto: I wanted to add something about the triptans. Part of the reason he favors rizatriptan and naratriptan is that they are newer. He thinks they tend to have fewer side effects. But he did mention sumatriptan because it comes in the most different formulations. If patients have severe nausea, there is a subcutaneous version of sumatriptan and also an intranasal version.

The new kids on the block are the CGRP receptor antagonists, and they are available for preventive and abortive therapy. The abortive therapies are probably what people will be seeing most often in primary care – ubrogepant and rimegepant. Patients can take ubrogepant for abortive therapy and then repeat it if necessary. That’s similar to what patients are used to with the triptans. Rimegepant is taken once daily for abortive therapy or every other day as a preventive agent. Those are two of the agents that you might see patients taking. I’ve certainly started to see them.

There are also a whole bunch of monoclonal antibodies that affect the CGRP pathway. Those are given either once a month by subcutaneous injection or once every 3 months, and one is an infusion. They are pretty safe, and the big appeal is that they can be used in patients with cardiovascular disease. He also said that he has some patients who take them because triptans can cause the medication overuse side effect, but the CGRP receptor antagonists don’t. It’s an option for some patients to take the CGRP receptor antagonists on certain days for abortive therapy and then they can take the triptans the rest of the month.

Dr. Weber said that in his practice, these new drugs have really been great, which I can imagine, if you’re a specialist, patients have exhausted many of the typical therapies we offer in primary care.

Paul, bring us home here. What else should we tell the audience about? In primary care, what can we offer these patients?

Dr. Williams: A lot of the stuff we can offer works, by the way. It’s exciting to have fancy new medications to use, but you don’t even necessarily need to get to that point. We have a lot of medications that we can use for migraine prophylaxis, such as the beta-blockers and antihypertensives. Candesartan was a new one to me, an angiotensin receptor blocker that apparently has good evidence for migraine prophylaxis and Dr. Weber swears by it. We talked about some of the antiseizure medications, such as topiramate, which is probably the one with the most comfort in primary care. Some older folks may be using valproic acid or the tricyclic antidepressants (amitriptyline and nortriptyline) because people with migraine often will have comorbid anxiety or trouble sleeping, so I find that can sometimes be an effective medication or if they have comorbid neuropathic pain.

Another one that was new to me was venlafaxine as migraine prophylaxis. It’s not something I’d heard about before this episode. Certainly, for someone with chronic pain or a mood disorder that’s comorbid with migraines, it may be worth a shot. So there are options that we can exhaust first, and we may actually be doing our specialist friends a favor by trying one or two of these in advance, because then by the time the patient gets to the neurologist, it makes the prior authorization process much easier for the newer, fancier-pants medications that we’re all very excited about.

Dr. Watto: Paul, we’ve teased this fantastic podcast episode filled with so much more great stuff, so people should check out Headache Update: Making Migraines Less Painful with Dr. Kevin Weber.

Until next time, this has been another episode of The Curbsiders, bringing you a little knowledge food for your brain hole.

The Curbsiders is an internal medicine podcast, in which three board-certified internists interview experts on clinically important topics. In a collaboration with Medscape, the Curbsiders share clinical pearls and practice-changing knowledge from selected podcasts.

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

This transcript has been edited for clarity.

Matthew F. Watto, MD: Welcome back to The Curbsiders. I’m Dr. Matthew Watto, here with my very good friend, Dr. Paul Williams. It’s time to talk about headaches. We did a great recent podcast on migraines, Headache Update: Making Migraines Less Painful with Dr. Kevin Weber. One of the quotes from that episode that stayed with me was when he said, “I tell my patients to think about migraine as an irritable old miser set in their ways, and your brain is set in its ways. It doesn’t like changes in routine. It doesn’t like lack of sleep, it doesn’t like being hungry, it doesn’t like being thirsty, and it doesn’t like changes in the weather.” That’s a reminder of the good, old-fashioned primary care tips for taking care of headache.

Paul N. Williams, MD: That’s right. Conservative supportive management goes by the wayside because we focus on the medications. But I thought that was a really nice way to start the episode.

Dr. Watto: I asked him about cervicogenic headaches, which I guess you have to diagnose by giving a cervical steroid injection and see if the patient feels better, but he said he doesn’t do this. This is expert opinion territory. He asks his patients with chronic headache about cervical neck pain, because if they have it, he goes after it with physical therapy, which can help with the headaches. I thought that was a great pearl that I hadn’t heard before.

Give the audience a pearl from this great episode.

Dr. Williams: We talked about foundational treatments. We reviewed some of the abortive therapies and over-the-counter products. Some patients do quite well with acetaminophen or NSAIDs. We also talked about triptans, which are the standard medicines that we all know about. You can use those in combination, by the way. Patients can take their triptan with the NSAID that works best for them. They don’t have to be used one at a time, trying one and then trying the other one if the first one doesn’t help. Dr. Weber gave us practical guides in terms of which triptans he favors. He mentioned rizatriptan and naratriptan, which is one that I had not used with any frequency. I’ve seen rizatriptan a fair amount and that one seems to be covered by most insurances. He favors those two triptans.

He also reminded us that even though there is theoretical concern for serotonin toxicity because these are serotonergic and you’ll see these scary pop-ups in your electronic health record, that concern is almost purely theoretical. It hasn’t been borne out. They are really safe medications to use. But do use caution if you have a patient with known cardiovascular disease or cerebrovascular disease. We spent a fair amount of time talking about chest pressure as a common side effect. We also talked about some of the newer agents.

Dr. Watto: I wanted to add something about the triptans. Part of the reason he favors rizatriptan and naratriptan is that they are newer. He thinks they tend to have fewer side effects. But he did mention sumatriptan because it comes in the most different formulations. If patients have severe nausea, there is a subcutaneous version of sumatriptan and also an intranasal version.

The new kids on the block are the CGRP receptor antagonists, and they are available for preventive and abortive therapy. The abortive therapies are probably what people will be seeing most often in primary care – ubrogepant and rimegepant. Patients can take ubrogepant for abortive therapy and then repeat it if necessary. That’s similar to what patients are used to with the triptans. Rimegepant is taken once daily for abortive therapy or every other day as a preventive agent. Those are two of the agents that you might see patients taking. I’ve certainly started to see them.

There are also a whole bunch of monoclonal antibodies that affect the CGRP pathway. Those are given either once a month by subcutaneous injection or once every 3 months, and one is an infusion. They are pretty safe, and the big appeal is that they can be used in patients with cardiovascular disease. He also said that he has some patients who take them because triptans can cause the medication overuse side effect, but the CGRP receptor antagonists don’t. It’s an option for some patients to take the CGRP receptor antagonists on certain days for abortive therapy and then they can take the triptans the rest of the month.

Dr. Weber said that in his practice, these new drugs have really been great, which I can imagine, if you’re a specialist, patients have exhausted many of the typical therapies we offer in primary care.

Paul, bring us home here. What else should we tell the audience about? In primary care, what can we offer these patients?

Dr. Williams: A lot of the stuff we can offer works, by the way. It’s exciting to have fancy new medications to use, but you don’t even necessarily need to get to that point. We have a lot of medications that we can use for migraine prophylaxis, such as the beta-blockers and antihypertensives. Candesartan was a new one to me, an angiotensin receptor blocker that apparently has good evidence for migraine prophylaxis and Dr. Weber swears by it. We talked about some of the antiseizure medications, such as topiramate, which is probably the one with the most comfort in primary care. Some older folks may be using valproic acid or the tricyclic antidepressants (amitriptyline and nortriptyline) because people with migraine often will have comorbid anxiety or trouble sleeping, so I find that can sometimes be an effective medication or if they have comorbid neuropathic pain.

Another one that was new to me was venlafaxine as migraine prophylaxis. It’s not something I’d heard about before this episode. Certainly, for someone with chronic pain or a mood disorder that’s comorbid with migraines, it may be worth a shot. So there are options that we can exhaust first, and we may actually be doing our specialist friends a favor by trying one or two of these in advance, because then by the time the patient gets to the neurologist, it makes the prior authorization process much easier for the newer, fancier-pants medications that we’re all very excited about.

Dr. Watto: Paul, we’ve teased this fantastic podcast episode filled with so much more great stuff, so people should check out Headache Update: Making Migraines Less Painful with Dr. Kevin Weber.

Until next time, this has been another episode of The Curbsiders, bringing you a little knowledge food for your brain hole.

The Curbsiders is an internal medicine podcast, in which three board-certified internists interview experts on clinically important topics. In a collaboration with Medscape, the Curbsiders share clinical pearls and practice-changing knowledge from selected podcasts.

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

This transcript has been edited for clarity.

Matthew F. Watto, MD: Welcome back to The Curbsiders. I’m Dr. Matthew Watto, here with my very good friend, Dr. Paul Williams. It’s time to talk about headaches. We did a great recent podcast on migraines, Headache Update: Making Migraines Less Painful with Dr. Kevin Weber. One of the quotes from that episode that stayed with me was when he said, “I tell my patients to think about migraine as an irritable old miser set in their ways, and your brain is set in its ways. It doesn’t like changes in routine. It doesn’t like lack of sleep, it doesn’t like being hungry, it doesn’t like being thirsty, and it doesn’t like changes in the weather.” That’s a reminder of the good, old-fashioned primary care tips for taking care of headache.

Paul N. Williams, MD: That’s right. Conservative supportive management goes by the wayside because we focus on the medications. But I thought that was a really nice way to start the episode.

Dr. Watto: I asked him about cervicogenic headaches, which I guess you have to diagnose by giving a cervical steroid injection and see if the patient feels better, but he said he doesn’t do this. This is expert opinion territory. He asks his patients with chronic headache about cervical neck pain, because if they have it, he goes after it with physical therapy, which can help with the headaches. I thought that was a great pearl that I hadn’t heard before.

Give the audience a pearl from this great episode.

Dr. Williams: We talked about foundational treatments. We reviewed some of the abortive therapies and over-the-counter products. Some patients do quite well with acetaminophen or NSAIDs. We also talked about triptans, which are the standard medicines that we all know about. You can use those in combination, by the way. Patients can take their triptan with the NSAID that works best for them. They don’t have to be used one at a time, trying one and then trying the other one if the first one doesn’t help. Dr. Weber gave us practical guides in terms of which triptans he favors. He mentioned rizatriptan and naratriptan, which is one that I had not used with any frequency. I’ve seen rizatriptan a fair amount and that one seems to be covered by most insurances. He favors those two triptans.

He also reminded us that even though there is theoretical concern for serotonin toxicity because these are serotonergic and you’ll see these scary pop-ups in your electronic health record, that concern is almost purely theoretical. It hasn’t been borne out. They are really safe medications to use. But do use caution if you have a patient with known cardiovascular disease or cerebrovascular disease. We spent a fair amount of time talking about chest pressure as a common side effect. We also talked about some of the newer agents.

Dr. Watto: I wanted to add something about the triptans. Part of the reason he favors rizatriptan and naratriptan is that they are newer. He thinks they tend to have fewer side effects. But he did mention sumatriptan because it comes in the most different formulations. If patients have severe nausea, there is a subcutaneous version of sumatriptan and also an intranasal version.

The new kids on the block are the CGRP receptor antagonists, and they are available for preventive and abortive therapy. The abortive therapies are probably what people will be seeing most often in primary care – ubrogepant and rimegepant. Patients can take ubrogepant for abortive therapy and then repeat it if necessary. That’s similar to what patients are used to with the triptans. Rimegepant is taken once daily for abortive therapy or every other day as a preventive agent. Those are two of the agents that you might see patients taking. I’ve certainly started to see them.

There are also a whole bunch of monoclonal antibodies that affect the CGRP pathway. Those are given either once a month by subcutaneous injection or once every 3 months, and one is an infusion. They are pretty safe, and the big appeal is that they can be used in patients with cardiovascular disease. He also said that he has some patients who take them because triptans can cause the medication overuse side effect, but the CGRP receptor antagonists don’t. It’s an option for some patients to take the CGRP receptor antagonists on certain days for abortive therapy and then they can take the triptans the rest of the month.

Dr. Weber said that in his practice, these new drugs have really been great, which I can imagine, if you’re a specialist, patients have exhausted many of the typical therapies we offer in primary care.

Paul, bring us home here. What else should we tell the audience about? In primary care, what can we offer these patients?

Dr. Williams: A lot of the stuff we can offer works, by the way. It’s exciting to have fancy new medications to use, but you don’t even necessarily need to get to that point. We have a lot of medications that we can use for migraine prophylaxis, such as the beta-blockers and antihypertensives. Candesartan was a new one to me, an angiotensin receptor blocker that apparently has good evidence for migraine prophylaxis and Dr. Weber swears by it. We talked about some of the antiseizure medications, such as topiramate, which is probably the one with the most comfort in primary care. Some older folks may be using valproic acid or the tricyclic antidepressants (amitriptyline and nortriptyline) because people with migraine often will have comorbid anxiety or trouble sleeping, so I find that can sometimes be an effective medication or if they have comorbid neuropathic pain.

Another one that was new to me was venlafaxine as migraine prophylaxis. It’s not something I’d heard about before this episode. Certainly, for someone with chronic pain or a mood disorder that’s comorbid with migraines, it may be worth a shot. So there are options that we can exhaust first, and we may actually be doing our specialist friends a favor by trying one or two of these in advance, because then by the time the patient gets to the neurologist, it makes the prior authorization process much easier for the newer, fancier-pants medications that we’re all very excited about.

