Cardiology News

Exercise training – but not testosterone therapy – improved vascular health in aging men with widening midsections and low to normal testosterone, new research suggests.

kali9/iStockphoto.com

“Previous studies have suggested that men with higher levels of testosterone, who were more physically active, might have better health outcomes,” Bu Beng Yeap, MBBS, PhD, University of Western Australia, Perth, said in an interview. “We formulated the hypothesis that the combination of testosterone treatment and exercise training would improve the health of arteries more than either alone.”

To test this hypothesis, the investigators randomly assigned 80 men, aged 50-70 years, to 12 weeks of 5% testosterone cream 2 mL applied daily or placebo plus a supervised exercise program that included machine-based resistance and aerobic (cycling) exercises two to three times a week or no additional exercise.

The men (mean age, 59 years) had low-normal testosterone (6-14 nmol/L), a waist circumference of at least 95 cm (37.4 inches), and no known cardiovascular disease (CVD), type 1 diabetes, or other clinically significant illnesses. Current smokers and men on testosterone or medications that would alter testosterone levels were also excluded.

High-resolution ultrasound of the brachial artery was used to assess flow-mediated dilation (FMD) and sublingual glyceryl trinitrate (GTN) responses. FMD has been shown to be predictive of CVD risk, with a 1% increase in FMD associated with a 9%-13% decrease in future CVD events.

Based on participants’ daily dairies, testosterone adherence was 97.6%. Exercise adherence was 96.5% for twice-weekly attendance and 80.0% for thrice-weekly attendance, with no between-group differences.

As reported Feb. 22, 2021, in Hypertension, testosterone levels increased, on average, 3.0 nmol/L in both testosterone groups by week 12 (P = .003). In all, 62% of these men had levels of the hormone exceeding 14 nmol/L, compared with 29% of those receiving placebo.

Testosterone levels improved with exercise training plus placebo by 0.9 nmol/L, but fell with no exercise and placebo by 0.9 nmol/L.

In terms of vascular function, exercise training increased FMD when expressed as both the delta change (mm; P = .004) and relative rise from baseline diameter (%; P = .033).

There was no effect of exercise on GTN%, which is generally in line with exercise literature indicating that shear-mediated adaptations in response to episodic exercise occur largely in endothelial cells, the authors noted.

Testosterone did not affect any measures of FMD nor was there an effect on GTN response, despite previous evidence that lower testosterone doses might enhance smooth muscle function.

“Our main finding was that testosterone – at this dose over this duration of treatment – did not have a beneficial effect on artery health, nor did it enhance the effect of exercise,” said Dr. Yeap, who is also president of the Endocrine Society of Australia. “For middle-aged and older men wanting to improve the health of their arteries, exercise is better than testosterone!”

Shalender Bhasin, MBBS, director of research programs in men’s health, aging, and metabolism at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston, said the study is interesting from a mechanistic perspective and adds to the overall body of evidence on how testosterone affects performance, but was narrowly focused.

“They looked at very specific markers and what they’re showing is that this is not the mechanism by which testosterone improves performance,” he said. “That may be so, but it doesn’t negate the finding that testosterone improves endurance and has other vascular effects: it increases capillarity, increases blood flow to the tissues, and improves myocardial function.”

Although well done, the study doesn’t get at the larger question of whether testosterone increases cardiovascular risk, observed Dr. Bhasin. “None of the randomized studies have been large enough or long enough to determine the effect on cardiovascular events rates. There’s a lot of argument on both sides but we need some data to address that.”

The 6,000-patient TRAVERSE trial is specifically looking at long-term major cardiovascular events with topical testosterone, compared with placebo, in hypogonadal men aged 45-80 years age who have evidence of or are at increased risk for CVD. The study, which is set to be completed in April 2022, should also provide information on fracture risk in these men, said Dr. Bhasin, one of the trial’s principal investigators and lead author of the Endocrine Society’s 2018 clinical practice guideline on testosterone therapy for hypogonadism in men.

William Evans, MD, adjunct professor of human nutrition, University of California, Berkley, said in an interview that the positive effects of testosterone occur at much lower doses in men and women who are hypogonadal but, in this particular population, exercise is the key and the major recommendation.

