Diana Swift

FROM BMJ

The lifetime risk of atrial fibrillation (AF) increased from 2000 to 2022 from one in four to one in three, a Danish population-based study of temporal trends found.

Heart failure was the most frequent complication linked to this arrhythmia, with a lifetime risk of two in five, twice that of stroke, according to investigators led by Nicklas Vinter, MD, PhD, a postdoctoral researcher at the Danish Center for Health Service Research in the Department of Clinical Medicine at Aalborg University, Denmark.

Published in BMJ, the study found the lifetime risks of post-AF stroke, ischemic stroke, and myocardial infarction improved only modestly over time and remained high, with virtually no improvement in the lifetime risk of heart failure.

Vinter_Nicklas_Denmark_web.jpg

The Study

The cohort consisted of 3.5 million individuals (51.7% women) who did not have AF as of age 45 or older. These individuals were followed until incident AF, migration, death, or end of follow-up, whichever came first.

All 362,721 individuals with incident AF (53.6% men) but no prevalent complication were further followed over two time periods (2000-2010 and 2011-2020) until incident heart failure, stroke, or myocardial infarction.

Among the findings:

• Lifetime AF risk increased from 24.2% in 2000-2010 to 30.9% in 2011-2022, for a difference of 6.7% (95% confidence interval [CI], 6.5%-6.8%).
• Lifetime AF risk rose across all subgroups over time, with a larger increase in men and individuals with heart failure, myocardial infarction, stroke, diabetes, and chronic kidney disease.
• Lifetime risk of heart failure was 42.9% in 2000-2010 and 42.1% in 2011-2022, for a difference of −0.8% (95% CI, −3.8% to 2.2%).
• The lifetime risks of post-AF stroke and of myocardial infarction decreased slightly between the two periods, from 22.4% to 19.9% for stroke (difference −2.5%, 95% CI, −4.2% to −0.7%) and from 13.7% to 9.8% for myocardial infarction (−3.9%, 95% CI, −5.3% to −2.4%). No differential decrease between men and women emerged.

“Our novel quantification of the long-term downstream consequences of atrial fibrillation highlights the critical need for treatments to further decrease stroke risk as well as for heart failure prevention strategies among patients with atrial fibrillation,” the Danish researchers wrote.

Offering an outsider’s perspective, John P. Higgins, MD, MBA, MPhil, a sports cardiologist at McGovern Medical School at The University of Texas Health Science Center at Houston, said, “Think of atrial fibrillation as a barometer of underlying stress on the heart. When blood pressure is high, or a patient has underlying asymptomatic coronary artery disease or heart failure, they are more likely to have episodes of atrial fibrillation.”

Higgins_John_P_TX_web.jpg

Wu_Jianhua_UK_web.JPG

FROM BMJ

The lifetime risk of atrial fibrillation (AF) increased from 2000 to 2022 from one in four to one in three, a Danish population-based study of temporal trends found.

Heart failure was the most frequent complication linked to this arrhythmia, with a lifetime risk of two in five, twice that of stroke, according to investigators led by Nicklas Vinter, MD, PhD, a postdoctoral researcher at the Danish Center for Health Service Research in the Department of Clinical Medicine at Aalborg University, Denmark.

Published in BMJ, the study found the lifetime risks of post-AF stroke, ischemic stroke, and myocardial infarction improved only modestly over time and remained high, with virtually no improvement in the lifetime risk of heart failure.

Vinter_Nicklas_Denmark_web.jpg

The Study

The cohort consisted of 3.5 million individuals (51.7% women) who did not have AF as of age 45 or older. These individuals were followed until incident AF, migration, death, or end of follow-up, whichever came first.

All 362,721 individuals with incident AF (53.6% men) but no prevalent complication were further followed over two time periods (2000-2010 and 2011-2020) until incident heart failure, stroke, or myocardial infarction.

Among the findings:

• Lifetime AF risk increased from 24.2% in 2000-2010 to 30.9% in 2011-2022, for a difference of 6.7% (95% confidence interval [CI], 6.5%-6.8%).
• Lifetime AF risk rose across all subgroups over time, with a larger increase in men and individuals with heart failure, myocardial infarction, stroke, diabetes, and chronic kidney disease.
• Lifetime risk of heart failure was 42.9% in 2000-2010 and 42.1% in 2011-2022, for a difference of −0.8% (95% CI, −3.8% to 2.2%).
• The lifetime risks of post-AF stroke and of myocardial infarction decreased slightly between the two periods, from 22.4% to 19.9% for stroke (difference −2.5%, 95% CI, −4.2% to −0.7%) and from 13.7% to 9.8% for myocardial infarction (−3.9%, 95% CI, −5.3% to −2.4%). No differential decrease between men and women emerged.

“Our novel quantification of the long-term downstream consequences of atrial fibrillation highlights the critical need for treatments to further decrease stroke risk as well as for heart failure prevention strategies among patients with atrial fibrillation,” the Danish researchers wrote.

Offering an outsider’s perspective, John P. Higgins, MD, MBA, MPhil, a sports cardiologist at McGovern Medical School at The University of Texas Health Science Center at Houston, said, “Think of atrial fibrillation as a barometer of underlying stress on the heart. When blood pressure is high, or a patient has underlying asymptomatic coronary artery disease or heart failure, they are more likely to have episodes of atrial fibrillation.”

Higgins_John_P_TX_web.jpg

Wu_Jianhua_UK_web.JPG

FROM BMJ

The lifetime risk of atrial fibrillation (AF) increased from 2000 to 2022 from one in four to one in three, a Danish population-based study of temporal trends found.

Heart failure was the most frequent complication linked to this arrhythmia, with a lifetime risk of two in five, twice that of stroke, according to investigators led by Nicklas Vinter, MD, PhD, a postdoctoral researcher at the Danish Center for Health Service Research in the Department of Clinical Medicine at Aalborg University, Denmark.

Published in BMJ, the study found the lifetime risks of post-AF stroke, ischemic stroke, and myocardial infarction improved only modestly over time and remained high, with virtually no improvement in the lifetime risk of heart failure.

Vinter_Nicklas_Denmark_web.jpg

The Study

The cohort consisted of 3.5 million individuals (51.7% women) who did not have AF as of age 45 or older. These individuals were followed until incident AF, migration, death, or end of follow-up, whichever came first.

All 362,721 individuals with incident AF (53.6% men) but no prevalent complication were further followed over two time periods (2000-2010 and 2011-2020) until incident heart failure, stroke, or myocardial infarction.

Among the findings:

• Lifetime AF risk increased from 24.2% in 2000-2010 to 30.9% in 2011-2022, for a difference of 6.7% (95% confidence interval [CI], 6.5%-6.8%).
• Lifetime AF risk rose across all subgroups over time, with a larger increase in men and individuals with heart failure, myocardial infarction, stroke, diabetes, and chronic kidney disease.
• Lifetime risk of heart failure was 42.9% in 2000-2010 and 42.1% in 2011-2022, for a difference of −0.8% (95% CI, −3.8% to 2.2%).
• The lifetime risks of post-AF stroke and of myocardial infarction decreased slightly between the two periods, from 22.4% to 19.9% for stroke (difference −2.5%, 95% CI, −4.2% to −0.7%) and from 13.7% to 9.8% for myocardial infarction (−3.9%, 95% CI, −5.3% to −2.4%). No differential decrease between men and women emerged.

“Our novel quantification of the long-term downstream consequences of atrial fibrillation highlights the critical need for treatments to further decrease stroke risk as well as for heart failure prevention strategies among patients with atrial fibrillation,” the Danish researchers wrote.

Offering an outsider’s perspective, John P. Higgins, MD, MBA, MPhil, a sports cardiologist at McGovern Medical School at The University of Texas Health Science Center at Houston, said, “Think of atrial fibrillation as a barometer of underlying stress on the heart. When blood pressure is high, or a patient has underlying asymptomatic coronary artery disease or heart failure, they are more likely to have episodes of atrial fibrillation.”

Higgins_John_P_TX_web.jpg

Wu_Jianhua_UK_web.JPG

Antibiotics had no measurable effect on the severity or duration of coughs due to acute lower respiratory tract infection (LRTI, or acute bronchitis), a large prospective study found.

In fact, those receiving an antibiotic in the primary- and urgent-care setting had a small but significant increase in overall length of illness (17.5 vs 15.9 days; P = .05) — largely because patients with longer illness before the index visit were more likely to receive these drugs. The study adds further support for reducing the prescription of antibiotics for LRTIs.

“Importantly, the pathogen data demonstrated that the length of time until illness resolution for those with bacterial infection was the same as for those not receiving an antibiotic versus those receiving one (17.3 vs 17.4 days),” researchers led by Daniel J. Merenstein, MD, a professor and director of research programs, family medicine, at Georgetown University Medical Center in Washington, wrote in the Journal of General Internal Medicine (doi: 10.1007/s11606-024-08758-y).

Merenstein_Daniel_DC_web.jpg

Risks

Overuse of antibiotics can result in dizziness, nausea, diarrhea, and rash, along with a roughly 4% chance of serious adverse effects including anaphylaxis; Stevens-Johnson syndrome, a serious skin and mucous membrane disorder; and Clostridioides difficile-associated diarrhea.

An estimated half of all antibiotic prescriptions for acute respiratory conditions are unnecessary. Before the COVID-19 pandemic, antibiotics were prescribed about 70% of the time for a diagnosis of uncomplicated cough and LRTI. The viral pandemic did not change this practice according to a meta-analysis of 130 studies showing that 78% of COVID-19 patients were prescribed an antibiotic.
 

The study

The study looked at a cohort of 718 patients, with a mean age of 38.9 years, 65.3% female, of whom 207 received an antibiotic and 511 did not. Of those with baseline data, 29% had an antibiotic prescribed at baseline, the most common (in 85%) being amoxicillin-clavulanate, azithromycin, doxycycline, and amoxicillin. Antibiotics had no effect on the duration or overall severity of cough in viral, bacterial, or mixed infections. Receipt of an antibiotic did, however, reduce the likelihood of a follow-up visit: 14.1% vs 8.2% (adjusted odds ratio, 0.47; 95% confidence interval, 0.26-0.84) — perhaps because it removed the motivation for seeking another consultation. Antibiotic recipients were more likely to receive a systemic corticosteroid (31.9% vs 4.5%, P <.001) and were also more likely to receive an albuterol inhaler (22.7% vs 7.6%, P <.001).

Jeffrey A. Linder, MD, MPH, a primary care physician and chief of internal medicine and geriatrics at Northwestern University Feinberg School of Medicine in Chicago, agrees that in the vast majority of LRTIs — usually acute bronchitis — antibiotics do not speed the healing process. “Forty years of research show that antibiotics do not make acute bronchitis go away any faster,” Dr. Linder, who was not involved in the current study, said in an interview. “There’s even growing evidence that a lot of pneumonia is viral as well, and 10 or 20 years from now we may often not be giving antibiotics for pneumonia because we’ll be able to see better if it’s caused by a virus.”

Linder_Jeffrey_CHICAGO_web.jpg

Antibiotics had no measurable effect on the severity or duration of coughs due to acute lower respiratory tract infection (LRTI, or acute bronchitis), a large prospective study found.

In fact, those receiving an antibiotic in the primary- and urgent-care setting had a small but significant increase in overall length of illness (17.5 vs 15.9 days; P = .05) — largely because patients with longer illness before the index visit were more likely to receive these drugs. The study adds further support for reducing the prescription of antibiotics for LRTIs.

“Importantly, the pathogen data demonstrated that the length of time until illness resolution for those with bacterial infection was the same as for those not receiving an antibiotic versus those receiving one (17.3 vs 17.4 days),” researchers led by Daniel J. Merenstein, MD, a professor and director of research programs, family medicine, at Georgetown University Medical Center in Washington, wrote in the Journal of General Internal Medicine (doi: 10.1007/s11606-024-08758-y).

Merenstein_Daniel_DC_web.jpg

Risks

Overuse of antibiotics can result in dizziness, nausea, diarrhea, and rash, along with a roughly 4% chance of serious adverse effects including anaphylaxis; Stevens-Johnson syndrome, a serious skin and mucous membrane disorder; and Clostridioides difficile-associated diarrhea.

An estimated half of all antibiotic prescriptions for acute respiratory conditions are unnecessary. Before the COVID-19 pandemic, antibiotics were prescribed about 70% of the time for a diagnosis of uncomplicated cough and LRTI. The viral pandemic did not change this practice according to a meta-analysis of 130 studies showing that 78% of COVID-19 patients were prescribed an antibiotic.
 

The study

The study looked at a cohort of 718 patients, with a mean age of 38.9 years, 65.3% female, of whom 207 received an antibiotic and 511 did not. Of those with baseline data, 29% had an antibiotic prescribed at baseline, the most common (in 85%) being amoxicillin-clavulanate, azithromycin, doxycycline, and amoxicillin. Antibiotics had no effect on the duration or overall severity of cough in viral, bacterial, or mixed infections. Receipt of an antibiotic did, however, reduce the likelihood of a follow-up visit: 14.1% vs 8.2% (adjusted odds ratio, 0.47; 95% confidence interval, 0.26-0.84) — perhaps because it removed the motivation for seeking another consultation. Antibiotic recipients were more likely to receive a systemic corticosteroid (31.9% vs 4.5%, P <.001) and were also more likely to receive an albuterol inhaler (22.7% vs 7.6%, P <.001).

Jeffrey A. Linder, MD, MPH, a primary care physician and chief of internal medicine and geriatrics at Northwestern University Feinberg School of Medicine in Chicago, agrees that in the vast majority of LRTIs — usually acute bronchitis — antibiotics do not speed the healing process. “Forty years of research show that antibiotics do not make acute bronchitis go away any faster,” Dr. Linder, who was not involved in the current study, said in an interview. “There’s even growing evidence that a lot of pneumonia is viral as well, and 10 or 20 years from now we may often not be giving antibiotics for pneumonia because we’ll be able to see better if it’s caused by a virus.”

Linder_Jeffrey_CHICAGO_web.jpg

Antibiotics had no measurable effect on the severity or duration of coughs due to acute lower respiratory tract infection (LRTI, or acute bronchitis), a large prospective study found.

In fact, those receiving an antibiotic in the primary- and urgent-care setting had a small but significant increase in overall length of illness (17.5 vs 15.9 days; P = .05) — largely because patients with longer illness before the index visit were more likely to receive these drugs. The study adds further support for reducing the prescription of antibiotics for LRTIs.

