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Rates of perinatal HIV have dropped so much that the disease is effectively eliminated in the United States, with less than 1 baby for every 100,000 live births having the virus, a new study released by researchers at the Centers for Disease Control and Prevention finds.

The report marks significant progress on the U.S. government’s goal to eradicate perinatal HIV, an immune-weakening and potentially deadly virus that is passed from mother to baby during pregnancy. Just 32 children in the country were diagnosed in 2019, compared with twice as many in 2010, according to the CDC.

Mothers who are HIV positive can prevent transmission of the infection by receiving antiretroviral therapy, according to Monica Gandhi, MD, MPH, a professor of medicine at University of California, San Francisco’s division of HIV, infectious disease and global medicine.

Dr. Gandhi said she could recall only one case of perinatal HIV in the San Francisco area over the last decade.

“This country has been really aggressive about counseling women who are pregnant and getting mothers in care,” Dr. Gandhi said.

The treatment method was discovered more than 30 years ago. Prior to the therapy and ensuing awareness campaigns to prevent transmission, mothers with HIV would typically pass the virus to their child in utero, during delivery, or while breastfeeding.

“There should be zero children born with HIV, given that we’ve had these drugs for so long,” Dr. Ghandi said. 
 

Disparities persist

But challenges remain in some communities, where babies born to Black mothers are disproportionately affected by the disease, the new study found. “Racial and ethnic differences in perinatal HIV diagnoses persisted through the 10-year period,” the report’s authors concluded. “The highest rates of perinatal HIV diagnoses were seen among infants born to Black women.”

Although rates of perinatal HIV declined for babies born to Black mothers over the decade-long study, the diagnosis rate was above the goal of elimination at 3.1 for every 100,000 live births, according to the data.

Meanwhile, transmission rates hovered around 1%-2% for Latinx and Hispanic women and mothers who identified as “other races,” including Native American.

Despite the availability of medication, expectant mothers may face several hurdles to getting the daily treatment they need to prevent transmission to their fetus, according to Jennifer Jao, MD, MPH, a physician of infectious diseases at Lurie Children’s Hospital of Chicago.

They might have trouble securing health insurance or finding transportation to doctor’s appointments, or face other problems like lacking secure housing or food – all factors that prevent them from prioritizing the care.

“All of those things play into the mix,” Dr. Jao said. “We see over and over again that closing the gap means you’ve got to reach the women who are pregnant and who don’t have resources.”
 

Progress in ‘danger’

Experts said they’re not sure what the impact of the COVID-19 pandemic, accompanied by a recent uptick in sexually transmitted diseases, will be on rates of perinatal HIV. Some women were unable to access prenatal health care during the pandemic because they couldn’t access public transportation or childcare, the U.S. Government Accountability Office said in 2022.

Globally, a decline in rates of HIV and AIDS rates has slowed, prompting the World Health Organization to warn last year that progress on the disease is in danger. Researchers only included HIV rates in the United States through 2019, so the data are outdated, Dr. Gandhi noted.

“All of this put together means we don’t know where we are with perinatal transmission over the last 3 years,” she said.

In an accompanying editorial, coauthors Nahida Chakhtoura, MD, MsGH, and Bill Kapogiannis, MD, both with the National Institutes of Health, urge health care professionals to take an active role in eliminating these racial and ethnic disparities in an effort to – as the title of their editorial proclaims – achieve a “road to zero perinatal HIV transmission” in the United States.

“The more proactive we are in identifying and promptly addressing systematic deficiencies that exacerbate health inequities in cutting-edge research innovations and optimal clinical service provision,” they write, “the less reactive we will need to be when new transmissible infections appear at our doorstep.”

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

Rates of perinatal HIV have dropped so much that the disease is effectively eliminated in the United States, with less than 1 baby for every 100,000 live births having the virus, a new study released by researchers at the Centers for Disease Control and Prevention finds.

The report marks significant progress on the U.S. government’s goal to eradicate perinatal HIV, an immune-weakening and potentially deadly virus that is passed from mother to baby during pregnancy. Just 32 children in the country were diagnosed in 2019, compared with twice as many in 2010, according to the CDC.

Mothers who are HIV positive can prevent transmission of the infection by receiving antiretroviral therapy, according to Monica Gandhi, MD, MPH, a professor of medicine at University of California, San Francisco’s division of HIV, infectious disease and global medicine.

Dr. Gandhi said she could recall only one case of perinatal HIV in the San Francisco area over the last decade.

“This country has been really aggressive about counseling women who are pregnant and getting mothers in care,” Dr. Gandhi said.

The treatment method was discovered more than 30 years ago. Prior to the therapy and ensuing awareness campaigns to prevent transmission, mothers with HIV would typically pass the virus to their child in utero, during delivery, or while breastfeeding.

“There should be zero children born with HIV, given that we’ve had these drugs for so long,” Dr. Ghandi said. 
 

Disparities persist

But challenges remain in some communities, where babies born to Black mothers are disproportionately affected by the disease, the new study found. “Racial and ethnic differences in perinatal HIV diagnoses persisted through the 10-year period,” the report’s authors concluded. “The highest rates of perinatal HIV diagnoses were seen among infants born to Black women.”

Although rates of perinatal HIV declined for babies born to Black mothers over the decade-long study, the diagnosis rate was above the goal of elimination at 3.1 for every 100,000 live births, according to the data.

Meanwhile, transmission rates hovered around 1%-2% for Latinx and Hispanic women and mothers who identified as “other races,” including Native American.

Despite the availability of medication, expectant mothers may face several hurdles to getting the daily treatment they need to prevent transmission to their fetus, according to Jennifer Jao, MD, MPH, a physician of infectious diseases at Lurie Children’s Hospital of Chicago.

They might have trouble securing health insurance or finding transportation to doctor’s appointments, or face other problems like lacking secure housing or food – all factors that prevent them from prioritizing the care.

“All of those things play into the mix,” Dr. Jao said. “We see over and over again that closing the gap means you’ve got to reach the women who are pregnant and who don’t have resources.”
 

Progress in ‘danger’

Experts said they’re not sure what the impact of the COVID-19 pandemic, accompanied by a recent uptick in sexually transmitted diseases, will be on rates of perinatal HIV. Some women were unable to access prenatal health care during the pandemic because they couldn’t access public transportation or childcare, the U.S. Government Accountability Office said in 2022.

Globally, a decline in rates of HIV and AIDS rates has slowed, prompting the World Health Organization to warn last year that progress on the disease is in danger. Researchers only included HIV rates in the United States through 2019, so the data are outdated, Dr. Gandhi noted.

“All of this put together means we don’t know where we are with perinatal transmission over the last 3 years,” she said.

In an accompanying editorial, coauthors Nahida Chakhtoura, MD, MsGH, and Bill Kapogiannis, MD, both with the National Institutes of Health, urge health care professionals to take an active role in eliminating these racial and ethnic disparities in an effort to – as the title of their editorial proclaims – achieve a “road to zero perinatal HIV transmission” in the United States.

“The more proactive we are in identifying and promptly addressing systematic deficiencies that exacerbate health inequities in cutting-edge research innovations and optimal clinical service provision,” they write, “the less reactive we will need to be when new transmissible infections appear at our doorstep.”

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

Rates of perinatal HIV have dropped so much that the disease is effectively eliminated in the United States, with less than 1 baby for every 100,000 live births having the virus, a new study released by researchers at the Centers for Disease Control and Prevention finds.

The report marks significant progress on the U.S. government’s goal to eradicate perinatal HIV, an immune-weakening and potentially deadly virus that is passed from mother to baby during pregnancy. Just 32 children in the country were diagnosed in 2019, compared with twice as many in 2010, according to the CDC.

Mothers who are HIV positive can prevent transmission of the infection by receiving antiretroviral therapy, according to Monica Gandhi, MD, MPH, a professor of medicine at University of California, San Francisco’s division of HIV, infectious disease and global medicine.

Dr. Gandhi said she could recall only one case of perinatal HIV in the San Francisco area over the last decade.

“This country has been really aggressive about counseling women who are pregnant and getting mothers in care,” Dr. Gandhi said.

The treatment method was discovered more than 30 years ago. Prior to the therapy and ensuing awareness campaigns to prevent transmission, mothers with HIV would typically pass the virus to their child in utero, during delivery, or while breastfeeding.

“There should be zero children born with HIV, given that we’ve had these drugs for so long,” Dr. Ghandi said. 
 

Disparities persist

But challenges remain in some communities, where babies born to Black mothers are disproportionately affected by the disease, the new study found. “Racial and ethnic differences in perinatal HIV diagnoses persisted through the 10-year period,” the report’s authors concluded. “The highest rates of perinatal HIV diagnoses were seen among infants born to Black women.”

Although rates of perinatal HIV declined for babies born to Black mothers over the decade-long study, the diagnosis rate was above the goal of elimination at 3.1 for every 100,000 live births, according to the data.

