Federal Practitioner

Physical exercise is associated with a reduction in suicide attempts, new research suggests.

A meta-analysis of 17 randomized controlled trials (RCTs), which included more than 1,000 participants with mental or physical illnesses, showed there was a significant reduction in suicide attempts in participants randomly assigned to receive exercise interventions, compared with inactive controls. However, there were no differences between the exercise and the control groups in suicidal ideation or mortality.

On the other hand, there was also no significant difference in dropout rates between those randomly assigned to exercise versus inactive controls, suggesting that people with mental or physical impairments are able to adhere to exercise regimens.

“A common misconception is that patients, particularly those suffering from mental of physical illness, are not willing or motivated enough to participate in an exercise [regimen], and this has led to primary care providers underprescribing exercise to those with mental or physical illness,” lead author Nicholas Fabiano, MD, a resident in the department of psychiatry at the University of Ottawa, told this news organization.

As a result of the study findings, “we recommend that providers do not have apprehension about prescribing exercise to patients with physical or mental illness. Exercise may be an effective way to reduce suicidal behaviors” in these patients, he said.

The study was published online  in the Journal of Affective Disorders.
 

Physical, mental health strongly linked

Existing literature has “demonstrated a protective effect of physical activity on suicidal ideation in the general population,” but to date there have been no systematic reviews or meta-analyses investigating its impact on suicide-related outcomes in patients with physical or mental illness, the authors write.

“Those with mental or physical illness are at increased risk of suicide, compared to the general population,” Dr. Fabiano commented.

“We often split up ‘mental health’ and ‘physical health’ in medicine; however, I believe that the two are more on a continuum and a holistic term, such as ‘health,’ should be used instead,” he added.

He noted that mental and physical health are “inexorably intertwined” and those with physical illness are more prone to developing mental illness, whereas those with mental illness are more likely to suffer from a variety of other medical conditions. “Therefore, when treating those with mental illness, it is also imperative that we bolster one’s physical health through easily accessible activities such as exercise,” he said.

The goal of the study was to determine whether individuals with “any mental, physical, clinical, or subclinical condition” might benefit from exercise, particularly in relation to suicide-related outcomes. They searched multiple databases from inception to June 2022 to identify RCTs investigating exercise and suicidal ideation in participants with physical or mental conditions.

Of 673 studies, 17 met the inclusion criteria (total of 1,021 participants). Participants’ mean age was 42.7 years, 82% were female, and 54% were randomly assigned to an exercise intervention.

Most studies (82%) focused on clinical versus subclinical outcomes. Depression was the most commonly included condition (59%). Aerobic exercise (53%) was the most common form of exercise used in the active study groups. This was followed by mind-body exercise and strength training (53%, 17.6%, and 17.6%, respectively). The mean follow-up time was 10 weeks.
 

Reduced impulsivity

The researchers found a difference in post-intervention suicidal ideation when they compared exercise participants to all control and inactive control participants (standardized mean difference, –1.09; 95% confidence interval, –3.08 to 0.90; P = .20, k = 5). However, the difference was not statistically significant.

Similarly, there was no significant difference (P = .60) in suicidal ideation incidence for subgroup analyses that stratified data among participants with depression, sickle cell disease, and suicidality.

All-cause discontinuation also did not significantly differ between participants who were randomly assigned to exercise interventions versus all controls or inactive controls (odds ratio, 0.85; 95% CI, 0.38-1.94; P = .86, k = 12 and OR, 0.81; 95% CI, 0.25-2.68; P = .70). All-cause discontinuation also did not differ between participants randomized to exercise versus active controls (OR, 0.94; 95% CI, 0.38-2.32; P = .79, k = 3).

Likewise, there were nonsignificant differences between participants who underwent aerobic exercise and strength training (P = .20).

However, there were some nonsignificant differences when comparing participants with depression and stress who received the exercise intervention versus controls (P = .46).

There was a significant reduction in suicide attempts in individuals who participated in exercise interventions versus inactive controls (OR, 0.23; 95% CI, 0.09-0.67; P = .04, k = 2). On the other hand, there was no significant difference in mortality (P = .70).

Most of the studies (82%) were “at high risk of bias,” the authors note. In addition, the analysis was limited because the included studies were “few, underpowered, and heterogeneous.”

Dr. Fabiano hypothesized that the lack of effect on suicidal ideation or mortality is “likely due to the limited sample size.” As additional RCTs are conducted, Dr. Fabiano expects to see decreases in both suicidal ideation and suicide attempts.

The findings may “be explained by the ideation-to-action framework, which suggests that the development of suicidal ideation and the progression to suicide attempts are distinct processes with different influential factors,” he said.

Increased levels of exercise have been “shown to reduce emotional impulsivity and, as it has been shown that most suicide attempts are characterized by impulsivity and low lethality, we hypothesize that regular exercise serves as a protective factor against suicide attempts,” he said.
 

Not useful?

Commenting on the study, Fabien Legrand, PhD, a lecturer in clinical psychology, University of Reims Champagne-Ardenne, Reims, France, said that the impact of physical activity is of “particular interest” to him because it is closely linked to his research activity, where he has “been exploring the antidepressant effects of exercise for more than 15 years.”

A small pilot study conducted by Dr. Legrand and colleagues found rigorous physical activity to be helpful in reducing hopelessness in psychiatric patients, compared with controls. “This result is of particular relevance for suicidal patients, since it has long been documented that hopelessness is one of the main triggers of suicide ideation and suicide attempts,” he said.

Initially, Dr. Legrand “warmly welcomed” the current review and meta-analysis on the exercise and suicide. However, he felt that the paper fell short in accomplishing its intended goal. “After a thorough reading of the paper, I don’t think that the information provided can be used in any way,” he stated.

“The paper’s title – ‘Effects of Physical Exercise on Suicidal Ideation and Behavior’ – does not do justice to its content, since 9 of the included 17 RCTs did not measure changes in suicidal ideation and/or suicidal behavior following participation in an exercise program,” noted Dr. Legrand, who was not involved with authorship or the current analysis.

The study was funded by the University of Ottawa department of psychiatry. Dr. Fabiano declares no relevant financial relationships. The other authors’ disclosures are listed in the original article. Dr. Legrand declares no relevant financial relationships.

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

Physical exercise is associated with a reduction in suicide attempts, new research suggests.

A meta-analysis of 17 randomized controlled trials (RCTs), which included more than 1,000 participants with mental or physical illnesses, showed there was a significant reduction in suicide attempts in participants randomly assigned to receive exercise interventions, compared with inactive controls. However, there were no differences between the exercise and the control groups in suicidal ideation or mortality.

On the other hand, there was also no significant difference in dropout rates between those randomly assigned to exercise versus inactive controls, suggesting that people with mental or physical impairments are able to adhere to exercise regimens.

“A common misconception is that patients, particularly those suffering from mental of physical illness, are not willing or motivated enough to participate in an exercise [regimen], and this has led to primary care providers underprescribing exercise to those with mental or physical illness,” lead author Nicholas Fabiano, MD, a resident in the department of psychiatry at the University of Ottawa, told this news organization.

As a result of the study findings, “we recommend that providers do not have apprehension about prescribing exercise to patients with physical or mental illness. Exercise may be an effective way to reduce suicidal behaviors” in these patients, he said.

The study was published online  in the Journal of Affective Disorders.
 

Physical, mental health strongly linked

Existing literature has “demonstrated a protective effect of physical activity on suicidal ideation in the general population,” but to date there have been no systematic reviews or meta-analyses investigating its impact on suicide-related outcomes in patients with physical or mental illness, the authors write.

“Those with mental or physical illness are at increased risk of suicide, compared to the general population,” Dr. Fabiano commented.

“We often split up ‘mental health’ and ‘physical health’ in medicine; however, I believe that the two are more on a continuum and a holistic term, such as ‘health,’ should be used instead,” he added.

He noted that mental and physical health are “inexorably intertwined” and those with physical illness are more prone to developing mental illness, whereas those with mental illness are more likely to suffer from a variety of other medical conditions. “Therefore, when treating those with mental illness, it is also imperative that we bolster one’s physical health through easily accessible activities such as exercise,” he said.

The goal of the study was to determine whether individuals with “any mental, physical, clinical, or subclinical condition” might benefit from exercise, particularly in relation to suicide-related outcomes. They searched multiple databases from inception to June 2022 to identify RCTs investigating exercise and suicidal ideation in participants with physical or mental conditions.

Of 673 studies, 17 met the inclusion criteria (total of 1,021 participants). Participants’ mean age was 42.7 years, 82% were female, and 54% were randomly assigned to an exercise intervention.

Most studies (82%) focused on clinical versus subclinical outcomes. Depression was the most commonly included condition (59%). Aerobic exercise (53%) was the most common form of exercise used in the active study groups. This was followed by mind-body exercise and strength training (53%, 17.6%, and 17.6%, respectively). The mean follow-up time was 10 weeks.
 

Reduced impulsivity

The researchers found a difference in post-intervention suicidal ideation when they compared exercise participants to all control and inactive control participants (standardized mean difference, –1.09; 95% confidence interval, –3.08 to 0.90; P = .20, k = 5). However, the difference was not statistically significant.

Similarly, there was no significant difference (P = .60) in suicidal ideation incidence for subgroup analyses that stratified data among participants with depression, sickle cell disease, and suicidality.

All-cause discontinuation also did not significantly differ between participants who were randomly assigned to exercise interventions versus all controls or inactive controls (odds ratio, 0.85; 95% CI, 0.38-1.94; P = .86, k = 12 and OR, 0.81; 95% CI, 0.25-2.68; P = .70). All-cause discontinuation also did not differ between participants randomized to exercise versus active controls (OR, 0.94; 95% CI, 0.38-2.32; P = .79, k = 3).

Likewise, there were nonsignificant differences between participants who underwent aerobic exercise and strength training (P = .20).

However, there were some nonsignificant differences when comparing participants with depression and stress who received the exercise intervention versus controls (P = .46).

There was a significant reduction in suicide attempts in individuals who participated in exercise interventions versus inactive controls (OR, 0.23; 95% CI, 0.09-0.67; P = .04, k = 2). On the other hand, there was no significant difference in mortality (P = .70).

Most of the studies (82%) were “at high risk of bias,” the authors note. In addition, the analysis was limited because the included studies were “few, underpowered, and heterogeneous.”

Dr. Fabiano hypothesized that the lack of effect on suicidal ideation or mortality is “likely due to the limited sample size.” As additional RCTs are conducted, Dr. Fabiano expects to see decreases in both suicidal ideation and suicide attempts.

The findings may “be explained by the ideation-to-action framework, which suggests that the development of suicidal ideation and the progression to suicide attempts are distinct processes with different influential factors,” he said.

Increased levels of exercise have been “shown to reduce emotional impulsivity and, as it has been shown that most suicide attempts are characterized by impulsivity and low lethality, we hypothesize that regular exercise serves as a protective factor against suicide attempts,” he said.
 

Not useful?

Commenting on the study, Fabien Legrand, PhD, a lecturer in clinical psychology, University of Reims Champagne-Ardenne, Reims, France, said that the impact of physical activity is of “particular interest” to him because it is closely linked to his research activity, where he has “been exploring the antidepressant effects of exercise for more than 15 years.”

A small pilot study conducted by Dr. Legrand and colleagues found rigorous physical activity to be helpful in reducing hopelessness in psychiatric patients, compared with controls. “This result is of particular relevance for suicidal patients, since it has long been documented that hopelessness is one of the main triggers of suicide ideation and suicide attempts,” he said.

Initially, Dr. Legrand “warmly welcomed” the current review and meta-analysis on the exercise and suicide. However, he felt that the paper fell short in accomplishing its intended goal. “After a thorough reading of the paper, I don’t think that the information provided can be used in any way,” he stated.

“The paper’s title – ‘Effects of Physical Exercise on Suicidal Ideation and Behavior’ – does not do justice to its content, since 9 of the included 17 RCTs did not measure changes in suicidal ideation and/or suicidal behavior following participation in an exercise program,” noted Dr. Legrand, who was not involved with authorship or the current analysis.

The study was funded by the University of Ottawa department of psychiatry. Dr. Fabiano declares no relevant financial relationships. The other authors’ disclosures are listed in the original article. Dr. Legrand declares no relevant financial relationships.

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

Physical exercise is associated with a reduction in suicide attempts, new research suggests.

A meta-analysis of 17 randomized controlled trials (RCTs), which included more than 1,000 participants with mental or physical illnesses, showed there was a significant reduction in suicide attempts in participants randomly assigned to receive exercise interventions, compared with inactive controls. However, there were no differences between the exercise and the control groups in suicidal ideation or mortality.

On the other hand, there was also no significant difference in dropout rates between those randomly assigned to exercise versus inactive controls, suggesting that people with mental or physical impairments are able to adhere to exercise regimens.

“A common misconception is that patients, particularly those suffering from mental of physical illness, are not willing or motivated enough to participate in an exercise [regimen], and this has led to primary care providers underprescribing exercise to those with mental or physical illness,” lead author Nicholas Fabiano, MD, a resident in the department of psychiatry at the University of Ottawa, told this news organization.

As a result of the study findings, “we recommend that providers do not have apprehension about prescribing exercise to patients with physical or mental illness. Exercise may be an effective way to reduce suicidal behaviors” in these patients, he said.

The study was published online  in the Journal of Affective Disorders.
 

Physical, mental health strongly linked

Existing literature has “demonstrated a protective effect of physical activity on suicidal ideation in the general population,” but to date there have been no systematic reviews or meta-analyses investigating its impact on suicide-related outcomes in patients with physical or mental illness, the authors write.

“Those with mental or physical illness are at increased risk of suicide, compared to the general population,” Dr. Fabiano commented.

“We often split up ‘mental health’ and ‘physical health’ in medicine; however, I believe that the two are more on a continuum and a holistic term, such as ‘health,’ should be used instead,” he added.

He noted that mental and physical health are “inexorably intertwined” and those with physical illness are more prone to developing mental illness, whereas those with mental illness are more likely to suffer from a variety of other medical conditions. “Therefore, when treating those with mental illness, it is also imperative that we bolster one’s physical health through easily accessible activities such as exercise,” he said.