Dr. Watto: Paul, we’ve teased this fantastic podcast episode filled with so much more great stuff, so people should check out Headache Update: Making Migraines Less Painful with Dr. Kevin Weber.

Until next time, this has been another episode of The Curbsiders, bringing you a little knowledge food for your brain hole.

The Curbsiders is an internal medicine podcast, in which three board-certified internists interview experts on clinically important topics. In a collaboration with Medscape, the Curbsiders share clinical pearls and practice-changing knowledge from selected podcasts.

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

A small new study suggests – but doesn’t prove – that exposure to Wi-Fi signals from cell phones in pants pockets could disrupt male fertility. Researchers found that sperm placed next to an in-use iPhone on the Wi-Fi setting over 6 hours had less motility (50% vs. 38%, P = .024) and viability (60% vs. 47%, P = .003) than those set to 4G and 5G.

The findings, presented at the American Society for Reproductive Medicine’s 2022 meeting, don’t confirm that cell phones are harmful, lead author Kevin Y. Chu, MD, a Los Angeles urologist, said in an interview. “We cannot draw conclusions from this study, as the study population was too small. What we did observe was that Wi-Fi, which was previously less studied, may have had an impact on sperm. We did not see an effect on sperm quality by the 4G or 5G wireless spectrum.”

According to Dr. Chu, dozens of studies have examined the possible effect of cell phone exposure on sperm quality. “In human survey studies, there was no association of use and decline of sperm quality,” he said. “In human sperm in vitro studies, there was a decline of sperm motility and viability. And in animal studies, there was decline of sperm motility and viability.”

The new study is a pilot “to see if it is feasible to do a large-scale project” to analyze any possible effects from radiofrequency-electromagnetic radiation (RF-EMR) transmitted by cell phones, he said.

According to the study, cell phones emit radiation when they “transmit data for social media, web browsing, and music/podcast streaming,” and the rise of Bluetooth earbuds “presumably prolonged the amount of time the cell phone resides in the trouser pockets of men. This places the cell phone and its respective RF-EMR near the testicles for prolonged [periods].”

Researchers obtained semen samples from 27 men aged 25-35 who were fertile with normal sperm. Then they placed the samples on top of a current-generation iPhone that was set to talk mode via WhatsApp and transmitted/received signals via Wi-Fi, 4G, or 5G.

The researchers found no difference in sperm quality between control samples and those exposed to 4G or 5G (n = 9), but Wi-Fi (n = 18) seemed to have an effect. “We also tested conditions with the phone in a cover, as well as separating it by about 6 inches [from the sperm samples]. We found that both did dampen the effect of what we were seeing in comparison to direct exposure,” Dr. Chu said. “It appears that heat that is emanated from the device contributes to this effect.”

Dr. Chu cautioned that the study examined only ejaculated sperm, and “does not replicate real life where there is scrotal wall protection [and] pants material.”

For now, he said, there’s not enough evidence to allow clinicians to provide guidance to patients about possible links between cell phone exposure and male fertility. None of the study authors have changed their own use of cell phones as a result of the findings, he added.

Moving forward, he said, “continued research on exposure effects is needed and the current association should be considered cautiously as hypothesis generating.”

In an interview, University of Utah urologist James Hotaling, MD, who’s familiar with the study findings but didn’t take part in the research, said the authors “have done a good job looking at this issue,” but with acknowledged limitations.

The study size is very small, he said, “making generalizability difficult.” And “while the results, particularly on the Wi-Fi part, are interesting, they must be validated.”

In the big picture, he said, “the decline in sperm counts over the last 40 years is multifactorial so it cannot all be attributed to this. Finally, to really make the claim that Wi-Fi impacted fertility, you would need to have a much larger study and, ideally, look at pregnancy rates in couples trying to conceive.”

Overall, he said, the scientific community is “still skeptical” about a link between cell phone use and a decline in male fertility.

The study authors and Dr. Hotaling have no relevant disclosures.

A small new study suggests – but doesn’t prove – that exposure to Wi-Fi signals from cell phones in pants pockets could disrupt male fertility. Researchers found that sperm placed next to an in-use iPhone on the Wi-Fi setting over 6 hours had less motility (50% vs. 38%, P = .024) and viability (60% vs. 47%, P = .003) than those set to 4G and 5G.

The findings, presented at the American Society for Reproductive Medicine’s 2022 meeting, don’t confirm that cell phones are harmful, lead author Kevin Y. Chu, MD, a Los Angeles urologist, said in an interview. “We cannot draw conclusions from this study, as the study population was too small. What we did observe was that Wi-Fi, which was previously less studied, may have had an impact on sperm. We did not see an effect on sperm quality by the 4G or 5G wireless spectrum.”

According to Dr. Chu, dozens of studies have examined the possible effect of cell phone exposure on sperm quality. “In human survey studies, there was no association of use and decline of sperm quality,” he said. “In human sperm in vitro studies, there was a decline of sperm motility and viability. And in animal studies, there was decline of sperm motility and viability.”

The new study is a pilot “to see if it is feasible to do a large-scale project” to analyze any possible effects from radiofrequency-electromagnetic radiation (RF-EMR) transmitted by cell phones, he said.

According to the study, cell phones emit radiation when they “transmit data for social media, web browsing, and music/podcast streaming,” and the rise of Bluetooth earbuds “presumably prolonged the amount of time the cell phone resides in the trouser pockets of men. This places the cell phone and its respective RF-EMR near the testicles for prolonged [periods].”

Researchers obtained semen samples from 27 men aged 25-35 who were fertile with normal sperm. Then they placed the samples on top of a current-generation iPhone that was set to talk mode via WhatsApp and transmitted/received signals via Wi-Fi, 4G, or 5G.

The researchers found no difference in sperm quality between control samples and those exposed to 4G or 5G (n = 9), but Wi-Fi (n = 18) seemed to have an effect. “We also tested conditions with the phone in a cover, as well as separating it by about 6 inches [from the sperm samples]. We found that both did dampen the effect of what we were seeing in comparison to direct exposure,” Dr. Chu said. “It appears that heat that is emanated from the device contributes to this effect.”

Dr. Chu cautioned that the study examined only ejaculated sperm, and “does not replicate real life where there is scrotal wall protection [and] pants material.”

For now, he said, there’s not enough evidence to allow clinicians to provide guidance to patients about possible links between cell phone exposure and male fertility. None of the study authors have changed their own use of cell phones as a result of the findings, he added.

Moving forward, he said, “continued research on exposure effects is needed and the current association should be considered cautiously as hypothesis generating.”

In an interview, University of Utah urologist James Hotaling, MD, who’s familiar with the study findings but didn’t take part in the research, said the authors “have done a good job looking at this issue,” but with acknowledged limitations.

The study size is very small, he said, “making generalizability difficult.” And “while the results, particularly on the Wi-Fi part, are interesting, they must be validated.”

In the big picture, he said, “the decline in sperm counts over the last 40 years is multifactorial so it cannot all be attributed to this. Finally, to really make the claim that Wi-Fi impacted fertility, you would need to have a much larger study and, ideally, look at pregnancy rates in couples trying to conceive.”

Overall, he said, the scientific community is “still skeptical” about a link between cell phone use and a decline in male fertility.

The study authors and Dr. Hotaling have no relevant disclosures.

A small new study suggests – but doesn’t prove – that exposure to Wi-Fi signals from cell phones in pants pockets could disrupt male fertility. Researchers found that sperm placed next to an in-use iPhone on the Wi-Fi setting over 6 hours had less motility (50% vs. 38%, P = .024) and viability (60% vs. 47%, P = .003) than those set to 4G and 5G.

The findings, presented at the American Society for Reproductive Medicine’s 2022 meeting, don’t confirm that cell phones are harmful, lead author Kevin Y. Chu, MD, a Los Angeles urologist, said in an interview. “We cannot draw conclusions from this study, as the study population was too small. What we did observe was that Wi-Fi, which was previously less studied, may have had an impact on sperm. We did not see an effect on sperm quality by the 4G or 5G wireless spectrum.”

According to Dr. Chu, dozens of studies have examined the possible effect of cell phone exposure on sperm quality. “In human survey studies, there was no association of use and decline of sperm quality,” he said. “In human sperm in vitro studies, there was a decline of sperm motility and viability. And in animal studies, there was decline of sperm motility and viability.”

The new study is a pilot “to see if it is feasible to do a large-scale project” to analyze any possible effects from radiofrequency-electromagnetic radiation (RF-EMR) transmitted by cell phones, he said.

According to the study, cell phones emit radiation when they “transmit data for social media, web browsing, and music/podcast streaming,” and the rise of Bluetooth earbuds “presumably prolonged the amount of time the cell phone resides in the trouser pockets of men. This places the cell phone and its respective RF-EMR near the testicles for prolonged [periods].”

Researchers obtained semen samples from 27 men aged 25-35 who were fertile with normal sperm. Then they placed the samples on top of a current-generation iPhone that was set to talk mode via WhatsApp and transmitted/received signals via Wi-Fi, 4G, or 5G.

The researchers found no difference in sperm quality between control samples and those exposed to 4G or 5G (n = 9), but Wi-Fi (n = 18) seemed to have an effect. “We also tested conditions with the phone in a cover, as well as separating it by about 6 inches [from the sperm samples]. We found that both did dampen the effect of what we were seeing in comparison to direct exposure,” Dr. Chu said. “It appears that heat that is emanated from the device contributes to this effect.”

Dr. Chu cautioned that the study examined only ejaculated sperm, and “does not replicate real life where there is scrotal wall protection [and] pants material.”

For now, he said, there’s not enough evidence to allow clinicians to provide guidance to patients about possible links between cell phone exposure and male fertility. None of the study authors have changed their own use of cell phones as a result of the findings, he added.

Moving forward, he said, “continued research on exposure effects is needed and the current association should be considered cautiously as hypothesis generating.”

In an interview, University of Utah urologist James Hotaling, MD, who’s familiar with the study findings but didn’t take part in the research, said the authors “have done a good job looking at this issue,” but with acknowledged limitations.

The study size is very small, he said, “making generalizability difficult.” And “while the results, particularly on the Wi-Fi part, are interesting, they must be validated.”

In the big picture, he said, “the decline in sperm counts over the last 40 years is multifactorial so it cannot all be attributed to this. Finally, to really make the claim that Wi-Fi impacted fertility, you would need to have a much larger study and, ideally, look at pregnancy rates in couples trying to conceive.”

Overall, he said, the scientific community is “still skeptical” about a link between cell phone use and a decline in male fertility.

The study authors and Dr. Hotaling have no relevant disclosures.

MONTREAL – Patients who discontinue levothyroxine for subclinical hypothyroidism may gravitate towards becoming mildly hypothyroid again, but they importantly show no differences in terms of symptoms and quality of life – and sometimes show even improvement – compared with those who continue treatment, new research shows.

“Our results show feasibility of patient enrollment and safety of discontinuing levothyroxine in patients with subclinical hypothyroidism,” said first author Spyridoula Maraka, MD, when presenting the findings at the American Thyroid Association annual meeting.

Recommendations against levothyroxine for subclinical hypothyroidism

Subclinical hypothyroidism is commonly over-diagnosed, and treatment with thyroid hormone replacement, levothyroxine, has been shown to provide little, if any, benefit in terms of quality of life or relief of thyroid-related symptoms for these patients.

The treatment is meanwhile associated with burdens including cost and lifestyle adjustments, and one guideline panel recently issued a strong recommendation against routine levothyroxine use in most adults with subclinical hypothyroidism.

Nevertheless, levothyroxine treatment has soared in popularity and become one of the most commonly prescribed drugs in the United States.

With research lacking on one key solution of discontinuation of the therapy, Dr. Maraka, who is part of the Division of Endocrinology and Metabolism at the University of Arkansas for Medical Sciences, Little Rock, and colleagues conducted a double-blind, placebo-controlled trial at the Central Arkansas Veterans Healthcare System. In total, 50 patients treated for subclinical hypothyroidism were randomized 1:1 to continue receiving levothyroxine (25-75 mcg daily) or to discontinue treatment and receive a placebo instead, with a planned 6-month follow-up.

In the current interim analysis, Dr. Maraka reported results for the first 40 patients, including 20 randomized to levothyroxine and 20 to discontinuation.

There were no significant differences between the discontinuation and levothyroxine groups at baseline, which were of a similar age (66.2 vs. 70.8 years) and gender (75% women vs. 85% men).

The groups had similar baseline thyroid-stimulating hormone (TSH) levels (3.0 vs. 2.6 mIU/L), free T4 (both 0.9 ng/dL), thyroid peroxidase antibody positivity (17% vs. 11%), and similar clinical symptoms. All patients had at least one elevated TSH reading prior to starting levothyroxine.

With a follow-up of 6-8 weeks, 36.8% of patients in the discontinuation group had subclinical hypothyroidism, compared with 10% of patients who remained on levothyroxine (P = .0648), TSH levels were 5.5 versus 2.7 mIU/L (P = .001) and free T4 levels were 0.8 versus 0.9 ng/dL (P = .011).
 

No differences in symptoms, quality of life between groups

Importantly, there were no significant differences between the discontinuation versus levothyroxine groups in terms of symptoms, and even some improvements with discontinuation, including Thyroid-Specific Quality of Life Patient-Reported Outcome (ThyPRO)-Hypothyroid Symptoms score (4.6 reduction vs. 2.2 increase), tiredness (2.6 reduction vs. 1.1 increase), and EuroQoL 5-Dimension Self-Report Questionnaire (EQ-5D) quality of life score, for which there were no differences between groups.