Meanwhile, transmission rates hovered around 1%-2% for Latinx and Hispanic women and mothers who identified as “other races,” including Native American.

Despite the availability of medication, expectant mothers may face several hurdles to getting the daily treatment they need to prevent transmission to their fetus, according to Jennifer Jao, MD, MPH, a physician of infectious diseases at Lurie Children’s Hospital of Chicago.

They might have trouble securing health insurance or finding transportation to doctor’s appointments, or face other problems like lacking secure housing or food – all factors that prevent them from prioritizing the care.

“All of those things play into the mix,” Dr. Jao said. “We see over and over again that closing the gap means you’ve got to reach the women who are pregnant and who don’t have resources.”
 

Progress in ‘danger’

Experts said they’re not sure what the impact of the COVID-19 pandemic, accompanied by a recent uptick in sexually transmitted diseases, will be on rates of perinatal HIV. Some women were unable to access prenatal health care during the pandemic because they couldn’t access public transportation or childcare, the U.S. Government Accountability Office said in 2022.

Globally, a decline in rates of HIV and AIDS rates has slowed, prompting the World Health Organization to warn last year that progress on the disease is in danger. Researchers only included HIV rates in the United States through 2019, so the data are outdated, Dr. Gandhi noted.

“All of this put together means we don’t know where we are with perinatal transmission over the last 3 years,” she said.

In an accompanying editorial, coauthors Nahida Chakhtoura, MD, MsGH, and Bill Kapogiannis, MD, both with the National Institutes of Health, urge health care professionals to take an active role in eliminating these racial and ethnic disparities in an effort to – as the title of their editorial proclaims – achieve a “road to zero perinatal HIV transmission” in the United States.

“The more proactive we are in identifying and promptly addressing systematic deficiencies that exacerbate health inequities in cutting-edge research innovations and optimal clinical service provision,” they write, “the less reactive we will need to be when new transmissible infections appear at our doorstep.”

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

The Food and Drug Administration approved omidubicel-onlv (Omisirge) for reducing infections and hastening neutrophil recovery for blood cancer patients aged 12 years and older who are undergoing allogeneic umbilical cord blood stem cell transplants.

Omidubicel is made from umbilical cord donor stem cells that are processed with nicotinamide, a form of vitamin B₃, to enhance and expand the number of progenitor cells, the product’s maker, Jerusalem-based Gamida Cell, explained in a press announcement.

The FDA approval was based on phase 3 testing that pitted the use of omidubicel in 62 patients against standard unmanipulated cord blood transplants in 63 patients following myeloablative conditioning.

The median time to neutrophil recovery was 12 days in the omidubicel group, compared with 22 days with standard care. Overall, 87% of patients who received omidubicel achieved neutrophil recovery versus 83% of patients with standard transplants.

The incidence of grade 2/3 bacterial or grade 3 fungal infections 100 days following transplant was 39% with omidubicel versus 60% with standard transplants.

The FDA’s “approval is an important advance in cell therapy treatment in patients with blood cancers. Hastening the return of the body’s white blood cells can reduce the possibility of serious or overwhelming infection associated with stem cell transplantation,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in an agency press release.

Abbey Jenkins, president and CEO of Gamida, called the approval “a major advancement in the treatment of patients with hematologic malignancies that we believe may increase access to stem cell transplant and help improve patient outcomes.”

The most common grade 3–5 adverse reactions in the approval study were pain (33%), mucosal inflammation (31%), hypertension (25%), and gastrointestinal toxicity (19%).

Adverse events are consistent with allogeneic hematopoietic stem cell transplantation. Among 117 patients who received omidubicel for any indication, infusion reactions occurred in 47% of patients, acute graft-versus-host disease occurred in 58%, chronic GVHD occurred in 35%, and graft failure occurred in 3%. Labeling includes a boxed warning of the possibilities. There is also a small risk of infections and malignancies from donor blood.

Omidubicel is manufactured in Gamida’s facility in Kiryat Gat, Israel. It is available for order now and is expected to be delivered to transplant centers within 30 days after the start of manufacturing, the company said.

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

The Food and Drug Administration approved omidubicel-onlv (Omisirge) for reducing infections and hastening neutrophil recovery for blood cancer patients aged 12 years and older who are undergoing allogeneic umbilical cord blood stem cell transplants.

Omidubicel is made from umbilical cord donor stem cells that are processed with nicotinamide, a form of vitamin B₃, to enhance and expand the number of progenitor cells, the product’s maker, Jerusalem-based Gamida Cell, explained in a press announcement.

The FDA approval was based on phase 3 testing that pitted the use of omidubicel in 62 patients against standard unmanipulated cord blood transplants in 63 patients following myeloablative conditioning.

The median time to neutrophil recovery was 12 days in the omidubicel group, compared with 22 days with standard care. Overall, 87% of patients who received omidubicel achieved neutrophil recovery versus 83% of patients with standard transplants.

The incidence of grade 2/3 bacterial or grade 3 fungal infections 100 days following transplant was 39% with omidubicel versus 60% with standard transplants.

The FDA’s “approval is an important advance in cell therapy treatment in patients with blood cancers. Hastening the return of the body’s white blood cells can reduce the possibility of serious or overwhelming infection associated with stem cell transplantation,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in an agency press release.

Abbey Jenkins, president and CEO of Gamida, called the approval “a major advancement in the treatment of patients with hematologic malignancies that we believe may increase access to stem cell transplant and help improve patient outcomes.”

The most common grade 3–5 adverse reactions in the approval study were pain (33%), mucosal inflammation (31%), hypertension (25%), and gastrointestinal toxicity (19%).

Adverse events are consistent with allogeneic hematopoietic stem cell transplantation. Among 117 patients who received omidubicel for any indication, infusion reactions occurred in 47% of patients, acute graft-versus-host disease occurred in 58%, chronic GVHD occurred in 35%, and graft failure occurred in 3%. Labeling includes a boxed warning of the possibilities. There is also a small risk of infections and malignancies from donor blood.

Omidubicel is manufactured in Gamida’s facility in Kiryat Gat, Israel. It is available for order now and is expected to be delivered to transplant centers within 30 days after the start of manufacturing, the company said.

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

The Food and Drug Administration approved omidubicel-onlv (Omisirge) for reducing infections and hastening neutrophil recovery for blood cancer patients aged 12 years and older who are undergoing allogeneic umbilical cord blood stem cell transplants.

Omidubicel is made from umbilical cord donor stem cells that are processed with nicotinamide, a form of vitamin B₃, to enhance and expand the number of progenitor cells, the product’s maker, Jerusalem-based Gamida Cell, explained in a press announcement.

The FDA approval was based on phase 3 testing that pitted the use of omidubicel in 62 patients against standard unmanipulated cord blood transplants in 63 patients following myeloablative conditioning.

The median time to neutrophil recovery was 12 days in the omidubicel group, compared with 22 days with standard care. Overall, 87% of patients who received omidubicel achieved neutrophil recovery versus 83% of patients with standard transplants.

The incidence of grade 2/3 bacterial or grade 3 fungal infections 100 days following transplant was 39% with omidubicel versus 60% with standard transplants.

The FDA’s “approval is an important advance in cell therapy treatment in patients with blood cancers. Hastening the return of the body’s white blood cells can reduce the possibility of serious or overwhelming infection associated with stem cell transplantation,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in an agency press release.

Abbey Jenkins, president and CEO of Gamida, called the approval “a major advancement in the treatment of patients with hematologic malignancies that we believe may increase access to stem cell transplant and help improve patient outcomes.”

The most common grade 3–5 adverse reactions in the approval study were pain (33%), mucosal inflammation (31%), hypertension (25%), and gastrointestinal toxicity (19%).

Adverse events are consistent with allogeneic hematopoietic stem cell transplantation. Among 117 patients who received omidubicel for any indication, infusion reactions occurred in 47% of patients, acute graft-versus-host disease occurred in 58%, chronic GVHD occurred in 35%, and graft failure occurred in 3%. Labeling includes a boxed warning of the possibilities. There is also a small risk of infections and malignancies from donor blood.

Omidubicel is manufactured in Gamida’s facility in Kiryat Gat, Israel. It is available for order now and is expected to be delivered to transplant centers within 30 days after the start of manufacturing, the company said.

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

Individuals at increased risk of type 2 diabetes may be able to reduce their risk via a novel intervention combining intermittent fasting (IF) with early time-restricted eating, indicate the results of a randomized controlled trial.

The study involved more than 200 individuals randomized to one of three groups: eat only in the morning (from 8:00 a.m. to noon) followed by 20 hours of fasting 3 days per week and eat as desired on the other days; daily calorie restriction to 70% of requirements; or standard weight loss advice.

The IF plus early time-restricted eating intervention was associated with a significant improvement in a key measure of glucose control versus calorie restriction at 6 months, while both interventions were linked to benefits in terms of cardiovascular risk markers and body composition, compared with the standard weight loss advice.