“Testosterone has been overprescribed and overadvertised for essentially a lifetime of sedentary living, and it’s advertised as a way to get all that back without having to work for it,” he said. “Exercise has a profound and positive effect on control of blood pressure, function, and strength, and testosterone may only affect in people who are sick, people who have really low levels.”

The study was funded by the Heart Foundation of Australia. Lawley Pharmaceuticals provided the study medication and placebo. Dr. Yeap has received speaker honoraria and conference support from Bayer, Eli Lilly, and Besins Healthcare; research support from Bayer, Lily, and Lawley; and served as an adviser for Lily, Besins Healthcare, Ferring, and Lawley. Dr. Shalender reports consultation or advisement for GTx, Pfizer, and TAP; grant or other research support from Solvay and GlaxoSmithKline; and honoraria from Solvay and Auxilium. Dr. Evans reported having no relevant conflicts of interest.

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

Exercise training – but not testosterone therapy – improved vascular health in aging men with widening midsections and low to normal testosterone, new research suggests.

kali9/iStockphoto.com

“Previous studies have suggested that men with higher levels of testosterone, who were more physically active, might have better health outcomes,” Bu Beng Yeap, MBBS, PhD, University of Western Australia, Perth, said in an interview. “We formulated the hypothesis that the combination of testosterone treatment and exercise training would improve the health of arteries more than either alone.”

To test this hypothesis, the investigators randomly assigned 80 men, aged 50-70 years, to 12 weeks of 5% testosterone cream 2 mL applied daily or placebo plus a supervised exercise program that included machine-based resistance and aerobic (cycling) exercises two to three times a week or no additional exercise.

The men (mean age, 59 years) had low-normal testosterone (6-14 nmol/L), a waist circumference of at least 95 cm (37.4 inches), and no known cardiovascular disease (CVD), type 1 diabetes, or other clinically significant illnesses. Current smokers and men on testosterone or medications that would alter testosterone levels were also excluded.

High-resolution ultrasound of the brachial artery was used to assess flow-mediated dilation (FMD) and sublingual glyceryl trinitrate (GTN) responses. FMD has been shown to be predictive of CVD risk, with a 1% increase in FMD associated with a 9%-13% decrease in future CVD events.

Based on participants’ daily dairies, testosterone adherence was 97.6%. Exercise adherence was 96.5% for twice-weekly attendance and 80.0% for thrice-weekly attendance, with no between-group differences.

As reported Feb. 22, 2021, in Hypertension, testosterone levels increased, on average, 3.0 nmol/L in both testosterone groups by week 12 (P = .003). In all, 62% of these men had levels of the hormone exceeding 14 nmol/L, compared with 29% of those receiving placebo.

Testosterone levels improved with exercise training plus placebo by 0.9 nmol/L, but fell with no exercise and placebo by 0.9 nmol/L.

In terms of vascular function, exercise training increased FMD when expressed as both the delta change (mm; P = .004) and relative rise from baseline diameter (%; P = .033).

There was no effect of exercise on GTN%, which is generally in line with exercise literature indicating that shear-mediated adaptations in response to episodic exercise occur largely in endothelial cells, the authors noted.

Testosterone did not affect any measures of FMD nor was there an effect on GTN response, despite previous evidence that lower testosterone doses might enhance smooth muscle function.

“Our main finding was that testosterone – at this dose over this duration of treatment – did not have a beneficial effect on artery health, nor did it enhance the effect of exercise,” said Dr. Yeap, who is also president of the Endocrine Society of Australia. “For middle-aged and older men wanting to improve the health of their arteries, exercise is better than testosterone!”

Shalender Bhasin, MBBS, director of research programs in men’s health, aging, and metabolism at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston, said the study is interesting from a mechanistic perspective and adds to the overall body of evidence on how testosterone affects performance, but was narrowly focused.

“They looked at very specific markers and what they’re showing is that this is not the mechanism by which testosterone improves performance,” he said. “That may be so, but it doesn’t negate the finding that testosterone improves endurance and has other vascular effects: it increases capillarity, increases blood flow to the tissues, and improves myocardial function.”

Although well done, the study doesn’t get at the larger question of whether testosterone increases cardiovascular risk, observed Dr. Bhasin. “None of the randomized studies have been large enough or long enough to determine the effect on cardiovascular events rates. There’s a lot of argument on both sides but we need some data to address that.”

