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Rosuvastatin for cholesterol lowering was associated with slightly greater risks for kidney harm than atorvastatin, risks that were greater at higher-dose levels, in a large retrospective cohort study.

The most potent statin on the market, rosuvastatin has been linked with excess risk for kidney damage compared with atorvastatin in case reports and small trials, but there has been little surveillance of the issue following its approval in 2003.

The current analysis “is one of the first and largest real-world studies” examining rosuvastatin versus atorvastatin for risk for hematuria, proteinuria, and kidney failure with replacement therapy – dialysis or transplantation – across a range of estimated glomerular filtration rates (eGFR) in a heterogeneous population, the researchers write.

“Our findings suggest the need for greater care in prescribing and monitoring of rosuvastatin, particularly in patients who are receiving high doses” or have severe chronic kidney disease (CKD), they concluded in their report published online in the Journal of the American Society of Nephrology.

The analysis included close to 1 million patients in the United States who were newly prescribed rosuvastatin or atorvastatin from 2011 through 2019; they were followed a median of 3.1 years. Among the findings:

• Users of rosuvastatin had an 8% higher risk for hematuria, a 17% higher risk for proteinuria, and a 15% higher risk for kidney failure with replacement therapy, compared with those on atorvastatin
• The two groups avoided MI and stroke to similar extents
• About 44% of patients with severe CKD G4+ (eGFR < 30 mL/min per 1.73 m2) were prescribed a higher rosuvastatin dosage than the maximum 10 mg/day recommended for such patients by the Food and Drug Administration.

From this study, “we do not know why the adherence of FDA dosing recommendation for rosuvastatin in patients with severe CKD is low,” lead author Jung-Im Shin, MD, PhD, said in an interview.

“It is likely that not many clinicians are aware of rosuvastatin’s dosing recommendations [in severe CKD], or potential risks of hematuria or proteinuria,” speculated Dr. Shin, assistant professor at Johns Hopkins University, Baltimore.

“High-dose rosuvastatin [and its cardiovascular benefits] may not merit the risk, even if small, particularly in low eGFR,” she said. “Our study provides the opportunity to increase awareness of this clinical issue.”

“Future studies are warranted to shed light on the discrepancy between real-world practice and FDA dosing recommendations for high-dose rosuvastatin,” the researchers noted.

‘Greater awareness and education are key’

Invited to comment, Swapnil Hiremath, MD, a nephrologist at the Ottawa Hospital Research Institute, noted that the higher risk for nephrotoxicity with high-dose rosuvastatin versus high-dose atorvastatin was shown in the PLANET 1 trial published in 2015 and in, for example, a case report published in 2016 – which the researchers also mention.

“I was personally surprised” at the high proportion of patients with severe CKD who received higher than recommended doses of rosuvastatin, said Dr. Hiremath, who is also an associate professor at the University of Ottawa and a Freely Filtered podcaster, and not associated with the current study.

“We do see this occasionally,” he continued, “but either because someone is targeting LDL [cholesterol] and hasn’t noted the GFR, or possibly the patient was started on a high dose a long time ago and the kidney function has declined, and no one has noted the high dose.”

“Greater awareness and education are key,” observed Dr. Hiremath. “My personal bias is to have renal pharmacists involved in multidisciplinary clinics when GFR [is] less than 30 or so,” he said. “There are so many other tricky medicine/interaction issues” in patients with kidney disease.

Nevertheless, “I would be careful in drawing too many conclusions from an observational study,” Dr. Hiremath added. “There’s always the threat of residual confounding and selection bias,” which the researchers acknowledge, “and especially competing risks.”

For example, “if there is less cardiovascular death with rosuvastatin, then more people will remain alive to develop kidney failure.”
 

Dosing in practice unclear

Atorvastatin at 40-mg and 80-mg dosages and rosuvastatin at 20 mg and 40 mg are the only two statins considered high-intensity, the researchers noted.

Development of an 80-mg dosage for rosuvastatin was dropped because of hematuria and proteinuria safety signals highlighted at the time of rosuvastatin’s FDA approval.

However, there has been little postmarketing surveillance to assess real-world risk from high-intensity rosuvastatin, and it remains unclear whether and to what extent clinical practice adheres to the starting dosage recommended by the FDA in severe CKD, 5 mg/day with a maximum of 10 mg/day, the report noted.

The researchers analyzed deidentified electronic health record data from 40 health care organizations in the United States from the OptumLabs Data Warehouse database. They entered 152,101 new rosuvastatin users and 795,799 new atorvastatin users, and excluded patients with a history of rhabdomyolysis.

Patients in the two groups were similar with respect to CKD prevalence, cardiovascular risk factors, and demographics. Their age averaged 60 years, 48% were women, and 82% were White.

Hematuria was defined as dipstick hematuria > + or the presence of more than 3 red blood cells per high-power field in urine microscopy, at least twice. Proteinuria was defined as dipstick proteinuria > ++ or urine albumin-to-creatinine ratio greater than 300 mg/g at least twice.

Overall, 2.9% of patients had hematuria (3.4% of the rosuvastatin group and 2.8% of those taking atorvastatin) and 1% of patients had proteinuria (1.2% and 0.9%, respectively).

After balancing baseline characteristics in both groups using inverse probability of treatment weighting, rosuvastatin treatment, compared with atorvastatin, was associated with significantly greater risks for hematuria (hazard ratio, 1.08), proteinuria (HR, 1.17), and kidney failure requiring replacement therapy (HR, 1.15).  

Patients with eGFR less than 30 mL/min per 1.73 m2 had an approximately twofold higher risk for hematuria and ninefold higher risk for proteinuria during the follow-up compared with patients with eGFR of at least 60 mL/min per 1.73 m2.

Patients with eGFR less than 30 mL/min per 1.73 m2 were commonly prescribed high-dose rosuvastatin (29.9% received the 20-mg dose and 14% the 40-mg dose), contrary to the labeling recommendation.

Dr. Shin reported receiving research Funding from the National Institutes of Health and Merck; disclosures for the other authors are in the report. Dr. Hiremath reported having no relevant financial relationships.

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

Rosuvastatin for cholesterol lowering was associated with slightly greater risks for kidney harm than atorvastatin, risks that were greater at higher-dose levels, in a large retrospective cohort study.

The most potent statin on the market, rosuvastatin has been linked with excess risk for kidney damage compared with atorvastatin in case reports and small trials, but there has been little surveillance of the issue following its approval in 2003.

The current analysis “is one of the first and largest real-world studies” examining rosuvastatin versus atorvastatin for risk for hematuria, proteinuria, and kidney failure with replacement therapy – dialysis or transplantation – across a range of estimated glomerular filtration rates (eGFR) in a heterogeneous population, the researchers write.

“Our findings suggest the need for greater care in prescribing and monitoring of rosuvastatin, particularly in patients who are receiving high doses” or have severe chronic kidney disease (CKD), they concluded in their report published online in the Journal of the American Society of Nephrology.

The analysis included close to 1 million patients in the United States who were newly prescribed rosuvastatin or atorvastatin from 2011 through 2019; they were followed a median of 3.1 years. Among the findings:

• Users of rosuvastatin had an 8% higher risk for hematuria, a 17% higher risk for proteinuria, and a 15% higher risk for kidney failure with replacement therapy, compared with those on atorvastatin
• The two groups avoided MI and stroke to similar extents
• About 44% of patients with severe CKD G4+ (eGFR < 30 mL/min per 1.73 m2) were prescribed a higher rosuvastatin dosage than the maximum 10 mg/day recommended for such patients by the Food and Drug Administration.

From this study, “we do not know why the adherence of FDA dosing recommendation for rosuvastatin in patients with severe CKD is low,” lead author Jung-Im Shin, MD, PhD, said in an interview.

“It is likely that not many clinicians are aware of rosuvastatin’s dosing recommendations [in severe CKD], or potential risks of hematuria or proteinuria,” speculated Dr. Shin, assistant professor at Johns Hopkins University, Baltimore.

“High-dose rosuvastatin [and its cardiovascular benefits] may not merit the risk, even if small, particularly in low eGFR,” she said. “Our study provides the opportunity to increase awareness of this clinical issue.”

“Future studies are warranted to shed light on the discrepancy between real-world practice and FDA dosing recommendations for high-dose rosuvastatin,” the researchers noted.

‘Greater awareness and education are key’

Invited to comment, Swapnil Hiremath, MD, a nephrologist at the Ottawa Hospital Research Institute, noted that the higher risk for nephrotoxicity with high-dose rosuvastatin versus high-dose atorvastatin was shown in the PLANET 1 trial published in 2015 and in, for example, a case report published in 2016 – which the researchers also mention.

“I was personally surprised” at the high proportion of patients with severe CKD who received higher than recommended doses of rosuvastatin, said Dr. Hiremath, who is also an associate professor at the University of Ottawa and a Freely Filtered podcaster, and not associated with the current study.

“We do see this occasionally,” he continued, “but either because someone is targeting LDL [cholesterol] and hasn’t noted the GFR, or possibly the patient was started on a high dose a long time ago and the kidney function has declined, and no one has noted the high dose.”

“Greater awareness and education are key,” observed Dr. Hiremath. “My personal bias is to have renal pharmacists involved in multidisciplinary clinics when GFR [is] less than 30 or so,” he said. “There are so many other tricky medicine/interaction issues” in patients with kidney disease.

Nevertheless, “I would be careful in drawing too many conclusions from an observational study,” Dr. Hiremath added. “There’s always the threat of residual confounding and selection bias,” which the researchers acknowledge, “and especially competing risks.”

For example, “if there is less cardiovascular death with rosuvastatin, then more people will remain alive to develop kidney failure.”
 

Dosing in practice unclear

Atorvastatin at 40-mg and 80-mg dosages and rosuvastatin at 20 mg and 40 mg are the only two statins considered high-intensity, the researchers noted.

Development of an 80-mg dosage for rosuvastatin was dropped because of hematuria and proteinuria safety signals highlighted at the time of rosuvastatin’s FDA approval.

However, there has been little postmarketing surveillance to assess real-world risk from high-intensity rosuvastatin, and it remains unclear whether and to what extent clinical practice adheres to the starting dosage recommended by the FDA in severe CKD, 5 mg/day with a maximum of 10 mg/day, the report noted.

The researchers analyzed deidentified electronic health record data from 40 health care organizations in the United States from the OptumLabs Data Warehouse database. They entered 152,101 new rosuvastatin users and 795,799 new atorvastatin users, and excluded patients with a history of rhabdomyolysis.

Patients in the two groups were similar with respect to CKD prevalence, cardiovascular risk factors, and demographics. Their age averaged 60 years, 48% were women, and 82% were White.

Hematuria was defined as dipstick hematuria > + or the presence of more than 3 red blood cells per high-power field in urine microscopy, at least twice. Proteinuria was defined as dipstick proteinuria > ++ or urine albumin-to-creatinine ratio greater than 300 mg/g at least twice.

Overall, 2.9% of patients had hematuria (3.4% of the rosuvastatin group and 2.8% of those taking atorvastatin) and 1% of patients had proteinuria (1.2% and 0.9%, respectively).

After balancing baseline characteristics in both groups using inverse probability of treatment weighting, rosuvastatin treatment, compared with atorvastatin, was associated with significantly greater risks for hematuria (hazard ratio, 1.08), proteinuria (HR, 1.17), and kidney failure requiring replacement therapy (HR, 1.15).  

Patients with eGFR less than 30 mL/min per 1.73 m2 had an approximately twofold higher risk for hematuria and ninefold higher risk for proteinuria during the follow-up compared with patients with eGFR of at least 60 mL/min per 1.73 m2.

Patients with eGFR less than 30 mL/min per 1.73 m2 were commonly prescribed high-dose rosuvastatin (29.9% received the 20-mg dose and 14% the 40-mg dose), contrary to the labeling recommendation.

Dr. Shin reported receiving research Funding from the National Institutes of Health and Merck; disclosures for the other authors are in the report. Dr. Hiremath reported having no relevant financial relationships.

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

Rosuvastatin for cholesterol lowering was associated with slightly greater risks for kidney harm than atorvastatin, risks that were greater at higher-dose levels, in a large retrospective cohort study.

The most potent statin on the market, rosuvastatin has been linked with excess risk for kidney damage compared with atorvastatin in case reports and small trials, but there has been little surveillance of the issue following its approval in 2003.

The current analysis “is one of the first and largest real-world studies” examining rosuvastatin versus atorvastatin for risk for hematuria, proteinuria, and kidney failure with replacement therapy – dialysis or transplantation – across a range of estimated glomerular filtration rates (eGFR) in a heterogeneous population, the researchers write.

“Our findings suggest the need for greater care in prescribing and monitoring of rosuvastatin, particularly in patients who are receiving high doses” or have severe chronic kidney disease (CKD), they concluded in their report published online in the Journal of the American Society of Nephrology.

The analysis included close to 1 million patients in the United States who were newly prescribed rosuvastatin or atorvastatin from 2011 through 2019; they were followed a median of 3.1 years. Among the findings:

• Users of rosuvastatin had an 8% higher risk for hematuria, a 17% higher risk for proteinuria, and a 15% higher risk for kidney failure with replacement therapy, compared with those on atorvastatin
• The two groups avoided MI and stroke to similar extents
• About 44% of patients with severe CKD G4+ (eGFR < 30 mL/min per 1.73 m2) were prescribed a higher rosuvastatin dosage than the maximum 10 mg/day recommended for such patients by the Food and Drug Administration.

From this study, “we do not know why the adherence of FDA dosing recommendation for rosuvastatin in patients with severe CKD is low,” lead author Jung-Im Shin, MD, PhD, said in an interview.

“It is likely that not many clinicians are aware of rosuvastatin’s dosing recommendations [in severe CKD], or potential risks of hematuria or proteinuria,” speculated Dr. Shin, assistant professor at Johns Hopkins University, Baltimore.

“High-dose rosuvastatin [and its cardiovascular benefits] may not merit the risk, even if small, particularly in low eGFR,” she said. “Our study provides the opportunity to increase awareness of this clinical issue.”

“Future studies are warranted to shed light on the discrepancy between real-world practice and FDA dosing recommendations for high-dose rosuvastatin,” the researchers noted.

‘Greater awareness and education are key’

Invited to comment, Swapnil Hiremath, MD, a nephrologist at the Ottawa Hospital Research Institute, noted that the higher risk for nephrotoxicity with high-dose rosuvastatin versus high-dose atorvastatin was shown in the PLANET 1 trial published in 2015 and in, for example, a case report published in 2016 – which the researchers also mention.

“I was personally surprised” at the high proportion of patients with severe CKD who received higher than recommended doses of rosuvastatin, said Dr. Hiremath, who is also an associate professor at the University of Ottawa and a Freely Filtered podcaster, and not associated with the current study.

“We do see this occasionally,” he continued, “but either because someone is targeting LDL [cholesterol] and hasn’t noted the GFR, or possibly the patient was started on a high dose a long time ago and the kidney function has declined, and no one has noted the high dose.”

“Greater awareness and education are key,” observed Dr. Hiremath. “My personal bias is to have renal pharmacists involved in multidisciplinary clinics when GFR [is] less than 30 or so,” he said. “There are so many other tricky medicine/interaction issues” in patients with kidney disease.

Nevertheless, “I would be careful in drawing too many conclusions from an observational study,” Dr. Hiremath added. “There’s always the threat of residual confounding and selection bias,” which the researchers acknowledge, “and especially competing risks.”

For example, “if there is less cardiovascular death with rosuvastatin, then more people will remain alive to develop kidney failure.”
 

