Clinical Endocrinology News

Women who’ve had endometriosis carry an elevated risk of stroke with them for the rest of their lives, with the greatest risk found in women who’ve had a hysterectomy with an oophorectomy, according to a cohort study of the Nurses’ Health Study.

“This is yet additional evidence that those girls and women with endometriosis are having effects across their lives and in multiple aspects of their health and well-being,” senior study author Stacey A. Missmer, ScD, of the Michigan State University, East Lansing, said in an interview. “This is not, in quotes ‘just a gynecologic condition,’ ” Dr. Missmer added. “It is not strictly about the pelvic pain or infertility, but it really is about the whole health across the life course.”

The study included 112,056 women in the NHSII cohort study who were followed from 1989 to June 2017, documenting 893 incident cases of stroke among them – an incidence of less than 1%. Endometriosis was reported in 5,244 women, and 93% of the cohort were White.

Multivariate adjusted models showed that women who had laparoscopically confirmed endometriosis had a 34% greater risk of stroke than women without a history of endometriosis. Leslie V. Farland, ScD, of the University of Arizona, Tucson, was lead author of the study.

While previous studies have demonstrated an increased risk of cardiovascular disease, heart attack, angina, and atherosclerosis in women who’ve had endometriosis, this is the first study that has confirmed an additional increased risk of stroke, Dr. Missmer said.

Another novel finding, Dr. Missmer said, is that while the CVD risks for these women “seem to peak at an earlier age,” the study found no age differences for stroke risk. “That also reinforces that these stroke events are often happening in an age range typical for stroke, which is further removed from when women are thinking about their gynecologic health specifically.”

These findings don’t translate into a significantly greater risk for stroke overall in women who’ve had endometriosis, Dr. Missmer said. She characterized the risk as “not negligible, but it’s not a huge increased risk.” The absolute risk is still fairly low, she said.

“We don’t want to give the impression that all women with endometriosis need to be panicked or fearful about stroke, she said. “Rather, the messaging is that this yet another bit of evidence that whole health care for those with endometriosis is important.”

Women who’ve had endometriosis and their primary care providers need to be attuned to stroke risk, she said. “This is a critical condition that primary care physicians need to engage around, and perhaps if symptoms related to cardiovascular and cerebrovascular disease emerge in their patients, they need to be engaging cardiology and similar types of support. This is not just about the gynecologists.”

The study also explored other factors that may contribute to stroke risk, with the most significant being hysterectomy with bilateral oophorectomy, Dr. Missmer said.

This study was unique because it used laparoscopically confirmed rather than self-reported endometriosis, said Louise D. McCullough, MD, neurology chair at the University of Texas Health Science Center, Houston. Another strength of the study she noted was its longitudinal design, although the cohort study design yielded a low number of stroke patients.

“Regardless, I do think it was a very important study because we have a growing recognition about how women’s health and factors such as pregnancy, infertility, parity, complications, and gonadal hormones such as estrogen can influence a woman’s stroke risk much later in life,” Dr. McCullough said in an interview.

Future studies into the relationship between endometriosis and CVD and stroke risk should focus on the mechanism behind the inflammation that occurs in endometriosis, Dr. McCullough said. “Part of it is probably the loss of hormones if a patient has to have an oophorectomy, but part of it is just what do these diseases do for a woman’s later risk – and for primary care physicians, ob.gyns., and stroke neurologists to recognize that these are questions we should ask: Have you ever  had eclampsia or preeclampsia? Did you have endometriosis? Have you had miscarriages?”

The study received funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute for Neurological Disorders and Stroke. Dr. Missmer disclosed relationships with Shanghai Huilun Biotechnology, Roche, and AbbVie. Dr. McCullough has no relevant disclosures.


 

Women who’ve had endometriosis carry an elevated risk of stroke with them for the rest of their lives, with the greatest risk found in women who’ve had a hysterectomy with an oophorectomy, according to a cohort study of the Nurses’ Health Study.

“This is yet additional evidence that those girls and women with endometriosis are having effects across their lives and in multiple aspects of their health and well-being,” senior study author Stacey A. Missmer, ScD, of the Michigan State University, East Lansing, said in an interview. “This is not, in quotes ‘just a gynecologic condition,’ ” Dr. Missmer added. “It is not strictly about the pelvic pain or infertility, but it really is about the whole health across the life course.”

The study included 112,056 women in the NHSII cohort study who were followed from 1989 to June 2017, documenting 893 incident cases of stroke among them – an incidence of less than 1%. Endometriosis was reported in 5,244 women, and 93% of the cohort were White.

Multivariate adjusted models showed that women who had laparoscopically confirmed endometriosis had a 34% greater risk of stroke than women without a history of endometriosis. Leslie V. Farland, ScD, of the University of Arizona, Tucson, was lead author of the study.

While previous studies have demonstrated an increased risk of cardiovascular disease, heart attack, angina, and atherosclerosis in women who’ve had endometriosis, this is the first study that has confirmed an additional increased risk of stroke, Dr. Missmer said.

Another novel finding, Dr. Missmer said, is that while the CVD risks for these women “seem to peak at an earlier age,” the study found no age differences for stroke risk. “That also reinforces that these stroke events are often happening in an age range typical for stroke, which is further removed from when women are thinking about their gynecologic health specifically.”

These findings don’t translate into a significantly greater risk for stroke overall in women who’ve had endometriosis, Dr. Missmer said. She characterized the risk as “not negligible, but it’s not a huge increased risk.” The absolute risk is still fairly low, she said.

“We don’t want to give the impression that all women with endometriosis need to be panicked or fearful about stroke, she said. “Rather, the messaging is that this yet another bit of evidence that whole health care for those with endometriosis is important.”

Women who’ve had endometriosis and their primary care providers need to be attuned to stroke risk, she said. “This is a critical condition that primary care physicians need to engage around, and perhaps if symptoms related to cardiovascular and cerebrovascular disease emerge in their patients, they need to be engaging cardiology and similar types of support. This is not just about the gynecologists.”

The study also explored other factors that may contribute to stroke risk, with the most significant being hysterectomy with bilateral oophorectomy, Dr. Missmer said.

This study was unique because it used laparoscopically confirmed rather than self-reported endometriosis, said Louise D. McCullough, MD, neurology chair at the University of Texas Health Science Center, Houston. Another strength of the study she noted was its longitudinal design, although the cohort study design yielded a low number of stroke patients.

“Regardless, I do think it was a very important study because we have a growing recognition about how women’s health and factors such as pregnancy, infertility, parity, complications, and gonadal hormones such as estrogen can influence a woman’s stroke risk much later in life,” Dr. McCullough said in an interview.

Future studies into the relationship between endometriosis and CVD and stroke risk should focus on the mechanism behind the inflammation that occurs in endometriosis, Dr. McCullough said. “Part of it is probably the loss of hormones if a patient has to have an oophorectomy, but part of it is just what do these diseases do for a woman’s later risk – and for primary care physicians, ob.gyns., and stroke neurologists to recognize that these are questions we should ask: Have you ever  had eclampsia or preeclampsia? Did you have endometriosis? Have you had miscarriages?”

The study received funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute for Neurological Disorders and Stroke. Dr. Missmer disclosed relationships with Shanghai Huilun Biotechnology, Roche, and AbbVie. Dr. McCullough has no relevant disclosures.


 

Women who’ve had endometriosis carry an elevated risk of stroke with them for the rest of their lives, with the greatest risk found in women who’ve had a hysterectomy with an oophorectomy, according to a cohort study of the Nurses’ Health Study.

“This is yet additional evidence that those girls and women with endometriosis are having effects across their lives and in multiple aspects of their health and well-being,” senior study author Stacey A. Missmer, ScD, of the Michigan State University, East Lansing, said in an interview. “This is not, in quotes ‘just a gynecologic condition,’ ” Dr. Missmer added. “It is not strictly about the pelvic pain or infertility, but it really is about the whole health across the life course.”

The study included 112,056 women in the NHSII cohort study who were followed from 1989 to June 2017, documenting 893 incident cases of stroke among them – an incidence of less than 1%. Endometriosis was reported in 5,244 women, and 93% of the cohort were White.

Multivariate adjusted models showed that women who had laparoscopically confirmed endometriosis had a 34% greater risk of stroke than women without a history of endometriosis. Leslie V. Farland, ScD, of the University of Arizona, Tucson, was lead author of the study.

While previous studies have demonstrated an increased risk of cardiovascular disease, heart attack, angina, and atherosclerosis in women who’ve had endometriosis, this is the first study that has confirmed an additional increased risk of stroke, Dr. Missmer said.

Another novel finding, Dr. Missmer said, is that while the CVD risks for these women “seem to peak at an earlier age,” the study found no age differences for stroke risk. “That also reinforces that these stroke events are often happening in an age range typical for stroke, which is further removed from when women are thinking about their gynecologic health specifically.”

These findings don’t translate into a significantly greater risk for stroke overall in women who’ve had endometriosis, Dr. Missmer said. She characterized the risk as “not negligible, but it’s not a huge increased risk.” The absolute risk is still fairly low, she said.

“We don’t want to give the impression that all women with endometriosis need to be panicked or fearful about stroke, she said. “Rather, the messaging is that this yet another bit of evidence that whole health care for those with endometriosis is important.”

Women who’ve had endometriosis and their primary care providers need to be attuned to stroke risk, she said. “This is a critical condition that primary care physicians need to engage around, and perhaps if symptoms related to cardiovascular and cerebrovascular disease emerge in their patients, they need to be engaging cardiology and similar types of support. This is not just about the gynecologists.”

The study also explored other factors that may contribute to stroke risk, with the most significant being hysterectomy with bilateral oophorectomy, Dr. Missmer said.

This study was unique because it used laparoscopically confirmed rather than self-reported endometriosis, said Louise D. McCullough, MD, neurology chair at the University of Texas Health Science Center, Houston. Another strength of the study she noted was its longitudinal design, although the cohort study design yielded a low number of stroke patients.

“Regardless, I do think it was a very important study because we have a growing recognition about how women’s health and factors such as pregnancy, infertility, parity, complications, and gonadal hormones such as estrogen can influence a woman’s stroke risk much later in life,” Dr. McCullough said in an interview.

Future studies into the relationship between endometriosis and CVD and stroke risk should focus on the mechanism behind the inflammation that occurs in endometriosis, Dr. McCullough said. “Part of it is probably the loss of hormones if a patient has to have an oophorectomy, but part of it is just what do these diseases do for a woman’s later risk – and for primary care physicians, ob.gyns., and stroke neurologists to recognize that these are questions we should ask: Have you ever  had eclampsia or preeclampsia? Did you have endometriosis? Have you had miscarriages?”

The study received funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute for Neurological Disorders and Stroke. Dr. Missmer disclosed relationships with Shanghai Huilun Biotechnology, Roche, and AbbVie. Dr. McCullough has no relevant disclosures.


 

Cutting out almost all salt when preparing meals was associated with a worse prognosis in patients with heart failure with preserved ejection fraction (HFpEF), according to the results of a new study.

Results from a post hoc analysis of the TOPCAT trial show that those with a cooking salt score of zero were at significantly higher risk of the primary outcome of cardiovascular (CV) death, HF hospitalization, and aborted cardiac arrest than those whose score was above zero. Survival was similar in both groups.

“Some patients restrict dietary salt intake as least as possible according to their physicians’ words or their own understanding. However, the present study found that, in patients with heart failure with preserved ejection fraction, overstrict salt restriction could lead to poor prognosis – mainly heart failure hospitalization,” explained professor Chen Liu, MD, and Weihao Liang, MD, Sun Yat-sen University First Affiliated Hospital, Guangzhou, Guangdong, China.

Krisana Antharith / EyeEm / Getty Images

“Thus, when giving salt restriction advice to patients with heart failure with preserved ejection fraction, physicians should be careful instead of just saying “as least as possible,” they said in an email to this news organization.

The study was published in the journal Heart.

The authors note that HF guidelines recommend reduced salt intake, but there’s a lack of high-quality evidence to support those recommendations and no consensus on how low to go.

Previous studies have shown that reduced dietary sodium intake was associated with worse survival and higher readmission rate in patients with HF, whereas the SODIUM HF trial reported earlier this year that dietary sodium intake of less than 100 mmol (1,500 mg) per day did not improve 1-year clinical outcomes but moderately improved quality of life and New York Heart Association functional class.

“In daily clinical practice, we noticed that some physicians advised patients with heart failure to take salt as least as possible, but it could lead to hyponatremia and loss of appetite, which has been frequently reported to be associated with poor prognosis. Thus, we wanted to investigate the potential effect of overstrict salt restriction,” Dr. Liu and Dr. Liang explained.

The investigators examined data from 1,713 participants aged 50 and older with HFpEF (left ventricular ejection fraction 45% or greater) in the phase 3 TOPCAT trial, excluding those from Russia and Georgia. Patients self-reported how much salt they added to cooking staples, such as rice, pasta, potatoes, soup, meat, and vegetables, and were scored as 0 (none), 1 (⅛ teaspoon), 2 (¼ teaspoon), and 3 (½ teaspoon or more) points. Median follow-up was 2.9 years.

TOPCAT failed to show that spironolactone improved CV outcomes over placebo, but regional differences in data from Russia/Georgia and the Americas have raised concerns about its validity.

In the present analysis, almost half the participants (816) had a cooking salt score of 0, 56.4% were male, and 80.8% were White. They were more likely than participants with a salt score greater than zero to have a previous HF hospitalization, diabetes, poor renal function, and a lower ejection fraction (57% vs. 60%). Half were randomly assigned to spironolactone.

Compared with patients with a cooking salt score of 0, patients with a cooking salt score greater than 0 had significantly lower risks of the primary outcome (hazard ratio, 0.760; P = .002) and HF hospitalization (HR, 0.737; P = .003) but not all-cause (HR, 0.838) or CV (HR, 0.782) death.

The findings were consistent after full adjustment, with hazard ratios of 0.834 (P = .046), 0.791 (P = .024), 0.944, and 0.872, respectively.

Results of subgroup analyses suggested that patients aged 70 years or younger (HR, 0.644) and those of Black and other ethnicities (HR, 0.574) were at greater risk of the primary outcome from aggressive restriction of cooking salt.

“It was an interesting but unproved finding,” Dr. Liu and Dr. Liang observed. “One possible explanation is the difference in RAAS [renin-angiotensin-aldosterone system] physiology and its response to salt restriction among races, and the other is the difference in accustomed food, because the cooking salt score only accounted for sodium added during cooking but not sodium from ingredients.”