The 6,000-patient TRAVERSE trial is specifically looking at long-term major cardiovascular events with topical testosterone, compared with placebo, in hypogonadal men aged 45-80 years age who have evidence of or are at increased risk for CVD. The study, which is set to be completed in April 2022, should also provide information on fracture risk in these men, said Dr. Bhasin, one of the trial’s principal investigators and lead author of the Endocrine Society’s 2018 clinical practice guideline on testosterone therapy for hypogonadism in men.

William Evans, MD, adjunct professor of human nutrition, University of California, Berkley, said in an interview that the positive effects of testosterone occur at much lower doses in men and women who are hypogonadal but, in this particular population, exercise is the key and the major recommendation.

“Testosterone has been overprescribed and overadvertised for essentially a lifetime of sedentary living, and it’s advertised as a way to get all that back without having to work for it,” he said. “Exercise has a profound and positive effect on control of blood pressure, function, and strength, and testosterone may only affect in people who are sick, people who have really low levels.”

The study was funded by the Heart Foundation of Australia. Lawley Pharmaceuticals provided the study medication and placebo. Dr. Yeap has received speaker honoraria and conference support from Bayer, Eli Lilly, and Besins Healthcare; research support from Bayer, Lily, and Lawley; and served as an adviser for Lily, Besins Healthcare, Ferring, and Lawley. Dr. Shalender reports consultation or advisement for GTx, Pfizer, and TAP; grant or other research support from Solvay and GlaxoSmithKline; and honoraria from Solvay and Auxilium. Dr. Evans reported having no relevant conflicts of interest.

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

Exercise training – but not testosterone therapy – improved vascular health in aging men with widening midsections and low to normal testosterone, new research suggests.

kali9/iStockphoto.com

“Previous studies have suggested that men with higher levels of testosterone, who were more physically active, might have better health outcomes,” Bu Beng Yeap, MBBS, PhD, University of Western Australia, Perth, said in an interview. “We formulated the hypothesis that the combination of testosterone treatment and exercise training would improve the health of arteries more than either alone.”

To test this hypothesis, the investigators randomly assigned 80 men, aged 50-70 years, to 12 weeks of 5% testosterone cream 2 mL applied daily or placebo plus a supervised exercise program that included machine-based resistance and aerobic (cycling) exercises two to three times a week or no additional exercise.

The men (mean age, 59 years) had low-normal testosterone (6-14 nmol/L), a waist circumference of at least 95 cm (37.4 inches), and no known cardiovascular disease (CVD), type 1 diabetes, or other clinically significant illnesses. Current smokers and men on testosterone or medications that would alter testosterone levels were also excluded.

High-resolution ultrasound of the brachial artery was used to assess flow-mediated dilation (FMD) and sublingual glyceryl trinitrate (GTN) responses. FMD has been shown to be predictive of CVD risk, with a 1% increase in FMD associated with a 9%-13% decrease in future CVD events.

Based on participants’ daily dairies, testosterone adherence was 97.6%. Exercise adherence was 96.5% for twice-weekly attendance and 80.0% for thrice-weekly attendance, with no between-group differences.

As reported Feb. 22, 2021, in Hypertension, testosterone levels increased, on average, 3.0 nmol/L in both testosterone groups by week 12 (P = .003). In all, 62% of these men had levels of the hormone exceeding 14 nmol/L, compared with 29% of those receiving placebo.

Testosterone levels improved with exercise training plus placebo by 0.9 nmol/L, but fell with no exercise and placebo by 0.9 nmol/L.

In terms of vascular function, exercise training increased FMD when expressed as both the delta change (mm; P = .004) and relative rise from baseline diameter (%; P = .033).

There was no effect of exercise on GTN%, which is generally in line with exercise literature indicating that shear-mediated adaptations in response to episodic exercise occur largely in endothelial cells, the authors noted.

Testosterone did not affect any measures of FMD nor was there an effect on GTN response, despite previous evidence that lower testosterone doses might enhance smooth muscle function.

“Our main finding was that testosterone – at this dose over this duration of treatment – did not have a beneficial effect on artery health, nor did it enhance the effect of exercise,” said Dr. Yeap, who is also president of the Endocrine Society of Australia. “For middle-aged and older men wanting to improve the health of their arteries, exercise is better than testosterone!”

Shalender Bhasin, MBBS, director of research programs in men’s health, aging, and metabolism at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston, said the study is interesting from a mechanistic perspective and adds to the overall body of evidence on how testosterone affects performance, but was narrowly focused.