Dosing in practice unclear

Atorvastatin at 40-mg and 80-mg dosages and rosuvastatin at 20 mg and 40 mg are the only two statins considered high-intensity, the researchers noted.

Development of an 80-mg dosage for rosuvastatin was dropped because of hematuria and proteinuria safety signals highlighted at the time of rosuvastatin’s FDA approval.

However, there has been little postmarketing surveillance to assess real-world risk from high-intensity rosuvastatin, and it remains unclear whether and to what extent clinical practice adheres to the starting dosage recommended by the FDA in severe CKD, 5 mg/day with a maximum of 10 mg/day, the report noted.

The researchers analyzed deidentified electronic health record data from 40 health care organizations in the United States from the OptumLabs Data Warehouse database. They entered 152,101 new rosuvastatin users and 795,799 new atorvastatin users, and excluded patients with a history of rhabdomyolysis.

Patients in the two groups were similar with respect to CKD prevalence, cardiovascular risk factors, and demographics. Their age averaged 60 years, 48% were women, and 82% were White.

Hematuria was defined as dipstick hematuria > + or the presence of more than 3 red blood cells per high-power field in urine microscopy, at least twice. Proteinuria was defined as dipstick proteinuria > ++ or urine albumin-to-creatinine ratio greater than 300 mg/g at least twice.

Overall, 2.9% of patients had hematuria (3.4% of the rosuvastatin group and 2.8% of those taking atorvastatin) and 1% of patients had proteinuria (1.2% and 0.9%, respectively).

After balancing baseline characteristics in both groups using inverse probability of treatment weighting, rosuvastatin treatment, compared with atorvastatin, was associated with significantly greater risks for hematuria (hazard ratio, 1.08), proteinuria (HR, 1.17), and kidney failure requiring replacement therapy (HR, 1.15).  

Patients with eGFR less than 30 mL/min per 1.73 m2 had an approximately twofold higher risk for hematuria and ninefold higher risk for proteinuria during the follow-up compared with patients with eGFR of at least 60 mL/min per 1.73 m2.

Patients with eGFR less than 30 mL/min per 1.73 m2 were commonly prescribed high-dose rosuvastatin (29.9% received the 20-mg dose and 14% the 40-mg dose), contrary to the labeling recommendation.

Dr. Shin reported receiving research Funding from the National Institutes of Health and Merck; disclosures for the other authors are in the report. Dr. Hiremath reported having no relevant financial relationships.

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

For patients with advanced hepatocellular carcinoma (HCC), immune checkpoint inhibitors (ICIs) may be the safer choice over tyrosine kinase inhibitors (TKIs), shows a new systematic review and meta-analysis.

The study, which was published online in JAMA Network Open, found that ICIs were associated with fewer serious adverse events, such as death, illness requiring hospitalization or illness leading to disability.

The findings are based on a meta-analysis of 30 randomized clinical trials and 12,921 patients. The analysis found a greater frequency of serious adverse events among those treated with TKIs than those treated with ICIs, though the rates of less serious liver-related adverse events were similar.

“When considering objective response rates, combination therapy with atezolizumab and bevacizumab or lenvatinib alone likely offer the most promise in the neoadjuvant setting in terms of objective response and toxic effects without preventing patients from reaching surgery,” the authors wrote.

Most newly diagnosed cases of HCC are unresectable, which leads to palliative treatment. When disease is advanced, systemic treatment is generally chosen, and new options introduced in the past decade have boosted survival. Many of these approaches feature ICIs and TKIs.

HCC therapy continues to evolve, with targeted surgical and locoregional therapies like ablation and embolization, and it’s important to understand how side effects from ICIs and TKIs might impact follow-on procedures.

Neoadjuvant therapy can avoid delays to adjuvant chemotherapy that might occur due to surgical complications. Neoadjuvant therapy also has the potential to downstage the disease from advanced to resectable, and it can provide greater opportunity for patient selection based on both tumor biology and patient characteristics.

However, advanced HCC is a complicated condition. Patients typically have cirrhosis and require an adequate functional liver remnant. Neoadjuvant locoregional treatment has been studied in HCC. A systematic review of 55 studies found no significant difference in disease-free or overall survival between preoperative or postoperative transarterial chemoembolization in resectable HCC. There is some weak evidence that locoregional therapies may achieve downstaging or maintain candidacy past 6 months.

The median age of participants was 62 years. Among the included studies, on average, 84% of patients were male. The mean fraction of patients with disease originating outside the liver was 61%, and the mean percentage with microvascular invasion was 28%. A mean of 82% had stage C according to Barcelona Clinic Liver Center staging.

21% of patients who received TKIs (95% confidence interval, 16%-26%) experienced liver toxicities versus 24% (95% CI, 13%-35%) of patients receiving ICIs. Severe adverse events were more common with TKIs, with a frequency of 46% (95% CI, 40%-51%), compared with 24% of those who received ICIs (95% CI, 13%-35%).

TKIs other than sorafenib were associated with higher rates of severe adverse events (risk ratio, 1.24; 95% CI, 1.07-1.44). ICIs and sorafenib had similar rates of liver toxic effects and severe adverse events.

The study has some limitations, including variations within the included studies in the way adverse events were reported, and there was variation in the inclusion criteria.

For patients with advanced hepatocellular carcinoma (HCC), immune checkpoint inhibitors (ICIs) may be the safer choice over tyrosine kinase inhibitors (TKIs), shows a new systematic review and meta-analysis.

The study, which was published online in JAMA Network Open, found that ICIs were associated with fewer serious adverse events, such as death, illness requiring hospitalization or illness leading to disability.

The findings are based on a meta-analysis of 30 randomized clinical trials and 12,921 patients. The analysis found a greater frequency of serious adverse events among those treated with TKIs than those treated with ICIs, though the rates of less serious liver-related adverse events were similar.

“When considering objective response rates, combination therapy with atezolizumab and bevacizumab or lenvatinib alone likely offer the most promise in the neoadjuvant setting in terms of objective response and toxic effects without preventing patients from reaching surgery,” the authors wrote.

Most newly diagnosed cases of HCC are unresectable, which leads to palliative treatment. When disease is advanced, systemic treatment is generally chosen, and new options introduced in the past decade have boosted survival. Many of these approaches feature ICIs and TKIs.

HCC therapy continues to evolve, with targeted surgical and locoregional therapies like ablation and embolization, and it’s important to understand how side effects from ICIs and TKIs might impact follow-on procedures.

Neoadjuvant therapy can avoid delays to adjuvant chemotherapy that might occur due to surgical complications. Neoadjuvant therapy also has the potential to downstage the disease from advanced to resectable, and it can provide greater opportunity for patient selection based on both tumor biology and patient characteristics.

However, advanced HCC is a complicated condition. Patients typically have cirrhosis and require an adequate functional liver remnant. Neoadjuvant locoregional treatment has been studied in HCC. A systematic review of 55 studies found no significant difference in disease-free or overall survival between preoperative or postoperative transarterial chemoembolization in resectable HCC. There is some weak evidence that locoregional therapies may achieve downstaging or maintain candidacy past 6 months.

The median age of participants was 62 years. Among the included studies, on average, 84% of patients were male. The mean fraction of patients with disease originating outside the liver was 61%, and the mean percentage with microvascular invasion was 28%. A mean of 82% had stage C according to Barcelona Clinic Liver Center staging.

21% of patients who received TKIs (95% confidence interval, 16%-26%) experienced liver toxicities versus 24% (95% CI, 13%-35%) of patients receiving ICIs. Severe adverse events were more common with TKIs, with a frequency of 46% (95% CI, 40%-51%), compared with 24% of those who received ICIs (95% CI, 13%-35%).

TKIs other than sorafenib were associated with higher rates of severe adverse events (risk ratio, 1.24; 95% CI, 1.07-1.44). ICIs and sorafenib had similar rates of liver toxic effects and severe adverse events.

The study has some limitations, including variations within the included studies in the way adverse events were reported, and there was variation in the inclusion criteria.

For patients with advanced hepatocellular carcinoma (HCC), immune checkpoint inhibitors (ICIs) may be the safer choice over tyrosine kinase inhibitors (TKIs), shows a new systematic review and meta-analysis.

The study, which was published online in JAMA Network Open, found that ICIs were associated with fewer serious adverse events, such as death, illness requiring hospitalization or illness leading to disability.

The findings are based on a meta-analysis of 30 randomized clinical trials and 12,921 patients. The analysis found a greater frequency of serious adverse events among those treated with TKIs than those treated with ICIs, though the rates of less serious liver-related adverse events were similar.

“When considering objective response rates, combination therapy with atezolizumab and bevacizumab or lenvatinib alone likely offer the most promise in the neoadjuvant setting in terms of objective response and toxic effects without preventing patients from reaching surgery,” the authors wrote.

Most newly diagnosed cases of HCC are unresectable, which leads to palliative treatment. When disease is advanced, systemic treatment is generally chosen, and new options introduced in the past decade have boosted survival. Many of these approaches feature ICIs and TKIs.

HCC therapy continues to evolve, with targeted surgical and locoregional therapies like ablation and embolization, and it’s important to understand how side effects from ICIs and TKIs might impact follow-on procedures.

Neoadjuvant therapy can avoid delays to adjuvant chemotherapy that might occur due to surgical complications. Neoadjuvant therapy also has the potential to downstage the disease from advanced to resectable, and it can provide greater opportunity for patient selection based on both tumor biology and patient characteristics.

However, advanced HCC is a complicated condition. Patients typically have cirrhosis and require an adequate functional liver remnant. Neoadjuvant locoregional treatment has been studied in HCC. A systematic review of 55 studies found no significant difference in disease-free or overall survival between preoperative or postoperative transarterial chemoembolization in resectable HCC. There is some weak evidence that locoregional therapies may achieve downstaging or maintain candidacy past 6 months.

The median age of participants was 62 years. Among the included studies, on average, 84% of patients were male. The mean fraction of patients with disease originating outside the liver was 61%, and the mean percentage with microvascular invasion was 28%. A mean of 82% had stage C according to Barcelona Clinic Liver Center staging.

21% of patients who received TKIs (95% confidence interval, 16%-26%) experienced liver toxicities versus 24% (95% CI, 13%-35%) of patients receiving ICIs. Severe adverse events were more common with TKIs, with a frequency of 46% (95% CI, 40%-51%), compared with 24% of those who received ICIs (95% CI, 13%-35%).

TKIs other than sorafenib were associated with higher rates of severe adverse events (risk ratio, 1.24; 95% CI, 1.07-1.44). ICIs and sorafenib had similar rates of liver toxic effects and severe adverse events.

The study has some limitations, including variations within the included studies in the way adverse events were reported, and there was variation in the inclusion criteria.

An overreliance on spirometry to identify emphysema led to missed cases in Black individuals, particularly men, based on a secondary data analysis of 2,674 people.

“Over the last few years, there has been growing debate around the use of race adjustment in diagnostic algorithms and equations commonly used in medicine,” lead author Gabrielle Yi-Hui Liu, MD, said in an interview. “Whereas, previously it was common to accept racial or ethnic differences in clinical measures and outcomes as inherent differences among populations, there is now more recognition of how racism, socioeconomic status, and environmental exposures can cause these racial differences. Our initial interest in this study was to examine how the use of race-specific spirometry reference equations, and the use of spirometry in general, may be contributing to racial disparities.”

“Previous studies have suggested that the use of race-specific equations in spirometry can exacerbate racial inequities in healthcare outcomes by under-recognition of early disease in Black adults, and this study adds to that evidence,” said Suman Pal, MBBS, of the University of New Mexico, Albuquerque, in an interview.
“By examining the crucial ways in which systemic factors in medicine, such as race-specific equations, exacerbate racial inequities in healthcare, this study is a timely analysis in a moment of national reckoning of structural racism,” said Dr. Pal, who was not involved in the study.

jgaunion/Thinkstock

In a study published in Annals of Internal Medicine, Dr. Liu and colleagues at Northwestern University, Chicago, conducted a secondary analysis of data from the CARDIA Lung study (Coronary Artery Risk Development In Young Adults).

The primary outcome of the study was the prevalence of emphysema among participants with various measures of normal spirometry results, stratified by sex and race. The normal results included an forced expiratory volume in 1 second (FEV₁₎–forced vital capacity (FVC) ratio greater than or equal to 0.7 or greater than or equal to the lower limit of normal. The participants also were stratified by FEV₁ percent predicted, using race-specific reference equations, for FEV₁ between 80% and 99% of predicted, or an FEV₁ between 100% and 120% of predicted.

The study population included 485 Black men, 762 Black women, 659 White men, and 768 White women who received both a CT scan (in 2010-2011) and spirometry (obtained in 2015-2016) in the CARDIA study. The mean age of the participants at the spirometry exam was 55 years.

A total of 5.3% of the participants had emphysema after stratifying by FEV₁-FVC ratio. The prevalence was significantly higher for Black men, compared with White men (12.3% vs. 4.0%; relative risk, 3.0), and for Black women, compared with White women (5.0% vs. 2.6%; RR, 1.9).

The association between Black race and emphysema risk persisted but decreased when the researchers used a race-neutral estimate.

When the participants were stratified by race-specific FEV₁ percent predicted, 6.5% of individuals with a race-specific FEV₁ between 80% and 99% had emphysema. After controlling for factors including age and smoking, emphysema was significantly more prevalent in Black men versus White men (15.5% vs. 4.0%) and in Black women, compared with White women (6.6% vs. 3.4%).

The racial difference persisted in men with a race-specific FEV₁ between 100% and 120% of predicted. Of these, 4.0% had emphysema. The prevalence was significantly higher in Black men, compared with White men (13.9% vs. 2.2%), but similar between Black women and White women (2.6% vs. 2.0%).

The use of race-neutral equations reduced, but did not eliminate, these disparities, the researchers said.

The findings were limited by the lack of CT imaging data from the same visit as the final spirometry collection, the researchers noted. “Given that imaging was obtained 5 years before spirometry and emphysema is an irreversible finding, this may have led to an overall underestimation of the prevalence of emphysema.”
 

Spirometry alone misses cases

“We were surprised by the substantial rates of emphysema we saw among Black men in our cohort with normal spirometry,” Dr. Liu said in an interview. “We did not expect to find than more than one in eight Black men with an FEV₁ between 100% and 120% predicted would have emphysema – a rate more than six times higher than White men with the same range of FEV₁.”

“One takeaway is that we are likely missing a lot of people with impaired respiratory health or true lung disease by only using spirometry to diagnose COPD,” said Dr. Liu. In clinical practice, “physicians should consider ordering CT scans on patients with normal spirometry who have respiratory symptoms such as cough or shortness of breath. If emphysema is found, physicians should discuss mitigating any potential risk factors and consider the use of COPD medications such as inhalers.

“Our findings also support using race-neutral reference equations to interpret spirometry instead of race-specific equations. Racial disparities in rates of emphysema among those with ‘normal’ FEV₁ [between 80% and 120% predicted], were attenuated or eliminated when race-neutral equations were used to calculate FEV₁. This suggests that race-specific equations are normalizing worse lung health in Black adults,” Dr. Liu explained.

“We need to continue research into additional tools that can be used to assess respiratory health and diagnose COPD, while keeping in mind how these tools may affect racial disparities,” said Dr. Liu. “Our study suggests that our reliance on spirometry measures such as FEV₁/FVC ratio and FEV₁ is missing a number of people with respiratory symptoms and CT evidence of lung disease, and that this is disproportionately affecting Black adults in the United States.” Looking ahead, “it is important to find better tools to identify people with impaired respiratory health or early manifestations of disease so we can intercept chronic lung disease before it becomes clinically apparent and patients have sustained significant lung damage.”