However, the research, published in Nature Medicine, showed that the additional benefit of IF plus early time-restricted eating did not persist, and less than half of participants were still following the plan at 18 months, compared with almost 80% of those in the calorie-restriction group.

“Following a time-restricted, IF diet could help lower the chances of developing type 2 diabetes,” senior author Leonie K. Heilbronn, PhD, University of Adelaide, South Australia, said in a press release.

This is “the largest study in the world to date, and the first powered to assess how the body processes and uses glucose after eating a meal,” with the latter being a better indicator of diabetes risk than a fasting glucose test, added first author Xiao Tong Teong, a PhD student, also at the University of Adelaide.

“The results of this study add to the growing body of evidence to indicate that meal timing and fasting advice extends the health benefits of a restricted-calorie diet, independently from weight loss, and this may be influential in clinical practice,” Ms. Teong added.
 

Adherence difficult to IF plus early time-restricted eating

Asked to comment, Krista Varady, PhD, said that the study design “would have been stronger if the time-restricted eating and IF interventions were separated” and compared.

“Time-restricted eating has been shown to naturally reduce calorie intake by 300-500 kcal/day,” she said in an interview, “so I’m not sure why the investigators chose to combine [it] with IF. It ... defeats the point of time-restricted eating.”

Dr. Varady, who recently coauthored a review of the clinical application of IF for weight loss, also doubted whether individuals would adhere to combined early time-restricted eating and IF. “In all honesty, I don’t think anyone would follow this diet for very long,” she said.

She added that the feasibility of this particular approach is “very questionable. In general, people don’t like diets that require them to skip dinner with family/friends on multiple days of the week,” explained Dr. Varady, professor of nutrition at the University of Illinois, Chicago.  “These regimens make social eating very difficult, which results in high attrition.

“Indeed, evidence from a recent large-scale observational study of nearly 800,000 adults shows that Americans who engage in time-restricted eating placed their eating window in the afternoon or evening,” she noted.

Dr. Varady therefore suggested that future trials should test “more feasible time-restricted eating approaches,” such as those with later eating windows and without “vigilant calorie monitoring.”

“These types of diets are much easier to follow and are more likely to produce lasting weight and glycemic control in people with obesity and prediabetes,” she observed.
 

A novel way to cut calories?

The Australian authors say there is growing interest in extending the established health benefits of calorie restriction through new approaches such as timing of meals and prolonged fasting, with IF – defined as fasting interspersed with days of ad libitum eating – gaining in popularity as an alternative to simple calorie restriction.

Time-restricted eating, which emphasizes shorter daily eating windows in alignment with circadian rhythms, has also become popular in recent years, although the authors acknowledge that current evidence suggests any benefits over calorie restriction alone in terms of body composition, blood lipids, or glucose parameters are small.

To examine the combination of IF plus early time-restricted eating, in the DIRECT trial, the team recruited individuals aged 35-75 years who had a score of at least 12 on the Australian Type 2 Diabetes Risk Assessment Tool but did not have a diagnosis of diabetes and had stable weight for more than 6 months prior to study entry.

The participants were randomized to one of three groups:

• IF plus early time-restricted eating, which allowed consumption of 30% of calculated baseline energy requirements between 8:00 a.m. and midday, followed by a 20-hour fast from midday on 3 nonconsecutive days per week. They consumed their regular diet on nonfasting days.
• Calorie restriction, where they consumed 70% of daily calculated baseline energy requirements each day and were given rotating menu plans, but no specific mealtimes.
• Standard care, where they were given a booklet on current guidelines, with no counseling or meal replacement.

There were clinic visits every 2 weeks for the first 6 months of follow-up, and then monthly visits for 12 months. The two intervention groups had one-on-one diet counseling for the first 6 months. All groups were instructed to maintain their usual physical activity levels.

A total of 209 individuals were enrolled between Sept. 26, 2018, and May 4, 2020. Their mean age was 58 years, and 57% were women. Mean body mass index was 34.8 kg/m².

In all, 40.7% of participants were allocated to IF plus early time-restricted eating, 39.7% to calorie restriction, and the remaining 19.6% to standard care.

The results showed that IF plus early time-restricted eating was associated with a significantly greater improvement in the primary outcome of postprandial glucose area under the curve (AUC) at month 6 compared with calorie restriction, at –10.1 mg/dL/min versus –3.6 mg/dL/min (P = .03).

“To our knowledge, no [prior] studies have been powered for postprandial assessments of glycemia, which are better indicators of diabetes risk than fasting assessment,” the authors underlined.

IF plus early time-restricted eating was also associated with greater reductions in postprandial insulin AUC versus calorie restriction at 6 months (P = .04). However, the differences between the IF plus early time-restricted eating and calorie restriction groups for postmeal insulin did not remain significant at 18 months of follow-up.

Both IF plus early time-restricted eating and calorie restriction were associated with greater reductions in A1c levels at 6 months versus standard care, but there was no significant difference between the two active interventions (P = .46).

Both interventions were also associated with improvements in markers of cardiovascular risk versus standard care, such as systolic blood pressure at 2 months, diastolic blood pressure at 6 months, and fasting triglycerides at both time points, with no significant differences between the two intervention groups.

IF plus early time-restricted eating and calorie restriction were also both associated with greater reductions in BMI and fat mass in the first 6 months, as well as in waist circumference.
 

Calorie restriction easier to stick to, less likely to cause fatigue

When offered the chance to modify their diet plan at 6 months, 46% of participants in the IF plus early time-restricted eating group said they would maintain 3 days of restrictions per week, while 51% chose to reduce the restrictions to 2 days per week.

In contrast, 97% of those who completed the calorie-restriction plan indicated they would continue with their current diet plan.

At 18 months, 42% of participants in the IF plus early time-restricted eating group said they still undertook 2-3 days of restrictions per week, while 78% of those assigned to calorie restriction reported that they followed a calorie-restricted diet.

Fatigue was more common with IF plus early time-restricted eating, reported by 56% of participants versus 37% of those following calorie restriction, and 35% of those in the standard care group at 6 months. Headaches and constipation were more common in the intervention groups than with standard care.

The study was supported by a National Health and Medical Research Council Project Grant, an Australian Government Research Training Program Scholarship from the University of Adelaide, and a Diabetes Australia Research Program Grant.

No relevant financial relationships were declared.
 

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

Individuals at increased risk of type 2 diabetes may be able to reduce their risk via a novel intervention combining intermittent fasting (IF) with early time-restricted eating, indicate the results of a randomized controlled trial.

The study involved more than 200 individuals randomized to one of three groups: eat only in the morning (from 8:00 a.m. to noon) followed by 20 hours of fasting 3 days per week and eat as desired on the other days; daily calorie restriction to 70% of requirements; or standard weight loss advice.

The IF plus early time-restricted eating intervention was associated with a significant improvement in a key measure of glucose control versus calorie restriction at 6 months, while both interventions were linked to benefits in terms of cardiovascular risk markers and body composition, compared with the standard weight loss advice.

However, the research, published in Nature Medicine, showed that the additional benefit of IF plus early time-restricted eating did not persist, and less than half of participants were still following the plan at 18 months, compared with almost 80% of those in the calorie-restriction group.

“Following a time-restricted, IF diet could help lower the chances of developing type 2 diabetes,” senior author Leonie K. Heilbronn, PhD, University of Adelaide, South Australia, said in a press release.

This is “the largest study in the world to date, and the first powered to assess how the body processes and uses glucose after eating a meal,” with the latter being a better indicator of diabetes risk than a fasting glucose test, added first author Xiao Tong Teong, a PhD student, also at the University of Adelaide.

“The results of this study add to the growing body of evidence to indicate that meal timing and fasting advice extends the health benefits of a restricted-calorie diet, independently from weight loss, and this may be influential in clinical practice,” Ms. Teong added.
 

Adherence difficult to IF plus early time-restricted eating

Asked to comment, Krista Varady, PhD, said that the study design “would have been stronger if the time-restricted eating and IF interventions were separated” and compared.

“Time-restricted eating has been shown to naturally reduce calorie intake by 300-500 kcal/day,” she said in an interview, “so I’m not sure why the investigators chose to combine [it] with IF. It ... defeats the point of time-restricted eating.”

Dr. Varady, who recently coauthored a review of the clinical application of IF for weight loss, also doubted whether individuals would adhere to combined early time-restricted eating and IF. “In all honesty, I don’t think anyone would follow this diet for very long,” she said.

She added that the feasibility of this particular approach is “very questionable. In general, people don’t like diets that require them to skip dinner with family/friends on multiple days of the week,” explained Dr. Varady, professor of nutrition at the University of Illinois, Chicago.  “These regimens make social eating very difficult, which results in high attrition.

“Indeed, evidence from a recent large-scale observational study of nearly 800,000 adults shows that Americans who engage in time-restricted eating placed their eating window in the afternoon or evening,” she noted.

Dr. Varady therefore suggested that future trials should test “more feasible time-restricted eating approaches,” such as those with later eating windows and without “vigilant calorie monitoring.”