There were no reports of overt hypothyroidism; hyperthyroidism; cardiovascular events including atrial fibrillation, stroke, or heart failure; osteoporotic fractures; or deaths.

One patient in the discontinuation group had a TSH level of 11 mIU/L at 6-8 weeks and switched to open-label levothyroxine 75 mcg daily. Another patient in the discontinuation group switched to open-label levothyroxine 75 mcg daily at 10 weeks due to fatigue; however, the patient was diagnosed with metastatic colon cancer 1 month later.

The finding that only about a third of patients who discontinued levothyroxine developed subclinical hypothyroidism was lower than expected, Dr. Maraka noted.

“This was ... unexpected ... for us,” she said. “We were expecting a larger number of patients to develop hypothyroidism, but to our surprise, that was not the case.”

“But what is more important is that there was no difference in the quality of life measures,” she added. “If anything, the placebo group was a little better, though the [differences] were not statistically significant.”

Dr. Maraka also noted that in further research and a final 6-month analysis, the authors will look at factors associated with developing subclinical hypothyroidism after treatment discontinuation, among other issues.
 

Discontinuation of levothyroxine is manageable

The results are encouraging, as they provide assurance that discontinuation of levothyroxine is manageable.

“This research will pave the way for initiatives to promote levothyroxine deprescription and implementation of evidence-based care for patients with subclinical hypothyroidism,” she said.

In further comments, Dr. Hennessey noted that the dilemma of having patients on levothyroxine who may not be benefitting from treatment is “significant,” with patients sometimes reluctant to discontinue treatment due to concerns of developing hypothyroidism-associated symptoms such as brain fog and weight gain.

He noted, however, that “many with mildly elevated TSH actually go on to normalize with time, so they are not really hypothyroid, [and] if we remove thyroxine from people with normal thyroid function, they will remain normal.”

Dr. Maraka has reported no relevant financial relationships. Dr. Hennessey has reported consulting for pharmaceutical companies to design clinical studies for thyroid medications.

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

MONTREAL – Patients who discontinue levothyroxine for subclinical hypothyroidism may gravitate towards becoming mildly hypothyroid again, but they importantly show no differences in terms of symptoms and quality of life – and sometimes show even improvement – compared with those who continue treatment, new research shows.

“Our results show feasibility of patient enrollment and safety of discontinuing levothyroxine in patients with subclinical hypothyroidism,” said first author Spyridoula Maraka, MD, when presenting the findings at the American Thyroid Association annual meeting.

Recommendations against levothyroxine for subclinical hypothyroidism

Subclinical hypothyroidism is commonly over-diagnosed, and treatment with thyroid hormone replacement, levothyroxine, has been shown to provide little, if any, benefit in terms of quality of life or relief of thyroid-related symptoms for these patients.

The treatment is meanwhile associated with burdens including cost and lifestyle adjustments, and one guideline panel recently issued a strong recommendation against routine levothyroxine use in most adults with subclinical hypothyroidism.

Nevertheless, levothyroxine treatment has soared in popularity and become one of the most commonly prescribed drugs in the United States.

With research lacking on one key solution of discontinuation of the therapy, Dr. Maraka, who is part of the Division of Endocrinology and Metabolism at the University of Arkansas for Medical Sciences, Little Rock, and colleagues conducted a double-blind, placebo-controlled trial at the Central Arkansas Veterans Healthcare System. In total, 50 patients treated for subclinical hypothyroidism were randomized 1:1 to continue receiving levothyroxine (25-75 mcg daily) or to discontinue treatment and receive a placebo instead, with a planned 6-month follow-up.

In the current interim analysis, Dr. Maraka reported results for the first 40 patients, including 20 randomized to levothyroxine and 20 to discontinuation.

There were no significant differences between the discontinuation and levothyroxine groups at baseline, which were of a similar age (66.2 vs. 70.8 years) and gender (75% women vs. 85% men).

The groups had similar baseline thyroid-stimulating hormone (TSH) levels (3.0 vs. 2.6 mIU/L), free T4 (both 0.9 ng/dL), thyroid peroxidase antibody positivity (17% vs. 11%), and similar clinical symptoms. All patients had at least one elevated TSH reading prior to starting levothyroxine.

With a follow-up of 6-8 weeks, 36.8% of patients in the discontinuation group had subclinical hypothyroidism, compared with 10% of patients who remained on levothyroxine (P = .0648), TSH levels were 5.5 versus 2.7 mIU/L (P = .001) and free T4 levels were 0.8 versus 0.9 ng/dL (P = .011).
 

No differences in symptoms, quality of life between groups

Importantly, there were no significant differences between the discontinuation versus levothyroxine groups in terms of symptoms, and even some improvements with discontinuation, including Thyroid-Specific Quality of Life Patient-Reported Outcome (ThyPRO)-Hypothyroid Symptoms score (4.6 reduction vs. 2.2 increase), tiredness (2.6 reduction vs. 1.1 increase), and EuroQoL 5-Dimension Self-Report Questionnaire (EQ-5D) quality of life score, for which there were no differences between groups.

There were no reports of overt hypothyroidism; hyperthyroidism; cardiovascular events including atrial fibrillation, stroke, or heart failure; osteoporotic fractures; or deaths.

One patient in the discontinuation group had a TSH level of 11 mIU/L at 6-8 weeks and switched to open-label levothyroxine 75 mcg daily. Another patient in the discontinuation group switched to open-label levothyroxine 75 mcg daily at 10 weeks due to fatigue; however, the patient was diagnosed with metastatic colon cancer 1 month later.

The finding that only about a third of patients who discontinued levothyroxine developed subclinical hypothyroidism was lower than expected, Dr. Maraka noted.

“This was ... unexpected ... for us,” she said. “We were expecting a larger number of patients to develop hypothyroidism, but to our surprise, that was not the case.”

“But what is more important is that there was no difference in the quality of life measures,” she added. “If anything, the placebo group was a little better, though the [differences] were not statistically significant.”

Dr. Maraka also noted that in further research and a final 6-month analysis, the authors will look at factors associated with developing subclinical hypothyroidism after treatment discontinuation, among other issues.
 

Discontinuation of levothyroxine is manageable

The results are encouraging, as they provide assurance that discontinuation of levothyroxine is manageable.

“This research will pave the way for initiatives to promote levothyroxine deprescription and implementation of evidence-based care for patients with subclinical hypothyroidism,” she said.

In further comments, Dr. Hennessey noted that the dilemma of having patients on levothyroxine who may not be benefitting from treatment is “significant,” with patients sometimes reluctant to discontinue treatment due to concerns of developing hypothyroidism-associated symptoms such as brain fog and weight gain.

He noted, however, that “many with mildly elevated TSH actually go on to normalize with time, so they are not really hypothyroid, [and] if we remove thyroxine from people with normal thyroid function, they will remain normal.”

Dr. Maraka has reported no relevant financial relationships. Dr. Hennessey has reported consulting for pharmaceutical companies to design clinical studies for thyroid medications.

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

MONTREAL – Patients who discontinue levothyroxine for subclinical hypothyroidism may gravitate towards becoming mildly hypothyroid again, but they importantly show no differences in terms of symptoms and quality of life – and sometimes show even improvement – compared with those who continue treatment, new research shows.

“Our results show feasibility of patient enrollment and safety of discontinuing levothyroxine in patients with subclinical hypothyroidism,” said first author Spyridoula Maraka, MD, when presenting the findings at the American Thyroid Association annual meeting.

Recommendations against levothyroxine for subclinical hypothyroidism

Subclinical hypothyroidism is commonly over-diagnosed, and treatment with thyroid hormone replacement, levothyroxine, has been shown to provide little, if any, benefit in terms of quality of life or relief of thyroid-related symptoms for these patients.

The treatment is meanwhile associated with burdens including cost and lifestyle adjustments, and one guideline panel recently issued a strong recommendation against routine levothyroxine use in most adults with subclinical hypothyroidism.

Nevertheless, levothyroxine treatment has soared in popularity and become one of the most commonly prescribed drugs in the United States.

With research lacking on one key solution of discontinuation of the therapy, Dr. Maraka, who is part of the Division of Endocrinology and Metabolism at the University of Arkansas for Medical Sciences, Little Rock, and colleagues conducted a double-blind, placebo-controlled trial at the Central Arkansas Veterans Healthcare System. In total, 50 patients treated for subclinical hypothyroidism were randomized 1:1 to continue receiving levothyroxine (25-75 mcg daily) or to discontinue treatment and receive a placebo instead, with a planned 6-month follow-up.

In the current interim analysis, Dr. Maraka reported results for the first 40 patients, including 20 randomized to levothyroxine and 20 to discontinuation.

There were no significant differences between the discontinuation and levothyroxine groups at baseline, which were of a similar age (66.2 vs. 70.8 years) and gender (75% women vs. 85% men).

The groups had similar baseline thyroid-stimulating hormone (TSH) levels (3.0 vs. 2.6 mIU/L), free T4 (both 0.9 ng/dL), thyroid peroxidase antibody positivity (17% vs. 11%), and similar clinical symptoms. All patients had at least one elevated TSH reading prior to starting levothyroxine.

With a follow-up of 6-8 weeks, 36.8% of patients in the discontinuation group had subclinical hypothyroidism, compared with 10% of patients who remained on levothyroxine (P = .0648), TSH levels were 5.5 versus 2.7 mIU/L (P = .001) and free T4 levels were 0.8 versus 0.9 ng/dL (P = .011).
 

No differences in symptoms, quality of life between groups

Importantly, there were no significant differences between the discontinuation versus levothyroxine groups in terms of symptoms, and even some improvements with discontinuation, including Thyroid-Specific Quality of Life Patient-Reported Outcome (ThyPRO)-Hypothyroid Symptoms score (4.6 reduction vs. 2.2 increase), tiredness (2.6 reduction vs. 1.1 increase), and EuroQoL 5-Dimension Self-Report Questionnaire (EQ-5D) quality of life score, for which there were no differences between groups.

There were no reports of overt hypothyroidism; hyperthyroidism; cardiovascular events including atrial fibrillation, stroke, or heart failure; osteoporotic fractures; or deaths.

One patient in the discontinuation group had a TSH level of 11 mIU/L at 6-8 weeks and switched to open-label levothyroxine 75 mcg daily. Another patient in the discontinuation group switched to open-label levothyroxine 75 mcg daily at 10 weeks due to fatigue; however, the patient was diagnosed with metastatic colon cancer 1 month later.

The finding that only about a third of patients who discontinued levothyroxine developed subclinical hypothyroidism was lower than expected, Dr. Maraka noted.

“This was ... unexpected ... for us,” she said. “We were expecting a larger number of patients to develop hypothyroidism, but to our surprise, that was not the case.”

“But what is more important is that there was no difference in the quality of life measures,” she added. “If anything, the placebo group was a little better, though the [differences] were not statistically significant.”

Dr. Maraka also noted that in further research and a final 6-month analysis, the authors will look at factors associated with developing subclinical hypothyroidism after treatment discontinuation, among other issues.
 

Discontinuation of levothyroxine is manageable

The results are encouraging, as they provide assurance that discontinuation of levothyroxine is manageable.

“This research will pave the way for initiatives to promote levothyroxine deprescription and implementation of evidence-based care for patients with subclinical hypothyroidism,” she said.

In further comments, Dr. Hennessey noted that the dilemma of having patients on levothyroxine who may not be benefitting from treatment is “significant,” with patients sometimes reluctant to discontinue treatment due to concerns of developing hypothyroidism-associated symptoms such as brain fog and weight gain.

He noted, however, that “many with mildly elevated TSH actually go on to normalize with time, so they are not really hypothyroid, [and] if we remove thyroxine from people with normal thyroid function, they will remain normal.”

Dr. Maraka has reported no relevant financial relationships. Dr. Hennessey has reported consulting for pharmaceutical companies to design clinical studies for thyroid medications.

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

Today’s health care professionals run the very real risk of being sued. This is especially true when a patient dies unexpectedly. But many times, doctors find that they’re defending themselves against very serious charges, such as murder and attempted murder.

In Mexico, a physician can be wrongfully accused of such crimes, as was Azucena Calvillo, MD, last year in Durango. The case drew much media attention, and the accusations were so implausible and ridiculous that the charges were dropped and the case was dismissed.

There are instances in which the authorities create a circuslike atmosphere by making farcical and false accusations against healthcare professionals. Still, there are medical murderers – and these killers are among the most difficult to identify. As John E. Douglas put it, “Medical murderers (physicians, nurses, elder care workers) can have a long list of victims, longer than other kinds of serial killers.” Ted Bundy, one of the most written-about serial killers, confessed to 30 murders. The cases discussed below involve from 60 to 200.

Mr. Douglas was a special agent with the United States Federal Bureau of Investigation. He is the author of Mindhunter, a nonfiction crime book in which he recounts the early days of the FBI’s Behavioral Science Unit and how he and his colleagues began to study the criminal profiles of serial killers. The book has been adapted into a Netflix TV series of the same name.

He is also one of the authors of Crime Classification Manual: A Standard System for Investigating and Classifying Violent Crime. In this book, there are descriptions of criminal profiles of medical murderers.

According to the authors, there are two types of medical murders: pseudo-mercy homicide and pseudo-hero homicide. Each type is associated with a different motive. In the former, the murderers believe that they’re alleviating the patient’s suffering; in the latter, the murderers create a medical emergency so that they can play the hero in what they know will be an unsuccessful attempt to save the patient’s life.
 