“They looked at very specific markers and what they’re showing is that this is not the mechanism by which testosterone improves performance,” he said. “That may be so, but it doesn’t negate the finding that testosterone improves endurance and has other vascular effects: it increases capillarity, increases blood flow to the tissues, and improves myocardial function.”

Although well done, the study doesn’t get at the larger question of whether testosterone increases cardiovascular risk, observed Dr. Bhasin. “None of the randomized studies have been large enough or long enough to determine the effect on cardiovascular events rates. There’s a lot of argument on both sides but we need some data to address that.”

The 6,000-patient TRAVERSE trial is specifically looking at long-term major cardiovascular events with topical testosterone, compared with placebo, in hypogonadal men aged 45-80 years age who have evidence of or are at increased risk for CVD. The study, which is set to be completed in April 2022, should also provide information on fracture risk in these men, said Dr. Bhasin, one of the trial’s principal investigators and lead author of the Endocrine Society’s 2018 clinical practice guideline on testosterone therapy for hypogonadism in men.

William Evans, MD, adjunct professor of human nutrition, University of California, Berkley, said in an interview that the positive effects of testosterone occur at much lower doses in men and women who are hypogonadal but, in this particular population, exercise is the key and the major recommendation.

“Testosterone has been overprescribed and overadvertised for essentially a lifetime of sedentary living, and it’s advertised as a way to get all that back without having to work for it,” he said. “Exercise has a profound and positive effect on control of blood pressure, function, and strength, and testosterone may only affect in people who are sick, people who have really low levels.”

The study was funded by the Heart Foundation of Australia. Lawley Pharmaceuticals provided the study medication and placebo. Dr. Yeap has received speaker honoraria and conference support from Bayer, Eli Lilly, and Besins Healthcare; research support from Bayer, Lily, and Lawley; and served as an adviser for Lily, Besins Healthcare, Ferring, and Lawley. Dr. Shalender reports consultation or advisement for GTx, Pfizer, and TAP; grant or other research support from Solvay and GlaxoSmithKline; and honoraria from Solvay and Auxilium. Dr. Evans reported having no relevant conflicts of interest.

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

In patients with acute ischemic stroke, the use of thrombolysis in the late window of 4.5-9 hours after symptom onset was not associated with an increase in clot migration that would cause reduced clot accessibility to endovascular therapy, a new analysis from the EXTEND trial shows.

“There was no significant difference in the incidence of clot migration leading to clot inaccessibility in patients who received placebo or (intravenous) thrombolysis,” the authors report.

“Our results found no convincing evidence against the use of bridging thrombolysis before endovascular therapy in patients with acute ischemic stroke who present outside the 4.5-hour window,” they conclude.

“This information is important because it provides some comfort for neurointerventionists that IV thrombolysis does not unduly increase the risk of clot migration,” senior author, Bernard Yan, DMedSci, FRACP, told this news organization.

The study was published online in Stroke on Feb. 16.

The Australian researchers explain that endovascular thrombectomy is the standard of care in patients presenting with acute ischemic stroke caused by large-vessel occlusion, and current treatment guidelines recommend bridging thrombolysis for all patients receiving thrombectomy within the 4.5-hour time window.

While thrombectomy is also recommended in selected patients up to 24 hours after onset of symptoms, it remains unclear whether thrombolysis pretreatment should be administered in this setting.

One of the issues that might affect use of thrombolysis is distal clot migration. As proximal clot location is a crucial factor determining suitability for endovascular clot retrieval, distal migration may prevent successful thrombectomy, they note.   

“Clot migration can happen any time and makes life more difficult for the neurointerventionist who performs the endovascular clot retrieval,” added Dr. Yan, who is a neurologist and neurointerventionist at the Royal Melbourne Hospital, Australia.

In the current paper, the researchers report a retrospective analysis of data from the EXTEND trial of late thrombolysis, defined as 4.5-9 hours after symptom onset, to investigate the association between thrombolysis and clot migration leading to clot irretrievability.

The analysis included a total of 220 patients (109 patients in the placebo group and 111 in the thrombolysis group).

Results showed that retrievable clot was seen on baseline imaging in 69% of patients in the placebo group and 61% in the thrombolysis group. Clot resolution occurred in 28% of patients in the placebo group and 50% in the thrombolysis group. 

