Journal of Clinical Outcomes Management

The study covered in this summary was published in medRxiv.org as a preprint and has not yet been peer reviewed.

Key takeaways

• Right ventricular (RV) dilation or dysfunction in patients hospitalized with acute COVID-19 is associated with an elevated risk for in-hospital death.
• The impact of RV dilation or dysfunction on in-hospital mortality is similar for patients with acute COVID-19 and those with influenza, pneumonia, or acute respiratory distress syndrome (ARDS), but COVID-19 patients have greater absolute in-hospital mortality.
• RV dilatation or dysfunction in patients with acute COVID-19 is associated with a diagnosis of venous thromboembolism and subsequent intubation and mechanical ventilation.

Why this matters

• Right ventricular dysfunction increases mortality risk in acute COVID-19, and this study shows that RV dilation and dysfunction among such hospitalized patients has a similar impact on risk for in-hospital death in acute COVID-19 and in other respiratory illnesses.
• The findings suggest that abnormal RV findings should be considered a mortality risk marker in patients with acute respiratory illness, especially COVID-19.

Study design

• The retrospective study involved 225 consecutive patients admitted for acute COVID-19 from March 2020 to February 2021 at four major hospitals in the same metropolitan region and a control group of 6,150 adults admitted to the hospital for influenza, pneumonia, or ARDS; mean age in the study cohort was 63 years.
• All participants underwent echocardiography during their hospitalization, including evaluation of any RV dilation or dysfunction.
• Associations between RV measurements and in-hospital mortality, the primary outcome, were adjusted for potential confounders.

Key results

• Patients in the COVID-19 group were more likely than were those in the control group to be male (66% vs. 54%; P < .001), to identify as Hispanic (38% vs. 15%; P < .001), and to have a higher mean body mass index (29.4 vs. 27.9 kg/m²; P = .008).
• Compared with the control group, patients in the COVID-19 group more often required admission to the intensive care unit (75% vs. 54%; P < .001), mechanical ventilation (P < .001), and initiation of renal replacement therapy (P = .002), and more often were diagnosed with deep-vein thrombosis or pulmonary embolism (25% vs. 14%; P < .001). The median length of hospital stay was 20 days in the COVID-19 group, compared with 10 days in the control group (P < .001).
• In-hospital mortality was 21.3% in the COVID-19 group and 11.8% in the control group (P = .001). Those hospitalized with COVID-19 had an adjusted relative risk (RR) of 1.54 (95% confidence interval [CI], 1.06-2.24; P = .02) for in-hospital mortality, compared with those hospitalized for other respiratory illnesses.
• Mild RV dilation was associated with an adjusted RR of 1.4 (95% CI, 1.17-1.69; P = .0003) for in-hospital death, and moderate to severe RV dilation was associated with an adjusted RR of 2.0 (95% CI, 1.62-2.47; P < .0001).
• The corresponding adjusted risks for mild RV dysfunction and greater-than-mild RV dysfunction were, respectively, 1.39 (95% CI, 1.10-1.77; P = .007) and 1.68 (95% CI, 1.17-2.42; P = .005).
• The RR for in-hospital mortality associated with RV dilation and dysfunction was similar in those with COVID-19 and those with other respiratory illness, but the former had a higher baseline risk that yielded a greater absolute risk in the COVID-19 group.

Limitations

• The study was based primarily on a retrospective review of electronic health records, which poses a risk for misclassification. 
• Echocardiography was performed without blinding operators to patient clinical status, and echocardiograms were interpreted in a single university hospital system, so were not externally validated.
• Because echocardiograms obtained during hospitalization could not be compared with previous echocardiograms, it could not be determined whether any of the patients had preexisting RV dilation or dysfunction.
• Strain imaging was not feasible in many cases.

Disclosures

• The study received no commercial funding.
• The authors disclosed no financial relationships.

This is a summary of a preprint research study, Association of Right Ventricular Dilation and Dysfunction on Echocardiogram With In-Hospital Mortality Among Patients Hospitalized with COVID-19 Compared With Other Acute Respiratory Illness, written by researchers at the University of California, San Francisco, department of medicine, and Zuckerberg San Francisco General Hospital, division of cardiology. A version of this article first appeared on Medscape.com.

The study covered in this summary was published in medRxiv.org as a preprint and has not yet been peer reviewed.

Key takeaways

• Right ventricular (RV) dilation or dysfunction in patients hospitalized with acute COVID-19 is associated with an elevated risk for in-hospital death.
• The impact of RV dilation or dysfunction on in-hospital mortality is similar for patients with acute COVID-19 and those with influenza, pneumonia, or acute respiratory distress syndrome (ARDS), but COVID-19 patients have greater absolute in-hospital mortality.
• RV dilatation or dysfunction in patients with acute COVID-19 is associated with a diagnosis of venous thromboembolism and subsequent intubation and mechanical ventilation.

Why this matters

• Right ventricular dysfunction increases mortality risk in acute COVID-19, and this study shows that RV dilation and dysfunction among such hospitalized patients has a similar impact on risk for in-hospital death in acute COVID-19 and in other respiratory illnesses.
• The findings suggest that abnormal RV findings should be considered a mortality risk marker in patients with acute respiratory illness, especially COVID-19.

Study design

• The retrospective study involved 225 consecutive patients admitted for acute COVID-19 from March 2020 to February 2021 at four major hospitals in the same metropolitan region and a control group of 6,150 adults admitted to the hospital for influenza, pneumonia, or ARDS; mean age in the study cohort was 63 years.
• All participants underwent echocardiography during their hospitalization, including evaluation of any RV dilation or dysfunction.
• Associations between RV measurements and in-hospital mortality, the primary outcome, were adjusted for potential confounders.

Key results

• Patients in the COVID-19 group were more likely than were those in the control group to be male (66% vs. 54%; P < .001), to identify as Hispanic (38% vs. 15%; P < .001), and to have a higher mean body mass index (29.4 vs. 27.9 kg/m²; P = .008).
• Compared with the control group, patients in the COVID-19 group more often required admission to the intensive care unit (75% vs. 54%; P < .001), mechanical ventilation (P < .001), and initiation of renal replacement therapy (P = .002), and more often were diagnosed with deep-vein thrombosis or pulmonary embolism (25% vs. 14%; P < .001). The median length of hospital stay was 20 days in the COVID-19 group, compared with 10 days in the control group (P < .001).
• In-hospital mortality was 21.3% in the COVID-19 group and 11.8% in the control group (P = .001). Those hospitalized with COVID-19 had an adjusted relative risk (RR) of 1.54 (95% confidence interval [CI], 1.06-2.24; P = .02) for in-hospital mortality, compared with those hospitalized for other respiratory illnesses.
• Mild RV dilation was associated with an adjusted RR of 1.4 (95% CI, 1.17-1.69; P = .0003) for in-hospital death, and moderate to severe RV dilation was associated with an adjusted RR of 2.0 (95% CI, 1.62-2.47; P < .0001).
• The corresponding adjusted risks for mild RV dysfunction and greater-than-mild RV dysfunction were, respectively, 1.39 (95% CI, 1.10-1.77; P = .007) and 1.68 (95% CI, 1.17-2.42; P = .005).
• The RR for in-hospital mortality associated with RV dilation and dysfunction was similar in those with COVID-19 and those with other respiratory illness, but the former had a higher baseline risk that yielded a greater absolute risk in the COVID-19 group.

Limitations

• The study was based primarily on a retrospective review of electronic health records, which poses a risk for misclassification. 
• Echocardiography was performed without blinding operators to patient clinical status, and echocardiograms were interpreted in a single university hospital system, so were not externally validated.
• Because echocardiograms obtained during hospitalization could not be compared with previous echocardiograms, it could not be determined whether any of the patients had preexisting RV dilation or dysfunction.
• Strain imaging was not feasible in many cases.

Disclosures

• The study received no commercial funding.
• The authors disclosed no financial relationships.

This is a summary of a preprint research study, Association of Right Ventricular Dilation and Dysfunction on Echocardiogram With In-Hospital Mortality Among Patients Hospitalized with COVID-19 Compared With Other Acute Respiratory Illness, written by researchers at the University of California, San Francisco, department of medicine, and Zuckerberg San Francisco General Hospital, division of cardiology. A version of this article first appeared on Medscape.com.

The study covered in this summary was published in medRxiv.org as a preprint and has not yet been peer reviewed.

Key takeaways

• Right ventricular (RV) dilation or dysfunction in patients hospitalized with acute COVID-19 is associated with an elevated risk for in-hospital death.
• The impact of RV dilation or dysfunction on in-hospital mortality is similar for patients with acute COVID-19 and those with influenza, pneumonia, or acute respiratory distress syndrome (ARDS), but COVID-19 patients have greater absolute in-hospital mortality.
• RV dilatation or dysfunction in patients with acute COVID-19 is associated with a diagnosis of venous thromboembolism and subsequent intubation and mechanical ventilation.

Why this matters

• Right ventricular dysfunction increases mortality risk in acute COVID-19, and this study shows that RV dilation and dysfunction among such hospitalized patients has a similar impact on risk for in-hospital death in acute COVID-19 and in other respiratory illnesses.
• The findings suggest that abnormal RV findings should be considered a mortality risk marker in patients with acute respiratory illness, especially COVID-19.

Study design

• The retrospective study involved 225 consecutive patients admitted for acute COVID-19 from March 2020 to February 2021 at four major hospitals in the same metropolitan region and a control group of 6,150 adults admitted to the hospital for influenza, pneumonia, or ARDS; mean age in the study cohort was 63 years.
• All participants underwent echocardiography during their hospitalization, including evaluation of any RV dilation or dysfunction.
• Associations between RV measurements and in-hospital mortality, the primary outcome, were adjusted for potential confounders.

Key results

• Patients in the COVID-19 group were more likely than were those in the control group to be male (66% vs. 54%; P < .001), to identify as Hispanic (38% vs. 15%; P < .001), and to have a higher mean body mass index (29.4 vs. 27.9 kg/m²; P = .008).
• Compared with the control group, patients in the COVID-19 group more often required admission to the intensive care unit (75% vs. 54%; P < .001), mechanical ventilation (P < .001), and initiation of renal replacement therapy (P = .002), and more often were diagnosed with deep-vein thrombosis or pulmonary embolism (25% vs. 14%; P < .001). The median length of hospital stay was 20 days in the COVID-19 group, compared with 10 days in the control group (P < .001).
• In-hospital mortality was 21.3% in the COVID-19 group and 11.8% in the control group (P = .001). Those hospitalized with COVID-19 had an adjusted relative risk (RR) of 1.54 (95% confidence interval [CI], 1.06-2.24; P = .02) for in-hospital mortality, compared with those hospitalized for other respiratory illnesses.
• Mild RV dilation was associated with an adjusted RR of 1.4 (95% CI, 1.17-1.69; P = .0003) for in-hospital death, and moderate to severe RV dilation was associated with an adjusted RR of 2.0 (95% CI, 1.62-2.47; P < .0001).
• The corresponding adjusted risks for mild RV dysfunction and greater-than-mild RV dysfunction were, respectively, 1.39 (95% CI, 1.10-1.77; P = .007) and 1.68 (95% CI, 1.17-2.42; P = .005).
• The RR for in-hospital mortality associated with RV dilation and dysfunction was similar in those with COVID-19 and those with other respiratory illness, but the former had a higher baseline risk that yielded a greater absolute risk in the COVID-19 group.

Limitations

• The study was based primarily on a retrospective review of electronic health records, which poses a risk for misclassification. 
• Echocardiography was performed without blinding operators to patient clinical status, and echocardiograms were interpreted in a single university hospital system, so were not externally validated.
• Because echocardiograms obtained during hospitalization could not be compared with previous echocardiograms, it could not be determined whether any of the patients had preexisting RV dilation or dysfunction.
• Strain imaging was not feasible in many cases.

Disclosures

• The study received no commercial funding.
• The authors disclosed no financial relationships.

This is a summary of a preprint research study, Association of Right Ventricular Dilation and Dysfunction on Echocardiogram With In-Hospital Mortality Among Patients Hospitalized with COVID-19 Compared With Other Acute Respiratory Illness, written by researchers at the University of California, San Francisco, department of medicine, and Zuckerberg San Francisco General Hospital, division of cardiology. A version of this article first appeared on Medscape.com.

Transmission of anxiety appears to be sex-specific – spreading from mothers to daughters and from fathers to sons, new research shows.

The new findings suggest that children learn anxious behavior from their parents, study investigator Barbara Pavlova, PhD, clinical psychologist with Nova Scotia Health Authority, told this news organization.

“This means that transmission of anxiety from parents to children may be preventable,” said Dr. Pavlova, assistant professor, department of psychiatry, Dalhousie University, Halifax, Canada.

Vlad Drobinin

Parental anxiety a disruptor

Anxiety disorders run in families. Both genes and environment are thought to be at play, but there are few data on sex-specific transmission from parent to child.

To investigate, the researchers conducted a cross-sectional study of 203 girls and 195 boys and their parents. The average age of the children was 11 years, and they had a familial risk for mood disorders.

Anxiety disorder in a same-sex parent was significantly associated with anxiety disorder in offspring (odds ratio, 2.85; 95% confidence interval, 1.52-5.34; P = .001) but not in an opposite-sex parent (OR, 1.51; 95% CI, 0.81-2.81; P = .20).

Living with a same-sex parent without anxiety was associated with lower rates of offspring anxiety (OR, 0.38; 95% CI, 0.22-0.67; P = .001).

Among all 398 children, 108 (27%) had been diagnosed with one or more anxiety disorders, including generalized anxiety disorder (7.8%), social anxiety disorder (6.3%), separation anxiety disorder (8.6%), specific phobia (8%), and anxiety disorder not otherwise specified (5%).

Rates of anxiety disorders in children increased with age, from 14% in those younger than 9 years to 52% in those older than 15 years. Anxiety disorders were similarly common among boys (24%) and girls (30%).

Rates of anxiety disorders were lowest (24%) in children of two parents without anxiety disorders and highest (41%) in cases in which both parents had anxiety disorders.

The findings point to the possible role of environmental factors, “such as modeling and vicarious learning,” in the transmission of anxiety from parents to their children, the researchers note.

“A child receives [a] similar amount of genetic information from each biological parent. A strong same-sex parent effect suggests children learn resilience by modeling the behavior of their same-sex parent. A parent’s anxiety disorder may disrupt this protective learning,” said Dr. Pavlova.
 

Early diagnosis, treatment essential

Reached for comment, Jill Emanuele, PhD, vice president of clinical training for the Child MIND Institute, New York, said that when it comes to anxiety, it’s important to assess and treat both the parent and the child.

“We know that both environment and genetics play a role in anxiety disorders. From a clinical perspective, if we see a parent with an anxiety disorder, we know that there is a chance that that is also going to affect the child – whether or not the child has an anxiety disorder,” Dr. Emanuele said in an interview.

“Anxiety disorders are the most common psychiatric disorders diagnosed. We also know that anxiety disorders emerge earlier than mood disorders and certainly can emerge in childhood. It’s important to address anxiety early because those same problems can continue into adulthood if left untreated,” Dr. Emanuele added.

The study was supported by the Canada Research Chairs Program, the Canadian Institutes of Health Research, the Brain & Behavior Research Foundation, the Nova Scotia Health Research Foundation, and the Dalhousie Medical Research Foundation. The authors have disclosed no relevant financial relationships. Dr. Emanuele is a board member with the Anxiety and Depression Association of America.

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

Transmission of anxiety appears to be sex-specific – spreading from mothers to daughters and from fathers to sons, new research shows.

The new findings suggest that children learn anxious behavior from their parents, study investigator Barbara Pavlova, PhD, clinical psychologist with Nova Scotia Health Authority, told this news organization.

“This means that transmission of anxiety from parents to children may be preventable,” said Dr. Pavlova, assistant professor, department of psychiatry, Dalhousie University, Halifax, Canada.

Vlad Drobinin

Parental anxiety a disruptor

Anxiety disorders run in families. Both genes and environment are thought to be at play, but there are few data on sex-specific transmission from parent to child.

To investigate, the researchers conducted a cross-sectional study of 203 girls and 195 boys and their parents. The average age of the children was 11 years, and they had a familial risk for mood disorders.