“Importantly, the pathogen data demonstrated that the length of time until illness resolution for those with bacterial infection was the same as for those not receiving an antibiotic versus those receiving one (17.3 vs 17.4 days),” researchers led by Daniel J. Merenstein, MD, a professor and director of research programs, family medicine, at Georgetown University Medical Center in Washington, wrote in the Journal of General Internal Medicine (doi: 10.1007/s11606-024-08758-y).

Merenstein_Daniel_DC_web.jpg

Risks

Overuse of antibiotics can result in dizziness, nausea, diarrhea, and rash, along with a roughly 4% chance of serious adverse effects including anaphylaxis; Stevens-Johnson syndrome, a serious skin and mucous membrane disorder; and Clostridioides difficile-associated diarrhea.

An estimated half of all antibiotic prescriptions for acute respiratory conditions are unnecessary. Before the COVID-19 pandemic, antibiotics were prescribed about 70% of the time for a diagnosis of uncomplicated cough and LRTI. The viral pandemic did not change this practice according to a meta-analysis of 130 studies showing that 78% of COVID-19 patients were prescribed an antibiotic.
 

The study

The study looked at a cohort of 718 patients, with a mean age of 38.9 years, 65.3% female, of whom 207 received an antibiotic and 511 did not. Of those with baseline data, 29% had an antibiotic prescribed at baseline, the most common (in 85%) being amoxicillin-clavulanate, azithromycin, doxycycline, and amoxicillin. Antibiotics had no effect on the duration or overall severity of cough in viral, bacterial, or mixed infections. Receipt of an antibiotic did, however, reduce the likelihood of a follow-up visit: 14.1% vs 8.2% (adjusted odds ratio, 0.47; 95% confidence interval, 0.26-0.84) — perhaps because it removed the motivation for seeking another consultation. Antibiotic recipients were more likely to receive a systemic corticosteroid (31.9% vs 4.5%, P <.001) and were also more likely to receive an albuterol inhaler (22.7% vs 7.6%, P <.001).

Jeffrey A. Linder, MD, MPH, a primary care physician and chief of internal medicine and geriatrics at Northwestern University Feinberg School of Medicine in Chicago, agrees that in the vast majority of LRTIs — usually acute bronchitis — antibiotics do not speed the healing process. “Forty years of research show that antibiotics do not make acute bronchitis go away any faster,” Dr. Linder, who was not involved in the current study, said in an interview. “There’s even growing evidence that a lot of pneumonia is viral as well, and 10 or 20 years from now we may often not be giving antibiotics for pneumonia because we’ll be able to see better if it’s caused by a virus.”

Linder_Jeffrey_CHICAGO_web.jpg

Large-scale salt substitution holds promise for reducing mortality with no elevated risk of serious harms, especially for older people at increased cardiovascular disease (CVD) risk, a systematic review and meta-analysis by Australian researchers suggested.

The study, published in Annals of Internal Medicine, adds more evidence that broad adoption of potassium-rich salt substitutes for food preparation could have a significant effect on population health.

Although the supporting evidence was of low certainty, the analysis of 16 international randomized controlled trials of various interventions with 35,321 participants found salt substitution to be associated with an absolute reduction of 5 in 1000 in all-cause mortality (confidence interval, –3 to –7) and 3 in 1000 in CVD mortality (CI, –1 to –5).

Led by Hannah Greenwood, BPsychSc, a cardiovascular researcher at the Institute for Evidence-Based Healthcare at Bond University in Gold Coast, Queensland, the investigators also found very low certainty evidence of an absolute reduction of 8 in 1000 in major adverse cardiovascular events (CI, 0 to –15), with a 1 in 1000 decrease in more serious adverse events (CI, 4 to –2) in the same population.

Seven of the 16 studies were conducted in China and Taiwan and seven were conducted in populations of older age (mean age 62 years) and/or at higher cardiovascular risk.

With most of the data deriving from populations of older age at higher-than-average CV risk and/or eating an Asian diet, the findings’ generalizability to populations following a Western diet and/or at average CVD risk is limited, the researchers acknowledged.

“We are less certain about the effects in Western, younger, and healthy population groups,” corresponding author Loai Albarqouni, MD, MSc, PhD, assistant professor at the Institute for Evidence-Based Healthcare, said in an interview. “While we saw small, clinically meaningful reductions in cardiovascular deaths and events, effectiveness should be better established before salt substitutes are recommended more broadly, though they are promising.”

In addition, he said, since the longest follow-up of substitute use was 10 years, “we can’t speak to benefits or harms beyond this time frame.”

Albarqouni_Loai_AUSTRALIA_web.jpg

Laing_Emma_GA_web.jpg

Miranda_J_Jaime_AUSTRALIA_web.jpg

Large-scale salt substitution holds promise for reducing mortality with no elevated risk of serious harms, especially for older people at increased cardiovascular disease (CVD) risk, a systematic review and meta-analysis by Australian researchers suggested.

The study, published in Annals of Internal Medicine, adds more evidence that broad adoption of potassium-rich salt substitutes for food preparation could have a significant effect on population health.

Although the supporting evidence was of low certainty, the analysis of 16 international randomized controlled trials of various interventions with 35,321 participants found salt substitution to be associated with an absolute reduction of 5 in 1000 in all-cause mortality (confidence interval, –3 to –7) and 3 in 1000 in CVD mortality (CI, –1 to –5).

Led by Hannah Greenwood, BPsychSc, a cardiovascular researcher at the Institute for Evidence-Based Healthcare at Bond University in Gold Coast, Queensland, the investigators also found very low certainty evidence of an absolute reduction of 8 in 1000 in major adverse cardiovascular events (CI, 0 to –15), with a 1 in 1000 decrease in more serious adverse events (CI, 4 to –2) in the same population.

Seven of the 16 studies were conducted in China and Taiwan and seven were conducted in populations of older age (mean age 62 years) and/or at higher cardiovascular risk.

With most of the data deriving from populations of older age at higher-than-average CV risk and/or eating an Asian diet, the findings’ generalizability to populations following a Western diet and/or at average CVD risk is limited, the researchers acknowledged.

“We are less certain about the effects in Western, younger, and healthy population groups,” corresponding author Loai Albarqouni, MD, MSc, PhD, assistant professor at the Institute for Evidence-Based Healthcare, said in an interview. “While we saw small, clinically meaningful reductions in cardiovascular deaths and events, effectiveness should be better established before salt substitutes are recommended more broadly, though they are promising.”

In addition, he said, since the longest follow-up of substitute use was 10 years, “we can’t speak to benefits or harms beyond this time frame.”

Albarqouni_Loai_AUSTRALIA_web.jpg

Laing_Emma_GA_web.jpg

Miranda_J_Jaime_AUSTRALIA_web.jpg

Large-scale salt substitution holds promise for reducing mortality with no elevated risk of serious harms, especially for older people at increased cardiovascular disease (CVD) risk, a systematic review and meta-analysis by Australian researchers suggested.

The study, published in Annals of Internal Medicine, adds more evidence that broad adoption of potassium-rich salt substitutes for food preparation could have a significant effect on population health.

Although the supporting evidence was of low certainty, the analysis of 16 international randomized controlled trials of various interventions with 35,321 participants found salt substitution to be associated with an absolute reduction of 5 in 1000 in all-cause mortality (confidence interval, –3 to –7) and 3 in 1000 in CVD mortality (CI, –1 to –5).

Led by Hannah Greenwood, BPsychSc, a cardiovascular researcher at the Institute for Evidence-Based Healthcare at Bond University in Gold Coast, Queensland, the investigators also found very low certainty evidence of an absolute reduction of 8 in 1000 in major adverse cardiovascular events (CI, 0 to –15), with a 1 in 1000 decrease in more serious adverse events (CI, 4 to –2) in the same population.

Seven of the 16 studies were conducted in China and Taiwan and seven were conducted in populations of older age (mean age 62 years) and/or at higher cardiovascular risk.

With most of the data deriving from populations of older age at higher-than-average CV risk and/or eating an Asian diet, the findings’ generalizability to populations following a Western diet and/or at average CVD risk is limited, the researchers acknowledged.

“We are less certain about the effects in Western, younger, and healthy population groups,” corresponding author Loai Albarqouni, MD, MSc, PhD, assistant professor at the Institute for Evidence-Based Healthcare, said in an interview. “While we saw small, clinically meaningful reductions in cardiovascular deaths and events, effectiveness should be better established before salt substitutes are recommended more broadly, though they are promising.”

In addition, he said, since the longest follow-up of substitute use was 10 years, “we can’t speak to benefits or harms beyond this time frame.”

Albarqouni_Loai_AUSTRALIA_web.jpg

Laing_Emma_GA_web.jpg

Miranda_J_Jaime_AUSTRALIA_web.jpg

Premenstrual disorders (PMDs) and perinatal depression (PND) appear to have a bidirectional association, a Swedish national registry-based analysis found.

In women with PND, 2.9% had PMDs before pregnancy vs 0.6% in a matched cohort of unaffected women, according to an international team led by Quian Yang, MD, PhD, of the Institute of Environmental Medicine at the Karolinska Institutet in Stockholm, Sweden. Their study appears in PLoS Medicine.

“Preconception and maternity care providers should be aware of the risk of developing perinatal depression among women with a history of PMDs,” Dr. Yang said in an interview. “Healthcare providers may inform women with perinatal depression about the potential risk of PMDs when menstruation returns after childbirth.” She recommended screening as part of routine perinatal care to identify and treat the condition at an early stage. Counseling and medication may help prevent adverse consequences.

In other findings, the correlation with PMDs held for both prenatal and postnatal depression, regardless of any history of psychiatric disorders and also in full-sister comparisons, the authors noted, with a stronger correlation in the absence of psychiatric disorders (P for interaction <.001).

“Interestingly, we noted a stronger association between PMDs and subsequent PND than the association in the other direction, Dr. Yang said. And although many experience PMD symptom onset in adolescence, symptom worsening has been reported with increasing age and parity. “It is possible that women with milder premenstrual symptoms experienced worse symptoms after pregnancy and are therefore first diagnosed with PMD after pregnancy,” the authors hypothesized.

Both PMDs and PND share depressive symptomatology and onset coinciding with hormonal fluctuations, particularly estrogen and progesterone, suggesting a shared etiology, Dr. Yang explained. “It’s plausible that an abnormal response to natural hormone fluctuations predisposes women to both PMDs and PND. However, the underlying mechanism is complex, and future research is needed to reveal the underlying etiology.”

Affecting a majority of women of reproductive age to some degree, PMDs in certain women can cause significant functional impairment and, when severe, have been linked to increased risks of accidents and suicidal behavior. The psychological symptoms of the more serious form, premenstrual dysphoric disorder, for example, are associated with a 50%-78% lifetime risk for psychiatric disorders, including major depressive, dysthymic, seasonal affective, and generalized anxiety disorders, as well as suicidality.

Mood disorders are common in pregnancy and the postpartum period.

The Swedish Study

In 1.8 million singleton pregnancies in Sweden during 2001-2018, the investigators identified 84,949 women with PND and 849,482 unaffected women and individually matched them 10:1 by age and calendar year. Incident PND and PMDs were identified through clinical diagnoses or prescribed medications, and adjustment was made for such demographics as country of birth, educational level, region of residency, and cohabitation status.

In an initial matched-cohort case-control study with a mean follow-up of 6.9 years, PMDs were associated with a nearly five times higher risk of subsequent PND (odds ratio, 4.76; 95% CI, 4.52-5.01; P <.001).

In another matched cohort with a mean follow-up of 7.0 years, there were 4227 newly diagnosed PMDs in women with PND (incidence rate [IR], 7.6/1000 person-years) and 21,326 among controls (IR, 3.8/1000). Compared with matched controls, women with PND were at almost twice the risk of subsequent PMDs (hazard ratio, 1.81; 95% CI, 1.74-1.88; P <.001).

Dr. Bernard_Harlow_2_web.jpg

Commenting on the study but not involved in it, Bernard L. Harlow, PhD, a professor of epidemiology at Boston University School of Public Health in Massachusetts who specializes in epidemiologic studies of female reproductive disorders, said he was not surprised at these findings, which clearly support the need for PMD screening in mothers-to-be. “Anything that is easy to measure and noninvasive that will minimize the risk of postpartum depression should be part of the standard of care during the prenatal period.” As to safety: If treatment is indicated, he added, “studies have shown that the risk to the mother and child is much greater if the mother’s mood disorder is not controlled than any risk to the baby due to depression treatment.” But though PMDs may be predictive of PND, there are still barriers to actual PND care. A 2023 analysis reported that 65% of mothers-to-be who screened positive for metal health comorbidities were not referred for treatment.

Dr. Yang and colleagues acknowledged that their findings may not be generalizable to mild forms of these disorders since the data were based on clinical diagnoses and prescriptions.

The study was supported by the Chinese Scholarship Council, the Swedish Research Council for Health, Working Life and Welfare, the Karolinska Institutet, and the Icelandic Research Fund. The authors and Dr. Harlow had no relevant competing interests to disclose.

Premenstrual disorders (PMDs) and perinatal depression (PND) appear to have a bidirectional association, a Swedish national registry-based analysis found.

In women with PND, 2.9% had PMDs before pregnancy vs 0.6% in a matched cohort of unaffected women, according to an international team led by Quian Yang, MD, PhD, of the Institute of Environmental Medicine at the Karolinska Institutet in Stockholm, Sweden. Their study appears in PLoS Medicine.

“Preconception and maternity care providers should be aware of the risk of developing perinatal depression among women with a history of PMDs,” Dr. Yang said in an interview. “Healthcare providers may inform women with perinatal depression about the potential risk of PMDs when menstruation returns after childbirth.” She recommended screening as part of routine perinatal care to identify and treat the condition at an early stage. Counseling and medication may help prevent adverse consequences.

In other findings, the correlation with PMDs held for both prenatal and postnatal depression, regardless of any history of psychiatric disorders and also in full-sister comparisons, the authors noted, with a stronger correlation in the absence of psychiatric disorders (P for interaction <.001).

“Interestingly, we noted a stronger association between PMDs and subsequent PND than the association in the other direction, Dr. Yang said. And although many experience PMD symptom onset in adolescence, symptom worsening has been reported with increasing age and parity. “It is possible that women with milder premenstrual symptoms experienced worse symptoms after pregnancy and are therefore first diagnosed with PMD after pregnancy,” the authors hypothesized.

Both PMDs and PND share depressive symptomatology and onset coinciding with hormonal fluctuations, particularly estrogen and progesterone, suggesting a shared etiology, Dr. Yang explained. “It’s plausible that an abnormal response to natural hormone fluctuations predisposes women to both PMDs and PND. However, the underlying mechanism is complex, and future research is needed to reveal the underlying etiology.”