No significant difference was observed in the incidence of clot migration leading to inaccessibility between groups. Clot migration from a retrievable to nonretrievable location occurred in 19% of the placebo group and 14% of the thrombolysis group, with an odds ratio for clot migration in the thrombolysis group of 0.70 (95% confidence interval, 0.35-1.44). This outcome was consistent across subgroups.

The researchers note that, to their knowledge, this is the first randomized controlled study to assess the effect of thrombolysis on clot migration and accessibility in an extended time window.

They acknowledge that a limitation of this study is that they only assessed clot migration from a retrievable to a nonretrievable location; therefore, the true frequency of any clot migration occurring was likely to be higher, and this could explain why other reports have found higher odds ratios of clot migration.

But they point out that they chose to limit their analysis in this way specifically to guide decision-making regarding bridging thrombolysis incorporating endovascular therapy in the extended time window.

“The findings of this study are highly relevant in the current clinical environment, where there are multiple ongoing trials looking at removing thrombolysis pretreatment within the 4.5-hour time window in thrombectomy patients,” the authors write.  

“We have demonstrated that thrombolysis in the 4.5- to 9-hour window is not associated with reduced clot accessibility, and this information will be useful in future trial designs incorporating this extended time window,” they add.

Commenting on the study for this news organization, Michael Hill, MD, University of Calgary (Alta.), said: “Thrombus migration does happen and is likely part of the natural history of ischemic stroke, which may be influenced by therapeutics such as thrombolysis. This paper’s top-line result is that thrombus migration occurs in both treated and untreated groups – and therefore that this is really an observation of natural history.”

Dr. Hill says that, at present, patients should be treated with thrombolysis before endovascular therapy if they are eligible, and these results do not change that recommendation. 

“The results of the ongoing trials comparing direct thrombectomy with thrombolysis plus thrombectomy will help to understand the potential clinical outcome relevance of this phenomenon,” he added.

The EXTEND trial was supported by grants from the Australian National Health and Medical Research Council of Australia and the Commonwealth Scientific and Industrial Research Organization Flagship Program. Dr. Yan reported no relevant financial relationships.

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

In patients with acute ischemic stroke, the use of thrombolysis in the late window of 4.5-9 hours after symptom onset was not associated with an increase in clot migration that would cause reduced clot accessibility to endovascular therapy, a new analysis from the EXTEND trial shows.

“There was no significant difference in the incidence of clot migration leading to clot inaccessibility in patients who received placebo or (intravenous) thrombolysis,” the authors report.

“Our results found no convincing evidence against the use of bridging thrombolysis before endovascular therapy in patients with acute ischemic stroke who present outside the 4.5-hour window,” they conclude.

“This information is important because it provides some comfort for neurointerventionists that IV thrombolysis does not unduly increase the risk of clot migration,” senior author, Bernard Yan, DMedSci, FRACP, told this news organization.

The study was published online in Stroke on Feb. 16.

The Australian researchers explain that endovascular thrombectomy is the standard of care in patients presenting with acute ischemic stroke caused by large-vessel occlusion, and current treatment guidelines recommend bridging thrombolysis for all patients receiving thrombectomy within the 4.5-hour time window.

While thrombectomy is also recommended in selected patients up to 24 hours after onset of symptoms, it remains unclear whether thrombolysis pretreatment should be administered in this setting.

One of the issues that might affect use of thrombolysis is distal clot migration. As proximal clot location is a crucial factor determining suitability for endovascular clot retrieval, distal migration may prevent successful thrombectomy, they note.   

“Clot migration can happen any time and makes life more difficult for the neurointerventionist who performs the endovascular clot retrieval,” added Dr. Yan, who is a neurologist and neurointerventionist at the Royal Melbourne Hospital, Australia.

In the current paper, the researchers report a retrospective analysis of data from the EXTEND trial of late thrombolysis, defined as 4.5-9 hours after symptom onset, to investigate the association between thrombolysis and clot migration leading to clot irretrievability.

The analysis included a total of 220 patients (109 patients in the placebo group and 111 in the thrombolysis group).

Results showed that retrievable clot was seen on baseline imaging in 69% of patients in the placebo group and 61% in the thrombolysis group. Clot resolution occurred in 28% of patients in the placebo group and 50% in the thrombolysis group. 