Spearman correlation analyses showed that the cooking salt score correlated significantly with systolic and diastolic blood pressure, serum sodium, and chloronium levels but not with plasma volume status, suggesting that low sodium intake did not have an intravascular volume contraction effect on patients with HFpEF.

The authors pointed out that the salt score was self-reported, hemodynamic parameters were seldom acquired in TOPCAT, and that reverse causation between low dietary sodium intake and worse HF might still exist, despite a propensity score-matching sensitivity analysis.

Reached for comment, Mary Norine Walsh, MD, the medical director of heart failure and cardiac transplantation, Ascension St. Vincent Heart Center, Indianapolis, said in an email that the authors appropriately excluded patients enrolled from Russia and Georgia because of concerns about the representativeness of patients with HFpEF in these two countries, which has been previously demonstrated.

“What limits the importance of the authors’ findings, which they acknowledge, is that the sodium intake for each patient was self-reported,” she said. “No confirmatory testing was done and recall bias could clearly have played a role.”

“Last, many patients with HFpEF have significant volume overload and dyspnea and appropriate sodium restriction is needed to help address symptoms and achieve a euvolemic state,” added Dr. Walsh, a past president of the American College of Cardiology.

Future trials are needed to determine an optimal salt restriction range for patients with heart failure, Dr. Liu and Dr. Liang suggested. “A randomized controlled trial may be hard to achieve because it is difficult to set a perfect control group. Therefore, an analysis using real-world data with a dose-response curve could be ideal.”

The study was funded by the National Natural Science Foundation of China, Guangdong Natural Science Foundation, and China Postdoctoral Science Foundation. The authors report no relevant financial relationships.

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

Cutting out almost all salt when preparing meals was associated with a worse prognosis in patients with heart failure with preserved ejection fraction (HFpEF), according to the results of a new study.

Results from a post hoc analysis of the TOPCAT trial show that those with a cooking salt score of zero were at significantly higher risk of the primary outcome of cardiovascular (CV) death, HF hospitalization, and aborted cardiac arrest than those whose score was above zero. Survival was similar in both groups.

“Some patients restrict dietary salt intake as least as possible according to their physicians’ words or their own understanding. However, the present study found that, in patients with heart failure with preserved ejection fraction, overstrict salt restriction could lead to poor prognosis – mainly heart failure hospitalization,” explained professor Chen Liu, MD, and Weihao Liang, MD, Sun Yat-sen University First Affiliated Hospital, Guangzhou, Guangdong, China.

Krisana Antharith / EyeEm / Getty Images

“Thus, when giving salt restriction advice to patients with heart failure with preserved ejection fraction, physicians should be careful instead of just saying “as least as possible,” they said in an email to this news organization.

The study was published in the journal Heart.

The authors note that HF guidelines recommend reduced salt intake, but there’s a lack of high-quality evidence to support those recommendations and no consensus on how low to go.

Previous studies have shown that reduced dietary sodium intake was associated with worse survival and higher readmission rate in patients with HF, whereas the SODIUM HF trial reported earlier this year that dietary sodium intake of less than 100 mmol (1,500 mg) per day did not improve 1-year clinical outcomes but moderately improved quality of life and New York Heart Association functional class.

“In daily clinical practice, we noticed that some physicians advised patients with heart failure to take salt as least as possible, but it could lead to hyponatremia and loss of appetite, which has been frequently reported to be associated with poor prognosis. Thus, we wanted to investigate the potential effect of overstrict salt restriction,” Dr. Liu and Dr. Liang explained.

The investigators examined data from 1,713 participants aged 50 and older with HFpEF (left ventricular ejection fraction 45% or greater) in the phase 3 TOPCAT trial, excluding those from Russia and Georgia. Patients self-reported how much salt they added to cooking staples, such as rice, pasta, potatoes, soup, meat, and vegetables, and were scored as 0 (none), 1 (⅛ teaspoon), 2 (¼ teaspoon), and 3 (½ teaspoon or more) points. Median follow-up was 2.9 years.

TOPCAT failed to show that spironolactone improved CV outcomes over placebo, but regional differences in data from Russia/Georgia and the Americas have raised concerns about its validity.

In the present analysis, almost half the participants (816) had a cooking salt score of 0, 56.4% were male, and 80.8% were White. They were more likely than participants with a salt score greater than zero to have a previous HF hospitalization, diabetes, poor renal function, and a lower ejection fraction (57% vs. 60%). Half were randomly assigned to spironolactone.

Compared with patients with a cooking salt score of 0, patients with a cooking salt score greater than 0 had significantly lower risks of the primary outcome (hazard ratio, 0.760; P = .002) and HF hospitalization (HR, 0.737; P = .003) but not all-cause (HR, 0.838) or CV (HR, 0.782) death.

The findings were consistent after full adjustment, with hazard ratios of 0.834 (P = .046), 0.791 (P = .024), 0.944, and 0.872, respectively.

Results of subgroup analyses suggested that patients aged 70 years or younger (HR, 0.644) and those of Black and other ethnicities (HR, 0.574) were at greater risk of the primary outcome from aggressive restriction of cooking salt.

“It was an interesting but unproved finding,” Dr. Liu and Dr. Liang observed. “One possible explanation is the difference in RAAS [renin-angiotensin-aldosterone system] physiology and its response to salt restriction among races, and the other is the difference in accustomed food, because the cooking salt score only accounted for sodium added during cooking but not sodium from ingredients.”

Spearman correlation analyses showed that the cooking salt score correlated significantly with systolic and diastolic blood pressure, serum sodium, and chloronium levels but not with plasma volume status, suggesting that low sodium intake did not have an intravascular volume contraction effect on patients with HFpEF.

The authors pointed out that the salt score was self-reported, hemodynamic parameters were seldom acquired in TOPCAT, and that reverse causation between low dietary sodium intake and worse HF might still exist, despite a propensity score-matching sensitivity analysis.

Reached for comment, Mary Norine Walsh, MD, the medical director of heart failure and cardiac transplantation, Ascension St. Vincent Heart Center, Indianapolis, said in an email that the authors appropriately excluded patients enrolled from Russia and Georgia because of concerns about the representativeness of patients with HFpEF in these two countries, which has been previously demonstrated.

“What limits the importance of the authors’ findings, which they acknowledge, is that the sodium intake for each patient was self-reported,” she said. “No confirmatory testing was done and recall bias could clearly have played a role.”

“Last, many patients with HFpEF have significant volume overload and dyspnea and appropriate sodium restriction is needed to help address symptoms and achieve a euvolemic state,” added Dr. Walsh, a past president of the American College of Cardiology.

Future trials are needed to determine an optimal salt restriction range for patients with heart failure, Dr. Liu and Dr. Liang suggested. “A randomized controlled trial may be hard to achieve because it is difficult to set a perfect control group. Therefore, an analysis using real-world data with a dose-response curve could be ideal.”

The study was funded by the National Natural Science Foundation of China, Guangdong Natural Science Foundation, and China Postdoctoral Science Foundation. The authors report no relevant financial relationships.

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

Cutting out almost all salt when preparing meals was associated with a worse prognosis in patients with heart failure with preserved ejection fraction (HFpEF), according to the results of a new study.

Results from a post hoc analysis of the TOPCAT trial show that those with a cooking salt score of zero were at significantly higher risk of the primary outcome of cardiovascular (CV) death, HF hospitalization, and aborted cardiac arrest than those whose score was above zero. Survival was similar in both groups.

“Some patients restrict dietary salt intake as least as possible according to their physicians’ words or their own understanding. However, the present study found that, in patients with heart failure with preserved ejection fraction, overstrict salt restriction could lead to poor prognosis – mainly heart failure hospitalization,” explained professor Chen Liu, MD, and Weihao Liang, MD, Sun Yat-sen University First Affiliated Hospital, Guangzhou, Guangdong, China.

Krisana Antharith / EyeEm / Getty Images

“Thus, when giving salt restriction advice to patients with heart failure with preserved ejection fraction, physicians should be careful instead of just saying “as least as possible,” they said in an email to this news organization.

The study was published in the journal Heart.

The authors note that HF guidelines recommend reduced salt intake, but there’s a lack of high-quality evidence to support those recommendations and no consensus on how low to go.

Previous studies have shown that reduced dietary sodium intake was associated with worse survival and higher readmission rate in patients with HF, whereas the SODIUM HF trial reported earlier this year that dietary sodium intake of less than 100 mmol (1,500 mg) per day did not improve 1-year clinical outcomes but moderately improved quality of life and New York Heart Association functional class.

“In daily clinical practice, we noticed that some physicians advised patients with heart failure to take salt as least as possible, but it could lead to hyponatremia and loss of appetite, which has been frequently reported to be associated with poor prognosis. Thus, we wanted to investigate the potential effect of overstrict salt restriction,” Dr. Liu and Dr. Liang explained.

The investigators examined data from 1,713 participants aged 50 and older with HFpEF (left ventricular ejection fraction 45% or greater) in the phase 3 TOPCAT trial, excluding those from Russia and Georgia. Patients self-reported how much salt they added to cooking staples, such as rice, pasta, potatoes, soup, meat, and vegetables, and were scored as 0 (none), 1 (⅛ teaspoon), 2 (¼ teaspoon), and 3 (½ teaspoon or more) points. Median follow-up was 2.9 years.

TOPCAT failed to show that spironolactone improved CV outcomes over placebo, but regional differences in data from Russia/Georgia and the Americas have raised concerns about its validity.

In the present analysis, almost half the participants (816) had a cooking salt score of 0, 56.4% were male, and 80.8% were White. They were more likely than participants with a salt score greater than zero to have a previous HF hospitalization, diabetes, poor renal function, and a lower ejection fraction (57% vs. 60%). Half were randomly assigned to spironolactone.

Compared with patients with a cooking salt score of 0, patients with a cooking salt score greater than 0 had significantly lower risks of the primary outcome (hazard ratio, 0.760; P = .002) and HF hospitalization (HR, 0.737; P = .003) but not all-cause (HR, 0.838) or CV (HR, 0.782) death.

The findings were consistent after full adjustment, with hazard ratios of 0.834 (P = .046), 0.791 (P = .024), 0.944, and 0.872, respectively.

Results of subgroup analyses suggested that patients aged 70 years or younger (HR, 0.644) and those of Black and other ethnicities (HR, 0.574) were at greater risk of the primary outcome from aggressive restriction of cooking salt.

“It was an interesting but unproved finding,” Dr. Liu and Dr. Liang observed. “One possible explanation is the difference in RAAS [renin-angiotensin-aldosterone system] physiology and its response to salt restriction among races, and the other is the difference in accustomed food, because the cooking salt score only accounted for sodium added during cooking but not sodium from ingredients.”

Spearman correlation analyses showed that the cooking salt score correlated significantly with systolic and diastolic blood pressure, serum sodium, and chloronium levels but not with plasma volume status, suggesting that low sodium intake did not have an intravascular volume contraction effect on patients with HFpEF.

The authors pointed out that the salt score was self-reported, hemodynamic parameters were seldom acquired in TOPCAT, and that reverse causation between low dietary sodium intake and worse HF might still exist, despite a propensity score-matching sensitivity analysis.

Reached for comment, Mary Norine Walsh, MD, the medical director of heart failure and cardiac transplantation, Ascension St. Vincent Heart Center, Indianapolis, said in an email that the authors appropriately excluded patients enrolled from Russia and Georgia because of concerns about the representativeness of patients with HFpEF in these two countries, which has been previously demonstrated.

“What limits the importance of the authors’ findings, which they acknowledge, is that the sodium intake for each patient was self-reported,” she said. “No confirmatory testing was done and recall bias could clearly have played a role.”

“Last, many patients with HFpEF have significant volume overload and dyspnea and appropriate sodium restriction is needed to help address symptoms and achieve a euvolemic state,” added Dr. Walsh, a past president of the American College of Cardiology.

Future trials are needed to determine an optimal salt restriction range for patients with heart failure, Dr. Liu and Dr. Liang suggested. “A randomized controlled trial may be hard to achieve because it is difficult to set a perfect control group. Therefore, an analysis using real-world data with a dose-response curve could be ideal.”

The study was funded by the National Natural Science Foundation of China, Guangdong Natural Science Foundation, and China Postdoctoral Science Foundation. The authors report no relevant financial relationships.

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

President Joe Biden has tested positive for COVID-19, the White House announced today.

Biden, 79, is experiencing “very mild” symptoms, White House Press Secretary Karine Jean-Pierre said in a statement. The president is fully vaccinated and has been boosted twice and has started taking the antiviral Paxlovid since testing positive, Ms. Jean-Pierre said.

President Biden plans to isolate at the White House and “will continue to carry out all of his duties fully during that time,” the statement said.

“He has been in contact with members of the White House staff by phone this morning, and will participate in his planned meetings at the White House this morning via phone and Zoom from the residence.”

President Biden will return to in-person work after he tests negative.

This is a developing story. Please check back for updates. A version of this article first appeared on WebMD.com .

President Joe Biden has tested positive for COVID-19, the White House announced today.

Biden, 79, is experiencing “very mild” symptoms, White House Press Secretary Karine Jean-Pierre said in a statement. The president is fully vaccinated and has been boosted twice and has started taking the antiviral Paxlovid since testing positive, Ms. Jean-Pierre said.

President Biden plans to isolate at the White House and “will continue to carry out all of his duties fully during that time,” the statement said.

“He has been in contact with members of the White House staff by phone this morning, and will participate in his planned meetings at the White House this morning via phone and Zoom from the residence.”

President Biden will return to in-person work after he tests negative.

This is a developing story. Please check back for updates. A version of this article first appeared on WebMD.com .

President Joe Biden has tested positive for COVID-19, the White House announced today.

Biden, 79, is experiencing “very mild” symptoms, White House Press Secretary Karine Jean-Pierre said in a statement. The president is fully vaccinated and has been boosted twice and has started taking the antiviral Paxlovid since testing positive, Ms. Jean-Pierre said.

President Biden plans to isolate at the White House and “will continue to carry out all of his duties fully during that time,” the statement said.

“He has been in contact with members of the White House staff by phone this morning, and will participate in his planned meetings at the White House this morning via phone and Zoom from the residence.”

President Biden will return to in-person work after he tests negative.

This is a developing story. Please check back for updates. A version of this article first appeared on WebMD.com .

After a year of uncertainty and decline because of the COVID-19 pandemic, demand for clinicians has rebounded – and the job market for new physicians and advanced practitioners is back to normal, or more accurately “the new normal,” according to a recently released report from Merritt Hawkins, the physician search division of AMN Healthcare.