The CARDIA study was supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham, Northwestern University, the University of Minnesota, and the Kaiser Foundation Research Institute. Dr. Liu was supported by a grant from the National Institutes of Health. The researchers had no financial conflicts to disclose. Dr. Pal had no financial conflicts to disclose.

*This article was updated 7/22/2022.

An overreliance on spirometry to identify emphysema led to missed cases in Black individuals, particularly men, based on a secondary data analysis of 2,674 people.

“Over the last few years, there has been growing debate around the use of race adjustment in diagnostic algorithms and equations commonly used in medicine,” lead author Gabrielle Yi-Hui Liu, MD, said in an interview. “Whereas, previously it was common to accept racial or ethnic differences in clinical measures and outcomes as inherent differences among populations, there is now more recognition of how racism, socioeconomic status, and environmental exposures can cause these racial differences. Our initial interest in this study was to examine how the use of race-specific spirometry reference equations, and the use of spirometry in general, may be contributing to racial disparities.”

“Previous studies have suggested that the use of race-specific equations in spirometry can exacerbate racial inequities in healthcare outcomes by under-recognition of early disease in Black adults, and this study adds to that evidence,” said Suman Pal, MBBS, of the University of New Mexico, Albuquerque, in an interview.
“By examining the crucial ways in which systemic factors in medicine, such as race-specific equations, exacerbate racial inequities in healthcare, this study is a timely analysis in a moment of national reckoning of structural racism,” said Dr. Pal, who was not involved in the study.

jgaunion/Thinkstock

In a study published in Annals of Internal Medicine, Dr. Liu and colleagues at Northwestern University, Chicago, conducted a secondary analysis of data from the CARDIA Lung study (Coronary Artery Risk Development In Young Adults).

The primary outcome of the study was the prevalence of emphysema among participants with various measures of normal spirometry results, stratified by sex and race. The normal results included an forced expiratory volume in 1 second (FEV₁₎–forced vital capacity (FVC) ratio greater than or equal to 0.7 or greater than or equal to the lower limit of normal. The participants also were stratified by FEV₁ percent predicted, using race-specific reference equations, for FEV₁ between 80% and 99% of predicted, or an FEV₁ between 100% and 120% of predicted.

The study population included 485 Black men, 762 Black women, 659 White men, and 768 White women who received both a CT scan (in 2010-2011) and spirometry (obtained in 2015-2016) in the CARDIA study. The mean age of the participants at the spirometry exam was 55 years.

A total of 5.3% of the participants had emphysema after stratifying by FEV₁-FVC ratio. The prevalence was significantly higher for Black men, compared with White men (12.3% vs. 4.0%; relative risk, 3.0), and for Black women, compared with White women (5.0% vs. 2.6%; RR, 1.9).

The association between Black race and emphysema risk persisted but decreased when the researchers used a race-neutral estimate.

When the participants were stratified by race-specific FEV₁ percent predicted, 6.5% of individuals with a race-specific FEV₁ between 80% and 99% had emphysema. After controlling for factors including age and smoking, emphysema was significantly more prevalent in Black men versus White men (15.5% vs. 4.0%) and in Black women, compared with White women (6.6% vs. 3.4%).

The racial difference persisted in men with a race-specific FEV₁ between 100% and 120% of predicted. Of these, 4.0% had emphysema. The prevalence was significantly higher in Black men, compared with White men (13.9% vs. 2.2%), but similar between Black women and White women (2.6% vs. 2.0%).

The use of race-neutral equations reduced, but did not eliminate, these disparities, the researchers said.

The findings were limited by the lack of CT imaging data from the same visit as the final spirometry collection, the researchers noted. “Given that imaging was obtained 5 years before spirometry and emphysema is an irreversible finding, this may have led to an overall underestimation of the prevalence of emphysema.”
 

Spirometry alone misses cases

“We were surprised by the substantial rates of emphysema we saw among Black men in our cohort with normal spirometry,” Dr. Liu said in an interview. “We did not expect to find than more than one in eight Black men with an FEV₁ between 100% and 120% predicted would have emphysema – a rate more than six times higher than White men with the same range of FEV₁.”

“One takeaway is that we are likely missing a lot of people with impaired respiratory health or true lung disease by only using spirometry to diagnose COPD,” said Dr. Liu. In clinical practice, “physicians should consider ordering CT scans on patients with normal spirometry who have respiratory symptoms such as cough or shortness of breath. If emphysema is found, physicians should discuss mitigating any potential risk factors and consider the use of COPD medications such as inhalers.

“Our findings also support using race-neutral reference equations to interpret spirometry instead of race-specific equations. Racial disparities in rates of emphysema among those with ‘normal’ FEV₁ [between 80% and 120% predicted], were attenuated or eliminated when race-neutral equations were used to calculate FEV₁. This suggests that race-specific equations are normalizing worse lung health in Black adults,” Dr. Liu explained.

“We need to continue research into additional tools that can be used to assess respiratory health and diagnose COPD, while keeping in mind how these tools may affect racial disparities,” said Dr. Liu. “Our study suggests that our reliance on spirometry measures such as FEV₁/FVC ratio and FEV₁ is missing a number of people with respiratory symptoms and CT evidence of lung disease, and that this is disproportionately affecting Black adults in the United States.” Looking ahead, “it is important to find better tools to identify people with impaired respiratory health or early manifestations of disease so we can intercept chronic lung disease before it becomes clinically apparent and patients have sustained significant lung damage.”

The CARDIA study was supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham, Northwestern University, the University of Minnesota, and the Kaiser Foundation Research Institute. Dr. Liu was supported by a grant from the National Institutes of Health. The researchers had no financial conflicts to disclose. Dr. Pal had no financial conflicts to disclose.

*This article was updated 7/22/2022.

An overreliance on spirometry to identify emphysema led to missed cases in Black individuals, particularly men, based on a secondary data analysis of 2,674 people.

“Over the last few years, there has been growing debate around the use of race adjustment in diagnostic algorithms and equations commonly used in medicine,” lead author Gabrielle Yi-Hui Liu, MD, said in an interview. “Whereas, previously it was common to accept racial or ethnic differences in clinical measures and outcomes as inherent differences among populations, there is now more recognition of how racism, socioeconomic status, and environmental exposures can cause these racial differences. Our initial interest in this study was to examine how the use of race-specific spirometry reference equations, and the use of spirometry in general, may be contributing to racial disparities.”

“Previous studies have suggested that the use of race-specific equations in spirometry can exacerbate racial inequities in healthcare outcomes by under-recognition of early disease in Black adults, and this study adds to that evidence,” said Suman Pal, MBBS, of the University of New Mexico, Albuquerque, in an interview.
“By examining the crucial ways in which systemic factors in medicine, such as race-specific equations, exacerbate racial inequities in healthcare, this study is a timely analysis in a moment of national reckoning of structural racism,” said Dr. Pal, who was not involved in the study.

jgaunion/Thinkstock

In a study published in Annals of Internal Medicine, Dr. Liu and colleagues at Northwestern University, Chicago, conducted a secondary analysis of data from the CARDIA Lung study (Coronary Artery Risk Development In Young Adults).

The primary outcome of the study was the prevalence of emphysema among participants with various measures of normal spirometry results, stratified by sex and race. The normal results included an forced expiratory volume in 1 second (FEV₁₎–forced vital capacity (FVC) ratio greater than or equal to 0.7 or greater than or equal to the lower limit of normal. The participants also were stratified by FEV₁ percent predicted, using race-specific reference equations, for FEV₁ between 80% and 99% of predicted, or an FEV₁ between 100% and 120% of predicted.

The study population included 485 Black men, 762 Black women, 659 White men, and 768 White women who received both a CT scan (in 2010-2011) and spirometry (obtained in 2015-2016) in the CARDIA study. The mean age of the participants at the spirometry exam was 55 years.

A total of 5.3% of the participants had emphysema after stratifying by FEV₁-FVC ratio. The prevalence was significantly higher for Black men, compared with White men (12.3% vs. 4.0%; relative risk, 3.0), and for Black women, compared with White women (5.0% vs. 2.6%; RR, 1.9).

The association between Black race and emphysema risk persisted but decreased when the researchers used a race-neutral estimate.

When the participants were stratified by race-specific FEV₁ percent predicted, 6.5% of individuals with a race-specific FEV₁ between 80% and 99% had emphysema. After controlling for factors including age and smoking, emphysema was significantly more prevalent in Black men versus White men (15.5% vs. 4.0%) and in Black women, compared with White women (6.6% vs. 3.4%).

The racial difference persisted in men with a race-specific FEV₁ between 100% and 120% of predicted. Of these, 4.0% had emphysema. The prevalence was significantly higher in Black men, compared with White men (13.9% vs. 2.2%), but similar between Black women and White women (2.6% vs. 2.0%).

The use of race-neutral equations reduced, but did not eliminate, these disparities, the researchers said.

The findings were limited by the lack of CT imaging data from the same visit as the final spirometry collection, the researchers noted. “Given that imaging was obtained 5 years before spirometry and emphysema is an irreversible finding, this may have led to an overall underestimation of the prevalence of emphysema.”
 

Spirometry alone misses cases

“We were surprised by the substantial rates of emphysema we saw among Black men in our cohort with normal spirometry,” Dr. Liu said in an interview. “We did not expect to find than more than one in eight Black men with an FEV₁ between 100% and 120% predicted would have emphysema – a rate more than six times higher than White men with the same range of FEV₁.”

“One takeaway is that we are likely missing a lot of people with impaired respiratory health or true lung disease by only using spirometry to diagnose COPD,” said Dr. Liu. In clinical practice, “physicians should consider ordering CT scans on patients with normal spirometry who have respiratory symptoms such as cough or shortness of breath. If emphysema is found, physicians should discuss mitigating any potential risk factors and consider the use of COPD medications such as inhalers.

“Our findings also support using race-neutral reference equations to interpret spirometry instead of race-specific equations. Racial disparities in rates of emphysema among those with ‘normal’ FEV₁ [between 80% and 120% predicted], were attenuated or eliminated when race-neutral equations were used to calculate FEV₁. This suggests that race-specific equations are normalizing worse lung health in Black adults,” Dr. Liu explained.

“We need to continue research into additional tools that can be used to assess respiratory health and diagnose COPD, while keeping in mind how these tools may affect racial disparities,” said Dr. Liu. “Our study suggests that our reliance on spirometry measures such as FEV₁/FVC ratio and FEV₁ is missing a number of people with respiratory symptoms and CT evidence of lung disease, and that this is disproportionately affecting Black adults in the United States.” Looking ahead, “it is important to find better tools to identify people with impaired respiratory health or early manifestations of disease so we can intercept chronic lung disease before it becomes clinically apparent and patients have sustained significant lung damage.”

The CARDIA study was supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham, Northwestern University, the University of Minnesota, and the Kaiser Foundation Research Institute. Dr. Liu was supported by a grant from the National Institutes of Health. The researchers had no financial conflicts to disclose. Dr. Pal had no financial conflicts to disclose.

*This article was updated 7/22/2022.

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

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

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

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

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

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

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

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

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

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

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

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

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

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


 

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

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

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

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

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

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

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

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

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

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

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

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

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

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


 

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

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

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

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

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

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

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

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

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

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

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

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

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

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


 

Medically reviewed by Jennifer Casarella, MD

Dan Miller has parked his Nissan Altima on the side of the road near a field outside Chicago and is holding a gun to his head. 

Haunted for years by the compounded trauma of tours of duty in the Middle East and his work as a police officer in Chicago, at that moment, Dr. Miller saw no reason to live. And there were troubles at home with his wife and children, who had grown fearful of his behavior.

“My whole world was falling apart,” he says of that dark night in 2014. “It left a hole I didn’t know how to fill.”

He chose not to pull the trigger after a brochure on the passenger seat of his car gave him an unexpected perspective – and launched him on a path to help others in his situation.

Had Mr. Miller taken his life that night, he would have joined thousands of other veterans who died by suicide. About 17 U.S. veterans lose their lives this way each day, on average, according to the Department of Veterans Affairs. In 2019, the last year for which records are available, 6,261 veterans took their own lives – and the suicide rate for veterans was 52% higher than for nonveterans, the agency’s records show. 

The problem has become so severe that the Veterans Health Administration now uses artificial intelligence (AI) to help identify veterans at the highest risk of suicide – and reach out to them before a crisis strikes.

But that wasn’t available when Dan Miller’s life was unraveling.

In the years leading up to his near-suicide, his wife had pushed him to get help. “She said, ‘You’re not the same person you were when you left. The kids are scared of you. The pets are scared of you,” he recalls.

He resisted, even when his wife threatened divorce. Rising through the ranks of the Marines, Mr. Miller had become more emotionally isolated. He feared losing his job and the respect of others if he let anyone know what he was going through.

Finally, he gave the VHA a chance. He went in for an initial consultation in 2010 and didn’t find it helpful. He didn’t like being told what to do. So he stopped. He turned to obsessive exercise and excessive drinking.

That day in 2014, Mr. Miller’s wife told him she was taking the kids out for a playdate. After she left, he was served with divorce papers. Less than an hour later, he was parked in his car with his gun, ready to end his life.

But if it all had happened just a few years later, things might never have gotten to that point.
 

Scanning for suicide risk

In 2017, the VHA piloted its AI program, called REACH VET, that aims to help prevent veterans from dying by suicide.

Every month, a computer scans the electronic health records of all VHA patients who’ve had a health care visit for any reason in the last 2 years. It checks more than 140 variables and weights them to estimate someone’s overall suicide risk at that moment in time.

To build the risk algorithm, a computer combed through the medical records of 6,360 veterans confirmed to have died by suicide between 2009 and 2011. (The VHA continually updates the list of variables from the health records of VHA patients, including those who have died by suicide since then and others.)

Some variables are things you’d expect:

• A past suicide attempt.
• A diagnosis of depression or other mental illness.
• A diagnosis of a terminal illness.

Others are more surprising. For example, a diagnosis of arthritis or diabetes adds weight.

REACH VET flags the riskiest cases – the top 0.1% – for a mental health or primary care provider to review. They reach out to the patient to tell them how and why their record was flagged, discuss any recommended treatment changes, and ask them to come in for a visit.

“It’s an opportunity to talk about their risk factors, which is designed to lead to a conversation about safety planning,” says clinical psychologist Matthew Miller, PhD, national director of the U.S. Department of Veterans Affairs’ Suicide Prevention Program. He’s not related to Dan Miller.

Making a suicide safety plan

A safety plan is a document that outlines how a person can help prevent their own suicide in a crisis. 

The plan may include:

• A list of personal triggers or warning signs.
• What’s helped them in the past.
• Names of people or organizations who can support them.
• Plans to remove means of suicide, such as guns, from their environment.
• Their reasons for living.

In people at risk for suicide, research shows that having a safety plan reduces suicidal thoughts and attempts, lowers rates of depression and hopelessness, and boosts veterans’ engagement with the health care system. It may also help people manage things that trigger their suicidal thoughts.
 

Getting the call

What if REACH VET had been around when Dan Miller was in crisis – and he’d gotten a call from the VHA?

“It absolutely, positively would have helped because one of the biggest things on that day when I got served was feeling completely alone and that I had no one to turn to,” Mr. Miller says. He’s now a speaker for the Wounded Warrior Project, a nonprofit that serves veterans and active-duty service people.