Affecting a majority of women of reproductive age to some degree, PMDs in certain women can cause significant functional impairment and, when severe, have been linked to increased risks of accidents and suicidal behavior. The psychological symptoms of the more serious form, premenstrual dysphoric disorder, for example, are associated with a 50%-78% lifetime risk for psychiatric disorders, including major depressive, dysthymic, seasonal affective, and generalized anxiety disorders, as well as suicidality.

Mood disorders are common in pregnancy and the postpartum period.

The Swedish Study

In 1.8 million singleton pregnancies in Sweden during 2001-2018, the investigators identified 84,949 women with PND and 849,482 unaffected women and individually matched them 10:1 by age and calendar year. Incident PND and PMDs were identified through clinical diagnoses or prescribed medications, and adjustment was made for such demographics as country of birth, educational level, region of residency, and cohabitation status.

In an initial matched-cohort case-control study with a mean follow-up of 6.9 years, PMDs were associated with a nearly five times higher risk of subsequent PND (odds ratio, 4.76; 95% CI, 4.52-5.01; P <.001).

In another matched cohort with a mean follow-up of 7.0 years, there were 4227 newly diagnosed PMDs in women with PND (incidence rate [IR], 7.6/1000 person-years) and 21,326 among controls (IR, 3.8/1000). Compared with matched controls, women with PND were at almost twice the risk of subsequent PMDs (hazard ratio, 1.81; 95% CI, 1.74-1.88; P <.001).

Dr. Bernard_Harlow_2_web.jpg

Commenting on the study but not involved in it, Bernard L. Harlow, PhD, a professor of epidemiology at Boston University School of Public Health in Massachusetts who specializes in epidemiologic studies of female reproductive disorders, said he was not surprised at these findings, which clearly support the need for PMD screening in mothers-to-be. “Anything that is easy to measure and noninvasive that will minimize the risk of postpartum depression should be part of the standard of care during the prenatal period.” As to safety: If treatment is indicated, he added, “studies have shown that the risk to the mother and child is much greater if the mother’s mood disorder is not controlled than any risk to the baby due to depression treatment.” But though PMDs may be predictive of PND, there are still barriers to actual PND care. A 2023 analysis reported that 65% of mothers-to-be who screened positive for metal health comorbidities were not referred for treatment.

Dr. Yang and colleagues acknowledged that their findings may not be generalizable to mild forms of these disorders since the data were based on clinical diagnoses and prescriptions.

The study was supported by the Chinese Scholarship Council, the Swedish Research Council for Health, Working Life and Welfare, the Karolinska Institutet, and the Icelandic Research Fund. The authors and Dr. Harlow had no relevant competing interests to disclose.

Premenstrual disorders (PMDs) and perinatal depression (PND) appear to have a bidirectional association, a Swedish national registry-based analysis found.

In women with PND, 2.9% had PMDs before pregnancy vs 0.6% in a matched cohort of unaffected women, according to an international team led by Quian Yang, MD, PhD, of the Institute of Environmental Medicine at the Karolinska Institutet in Stockholm, Sweden. Their study appears in PLoS Medicine.

“Preconception and maternity care providers should be aware of the risk of developing perinatal depression among women with a history of PMDs,” Dr. Yang said in an interview. “Healthcare providers may inform women with perinatal depression about the potential risk of PMDs when menstruation returns after childbirth.” She recommended screening as part of routine perinatal care to identify and treat the condition at an early stage. Counseling and medication may help prevent adverse consequences.

In other findings, the correlation with PMDs held for both prenatal and postnatal depression, regardless of any history of psychiatric disorders and also in full-sister comparisons, the authors noted, with a stronger correlation in the absence of psychiatric disorders (P for interaction <.001).

“Interestingly, we noted a stronger association between PMDs and subsequent PND than the association in the other direction, Dr. Yang said. And although many experience PMD symptom onset in adolescence, symptom worsening has been reported with increasing age and parity. “It is possible that women with milder premenstrual symptoms experienced worse symptoms after pregnancy and are therefore first diagnosed with PMD after pregnancy,” the authors hypothesized.

Both PMDs and PND share depressive symptomatology and onset coinciding with hormonal fluctuations, particularly estrogen and progesterone, suggesting a shared etiology, Dr. Yang explained. “It’s plausible that an abnormal response to natural hormone fluctuations predisposes women to both PMDs and PND. However, the underlying mechanism is complex, and future research is needed to reveal the underlying etiology.”

Affecting a majority of women of reproductive age to some degree, PMDs in certain women can cause significant functional impairment and, when severe, have been linked to increased risks of accidents and suicidal behavior. The psychological symptoms of the more serious form, premenstrual dysphoric disorder, for example, are associated with a 50%-78% lifetime risk for psychiatric disorders, including major depressive, dysthymic, seasonal affective, and generalized anxiety disorders, as well as suicidality.

Mood disorders are common in pregnancy and the postpartum period.

The Swedish Study

In 1.8 million singleton pregnancies in Sweden during 2001-2018, the investigators identified 84,949 women with PND and 849,482 unaffected women and individually matched them 10:1 by age and calendar year. Incident PND and PMDs were identified through clinical diagnoses or prescribed medications, and adjustment was made for such demographics as country of birth, educational level, region of residency, and cohabitation status.

In an initial matched-cohort case-control study with a mean follow-up of 6.9 years, PMDs were associated with a nearly five times higher risk of subsequent PND (odds ratio, 4.76; 95% CI, 4.52-5.01; P <.001).

In another matched cohort with a mean follow-up of 7.0 years, there were 4227 newly diagnosed PMDs in women with PND (incidence rate [IR], 7.6/1000 person-years) and 21,326 among controls (IR, 3.8/1000). Compared with matched controls, women with PND were at almost twice the risk of subsequent PMDs (hazard ratio, 1.81; 95% CI, 1.74-1.88; P <.001).

Dr. Bernard_Harlow_2_web.jpg

Commenting on the study but not involved in it, Bernard L. Harlow, PhD, a professor of epidemiology at Boston University School of Public Health in Massachusetts who specializes in epidemiologic studies of female reproductive disorders, said he was not surprised at these findings, which clearly support the need for PMD screening in mothers-to-be. “Anything that is easy to measure and noninvasive that will minimize the risk of postpartum depression should be part of the standard of care during the prenatal period.” As to safety: If treatment is indicated, he added, “studies have shown that the risk to the mother and child is much greater if the mother’s mood disorder is not controlled than any risk to the baby due to depression treatment.” But though PMDs may be predictive of PND, there are still barriers to actual PND care. A 2023 analysis reported that 65% of mothers-to-be who screened positive for metal health comorbidities were not referred for treatment.

Dr. Yang and colleagues acknowledged that their findings may not be generalizable to mild forms of these disorders since the data were based on clinical diagnoses and prescriptions.

The study was supported by the Chinese Scholarship Council, the Swedish Research Council for Health, Working Life and Welfare, the Karolinska Institutet, and the Icelandic Research Fund. The authors and Dr. Harlow had no relevant competing interests to disclose.

Reintervention rates after uterus-preserving surgery for leiomyomata were lowest after vaginal myomectomy, the most frequent among four therapeutic approaches, a large cohort study reported.

Accounting for censoring, the 7-year reintervention risk for vaginal myomectomy was 20.6%, followed by uterine artery embolization (26%), endometrial ablation (35.5%), and hysteroscopic myomectomy (37%).

Hysterectomies accounted for 63.2% of reinterventions according to lead author Susanna D. Mitro, PhD, a research scientist in the Division of Research and Department of Obstetrics and Gynecology at Kaiser Permanente Northern California, Oakland, and colleagues.

Mitro_Susanna_CA_web.jpg

The Study

In a cohort of 10,324 patients ages 18-50, 19.9% were Asian, 21.2% Black, 21.3% Hispanic, and 32.5% White, with 5.2% of other races and ethnicities. The most affected age groups were 41-45 and 46-50 years. All participants underwent a first uterus-preserving procedure after leiomyoma diagnosis according to 2009-2021 electronic health records at Kaiser Permanente Northern California.

Reintervention referred to a second uterus-preserving procedure or hysterectomy. Median follow-up was 3.8 years (interquartile range, 1.8-7.4 years), and the proportions of index procedures were as follows: 18% (1857) for hysteroscopic myomectomy; 16.2% (1669) for uterine artery embolization; 21.4% (2211) for endometrial ablations; and 44.4% (4,587) for myomectomy.

Reintervention rates were higher in younger patients after uterine artery embolization, with patients ages 18-35 at the index procedure having 1.4-3.7 times greater reintervention rates than patients ages 46-50 years. Reintervention rates for hysteroscopic myomectomy varied by parity, with multiparous patients at 35% greater risk than their nulliparous counterparts.

On the age issue, the authors note that symptom recurrence may be less common in older patients, perhaps because of the onset of menopause. “Alternatively, findings may be explained by age-specific care strategies: Older patients experiencing symptom recurrence may prefer to wait until the onset of menopause rather than pursuing another surgical treatment,” they wrote.

A recent study with 7 years’ follow-up reported a 2.4 times greater risk of hysterectomy after uterine artery embolization versus myomectomy. Reintervention rates may be lower after myomectomy because otherwise asymptomatic patients pursue myomectomy to treat infertility, the authors wrote. Alternatively, myomectomy may more completely remove leiomyomas.

These common benign tumors take a toll on healthcare resources, in 2012 costing up to $9.4 billion annually (in 2010 dollars) for related surgeries, medications, and procedures. Leiomyomas are reportedly the most frequent reason for hysterectomy.

Robust data on the optimal therapeutic approach to fibroids have been sparse, however, with a 2017 comparative-effectiveness review from the Agency for Healthcare Research and Quality reporting that evidence on leiomyoma treatments was insufficient to guide clinical care. Few well-conducted trials of leiomyoma treatment have directly compared different treatment options, the authors noted.

The rate of myomectomy is reported to be 9.2 per 10,000 woman-years in Black women and 1.3 per 10,000 woman years in White women, and the recurrence rate after myomectomy can be as great as 60% when patients are followed up to 5 years.

The authors said their findings “may be a reference to discuss expectations for treatment outcomes when choosing initial uterus-preserving treatment for leiomyomas, especially for patients receiving treatment years before the likely onset of menopause.”

This research was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health. Coauthor Dr. Lauren Wise is a paid consultant for AbbVie and has received in-kind donations from Swiss Precision Diagnostics and Kindara.com; she has also received payment from the Gates Foundation.

Reintervention rates after uterus-preserving surgery for leiomyomata were lowest after vaginal myomectomy, the most frequent among four therapeutic approaches, a large cohort study reported.

Accounting for censoring, the 7-year reintervention risk for vaginal myomectomy was 20.6%, followed by uterine artery embolization (26%), endometrial ablation (35.5%), and hysteroscopic myomectomy (37%).

Hysterectomies accounted for 63.2% of reinterventions according to lead author Susanna D. Mitro, PhD, a research scientist in the Division of Research and Department of Obstetrics and Gynecology at Kaiser Permanente Northern California, Oakland, and colleagues.

Mitro_Susanna_CA_web.jpg

The Study

In a cohort of 10,324 patients ages 18-50, 19.9% were Asian, 21.2% Black, 21.3% Hispanic, and 32.5% White, with 5.2% of other races and ethnicities. The most affected age groups were 41-45 and 46-50 years. All participants underwent a first uterus-preserving procedure after leiomyoma diagnosis according to 2009-2021 electronic health records at Kaiser Permanente Northern California.

Reintervention referred to a second uterus-preserving procedure or hysterectomy. Median follow-up was 3.8 years (interquartile range, 1.8-7.4 years), and the proportions of index procedures were as follows: 18% (1857) for hysteroscopic myomectomy; 16.2% (1669) for uterine artery embolization; 21.4% (2211) for endometrial ablations; and 44.4% (4,587) for myomectomy.

Reintervention rates were higher in younger patients after uterine artery embolization, with patients ages 18-35 at the index procedure having 1.4-3.7 times greater reintervention rates than patients ages 46-50 years. Reintervention rates for hysteroscopic myomectomy varied by parity, with multiparous patients at 35% greater risk than their nulliparous counterparts.

On the age issue, the authors note that symptom recurrence may be less common in older patients, perhaps because of the onset of menopause. “Alternatively, findings may be explained by age-specific care strategies: Older patients experiencing symptom recurrence may prefer to wait until the onset of menopause rather than pursuing another surgical treatment,” they wrote.

A recent study with 7 years’ follow-up reported a 2.4 times greater risk of hysterectomy after uterine artery embolization versus myomectomy. Reintervention rates may be lower after myomectomy because otherwise asymptomatic patients pursue myomectomy to treat infertility, the authors wrote. Alternatively, myomectomy may more completely remove leiomyomas.

These common benign tumors take a toll on healthcare resources, in 2012 costing up to $9.4 billion annually (in 2010 dollars) for related surgeries, medications, and procedures. Leiomyomas are reportedly the most frequent reason for hysterectomy.

Robust data on the optimal therapeutic approach to fibroids have been sparse, however, with a 2017 comparative-effectiveness review from the Agency for Healthcare Research and Quality reporting that evidence on leiomyoma treatments was insufficient to guide clinical care. Few well-conducted trials of leiomyoma treatment have directly compared different treatment options, the authors noted.

The rate of myomectomy is reported to be 9.2 per 10,000 woman-years in Black women and 1.3 per 10,000 woman years in White women, and the recurrence rate after myomectomy can be as great as 60% when patients are followed up to 5 years.

The authors said their findings “may be a reference to discuss expectations for treatment outcomes when choosing initial uterus-preserving treatment for leiomyomas, especially for patients receiving treatment years before the likely onset of menopause.”

This research was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health. Coauthor Dr. Lauren Wise is a paid consultant for AbbVie and has received in-kind donations from Swiss Precision Diagnostics and Kindara.com; she has also received payment from the Gates Foundation.

Reintervention rates after uterus-preserving surgery for leiomyomata were lowest after vaginal myomectomy, the most frequent among four therapeutic approaches, a large cohort study reported.

Accounting for censoring, the 7-year reintervention risk for vaginal myomectomy was 20.6%, followed by uterine artery embolization (26%), endometrial ablation (35.5%), and hysteroscopic myomectomy (37%).

Hysterectomies accounted for 63.2% of reinterventions according to lead author Susanna D. Mitro, PhD, a research scientist in the Division of Research and Department of Obstetrics and Gynecology at Kaiser Permanente Northern California, Oakland, and colleagues.