The study is based on an analysis of job search and consulting assignments that the firm conducted on behalf of its health care organization clients from April 1, 2021, to March 31, 2022.

“Search engagements were down a little over 30% in 2020, but by the end of 2021, everything started spiking dramatically to the point of where we were at a 34-year high,” Michael Belkin, divisional vice president with Merritt Hawkins, told this news organization. “The pendulum has gone all the way back. People are more interested in going out and seeing their physicians.”

Demand for physicians was suppressed during the peak of the pandemic, as many hospitals curtailed elective procedures and many patients refrained from entering a medical facility. A large backlog of patients needing care subsequently developed.

This, combined with an aging population and widespread chronic medical conditions, has caused a strong surge in demand for physicians and advanced practitioners, according to the report.

In addition to the volume of searches increasing, physician starting salaries have rebounded from the COVID-19 downturn.

Average starting salaries of 14 physician specialties tracked in 2021/2022 increased, while only 3 decreased. Orthopedic surgeons were offered an average of $565,000 to start, exclusive of signing bonuses and other incentives, up from $546,000 the previous year. Urologists were offered an average of $510,000 to start, up from $497,000; gastroenterologists were offered $474,000, up from $453,000; while radiologists were offered $455,000, up from $401,000.

Similarly, a recent Medscape study based on responses from more than 13,000 U.S. physicians across 29 specialties found that income for all physician specialists increased, with otolaryngologists, gastroenterologists, and dermatologists experiencing the greatest gains.
 

A new reality

While the job market for physicians and advanced practitioners has seemingly recovered, there are many differences between today’s working environment for clinicians and what existed during the pandemic.

First, specialists are now stepping into the spotlight, a position that primary care clinicians previously held. The majority of Merritt Hawkins’ search engagements (64%) in 2021/2022 were for physician specialists, including cardiologists, gastroenterologists, orthopedic surgeons, neurologists, oncologists, and others. Only 17% of the search engagements were for primary care physicians, down from 18% in 2020/2021 and 20% in 2019/2020.

“We’ve seen specialties bounce back faster. Of course, you’ve got the aging population; you’ve got people that want that specialized care,” Mr. Belkin said.

Advanced practitioners also are playing a more significant role in the postpandemic word. In fact, 19% of Merritt Hawkins’ search engagements were for advanced practitioners, including nurse practitioners (NPs), physician assistants, and certified registered nurse anesthetists, up from 18% the previous year and just 13% the year prior to that, indicating growing demand for nonphysician providers.

NPs, in fact, topped the list of most requested search engagements, underscoring a shift from traditional physician office-based primary care delivery settings toward “convenient care” settings such as urgent care centers and retail clinics that are largely staffed by NPs and other advanced practitioners.

Advanced practitioners are taking on more responsibility for primary care simply because there is a large number of these professionals ready to take on the challenge.

The health care industry was “not able to produce enough primary care physicians over the last decade. So advanced practitioners, I believe, have slowly started to work alongside those primary care physicians. In a lot of areas such as your retail space, your CVS, your Walmart, your Walgreens, your standalone urgent cares, they’ve stepped up,” Mr. Belkin said.

Advanced practitioners also are providing the convenience that consumers are increasingly demanding.

“We are a society that wants things immediately ... but it’s still a challenge to schedule an appointment with a physician. However, it’s less of a challenge to get into a retail clinic or an urgent care center or to schedule something through telehealth,” Mr. Belkin noted.
 

More than just money

With the job market strong, the challenge for health care organizations is to create competitive recruiting packages. Sure enough, 92% of candidates were offered signing bonuses in 2021/2022 compared with just 61% in 2020/2021.

The financial incentives, however, might not be enough. In this environment, health care organizations need to go beyond simply offering competitive salaries to new recruits. For example, clinicians are seeking flexibility, as many potential hires are seeking remote positions. In fact, 18% of radiology search engagements were for teleradiologists, while 15% of its search engagements for psychiatrists were for telepsychiatrists in 2021/2022.

“Right now, quality of life is a very important factor. It’s work-life balance. It’s sensitivity to the stresses that we just experienced over the last 2.5 years,” Mr. Belkin concluded. “There’s more sensitivity around the culture of the organizations. What’s the leadership like? How did the organization handle the pandemic? How do they respond?”

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

After a year of uncertainty and decline because of the COVID-19 pandemic, demand for clinicians has rebounded – and the job market for new physicians and advanced practitioners is back to normal, or more accurately “the new normal,” according to a recently released report from Merritt Hawkins, the physician search division of AMN Healthcare.

The study is based on an analysis of job search and consulting assignments that the firm conducted on behalf of its health care organization clients from April 1, 2021, to March 31, 2022.

“Search engagements were down a little over 30% in 2020, but by the end of 2021, everything started spiking dramatically to the point of where we were at a 34-year high,” Michael Belkin, divisional vice president with Merritt Hawkins, told this news organization. “The pendulum has gone all the way back. People are more interested in going out and seeing their physicians.”

Demand for physicians was suppressed during the peak of the pandemic, as many hospitals curtailed elective procedures and many patients refrained from entering a medical facility. A large backlog of patients needing care subsequently developed.

This, combined with an aging population and widespread chronic medical conditions, has caused a strong surge in demand for physicians and advanced practitioners, according to the report.

In addition to the volume of searches increasing, physician starting salaries have rebounded from the COVID-19 downturn.

Average starting salaries of 14 physician specialties tracked in 2021/2022 increased, while only 3 decreased. Orthopedic surgeons were offered an average of $565,000 to start, exclusive of signing bonuses and other incentives, up from $546,000 the previous year. Urologists were offered an average of $510,000 to start, up from $497,000; gastroenterologists were offered $474,000, up from $453,000; while radiologists were offered $455,000, up from $401,000.

Similarly, a recent Medscape study based on responses from more than 13,000 U.S. physicians across 29 specialties found that income for all physician specialists increased, with otolaryngologists, gastroenterologists, and dermatologists experiencing the greatest gains.
 

A new reality

While the job market for physicians and advanced practitioners has seemingly recovered, there are many differences between today’s working environment for clinicians and what existed during the pandemic.

First, specialists are now stepping into the spotlight, a position that primary care clinicians previously held. The majority of Merritt Hawkins’ search engagements (64%) in 2021/2022 were for physician specialists, including cardiologists, gastroenterologists, orthopedic surgeons, neurologists, oncologists, and others. Only 17% of the search engagements were for primary care physicians, down from 18% in 2020/2021 and 20% in 2019/2020.

“We’ve seen specialties bounce back faster. Of course, you’ve got the aging population; you’ve got people that want that specialized care,” Mr. Belkin said.

Advanced practitioners also are playing a more significant role in the postpandemic word. In fact, 19% of Merritt Hawkins’ search engagements were for advanced practitioners, including nurse practitioners (NPs), physician assistants, and certified registered nurse anesthetists, up from 18% the previous year and just 13% the year prior to that, indicating growing demand for nonphysician providers.

NPs, in fact, topped the list of most requested search engagements, underscoring a shift from traditional physician office-based primary care delivery settings toward “convenient care” settings such as urgent care centers and retail clinics that are largely staffed by NPs and other advanced practitioners.

Advanced practitioners are taking on more responsibility for primary care simply because there is a large number of these professionals ready to take on the challenge.

The health care industry was “not able to produce enough primary care physicians over the last decade. So advanced practitioners, I believe, have slowly started to work alongside those primary care physicians. In a lot of areas such as your retail space, your CVS, your Walmart, your Walgreens, your standalone urgent cares, they’ve stepped up,” Mr. Belkin said.

Advanced practitioners also are providing the convenience that consumers are increasingly demanding.

“We are a society that wants things immediately ... but it’s still a challenge to schedule an appointment with a physician. However, it’s less of a challenge to get into a retail clinic or an urgent care center or to schedule something through telehealth,” Mr. Belkin noted.
 

More than just money

With the job market strong, the challenge for health care organizations is to create competitive recruiting packages. Sure enough, 92% of candidates were offered signing bonuses in 2021/2022 compared with just 61% in 2020/2021.

The financial incentives, however, might not be enough. In this environment, health care organizations need to go beyond simply offering competitive salaries to new recruits. For example, clinicians are seeking flexibility, as many potential hires are seeking remote positions. In fact, 18% of radiology search engagements were for teleradiologists, while 15% of its search engagements for psychiatrists were for telepsychiatrists in 2021/2022.

“Right now, quality of life is a very important factor. It’s work-life balance. It’s sensitivity to the stresses that we just experienced over the last 2.5 years,” Mr. Belkin concluded. “There’s more sensitivity around the culture of the organizations. What’s the leadership like? How did the organization handle the pandemic? How do they respond?”

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

After a year of uncertainty and decline because of the COVID-19 pandemic, demand for clinicians has rebounded – and the job market for new physicians and advanced practitioners is back to normal, or more accurately “the new normal,” according to a recently released report from Merritt Hawkins, the physician search division of AMN Healthcare.

The study is based on an analysis of job search and consulting assignments that the firm conducted on behalf of its health care organization clients from April 1, 2021, to March 31, 2022.

“Search engagements were down a little over 30% in 2020, but by the end of 2021, everything started spiking dramatically to the point of where we were at a 34-year high,” Michael Belkin, divisional vice president with Merritt Hawkins, told this news organization. “The pendulum has gone all the way back. People are more interested in going out and seeing their physicians.”

Demand for physicians was suppressed during the peak of the pandemic, as many hospitals curtailed elective procedures and many patients refrained from entering a medical facility. A large backlog of patients needing care subsequently developed.

This, combined with an aging population and widespread chronic medical conditions, has caused a strong surge in demand for physicians and advanced practitioners, according to the report.

In addition to the volume of searches increasing, physician starting salaries have rebounded from the COVID-19 downturn.

Average starting salaries of 14 physician specialties tracked in 2021/2022 increased, while only 3 decreased. Orthopedic surgeons were offered an average of $565,000 to start, exclusive of signing bonuses and other incentives, up from $546,000 the previous year. Urologists were offered an average of $510,000 to start, up from $497,000; gastroenterologists were offered $474,000, up from $453,000; while radiologists were offered $455,000, up from $401,000.

Similarly, a recent Medscape study based on responses from more than 13,000 U.S. physicians across 29 specialties found that income for all physician specialists increased, with otolaryngologists, gastroenterologists, and dermatologists experiencing the greatest gains.
 

A new reality

While the job market for physicians and advanced practitioners has seemingly recovered, there are many differences between today’s working environment for clinicians and what existed during the pandemic.

First, specialists are now stepping into the spotlight, a position that primary care clinicians previously held. The majority of Merritt Hawkins’ search engagements (64%) in 2021/2022 were for physician specialists, including cardiologists, gastroenterologists, orthopedic surgeons, neurologists, oncologists, and others. Only 17% of the search engagements were for primary care physicians, down from 18% in 2020/2021 and 20% in 2019/2020.

“We’ve seen specialties bounce back faster. Of course, you’ve got the aging population; you’ve got people that want that specialized care,” Mr. Belkin said.

Advanced practitioners also are playing a more significant role in the postpandemic word. In fact, 19% of Merritt Hawkins’ search engagements were for advanced practitioners, including nurse practitioners (NPs), physician assistants, and certified registered nurse anesthetists, up from 18% the previous year and just 13% the year prior to that, indicating growing demand for nonphysician providers.

NPs, in fact, topped the list of most requested search engagements, underscoring a shift from traditional physician office-based primary care delivery settings toward “convenient care” settings such as urgent care centers and retail clinics that are largely staffed by NPs and other advanced practitioners.

Advanced practitioners are taking on more responsibility for primary care simply because there is a large number of these professionals ready to take on the challenge.

The health care industry was “not able to produce enough primary care physicians over the last decade. So advanced practitioners, I believe, have slowly started to work alongside those primary care physicians. In a lot of areas such as your retail space, your CVS, your Walmart, your Walgreens, your standalone urgent cares, they’ve stepped up,” Mr. Belkin said.

Advanced practitioners also are providing the convenience that consumers are increasingly demanding.

“We are a society that wants things immediately ... but it’s still a challenge to schedule an appointment with a physician. However, it’s less of a challenge to get into a retail clinic or an urgent care center or to schedule something through telehealth,” Mr. Belkin noted.
 

More than just money

With the job market strong, the challenge for health care organizations is to create competitive recruiting packages. Sure enough, 92% of candidates were offered signing bonuses in 2021/2022 compared with just 61% in 2020/2021.

The financial incentives, however, might not be enough. In this environment, health care organizations need to go beyond simply offering competitive salaries to new recruits. For example, clinicians are seeking flexibility, as many potential hires are seeking remote positions. In fact, 18% of radiology search engagements were for teleradiologists, while 15% of its search engagements for psychiatrists were for telepsychiatrists in 2021/2022.

“Right now, quality of life is a very important factor. It’s work-life balance. It’s sensitivity to the stresses that we just experienced over the last 2.5 years,” Mr. Belkin concluded. “There’s more sensitivity around the culture of the organizations. What’s the leadership like? How did the organization handle the pandemic? How do they respond?”

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

In a video posted to TikTok by the comedian Will Flanary, MD, better known to his followers as Dr. Glaucomflecken, he imitates a neurosurgical residency interview. With glasses perched on the bridge of his nose, Dr. Glaucomflecken poses as the attending, asking: “What are your weaknesses?”

The residency applicant answers without hesitation: “My physiological need for sleep.” “What are your strengths?” The resident replies with the hard, steely stare of the determined and uninitiated: “My desire to eliminate my physiological need for sleep.”

If you follow Dr. Glaucomflecken on Twitter, you might know the skit I’m referencing. For many physicians and physicians-in-training, what makes the satire successful is its reflection of reality.

Many things have changed in medicine since his time, but the tired trope of the sleepless surgeon hangs on. Undaunted, I spent my second and third year of medical school accumulating accolades, conducting research, and connecting with mentors with the singular goal of joining the surgical ranks.

Midway through my third year, I completed a month-long surgical subinternship designed to give students a taste of what life would look like as an intern. I loved the operating room; it felt like the difference between being on dry land and being underwater. There were fewer distractions – your patient in the spotlight while everything else receded to the shadows.

However, as the month wore on, something stronger took hold. I couldn’t keep my eyes open in the darkened operating rooms and had to decline stools, fearing that I would fall asleep if I sat down.

On early morning prerounds, it’s 4:50 a.m. when I glance at the clock and pull back the curtain, already apologizing. My patient rolls over, flashing a wry smile. “Do you ever go home?” I’ve seen residents respond to this exact question in various ways. I live here. Yes. No. Soon. Not enough. My partner doesn’t think so.