“These types of diets are much easier to follow and are more likely to produce lasting weight and glycemic control in people with obesity and prediabetes,” she observed.
 

A novel way to cut calories?

The Australian authors say there is growing interest in extending the established health benefits of calorie restriction through new approaches such as timing of meals and prolonged fasting, with IF – defined as fasting interspersed with days of ad libitum eating – gaining in popularity as an alternative to simple calorie restriction.

Time-restricted eating, which emphasizes shorter daily eating windows in alignment with circadian rhythms, has also become popular in recent years, although the authors acknowledge that current evidence suggests any benefits over calorie restriction alone in terms of body composition, blood lipids, or glucose parameters are small.

To examine the combination of IF plus early time-restricted eating, in the DIRECT trial, the team recruited individuals aged 35-75 years who had a score of at least 12 on the Australian Type 2 Diabetes Risk Assessment Tool but did not have a diagnosis of diabetes and had stable weight for more than 6 months prior to study entry.

The participants were randomized to one of three groups:

• IF plus early time-restricted eating, which allowed consumption of 30% of calculated baseline energy requirements between 8:00 a.m. and midday, followed by a 20-hour fast from midday on 3 nonconsecutive days per week. They consumed their regular diet on nonfasting days.
• Calorie restriction, where they consumed 70% of daily calculated baseline energy requirements each day and were given rotating menu plans, but no specific mealtimes.
• Standard care, where they were given a booklet on current guidelines, with no counseling or meal replacement.

There were clinic visits every 2 weeks for the first 6 months of follow-up, and then monthly visits for 12 months. The two intervention groups had one-on-one diet counseling for the first 6 months. All groups were instructed to maintain their usual physical activity levels.

A total of 209 individuals were enrolled between Sept. 26, 2018, and May 4, 2020. Their mean age was 58 years, and 57% were women. Mean body mass index was 34.8 kg/m².

In all, 40.7% of participants were allocated to IF plus early time-restricted eating, 39.7% to calorie restriction, and the remaining 19.6% to standard care.

The results showed that IF plus early time-restricted eating was associated with a significantly greater improvement in the primary outcome of postprandial glucose area under the curve (AUC) at month 6 compared with calorie restriction, at –10.1 mg/dL/min versus –3.6 mg/dL/min (P = .03).

“To our knowledge, no [prior] studies have been powered for postprandial assessments of glycemia, which are better indicators of diabetes risk than fasting assessment,” the authors underlined.

IF plus early time-restricted eating was also associated with greater reductions in postprandial insulin AUC versus calorie restriction at 6 months (P = .04). However, the differences between the IF plus early time-restricted eating and calorie restriction groups for postmeal insulin did not remain significant at 18 months of follow-up.

Both IF plus early time-restricted eating and calorie restriction were associated with greater reductions in A1c levels at 6 months versus standard care, but there was no significant difference between the two active interventions (P = .46).

Both interventions were also associated with improvements in markers of cardiovascular risk versus standard care, such as systolic blood pressure at 2 months, diastolic blood pressure at 6 months, and fasting triglycerides at both time points, with no significant differences between the two intervention groups.

IF plus early time-restricted eating and calorie restriction were also both associated with greater reductions in BMI and fat mass in the first 6 months, as well as in waist circumference.
 

Calorie restriction easier to stick to, less likely to cause fatigue

When offered the chance to modify their diet plan at 6 months, 46% of participants in the IF plus early time-restricted eating group said they would maintain 3 days of restrictions per week, while 51% chose to reduce the restrictions to 2 days per week.

In contrast, 97% of those who completed the calorie-restriction plan indicated they would continue with their current diet plan.

At 18 months, 42% of participants in the IF plus early time-restricted eating group said they still undertook 2-3 days of restrictions per week, while 78% of those assigned to calorie restriction reported that they followed a calorie-restricted diet.

Fatigue was more common with IF plus early time-restricted eating, reported by 56% of participants versus 37% of those following calorie restriction, and 35% of those in the standard care group at 6 months. Headaches and constipation were more common in the intervention groups than with standard care.

The study was supported by a National Health and Medical Research Council Project Grant, an Australian Government Research Training Program Scholarship from the University of Adelaide, and a Diabetes Australia Research Program Grant.

No relevant financial relationships were declared.
 

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

Individuals at increased risk of type 2 diabetes may be able to reduce their risk via a novel intervention combining intermittent fasting (IF) with early time-restricted eating, indicate the results of a randomized controlled trial.

The study involved more than 200 individuals randomized to one of three groups: eat only in the morning (from 8:00 a.m. to noon) followed by 20 hours of fasting 3 days per week and eat as desired on the other days; daily calorie restriction to 70% of requirements; or standard weight loss advice.

The IF plus early time-restricted eating intervention was associated with a significant improvement in a key measure of glucose control versus calorie restriction at 6 months, while both interventions were linked to benefits in terms of cardiovascular risk markers and body composition, compared with the standard weight loss advice.

However, the research, published in Nature Medicine, showed that the additional benefit of IF plus early time-restricted eating did not persist, and less than half of participants were still following the plan at 18 months, compared with almost 80% of those in the calorie-restriction group.

“Following a time-restricted, IF diet could help lower the chances of developing type 2 diabetes,” senior author Leonie K. Heilbronn, PhD, University of Adelaide, South Australia, said in a press release.

This is “the largest study in the world to date, and the first powered to assess how the body processes and uses glucose after eating a meal,” with the latter being a better indicator of diabetes risk than a fasting glucose test, added first author Xiao Tong Teong, a PhD student, also at the University of Adelaide.

“The results of this study add to the growing body of evidence to indicate that meal timing and fasting advice extends the health benefits of a restricted-calorie diet, independently from weight loss, and this may be influential in clinical practice,” Ms. Teong added.
 

Adherence difficult to IF plus early time-restricted eating

Asked to comment, Krista Varady, PhD, said that the study design “would have been stronger if the time-restricted eating and IF interventions were separated” and compared.

“Time-restricted eating has been shown to naturally reduce calorie intake by 300-500 kcal/day,” she said in an interview, “so I’m not sure why the investigators chose to combine [it] with IF. It ... defeats the point of time-restricted eating.”

Dr. Varady, who recently coauthored a review of the clinical application of IF for weight loss, also doubted whether individuals would adhere to combined early time-restricted eating and IF. “In all honesty, I don’t think anyone would follow this diet for very long,” she said.

She added that the feasibility of this particular approach is “very questionable. In general, people don’t like diets that require them to skip dinner with family/friends on multiple days of the week,” explained Dr. Varady, professor of nutrition at the University of Illinois, Chicago.  “These regimens make social eating very difficult, which results in high attrition.

“Indeed, evidence from a recent large-scale observational study of nearly 800,000 adults shows that Americans who engage in time-restricted eating placed their eating window in the afternoon or evening,” she noted.

Dr. Varady therefore suggested that future trials should test “more feasible time-restricted eating approaches,” such as those with later eating windows and without “vigilant calorie monitoring.”

“These types of diets are much easier to follow and are more likely to produce lasting weight and glycemic control in people with obesity and prediabetes,” she observed.
 

A novel way to cut calories?

The Australian authors say there is growing interest in extending the established health benefits of calorie restriction through new approaches such as timing of meals and prolonged fasting, with IF – defined as fasting interspersed with days of ad libitum eating – gaining in popularity as an alternative to simple calorie restriction.

Time-restricted eating, which emphasizes shorter daily eating windows in alignment with circadian rhythms, has also become popular in recent years, although the authors acknowledge that current evidence suggests any benefits over calorie restriction alone in terms of body composition, blood lipids, or glucose parameters are small.

To examine the combination of IF plus early time-restricted eating, in the DIRECT trial, the team recruited individuals aged 35-75 years who had a score of at least 12 on the Australian Type 2 Diabetes Risk Assessment Tool but did not have a diagnosis of diabetes and had stable weight for more than 6 months prior to study entry.

The participants were randomized to one of three groups:

• IF plus early time-restricted eating, which allowed consumption of 30% of calculated baseline energy requirements between 8:00 a.m. and midday, followed by a 20-hour fast from midday on 3 nonconsecutive days per week. They consumed their regular diet on nonfasting days.
• Calorie restriction, where they consumed 70% of daily calculated baseline energy requirements each day and were given rotating menu plans, but no specific mealtimes.
• Standard care, where they were given a booklet on current guidelines, with no counseling or meal replacement.

There were clinic visits every 2 weeks for the first 6 months of follow-up, and then monthly visits for 12 months. The two intervention groups had one-on-one diet counseling for the first 6 months. All groups were instructed to maintain their usual physical activity levels.

A total of 209 individuals were enrolled between Sept. 26, 2018, and May 4, 2020. Their mean age was 58 years, and 57% were women. Mean body mass index was 34.8 kg/m².