The goal of the study was to determine whether individuals with “any mental, physical, clinical, or subclinical condition” might benefit from exercise, particularly in relation to suicide-related outcomes. They searched multiple databases from inception to June 2022 to identify RCTs investigating exercise and suicidal ideation in participants with physical or mental conditions.

Of 673 studies, 17 met the inclusion criteria (total of 1,021 participants). Participants’ mean age was 42.7 years, 82% were female, and 54% were randomly assigned to an exercise intervention.

Most studies (82%) focused on clinical versus subclinical outcomes. Depression was the most commonly included condition (59%). Aerobic exercise (53%) was the most common form of exercise used in the active study groups. This was followed by mind-body exercise and strength training (53%, 17.6%, and 17.6%, respectively). The mean follow-up time was 10 weeks.
 

Reduced impulsivity

The researchers found a difference in post-intervention suicidal ideation when they compared exercise participants to all control and inactive control participants (standardized mean difference, –1.09; 95% confidence interval, –3.08 to 0.90; P = .20, k = 5). However, the difference was not statistically significant.

Similarly, there was no significant difference (P = .60) in suicidal ideation incidence for subgroup analyses that stratified data among participants with depression, sickle cell disease, and suicidality.

All-cause discontinuation also did not significantly differ between participants who were randomly assigned to exercise interventions versus all controls or inactive controls (odds ratio, 0.85; 95% CI, 0.38-1.94; P = .86, k = 12 and OR, 0.81; 95% CI, 0.25-2.68; P = .70). All-cause discontinuation also did not differ between participants randomized to exercise versus active controls (OR, 0.94; 95% CI, 0.38-2.32; P = .79, k = 3).

Likewise, there were nonsignificant differences between participants who underwent aerobic exercise and strength training (P = .20).

However, there were some nonsignificant differences when comparing participants with depression and stress who received the exercise intervention versus controls (P = .46).

There was a significant reduction in suicide attempts in individuals who participated in exercise interventions versus inactive controls (OR, 0.23; 95% CI, 0.09-0.67; P = .04, k = 2). On the other hand, there was no significant difference in mortality (P = .70).

Most of the studies (82%) were “at high risk of bias,” the authors note. In addition, the analysis was limited because the included studies were “few, underpowered, and heterogeneous.”

Dr. Fabiano hypothesized that the lack of effect on suicidal ideation or mortality is “likely due to the limited sample size.” As additional RCTs are conducted, Dr. Fabiano expects to see decreases in both suicidal ideation and suicide attempts.

The findings may “be explained by the ideation-to-action framework, which suggests that the development of suicidal ideation and the progression to suicide attempts are distinct processes with different influential factors,” he said.

Increased levels of exercise have been “shown to reduce emotional impulsivity and, as it has been shown that most suicide attempts are characterized by impulsivity and low lethality, we hypothesize that regular exercise serves as a protective factor against suicide attempts,” he said.
 

Not useful?

Commenting on the study, Fabien Legrand, PhD, a lecturer in clinical psychology, University of Reims Champagne-Ardenne, Reims, France, said that the impact of physical activity is of “particular interest” to him because it is closely linked to his research activity, where he has “been exploring the antidepressant effects of exercise for more than 15 years.”

A small pilot study conducted by Dr. Legrand and colleagues found rigorous physical activity to be helpful in reducing hopelessness in psychiatric patients, compared with controls. “This result is of particular relevance for suicidal patients, since it has long been documented that hopelessness is one of the main triggers of suicide ideation and suicide attempts,” he said.

Initially, Dr. Legrand “warmly welcomed” the current review and meta-analysis on the exercise and suicide. However, he felt that the paper fell short in accomplishing its intended goal. “After a thorough reading of the paper, I don’t think that the information provided can be used in any way,” he stated.

“The paper’s title – ‘Effects of Physical Exercise on Suicidal Ideation and Behavior’ – does not do justice to its content, since 9 of the included 17 RCTs did not measure changes in suicidal ideation and/or suicidal behavior following participation in an exercise program,” noted Dr. Legrand, who was not involved with authorship or the current analysis.

The study was funded by the University of Ottawa department of psychiatry. Dr. Fabiano declares no relevant financial relationships. The other authors’ disclosures are listed in the original article. Dr. Legrand declares no relevant financial relationships.

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

Women who underwent bilateral salpingo-oophorectomy with a benign hysterectomy had a higher 10-year mortality rate across all ages than those who had hysterectomies alone, based on data from more than 140,000 individuals.

Although bilateral salpingo-oophorectomy (BSO) with hysterectomy has been shown to reduce the risk for ovarian cancer in women at increased risk, current guidelines are touting ovarian conservation, especially in premenopausal women, wrote Mathilde Gottschau, MD, of the Danish Cancer Society Research Center, Copenhagen, and colleagues. However, post-hysterectomy outcomes in women with and without BSO have not been well examined.

In a study published in the Annals of Internal Medicine, the researchers reviewed data from a nationwide registry of women in Denmark aged 20 years and older who underwent benign hysterectomies with BSO (22,974 women) and without BSO (120,011 women) between 1977 and 2017. The women were divided into subgroups based on age; those younger than 45 years were defined as premenopausal, those aged 45-54 years were defined as perimenopausal, those aged 55-64 were defined as early postmenopausal, and those aged 65 and older were defined as late menopausal.

The primary outcomes were hospitalization for cardiovascular disease, cancer incidence, and all-cause mortality over a median follow-up period of 22 years.

For women younger than 45 years, the 10-year cumulative risk for all cancer was lower with BSO than without, but the risk of overall cardiovascular disease was higher with BSO, with higher levels of ischemic heart disease and stroke, compared with women without BSO. The 10-year cumulative mortality was higher with BSO than without (2.16% vs. 1.94%).

For women aged 45-54 years, the 10-year cumulative cancer risk was higher in those with BSO than those without BSO (risk difference, 0.73 percentage points) associated mainly with nonbreast cancer, and both 10-year and 20-year mortality were higher in those with BSO than those without.

For women aged 55-65 years, the 10-year cumulative cancer risk was higher in those with BSO than those without BSO. Cumulative overall mortality was higher at 10 years for those with BSO, but lower at 20 years.

For women aged 65 years and older, both 10-year and 20-year cumulative overall cancer risk was higher with BSO than without (RD, 2.54 and 4.57 percentage points, respectively). Cumulative mortality was higher in the BSO group at 10 years, but lower at 20 years.

The study findings were limited by several factors including the use of age to determine menopausal status and the lack of genetic predisposition data, and the focus only on a relatively homogeneous population that may not be generalizable to other populations, the researchers noted.

However, the results were strengthened by the use of a nationwide registry and the long-term follow-up period, they said. The current study indicates that the health risks outweigh the potential benefits of BSO with benign hysterectomy for premenopausal women and supports the current guidelines for ovarian conservation in these women with low lifetime ovarian cancer risk, they said. For postmenopausal women, the data support a cautious approach to BSO given the lack of a clear survival benefit and cancer excess, they concluded.
 

Delayed diagnosis of ovarian cancers favors BSO

“The question of removing ovaries at the time of benign hysterectomy to prevent ovarian cancer in low-risk women has been widely debated,” which has contributed to the variation in incidence rates of unilateral and bilateral oophorectomy over time, wrote Elizabeth Casiano Evans, MD, of the University of Texas, San Antonio, and Deslyn T.G. Hobson, MD, of Wayne State University, Detroit, in an accompanying editorial.

Ovarian cancer often goes undiagnosed until an advanced stage, and BSO can significantly reduce risk in women with BRCA1 and BRCA2 mutations, they noted.

For women without increased risk, those who are premenopausal may wish to preserve ovarian function, but women also may benefit from improvements in a range of menopause-related symptoms including vasomotor and urogenital symptoms, sexual dysfunction, and psychiatric and cognitive symptoms, they said.

“In addition, salpingectomy alone has a role in significantly reducing ovarian cancer incidence without compromising ovarian function because the fallopian tube has been found to be at the origin of many ovarian cancer cases,” they noted. In the current study, “the crude ovarian cancer risk was lower with BSO” across all age groups, the editorialists said.

The choice of whether to include BSO at the time of benign hysterectomy is complicated, with many factors to consider, the editorialists wrote, and the current study supports the need for informed, shared decision-making between clinicians and patients.

The study was supported by the Danish Cancer Society’s Scientific Committee and the Mermaid Project. The researchers had no financial conflicts to disclose. The editorial authors had no financial conflicts to disclose.
 

Women who underwent bilateral salpingo-oophorectomy with a benign hysterectomy had a higher 10-year mortality rate across all ages than those who had hysterectomies alone, based on data from more than 140,000 individuals.

Although bilateral salpingo-oophorectomy (BSO) with hysterectomy has been shown to reduce the risk for ovarian cancer in women at increased risk, current guidelines are touting ovarian conservation, especially in premenopausal women, wrote Mathilde Gottschau, MD, of the Danish Cancer Society Research Center, Copenhagen, and colleagues. However, post-hysterectomy outcomes in women with and without BSO have not been well examined.

In a study published in the Annals of Internal Medicine, the researchers reviewed data from a nationwide registry of women in Denmark aged 20 years and older who underwent benign hysterectomies with BSO (22,974 women) and without BSO (120,011 women) between 1977 and 2017. The women were divided into subgroups based on age; those younger than 45 years were defined as premenopausal, those aged 45-54 years were defined as perimenopausal, those aged 55-64 were defined as early postmenopausal, and those aged 65 and older were defined as late menopausal.

The primary outcomes were hospitalization for cardiovascular disease, cancer incidence, and all-cause mortality over a median follow-up period of 22 years.

For women younger than 45 years, the 10-year cumulative risk for all cancer was lower with BSO than without, but the risk of overall cardiovascular disease was higher with BSO, with higher levels of ischemic heart disease and stroke, compared with women without BSO. The 10-year cumulative mortality was higher with BSO than without (2.16% vs. 1.94%).

For women aged 45-54 years, the 10-year cumulative cancer risk was higher in those with BSO than those without BSO (risk difference, 0.73 percentage points) associated mainly with nonbreast cancer, and both 10-year and 20-year mortality were higher in those with BSO than those without.

For women aged 55-65 years, the 10-year cumulative cancer risk was higher in those with BSO than those without BSO. Cumulative overall mortality was higher at 10 years for those with BSO, but lower at 20 years.

For women aged 65 years and older, both 10-year and 20-year cumulative overall cancer risk was higher with BSO than without (RD, 2.54 and 4.57 percentage points, respectively). Cumulative mortality was higher in the BSO group at 10 years, but lower at 20 years.

The study findings were limited by several factors including the use of age to determine menopausal status and the lack of genetic predisposition data, and the focus only on a relatively homogeneous population that may not be generalizable to other populations, the researchers noted.

However, the results were strengthened by the use of a nationwide registry and the long-term follow-up period, they said. The current study indicates that the health risks outweigh the potential benefits of BSO with benign hysterectomy for premenopausal women and supports the current guidelines for ovarian conservation in these women with low lifetime ovarian cancer risk, they said. For postmenopausal women, the data support a cautious approach to BSO given the lack of a clear survival benefit and cancer excess, they concluded.
 

Delayed diagnosis of ovarian cancers favors BSO

“The question of removing ovaries at the time of benign hysterectomy to prevent ovarian cancer in low-risk women has been widely debated,” which has contributed to the variation in incidence rates of unilateral and bilateral oophorectomy over time, wrote Elizabeth Casiano Evans, MD, of the University of Texas, San Antonio, and Deslyn T.G. Hobson, MD, of Wayne State University, Detroit, in an accompanying editorial.

Ovarian cancer often goes undiagnosed until an advanced stage, and BSO can significantly reduce risk in women with BRCA1 and BRCA2 mutations, they noted.

For women without increased risk, those who are premenopausal may wish to preserve ovarian function, but women also may benefit from improvements in a range of menopause-related symptoms including vasomotor and urogenital symptoms, sexual dysfunction, and psychiatric and cognitive symptoms, they said.

“In addition, salpingectomy alone has a role in significantly reducing ovarian cancer incidence without compromising ovarian function because the fallopian tube has been found to be at the origin of many ovarian cancer cases,” they noted. In the current study, “the crude ovarian cancer risk was lower with BSO” across all age groups, the editorialists said.

The choice of whether to include BSO at the time of benign hysterectomy is complicated, with many factors to consider, the editorialists wrote, and the current study supports the need for informed, shared decision-making between clinicians and patients.

The study was supported by the Danish Cancer Society’s Scientific Committee and the Mermaid Project. The researchers had no financial conflicts to disclose. The editorial authors had no financial conflicts to disclose.
 

Women who underwent bilateral salpingo-oophorectomy with a benign hysterectomy had a higher 10-year mortality rate across all ages than those who had hysterectomies alone, based on data from more than 140,000 individuals.

Although bilateral salpingo-oophorectomy (BSO) with hysterectomy has been shown to reduce the risk for ovarian cancer in women at increased risk, current guidelines are touting ovarian conservation, especially in premenopausal women, wrote Mathilde Gottschau, MD, of the Danish Cancer Society Research Center, Copenhagen, and colleagues. However, post-hysterectomy outcomes in women with and without BSO have not been well examined.

In a study published in the Annals of Internal Medicine, the researchers reviewed data from a nationwide registry of women in Denmark aged 20 years and older who underwent benign hysterectomies with BSO (22,974 women) and without BSO (120,011 women) between 1977 and 2017. The women were divided into subgroups based on age; those younger than 45 years were defined as premenopausal, those aged 45-54 years were defined as perimenopausal, those aged 55-64 were defined as early postmenopausal, and those aged 65 and older were defined as late menopausal.

The primary outcomes were hospitalization for cardiovascular disease, cancer incidence, and all-cause mortality over a median follow-up period of 22 years.

For women younger than 45 years, the 10-year cumulative risk for all cancer was lower with BSO than without, but the risk of overall cardiovascular disease was higher with BSO, with higher levels of ischemic heart disease and stroke, compared with women without BSO. The 10-year cumulative mortality was higher with BSO than without (2.16% vs. 1.94%).