There are days and, yes, years when we are led to believe this is what we live for: to be constantly available to our patients. It feels like a hollow victory when the patient, 2 days out from a total colectomy, begins to worry about your personal life. I ask her how she slept (not enough), any fevers (no), vomiting (no), urinating (I pause – she has a catheter).

My favorite part of these early morning rounds is the pause in my scripted litany of questions to listen to heart and lungs. It never fails to feel sacred: Patients become so quiet and still that I can’t help but think they have faith in me. Without prompting, she slides the back of her hospital gown forward like a curtain, already taking deep breaths so I can hear her lungs.

I look outside. The streetlights are still on, and from the seventh-floor window, I can watch staff making their way through the sliding double-doors, just beyond the yellowed pools of streetlight. I smile. I love medicine. I’m so tired.

For many in medicine, we are treated, and thus behave, as though our ability to manipulate physiology should also apply within the borders of our bodies: commanding less sleep, food, or bathroom breaks.

It places health care workers solidly in the realm of superhuman, living beyond one’s corporeal needs. The pandemic only heightened this misappropriation – adding hero and setting out a pedestal for health care workers to make their ungainly ascent. This kind of unsolicited admiration implicitly implies inhumanness, an otherness.

What would it look like if we started treating ourselves less like physicians and more like patients? I wish I was offering a solution, but really this is just a story. Maybe it’s not more sleep you need but something just as critical to the delicate physiologic and psychological scales of well-being.

To students rising through the ranks of medical training, identify what it is you need early and often. I can count on one hand how many physicians I’ve seen take a lunch break – even 10 minutes. Embrace hard work and self-preservation equally. My hope is that if enough of us take this path, it just might become a matter of course.

Dr. Meffert is a resident in the department of emergency medicine, MedStar Georgetown University Hospital, Washington Hospital Center, Washington. Dr. Meffert disclosed no relevant financial relationships.

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

In a video posted to TikTok by the comedian Will Flanary, MD, better known to his followers as Dr. Glaucomflecken, he imitates a neurosurgical residency interview. With glasses perched on the bridge of his nose, Dr. Glaucomflecken poses as the attending, asking: “What are your weaknesses?”

The residency applicant answers without hesitation: “My physiological need for sleep.” “What are your strengths?” The resident replies with the hard, steely stare of the determined and uninitiated: “My desire to eliminate my physiological need for sleep.”

If you follow Dr. Glaucomflecken on Twitter, you might know the skit I’m referencing. For many physicians and physicians-in-training, what makes the satire successful is its reflection of reality.

Many things have changed in medicine since his time, but the tired trope of the sleepless surgeon hangs on. Undaunted, I spent my second and third year of medical school accumulating accolades, conducting research, and connecting with mentors with the singular goal of joining the surgical ranks.

Midway through my third year, I completed a month-long surgical subinternship designed to give students a taste of what life would look like as an intern. I loved the operating room; it felt like the difference between being on dry land and being underwater. There were fewer distractions – your patient in the spotlight while everything else receded to the shadows.

However, as the month wore on, something stronger took hold. I couldn’t keep my eyes open in the darkened operating rooms and had to decline stools, fearing that I would fall asleep if I sat down.

On early morning prerounds, it’s 4:50 a.m. when I glance at the clock and pull back the curtain, already apologizing. My patient rolls over, flashing a wry smile. “Do you ever go home?” I’ve seen residents respond to this exact question in various ways. I live here. Yes. No. Soon. Not enough. My partner doesn’t think so.

There are days and, yes, years when we are led to believe this is what we live for: to be constantly available to our patients. It feels like a hollow victory when the patient, 2 days out from a total colectomy, begins to worry about your personal life. I ask her how she slept (not enough), any fevers (no), vomiting (no), urinating (I pause – she has a catheter).

My favorite part of these early morning rounds is the pause in my scripted litany of questions to listen to heart and lungs. It never fails to feel sacred: Patients become so quiet and still that I can’t help but think they have faith in me. Without prompting, she slides the back of her hospital gown forward like a curtain, already taking deep breaths so I can hear her lungs.

I look outside. The streetlights are still on, and from the seventh-floor window, I can watch staff making their way through the sliding double-doors, just beyond the yellowed pools of streetlight. I smile. I love medicine. I’m so tired.

For many in medicine, we are treated, and thus behave, as though our ability to manipulate physiology should also apply within the borders of our bodies: commanding less sleep, food, or bathroom breaks.

It places health care workers solidly in the realm of superhuman, living beyond one’s corporeal needs. The pandemic only heightened this misappropriation – adding hero and setting out a pedestal for health care workers to make their ungainly ascent. This kind of unsolicited admiration implicitly implies inhumanness, an otherness.

What would it look like if we started treating ourselves less like physicians and more like patients? I wish I was offering a solution, but really this is just a story. Maybe it’s not more sleep you need but something just as critical to the delicate physiologic and psychological scales of well-being.

To students rising through the ranks of medical training, identify what it is you need early and often. I can count on one hand how many physicians I’ve seen take a lunch break – even 10 minutes. Embrace hard work and self-preservation equally. My hope is that if enough of us take this path, it just might become a matter of course.

Dr. Meffert is a resident in the department of emergency medicine, MedStar Georgetown University Hospital, Washington Hospital Center, Washington. Dr. Meffert disclosed no relevant financial relationships.

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

In a video posted to TikTok by the comedian Will Flanary, MD, better known to his followers as Dr. Glaucomflecken, he imitates a neurosurgical residency interview. With glasses perched on the bridge of his nose, Dr. Glaucomflecken poses as the attending, asking: “What are your weaknesses?”

The residency applicant answers without hesitation: “My physiological need for sleep.” “What are your strengths?” The resident replies with the hard, steely stare of the determined and uninitiated: “My desire to eliminate my physiological need for sleep.”

If you follow Dr. Glaucomflecken on Twitter, you might know the skit I’m referencing. For many physicians and physicians-in-training, what makes the satire successful is its reflection of reality.

Many things have changed in medicine since his time, but the tired trope of the sleepless surgeon hangs on. Undaunted, I spent my second and third year of medical school accumulating accolades, conducting research, and connecting with mentors with the singular goal of joining the surgical ranks.

Midway through my third year, I completed a month-long surgical subinternship designed to give students a taste of what life would look like as an intern. I loved the operating room; it felt like the difference between being on dry land and being underwater. There were fewer distractions – your patient in the spotlight while everything else receded to the shadows.

However, as the month wore on, something stronger took hold. I couldn’t keep my eyes open in the darkened operating rooms and had to decline stools, fearing that I would fall asleep if I sat down.

On early morning prerounds, it’s 4:50 a.m. when I glance at the clock and pull back the curtain, already apologizing. My patient rolls over, flashing a wry smile. “Do you ever go home?” I’ve seen residents respond to this exact question in various ways. I live here. Yes. No. Soon. Not enough. My partner doesn’t think so.

There are days and, yes, years when we are led to believe this is what we live for: to be constantly available to our patients. It feels like a hollow victory when the patient, 2 days out from a total colectomy, begins to worry about your personal life. I ask her how she slept (not enough), any fevers (no), vomiting (no), urinating (I pause – she has a catheter).

My favorite part of these early morning rounds is the pause in my scripted litany of questions to listen to heart and lungs. It never fails to feel sacred: Patients become so quiet and still that I can’t help but think they have faith in me. Without prompting, she slides the back of her hospital gown forward like a curtain, already taking deep breaths so I can hear her lungs.

I look outside. The streetlights are still on, and from the seventh-floor window, I can watch staff making their way through the sliding double-doors, just beyond the yellowed pools of streetlight. I smile. I love medicine. I’m so tired.

For many in medicine, we are treated, and thus behave, as though our ability to manipulate physiology should also apply within the borders of our bodies: commanding less sleep, food, or bathroom breaks.

It places health care workers solidly in the realm of superhuman, living beyond one’s corporeal needs. The pandemic only heightened this misappropriation – adding hero and setting out a pedestal for health care workers to make their ungainly ascent. This kind of unsolicited admiration implicitly implies inhumanness, an otherness.

What would it look like if we started treating ourselves less like physicians and more like patients? I wish I was offering a solution, but really this is just a story. Maybe it’s not more sleep you need but something just as critical to the delicate physiologic and psychological scales of well-being.

To students rising through the ranks of medical training, identify what it is you need early and often. I can count on one hand how many physicians I’ve seen take a lunch break – even 10 minutes. Embrace hard work and self-preservation equally. My hope is that if enough of us take this path, it just might become a matter of course.

Dr. Meffert is a resident in the department of emergency medicine, MedStar Georgetown University Hospital, Washington Hospital Center, Washington. Dr. Meffert disclosed no relevant financial relationships.

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

Charcoal won’t let high-fat diet weigh you down

Do you want to be the funniest person alive? Of course you do. It’s really simple too, just one joke can make you the greatest comedian of all time. All you have to do is go camping and cook food over a roaring campfire. When someone drops food into the fire (which they always will), get ready. Once they fish out the offending food, which is almost certainly coated in hot coals, tell them: “Ah, eat it anyway. A little texture never hurt!” Trust us, most hilarious and original gag of all time.

But before your hapless friend brushes off his hot dog and forces a laugh, consider this: Japanese researchers have found that a charcoal supplement can prevent weight gain in mice consuming a high-fat diet. Charcoal is actually quite the helpful substance, and not just for grilling. It’s been used as medicine for hundreds of years and even today is used as a treatment for drug overdose and excess gas and flatulence.

PxHere

The study involved two groups of mice: One was fed a normal diet, the other a high-fat diet. After 12 weeks, the high-fat diet mice had gained weight. At that point, edible activated charcoal was added to their diet. From that point, weight gain was similar between the two groups, and the amount of bile acid, cholesterol, triglyceride, and fatty acid excreted by the high-fat mice increased by two to four times.

The researchers supported the notion that consuming an activated charcoal supplement before or while eating fatty food could prevent weight gain from said fatty food. Which works out well for the classic American barbecue, which is traditionally both high in fat and charcoal. All you have to do is buy some extra charcoal briquettes to pass around and munch on with your friends. Now that’s a party we can get behind.
 

There’s awake, and then there’s neurologically awake

Time to toss another urban legend onto the trash heap of history. Say goodbye to the benefits of uninterrupted sleep. It’s a fraud, a fake, a myth, a hit or myth, a swing and a myth, an old wives’ tale. You can stuff it and put it on a shelf next to Bigfoot, the Slender Man, and Twinkies.

JackF/thinkstockphotos.com

We all thought we needed 8 hours of uninterrupted sleep every night, but guess who we forgot to tell? Our brains. They’ve been doing exactly the opposite all along, laughing at us the whole time. Smug SOBs.

To straighten out this mess, let’s bring in a scientist, Celia Kjaerby of the Center for Translational Neuromedicine at the University of Copenhagen: “You may think that sleep is a constant state that you are in, and then you wake up. But there is a lot more to sleep than meets the eye. We have learned that noradrenaline causes you to wake up more than 100 times a night. And that is during perfectly normal sleep.”

Those 100 or so sleep interruptions are so brief that we don’t even notice, but they are very important, according to a study conducted at the university. Those tiny little wake-up calls are “the essence for the part of sleep that makes us wake up rested and which enables us to remember what we learned the day before. ... The very short awakenings are created by waves of norepinephrine [and they] reset the brain so that it is ready to store memory when you dive back into sleep,” lead author Maiken Nedergaard, MD, explained.

The investigators compared the level of noradrenaline in sleeping mice with their electrical activity and found that the hormone constantly increased and decreased in a wavelike pattern. A high level meant that the animal was neurologically awake. Deeper valleys between the high points meant better sleep, and the mice with the “highest number of deep noradrenaline valleys were also the ones with the best memory,” the team said in their written statement.

Not just the best memory, they said, but “super memory.” That, of course, was enough to get the attention of Marvel Comics, so the next Disney superhero blockbuster will feature Nocturna, the queen of the night. Her power? Never forgets. Her archnemesis? The Insomniac. Her catchphrase? “Let me sleep on it.”

Words can hurt, literally

Growing up, we’re sure you heard the “sticks and stones” rhyme. Maybe you’ve even recited it once or twice to defend yourself. Well, forget it, because words can hurt and your brain knows it.

PxHere

In a new study published in Frontiers in Communication, Marijn Struiksma, PhD, of Utrecht University, and colleagues incorporated the use of electroencephalography (EEG) and skin conductance on 79 women to see how words (specifically insults) actually affect the human body.

Each subject was asked to read three different types of statements: an insult, a compliment, and something factual but neutral. Half of the statements contained the subject’s name and half used somebody else’s. The participants were told that these statements were collected from three men.

Nobody interacted with each other, and the setting was completely clinical, yet the results were unmistakable. The EEG showed an effect in P2 amplitude with repetitive insults, no matter who it was about. Even though the insults weren’t real and the participants were aware of it, the brain still recognized them as hurtful, coming across as “mini slaps in the face,” Dr. Struiksma noted in a written statement.

The researchers noted that more needs to be done to better understand the long-term effects that insults can have and create a deeper understanding between words and emotion, but studying the effects of insults in a real-life setting is ethically tricky. This study is a start.

So, yeah, sticks and stones can break your bones, but words will actually hurt you.

This article was updated 7/21/22.

Charcoal won’t let high-fat diet weigh you down

Do you want to be the funniest person alive? Of course you do. It’s really simple too, just one joke can make you the greatest comedian of all time. All you have to do is go camping and cook food over a roaring campfire. When someone drops food into the fire (which they always will), get ready. Once they fish out the offending food, which is almost certainly coated in hot coals, tell them: “Ah, eat it anyway. A little texture never hurt!” Trust us, most hilarious and original gag of all time.

But before your hapless friend brushes off his hot dog and forces a laugh, consider this: Japanese researchers have found that a charcoal supplement can prevent weight gain in mice consuming a high-fat diet. Charcoal is actually quite the helpful substance, and not just for grilling. It’s been used as medicine for hundreds of years and even today is used as a treatment for drug overdose and excess gas and flatulence.

PxHere

The study involved two groups of mice: One was fed a normal diet, the other a high-fat diet. After 12 weeks, the high-fat diet mice had gained weight. At that point, edible activated charcoal was added to their diet. From that point, weight gain was similar between the two groups, and the amount of bile acid, cholesterol, triglyceride, and fatty acid excreted by the high-fat mice increased by two to four times.