Pseudo-mercy homicide

An example of pseudo-mercy homicide is the infamous case of Harold Shipman, MD, who was convicted of killing 15 people, although an investigation found that more than 200 persons, and possibly as many as 250, died at his hands. In Prescription for Murder: The True Story of Dr. Harold Frederick Shipman, biographer Brian Whittle writes that the general practitioner is England’s (if not the world’s) most prolific serial killer. Dr. Shipman is the only physician in that country’s history to have been convicted of killing his patients.

His modus operandi? Injecting morphine. Most of his victims were elderly women. And though unconfirmed, his youngest victim may have been only 4 years old. It was the death of 81-year-old Kathleen Grundy that led to the physician’s arrest. Her family became extremely suspicious when they learned that her will named Dr. Shipman as the beneficiary of her entire estate.

He always denied being involved in the murders, for which authorities have yet to determine a motive. The speculation is that he enjoyed watching people die. Almost none of the cases attributed to Dr. Shipman involved a critically ill individual with a life-threatening condition. Therefore, his acts were not real acts of mercy. He would make a house call to carry out a routine visit. Once in the patient’s home, he would inject a lethal dose of morphine. Sometimes, relatives and physicians alike would be struck by the strange turn of events.

In 2004, Dr. Shipman committed suicide in prison. His case led to numerous changes to British law with respect to the use of controlled substances, the issuance of death certificates, and the procedure for reporting healthcare staff suspected of engaging in illegal activities. Biographer Whittle concluded, “It is very unlikely that the world will ever see another physician as unrelentingly wicked as Dr. Shipman.”
 

Pseudo-hero homicide

The pseudo-hero creates serious situations, generally by administering drugs, and then tries to save the patient. Mr. Douglas presents a terrifying case study: Genene Jones, a nurse known as the “Angel of Death.”

Many of Ms. Jones’ colleagues considered her an excellent nurse, an expert at handling unexpected emergencies. If a child died while she was on duty, she would sometimes accompany their body to the morgue. She would even sing children’s songs to their lifeless body. When people started to question the number of deaths that were occurring during her shifts, the staff stood up for Ms. Jones, saying that it was because she took on the most serious cases.

Ms. Jones was found out when a vial of succinylcholine went missing. After it was located, a physician, who had been suspicious of the nurse, noticed that there were two puncture holes in the stopper. None of the staff could offer any explanation. A few days before this event, that same physician had left a healthy 15-month-old girl in Jones’ care. Within a few minutes, the child was showing signs of paralysis and started to have seizures. It appears that Ms. Jones had used succinylcholine to make it appear that the children were sick or were experiencing some sort of emergency so that she could then attempt to save them, and they could die in her arms.

This case highlights the need for mortality review committees and for proper statistical analysis to discern trends in deaths and complications among patients. Genene Jones was convicted of killing the 15-month-old girl and was sentenced to 99 years in prison. Authorities suspect that the nurse was responsible for the deaths of up to 60 children.
 

A new criminal profile?

Through the podcast and subsequent TV series Dr. Death, many people have come to know of a more recent medical murderer: Christopher Duntsch, MD, PhD. The Texas neurosurgeon killed at least two patients, and his actions left several others with adverse outcomes and serious injuries.

These acts occurred during surgical procedures. Witnesses said that the deaths and injuries were the result of unprecedented, egregious negligence, as though the operations had been performed by someone who had never been trained in the specialty. This is something that resonates very strongly for those who are aware of what’s going on in Mexico, where it’s well known that many physicians who lack specialty training perform operations (mainly cosmetic surgery). No doubt cases such as Dr. Duntsch’s are more frequent in Mexico.

What makes the situation in the United States involving Christopher Duntsch so astonishing is that it resulted from a perfect storm of a physician whom some colleagues described as a “sociopath” and legal loopholes in the country’s healthcare system. Apparently, during his residency, Dr. Duntsch never developed the skills necessary to perform operations. He spent more time carrying out research and engaging in other activities than in participating in the operating room. This is a case that calls into question the way specialists are trained, as it seems that what matters is not how much time they’re spending inside the hospital but what they’re doing and learning there.

Dr. Duntsch’s license was suspended and then permanently revoked. He is currently serving a life sentence. Through the podcast or the TV series, one comes to realize that it’s not easy to catch medical murderers. They are among the most difficult to identify – serial killers who commit numerous homicides before they are captured. Reading about the case of Christopher Duntsch, one might ask, What’s his criminal profile: pseudo-hero? Pseudo-mercy? It is hard to say. Maybe his is a different kind of profile – one that will open a new chapter in the books on medical murderers.

Dr. Sarmiento studied medicine and did his residency in anatomic pathology, internal medicine, and clinical hematology. He went on to study at Central University City Campus Law School, National Autonomous University of Mexico. He now runs a law firm that, among other things, advises physicians on matters of civil liability, administrative processes, and the legal implications of practicing medicine.

This article was translated from the Medscape Spanish edition.

Today’s health care professionals run the very real risk of being sued. This is especially true when a patient dies unexpectedly. But many times, doctors find that they’re defending themselves against very serious charges, such as murder and attempted murder.

In Mexico, a physician can be wrongfully accused of such crimes, as was Azucena Calvillo, MD, last year in Durango. The case drew much media attention, and the accusations were so implausible and ridiculous that the charges were dropped and the case was dismissed.

There are instances in which the authorities create a circuslike atmosphere by making farcical and false accusations against healthcare professionals. Still, there are medical murderers – and these killers are among the most difficult to identify. As John E. Douglas put it, “Medical murderers (physicians, nurses, elder care workers) can have a long list of victims, longer than other kinds of serial killers.” Ted Bundy, one of the most written-about serial killers, confessed to 30 murders. The cases discussed below involve from 60 to 200.

Mr. Douglas was a special agent with the United States Federal Bureau of Investigation. He is the author of Mindhunter, a nonfiction crime book in which he recounts the early days of the FBI’s Behavioral Science Unit and how he and his colleagues began to study the criminal profiles of serial killers. The book has been adapted into a Netflix TV series of the same name.

He is also one of the authors of Crime Classification Manual: A Standard System for Investigating and Classifying Violent Crime. In this book, there are descriptions of criminal profiles of medical murderers.

According to the authors, there are two types of medical murders: pseudo-mercy homicide and pseudo-hero homicide. Each type is associated with a different motive. In the former, the murderers believe that they’re alleviating the patient’s suffering; in the latter, the murderers create a medical emergency so that they can play the hero in what they know will be an unsuccessful attempt to save the patient’s life.
 

Pseudo-mercy homicide

An example of pseudo-mercy homicide is the infamous case of Harold Shipman, MD, who was convicted of killing 15 people, although an investigation found that more than 200 persons, and possibly as many as 250, died at his hands. In Prescription for Murder: The True Story of Dr. Harold Frederick Shipman, biographer Brian Whittle writes that the general practitioner is England’s (if not the world’s) most prolific serial killer. Dr. Shipman is the only physician in that country’s history to have been convicted of killing his patients.

His modus operandi? Injecting morphine. Most of his victims were elderly women. And though unconfirmed, his youngest victim may have been only 4 years old. It was the death of 81-year-old Kathleen Grundy that led to the physician’s arrest. Her family became extremely suspicious when they learned that her will named Dr. Shipman as the beneficiary of her entire estate.

He always denied being involved in the murders, for which authorities have yet to determine a motive. The speculation is that he enjoyed watching people die. Almost none of the cases attributed to Dr. Shipman involved a critically ill individual with a life-threatening condition. Therefore, his acts were not real acts of mercy. He would make a house call to carry out a routine visit. Once in the patient’s home, he would inject a lethal dose of morphine. Sometimes, relatives and physicians alike would be struck by the strange turn of events.

In 2004, Dr. Shipman committed suicide in prison. His case led to numerous changes to British law with respect to the use of controlled substances, the issuance of death certificates, and the procedure for reporting healthcare staff suspected of engaging in illegal activities. Biographer Whittle concluded, “It is very unlikely that the world will ever see another physician as unrelentingly wicked as Dr. Shipman.”
 

Pseudo-hero homicide

The pseudo-hero creates serious situations, generally by administering drugs, and then tries to save the patient. Mr. Douglas presents a terrifying case study: Genene Jones, a nurse known as the “Angel of Death.”

Many of Ms. Jones’ colleagues considered her an excellent nurse, an expert at handling unexpected emergencies. If a child died while she was on duty, she would sometimes accompany their body to the morgue. She would even sing children’s songs to their lifeless body. When people started to question the number of deaths that were occurring during her shifts, the staff stood up for Ms. Jones, saying that it was because she took on the most serious cases.

Ms. Jones was found out when a vial of succinylcholine went missing. After it was located, a physician, who had been suspicious of the nurse, noticed that there were two puncture holes in the stopper. None of the staff could offer any explanation. A few days before this event, that same physician had left a healthy 15-month-old girl in Jones’ care. Within a few minutes, the child was showing signs of paralysis and started to have seizures. It appears that Ms. Jones had used succinylcholine to make it appear that the children were sick or were experiencing some sort of emergency so that she could then attempt to save them, and they could die in her arms.

This case highlights the need for mortality review committees and for proper statistical analysis to discern trends in deaths and complications among patients. Genene Jones was convicted of killing the 15-month-old girl and was sentenced to 99 years in prison. Authorities suspect that the nurse was responsible for the deaths of up to 60 children.
 

A new criminal profile?

Through the podcast and subsequent TV series Dr. Death, many people have come to know of a more recent medical murderer: Christopher Duntsch, MD, PhD. The Texas neurosurgeon killed at least two patients, and his actions left several others with adverse outcomes and serious injuries.

These acts occurred during surgical procedures. Witnesses said that the deaths and injuries were the result of unprecedented, egregious negligence, as though the operations had been performed by someone who had never been trained in the specialty. This is something that resonates very strongly for those who are aware of what’s going on in Mexico, where it’s well known that many physicians who lack specialty training perform operations (mainly cosmetic surgery). No doubt cases such as Dr. Duntsch’s are more frequent in Mexico.

What makes the situation in the United States involving Christopher Duntsch so astonishing is that it resulted from a perfect storm of a physician whom some colleagues described as a “sociopath” and legal loopholes in the country’s healthcare system. Apparently, during his residency, Dr. Duntsch never developed the skills necessary to perform operations. He spent more time carrying out research and engaging in other activities than in participating in the operating room. This is a case that calls into question the way specialists are trained, as it seems that what matters is not how much time they’re spending inside the hospital but what they’re doing and learning there.

Dr. Duntsch’s license was suspended and then permanently revoked. He is currently serving a life sentence. Through the podcast or the TV series, one comes to realize that it’s not easy to catch medical murderers. They are among the most difficult to identify – serial killers who commit numerous homicides before they are captured. Reading about the case of Christopher Duntsch, one might ask, What’s his criminal profile: pseudo-hero? Pseudo-mercy? It is hard to say. Maybe his is a different kind of profile – one that will open a new chapter in the books on medical murderers.

Dr. Sarmiento studied medicine and did his residency in anatomic pathology, internal medicine, and clinical hematology. He went on to study at Central University City Campus Law School, National Autonomous University of Mexico. He now runs a law firm that, among other things, advises physicians on matters of civil liability, administrative processes, and the legal implications of practicing medicine.

This article was translated from the Medscape Spanish edition.

Today’s health care professionals run the very real risk of being sued. This is especially true when a patient dies unexpectedly. But many times, doctors find that they’re defending themselves against very serious charges, such as murder and attempted murder.

In Mexico, a physician can be wrongfully accused of such crimes, as was Azucena Calvillo, MD, last year in Durango. The case drew much media attention, and the accusations were so implausible and ridiculous that the charges were dropped and the case was dismissed.

There are instances in which the authorities create a circuslike atmosphere by making farcical and false accusations against healthcare professionals. Still, there are medical murderers – and these killers are among the most difficult to identify. As John E. Douglas put it, “Medical murderers (physicians, nurses, elder care workers) can have a long list of victims, longer than other kinds of serial killers.” Ted Bundy, one of the most written-about serial killers, confessed to 30 murders. The cases discussed below involve from 60 to 200.

Mr. Douglas was a special agent with the United States Federal Bureau of Investigation. He is the author of Mindhunter, a nonfiction crime book in which he recounts the early days of the FBI’s Behavioral Science Unit and how he and his colleagues began to study the criminal profiles of serial killers. The book has been adapted into a Netflix TV series of the same name.

He is also one of the authors of Crime Classification Manual: A Standard System for Investigating and Classifying Violent Crime. In this book, there are descriptions of criminal profiles of medical murderers.

According to the authors, there are two types of medical murders: pseudo-mercy homicide and pseudo-hero homicide. Each type is associated with a different motive. In the former, the murderers believe that they’re alleviating the patient’s suffering; in the latter, the murderers create a medical emergency so that they can play the hero in what they know will be an unsuccessful attempt to save the patient’s life.
 

Pseudo-mercy homicide

An example of pseudo-mercy homicide is the infamous case of Harold Shipman, MD, who was convicted of killing 15 people, although an investigation found that more than 200 persons, and possibly as many as 250, died at his hands. In Prescription for Murder: The True Story of Dr. Harold Frederick Shipman, biographer Brian Whittle writes that the general practitioner is England’s (if not the world’s) most prolific serial killer. Dr. Shipman is the only physician in that country’s history to have been convicted of killing his patients.