Vets’ reactions to the unexpected VHA phone call, psychologist Dr. Miller says, “run the gamut from ‘Thank you for contacting me. Let’s talk,’ to ‘What are you talking about? Leave me alone!’ ”

Nothing stops all suicides. But REACH VET is having an impact. In a clinical trial, vets contacted through REACH VET had more doctor visits, were more likely to have a written suicide prevention safety plan, and had fewer hospital admissions for mental health, ER visits, and suicide attempts.
 

An assist from AI

Even simple outreach can make a big difference. And there’s research to prove it.

One study included 4,730 veterans recently discharged from psychiatric care at the VHA, a group considered at high risk for suicide. 

Half of them got 13 caring emails from hospital staff in the weeks after leaving the hospital. The emails mentioned personal things the patient had shared, like a love of hiking, and wished them well. The other veterans got routine follow-up but no emails.

Two years later, those who got the caring emails were less likely to have died by suicide than the other vets. The study was published in 2014 in Contemporary Clinical Trials.

Researchers have done studies like this many times: with handwritten notes from the primary care doctor, postcards from the ER, and so forth. The results never vary: The notes reduce suicide risk.

“If we could use AI to identify people to receive notes or phone calls, it would be a very effective and inexpensive way to guide follow-up care,” says Rebecca Bernert, PhD, director and founder of the Suicide Prevention Research Laboratory at Stanford (Calif.) University.
 

AI doesn’t replace clinical judgment.

“AI can capture data that we miss due to the limits of our humanity,” psychologist Dr. Miller says. “There’s suicide prevention processes founded on big data and AI, and there are processes founded in clinical intuition and acumen.”

AI is only as good as the data it’s based on. If that data lacks diversity, it may miss things. And variables that apply to veterans may differ in civilians.
 

Stopping suicidal thoughts

Google is putting AI to work against suicide, too. Its MUM (Multitask Unified Model) technology seeks to understand the intent behind what we google.

MUM powers Google Search. It can often tell the difference between a search for information about suicide for someone writing a research paper on the topic and a search for information on how or where to carry out a suicide.

When Google Search detects that someone in the United States might be in crisis and at risk of suicide, the first search results that person gets are the number for the National Suicide Prevention Lifeline and other resources for people in crisis.

Google Home Assistant works in the same way. When a user makes a query that signals a suicide-related crisis, the gadget serves up resources that offer help.

MUM is working to understand the nuances of crisis language in 75 languages so that Google Search can provide people in crisis with hotlines or other resources in many countries.

“We want to find partners that are accessible to users in terms of hours of operation. We have a strong preference for finding partners that promise confidentiality and privacy to the extent that those are permitted [in that country],” says Anne Merritt, MD, a product manager at Google Search.

Other companies are working on apps that use AI to spot suicide risk in other ways, including voice technology that may notice subtle changes in the voice of someone who’s depressed and may be thinking of suicide. Those are still in development but show promise. Keep in mind that apps do not require government approval, so if you try one, be sure to let your health care provider know.
 

Changing the channel

Seeing a hotline number on your phone or computer screen can help, Dan Miller says. “If I happened to be online, searching maybe for a bridge to jump off of ... and suddenly that pops up on the screen, it’s like it changes the channel.”

It may not work for everyone, he says, but that search result could interrupt someone’s suicidal train of thought.

That’s crucial, psychologist Dr. Miller says, because most suicide attempts escalate from first thought to potentially fatal action in just 1 hour. That’s how fast it happened for Dan Miller in 2014.

“When you’re able to put time and space between the suicidal thought and the access to the method to act on that thought, you save lives,” Dr. Bernert says.
 

Making a different choice

An interruption in Mr. Miller’s thinking is what had saved his life.

Holding the gun to his head, Mr. Miller looked over at the passenger seat at a brochure from Wounded Warrior Project, which he had just learned about. Mr. Miller noticed a photo of a man in a wheelchair, a veteran like him, who had no legs. He thought that the man looked worse off than him but hadn’t given up.

Mr. Miller put down his gun and decided to get help.

Recovering from a near suicide attempt, he says, is a journey. It doesn’t happen overnight. Now, 8 years later, Mr. Miller is planning a brief break from the speaker circuit. He plans to spend 2 weeks in an outpatient counseling program for posttraumatic stress disorder and traumatic brain injury.

“Telling my story to strangers – part of it is healing me in a way, but I’m learning that repeating the story over and over again is also keeping me from letting it go. And I’m still healing.”

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

Medically reviewed by Jennifer Casarella, MD

Dan Miller has parked his Nissan Altima on the side of the road near a field outside Chicago and is holding a gun to his head. 

Haunted for years by the compounded trauma of tours of duty in the Middle East and his work as a police officer in Chicago, at that moment, Dr. Miller saw no reason to live. And there were troubles at home with his wife and children, who had grown fearful of his behavior.

“My whole world was falling apart,” he says of that dark night in 2014. “It left a hole I didn’t know how to fill.”

He chose not to pull the trigger after a brochure on the passenger seat of his car gave him an unexpected perspective – and launched him on a path to help others in his situation.

Had Mr. Miller taken his life that night, he would have joined thousands of other veterans who died by suicide. About 17 U.S. veterans lose their lives this way each day, on average, according to the Department of Veterans Affairs. In 2019, the last year for which records are available, 6,261 veterans took their own lives – and the suicide rate for veterans was 52% higher than for nonveterans, the agency’s records show. 

The problem has become so severe that the Veterans Health Administration now uses artificial intelligence (AI) to help identify veterans at the highest risk of suicide – and reach out to them before a crisis strikes.

But that wasn’t available when Dan Miller’s life was unraveling.

In the years leading up to his near-suicide, his wife had pushed him to get help. “She said, ‘You’re not the same person you were when you left. The kids are scared of you. The pets are scared of you,” he recalls.

He resisted, even when his wife threatened divorce. Rising through the ranks of the Marines, Mr. Miller had become more emotionally isolated. He feared losing his job and the respect of others if he let anyone know what he was going through.

Finally, he gave the VHA a chance. He went in for an initial consultation in 2010 and didn’t find it helpful. He didn’t like being told what to do. So he stopped. He turned to obsessive exercise and excessive drinking.

That day in 2014, Mr. Miller’s wife told him she was taking the kids out for a playdate. After she left, he was served with divorce papers. Less than an hour later, he was parked in his car with his gun, ready to end his life.

But if it all had happened just a few years later, things might never have gotten to that point.
 

Scanning for suicide risk

In 2017, the VHA piloted its AI program, called REACH VET, that aims to help prevent veterans from dying by suicide.

Every month, a computer scans the electronic health records of all VHA patients who’ve had a health care visit for any reason in the last 2 years. It checks more than 140 variables and weights them to estimate someone’s overall suicide risk at that moment in time.

To build the risk algorithm, a computer combed through the medical records of 6,360 veterans confirmed to have died by suicide between 2009 and 2011. (The VHA continually updates the list of variables from the health records of VHA patients, including those who have died by suicide since then and others.)

Some variables are things you’d expect:

• A past suicide attempt.
• A diagnosis of depression or other mental illness.
• A diagnosis of a terminal illness.

Others are more surprising. For example, a diagnosis of arthritis or diabetes adds weight.

REACH VET flags the riskiest cases – the top 0.1% – for a mental health or primary care provider to review. They reach out to the patient to tell them how and why their record was flagged, discuss any recommended treatment changes, and ask them to come in for a visit.

“It’s an opportunity to talk about their risk factors, which is designed to lead to a conversation about safety planning,” says clinical psychologist Matthew Miller, PhD, national director of the U.S. Department of Veterans Affairs’ Suicide Prevention Program. He’s not related to Dan Miller.

Making a suicide safety plan

A safety plan is a document that outlines how a person can help prevent their own suicide in a crisis. 

The plan may include:

• A list of personal triggers or warning signs.
• What’s helped them in the past.
• Names of people or organizations who can support them.
• Plans to remove means of suicide, such as guns, from their environment.
• Their reasons for living.

In people at risk for suicide, research shows that having a safety plan reduces suicidal thoughts and attempts, lowers rates of depression and hopelessness, and boosts veterans’ engagement with the health care system. It may also help people manage things that trigger their suicidal thoughts.
 

Getting the call

What if REACH VET had been around when Dan Miller was in crisis – and he’d gotten a call from the VHA?

“It absolutely, positively would have helped because one of the biggest things on that day when I got served was feeling completely alone and that I had no one to turn to,” Mr. Miller says. He’s now a speaker for the Wounded Warrior Project, a nonprofit that serves veterans and active-duty service people.

Vets’ reactions to the unexpected VHA phone call, psychologist Dr. Miller says, “run the gamut from ‘Thank you for contacting me. Let’s talk,’ to ‘What are you talking about? Leave me alone!’ ”

Nothing stops all suicides. But REACH VET is having an impact. In a clinical trial, vets contacted through REACH VET had more doctor visits, were more likely to have a written suicide prevention safety plan, and had fewer hospital admissions for mental health, ER visits, and suicide attempts.
 

An assist from AI

Even simple outreach can make a big difference. And there’s research to prove it.

One study included 4,730 veterans recently discharged from psychiatric care at the VHA, a group considered at high risk for suicide. 

Half of them got 13 caring emails from hospital staff in the weeks after leaving the hospital. The emails mentioned personal things the patient had shared, like a love of hiking, and wished them well. The other veterans got routine follow-up but no emails.

Two years later, those who got the caring emails were less likely to have died by suicide than the other vets. The study was published in 2014 in Contemporary Clinical Trials.

Researchers have done studies like this many times: with handwritten notes from the primary care doctor, postcards from the ER, and so forth. The results never vary: The notes reduce suicide risk.

“If we could use AI to identify people to receive notes or phone calls, it would be a very effective and inexpensive way to guide follow-up care,” says Rebecca Bernert, PhD, director and founder of the Suicide Prevention Research Laboratory at Stanford (Calif.) University.
 

AI doesn’t replace clinical judgment.

“AI can capture data that we miss due to the limits of our humanity,” psychologist Dr. Miller says. “There’s suicide prevention processes founded on big data and AI, and there are processes founded in clinical intuition and acumen.”

AI is only as good as the data it’s based on. If that data lacks diversity, it may miss things. And variables that apply to veterans may differ in civilians.
 

Stopping suicidal thoughts

Google is putting AI to work against suicide, too. Its MUM (Multitask Unified Model) technology seeks to understand the intent behind what we google.

MUM powers Google Search. It can often tell the difference between a search for information about suicide for someone writing a research paper on the topic and a search for information on how or where to carry out a suicide.

When Google Search detects that someone in the United States might be in crisis and at risk of suicide, the first search results that person gets are the number for the National Suicide Prevention Lifeline and other resources for people in crisis.

Google Home Assistant works in the same way. When a user makes a query that signals a suicide-related crisis, the gadget serves up resources that offer help.

MUM is working to understand the nuances of crisis language in 75 languages so that Google Search can provide people in crisis with hotlines or other resources in many countries.

“We want to find partners that are accessible to users in terms of hours of operation. We have a strong preference for finding partners that promise confidentiality and privacy to the extent that those are permitted [in that country],” says Anne Merritt, MD, a product manager at Google Search.

Other companies are working on apps that use AI to spot suicide risk in other ways, including voice technology that may notice subtle changes in the voice of someone who’s depressed and may be thinking of suicide. Those are still in development but show promise. Keep in mind that apps do not require government approval, so if you try one, be sure to let your health care provider know.
 

Changing the channel

Seeing a hotline number on your phone or computer screen can help, Dan Miller says. “If I happened to be online, searching maybe for a bridge to jump off of ... and suddenly that pops up on the screen, it’s like it changes the channel.”

It may not work for everyone, he says, but that search result could interrupt someone’s suicidal train of thought.

That’s crucial, psychologist Dr. Miller says, because most suicide attempts escalate from first thought to potentially fatal action in just 1 hour. That’s how fast it happened for Dan Miller in 2014.

“When you’re able to put time and space between the suicidal thought and the access to the method to act on that thought, you save lives,” Dr. Bernert says.
 

Making a different choice

An interruption in Mr. Miller’s thinking is what had saved his life.

Holding the gun to his head, Mr. Miller looked over at the passenger seat at a brochure from Wounded Warrior Project, which he had just learned about. Mr. Miller noticed a photo of a man in a wheelchair, a veteran like him, who had no legs. He thought that the man looked worse off than him but hadn’t given up.

Mr. Miller put down his gun and decided to get help.

Recovering from a near suicide attempt, he says, is a journey. It doesn’t happen overnight. Now, 8 years later, Mr. Miller is planning a brief break from the speaker circuit. He plans to spend 2 weeks in an outpatient counseling program for posttraumatic stress disorder and traumatic brain injury.

“Telling my story to strangers – part of it is healing me in a way, but I’m learning that repeating the story over and over again is also keeping me from letting it go. And I’m still healing.”

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

Medically reviewed by Jennifer Casarella, MD

Dan Miller has parked his Nissan Altima on the side of the road near a field outside Chicago and is holding a gun to his head. 

Haunted for years by the compounded trauma of tours of duty in the Middle East and his work as a police officer in Chicago, at that moment, Dr. Miller saw no reason to live. And there were troubles at home with his wife and children, who had grown fearful of his behavior.

“My whole world was falling apart,” he says of that dark night in 2014. “It left a hole I didn’t know how to fill.”

He chose not to pull the trigger after a brochure on the passenger seat of his car gave him an unexpected perspective – and launched him on a path to help others in his situation.

Had Mr. Miller taken his life that night, he would have joined thousands of other veterans who died by suicide. About 17 U.S. veterans lose their lives this way each day, on average, according to the Department of Veterans Affairs. In 2019, the last year for which records are available, 6,261 veterans took their own lives – and the suicide rate for veterans was 52% higher than for nonveterans, the agency’s records show. 

The problem has become so severe that the Veterans Health Administration now uses artificial intelligence (AI) to help identify veterans at the highest risk of suicide – and reach out to them before a crisis strikes.

But that wasn’t available when Dan Miller’s life was unraveling.

In the years leading up to his near-suicide, his wife had pushed him to get help. “She said, ‘You’re not the same person you were when you left. The kids are scared of you. The pets are scared of you,” he recalls.

He resisted, even when his wife threatened divorce. Rising through the ranks of the Marines, Mr. Miller had become more emotionally isolated. He feared losing his job and the respect of others if he let anyone know what he was going through.

Finally, he gave the VHA a chance. He went in for an initial consultation in 2010 and didn’t find it helpful. He didn’t like being told what to do. So he stopped. He turned to obsessive exercise and excessive drinking.

That day in 2014, Mr. Miller’s wife told him she was taking the kids out for a playdate. After she left, he was served with divorce papers. Less than an hour later, he was parked in his car with his gun, ready to end his life.

But if it all had happened just a few years later, things might never have gotten to that point.
 

Scanning for suicide risk

In 2017, the VHA piloted its AI program, called REACH VET, that aims to help prevent veterans from dying by suicide.

Every month, a computer scans the electronic health records of all VHA patients who’ve had a health care visit for any reason in the last 2 years. It checks more than 140 variables and weights them to estimate someone’s overall suicide risk at that moment in time.

To build the risk algorithm, a computer combed through the medical records of 6,360 veterans confirmed to have died by suicide between 2009 and 2011. (The VHA continually updates the list of variables from the health records of VHA patients, including those who have died by suicide since then and others.)

Some variables are things you’d expect:

• A past suicide attempt.
• A diagnosis of depression or other mental illness.
• A diagnosis of a terminal illness.

Others are more surprising. For example, a diagnosis of arthritis or diabetes adds weight.