The researchers supported the notion that consuming an activated charcoal supplement before or while eating fatty food could prevent weight gain from said fatty food. Which works out well for the classic American barbecue, which is traditionally both high in fat and charcoal. All you have to do is buy some extra charcoal briquettes to pass around and munch on with your friends. Now that’s a party we can get behind.
 

There’s awake, and then there’s neurologically awake

Time to toss another urban legend onto the trash heap of history. Say goodbye to the benefits of uninterrupted sleep. It’s a fraud, a fake, a myth, a hit or myth, a swing and a myth, an old wives’ tale. You can stuff it and put it on a shelf next to Bigfoot, the Slender Man, and Twinkies.

JackF/thinkstockphotos.com

We all thought we needed 8 hours of uninterrupted sleep every night, but guess who we forgot to tell? Our brains. They’ve been doing exactly the opposite all along, laughing at us the whole time. Smug SOBs.

To straighten out this mess, let’s bring in a scientist, Celia Kjaerby of the Center for Translational Neuromedicine at the University of Copenhagen: “You may think that sleep is a constant state that you are in, and then you wake up. But there is a lot more to sleep than meets the eye. We have learned that noradrenaline causes you to wake up more than 100 times a night. And that is during perfectly normal sleep.”

Those 100 or so sleep interruptions are so brief that we don’t even notice, but they are very important, according to a study conducted at the university. Those tiny little wake-up calls are “the essence for the part of sleep that makes us wake up rested and which enables us to remember what we learned the day before. ... The very short awakenings are created by waves of norepinephrine [and they] reset the brain so that it is ready to store memory when you dive back into sleep,” lead author Maiken Nedergaard, MD, explained.

The investigators compared the level of noradrenaline in sleeping mice with their electrical activity and found that the hormone constantly increased and decreased in a wavelike pattern. A high level meant that the animal was neurologically awake. Deeper valleys between the high points meant better sleep, and the mice with the “highest number of deep noradrenaline valleys were also the ones with the best memory,” the team said in their written statement.

Not just the best memory, they said, but “super memory.” That, of course, was enough to get the attention of Marvel Comics, so the next Disney superhero blockbuster will feature Nocturna, the queen of the night. Her power? Never forgets. Her archnemesis? The Insomniac. Her catchphrase? “Let me sleep on it.”

Words can hurt, literally

Growing up, we’re sure you heard the “sticks and stones” rhyme. Maybe you’ve even recited it once or twice to defend yourself. Well, forget it, because words can hurt and your brain knows it.

PxHere

In a new study published in Frontiers in Communication, Marijn Struiksma, PhD, of Utrecht University, and colleagues incorporated the use of electroencephalography (EEG) and skin conductance on 79 women to see how words (specifically insults) actually affect the human body.

Each subject was asked to read three different types of statements: an insult, a compliment, and something factual but neutral. Half of the statements contained the subject’s name and half used somebody else’s. The participants were told that these statements were collected from three men.

Nobody interacted with each other, and the setting was completely clinical, yet the results were unmistakable. The EEG showed an effect in P2 amplitude with repetitive insults, no matter who it was about. Even though the insults weren’t real and the participants were aware of it, the brain still recognized them as hurtful, coming across as “mini slaps in the face,” Dr. Struiksma noted in a written statement.

The researchers noted that more needs to be done to better understand the long-term effects that insults can have and create a deeper understanding between words and emotion, but studying the effects of insults in a real-life setting is ethically tricky. This study is a start.

So, yeah, sticks and stones can break your bones, but words will actually hurt you.

This article was updated 7/21/22.

Charcoal won’t let high-fat diet weigh you down

Do you want to be the funniest person alive? Of course you do. It’s really simple too, just one joke can make you the greatest comedian of all time. All you have to do is go camping and cook food over a roaring campfire. When someone drops food into the fire (which they always will), get ready. Once they fish out the offending food, which is almost certainly coated in hot coals, tell them: “Ah, eat it anyway. A little texture never hurt!” Trust us, most hilarious and original gag of all time.

But before your hapless friend brushes off his hot dog and forces a laugh, consider this: Japanese researchers have found that a charcoal supplement can prevent weight gain in mice consuming a high-fat diet. Charcoal is actually quite the helpful substance, and not just for grilling. It’s been used as medicine for hundreds of years and even today is used as a treatment for drug overdose and excess gas and flatulence.

PxHere

The study involved two groups of mice: One was fed a normal diet, the other a high-fat diet. After 12 weeks, the high-fat diet mice had gained weight. At that point, edible activated charcoal was added to their diet. From that point, weight gain was similar between the two groups, and the amount of bile acid, cholesterol, triglyceride, and fatty acid excreted by the high-fat mice increased by two to four times.

The researchers supported the notion that consuming an activated charcoal supplement before or while eating fatty food could prevent weight gain from said fatty food. Which works out well for the classic American barbecue, which is traditionally both high in fat and charcoal. All you have to do is buy some extra charcoal briquettes to pass around and munch on with your friends. Now that’s a party we can get behind.
 

There’s awake, and then there’s neurologically awake

Time to toss another urban legend onto the trash heap of history. Say goodbye to the benefits of uninterrupted sleep. It’s a fraud, a fake, a myth, a hit or myth, a swing and a myth, an old wives’ tale. You can stuff it and put it on a shelf next to Bigfoot, the Slender Man, and Twinkies.

JackF/thinkstockphotos.com

We all thought we needed 8 hours of uninterrupted sleep every night, but guess who we forgot to tell? Our brains. They’ve been doing exactly the opposite all along, laughing at us the whole time. Smug SOBs.

To straighten out this mess, let’s bring in a scientist, Celia Kjaerby of the Center for Translational Neuromedicine at the University of Copenhagen: “You may think that sleep is a constant state that you are in, and then you wake up. But there is a lot more to sleep than meets the eye. We have learned that noradrenaline causes you to wake up more than 100 times a night. And that is during perfectly normal sleep.”

Those 100 or so sleep interruptions are so brief that we don’t even notice, but they are very important, according to a study conducted at the university. Those tiny little wake-up calls are “the essence for the part of sleep that makes us wake up rested and which enables us to remember what we learned the day before. ... The very short awakenings are created by waves of norepinephrine [and they] reset the brain so that it is ready to store memory when you dive back into sleep,” lead author Maiken Nedergaard, MD, explained.

The investigators compared the level of noradrenaline in sleeping mice with their electrical activity and found that the hormone constantly increased and decreased in a wavelike pattern. A high level meant that the animal was neurologically awake. Deeper valleys between the high points meant better sleep, and the mice with the “highest number of deep noradrenaline valleys were also the ones with the best memory,” the team said in their written statement.

Not just the best memory, they said, but “super memory.” That, of course, was enough to get the attention of Marvel Comics, so the next Disney superhero blockbuster will feature Nocturna, the queen of the night. Her power? Never forgets. Her archnemesis? The Insomniac. Her catchphrase? “Let me sleep on it.”

Words can hurt, literally

Growing up, we’re sure you heard the “sticks and stones” rhyme. Maybe you’ve even recited it once or twice to defend yourself. Well, forget it, because words can hurt and your brain knows it.

PxHere

In a new study published in Frontiers in Communication, Marijn Struiksma, PhD, of Utrecht University, and colleagues incorporated the use of electroencephalography (EEG) and skin conductance on 79 women to see how words (specifically insults) actually affect the human body.

Each subject was asked to read three different types of statements: an insult, a compliment, and something factual but neutral. Half of the statements contained the subject’s name and half used somebody else’s. The participants were told that these statements were collected from three men.

Nobody interacted with each other, and the setting was completely clinical, yet the results were unmistakable. The EEG showed an effect in P2 amplitude with repetitive insults, no matter who it was about. Even though the insults weren’t real and the participants were aware of it, the brain still recognized them as hurtful, coming across as “mini slaps in the face,” Dr. Struiksma noted in a written statement.

The researchers noted that more needs to be done to better understand the long-term effects that insults can have and create a deeper understanding between words and emotion, but studying the effects of insults in a real-life setting is ethically tricky. This study is a start.

So, yeah, sticks and stones can break your bones, but words will actually hurt you.

This article was updated 7/21/22.

Hormone therapy did not increase mortality in postmenopausal women treated for early-stage estrogen receptor–positive breast cancer, but, in longitudinal data from Denmark, there was a recurrence risk with vaginal estrogen therapy among those treated with aromatase inhibitors.

Genitourinary syndrome of menopause (GSM) – including vaginal dryness, burning, and urinary incontinence – is common in women treated for breast cancer. Adjuvant endocrine therapy, particularly aromatase inhibitors, can aggravate these symptoms. Both local and systemic estrogen therapy are recommended for alleviating GSM symptoms in healthy women, but concerns have been raised about their use in women with breast cancer. Previous studies examining this have suggested possible risks for breast cancer recurrence, but those studies have had several limitations including small samples and short follow-up, particularly for vaginal estrogen therapy.

In the new study, from a national Danish cohort of 8,461 postmenopausal women diagnosed between 1997 and 2004 and treated for early-stage invasive estrogen receptor–positive nonmetastatic breast cancer, neither systemic menopausal hormone therapy (MHT) nor local vaginal estrogen therapy (VET) were associated with an overall increased risk for either breast cancer recurrence or mortality. However, in the subset who had received an aromatase inhibitor – with or without tamoxifen – there was a statistically significant increased risk for breast cancer recurrence, but not mortality.

The results were published in the Journal of the National Cancer Institute.

“The data are reassuring for the majority of women with no adjuvant therapy or tamoxifen. But for those using adjuvant aromatase inhibitors, there might be a small risk,” study lead author Søren Cold, MD, PhD, senior oncologist in the department of oncology at Odense (Denmark) University Hospital, Odense, said in an interview.

Moreover, Dr. Cold noted, while this study didn’t find an increased recurrence risk with MHT for women taking aromatase inhibitors, other studies have. One in particular was stopped because of harm. The reason for the difference here is likely that the previous sample was small – just 133 women.

“Our study is mainly focusing on the use of vaginal estrogen. We had so few patients using systemic menopausal hormone therapy, those data don’t mean much. ... The risk with systemic therapy has been established. The vaginal use hasn’t been thoroughly studied before,” he noted.
 

Breast cancer recurrence elevated with VET and aromatase inhibitors

The study pool was 9,710 women who underwent complete resection for estrogen-positive breast cancer and were all allocated to 5 years of adjuvant endocrine treatment or no adjuvant treatment, according to guidelines. Overall, 3,112 received no adjuvant endocrine treatment, 2,007 were treated with tamoxifen only, 403 with an aromatase inhibitor, and 2,939 with a sequence of tamoxifen and an aromatase inhibitor.

After exclusion of 1,249 who had received VET or MHT prior to breast cancer diagnosis, there were 6,391 not prescribed any estrogen hormonal treatment, 1,957 prescribed VET, and 133 prescribed MHT with or without VET.

During an estimated median 9.8 years’ follow-up, 1,333 women (16%) had a breast cancer recurrence. Of those, 111 had received VET, 16 MHT, and 1,206 neither. Compared with those receiving no hormonal treatment, the adjusted risk of recurrence was similar for the VET users (hazard ratio, 1.08; 95% confidence interval, 0.89-1.32).

However, there was an increased risk for recurrence associated with initiating VET during aromatase inhibitor treatment (HR, 1.39, 95% CI, 1.04-1.85). For women receiving MHT, the adjusted relative risk of recurrence with aromatase inhibitors wasn’t significant (HR, 1.05; 95% CI, 0.62-1.78).

Overall, compared with women who never used hormonal treatment, the absolute 10-year breast cancer recurrence risk was 19.2% for never-users of VET or MHT, 15.4% in VET users, and 17.1% in MHT users.
 

No differences found for mortality

Of the 8,461 women in the study, 40% (3,370) died during an estimated median follow-up of 15.2 years. Of those, 497 had received VET, 47 MHT, and 2,826 neither. Compared with the never-users of estrogen therapy, the adjusted HR for overall survival in VET users was 0.78 (95% CI, 0.71-0.87). The analysis stratified by adjuvant endocrine therapy didn’t show an increase in VET users by use of aromatase inhibitors (aHR, 0.94, 95% CI, 0.70-1.26). The same was found for women prescribed MHT, compared with never-users (aHR, 0.94; 95% CI, 0.70-1.26).

Never-users of VET or MHT had an absolute 10-year overall survival of 73.8% versus 79.5% and 80.5% among the women who used VET or MHT, respectively.

Asked to comment, Nanette Santoro, MD, professor and E. Stewart Taylor Chair of Obstetrics & Gynecology at the University of Colorado at Denver, Aurora, said in an interview: “It is important to look at this issue. These findings raise but don’t answer the question that vaginal estradiol may not be as safe as we hope it is for women with breast cancer using an aromatase inhibitor.”

However, she also pointed out that “the overall increase in risk is not enormous; mortality risk was not increased. Women need to consider that there may be some risk associated with this option in their decision making about taking it. Having a satisfying sex life is also important for many women! It is really compassionate use for quality of life, so there is always that unknown element of risk in the discussion. That unknown risk has to be balanced against the benefit that the estrogen provides.”

And, Dr. Santoro also noted that the use of prescription data poses limitations. “It cannot tell us what was going on in the minds of the patient and the prescriber. There may be differences in the prescriber’s impression of the patient’s risk of recurrence that influenced the decision to provide a prescription. ... Women using AIs [aromatase inhibitors] often get pretty severe vaginal dryness symptoms and may need more estrogen to be comfortable with intercourse, but we really cannot tell this from what is in this paper.”

Indeed, Dr. Cold said: “We admit it’s not a randomized study, but we’ve done what was possible to take [confounding] factors into account, including age, tumor size, nodal status, histology, and comorbidities.”

He suggested that a potential therapeutic approach to reducing the recurrence risk might be to switch VET-treated women to tamoxifen after 2-3 years of aromatase inhibitors.

This work was supported by Breast Friends, a part of the Danish Cancer Society. Dr. Cold received support from Breast Friends for the current study. Some of the other coauthors have pharmaceutical company disclosures. Dr. Santoro is a member of the scientific advisory boards for Astellas, Menogenix, Que Oncology, and Amazon Ember, and is a consultant for Ansh Labs.

Hormone therapy did not increase mortality in postmenopausal women treated for early-stage estrogen receptor–positive breast cancer, but, in longitudinal data from Denmark, there was a recurrence risk with vaginal estrogen therapy among those treated with aromatase inhibitors.