For women aged 45-54 years, the 10-year cumulative cancer risk was higher in those with BSO than those without BSO (risk difference, 0.73 percentage points) associated mainly with nonbreast cancer, and both 10-year and 20-year mortality were higher in those with BSO than those without.

For women aged 55-65 years, the 10-year cumulative cancer risk was higher in those with BSO than those without BSO. Cumulative overall mortality was higher at 10 years for those with BSO, but lower at 20 years.

For women aged 65 years and older, both 10-year and 20-year cumulative overall cancer risk was higher with BSO than without (RD, 2.54 and 4.57 percentage points, respectively). Cumulative mortality was higher in the BSO group at 10 years, but lower at 20 years.

The study findings were limited by several factors including the use of age to determine menopausal status and the lack of genetic predisposition data, and the focus only on a relatively homogeneous population that may not be generalizable to other populations, the researchers noted.

However, the results were strengthened by the use of a nationwide registry and the long-term follow-up period, they said. The current study indicates that the health risks outweigh the potential benefits of BSO with benign hysterectomy for premenopausal women and supports the current guidelines for ovarian conservation in these women with low lifetime ovarian cancer risk, they said. For postmenopausal women, the data support a cautious approach to BSO given the lack of a clear survival benefit and cancer excess, they concluded.
 

Delayed diagnosis of ovarian cancers favors BSO

“The question of removing ovaries at the time of benign hysterectomy to prevent ovarian cancer in low-risk women has been widely debated,” which has contributed to the variation in incidence rates of unilateral and bilateral oophorectomy over time, wrote Elizabeth Casiano Evans, MD, of the University of Texas, San Antonio, and Deslyn T.G. Hobson, MD, of Wayne State University, Detroit, in an accompanying editorial.

Ovarian cancer often goes undiagnosed until an advanced stage, and BSO can significantly reduce risk in women with BRCA1 and BRCA2 mutations, they noted.

For women without increased risk, those who are premenopausal may wish to preserve ovarian function, but women also may benefit from improvements in a range of menopause-related symptoms including vasomotor and urogenital symptoms, sexual dysfunction, and psychiatric and cognitive symptoms, they said.

“In addition, salpingectomy alone has a role in significantly reducing ovarian cancer incidence without compromising ovarian function because the fallopian tube has been found to be at the origin of many ovarian cancer cases,” they noted. In the current study, “the crude ovarian cancer risk was lower with BSO” across all age groups, the editorialists said.

The choice of whether to include BSO at the time of benign hysterectomy is complicated, with many factors to consider, the editorialists wrote, and the current study supports the need for informed, shared decision-making between clinicians and patients.

The study was supported by the Danish Cancer Society’s Scientific Committee and the Mermaid Project. The researchers had no financial conflicts to disclose. The editorial authors had no financial conflicts to disclose.
 

NEW YORK – Most patients with chronic lymphocytic leukemia (CLL) who relapse after treatment with a single agent Bruton’s tyrosine kinase (BTK) inhibitor have one of several high-risk characteristics, including complex karyotype, 17p-chromosome deletion, or a TP53 mutation. In contrast, genomically stable patients have a 4-year progression-free survival (PFS) rate of about 98% on single agent Bruton’s tyrosine kinase inhibitor therapy.

Dr. Furman

“In people who are genomically unstable, almost half will have their CLL progress on single agent BTK inhibitor therapy. These patients, I’d like to treat with combination of a Bruton’s tyrosine kinase inhibitor plus venetoclax,” said Richard R. Furman, MD, Morton Coleman MD Distinguished Professor of medicine at Weill Cornell Medicine/New York Presbyterian Hospital. He presented on treating relapsed CLL at the Great Debates and Updates Hematologic Malignancies Conference in New York, April 13-15.

The efficacy of venetoclax (VX) in treating high risk CLL patients was demonstrated in the 2019 CLL14 trial (NCT02242942) in which the main entry criteria were being treatment-naive and being considered “unfit” for treatment, meaning that a patient’s Cumulative Illness Rating Scale score was >6, or they presented with decreased kidney function. Study participants were treated with six cycles of either venetoclax-obinutuzumab (VO) or chlorambucil-obinutuzumab (CO); the 4-year PFS was 74% vs. 35.4% (P < .0001) respectively. After 12 cycles of treatment, the 74% of patients in the VO group achieved undetectable minimal residual disease rate (MRD) vs. 32% in the CO group.

Achievement of MRD did predict for outcome, but Dr. Furman concluded that while MRD is a powerful prognostic tool, it is not clinically useful given the inability of its results to guide therapy. He went on to emphasize that “of those patients who achieved MRD levels of 10-4 after 12 cycles of venetoclax, 50% had worsening and 50% had improvement of the residual disease, suggesting that we do not know the optimal duration of venetoclax treatment, as half of the patients still continue to derive benefit.”

Dr. Furman noted that ibrutinib (IB) and the second-generation drugs zanubrutinib (ZB) and acalabrutinib (AL) are all effective, but that the second-generation Bruton’s tyrosine kinase inhibitors enable patients to derive the benefit of remaining on treatment longer, because the rate of concerning cardiac complications is lower than with IB.

The ALPINE trial (NCT03734016) confirmed ZB’s significantly improved overall response rate at 78.3% vs. IB’s 62.5%, as well as a lower rate of atrial fibrillation (2.5%) vs. IB (10.1%).

Noninferiority of AL vs. IB in high-risk relapsed CLL patients was demonstrated in the ELEVATE-RR trial (NCT02477696) with both drugs having a median PFS of 38.4 months. With a median follow up of 41 months, AL demonstrated less atrial fibrillation/atrial flutter, compared with IB (9.4% vs. 16.0%) with no difference in grade > 3 infections. Furthermore, AL’s half-life being shorter than that of IB means that side effects are shorter lived.

“That’s the advantage of the second generation of Bruton’s tyrosine kinase inhibitors,” said Stefan Glück, MD, PhD, a hematologic oncologist and independent consultant who was formerly affiliated with the Sylvester Comprehensive Cancer Center and taught at the Miller School of Medicine at the University of Miami.

Dr. Glück added that “acalabrutinib and zanubrutinib have demonstrated strong efficacy and safety. When patients no longer respond to these drugs, the addition of VX is crucial. It has a completely different mechanism of action and can reverse resistance to Bruton’s tyrosine kinase inhibitors, allowing them to start working again.”

Dr. Furman also discussed proteolysis-targeting chimeras (PROTACs), one area that he expects to make a significant impact as a future therapy for CLL and many other malignancies. Despite the fact these agents are in phase I studies, he commented that “they appear, thus far, to have tremendous potential.”

Dr. Furman disclosed relationships with Abbvie, Acerta/AstraZeneca, Beigene, Jansen, TG Therapeutics, Genentech-Roche, Incyte Corporation, Loxo Oncology, MEI Pharma, Morphosys, Pharmacyclics, Sanofi/Genzyme, and X4 Pharmaceuticals. Dr. Glück reported no conflicts of interest.
 

NEW YORK – Most patients with chronic lymphocytic leukemia (CLL) who relapse after treatment with a single agent Bruton’s tyrosine kinase (BTK) inhibitor have one of several high-risk characteristics, including complex karyotype, 17p-chromosome deletion, or a TP53 mutation. In contrast, genomically stable patients have a 4-year progression-free survival (PFS) rate of about 98% on single agent Bruton’s tyrosine kinase inhibitor therapy.

Dr. Furman

“In people who are genomically unstable, almost half will have their CLL progress on single agent BTK inhibitor therapy. These patients, I’d like to treat with combination of a Bruton’s tyrosine kinase inhibitor plus venetoclax,” said Richard R. Furman, MD, Morton Coleman MD Distinguished Professor of medicine at Weill Cornell Medicine/New York Presbyterian Hospital. He presented on treating relapsed CLL at the Great Debates and Updates Hematologic Malignancies Conference in New York, April 13-15.

The efficacy of venetoclax (VX) in treating high risk CLL patients was demonstrated in the 2019 CLL14 trial (NCT02242942) in which the main entry criteria were being treatment-naive and being considered “unfit” for treatment, meaning that a patient’s Cumulative Illness Rating Scale score was >6, or they presented with decreased kidney function. Study participants were treated with six cycles of either venetoclax-obinutuzumab (VO) or chlorambucil-obinutuzumab (CO); the 4-year PFS was 74% vs. 35.4% (P < .0001) respectively. After 12 cycles of treatment, the 74% of patients in the VO group achieved undetectable minimal residual disease rate (MRD) vs. 32% in the CO group.

Achievement of MRD did predict for outcome, but Dr. Furman concluded that while MRD is a powerful prognostic tool, it is not clinically useful given the inability of its results to guide therapy. He went on to emphasize that “of those patients who achieved MRD levels of 10-4 after 12 cycles of venetoclax, 50% had worsening and 50% had improvement of the residual disease, suggesting that we do not know the optimal duration of venetoclax treatment, as half of the patients still continue to derive benefit.”

Dr. Furman noted that ibrutinib (IB) and the second-generation drugs zanubrutinib (ZB) and acalabrutinib (AL) are all effective, but that the second-generation Bruton’s tyrosine kinase inhibitors enable patients to derive the benefit of remaining on treatment longer, because the rate of concerning cardiac complications is lower than with IB.

The ALPINE trial (NCT03734016) confirmed ZB’s significantly improved overall response rate at 78.3% vs. IB’s 62.5%, as well as a lower rate of atrial fibrillation (2.5%) vs. IB (10.1%).

Noninferiority of AL vs. IB in high-risk relapsed CLL patients was demonstrated in the ELEVATE-RR trial (NCT02477696) with both drugs having a median PFS of 38.4 months. With a median follow up of 41 months, AL demonstrated less atrial fibrillation/atrial flutter, compared with IB (9.4% vs. 16.0%) with no difference in grade > 3 infections. Furthermore, AL’s half-life being shorter than that of IB means that side effects are shorter lived.

“That’s the advantage of the second generation of Bruton’s tyrosine kinase inhibitors,” said Stefan Glück, MD, PhD, a hematologic oncologist and independent consultant who was formerly affiliated with the Sylvester Comprehensive Cancer Center and taught at the Miller School of Medicine at the University of Miami.

Dr. Glück added that “acalabrutinib and zanubrutinib have demonstrated strong efficacy and safety. When patients no longer respond to these drugs, the addition of VX is crucial. It has a completely different mechanism of action and can reverse resistance to Bruton’s tyrosine kinase inhibitors, allowing them to start working again.”

Dr. Furman also discussed proteolysis-targeting chimeras (PROTACs), one area that he expects to make a significant impact as a future therapy for CLL and many other malignancies. Despite the fact these agents are in phase I studies, he commented that “they appear, thus far, to have tremendous potential.”

Dr. Furman disclosed relationships with Abbvie, Acerta/AstraZeneca, Beigene, Jansen, TG Therapeutics, Genentech-Roche, Incyte Corporation, Loxo Oncology, MEI Pharma, Morphosys, Pharmacyclics, Sanofi/Genzyme, and X4 Pharmaceuticals. Dr. Glück reported no conflicts of interest.
 

NEW YORK – Most patients with chronic lymphocytic leukemia (CLL) who relapse after treatment with a single agent Bruton’s tyrosine kinase (BTK) inhibitor have one of several high-risk characteristics, including complex karyotype, 17p-chromosome deletion, or a TP53 mutation. In contrast, genomically stable patients have a 4-year progression-free survival (PFS) rate of about 98% on single agent Bruton’s tyrosine kinase inhibitor therapy.

Dr. Furman

“In people who are genomically unstable, almost half will have their CLL progress on single agent BTK inhibitor therapy. These patients, I’d like to treat with combination of a Bruton’s tyrosine kinase inhibitor plus venetoclax,” said Richard R. Furman, MD, Morton Coleman MD Distinguished Professor of medicine at Weill Cornell Medicine/New York Presbyterian Hospital. He presented on treating relapsed CLL at the Great Debates and Updates Hematologic Malignancies Conference in New York, April 13-15.

The efficacy of venetoclax (VX) in treating high risk CLL patients was demonstrated in the 2019 CLL14 trial (NCT02242942) in which the main entry criteria were being treatment-naive and being considered “unfit” for treatment, meaning that a patient’s Cumulative Illness Rating Scale score was >6, or they presented with decreased kidney function. Study participants were treated with six cycles of either venetoclax-obinutuzumab (VO) or chlorambucil-obinutuzumab (CO); the 4-year PFS was 74% vs. 35.4% (P < .0001) respectively. After 12 cycles of treatment, the 74% of patients in the VO group achieved undetectable minimal residual disease rate (MRD) vs. 32% in the CO group.

Achievement of MRD did predict for outcome, but Dr. Furman concluded that while MRD is a powerful prognostic tool, it is not clinically useful given the inability of its results to guide therapy. He went on to emphasize that “of those patients who achieved MRD levels of 10-4 after 12 cycles of venetoclax, 50% had worsening and 50% had improvement of the residual disease, suggesting that we do not know the optimal duration of venetoclax treatment, as half of the patients still continue to derive benefit.”

Dr. Furman noted that ibrutinib (IB) and the second-generation drugs zanubrutinib (ZB) and acalabrutinib (AL) are all effective, but that the second-generation Bruton’s tyrosine kinase inhibitors enable patients to derive the benefit of remaining on treatment longer, because the rate of concerning cardiac complications is lower than with IB.

The ALPINE trial (NCT03734016) confirmed ZB’s significantly improved overall response rate at 78.3% vs. IB’s 62.5%, as well as a lower rate of atrial fibrillation (2.5%) vs. IB (10.1%).

Noninferiority of AL vs. IB in high-risk relapsed CLL patients was demonstrated in the ELEVATE-RR trial (NCT02477696) with both drugs having a median PFS of 38.4 months. With a median follow up of 41 months, AL demonstrated less atrial fibrillation/atrial flutter, compared with IB (9.4% vs. 16.0%) with no difference in grade > 3 infections. Furthermore, AL’s half-life being shorter than that of IB means that side effects are shorter lived.