In all, 40.7% of participants were allocated to IF plus early time-restricted eating, 39.7% to calorie restriction, and the remaining 19.6% to standard care.

The results showed that IF plus early time-restricted eating was associated with a significantly greater improvement in the primary outcome of postprandial glucose area under the curve (AUC) at month 6 compared with calorie restriction, at –10.1 mg/dL/min versus –3.6 mg/dL/min (P = .03).

“To our knowledge, no [prior] studies have been powered for postprandial assessments of glycemia, which are better indicators of diabetes risk than fasting assessment,” the authors underlined.

IF plus early time-restricted eating was also associated with greater reductions in postprandial insulin AUC versus calorie restriction at 6 months (P = .04). However, the differences between the IF plus early time-restricted eating and calorie restriction groups for postmeal insulin did not remain significant at 18 months of follow-up.

Both IF plus early time-restricted eating and calorie restriction were associated with greater reductions in A1c levels at 6 months versus standard care, but there was no significant difference between the two active interventions (P = .46).

Both interventions were also associated with improvements in markers of cardiovascular risk versus standard care, such as systolic blood pressure at 2 months, diastolic blood pressure at 6 months, and fasting triglycerides at both time points, with no significant differences between the two intervention groups.

IF plus early time-restricted eating and calorie restriction were also both associated with greater reductions in BMI and fat mass in the first 6 months, as well as in waist circumference.
 

Calorie restriction easier to stick to, less likely to cause fatigue

When offered the chance to modify their diet plan at 6 months, 46% of participants in the IF plus early time-restricted eating group said they would maintain 3 days of restrictions per week, while 51% chose to reduce the restrictions to 2 days per week.

In contrast, 97% of those who completed the calorie-restriction plan indicated they would continue with their current diet plan.

At 18 months, 42% of participants in the IF plus early time-restricted eating group said they still undertook 2-3 days of restrictions per week, while 78% of those assigned to calorie restriction reported that they followed a calorie-restricted diet.

Fatigue was more common with IF plus early time-restricted eating, reported by 56% of participants versus 37% of those following calorie restriction, and 35% of those in the standard care group at 6 months. Headaches and constipation were more common in the intervention groups than with standard care.

The study was supported by a National Health and Medical Research Council Project Grant, an Australian Government Research Training Program Scholarship from the University of Adelaide, and a Diabetes Australia Research Program Grant.

No relevant financial relationships were declared.
 

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

The U.S. Food and Drug Administration has granted breakthrough device designation to the Avantis spinal cord stimulation system (Reach Neuro), which has been shown in early testing to restore arm and hand movement in patients with post-stroke upper limb paresis.

“We are excited about the FDA’s recognition of our technology’s potential to change the lives of millions of people living with disability,” Marc Powell, PhD, CEO, and co-founder of Reach Neuro, said in a company news release.

“The breakthrough device designation is an incredible opportunity to work closely with FDA experts to expedite the clinical translation of the Avantis system,” Dr. Powell added.

Results of the first-in-human study of the system were published in Nature Medicine.

Investigators percutaneously implanted two linear leads in the dorsolateral epidural space targeting neural circuits that control arm and hand muscles in two chronic post-stroke patients.

In both patients, continuous stimulation of the targeted neural circuits led to significant and immediate improvement in arm and hand strength and dexterity. This enabled the patients to perform movements that they couldn’t perform without spinal cord stimulation.

The process also enabled fine motor skills, such as opening a lock and using utensils to eat independently – tasks that one patient had not been able to do for 9 years.

“Having the stimulation working and being able to move my arm/hand again after 9 years was one of the most surreal experiences of my life – it was as if my brain was in control of my arm again. This technology gave me such immense hope that one day I will regain a sense of independence again,” study participant Heather Rendulic said in the news release.

Surprisingly, some improvements were retained up to 1 month after the study, even without stimulation. No serious adverse events were reported.

Nearly three-quarters of patients with stroke experience lasting deficits in motor control of their arm and hand as a result of permanent damage to the brain’s ability to send signals to muscles.

The early results with the Avantis system provide “promising, albeit preliminary, evidence that spinal cord stimulation could be an assistive as well as a restorative approach for upper-limb recovery after stroke,” the study team said in Nature Medicine.

Reach Neuro was founded in 2021 as a spinout company of the University of Pittsburgh and Carnegie Mellon University, also in Pittsburgh, where the technology is currently being tested in a clinical trial funded by the National Institutes of Health.

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

The U.S. Food and Drug Administration has granted breakthrough device designation to the Avantis spinal cord stimulation system (Reach Neuro), which has been shown in early testing to restore arm and hand movement in patients with post-stroke upper limb paresis.

“We are excited about the FDA’s recognition of our technology’s potential to change the lives of millions of people living with disability,” Marc Powell, PhD, CEO, and co-founder of Reach Neuro, said in a company news release.

“The breakthrough device designation is an incredible opportunity to work closely with FDA experts to expedite the clinical translation of the Avantis system,” Dr. Powell added.

Results of the first-in-human study of the system were published in Nature Medicine.

Investigators percutaneously implanted two linear leads in the dorsolateral epidural space targeting neural circuits that control arm and hand muscles in two chronic post-stroke patients.

In both patients, continuous stimulation of the targeted neural circuits led to significant and immediate improvement in arm and hand strength and dexterity. This enabled the patients to perform movements that they couldn’t perform without spinal cord stimulation.

The process also enabled fine motor skills, such as opening a lock and using utensils to eat independently – tasks that one patient had not been able to do for 9 years.

“Having the stimulation working and being able to move my arm/hand again after 9 years was one of the most surreal experiences of my life – it was as if my brain was in control of my arm again. This technology gave me such immense hope that one day I will regain a sense of independence again,” study participant Heather Rendulic said in the news release.

Surprisingly, some improvements were retained up to 1 month after the study, even without stimulation. No serious adverse events were reported.

Nearly three-quarters of patients with stroke experience lasting deficits in motor control of their arm and hand as a result of permanent damage to the brain’s ability to send signals to muscles.

The early results with the Avantis system provide “promising, albeit preliminary, evidence that spinal cord stimulation could be an assistive as well as a restorative approach for upper-limb recovery after stroke,” the study team said in Nature Medicine.

Reach Neuro was founded in 2021 as a spinout company of the University of Pittsburgh and Carnegie Mellon University, also in Pittsburgh, where the technology is currently being tested in a clinical trial funded by the National Institutes of Health.

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

The U.S. Food and Drug Administration has granted breakthrough device designation to the Avantis spinal cord stimulation system (Reach Neuro), which has been shown in early testing to restore arm and hand movement in patients with post-stroke upper limb paresis.

“We are excited about the FDA’s recognition of our technology’s potential to change the lives of millions of people living with disability,” Marc Powell, PhD, CEO, and co-founder of Reach Neuro, said in a company news release.

“The breakthrough device designation is an incredible opportunity to work closely with FDA experts to expedite the clinical translation of the Avantis system,” Dr. Powell added.

Results of the first-in-human study of the system were published in Nature Medicine.

Investigators percutaneously implanted two linear leads in the dorsolateral epidural space targeting neural circuits that control arm and hand muscles in two chronic post-stroke patients.

In both patients, continuous stimulation of the targeted neural circuits led to significant and immediate improvement in arm and hand strength and dexterity. This enabled the patients to perform movements that they couldn’t perform without spinal cord stimulation.

The process also enabled fine motor skills, such as opening a lock and using utensils to eat independently – tasks that one patient had not been able to do for 9 years.

“Having the stimulation working and being able to move my arm/hand again after 9 years was one of the most surreal experiences of my life – it was as if my brain was in control of my arm again. This technology gave me such immense hope that one day I will regain a sense of independence again,” study participant Heather Rendulic said in the news release.

Surprisingly, some improvements were retained up to 1 month after the study, even without stimulation. No serious adverse events were reported.

Nearly three-quarters of patients with stroke experience lasting deficits in motor control of their arm and hand as a result of permanent damage to the brain’s ability to send signals to muscles.

The early results with the Avantis system provide “promising, albeit preliminary, evidence that spinal cord stimulation could be an assistive as well as a restorative approach for upper-limb recovery after stroke,” the study team said in Nature Medicine.

Reach Neuro was founded in 2021 as a spinout company of the University of Pittsburgh and Carnegie Mellon University, also in Pittsburgh, where the technology is currently being tested in a clinical trial funded by the National Institutes of Health.

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

Pediatricians increasingly are stepping in to prescribe drugs for anxiety and depression independently, easing the burden on subspecialists amid the child and adolescent mental health crisis, but a review of electronic health records highlights areas for improvement in delivering the care.

The findings were published online in Pediatrics.

The researchers, led by Talia R. Lester, MD, with the division of developmental behavioral pediatrics in the quantitative science unit at Stanford (Calif.) University, identified 1,685 patients aged 6-18 years who had at least one visit with a diagnosis of anxiety and/or depression in a large primary care network in northern California and who were prescribed an SSRI by a network primary care pediatrician (PCP). The team randomly chose 110 patients and reviewed charts from the visit when the SSRI was first prescribed (medication visit); the immediately previous visit; and immediately subsequent visit.
 