Anxiety disorder in a same-sex parent was significantly associated with anxiety disorder in offspring (odds ratio, 2.85; 95% confidence interval, 1.52-5.34; P = .001) but not in an opposite-sex parent (OR, 1.51; 95% CI, 0.81-2.81; P = .20).

Living with a same-sex parent without anxiety was associated with lower rates of offspring anxiety (OR, 0.38; 95% CI, 0.22-0.67; P = .001).

Among all 398 children, 108 (27%) had been diagnosed with one or more anxiety disorders, including generalized anxiety disorder (7.8%), social anxiety disorder (6.3%), separation anxiety disorder (8.6%), specific phobia (8%), and anxiety disorder not otherwise specified (5%).

Rates of anxiety disorders in children increased with age, from 14% in those younger than 9 years to 52% in those older than 15 years. Anxiety disorders were similarly common among boys (24%) and girls (30%).

Rates of anxiety disorders were lowest (24%) in children of two parents without anxiety disorders and highest (41%) in cases in which both parents had anxiety disorders.

The findings point to the possible role of environmental factors, “such as modeling and vicarious learning,” in the transmission of anxiety from parents to their children, the researchers note.

“A child receives [a] similar amount of genetic information from each biological parent. A strong same-sex parent effect suggests children learn resilience by modeling the behavior of their same-sex parent. A parent’s anxiety disorder may disrupt this protective learning,” said Dr. Pavlova.
 

Early diagnosis, treatment essential

Reached for comment, Jill Emanuele, PhD, vice president of clinical training for the Child MIND Institute, New York, said that when it comes to anxiety, it’s important to assess and treat both the parent and the child.

“We know that both environment and genetics play a role in anxiety disorders. From a clinical perspective, if we see a parent with an anxiety disorder, we know that there is a chance that that is also going to affect the child – whether or not the child has an anxiety disorder,” Dr. Emanuele said in an interview.

“Anxiety disorders are the most common psychiatric disorders diagnosed. We also know that anxiety disorders emerge earlier than mood disorders and certainly can emerge in childhood. It’s important to address anxiety early because those same problems can continue into adulthood if left untreated,” Dr. Emanuele added.

The study was supported by the Canada Research Chairs Program, the Canadian Institutes of Health Research, the Brain & Behavior Research Foundation, the Nova Scotia Health Research Foundation, and the Dalhousie Medical Research Foundation. The authors have disclosed no relevant financial relationships. Dr. Emanuele is a board member with the Anxiety and Depression Association of America.

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

Transmission of anxiety appears to be sex-specific – spreading from mothers to daughters and from fathers to sons, new research shows.

The new findings suggest that children learn anxious behavior from their parents, study investigator Barbara Pavlova, PhD, clinical psychologist with Nova Scotia Health Authority, told this news organization.

“This means that transmission of anxiety from parents to children may be preventable,” said Dr. Pavlova, assistant professor, department of psychiatry, Dalhousie University, Halifax, Canada.

Vlad Drobinin

Parental anxiety a disruptor

Anxiety disorders run in families. Both genes and environment are thought to be at play, but there are few data on sex-specific transmission from parent to child.

To investigate, the researchers conducted a cross-sectional study of 203 girls and 195 boys and their parents. The average age of the children was 11 years, and they had a familial risk for mood disorders.

Anxiety disorder in a same-sex parent was significantly associated with anxiety disorder in offspring (odds ratio, 2.85; 95% confidence interval, 1.52-5.34; P = .001) but not in an opposite-sex parent (OR, 1.51; 95% CI, 0.81-2.81; P = .20).

Living with a same-sex parent without anxiety was associated with lower rates of offspring anxiety (OR, 0.38; 95% CI, 0.22-0.67; P = .001).

Among all 398 children, 108 (27%) had been diagnosed with one or more anxiety disorders, including generalized anxiety disorder (7.8%), social anxiety disorder (6.3%), separation anxiety disorder (8.6%), specific phobia (8%), and anxiety disorder not otherwise specified (5%).

Rates of anxiety disorders in children increased with age, from 14% in those younger than 9 years to 52% in those older than 15 years. Anxiety disorders were similarly common among boys (24%) and girls (30%).

Rates of anxiety disorders were lowest (24%) in children of two parents without anxiety disorders and highest (41%) in cases in which both parents had anxiety disorders.

The findings point to the possible role of environmental factors, “such as modeling and vicarious learning,” in the transmission of anxiety from parents to their children, the researchers note.

“A child receives [a] similar amount of genetic information from each biological parent. A strong same-sex parent effect suggests children learn resilience by modeling the behavior of their same-sex parent. A parent’s anxiety disorder may disrupt this protective learning,” said Dr. Pavlova.
 

Early diagnosis, treatment essential

Reached for comment, Jill Emanuele, PhD, vice president of clinical training for the Child MIND Institute, New York, said that when it comes to anxiety, it’s important to assess and treat both the parent and the child.

“We know that both environment and genetics play a role in anxiety disorders. From a clinical perspective, if we see a parent with an anxiety disorder, we know that there is a chance that that is also going to affect the child – whether or not the child has an anxiety disorder,” Dr. Emanuele said in an interview.

“Anxiety disorders are the most common psychiatric disorders diagnosed. We also know that anxiety disorders emerge earlier than mood disorders and certainly can emerge in childhood. It’s important to address anxiety early because those same problems can continue into adulthood if left untreated,” Dr. Emanuele added.

The study was supported by the Canada Research Chairs Program, the Canadian Institutes of Health Research, the Brain & Behavior Research Foundation, the Nova Scotia Health Research Foundation, and the Dalhousie Medical Research Foundation. The authors have disclosed no relevant financial relationships. Dr. Emanuele is a board member with the Anxiety and Depression Association of America.

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

Patients who take methotrexate for a variety of immune-mediated inflammatory diseases and pause taking the drug following receipt of a COVID-19 vaccine dose did not have a higher risk of disease flare and had higher antireceptor binding domain (anti-RBD) antibody titers and increased immunogenicity when compared with continuing the drug, three recent studies suggest.

In one study, British researchers examined the effects of a 2-week break in methotrexate therapy on anti-RBD titers following receipt of a third COVID-19 vaccine dose. In their paper published in The Lancet: Respiratory Medicine, they reported results from a randomized, open-label, superiority trial that suggested pausing the drug improved immunogenicity, compared with no break.

In two trials presented at the European Alliance of Associations for Rheumatology (EULAR) 2022 Congress, a team from India set out to determine whether holding methotrexate after receiving both doses of a COVID-19 vaccine, or holding it only after the second dose, was safe and effective. They found that pausing methotrexate only following the second dose contributed to a lower flare risk, and that patients had higher anti-RBD titers when holding methotrexate for 2 weeks following each dose.
 

Pausing methotrexate after booster

The 2-week methotrexate break and booster vaccine dose data in the Vaccine Response On Off Methotrexate (VROOM) trial showed that after a month, the geometric mean antispike 1 (S1)-RBD antibody titer was 10,798 U/mL (95% confidence interval [CI], 8,970-12,997) in the group that continued methotrexate and 22,750 U/mL (95% CI, 19,314-26,796) in the group that suspended methotrexate; the geometric mean ratio was 2.19 (P < .0001; mixed-effects model), reported Abhishek Abhishek, MD, PhD, professor of rheumatology at the University of Nottingham in Nottingham, England, and colleagues.

Prior research showed that stopping methotrexate therapy for 2 weeks following the seasonal influenza vaccine contributed to better vaccine immunity among patients with rheumatoid arthritis, but there was no impact of stopping the drug for up to 4 weeks before vaccination on vaccine-related immunity, the researchers noted.

It is crucial in maximizing long-lasting vaccine protection in people who are possibly susceptible through immune suppression at this point in the COVID-19 vaccination regimen, the study team noted.

“Evidence from this study will be useful for policymakers, national immunization advisory committees, and specialist societies formulating recommendations on the use of methotrexate around the time of COVID-19 vaccination. This evidence will help patients and clinicians make informed choices about the risks and benefits of interrupting methotrexate treatment around the time of COVID-19 vaccination, with implications for the potential to extend such approaches to other therapeutics,” they wrote.

In American College of Rheumatology (ACR) guidance for COVID-19 vaccination, the organization advised against using standard synthetic disease-modifying antirheumatic medicines such as methotrexate “for 1-2 weeks (as disease activity allows) after each COVID-19 vaccine dose,” given the at-risk population and public health concerns, Jeffrey A. Sparks, MD, MMSc, assistant professor of medicine and associate physician at Brigham and Women’s Hospital and Harvard Medical School, Boston, and Sara K. Tedeschi, MD, MPH, assistant professor of medicine at Harvard Medical School, noted in an accompanying editorial in The Lancet: Respiratory Medicine.

However, when the ACR developed this statement, there was only one trial involving patients with rheumatoid arthritis who paused methotrexate following seasonal influenza vaccination, the editorialists said.

Expert commentary

This current study is consistent with other studies over the last several months showing that methotrexate harms both humoral and cell-mediated COVID-19 responses, noted Kevin Winthrop, MD, MPH, professor of infectious disease and public health at Oregon Health & Science University, Portland, who was not involved in the study. “And so now the new wave of studies are like this one, where they are holding methotrexate experimentally and seeing if it makes a difference,” he said.

“The one shortcoming of this study – and so far, the studies to date – is that no one has looked at whether the experimental hold has resulted in a change in T-cell responses, which ... we are [now] recognizing [the importance of] more and more in long-term protection, particularly in severe disease. Theoretically, holding [methotrexate] might help enhance T-cell responses, but that hasn’t been shown experimentally.”

Dr. Winthrop pointed out that one might get the same benefit from holding methotrexate for 1 week instead of 2 and that there likely is a reduced risk of flare-up from underlying autoimmune disease.

It is still not certain that this benefit extends to other vaccines, Dr. Winthrop noted. “It is probably true for most vaccines that if you hold methotrexate for 1 or 2 weeks, you might see some short-term benefit in responsiveness, but you don’t know that there is any clinical meaningfulness of this. That’s going to take other long-term studies. You don’t know how long this benefit lasts.”
 

Pausing methotrexate during initial COVID vaccine doses

Patients with either rheumatoid arthritis or psoriatic arthritis had higher anti-RBD antibody titers when methotrexate was stopped after both doses of the AstraZeneca vaccine, or simply after the second dose, than when methotrexate was continued, according to results from two single-center, randomized controlled trials called MIVAC I and II, Anu Sreekanth, MD, of Sree Sudheendra Medical Mission in Kochi, Kerala, India, and colleagues reported at EULAR 2022.

Results from MIVAC I indicated that there was a higher flare rate when methotrexate was stopped after both vaccine doses, but there was no difference in flare rate in MIVAC II when methotrexate was stopped only after the second dose as opposed to stopping it after both doses.

In the MIVAC I trial, 158 unvaccinated patients were randomized 1:1 to a cohort in which methotrexate was held for 2 weeks after both doses and a cohort in which methotrexate was continued despite the vaccine. In MIVAC II, 157 patients continued methotrexate while receiving the first vaccine dose. These patients were subsequently randomized either to continue or to stop methotrexate for 2 weeks following the second dose.

The findings from MIVAC I demonstrated the flare rate was lower in the methotrexate-continue group than in the methotrexate-pause group (8% vs. 25%; P = .005) and that the median anti-RBD titer was significantly higher for the methotrexate-pause group than the methotrexate-continue group (2,484 vs. 1,147; P = .001).

The results from MIVAC II trial indicated that there was no difference in flare rates between the two study groups (7.9% vs. 11.8%; P = .15). Yet, the median anti-RBD titer was significantly higher in the methotrexate-pause cohort than in the methotrexate-continue cohort (2,553 vs. 990; P = .001).

The report suggests there is a flare risk when methotrexate is stopped, Dr. Sreekanth noted. “It appears more logical to hold only after the second dose, as comparable anti-RBD titers are generated” with either approach, Dr. Sreekanth said.

Expert commentary: MIVAC I and II

Inés Colmegna, MD, associate professor at McGill University in Montreal, noted that it was intriguing that the risk of flares in MIVAC II is half of that reported after each of the doses of MIVAC I. “It is also worth emphasizing that despite the reported frequency of flares, the actual disease activity [as measured by the Disease Activity Score in 28 joints] in patients who did or did not withhold methotrexate was similar.

“MIVAC I and II have practical implications as they help to adequately inform patients about the risk and benefit trade of withholding methotrexate post–COVID-19 vaccination,” Dr. Colmegna told this news organization.

“Additional information would help to [further] interpret the findings of these studies, including whether any of the participants were taking any other DMARDs; data on the severity of the flares and functional impact; analysis of factors that predict the risk of flares, such as higher doses of methotrexate; [and change in] disease activity scores pre- and postvaccination,” Dr. Colmegna concluded.

Dr. Abhishek disclosed relationships with Springer, UpTodate, Oxford, Immunotec, AstraZeneca, Inflazome, NGM Biopharmaceuticals, Menarini Pharmaceuticals, and Cadila Pharmaceuticals. Dr. Abhishek is cochair of the ACR/EULAR CPPD Classification Criteria Working Group and the OMERACT CPPD Working Group. Dr. Sparks disclosed relationships with Gilead, Boehringer Ingelheim, Amgen, Bristol-Myers Squibb, and AbbVie, unrelated to this study. Dr. Tedeschi disclosed relationships with ModernaTx and NGM Biopharmaceuticals. Dr. Winthrop disclosed a research grant and serving as a scientific consultant for Pfizer. Dr. Sreekanth  and Dr. Colmegna have disclosed no relevant financial relationships.

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

Patients who take methotrexate for a variety of immune-mediated inflammatory diseases and pause taking the drug following receipt of a COVID-19 vaccine dose did not have a higher risk of disease flare and had higher antireceptor binding domain (anti-RBD) antibody titers and increased immunogenicity when compared with continuing the drug, three recent studies suggest.

In one study, British researchers examined the effects of a 2-week break in methotrexate therapy on anti-RBD titers following receipt of a third COVID-19 vaccine dose. In their paper published in The Lancet: Respiratory Medicine, they reported results from a randomized, open-label, superiority trial that suggested pausing the drug improved immunogenicity, compared with no break.

In two trials presented at the European Alliance of Associations for Rheumatology (EULAR) 2022 Congress, a team from India set out to determine whether holding methotrexate after receiving both doses of a COVID-19 vaccine, or holding it only after the second dose, was safe and effective. They found that pausing methotrexate only following the second dose contributed to a lower flare risk, and that patients had higher anti-RBD titers when holding methotrexate for 2 weeks following each dose.
 

Pausing methotrexate after booster

The 2-week methotrexate break and booster vaccine dose data in the Vaccine Response On Off Methotrexate (VROOM) trial showed that after a month, the geometric mean antispike 1 (S1)-RBD antibody titer was 10,798 U/mL (95% confidence interval [CI], 8,970-12,997) in the group that continued methotrexate and 22,750 U/mL (95% CI, 19,314-26,796) in the group that suspended methotrexate; the geometric mean ratio was 2.19 (P < .0001; mixed-effects model), reported Abhishek Abhishek, MD, PhD, professor of rheumatology at the University of Nottingham in Nottingham, England, and colleagues.

Prior research showed that stopping methotrexate therapy for 2 weeks following the seasonal influenza vaccine contributed to better vaccine immunity among patients with rheumatoid arthritis, but there was no impact of stopping the drug for up to 4 weeks before vaccination on vaccine-related immunity, the researchers noted.

It is crucial in maximizing long-lasting vaccine protection in people who are possibly susceptible through immune suppression at this point in the COVID-19 vaccination regimen, the study team noted.

“Evidence from this study will be useful for policymakers, national immunization advisory committees, and specialist societies formulating recommendations on the use of methotrexate around the time of COVID-19 vaccination. This evidence will help patients and clinicians make informed choices about the risks and benefits of interrupting methotrexate treatment around the time of COVID-19 vaccination, with implications for the potential to extend such approaches to other therapeutics,” they wrote.

In American College of Rheumatology (ACR) guidance for COVID-19 vaccination, the organization advised against using standard synthetic disease-modifying antirheumatic medicines such as methotrexate “for 1-2 weeks (as disease activity allows) after each COVID-19 vaccine dose,” given the at-risk population and public health concerns, Jeffrey A. Sparks, MD, MMSc, assistant professor of medicine and associate physician at Brigham and Women’s Hospital and Harvard Medical School, Boston, and Sara K. Tedeschi, MD, MPH, assistant professor of medicine at Harvard Medical School, noted in an accompanying editorial in The Lancet: Respiratory Medicine.