No significant difference was observed in the incidence of clot migration leading to inaccessibility between groups. Clot migration from a retrievable to nonretrievable location occurred in 19% of the placebo group and 14% of the thrombolysis group, with an odds ratio for clot migration in the thrombolysis group of 0.70 (95% confidence interval, 0.35-1.44). This outcome was consistent across subgroups.

The researchers note that, to their knowledge, this is the first randomized controlled study to assess the effect of thrombolysis on clot migration and accessibility in an extended time window.

They acknowledge that a limitation of this study is that they only assessed clot migration from a retrievable to a nonretrievable location; therefore, the true frequency of any clot migration occurring was likely to be higher, and this could explain why other reports have found higher odds ratios of clot migration.

But they point out that they chose to limit their analysis in this way specifically to guide decision-making regarding bridging thrombolysis incorporating endovascular therapy in the extended time window.

“The findings of this study are highly relevant in the current clinical environment, where there are multiple ongoing trials looking at removing thrombolysis pretreatment within the 4.5-hour time window in thrombectomy patients,” the authors write.  

“We have demonstrated that thrombolysis in the 4.5- to 9-hour window is not associated with reduced clot accessibility, and this information will be useful in future trial designs incorporating this extended time window,” they add.

Commenting on the study for this news organization, Michael Hill, MD, University of Calgary (Alta.), said: “Thrombus migration does happen and is likely part of the natural history of ischemic stroke, which may be influenced by therapeutics such as thrombolysis. This paper’s top-line result is that thrombus migration occurs in both treated and untreated groups – and therefore that this is really an observation of natural history.”

Dr. Hill says that, at present, patients should be treated with thrombolysis before endovascular therapy if they are eligible, and these results do not change that recommendation. 

“The results of the ongoing trials comparing direct thrombectomy with thrombolysis plus thrombectomy will help to understand the potential clinical outcome relevance of this phenomenon,” he added.

The EXTEND trial was supported by grants from the Australian National Health and Medical Research Council of Australia and the Commonwealth Scientific and Industrial Research Organization Flagship Program. Dr. Yan reported no relevant financial relationships.

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

In patients with acute ischemic stroke, the use of thrombolysis in the late window of 4.5-9 hours after symptom onset was not associated with an increase in clot migration that would cause reduced clot accessibility to endovascular therapy, a new analysis from the EXTEND trial shows.

“There was no significant difference in the incidence of clot migration leading to clot inaccessibility in patients who received placebo or (intravenous) thrombolysis,” the authors report.

“Our results found no convincing evidence against the use of bridging thrombolysis before endovascular therapy in patients with acute ischemic stroke who present outside the 4.5-hour window,” they conclude.

“This information is important because it provides some comfort for neurointerventionists that IV thrombolysis does not unduly increase the risk of clot migration,” senior author, Bernard Yan, DMedSci, FRACP, told this news organization.

The study was published online in Stroke on Feb. 16.

The Australian researchers explain that endovascular thrombectomy is the standard of care in patients presenting with acute ischemic stroke caused by large-vessel occlusion, and current treatment guidelines recommend bridging thrombolysis for all patients receiving thrombectomy within the 4.5-hour time window.

While thrombectomy is also recommended in selected patients up to 24 hours after onset of symptoms, it remains unclear whether thrombolysis pretreatment should be administered in this setting.

One of the issues that might affect use of thrombolysis is distal clot migration. As proximal clot location is a crucial factor determining suitability for endovascular clot retrieval, distal migration may prevent successful thrombectomy, they note.   

“Clot migration can happen any time and makes life more difficult for the neurointerventionist who performs the endovascular clot retrieval,” added Dr. Yan, who is a neurologist and neurointerventionist at the Royal Melbourne Hospital, Australia.

In the current paper, the researchers report a retrospective analysis of data from the EXTEND trial of late thrombolysis, defined as 4.5-9 hours after symptom onset, to investigate the association between thrombolysis and clot migration leading to clot irretrievability.

The analysis included a total of 220 patients (109 patients in the placebo group and 111 in the thrombolysis group).

Results showed that retrievable clot was seen on baseline imaging in 69% of patients in the placebo group and 61% in the thrombolysis group. Clot resolution occurred in 28% of patients in the placebo group and 50% in the thrombolysis group. 