Mitro_Susanna_CA_web.jpg

The Study

In a cohort of 10,324 patients ages 18-50, 19.9% were Asian, 21.2% Black, 21.3% Hispanic, and 32.5% White, with 5.2% of other races and ethnicities. The most affected age groups were 41-45 and 46-50 years. All participants underwent a first uterus-preserving procedure after leiomyoma diagnosis according to 2009-2021 electronic health records at Kaiser Permanente Northern California.

Reintervention referred to a second uterus-preserving procedure or hysterectomy. Median follow-up was 3.8 years (interquartile range, 1.8-7.4 years), and the proportions of index procedures were as follows: 18% (1857) for hysteroscopic myomectomy; 16.2% (1669) for uterine artery embolization; 21.4% (2211) for endometrial ablations; and 44.4% (4,587) for myomectomy.

Reintervention rates were higher in younger patients after uterine artery embolization, with patients ages 18-35 at the index procedure having 1.4-3.7 times greater reintervention rates than patients ages 46-50 years. Reintervention rates for hysteroscopic myomectomy varied by parity, with multiparous patients at 35% greater risk than their nulliparous counterparts.

On the age issue, the authors note that symptom recurrence may be less common in older patients, perhaps because of the onset of menopause. “Alternatively, findings may be explained by age-specific care strategies: Older patients experiencing symptom recurrence may prefer to wait until the onset of menopause rather than pursuing another surgical treatment,” they wrote.

A recent study with 7 years’ follow-up reported a 2.4 times greater risk of hysterectomy after uterine artery embolization versus myomectomy. Reintervention rates may be lower after myomectomy because otherwise asymptomatic patients pursue myomectomy to treat infertility, the authors wrote. Alternatively, myomectomy may more completely remove leiomyomas.

These common benign tumors take a toll on healthcare resources, in 2012 costing up to $9.4 billion annually (in 2010 dollars) for related surgeries, medications, and procedures. Leiomyomas are reportedly the most frequent reason for hysterectomy.

Robust data on the optimal therapeutic approach to fibroids have been sparse, however, with a 2017 comparative-effectiveness review from the Agency for Healthcare Research and Quality reporting that evidence on leiomyoma treatments was insufficient to guide clinical care. Few well-conducted trials of leiomyoma treatment have directly compared different treatment options, the authors noted.

The rate of myomectomy is reported to be 9.2 per 10,000 woman-years in Black women and 1.3 per 10,000 woman years in White women, and the recurrence rate after myomectomy can be as great as 60% when patients are followed up to 5 years.

The authors said their findings “may be a reference to discuss expectations for treatment outcomes when choosing initial uterus-preserving treatment for leiomyomas, especially for patients receiving treatment years before the likely onset of menopause.”

This research was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health. Coauthor Dr. Lauren Wise is a paid consultant for AbbVie and has received in-kind donations from Swiss Precision Diagnostics and Kindara.com; she has also received payment from the Gates Foundation.

A next-generation stool DNA test for colorectal cancer (CRC) screening had higher sensitivity for all screening-relevant lesions but lower specificity than a currently available fecal immunochemical test (FIT), according to the large prospective BLUE-C study.

The multi-target assay by Exact Sciences Corporation, the makers of Cologuard, includes new biomarkers designed to increase specificity without decreasing sensitivity. It showed a sensitivity for CRC of almost 94%, with more than 43% sensitivity for advanced precancerous lesions and nearly 91% specificity for advanced neoplasia, according to the study results, which were published in The New England Journal of Medicine.

Imperiale_Thomas_IN_web.jpg

Adherence to CRC screening in the United States is well below the 80% national target, and the quest continues for noninvasive screening assays that might improve screening adherence, noted lead author Thomas F. Imperiale, MD, AGAF, a professor of medicine at Indiana University School of medicine in Indianapolis, and colleagues.

“The test’s manufacturer developed a new version of its existing Cologuard FIT/DNA test because it took to heart the feedback from primary care providers and gastroenterologists about the test’s low specificity,” Dr. Imperiale said in an interview. “The goal of the new test was to improve specificity without losing, and perhaps even gaining, some sensitivity — a goal that is not easily accomplished when you’re trying to improve on a sensitivity for colorectal cancer that was already 92.3% in the current version of Cologuard.”

Compared with the earlier version of Cologuard, he added, the new generation retained sensitivity for CRC and advanced precancerous lesions or polyps while improving specificity by 30% (90.6% vs 86.6%) for advanced neoplasia — a combination of CRC and advanced precancerous lesions, he said. “This with the caveat, however, that the two versions were not compared head-to-head in this new study,” Dr. Imperiale said.

The higher specificity for advanced lesions is expected to translate to a lower false positive rate. Lowering false positive rates is crucial because that reduces the need for costly, invasive, and unnecessary colonoscopies, said Aasma Shaukat, MD, MPH, AGAF, director of outcomes research in NYU Langone Health’s division of gastroenterology and hepatology in New York City.

Shaukat_Aasma_NY_web.jpg

“Many physicians felt there were too many false positives with the existing version, and that is anxiety-provoking in patients and providers,” said Dr. Shaukat, who was not involved in the study.

In her view, however, the test’s moderate improvements in detecting certain lesions does not make it demonstrably superior to its predecessor, and there is always the possibility of higher cost to consider.

While acknowledging that a higher sensitivity for all advanced precancerous lesions would have been welcome, Dr. Imperiale said the test detected 75% of the most worrisome of such lesions — “the ones containing high-grade dysplastic cells and suggesting near-term conversion to cancer. And its ability to detect other advanced lesions improved as the size of the lesions increased.”
 

Testing details

Almost 21,000 asymptomatic participants age 40 years and older undergoing screening colonoscopy were evaluated at 186 US sites during the period 2019 to 2023. Of the cohort, 98 had CRC, 2144 had advanced precancerous lesions, 6973 had nonadvanced adenomas, and 10,961 had nonneoplastic findings or negative colonoscopy.

Advanced precancerous lesions included one or more adenomas or sessile serrated lesions measuring at least 1 cm in the longest dimension, lesions with villous histologic features, and high-grade dysplasia. The new DNA test identified 92 of 98 participants with CRC and 76 of 82 participants with screening-relevant cancers. Among the findings for the new assay:

• Sensitivity for any-stage CRC was 93.9% (95% confidence interval [CI], 87.1- 97.7)
• Sensitivity for advanced precancerous lesions was 43.4% (95% CI, 41.3-45.6)
• Sensitivity for high-grade dysplasia was 74.6% (95% CI, 65.6-82.3)
• Specificity for advanced neoplasia was 90.6% (95% CI, 90.1- 91.0).
• Specificity for nonneoplastic findings or negative colonoscopy was 92.7% (95% CI, 92.2-93.1)
• Specificity for negative colonoscopy was 93.3 (95% CI, 92.8-93.9)
• No adverse events occurred.

In the comparator assay, OC-AUTO FIT by Polymedco, sensitivity was 67.3% (95% CI, 57.1-76.5) for CRC, 23.3% (95% CI, 21.5-25.2) for advanced precancerous lesions, and 47.4% (95% CI, 37.9-56.9) for high-grade dysplasia. In the comparator FIT, however, specificity was better across all age groups — at 94.8% (95% CI, 94.4-95.1) for advanced neoplasia, 95.7% (95% CI, 95.3- 96.1) for nonneoplastic findings, and 96.0% (95% CI, 95.5-96.4) for negative colonoscopy.

In another article in the same issue of NEJM, Guardant Health’s cell-free DNA blood-based test had 83% sensitivity for CRC, 90% specificity for advanced neoplasia, and 13% sensitivity for advanced precancerous lesions in an average-risk population.

An age-related decrease in specificity was observed with the new Cologuard test, but that did not concern Dr. Imperiale because the same observation was made with the current version. “In fact, the next-gen version appears to have less of an age-related decrease in specificity than the current version, although, again, the two versions were not tested head-to-head,” he noted.

The effect of age-related background methylation of DNA is well known, he explained. “Clinicians and older patients in the screening age range do need to be aware of this effect on specificity before ordering or agreeing to do the test. I do not see this as a stumbling block to implementation, but it does require discussion between patient and ordering provider.”

The new version of the DNA test is expected to be available in about a year.

According to Dr. Imperiale, further research is needed to ascertain the test’s acceptability and adherence rates and to quantify its yield in population-based screening. Determining its cost-effectiveness and making it easier to use are other goals. “And most importantly, the degree of reduction in the incidence and mortality from colorectal cancer,” he said.

Cost-effectiveness and the selection of the testing interval may play roles in adherence, particularly in populations with lower rates of screening adherence than the general population, John M. Carethers, MD, AGAF, of the University of California, San Diego, noted in a related editorial.

“Adherence to screening varies according to age group, including persons in the 45- to 49-year age group who are now eligible for average-risk screening,” he wrote. “It is hoped that these newer tests will increase use and adherence and elevate the percentage of the population undergoing screening in order to reduce deaths from colorectal cancer.”

This study was sponsored by Exact Sciences Corporation, which conducted the stool testing at its laboratories.

Dr. Imperiale had no competing interests to disclose. Several study co-authors reported employment with Exact Sciences, or stock and intellectual property ownership. Dr. Shaukat disclosed consulting for Freenome. Dr. Carethers reported ties to Avantor Inc. and Geneoscopy.

A next-generation stool DNA test for colorectal cancer (CRC) screening had higher sensitivity for all screening-relevant lesions but lower specificity than a currently available fecal immunochemical test (FIT), according to the large prospective BLUE-C study.

The multi-target assay by Exact Sciences Corporation, the makers of Cologuard, includes new biomarkers designed to increase specificity without decreasing sensitivity. It showed a sensitivity for CRC of almost 94%, with more than 43% sensitivity for advanced precancerous lesions and nearly 91% specificity for advanced neoplasia, according to the study results, which were published in The New England Journal of Medicine.

Imperiale_Thomas_IN_web.jpg

Adherence to CRC screening in the United States is well below the 80% national target, and the quest continues for noninvasive screening assays that might improve screening adherence, noted lead author Thomas F. Imperiale, MD, AGAF, a professor of medicine at Indiana University School of medicine in Indianapolis, and colleagues.

“The test’s manufacturer developed a new version of its existing Cologuard FIT/DNA test because it took to heart the feedback from primary care providers and gastroenterologists about the test’s low specificity,” Dr. Imperiale said in an interview. “The goal of the new test was to improve specificity without losing, and perhaps even gaining, some sensitivity — a goal that is not easily accomplished when you’re trying to improve on a sensitivity for colorectal cancer that was already 92.3% in the current version of Cologuard.”

Compared with the earlier version of Cologuard, he added, the new generation retained sensitivity for CRC and advanced precancerous lesions or polyps while improving specificity by 30% (90.6% vs 86.6%) for advanced neoplasia — a combination of CRC and advanced precancerous lesions, he said. “This with the caveat, however, that the two versions were not compared head-to-head in this new study,” Dr. Imperiale said.

The higher specificity for advanced lesions is expected to translate to a lower false positive rate. Lowering false positive rates is crucial because that reduces the need for costly, invasive, and unnecessary colonoscopies, said Aasma Shaukat, MD, MPH, AGAF, director of outcomes research in NYU Langone Health’s division of gastroenterology and hepatology in New York City.

Shaukat_Aasma_NY_web.jpg

“Many physicians felt there were too many false positives with the existing version, and that is anxiety-provoking in patients and providers,” said Dr. Shaukat, who was not involved in the study.

In her view, however, the test’s moderate improvements in detecting certain lesions does not make it demonstrably superior to its predecessor, and there is always the possibility of higher cost to consider.

While acknowledging that a higher sensitivity for all advanced precancerous lesions would have been welcome, Dr. Imperiale said the test detected 75% of the most worrisome of such lesions — “the ones containing high-grade dysplastic cells and suggesting near-term conversion to cancer. And its ability to detect other advanced lesions improved as the size of the lesions increased.”
 

Testing details

Almost 21,000 asymptomatic participants age 40 years and older undergoing screening colonoscopy were evaluated at 186 US sites during the period 2019 to 2023. Of the cohort, 98 had CRC, 2144 had advanced precancerous lesions, 6973 had nonadvanced adenomas, and 10,961 had nonneoplastic findings or negative colonoscopy.

Advanced precancerous lesions included one or more adenomas or sessile serrated lesions measuring at least 1 cm in the longest dimension, lesions with villous histologic features, and high-grade dysplasia. The new DNA test identified 92 of 98 participants with CRC and 76 of 82 participants with screening-relevant cancers. Among the findings for the new assay:

• Sensitivity for any-stage CRC was 93.9% (95% confidence interval [CI], 87.1- 97.7)
• Sensitivity for advanced precancerous lesions was 43.4% (95% CI, 41.3-45.6)
• Sensitivity for high-grade dysplasia was 74.6% (95% CI, 65.6-82.3)
• Specificity for advanced neoplasia was 90.6% (95% CI, 90.1- 91.0).
• Specificity for nonneoplastic findings or negative colonoscopy was 92.7% (95% CI, 92.2-93.1)
• Specificity for negative colonoscopy was 93.3 (95% CI, 92.8-93.9)
• No adverse events occurred.

In the comparator assay, OC-AUTO FIT by Polymedco, sensitivity was 67.3% (95% CI, 57.1-76.5) for CRC, 23.3% (95% CI, 21.5-25.2) for advanced precancerous lesions, and 47.4% (95% CI, 37.9-56.9) for high-grade dysplasia. In the comparator FIT, however, specificity was better across all age groups — at 94.8% (95% CI, 94.4-95.1) for advanced neoplasia, 95.7% (95% CI, 95.3- 96.1) for nonneoplastic findings, and 96.0% (95% CI, 95.5-96.4) for negative colonoscopy.

In another article in the same issue of NEJM, Guardant Health’s cell-free DNA blood-based test had 83% sensitivity for CRC, 90% specificity for advanced neoplasia, and 13% sensitivity for advanced precancerous lesions in an average-risk population.

An age-related decrease in specificity was observed with the new Cologuard test, but that did not concern Dr. Imperiale because the same observation was made with the current version. “In fact, the next-gen version appears to have less of an age-related decrease in specificity than the current version, although, again, the two versions were not tested head-to-head,” he noted.

The effect of age-related background methylation of DNA is well known, he explained. “Clinicians and older patients in the screening age range do need to be aware of this effect on specificity before ordering or agreeing to do the test. I do not see this as a stumbling block to implementation, but it does require discussion between patient and ordering provider.”

The new version of the DNA test is expected to be available in about a year.