Genitourinary syndrome of menopause (GSM) – including vaginal dryness, burning, and urinary incontinence – is common in women treated for breast cancer. Adjuvant endocrine therapy, particularly aromatase inhibitors, can aggravate these symptoms. Both local and systemic estrogen therapy are recommended for alleviating GSM symptoms in healthy women, but concerns have been raised about their use in women with breast cancer. Previous studies examining this have suggested possible risks for breast cancer recurrence, but those studies have had several limitations including small samples and short follow-up, particularly for vaginal estrogen therapy.

In the new study, from a national Danish cohort of 8,461 postmenopausal women diagnosed between 1997 and 2004 and treated for early-stage invasive estrogen receptor–positive nonmetastatic breast cancer, neither systemic menopausal hormone therapy (MHT) nor local vaginal estrogen therapy (VET) were associated with an overall increased risk for either breast cancer recurrence or mortality. However, in the subset who had received an aromatase inhibitor – with or without tamoxifen – there was a statistically significant increased risk for breast cancer recurrence, but not mortality.

The results were published in the Journal of the National Cancer Institute.

“The data are reassuring for the majority of women with no adjuvant therapy or tamoxifen. But for those using adjuvant aromatase inhibitors, there might be a small risk,” study lead author Søren Cold, MD, PhD, senior oncologist in the department of oncology at Odense (Denmark) University Hospital, Odense, said in an interview.

Moreover, Dr. Cold noted, while this study didn’t find an increased recurrence risk with MHT for women taking aromatase inhibitors, other studies have. One in particular was stopped because of harm. The reason for the difference here is likely that the previous sample was small – just 133 women.

“Our study is mainly focusing on the use of vaginal estrogen. We had so few patients using systemic menopausal hormone therapy, those data don’t mean much. ... The risk with systemic therapy has been established. The vaginal use hasn’t been thoroughly studied before,” he noted.
 

Breast cancer recurrence elevated with VET and aromatase inhibitors

The study pool was 9,710 women who underwent complete resection for estrogen-positive breast cancer and were all allocated to 5 years of adjuvant endocrine treatment or no adjuvant treatment, according to guidelines. Overall, 3,112 received no adjuvant endocrine treatment, 2,007 were treated with tamoxifen only, 403 with an aromatase inhibitor, and 2,939 with a sequence of tamoxifen and an aromatase inhibitor.

After exclusion of 1,249 who had received VET or MHT prior to breast cancer diagnosis, there were 6,391 not prescribed any estrogen hormonal treatment, 1,957 prescribed VET, and 133 prescribed MHT with or without VET.

During an estimated median 9.8 years’ follow-up, 1,333 women (16%) had a breast cancer recurrence. Of those, 111 had received VET, 16 MHT, and 1,206 neither. Compared with those receiving no hormonal treatment, the adjusted risk of recurrence was similar for the VET users (hazard ratio, 1.08; 95% confidence interval, 0.89-1.32).

However, there was an increased risk for recurrence associated with initiating VET during aromatase inhibitor treatment (HR, 1.39, 95% CI, 1.04-1.85). For women receiving MHT, the adjusted relative risk of recurrence with aromatase inhibitors wasn’t significant (HR, 1.05; 95% CI, 0.62-1.78).

Overall, compared with women who never used hormonal treatment, the absolute 10-year breast cancer recurrence risk was 19.2% for never-users of VET or MHT, 15.4% in VET users, and 17.1% in MHT users.
 

No differences found for mortality

Of the 8,461 women in the study, 40% (3,370) died during an estimated median follow-up of 15.2 years. Of those, 497 had received VET, 47 MHT, and 2,826 neither. Compared with the never-users of estrogen therapy, the adjusted HR for overall survival in VET users was 0.78 (95% CI, 0.71-0.87). The analysis stratified by adjuvant endocrine therapy didn’t show an increase in VET users by use of aromatase inhibitors (aHR, 0.94, 95% CI, 0.70-1.26). The same was found for women prescribed MHT, compared with never-users (aHR, 0.94; 95% CI, 0.70-1.26).

Never-users of VET or MHT had an absolute 10-year overall survival of 73.8% versus 79.5% and 80.5% among the women who used VET or MHT, respectively.

Asked to comment, Nanette Santoro, MD, professor and E. Stewart Taylor Chair of Obstetrics & Gynecology at the University of Colorado at Denver, Aurora, said in an interview: “It is important to look at this issue. These findings raise but don’t answer the question that vaginal estradiol may not be as safe as we hope it is for women with breast cancer using an aromatase inhibitor.”

However, she also pointed out that “the overall increase in risk is not enormous; mortality risk was not increased. Women need to consider that there may be some risk associated with this option in their decision making about taking it. Having a satisfying sex life is also important for many women! It is really compassionate use for quality of life, so there is always that unknown element of risk in the discussion. That unknown risk has to be balanced against the benefit that the estrogen provides.”

And, Dr. Santoro also noted that the use of prescription data poses limitations. “It cannot tell us what was going on in the minds of the patient and the prescriber. There may be differences in the prescriber’s impression of the patient’s risk of recurrence that influenced the decision to provide a prescription. ... Women using AIs [aromatase inhibitors] often get pretty severe vaginal dryness symptoms and may need more estrogen to be comfortable with intercourse, but we really cannot tell this from what is in this paper.”

Indeed, Dr. Cold said: “We admit it’s not a randomized study, but we’ve done what was possible to take [confounding] factors into account, including age, tumor size, nodal status, histology, and comorbidities.”

He suggested that a potential therapeutic approach to reducing the recurrence risk might be to switch VET-treated women to tamoxifen after 2-3 years of aromatase inhibitors.

This work was supported by Breast Friends, a part of the Danish Cancer Society. Dr. Cold received support from Breast Friends for the current study. Some of the other coauthors have pharmaceutical company disclosures. Dr. Santoro is a member of the scientific advisory boards for Astellas, Menogenix, Que Oncology, and Amazon Ember, and is a consultant for Ansh Labs.

Hormone therapy did not increase mortality in postmenopausal women treated for early-stage estrogen receptor–positive breast cancer, but, in longitudinal data from Denmark, there was a recurrence risk with vaginal estrogen therapy among those treated with aromatase inhibitors.

Genitourinary syndrome of menopause (GSM) – including vaginal dryness, burning, and urinary incontinence – is common in women treated for breast cancer. Adjuvant endocrine therapy, particularly aromatase inhibitors, can aggravate these symptoms. Both local and systemic estrogen therapy are recommended for alleviating GSM symptoms in healthy women, but concerns have been raised about their use in women with breast cancer. Previous studies examining this have suggested possible risks for breast cancer recurrence, but those studies have had several limitations including small samples and short follow-up, particularly for vaginal estrogen therapy.

In the new study, from a national Danish cohort of 8,461 postmenopausal women diagnosed between 1997 and 2004 and treated for early-stage invasive estrogen receptor–positive nonmetastatic breast cancer, neither systemic menopausal hormone therapy (MHT) nor local vaginal estrogen therapy (VET) were associated with an overall increased risk for either breast cancer recurrence or mortality. However, in the subset who had received an aromatase inhibitor – with or without tamoxifen – there was a statistically significant increased risk for breast cancer recurrence, but not mortality.

The results were published in the Journal of the National Cancer Institute.

“The data are reassuring for the majority of women with no adjuvant therapy or tamoxifen. But for those using adjuvant aromatase inhibitors, there might be a small risk,” study lead author Søren Cold, MD, PhD, senior oncologist in the department of oncology at Odense (Denmark) University Hospital, Odense, said in an interview.

Moreover, Dr. Cold noted, while this study didn’t find an increased recurrence risk with MHT for women taking aromatase inhibitors, other studies have. One in particular was stopped because of harm. The reason for the difference here is likely that the previous sample was small – just 133 women.

“Our study is mainly focusing on the use of vaginal estrogen. We had so few patients using systemic menopausal hormone therapy, those data don’t mean much. ... The risk with systemic therapy has been established. The vaginal use hasn’t been thoroughly studied before,” he noted.
 

Breast cancer recurrence elevated with VET and aromatase inhibitors

The study pool was 9,710 women who underwent complete resection for estrogen-positive breast cancer and were all allocated to 5 years of adjuvant endocrine treatment or no adjuvant treatment, according to guidelines. Overall, 3,112 received no adjuvant endocrine treatment, 2,007 were treated with tamoxifen only, 403 with an aromatase inhibitor, and 2,939 with a sequence of tamoxifen and an aromatase inhibitor.

After exclusion of 1,249 who had received VET or MHT prior to breast cancer diagnosis, there were 6,391 not prescribed any estrogen hormonal treatment, 1,957 prescribed VET, and 133 prescribed MHT with or without VET.

During an estimated median 9.8 years’ follow-up, 1,333 women (16%) had a breast cancer recurrence. Of those, 111 had received VET, 16 MHT, and 1,206 neither. Compared with those receiving no hormonal treatment, the adjusted risk of recurrence was similar for the VET users (hazard ratio, 1.08; 95% confidence interval, 0.89-1.32).

However, there was an increased risk for recurrence associated with initiating VET during aromatase inhibitor treatment (HR, 1.39, 95% CI, 1.04-1.85). For women receiving MHT, the adjusted relative risk of recurrence with aromatase inhibitors wasn’t significant (HR, 1.05; 95% CI, 0.62-1.78).

Overall, compared with women who never used hormonal treatment, the absolute 10-year breast cancer recurrence risk was 19.2% for never-users of VET or MHT, 15.4% in VET users, and 17.1% in MHT users.
 

No differences found for mortality

Of the 8,461 women in the study, 40% (3,370) died during an estimated median follow-up of 15.2 years. Of those, 497 had received VET, 47 MHT, and 2,826 neither. Compared with the never-users of estrogen therapy, the adjusted HR for overall survival in VET users was 0.78 (95% CI, 0.71-0.87). The analysis stratified by adjuvant endocrine therapy didn’t show an increase in VET users by use of aromatase inhibitors (aHR, 0.94, 95% CI, 0.70-1.26). The same was found for women prescribed MHT, compared with never-users (aHR, 0.94; 95% CI, 0.70-1.26).

Never-users of VET or MHT had an absolute 10-year overall survival of 73.8% versus 79.5% and 80.5% among the women who used VET or MHT, respectively.

Asked to comment, Nanette Santoro, MD, professor and E. Stewart Taylor Chair of Obstetrics & Gynecology at the University of Colorado at Denver, Aurora, said in an interview: “It is important to look at this issue. These findings raise but don’t answer the question that vaginal estradiol may not be as safe as we hope it is for women with breast cancer using an aromatase inhibitor.”

However, she also pointed out that “the overall increase in risk is not enormous; mortality risk was not increased. Women need to consider that there may be some risk associated with this option in their decision making about taking it. Having a satisfying sex life is also important for many women! It is really compassionate use for quality of life, so there is always that unknown element of risk in the discussion. That unknown risk has to be balanced against the benefit that the estrogen provides.”

And, Dr. Santoro also noted that the use of prescription data poses limitations. “It cannot tell us what was going on in the minds of the patient and the prescriber. There may be differences in the prescriber’s impression of the patient’s risk of recurrence that influenced the decision to provide a prescription. ... Women using AIs [aromatase inhibitors] often get pretty severe vaginal dryness symptoms and may need more estrogen to be comfortable with intercourse, but we really cannot tell this from what is in this paper.”

Indeed, Dr. Cold said: “We admit it’s not a randomized study, but we’ve done what was possible to take [confounding] factors into account, including age, tumor size, nodal status, histology, and comorbidities.”

He suggested that a potential therapeutic approach to reducing the recurrence risk might be to switch VET-treated women to tamoxifen after 2-3 years of aromatase inhibitors.

This work was supported by Breast Friends, a part of the Danish Cancer Society. Dr. Cold received support from Breast Friends for the current study. Some of the other coauthors have pharmaceutical company disclosures. Dr. Santoro is a member of the scientific advisory boards for Astellas, Menogenix, Que Oncology, and Amazon Ember, and is a consultant for Ansh Labs.

I was quite sure I had multiple sclerosis when I was a medical student. I first noticed symptoms during my neurology rotation. All the signs were there: Fatigue that was getting worse in the North Carolina heat (Uhthoff sign!). A tingle running down my neck (Lhermitte sign!). Blurry vision late at night while studying pathways in Lange Neurology. “Didn’t cousin Amy have MS?” I asked my Mom. I started researching which medical specialties didn’t require dexterity. My left eyelid began twitching and didn’t stop until I rotated to ob.gyn.

Fortunately, it was not multiple sclerosis I had, but rather nosophobia, also known as Medical Student’s Disease. The combination of intense study of symptoms, spotty knowledge of diagnoses, and grade anxiety makes nosophobia common in med students. Despite its name, it doesn’t afflict only doctors. Patients often come to us convinced they have a disease but without reason. So unshakable is their belief that multiple visits are often required to disabuse them of their self-diagnosis. I sometimes have to remind myself to appear concerned even when a “melanoma” is a freckle so small I can barely see it with a dermatoscope. Or a “genital wart” is a hair follicle that looks exactly like the hundreds on the patient’s scrotum. Tougher though, are the treatment-avoiders: patients whose imagined side effects lead them to stop or refuse treatment.

I recently saw a middle-aged man with erythroderma so severe he looked like a ghillie suit of scale. He had a lifelong history of atopic dermatitis and a 2-year history of avoiding treatments. At some point, he tried all the usual remedies: cyclosporine, methotrexate, azathioprine, light therapy, boxes of topicals. The last treatment had been dupilumab, which he tried for a few weeks. “Why did you stop that one?” I asked. The injections were making him go blind, he explained. “Not blurry? Blind?” I asked. Yes, he could not see at all after each injection. Perhaps he might have dry eyes or keratitis? Sure. But blindness? It seemed an unreasonable concern. Further discussion revealed that intolerance to medication side effects was why he had stopped all his other treatments.

Nocebo, from the Latin “I shall harm,” is the dark counterpart to the placebo. Patients experience imagined, or even real, adverse effects because they believe the treatment is causing them harm. This is true even though that treatment might not be having any unwanted physiologic effect. Statins are a good example. Studies have shown that most patient-reported side effects of statins are in fact nocebo effects rather than a result of pharmacologic causes.

Yet, many patients on statins report muscle pain or other concerns as unbearable. As a consequence, some patients who might have benefited from statins might be missing out on the protective gains. Nocebo effects are exacerbated by a common bias that causes deeper regret when bad outcomes result from an action taken as compared with bad outcomes that occurred from not taking action. It’s frustrating when there’s a standard of care treatment, but our patient can’t get past their fear of harm to try it.