His modus operandi? Injecting morphine. Most of his victims were elderly women. And though unconfirmed, his youngest victim may have been only 4 years old. It was the death of 81-year-old Kathleen Grundy that led to the physician’s arrest. Her family became extremely suspicious when they learned that her will named Dr. Shipman as the beneficiary of her entire estate.

He always denied being involved in the murders, for which authorities have yet to determine a motive. The speculation is that he enjoyed watching people die. Almost none of the cases attributed to Dr. Shipman involved a critically ill individual with a life-threatening condition. Therefore, his acts were not real acts of mercy. He would make a house call to carry out a routine visit. Once in the patient’s home, he would inject a lethal dose of morphine. Sometimes, relatives and physicians alike would be struck by the strange turn of events.

In 2004, Dr. Shipman committed suicide in prison. His case led to numerous changes to British law with respect to the use of controlled substances, the issuance of death certificates, and the procedure for reporting healthcare staff suspected of engaging in illegal activities. Biographer Whittle concluded, “It is very unlikely that the world will ever see another physician as unrelentingly wicked as Dr. Shipman.”
 

Pseudo-hero homicide

The pseudo-hero creates serious situations, generally by administering drugs, and then tries to save the patient. Mr. Douglas presents a terrifying case study: Genene Jones, a nurse known as the “Angel of Death.”

Many of Ms. Jones’ colleagues considered her an excellent nurse, an expert at handling unexpected emergencies. If a child died while she was on duty, she would sometimes accompany their body to the morgue. She would even sing children’s songs to their lifeless body. When people started to question the number of deaths that were occurring during her shifts, the staff stood up for Ms. Jones, saying that it was because she took on the most serious cases.

Ms. Jones was found out when a vial of succinylcholine went missing. After it was located, a physician, who had been suspicious of the nurse, noticed that there were two puncture holes in the stopper. None of the staff could offer any explanation. A few days before this event, that same physician had left a healthy 15-month-old girl in Jones’ care. Within a few minutes, the child was showing signs of paralysis and started to have seizures. It appears that Ms. Jones had used succinylcholine to make it appear that the children were sick or were experiencing some sort of emergency so that she could then attempt to save them, and they could die in her arms.

This case highlights the need for mortality review committees and for proper statistical analysis to discern trends in deaths and complications among patients. Genene Jones was convicted of killing the 15-month-old girl and was sentenced to 99 years in prison. Authorities suspect that the nurse was responsible for the deaths of up to 60 children.
 

A new criminal profile?

Through the podcast and subsequent TV series Dr. Death, many people have come to know of a more recent medical murderer: Christopher Duntsch, MD, PhD. The Texas neurosurgeon killed at least two patients, and his actions left several others with adverse outcomes and serious injuries.

These acts occurred during surgical procedures. Witnesses said that the deaths and injuries were the result of unprecedented, egregious negligence, as though the operations had been performed by someone who had never been trained in the specialty. This is something that resonates very strongly for those who are aware of what’s going on in Mexico, where it’s well known that many physicians who lack specialty training perform operations (mainly cosmetic surgery). No doubt cases such as Dr. Duntsch’s are more frequent in Mexico.

What makes the situation in the United States involving Christopher Duntsch so astonishing is that it resulted from a perfect storm of a physician whom some colleagues described as a “sociopath” and legal loopholes in the country’s healthcare system. Apparently, during his residency, Dr. Duntsch never developed the skills necessary to perform operations. He spent more time carrying out research and engaging in other activities than in participating in the operating room. This is a case that calls into question the way specialists are trained, as it seems that what matters is not how much time they’re spending inside the hospital but what they’re doing and learning there.

Dr. Duntsch’s license was suspended and then permanently revoked. He is currently serving a life sentence. Through the podcast or the TV series, one comes to realize that it’s not easy to catch medical murderers. They are among the most difficult to identify – serial killers who commit numerous homicides before they are captured. Reading about the case of Christopher Duntsch, one might ask, What’s his criminal profile: pseudo-hero? Pseudo-mercy? It is hard to say. Maybe his is a different kind of profile – one that will open a new chapter in the books on medical murderers.

Dr. Sarmiento studied medicine and did his residency in anatomic pathology, internal medicine, and clinical hematology. He went on to study at Central University City Campus Law School, National Autonomous University of Mexico. He now runs a law firm that, among other things, advises physicians on matters of civil liability, administrative processes, and the legal implications of practicing medicine.

This article was translated from the Medscape Spanish edition.

Psychiatrists have a long tradition of supporting LGBTQAI+ (lesbian, gay, bisexual, transgender, queer/questioning, asexual, intersex, and others) persons. In professional and public settings, we are educators, role models, and advocates for self-expression and personal empowerment. By better educating ourselves on the topic of gender and its variations, we can become champions of gender-affirming care.

Sex vs gender

A person’s sex is assigned at birth based on their physiological characteristics, including their genitalia and chromosome composition. Male, female, and intersex are a few recognized sexes. Gender or gender identity describe one’s innermost perception of self as a man, a woman, a variation of both, or neither, that may not always be visible to others. When sex and gender identity align, this is known as cisgender.¹

Gender identity

Gender identity is best described as a spectrum rather than a binary. Terms that fall under a gender binary include man, woman, trans man, and trans woman. A nonbinary gender identity is one outside the traditional binary of men or women. Being transgender simply means having a gender identity different than the sex assigned at birth. This includes persons whose gender identities cross the gender spectrum, such as trans men or trans women, and those who fall anywhere outside or in between genders. In this way, nonbinary persons are transgender.¹

The nonbinary spectrum

The term nonbinary encompasses many gender-nonconforming identities, such as agender, bigender, demigender, genderfluid, genderqueer, intergender, or pangender. Agender people have little connection to gender. Bigender individuals identify as 2 separate genders. Demigender persons feel a partial connection to a gender. Genderfluid individuals have a gender experience that is fluid and can change over time. Genderqueer people have a gender identity that falls in between or outside the binary. Intergender people have a gender identity between genders or identify as a combination of genders. Pangender people identify with a combination of genders. Note that patients may use some of these terms interchangeably or ascribe to them different meanings.² As the language around gender continues to evolve, psychiatrists should ask patients from a place of nonjudgmental curiosity what gender terms they use, how they define them, and what their gender means to them.

Gender expression and transitioning

Transitioning is what a transgender person does to align their gender identity and expression.³ Gender expression is the external manifestation of gender, including names, pronouns, clothing, haircuts, behaviors, voice, body characteristics, and more.¹ Transgender individuals can transition using a combination of social (name, pronouns, dress), legal (changing sex on legal documents, name change), or medical (surgeries, hormone therapies, puberty blockade) means. Transitions often help ease gender dysphoria, which is the clinically significant distress a person experiences when their sex assigned at birth does not align with their gender identity.³ Note that not all transgender persons choose to change their gender expression, and not all transgender individuals experience gender dysphoria. In this case, the proper medical term is gender incongruence, which is simply when someone’s gender identity does not align with their sex assigned at birth.⁴

Names and pronouns

For many transgender persons, names and pronouns are an important part of their gender transition and expression.² Most of us have gotten into the habit of assuming pronouns because of socially established gender roles. This assumes that a person’s physical appearance matches their gender identity, which is not always the case.¹ To be more affirming, psychiatrists and other health care professionals should try to break the habit of assuming pronouns. Often, an easy way to learn someone’s pronouns is to introduce yourself with yours. For example, “I am Dr. Agapoff. I use they/them/theirs pronouns. It is nice to meet you.” This creates a safe and open space for the other person to share their gender identity if they choose.

Why it’s important

One does not have to be a gender specialist to deliver gender-affirming care. As psychiatrists, having a basic understanding of the differences between sex, gender identity, and gender expression can help us build rapport and support our patients who are transgender. Based on the many kinds of gender identity and expression, judging someone’s gender based solely upon physical appearance is misguided at best and harmful at worst. Even people who are cisgender have many kinds of gender expression. For this reason, psychiatrists should approach gender with the same openness and curiosity as sexual orientation or other important considerations of emotional and physical health. Gender-informed care starts with us.

Psychiatrists have a long tradition of supporting LGBTQAI+ (lesbian, gay, bisexual, transgender, queer/questioning, asexual, intersex, and others) persons. In professional and public settings, we are educators, role models, and advocates for self-expression and personal empowerment. By better educating ourselves on the topic of gender and its variations, we can become champions of gender-affirming care.

Sex vs gender

A person’s sex is assigned at birth based on their physiological characteristics, including their genitalia and chromosome composition. Male, female, and intersex are a few recognized sexes. Gender or gender identity describe one’s innermost perception of self as a man, a woman, a variation of both, or neither, that may not always be visible to others. When sex and gender identity align, this is known as cisgender.¹

Gender identity

Gender identity is best described as a spectrum rather than a binary. Terms that fall under a gender binary include man, woman, trans man, and trans woman. A nonbinary gender identity is one outside the traditional binary of men or women. Being transgender simply means having a gender identity different than the sex assigned at birth. This includes persons whose gender identities cross the gender spectrum, such as trans men or trans women, and those who fall anywhere outside or in between genders. In this way, nonbinary persons are transgender.¹

The nonbinary spectrum

The term nonbinary encompasses many gender-nonconforming identities, such as agender, bigender, demigender, genderfluid, genderqueer, intergender, or pangender. Agender people have little connection to gender. Bigender individuals identify as 2 separate genders. Demigender persons feel a partial connection to a gender. Genderfluid individuals have a gender experience that is fluid and can change over time. Genderqueer people have a gender identity that falls in between or outside the binary. Intergender people have a gender identity between genders or identify as a combination of genders. Pangender people identify with a combination of genders. Note that patients may use some of these terms interchangeably or ascribe to them different meanings.² As the language around gender continues to evolve, psychiatrists should ask patients from a place of nonjudgmental curiosity what gender terms they use, how they define them, and what their gender means to them.

Gender expression and transitioning

Transitioning is what a transgender person does to align their gender identity and expression.³ Gender expression is the external manifestation of gender, including names, pronouns, clothing, haircuts, behaviors, voice, body characteristics, and more.¹ Transgender individuals can transition using a combination of social (name, pronouns, dress), legal (changing sex on legal documents, name change), or medical (surgeries, hormone therapies, puberty blockade) means. Transitions often help ease gender dysphoria, which is the clinically significant distress a person experiences when their sex assigned at birth does not align with their gender identity.³ Note that not all transgender persons choose to change their gender expression, and not all transgender individuals experience gender dysphoria. In this case, the proper medical term is gender incongruence, which is simply when someone’s gender identity does not align with their sex assigned at birth.⁴

Names and pronouns

For many transgender persons, names and pronouns are an important part of their gender transition and expression.² Most of us have gotten into the habit of assuming pronouns because of socially established gender roles. This assumes that a person’s physical appearance matches their gender identity, which is not always the case.¹ To be more affirming, psychiatrists and other health care professionals should try to break the habit of assuming pronouns. Often, an easy way to learn someone’s pronouns is to introduce yourself with yours. For example, “I am Dr. Agapoff. I use they/them/theirs pronouns. It is nice to meet you.” This creates a safe and open space for the other person to share their gender identity if they choose.

Why it’s important

One does not have to be a gender specialist to deliver gender-affirming care. As psychiatrists, having a basic understanding of the differences between sex, gender identity, and gender expression can help us build rapport and support our patients who are transgender. Based on the many kinds of gender identity and expression, judging someone’s gender based solely upon physical appearance is misguided at best and harmful at worst. Even people who are cisgender have many kinds of gender expression. For this reason, psychiatrists should approach gender with the same openness and curiosity as sexual orientation or other important considerations of emotional and physical health. Gender-informed care starts with us.

Psychiatrists have a long tradition of supporting LGBTQAI+ (lesbian, gay, bisexual, transgender, queer/questioning, asexual, intersex, and others) persons. In professional and public settings, we are educators, role models, and advocates for self-expression and personal empowerment. By better educating ourselves on the topic of gender and its variations, we can become champions of gender-affirming care.

Sex vs gender

A person’s sex is assigned at birth based on their physiological characteristics, including their genitalia and chromosome composition. Male, female, and intersex are a few recognized sexes. Gender or gender identity describe one’s innermost perception of self as a man, a woman, a variation of both, or neither, that may not always be visible to others. When sex and gender identity align, this is known as cisgender.¹

Gender identity

Gender identity is best described as a spectrum rather than a binary. Terms that fall under a gender binary include man, woman, trans man, and trans woman. A nonbinary gender identity is one outside the traditional binary of men or women. Being transgender simply means having a gender identity different than the sex assigned at birth. This includes persons whose gender identities cross the gender spectrum, such as trans men or trans women, and those who fall anywhere outside or in between genders. In this way, nonbinary persons are transgender.¹

The nonbinary spectrum

The term nonbinary encompasses many gender-nonconforming identities, such as agender, bigender, demigender, genderfluid, genderqueer, intergender, or pangender. Agender people have little connection to gender. Bigender individuals identify as 2 separate genders. Demigender persons feel a partial connection to a gender. Genderfluid individuals have a gender experience that is fluid and can change over time. Genderqueer people have a gender identity that falls in between or outside the binary. Intergender people have a gender identity between genders or identify as a combination of genders. Pangender people identify with a combination of genders. Note that patients may use some of these terms interchangeably or ascribe to them different meanings.² As the language around gender continues to evolve, psychiatrists should ask patients from a place of nonjudgmental curiosity what gender terms they use, how they define them, and what their gender means to them.