According to Dr. Imperiale, further research is needed to ascertain the test’s acceptability and adherence rates and to quantify its yield in population-based screening. Determining its cost-effectiveness and making it easier to use are other goals. “And most importantly, the degree of reduction in the incidence and mortality from colorectal cancer,” he said.

Cost-effectiveness and the selection of the testing interval may play roles in adherence, particularly in populations with lower rates of screening adherence than the general population, John M. Carethers, MD, AGAF, of the University of California, San Diego, noted in a related editorial.

“Adherence to screening varies according to age group, including persons in the 45- to 49-year age group who are now eligible for average-risk screening,” he wrote. “It is hoped that these newer tests will increase use and adherence and elevate the percentage of the population undergoing screening in order to reduce deaths from colorectal cancer.”

This study was sponsored by Exact Sciences Corporation, which conducted the stool testing at its laboratories.

Dr. Imperiale had no competing interests to disclose. Several study co-authors reported employment with Exact Sciences, or stock and intellectual property ownership. Dr. Shaukat disclosed consulting for Freenome. Dr. Carethers reported ties to Avantor Inc. and Geneoscopy.

A next-generation stool DNA test for colorectal cancer (CRC) screening had higher sensitivity for all screening-relevant lesions but lower specificity than a currently available fecal immunochemical test (FIT), according to the large prospective BLUE-C study.

The multi-target assay by Exact Sciences Corporation, the makers of Cologuard, includes new biomarkers designed to increase specificity without decreasing sensitivity. It showed a sensitivity for CRC of almost 94%, with more than 43% sensitivity for advanced precancerous lesions and nearly 91% specificity for advanced neoplasia, according to the study results, which were published in The New England Journal of Medicine.

Imperiale_Thomas_IN_web.jpg

Adherence to CRC screening in the United States is well below the 80% national target, and the quest continues for noninvasive screening assays that might improve screening adherence, noted lead author Thomas F. Imperiale, MD, AGAF, a professor of medicine at Indiana University School of medicine in Indianapolis, and colleagues.

“The test’s manufacturer developed a new version of its existing Cologuard FIT/DNA test because it took to heart the feedback from primary care providers and gastroenterologists about the test’s low specificity,” Dr. Imperiale said in an interview. “The goal of the new test was to improve specificity without losing, and perhaps even gaining, some sensitivity — a goal that is not easily accomplished when you’re trying to improve on a sensitivity for colorectal cancer that was already 92.3% in the current version of Cologuard.”

Compared with the earlier version of Cologuard, he added, the new generation retained sensitivity for CRC and advanced precancerous lesions or polyps while improving specificity by 30% (90.6% vs 86.6%) for advanced neoplasia — a combination of CRC and advanced precancerous lesions, he said. “This with the caveat, however, that the two versions were not compared head-to-head in this new study,” Dr. Imperiale said.

The higher specificity for advanced lesions is expected to translate to a lower false positive rate. Lowering false positive rates is crucial because that reduces the need for costly, invasive, and unnecessary colonoscopies, said Aasma Shaukat, MD, MPH, AGAF, director of outcomes research in NYU Langone Health’s division of gastroenterology and hepatology in New York City.

Shaukat_Aasma_NY_web.jpg

“Many physicians felt there were too many false positives with the existing version, and that is anxiety-provoking in patients and providers,” said Dr. Shaukat, who was not involved in the study.

In her view, however, the test’s moderate improvements in detecting certain lesions does not make it demonstrably superior to its predecessor, and there is always the possibility of higher cost to consider.

While acknowledging that a higher sensitivity for all advanced precancerous lesions would have been welcome, Dr. Imperiale said the test detected 75% of the most worrisome of such lesions — “the ones containing high-grade dysplastic cells and suggesting near-term conversion to cancer. And its ability to detect other advanced lesions improved as the size of the lesions increased.”
 

Testing details

Almost 21,000 asymptomatic participants age 40 years and older undergoing screening colonoscopy were evaluated at 186 US sites during the period 2019 to 2023. Of the cohort, 98 had CRC, 2144 had advanced precancerous lesions, 6973 had nonadvanced adenomas, and 10,961 had nonneoplastic findings or negative colonoscopy.

Advanced precancerous lesions included one or more adenomas or sessile serrated lesions measuring at least 1 cm in the longest dimension, lesions with villous histologic features, and high-grade dysplasia. The new DNA test identified 92 of 98 participants with CRC and 76 of 82 participants with screening-relevant cancers. Among the findings for the new assay:

• Sensitivity for any-stage CRC was 93.9% (95% confidence interval [CI], 87.1- 97.7)
• Sensitivity for advanced precancerous lesions was 43.4% (95% CI, 41.3-45.6)
• Sensitivity for high-grade dysplasia was 74.6% (95% CI, 65.6-82.3)
• Specificity for advanced neoplasia was 90.6% (95% CI, 90.1- 91.0).
• Specificity for nonneoplastic findings or negative colonoscopy was 92.7% (95% CI, 92.2-93.1)
• Specificity for negative colonoscopy was 93.3 (95% CI, 92.8-93.9)
• No adverse events occurred.

In the comparator assay, OC-AUTO FIT by Polymedco, sensitivity was 67.3% (95% CI, 57.1-76.5) for CRC, 23.3% (95% CI, 21.5-25.2) for advanced precancerous lesions, and 47.4% (95% CI, 37.9-56.9) for high-grade dysplasia. In the comparator FIT, however, specificity was better across all age groups — at 94.8% (95% CI, 94.4-95.1) for advanced neoplasia, 95.7% (95% CI, 95.3- 96.1) for nonneoplastic findings, and 96.0% (95% CI, 95.5-96.4) for negative colonoscopy.

In another article in the same issue of NEJM, Guardant Health’s cell-free DNA blood-based test had 83% sensitivity for CRC, 90% specificity for advanced neoplasia, and 13% sensitivity for advanced precancerous lesions in an average-risk population.

An age-related decrease in specificity was observed with the new Cologuard test, but that did not concern Dr. Imperiale because the same observation was made with the current version. “In fact, the next-gen version appears to have less of an age-related decrease in specificity than the current version, although, again, the two versions were not tested head-to-head,” he noted.

The effect of age-related background methylation of DNA is well known, he explained. “Clinicians and older patients in the screening age range do need to be aware of this effect on specificity before ordering or agreeing to do the test. I do not see this as a stumbling block to implementation, but it does require discussion between patient and ordering provider.”

The new version of the DNA test is expected to be available in about a year.

According to Dr. Imperiale, further research is needed to ascertain the test’s acceptability and adherence rates and to quantify its yield in population-based screening. Determining its cost-effectiveness and making it easier to use are other goals. “And most importantly, the degree of reduction in the incidence and mortality from colorectal cancer,” he said.

Cost-effectiveness and the selection of the testing interval may play roles in adherence, particularly in populations with lower rates of screening adherence than the general population, John M. Carethers, MD, AGAF, of the University of California, San Diego, noted in a related editorial.

“Adherence to screening varies according to age group, including persons in the 45- to 49-year age group who are now eligible for average-risk screening,” he wrote. “It is hoped that these newer tests will increase use and adherence and elevate the percentage of the population undergoing screening in order to reduce deaths from colorectal cancer.”

This study was sponsored by Exact Sciences Corporation, which conducted the stool testing at its laboratories.

Dr. Imperiale had no competing interests to disclose. Several study co-authors reported employment with Exact Sciences, or stock and intellectual property ownership. Dr. Shaukat disclosed consulting for Freenome. Dr. Carethers reported ties to Avantor Inc. and Geneoscopy.

While primary care physicians are uniquely positioned to identify mistreated minors, there is insufficient evidence of benefits and harms to support primary care interventions to prevent maltreatment in children who have no indicative signs or symptoms. That is the conclusion of the US Preventive Services Task Force (USPSTF) in an update of its 2018 statement published in JAMA Network Open.

This gap, however, might be partially filled by addressing in young patients the known social determinants of health such as economic stability, food, shelter, and healthcare access. The USPSTF statement is based on a simultaneously published evidence review and synthesis compiled by Meera Viswanathan, PhD, of the RTI International-University of North Carolina at Chapel Hill Evidence-Based Practice Center in Triangle Park, NC, and colleagues.

Viswanathan_Meera_NC_web.jpg

Barry_Michael_J_MA_web.jpg

A Common and Costly Problem

Child abuse or neglect is widespread and has long-lasting adverse effects. In 2021, the statement noted, Child Protective Services identified 600,000 children as abused or neglected, with 1821 related deaths. Most (76%) experienced neglect, but many were subjected to physical abuse (16%), sexual abuse (10%), and sex trafficking (0.2%). Of the 1820 who died, 78% experienced neglect and 43% experienced physical abuse alone or combined with maltreatment such as neglect and psychological abuse.

Benefits aside, among the potential harms of intervention, the USPSTF noted, is family stigma and bias toward non-White and low-income groups. There may be a greater probability of clinicians’ disproportionately reporting abuse for the children of Black, Hispanic, indigenous, and one-parent households. Some studies indicate that more cases of maltreatment are missed in White children, the review authors noted.

“Additional evidence is needed to clarify potential linkages between improvements in social determinants of health and child maltreatment prevention,” the USPSTF panelists concluded. They acknowledged that their recommendation does not address the effectiveness of interventions such as home visits to improve family well-being.

In an accompanying editorial Samantha Schilling, MD, MSHP, of the Department of Pediatrics at the University of North Carolina at Chapel Hill, and colleagues from the Children’s Hospital of Philadelphia in Pennsylvania admitted they were “disheartened, but not surprised” at the USPSTF’s conclusions and urged that prevention measures be continued. “It is not yet time to wave the white flag of surrender and abandon primary care–based efforts to mitigate risks for child abuse and neglect.

Schilling_Samantha_NC_web.jpg

While primary care physicians are uniquely positioned to identify mistreated minors, there is insufficient evidence of benefits and harms to support primary care interventions to prevent maltreatment in children who have no indicative signs or symptoms. That is the conclusion of the US Preventive Services Task Force (USPSTF) in an update of its 2018 statement published in JAMA Network Open.

This gap, however, might be partially filled by addressing in young patients the known social determinants of health such as economic stability, food, shelter, and healthcare access. The USPSTF statement is based on a simultaneously published evidence review and synthesis compiled by Meera Viswanathan, PhD, of the RTI International-University of North Carolina at Chapel Hill Evidence-Based Practice Center in Triangle Park, NC, and colleagues.

Viswanathan_Meera_NC_web.jpg

Barry_Michael_J_MA_web.jpg

A Common and Costly Problem

Child abuse or neglect is widespread and has long-lasting adverse effects. In 2021, the statement noted, Child Protective Services identified 600,000 children as abused or neglected, with 1821 related deaths. Most (76%) experienced neglect, but many were subjected to physical abuse (16%), sexual abuse (10%), and sex trafficking (0.2%). Of the 1820 who died, 78% experienced neglect and 43% experienced physical abuse alone or combined with maltreatment such as neglect and psychological abuse.

Benefits aside, among the potential harms of intervention, the USPSTF noted, is family stigma and bias toward non-White and low-income groups. There may be a greater probability of clinicians’ disproportionately reporting abuse for the children of Black, Hispanic, indigenous, and one-parent households. Some studies indicate that more cases of maltreatment are missed in White children, the review authors noted.

“Additional evidence is needed to clarify potential linkages between improvements in social determinants of health and child maltreatment prevention,” the USPSTF panelists concluded. They acknowledged that their recommendation does not address the effectiveness of interventions such as home visits to improve family well-being.

In an accompanying editorial Samantha Schilling, MD, MSHP, of the Department of Pediatrics at the University of North Carolina at Chapel Hill, and colleagues from the Children’s Hospital of Philadelphia in Pennsylvania admitted they were “disheartened, but not surprised” at the USPSTF’s conclusions and urged that prevention measures be continued. “It is not yet time to wave the white flag of surrender and abandon primary care–based efforts to mitigate risks for child abuse and neglect.

Schilling_Samantha_NC_web.jpg

While primary care physicians are uniquely positioned to identify mistreated minors, there is insufficient evidence of benefits and harms to support primary care interventions to prevent maltreatment in children who have no indicative signs or symptoms. That is the conclusion of the US Preventive Services Task Force (USPSTF) in an update of its 2018 statement published in JAMA Network Open.

This gap, however, might be partially filled by addressing in young patients the known social determinants of health such as economic stability, food, shelter, and healthcare access. The USPSTF statement is based on a simultaneously published evidence review and synthesis compiled by Meera Viswanathan, PhD, of the RTI International-University of North Carolina at Chapel Hill Evidence-Based Practice Center in Triangle Park, NC, and colleagues.

Viswanathan_Meera_NC_web.jpg

Barry_Michael_J_MA_web.jpg

A Common and Costly Problem

Child abuse or neglect is widespread and has long-lasting adverse effects. In 2021, the statement noted, Child Protective Services identified 600,000 children as abused or neglected, with 1821 related deaths. Most (76%) experienced neglect, but many were subjected to physical abuse (16%), sexual abuse (10%), and sex trafficking (0.2%). Of the 1820 who died, 78% experienced neglect and 43% experienced physical abuse alone or combined with maltreatment such as neglect and psychological abuse.

Benefits aside, among the potential harms of intervention, the USPSTF noted, is family stigma and bias toward non-White and low-income groups. There may be a greater probability of clinicians’ disproportionately reporting abuse for the children of Black, Hispanic, indigenous, and one-parent households. Some studies indicate that more cases of maltreatment are missed in White children, the review authors noted.

“Additional evidence is needed to clarify potential linkages between improvements in social determinants of health and child maltreatment prevention,” the USPSTF panelists concluded. They acknowledged that their recommendation does not address the effectiveness of interventions such as home visits to improve family well-being.

In an accompanying editorial Samantha Schilling, MD, MSHP, of the Department of Pediatrics at the University of North Carolina at Chapel Hill, and colleagues from the Children’s Hospital of Philadelphia in Pennsylvania admitted they were “disheartened, but not surprised” at the USPSTF’s conclusions and urged that prevention measures be continued. “It is not yet time to wave the white flag of surrender and abandon primary care–based efforts to mitigate risks for child abuse and neglect.

Schilling_Samantha_NC_web.jpg

Some doctors may be scratching their heads over a new analysis reporting that combined calcium and vitamin D (CaD) supplements appear to be associated with a slight 6% increase in cardiovascular (CVD) mortality, a slight 7% decrease in cancer risk, and no effect on osteoporotic fracture in postmenopausal women.

The study, in Annals of Internal Medicine, found no effect of supplementation on all-cause mortality.

The findings emerged from an analysis of more than 20 years’ follow-up data on a randomized trial in postmenopausal women conducted as part of the Women’s Health Initiative (WHI).