“That’s the advantage of the second generation of Bruton’s tyrosine kinase inhibitors,” said Stefan Glück, MD, PhD, a hematologic oncologist and independent consultant who was formerly affiliated with the Sylvester Comprehensive Cancer Center and taught at the Miller School of Medicine at the University of Miami.

Dr. Glück added that “acalabrutinib and zanubrutinib have demonstrated strong efficacy and safety. When patients no longer respond to these drugs, the addition of VX is crucial. It has a completely different mechanism of action and can reverse resistance to Bruton’s tyrosine kinase inhibitors, allowing them to start working again.”

Dr. Furman also discussed proteolysis-targeting chimeras (PROTACs), one area that he expects to make a significant impact as a future therapy for CLL and many other malignancies. Despite the fact these agents are in phase I studies, he commented that “they appear, thus far, to have tremendous potential.”

Dr. Furman disclosed relationships with Abbvie, Acerta/AstraZeneca, Beigene, Jansen, TG Therapeutics, Genentech-Roche, Incyte Corporation, Loxo Oncology, MEI Pharma, Morphosys, Pharmacyclics, Sanofi/Genzyme, and X4 Pharmaceuticals. Dr. Glück reported no conflicts of interest.
 

Weight loss in otherwise healthy older adults is linked to an increased risk of mortality, even from conditions not typically associated with weight change, with a substantially stronger link in men versus women, suggesting the need for clinicians to be alert to such changes.

“Our study emphasizes the importance of weight loss even in relatively healthy individuals who are free from evident cardiovascular disease [CVD], dementia, physical disability, or life-limiting chronic illness,” first author Monira Hussain, MBBS, MPH, PhD, said in an interview.

“Clinicians should be aware that even minor weight loss of 5% or more in older adults without life-limiting illnesses can increase mortality risk,” Dr. Hussain said. “Regular monitoring of weight changes can help early identification of associated risks.”

The study was published online in JAMA Network Open.

The researchers noted that data on the significance of weight changes among older individuals who are otherwise relatively healthy and not diagnosed with life-limited diseases are limited, with the exception that “it is widely acknowledged that weight loss may precede a diagnosis of cancer.” But the association with the other types of non–cancer-related premature death is notable.

“In our study, weight loss also preceded an increased mortality from CVD and other causes, [such as] deaths from trauma, dementia, Parkinson disease, and other less common causes.”

Therefore, “a likely explanation for these findings is that weight loss can be an early prodromal indicator of the presence of various life-shortening diseases,” Dr. Hussain, of Monash University, Melbourne, and colleagues wrote.

In terms of why weight loss shows such a stronger link to mortality in older men, compared with women, Dr. Hussain speculated that this may be caused by “differences in body composition,” between the two sexes. “Men have a higher proportion of muscle and bone mass, and weight loss [in men] primarily involves loss of these tissues.”
 

10% weight loss quadrupled risk of premature death among men

To investigate this phenomenon, the researchers conducted a post hoc analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized trial, which included information on a variety of body size parameters, such as weight and waist circumference, measured annually, from a large population of healthy individuals with no evident CVD, dementia, physical disability, or life-limiting chronic illness.

The 16,523 participants included in the study had a mean age of 75 years and 55.6% were women. During a mean follow-up of 4.4 years, 1,256 deaths occurred in the cohort.

Looking at rates of all-cause mortality, stratified by gender, the results showed that among men who had a 5%-10% decrease in weight over the course of the study, the risk of all-cause mortality was 33% higher than that of men who had a stable weight (less than 5% change; hazard ratio, 1.33).

Among men who had a more than 10% decrease in weight, the mortality risk was as much as 289%, or nearly four times higher compared with those with a stable weight (HR, 3.89).

For women, the mortality risk was also increased, however, to a lesser degree. A 5%-10% loss of body weight was associated with a 26% increased mortality risk (HR, 1.26), and a loss of more than 10% was linked to a 114% increased risk of all-cause mortality (HR, 2.14).

In terms of cancer-specific deaths, the risk was significantly increased only among men who had a greater than 10% weight decrease (HR, 3.49), while the increased risk in women was observed with a 5%-10% decrease in weight (HR, 1.44) as well as a more than 10% decrease (HR, 2.78).

The risk of CVD-specific death was significantly increased with a more than 10% decrease in weight in both sexes, but the risk was again higher among men (HR, 3.14) than women (HR, 1.92), compared with stable weight groups.

And the noncancer, non–CVD-specific mortality risk was nearly five times higher among men who had a more than 10% decrease in weight versus stable weight (HR, 4.98); however, the association was not significant among women (HR, 1.49).

Looking at the effects of change in waist circumference, a decrease of more than 10% was associated with a higher risk in all-cause mortality that was again higher for men (HR, 2.14) versus women (HR, 1.34); however, no link with all-cause mortality was observed with a less than 10% decrease in either sex.

A greater than 10% decrease in waist circumference was also associated with higher risk of cancer death for men and women, and higher noncancer, non-CVD death among men, but not women, while there was no association between waist circumference and CVD mortality in men or women.
 

Association with mortality remained after adjustment for hospitalization

The results persisted after adjustment for age, frailty status, baseline body mass index, country of birth, smoking, hypertension, diabetes, and hospitalization in the previous 24 months.

The adjustment for recent hospitalization was especially important for ruling out weight loss that may have occurred because of hospitalization for acute conditions that could have contributed to mortality, the authors noted.

The authors reported no relevant financial relationships.

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

Weight loss in otherwise healthy older adults is linked to an increased risk of mortality, even from conditions not typically associated with weight change, with a substantially stronger link in men versus women, suggesting the need for clinicians to be alert to such changes.

“Our study emphasizes the importance of weight loss even in relatively healthy individuals who are free from evident cardiovascular disease [CVD], dementia, physical disability, or life-limiting chronic illness,” first author Monira Hussain, MBBS, MPH, PhD, said in an interview.

“Clinicians should be aware that even minor weight loss of 5% or more in older adults without life-limiting illnesses can increase mortality risk,” Dr. Hussain said. “Regular monitoring of weight changes can help early identification of associated risks.”

The study was published online in JAMA Network Open.

The researchers noted that data on the significance of weight changes among older individuals who are otherwise relatively healthy and not diagnosed with life-limited diseases are limited, with the exception that “it is widely acknowledged that weight loss may precede a diagnosis of cancer.” But the association with the other types of non–cancer-related premature death is notable.

“In our study, weight loss also preceded an increased mortality from CVD and other causes, [such as] deaths from trauma, dementia, Parkinson disease, and other less common causes.”

Therefore, “a likely explanation for these findings is that weight loss can be an early prodromal indicator of the presence of various life-shortening diseases,” Dr. Hussain, of Monash University, Melbourne, and colleagues wrote.

In terms of why weight loss shows such a stronger link to mortality in older men, compared with women, Dr. Hussain speculated that this may be caused by “differences in body composition,” between the two sexes. “Men have a higher proportion of muscle and bone mass, and weight loss [in men] primarily involves loss of these tissues.”
 

10% weight loss quadrupled risk of premature death among men

To investigate this phenomenon, the researchers conducted a post hoc analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized trial, which included information on a variety of body size parameters, such as weight and waist circumference, measured annually, from a large population of healthy individuals with no evident CVD, dementia, physical disability, or life-limiting chronic illness.

The 16,523 participants included in the study had a mean age of 75 years and 55.6% were women. During a mean follow-up of 4.4 years, 1,256 deaths occurred in the cohort.

Looking at rates of all-cause mortality, stratified by gender, the results showed that among men who had a 5%-10% decrease in weight over the course of the study, the risk of all-cause mortality was 33% higher than that of men who had a stable weight (less than 5% change; hazard ratio, 1.33).

Among men who had a more than 10% decrease in weight, the mortality risk was as much as 289%, or nearly four times higher compared with those with a stable weight (HR, 3.89).

For women, the mortality risk was also increased, however, to a lesser degree. A 5%-10% loss of body weight was associated with a 26% increased mortality risk (HR, 1.26), and a loss of more than 10% was linked to a 114% increased risk of all-cause mortality (HR, 2.14).

In terms of cancer-specific deaths, the risk was significantly increased only among men who had a greater than 10% weight decrease (HR, 3.49), while the increased risk in women was observed with a 5%-10% decrease in weight (HR, 1.44) as well as a more than 10% decrease (HR, 2.78).

The risk of CVD-specific death was significantly increased with a more than 10% decrease in weight in both sexes, but the risk was again higher among men (HR, 3.14) than women (HR, 1.92), compared with stable weight groups.

And the noncancer, non–CVD-specific mortality risk was nearly five times higher among men who had a more than 10% decrease in weight versus stable weight (HR, 4.98); however, the association was not significant among women (HR, 1.49).

Looking at the effects of change in waist circumference, a decrease of more than 10% was associated with a higher risk in all-cause mortality that was again higher for men (HR, 2.14) versus women (HR, 1.34); however, no link with all-cause mortality was observed with a less than 10% decrease in either sex.

A greater than 10% decrease in waist circumference was also associated with higher risk of cancer death for men and women, and higher noncancer, non-CVD death among men, but not women, while there was no association between waist circumference and CVD mortality in men or women.
 

Association with mortality remained after adjustment for hospitalization

The results persisted after adjustment for age, frailty status, baseline body mass index, country of birth, smoking, hypertension, diabetes, and hospitalization in the previous 24 months.

The adjustment for recent hospitalization was especially important for ruling out weight loss that may have occurred because of hospitalization for acute conditions that could have contributed to mortality, the authors noted.

The authors reported no relevant financial relationships.

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

Weight loss in otherwise healthy older adults is linked to an increased risk of mortality, even from conditions not typically associated with weight change, with a substantially stronger link in men versus women, suggesting the need for clinicians to be alert to such changes.

“Our study emphasizes the importance of weight loss even in relatively healthy individuals who are free from evident cardiovascular disease [CVD], dementia, physical disability, or life-limiting chronic illness,” first author Monira Hussain, MBBS, MPH, PhD, said in an interview.

“Clinicians should be aware that even minor weight loss of 5% or more in older adults without life-limiting illnesses can increase mortality risk,” Dr. Hussain said. “Regular monitoring of weight changes can help early identification of associated risks.”

The study was published online in JAMA Network Open.

The researchers noted that data on the significance of weight changes among older individuals who are otherwise relatively healthy and not diagnosed with life-limited diseases are limited, with the exception that “it is widely acknowledged that weight loss may precede a diagnosis of cancer.” But the association with the other types of non–cancer-related premature death is notable.

“In our study, weight loss also preceded an increased mortality from CVD and other causes, [such as] deaths from trauma, dementia, Parkinson disease, and other less common causes.”

Therefore, “a likely explanation for these findings is that weight loss can be an early prodromal indicator of the presence of various life-shortening diseases,” Dr. Hussain, of Monash University, Melbourne, and colleagues wrote.

In terms of why weight loss shows such a stronger link to mortality in older men, compared with women, Dr. Hussain speculated that this may be caused by “differences in body composition,” between the two sexes. “Men have a higher proportion of muscle and bone mass, and weight loss [in men] primarily involves loss of these tissues.”
 

10% weight loss quadrupled risk of premature death among men

To investigate this phenomenon, the researchers conducted a post hoc analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized trial, which included information on a variety of body size parameters, such as weight and waist circumference, measured annually, from a large population of healthy individuals with no evident CVD, dementia, physical disability, or life-limiting chronic illness.

The 16,523 participants included in the study had a mean age of 75 years and 55.6% were women. During a mean follow-up of 4.4 years, 1,256 deaths occurred in the cohort.

Looking at rates of all-cause mortality, stratified by gender, the results showed that among men who had a 5%-10% decrease in weight over the course of the study, the risk of all-cause mortality was 33% higher than that of men who had a stable weight (less than 5% change; hazard ratio, 1.33).

Among men who had a more than 10% decrease in weight, the mortality risk was as much as 289%, or nearly four times higher compared with those with a stable weight (HR, 3.89).

For women, the mortality risk was also increased, however, to a lesser degree. A 5%-10% loss of body weight was associated with a 26% increased mortality risk (HR, 1.26), and a loss of more than 10% was linked to a 114% increased risk of all-cause mortality (HR, 2.14).

In terms of cancer-specific deaths, the risk was significantly increased only among men who had a greater than 10% weight decrease (HR, 3.49), while the increased risk in women was observed with a 5%-10% decrease in weight (HR, 1.44) as well as a more than 10% decrease (HR, 2.78).

The risk of CVD-specific death was significantly increased with a more than 10% decrease in weight in both sexes, but the risk was again higher among men (HR, 3.14) than women (HR, 1.92), compared with stable weight groups.

And the noncancer, non–CVD-specific mortality risk was nearly five times higher among men who had a more than 10% decrease in weight versus stable weight (HR, 4.98); however, the association was not significant among women (HR, 1.49).

Looking at the effects of change in waist circumference, a decrease of more than 10% was associated with a higher risk in all-cause mortality that was again higher for men (HR, 2.14) versus women (HR, 1.34); however, no link with all-cause mortality was observed with a less than 10% decrease in either sex.

A greater than 10% decrease in waist circumference was also associated with higher risk of cancer death for men and women, and higher noncancer, non-CVD death among men, but not women, while there was no association between waist circumference and CVD mortality in men or women.
 

Association with mortality remained after adjustment for hospitalization

The results persisted after adjustment for age, frailty status, baseline body mass index, country of birth, smoking, hypertension, diabetes, and hospitalization in the previous 24 months.

The adjustment for recent hospitalization was especially important for ruling out weight loss that may have occurred because of hospitalization for acute conditions that could have contributed to mortality, the authors noted.

The authors reported no relevant financial relationships.

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

The new COVID-19 strain known as “Arcturus” has increased in the United States so much that it has been added to the Centers for Disease and Control’s watch list.

Officially labeled XBB.1.16, Arcturus is a subvariant of Omicron that was first seen in India and has been on the World Health Organization’s watchlist since the end of March. The CDC’s most recent update now lists Arcturus as causing 7% of U.S. coronavirus cases, landing it in second place behind its long-predominant Omicron cousin XBB.1.5, which causes 78% of cases.