REACH VET flags the riskiest cases – the top 0.1% – for a mental health or primary care provider to review. They reach out to the patient to tell them how and why their record was flagged, discuss any recommended treatment changes, and ask them to come in for a visit.

“It’s an opportunity to talk about their risk factors, which is designed to lead to a conversation about safety planning,” says clinical psychologist Matthew Miller, PhD, national director of the U.S. Department of Veterans Affairs’ Suicide Prevention Program. He’s not related to Dan Miller.

Making a suicide safety plan

A safety plan is a document that outlines how a person can help prevent their own suicide in a crisis. 

The plan may include:

• A list of personal triggers or warning signs.
• What’s helped them in the past.
• Names of people or organizations who can support them.
• Plans to remove means of suicide, such as guns, from their environment.
• Their reasons for living.

In people at risk for suicide, research shows that having a safety plan reduces suicidal thoughts and attempts, lowers rates of depression and hopelessness, and boosts veterans’ engagement with the health care system. It may also help people manage things that trigger their suicidal thoughts.
 

Getting the call

What if REACH VET had been around when Dan Miller was in crisis – and he’d gotten a call from the VHA?

“It absolutely, positively would have helped because one of the biggest things on that day when I got served was feeling completely alone and that I had no one to turn to,” Mr. Miller says. He’s now a speaker for the Wounded Warrior Project, a nonprofit that serves veterans and active-duty service people.

Vets’ reactions to the unexpected VHA phone call, psychologist Dr. Miller says, “run the gamut from ‘Thank you for contacting me. Let’s talk,’ to ‘What are you talking about? Leave me alone!’ ”

Nothing stops all suicides. But REACH VET is having an impact. In a clinical trial, vets contacted through REACH VET had more doctor visits, were more likely to have a written suicide prevention safety plan, and had fewer hospital admissions for mental health, ER visits, and suicide attempts.
 

An assist from AI

Even simple outreach can make a big difference. And there’s research to prove it.

One study included 4,730 veterans recently discharged from psychiatric care at the VHA, a group considered at high risk for suicide. 

Half of them got 13 caring emails from hospital staff in the weeks after leaving the hospital. The emails mentioned personal things the patient had shared, like a love of hiking, and wished them well. The other veterans got routine follow-up but no emails.

Two years later, those who got the caring emails were less likely to have died by suicide than the other vets. The study was published in 2014 in Contemporary Clinical Trials.

Researchers have done studies like this many times: with handwritten notes from the primary care doctor, postcards from the ER, and so forth. The results never vary: The notes reduce suicide risk.

“If we could use AI to identify people to receive notes or phone calls, it would be a very effective and inexpensive way to guide follow-up care,” says Rebecca Bernert, PhD, director and founder of the Suicide Prevention Research Laboratory at Stanford (Calif.) University.
 

AI doesn’t replace clinical judgment.

“AI can capture data that we miss due to the limits of our humanity,” psychologist Dr. Miller says. “There’s suicide prevention processes founded on big data and AI, and there are processes founded in clinical intuition and acumen.”

AI is only as good as the data it’s based on. If that data lacks diversity, it may miss things. And variables that apply to veterans may differ in civilians.
 

Stopping suicidal thoughts

Google is putting AI to work against suicide, too. Its MUM (Multitask Unified Model) technology seeks to understand the intent behind what we google.

MUM powers Google Search. It can often tell the difference between a search for information about suicide for someone writing a research paper on the topic and a search for information on how or where to carry out a suicide.

When Google Search detects that someone in the United States might be in crisis and at risk of suicide, the first search results that person gets are the number for the National Suicide Prevention Lifeline and other resources for people in crisis.

Google Home Assistant works in the same way. When a user makes a query that signals a suicide-related crisis, the gadget serves up resources that offer help.

MUM is working to understand the nuances of crisis language in 75 languages so that Google Search can provide people in crisis with hotlines or other resources in many countries.

“We want to find partners that are accessible to users in terms of hours of operation. We have a strong preference for finding partners that promise confidentiality and privacy to the extent that those are permitted [in that country],” says Anne Merritt, MD, a product manager at Google Search.

Other companies are working on apps that use AI to spot suicide risk in other ways, including voice technology that may notice subtle changes in the voice of someone who’s depressed and may be thinking of suicide. Those are still in development but show promise. Keep in mind that apps do not require government approval, so if you try one, be sure to let your health care provider know.
 

Changing the channel

Seeing a hotline number on your phone or computer screen can help, Dan Miller says. “If I happened to be online, searching maybe for a bridge to jump off of ... and suddenly that pops up on the screen, it’s like it changes the channel.”

It may not work for everyone, he says, but that search result could interrupt someone’s suicidal train of thought.

That’s crucial, psychologist Dr. Miller says, because most suicide attempts escalate from first thought to potentially fatal action in just 1 hour. That’s how fast it happened for Dan Miller in 2014.

“When you’re able to put time and space between the suicidal thought and the access to the method to act on that thought, you save lives,” Dr. Bernert says.
 

Making a different choice

An interruption in Mr. Miller’s thinking is what had saved his life.

Holding the gun to his head, Mr. Miller looked over at the passenger seat at a brochure from Wounded Warrior Project, which he had just learned about. Mr. Miller noticed a photo of a man in a wheelchair, a veteran like him, who had no legs. He thought that the man looked worse off than him but hadn’t given up.

Mr. Miller put down his gun and decided to get help.

Recovering from a near suicide attempt, he says, is a journey. It doesn’t happen overnight. Now, 8 years later, Mr. Miller is planning a brief break from the speaker circuit. He plans to spend 2 weeks in an outpatient counseling program for posttraumatic stress disorder and traumatic brain injury.

“Telling my story to strangers – part of it is healing me in a way, but I’m learning that repeating the story over and over again is also keeping me from letting it go. And I’m still healing.”

A version of this article first appeared on WebMD.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.

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.

Young adults aged 15-34 years derive no significant health benefits from alcohol consumption, but moderate drinking may benefit the over-40 crowd, according to a new analysis.

The health risks and benefits of moderate alcohol consumption are complex and remain a hot topic of debate. The data suggest that small amounts of alcohol may reduce the risk of certain health outcomes over time, but increase the risk of others, wrote Dana Bryazka, MS, a researcher at the Institute for Health Metrics and Evaluation (IHME) at the University of Washington, Seattle, and colleagues, in a paper published in the Lancet.

“The amount of alcohol that minimizes health loss is likely to depend on the distribution of underlying causes of disease burden in a given population. Since this distribution varies widely by geography, age, sex, and time, the level of alcohol consumption associated with the lowest risk to health would depend on the age structure and disease composition of that population,” the researchers wrote.

“We estimate that 1.78 million people worldwide died due to alcohol use in 2020,” Ms. Bryazka said in an interview. “It is important that alcohol consumption guidelines and policies are updated to minimize this harm, particularly in the populations at greatest risk,” she said.  

“Existing alcohol consumption guidelines frequently vary by sex, with higher consumption thresholds set for males compared to females. Interestingly, with the currently available data we do not see evidence that risk of alcohol use varies by sex,” she noted.
 

Methods and results

In the study, the researchers conducted a systematic analysis of burden-weighted dose-response relative risk curves across 22 health outcomes. They used disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for the years 1990-2020 for 21 regions, including 204 countries and territories. The data were analyzed by 5-year age group, sex, and year for individuals aged 15-95 years and older. The researchers estimated the theoretical minimum risk exposure level (TMREL) and nondrinker equivalent (NDE), meaning the amount of alcohol at which the health risk equals that of a nondrinker.

One standard drink was defined as 10 g of pure alcohol, equivalent to a small glass of red wine (100 mL or 3.4 fluid ounces) at 13% alcohol by volume, a can or bottle of beer (375 mL or 12 fluid ounces) at 3.5% alcohol by volume, or a shot of whiskey or other spirits (30 mL or 1.0 fluid ounces) at 40% alcohol by volume.

Overall, the TMREL was low regardless of age, sex, time, or geography, and varied from 0 to 1.87 standard drinks per day. However, it was lowest for males aged 15-39 years (0.136 drinks per day) and only slightly higher for females aged 15-39 (0.273), representing 1-2 tenths of a standard drink.

For adults aged 40 and older without any underlying health conditions, drinking a small amount of alcohol may provide some benefits, such as reducing the risk of ischemic heart disease, stroke, and diabetes, the researchers noted. In general, for individuals aged 40-64 years, TMRELs ranged from about half a standard drink per day (0.527 drinks for males and 0.562 standard drinks per day for females) to almost two standard drinks (1.69 standard drinks per day for males and 1.82 for females). For those older than 65 years, the TMRELs represented just over 3 standard drinks per day (3.19 for males and 3.51 for females). For individuals aged 40 years and older, the distribution of disease burden varied by region, but was J-shaped across all regions, the researchers noted.

The researchers also found that those individuals consuming harmful amounts of alcohol were most likely to be aged 15-39 (59.1%) and male (76.9%).

The study findings were limited by several factors including the observational design and lack of data on drinking patterns, such as binge drinking, the researchers noted. Other limitations include the lack of data reflecting patterns of alcohol consumption during the COVID-19 pandemic, and exclusion of outcomes often associated with alcohol use, such as depression, anxiety, and dementia, that might reduce estimates of TMREL and NDE.

However, the results add to the ongoing discussion of the relationship between moderate alcohol consumption and health, the researchers said.

“The findings of this study support the development of tailored guidelines and recommendations on alcohol consumption by age and across regions and highlight that existing low consumption thresholds are too high for younger populations in all regions,” they concluded.
 

Consider individual factors when counseling patients

The takeaway message for primary care is that alcohol consumed in moderation can reduce the risk of ischemic heart disease, stroke, and diabetes, Ms. Bryazka noted. “However, it also increases the risk of many cancers, intentional and unintentional injuries, and infectious diseases like tuberculosis,” she said. “Of these health outcomes, young people are most likely to experience injuries, and as a result, we find that there are significant health risks associated with consuming alcohol for young people. Among older individuals, the relative proportions of these outcomes vary by geography, and so do the risks associated with consuming alcohol,” she explained.

“Importantly, our analysis was conducted at the population level; when evaluating risk at the individual level, it is also important to consider other factors such as the presence of comorbidities and interactions between alcohol and medications,” she emphasized.
 

Health and alcohol interaction is complicated

“These findings seemingly contradict a previous [Global Burden of Diseases, Injuries, and Risk Factors Study] estimate published in The Lancet, which emphasized that any alcohol use, regardless of amount, leads to health loss across populations,” wrote Robyn Burton, PhD, and Nick Sheron, MD, both of King’s College, London, in an accompanying comment.

However, the novel methods of weighting relative risk curves according to levels of underlying disease drive the difference in results, along with disaggregated estimates by age, sex, and region, they said.

“Across most geographical regions in this latest analysis, injuries accounted for most alcohol-related harm in younger age groups. This led to a minimum risk level of zero, or very close to zero, among individuals aged 15-39 years across all geographical regions,” which is lower than the level for older adults because of the shift in alcohol-related disease burden towards cardiovascular disease and cancers, they said. “This highlights the need to consider existing rates of disease in a population when trying to determine the total harm posed by alcohol,” the commentators wrote.

In an additional commentary, Tony Rao, MD, a visiting clinical research fellow in psychiatry at King’s College, London, noted that “the elephant in the room with this study is the interpretation of risk based on outcomes for cardiovascular disease – particularly in older people. We know that any purported health benefits from alcohol on the heart and circulation are balanced out by the increased risk from other conditions such as cancer, liver disease, and mental disorders such as depression and dementia,” Dr. Rao said. “If we are to simply draw the conclusion that older people should continue or start drinking small amounts because it protects against diseases affecting heart and circulation – which still remains controversial – other lifestyle changes or the use of drugs targeted at individual cardiovascular disorders seem like a less harmful way of improving health and wellbeing.”

Data can guide clinical practice

No previous study has examined the effect of the theoretical minimum risk of alcohol consumption by geography, age, sex, and time in the context of background disease rates, said Noel Deep, MD, in an interview.

“This study enabled the researchers to quantify the proportion of the population that consumed alcohol in amounts that exceeded the thresholds by location, age, sex, and year, and this can serve as a guide in our efforts to target the control of alcohol intake by individuals,” said Dr. Deep, a general internist in private practice in Antigo, Wisc. He also serves as chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo.

The first take-home message for clinicians is that even low levels of alcohol consumption can have deleterious effects on the health of patients, and patients should be advised accordingly based on the prevalence of diseases in that community and geographic area, Dr. Deep said. “Secondly, clinicians should also consider the risk of alcohol consumption on all forms of health impacts in a given population rather than just focusing on alcohol-related health conditions,” he added.

“This study provides us with the data to tailor our efforts in educating the clinicians and the public about the relationship between alcohol consumption and disease outcomes based on the observed disease rates in each population,” Dr. Deep explained. “The data should provide another reason for physicians to advise their younger patients, especially the younger males, to avoid or minimize alcohol use,” he said. The data also can help clinicians formulate public health messaging and community education to reduce harmful alcohol use, he added.

As for additional research, Dr. Deep said he would like to see data on the difference in the health-related effects of alcohol in binge-drinkers vs. those who regularly consume alcohol on a daily basis. “It would probably also be helpful to figure out what type of alcohol is being studied and the quality of the alcohol,” he said.

The study was supported by the Bill and Melinda Gates Foundation. Ms. Bryazka and colleagues had no financial conflicts to disclose. Dr. Burton disclosed serving as a consultant to the World Health Organization European Office for the Prevention and Control of Noncommunicable Diseases. Dr. Sheron had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose, but serves on the Editorial Advisory Board of Internal Medicine News.

The study was supported by the Bill and Melinda Gates Foundation.

Young adults aged 15-34 years derive no significant health benefits from alcohol consumption, but moderate drinking may benefit the over-40 crowd, according to a new analysis.

The health risks and benefits of moderate alcohol consumption are complex and remain a hot topic of debate. The data suggest that small amounts of alcohol may reduce the risk of certain health outcomes over time, but increase the risk of others, wrote Dana Bryazka, MS, a researcher at the Institute for Health Metrics and Evaluation (IHME) at the University of Washington, Seattle, and colleagues, in a paper published in the Lancet.

“The amount of alcohol that minimizes health loss is likely to depend on the distribution of underlying causes of disease burden in a given population. Since this distribution varies widely by geography, age, sex, and time, the level of alcohol consumption associated with the lowest risk to health would depend on the age structure and disease composition of that population,” the researchers wrote.

“We estimate that 1.78 million people worldwide died due to alcohol use in 2020,” Ms. Bryazka said in an interview. “It is important that alcohol consumption guidelines and policies are updated to minimize this harm, particularly in the populations at greatest risk,” she said.  

“Existing alcohol consumption guidelines frequently vary by sex, with higher consumption thresholds set for males compared to females. Interestingly, with the currently available data we do not see evidence that risk of alcohol use varies by sex,” she noted.
 

Methods and results

In the study, the researchers conducted a systematic analysis of burden-weighted dose-response relative risk curves across 22 health outcomes. They used disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for the years 1990-2020 for 21 regions, including 204 countries and territories. The data were analyzed by 5-year age group, sex, and year for individuals aged 15-95 years and older. The researchers estimated the theoretical minimum risk exposure level (TMREL) and nondrinker equivalent (NDE), meaning the amount of alcohol at which the health risk equals that of a nondrinker.