Cynthia A. Thomson, PhD, RD, first author and cancer prevention scientist at the Arizona Cancer Center and a professor of health promotion sciences at the University of Arizona in Tucson said the findings recommend individualized assessment of the need for supplements for older women as they consider them in hopes of preventing fractures.

Thomson_Cynthia_AZ_web.jpg

Study Details

The investigators conducted postintervention follow-up of the WHI’s 7-year multicenter randomized intervention trial of CaD vs placebo.

Since existing evidence of long-term health outcomes was limited, the trial, begun in 1999 and closed in 2005, enrolled 36,282 postmenopausal women (mean age 62) with no history of breast or colorectal cancer. They were randomly assigned 1:1 to supplementation with 1000 mg of calcium carbonate (400 mg elemental calcium) plus 400 IU of vitamin D3 daily or placebo, taken twice daily in half doses.

Study outcomes were incidence of CRC, total and invasive breast cancer; disease-specific and all-cause mortality; total CVD; and hip fracture measured through December 2020, with analyses stratified by personal supplement usage.

Cancer. CaD was associated with reduced incident total cancer, CRC, and invasive breast cancer — notably among participants not taking CaD before randomization. Cancer incidence estimates varied widely, the authors noted, when stratified by supplement use before randomization. Noting that CaD seemed to have more cancer-related impact in those without prior supplementation, the authors suggested supplementation may affect cancer biology primarily by augmenting nutrient insufficiency.

An estimated 7% reduction in cancer mortality was observed after a median cumulative follow-up of 22.3 years: 1817 vs 1943 deaths (hazard ratio, 0.93; 95% CI, 0.87-0.99).

CVD. An estimated 6% increase in CVD mortality was seen in the CaD group: 2621 vs 2420 deaths (HR, 1.06; 95% CI, 1.01-1.12). Pretrial supplement users were found to be at higher CVD risk.

Hip fracture. No effect on hip fracture risk was measured, but the authors cautioned that hip fracture and CVD outcomes were available only for a subset of participants, and the effects of calcium alone vs vitamin D alone vs the combination could not be disentangled.

In a small subgroup analysis, some CaD users were seen to respond in terms of bone mineral density but since only 4 of the study’s 40 sites collected such information, the study was underpowered to examine the effect. ”Many other studies, however, show a response to supplementation in women who already have bone mineral deficits,” Dr. Thomson said.
 

The Calcification Question

One of the possible mechanisms of harm is that high-dose calcium supplements can increase the rate of blood coagulation and promote vascular calcification, said Emma Laing, PhD, RD, director of dietetics at the University of Georgia in Athens and a spokesperson for the Chicago-based Academy of Nutrition and Dietetics.

Laing_Emma_GA_web.jpg

“Other factors that should be considered when determining a patient’s CVD risk are race, genetic predisposition, medical and social history, response to stress, and lifestyle behaviors, as well as the length of time supplements have been consumed,” added Dr. Laing, who was not involved in the WHI analysis.

“We asked ourselves if CaD supplements might contribute to calcification of the coronary arteries, since some believe this to be the case, although the literature is mixed,” said Dr. Thomson.

“So we did a shorter ancillary study in a small sample of several hundred [women] to see if there was any increase in calcification” and no difference was seen on imaging across the two arms. “However, women who were already on supplements before entering the study seemed to be at higher CVD risk,” she said.

Added study coauthor JoAnn E. Manson, MD, DrPH, chief of the division of preventive medicine at Brigham and Women’s Hospital and professor of women’s health at Harvard Medical School, both in Boston: “With no increase or decrease in coronary artery calcium at the end of the trial, we don’t believe starting or continuing calcium/vitamin D supplements should require screening for coronary artery disease.”

Manson_JoAnn_E_BOSTON_web.jpg

Vitamin D Supplementation

As for vitamin D only supplementation, an updated meta-analysis including more than 83,000 individuals showed that it confers no cardiovascular protection and is therefore not indicated for this purpose.
 

Practice Considerations

Offering an outsider’s perspective, Sarah G. Candler, MD, MPH, an internist in Houston specializing in primary care for older high-risk adults, said: “Unfortunately, this latest study continues the trend of creating more questions than answers. If the adverse outcome of CVD death is a result of supplementation, it is unclear if this is due to the vitamin D, the calcium, or both. And it is unclear if this is dose dependent, time dependent, or due to concurrent risk factors unique to certain populations.

Candler_Sarah_TX_web.jpg

“It is recommended that patients at risk of osteoporosis based on age, sex, medications, and lifestyle be screened for osteoporosis and treated accordingly, including supplementation with CaD,” Dr. Candler said. “It remains unclear whether supplementation with CaD in the absence of osteoporosis and osteopenia is net beneficial or harmful, and at this time I would not recommend it to my patients.” 

Added Dr. Manson: “The very small increase seen in cardiovascular mortality wouldn’t be a reason to discontinue supplementation among women who have been advised by their healthcare providers to take these supplements for bone health or other purposes.

“Among those at usual risk of fracture, we recommend trying to obtain adequate calcium and vitamin D from food sources first and to use supplements only for the purpose of filling gaps in intake,” Dr. Manson continued. Overall, the findings support the national recommended dietary allowances for daily calcium intake of 1200 mg and daily vitamin D intake of 600-800 IU among postmenopausal women for maintenance of bone health, she said.

While a 2022 study found that vitamin D supplementation alone did not prevent fractures in healthy adults, other research has shown that a calcium/vitamin D combination is more likely to protect the skeleton.

“Patients at risk for fractures will probably benefit from calcium and/or vitamin D supplementation if they do not meet dietary intake requirements, have malabsorption syndromes, are taking medications that affect nutrient absorption, or if they are older and not regularly exposed to sunlight,” said Dr. Laing. “A combination of biochemical, imaging, functional, and dietary intake data can help determine if a supplement is warranted.”

She stressed that additional research is needed in more diverse populations before changing practice guidelines. “However, doctors should continue to weigh the risks and benefits of prescribing supplements for each patient.”

The WHI program is funded by the National Heart, Lung, and Blood Institute. Dr. Thomson disclosed no competing interests. Dr. Manson reported a relationship with Mars Edge. Multiple authors reported grant support from government funding agencies. The outside commentators had no relevant competing interests to disclose.

Some doctors may be scratching their heads over a new analysis reporting that combined calcium and vitamin D (CaD) supplements appear to be associated with a slight 6% increase in cardiovascular (CVD) mortality, a slight 7% decrease in cancer risk, and no effect on osteoporotic fracture in postmenopausal women.

The study, in Annals of Internal Medicine, found no effect of supplementation on all-cause mortality.

The findings emerged from an analysis of more than 20 years’ follow-up data on a randomized trial in postmenopausal women conducted as part of the Women’s Health Initiative (WHI).

Cynthia A. Thomson, PhD, RD, first author and cancer prevention scientist at the Arizona Cancer Center and a professor of health promotion sciences at the University of Arizona in Tucson said the findings recommend individualized assessment of the need for supplements for older women as they consider them in hopes of preventing fractures.

Thomson_Cynthia_AZ_web.jpg

Study Details

The investigators conducted postintervention follow-up of the WHI’s 7-year multicenter randomized intervention trial of CaD vs placebo.

Since existing evidence of long-term health outcomes was limited, the trial, begun in 1999 and closed in 2005, enrolled 36,282 postmenopausal women (mean age 62) with no history of breast or colorectal cancer. They were randomly assigned 1:1 to supplementation with 1000 mg of calcium carbonate (400 mg elemental calcium) plus 400 IU of vitamin D3 daily or placebo, taken twice daily in half doses.

Study outcomes were incidence of CRC, total and invasive breast cancer; disease-specific and all-cause mortality; total CVD; and hip fracture measured through December 2020, with analyses stratified by personal supplement usage.

Cancer. CaD was associated with reduced incident total cancer, CRC, and invasive breast cancer — notably among participants not taking CaD before randomization. Cancer incidence estimates varied widely, the authors noted, when stratified by supplement use before randomization. Noting that CaD seemed to have more cancer-related impact in those without prior supplementation, the authors suggested supplementation may affect cancer biology primarily by augmenting nutrient insufficiency.

An estimated 7% reduction in cancer mortality was observed after a median cumulative follow-up of 22.3 years: 1817 vs 1943 deaths (hazard ratio, 0.93; 95% CI, 0.87-0.99).

CVD. An estimated 6% increase in CVD mortality was seen in the CaD group: 2621 vs 2420 deaths (HR, 1.06; 95% CI, 1.01-1.12). Pretrial supplement users were found to be at higher CVD risk.

Hip fracture. No effect on hip fracture risk was measured, but the authors cautioned that hip fracture and CVD outcomes were available only for a subset of participants, and the effects of calcium alone vs vitamin D alone vs the combination could not be disentangled.

In a small subgroup analysis, some CaD users were seen to respond in terms of bone mineral density but since only 4 of the study’s 40 sites collected such information, the study was underpowered to examine the effect. ”Many other studies, however, show a response to supplementation in women who already have bone mineral deficits,” Dr. Thomson said.
 

The Calcification Question

One of the possible mechanisms of harm is that high-dose calcium supplements can increase the rate of blood coagulation and promote vascular calcification, said Emma Laing, PhD, RD, director of dietetics at the University of Georgia in Athens and a spokesperson for the Chicago-based Academy of Nutrition and Dietetics.

Laing_Emma_GA_web.jpg

“Other factors that should be considered when determining a patient’s CVD risk are race, genetic predisposition, medical and social history, response to stress, and lifestyle behaviors, as well as the length of time supplements have been consumed,” added Dr. Laing, who was not involved in the WHI analysis.

“We asked ourselves if CaD supplements might contribute to calcification of the coronary arteries, since some believe this to be the case, although the literature is mixed,” said Dr. Thomson.

“So we did a shorter ancillary study in a small sample of several hundred [women] to see if there was any increase in calcification” and no difference was seen on imaging across the two arms. “However, women who were already on supplements before entering the study seemed to be at higher CVD risk,” she said.

Added study coauthor JoAnn E. Manson, MD, DrPH, chief of the division of preventive medicine at Brigham and Women’s Hospital and professor of women’s health at Harvard Medical School, both in Boston: “With no increase or decrease in coronary artery calcium at the end of the trial, we don’t believe starting or continuing calcium/vitamin D supplements should require screening for coronary artery disease.”

Manson_JoAnn_E_BOSTON_web.jpg

Vitamin D Supplementation

As for vitamin D only supplementation, an updated meta-analysis including more than 83,000 individuals showed that it confers no cardiovascular protection and is therefore not indicated for this purpose.
 

Practice Considerations

Offering an outsider’s perspective, Sarah G. Candler, MD, MPH, an internist in Houston specializing in primary care for older high-risk adults, said: “Unfortunately, this latest study continues the trend of creating more questions than answers. If the adverse outcome of CVD death is a result of supplementation, it is unclear if this is due to the vitamin D, the calcium, or both. And it is unclear if this is dose dependent, time dependent, or due to concurrent risk factors unique to certain populations.

Candler_Sarah_TX_web.jpg

“It is recommended that patients at risk of osteoporosis based on age, sex, medications, and lifestyle be screened for osteoporosis and treated accordingly, including supplementation with CaD,” Dr. Candler said. “It remains unclear whether supplementation with CaD in the absence of osteoporosis and osteopenia is net beneficial or harmful, and at this time I would not recommend it to my patients.” 

Added Dr. Manson: “The very small increase seen in cardiovascular mortality wouldn’t be a reason to discontinue supplementation among women who have been advised by their healthcare providers to take these supplements for bone health or other purposes.

“Among those at usual risk of fracture, we recommend trying to obtain adequate calcium and vitamin D from food sources first and to use supplements only for the purpose of filling gaps in intake,” Dr. Manson continued. Overall, the findings support the national recommended dietary allowances for daily calcium intake of 1200 mg and daily vitamin D intake of 600-800 IU among postmenopausal women for maintenance of bone health, she said.

While a 2022 study found that vitamin D supplementation alone did not prevent fractures in healthy adults, other research has shown that a calcium/vitamin D combination is more likely to protect the skeleton.

“Patients at risk for fractures will probably benefit from calcium and/or vitamin D supplementation if they do not meet dietary intake requirements, have malabsorption syndromes, are taking medications that affect nutrient absorption, or if they are older and not regularly exposed to sunlight,” said Dr. Laing. “A combination of biochemical, imaging, functional, and dietary intake data can help determine if a supplement is warranted.”

She stressed that additional research is needed in more diverse populations before changing practice guidelines. “However, doctors should continue to weigh the risks and benefits of prescribing supplements for each patient.”

The WHI program is funded by the National Heart, Lung, and Blood Institute. Dr. Thomson disclosed no competing interests. Dr. Manson reported a relationship with Mars Edge. Multiple authors reported grant support from government funding agencies. The outside commentators had no relevant competing interests to disclose.

Some doctors may be scratching their heads over a new analysis reporting that combined calcium and vitamin D (CaD) supplements appear to be associated with a slight 6% increase in cardiovascular (CVD) mortality, a slight 7% decrease in cancer risk, and no effect on osteoporotic fracture in postmenopausal women.

The study, in Annals of Internal Medicine, found no effect of supplementation on all-cause mortality.

The findings emerged from an analysis of more than 20 years’ follow-up data on a randomized trial in postmenopausal women conducted as part of the Women’s Health Initiative (WHI).

Cynthia A. Thomson, PhD, RD, first author and cancer prevention scientist at the Arizona Cancer Center and a professor of health promotion sciences at the University of Arizona in Tucson said the findings recommend individualized assessment of the need for supplements for older women as they consider them in hopes of preventing fractures.

Thomson_Cynthia_AZ_web.jpg

Study Details

The investigators conducted postintervention follow-up of the WHI’s 7-year multicenter randomized intervention trial of CaD vs placebo.

Since existing evidence of long-term health outcomes was limited, the trial, begun in 1999 and closed in 2005, enrolled 36,282 postmenopausal women (mean age 62) with no history of breast or colorectal cancer. They were randomly assigned 1:1 to supplementation with 1000 mg of calcium carbonate (400 mg elemental calcium) plus 400 IU of vitamin D3 daily or placebo, taken twice daily in half doses.

Study outcomes were incidence of CRC, total and invasive breast cancer; disease-specific and all-cause mortality; total CVD; and hip fracture measured through December 2020, with analyses stratified by personal supplement usage.