However, when the ACR developed this statement, there was only one trial involving patients with rheumatoid arthritis who paused methotrexate following seasonal influenza vaccination, the editorialists said.

Expert commentary

This current study is consistent with other studies over the last several months showing that methotrexate harms both humoral and cell-mediated COVID-19 responses, noted Kevin Winthrop, MD, MPH, professor of infectious disease and public health at Oregon Health & Science University, Portland, who was not involved in the study. “And so now the new wave of studies are like this one, where they are holding methotrexate experimentally and seeing if it makes a difference,” he said.

“The one shortcoming of this study – and so far, the studies to date – is that no one has looked at whether the experimental hold has resulted in a change in T-cell responses, which ... we are [now] recognizing [the importance of] more and more in long-term protection, particularly in severe disease. Theoretically, holding [methotrexate] might help enhance T-cell responses, but that hasn’t been shown experimentally.”

Dr. Winthrop pointed out that one might get the same benefit from holding methotrexate for 1 week instead of 2 and that there likely is a reduced risk of flare-up from underlying autoimmune disease.

It is still not certain that this benefit extends to other vaccines, Dr. Winthrop noted. “It is probably true for most vaccines that if you hold methotrexate for 1 or 2 weeks, you might see some short-term benefit in responsiveness, but you don’t know that there is any clinical meaningfulness of this. That’s going to take other long-term studies. You don’t know how long this benefit lasts.”
 

Pausing methotrexate during initial COVID vaccine doses

Patients with either rheumatoid arthritis or psoriatic arthritis had higher anti-RBD antibody titers when methotrexate was stopped after both doses of the AstraZeneca vaccine, or simply after the second dose, than when methotrexate was continued, according to results from two single-center, randomized controlled trials called MIVAC I and II, Anu Sreekanth, MD, of Sree Sudheendra Medical Mission in Kochi, Kerala, India, and colleagues reported at EULAR 2022.

Results from MIVAC I indicated that there was a higher flare rate when methotrexate was stopped after both vaccine doses, but there was no difference in flare rate in MIVAC II when methotrexate was stopped only after the second dose as opposed to stopping it after both doses.

In the MIVAC I trial, 158 unvaccinated patients were randomized 1:1 to a cohort in which methotrexate was held for 2 weeks after both doses and a cohort in which methotrexate was continued despite the vaccine. In MIVAC II, 157 patients continued methotrexate while receiving the first vaccine dose. These patients were subsequently randomized either to continue or to stop methotrexate for 2 weeks following the second dose.

The findings from MIVAC I demonstrated the flare rate was lower in the methotrexate-continue group than in the methotrexate-pause group (8% vs. 25%; P = .005) and that the median anti-RBD titer was significantly higher for the methotrexate-pause group than the methotrexate-continue group (2,484 vs. 1,147; P = .001).

The results from MIVAC II trial indicated that there was no difference in flare rates between the two study groups (7.9% vs. 11.8%; P = .15). Yet, the median anti-RBD titer was significantly higher in the methotrexate-pause cohort than in the methotrexate-continue cohort (2,553 vs. 990; P = .001).

The report suggests there is a flare risk when methotrexate is stopped, Dr. Sreekanth noted. “It appears more logical to hold only after the second dose, as comparable anti-RBD titers are generated” with either approach, Dr. Sreekanth said.

Expert commentary: MIVAC I and II

Inés Colmegna, MD, associate professor at McGill University in Montreal, noted that it was intriguing that the risk of flares in MIVAC II is half of that reported after each of the doses of MIVAC I. “It is also worth emphasizing that despite the reported frequency of flares, the actual disease activity [as measured by the Disease Activity Score in 28 joints] in patients who did or did not withhold methotrexate was similar.

“MIVAC I and II have practical implications as they help to adequately inform patients about the risk and benefit trade of withholding methotrexate post–COVID-19 vaccination,” Dr. Colmegna told this news organization.

“Additional information would help to [further] interpret the findings of these studies, including whether any of the participants were taking any other DMARDs; data on the severity of the flares and functional impact; analysis of factors that predict the risk of flares, such as higher doses of methotrexate; [and change in] disease activity scores pre- and postvaccination,” Dr. Colmegna concluded.

Dr. Abhishek disclosed relationships with Springer, UpTodate, Oxford, Immunotec, AstraZeneca, Inflazome, NGM Biopharmaceuticals, Menarini Pharmaceuticals, and Cadila Pharmaceuticals. Dr. Abhishek is cochair of the ACR/EULAR CPPD Classification Criteria Working Group and the OMERACT CPPD Working Group. Dr. Sparks disclosed relationships with Gilead, Boehringer Ingelheim, Amgen, Bristol-Myers Squibb, and AbbVie, unrelated to this study. Dr. Tedeschi disclosed relationships with ModernaTx and NGM Biopharmaceuticals. Dr. Winthrop disclosed a research grant and serving as a scientific consultant for Pfizer. Dr. Sreekanth  and Dr. Colmegna have disclosed no relevant financial relationships.

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

Patients who take methotrexate for a variety of immune-mediated inflammatory diseases and pause taking the drug following receipt of a COVID-19 vaccine dose did not have a higher risk of disease flare and had higher antireceptor binding domain (anti-RBD) antibody titers and increased immunogenicity when compared with continuing the drug, three recent studies suggest.

In one study, British researchers examined the effects of a 2-week break in methotrexate therapy on anti-RBD titers following receipt of a third COVID-19 vaccine dose. In their paper published in The Lancet: Respiratory Medicine, they reported results from a randomized, open-label, superiority trial that suggested pausing the drug improved immunogenicity, compared with no break.

In two trials presented at the European Alliance of Associations for Rheumatology (EULAR) 2022 Congress, a team from India set out to determine whether holding methotrexate after receiving both doses of a COVID-19 vaccine, or holding it only after the second dose, was safe and effective. They found that pausing methotrexate only following the second dose contributed to a lower flare risk, and that patients had higher anti-RBD titers when holding methotrexate for 2 weeks following each dose.
 

Pausing methotrexate after booster

The 2-week methotrexate break and booster vaccine dose data in the Vaccine Response On Off Methotrexate (VROOM) trial showed that after a month, the geometric mean antispike 1 (S1)-RBD antibody titer was 10,798 U/mL (95% confidence interval [CI], 8,970-12,997) in the group that continued methotrexate and 22,750 U/mL (95% CI, 19,314-26,796) in the group that suspended methotrexate; the geometric mean ratio was 2.19 (P < .0001; mixed-effects model), reported Abhishek Abhishek, MD, PhD, professor of rheumatology at the University of Nottingham in Nottingham, England, and colleagues.

Prior research showed that stopping methotrexate therapy for 2 weeks following the seasonal influenza vaccine contributed to better vaccine immunity among patients with rheumatoid arthritis, but there was no impact of stopping the drug for up to 4 weeks before vaccination on vaccine-related immunity, the researchers noted.

It is crucial in maximizing long-lasting vaccine protection in people who are possibly susceptible through immune suppression at this point in the COVID-19 vaccination regimen, the study team noted.

“Evidence from this study will be useful for policymakers, national immunization advisory committees, and specialist societies formulating recommendations on the use of methotrexate around the time of COVID-19 vaccination. This evidence will help patients and clinicians make informed choices about the risks and benefits of interrupting methotrexate treatment around the time of COVID-19 vaccination, with implications for the potential to extend such approaches to other therapeutics,” they wrote.

In American College of Rheumatology (ACR) guidance for COVID-19 vaccination, the organization advised against using standard synthetic disease-modifying antirheumatic medicines such as methotrexate “for 1-2 weeks (as disease activity allows) after each COVID-19 vaccine dose,” given the at-risk population and public health concerns, Jeffrey A. Sparks, MD, MMSc, assistant professor of medicine and associate physician at Brigham and Women’s Hospital and Harvard Medical School, Boston, and Sara K. Tedeschi, MD, MPH, assistant professor of medicine at Harvard Medical School, noted in an accompanying editorial in The Lancet: Respiratory Medicine.

However, when the ACR developed this statement, there was only one trial involving patients with rheumatoid arthritis who paused methotrexate following seasonal influenza vaccination, the editorialists said.

Expert commentary

This current study is consistent with other studies over the last several months showing that methotrexate harms both humoral and cell-mediated COVID-19 responses, noted Kevin Winthrop, MD, MPH, professor of infectious disease and public health at Oregon Health & Science University, Portland, who was not involved in the study. “And so now the new wave of studies are like this one, where they are holding methotrexate experimentally and seeing if it makes a difference,” he said.

“The one shortcoming of this study – and so far, the studies to date – is that no one has looked at whether the experimental hold has resulted in a change in T-cell responses, which ... we are [now] recognizing [the importance of] more and more in long-term protection, particularly in severe disease. Theoretically, holding [methotrexate] might help enhance T-cell responses, but that hasn’t been shown experimentally.”

Dr. Winthrop pointed out that one might get the same benefit from holding methotrexate for 1 week instead of 2 and that there likely is a reduced risk of flare-up from underlying autoimmune disease.

It is still not certain that this benefit extends to other vaccines, Dr. Winthrop noted. “It is probably true for most vaccines that if you hold methotrexate for 1 or 2 weeks, you might see some short-term benefit in responsiveness, but you don’t know that there is any clinical meaningfulness of this. That’s going to take other long-term studies. You don’t know how long this benefit lasts.”
 

Pausing methotrexate during initial COVID vaccine doses

Patients with either rheumatoid arthritis or psoriatic arthritis had higher anti-RBD antibody titers when methotrexate was stopped after both doses of the AstraZeneca vaccine, or simply after the second dose, than when methotrexate was continued, according to results from two single-center, randomized controlled trials called MIVAC I and II, Anu Sreekanth, MD, of Sree Sudheendra Medical Mission in Kochi, Kerala, India, and colleagues reported at EULAR 2022.

Results from MIVAC I indicated that there was a higher flare rate when methotrexate was stopped after both vaccine doses, but there was no difference in flare rate in MIVAC II when methotrexate was stopped only after the second dose as opposed to stopping it after both doses.

In the MIVAC I trial, 158 unvaccinated patients were randomized 1:1 to a cohort in which methotrexate was held for 2 weeks after both doses and a cohort in which methotrexate was continued despite the vaccine. In MIVAC II, 157 patients continued methotrexate while receiving the first vaccine dose. These patients were subsequently randomized either to continue or to stop methotrexate for 2 weeks following the second dose.

The findings from MIVAC I demonstrated the flare rate was lower in the methotrexate-continue group than in the methotrexate-pause group (8% vs. 25%; P = .005) and that the median anti-RBD titer was significantly higher for the methotrexate-pause group than the methotrexate-continue group (2,484 vs. 1,147; P = .001).

The results from MIVAC II trial indicated that there was no difference in flare rates between the two study groups (7.9% vs. 11.8%; P = .15). Yet, the median anti-RBD titer was significantly higher in the methotrexate-pause cohort than in the methotrexate-continue cohort (2,553 vs. 990; P = .001).

The report suggests there is a flare risk when methotrexate is stopped, Dr. Sreekanth noted. “It appears more logical to hold only after the second dose, as comparable anti-RBD titers are generated” with either approach, Dr. Sreekanth said.

Expert commentary: MIVAC I and II

Inés Colmegna, MD, associate professor at McGill University in Montreal, noted that it was intriguing that the risk of flares in MIVAC II is half of that reported after each of the doses of MIVAC I. “It is also worth emphasizing that despite the reported frequency of flares, the actual disease activity [as measured by the Disease Activity Score in 28 joints] in patients who did or did not withhold methotrexate was similar.

“MIVAC I and II have practical implications as they help to adequately inform patients about the risk and benefit trade of withholding methotrexate post–COVID-19 vaccination,” Dr. Colmegna told this news organization.

“Additional information would help to [further] interpret the findings of these studies, including whether any of the participants were taking any other DMARDs; data on the severity of the flares and functional impact; analysis of factors that predict the risk of flares, such as higher doses of methotrexate; [and change in] disease activity scores pre- and postvaccination,” Dr. Colmegna concluded.

Dr. Abhishek disclosed relationships with Springer, UpTodate, Oxford, Immunotec, AstraZeneca, Inflazome, NGM Biopharmaceuticals, Menarini Pharmaceuticals, and Cadila Pharmaceuticals. Dr. Abhishek is cochair of the ACR/EULAR CPPD Classification Criteria Working Group and the OMERACT CPPD Working Group. Dr. Sparks disclosed relationships with Gilead, Boehringer Ingelheim, Amgen, Bristol-Myers Squibb, and AbbVie, unrelated to this study. Dr. Tedeschi disclosed relationships with ModernaTx and NGM Biopharmaceuticals. Dr. Winthrop disclosed a research grant and serving as a scientific consultant for Pfizer. Dr. Sreekanth  and Dr. Colmegna have disclosed no relevant financial relationships.

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

Walking 10,000 steps per day may reduce the risk of death for those who have trouble regulating their blood sugar, according to the findings from a study of almost 1,700 American adults with prediabetes or diabetes.

Researchers from the University of Seville, Spain, evaluated U.S. adults with prediabetes and diabetes using data from the Centers for Disease Control and Prevention’s National Health and Nutrition Examination Survey, collected between 2005 and 2006.

The findings were published this month in Diabetes Care.

Ariel Skelley/Getty Images

Of the total, 1,194 adults had prediabetes, and 493 had diabetes. People with diabetes in the study were diagnosed by a doctor or had a fasting blood glucose level higher than 126 mg/dL. People with prediabetes in the study were also diagnosed by a doctor or had a fasting glucose level from 100 to 125 mg/dL.

Over half (56%) of prediabetic adults were male (average age 55 years), and they took an average of 8,500 steps per day. Half (51%) of the diabetic adults were also male (average age 61 years), and they took fewer steps per day – about 6,300.

The people in the study wore an accelerometer on their waist to count their steps for 7 consecutive days. The researchers adjusted for age, sex, ethnicity, smoking, alcohol use, diet, and use of diabetes medications.

Over 9 years, 200 people with prediabetes and 138 with diabetes died. Based on those who survived after follow-up, walking nearly 10,000 steps per day was best for reducing the risk of death from any cause for people with prediabetes and diabetes.

But about 20% of people in the study were removed from the analysis because they had invalid accelerometry data. Adults who are healthy enough to walk 10,000 steps may have different rates of death from those who aren’t, according to the study authors, who called for more research to compare these two groups.

If 10,000 steps seem like a daunting task, talking to a doctor about finding a routine that works for your physical ability could be helpful, the study authors suggest.

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

Walking 10,000 steps per day may reduce the risk of death for those who have trouble regulating their blood sugar, according to the findings from a study of almost 1,700 American adults with prediabetes or diabetes.

Researchers from the University of Seville, Spain, evaluated U.S. adults with prediabetes and diabetes using data from the Centers for Disease Control and Prevention’s National Health and Nutrition Examination Survey, collected between 2005 and 2006.

The findings were published this month in Diabetes Care.

Ariel Skelley/Getty Images

Of the total, 1,194 adults had prediabetes, and 493 had diabetes. People with diabetes in the study were diagnosed by a doctor or had a fasting blood glucose level higher than 126 mg/dL. People with prediabetes in the study were also diagnosed by a doctor or had a fasting glucose level from 100 to 125 mg/dL.

Over half (56%) of prediabetic adults were male (average age 55 years), and they took an average of 8,500 steps per day. Half (51%) of the diabetic adults were also male (average age 61 years), and they took fewer steps per day – about 6,300.

The people in the study wore an accelerometer on their waist to count their steps for 7 consecutive days. The researchers adjusted for age, sex, ethnicity, smoking, alcohol use, diet, and use of diabetes medications.

Over 9 years, 200 people with prediabetes and 138 with diabetes died. Based on those who survived after follow-up, walking nearly 10,000 steps per day was best for reducing the risk of death from any cause for people with prediabetes and diabetes.

But about 20% of people in the study were removed from the analysis because they had invalid accelerometry data. Adults who are healthy enough to walk 10,000 steps may have different rates of death from those who aren’t, according to the study authors, who called for more research to compare these two groups.

If 10,000 steps seem like a daunting task, talking to a doctor about finding a routine that works for your physical ability could be helpful, the study authors suggest.