Encouraging signs

The chart reviews showed some encouraging signs. For example, when pediatricians prescribe an SSRI, 82% are appropriately documenting rationales for starting the medication at the medication visit. However, they are not monitoring medication side effects systematically, according to the report. Of 69 patients with a visit after the medication visit, fewer than half (48%) had documentation of monitoring for side effects.

Three areas for improvement

The researchers identified three main shortfall areas and suggested improvements.

PCPs often referred patients for unspecified therapy at the medication visit; however, they rarely prescribed evidence-based therapies such as cognitive-behavioral therapy (CBT) (4% of patients). The authors suggested embedding a summary of evidence-based treatment into order sets.

Secondly, PCPs are not often using screening tools. The data show only 26% of patients had a documented depression- or anxiety-specific screening tool result at the medication visit. The authors recommend making the screening tools accessible through the EHR to increase use.

The researchers also found many patients didn’t have a follow-up visit after SSRI medication was prescribed. Even when they did, the range was so wide between the medication visit and the follow-up (7-365 days) that it’s clear pediatricians are taking inconsistent approaches to scheduling follow-up.
 

Half are seeing only their primary care pediatrician

About half of children and adolescents prescribed an SSRI by a pediatrician for mental health reasons were seeing only their primary care pediatrician, the data showed.

Eric M. Butter, PhD, chief of psychology at Nationwide Children’s Hospital and Ohio State University, Columbus, pointed out in an accompanying editorial that some of the news in pediatricians’ expanded role is particularly encouraging.

Pediatricians, he noted, are making medication decisions consistent with decisions a subspecialist would make.

Of cases in which a subspecialist became involved after a pediatrician initiated medication, subspecialists changed the medication for only two patients, which “is encouraging because it validates pediatricians’ decisions,” Dr. Butter said.

It’s important for pediatricians to understand key evidence-based programs that can work in combination with medications to achieve better results, Dr. Butter said. For example, CBT can help with depression “and break the cycle of avoidance that worsens symptoms of anxiety.”

He highlighted Interpersonal Therapy for Adolescents, a 12-session treatment that “can also address depression by improving patients’ personal relationships.”

“No primary care pediatrician will have the training or time to implement the many treatments that are available,” Dr. Butter wrote. “However, pediatricians can work to understand the key features of the evidence-based treatments referenced by Lester et al.”
 

Most concerning statistics

Dr. Butter said the most concerning shortcoming in the pediatricians’ health care delivery was lack of referral for evidence-based psychological treatments and low rates for referral to access supports from schools through programs such as the education 504 plan and Individualized Education Plans.

Dr. Lester’s team found that pediatricians recommended that patients receive support from such programs in only 8% of cases.

“The children’s mental health crisis requires all child-serving health care providers to do more. Improved care for anxiety and depression in pediatric primary care is needed and does not have to be overly burdensome to pediatricians,” Dr. Butter wrote.

The authors and Dr. Butter declared no relevant financial relationships.

Pediatricians increasingly are stepping in to prescribe drugs for anxiety and depression independently, easing the burden on subspecialists amid the child and adolescent mental health crisis, but a review of electronic health records highlights areas for improvement in delivering the care.

The findings were published online in Pediatrics.

The researchers, led by Talia R. Lester, MD, with the division of developmental behavioral pediatrics in the quantitative science unit at Stanford (Calif.) University, identified 1,685 patients aged 6-18 years who had at least one visit with a diagnosis of anxiety and/or depression in a large primary care network in northern California and who were prescribed an SSRI by a network primary care pediatrician (PCP). The team randomly chose 110 patients and reviewed charts from the visit when the SSRI was first prescribed (medication visit); the immediately previous visit; and immediately subsequent visit.
 

Encouraging signs

The chart reviews showed some encouraging signs. For example, when pediatricians prescribe an SSRI, 82% are appropriately documenting rationales for starting the medication at the medication visit. However, they are not monitoring medication side effects systematically, according to the report. Of 69 patients with a visit after the medication visit, fewer than half (48%) had documentation of monitoring for side effects.

Three areas for improvement

The researchers identified three main shortfall areas and suggested improvements.

PCPs often referred patients for unspecified therapy at the medication visit; however, they rarely prescribed evidence-based therapies such as cognitive-behavioral therapy (CBT) (4% of patients). The authors suggested embedding a summary of evidence-based treatment into order sets.

Secondly, PCPs are not often using screening tools. The data show only 26% of patients had a documented depression- or anxiety-specific screening tool result at the medication visit. The authors recommend making the screening tools accessible through the EHR to increase use.

The researchers also found many patients didn’t have a follow-up visit after SSRI medication was prescribed. Even when they did, the range was so wide between the medication visit and the follow-up (7-365 days) that it’s clear pediatricians are taking inconsistent approaches to scheduling follow-up.
 

Half are seeing only their primary care pediatrician

About half of children and adolescents prescribed an SSRI by a pediatrician for mental health reasons were seeing only their primary care pediatrician, the data showed.

Eric M. Butter, PhD, chief of psychology at Nationwide Children’s Hospital and Ohio State University, Columbus, pointed out in an accompanying editorial that some of the news in pediatricians’ expanded role is particularly encouraging.

Pediatricians, he noted, are making medication decisions consistent with decisions a subspecialist would make.

Of cases in which a subspecialist became involved after a pediatrician initiated medication, subspecialists changed the medication for only two patients, which “is encouraging because it validates pediatricians’ decisions,” Dr. Butter said.

It’s important for pediatricians to understand key evidence-based programs that can work in combination with medications to achieve better results, Dr. Butter said. For example, CBT can help with depression “and break the cycle of avoidance that worsens symptoms of anxiety.”

He highlighted Interpersonal Therapy for Adolescents, a 12-session treatment that “can also address depression by improving patients’ personal relationships.”

“No primary care pediatrician will have the training or time to implement the many treatments that are available,” Dr. Butter wrote. “However, pediatricians can work to understand the key features of the evidence-based treatments referenced by Lester et al.”
 

Most concerning statistics

Dr. Butter said the most concerning shortcoming in the pediatricians’ health care delivery was lack of referral for evidence-based psychological treatments and low rates for referral to access supports from schools through programs such as the education 504 plan and Individualized Education Plans.

Dr. Lester’s team found that pediatricians recommended that patients receive support from such programs in only 8% of cases.

“The children’s mental health crisis requires all child-serving health care providers to do more. Improved care for anxiety and depression in pediatric primary care is needed and does not have to be overly burdensome to pediatricians,” Dr. Butter wrote.

The authors and Dr. Butter declared no relevant financial relationships.

Pediatricians increasingly are stepping in to prescribe drugs for anxiety and depression independently, easing the burden on subspecialists amid the child and adolescent mental health crisis, but a review of electronic health records highlights areas for improvement in delivering the care.

The findings were published online in Pediatrics.

The researchers, led by Talia R. Lester, MD, with the division of developmental behavioral pediatrics in the quantitative science unit at Stanford (Calif.) University, identified 1,685 patients aged 6-18 years who had at least one visit with a diagnosis of anxiety and/or depression in a large primary care network in northern California and who were prescribed an SSRI by a network primary care pediatrician (PCP). The team randomly chose 110 patients and reviewed charts from the visit when the SSRI was first prescribed (medication visit); the immediately previous visit; and immediately subsequent visit.
 

Encouraging signs

The chart reviews showed some encouraging signs. For example, when pediatricians prescribe an SSRI, 82% are appropriately documenting rationales for starting the medication at the medication visit. However, they are not monitoring medication side effects systematically, according to the report. Of 69 patients with a visit after the medication visit, fewer than half (48%) had documentation of monitoring for side effects.

Three areas for improvement

The researchers identified three main shortfall areas and suggested improvements.

PCPs often referred patients for unspecified therapy at the medication visit; however, they rarely prescribed evidence-based therapies such as cognitive-behavioral therapy (CBT) (4% of patients). The authors suggested embedding a summary of evidence-based treatment into order sets.

Secondly, PCPs are not often using screening tools. The data show only 26% of patients had a documented depression- or anxiety-specific screening tool result at the medication visit. The authors recommend making the screening tools accessible through the EHR to increase use.

The researchers also found many patients didn’t have a follow-up visit after SSRI medication was prescribed. Even when they did, the range was so wide between the medication visit and the follow-up (7-365 days) that it’s clear pediatricians are taking inconsistent approaches to scheduling follow-up.
 

Half are seeing only their primary care pediatrician

About half of children and adolescents prescribed an SSRI by a pediatrician for mental health reasons were seeing only their primary care pediatrician, the data showed.

Eric M. Butter, PhD, chief of psychology at Nationwide Children’s Hospital and Ohio State University, Columbus, pointed out in an accompanying editorial that some of the news in pediatricians’ expanded role is particularly encouraging.