Gender expression and transitioning

Transitioning is what a transgender person does to align their gender identity and expression.³ Gender expression is the external manifestation of gender, including names, pronouns, clothing, haircuts, behaviors, voice, body characteristics, and more.¹ Transgender individuals can transition using a combination of social (name, pronouns, dress), legal (changing sex on legal documents, name change), or medical (surgeries, hormone therapies, puberty blockade) means. Transitions often help ease gender dysphoria, which is the clinically significant distress a person experiences when their sex assigned at birth does not align with their gender identity.³ Note that not all transgender persons choose to change their gender expression, and not all transgender individuals experience gender dysphoria. In this case, the proper medical term is gender incongruence, which is simply when someone’s gender identity does not align with their sex assigned at birth.⁴

Names and pronouns

For many transgender persons, names and pronouns are an important part of their gender transition and expression.² Most of us have gotten into the habit of assuming pronouns because of socially established gender roles. This assumes that a person’s physical appearance matches their gender identity, which is not always the case.¹ To be more affirming, psychiatrists and other health care professionals should try to break the habit of assuming pronouns. Often, an easy way to learn someone’s pronouns is to introduce yourself with yours. For example, “I am Dr. Agapoff. I use they/them/theirs pronouns. It is nice to meet you.” This creates a safe and open space for the other person to share their gender identity if they choose.

Why it’s important

One does not have to be a gender specialist to deliver gender-affirming care. As psychiatrists, having a basic understanding of the differences between sex, gender identity, and gender expression can help us build rapport and support our patients who are transgender. Based on the many kinds of gender identity and expression, judging someone’s gender based solely upon physical appearance is misguided at best and harmful at worst. Even people who are cisgender have many kinds of gender expression. For this reason, psychiatrists should approach gender with the same openness and curiosity as sexual orientation or other important considerations of emotional and physical health. Gender-informed care starts with us.

VIENNA – Following a healthy, balanced diet and avoiding excessive consumption of stressful news helped prevent anxiety and depressive symptoms during the COVID-19 pandemic, new research suggests.

Results from a longitudinal Spanish survey study of more than 1,000 adults showed that being outside, relaxing, participating in physical activities, and drinking plenty of water were also beneficial. However, social contact with friends and relatives, following a routine, and pursuing hobbies had no significant impact.

“This was a little surprising,” lead author Joaquim Radua, MD, PhD, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, said in a release.

“Like many people, we had assumed that personal contact would play a bigger part in avoiding anxiety and depression during stressful times,” he added.

However, Dr. Radua said that because the study was conducted during the COVID-19 pandemic, “people who socialized may also have been anxious about getting infected.”

Consequently, “it may be that this specific behavior cannot be extrapolated to other times, when there is no pandemic,” he said.

The findings were presented at the 35th European College of Neuropsychopharmacology (ECNP) Congress.
 

Correlational versus longitudinal studies

Dr. Radua emphasized that individuals “should socialize,” of course.

“We think it’s important that people continue to follow what works for them and that if you enjoy seeing friends or following a hobby, you continue to do so,” he said.

“Our work was centered on COVID, but we now need to see if these factors apply to other stressful circumstances. These simple behaviors may prevent anxiety and depression, and prevention is better than cure,” he added.

The researchers note that, in “times of uncertainty” such as the COVID-19 pandemic, many individuals experience increases in both anxiety and depressive symptoms.

Although a range of behaviors are recommended to help people cope, the investigators add that some of the recommendations are based on correlational studies.

Indeed, the researchers previously identified a correlation between following a healthy/balanced diet, among other measures, and lower anxiety and depressive symptoms during the pandemic.

However, it is unclear from cross-sectional studies whether the behavior alters the symptoms, in which case the behavior could be considered “helpful,” or conversely whether the symptoms alter an individual’s behavior, in which case the behaviors “may be useless,” the investigators note.

The investigative team therefore set out to provide more robust evidence for making recommendations and conducted a prospective longitudinal study.

They recruited 1,049 adults online via social networks, matching them to the regional, age and sex, and urbanicity distribution of the overall Spanish population.

Every 2 weeks for 12 months, the researchers administered the General Anxiety Disorder (GAD)-7, the Patient Health Questionnaire (PHQ)-9, and a two-item ecological momentary assessment to minimize recall bias, among other measures. They also asked about 10 self-report coping behaviors.
 

Significant coping behaviors

The study was completed by 942 individuals, indicating a retention of 90%.

Among both completers and non-completers there was an over-representation of individuals aged 18-34 years and women, compared with the general population, and fewer participants aged at least 65 years.

Pre-recruitment, the mean baseline GAD-7 score among completers was 7.4, falling to around 5.5 at the time of the first questionnaire. Scores on the PHQ-9 were 7.6 and 5.6, respectively.

Performing population-weighted autoregressive moving average models to analyze the relationship between the current frequency of the coping behaviors and future changes in anxiety and depressive symptoms, the investigators found that the greatest effect was from following a healthy, balanced diet, with an impact size of 0.95.

This was followed by avoiding too much stressful news (impact size, 0.91), staying outdoors or looking outside (0.40), doing relaxing activities (0.33), participating in physical exercise (0.32), and drinking water to hydrate (0.25).

Overall, these coping behaviors were associated with a significant reduction in anxiety and depressive symptoms (all, P < .001).

On the other hand, there was no impact on future symptoms from socializing with friends and relatives, whether or not they lived in the same household. There was also no effect from following a routine, pursuing hobbies, or performing home tasks.

The researchers note that similar results were obtained when excluding participants with hazardous alcohol consumption, defined as a score on the Alcohol Use Disorders Identification Test of 8 or higher.

However, they point out that despite its prospective design and large cohort, the study was not interventional. Therefore, they “cannot rule out the possibility that decreasing the frequency of a behavior is an early sign of some mechanism that later leads to increased anxiety and depression symptoms.”

Nevertheless, they believe that possibility “seems unlikely.”
 

Reflective of a unique time?

Commenting on the findings, Catherine Harmer, PhD, director of the Psychopharmacology and Emotional Research Lab, department of psychiatry, University of Oxford (England), said in the release this was an “interesting study” that “provides some important insights as to which behaviors may protect our mental health during times of significant stress.”

She said the finding that social contact was not beneficial was “surprising” but may reflect the fact that, during the pandemic, it was “stressful even to have those social contacts, even if we managed to meet a friend outside.”

The results of the study may therefore be “reflective of the unique experience” of the COVID-19 pandemic, said Dr. Harmer, who was not involved with the research.

“I wouldn’t think that reading too much news would generally be something that has a negative impact on depression and anxiety, but I think it was very much at the time,” she said.

With the pandemic overwhelming one country after another, “the more you read about it, the more frightening it was,” she added, noting that it is “easy to forget how frightened we were at the beginning.”

Dr. Harmer noted that “it would be interesting” if the study was repeated and the same factors came out – or if they were unique to that time.

This would be “useful to know, as these times may come again. And the more information we have to cope with a pandemic, the better,” she concluded.

The research was supported by the AXA Research Fund via an AXA Award granted to Dr. Radua from the call for projects “mitigating risk in the wake of the COVID-19 pandemic.” The investigators and Dr. Harmer report no relevant financial relationships.

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

VIENNA – Following a healthy, balanced diet and avoiding excessive consumption of stressful news helped prevent anxiety and depressive symptoms during the COVID-19 pandemic, new research suggests.

Results from a longitudinal Spanish survey study of more than 1,000 adults showed that being outside, relaxing, participating in physical activities, and drinking plenty of water were also beneficial. However, social contact with friends and relatives, following a routine, and pursuing hobbies had no significant impact.

“This was a little surprising,” lead author Joaquim Radua, MD, PhD, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, said in a release.

“Like many people, we had assumed that personal contact would play a bigger part in avoiding anxiety and depression during stressful times,” he added.

However, Dr. Radua said that because the study was conducted during the COVID-19 pandemic, “people who socialized may also have been anxious about getting infected.”

Consequently, “it may be that this specific behavior cannot be extrapolated to other times, when there is no pandemic,” he said.

The findings were presented at the 35th European College of Neuropsychopharmacology (ECNP) Congress.
 

Correlational versus longitudinal studies

Dr. Radua emphasized that individuals “should socialize,” of course.

“We think it’s important that people continue to follow what works for them and that if you enjoy seeing friends or following a hobby, you continue to do so,” he said.

“Our work was centered on COVID, but we now need to see if these factors apply to other stressful circumstances. These simple behaviors may prevent anxiety and depression, and prevention is better than cure,” he added.

The researchers note that, in “times of uncertainty” such as the COVID-19 pandemic, many individuals experience increases in both anxiety and depressive symptoms.

Although a range of behaviors are recommended to help people cope, the investigators add that some of the recommendations are based on correlational studies.

Indeed, the researchers previously identified a correlation between following a healthy/balanced diet, among other measures, and lower anxiety and depressive symptoms during the pandemic.

However, it is unclear from cross-sectional studies whether the behavior alters the symptoms, in which case the behavior could be considered “helpful,” or conversely whether the symptoms alter an individual’s behavior, in which case the behaviors “may be useless,” the investigators note.

The investigative team therefore set out to provide more robust evidence for making recommendations and conducted a prospective longitudinal study.

They recruited 1,049 adults online via social networks, matching them to the regional, age and sex, and urbanicity distribution of the overall Spanish population.

Every 2 weeks for 12 months, the researchers administered the General Anxiety Disorder (GAD)-7, the Patient Health Questionnaire (PHQ)-9, and a two-item ecological momentary assessment to minimize recall bias, among other measures. They also asked about 10 self-report coping behaviors.
 

Significant coping behaviors

The study was completed by 942 individuals, indicating a retention of 90%.

Among both completers and non-completers there was an over-representation of individuals aged 18-34 years and women, compared with the general population, and fewer participants aged at least 65 years.

Pre-recruitment, the mean baseline GAD-7 score among completers was 7.4, falling to around 5.5 at the time of the first questionnaire. Scores on the PHQ-9 were 7.6 and 5.6, respectively.

Performing population-weighted autoregressive moving average models to analyze the relationship between the current frequency of the coping behaviors and future changes in anxiety and depressive symptoms, the investigators found that the greatest effect was from following a healthy, balanced diet, with an impact size of 0.95.

This was followed by avoiding too much stressful news (impact size, 0.91), staying outdoors or looking outside (0.40), doing relaxing activities (0.33), participating in physical exercise (0.32), and drinking water to hydrate (0.25).

Overall, these coping behaviors were associated with a significant reduction in anxiety and depressive symptoms (all, P < .001).

On the other hand, there was no impact on future symptoms from socializing with friends and relatives, whether or not they lived in the same household. There was also no effect from following a routine, pursuing hobbies, or performing home tasks.

The researchers note that similar results were obtained when excluding participants with hazardous alcohol consumption, defined as a score on the Alcohol Use Disorders Identification Test of 8 or higher.

However, they point out that despite its prospective design and large cohort, the study was not interventional. Therefore, they “cannot rule out the possibility that decreasing the frequency of a behavior is an early sign of some mechanism that later leads to increased anxiety and depression symptoms.”

Nevertheless, they believe that possibility “seems unlikely.”
 

Reflective of a unique time?

Commenting on the findings, Catherine Harmer, PhD, director of the Psychopharmacology and Emotional Research Lab, department of psychiatry, University of Oxford (England), said in the release this was an “interesting study” that “provides some important insights as to which behaviors may protect our mental health during times of significant stress.”

She said the finding that social contact was not beneficial was “surprising” but may reflect the fact that, during the pandemic, it was “stressful even to have those social contacts, even if we managed to meet a friend outside.”

The results of the study may therefore be “reflective of the unique experience” of the COVID-19 pandemic, said Dr. Harmer, who was not involved with the research.

“I wouldn’t think that reading too much news would generally be something that has a negative impact on depression and anxiety, but I think it was very much at the time,” she said.

With the pandemic overwhelming one country after another, “the more you read about it, the more frightening it was,” she added, noting that it is “easy to forget how frightened we were at the beginning.”

Dr. Harmer noted that “it would be interesting” if the study was repeated and the same factors came out – or if they were unique to that time.

This would be “useful to know, as these times may come again. And the more information we have to cope with a pandemic, the better,” she concluded.

The research was supported by the AXA Research Fund via an AXA Award granted to Dr. Radua from the call for projects “mitigating risk in the wake of the COVID-19 pandemic.” The investigators and Dr. Harmer report no relevant financial relationships.

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

VIENNA – Following a healthy, balanced diet and avoiding excessive consumption of stressful news helped prevent anxiety and depressive symptoms during the COVID-19 pandemic, new research suggests.

Results from a longitudinal Spanish survey study of more than 1,000 adults showed that being outside, relaxing, participating in physical activities, and drinking plenty of water were also beneficial. However, social contact with friends and relatives, following a routine, and pursuing hobbies had no significant impact.

“This was a little surprising,” lead author Joaquim Radua, MD, PhD, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, said in a release.

“Like many people, we had assumed that personal contact would play a bigger part in avoiding anxiety and depression during stressful times,” he added.

However, Dr. Radua said that because the study was conducted during the COVID-19 pandemic, “people who socialized may also have been anxious about getting infected.”

Consequently, “it may be that this specific behavior cannot be extrapolated to other times, when there is no pandemic,” he said.