Arcturus is more transmissible but not more dangerous than recent chart-topping strains, experts say.

“It is causing increasing case counts in certain parts of the world, including India. We’re not seeing high rates of XBB.1.16 yet in the United States, but it may become more prominent in coming weeks,” Mayo Clinic viral disease expert Matthew Binnicker, PhD, told The Seattle Times.

Arcturus has been causing a new symptom in children, Indian medical providers have reported.

“One new feature of cases caused by this variant is that it seems to be causing conjunctivitis, or red and itchy eyes, in young patients,” Dr. Binnicker said. “This is not something that we’ve seen with prior strains of the virus.”

More than 11,000 people in the United States remained hospitalized with COVID at the end of last week, and 1,327 people died of the virus last week, CDC data show. To date, 6.9 million people worldwide have died from COVID, the WHO says. Of those deaths, more than 1.1 million occurred in the U.S.

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

The new COVID-19 strain known as “Arcturus” has increased in the United States so much that it has been added to the Centers for Disease and Control’s watch list.

Officially labeled XBB.1.16, Arcturus is a subvariant of Omicron that was first seen in India and has been on the World Health Organization’s watchlist since the end of March. The CDC’s most recent update now lists Arcturus as causing 7% of U.S. coronavirus cases, landing it in second place behind its long-predominant Omicron cousin XBB.1.5, which causes 78% of cases.

Arcturus is more transmissible but not more dangerous than recent chart-topping strains, experts say.

“It is causing increasing case counts in certain parts of the world, including India. We’re not seeing high rates of XBB.1.16 yet in the United States, but it may become more prominent in coming weeks,” Mayo Clinic viral disease expert Matthew Binnicker, PhD, told The Seattle Times.

Arcturus has been causing a new symptom in children, Indian medical providers have reported.

“One new feature of cases caused by this variant is that it seems to be causing conjunctivitis, or red and itchy eyes, in young patients,” Dr. Binnicker said. “This is not something that we’ve seen with prior strains of the virus.”

More than 11,000 people in the United States remained hospitalized with COVID at the end of last week, and 1,327 people died of the virus last week, CDC data show. To date, 6.9 million people worldwide have died from COVID, the WHO says. Of those deaths, more than 1.1 million occurred in the U.S.

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

The new COVID-19 strain known as “Arcturus” has increased in the United States so much that it has been added to the Centers for Disease and Control’s watch list.

Officially labeled XBB.1.16, Arcturus is a subvariant of Omicron that was first seen in India and has been on the World Health Organization’s watchlist since the end of March. The CDC’s most recent update now lists Arcturus as causing 7% of U.S. coronavirus cases, landing it in second place behind its long-predominant Omicron cousin XBB.1.5, which causes 78% of cases.

Arcturus is more transmissible but not more dangerous than recent chart-topping strains, experts say.

“It is causing increasing case counts in certain parts of the world, including India. We’re not seeing high rates of XBB.1.16 yet in the United States, but it may become more prominent in coming weeks,” Mayo Clinic viral disease expert Matthew Binnicker, PhD, told The Seattle Times.

Arcturus has been causing a new symptom in children, Indian medical providers have reported.

“One new feature of cases caused by this variant is that it seems to be causing conjunctivitis, or red and itchy eyes, in young patients,” Dr. Binnicker said. “This is not something that we’ve seen with prior strains of the virus.”

More than 11,000 people in the United States remained hospitalized with COVID at the end of last week, and 1,327 people died of the virus last week, CDC data show. To date, 6.9 million people worldwide have died from COVID, the WHO says. Of those deaths, more than 1.1 million occurred in the U.S.

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

Among patients with unresectable desmoplastic melanoma (DM), a prospective trial showed that single-agent treatment with the programmed death 1 (PD-1) inhibitor pembrolizumab led to a dramatic overall response rate.

The findings could represent a new standard of treatment for this extremely rare tumor.

The study was inspired by a previous retrospective analysis which found an overall response rate of 77% and a complete response of 32% to anti–PD-1 monotherapy.

The ORR is about double what is seen in melanoma more generally, according to Kari Kendra, MD, PhD, who presented the study at the annual meeting of the American Association for Cancer Research.

“Our study was a positive study. Of note, in the retrospective study, they saw a complete response rate of 32%, which was amazingly similar to what we found. [The findings support] the use of single agent anti–PD-1 immunotherapy as first line treatment for most patients with unresectable desmoplastic melanoma. [There was 89% overall response and we saw] dramatic responses across the board,” said Dr. Kendra, who is a medical oncologist at Ohio State University Wexner Medical Center, Columbus.

The findings drew a strong reaction. “In a rare tumor session, to see response curves like that, it’s just outstanding,” said the session’s cochair Brian Van Tine, MD, PhD, who is a professor of medical oncology at Washington University in St. Louis.

“This really is one of the highest tumor response rates to immunotherapy that we are seeing in any cancer. And I think may also highlight the fact that we shouldn’t think of all cutaneous melanomas as one disease, given the heterogeneity in tumor responses based on some of the pathologic and molecular characteristics,” said Zeynep Aroglu, MD, who served as a discussant but was also one of the investigators who enrolled patients for the trial.

Desmoplastic melanoma represents about 4% of all cutaneous melanoma diagnoses, and its unique pathology can make it difficult to diagnose. That often leads to a late diagnosis, according to Dr. Aroglu. They typically occur in elderly patients, in the head and neck area, and are associated with sun exposure. DM also tends to have a high mutation burden, Dr. Aroglu said during the session.

It remains to be seen why there is such a high response rate in this tumor type, even among tumor types with mutation burdens that are nearly as high. DM tumors are often driven by neurofibromatosis type 1, but other tumors driven by NF-1 don’t have as high of a response rate to immunotherapy. The tumor environment could also play a role, she said.

“Is it a combination of all these factors? I think some of the ongoing analysis of tumor samples that Dr. Kendra mentioned may help to answer some of these questions,” Dr. Aroglu continued.

She also noted that the melanoma field is increasingly turning to combination of anti–PD-1 therapy with agents like that target LAG3 or CTLA4. Such combinations can achieve higher response rates, but at a cost of higher rates of grade 3-4 adverse events than anti–PD-1 inhibitors alone. “I wonder if for desmoplastic melanomas in light of this data, do we consider de-escalating therapy, given these very high response rates to PD-1 alone, given also the elderly age of many of these patients, because even the PD-1–LAG3 combo still has a higher rate of toxicity than PD-1 monotherapy. Perhaps the immunotherapy combinations can be reserved for those rare desmoplastic patients who are resistant to PD-1 alone,” said Dr. Aroglu.
 

Study details and adverse events

Twenty-seven patients were enrolled in the study; 93% were male, all were White, and 22% had elevated baseline lactate dehydrogenase. About 63% had disease located in the head and neck area, 33% experienced a complete response (P < .001), and 56% had a partial response for an ORR of 89%. The result surpassed the primary endpoint target of at least a 20% complete response rate.

The 2-year progression-free survival was 74%, and 2-year overall survival was 89%. The most common toxicities were fatigue (56%), diarrhea (33%), maculopapular rash (30%), pruritus (22%), anemia (19%), arthralgia (19%), and decreased lymphocyte count (19%). There were two grade 4 adverse events: a lipase increase and a lung infection accompanied by sepsis.

The researchers also carried out whole exome sequencing of biopsies and found that 67% had NF-1 loss of function mutations.

Dr. Aroglu has served on advisory boards for Pfizer, Array, Eisai, Genentech, Natera, Novartis, OncoSec, and Regeneron. She has received research support from Boehringer Ingelheim, Pfizer, and Novartis. Dr. Kendra has received institutional support from Bristol Myers-Squibb and trial support from CheckMate Pharmaceuticals, GlaxoSmithKline, Immunocore, Medspace, Merck, Novartis, and Varian Medical Systems. Dr. Van Tine has financial relationships with a wide range of pharmaceutical companies.

Among patients with unresectable desmoplastic melanoma (DM), a prospective trial showed that single-agent treatment with the programmed death 1 (PD-1) inhibitor pembrolizumab led to a dramatic overall response rate.

The findings could represent a new standard of treatment for this extremely rare tumor.

The study was inspired by a previous retrospective analysis which found an overall response rate of 77% and a complete response of 32% to anti–PD-1 monotherapy.

The ORR is about double what is seen in melanoma more generally, according to Kari Kendra, MD, PhD, who presented the study at the annual meeting of the American Association for Cancer Research.

“Our study was a positive study. Of note, in the retrospective study, they saw a complete response rate of 32%, which was amazingly similar to what we found. [The findings support] the use of single agent anti–PD-1 immunotherapy as first line treatment for most patients with unresectable desmoplastic melanoma. [There was 89% overall response and we saw] dramatic responses across the board,” said Dr. Kendra, who is a medical oncologist at Ohio State University Wexner Medical Center, Columbus.

The findings drew a strong reaction. “In a rare tumor session, to see response curves like that, it’s just outstanding,” said the session’s cochair Brian Van Tine, MD, PhD, who is a professor of medical oncology at Washington University in St. Louis.

“This really is one of the highest tumor response rates to immunotherapy that we are seeing in any cancer. And I think may also highlight the fact that we shouldn’t think of all cutaneous melanomas as one disease, given the heterogeneity in tumor responses based on some of the pathologic and molecular characteristics,” said Zeynep Aroglu, MD, who served as a discussant but was also one of the investigators who enrolled patients for the trial.

Desmoplastic melanoma represents about 4% of all cutaneous melanoma diagnoses, and its unique pathology can make it difficult to diagnose. That often leads to a late diagnosis, according to Dr. Aroglu. They typically occur in elderly patients, in the head and neck area, and are associated with sun exposure. DM also tends to have a high mutation burden, Dr. Aroglu said during the session.

It remains to be seen why there is such a high response rate in this tumor type, even among tumor types with mutation burdens that are nearly as high. DM tumors are often driven by neurofibromatosis type 1, but other tumors driven by NF-1 don’t have as high of a response rate to immunotherapy. The tumor environment could also play a role, she said.

“Is it a combination of all these factors? I think some of the ongoing analysis of tumor samples that Dr. Kendra mentioned may help to answer some of these questions,” Dr. Aroglu continued.

She also noted that the melanoma field is increasingly turning to combination of anti–PD-1 therapy with agents like that target LAG3 or CTLA4. Such combinations can achieve higher response rates, but at a cost of higher rates of grade 3-4 adverse events than anti–PD-1 inhibitors alone. “I wonder if for desmoplastic melanomas in light of this data, do we consider de-escalating therapy, given these very high response rates to PD-1 alone, given also the elderly age of many of these patients, because even the PD-1–LAG3 combo still has a higher rate of toxicity than PD-1 monotherapy. Perhaps the immunotherapy combinations can be reserved for those rare desmoplastic patients who are resistant to PD-1 alone,” said Dr. Aroglu.
 

Study details and adverse events

Twenty-seven patients were enrolled in the study; 93% were male, all were White, and 22% had elevated baseline lactate dehydrogenase. About 63% had disease located in the head and neck area, 33% experienced a complete response (P < .001), and 56% had a partial response for an ORR of 89%. The result surpassed the primary endpoint target of at least a 20% complete response rate.

The 2-year progression-free survival was 74%, and 2-year overall survival was 89%. The most common toxicities were fatigue (56%), diarrhea (33%), maculopapular rash (30%), pruritus (22%), anemia (19%), arthralgia (19%), and decreased lymphocyte count (19%). There were two grade 4 adverse events: a lipase increase and a lung infection accompanied by sepsis.

The researchers also carried out whole exome sequencing of biopsies and found that 67% had NF-1 loss of function mutations.

Dr. Aroglu has served on advisory boards for Pfizer, Array, Eisai, Genentech, Natera, Novartis, OncoSec, and Regeneron. She has received research support from Boehringer Ingelheim, Pfizer, and Novartis. Dr. Kendra has received institutional support from Bristol Myers-Squibb and trial support from CheckMate Pharmaceuticals, GlaxoSmithKline, Immunocore, Medspace, Merck, Novartis, and Varian Medical Systems. Dr. Van Tine has financial relationships with a wide range of pharmaceutical companies.

Among patients with unresectable desmoplastic melanoma (DM), a prospective trial showed that single-agent treatment with the programmed death 1 (PD-1) inhibitor pembrolizumab led to a dramatic overall response rate.

The findings could represent a new standard of treatment for this extremely rare tumor.

The study was inspired by a previous retrospective analysis which found an overall response rate of 77% and a complete response of 32% to anti–PD-1 monotherapy.

The ORR is about double what is seen in melanoma more generally, according to Kari Kendra, MD, PhD, who presented the study at the annual meeting of the American Association for Cancer Research.

“Our study was a positive study. Of note, in the retrospective study, they saw a complete response rate of 32%, which was amazingly similar to what we found. [The findings support] the use of single agent anti–PD-1 immunotherapy as first line treatment for most patients with unresectable desmoplastic melanoma. [There was 89% overall response and we saw] dramatic responses across the board,” said Dr. Kendra, who is a medical oncologist at Ohio State University Wexner Medical Center, Columbus.

The findings drew a strong reaction. “In a rare tumor session, to see response curves like that, it’s just outstanding,” said the session’s cochair Brian Van Tine, MD, PhD, who is a professor of medical oncology at Washington University in St. Louis.

“This really is one of the highest tumor response rates to immunotherapy that we are seeing in any cancer. And I think may also highlight the fact that we shouldn’t think of all cutaneous melanomas as one disease, given the heterogeneity in tumor responses based on some of the pathologic and molecular characteristics,” said Zeynep Aroglu, MD, who served as a discussant but was also one of the investigators who enrolled patients for the trial.

Desmoplastic melanoma represents about 4% of all cutaneous melanoma diagnoses, and its unique pathology can make it difficult to diagnose. That often leads to a late diagnosis, according to Dr. Aroglu. They typically occur in elderly patients, in the head and neck area, and are associated with sun exposure. DM also tends to have a high mutation burden, Dr. Aroglu said during the session.