One standard drink was defined as 10 g of pure alcohol, equivalent to a small glass of red wine (100 mL or 3.4 fluid ounces) at 13% alcohol by volume, a can or bottle of beer (375 mL or 12 fluid ounces) at 3.5% alcohol by volume, or a shot of whiskey or other spirits (30 mL or 1.0 fluid ounces) at 40% alcohol by volume.

Overall, the TMREL was low regardless of age, sex, time, or geography, and varied from 0 to 1.87 standard drinks per day. However, it was lowest for males aged 15-39 years (0.136 drinks per day) and only slightly higher for females aged 15-39 (0.273), representing 1-2 tenths of a standard drink.

For adults aged 40 and older without any underlying health conditions, drinking a small amount of alcohol may provide some benefits, such as reducing the risk of ischemic heart disease, stroke, and diabetes, the researchers noted. In general, for individuals aged 40-64 years, TMRELs ranged from about half a standard drink per day (0.527 drinks for males and 0.562 standard drinks per day for females) to almost two standard drinks (1.69 standard drinks per day for males and 1.82 for females). For those older than 65 years, the TMRELs represented just over 3 standard drinks per day (3.19 for males and 3.51 for females). For individuals aged 40 years and older, the distribution of disease burden varied by region, but was J-shaped across all regions, the researchers noted.

The researchers also found that those individuals consuming harmful amounts of alcohol were most likely to be aged 15-39 (59.1%) and male (76.9%).

The study findings were limited by several factors including the observational design and lack of data on drinking patterns, such as binge drinking, the researchers noted. Other limitations include the lack of data reflecting patterns of alcohol consumption during the COVID-19 pandemic, and exclusion of outcomes often associated with alcohol use, such as depression, anxiety, and dementia, that might reduce estimates of TMREL and NDE.

However, the results add to the ongoing discussion of the relationship between moderate alcohol consumption and health, the researchers said.

“The findings of this study support the development of tailored guidelines and recommendations on alcohol consumption by age and across regions and highlight that existing low consumption thresholds are too high for younger populations in all regions,” they concluded.
 

Consider individual factors when counseling patients

The takeaway message for primary care is that alcohol consumed in moderation can reduce the risk of ischemic heart disease, stroke, and diabetes, Ms. Bryazka noted. “However, it also increases the risk of many cancers, intentional and unintentional injuries, and infectious diseases like tuberculosis,” she said. “Of these health outcomes, young people are most likely to experience injuries, and as a result, we find that there are significant health risks associated with consuming alcohol for young people. Among older individuals, the relative proportions of these outcomes vary by geography, and so do the risks associated with consuming alcohol,” she explained.

“Importantly, our analysis was conducted at the population level; when evaluating risk at the individual level, it is also important to consider other factors such as the presence of comorbidities and interactions between alcohol and medications,” she emphasized.
 

Health and alcohol interaction is complicated

“These findings seemingly contradict a previous [Global Burden of Diseases, Injuries, and Risk Factors Study] estimate published in The Lancet, which emphasized that any alcohol use, regardless of amount, leads to health loss across populations,” wrote Robyn Burton, PhD, and Nick Sheron, MD, both of King’s College, London, in an accompanying comment.

However, the novel methods of weighting relative risk curves according to levels of underlying disease drive the difference in results, along with disaggregated estimates by age, sex, and region, they said.

“Across most geographical regions in this latest analysis, injuries accounted for most alcohol-related harm in younger age groups. This led to a minimum risk level of zero, or very close to zero, among individuals aged 15-39 years across all geographical regions,” which is lower than the level for older adults because of the shift in alcohol-related disease burden towards cardiovascular disease and cancers, they said. “This highlights the need to consider existing rates of disease in a population when trying to determine the total harm posed by alcohol,” the commentators wrote.

In an additional commentary, Tony Rao, MD, a visiting clinical research fellow in psychiatry at King’s College, London, noted that “the elephant in the room with this study is the interpretation of risk based on outcomes for cardiovascular disease – particularly in older people. We know that any purported health benefits from alcohol on the heart and circulation are balanced out by the increased risk from other conditions such as cancer, liver disease, and mental disorders such as depression and dementia,” Dr. Rao said. “If we are to simply draw the conclusion that older people should continue or start drinking small amounts because it protects against diseases affecting heart and circulation – which still remains controversial – other lifestyle changes or the use of drugs targeted at individual cardiovascular disorders seem like a less harmful way of improving health and wellbeing.”

Data can guide clinical practice

No previous study has examined the effect of the theoretical minimum risk of alcohol consumption by geography, age, sex, and time in the context of background disease rates, said Noel Deep, MD, in an interview.

“This study enabled the researchers to quantify the proportion of the population that consumed alcohol in amounts that exceeded the thresholds by location, age, sex, and year, and this can serve as a guide in our efforts to target the control of alcohol intake by individuals,” said Dr. Deep, a general internist in private practice in Antigo, Wisc. He also serves as chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo.

The first take-home message for clinicians is that even low levels of alcohol consumption can have deleterious effects on the health of patients, and patients should be advised accordingly based on the prevalence of diseases in that community and geographic area, Dr. Deep said. “Secondly, clinicians should also consider the risk of alcohol consumption on all forms of health impacts in a given population rather than just focusing on alcohol-related health conditions,” he added.

“This study provides us with the data to tailor our efforts in educating the clinicians and the public about the relationship between alcohol consumption and disease outcomes based on the observed disease rates in each population,” Dr. Deep explained. “The data should provide another reason for physicians to advise their younger patients, especially the younger males, to avoid or minimize alcohol use,” he said. The data also can help clinicians formulate public health messaging and community education to reduce harmful alcohol use, he added.

As for additional research, Dr. Deep said he would like to see data on the difference in the health-related effects of alcohol in binge-drinkers vs. those who regularly consume alcohol on a daily basis. “It would probably also be helpful to figure out what type of alcohol is being studied and the quality of the alcohol,” he said.

The study was supported by the Bill and Melinda Gates Foundation. Ms. Bryazka and colleagues had no financial conflicts to disclose. Dr. Burton disclosed serving as a consultant to the World Health Organization European Office for the Prevention and Control of Noncommunicable Diseases. Dr. Sheron had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose, but serves on the Editorial Advisory Board of Internal Medicine News.

The study was supported by the Bill and Melinda Gates Foundation.

Young adults aged 15-34 years derive no significant health benefits from alcohol consumption, but moderate drinking may benefit the over-40 crowd, according to a new analysis.

The health risks and benefits of moderate alcohol consumption are complex and remain a hot topic of debate. The data suggest that small amounts of alcohol may reduce the risk of certain health outcomes over time, but increase the risk of others, wrote Dana Bryazka, MS, a researcher at the Institute for Health Metrics and Evaluation (IHME) at the University of Washington, Seattle, and colleagues, in a paper published in the Lancet.

“The amount of alcohol that minimizes health loss is likely to depend on the distribution of underlying causes of disease burden in a given population. Since this distribution varies widely by geography, age, sex, and time, the level of alcohol consumption associated with the lowest risk to health would depend on the age structure and disease composition of that population,” the researchers wrote.

“We estimate that 1.78 million people worldwide died due to alcohol use in 2020,” Ms. Bryazka said in an interview. “It is important that alcohol consumption guidelines and policies are updated to minimize this harm, particularly in the populations at greatest risk,” she said.  

“Existing alcohol consumption guidelines frequently vary by sex, with higher consumption thresholds set for males compared to females. Interestingly, with the currently available data we do not see evidence that risk of alcohol use varies by sex,” she noted.
 

Methods and results

In the study, the researchers conducted a systematic analysis of burden-weighted dose-response relative risk curves across 22 health outcomes. They used disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for the years 1990-2020 for 21 regions, including 204 countries and territories. The data were analyzed by 5-year age group, sex, and year for individuals aged 15-95 years and older. The researchers estimated the theoretical minimum risk exposure level (TMREL) and nondrinker equivalent (NDE), meaning the amount of alcohol at which the health risk equals that of a nondrinker.

One standard drink was defined as 10 g of pure alcohol, equivalent to a small glass of red wine (100 mL or 3.4 fluid ounces) at 13% alcohol by volume, a can or bottle of beer (375 mL or 12 fluid ounces) at 3.5% alcohol by volume, or a shot of whiskey or other spirits (30 mL or 1.0 fluid ounces) at 40% alcohol by volume.

Overall, the TMREL was low regardless of age, sex, time, or geography, and varied from 0 to 1.87 standard drinks per day. However, it was lowest for males aged 15-39 years (0.136 drinks per day) and only slightly higher for females aged 15-39 (0.273), representing 1-2 tenths of a standard drink.

For adults aged 40 and older without any underlying health conditions, drinking a small amount of alcohol may provide some benefits, such as reducing the risk of ischemic heart disease, stroke, and diabetes, the researchers noted. In general, for individuals aged 40-64 years, TMRELs ranged from about half a standard drink per day (0.527 drinks for males and 0.562 standard drinks per day for females) to almost two standard drinks (1.69 standard drinks per day for males and 1.82 for females). For those older than 65 years, the TMRELs represented just over 3 standard drinks per day (3.19 for males and 3.51 for females). For individuals aged 40 years and older, the distribution of disease burden varied by region, but was J-shaped across all regions, the researchers noted.

The researchers also found that those individuals consuming harmful amounts of alcohol were most likely to be aged 15-39 (59.1%) and male (76.9%).

The study findings were limited by several factors including the observational design and lack of data on drinking patterns, such as binge drinking, the researchers noted. Other limitations include the lack of data reflecting patterns of alcohol consumption during the COVID-19 pandemic, and exclusion of outcomes often associated with alcohol use, such as depression, anxiety, and dementia, that might reduce estimates of TMREL and NDE.

However, the results add to the ongoing discussion of the relationship between moderate alcohol consumption and health, the researchers said.

“The findings of this study support the development of tailored guidelines and recommendations on alcohol consumption by age and across regions and highlight that existing low consumption thresholds are too high for younger populations in all regions,” they concluded.
 

Consider individual factors when counseling patients

The takeaway message for primary care is that alcohol consumed in moderation can reduce the risk of ischemic heart disease, stroke, and diabetes, Ms. Bryazka noted. “However, it also increases the risk of many cancers, intentional and unintentional injuries, and infectious diseases like tuberculosis,” she said. “Of these health outcomes, young people are most likely to experience injuries, and as a result, we find that there are significant health risks associated with consuming alcohol for young people. Among older individuals, the relative proportions of these outcomes vary by geography, and so do the risks associated with consuming alcohol,” she explained.

“Importantly, our analysis was conducted at the population level; when evaluating risk at the individual level, it is also important to consider other factors such as the presence of comorbidities and interactions between alcohol and medications,” she emphasized.
 

Health and alcohol interaction is complicated

“These findings seemingly contradict a previous [Global Burden of Diseases, Injuries, and Risk Factors Study] estimate published in The Lancet, which emphasized that any alcohol use, regardless of amount, leads to health loss across populations,” wrote Robyn Burton, PhD, and Nick Sheron, MD, both of King’s College, London, in an accompanying comment.

However, the novel methods of weighting relative risk curves according to levels of underlying disease drive the difference in results, along with disaggregated estimates by age, sex, and region, they said.

“Across most geographical regions in this latest analysis, injuries accounted for most alcohol-related harm in younger age groups. This led to a minimum risk level of zero, or very close to zero, among individuals aged 15-39 years across all geographical regions,” which is lower than the level for older adults because of the shift in alcohol-related disease burden towards cardiovascular disease and cancers, they said. “This highlights the need to consider existing rates of disease in a population when trying to determine the total harm posed by alcohol,” the commentators wrote.

In an additional commentary, Tony Rao, MD, a visiting clinical research fellow in psychiatry at King’s College, London, noted that “the elephant in the room with this study is the interpretation of risk based on outcomes for cardiovascular disease – particularly in older people. We know that any purported health benefits from alcohol on the heart and circulation are balanced out by the increased risk from other conditions such as cancer, liver disease, and mental disorders such as depression and dementia,” Dr. Rao said. “If we are to simply draw the conclusion that older people should continue or start drinking small amounts because it protects against diseases affecting heart and circulation – which still remains controversial – other lifestyle changes or the use of drugs targeted at individual cardiovascular disorders seem like a less harmful way of improving health and wellbeing.”

Data can guide clinical practice

No previous study has examined the effect of the theoretical minimum risk of alcohol consumption by geography, age, sex, and time in the context of background disease rates, said Noel Deep, MD, in an interview.

“This study enabled the researchers to quantify the proportion of the population that consumed alcohol in amounts that exceeded the thresholds by location, age, sex, and year, and this can serve as a guide in our efforts to target the control of alcohol intake by individuals,” said Dr. Deep, a general internist in private practice in Antigo, Wisc. He also serves as chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo.

The first take-home message for clinicians is that even low levels of alcohol consumption can have deleterious effects on the health of patients, and patients should be advised accordingly based on the prevalence of diseases in that community and geographic area, Dr. Deep said. “Secondly, clinicians should also consider the risk of alcohol consumption on all forms of health impacts in a given population rather than just focusing on alcohol-related health conditions,” he added.

“This study provides us with the data to tailor our efforts in educating the clinicians and the public about the relationship between alcohol consumption and disease outcomes based on the observed disease rates in each population,” Dr. Deep explained. “The data should provide another reason for physicians to advise their younger patients, especially the younger males, to avoid or minimize alcohol use,” he said. The data also can help clinicians formulate public health messaging and community education to reduce harmful alcohol use, he added.

As for additional research, Dr. Deep said he would like to see data on the difference in the health-related effects of alcohol in binge-drinkers vs. those who regularly consume alcohol on a daily basis. “It would probably also be helpful to figure out what type of alcohol is being studied and the quality of the alcohol,” he said.

The study was supported by the Bill and Melinda Gates Foundation. Ms. Bryazka and colleagues had no financial conflicts to disclose. Dr. Burton disclosed serving as a consultant to the World Health Organization European Office for the Prevention and Control of Noncommunicable Diseases. Dr. Sheron had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose, but serves on the Editorial Advisory Board of Internal Medicine News.

The study was supported by the Bill and Melinda Gates Foundation.

Body clocks and the shifting risks of stroke

Health care professionals, we’re sure, are no strangers to rotating shifts. And, as practitioners of the shiftly arts, you should know new research shows that working those kinds of hours can have lasting effects on your health. And it’s all based on your sleep-wake cycle.

Wildpixel/thinkstockphotos.com

In a study published in Neurobiology of Sleep and Circadian Rhythms, investigators at Texas A&M University looked at the effects of working these kinds of shifts for a long period of time and then returning to a regular 24-hour cycle later in life. The study piggybacks on a previous study, which showed that rats on shift schedules had more severe stroke outcomes than those who were on a 24-hour cycle.

The current study demonstrates that working rotating shifts does have a lasting effect, by way of messing with the sleep-wake cycle. Based on the research, the rats that performed those kinds of shifts never got back to a normal schedule. When strokes occurred, outcomes were much worse, and the females had a higher mortality rate and more severe functional deficits than the males.

Now for the “good” news: Even if you’re among those who haven’t worked a rotating shift, you may not be safe either.

People who have regular working hours have a tendency to take work home and stay up late, especially with so many moving to a remote-work model. And if you’re staying up late on the weekends you’re producing what lead author David J. Earnest, PhD, called “social jet lag,” which messes with your circadian rhythm to wind you down for sleep. All of these things can lead to the same kind of effects that working rotating shifts has on your health, he said in a written statement.

How do you combat this? Dr. Earnest recommended creating a sleep schedule and setting regular mealtimes. Also ease up on high-fat foods, drinking, and smoking. The connection between your brain and gut also could play a part in how severe a stroke can be.