Pediatricians, he noted, are making medication decisions consistent with decisions a subspecialist would make.

Of cases in which a subspecialist became involved after a pediatrician initiated medication, subspecialists changed the medication for only two patients, which “is encouraging because it validates pediatricians’ decisions,” Dr. Butter said.

It’s important for pediatricians to understand key evidence-based programs that can work in combination with medications to achieve better results, Dr. Butter said. For example, CBT can help with depression “and break the cycle of avoidance that worsens symptoms of anxiety.”

He highlighted Interpersonal Therapy for Adolescents, a 12-session treatment that “can also address depression by improving patients’ personal relationships.”

“No primary care pediatrician will have the training or time to implement the many treatments that are available,” Dr. Butter wrote. “However, pediatricians can work to understand the key features of the evidence-based treatments referenced by Lester et al.”
 

Most concerning statistics

Dr. Butter said the most concerning shortcoming in the pediatricians’ health care delivery was lack of referral for evidence-based psychological treatments and low rates for referral to access supports from schools through programs such as the education 504 plan and Individualized Education Plans.

Dr. Lester’s team found that pediatricians recommended that patients receive support from such programs in only 8% of cases.

“The children’s mental health crisis requires all child-serving health care providers to do more. Improved care for anxiety and depression in pediatric primary care is needed and does not have to be overly burdensome to pediatricians,” Dr. Butter wrote.

The authors and Dr. Butter declared no relevant financial relationships.

The sex of a red blood cell donor has no effect on the survival of a transfusion recipient, data suggest.

In a randomized clinical trial with almost 9,000 patients, the adjusted hazard ratio of death among recipients of female donors’ blood, compared with recipients of male donors’ blood, was 0.98. The data contradict the finding of previous observational studies that donor sex is associated with recipient outcomes.

“The key finding was that we actually had a null result,” study author Dean Fergusson, MD, PhD, senior scientist at the Ottawa Hospital Research Institute, said in an interview. “We went in thinking that male donor blood would confer a benefit over female donor blood, and we found that there’s absolutely no difference between the donor sexes on recipient outcomes – mortality and other major secondary outcomes,” Dr. Fergusson added.

The study was published in the New England Journal of Medicine.
 

Differences ‘don’t matter’

A 2015 article from the National Heart, Lung, and Blood Institute identified a potential effect of donor sex on transfusion recipient survival. Since then, several observational studies have suggested that donor sex may influence survival after transfusion. This research includes two large studies, one from Canada and one from the Netherlands, that reported a heightened risk of death among recipients of red-cell units from female donors or donors who had been pregnant. Other studies, however, yielded conflicting results.

“The rationale was that female blood, because of biochemical properties, different hormones, exposure to babies and other males, all led to a different product, if you will, and these subtle changes could affect the blood product in terms of shelf life and potency,” said Dr. Fergusson. “That itself would have downstream effects on the recipient.”

The current double-blind study included 8,719 patients who received transfusions from September 2018 to December 2020 at three academic medical centers in Canada. Of this group, 5,190 received male donor blood, and 3,529 received blood from female donors.

The researchers randomly assigned patients in a 60:40 ratio to male and female donor groups. Data collection and follow-up were performed by the Ottawa Hospital Data Warehouse, Canadian Blood Services, and ICES, an independent research institute. Patient characteristics were similar in both trial groups at baseline.

After an average follow-up of 11.2 months, with a maximum follow-up of 29 months, 1,141 patients in the female donor group and 1,712 in the male donor group died. The study found no statistically significant difference in overall survival between the two groups. The unadjusted HR for death, with the male group as the reference, was 0.97, and the adjusted HR was 0.98. The rates of overall survival were 58% and 56.1% in the female and male donor groups, respectively.

The study did not prove that differences in outcome based on donor sex do not exist, said Dr. Fergusson. “But those differences really don’t matter in the recipient.”

The design of the trial itself was unique, Dr. Fergusson said. After patients consented to participate and underwent randomization, the study used routinely collected data from the participating hospitals’ electronic medical records rather than collect data anew for each patient. “That had a profound effect on the efficiency of the trial. We did this trial for a cost of less than $300,000, and typically it would cost $9 million by using high-quality electronic health data.”

The study also evaluated several secondary outcomes. Recipients of female donor blood had twice the incidence of MRSA infection. In addition, an unadjusted subgroup analysis suggested a 10% lower risk of death among male patients assigned to the female donor group, compared with those assigned to the male donor group.

The risk of death was almost three times higher among patients in the female donor group who received units from donors aged 20-29.9 years (HR, 2.93). “The inconsistency of the point estimates across groups and the multiplicity of analyses increase the risk that those findings were due to chance,” according to the authors.
 

Big data

Commenting on the study, Jeannie Callum, MD, professor and director of transfusion medicine at Queen’s University, Kingston, Ont., said that the use of routinely collected data from the participating hospitals’ electronic medical records was “one of the really great things about this paper.”

This use of Big Data “allows you to do a trial like this with almost 9,000 patients without spending millions and millions of dollars to have people go through charts and record data,” she added.

Dr. Callum also pointed out some of the trial’s limitations. “One of the things that kind of detracts from the study in my mind is that they randomized everybody that was getting a transfusion, but outpatients getting a transfusion have a very low mortality rate. So, you have a group of patients that are never going to have that endpoint being included in the study, and that might’ve diluted the findings.”

About 11.4% of participants received blood from a donor group other than the one to which they had been assigned, and this factor may further dilute the findings, said Dr. Callum. “That’s a difficult thing to avoid.” She noted that a trial in which she is collaborating, called Sex Matters, may answer some of these questions about the use of female versus male donor blood.

The investigators also noted that the findings may not be generalizable to other countries. “Just because we didn’t find something in Canada with our blood production system doesn’t mean that the United States might not find it different, because how they manufacture their red blood cells for transfusion is different than how we do them in Canada,” said Dr. Callum.

Nonetheless, this study shows the potential of using Big Data in medicine. “This is the future of large randomized clinical trials to quickly answer questions,” said Dr. Callum. “In the United States, Canada, and other countries that have these large electronic medical records systems, this kind of trial would be able to be done in other centers.”

The study was funded by the Canadian Institutes of Health Research. Dr. Fergusson and Dr. Callum disclosed no relevant financial relationships.

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

The sex of a red blood cell donor has no effect on the survival of a transfusion recipient, data suggest.

In a randomized clinical trial with almost 9,000 patients, the adjusted hazard ratio of death among recipients of female donors’ blood, compared with recipients of male donors’ blood, was 0.98. The data contradict the finding of previous observational studies that donor sex is associated with recipient outcomes.

“The key finding was that we actually had a null result,” study author Dean Fergusson, MD, PhD, senior scientist at the Ottawa Hospital Research Institute, said in an interview. “We went in thinking that male donor blood would confer a benefit over female donor blood, and we found that there’s absolutely no difference between the donor sexes on recipient outcomes – mortality and other major secondary outcomes,” Dr. Fergusson added.

The study was published in the New England Journal of Medicine.
 

Differences ‘don’t matter’

A 2015 article from the National Heart, Lung, and Blood Institute identified a potential effect of donor sex on transfusion recipient survival. Since then, several observational studies have suggested that donor sex may influence survival after transfusion. This research includes two large studies, one from Canada and one from the Netherlands, that reported a heightened risk of death among recipients of red-cell units from female donors or donors who had been pregnant. Other studies, however, yielded conflicting results.

“The rationale was that female blood, because of biochemical properties, different hormones, exposure to babies and other males, all led to a different product, if you will, and these subtle changes could affect the blood product in terms of shelf life and potency,” said Dr. Fergusson. “That itself would have downstream effects on the recipient.”

The current double-blind study included 8,719 patients who received transfusions from September 2018 to December 2020 at three academic medical centers in Canada. Of this group, 5,190 received male donor blood, and 3,529 received blood from female donors.

The researchers randomly assigned patients in a 60:40 ratio to male and female donor groups. Data collection and follow-up were performed by the Ottawa Hospital Data Warehouse, Canadian Blood Services, and ICES, an independent research institute. Patient characteristics were similar in both trial groups at baseline.

After an average follow-up of 11.2 months, with a maximum follow-up of 29 months, 1,141 patients in the female donor group and 1,712 in the male donor group died. The study found no statistically significant difference in overall survival between the two groups. The unadjusted HR for death, with the male group as the reference, was 0.97, and the adjusted HR was 0.98. The rates of overall survival were 58% and 56.1% in the female and male donor groups, respectively.

The study did not prove that differences in outcome based on donor sex do not exist, said Dr. Fergusson. “But those differences really don’t matter in the recipient.”

The design of the trial itself was unique, Dr. Fergusson said. After patients consented to participate and underwent randomization, the study used routinely collected data from the participating hospitals’ electronic medical records rather than collect data anew for each patient. “That had a profound effect on the efficiency of the trial. We did this trial for a cost of less than $300,000, and typically it would cost $9 million by using high-quality electronic health data.”