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

Walking 10,000 steps per day may reduce the risk of death for those who have trouble regulating their blood sugar, according to the findings from a study of almost 1,700 American adults with prediabetes or diabetes.

Researchers from the University of Seville, Spain, evaluated U.S. adults with prediabetes and diabetes using data from the Centers for Disease Control and Prevention’s National Health and Nutrition Examination Survey, collected between 2005 and 2006.

The findings were published this month in Diabetes Care.

Ariel Skelley/Getty Images

Of the total, 1,194 adults had prediabetes, and 493 had diabetes. People with diabetes in the study were diagnosed by a doctor or had a fasting blood glucose level higher than 126 mg/dL. People with prediabetes in the study were also diagnosed by a doctor or had a fasting glucose level from 100 to 125 mg/dL.

Over half (56%) of prediabetic adults were male (average age 55 years), and they took an average of 8,500 steps per day. Half (51%) of the diabetic adults were also male (average age 61 years), and they took fewer steps per day – about 6,300.

The people in the study wore an accelerometer on their waist to count their steps for 7 consecutive days. The researchers adjusted for age, sex, ethnicity, smoking, alcohol use, diet, and use of diabetes medications.

Over 9 years, 200 people with prediabetes and 138 with diabetes died. Based on those who survived after follow-up, walking nearly 10,000 steps per day was best for reducing the risk of death from any cause for people with prediabetes and diabetes.

But about 20% of people in the study were removed from the analysis because they had invalid accelerometry data. Adults who are healthy enough to walk 10,000 steps may have different rates of death from those who aren’t, according to the study authors, who called for more research to compare these two groups.

If 10,000 steps seem like a daunting task, talking to a doctor about finding a routine that works for your physical ability could be helpful, the study authors suggest.

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

The addition of social determinants of health (SDOH) to machine-learning risk-prediction models improved forecasts of in-hospital mortality in Black adults hospitalized for heart failure (HF) but didn’t show similar ability in non-Black patients, in a study based in part on the American Heart Association–sponsored Get with the Guidelines in Heart Failure (GWTG-HF) registry.

The novel risk-prediction tool bolstered by SDOH at the zip-code level – including household income, number of adults without a high-school degree, poverty and unemployment rates, and other factors – stratified risk more sharply in Black patients than more standard models, including some based on multivariable logistic regression.

“Traditional risk models that exist for heart failure assign lower risks to Black individuals if everything else is held constant,” Ambarish Pandey, MD, MSCS, University of Texas Southwestern Medical Center, Dallas, told this news organization.

“I think that is problematic, because if Black patients are considered lower risk, they may not get appropriate risk-based therapies that are being provided. We wanted to move away from this approach and use a more race-agnostic approach,” said Dr. Pandey, who is senior author on the study published  in JAMA Cardiology, with lead author Matthew W. Segar, MD, Texas Heart Institute, Houston.

The training dataset for the prediction model consisted of 123,634 patients hospitalized with HF (mean age, 71 years), of whom 47% were women, enrolled in the GWTG-HF registry from 2010 through 2020.

The machine-learning models showed “excellent performance” when applied to an internal subset cohort of 82,420 patients, with a C statistic of 0.81 for Black patients and 0.82 for non-Black patients, the authors report, and in a real-world cohort of 553,506 patients, with C statistics of 0.74 and 0.75, respectively. The models performed similarly well, they write, in an external validation cohort derived from the ARIC registry, with C statistics of 0.79 and 0.80, respectively.

The machine-learning models’ performance surpassed that of the GWTG-HF risk-score model, C statistics 0.69 for both Black and non-Black patients, and other logistic regression models in which race was a covariate, the authors state.

“We also observed significant race-specific differences in the population-attributable risk of in-hospital mortality associated with the SDOH, with a significantly greater contribution of these parameters to the overall in-hospital mortality risk in Black patients versus non-Black patients,” they write.

For Black patients, five of the SDOH parameters were among the top 20 covariate predictors of in-hospital mortality: mean income level, vacancy and unemployment rates, proportion of the population without a high school degree, and proportion older than 65 years. Together they accounted for 11.6% of population-attributable risk for in-hospital death.

Only one SDOH parameter – percentage of population older than 65 years – made the top 20 for non-Black patients, with a population-attributable risk of 0.5%, the group reports.

“I hope our work spurs future investigations to better understand how social determinants contribute to risk and how they can be incorporated in management of these patients,” Dr. Pandey said.

“I commend the authors for attempting to address SDOH as a potential contributor to some of the differences in outcomes among patients with heart failure,” writes Eldrin F. Lewis, MD, MPH, Stanford University School of Medicine, Palo Alto, Calif., in an accompanying editorial.

“It is imperative that we use these newer techniques to go beyond simply predicting which groups are at heightened risk and leverage the data to create solutions that will reduce those risks for the individual patient,” Dr. Lewis states.

“We should use these tools to reduce racial and ethnic differences in the operations of health care systems, potential bias in management decisions, and inactivity due to the difficulty in getting guideline-directed medical therapy into the hands of people who may have limited resources with minimal out-of-pocket costs,” he writes.

The models assessed in the current report “set a new bar for risk prediction: Integration of a comprehensive set of demographics, comorbidities, and social determinants with machine learning obviates race and ethnicity in risk prediction,” contend JAMA Cardiology deputy editor Clyde W. Yancy, MD, and associate editor Sadiya S. Khan, MD, both from Northwestern University Feinberg School of Medicine, Chicago, in an accompanying editor’s note.

“This more careful incorporation of individual-level, neighborhood-level, and hospital-level social factors,” they conclude, “is now a candidate template for future risk models.”

Dr. Pandey discloses grant funding from Applied Therapeutics and Gilead Sciences; consulting for or serving as an advisor to Tricog Health, Eli Lilly, Rivus, and Roche Diagnostics; receiving nonfinancial support from Pfizer and Merck; and research support from the Texas Health Resources Clinical Scholarship, the Gilead Sciences Research Scholar Program, the National Institute on Aging GEMSSTAR Grant, and Applied Therapeutics. Dr. Segar discloses receiving nonfinancial support from Pfizer and Merck. Other disclosures are in the report. Dr. Lewis reported no disclosures. Dr. Yancy and Dr. Khan had no relevant disclosures.

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

The addition of social determinants of health (SDOH) to machine-learning risk-prediction models improved forecasts of in-hospital mortality in Black adults hospitalized for heart failure (HF) but didn’t show similar ability in non-Black patients, in a study based in part on the American Heart Association–sponsored Get with the Guidelines in Heart Failure (GWTG-HF) registry.

The novel risk-prediction tool bolstered by SDOH at the zip-code level – including household income, number of adults without a high-school degree, poverty and unemployment rates, and other factors – stratified risk more sharply in Black patients than more standard models, including some based on multivariable logistic regression.

“Traditional risk models that exist for heart failure assign lower risks to Black individuals if everything else is held constant,” Ambarish Pandey, MD, MSCS, University of Texas Southwestern Medical Center, Dallas, told this news organization.

“I think that is problematic, because if Black patients are considered lower risk, they may not get appropriate risk-based therapies that are being provided. We wanted to move away from this approach and use a more race-agnostic approach,” said Dr. Pandey, who is senior author on the study published  in JAMA Cardiology, with lead author Matthew W. Segar, MD, Texas Heart Institute, Houston.

The training dataset for the prediction model consisted of 123,634 patients hospitalized with HF (mean age, 71 years), of whom 47% were women, enrolled in the GWTG-HF registry from 2010 through 2020.

The machine-learning models showed “excellent performance” when applied to an internal subset cohort of 82,420 patients, with a C statistic of 0.81 for Black patients and 0.82 for non-Black patients, the authors report, and in a real-world cohort of 553,506 patients, with C statistics of 0.74 and 0.75, respectively. The models performed similarly well, they write, in an external validation cohort derived from the ARIC registry, with C statistics of 0.79 and 0.80, respectively.

The machine-learning models’ performance surpassed that of the GWTG-HF risk-score model, C statistics 0.69 for both Black and non-Black patients, and other logistic regression models in which race was a covariate, the authors state.

“We also observed significant race-specific differences in the population-attributable risk of in-hospital mortality associated with the SDOH, with a significantly greater contribution of these parameters to the overall in-hospital mortality risk in Black patients versus non-Black patients,” they write.

For Black patients, five of the SDOH parameters were among the top 20 covariate predictors of in-hospital mortality: mean income level, vacancy and unemployment rates, proportion of the population without a high school degree, and proportion older than 65 years. Together they accounted for 11.6% of population-attributable risk for in-hospital death.

Only one SDOH parameter – percentage of population older than 65 years – made the top 20 for non-Black patients, with a population-attributable risk of 0.5%, the group reports.

“I hope our work spurs future investigations to better understand how social determinants contribute to risk and how they can be incorporated in management of these patients,” Dr. Pandey said.

“I commend the authors for attempting to address SDOH as a potential contributor to some of the differences in outcomes among patients with heart failure,” writes Eldrin F. Lewis, MD, MPH, Stanford University School of Medicine, Palo Alto, Calif., in an accompanying editorial.

“It is imperative that we use these newer techniques to go beyond simply predicting which groups are at heightened risk and leverage the data to create solutions that will reduce those risks for the individual patient,” Dr. Lewis states.

“We should use these tools to reduce racial and ethnic differences in the operations of health care systems, potential bias in management decisions, and inactivity due to the difficulty in getting guideline-directed medical therapy into the hands of people who may have limited resources with minimal out-of-pocket costs,” he writes.

The models assessed in the current report “set a new bar for risk prediction: Integration of a comprehensive set of demographics, comorbidities, and social determinants with machine learning obviates race and ethnicity in risk prediction,” contend JAMA Cardiology deputy editor Clyde W. Yancy, MD, and associate editor Sadiya S. Khan, MD, both from Northwestern University Feinberg School of Medicine, Chicago, in an accompanying editor’s note.

“This more careful incorporation of individual-level, neighborhood-level, and hospital-level social factors,” they conclude, “is now a candidate template for future risk models.”

Dr. Pandey discloses grant funding from Applied Therapeutics and Gilead Sciences; consulting for or serving as an advisor to Tricog Health, Eli Lilly, Rivus, and Roche Diagnostics; receiving nonfinancial support from Pfizer and Merck; and research support from the Texas Health Resources Clinical Scholarship, the Gilead Sciences Research Scholar Program, the National Institute on Aging GEMSSTAR Grant, and Applied Therapeutics. Dr. Segar discloses receiving nonfinancial support from Pfizer and Merck. Other disclosures are in the report. Dr. Lewis reported no disclosures. Dr. Yancy and Dr. Khan had no relevant disclosures.

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

The addition of social determinants of health (SDOH) to machine-learning risk-prediction models improved forecasts of in-hospital mortality in Black adults hospitalized for heart failure (HF) but didn’t show similar ability in non-Black patients, in a study based in part on the American Heart Association–sponsored Get with the Guidelines in Heart Failure (GWTG-HF) registry.

The novel risk-prediction tool bolstered by SDOH at the zip-code level – including household income, number of adults without a high-school degree, poverty and unemployment rates, and other factors – stratified risk more sharply in Black patients than more standard models, including some based on multivariable logistic regression.

“Traditional risk models that exist for heart failure assign lower risks to Black individuals if everything else is held constant,” Ambarish Pandey, MD, MSCS, University of Texas Southwestern Medical Center, Dallas, told this news organization.

“I think that is problematic, because if Black patients are considered lower risk, they may not get appropriate risk-based therapies that are being provided. We wanted to move away from this approach and use a more race-agnostic approach,” said Dr. Pandey, who is senior author on the study published  in JAMA Cardiology, with lead author Matthew W. Segar, MD, Texas Heart Institute, Houston.

The training dataset for the prediction model consisted of 123,634 patients hospitalized with HF (mean age, 71 years), of whom 47% were women, enrolled in the GWTG-HF registry from 2010 through 2020.

The machine-learning models showed “excellent performance” when applied to an internal subset cohort of 82,420 patients, with a C statistic of 0.81 for Black patients and 0.82 for non-Black patients, the authors report, and in a real-world cohort of 553,506 patients, with C statistics of 0.74 and 0.75, respectively. The models performed similarly well, they write, in an external validation cohort derived from the ARIC registry, with C statistics of 0.79 and 0.80, respectively.

The machine-learning models’ performance surpassed that of the GWTG-HF risk-score model, C statistics 0.69 for both Black and non-Black patients, and other logistic regression models in which race was a covariate, the authors state.

“We also observed significant race-specific differences in the population-attributable risk of in-hospital mortality associated with the SDOH, with a significantly greater contribution of these parameters to the overall in-hospital mortality risk in Black patients versus non-Black patients,” they write.

For Black patients, five of the SDOH parameters were among the top 20 covariate predictors of in-hospital mortality: mean income level, vacancy and unemployment rates, proportion of the population without a high school degree, and proportion older than 65 years. Together they accounted for 11.6% of population-attributable risk for in-hospital death.

Only one SDOH parameter – percentage of population older than 65 years – made the top 20 for non-Black patients, with a population-attributable risk of 0.5%, the group reports.

“I hope our work spurs future investigations to better understand how social determinants contribute to risk and how they can be incorporated in management of these patients,” Dr. Pandey said.

“I commend the authors for attempting to address SDOH as a potential contributor to some of the differences in outcomes among patients with heart failure,” writes Eldrin F. Lewis, MD, MPH, Stanford University School of Medicine, Palo Alto, Calif., in an accompanying editorial.

“It is imperative that we use these newer techniques to go beyond simply predicting which groups are at heightened risk and leverage the data to create solutions that will reduce those risks for the individual patient,” Dr. Lewis states.

“We should use these tools to reduce racial and ethnic differences in the operations of health care systems, potential bias in management decisions, and inactivity due to the difficulty in getting guideline-directed medical therapy into the hands of people who may have limited resources with minimal out-of-pocket costs,” he writes.

The models assessed in the current report “set a new bar for risk prediction: Integration of a comprehensive set of demographics, comorbidities, and social determinants with machine learning obviates race and ethnicity in risk prediction,” contend JAMA Cardiology deputy editor Clyde W. Yancy, MD, and associate editor Sadiya S. Khan, MD, both from Northwestern University Feinberg School of Medicine, Chicago, in an accompanying editor’s note.

“This more careful incorporation of individual-level, neighborhood-level, and hospital-level social factors,” they conclude, “is now a candidate template for future risk models.”

Dr. Pandey discloses grant funding from Applied Therapeutics and Gilead Sciences; consulting for or serving as an advisor to Tricog Health, Eli Lilly, Rivus, and Roche Diagnostics; receiving nonfinancial support from Pfizer and Merck; and research support from the Texas Health Resources Clinical Scholarship, the Gilead Sciences Research Scholar Program, the National Institute on Aging GEMSSTAR Grant, and Applied Therapeutics. Dr. Segar discloses receiving nonfinancial support from Pfizer and Merck. Other disclosures are in the report. Dr. Lewis reported no disclosures. Dr. Yancy and Dr. Khan had no relevant disclosures.

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

Iron accumulation in the brain as a result of alcohol consumption may explain why even moderate drinking is linked to compromised cognitive function.

Results of a large observational study suggest brain iron accumulation is a “plausible pathway” through which alcohol negatively affects cognition, study Anya Topiwala, MD, PhD, senior clinical researcher, Nuffield Department of Population Health, University of Oxford, England, said in an interview.

Study participants who drank 56 grams of alcohol a week had higher brain iron levels. The U.K. guideline for “low risk” alcohol consumption is less than 14 units weekly, or 112 grams.

“We are finding harmful associations with iron within those low-risk alcohol intake guidelines,” said Dr. Topiwala.

The study was published online  in PLOS Medicine.
 

Early intervention opportunity?

Previous research suggests higher brain iron may be involved in the pathophysiology of Alzheimer’s and Parkinson’s diseases. However, it’s unclear whether deposition plays a role in alcohol’s effect on the brain and if it does, whether this could present an opportunity for early intervention with, for example, chelating agents.

The study included 20,729 participants in the UK Biobank study, which recruited volunteers from 2006 to 2010. Participants had a mean age of 54.8 years, and 48.6% were female.

Participants self-identified as current, never, or previous alcohol consumers. For current drinkers, researchers calculated the total weekly number of U.K. units of alcohol consumed. One unit is 8 grams. A standard drink in the United States is 14 grams. They categorized weekly consumption into quintiles and used the lowest quintile as the reference category.