No significant difference was observed in the incidence of clot migration leading to inaccessibility between groups. Clot migration from a retrievable to nonretrievable location occurred in 19% of the placebo group and 14% of the thrombolysis group, with an odds ratio for clot migration in the thrombolysis group of 0.70 (95% confidence interval, 0.35-1.44). This outcome was consistent across subgroups.

The researchers note that, to their knowledge, this is the first randomized controlled study to assess the effect of thrombolysis on clot migration and accessibility in an extended time window.

They acknowledge that a limitation of this study is that they only assessed clot migration from a retrievable to a nonretrievable location; therefore, the true frequency of any clot migration occurring was likely to be higher, and this could explain why other reports have found higher odds ratios of clot migration.

But they point out that they chose to limit their analysis in this way specifically to guide decision-making regarding bridging thrombolysis incorporating endovascular therapy in the extended time window.

“The findings of this study are highly relevant in the current clinical environment, where there are multiple ongoing trials looking at removing thrombolysis pretreatment within the 4.5-hour time window in thrombectomy patients,” the authors write.  

“We have demonstrated that thrombolysis in the 4.5- to 9-hour window is not associated with reduced clot accessibility, and this information will be useful in future trial designs incorporating this extended time window,” they add.

Commenting on the study for this news organization, Michael Hill, MD, University of Calgary (Alta.), said: “Thrombus migration does happen and is likely part of the natural history of ischemic stroke, which may be influenced by therapeutics such as thrombolysis. This paper’s top-line result is that thrombus migration occurs in both treated and untreated groups – and therefore that this is really an observation of natural history.”

Dr. Hill says that, at present, patients should be treated with thrombolysis before endovascular therapy if they are eligible, and these results do not change that recommendation. 

“The results of the ongoing trials comparing direct thrombectomy with thrombolysis plus thrombectomy will help to understand the potential clinical outcome relevance of this phenomenon,” he added.

The EXTEND trial was supported by grants from the Australian National Health and Medical Research Council of Australia and the Commonwealth Scientific and Industrial Research Organization Flagship Program. Dr. Yan reported no relevant financial relationships.

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

People who mostly ate foods with a low glycemic index had a lower likelihood of premature death and major cardiovascular disease (CVD) events, compared with those whose diet included more “poor-quality” food with a high glycemic index.

The results from the global PURE study of nearly 120,000 people provide evidence that helps cement glycemic index as a key measure of dietary health.

This new analysis from PURE (Prospective Urban and Rural Epidemiological Study) – a massive prospective epidemiologic study – shows people with a diet in the highest quintile of glycemic index had a significant 25% higher rate of combined total deaths and major CVD events during a median follow-up of nearly 10 years, compared with those with a diet in the lowest glycemic index quintile, in the report published online on Feb. 24, 2021, in the New England Journal of Medicine.

David J.A. Jenkins, MD, PhD, DSc, lead author, said people do not necessarily need to closely track the glycemic index of what they eat to follow the guidance that lower is better.

The link between lower glycemic load and fewer CVD events was even stronger among people with an established history of CVD at study entry. In this subset, which included 9% of the total cohort, people in the highest quintile for glycemic index consumption had a 51% higher rate of the composite primary endpoint, compared with those in the lowest quintile, in an analysis that adjusted for several potential confounders.

A simple but accurate and effective public health message is to follow existing dietary recommendations to eat better-quality food – more unprocessed fruits, vegetables, legumes, and whole grains – Dr. Jenkins advised. Those who prefer a more detailed approach could use the comprehensive glycemic index tables compiled by researchers at the University of Sydney.
 

‘All carbohydrates are not the same’

“What we’re saying is that all carbohydrates are not the same. Some seem to increase the risk for CVD, and others seem protective. This is not new, but worth restating in an era of low-carb and no-carb diets,” said Dr. Jenkins.

Low-glycemic-index foods are generally unprocessed foods in their native state, including fruits, vegetables, legumes, and unrefined whole grains. High-glycemic-index foods contain processed and refined carbohydrates that deliver jolts of glucose soon after eating, as the sugar in these carbohydrates quickly moves from the gut to the bloodstream.

An association between a diet with a lower glycemic index and better outcomes had appeared in prior reports from other studies, but not as unambiguously as in the new data from PURE, likely because of fewer study participants in previous studies.

Another feature of PURE that adds to the generalizability of the findings is the diversity of adults included in the study, from 20 countries on five continents.