So continue to work hard, but not too hard.

Got 3 minutes? You got time for culture

Much like a Krabby Patty, art is good for your soul. Seriously, staring at a 500-year-old painting may not seem like much, but research has proven time and again that going to a museum and looking at paintings by long-dead artists you probably know better as pizza-eating superhero turtles improves mood, stress, and well-being.

National Gallery of Art/rawpixel

A couple of years ago, however, museums and art galleries ran into a big virus-shaped problem. You may have heard of it. All of a sudden it became a very bad idea for people to gather together in one building and huddle around the Mona Lisa, which, by the way, is a lot smaller in person than you might expect. But, rather than sit around with a bunch of priceless art for an indeterminate amount of time, museums brought their exhibits to the Internet so that people from all over the world could see great works from their couches.

This is absolutely a good thing for public access, but do these virtual art exhibits provide the same health benefits as going to a museum in person? That’s what a group of European researchers aimed to find out, and in a study published in Frontiers of Psychology, that’s exactly what they found.

Their directive to the 84 study participants was simple: Take a well-being survey, engage with either of a pair of online exhibits (a Monet painting and a display of Japanese culinary traditions) for just 3 minutes, then take another well-being assessment. The results were quite clear: Even just a couple of minutes of viewing art online improved all the well-being categories on the survey, such as lowering anxiety, negative mood, and loneliness, as well as increasing subjective well-being. Also, the more beautiful or meaningful a person found the art, the more their mood and well-being improved.

The researchers noted that these results could help access in places where access to art is limited, such as waiting rooms, hospitals, and rural areas. Let’s just hope it sticks to that, and that big businesses don’t take notice. Just imagine them plastering ads with classic Renaissance artworks. After all, art makes you feel good, and you know what else feels good on a hot summer day? An ice-cold Coca-Cola! By the way, we’re taking offers, advertising agencies. The LOTME staff can absolutely be bought.

Appetite for etymology

Today on “It’s a Thing,” we examine various states of hunger and what they should be called. Our first guest is that historically hungry royal person, King Henry VIII of England. Your majesty, have you ever been “hangry?”

PxHere

KH8: First, let me thank you for inviting me on the show, Maurice. I’m a huge fan. A recent study done in the United Kingdom and Austria showed that “hunger is associated with greater levels of anger and irritability, as well as lower levels of pleasure,” according to a Eurekalert statement. So, yes, I have been “hangry.”

Maurice: Now to our next guest. Martha Stewart, can you add anything about that study?

Martha: Happy to, Maurice. The 64 participants used a smartphone app to record their hunger levels and emotional states five times a day for 21 days. It’s the first time that “hanger” was studied outside a lab, and it showed that hunger “was associated with 37% of the variance in irritability, 34% of the variance in anger, and 38% of the variance in pleasure recorded by the participants,” the investigators said in that statement.

Maurice: It’s official, then. Hangry is a thing, and we don’t need to put it in quotes anymore. Now let’s meet our third and final guest, Betty Crocker. Betty, I’m told you have a study to plug.

Betty: That’s right, Mo. Researchers at Tel Aviv University looked at survey data from almost 3,000 men and women and found that men ate 17% more food during the warmer months (March to September) than they did the rest of the year. Among women, however, caloric intake did not change.

KH8: I saw that study. Didn’t they put 27 people out in the sun and then take blood samples?

Betty: Indeed they did, Hank. After 25 minutes of sun exposure, the 13 men felt hungrier than before, but the 14 women did not. The men also had higher levels of ghrelin, an appetite-stimulating hormone, than the women.

Maurice: To sum all this up, then, we’ve got angry and hungry officially combining to make hangry, and now it looks like the sun is causing hunger in men, which makes them … sungry?

Martha: It’s a thing.

Chicken cutlets with a side of COVID

You stopped at the drive through at McDonald’s on the way home from work, and while you’re looking for something sweet in the refrigerator for dessert, you see that chicken breast that expires today.

Richard Franki/MDedge News

Freezing meat that’s about to expire might be your go-to so it doesn’t go to waste, but it’s been found that SARS-CoV-2 can live in meat that’s been in the refrigerator or freezer for more than a month.

Researchers exposed chicken, beef, pork, and salmon to surrogate viruses that are similar to COVID but not as harmful and stored them in freezers at –4° F and in the refrigerator at 39.2° F. “We even found that the viruses could be cultured after [being frozen for] that length of time,” lead author Emily Bailey, PhD, of Campbell University in Buies Creek, N.C., said in Study Finds.

The team began its research after hearing of COVID-19 outbreaks where there were no reports of community transmission, such as in Southeast Asia. Tracing eventually led to packaged meats as the culprits in those cases. SARS-CoV-2 is able to replicate in the gut, as well as the respiratory tract, so it could affect the gut before respiratory symptoms start. It is crucial to ensure cross contamination doesn’t occur, and inadequate sanitation prior to packaging needs to be addressed, the investigators said.

Honestly, we didn’t think anything could survive in a freezer for that long, but SARS-CoV-2 is a fighter.

Body clocks and the shifting risks of stroke

Health care professionals, we’re sure, are no strangers to rotating shifts. And, as practitioners of the shiftly arts, you should know new research shows that working those kinds of hours can have lasting effects on your health. And it’s all based on your sleep-wake cycle.

Wildpixel/thinkstockphotos.com

In a study published in Neurobiology of Sleep and Circadian Rhythms, investigators at Texas A&M University looked at the effects of working these kinds of shifts for a long period of time and then returning to a regular 24-hour cycle later in life. The study piggybacks on a previous study, which showed that rats on shift schedules had more severe stroke outcomes than those who were on a 24-hour cycle.

The current study demonstrates that working rotating shifts does have a lasting effect, by way of messing with the sleep-wake cycle. Based on the research, the rats that performed those kinds of shifts never got back to a normal schedule. When strokes occurred, outcomes were much worse, and the females had a higher mortality rate and more severe functional deficits than the males.

Now for the “good” news: Even if you’re among those who haven’t worked a rotating shift, you may not be safe either.

People who have regular working hours have a tendency to take work home and stay up late, especially with so many moving to a remote-work model. And if you’re staying up late on the weekends you’re producing what lead author David J. Earnest, PhD, called “social jet lag,” which messes with your circadian rhythm to wind you down for sleep. All of these things can lead to the same kind of effects that working rotating shifts has on your health, he said in a written statement.

How do you combat this? Dr. Earnest recommended creating a sleep schedule and setting regular mealtimes. Also ease up on high-fat foods, drinking, and smoking. The connection between your brain and gut also could play a part in how severe a stroke can be.

So continue to work hard, but not too hard.

Got 3 minutes? You got time for culture

Much like a Krabby Patty, art is good for your soul. Seriously, staring at a 500-year-old painting may not seem like much, but research has proven time and again that going to a museum and looking at paintings by long-dead artists you probably know better as pizza-eating superhero turtles improves mood, stress, and well-being.

National Gallery of Art/rawpixel

A couple of years ago, however, museums and art galleries ran into a big virus-shaped problem. You may have heard of it. All of a sudden it became a very bad idea for people to gather together in one building and huddle around the Mona Lisa, which, by the way, is a lot smaller in person than you might expect. But, rather than sit around with a bunch of priceless art for an indeterminate amount of time, museums brought their exhibits to the Internet so that people from all over the world could see great works from their couches.

This is absolutely a good thing for public access, but do these virtual art exhibits provide the same health benefits as going to a museum in person? That’s what a group of European researchers aimed to find out, and in a study published in Frontiers of Psychology, that’s exactly what they found.

Their directive to the 84 study participants was simple: Take a well-being survey, engage with either of a pair of online exhibits (a Monet painting and a display of Japanese culinary traditions) for just 3 minutes, then take another well-being assessment. The results were quite clear: Even just a couple of minutes of viewing art online improved all the well-being categories on the survey, such as lowering anxiety, negative mood, and loneliness, as well as increasing subjective well-being. Also, the more beautiful or meaningful a person found the art, the more their mood and well-being improved.

The researchers noted that these results could help access in places where access to art is limited, such as waiting rooms, hospitals, and rural areas. Let’s just hope it sticks to that, and that big businesses don’t take notice. Just imagine them plastering ads with classic Renaissance artworks. After all, art makes you feel good, and you know what else feels good on a hot summer day? An ice-cold Coca-Cola! By the way, we’re taking offers, advertising agencies. The LOTME staff can absolutely be bought.

Appetite for etymology

Today on “It’s a Thing,” we examine various states of hunger and what they should be called. Our first guest is that historically hungry royal person, King Henry VIII of England. Your majesty, have you ever been “hangry?”

PxHere

KH8: First, let me thank you for inviting me on the show, Maurice. I’m a huge fan. A recent study done in the United Kingdom and Austria showed that “hunger is associated with greater levels of anger and irritability, as well as lower levels of pleasure,” according to a Eurekalert statement. So, yes, I have been “hangry.”

Maurice: Now to our next guest. Martha Stewart, can you add anything about that study?

Martha: Happy to, Maurice. The 64 participants used a smartphone app to record their hunger levels and emotional states five times a day for 21 days. It’s the first time that “hanger” was studied outside a lab, and it showed that hunger “was associated with 37% of the variance in irritability, 34% of the variance in anger, and 38% of the variance in pleasure recorded by the participants,” the investigators said in that statement.

Maurice: It’s official, then. Hangry is a thing, and we don’t need to put it in quotes anymore. Now let’s meet our third and final guest, Betty Crocker. Betty, I’m told you have a study to plug.

Betty: That’s right, Mo. Researchers at Tel Aviv University looked at survey data from almost 3,000 men and women and found that men ate 17% more food during the warmer months (March to September) than they did the rest of the year. Among women, however, caloric intake did not change.

KH8: I saw that study. Didn’t they put 27 people out in the sun and then take blood samples?

Betty: Indeed they did, Hank. After 25 minutes of sun exposure, the 13 men felt hungrier than before, but the 14 women did not. The men also had higher levels of ghrelin, an appetite-stimulating hormone, than the women.

Maurice: To sum all this up, then, we’ve got angry and hungry officially combining to make hangry, and now it looks like the sun is causing hunger in men, which makes them … sungry?

Martha: It’s a thing.

Chicken cutlets with a side of COVID

You stopped at the drive through at McDonald’s on the way home from work, and while you’re looking for something sweet in the refrigerator for dessert, you see that chicken breast that expires today.

Richard Franki/MDedge News

Freezing meat that’s about to expire might be your go-to so it doesn’t go to waste, but it’s been found that SARS-CoV-2 can live in meat that’s been in the refrigerator or freezer for more than a month.

Researchers exposed chicken, beef, pork, and salmon to surrogate viruses that are similar to COVID but not as harmful and stored them in freezers at –4° F and in the refrigerator at 39.2° F. “We even found that the viruses could be cultured after [being frozen for] that length of time,” lead author Emily Bailey, PhD, of Campbell University in Buies Creek, N.C., said in Study Finds.

The team began its research after hearing of COVID-19 outbreaks where there were no reports of community transmission, such as in Southeast Asia. Tracing eventually led to packaged meats as the culprits in those cases. SARS-CoV-2 is able to replicate in the gut, as well as the respiratory tract, so it could affect the gut before respiratory symptoms start. It is crucial to ensure cross contamination doesn’t occur, and inadequate sanitation prior to packaging needs to be addressed, the investigators said.

Honestly, we didn’t think anything could survive in a freezer for that long, but SARS-CoV-2 is a fighter.

Body clocks and the shifting risks of stroke

Health care professionals, we’re sure, are no strangers to rotating shifts. And, as practitioners of the shiftly arts, you should know new research shows that working those kinds of hours can have lasting effects on your health. And it’s all based on your sleep-wake cycle.

Wildpixel/thinkstockphotos.com

In a study published in Neurobiology of Sleep and Circadian Rhythms, investigators at Texas A&M University looked at the effects of working these kinds of shifts for a long period of time and then returning to a regular 24-hour cycle later in life. The study piggybacks on a previous study, which showed that rats on shift schedules had more severe stroke outcomes than those who were on a 24-hour cycle.

The current study demonstrates that working rotating shifts does have a lasting effect, by way of messing with the sleep-wake cycle. Based on the research, the rats that performed those kinds of shifts never got back to a normal schedule. When strokes occurred, outcomes were much worse, and the females had a higher mortality rate and more severe functional deficits than the males.

Now for the “good” news: Even if you’re among those who haven’t worked a rotating shift, you may not be safe either.

People who have regular working hours have a tendency to take work home and stay up late, especially with so many moving to a remote-work model. And if you’re staying up late on the weekends you’re producing what lead author David J. Earnest, PhD, called “social jet lag,” which messes with your circadian rhythm to wind you down for sleep. All of these things can lead to the same kind of effects that working rotating shifts has on your health, he said in a written statement.

How do you combat this? Dr. Earnest recommended creating a sleep schedule and setting regular mealtimes. Also ease up on high-fat foods, drinking, and smoking. The connection between your brain and gut also could play a part in how severe a stroke can be.

So continue to work hard, but not too hard.

Got 3 minutes? You got time for culture

Much like a Krabby Patty, art is good for your soul. Seriously, staring at a 500-year-old painting may not seem like much, but research has proven time and again that going to a museum and looking at paintings by long-dead artists you probably know better as pizza-eating superhero turtles improves mood, stress, and well-being.

National Gallery of Art/rawpixel

A couple of years ago, however, museums and art galleries ran into a big virus-shaped problem. You may have heard of it. All of a sudden it became a very bad idea for people to gather together in one building and huddle around the Mona Lisa, which, by the way, is a lot smaller in person than you might expect. But, rather than sit around with a bunch of priceless art for an indeterminate amount of time, museums brought their exhibits to the Internet so that people from all over the world could see great works from their couches.

This is absolutely a good thing for public access, but do these virtual art exhibits provide the same health benefits as going to a museum in person? That’s what a group of European researchers aimed to find out, and in a study published in Frontiers of Psychology, that’s exactly what they found.

Their directive to the 84 study participants was simple: Take a well-being survey, engage with either of a pair of online exhibits (a Monet painting and a display of Japanese culinary traditions) for just 3 minutes, then take another well-being assessment. The results were quite clear: Even just a couple of minutes of viewing art online improved all the well-being categories on the survey, such as lowering anxiety, negative mood, and loneliness, as well as increasing subjective well-being. Also, the more beautiful or meaningful a person found the art, the more their mood and well-being improved.

The researchers noted that these results could help access in places where access to art is limited, such as waiting rooms, hospitals, and rural areas. Let’s just hope it sticks to that, and that big businesses don’t take notice. Just imagine them plastering ads with classic Renaissance artworks. After all, art makes you feel good, and you know what else feels good on a hot summer day? An ice-cold Coca-Cola! By the way, we’re taking offers, advertising agencies. The LOTME staff can absolutely be bought.

Appetite for etymology

Today on “It’s a Thing,” we examine various states of hunger and what they should be called. Our first guest is that historically hungry royal person, King Henry VIII of England. Your majesty, have you ever been “hangry?”

PxHere

KH8: First, let me thank you for inviting me on the show, Maurice. I’m a huge fan. A recent study done in the United Kingdom and Austria showed that “hunger is associated with greater levels of anger and irritability, as well as lower levels of pleasure,” according to a Eurekalert statement. So, yes, I have been “hangry.”

Maurice: Now to our next guest. Martha Stewart, can you add anything about that study?