It remains to be seen why there is such a high response rate in this tumor type, even among tumor types with mutation burdens that are nearly as high. DM tumors are often driven by neurofibromatosis type 1, but other tumors driven by NF-1 don’t have as high of a response rate to immunotherapy. The tumor environment could also play a role, she said.

“Is it a combination of all these factors? I think some of the ongoing analysis of tumor samples that Dr. Kendra mentioned may help to answer some of these questions,” Dr. Aroglu continued.

She also noted that the melanoma field is increasingly turning to combination of anti–PD-1 therapy with agents like that target LAG3 or CTLA4. Such combinations can achieve higher response rates, but at a cost of higher rates of grade 3-4 adverse events than anti–PD-1 inhibitors alone. “I wonder if for desmoplastic melanomas in light of this data, do we consider de-escalating therapy, given these very high response rates to PD-1 alone, given also the elderly age of many of these patients, because even the PD-1–LAG3 combo still has a higher rate of toxicity than PD-1 monotherapy. Perhaps the immunotherapy combinations can be reserved for those rare desmoplastic patients who are resistant to PD-1 alone,” said Dr. Aroglu.
 

Study details and adverse events

Twenty-seven patients were enrolled in the study; 93% were male, all were White, and 22% had elevated baseline lactate dehydrogenase. About 63% had disease located in the head and neck area, 33% experienced a complete response (P < .001), and 56% had a partial response for an ORR of 89%. The result surpassed the primary endpoint target of at least a 20% complete response rate.

The 2-year progression-free survival was 74%, and 2-year overall survival was 89%. The most common toxicities were fatigue (56%), diarrhea (33%), maculopapular rash (30%), pruritus (22%), anemia (19%), arthralgia (19%), and decreased lymphocyte count (19%). There were two grade 4 adverse events: a lipase increase and a lung infection accompanied by sepsis.

The researchers also carried out whole exome sequencing of biopsies and found that 67% had NF-1 loss of function mutations.

Dr. Aroglu has served on advisory boards for Pfizer, Array, Eisai, Genentech, Natera, Novartis, OncoSec, and Regeneron. She has received research support from Boehringer Ingelheim, Pfizer, and Novartis. Dr. Kendra has received institutional support from Bristol Myers-Squibb and trial support from CheckMate Pharmaceuticals, GlaxoSmithKline, Immunocore, Medspace, Merck, Novartis, and Varian Medical Systems. Dr. Van Tine has financial relationships with a wide range of pharmaceutical companies.

Universal screening of all U.S. adults aged 35-70 years for prediabetes and type 2 diabetes, regardless of body mass index, would provide the fairest means of detection, according to a new analysis.

This would better detect prediabetes and diabetes in ethnic groups that have a higher risk of diabetes at lower cutoffs. Compared with White individuals, Black or Hispanic adults have a higher risk of developing type 2 diabetes at a younger age, and Asian, Hispanic, and Black Americans all have a higher risk of developing it at a lower BMI. 

In the new study, researchers examined six different screening scenarios in a nationally representative sample without diabetes.

They compared screening for prediabetes and type 2 diabetes using criteria from the 2021 U.S. Preventive Services Task Force (USPSTF) recommendations with the 2015 USPSTF recommendations, as well as four other screening thresholds with lower age or weight.

Universal screening for prediabetes and diabetes at age 35-70, regardless of BMI – which appears to be the sweet spot for most equitable detection in different races – may be easier to put into practice because it will mean clinicians don’t have to remember alternate cutoffs for different patient groups, the researchers suggested.

“All major racial and ethnic minority groups develop diabetes at lower weights than White adults, and it’s most pronounced for Asian Americans,” lead author Matthew J. O’Brien, MD, explained in a press release.

“If we make decisions about diabetes testing based on weight we will miss some people from racial and ethnic minority groups who are developing prediabetes and diabetes at lower weights,” said Dr. O’Brien, of Northwestern University, Chicago.

Going forward, to achieve equity in diagnosing prediabetes and diabetes “also requires addressing structural barriers [facing racial and ethnic minorities], which include not having a usual source of primary care, lacking health insurance, or having copays for screening tests based on insurance coverage,” the authors noted in their paper, published online in the American Journal of Preventive Medicine.

There is also a need for further study to examine the cost-effectiveness of any approach, and to study the impact of screening criteria on diagnosis, treatment, and outcomes in diverse populations.
 

Nationally representative sample, six screening scenarios

In the overall U.S. population, 81% of adults with prediabetes are unaware they have it, said Dr. O’Brien and colleagues, and 23% of diabetes cases are undiagnosed.

And Black, Hispanic, or Asian individuals have a nearly twofold higher prevalence of diabetes compared with White individuals.

The 2021 USPSTF recommendations state that clinicians should screen asymptomatic adults aged 35-70 years with overweight/obesity (BMI ≥ 25 kg/m²) and “should consider screening at an earlier age in persons from groups with disproportionately high incidence and prevalence (American Indian/Alaska Native, Asian American, Black, Hispanic/Latino, or Native Hawaiian/Pacific Islander persons) or in persons who have a family history of diabetes, a history of gestational diabetes, or a history of polycystic ovarian syndrome, and at a lower BMI in Asian American persons. Data suggest that a BMI of 23 or greater may be an appropriate cut point in Asian American persons.”

Dr. O’Brien and colleagues identified 3,243 nonpregnant adults without diagnosed diabetes who participated in the National Health and Nutrition Examination Survey (NHANES) in 2017-2020 and had an A1c blood test. (Half also had a fasting plasma glucose test.)

First, they compared screening using the more recent and earlier USPSTF criteria: BMI of at least 25 kg/m² and age 35-70 (2021 criteria) and BMI of at least 25 kg/m² and age 40-70 (2015 criteria).

They estimated that 13.9 million more adults would be eligible for screening using the 2021 versus the 2015 screening criteria.

The increases in screening eligibility were highest in Hispanic individuals (30.6%), followed by Asian individuals (17.9%), White individuals (14.0%), and Black individuals (13.9%).

Using the USPSTF 2021 versus 2015 screening criteria resulted in marginally higher sensitivity (58.6% vs. 52.9%) but lower specificity (69.3% vs. 76.4%) overall, as well as within each racial group.

Next, the researchers examined screening at two lower age cutoffs and two lower BMI cutoffs: BMI of at least 25 kg/m² and age 30-70, BMI of at least 25 kg/m² and age 18-70, age 35-70 and BMI of at least 23 kg/m², and age 35-70 and any BMI.

Screening at these lower age and weight thresholds resulted in even greater sensitivity and lower specificity than using the 2021 USPSTF criteria, especially among Hispanic, non-Hispanic Black, and Asian adults.

However, screening all adults aged 35-70 years regardless of BMI yielded the most equitable detection of prediabetes and diabetes – with a sensitivity of 67.8% and a specificity of 52.1% in the overall population, and a sensitivity of 70.1%, 70.4%, 68.4%, and 67.6%, and a specificity of 53.8%, 59.9%, 56.2%, and 48.9%, in the Asian, Black, Hispanic, and White subgroups, respectively.

The American Diabetes Association currently recommends screening all adults aged ≥ 35 years, or at any age if they have overweight/obesity and an additional diabetes risk factor, the researchers noted.

The study was partly funded by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. The authors have reported no relevant financial relationships.
 

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

Universal screening of all U.S. adults aged 35-70 years for prediabetes and type 2 diabetes, regardless of body mass index, would provide the fairest means of detection, according to a new analysis.

This would better detect prediabetes and diabetes in ethnic groups that have a higher risk of diabetes at lower cutoffs. Compared with White individuals, Black or Hispanic adults have a higher risk of developing type 2 diabetes at a younger age, and Asian, Hispanic, and Black Americans all have a higher risk of developing it at a lower BMI. 

In the new study, researchers examined six different screening scenarios in a nationally representative sample without diabetes.

They compared screening for prediabetes and type 2 diabetes using criteria from the 2021 U.S. Preventive Services Task Force (USPSTF) recommendations with the 2015 USPSTF recommendations, as well as four other screening thresholds with lower age or weight.

Universal screening for prediabetes and diabetes at age 35-70, regardless of BMI – which appears to be the sweet spot for most equitable detection in different races – may be easier to put into practice because it will mean clinicians don’t have to remember alternate cutoffs for different patient groups, the researchers suggested.

“All major racial and ethnic minority groups develop diabetes at lower weights than White adults, and it’s most pronounced for Asian Americans,” lead author Matthew J. O’Brien, MD, explained in a press release.

“If we make decisions about diabetes testing based on weight we will miss some people from racial and ethnic minority groups who are developing prediabetes and diabetes at lower weights,” said Dr. O’Brien, of Northwestern University, Chicago.

Going forward, to achieve equity in diagnosing prediabetes and diabetes “also requires addressing structural barriers [facing racial and ethnic minorities], which include not having a usual source of primary care, lacking health insurance, or having copays for screening tests based on insurance coverage,” the authors noted in their paper, published online in the American Journal of Preventive Medicine.

There is also a need for further study to examine the cost-effectiveness of any approach, and to study the impact of screening criteria on diagnosis, treatment, and outcomes in diverse populations.
 

Nationally representative sample, six screening scenarios

In the overall U.S. population, 81% of adults with prediabetes are unaware they have it, said Dr. O’Brien and colleagues, and 23% of diabetes cases are undiagnosed.

And Black, Hispanic, or Asian individuals have a nearly twofold higher prevalence of diabetes compared with White individuals.

The 2021 USPSTF recommendations state that clinicians should screen asymptomatic adults aged 35-70 years with overweight/obesity (BMI ≥ 25 kg/m²) and “should consider screening at an earlier age in persons from groups with disproportionately high incidence and prevalence (American Indian/Alaska Native, Asian American, Black, Hispanic/Latino, or Native Hawaiian/Pacific Islander persons) or in persons who have a family history of diabetes, a history of gestational diabetes, or a history of polycystic ovarian syndrome, and at a lower BMI in Asian American persons. Data suggest that a BMI of 23 or greater may be an appropriate cut point in Asian American persons.”

Dr. O’Brien and colleagues identified 3,243 nonpregnant adults without diagnosed diabetes who participated in the National Health and Nutrition Examination Survey (NHANES) in 2017-2020 and had an A1c blood test. (Half also had a fasting plasma glucose test.)

First, they compared screening using the more recent and earlier USPSTF criteria: BMI of at least 25 kg/m² and age 35-70 (2021 criteria) and BMI of at least 25 kg/m² and age 40-70 (2015 criteria).

They estimated that 13.9 million more adults would be eligible for screening using the 2021 versus the 2015 screening criteria.

The increases in screening eligibility were highest in Hispanic individuals (30.6%), followed by Asian individuals (17.9%), White individuals (14.0%), and Black individuals (13.9%).

Using the USPSTF 2021 versus 2015 screening criteria resulted in marginally higher sensitivity (58.6% vs. 52.9%) but lower specificity (69.3% vs. 76.4%) overall, as well as within each racial group.

Next, the researchers examined screening at two lower age cutoffs and two lower BMI cutoffs: BMI of at least 25 kg/m² and age 30-70, BMI of at least 25 kg/m² and age 18-70, age 35-70 and BMI of at least 23 kg/m², and age 35-70 and any BMI.

Screening at these lower age and weight thresholds resulted in even greater sensitivity and lower specificity than using the 2021 USPSTF criteria, especially among Hispanic, non-Hispanic Black, and Asian adults.

However, screening all adults aged 35-70 years regardless of BMI yielded the most equitable detection of prediabetes and diabetes – with a sensitivity of 67.8% and a specificity of 52.1% in the overall population, and a sensitivity of 70.1%, 70.4%, 68.4%, and 67.6%, and a specificity of 53.8%, 59.9%, 56.2%, and 48.9%, in the Asian, Black, Hispanic, and White subgroups, respectively.

The American Diabetes Association currently recommends screening all adults aged ≥ 35 years, or at any age if they have overweight/obesity and an additional diabetes risk factor, the researchers noted.

The study was partly funded by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. The authors have reported no relevant financial relationships.
 

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

Universal screening of all U.S. adults aged 35-70 years for prediabetes and type 2 diabetes, regardless of body mass index, would provide the fairest means of detection, according to a new analysis.

This would better detect prediabetes and diabetes in ethnic groups that have a higher risk of diabetes at lower cutoffs. Compared with White individuals, Black or Hispanic adults have a higher risk of developing type 2 diabetes at a younger age, and Asian, Hispanic, and Black Americans all have a higher risk of developing it at a lower BMI. 

In the new study, researchers examined six different screening scenarios in a nationally representative sample without diabetes.

They compared screening for prediabetes and type 2 diabetes using criteria from the 2021 U.S. Preventive Services Task Force (USPSTF) recommendations with the 2015 USPSTF recommendations, as well as four other screening thresholds with lower age or weight.

Universal screening for prediabetes and diabetes at age 35-70, regardless of BMI – which appears to be the sweet spot for most equitable detection in different races – may be easier to put into practice because it will mean clinicians don’t have to remember alternate cutoffs for different patient groups, the researchers suggested.

“All major racial and ethnic minority groups develop diabetes at lower weights than White adults, and it’s most pronounced for Asian Americans,” lead author Matthew J. O’Brien, MD, explained in a press release.

“If we make decisions about diabetes testing based on weight we will miss some people from racial and ethnic minority groups who are developing prediabetes and diabetes at lower weights,” said Dr. O’Brien, of Northwestern University, Chicago.

Going forward, to achieve equity in diagnosing prediabetes and diabetes “also requires addressing structural barriers [facing racial and ethnic minorities], which include not having a usual source of primary care, lacking health insurance, or having copays for screening tests based on insurance coverage,” the authors noted in their paper, published online in the American Journal of Preventive Medicine.

There is also a need for further study to examine the cost-effectiveness of any approach, and to study the impact of screening criteria on diagnosis, treatment, and outcomes in diverse populations.
 

Nationally representative sample, six screening scenarios

In the overall U.S. population, 81% of adults with prediabetes are unaware they have it, said Dr. O’Brien and colleagues, and 23% of diabetes cases are undiagnosed.

And Black, Hispanic, or Asian individuals have a nearly twofold higher prevalence of diabetes compared with White individuals.