Participants underwent MRI to determine brain iron levels. Areas of interest were deep brain structures in the basal ganglia.

Mean weekly alcohol consumption was 17.7 units, which is higher than U.K. guidelines for low-risk consumption. “Half of the sample were drinking above what is recommended,” said Dr. Topiwala.

Alcohol consumption was associated with markers of higher iron in the bilateral putamen (beta, 0.08 standard deviation; 95% confidence interval, 0.06-0.09; P < .001), caudate (beta, 0.05; 95% CI, 0.04-0.07; P < .001), and substantia nigra (beta, 0.03; 95% CI; 0.02-0.05; P < .001).
 

Poorer performance

Drinking more than 7 units (56 grams) weekly was associated with higher susceptibility for all brain regions, except the thalamus.

Controlling for menopause status did not alter associations between alcohol and susceptibility for any brain region. This was also the case when excluding blood pressure and cholesterol as covariates.

There were significant interactions with age in the bilateral putamen and caudate but not with sex, smoking, or Townsend Deprivation Index, which includes such factors as unemployment and living conditions.

To gather data on liver iron levels, participants underwent abdominal imaging at the same time as brain imaging. Dr. Topiwala explained that the liver is a primary storage center for iron, so it was used as “a kind of surrogate marker” of iron in the body.

The researchers showed an indirect effect of alcohol through systemic iron. A 1 SD increase in weekly alcohol consumption was associated with a 0.05 mg/g (95% CI, 0.02-0.07; P < .001) increase in liver iron. In addition, a 1 mg/g increase in liver iron was associated with a 0.44 (95% CI, 0.35-0.52; P < .001) SD increase in left putamen susceptibility.

In this sample, 32% (95% CI, 22-49; P < .001) of alcohol’s total effect on left putamen susceptibility was mediated via higher systemic iron levels.

To minimize the impact of other factors influencing the association between alcohol consumption and brain iron – and the possibility that people with more brain iron drink more – researchers used Mendelian randomization that considers genetically predicted alcohol intake. This analysis supported findings of associations between alcohol consumption and brain iron.

Participants completed a cognitive battery, which included trail-making tests that reflect executive function, puzzle tests that assess fluid intelligence or logic and reasoning, and task-based tests using the “Snap” card game to measure reaction time.

Investigators found the more iron that was present in certain brain regions, the poorer participants’ cognitive performance.

Patients should know about the risks of moderate alcohol intake so they can make decisions about drinking, said Dr. Topiwala. “They should be aware that 14 units of alcohol per week is not a zero risk.”
 

Novel research

Commenting for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations, Alzheimer’s Association, noted the study’s large size as a strength of the research.

She noted previous research has shown an association between higher iron levels and alcohol dependence and worse cognitive function, but the potential connection of brain iron levels, moderate alcohol consumption, and cognition has not been studied to date.

“This paper aims to look at whether there is a potential biological link between moderate alcohol consumption and cognition through iron-related pathways.”

The authors suggest more work is needed to understand whether alcohol consumption impacts iron-related biologies to affect downstream cognition, said Dr. Snyder. “Although this study does not answer that question, it does highlight some important questions.”

Study authors received funding from Wellcome Trust, UK Medical Research Council, National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, BHF Centre of Research Excellence, British Heart Foundation, NIHR Cambridge Biomedical Research Centre, U.S. Department of Veterans Affairs, China Scholarship Council, and Li Ka Shing Centre for Health Information and Discovery. Dr. Topiwala has disclosed no relevant financial relationships.

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

Iron accumulation in the brain as a result of alcohol consumption may explain why even moderate drinking is linked to compromised cognitive function.

Results of a large observational study suggest brain iron accumulation is a “plausible pathway” through which alcohol negatively affects cognition, study Anya Topiwala, MD, PhD, senior clinical researcher, Nuffield Department of Population Health, University of Oxford, England, said in an interview.

Study participants who drank 56 grams of alcohol a week had higher brain iron levels. The U.K. guideline for “low risk” alcohol consumption is less than 14 units weekly, or 112 grams.

“We are finding harmful associations with iron within those low-risk alcohol intake guidelines,” said Dr. Topiwala.

The study was published online  in PLOS Medicine.
 

Early intervention opportunity?

Previous research suggests higher brain iron may be involved in the pathophysiology of Alzheimer’s and Parkinson’s diseases. However, it’s unclear whether deposition plays a role in alcohol’s effect on the brain and if it does, whether this could present an opportunity for early intervention with, for example, chelating agents.

The study included 20,729 participants in the UK Biobank study, which recruited volunteers from 2006 to 2010. Participants had a mean age of 54.8 years, and 48.6% were female.

Participants self-identified as current, never, or previous alcohol consumers. For current drinkers, researchers calculated the total weekly number of U.K. units of alcohol consumed. One unit is 8 grams. A standard drink in the United States is 14 grams. They categorized weekly consumption into quintiles and used the lowest quintile as the reference category.

Participants underwent MRI to determine brain iron levels. Areas of interest were deep brain structures in the basal ganglia.

Mean weekly alcohol consumption was 17.7 units, which is higher than U.K. guidelines for low-risk consumption. “Half of the sample were drinking above what is recommended,” said Dr. Topiwala.

Alcohol consumption was associated with markers of higher iron in the bilateral putamen (beta, 0.08 standard deviation; 95% confidence interval, 0.06-0.09; P < .001), caudate (beta, 0.05; 95% CI, 0.04-0.07; P < .001), and substantia nigra (beta, 0.03; 95% CI; 0.02-0.05; P < .001).
 

Poorer performance

Drinking more than 7 units (56 grams) weekly was associated with higher susceptibility for all brain regions, except the thalamus.

Controlling for menopause status did not alter associations between alcohol and susceptibility for any brain region. This was also the case when excluding blood pressure and cholesterol as covariates.

There were significant interactions with age in the bilateral putamen and caudate but not with sex, smoking, or Townsend Deprivation Index, which includes such factors as unemployment and living conditions.

To gather data on liver iron levels, participants underwent abdominal imaging at the same time as brain imaging. Dr. Topiwala explained that the liver is a primary storage center for iron, so it was used as “a kind of surrogate marker” of iron in the body.

The researchers showed an indirect effect of alcohol through systemic iron. A 1 SD increase in weekly alcohol consumption was associated with a 0.05 mg/g (95% CI, 0.02-0.07; P < .001) increase in liver iron. In addition, a 1 mg/g increase in liver iron was associated with a 0.44 (95% CI, 0.35-0.52; P < .001) SD increase in left putamen susceptibility.

In this sample, 32% (95% CI, 22-49; P < .001) of alcohol’s total effect on left putamen susceptibility was mediated via higher systemic iron levels.

To minimize the impact of other factors influencing the association between alcohol consumption and brain iron – and the possibility that people with more brain iron drink more – researchers used Mendelian randomization that considers genetically predicted alcohol intake. This analysis supported findings of associations between alcohol consumption and brain iron.

Participants completed a cognitive battery, which included trail-making tests that reflect executive function, puzzle tests that assess fluid intelligence or logic and reasoning, and task-based tests using the “Snap” card game to measure reaction time.

Investigators found the more iron that was present in certain brain regions, the poorer participants’ cognitive performance.

Patients should know about the risks of moderate alcohol intake so they can make decisions about drinking, said Dr. Topiwala. “They should be aware that 14 units of alcohol per week is not a zero risk.”
 

Novel research

Commenting for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations, Alzheimer’s Association, noted the study’s large size as a strength of the research.

She noted previous research has shown an association between higher iron levels and alcohol dependence and worse cognitive function, but the potential connection of brain iron levels, moderate alcohol consumption, and cognition has not been studied to date.

“This paper aims to look at whether there is a potential biological link between moderate alcohol consumption and cognition through iron-related pathways.”

The authors suggest more work is needed to understand whether alcohol consumption impacts iron-related biologies to affect downstream cognition, said Dr. Snyder. “Although this study does not answer that question, it does highlight some important questions.”

Study authors received funding from Wellcome Trust, UK Medical Research Council, National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, BHF Centre of Research Excellence, British Heart Foundation, NIHR Cambridge Biomedical Research Centre, U.S. Department of Veterans Affairs, China Scholarship Council, and Li Ka Shing Centre for Health Information and Discovery. Dr. Topiwala has disclosed no relevant financial relationships.

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

Iron accumulation in the brain as a result of alcohol consumption may explain why even moderate drinking is linked to compromised cognitive function.

Results of a large observational study suggest brain iron accumulation is a “plausible pathway” through which alcohol negatively affects cognition, study Anya Topiwala, MD, PhD, senior clinical researcher, Nuffield Department of Population Health, University of Oxford, England, said in an interview.

Study participants who drank 56 grams of alcohol a week had higher brain iron levels. The U.K. guideline for “low risk” alcohol consumption is less than 14 units weekly, or 112 grams.

“We are finding harmful associations with iron within those low-risk alcohol intake guidelines,” said Dr. Topiwala.

The study was published online  in PLOS Medicine.
 

Early intervention opportunity?

Previous research suggests higher brain iron may be involved in the pathophysiology of Alzheimer’s and Parkinson’s diseases. However, it’s unclear whether deposition plays a role in alcohol’s effect on the brain and if it does, whether this could present an opportunity for early intervention with, for example, chelating agents.

The study included 20,729 participants in the UK Biobank study, which recruited volunteers from 2006 to 2010. Participants had a mean age of 54.8 years, and 48.6% were female.

Participants self-identified as current, never, or previous alcohol consumers. For current drinkers, researchers calculated the total weekly number of U.K. units of alcohol consumed. One unit is 8 grams. A standard drink in the United States is 14 grams. They categorized weekly consumption into quintiles and used the lowest quintile as the reference category.

Participants underwent MRI to determine brain iron levels. Areas of interest were deep brain structures in the basal ganglia.

Mean weekly alcohol consumption was 17.7 units, which is higher than U.K. guidelines for low-risk consumption. “Half of the sample were drinking above what is recommended,” said Dr. Topiwala.

Alcohol consumption was associated with markers of higher iron in the bilateral putamen (beta, 0.08 standard deviation; 95% confidence interval, 0.06-0.09; P < .001), caudate (beta, 0.05; 95% CI, 0.04-0.07; P < .001), and substantia nigra (beta, 0.03; 95% CI; 0.02-0.05; P < .001).
 

Poorer performance

Drinking more than 7 units (56 grams) weekly was associated with higher susceptibility for all brain regions, except the thalamus.

Controlling for menopause status did not alter associations between alcohol and susceptibility for any brain region. This was also the case when excluding blood pressure and cholesterol as covariates.

There were significant interactions with age in the bilateral putamen and caudate but not with sex, smoking, or Townsend Deprivation Index, which includes such factors as unemployment and living conditions.

To gather data on liver iron levels, participants underwent abdominal imaging at the same time as brain imaging. Dr. Topiwala explained that the liver is a primary storage center for iron, so it was used as “a kind of surrogate marker” of iron in the body.

The researchers showed an indirect effect of alcohol through systemic iron. A 1 SD increase in weekly alcohol consumption was associated with a 0.05 mg/g (95% CI, 0.02-0.07; P < .001) increase in liver iron. In addition, a 1 mg/g increase in liver iron was associated with a 0.44 (95% CI, 0.35-0.52; P < .001) SD increase in left putamen susceptibility.

In this sample, 32% (95% CI, 22-49; P < .001) of alcohol’s total effect on left putamen susceptibility was mediated via higher systemic iron levels.

To minimize the impact of other factors influencing the association between alcohol consumption and brain iron – and the possibility that people with more brain iron drink more – researchers used Mendelian randomization that considers genetically predicted alcohol intake. This analysis supported findings of associations between alcohol consumption and brain iron.

Participants completed a cognitive battery, which included trail-making tests that reflect executive function, puzzle tests that assess fluid intelligence or logic and reasoning, and task-based tests using the “Snap” card game to measure reaction time.

Investigators found the more iron that was present in certain brain regions, the poorer participants’ cognitive performance.

Patients should know about the risks of moderate alcohol intake so they can make decisions about drinking, said Dr. Topiwala. “They should be aware that 14 units of alcohol per week is not a zero risk.”
 

Novel research

Commenting for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations, Alzheimer’s Association, noted the study’s large size as a strength of the research.

She noted previous research has shown an association between higher iron levels and alcohol dependence and worse cognitive function, but the potential connection of brain iron levels, moderate alcohol consumption, and cognition has not been studied to date.

“This paper aims to look at whether there is a potential biological link between moderate alcohol consumption and cognition through iron-related pathways.”

The authors suggest more work is needed to understand whether alcohol consumption impacts iron-related biologies to affect downstream cognition, said Dr. Snyder. “Although this study does not answer that question, it does highlight some important questions.”

Study authors received funding from Wellcome Trust, UK Medical Research Council, National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, BHF Centre of Research Excellence, British Heart Foundation, NIHR Cambridge Biomedical Research Centre, U.S. Department of Veterans Affairs, China Scholarship Council, and Li Ka Shing Centre for Health Information and Discovery. Dr. Topiwala has disclosed no relevant financial relationships.

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

Two drugs have emerged as the optimal medications for treating insomnia based on the “best-available evidence,” but there are caveats.

In a comprehensive comparative-effectiveness analysis, lemborexant and eszopiclone showed the best efficacy, acceptability, and tolerability for acute and long-term insomnia treatment.

However, eszopiclone may cause substantial side effects – and safety data on lemborexant were inconclusive, the researchers note.

Not surprisingly, short-acting, intermediate-acting, and long-acting benzodiazepines were effective in the acute treatment of insomnia, but they have unfavorable tolerability and safety profiles, and there are no long-term data on these issues.

For many insomnia medications, there is a “striking” and “appalling” lack of long-term data, study investigator Andrea Cipriani, MD, PhD, professor of psychiatry, University of Oxford, United Kingdom, noted during a press briefing.

“This is a call for regulators to raise the bar and ask for long-term data when companies submit an application for licensing insomnia drugs,” Dr. Cipriani said.

The findings were published online  in The Lancet.
 

Prevalent, debilitating

Insomnia is highly prevalent, affecting up to 1 in 5 adults, and can have a profound impact on health, well-being, and productivity.

Sleep hygiene and cognitive-behavioral therapy for insomnia (CBT-I) are recommended first-line treatments, but they are often unavailable, which often leads patients and clinicians to turn to medications.

However, “insomnia drugs are not all created equal. Even within the same drug class there are differences,” Dr. Cipriani said.

In a large-scale systematic review and network meta-analysis, the researchers analyzed data from 154 double-blind, randomized controlled trials of medications (licensed or not) used for acute and long-term treatment of insomnia in 44,089 adults (mean age, 51.7 years; 63% women).

Results showed, for the acute treatment of insomnia, benzodiazepines, doxylamine, eszopiclone, lemborexant, seltorexant, zolpidem, and zopiclone were more effective than placebo (standardized mean difference range, 0.36-0.83; high-to-moderate certainty of evidence).

In addition, benzodiazepines, eszopiclone, zolpidem, and zopiclone were more effective than melatonin, ramelteon, and zaleplon (SMD, 0.27-0.71; moderate-to-very low certainty of evidence).

“Our results show that the melatonergic drugs melatonin and ramelteon are not really effective. The data do not support the regular use of these drugs,” co-investigator Phil Cowen, PhD, professor of psychopharmacology, University of Oxford, said at the briefing.
 

Best available evidence

What little long-term data is available suggest eszopiclone and lemborexant are more effective than placebo. Plus, eszopiclone is more effective than ramelteon and zolpidem but with “very low” certainty of evidence, the researchers report.

“There was insufficient evidence to support the prescription of benzodiazepines and zolpidem in long-term treatment,” they write.

Another problem was lack of data on other important outcomes, they add.  

“We wanted to look at hangover effects, daytime sleepiness, [and] rebound effect, but often there was no data reported in trials. We need to collect data about these outcomes because they matter to clinicians and patients,” Dr. Cipriani said.

Summing up, the researchers note the current findings represent the “best available evidence base to guide the choice about pharmacological treatment for insomnia disorder in adults and will assist in shared decisionmaking between patients, carers, and their clinicians, as well as policy makers.”

They caution, however, that all statements comparing the merits of one drug with another “should be tempered by the potential limitations of the current analysis, the quality of the available evidence, the characteristics of the patient populations, and the uncertainties that might result from choice of dose or treatment setting.”