Despite my recommendations, my eczema patient insisted on continuing his nontreatment rather than take any risks with treatments for now. There are ways I might help, but I expect it will require additional visits to build trust. Today, the best I can do is to understand and respect him. At least he doesn’t think he has a genital wart – I’m not sure how I’d treat it if he did.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

I was quite sure I had multiple sclerosis when I was a medical student. I first noticed symptoms during my neurology rotation. All the signs were there: Fatigue that was getting worse in the North Carolina heat (Uhthoff sign!). A tingle running down my neck (Lhermitte sign!). Blurry vision late at night while studying pathways in Lange Neurology. “Didn’t cousin Amy have MS?” I asked my Mom. I started researching which medical specialties didn’t require dexterity. My left eyelid began twitching and didn’t stop until I rotated to ob.gyn.

Fortunately, it was not multiple sclerosis I had, but rather nosophobia, also known as Medical Student’s Disease. The combination of intense study of symptoms, spotty knowledge of diagnoses, and grade anxiety makes nosophobia common in med students. Despite its name, it doesn’t afflict only doctors. Patients often come to us convinced they have a disease but without reason. So unshakable is their belief that multiple visits are often required to disabuse them of their self-diagnosis. I sometimes have to remind myself to appear concerned even when a “melanoma” is a freckle so small I can barely see it with a dermatoscope. Or a “genital wart” is a hair follicle that looks exactly like the hundreds on the patient’s scrotum. Tougher though, are the treatment-avoiders: patients whose imagined side effects lead them to stop or refuse treatment.

I recently saw a middle-aged man with erythroderma so severe he looked like a ghillie suit of scale. He had a lifelong history of atopic dermatitis and a 2-year history of avoiding treatments. At some point, he tried all the usual remedies: cyclosporine, methotrexate, azathioprine, light therapy, boxes of topicals. The last treatment had been dupilumab, which he tried for a few weeks. “Why did you stop that one?” I asked. The injections were making him go blind, he explained. “Not blurry? Blind?” I asked. Yes, he could not see at all after each injection. Perhaps he might have dry eyes or keratitis? Sure. But blindness? It seemed an unreasonable concern. Further discussion revealed that intolerance to medication side effects was why he had stopped all his other treatments.

Nocebo, from the Latin “I shall harm,” is the dark counterpart to the placebo. Patients experience imagined, or even real, adverse effects because they believe the treatment is causing them harm. This is true even though that treatment might not be having any unwanted physiologic effect. Statins are a good example. Studies have shown that most patient-reported side effects of statins are in fact nocebo effects rather than a result of pharmacologic causes.

Yet, many patients on statins report muscle pain or other concerns as unbearable. As a consequence, some patients who might have benefited from statins might be missing out on the protective gains. Nocebo effects are exacerbated by a common bias that causes deeper regret when bad outcomes result from an action taken as compared with bad outcomes that occurred from not taking action. It’s frustrating when there’s a standard of care treatment, but our patient can’t get past their fear of harm to try it.

Despite my recommendations, my eczema patient insisted on continuing his nontreatment rather than take any risks with treatments for now. There are ways I might help, but I expect it will require additional visits to build trust. Today, the best I can do is to understand and respect him. At least he doesn’t think he has a genital wart – I’m not sure how I’d treat it if he did.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

I was quite sure I had multiple sclerosis when I was a medical student. I first noticed symptoms during my neurology rotation. All the signs were there: Fatigue that was getting worse in the North Carolina heat (Uhthoff sign!). A tingle running down my neck (Lhermitte sign!). Blurry vision late at night while studying pathways in Lange Neurology. “Didn’t cousin Amy have MS?” I asked my Mom. I started researching which medical specialties didn’t require dexterity. My left eyelid began twitching and didn’t stop until I rotated to ob.gyn.

Fortunately, it was not multiple sclerosis I had, but rather nosophobia, also known as Medical Student’s Disease. The combination of intense study of symptoms, spotty knowledge of diagnoses, and grade anxiety makes nosophobia common in med students. Despite its name, it doesn’t afflict only doctors. Patients often come to us convinced they have a disease but without reason. So unshakable is their belief that multiple visits are often required to disabuse them of their self-diagnosis. I sometimes have to remind myself to appear concerned even when a “melanoma” is a freckle so small I can barely see it with a dermatoscope. Or a “genital wart” is a hair follicle that looks exactly like the hundreds on the patient’s scrotum. Tougher though, are the treatment-avoiders: patients whose imagined side effects lead them to stop or refuse treatment.

I recently saw a middle-aged man with erythroderma so severe he looked like a ghillie suit of scale. He had a lifelong history of atopic dermatitis and a 2-year history of avoiding treatments. At some point, he tried all the usual remedies: cyclosporine, methotrexate, azathioprine, light therapy, boxes of topicals. The last treatment had been dupilumab, which he tried for a few weeks. “Why did you stop that one?” I asked. The injections were making him go blind, he explained. “Not blurry? Blind?” I asked. Yes, he could not see at all after each injection. Perhaps he might have dry eyes or keratitis? Sure. But blindness? It seemed an unreasonable concern. Further discussion revealed that intolerance to medication side effects was why he had stopped all his other treatments.

Nocebo, from the Latin “I shall harm,” is the dark counterpart to the placebo. Patients experience imagined, or even real, adverse effects because they believe the treatment is causing them harm. This is true even though that treatment might not be having any unwanted physiologic effect. Statins are a good example. Studies have shown that most patient-reported side effects of statins are in fact nocebo effects rather than a result of pharmacologic causes.

Yet, many patients on statins report muscle pain or other concerns as unbearable. As a consequence, some patients who might have benefited from statins might be missing out on the protective gains. Nocebo effects are exacerbated by a common bias that causes deeper regret when bad outcomes result from an action taken as compared with bad outcomes that occurred from not taking action. It’s frustrating when there’s a standard of care treatment, but our patient can’t get past their fear of harm to try it.

Despite my recommendations, my eczema patient insisted on continuing his nontreatment rather than take any risks with treatments for now. There are ways I might help, but I expect it will require additional visits to build trust. Today, the best I can do is to understand and respect him. At least he doesn’t think he has a genital wart – I’m not sure how I’d treat it if he did.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Use of cholesterol-lowering statins was linked to a lower risk of developing a subtype of diabetes that occurs after acute pancreatitis, according to a new report.

The benefits of statins depended on the consistency of usage, with regular users having a lower risk of developing postpancreatitis diabetes than irregular users. The results were similar with low, moderate, and high statin doses, as well as in cases of both mild and severe acute pancreatitis.

“About 15% of patients with acute pancreatitis will develop diabetes mellitus in the next 5 years, and although we can monitor for it, we can’t do anything to prevent it,” Nikhil Thiruvengadam, MD, the lead study author and a gastroenterologist at Loma Linda (Calif.) University, told this news organization.

iStock/ThinkStock

“This could push you as a clinician to prescribe [a statin if you have a reason to] because it could provide two benefits instead of just one,” he said.

The study was published online in Clinical Gastroenterology and Hepatology.
 

Steady use mattered, not dose

Patients with acute pancreatitis face at least a twofold increased risk of developing postpancreatitis diabetes, the study authors write. Although previous studies have shown that statins can lower the incidence and severity of acute pancreatitis, they haven’t been studied for the prevention of postpancreatitis diabetes.

In a collaborative study with several other universities, Dr. Thiruvengadam and colleagues examined commercial insurance claims from the Optum Clinformatics database to assess the impact of statins on 118,479 patients without preexisting diabetes admitted for a first episode of acute pancreatitis between 2008 and 2020.

They compared patients who consistently used statins with irregular users and nonusers. Regular statin usage was defined as patients who had statin prescriptions filled for at least 80% of the year prior to their acute pancreatitis diagnosis. The analysis included 9,048 patients (7.6%) who used statins regularly, 27,272 (23%) who used statins irregularly, and 82,159 (69.3%) nonusers.

With a median follow-up of 3.5 years, the 5-year cumulative incidence of postpancreatitis diabetes was 7.5% among regular statin users and 12.7% among nonusers. Regular statin users had a 42% lower risk of developing postpancreatitis diabetes, compared with nonusers. Irregular statin users had a 15% lower risk of postpancreatitis diabetes.

In addition, the 5-year cumulative incidence of insulin-dependent postpancreatitis diabetes was 2.4% among regular statin users and 6.6% among nonusers. Regular statin users had a 52% lower risk of developing insulin-dependent diabetes as compared with nonusers.

Daily dosage didn’t demonstrate a linear dose-response relationship. That means high-dose statins may not be more effective in preventing diabetes as compared with lower doses, the study authors write.

Statin usage was effective across additional analyses, including sex, etiologies of pancreatitis, and in both mild and severe acute pancreatitis. According to the study authors, this suggests that a broad population of these patients may benefit from statins.

“We were pleasantly surprised by the variety of findings,” Dr. Thiruvengadam said. “We’re seeing strong signals, especially with consistency of usage.”
 

Ongoing studies

The results may seem paradoxical, the study authors write, given an epidemiologic association with a slight increase in new-onset diabetes with statin initiation. But, as other researchers have reported, postpancreatitis diabetes and type 2 diabetes have different clinical features and underlying pathophysiology. For example, patients with postpancreatitis diabetes have much higher rates of requiring insulin, hospitalization, and all-cause mortality, the study authors write.

In fact, postpancreatitis diabetes is thought to be driven by chronic low-grade inflammation attributable to interleukin-6 and tumor necrosis factor–alpha. Statins have been shown to reduce tumor necrosis factor–alpha secretion and the production of C-reactive protein in response to circulating interleukin-6 in hepatocytes, they write.

The results should inform long-term prospective studies of acute pancreatitis, the study authors write, as well as randomized controlled trials of statins.

In the meantime, gastroenterologists and primary care physicians who see outpatients after hospitalization for acute pancreatitis may consider using statins, particularly in those who may have another possible indication for statin therapy, such as mild hyperlipidemia.

“There appears to be a low-dose benefit, which is another reason why providers may consider using statins, though it’s not for everyone with pancreatitis,” Dr. Thiruvengadam said. “This could be an exploratory pathway and suggested for use in the right setting.”

The Type 1 Diabetes in Acute Pancreatitis Consortium, sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases, is conducting an observational cohort study at more than a dozen locations across the country to investigate the incidence, etiology, and pathophysiology of diabetes after acute pancreatitis.

“Diabetes is surprisingly common after even a single attack of acute pancreatitis,” Chris Forsmark, MD, professor of medicine and chief of the division of gastroenterology, hepatology, and nutrition at the University of Florida, Gainesville, told this news organization.

Dr. Forsmark, who wasn’t involved with this study, is a member of T1DAPC and one of the principal investigators in Florida.

“The reduction of risk by 42% is quite substantial,” he said. “Like all such studies, there is risk of bias and confounding in determining the actual risk. Nonetheless, the results provide a strong reason for confirmation in other datasets and for further study.”

The study didn’t report funding support. Dr. Thiruvengadam and Dr. Forsmark report no relevant financial relationships.

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

Use of cholesterol-lowering statins was linked to a lower risk of developing a subtype of diabetes that occurs after acute pancreatitis, according to a new report.

The benefits of statins depended on the consistency of usage, with regular users having a lower risk of developing postpancreatitis diabetes than irregular users. The results were similar with low, moderate, and high statin doses, as well as in cases of both mild and severe acute pancreatitis.

“About 15% of patients with acute pancreatitis will develop diabetes mellitus in the next 5 years, and although we can monitor for it, we can’t do anything to prevent it,” Nikhil Thiruvengadam, MD, the lead study author and a gastroenterologist at Loma Linda (Calif.) University, told this news organization.

iStock/ThinkStock

“This could push you as a clinician to prescribe [a statin if you have a reason to] because it could provide two benefits instead of just one,” he said.

The study was published online in Clinical Gastroenterology and Hepatology.
 

Steady use mattered, not dose

Patients with acute pancreatitis face at least a twofold increased risk of developing postpancreatitis diabetes, the study authors write. Although previous studies have shown that statins can lower the incidence and severity of acute pancreatitis, they haven’t been studied for the prevention of postpancreatitis diabetes.

In a collaborative study with several other universities, Dr. Thiruvengadam and colleagues examined commercial insurance claims from the Optum Clinformatics database to assess the impact of statins on 118,479 patients without preexisting diabetes admitted for a first episode of acute pancreatitis between 2008 and 2020.

They compared patients who consistently used statins with irregular users and nonusers. Regular statin usage was defined as patients who had statin prescriptions filled for at least 80% of the year prior to their acute pancreatitis diagnosis. The analysis included 9,048 patients (7.6%) who used statins regularly, 27,272 (23%) who used statins irregularly, and 82,159 (69.3%) nonusers.

With a median follow-up of 3.5 years, the 5-year cumulative incidence of postpancreatitis diabetes was 7.5% among regular statin users and 12.7% among nonusers. Regular statin users had a 42% lower risk of developing postpancreatitis diabetes, compared with nonusers. Irregular statin users had a 15% lower risk of postpancreatitis diabetes.

In addition, the 5-year cumulative incidence of insulin-dependent postpancreatitis diabetes was 2.4% among regular statin users and 6.6% among nonusers. Regular statin users had a 52% lower risk of developing insulin-dependent diabetes as compared with nonusers.

Daily dosage didn’t demonstrate a linear dose-response relationship. That means high-dose statins may not be more effective in preventing diabetes as compared with lower doses, the study authors write.

Statin usage was effective across additional analyses, including sex, etiologies of pancreatitis, and in both mild and severe acute pancreatitis. According to the study authors, this suggests that a broad population of these patients may benefit from statins.

“We were pleasantly surprised by the variety of findings,” Dr. Thiruvengadam said. “We’re seeing strong signals, especially with consistency of usage.”
 

Ongoing studies

The results may seem paradoxical, the study authors write, given an epidemiologic association with a slight increase in new-onset diabetes with statin initiation. But, as other researchers have reported, postpancreatitis diabetes and type 2 diabetes have different clinical features and underlying pathophysiology. For example, patients with postpancreatitis diabetes have much higher rates of requiring insulin, hospitalization, and all-cause mortality, the study authors write.

In fact, postpancreatitis diabetes is thought to be driven by chronic low-grade inflammation attributable to interleukin-6 and tumor necrosis factor–alpha. Statins have been shown to reduce tumor necrosis factor–alpha secretion and the production of C-reactive protein in response to circulating interleukin-6 in hepatocytes, they write.

The results should inform long-term prospective studies of acute pancreatitis, the study authors write, as well as randomized controlled trials of statins.

In the meantime, gastroenterologists and primary care physicians who see outpatients after hospitalization for acute pancreatitis may consider using statins, particularly in those who may have another possible indication for statin therapy, such as mild hyperlipidemia.