The 2021 USPSTF recommendations state that clinicians should screen asymptomatic adults aged 35-70 years with overweight/obesity (BMI ≥ 25 kg/m²) and “should consider screening at an earlier age in persons from groups with disproportionately high incidence and prevalence (American Indian/Alaska Native, Asian American, Black, Hispanic/Latino, or Native Hawaiian/Pacific Islander persons) or in persons who have a family history of diabetes, a history of gestational diabetes, or a history of polycystic ovarian syndrome, and at a lower BMI in Asian American persons. Data suggest that a BMI of 23 or greater may be an appropriate cut point in Asian American persons.”

Dr. O’Brien and colleagues identified 3,243 nonpregnant adults without diagnosed diabetes who participated in the National Health and Nutrition Examination Survey (NHANES) in 2017-2020 and had an A1c blood test. (Half also had a fasting plasma glucose test.)

First, they compared screening using the more recent and earlier USPSTF criteria: BMI of at least 25 kg/m² and age 35-70 (2021 criteria) and BMI of at least 25 kg/m² and age 40-70 (2015 criteria).

They estimated that 13.9 million more adults would be eligible for screening using the 2021 versus the 2015 screening criteria.

The increases in screening eligibility were highest in Hispanic individuals (30.6%), followed by Asian individuals (17.9%), White individuals (14.0%), and Black individuals (13.9%).

Using the USPSTF 2021 versus 2015 screening criteria resulted in marginally higher sensitivity (58.6% vs. 52.9%) but lower specificity (69.3% vs. 76.4%) overall, as well as within each racial group.

Next, the researchers examined screening at two lower age cutoffs and two lower BMI cutoffs: BMI of at least 25 kg/m² and age 30-70, BMI of at least 25 kg/m² and age 18-70, age 35-70 and BMI of at least 23 kg/m², and age 35-70 and any BMI.

Screening at these lower age and weight thresholds resulted in even greater sensitivity and lower specificity than using the 2021 USPSTF criteria, especially among Hispanic, non-Hispanic Black, and Asian adults.

However, screening all adults aged 35-70 years regardless of BMI yielded the most equitable detection of prediabetes and diabetes – with a sensitivity of 67.8% and a specificity of 52.1% in the overall population, and a sensitivity of 70.1%, 70.4%, 68.4%, and 67.6%, and a specificity of 53.8%, 59.9%, 56.2%, and 48.9%, in the Asian, Black, Hispanic, and White subgroups, respectively.

The American Diabetes Association currently recommends screening all adults aged ≥ 35 years, or at any age if they have overweight/obesity and an additional diabetes risk factor, the researchers noted.

The study was partly funded by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. The authors have reported no relevant financial relationships.
 

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

Vaccines for the world’s most deadly diseases, like cancer and heart disease, will likely be ready by 2030 and could save millions of lives, according to the top doctor at one of the world’s leading drug companies.

The announcement is yet another sign of what many are calling “the golden age” of vaccine development, which is largely credited to the pandemic’s use of mRNA technology to create COVID-19 vaccines.

“I think what we have learned in recent months is that if you ever thought that mRNA was just for infectious diseases, or just for COVID, the evidence now is that that’s absolutely not the case,” Moderna Chief Medical Officer Paul Burton, MD, PhD, told The Guardian. “It can be applied to all sorts of disease areas; we are in cancer, infectious disease, cardiovascular disease, autoimmune diseases, rare disease. We have studies in all of those areas, and they have all shown tremendous promise.”

The U.S. Food and Drug Administration recently designated two new Moderna vaccines as breakthrough therapies: a shot that prevents respiratory syncytial virus (RSV) in older people and a shot that helps prevent the recurrence of melanoma. The FDA’s breakthrough designation is given when a new treatment’s early trial results are substantially better than an existing therapy.

The mRNA vaccine technology that made headlines for its role in COVID-19 vaccines works by teaching the body how to make a specific protein to help the immune system prevent or target a certain disease.

Dr. Burton anticipates that mRNA technology will result in breakthroughs such as a cancer vaccine that can be personalized based on the features of a specific tumor.

“I think we will have mRNA-based therapies for rare diseases that were previously undruggable, and I think that 10 years from now, we will be approaching a world where you truly can identify the genetic cause of a disease and, with relative simplicity, go and edit that out and repair it using mRNA-based technology,” he said. 

The Moderna executive made the statements before its annual update on its vaccine pipeline projects, which the company calls “Vaccines Day.” The Massachusetts-based drugmaker said it has given someone the first dose of a “next-generation” COVID-19 vaccine in a phase III trial, has made progress on a Lyme disease shot, and is developing a vaccine for the highly contagious norovirus.

In all, Moderna expects “six major vaccine product launches in the next few years,” the company said in a statement, adding that it expects the COVID-19 booster market alone to be valued at $15 billion.

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

Vaccines for the world’s most deadly diseases, like cancer and heart disease, will likely be ready by 2030 and could save millions of lives, according to the top doctor at one of the world’s leading drug companies.

The announcement is yet another sign of what many are calling “the golden age” of vaccine development, which is largely credited to the pandemic’s use of mRNA technology to create COVID-19 vaccines.

“I think what we have learned in recent months is that if you ever thought that mRNA was just for infectious diseases, or just for COVID, the evidence now is that that’s absolutely not the case,” Moderna Chief Medical Officer Paul Burton, MD, PhD, told The Guardian. “It can be applied to all sorts of disease areas; we are in cancer, infectious disease, cardiovascular disease, autoimmune diseases, rare disease. We have studies in all of those areas, and they have all shown tremendous promise.”

The U.S. Food and Drug Administration recently designated two new Moderna vaccines as breakthrough therapies: a shot that prevents respiratory syncytial virus (RSV) in older people and a shot that helps prevent the recurrence of melanoma. The FDA’s breakthrough designation is given when a new treatment’s early trial results are substantially better than an existing therapy.

The mRNA vaccine technology that made headlines for its role in COVID-19 vaccines works by teaching the body how to make a specific protein to help the immune system prevent or target a certain disease.

Dr. Burton anticipates that mRNA technology will result in breakthroughs such as a cancer vaccine that can be personalized based on the features of a specific tumor.

“I think we will have mRNA-based therapies for rare diseases that were previously undruggable, and I think that 10 years from now, we will be approaching a world where you truly can identify the genetic cause of a disease and, with relative simplicity, go and edit that out and repair it using mRNA-based technology,” he said. 

The Moderna executive made the statements before its annual update on its vaccine pipeline projects, which the company calls “Vaccines Day.” The Massachusetts-based drugmaker said it has given someone the first dose of a “next-generation” COVID-19 vaccine in a phase III trial, has made progress on a Lyme disease shot, and is developing a vaccine for the highly contagious norovirus.

In all, Moderna expects “six major vaccine product launches in the next few years,” the company said in a statement, adding that it expects the COVID-19 booster market alone to be valued at $15 billion.

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

Vaccines for the world’s most deadly diseases, like cancer and heart disease, will likely be ready by 2030 and could save millions of lives, according to the top doctor at one of the world’s leading drug companies.

The announcement is yet another sign of what many are calling “the golden age” of vaccine development, which is largely credited to the pandemic’s use of mRNA technology to create COVID-19 vaccines.

“I think what we have learned in recent months is that if you ever thought that mRNA was just for infectious diseases, or just for COVID, the evidence now is that that’s absolutely not the case,” Moderna Chief Medical Officer Paul Burton, MD, PhD, told The Guardian. “It can be applied to all sorts of disease areas; we are in cancer, infectious disease, cardiovascular disease, autoimmune diseases, rare disease. We have studies in all of those areas, and they have all shown tremendous promise.”

The U.S. Food and Drug Administration recently designated two new Moderna vaccines as breakthrough therapies: a shot that prevents respiratory syncytial virus (RSV) in older people and a shot that helps prevent the recurrence of melanoma. The FDA’s breakthrough designation is given when a new treatment’s early trial results are substantially better than an existing therapy.

The mRNA vaccine technology that made headlines for its role in COVID-19 vaccines works by teaching the body how to make a specific protein to help the immune system prevent or target a certain disease.

Dr. Burton anticipates that mRNA technology will result in breakthroughs such as a cancer vaccine that can be personalized based on the features of a specific tumor.

“I think we will have mRNA-based therapies for rare diseases that were previously undruggable, and I think that 10 years from now, we will be approaching a world where you truly can identify the genetic cause of a disease and, with relative simplicity, go and edit that out and repair it using mRNA-based technology,” he said. 

The Moderna executive made the statements before its annual update on its vaccine pipeline projects, which the company calls “Vaccines Day.” The Massachusetts-based drugmaker said it has given someone the first dose of a “next-generation” COVID-19 vaccine in a phase III trial, has made progress on a Lyme disease shot, and is developing a vaccine for the highly contagious norovirus.

In all, Moderna expects “six major vaccine product launches in the next few years,” the company said in a statement, adding that it expects the COVID-19 booster market alone to be valued at $15 billion.

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

A new COVID-19 variant that recently landed on the World Health Organization’s radar may cause previously unseen symptoms in children, according to a new report.

While the variant, called “Arcturus,” hasn’t yet made the Centers for Disease Control and Prevention’s watchlist, a prominent pediatrician in India is seeing children with “itchy” or “sticky” eyes, as if they have conjunctivitis or pinkeye, according to  The Times of India. 

The new itchy eye symptom is in addition to a high fever and cough, Vipin M. Vashishtha, MD, said on Twitter, noting that pediatric COVID cases have picked up there for the first time in 6 months.

The country has also seen a rise in adenovirus cases among children with similar symptoms. COVID and adenovirus cannot be distinguished without testing, and many parents don’t want to have their children tested because the swabs are uncomfortable, The Times of India reported. One doctor told the newspaper that among every 10 children with COVID-like symptoms, 2 or 3 of them had tested positive on a COVID test taken at home.

Health officials in India are doing mock drills to check how prepared the country’s hospitals are as India sees cases rise, the BBC reported. India struggled during a COVID-19 surge in 2021, at which time sickened people were seen lying on sidewalks outside overflowing hospitals, and reports surfaced of a black market for private citizens to buy oxygen. 

Arcturus (formally, Omicron subvariant XBB.1.16) made news recently as it landed on the WHO’s radar after surfacing in India. A WHO official called it “one to watch.” The Times of India reported that 234 new cases of XBB.1.16 were included in the country’s latest 5,676 new infections, meaning the subvariant accounts for 4% of new COVID cases.
 

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

A new COVID-19 variant that recently landed on the World Health Organization’s radar may cause previously unseen symptoms in children, according to a new report.

While the variant, called “Arcturus,” hasn’t yet made the Centers for Disease Control and Prevention’s watchlist, a prominent pediatrician in India is seeing children with “itchy” or “sticky” eyes, as if they have conjunctivitis or pinkeye, according to  The Times of India. 

The new itchy eye symptom is in addition to a high fever and cough, Vipin M. Vashishtha, MD, said on Twitter, noting that pediatric COVID cases have picked up there for the first time in 6 months.

The country has also seen a rise in adenovirus cases among children with similar symptoms. COVID and adenovirus cannot be distinguished without testing, and many parents don’t want to have their children tested because the swabs are uncomfortable, The Times of India reported. One doctor told the newspaper that among every 10 children with COVID-like symptoms, 2 or 3 of them had tested positive on a COVID test taken at home.

Health officials in India are doing mock drills to check how prepared the country’s hospitals are as India sees cases rise, the BBC reported. India struggled during a COVID-19 surge in 2021, at which time sickened people were seen lying on sidewalks outside overflowing hospitals, and reports surfaced of a black market for private citizens to buy oxygen. 

Arcturus (formally, Omicron subvariant XBB.1.16) made news recently as it landed on the WHO’s radar after surfacing in India. A WHO official called it “one to watch.” The Times of India reported that 234 new cases of XBB.1.16 were included in the country’s latest 5,676 new infections, meaning the subvariant accounts for 4% of new COVID cases.
 

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

A new COVID-19 variant that recently landed on the World Health Organization’s radar may cause previously unseen symptoms in children, according to a new report.

While the variant, called “Arcturus,” hasn’t yet made the Centers for Disease Control and Prevention’s watchlist, a prominent pediatrician in India is seeing children with “itchy” or “sticky” eyes, as if they have conjunctivitis or pinkeye, according to  The Times of India. 

The new itchy eye symptom is in addition to a high fever and cough, Vipin M. Vashishtha, MD, said on Twitter, noting that pediatric COVID cases have picked up there for the first time in 6 months.

The country has also seen a rise in adenovirus cases among children with similar symptoms. COVID and adenovirus cannot be distinguished without testing, and many parents don’t want to have their children tested because the swabs are uncomfortable, The Times of India reported. One doctor told the newspaper that among every 10 children with COVID-like symptoms, 2 or 3 of them had tested positive on a COVID test taken at home.

Health officials in India are doing mock drills to check how prepared the country’s hospitals are as India sees cases rise, the BBC reported. India struggled during a COVID-19 surge in 2021, at which time sickened people were seen lying on sidewalks outside overflowing hospitals, and reports surfaced of a black market for private citizens to buy oxygen. 

Arcturus (formally, Omicron subvariant XBB.1.16) made news recently as it landed on the WHO’s radar after surfacing in India. A WHO official called it “one to watch.” The Times of India reported that 234 new cases of XBB.1.16 were included in the country’s latest 5,676 new infections, meaning the subvariant accounts for 4% of new COVID cases.
 

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

Pregnancies in users of combined oral contraceptives occur more often when more than two pills are missed or when missed-pill protocols are not followed, based on data from nearly 3,000 women.

Combined oral contraceptives (COCs) remain a popular method of pregnancy prevention worldwide, but efficacy and failure rates can be difficult to determine, as real-word use does not always mirror clinical trials, wrote Mitchell D. Creinin, MD, of the University of California, Davis, and colleagues. Clinical trials include perfect use or method-failure rates, but data on pregnancy risk based on reported adherence alone are lacking, they said.

To assess the effects of missed pills on COC efficacy, the researchers reviewed data from a pair of parallel phase 3 trials, focusing only on adherence to the pill dosing regimen. The findings were published in Obstetrics & Gynecology.