In addition, it is important to also consider nonpharmacologic treatments for insomnia disorder, as they are supported by “high-quality evidence and recommended as first-line treatment by guidelines,” the investigator write.
 

Shared decisionmaking

In an accompanying editorial, Myrto Samara, MD, University of Thessaly, Larissa, Greece, agrees with the researchers that discussion with patients is key.  

“For insomnia treatment, patient-physician shared decisionmaking is crucial to decide when a pharmacological intervention is deemed necessary and which drug [is] to be given by considering the trade-offs for efficacy and side effects,” Dr. Samara writes.  

The study was funded by the UK National Institute for Health Research (NIHR) Oxford Health Biomedical Research Center. Dr. Cipriani has received research and consultancy fees from the Italian Network for Pediatric Trials, CARIPLO Foundation, and Angelini Pharma, and is the chief and principal investigator of two trials of seltorexant in depression that are sponsored by Janssen. Dr. Samara has reported no relevant financial relationships.

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

Two drugs have emerged as the optimal medications for treating insomnia based on the “best-available evidence,” but there are caveats.

In a comprehensive comparative-effectiveness analysis, lemborexant and eszopiclone showed the best efficacy, acceptability, and tolerability for acute and long-term insomnia treatment.

However, eszopiclone may cause substantial side effects – and safety data on lemborexant were inconclusive, the researchers note.

Not surprisingly, short-acting, intermediate-acting, and long-acting benzodiazepines were effective in the acute treatment of insomnia, but they have unfavorable tolerability and safety profiles, and there are no long-term data on these issues.

For many insomnia medications, there is a “striking” and “appalling” lack of long-term data, study investigator Andrea Cipriani, MD, PhD, professor of psychiatry, University of Oxford, United Kingdom, noted during a press briefing.

“This is a call for regulators to raise the bar and ask for long-term data when companies submit an application for licensing insomnia drugs,” Dr. Cipriani said.

The findings were published online  in The Lancet.
 

Prevalent, debilitating

Insomnia is highly prevalent, affecting up to 1 in 5 adults, and can have a profound impact on health, well-being, and productivity.

Sleep hygiene and cognitive-behavioral therapy for insomnia (CBT-I) are recommended first-line treatments, but they are often unavailable, which often leads patients and clinicians to turn to medications.

However, “insomnia drugs are not all created equal. Even within the same drug class there are differences,” Dr. Cipriani said.

In a large-scale systematic review and network meta-analysis, the researchers analyzed data from 154 double-blind, randomized controlled trials of medications (licensed or not) used for acute and long-term treatment of insomnia in 44,089 adults (mean age, 51.7 years; 63% women).

Results showed, for the acute treatment of insomnia, benzodiazepines, doxylamine, eszopiclone, lemborexant, seltorexant, zolpidem, and zopiclone were more effective than placebo (standardized mean difference range, 0.36-0.83; high-to-moderate certainty of evidence).

In addition, benzodiazepines, eszopiclone, zolpidem, and zopiclone were more effective than melatonin, ramelteon, and zaleplon (SMD, 0.27-0.71; moderate-to-very low certainty of evidence).

“Our results show that the melatonergic drugs melatonin and ramelteon are not really effective. The data do not support the regular use of these drugs,” co-investigator Phil Cowen, PhD, professor of psychopharmacology, University of Oxford, said at the briefing.
 

Best available evidence

What little long-term data is available suggest eszopiclone and lemborexant are more effective than placebo. Plus, eszopiclone is more effective than ramelteon and zolpidem but with “very low” certainty of evidence, the researchers report.

“There was insufficient evidence to support the prescription of benzodiazepines and zolpidem in long-term treatment,” they write.

Another problem was lack of data on other important outcomes, they add.  

“We wanted to look at hangover effects, daytime sleepiness, [and] rebound effect, but often there was no data reported in trials. We need to collect data about these outcomes because they matter to clinicians and patients,” Dr. Cipriani said.

Summing up, the researchers note the current findings represent the “best available evidence base to guide the choice about pharmacological treatment for insomnia disorder in adults and will assist in shared decisionmaking between patients, carers, and their clinicians, as well as policy makers.”

They caution, however, that all statements comparing the merits of one drug with another “should be tempered by the potential limitations of the current analysis, the quality of the available evidence, the characteristics of the patient populations, and the uncertainties that might result from choice of dose or treatment setting.”

In addition, it is important to also consider nonpharmacologic treatments for insomnia disorder, as they are supported by “high-quality evidence and recommended as first-line treatment by guidelines,” the investigator write.
 

Shared decisionmaking

In an accompanying editorial, Myrto Samara, MD, University of Thessaly, Larissa, Greece, agrees with the researchers that discussion with patients is key.  

“For insomnia treatment, patient-physician shared decisionmaking is crucial to decide when a pharmacological intervention is deemed necessary and which drug [is] to be given by considering the trade-offs for efficacy and side effects,” Dr. Samara writes.  

The study was funded by the UK National Institute for Health Research (NIHR) Oxford Health Biomedical Research Center. Dr. Cipriani has received research and consultancy fees from the Italian Network for Pediatric Trials, CARIPLO Foundation, and Angelini Pharma, and is the chief and principal investigator of two trials of seltorexant in depression that are sponsored by Janssen. Dr. Samara has reported no relevant financial relationships.

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

Two drugs have emerged as the optimal medications for treating insomnia based on the “best-available evidence,” but there are caveats.

In a comprehensive comparative-effectiveness analysis, lemborexant and eszopiclone showed the best efficacy, acceptability, and tolerability for acute and long-term insomnia treatment.

However, eszopiclone may cause substantial side effects – and safety data on lemborexant were inconclusive, the researchers note.

Not surprisingly, short-acting, intermediate-acting, and long-acting benzodiazepines were effective in the acute treatment of insomnia, but they have unfavorable tolerability and safety profiles, and there are no long-term data on these issues.

For many insomnia medications, there is a “striking” and “appalling” lack of long-term data, study investigator Andrea Cipriani, MD, PhD, professor of psychiatry, University of Oxford, United Kingdom, noted during a press briefing.

“This is a call for regulators to raise the bar and ask for long-term data when companies submit an application for licensing insomnia drugs,” Dr. Cipriani said.

The findings were published online  in The Lancet.
 

Prevalent, debilitating

Insomnia is highly prevalent, affecting up to 1 in 5 adults, and can have a profound impact on health, well-being, and productivity.

Sleep hygiene and cognitive-behavioral therapy for insomnia (CBT-I) are recommended first-line treatments, but they are often unavailable, which often leads patients and clinicians to turn to medications.

However, “insomnia drugs are not all created equal. Even within the same drug class there are differences,” Dr. Cipriani said.

In a large-scale systematic review and network meta-analysis, the researchers analyzed data from 154 double-blind, randomized controlled trials of medications (licensed or not) used for acute and long-term treatment of insomnia in 44,089 adults (mean age, 51.7 years; 63% women).

Results showed, for the acute treatment of insomnia, benzodiazepines, doxylamine, eszopiclone, lemborexant, seltorexant, zolpidem, and zopiclone were more effective than placebo (standardized mean difference range, 0.36-0.83; high-to-moderate certainty of evidence).

In addition, benzodiazepines, eszopiclone, zolpidem, and zopiclone were more effective than melatonin, ramelteon, and zaleplon (SMD, 0.27-0.71; moderate-to-very low certainty of evidence).

“Our results show that the melatonergic drugs melatonin and ramelteon are not really effective. The data do not support the regular use of these drugs,” co-investigator Phil Cowen, PhD, professor of psychopharmacology, University of Oxford, said at the briefing.
 

Best available evidence

What little long-term data is available suggest eszopiclone and lemborexant are more effective than placebo. Plus, eszopiclone is more effective than ramelteon and zolpidem but with “very low” certainty of evidence, the researchers report.

“There was insufficient evidence to support the prescription of benzodiazepines and zolpidem in long-term treatment,” they write.

Another problem was lack of data on other important outcomes, they add.  

“We wanted to look at hangover effects, daytime sleepiness, [and] rebound effect, but often there was no data reported in trials. We need to collect data about these outcomes because they matter to clinicians and patients,” Dr. Cipriani said.

Summing up, the researchers note the current findings represent the “best available evidence base to guide the choice about pharmacological treatment for insomnia disorder in adults and will assist in shared decisionmaking between patients, carers, and their clinicians, as well as policy makers.”

They caution, however, that all statements comparing the merits of one drug with another “should be tempered by the potential limitations of the current analysis, the quality of the available evidence, the characteristics of the patient populations, and the uncertainties that might result from choice of dose or treatment setting.”

In addition, it is important to also consider nonpharmacologic treatments for insomnia disorder, as they are supported by “high-quality evidence and recommended as first-line treatment by guidelines,” the investigator write.
 

Shared decisionmaking

In an accompanying editorial, Myrto Samara, MD, University of Thessaly, Larissa, Greece, agrees with the researchers that discussion with patients is key.  

“For insomnia treatment, patient-physician shared decisionmaking is crucial to decide when a pharmacological intervention is deemed necessary and which drug [is] to be given by considering the trade-offs for efficacy and side effects,” Dr. Samara writes.  

The study was funded by the UK National Institute for Health Research (NIHR) Oxford Health Biomedical Research Center. Dr. Cipriani has received research and consultancy fees from the Italian Network for Pediatric Trials, CARIPLO Foundation, and Angelini Pharma, and is the chief and principal investigator of two trials of seltorexant in depression that are sponsored by Janssen. Dr. Samara has reported no relevant financial relationships.

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

When the COVID-19 pandemic first began, the general thought was that once people were infected, they were then protected from the virus.

But a new analysis by ABC News shows that more and more Americans are getting the virus again.

It’s hard to say how many. The ABC News analysis found at least 1.6 million reinfections in 24 states, but the actual number is probably a lot higher.

“These are not the real numbers because many people are not reporting cases,” Ali Mokdad, MD, an epidemiologist with the University of Washington, Seattle, told ABC.

The latest variant, BA.5, has become the dominant strain in the United States, making up more than 65% of all COVID-19 cases as of July 13, according to data from the CDC.

Prior infections and vaccines aren’t providing as much protection against the newly dominant BA.5 strain as they did against earlier variants.

But evidence doesn’t show this subvariant of Omicron to be more harmful than earlier, less transmissible versions.

Several factors are contributing to rising reinfections, experts say. For example, fewer people are wearing masks than in the first year or so of the pandemic. Dr. Mokdad said just 18% of Americans reported always wearing a mask in public at the end of May, down from 44% the year before.

The emergence of the Omicron variant, of which BA.5 is a subvariant, is indicating that less protection is being offered by prior infections.

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

When the COVID-19 pandemic first began, the general thought was that once people were infected, they were then protected from the virus.

But a new analysis by ABC News shows that more and more Americans are getting the virus again.

It’s hard to say how many. The ABC News analysis found at least 1.6 million reinfections in 24 states, but the actual number is probably a lot higher.

“These are not the real numbers because many people are not reporting cases,” Ali Mokdad, MD, an epidemiologist with the University of Washington, Seattle, told ABC.

The latest variant, BA.5, has become the dominant strain in the United States, making up more than 65% of all COVID-19 cases as of July 13, according to data from the CDC.

Prior infections and vaccines aren’t providing as much protection against the newly dominant BA.5 strain as they did against earlier variants.

But evidence doesn’t show this subvariant of Omicron to be more harmful than earlier, less transmissible versions.

Several factors are contributing to rising reinfections, experts say. For example, fewer people are wearing masks than in the first year or so of the pandemic. Dr. Mokdad said just 18% of Americans reported always wearing a mask in public at the end of May, down from 44% the year before.

The emergence of the Omicron variant, of which BA.5 is a subvariant, is indicating that less protection is being offered by prior infections.

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

When the COVID-19 pandemic first began, the general thought was that once people were infected, they were then protected from the virus.

But a new analysis by ABC News shows that more and more Americans are getting the virus again.

It’s hard to say how many. The ABC News analysis found at least 1.6 million reinfections in 24 states, but the actual number is probably a lot higher.

“These are not the real numbers because many people are not reporting cases,” Ali Mokdad, MD, an epidemiologist with the University of Washington, Seattle, told ABC.

The latest variant, BA.5, has become the dominant strain in the United States, making up more than 65% of all COVID-19 cases as of July 13, according to data from the CDC.

Prior infections and vaccines aren’t providing as much protection against the newly dominant BA.5 strain as they did against earlier variants.

But evidence doesn’t show this subvariant of Omicron to be more harmful than earlier, less transmissible versions.

Several factors are contributing to rising reinfections, experts say. For example, fewer people are wearing masks than in the first year or so of the pandemic. Dr. Mokdad said just 18% of Americans reported always wearing a mask in public at the end of May, down from 44% the year before.

The emergence of the Omicron variant, of which BA.5 is a subvariant, is indicating that less protection is being offered by prior infections.

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

Just before he took a call from a reporter asking about the impact of drug shortages in hematology, Bill Greene, PharmD, chief pharmaceutical officer at St. Jude Children’s Research Hospital, had spent an hour on the phone overseeing his institution’s response to a hematology drug shortage. The chemotherapy drug fludarabine, used to treat chronic lymphocytic leukemia, was in short supply.

“There are 5 different manufacturers, but none of them have had drug available over the past 2 weeks,” Dr. Greene said. “We’re trying to chase some emergency supplies to be able to continue treatment for patients who’ve had their treatments initiated and planned.”

Over the past several years, this predicament has become common at hematology clinics across the country. In fact, management of scarce medication resources has become a significant part of Dr. Greene’s workload these days, as critical drugs fail to show up on time or manufacturer supplies run low at his hospital in Memphis.

This shortage of hematology drugs got a new dose of national attention, thanks to a recent episode of CBS News’ “60 Minutes.” Through interviews with physicians and parents of children who suddenly could not get vital medications, the report highlighted the recent shortage of another leukemia drug, vincristine.

“As a cancer mom, we shouldn’t be fighting for our children to get a drug that is needed,” Cyndi Valenta was quoted as saying. She recalled that when the shortage began in 2019, her 13-year-old son, a leukemia patient at Loma Linda (Calif.) University Hospital, felt frightened. Ms. Valenta said she felt a “gut-wrenching feeling of just fear and anger.” They were finally able to get doses of the drug after launching a social media campaign.

Such drug shortages are especially widespread in oncology and hematology, according to a survey of oncology pharmacists at 68 organizations nationwide. Published in the May 2022 issue of Oncology Practice, the study showed that 63% of institutions reported one or more drug shortages every month, with a 34% increase in 2019, compared with 2018. Treatment delays, reduced doses, or alternative regimens were reported by 75% of respondents, the authors wrote.

The pharmacists surveyed between May 2019 and July 2020 were asked about the three most hard-to-get chemotherapy and supportive care agents. Vincristine topped the list, followed by vinblastine, IVIG, leucovorin, and BCG, as well as difficult-to-obtain ropine, erwinia asparaginase, etoposide, and leuprolide. Several of these drugs are used to treat conditions such as lymphoma and leukemia.

Eighty-two percent of respondents reported shortages of decitabine (IV), often used as part of a cocktail with vinblastine and other drugs to treat Hodgkin lymphoma.

The reasons for drug shortages are varied. The CBS News report declared that “pharmaceutical companies have stopped producing many life-saving generic drugs because they make too little profit,” and it suggested that the federal government isn’t doing enough.

But government action actually might be making a difference. According to the FDA, the number of new drug shortages has fallen dramatically from 250 in 2011 to 41 in 2021, and the number of prevented drug shortages rose from nearly 200 to more than 300 over that same period. Still, the number of ongoing drug shortages has risen from around 40 in 2017 to about 80 in 2021.

Reasons for the paucity of certain drugs are often unclear. In a June 12, 2022 post, for example, the American Society of Health-System Pharmacists’ drug shortage database noted that the chemotherapy drug fludarabine was in short supply and provided details about when some of the 5 manufacturers expected to have it available. (This is the shortage that Dr. Greene was trying to manage.) But 4 of the 5 manufacturers “did not provide a reason,” and the fifth blamed manufacturing delays.