Cancer. CaD was associated with reduced incident total cancer, CRC, and invasive breast cancer — notably among participants not taking CaD before randomization. Cancer incidence estimates varied widely, the authors noted, when stratified by supplement use before randomization. Noting that CaD seemed to have more cancer-related impact in those without prior supplementation, the authors suggested supplementation may affect cancer biology primarily by augmenting nutrient insufficiency.

An estimated 7% reduction in cancer mortality was observed after a median cumulative follow-up of 22.3 years: 1817 vs 1943 deaths (hazard ratio, 0.93; 95% CI, 0.87-0.99).

CVD. An estimated 6% increase in CVD mortality was seen in the CaD group: 2621 vs 2420 deaths (HR, 1.06; 95% CI, 1.01-1.12). Pretrial supplement users were found to be at higher CVD risk.

Hip fracture. No effect on hip fracture risk was measured, but the authors cautioned that hip fracture and CVD outcomes were available only for a subset of participants, and the effects of calcium alone vs vitamin D alone vs the combination could not be disentangled.

In a small subgroup analysis, some CaD users were seen to respond in terms of bone mineral density but since only 4 of the study’s 40 sites collected such information, the study was underpowered to examine the effect. ”Many other studies, however, show a response to supplementation in women who already have bone mineral deficits,” Dr. Thomson said.
 

The Calcification Question

One of the possible mechanisms of harm is that high-dose calcium supplements can increase the rate of blood coagulation and promote vascular calcification, said Emma Laing, PhD, RD, director of dietetics at the University of Georgia in Athens and a spokesperson for the Chicago-based Academy of Nutrition and Dietetics.

Laing_Emma_GA_web.jpg

“Other factors that should be considered when determining a patient’s CVD risk are race, genetic predisposition, medical and social history, response to stress, and lifestyle behaviors, as well as the length of time supplements have been consumed,” added Dr. Laing, who was not involved in the WHI analysis.

“We asked ourselves if CaD supplements might contribute to calcification of the coronary arteries, since some believe this to be the case, although the literature is mixed,” said Dr. Thomson.

“So we did a shorter ancillary study in a small sample of several hundred [women] to see if there was any increase in calcification” and no difference was seen on imaging across the two arms. “However, women who were already on supplements before entering the study seemed to be at higher CVD risk,” she said.

Added study coauthor JoAnn E. Manson, MD, DrPH, chief of the division of preventive medicine at Brigham and Women’s Hospital and professor of women’s health at Harvard Medical School, both in Boston: “With no increase or decrease in coronary artery calcium at the end of the trial, we don’t believe starting or continuing calcium/vitamin D supplements should require screening for coronary artery disease.”

Manson_JoAnn_E_BOSTON_web.jpg

Vitamin D Supplementation

As for vitamin D only supplementation, an updated meta-analysis including more than 83,000 individuals showed that it confers no cardiovascular protection and is therefore not indicated for this purpose.
 

Practice Considerations

Offering an outsider’s perspective, Sarah G. Candler, MD, MPH, an internist in Houston specializing in primary care for older high-risk adults, said: “Unfortunately, this latest study continues the trend of creating more questions than answers. If the adverse outcome of CVD death is a result of supplementation, it is unclear if this is due to the vitamin D, the calcium, or both. And it is unclear if this is dose dependent, time dependent, or due to concurrent risk factors unique to certain populations.

Candler_Sarah_TX_web.jpg

“It is recommended that patients at risk of osteoporosis based on age, sex, medications, and lifestyle be screened for osteoporosis and treated accordingly, including supplementation with CaD,” Dr. Candler said. “It remains unclear whether supplementation with CaD in the absence of osteoporosis and osteopenia is net beneficial or harmful, and at this time I would not recommend it to my patients.” 

Added Dr. Manson: “The very small increase seen in cardiovascular mortality wouldn’t be a reason to discontinue supplementation among women who have been advised by their healthcare providers to take these supplements for bone health or other purposes.

“Among those at usual risk of fracture, we recommend trying to obtain adequate calcium and vitamin D from food sources first and to use supplements only for the purpose of filling gaps in intake,” Dr. Manson continued. Overall, the findings support the national recommended dietary allowances for daily calcium intake of 1200 mg and daily vitamin D intake of 600-800 IU among postmenopausal women for maintenance of bone health, she said.

While a 2022 study found that vitamin D supplementation alone did not prevent fractures in healthy adults, other research has shown that a calcium/vitamin D combination is more likely to protect the skeleton.

“Patients at risk for fractures will probably benefit from calcium and/or vitamin D supplementation if they do not meet dietary intake requirements, have malabsorption syndromes, are taking medications that affect nutrient absorption, or if they are older and not regularly exposed to sunlight,” said Dr. Laing. “A combination of biochemical, imaging, functional, and dietary intake data can help determine if a supplement is warranted.”

She stressed that additional research is needed in more diverse populations before changing practice guidelines. “However, doctors should continue to weigh the risks and benefits of prescribing supplements for each patient.”

The WHI program is funded by the National Heart, Lung, and Blood Institute. Dr. Thomson disclosed no competing interests. Dr. Manson reported a relationship with Mars Edge. Multiple authors reported grant support from government funding agencies. The outside commentators had no relevant competing interests to disclose.

Based on a synthesis of best available evidence, the American Gastroenterological Association (AGA) has released clinical recommendations on fecal microbiota-based therapies (FMT) in adults with gastrointestinal diseases.

Addressing Clostridium difficile infection (CDI), Crohn’s disease (CD) ulcerative colitis (UC), pouchitis, and irritable bowel syndrome (IBS), the guidance supports FMT for the prevention of recurrent CDI but not for inflammatory bowel disease (IBD) or IBS — outside of clinical trials.

The AGA’s recommendations were published in Gastroenterology.

“Fecal microbiota–based therapies are effective therapy to prevent recurrent C. difficile in select patients,” the AGA guideline states. “Conventional fecal microbiota transplant is an adjuvant treatment for select adults hospitalized with severe or fulminant C. difficile infection not responding to standard of care antibiotics. Fecal microbiota transplant cannot yet be recommended in other gastrointestinal conditions.”

“We thought it was important to write this guideline because of the growing number of trials of FMT in IBD and IBS populations. It was also important with the new FDA-approved treatments on the market,” the guideline’s first author, Anne F. Peery, MD, MSCR, AGAF, told this news organization, noting that the recently approved products did not yield better results than those of conventional rectal FMT. “The guidelines will help clinicians understand the available therapies and how to use these treatments,” added Dr. Peery, associate professor in the Division of Gastroenterology and Hepatology at the University of North Carolina School of Medicine in Chapel Hill.

Although the existing evidence is of low or very low certainty, Dr. Peery acknowledged, gastroenterologists “should be comfortable with conventional FMT and also the new FDA-approved products. We spent a considerable amount of time developing implementation considerations, which is practical advice to help clinicians use the guideline recommendations.”

Peery_Anne_F_NC_envir_web.jpg

Recommendations

The eight-member panel suggested the following practices on behalf of the AGA Clinical Guidelines Committee:

• In immunocompetent adults with recurrent CDI, select use of FMT can be used after completion of standard-of-care antibiotics to prevent recurrence. It can be considered after the second recurrence (episode 3) of CDI or in select patients at high risk for either recurrent CDI or a morbid CDI recurrence. Recurrent CDI is defined as clinically significant diarrhea ≥ 3 unformed stools in 24 hours with a confirmatory positive test within 8 weeks of completing antibiotics. Select use includes patients who have recovered from severe, fulminant, or particularly treatment-refractory CDI and patients with significant comorbidities. Severe CDI involves a leukocyte count of ≥15 × 109 cells/L and/or creatinine ≥1.5 mg/dL, while fulminant CDI involves shock, ileus, or megacolon and can be fatal.
• In mildly or moderately immunocompromised adults with recurrent CDI, the guidance recommends select use of conventional fecal microbiota transplant.
• In severely immunocompromised adults or those undergoing cytotoxic treatment, the AGA advises against the use of any fecal microbiota-based therapies to prevent recurrent CDI.
• Conventional FMT is not advised in patients who have bowel perforation or obstruction or are severely immunocompromised.
• For CDI patients not interested in FMT, reasonable alternatives to prevent recurrence are a vancomycin taper, tapered-pulsed fidaxomicin, or bezlotoxumab.
• In adults hospitalized with severe or fulminant CDI not responding to standard-of-care antibiotics, the AGA recommends select use of conventional FM transplant.
• In the current absence of evidence, the guidance advises against the use of conventional fecal microbiota transplant as treatment for IBD or IBS except in the context of clinical trials.

“We felt the data for using FMT in the treatment of UC was promising, but there is still a lot more work to be done in IBD and IBS,” Dr. Peery said. For each disease section the guideline outlined directions for future research. It will be updated in 3-5 years as more evidence becomes available.

This guideline was fully funded by the AGA Institute. Dr. Peery and fellow panel member Dr. Benjamin Lebwohl are supported by grants the National Institute of Diabetes and Digestive and Kidney Diseases. Panel member Colleen R. Kelly, MD, is supported by the National Institute of Allergy and Infectious Diseases.

None of the panel members had any conflicts of interest to report.

Based on a synthesis of best available evidence, the American Gastroenterological Association (AGA) has released clinical recommendations on fecal microbiota-based therapies (FMT) in adults with gastrointestinal diseases.

Addressing Clostridium difficile infection (CDI), Crohn’s disease (CD) ulcerative colitis (UC), pouchitis, and irritable bowel syndrome (IBS), the guidance supports FMT for the prevention of recurrent CDI but not for inflammatory bowel disease (IBD) or IBS — outside of clinical trials.

The AGA’s recommendations were published in Gastroenterology.

“Fecal microbiota–based therapies are effective therapy to prevent recurrent C. difficile in select patients,” the AGA guideline states. “Conventional fecal microbiota transplant is an adjuvant treatment for select adults hospitalized with severe or fulminant C. difficile infection not responding to standard of care antibiotics. Fecal microbiota transplant cannot yet be recommended in other gastrointestinal conditions.”

“We thought it was important to write this guideline because of the growing number of trials of FMT in IBD and IBS populations. It was also important with the new FDA-approved treatments on the market,” the guideline’s first author, Anne F. Peery, MD, MSCR, AGAF, told this news organization, noting that the recently approved products did not yield better results than those of conventional rectal FMT. “The guidelines will help clinicians understand the available therapies and how to use these treatments,” added Dr. Peery, associate professor in the Division of Gastroenterology and Hepatology at the University of North Carolina School of Medicine in Chapel Hill.

Although the existing evidence is of low or very low certainty, Dr. Peery acknowledged, gastroenterologists “should be comfortable with conventional FMT and also the new FDA-approved products. We spent a considerable amount of time developing implementation considerations, which is practical advice to help clinicians use the guideline recommendations.”

Peery_Anne_F_NC_envir_web.jpg

Recommendations

The eight-member panel suggested the following practices on behalf of the AGA Clinical Guidelines Committee:

• In immunocompetent adults with recurrent CDI, select use of FMT can be used after completion of standard-of-care antibiotics to prevent recurrence. It can be considered after the second recurrence (episode 3) of CDI or in select patients at high risk for either recurrent CDI or a morbid CDI recurrence. Recurrent CDI is defined as clinically significant diarrhea ≥ 3 unformed stools in 24 hours with a confirmatory positive test within 8 weeks of completing antibiotics. Select use includes patients who have recovered from severe, fulminant, or particularly treatment-refractory CDI and patients with significant comorbidities. Severe CDI involves a leukocyte count of ≥15 × 109 cells/L and/or creatinine ≥1.5 mg/dL, while fulminant CDI involves shock, ileus, or megacolon and can be fatal.
• In mildly or moderately immunocompromised adults with recurrent CDI, the guidance recommends select use of conventional fecal microbiota transplant.
• In severely immunocompromised adults or those undergoing cytotoxic treatment, the AGA advises against the use of any fecal microbiota-based therapies to prevent recurrent CDI.
• Conventional FMT is not advised in patients who have bowel perforation or obstruction or are severely immunocompromised.
• For CDI patients not interested in FMT, reasonable alternatives to prevent recurrence are a vancomycin taper, tapered-pulsed fidaxomicin, or bezlotoxumab.
• In adults hospitalized with severe or fulminant CDI not responding to standard-of-care antibiotics, the AGA recommends select use of conventional FM transplant.
• In the current absence of evidence, the guidance advises against the use of conventional fecal microbiota transplant as treatment for IBD or IBS except in the context of clinical trials.

“We felt the data for using FMT in the treatment of UC was promising, but there is still a lot more work to be done in IBD and IBS,” Dr. Peery said. For each disease section the guideline outlined directions for future research. It will be updated in 3-5 years as more evidence becomes available.

This guideline was fully funded by the AGA Institute. Dr. Peery and fellow panel member Dr. Benjamin Lebwohl are supported by grants the National Institute of Diabetes and Digestive and Kidney Diseases. Panel member Colleen R. Kelly, MD, is supported by the National Institute of Allergy and Infectious Diseases.

None of the panel members had any conflicts of interest to report.

Based on a synthesis of best available evidence, the American Gastroenterological Association (AGA) has released clinical recommendations on fecal microbiota-based therapies (FMT) in adults with gastrointestinal diseases.

Addressing Clostridium difficile infection (CDI), Crohn’s disease (CD) ulcerative colitis (UC), pouchitis, and irritable bowel syndrome (IBS), the guidance supports FMT for the prevention of recurrent CDI but not for inflammatory bowel disease (IBD) or IBS — outside of clinical trials.

The AGA’s recommendations were published in Gastroenterology.

“Fecal microbiota–based therapies are effective therapy to prevent recurrent C. difficile in select patients,” the AGA guideline states. “Conventional fecal microbiota transplant is an adjuvant treatment for select adults hospitalized with severe or fulminant C. difficile infection not responding to standard of care antibiotics. Fecal microbiota transplant cannot yet be recommended in other gastrointestinal conditions.”

“We thought it was important to write this guideline because of the growing number of trials of FMT in IBD and IBS populations. It was also important with the new FDA-approved treatments on the market,” the guideline’s first author, Anne F. Peery, MD, MSCR, AGAF, told this news organization, noting that the recently approved products did not yield better results than those of conventional rectal FMT. “The guidelines will help clinicians understand the available therapies and how to use these treatments,” added Dr. Peery, associate professor in the Division of Gastroenterology and Hepatology at the University of North Carolina School of Medicine in Chapel Hill.

Although the existing evidence is of low or very low certainty, Dr. Peery acknowledged, gastroenterologists “should be comfortable with conventional FMT and also the new FDA-approved products. We spent a considerable amount of time developing implementation considerations, which is practical advice to help clinicians use the guideline recommendations.”