The study also evaluated several secondary outcomes. Recipients of female donor blood had twice the incidence of MRSA infection. In addition, an unadjusted subgroup analysis suggested a 10% lower risk of death among male patients assigned to the female donor group, compared with those assigned to the male donor group.

The risk of death was almost three times higher among patients in the female donor group who received units from donors aged 20-29.9 years (HR, 2.93). “The inconsistency of the point estimates across groups and the multiplicity of analyses increase the risk that those findings were due to chance,” according to the authors.
 

Big data

Commenting on the study, Jeannie Callum, MD, professor and director of transfusion medicine at Queen’s University, Kingston, Ont., said that the use of routinely collected data from the participating hospitals’ electronic medical records was “one of the really great things about this paper.”

This use of Big Data “allows you to do a trial like this with almost 9,000 patients without spending millions and millions of dollars to have people go through charts and record data,” she added.

Dr. Callum also pointed out some of the trial’s limitations. “One of the things that kind of detracts from the study in my mind is that they randomized everybody that was getting a transfusion, but outpatients getting a transfusion have a very low mortality rate. So, you have a group of patients that are never going to have that endpoint being included in the study, and that might’ve diluted the findings.”

About 11.4% of participants received blood from a donor group other than the one to which they had been assigned, and this factor may further dilute the findings, said Dr. Callum. “That’s a difficult thing to avoid.” She noted that a trial in which she is collaborating, called Sex Matters, may answer some of these questions about the use of female versus male donor blood.

The investigators also noted that the findings may not be generalizable to other countries. “Just because we didn’t find something in Canada with our blood production system doesn’t mean that the United States might not find it different, because how they manufacture their red blood cells for transfusion is different than how we do them in Canada,” said Dr. Callum.

Nonetheless, this study shows the potential of using Big Data in medicine. “This is the future of large randomized clinical trials to quickly answer questions,” said Dr. Callum. “In the United States, Canada, and other countries that have these large electronic medical records systems, this kind of trial would be able to be done in other centers.”

The study was funded by the Canadian Institutes of Health Research. Dr. Fergusson and Dr. Callum disclosed no relevant financial relationships.

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

The sex of a red blood cell donor has no effect on the survival of a transfusion recipient, data suggest.

In a randomized clinical trial with almost 9,000 patients, the adjusted hazard ratio of death among recipients of female donors’ blood, compared with recipients of male donors’ blood, was 0.98. The data contradict the finding of previous observational studies that donor sex is associated with recipient outcomes.

“The key finding was that we actually had a null result,” study author Dean Fergusson, MD, PhD, senior scientist at the Ottawa Hospital Research Institute, said in an interview. “We went in thinking that male donor blood would confer a benefit over female donor blood, and we found that there’s absolutely no difference between the donor sexes on recipient outcomes – mortality and other major secondary outcomes,” Dr. Fergusson added.

The study was published in the New England Journal of Medicine.
 

Differences ‘don’t matter’

A 2015 article from the National Heart, Lung, and Blood Institute identified a potential effect of donor sex on transfusion recipient survival. Since then, several observational studies have suggested that donor sex may influence survival after transfusion. This research includes two large studies, one from Canada and one from the Netherlands, that reported a heightened risk of death among recipients of red-cell units from female donors or donors who had been pregnant. Other studies, however, yielded conflicting results.

“The rationale was that female blood, because of biochemical properties, different hormones, exposure to babies and other males, all led to a different product, if you will, and these subtle changes could affect the blood product in terms of shelf life and potency,” said Dr. Fergusson. “That itself would have downstream effects on the recipient.”

The current double-blind study included 8,719 patients who received transfusions from September 2018 to December 2020 at three academic medical centers in Canada. Of this group, 5,190 received male donor blood, and 3,529 received blood from female donors.

The researchers randomly assigned patients in a 60:40 ratio to male and female donor groups. Data collection and follow-up were performed by the Ottawa Hospital Data Warehouse, Canadian Blood Services, and ICES, an independent research institute. Patient characteristics were similar in both trial groups at baseline.

After an average follow-up of 11.2 months, with a maximum follow-up of 29 months, 1,141 patients in the female donor group and 1,712 in the male donor group died. The study found no statistically significant difference in overall survival between the two groups. The unadjusted HR for death, with the male group as the reference, was 0.97, and the adjusted HR was 0.98. The rates of overall survival were 58% and 56.1% in the female and male donor groups, respectively.

The study did not prove that differences in outcome based on donor sex do not exist, said Dr. Fergusson. “But those differences really don’t matter in the recipient.”

The design of the trial itself was unique, Dr. Fergusson said. After patients consented to participate and underwent randomization, the study used routinely collected data from the participating hospitals’ electronic medical records rather than collect data anew for each patient. “That had a profound effect on the efficiency of the trial. We did this trial for a cost of less than $300,000, and typically it would cost $9 million by using high-quality electronic health data.”

The study also evaluated several secondary outcomes. Recipients of female donor blood had twice the incidence of MRSA infection. In addition, an unadjusted subgroup analysis suggested a 10% lower risk of death among male patients assigned to the female donor group, compared with those assigned to the male donor group.

The risk of death was almost three times higher among patients in the female donor group who received units from donors aged 20-29.9 years (HR, 2.93). “The inconsistency of the point estimates across groups and the multiplicity of analyses increase the risk that those findings were due to chance,” according to the authors.
 

Big data

Commenting on the study, Jeannie Callum, MD, professor and director of transfusion medicine at Queen’s University, Kingston, Ont., said that the use of routinely collected data from the participating hospitals’ electronic medical records was “one of the really great things about this paper.”

This use of Big Data “allows you to do a trial like this with almost 9,000 patients without spending millions and millions of dollars to have people go through charts and record data,” she added.

Dr. Callum also pointed out some of the trial’s limitations. “One of the things that kind of detracts from the study in my mind is that they randomized everybody that was getting a transfusion, but outpatients getting a transfusion have a very low mortality rate. So, you have a group of patients that are never going to have that endpoint being included in the study, and that might’ve diluted the findings.”

About 11.4% of participants received blood from a donor group other than the one to which they had been assigned, and this factor may further dilute the findings, said Dr. Callum. “That’s a difficult thing to avoid.” She noted that a trial in which she is collaborating, called Sex Matters, may answer some of these questions about the use of female versus male donor blood.

The investigators also noted that the findings may not be generalizable to other countries. “Just because we didn’t find something in Canada with our blood production system doesn’t mean that the United States might not find it different, because how they manufacture their red blood cells for transfusion is different than how we do them in Canada,” said Dr. Callum.

Nonetheless, this study shows the potential of using Big Data in medicine. “This is the future of large randomized clinical trials to quickly answer questions,” said Dr. Callum. “In the United States, Canada, and other countries that have these large electronic medical records systems, this kind of trial would be able to be done in other centers.”

The study was funded by the Canadian Institutes of Health Research. Dr. Fergusson and Dr. Callum disclosed no relevant financial relationships.

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

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

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

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

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

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

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

Physical, mental health strongly linked

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

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

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

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

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

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

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

Reduced impulsivity

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

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

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

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

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

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

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

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

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

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

Not useful?

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

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

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

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

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

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

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

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

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

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

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

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

Physical, mental health strongly linked

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

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

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

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

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

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

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

Reduced impulsivity

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

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

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

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

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

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

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

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

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

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

Not useful?

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

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

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

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

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

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

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

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

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

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

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

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

Physical, mental health strongly linked

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

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

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

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

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

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

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

Reduced impulsivity

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

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

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

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

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

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

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

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

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

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

Not useful?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Delayed diagnosis of ovarian cancers favors BSO

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Delayed diagnosis of ovarian cancers favors BSO

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Delayed diagnosis of ovarian cancers favors BSO

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

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

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

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

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

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

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

Dr. Furman

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

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

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

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

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

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

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

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

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

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

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

Dr. Furman

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

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

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

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

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

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

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

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

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

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

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

Dr. Furman

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

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

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

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

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

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

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

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

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

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

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

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

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

The study was published online in JAMA Network Open.

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

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

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

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

10% weight loss quadrupled risk of premature death among men

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

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

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

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

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

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

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

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

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

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

Association with mortality remained after adjustment for hospitalization

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

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

The authors reported no relevant financial relationships.

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

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

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

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

The study was published online in JAMA Network Open.

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

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

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

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

10% weight loss quadrupled risk of premature death among men

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

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

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

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

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

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

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

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

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

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

Association with mortality remained after adjustment for hospitalization

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

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

The authors reported no relevant financial relationships.

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

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

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

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

The study was published online in JAMA Network Open.

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

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

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

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

10% weight loss quadrupled risk of premature death among men

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

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

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

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

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

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

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

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

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

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

Association with mortality remained after adjustment for hospitalization

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

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

The authors reported no relevant financial relationships.

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