“There’s a lot of closely held trade secrets that hinder the ability to share good information,” said Dr. Greene. To make things more complicated, shipping times are often unreliable. “The product doesn’t show up today, we place another order. Sometimes it will show up tomorrow, sometimes it doesn’t,” he said. “If you’re not tracking it carefully, you deplete your own supply.”

Patients’ families have grown used to dealing with drug shortages, and “they’re less quick to blame personnel at our institution.”

How can hematologists cope with this issue? “The best thing in the immediate term is to advocate for their hospital to have a pharmacist dedicated to shortage monitoring and taking proactive steps to obviate shortages,” hematologist/oncologist Andrew Hantel, MD, an instructor at Dana-Farber Cancer Institute, Harvard Medical School, Boston, said in an interview.

“We have ongoing communications with other large cancer centers and the FDA to recognize shortages early and develop plans to make sure we stay ahead of them,” Dr. Hantel said. “Most often this involves assessing supply, use rates, alternative manufacturers, and additional measures the Food and Drug Administration can take (for example, importation), and occasionally working with clinical teams to see if other medications are feasible alternatives.”

If a drug is unavailable, it can also be helpful to discuss alternative approaches. “We did not have any frank shortages of vincristine,” Dr. Hantel said, “but we did focus on conservation measures and considered different ethically appropriate ways to distribute vincristine if there was a point at which we did not have enough for everyone who needed it.”

If a drug is in short supply, options can include delaying treatment, giving an alternative, or providing the rest of the regimen without the scarce drug, he said. In a 2021 report in The Lancet Hematology, Dr. Hantel and his colleagues offered “model solutions for ethical allocation during cancer medicine shortages.”

The authors of the May 2022 drug-shortage report highlighted an alternative regimen in hematology. They noted that manufacturing delays have limited the supply of dacarbazine, used for Hodgkin lymphoma. Due to the current shortages, they wrote, clinicians are considering the use of escalated bleomycin, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone, replacing dacarbazine with procarbazine and using the doxorubicin, bleomycin, vinblastine, procarbazine, and prednisone regimen, or replacing dacarbazine with cyclophosphamide.

Dr. Greene emphasized the importance of tracking the news and the drug shortage websites run by the FDA and the American Society of Health-System Pharmacists.

It’s also crucial to have a good relationship with your wholesaler, he added, and to communicate about these problems within your facility. At his hospital, the pharmaceutical staff holds a multi-disciplinary meeting at least weekly to discuss the supply of medications. As he put it, “it’s a challenging environment.”

Dr. Greene and Dr. Hantel reported no relevant disclosures.

Just before he took a call from a reporter asking about the impact of drug shortages in hematology, Bill Greene, PharmD, chief pharmaceutical officer at St. Jude Children’s Research Hospital, had spent an hour on the phone overseeing his institution’s response to a hematology drug shortage. The chemotherapy drug fludarabine, used to treat chronic lymphocytic leukemia, was in short supply.

“There are 5 different manufacturers, but none of them have had drug available over the past 2 weeks,” Dr. Greene said. “We’re trying to chase some emergency supplies to be able to continue treatment for patients who’ve had their treatments initiated and planned.”

Over the past several years, this predicament has become common at hematology clinics across the country. In fact, management of scarce medication resources has become a significant part of Dr. Greene’s workload these days, as critical drugs fail to show up on time or manufacturer supplies run low at his hospital in Memphis.

This shortage of hematology drugs got a new dose of national attention, thanks to a recent episode of CBS News’ “60 Minutes.” Through interviews with physicians and parents of children who suddenly could not get vital medications, the report highlighted the recent shortage of another leukemia drug, vincristine.

“As a cancer mom, we shouldn’t be fighting for our children to get a drug that is needed,” Cyndi Valenta was quoted as saying. She recalled that when the shortage began in 2019, her 13-year-old son, a leukemia patient at Loma Linda (Calif.) University Hospital, felt frightened. Ms. Valenta said she felt a “gut-wrenching feeling of just fear and anger.” They were finally able to get doses of the drug after launching a social media campaign.

Such drug shortages are especially widespread in oncology and hematology, according to a survey of oncology pharmacists at 68 organizations nationwide. Published in the May 2022 issue of Oncology Practice, the study showed that 63% of institutions reported one or more drug shortages every month, with a 34% increase in 2019, compared with 2018. Treatment delays, reduced doses, or alternative regimens were reported by 75% of respondents, the authors wrote.

The pharmacists surveyed between May 2019 and July 2020 were asked about the three most hard-to-get chemotherapy and supportive care agents. Vincristine topped the list, followed by vinblastine, IVIG, leucovorin, and BCG, as well as difficult-to-obtain ropine, erwinia asparaginase, etoposide, and leuprolide. Several of these drugs are used to treat conditions such as lymphoma and leukemia.

Eighty-two percent of respondents reported shortages of decitabine (IV), often used as part of a cocktail with vinblastine and other drugs to treat Hodgkin lymphoma.

The reasons for drug shortages are varied. The CBS News report declared that “pharmaceutical companies have stopped producing many life-saving generic drugs because they make too little profit,” and it suggested that the federal government isn’t doing enough.

But government action actually might be making a difference. According to the FDA, the number of new drug shortages has fallen dramatically from 250 in 2011 to 41 in 2021, and the number of prevented drug shortages rose from nearly 200 to more than 300 over that same period. Still, the number of ongoing drug shortages has risen from around 40 in 2017 to about 80 in 2021.

Reasons for the paucity of certain drugs are often unclear. In a June 12, 2022 post, for example, the American Society of Health-System Pharmacists’ drug shortage database noted that the chemotherapy drug fludarabine was in short supply and provided details about when some of the 5 manufacturers expected to have it available. (This is the shortage that Dr. Greene was trying to manage.) But 4 of the 5 manufacturers “did not provide a reason,” and the fifth blamed manufacturing delays.

“There’s a lot of closely held trade secrets that hinder the ability to share good information,” said Dr. Greene. To make things more complicated, shipping times are often unreliable. “The product doesn’t show up today, we place another order. Sometimes it will show up tomorrow, sometimes it doesn’t,” he said. “If you’re not tracking it carefully, you deplete your own supply.”

Patients’ families have grown used to dealing with drug shortages, and “they’re less quick to blame personnel at our institution.”

How can hematologists cope with this issue? “The best thing in the immediate term is to advocate for their hospital to have a pharmacist dedicated to shortage monitoring and taking proactive steps to obviate shortages,” hematologist/oncologist Andrew Hantel, MD, an instructor at Dana-Farber Cancer Institute, Harvard Medical School, Boston, said in an interview.

“We have ongoing communications with other large cancer centers and the FDA to recognize shortages early and develop plans to make sure we stay ahead of them,” Dr. Hantel said. “Most often this involves assessing supply, use rates, alternative manufacturers, and additional measures the Food and Drug Administration can take (for example, importation), and occasionally working with clinical teams to see if other medications are feasible alternatives.”

If a drug is unavailable, it can also be helpful to discuss alternative approaches. “We did not have any frank shortages of vincristine,” Dr. Hantel said, “but we did focus on conservation measures and considered different ethically appropriate ways to distribute vincristine if there was a point at which we did not have enough for everyone who needed it.”

If a drug is in short supply, options can include delaying treatment, giving an alternative, or providing the rest of the regimen without the scarce drug, he said. In a 2021 report in The Lancet Hematology, Dr. Hantel and his colleagues offered “model solutions for ethical allocation during cancer medicine shortages.”

The authors of the May 2022 drug-shortage report highlighted an alternative regimen in hematology. They noted that manufacturing delays have limited the supply of dacarbazine, used for Hodgkin lymphoma. Due to the current shortages, they wrote, clinicians are considering the use of escalated bleomycin, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone, replacing dacarbazine with procarbazine and using the doxorubicin, bleomycin, vinblastine, procarbazine, and prednisone regimen, or replacing dacarbazine with cyclophosphamide.

Dr. Greene emphasized the importance of tracking the news and the drug shortage websites run by the FDA and the American Society of Health-System Pharmacists.

It’s also crucial to have a good relationship with your wholesaler, he added, and to communicate about these problems within your facility. At his hospital, the pharmaceutical staff holds a multi-disciplinary meeting at least weekly to discuss the supply of medications. As he put it, “it’s a challenging environment.”

Dr. Greene and Dr. Hantel reported no relevant disclosures.

Just before he took a call from a reporter asking about the impact of drug shortages in hematology, Bill Greene, PharmD, chief pharmaceutical officer at St. Jude Children’s Research Hospital, had spent an hour on the phone overseeing his institution’s response to a hematology drug shortage. The chemotherapy drug fludarabine, used to treat chronic lymphocytic leukemia, was in short supply.

“There are 5 different manufacturers, but none of them have had drug available over the past 2 weeks,” Dr. Greene said. “We’re trying to chase some emergency supplies to be able to continue treatment for patients who’ve had their treatments initiated and planned.”

Over the past several years, this predicament has become common at hematology clinics across the country. In fact, management of scarce medication resources has become a significant part of Dr. Greene’s workload these days, as critical drugs fail to show up on time or manufacturer supplies run low at his hospital in Memphis.

This shortage of hematology drugs got a new dose of national attention, thanks to a recent episode of CBS News’ “60 Minutes.” Through interviews with physicians and parents of children who suddenly could not get vital medications, the report highlighted the recent shortage of another leukemia drug, vincristine.

“As a cancer mom, we shouldn’t be fighting for our children to get a drug that is needed,” Cyndi Valenta was quoted as saying. She recalled that when the shortage began in 2019, her 13-year-old son, a leukemia patient at Loma Linda (Calif.) University Hospital, felt frightened. Ms. Valenta said she felt a “gut-wrenching feeling of just fear and anger.” They were finally able to get doses of the drug after launching a social media campaign.

Such drug shortages are especially widespread in oncology and hematology, according to a survey of oncology pharmacists at 68 organizations nationwide. Published in the May 2022 issue of Oncology Practice, the study showed that 63% of institutions reported one or more drug shortages every month, with a 34% increase in 2019, compared with 2018. Treatment delays, reduced doses, or alternative regimens were reported by 75% of respondents, the authors wrote.

The pharmacists surveyed between May 2019 and July 2020 were asked about the three most hard-to-get chemotherapy and supportive care agents. Vincristine topped the list, followed by vinblastine, IVIG, leucovorin, and BCG, as well as difficult-to-obtain ropine, erwinia asparaginase, etoposide, and leuprolide. Several of these drugs are used to treat conditions such as lymphoma and leukemia.

Eighty-two percent of respondents reported shortages of decitabine (IV), often used as part of a cocktail with vinblastine and other drugs to treat Hodgkin lymphoma.

The reasons for drug shortages are varied. The CBS News report declared that “pharmaceutical companies have stopped producing many life-saving generic drugs because they make too little profit,” and it suggested that the federal government isn’t doing enough.

But government action actually might be making a difference. According to the FDA, the number of new drug shortages has fallen dramatically from 250 in 2011 to 41 in 2021, and the number of prevented drug shortages rose from nearly 200 to more than 300 over that same period. Still, the number of ongoing drug shortages has risen from around 40 in 2017 to about 80 in 2021.

Reasons for the paucity of certain drugs are often unclear. In a June 12, 2022 post, for example, the American Society of Health-System Pharmacists’ drug shortage database noted that the chemotherapy drug fludarabine was in short supply and provided details about when some of the 5 manufacturers expected to have it available. (This is the shortage that Dr. Greene was trying to manage.) But 4 of the 5 manufacturers “did not provide a reason,” and the fifth blamed manufacturing delays.

“There’s a lot of closely held trade secrets that hinder the ability to share good information,” said Dr. Greene. To make things more complicated, shipping times are often unreliable. “The product doesn’t show up today, we place another order. Sometimes it will show up tomorrow, sometimes it doesn’t,” he said. “If you’re not tracking it carefully, you deplete your own supply.”

Patients’ families have grown used to dealing with drug shortages, and “they’re less quick to blame personnel at our institution.”

How can hematologists cope with this issue? “The best thing in the immediate term is to advocate for their hospital to have a pharmacist dedicated to shortage monitoring and taking proactive steps to obviate shortages,” hematologist/oncologist Andrew Hantel, MD, an instructor at Dana-Farber Cancer Institute, Harvard Medical School, Boston, said in an interview.

“We have ongoing communications with other large cancer centers and the FDA to recognize shortages early and develop plans to make sure we stay ahead of them,” Dr. Hantel said. “Most often this involves assessing supply, use rates, alternative manufacturers, and additional measures the Food and Drug Administration can take (for example, importation), and occasionally working with clinical teams to see if other medications are feasible alternatives.”

If a drug is unavailable, it can also be helpful to discuss alternative approaches. “We did not have any frank shortages of vincristine,” Dr. Hantel said, “but we did focus on conservation measures and considered different ethically appropriate ways to distribute vincristine if there was a point at which we did not have enough for everyone who needed it.”

If a drug is in short supply, options can include delaying treatment, giving an alternative, or providing the rest of the regimen without the scarce drug, he said. In a 2021 report in The Lancet Hematology, Dr. Hantel and his colleagues offered “model solutions for ethical allocation during cancer medicine shortages.”

The authors of the May 2022 drug-shortage report highlighted an alternative regimen in hematology. They noted that manufacturing delays have limited the supply of dacarbazine, used for Hodgkin lymphoma. Due to the current shortages, they wrote, clinicians are considering the use of escalated bleomycin, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone, replacing dacarbazine with procarbazine and using the doxorubicin, bleomycin, vinblastine, procarbazine, and prednisone regimen, or replacing dacarbazine with cyclophosphamide.

Dr. Greene emphasized the importance of tracking the news and the drug shortage websites run by the FDA and the American Society of Health-System Pharmacists.

It’s also crucial to have a good relationship with your wholesaler, he added, and to communicate about these problems within your facility. At his hospital, the pharmaceutical staff holds a multi-disciplinary meeting at least weekly to discuss the supply of medications. As he put it, “it’s a challenging environment.”

Dr. Greene and Dr. Hantel reported no relevant disclosures.

An analysis of trends in lung cancer screening since March 2021 when the U.S. Preventive Services Task Force (USPSTF) expanded the eligibility criteria for lung cancer screening, shows that significantly more Black men have been screened for lung cancer, but not women or undereducated people.

The eligibility for lung cancer screening was expanded in 2021 to include men and women under 50 years old and people who smoke at least one pack of cigarettes a day for the last 20 years. “

“Expansion of screening criteria is a critical first step to achieving equity in lung cancer screening for all high-risk populations, but myriad challenges remain before individuals enter the door for screening,” wrote the authors, led by Julie A. Barta, MD, Thomas Jefferson University, Philadelphia. “Health policy changes must occur simultaneously with efforts to expand community outreach, overcome logistical barriers, and facilitate screening adherence. Only after comprehensive strategies to dismantle screening barriers are identified, validated, and implemented can there be a truly equitable landscape for lung cancer screening.”

For the study, published in JAMA Open Network, researchers examined rates of centralized lung cancer screening in the Baltimore area. In addition to expanding lung cancer screening generally, there was hope that the expanded criteria might increase uptake of screening in populations that are traditionally underserved, such as African American, Hispanic, and female patients. Of 815 people screened during the study period (March-December 2021), 161 were newly eligible for screening under the 2021 criteria.

“There’s been quite a bit of work in the field demonstrating that Black men and women develop lung cancer at more advanced stages of disease, and they often are diagnosed at younger ages and have fewer pack-years of smoking. So the hypothesis was that this would reduce some of the disparities seen in lung cancer screening by making more people eligible,” Dr. Barta said in an interview.

The researchers categorized participants as those who would have been eligible for screening under the USPSTF 2013 guideline (age 55 or older, 30 or more pack-years, quit within the past 15 years), and those who would be eligible under the 2021 guideline (age 50 or older, 20 or more pack-years, quit within the past 15 years). Of the 2021 cohort, 54.5% were African American, versus 39.5% of the 2013 cohort (P = .002). There were no differences between the cohorts with respect to education level or gender.

“Although we’ve seen some encouraging improvement in terms of getting more eligible patients into our screening program, there’s still a lot of work to be done in the field,” Dr. Barta said. “Diagnosing lung cancer at earlier stages of disease is more cost effective in general for the health care system than fighting lung cancer at advanced stages, which requires more complex and multimodal and prolonged therapies.”
 