“There appears to be a low-dose benefit, which is another reason why providers may consider using statins, though it’s not for everyone with pancreatitis,” Dr. Thiruvengadam said. “This could be an exploratory pathway and suggested for use in the right setting.”

The Type 1 Diabetes in Acute Pancreatitis Consortium, sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases, is conducting an observational cohort study at more than a dozen locations across the country to investigate the incidence, etiology, and pathophysiology of diabetes after acute pancreatitis.

“Diabetes is surprisingly common after even a single attack of acute pancreatitis,” Chris Forsmark, MD, professor of medicine and chief of the division of gastroenterology, hepatology, and nutrition at the University of Florida, Gainesville, told this news organization.

Dr. Forsmark, who wasn’t involved with this study, is a member of T1DAPC and one of the principal investigators in Florida.

“The reduction of risk by 42% is quite substantial,” he said. “Like all such studies, there is risk of bias and confounding in determining the actual risk. Nonetheless, the results provide a strong reason for confirmation in other datasets and for further study.”

The study didn’t report funding support. Dr. Thiruvengadam and Dr. Forsmark report no relevant financial relationships.

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

Use of cholesterol-lowering statins was linked to a lower risk of developing a subtype of diabetes that occurs after acute pancreatitis, according to a new report.

The benefits of statins depended on the consistency of usage, with regular users having a lower risk of developing postpancreatitis diabetes than irregular users. The results were similar with low, moderate, and high statin doses, as well as in cases of both mild and severe acute pancreatitis.

“About 15% of patients with acute pancreatitis will develop diabetes mellitus in the next 5 years, and although we can monitor for it, we can’t do anything to prevent it,” Nikhil Thiruvengadam, MD, the lead study author and a gastroenterologist at Loma Linda (Calif.) University, told this news organization.

iStock/ThinkStock

“This could push you as a clinician to prescribe [a statin if you have a reason to] because it could provide two benefits instead of just one,” he said.

The study was published online in Clinical Gastroenterology and Hepatology.
 

Steady use mattered, not dose

Patients with acute pancreatitis face at least a twofold increased risk of developing postpancreatitis diabetes, the study authors write. Although previous studies have shown that statins can lower the incidence and severity of acute pancreatitis, they haven’t been studied for the prevention of postpancreatitis diabetes.

In a collaborative study with several other universities, Dr. Thiruvengadam and colleagues examined commercial insurance claims from the Optum Clinformatics database to assess the impact of statins on 118,479 patients without preexisting diabetes admitted for a first episode of acute pancreatitis between 2008 and 2020.

They compared patients who consistently used statins with irregular users and nonusers. Regular statin usage was defined as patients who had statin prescriptions filled for at least 80% of the year prior to their acute pancreatitis diagnosis. The analysis included 9,048 patients (7.6%) who used statins regularly, 27,272 (23%) who used statins irregularly, and 82,159 (69.3%) nonusers.

With a median follow-up of 3.5 years, the 5-year cumulative incidence of postpancreatitis diabetes was 7.5% among regular statin users and 12.7% among nonusers. Regular statin users had a 42% lower risk of developing postpancreatitis diabetes, compared with nonusers. Irregular statin users had a 15% lower risk of postpancreatitis diabetes.

In addition, the 5-year cumulative incidence of insulin-dependent postpancreatitis diabetes was 2.4% among regular statin users and 6.6% among nonusers. Regular statin users had a 52% lower risk of developing insulin-dependent diabetes as compared with nonusers.

Daily dosage didn’t demonstrate a linear dose-response relationship. That means high-dose statins may not be more effective in preventing diabetes as compared with lower doses, the study authors write.

Statin usage was effective across additional analyses, including sex, etiologies of pancreatitis, and in both mild and severe acute pancreatitis. According to the study authors, this suggests that a broad population of these patients may benefit from statins.

“We were pleasantly surprised by the variety of findings,” Dr. Thiruvengadam said. “We’re seeing strong signals, especially with consistency of usage.”
 

Ongoing studies

The results may seem paradoxical, the study authors write, given an epidemiologic association with a slight increase in new-onset diabetes with statin initiation. But, as other researchers have reported, postpancreatitis diabetes and type 2 diabetes have different clinical features and underlying pathophysiology. For example, patients with postpancreatitis diabetes have much higher rates of requiring insulin, hospitalization, and all-cause mortality, the study authors write.

In fact, postpancreatitis diabetes is thought to be driven by chronic low-grade inflammation attributable to interleukin-6 and tumor necrosis factor–alpha. Statins have been shown to reduce tumor necrosis factor–alpha secretion and the production of C-reactive protein in response to circulating interleukin-6 in hepatocytes, they write.

The results should inform long-term prospective studies of acute pancreatitis, the study authors write, as well as randomized controlled trials of statins.

In the meantime, gastroenterologists and primary care physicians who see outpatients after hospitalization for acute pancreatitis may consider using statins, particularly in those who may have another possible indication for statin therapy, such as mild hyperlipidemia.

“There appears to be a low-dose benefit, which is another reason why providers may consider using statins, though it’s not for everyone with pancreatitis,” Dr. Thiruvengadam said. “This could be an exploratory pathway and suggested for use in the right setting.”

The Type 1 Diabetes in Acute Pancreatitis Consortium, sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases, is conducting an observational cohort study at more than a dozen locations across the country to investigate the incidence, etiology, and pathophysiology of diabetes after acute pancreatitis.

“Diabetes is surprisingly common after even a single attack of acute pancreatitis,” Chris Forsmark, MD, professor of medicine and chief of the division of gastroenterology, hepatology, and nutrition at the University of Florida, Gainesville, told this news organization.

Dr. Forsmark, who wasn’t involved with this study, is a member of T1DAPC and one of the principal investigators in Florida.

“The reduction of risk by 42% is quite substantial,” he said. “Like all such studies, there is risk of bias and confounding in determining the actual risk. Nonetheless, the results provide a strong reason for confirmation in other datasets and for further study.”

The study didn’t report funding support. Dr. Thiruvengadam and Dr. Forsmark report no relevant financial relationships.

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

Avocados are a rich source of fiber and healthy fat, but eating one a day for 6 months did not shrink waist size or belly fat, according to the findings of a new study.

But it did improve diet quality and led to modest lowering of total cholesterol.

More than 1,000 adults with overweight or obesity and a large waist – at least 35 inches in women and 40 inches in men – took part in this U.S. study, called the Habitual Diet and Avocado Trial (HAT).

tookapic/Pixabay

The people in the study were divided into two groups: usual diet plus one large avocado every day and usual diet with two avocados at most per month (control group).

Those in the avocado-a-day group were given a regular supply of fresh avocados along with written instructions for how to ripen and prepare them.

They had MRI scans to measure belly fat and fat around other organs at the beginning of the study and after 6 months.

After 6 months, the people who ate an avocado a day did not have less fat around their middles – the main trial outcome – compared with people in the control group.

But at 6 months, those in the avocado-a-day group had:

• No weight gain. People’s weight remained stable in both groups.
• Improved diet quality by 8 points on a 100-point scale
• A 2.9-mg/dL decrease in total cholesterol
• A 2.5-mg/dL decrease in LDL cholesterol

The study was done by researchers at Penn State University; Tufts University; Loma Linda University; and the University of California, Los Angeles, with coordinating support from Wake Forest University.

It was published in the Journal of the American Heart Association.

“While the avocados did not affect belly fat or weight gain, the study still provides evidence that avocados can be a beneficial addition to a well-balanced diet,” Penny M. Kris-Etherton, PhD, one of the researchers and a professor of nutritional sciences at Penn State University, University Park, said in a news release.

“Incorporating an avocado per day in this study did not cause weight gain and also caused a slight decrease in LDL cholesterol, which are all important findings for better health,” she said.

Similarly, study researcher Joan Sabaté, MD, a professor at Loma Linda (Calif.) University, said: “While one avocado a day did not lead to clinically significant improvements in abdominal fat and other cardiometabolic risk factors, consuming one avocado a day did not result in body weight gain.”

“This is positive,” he said, “because eating extra calories from avocados doesn’t impact body weight or abdominal fat, and it slightly decreases total and LDL cholesterol.”

Kristina S. Petersen, PhD, another of the researchers and an assistant professor of nutritional sciences at Texas Tech University, Lubbock, pointed out that people are generally poor at adhering to the Dietary Guidelines for Americans.

This study suggests that an avocado a day can improve diet quality, she noted, which “ is important because we know a higher diet quality is associated with lower risk of several diseases, including heart disease, type 2 diabetes, and some cancers.”

But the researchers also stressed that it is important to consider the diet as a whole.

“Consistent with prior observations, a change in dietary patterns rather than a single food or nutrient may be necessary to achieve clinically significant improvements” in belly fat and other risk factors for heart attack, stroke, and diabetes, they wrote. 

HAT was funded by the Hass Avocado Board, which also supplied the avocados.

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

Avocados are a rich source of fiber and healthy fat, but eating one a day for 6 months did not shrink waist size or belly fat, according to the findings of a new study.

But it did improve diet quality and led to modest lowering of total cholesterol.

More than 1,000 adults with overweight or obesity and a large waist – at least 35 inches in women and 40 inches in men – took part in this U.S. study, called the Habitual Diet and Avocado Trial (HAT).

tookapic/Pixabay

The people in the study were divided into two groups: usual diet plus one large avocado every day and usual diet with two avocados at most per month (control group).

Those in the avocado-a-day group were given a regular supply of fresh avocados along with written instructions for how to ripen and prepare them.

They had MRI scans to measure belly fat and fat around other organs at the beginning of the study and after 6 months.

After 6 months, the people who ate an avocado a day did not have less fat around their middles – the main trial outcome – compared with people in the control group.

But at 6 months, those in the avocado-a-day group had:

• No weight gain. People’s weight remained stable in both groups.
• Improved diet quality by 8 points on a 100-point scale
• A 2.9-mg/dL decrease in total cholesterol
• A 2.5-mg/dL decrease in LDL cholesterol

The study was done by researchers at Penn State University; Tufts University; Loma Linda University; and the University of California, Los Angeles, with coordinating support from Wake Forest University.

It was published in the Journal of the American Heart Association.

“While the avocados did not affect belly fat or weight gain, the study still provides evidence that avocados can be a beneficial addition to a well-balanced diet,” Penny M. Kris-Etherton, PhD, one of the researchers and a professor of nutritional sciences at Penn State University, University Park, said in a news release.

“Incorporating an avocado per day in this study did not cause weight gain and also caused a slight decrease in LDL cholesterol, which are all important findings for better health,” she said.

Similarly, study researcher Joan Sabaté, MD, a professor at Loma Linda (Calif.) University, said: “While one avocado a day did not lead to clinically significant improvements in abdominal fat and other cardiometabolic risk factors, consuming one avocado a day did not result in body weight gain.”

“This is positive,” he said, “because eating extra calories from avocados doesn’t impact body weight or abdominal fat, and it slightly decreases total and LDL cholesterol.”

Kristina S. Petersen, PhD, another of the researchers and an assistant professor of nutritional sciences at Texas Tech University, Lubbock, pointed out that people are generally poor at adhering to the Dietary Guidelines for Americans.

This study suggests that an avocado a day can improve diet quality, she noted, which “ is important because we know a higher diet quality is associated with lower risk of several diseases, including heart disease, type 2 diabetes, and some cancers.”

But the researchers also stressed that it is important to consider the diet as a whole.

“Consistent with prior observations, a change in dietary patterns rather than a single food or nutrient may be necessary to achieve clinically significant improvements” in belly fat and other risk factors for heart attack, stroke, and diabetes, they wrote. 

HAT was funded by the Hass Avocado Board, which also supplied the avocados.

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

Avocados are a rich source of fiber and healthy fat, but eating one a day for 6 months did not shrink waist size or belly fat, according to the findings of a new study.

But it did improve diet quality and led to modest lowering of total cholesterol.

More than 1,000 adults with overweight or obesity and a large waist – at least 35 inches in women and 40 inches in men – took part in this U.S. study, called the Habitual Diet and Avocado Trial (HAT).

tookapic/Pixabay

The people in the study were divided into two groups: usual diet plus one large avocado every day and usual diet with two avocados at most per month (control group).

Those in the avocado-a-day group were given a regular supply of fresh avocados along with written instructions for how to ripen and prepare them.

They had MRI scans to measure belly fat and fat around other organs at the beginning of the study and after 6 months.

After 6 months, the people who ate an avocado a day did not have less fat around their middles – the main trial outcome – compared with people in the control group.

But at 6 months, those in the avocado-a-day group had:

• No weight gain. People’s weight remained stable in both groups.
• Improved diet quality by 8 points on a 100-point scale
• A 2.9-mg/dL decrease in total cholesterol
• A 2.5-mg/dL decrease in LDL cholesterol

The study was done by researchers at Penn State University; Tufts University; Loma Linda University; and the University of California, Los Angeles, with coordinating support from Wake Forest University.

It was published in the Journal of the American Heart Association.

“While the avocados did not affect belly fat or weight gain, the study still provides evidence that avocados can be a beneficial addition to a well-balanced diet,” Penny M. Kris-Etherton, PhD, one of the researchers and a professor of nutritional sciences at Penn State University, University Park, said in a news release.

“Incorporating an avocado per day in this study did not cause weight gain and also caused a slight decrease in LDL cholesterol, which are all important findings for better health,” she said.

Similarly, study researcher Joan Sabaté, MD, a professor at Loma Linda (Calif.) University, said: “While one avocado a day did not lead to clinically significant improvements in abdominal fat and other cardiometabolic risk factors, consuming one avocado a day did not result in body weight gain.”

“This is positive,” he said, “because eating extra calories from avocados doesn’t impact body weight or abdominal fat, and it slightly decreases total and LDL cholesterol.”

Kristina S. Petersen, PhD, another of the researchers and an assistant professor of nutritional sciences at Texas Tech University, Lubbock, pointed out that people are generally poor at adhering to the Dietary Guidelines for Americans.

This study suggests that an avocado a day can improve diet quality, she noted, which “ is important because we know a higher diet quality is associated with lower risk of several diseases, including heart disease, type 2 diabetes, and some cancers.”

But the researchers also stressed that it is important to consider the diet as a whole.

“Consistent with prior observations, a change in dietary patterns rather than a single food or nutrient may be necessary to achieve clinically significant improvements” in belly fat and other risk factors for heart attack, stroke, and diabetes, they wrote. 

HAT was funded by the Hass Avocado Board, which also supplied the avocados.

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