Martha: Happy to, Maurice. The 64 participants used a smartphone app to record their hunger levels and emotional states five times a day for 21 days. It’s the first time that “hanger” was studied outside a lab, and it showed that hunger “was associated with 37% of the variance in irritability, 34% of the variance in anger, and 38% of the variance in pleasure recorded by the participants,” the investigators said in that statement.

Maurice: It’s official, then. Hangry is a thing, and we don’t need to put it in quotes anymore. Now let’s meet our third and final guest, Betty Crocker. Betty, I’m told you have a study to plug.

Betty: That’s right, Mo. Researchers at Tel Aviv University looked at survey data from almost 3,000 men and women and found that men ate 17% more food during the warmer months (March to September) than they did the rest of the year. Among women, however, caloric intake did not change.

KH8: I saw that study. Didn’t they put 27 people out in the sun and then take blood samples?

Betty: Indeed they did, Hank. After 25 minutes of sun exposure, the 13 men felt hungrier than before, but the 14 women did not. The men also had higher levels of ghrelin, an appetite-stimulating hormone, than the women.

Maurice: To sum all this up, then, we’ve got angry and hungry officially combining to make hangry, and now it looks like the sun is causing hunger in men, which makes them … sungry?

Martha: It’s a thing.

Chicken cutlets with a side of COVID

You stopped at the drive through at McDonald’s on the way home from work, and while you’re looking for something sweet in the refrigerator for dessert, you see that chicken breast that expires today.

Richard Franki/MDedge News

Freezing meat that’s about to expire might be your go-to so it doesn’t go to waste, but it’s been found that SARS-CoV-2 can live in meat that’s been in the refrigerator or freezer for more than a month.

Researchers exposed chicken, beef, pork, and salmon to surrogate viruses that are similar to COVID but not as harmful and stored them in freezers at –4° F and in the refrigerator at 39.2° F. “We even found that the viruses could be cultured after [being frozen for] that length of time,” lead author Emily Bailey, PhD, of Campbell University in Buies Creek, N.C., said in Study Finds.

The team began its research after hearing of COVID-19 outbreaks where there were no reports of community transmission, such as in Southeast Asia. Tracing eventually led to packaged meats as the culprits in those cases. SARS-CoV-2 is able to replicate in the gut, as well as the respiratory tract, so it could affect the gut before respiratory symptoms start. It is crucial to ensure cross contamination doesn’t occur, and inadequate sanitation prior to packaging needs to be addressed, the investigators said.

Honestly, we didn’t think anything could survive in a freezer for that long, but SARS-CoV-2 is a fighter.

CHICAGO – Pembrolizumab has shown promise as adjuvant therapy for stage IIB and IIC melanoma, shows the first interim analysis of the phase 3 KEYNOTE-716 study recently published in The Lancet.

The findings meet an unmet need as the recurrence risk in stage IIB and IIC melanoma is “underrecognized,” said author Georgina Long, MD, comedical director of the Melanoma Institute Australia, University of Sydney.

In fact, their risk of recurrence is similar to patients with stage IIIB disease, wrote David Killock, PhD, in a related commentary published in Nature Reviews.

The adjuvant treatment resulted in an 89% recurrence-free survival in patients who received pembrolizumab, compared with 83% of patients in the placebo group (hazard ratio, 0.65; P = .0066). These findings were used as the basis for Food and Drug Administration approval of pembrolizumab (Keytruda, Merck) for this patient population in December 2021.

Despite the positive findings, Dr. Killock called for more research on distant metastasis-free survival, overall survival, and quality of life data to “establish the true clinical benefit of adjuvant pembrolizumab.”

At the annual meeting of the American Society of Clinical Oncology, Dr. Long presented the third interim analysis which showed pembrolizumab reduced recurrence and distant metastases at 24 months, although the clinical benefit was relatively small at an approximately 8% improvement in recurrence-free survival and about a 6% improvement in distant metastasis-free survival. About 83% in the pembrolizumab group had treatment-related toxicities versus 64% in the placebo group. There were no deaths caused by treatment. About 90% of pembrolizumab-related endocrinopathies led to long-term hormone replacement.

In a discussion that followed the presentation at ASCO, Charlotte Eielson Ariyan, MD, PhD, said the results are bittersweet. Higher-risk stage IIC patients have a risk of recurrence of about 40%. “It’s high, but the absolute risk reduction is about 8%. This is a very personalized discussion with the patient and the physician in understanding their risk of toxicity is about 17% and higher than their absolute risk reduction with the treatment. For me, this is a bitter pill to swallow because you’re treating people longer and you’re not sure if you’re really helping them. Until we can further define who the highest-risk patients are, I think it’s hard to give it to everyone,” said Dr. Ariyan, who is a surgeon with Memorial Sloan Kettering Cancer Center, New York.

In addition to weighing short-term benefits and toxicity, there are longer-term concerns. Toxicity experienced from PD-1 inhibitors in the adjuvant setting could impact future treatment decisions. “We’re very lucky here in melanoma to know that systemic therapies are effective and we can cure people who recur. I would argue this is why we probably will never really see a difference in the survival benefit in this group because people who cross over will probably do well,” Dr. Ariyan said.

During the Q&A session, Vernon Sondek, MD, Moffitt Cancer Center, Tampa, encouraged physician colleagues to have an open mind about treatments. “Beware of dogma. We thought that adjuvant immunotherapy works much better in patients with ulcerated primary tumors. That’s a dogma in some parts of the world. Yet the T4a patients in KEYNOTE-716 dramatically outperformed the ulcerated T3b and T4b [patients]. We still don’t know what we don’t know.”
 

The study details

KEYNOTE-716 included 976 patients 12 years or older with newly diagnosed completely resected stage IIB or IIC melanoma with a negative sentinel lymph node. Patients were randomized to placebo or 200 mg pembrolizumab every 3 weeks, or 2 mg/kg in pediatric patients, over 17 cycles. Almost 40% of patients were age 65 or older. T3b and T4b were the most common melanoma subcategories at 41% and 35%, respectively.

The planned third interim analysis occurred after the occurrence of 146 distant metastases. After a median follow-up of 27.4 months, distant metastasis-free survival favored the pembrolizumab group (HR, 0.64; P = .0029). At 24 months, the pembrolizumab group had a higher distant metastasis-free survival at 88.1% versus 82.2% and a lower recurrence rate at 81.2% versus 72.8% (HR, 0.64; 95% confidence interval, 0.50-0.84).

At 24 months, only the T4a patients had a statistically significant reduction in distant metastases at 58% (HR, 0.42; 95% CI, 0.19-0.96), although there were numerical reductions in T3a (HR, 0.71; 95% CI, 0.41-1.22) and T4b (HR, 0.70; 95% CI, 0.44-1.33) patients. Of patients experiencing a distant metastasis, 73% of the placebo group had a first distant metastasis to the lung compared with 49% of the pembrolizumab group.

Dr. Long has held consulting or advisory roles for Merck Sharpe & Dohme, which funded this study.

CHICAGO – Pembrolizumab has shown promise as adjuvant therapy for stage IIB and IIC melanoma, shows the first interim analysis of the phase 3 KEYNOTE-716 study recently published in The Lancet.

The findings meet an unmet need as the recurrence risk in stage IIB and IIC melanoma is “underrecognized,” said author Georgina Long, MD, comedical director of the Melanoma Institute Australia, University of Sydney.

In fact, their risk of recurrence is similar to patients with stage IIIB disease, wrote David Killock, PhD, in a related commentary published in Nature Reviews.

The adjuvant treatment resulted in an 89% recurrence-free survival in patients who received pembrolizumab, compared with 83% of patients in the placebo group (hazard ratio, 0.65; P = .0066). These findings were used as the basis for Food and Drug Administration approval of pembrolizumab (Keytruda, Merck) for this patient population in December 2021.

Despite the positive findings, Dr. Killock called for more research on distant metastasis-free survival, overall survival, and quality of life data to “establish the true clinical benefit of adjuvant pembrolizumab.”

At the annual meeting of the American Society of Clinical Oncology, Dr. Long presented the third interim analysis which showed pembrolizumab reduced recurrence and distant metastases at 24 months, although the clinical benefit was relatively small at an approximately 8% improvement in recurrence-free survival and about a 6% improvement in distant metastasis-free survival. About 83% in the pembrolizumab group had treatment-related toxicities versus 64% in the placebo group. There were no deaths caused by treatment. About 90% of pembrolizumab-related endocrinopathies led to long-term hormone replacement.

In a discussion that followed the presentation at ASCO, Charlotte Eielson Ariyan, MD, PhD, said the results are bittersweet. Higher-risk stage IIC patients have a risk of recurrence of about 40%. “It’s high, but the absolute risk reduction is about 8%. This is a very personalized discussion with the patient and the physician in understanding their risk of toxicity is about 17% and higher than their absolute risk reduction with the treatment. For me, this is a bitter pill to swallow because you’re treating people longer and you’re not sure if you’re really helping them. Until we can further define who the highest-risk patients are, I think it’s hard to give it to everyone,” said Dr. Ariyan, who is a surgeon with Memorial Sloan Kettering Cancer Center, New York.

In addition to weighing short-term benefits and toxicity, there are longer-term concerns. Toxicity experienced from PD-1 inhibitors in the adjuvant setting could impact future treatment decisions. “We’re very lucky here in melanoma to know that systemic therapies are effective and we can cure people who recur. I would argue this is why we probably will never really see a difference in the survival benefit in this group because people who cross over will probably do well,” Dr. Ariyan said.

During the Q&A session, Vernon Sondek, MD, Moffitt Cancer Center, Tampa, encouraged physician colleagues to have an open mind about treatments. “Beware of dogma. We thought that adjuvant immunotherapy works much better in patients with ulcerated primary tumors. That’s a dogma in some parts of the world. Yet the T4a patients in KEYNOTE-716 dramatically outperformed the ulcerated T3b and T4b [patients]. We still don’t know what we don’t know.”
 

The study details

KEYNOTE-716 included 976 patients 12 years or older with newly diagnosed completely resected stage IIB or IIC melanoma with a negative sentinel lymph node. Patients were randomized to placebo or 200 mg pembrolizumab every 3 weeks, or 2 mg/kg in pediatric patients, over 17 cycles. Almost 40% of patients were age 65 or older. T3b and T4b were the most common melanoma subcategories at 41% and 35%, respectively.

The planned third interim analysis occurred after the occurrence of 146 distant metastases. After a median follow-up of 27.4 months, distant metastasis-free survival favored the pembrolizumab group (HR, 0.64; P = .0029). At 24 months, the pembrolizumab group had a higher distant metastasis-free survival at 88.1% versus 82.2% and a lower recurrence rate at 81.2% versus 72.8% (HR, 0.64; 95% confidence interval, 0.50-0.84).

At 24 months, only the T4a patients had a statistically significant reduction in distant metastases at 58% (HR, 0.42; 95% CI, 0.19-0.96), although there were numerical reductions in T3a (HR, 0.71; 95% CI, 0.41-1.22) and T4b (HR, 0.70; 95% CI, 0.44-1.33) patients. Of patients experiencing a distant metastasis, 73% of the placebo group had a first distant metastasis to the lung compared with 49% of the pembrolizumab group.

Dr. Long has held consulting or advisory roles for Merck Sharpe & Dohme, which funded this study.

CHICAGO – Pembrolizumab has shown promise as adjuvant therapy for stage IIB and IIC melanoma, shows the first interim analysis of the phase 3 KEYNOTE-716 study recently published in The Lancet.

The findings meet an unmet need as the recurrence risk in stage IIB and IIC melanoma is “underrecognized,” said author Georgina Long, MD, comedical director of the Melanoma Institute Australia, University of Sydney.

In fact, their risk of recurrence is similar to patients with stage IIIB disease, wrote David Killock, PhD, in a related commentary published in Nature Reviews.

The adjuvant treatment resulted in an 89% recurrence-free survival in patients who received pembrolizumab, compared with 83% of patients in the placebo group (hazard ratio, 0.65; P = .0066). These findings were used as the basis for Food and Drug Administration approval of pembrolizumab (Keytruda, Merck) for this patient population in December 2021.

Despite the positive findings, Dr. Killock called for more research on distant metastasis-free survival, overall survival, and quality of life data to “establish the true clinical benefit of adjuvant pembrolizumab.”

At the annual meeting of the American Society of Clinical Oncology, Dr. Long presented the third interim analysis which showed pembrolizumab reduced recurrence and distant metastases at 24 months, although the clinical benefit was relatively small at an approximately 8% improvement in recurrence-free survival and about a 6% improvement in distant metastasis-free survival. About 83% in the pembrolizumab group had treatment-related toxicities versus 64% in the placebo group. There were no deaths caused by treatment. About 90% of pembrolizumab-related endocrinopathies led to long-term hormone replacement.

In a discussion that followed the presentation at ASCO, Charlotte Eielson Ariyan, MD, PhD, said the results are bittersweet. Higher-risk stage IIC patients have a risk of recurrence of about 40%. “It’s high, but the absolute risk reduction is about 8%. This is a very personalized discussion with the patient and the physician in understanding their risk of toxicity is about 17% and higher than their absolute risk reduction with the treatment. For me, this is a bitter pill to swallow because you’re treating people longer and you’re not sure if you’re really helping them. Until we can further define who the highest-risk patients are, I think it’s hard to give it to everyone,” said Dr. Ariyan, who is a surgeon with Memorial Sloan Kettering Cancer Center, New York.

In addition to weighing short-term benefits and toxicity, there are longer-term concerns. Toxicity experienced from PD-1 inhibitors in the adjuvant setting could impact future treatment decisions. “We’re very lucky here in melanoma to know that systemic therapies are effective and we can cure people who recur. I would argue this is why we probably will never really see a difference in the survival benefit in this group because people who cross over will probably do well,” Dr. Ariyan said.

During the Q&A session, Vernon Sondek, MD, Moffitt Cancer Center, Tampa, encouraged physician colleagues to have an open mind about treatments. “Beware of dogma. We thought that adjuvant immunotherapy works much better in patients with ulcerated primary tumors. That’s a dogma in some parts of the world. Yet the T4a patients in KEYNOTE-716 dramatically outperformed the ulcerated T3b and T4b [patients]. We still don’t know what we don’t know.”
 

The study details

KEYNOTE-716 included 976 patients 12 years or older with newly diagnosed completely resected stage IIB or IIC melanoma with a negative sentinel lymph node. Patients were randomized to placebo or 200 mg pembrolizumab every 3 weeks, or 2 mg/kg in pediatric patients, over 17 cycles. Almost 40% of patients were age 65 or older. T3b and T4b were the most common melanoma subcategories at 41% and 35%, respectively.

The planned third interim analysis occurred after the occurrence of 146 distant metastases. After a median follow-up of 27.4 months, distant metastasis-free survival favored the pembrolizumab group (HR, 0.64; P = .0029). At 24 months, the pembrolizumab group had a higher distant metastasis-free survival at 88.1% versus 82.2% and a lower recurrence rate at 81.2% versus 72.8% (HR, 0.64; 95% confidence interval, 0.50-0.84).

At 24 months, only the T4a patients had a statistically significant reduction in distant metastases at 58% (HR, 0.42; 95% CI, 0.19-0.96), although there were numerical reductions in T3a (HR, 0.71; 95% CI, 0.41-1.22) and T4b (HR, 0.70; 95% CI, 0.44-1.33) patients. Of patients experiencing a distant metastasis, 73% of the placebo group had a first distant metastasis to the lung compared with 49% of the pembrolizumab group.

Dr. Long has held consulting or advisory roles for Merck Sharpe & Dohme, which funded this study.