Peery_Anne_F_NC_envir_web.jpg

Recommendations

The eight-member panel suggested the following practices on behalf of the AGA Clinical Guidelines Committee:

• In immunocompetent adults with recurrent CDI, select use of FMT can be used after completion of standard-of-care antibiotics to prevent recurrence. It can be considered after the second recurrence (episode 3) of CDI or in select patients at high risk for either recurrent CDI or a morbid CDI recurrence. Recurrent CDI is defined as clinically significant diarrhea ≥ 3 unformed stools in 24 hours with a confirmatory positive test within 8 weeks of completing antibiotics. Select use includes patients who have recovered from severe, fulminant, or particularly treatment-refractory CDI and patients with significant comorbidities. Severe CDI involves a leukocyte count of ≥15 × 109 cells/L and/or creatinine ≥1.5 mg/dL, while fulminant CDI involves shock, ileus, or megacolon and can be fatal.
• In mildly or moderately immunocompromised adults with recurrent CDI, the guidance recommends select use of conventional fecal microbiota transplant.
• In severely immunocompromised adults or those undergoing cytotoxic treatment, the AGA advises against the use of any fecal microbiota-based therapies to prevent recurrent CDI.
• Conventional FMT is not advised in patients who have bowel perforation or obstruction or are severely immunocompromised.
• For CDI patients not interested in FMT, reasonable alternatives to prevent recurrence are a vancomycin taper, tapered-pulsed fidaxomicin, or bezlotoxumab.
• In adults hospitalized with severe or fulminant CDI not responding to standard-of-care antibiotics, the AGA recommends select use of conventional FM transplant.
• In the current absence of evidence, the guidance advises against the use of conventional fecal microbiota transplant as treatment for IBD or IBS except in the context of clinical trials.

“We felt the data for using FMT in the treatment of UC was promising, but there is still a lot more work to be done in IBD and IBS,” Dr. Peery said. For each disease section the guideline outlined directions for future research. It will be updated in 3-5 years as more evidence becomes available.

This guideline was fully funded by the AGA Institute. Dr. Peery and fellow panel member Dr. Benjamin Lebwohl are supported by grants the National Institute of Diabetes and Digestive and Kidney Diseases. Panel member Colleen R. Kelly, MD, is supported by the National Institute of Allergy and Infectious Diseases.

None of the panel members had any conflicts of interest to report.

Long-term adherence to a plant-based diet was not tied to a greater risk of hip fracture and some plant-based regimens may actually reduce the risk, a large cohort study of postmenopausal women in the United States suggested.

Not all plant-centered regimens are healthful, however, and this study factored dietary quality into risk.

Writing in JAMA Network Open, the study authors compared the lowest to highest quintiles of Plant-Based Diet Index scores. They found the most recent intake of a healthy plant-based diet (hPDI) to be associated with a somewhat lower (21%) risk of fracture while the most recent intake of its unhealthy counterpart (uPDI) was linked to a somewhat higher (28%) risk.

“In addition, higher baseline scores in the uPDI were associated with higher risk of hip fracture,” wrote the researchers, led by Mercedes Sotos Prieto, PhD, a nutritional epidemiologist in the Department of Preventive Medicine and Public Health at the Autonomous University of Madrid.

Plant-based diets, characterized by higher consumption of plant foods and lower or no intake of animal foods, have raised concerns about their potential harm to bone health. In a recent meta-analysis, vegetarians, but particularly vegans with no consumption of any animal food, had a higher fracture risk and lower bone mineral density compared with omnivores.

Another study found that compared with meat eaters, fish eaters and vegetarians had a higher risk of hip fractures. These analyses, however, did not assess the quality of the plant-based diets.

167100_photo_web.jpg

“We hypothesized that the differences in the quality of the plant-based diets — whole grains, fruits, and vegetables vs refined carbohydrates or snacks, which are both plant-based but very different, would be important in the association for the risk of hip fracture,” Dr. Sotos Prieto said in an interview.
 

Study details

Her study drew on data from 70,285 postmenopausal White women who were in the US Nurses’ Health Study from 1984 through 2014; data were analyzed from Jan. 1 to July 31, 2023.

The mean age of the nurses was 54.92 years, and 2038 cases of hip fracture were reported during the study over as long as 30 years of follow-up.

Healthy plant foods included whole grains, fruits, vegetables, nuts, legumes, vegetable oils, and tea or coffee and received positive scores, whereas less healthy plant foods such as fruit juices, sweetened beverages, refined grains, potatoes, sweets, or desserts and animal foods received reversed scores. Dietary and lifestyle information was collected by self-reported questionnaires.

Individuals with higher hPDI scores were leaner, more physically active, less likely to be smokers, and more likely to use vitamin and calcium supplements. Not surprisingly, they also had higher intakes of dietary calcium and healthy plant foods and had lower intake of less healthy plant foods. “It’s plausible that reverse causation may account for the risk associations, as individuals with underlying health conditions that predisposed them to higher fracture risk may have changed their diet,” Dr. Sotos Prieto said. “In addition, baseline diet may reflect diet early on, which could be an important predictor of bone mineral density when there was more active bone turnover.”

Lack of information precluded adjustment for the use of anti-osteoporotic medication.

Neither the hPDI, with a hazard ratio (HR) for highest vs lowest quintile of 0.97 (95% confidence interval, 0.83-1.14) nor the uPDI, with an HR for highest vs lowest quintile of 1.02 (95% CI, 0.87-1.20) for diet adherence over the long term was associated with hip fracture risk.

For recent dietary intake in the highest vs lowest quintiles, however, the hPDI was associated with a 21% lower risk of hip fracture: HR, 0.79 (95% CI, 0.68-0.92; P = .02 for trend). In contrast, the uPDI was associated with a 28% higher risk: HR, 1.28 (95% CI, 1.09-1.51; P = .008 for trend).

Future studies in other populations are needed to confirm the results and enhance their generalizability, Dr. Sotos Prieto said. “Investigating the temporal dynamics of dietary patterns and their effects by examining how recent dietary changes may impact health outcomes over different timeframes is important.” In the meantime, people wishing to follow a plant-based diet should make sure it features high-quality foods.

This work was supported by Instituto de Salud Carlos III, State Secretary of Research, Development and Innovation of Spain, and the European Research Funds and European Social Fund, the Agencia Estatal de Investigación, the National Institutes of Health, and a Ramón y Cajal contract from the Ministry of Science, Innovation, and Universities. A coauthor reported a patent pending. No other disclosures were reported.

Long-term adherence to a plant-based diet was not tied to a greater risk of hip fracture and some plant-based regimens may actually reduce the risk, a large cohort study of postmenopausal women in the United States suggested.

Not all plant-centered regimens are healthful, however, and this study factored dietary quality into risk.

Writing in JAMA Network Open, the study authors compared the lowest to highest quintiles of Plant-Based Diet Index scores. They found the most recent intake of a healthy plant-based diet (hPDI) to be associated with a somewhat lower (21%) risk of fracture while the most recent intake of its unhealthy counterpart (uPDI) was linked to a somewhat higher (28%) risk.

“In addition, higher baseline scores in the uPDI were associated with higher risk of hip fracture,” wrote the researchers, led by Mercedes Sotos Prieto, PhD, a nutritional epidemiologist in the Department of Preventive Medicine and Public Health at the Autonomous University of Madrid.

Plant-based diets, characterized by higher consumption of plant foods and lower or no intake of animal foods, have raised concerns about their potential harm to bone health. In a recent meta-analysis, vegetarians, but particularly vegans with no consumption of any animal food, had a higher fracture risk and lower bone mineral density compared with omnivores.

Another study found that compared with meat eaters, fish eaters and vegetarians had a higher risk of hip fractures. These analyses, however, did not assess the quality of the plant-based diets.

167100_photo_web.jpg

“We hypothesized that the differences in the quality of the plant-based diets — whole grains, fruits, and vegetables vs refined carbohydrates or snacks, which are both plant-based but very different, would be important in the association for the risk of hip fracture,” Dr. Sotos Prieto said in an interview.
 

Study details

Her study drew on data from 70,285 postmenopausal White women who were in the US Nurses’ Health Study from 1984 through 2014; data were analyzed from Jan. 1 to July 31, 2023.

The mean age of the nurses was 54.92 years, and 2038 cases of hip fracture were reported during the study over as long as 30 years of follow-up.

Healthy plant foods included whole grains, fruits, vegetables, nuts, legumes, vegetable oils, and tea or coffee and received positive scores, whereas less healthy plant foods such as fruit juices, sweetened beverages, refined grains, potatoes, sweets, or desserts and animal foods received reversed scores. Dietary and lifestyle information was collected by self-reported questionnaires.

Individuals with higher hPDI scores were leaner, more physically active, less likely to be smokers, and more likely to use vitamin and calcium supplements. Not surprisingly, they also had higher intakes of dietary calcium and healthy plant foods and had lower intake of less healthy plant foods. “It’s plausible that reverse causation may account for the risk associations, as individuals with underlying health conditions that predisposed them to higher fracture risk may have changed their diet,” Dr. Sotos Prieto said. “In addition, baseline diet may reflect diet early on, which could be an important predictor of bone mineral density when there was more active bone turnover.”

Lack of information precluded adjustment for the use of anti-osteoporotic medication.

Neither the hPDI, with a hazard ratio (HR) for highest vs lowest quintile of 0.97 (95% confidence interval, 0.83-1.14) nor the uPDI, with an HR for highest vs lowest quintile of 1.02 (95% CI, 0.87-1.20) for diet adherence over the long term was associated with hip fracture risk.

For recent dietary intake in the highest vs lowest quintiles, however, the hPDI was associated with a 21% lower risk of hip fracture: HR, 0.79 (95% CI, 0.68-0.92; P = .02 for trend). In contrast, the uPDI was associated with a 28% higher risk: HR, 1.28 (95% CI, 1.09-1.51; P = .008 for trend).

Future studies in other populations are needed to confirm the results and enhance their generalizability, Dr. Sotos Prieto said. “Investigating the temporal dynamics of dietary patterns and their effects by examining how recent dietary changes may impact health outcomes over different timeframes is important.” In the meantime, people wishing to follow a plant-based diet should make sure it features high-quality foods.

This work was supported by Instituto de Salud Carlos III, State Secretary of Research, Development and Innovation of Spain, and the European Research Funds and European Social Fund, the Agencia Estatal de Investigación, the National Institutes of Health, and a Ramón y Cajal contract from the Ministry of Science, Innovation, and Universities. A coauthor reported a patent pending. No other disclosures were reported.

Long-term adherence to a plant-based diet was not tied to a greater risk of hip fracture and some plant-based regimens may actually reduce the risk, a large cohort study of postmenopausal women in the United States suggested.

Not all plant-centered regimens are healthful, however, and this study factored dietary quality into risk.

Writing in JAMA Network Open, the study authors compared the lowest to highest quintiles of Plant-Based Diet Index scores. They found the most recent intake of a healthy plant-based diet (hPDI) to be associated with a somewhat lower (21%) risk of fracture while the most recent intake of its unhealthy counterpart (uPDI) was linked to a somewhat higher (28%) risk.

“In addition, higher baseline scores in the uPDI were associated with higher risk of hip fracture,” wrote the researchers, led by Mercedes Sotos Prieto, PhD, a nutritional epidemiologist in the Department of Preventive Medicine and Public Health at the Autonomous University of Madrid.

Plant-based diets, characterized by higher consumption of plant foods and lower or no intake of animal foods, have raised concerns about their potential harm to bone health. In a recent meta-analysis, vegetarians, but particularly vegans with no consumption of any animal food, had a higher fracture risk and lower bone mineral density compared with omnivores.

Another study found that compared with meat eaters, fish eaters and vegetarians had a higher risk of hip fractures. These analyses, however, did not assess the quality of the plant-based diets.

167100_photo_web.jpg

“We hypothesized that the differences in the quality of the plant-based diets — whole grains, fruits, and vegetables vs refined carbohydrates or snacks, which are both plant-based but very different, would be important in the association for the risk of hip fracture,” Dr. Sotos Prieto said in an interview.
 

Study details

Her study drew on data from 70,285 postmenopausal White women who were in the US Nurses’ Health Study from 1984 through 2014; data were analyzed from Jan. 1 to July 31, 2023.

The mean age of the nurses was 54.92 years, and 2038 cases of hip fracture were reported during the study over as long as 30 years of follow-up.

Healthy plant foods included whole grains, fruits, vegetables, nuts, legumes, vegetable oils, and tea or coffee and received positive scores, whereas less healthy plant foods such as fruit juices, sweetened beverages, refined grains, potatoes, sweets, or desserts and animal foods received reversed scores. Dietary and lifestyle information was collected by self-reported questionnaires.

Individuals with higher hPDI scores were leaner, more physically active, less likely to be smokers, and more likely to use vitamin and calcium supplements. Not surprisingly, they also had higher intakes of dietary calcium and healthy plant foods and had lower intake of less healthy plant foods. “It’s plausible that reverse causation may account for the risk associations, as individuals with underlying health conditions that predisposed them to higher fracture risk may have changed their diet,” Dr. Sotos Prieto said. “In addition, baseline diet may reflect diet early on, which could be an important predictor of bone mineral density when there was more active bone turnover.”

Lack of information precluded adjustment for the use of anti-osteoporotic medication.

Neither the hPDI, with a hazard ratio (HR) for highest vs lowest quintile of 0.97 (95% confidence interval, 0.83-1.14) nor the uPDI, with an HR for highest vs lowest quintile of 1.02 (95% CI, 0.87-1.20) for diet adherence over the long term was associated with hip fracture risk.

For recent dietary intake in the highest vs lowest quintiles, however, the hPDI was associated with a 21% lower risk of hip fracture: HR, 0.79 (95% CI, 0.68-0.92; P = .02 for trend). In contrast, the uPDI was associated with a 28% higher risk: HR, 1.28 (95% CI, 1.09-1.51; P = .008 for trend).

Future studies in other populations are needed to confirm the results and enhance their generalizability, Dr. Sotos Prieto said. “Investigating the temporal dynamics of dietary patterns and their effects by examining how recent dietary changes may impact health outcomes over different timeframes is important.” In the meantime, people wishing to follow a plant-based diet should make sure it features high-quality foods.

This work was supported by Instituto de Salud Carlos III, State Secretary of Research, Development and Innovation of Spain, and the European Research Funds and European Social Fund, the Agencia Estatal de Investigación, the National Institutes of Health, and a Ramón y Cajal contract from the Ministry of Science, Innovation, and Universities. A coauthor reported a patent pending. No other disclosures were reported.