The findings were presented at the 35th European College of Neuropsychopharmacology (ECNP) Congress.
 

Correlational versus longitudinal studies

Dr. Radua emphasized that individuals “should socialize,” of course.

“We think it’s important that people continue to follow what works for them and that if you enjoy seeing friends or following a hobby, you continue to do so,” he said.

“Our work was centered on COVID, but we now need to see if these factors apply to other stressful circumstances. These simple behaviors may prevent anxiety and depression, and prevention is better than cure,” he added.

The researchers note that, in “times of uncertainty” such as the COVID-19 pandemic, many individuals experience increases in both anxiety and depressive symptoms.

Although a range of behaviors are recommended to help people cope, the investigators add that some of the recommendations are based on correlational studies.

Indeed, the researchers previously identified a correlation between following a healthy/balanced diet, among other measures, and lower anxiety and depressive symptoms during the pandemic.

However, it is unclear from cross-sectional studies whether the behavior alters the symptoms, in which case the behavior could be considered “helpful,” or conversely whether the symptoms alter an individual’s behavior, in which case the behaviors “may be useless,” the investigators note.

The investigative team therefore set out to provide more robust evidence for making recommendations and conducted a prospective longitudinal study.

They recruited 1,049 adults online via social networks, matching them to the regional, age and sex, and urbanicity distribution of the overall Spanish population.

Every 2 weeks for 12 months, the researchers administered the General Anxiety Disorder (GAD)-7, the Patient Health Questionnaire (PHQ)-9, and a two-item ecological momentary assessment to minimize recall bias, among other measures. They also asked about 10 self-report coping behaviors.
 

Significant coping behaviors

The study was completed by 942 individuals, indicating a retention of 90%.

Among both completers and non-completers there was an over-representation of individuals aged 18-34 years and women, compared with the general population, and fewer participants aged at least 65 years.

Pre-recruitment, the mean baseline GAD-7 score among completers was 7.4, falling to around 5.5 at the time of the first questionnaire. Scores on the PHQ-9 were 7.6 and 5.6, respectively.

Performing population-weighted autoregressive moving average models to analyze the relationship between the current frequency of the coping behaviors and future changes in anxiety and depressive symptoms, the investigators found that the greatest effect was from following a healthy, balanced diet, with an impact size of 0.95.

This was followed by avoiding too much stressful news (impact size, 0.91), staying outdoors or looking outside (0.40), doing relaxing activities (0.33), participating in physical exercise (0.32), and drinking water to hydrate (0.25).

Overall, these coping behaviors were associated with a significant reduction in anxiety and depressive symptoms (all, P < .001).

On the other hand, there was no impact on future symptoms from socializing with friends and relatives, whether or not they lived in the same household. There was also no effect from following a routine, pursuing hobbies, or performing home tasks.

The researchers note that similar results were obtained when excluding participants with hazardous alcohol consumption, defined as a score on the Alcohol Use Disorders Identification Test of 8 or higher.

However, they point out that despite its prospective design and large cohort, the study was not interventional. Therefore, they “cannot rule out the possibility that decreasing the frequency of a behavior is an early sign of some mechanism that later leads to increased anxiety and depression symptoms.”

Nevertheless, they believe that possibility “seems unlikely.”
 

Reflective of a unique time?

Commenting on the findings, Catherine Harmer, PhD, director of the Psychopharmacology and Emotional Research Lab, department of psychiatry, University of Oxford (England), said in the release this was an “interesting study” that “provides some important insights as to which behaviors may protect our mental health during times of significant stress.”

She said the finding that social contact was not beneficial was “surprising” but may reflect the fact that, during the pandemic, it was “stressful even to have those social contacts, even if we managed to meet a friend outside.”

The results of the study may therefore be “reflective of the unique experience” of the COVID-19 pandemic, said Dr. Harmer, who was not involved with the research.

“I wouldn’t think that reading too much news would generally be something that has a negative impact on depression and anxiety, but I think it was very much at the time,” she said.

With the pandemic overwhelming one country after another, “the more you read about it, the more frightening it was,” she added, noting that it is “easy to forget how frightened we were at the beginning.”

Dr. Harmer noted that “it would be interesting” if the study was repeated and the same factors came out – or if they were unique to that time.

This would be “useful to know, as these times may come again. And the more information we have to cope with a pandemic, the better,” she concluded.

The research was supported by the AXA Research Fund via an AXA Award granted to Dr. Radua from the call for projects “mitigating risk in the wake of the COVID-19 pandemic.” The investigators and Dr. Harmer report no relevant financial relationships.

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

New data from Israel provide further evidence that myocarditis is a rare adverse event of vaccination with the Pfizer/BioNTech mRNA COVID-19 vaccine in adolescents – one that predominantly occurs in males and typically after the second dose.

The new data also indicate a “mild and benign” clinical course of myocarditis after vaccination, with “favorable” long-term prognosis based on cardiac imaging findings.

Guy Witberg, MD, MPH, Rabin Medical Center, Petah Tikva, Israel, and colleagues report their latest observations in correspondence in The New England Journal of Medicine, online.

The group previously reported in December 2021 that the incidence of myocarditis in Israel after receipt of the Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine was highest among males between the ages of 16 and 29 (10.7 cases per 100,000).

The vaccine has since been approved for adolescents aged 12-15. Initial evidence for this age group, reported by Dr. Witberg and colleagues in March 2022, suggests a similar low incidence and mild course of myocarditis, although follow-up was limited to 30 days.

In their latest report, with follow-up out to 6 months, Dr. Witberg and colleagues identified nine probable or definite cases of myocarditis among 182,605 Israeli adolescents aged 12-15 who received the Pfizer/BioNTech mRNA vaccine – an incidence of 4.8 cases per 100,000.

Eight cases occurred after the second vaccine dose. All nine cases were mild.

Cardiac and inflammatory markers were elevated in all adolescent patients and electrocardiographic results were abnormal in two-thirds.

Eight patients had a normal ejection fraction, and four had a pericardial effusion. The patients spent 2-4 days hospitalized, and the in-hospital course was uneventful.

Echocardiographic findings were available a median of 10 days after discharge for eight patients. All echocardiograms showed a normal ejection fraction and resolution of pericardial effusion.

Five patients underwent cardiac MRI, including three scans performed at a median of 104 days after discharge. The scans showed “minimal evidence” of myocardial scarring or fibrosis, with evidence of late gadolinium enhancement ranging from 0% to 2%.

At a median of 206 days following discharge, all of the patients were alive, and none had been readmitted to the hospital, Dr. Witberg and colleagues report.

This research had no specific funding. Five authors have received research grants from Pfizer.

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

New data from Israel provide further evidence that myocarditis is a rare adverse event of vaccination with the Pfizer/BioNTech mRNA COVID-19 vaccine in adolescents – one that predominantly occurs in males and typically after the second dose.

The new data also indicate a “mild and benign” clinical course of myocarditis after vaccination, with “favorable” long-term prognosis based on cardiac imaging findings.

Guy Witberg, MD, MPH, Rabin Medical Center, Petah Tikva, Israel, and colleagues report their latest observations in correspondence in The New England Journal of Medicine, online.

The group previously reported in December 2021 that the incidence of myocarditis in Israel after receipt of the Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine was highest among males between the ages of 16 and 29 (10.7 cases per 100,000).

The vaccine has since been approved for adolescents aged 12-15. Initial evidence for this age group, reported by Dr. Witberg and colleagues in March 2022, suggests a similar low incidence and mild course of myocarditis, although follow-up was limited to 30 days.

In their latest report, with follow-up out to 6 months, Dr. Witberg and colleagues identified nine probable or definite cases of myocarditis among 182,605 Israeli adolescents aged 12-15 who received the Pfizer/BioNTech mRNA vaccine – an incidence of 4.8 cases per 100,000.

Eight cases occurred after the second vaccine dose. All nine cases were mild.

Cardiac and inflammatory markers were elevated in all adolescent patients and electrocardiographic results were abnormal in two-thirds.

Eight patients had a normal ejection fraction, and four had a pericardial effusion. The patients spent 2-4 days hospitalized, and the in-hospital course was uneventful.

Echocardiographic findings were available a median of 10 days after discharge for eight patients. All echocardiograms showed a normal ejection fraction and resolution of pericardial effusion.

Five patients underwent cardiac MRI, including three scans performed at a median of 104 days after discharge. The scans showed “minimal evidence” of myocardial scarring or fibrosis, with evidence of late gadolinium enhancement ranging from 0% to 2%.

At a median of 206 days following discharge, all of the patients were alive, and none had been readmitted to the hospital, Dr. Witberg and colleagues report.

This research had no specific funding. Five authors have received research grants from Pfizer.

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

New data from Israel provide further evidence that myocarditis is a rare adverse event of vaccination with the Pfizer/BioNTech mRNA COVID-19 vaccine in adolescents – one that predominantly occurs in males and typically after the second dose.

The new data also indicate a “mild and benign” clinical course of myocarditis after vaccination, with “favorable” long-term prognosis based on cardiac imaging findings.

Guy Witberg, MD, MPH, Rabin Medical Center, Petah Tikva, Israel, and colleagues report their latest observations in correspondence in The New England Journal of Medicine, online.

The group previously reported in December 2021 that the incidence of myocarditis in Israel after receipt of the Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine was highest among males between the ages of 16 and 29 (10.7 cases per 100,000).

The vaccine has since been approved for adolescents aged 12-15. Initial evidence for this age group, reported by Dr. Witberg and colleagues in March 2022, suggests a similar low incidence and mild course of myocarditis, although follow-up was limited to 30 days.

In their latest report, with follow-up out to 6 months, Dr. Witberg and colleagues identified nine probable or definite cases of myocarditis among 182,605 Israeli adolescents aged 12-15 who received the Pfizer/BioNTech mRNA vaccine – an incidence of 4.8 cases per 100,000.

Eight cases occurred after the second vaccine dose. All nine cases were mild.

Cardiac and inflammatory markers were elevated in all adolescent patients and electrocardiographic results were abnormal in two-thirds.

Eight patients had a normal ejection fraction, and four had a pericardial effusion. The patients spent 2-4 days hospitalized, and the in-hospital course was uneventful.

Echocardiographic findings were available a median of 10 days after discharge for eight patients. All echocardiograms showed a normal ejection fraction and resolution of pericardial effusion.

Five patients underwent cardiac MRI, including three scans performed at a median of 104 days after discharge. The scans showed “minimal evidence” of myocardial scarring or fibrosis, with evidence of late gadolinium enhancement ranging from 0% to 2%.

At a median of 206 days following discharge, all of the patients were alive, and none had been readmitted to the hospital, Dr. Witberg and colleagues report.

This research had no specific funding. Five authors have received research grants from Pfizer.

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

Birth parents are typically separated from their newborns following a cesarean section. However, a recent study published in the journal Nursing Open suggests immediate skin-to-skin contact may accelerate uterine contractions, reduce maternal blood loss, reduce newborn crying, improve patient satisfaction and comfort, and increase the rate of breastfeeding.

“[O]ur study contributes to scientific knowledge with key information to reduce maternal morbidity and mortality rates in mothers who have undergone scheduled cesarean sections,” José Miguel Pérez-Jiménez, MD, of the faculty of nursing, physiotherapy, and podiatry at Hospital Universitario Virgen Macarena, University of Sevilla, Spain, and colleagues wrote in their study. It promotes greater stability in the mothers by reducing the risk of postpartum hemorrhage, making it better to not separate mother and child in the first hours after this surgery, he said.

Dr. Pérez-Jiménez and colleagues evaluated 83 women who underwent a scheduled cesarean section in an unblinded, randomized controlled trial. The women were randomized to receive skin-to-skin contact in the operating room that continued in the postpartum unit, or the normal protocol after cesarean section that consisted of having the mother transferred to the postanesthesia recovery room while the newborn was sent to a maternity room with a parent or companion. Researchers assessed variables such as plasma hemoglobin, uterine contractions, breastfeeding, and postoperative pain, as well as subjective measures such as maternal satisfaction, comfort, previous cesarean section experience, and newborn crying.

Women who received usual care following cesarean section were more likely to have uterine contractions at the umbilical level compared with the skin-to-skin contact group (70% vs. 3%; P ≤ .0001), while the skin-to-skin group was more likely to have uterine contractions at the infraumbilical level (92.5% vs. 22.5%; P ≤ .0001). There was a statistically significant decrease in predischarge hemoglobin in the control group compared with the skin-to-skin group (10.522 vs. 11.075 g/dL; P ≤ .017); the level of hemoglobin reduction favored the skin-to-skin group (1.01 vs. 2.265 g/dL; P ≤ .0001). Women in the skin-to-skin group were more likely to report mild pain on a 10-point visual analog scale (VAS) after being transferred to the recovery room (1.48 vs. 6.23 points; P ≤ .0001) and being transferred to a maternity room or room in the postpartum unit (0.60 vs. 5.23 points; P ≤ .0001). Breastfeeding at birth was significantly higher among patients with immediate skin-to-skin contact compared with the control group (92.5% vs. 32.5%; P ≤ .0001), and continued at 1 month after birth (92.5% vs. 12.5%; P ≤ .0001). Newborns of mothers in the skin-to-skin group were significantly less likely to cry compared with newborns in the control group (90% vs. 55%; P ≤ .001).