New evidence: Chest CTs for lung cancer screening reduces incidence of advanced lung cancer

In an analysis of the SEER database presented in June at the annual meeting of the American Society of Clinical Oncology, the adoption of low-dose chest computed tomography (LDCT) led to fewer diagnoses of advanced lung cancer, although these declines varied significantly by race and ethnicity. Non-Hispanic Blacks seemed to benefit the most with a 55% decline (P < .01), while Hispanics had the lowest rate of decline at 41% (P < .01). The change was recommended by USPSTF in 2013 after the National Lung Screening Trial revealed a 20% relative reduction in mortality when CT scans were used instead of chest radiography. The Centers for Medicare and Medicaid Services approved coverage of the screen in 2015.

The SEER study looked at data from 400,343 individuals from 2004-2014 (preintervention) and 2015-2018 (postintervention). The age-adjusted incidence of advanced lung cancer declined during both periods, but the decline was sharper between 2015 and 2018, with three fewer cases per 100,000 people than 2004-2014 (P < .01). Similar patterns were seen in subanalyses of males and females, non-Hispanic Whites, non-Hispanic Blacks, and Hispanics. The relative declines were largest in women, non-Hispanic Blacks, and people who lived outside of Metropolitan areas.

During a Q&A session that followed the presentation, Robert Smith, PhD, pointed out that the bar for eligibility of lung cancer risk has been set quite high, following the eligibility criteria for clinical trials. He noted that many patients who could be eligible for screening are still missed because of a lack of clinical routines designed to identify eligible patients. “We are missing opportunities to prevent avertable lung cancer deaths,” said Dr. Smith, senior vice president of cancer screening at the American Cancer Society.

On the other hand, screening-prompted biopsies have the potential to cause harm, particularly in patients who already have lung disease, said Douglas Allen Arenberg, MD, professor at the University of Michigan, Ann Arbor. “I think that’s what scares most people is the potential downside, which is very hard to measure outside of a clinical trial,” said Dr. Arenberg, who served as a discussant for the presentation.

One way to reduce that risk is to identify biomarkers, either for screens or for incidentally-detected nodules, that have good negative predictive value. “If I had a blood test that is as good as a negative PET scan, I’m going to be much more likely to say, ‘Yeah, you’re 40 and your grandfather had lung cancer. Maybe you should get a CT. If we had that, we could screen a lot more people. Right now, I would discourage anybody who is at low risk from getting screened because when they come to me, the biggest opportunity I have to do harm is when I do a biopsy, and you always remember the ones that go wrong,” he said.

Dr. Arenberg also called for improvements in electronic medical records to better flag at-risk patients. “I think we as physicians have to demand more of the software developers that create these EMRs for us,” he said.

Another study in the same session used data from 1,391,088 patients drawn from the National Cancer Database between 2010 and 2017 to examine trends in diagnosis of stage I cancer. In 2010, 23.5% of patients were diagnosed as stage I, versus 29.1% in 2017. Stage I incidence increased from 25.8% to 31.7% in non–small cell lung cancer, but there was no statistically significant change in small cell lung cancer. As with the SEER database study, the researchers noted that the shift toward stage I diagnoses predated the recommendation of LDCT.

Dr. Arenberg suggested that the trend may come down to increased frequency of CT scans, which often collect incidental images of the lungs. He added that better access to care may also be helping to drive the change. “How much of that might have had something to do with the introduction 5 or 10 years earlier of the Affordable Care Act and people just simply having access to care and taking advantage of that?” Dr. Arenberg said.

But Dr. Arenberg said that not even screening can explain all the data. He referenced a stage shift in patients of all age groups in the National Cancer Database study, even those too young to be eligible for screening. “There’s something else going on here. It would be nice for us to understand what caused these trends, so perhaps we could accentuate that trend even more, but stage shifts are clearly occurring in lung cancer,” Dr. Arenberg said.

Dr. Barta has received grants from Genentech Health Equity Innovations Fund. Dr. Arenberg has no relevant financial disclosures. Dr. Smith’s potential disclosures could not be ascertained.

An analysis of trends in lung cancer screening since March 2021 when the U.S. Preventive Services Task Force (USPSTF) expanded the eligibility criteria for lung cancer screening, shows that significantly more Black men have been screened for lung cancer, but not women or undereducated people.

The eligibility for lung cancer screening was expanded in 2021 to include men and women under 50 years old and people who smoke at least one pack of cigarettes a day for the last 20 years. “

“Expansion of screening criteria is a critical first step to achieving equity in lung cancer screening for all high-risk populations, but myriad challenges remain before individuals enter the door for screening,” wrote the authors, led by Julie A. Barta, MD, Thomas Jefferson University, Philadelphia. “Health policy changes must occur simultaneously with efforts to expand community outreach, overcome logistical barriers, and facilitate screening adherence. Only after comprehensive strategies to dismantle screening barriers are identified, validated, and implemented can there be a truly equitable landscape for lung cancer screening.”

For the study, published in JAMA Open Network, researchers examined rates of centralized lung cancer screening in the Baltimore area. In addition to expanding lung cancer screening generally, there was hope that the expanded criteria might increase uptake of screening in populations that are traditionally underserved, such as African American, Hispanic, and female patients. Of 815 people screened during the study period (March-December 2021), 161 were newly eligible for screening under the 2021 criteria.

“There’s been quite a bit of work in the field demonstrating that Black men and women develop lung cancer at more advanced stages of disease, and they often are diagnosed at younger ages and have fewer pack-years of smoking. So the hypothesis was that this would reduce some of the disparities seen in lung cancer screening by making more people eligible,” Dr. Barta said in an interview.

The researchers categorized participants as those who would have been eligible for screening under the USPSTF 2013 guideline (age 55 or older, 30 or more pack-years, quit within the past 15 years), and those who would be eligible under the 2021 guideline (age 50 or older, 20 or more pack-years, quit within the past 15 years). Of the 2021 cohort, 54.5% were African American, versus 39.5% of the 2013 cohort (P = .002). There were no differences between the cohorts with respect to education level or gender.

“Although we’ve seen some encouraging improvement in terms of getting more eligible patients into our screening program, there’s still a lot of work to be done in the field,” Dr. Barta said. “Diagnosing lung cancer at earlier stages of disease is more cost effective in general for the health care system than fighting lung cancer at advanced stages, which requires more complex and multimodal and prolonged therapies.”
 

New evidence: Chest CTs for lung cancer screening reduces incidence of advanced lung cancer

In an analysis of the SEER database presented in June at the annual meeting of the American Society of Clinical Oncology, the adoption of low-dose chest computed tomography (LDCT) led to fewer diagnoses of advanced lung cancer, although these declines varied significantly by race and ethnicity. Non-Hispanic Blacks seemed to benefit the most with a 55% decline (P < .01), while Hispanics had the lowest rate of decline at 41% (P < .01). The change was recommended by USPSTF in 2013 after the National Lung Screening Trial revealed a 20% relative reduction in mortality when CT scans were used instead of chest radiography. The Centers for Medicare and Medicaid Services approved coverage of the screen in 2015.

The SEER study looked at data from 400,343 individuals from 2004-2014 (preintervention) and 2015-2018 (postintervention). The age-adjusted incidence of advanced lung cancer declined during both periods, but the decline was sharper between 2015 and 2018, with three fewer cases per 100,000 people than 2004-2014 (P < .01). Similar patterns were seen in subanalyses of males and females, non-Hispanic Whites, non-Hispanic Blacks, and Hispanics. The relative declines were largest in women, non-Hispanic Blacks, and people who lived outside of Metropolitan areas.

During a Q&A session that followed the presentation, Robert Smith, PhD, pointed out that the bar for eligibility of lung cancer risk has been set quite high, following the eligibility criteria for clinical trials. He noted that many patients who could be eligible for screening are still missed because of a lack of clinical routines designed to identify eligible patients. “We are missing opportunities to prevent avertable lung cancer deaths,” said Dr. Smith, senior vice president of cancer screening at the American Cancer Society.

On the other hand, screening-prompted biopsies have the potential to cause harm, particularly in patients who already have lung disease, said Douglas Allen Arenberg, MD, professor at the University of Michigan, Ann Arbor. “I think that’s what scares most people is the potential downside, which is very hard to measure outside of a clinical trial,” said Dr. Arenberg, who served as a discussant for the presentation.

One way to reduce that risk is to identify biomarkers, either for screens or for incidentally-detected nodules, that have good negative predictive value. “If I had a blood test that is as good as a negative PET scan, I’m going to be much more likely to say, ‘Yeah, you’re 40 and your grandfather had lung cancer. Maybe you should get a CT. If we had that, we could screen a lot more people. Right now, I would discourage anybody who is at low risk from getting screened because when they come to me, the biggest opportunity I have to do harm is when I do a biopsy, and you always remember the ones that go wrong,” he said.

Dr. Arenberg also called for improvements in electronic medical records to better flag at-risk patients. “I think we as physicians have to demand more of the software developers that create these EMRs for us,” he said.

Another study in the same session used data from 1,391,088 patients drawn from the National Cancer Database between 2010 and 2017 to examine trends in diagnosis of stage I cancer. In 2010, 23.5% of patients were diagnosed as stage I, versus 29.1% in 2017. Stage I incidence increased from 25.8% to 31.7% in non–small cell lung cancer, but there was no statistically significant change in small cell lung cancer. As with the SEER database study, the researchers noted that the shift toward stage I diagnoses predated the recommendation of LDCT.

Dr. Arenberg suggested that the trend may come down to increased frequency of CT scans, which often collect incidental images of the lungs. He added that better access to care may also be helping to drive the change. “How much of that might have had something to do with the introduction 5 or 10 years earlier of the Affordable Care Act and people just simply having access to care and taking advantage of that?” Dr. Arenberg said.

But Dr. Arenberg said that not even screening can explain all the data. He referenced a stage shift in patients of all age groups in the National Cancer Database study, even those too young to be eligible for screening. “There’s something else going on here. It would be nice for us to understand what caused these trends, so perhaps we could accentuate that trend even more, but stage shifts are clearly occurring in lung cancer,” Dr. Arenberg said.

Dr. Barta has received grants from Genentech Health Equity Innovations Fund. Dr. Arenberg has no relevant financial disclosures. Dr. Smith’s potential disclosures could not be ascertained.

An analysis of trends in lung cancer screening since March 2021 when the U.S. Preventive Services Task Force (USPSTF) expanded the eligibility criteria for lung cancer screening, shows that significantly more Black men have been screened for lung cancer, but not women or undereducated people.

The eligibility for lung cancer screening was expanded in 2021 to include men and women under 50 years old and people who smoke at least one pack of cigarettes a day for the last 20 years. “

“Expansion of screening criteria is a critical first step to achieving equity in lung cancer screening for all high-risk populations, but myriad challenges remain before individuals enter the door for screening,” wrote the authors, led by Julie A. Barta, MD, Thomas Jefferson University, Philadelphia. “Health policy changes must occur simultaneously with efforts to expand community outreach, overcome logistical barriers, and facilitate screening adherence. Only after comprehensive strategies to dismantle screening barriers are identified, validated, and implemented can there be a truly equitable landscape for lung cancer screening.”

For the study, published in JAMA Open Network, researchers examined rates of centralized lung cancer screening in the Baltimore area. In addition to expanding lung cancer screening generally, there was hope that the expanded criteria might increase uptake of screening in populations that are traditionally underserved, such as African American, Hispanic, and female patients. Of 815 people screened during the study period (March-December 2021), 161 were newly eligible for screening under the 2021 criteria.

“There’s been quite a bit of work in the field demonstrating that Black men and women develop lung cancer at more advanced stages of disease, and they often are diagnosed at younger ages and have fewer pack-years of smoking. So the hypothesis was that this would reduce some of the disparities seen in lung cancer screening by making more people eligible,” Dr. Barta said in an interview.

The researchers categorized participants as those who would have been eligible for screening under the USPSTF 2013 guideline (age 55 or older, 30 or more pack-years, quit within the past 15 years), and those who would be eligible under the 2021 guideline (age 50 or older, 20 or more pack-years, quit within the past 15 years). Of the 2021 cohort, 54.5% were African American, versus 39.5% of the 2013 cohort (P = .002). There were no differences between the cohorts with respect to education level or gender.

“Although we’ve seen some encouraging improvement in terms of getting more eligible patients into our screening program, there’s still a lot of work to be done in the field,” Dr. Barta said. “Diagnosing lung cancer at earlier stages of disease is more cost effective in general for the health care system than fighting lung cancer at advanced stages, which requires more complex and multimodal and prolonged therapies.”
 

New evidence: Chest CTs for lung cancer screening reduces incidence of advanced lung cancer

In an analysis of the SEER database presented in June at the annual meeting of the American Society of Clinical Oncology, the adoption of low-dose chest computed tomography (LDCT) led to fewer diagnoses of advanced lung cancer, although these declines varied significantly by race and ethnicity. Non-Hispanic Blacks seemed to benefit the most with a 55% decline (P < .01), while Hispanics had the lowest rate of decline at 41% (P < .01). The change was recommended by USPSTF in 2013 after the National Lung Screening Trial revealed a 20% relative reduction in mortality when CT scans were used instead of chest radiography. The Centers for Medicare and Medicaid Services approved coverage of the screen in 2015.

The SEER study looked at data from 400,343 individuals from 2004-2014 (preintervention) and 2015-2018 (postintervention). The age-adjusted incidence of advanced lung cancer declined during both periods, but the decline was sharper between 2015 and 2018, with three fewer cases per 100,000 people than 2004-2014 (P < .01). Similar patterns were seen in subanalyses of males and females, non-Hispanic Whites, non-Hispanic Blacks, and Hispanics. The relative declines were largest in women, non-Hispanic Blacks, and people who lived outside of Metropolitan areas.

During a Q&A session that followed the presentation, Robert Smith, PhD, pointed out that the bar for eligibility of lung cancer risk has been set quite high, following the eligibility criteria for clinical trials. He noted that many patients who could be eligible for screening are still missed because of a lack of clinical routines designed to identify eligible patients. “We are missing opportunities to prevent avertable lung cancer deaths,” said Dr. Smith, senior vice president of cancer screening at the American Cancer Society.

On the other hand, screening-prompted biopsies have the potential to cause harm, particularly in patients who already have lung disease, said Douglas Allen Arenberg, MD, professor at the University of Michigan, Ann Arbor. “I think that’s what scares most people is the potential downside, which is very hard to measure outside of a clinical trial,” said Dr. Arenberg, who served as a discussant for the presentation.

One way to reduce that risk is to identify biomarkers, either for screens or for incidentally-detected nodules, that have good negative predictive value. “If I had a blood test that is as good as a negative PET scan, I’m going to be much more likely to say, ‘Yeah, you’re 40 and your grandfather had lung cancer. Maybe you should get a CT. If we had that, we could screen a lot more people. Right now, I would discourage anybody who is at low risk from getting screened because when they come to me, the biggest opportunity I have to do harm is when I do a biopsy, and you always remember the ones that go wrong,” he said.

Dr. Arenberg also called for improvements in electronic medical records to better flag at-risk patients. “I think we as physicians have to demand more of the software developers that create these EMRs for us,” he said.

Another study in the same session used data from 1,391,088 patients drawn from the National Cancer Database between 2010 and 2017 to examine trends in diagnosis of stage I cancer. In 2010, 23.5% of patients were diagnosed as stage I, versus 29.1% in 2017. Stage I incidence increased from 25.8% to 31.7% in non–small cell lung cancer, but there was no statistically significant change in small cell lung cancer. As with the SEER database study, the researchers noted that the shift toward stage I diagnoses predated the recommendation of LDCT.

Dr. Arenberg suggested that the trend may come down to increased frequency of CT scans, which often collect incidental images of the lungs. He added that better access to care may also be helping to drive the change. “How much of that might have had something to do with the introduction 5 or 10 years earlier of the Affordable Care Act and people just simply having access to care and taking advantage of that?” Dr. Arenberg said.

But Dr. Arenberg said that not even screening can explain all the data. He referenced a stage shift in patients of all age groups in the National Cancer Database study, even those too young to be eligible for screening. “There’s something else going on here. It would be nice for us to understand what caused these trends, so perhaps we could accentuate that trend even more, but stage shifts are clearly occurring in lung cancer,” Dr. Arenberg said.

Dr. Barta has received grants from Genentech Health Equity Innovations Fund. Dr. Arenberg has no relevant financial disclosures. Dr. Smith’s potential disclosures could not be ascertained.