The study population included 1,864 individuals from the United States and Canada, and 1,553 from Europe and Russia.

The participants were healthy, sexually active adults aged 16-50 years in monogamous relationships from 2016 through 2018 who agreed to used estetrol 15 mg and drospirenone 3 mg for up to 13 28-day cycles as their only contraceptive method. Condom use was permitted for protection against sexually transmitted infections if needed. The 28-day COCs included 24 hormonal tablets and 4 placebo tablets. Participants received written instructions for what to do it they missed pills.

The primary outcome was the relationship between missed pills and pregnancies.

A total of 31 pregnancies occurred across both studies; none of these occurred during cycles in which other contraception was used. Of 22 pregnancies in participants who reported taking all pills, 21 reported daily pill use during the cycle in which pregnancy occurred. One participant reported not taking one pill and one participant reported not taking two pills; neither correctly followed the instructions for missed pills.

Pregnancies occurred in .09% of cycles in which participants reported taking all pills, and in 0.25%, 0.83%, and 1.6% of cycles in which participants reported missing one pill, two pills, or more than two pills, respectively.

“Pregnancy rates exceeded 1% only in participants who did not correctly follow missed-pill instructions,” the researchers noted.

Pregnancy rates per cycle ranged from 0% to 0.21%, and 48.4% of the pregnancies occurred during the first four cycles of COC use. Approximately one-third (32.3%) of pregnancies occurred within the first week of a new pill pack.

“Fertilization does not appear to be related to the timing of missed pills within the cycle because pregnancy did not occur more frequently earlier in the cycle (after the placebo pills),” the researchers wrote in their discussion. This finding contradicts previous research suggesting that contraceptive failure rates decrease over the first year of use, they said. In addition, the formulation of the pill used may affect pregnancy rates when pills are missed, as some hormones have longer half-lives, they noted.

The study findings were limited by several factors, including the lack of adjustment for outcomes based on reported sexual activity per cycle, and by the reliance on self-reports.

However, the results were strengthened by the use of the clinical outcomes of pregnancy as the primary outcome, rather than characteristics and predictors of participants who missed pills, the researchers said.

The cycle-based methodology used in the current study may provide insight on the relationship between COC adherence and pregnancy risk that can inform future studies, they concluded.
 

Findings highlight the importance of options

“With increasing restrictions on abortion care, offering more contraceptive options for people is critical,” Lauren Owens, MD, associate professor of obstetrics and gynecology at the University of Washington, Seattle, said in an interview. “That’s not to say that having another pill option makes up for the harm people are experiencing as they navigate abortion bans and legal interference in their health care, but no one pill works for all people, and having more options is helpful,” she said.

Dr. Owens noted that the rates of pregnancy in the current study were lower than she traditionally associates with COCs, “although I usually discuss annual failure rates with patients, not failure rates per cycle, and the latter will clearly be lower.” In the current study, “The authors hypothesize some of this may be due to the longer half-life that estetrol has compared to ethinyl estradiol, the estrogen form more commonly found in oral contraceptive pills,” she said.

From a clinical standpoint, “I appreciated the linkage between number of missed pills and pregnancies occurring,” Dr. Owens said. “This is a good reminder to clinicians to talk to patients ahead of time about what to do when missed pills occur and to provide resources in advance that patients can reference when needed,” she said.

“The authors published other studies on this pill in the last year and it seems to work well and have a reasonable safety profile,” Dr. Owens told this news organization. However, “We still need to broaden the methods available to patients, particularly methods that people producing sperm can use. In the face of ongoing and escalating attacks on access to contraceptive care and abortion care, it’s more important than ever to do what we can to improve options for patients,” she said.

The study was supported by Estetra SRL, an affiliate company of Mithra Pharmaceuticals. Dr. Creinin disclosed relationships with multiple companies including Gedeon Richter, Mayne, and Organon. He disclosed serving on the advisory boards for Evofem, Fuji Pharma, Gedeon Richter, GlaxoSmithKline, Mayne, Merck, OLIC, Organon, and Searchlight, and serving as a consultant for Estetra SRL (including the current study), Libbs, Mayne, and Medicines360; his university department receives contraceptive research funding from Chemo Research SL, Evofem, HRA Pharma, Medicines360, Merck, and Sebela. Dr. Owens had no relevant financial conflicts to disclose.

Pregnancies in users of combined oral contraceptives occur more often when more than two pills are missed or when missed-pill protocols are not followed, based on data from nearly 3,000 women.

Combined oral contraceptives (COCs) remain a popular method of pregnancy prevention worldwide, but efficacy and failure rates can be difficult to determine, as real-word use does not always mirror clinical trials, wrote Mitchell D. Creinin, MD, of the University of California, Davis, and colleagues. Clinical trials include perfect use or method-failure rates, but data on pregnancy risk based on reported adherence alone are lacking, they said.

To assess the effects of missed pills on COC efficacy, the researchers reviewed data from a pair of parallel phase 3 trials, focusing only on adherence to the pill dosing regimen. The findings were published in Obstetrics & Gynecology.

The study population included 1,864 individuals from the United States and Canada, and 1,553 from Europe and Russia.

The participants were healthy, sexually active adults aged 16-50 years in monogamous relationships from 2016 through 2018 who agreed to used estetrol 15 mg and drospirenone 3 mg for up to 13 28-day cycles as their only contraceptive method. Condom use was permitted for protection against sexually transmitted infections if needed. The 28-day COCs included 24 hormonal tablets and 4 placebo tablets. Participants received written instructions for what to do it they missed pills.

The primary outcome was the relationship between missed pills and pregnancies.

A total of 31 pregnancies occurred across both studies; none of these occurred during cycles in which other contraception was used. Of 22 pregnancies in participants who reported taking all pills, 21 reported daily pill use during the cycle in which pregnancy occurred. One participant reported not taking one pill and one participant reported not taking two pills; neither correctly followed the instructions for missed pills.

Pregnancies occurred in .09% of cycles in which participants reported taking all pills, and in 0.25%, 0.83%, and 1.6% of cycles in which participants reported missing one pill, two pills, or more than two pills, respectively.

“Pregnancy rates exceeded 1% only in participants who did not correctly follow missed-pill instructions,” the researchers noted.

Pregnancy rates per cycle ranged from 0% to 0.21%, and 48.4% of the pregnancies occurred during the first four cycles of COC use. Approximately one-third (32.3%) of pregnancies occurred within the first week of a new pill pack.

“Fertilization does not appear to be related to the timing of missed pills within the cycle because pregnancy did not occur more frequently earlier in the cycle (after the placebo pills),” the researchers wrote in their discussion. This finding contradicts previous research suggesting that contraceptive failure rates decrease over the first year of use, they said. In addition, the formulation of the pill used may affect pregnancy rates when pills are missed, as some hormones have longer half-lives, they noted.

The study findings were limited by several factors, including the lack of adjustment for outcomes based on reported sexual activity per cycle, and by the reliance on self-reports.

However, the results were strengthened by the use of the clinical outcomes of pregnancy as the primary outcome, rather than characteristics and predictors of participants who missed pills, the researchers said.

The cycle-based methodology used in the current study may provide insight on the relationship between COC adherence and pregnancy risk that can inform future studies, they concluded.
 

Findings highlight the importance of options

“With increasing restrictions on abortion care, offering more contraceptive options for people is critical,” Lauren Owens, MD, associate professor of obstetrics and gynecology at the University of Washington, Seattle, said in an interview. “That’s not to say that having another pill option makes up for the harm people are experiencing as they navigate abortion bans and legal interference in their health care, but no one pill works for all people, and having more options is helpful,” she said.

Dr. Owens noted that the rates of pregnancy in the current study were lower than she traditionally associates with COCs, “although I usually discuss annual failure rates with patients, not failure rates per cycle, and the latter will clearly be lower.” In the current study, “The authors hypothesize some of this may be due to the longer half-life that estetrol has compared to ethinyl estradiol, the estrogen form more commonly found in oral contraceptive pills,” she said.

From a clinical standpoint, “I appreciated the linkage between number of missed pills and pregnancies occurring,” Dr. Owens said. “This is a good reminder to clinicians to talk to patients ahead of time about what to do when missed pills occur and to provide resources in advance that patients can reference when needed,” she said.

“The authors published other studies on this pill in the last year and it seems to work well and have a reasonable safety profile,” Dr. Owens told this news organization. However, “We still need to broaden the methods available to patients, particularly methods that people producing sperm can use. In the face of ongoing and escalating attacks on access to contraceptive care and abortion care, it’s more important than ever to do what we can to improve options for patients,” she said.

The study was supported by Estetra SRL, an affiliate company of Mithra Pharmaceuticals. Dr. Creinin disclosed relationships with multiple companies including Gedeon Richter, Mayne, and Organon. He disclosed serving on the advisory boards for Evofem, Fuji Pharma, Gedeon Richter, GlaxoSmithKline, Mayne, Merck, OLIC, Organon, and Searchlight, and serving as a consultant for Estetra SRL (including the current study), Libbs, Mayne, and Medicines360; his university department receives contraceptive research funding from Chemo Research SL, Evofem, HRA Pharma, Medicines360, Merck, and Sebela. Dr. Owens had no relevant financial conflicts to disclose.

Pregnancies in users of combined oral contraceptives occur more often when more than two pills are missed or when missed-pill protocols are not followed, based on data from nearly 3,000 women.

Combined oral contraceptives (COCs) remain a popular method of pregnancy prevention worldwide, but efficacy and failure rates can be difficult to determine, as real-word use does not always mirror clinical trials, wrote Mitchell D. Creinin, MD, of the University of California, Davis, and colleagues. Clinical trials include perfect use or method-failure rates, but data on pregnancy risk based on reported adherence alone are lacking, they said.

To assess the effects of missed pills on COC efficacy, the researchers reviewed data from a pair of parallel phase 3 trials, focusing only on adherence to the pill dosing regimen. The findings were published in Obstetrics & Gynecology.

The study population included 1,864 individuals from the United States and Canada, and 1,553 from Europe and Russia.

The participants were healthy, sexually active adults aged 16-50 years in monogamous relationships from 2016 through 2018 who agreed to used estetrol 15 mg and drospirenone 3 mg for up to 13 28-day cycles as their only contraceptive method. Condom use was permitted for protection against sexually transmitted infections if needed. The 28-day COCs included 24 hormonal tablets and 4 placebo tablets. Participants received written instructions for what to do it they missed pills.

The primary outcome was the relationship between missed pills and pregnancies.

A total of 31 pregnancies occurred across both studies; none of these occurred during cycles in which other contraception was used. Of 22 pregnancies in participants who reported taking all pills, 21 reported daily pill use during the cycle in which pregnancy occurred. One participant reported not taking one pill and one participant reported not taking two pills; neither correctly followed the instructions for missed pills.

Pregnancies occurred in .09% of cycles in which participants reported taking all pills, and in 0.25%, 0.83%, and 1.6% of cycles in which participants reported missing one pill, two pills, or more than two pills, respectively.

“Pregnancy rates exceeded 1% only in participants who did not correctly follow missed-pill instructions,” the researchers noted.

Pregnancy rates per cycle ranged from 0% to 0.21%, and 48.4% of the pregnancies occurred during the first four cycles of COC use. Approximately one-third (32.3%) of pregnancies occurred within the first week of a new pill pack.

“Fertilization does not appear to be related to the timing of missed pills within the cycle because pregnancy did not occur more frequently earlier in the cycle (after the placebo pills),” the researchers wrote in their discussion. This finding contradicts previous research suggesting that contraceptive failure rates decrease over the first year of use, they said. In addition, the formulation of the pill used may affect pregnancy rates when pills are missed, as some hormones have longer half-lives, they noted.

The study findings were limited by several factors, including the lack of adjustment for outcomes based on reported sexual activity per cycle, and by the reliance on self-reports.

However, the results were strengthened by the use of the clinical outcomes of pregnancy as the primary outcome, rather than characteristics and predictors of participants who missed pills, the researchers said.

The cycle-based methodology used in the current study may provide insight on the relationship between COC adherence and pregnancy risk that can inform future studies, they concluded.
 

Findings highlight the importance of options

“With increasing restrictions on abortion care, offering more contraceptive options for people is critical,” Lauren Owens, MD, associate professor of obstetrics and gynecology at the University of Washington, Seattle, said in an interview. “That’s not to say that having another pill option makes up for the harm people are experiencing as they navigate abortion bans and legal interference in their health care, but no one pill works for all people, and having more options is helpful,” she said.

Dr. Owens noted that the rates of pregnancy in the current study were lower than she traditionally associates with COCs, “although I usually discuss annual failure rates with patients, not failure rates per cycle, and the latter will clearly be lower.” In the current study, “The authors hypothesize some of this may be due to the longer half-life that estetrol has compared to ethinyl estradiol, the estrogen form more commonly found in oral contraceptive pills,” she said.

From a clinical standpoint, “I appreciated the linkage between number of missed pills and pregnancies occurring,” Dr. Owens said. “This is a good reminder to clinicians to talk to patients ahead of time about what to do when missed pills occur and to provide resources in advance that patients can reference when needed,” she said.

“The authors published other studies on this pill in the last year and it seems to work well and have a reasonable safety profile,” Dr. Owens told this news organization. However, “We still need to broaden the methods available to patients, particularly methods that people producing sperm can use. In the face of ongoing and escalating attacks on access to contraceptive care and abortion care, it’s more important than ever to do what we can to improve options for patients,” she said.

The study was supported by Estetra SRL, an affiliate company of Mithra Pharmaceuticals. Dr. Creinin disclosed relationships with multiple companies including Gedeon Richter, Mayne, and Organon. He disclosed serving on the advisory boards for Evofem, Fuji Pharma, Gedeon Richter, GlaxoSmithKline, Mayne, Merck, OLIC, Organon, and Searchlight, and serving as a consultant for Estetra SRL (including the current study), Libbs, Mayne, and Medicines360; his university department receives contraceptive research funding from Chemo Research SL, Evofem, HRA Pharma, Medicines360, Merck, and Sebela. Dr. Owens had no relevant financial conflicts to disclose.