When asked to rate their satisfaction on a 10-point Likert scale, women in the skin-to-skin contact group rated their experience significantly higher than did the control group (9.98 vs. 6.5; P ≤ .0001), and all women who had previously had a cesarean section in the skin-to-skin group (30%) rated their experience at 10 points compared with their previous cesarean section without skin-to-skin contact.
 

Implementing skin-to-skin contact after cesarean section

Betsy M. Collins, MD, MPH, assistant professor of obstetrics and gynecology at Emory University, Atlanta, said in an interview that while some of the findings were largely unsurprising and “confirmed a lot of the things that we already know about skin-to-skin [contact],” one major finding was the “stark difference” in the percentage of new birth parents who started breastfeeding after skin-to-skin contact and were still breastfeeding at 1 month postpartum compared with birth parents in the control group. She was not involved with the study and noted that the results complement recommendations from the World Health Organization on starting breastfeeding within the first hour after birth and continuing breastfeeding through the first 6 months of life.

“That was likely one of the greatest take-home points from the study ... that early skin-to-skin really promoted initiation of breastfeeding,” Dr. Collins said.

Two reasons why skin-to-skin contact after cesarean section isn’t regularly provided is that it can be difficult for personnel and safety reasons to have an extra nurse to continue monitoring the health of the newborn in the operating room, and there is a lack of culture supporting of skin-to-skin contact in the OR, Dr. Collins explained.

“Just like anything else, if it’s built into your standard operating procedure, then you have everything set up in place to do that initial assessment of the infant and then get the baby skin-to-skin as quickly as possible,” she said. If it’s your standard operating procedure to not provide skin-to-skin contact, she said, then there is a little bit more inertia to overcome to start providing it as a standard procedure.

At her center, Dr. Collins said skin-to-skin contact is initiated as soon as possible after birth, even in the operating room. The steps to implementing that policy involved getting the anesthesiology department on board with supporting the policy in the OR and training the circulating nursing staff to ensure a that nurse is available to monitor the newborn.

“I think the most important thing to know is that it’s absolutely doable and that you just have to have a champion just like any other quality initiative,” she said. One of the best ways to do that is to have the patients themselves request it, she noted, compared with its being requested by a physician or nurse.

“I think some patients are disappointed when they have to undergo cesarean delivery or feel like they’re missing out if they can’t have a vaginal delivery,” Dr. Collins said. Immediate skin-to-skin contact is “very good for not only physiology, as we read about in this paper – all the things they said about the benefits of skin-to-skin [contact] are true – but it’s really good for mental health. That bonding begins right away.”

As a birth parent, being separated from your newborn for several hours after a cesarean section, on the other hand, can be “pretty devastating,” Dr. Collins said.

“I think this is something that, once it becomes a standard of care, it will be expected that most hospitals should be doing this,” she said.

The authors and Dr. Collins report no relevant conflicts of interest.

Birth parents are typically separated from their newborns following a cesarean section. However, a recent study published in the journal Nursing Open suggests immediate skin-to-skin contact may accelerate uterine contractions, reduce maternal blood loss, reduce newborn crying, improve patient satisfaction and comfort, and increase the rate of breastfeeding.

“[O]ur study contributes to scientific knowledge with key information to reduce maternal morbidity and mortality rates in mothers who have undergone scheduled cesarean sections,” José Miguel Pérez-Jiménez, MD, of the faculty of nursing, physiotherapy, and podiatry at Hospital Universitario Virgen Macarena, University of Sevilla, Spain, and colleagues wrote in their study. It promotes greater stability in the mothers by reducing the risk of postpartum hemorrhage, making it better to not separate mother and child in the first hours after this surgery, he said.

Dr. Pérez-Jiménez and colleagues evaluated 83 women who underwent a scheduled cesarean section in an unblinded, randomized controlled trial. The women were randomized to receive skin-to-skin contact in the operating room that continued in the postpartum unit, or the normal protocol after cesarean section that consisted of having the mother transferred to the postanesthesia recovery room while the newborn was sent to a maternity room with a parent or companion. Researchers assessed variables such as plasma hemoglobin, uterine contractions, breastfeeding, and postoperative pain, as well as subjective measures such as maternal satisfaction, comfort, previous cesarean section experience, and newborn crying.

Women who received usual care following cesarean section were more likely to have uterine contractions at the umbilical level compared with the skin-to-skin contact group (70% vs. 3%; P ≤ .0001), while the skin-to-skin group was more likely to have uterine contractions at the infraumbilical level (92.5% vs. 22.5%; P ≤ .0001). There was a statistically significant decrease in predischarge hemoglobin in the control group compared with the skin-to-skin group (10.522 vs. 11.075 g/dL; P ≤ .017); the level of hemoglobin reduction favored the skin-to-skin group (1.01 vs. 2.265 g/dL; P ≤ .0001). Women in the skin-to-skin group were more likely to report mild pain on a 10-point visual analog scale (VAS) after being transferred to the recovery room (1.48 vs. 6.23 points; P ≤ .0001) and being transferred to a maternity room or room in the postpartum unit (0.60 vs. 5.23 points; P ≤ .0001). Breastfeeding at birth was significantly higher among patients with immediate skin-to-skin contact compared with the control group (92.5% vs. 32.5%; P ≤ .0001), and continued at 1 month after birth (92.5% vs. 12.5%; P ≤ .0001). Newborns of mothers in the skin-to-skin group were significantly less likely to cry compared with newborns in the control group (90% vs. 55%; P ≤ .001).

When asked to rate their satisfaction on a 10-point Likert scale, women in the skin-to-skin contact group rated their experience significantly higher than did the control group (9.98 vs. 6.5; P ≤ .0001), and all women who had previously had a cesarean section in the skin-to-skin group (30%) rated their experience at 10 points compared with their previous cesarean section without skin-to-skin contact.
 

Implementing skin-to-skin contact after cesarean section

Betsy M. Collins, MD, MPH, assistant professor of obstetrics and gynecology at Emory University, Atlanta, said in an interview that while some of the findings were largely unsurprising and “confirmed a lot of the things that we already know about skin-to-skin [contact],” one major finding was the “stark difference” in the percentage of new birth parents who started breastfeeding after skin-to-skin contact and were still breastfeeding at 1 month postpartum compared with birth parents in the control group. She was not involved with the study and noted that the results complement recommendations from the World Health Organization on starting breastfeeding within the first hour after birth and continuing breastfeeding through the first 6 months of life.

“That was likely one of the greatest take-home points from the study ... that early skin-to-skin really promoted initiation of breastfeeding,” Dr. Collins said.

Two reasons why skin-to-skin contact after cesarean section isn’t regularly provided is that it can be difficult for personnel and safety reasons to have an extra nurse to continue monitoring the health of the newborn in the operating room, and there is a lack of culture supporting of skin-to-skin contact in the OR, Dr. Collins explained.

“Just like anything else, if it’s built into your standard operating procedure, then you have everything set up in place to do that initial assessment of the infant and then get the baby skin-to-skin as quickly as possible,” she said. If it’s your standard operating procedure to not provide skin-to-skin contact, she said, then there is a little bit more inertia to overcome to start providing it as a standard procedure.

At her center, Dr. Collins said skin-to-skin contact is initiated as soon as possible after birth, even in the operating room. The steps to implementing that policy involved getting the anesthesiology department on board with supporting the policy in the OR and training the circulating nursing staff to ensure a that nurse is available to monitor the newborn.

“I think the most important thing to know is that it’s absolutely doable and that you just have to have a champion just like any other quality initiative,” she said. One of the best ways to do that is to have the patients themselves request it, she noted, compared with its being requested by a physician or nurse.

“I think some patients are disappointed when they have to undergo cesarean delivery or feel like they’re missing out if they can’t have a vaginal delivery,” Dr. Collins said. Immediate skin-to-skin contact is “very good for not only physiology, as we read about in this paper – all the things they said about the benefits of skin-to-skin [contact] are true – but it’s really good for mental health. That bonding begins right away.”

As a birth parent, being separated from your newborn for several hours after a cesarean section, on the other hand, can be “pretty devastating,” Dr. Collins said.

“I think this is something that, once it becomes a standard of care, it will be expected that most hospitals should be doing this,” she said.

The authors and Dr. Collins report no relevant conflicts of interest.

Birth parents are typically separated from their newborns following a cesarean section. However, a recent study published in the journal Nursing Open suggests immediate skin-to-skin contact may accelerate uterine contractions, reduce maternal blood loss, reduce newborn crying, improve patient satisfaction and comfort, and increase the rate of breastfeeding.

“[O]ur study contributes to scientific knowledge with key information to reduce maternal morbidity and mortality rates in mothers who have undergone scheduled cesarean sections,” José Miguel Pérez-Jiménez, MD, of the faculty of nursing, physiotherapy, and podiatry at Hospital Universitario Virgen Macarena, University of Sevilla, Spain, and colleagues wrote in their study. It promotes greater stability in the mothers by reducing the risk of postpartum hemorrhage, making it better to not separate mother and child in the first hours after this surgery, he said.

Dr. Pérez-Jiménez and colleagues evaluated 83 women who underwent a scheduled cesarean section in an unblinded, randomized controlled trial. The women were randomized to receive skin-to-skin contact in the operating room that continued in the postpartum unit, or the normal protocol after cesarean section that consisted of having the mother transferred to the postanesthesia recovery room while the newborn was sent to a maternity room with a parent or companion. Researchers assessed variables such as plasma hemoglobin, uterine contractions, breastfeeding, and postoperative pain, as well as subjective measures such as maternal satisfaction, comfort, previous cesarean section experience, and newborn crying.

Women who received usual care following cesarean section were more likely to have uterine contractions at the umbilical level compared with the skin-to-skin contact group (70% vs. 3%; P ≤ .0001), while the skin-to-skin group was more likely to have uterine contractions at the infraumbilical level (92.5% vs. 22.5%; P ≤ .0001). There was a statistically significant decrease in predischarge hemoglobin in the control group compared with the skin-to-skin group (10.522 vs. 11.075 g/dL; P ≤ .017); the level of hemoglobin reduction favored the skin-to-skin group (1.01 vs. 2.265 g/dL; P ≤ .0001). Women in the skin-to-skin group were more likely to report mild pain on a 10-point visual analog scale (VAS) after being transferred to the recovery room (1.48 vs. 6.23 points; P ≤ .0001) and being transferred to a maternity room or room in the postpartum unit (0.60 vs. 5.23 points; P ≤ .0001). Breastfeeding at birth was significantly higher among patients with immediate skin-to-skin contact compared with the control group (92.5% vs. 32.5%; P ≤ .0001), and continued at 1 month after birth (92.5% vs. 12.5%; P ≤ .0001). Newborns of mothers in the skin-to-skin group were significantly less likely to cry compared with newborns in the control group (90% vs. 55%; P ≤ .001).

When asked to rate their satisfaction on a 10-point Likert scale, women in the skin-to-skin contact group rated their experience significantly higher than did the control group (9.98 vs. 6.5; P ≤ .0001), and all women who had previously had a cesarean section in the skin-to-skin group (30%) rated their experience at 10 points compared with their previous cesarean section without skin-to-skin contact.
 

Implementing skin-to-skin contact after cesarean section

Betsy M. Collins, MD, MPH, assistant professor of obstetrics and gynecology at Emory University, Atlanta, said in an interview that while some of the findings were largely unsurprising and “confirmed a lot of the things that we already know about skin-to-skin [contact],” one major finding was the “stark difference” in the percentage of new birth parents who started breastfeeding after skin-to-skin contact and were still breastfeeding at 1 month postpartum compared with birth parents in the control group. She was not involved with the study and noted that the results complement recommendations from the World Health Organization on starting breastfeeding within the first hour after birth and continuing breastfeeding through the first 6 months of life.

“That was likely one of the greatest take-home points from the study ... that early skin-to-skin really promoted initiation of breastfeeding,” Dr. Collins said.

Two reasons why skin-to-skin contact after cesarean section isn’t regularly provided is that it can be difficult for personnel and safety reasons to have an extra nurse to continue monitoring the health of the newborn in the operating room, and there is a lack of culture supporting of skin-to-skin contact in the OR, Dr. Collins explained.

“Just like anything else, if it’s built into your standard operating procedure, then you have everything set up in place to do that initial assessment of the infant and then get the baby skin-to-skin as quickly as possible,” she said. If it’s your standard operating procedure to not provide skin-to-skin contact, she said, then there is a little bit more inertia to overcome to start providing it as a standard procedure.

At her center, Dr. Collins said skin-to-skin contact is initiated as soon as possible after birth, even in the operating room. The steps to implementing that policy involved getting the anesthesiology department on board with supporting the policy in the OR and training the circulating nursing staff to ensure a that nurse is available to monitor the newborn.

“I think the most important thing to know is that it’s absolutely doable and that you just have to have a champion just like any other quality initiative,” she said. One of the best ways to do that is to have the patients themselves request it, she noted, compared with its being requested by a physician or nurse.

“I think some patients are disappointed when they have to undergo cesarean delivery or feel like they’re missing out if they can’t have a vaginal delivery,” Dr. Collins said. Immediate skin-to-skin contact is “very good for not only physiology, as we read about in this paper – all the things they said about the benefits of skin-to-skin [contact] are true – but it’s really good for mental health. That bonding begins right away.”

As a birth parent, being separated from your newborn for several hours after a cesarean section, on the other hand, can be “pretty devastating,” Dr. Collins said.

“I think this is something that, once it becomes a standard of care, it will be expected that most hospitals should be doing this,” she said.

The authors and Dr. Collins report no relevant conflicts of interest.