“This clinches it,” Dr. Jenkins declared in an interview.
 

New PURE data tip the evidence balance

The NEJM article includes a new meta-analysis that adds the PURE findings to data from two large prior reports that were each less conclusive. The new calculation with the PURE numbers helps establish a clearer association between a diet with a higher glycemic index and the endpoint of CVD death, showing an overall 26% increase in the outcome.

The PURE data are especially informative because the investigators collected additional information on a range of potential confounders they incorporated into their analyses.

“We were able to include a lot of documentation on many potential confounders. That’s a strength of our data,” noted Dr. Jenkins, a professor of nutritional science and medicine at the University of Toronto.

Higher BMI associated with greater glycemic index effect

Another important analysis in the new report calculated the impact of a higher glycemic index diet among people with a body mass index (BMI) of less than 25 kg/m2 as well as higher BMIs.

Among people in the lower BMI subgroup, greater intake of high-glycemic-index foods showed slightly more incident primary outcome events. In contrast, people with a BMI of 25 or greater showed a steady increment in primary outcome events as the glycemic index of their diet increased.

People with higher BMIs in the quartile that ate the greatest amount of high-glycemic =-index foods had a significant 38% higher rate of primary outcome events, compared with people with similar BMIs in the lowest quartile for high-glycemic-index intake.

However, the study showed no impact on the primary association of high glycemic index and increased adverse outcomes by exercise habits, smoking, use of blood pressure medications, or use of statins. 

The new report complements a separate analysis from PURE published just a few weeks earlier in the BMJ that established a significant association between increased consumption of whole grains and fewer CVD events, compared with people who had more refined grains in their diet, as reported by this news organization.

This prior report on whole versus refined grains, which Dr. Jenkins coauthored, looked at carbohydrate quality using a two-pronged approach, while glycemic index is a continuous variable that provides more nuance and takes into account carbohydrates from sources other than grains, Dr. Jenkins said.

PURE enrolled roughly 225,000 people aged 35-70 years at entry. The glycemic index analysis focused on 119,575 people who had data available for the primary outcome. During a median follow-up of 9.5 years, these people had 14,075 primary outcome events, including 8,780 deaths.

Analyses that looked at the individual outcomes that comprised the composite endpoint showed significant associations between a high-glycemic-index diet and total mortality, CVD death, non-CVD death, and stroke, but showed no significant link with myocardial infarction or heart failure. These findings are consistent with prior results of other studies that showed a stronger link between stroke and a high glycemic index diet, compared with other nonfatal CVD events.

Dr. Jenkins suggested that the significant excess of non-CVD deaths linked with a high-glycemic-index diet may stem from the impact of this type of diet on cancer-associated mortality.

PURE received partial funding through unrestricted grants from several drug companies. Dr. Jenkins has reported receiving gifts from several food-related trade associations and food companies, as well as research grants from two legume-oriented trade associations.

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

People who mostly ate foods with a low glycemic index had a lower likelihood of premature death and major cardiovascular disease (CVD) events, compared with those whose diet included more “poor-quality” food with a high glycemic index.

The results from the global PURE study of nearly 120,000 people provide evidence that helps cement glycemic index as a key measure of dietary health.

This new analysis from PURE (Prospective Urban and Rural Epidemiological Study) – a massive prospective epidemiologic study – shows people with a diet in the highest quintile of glycemic index had a significant 25% higher rate of combined total deaths and major CVD events during a median follow-up of nearly 10 years, compared with those with a diet in the lowest glycemic index quintile, in the report published online on Feb. 24, 2021, in the New England Journal of Medicine.

David J.A. Jenkins, MD, PhD, DSc, lead author, said people do not necessarily need to closely track the glycemic index of what they eat to follow the guidance that lower is better.

The link between lower glycemic load and fewer CVD events was even stronger among people with an established history of CVD at study entry. In this subset, which included 9% of the total cohort, people in the highest quintile for glycemic index consumption had a 51% higher rate of the composite primary endpoint, compared with those in the lowest quintile, in an analysis that adjusted for several potential confounders.

A simple but accurate and effective public health message is to follow existing dietary recommendations to eat better-quality food – more unprocessed fruits, vegetables, legumes, and whole grains – Dr. Jenkins advised. Those who prefer a more detailed approach could use the comprehensive glycemic index tables compiled by researchers at the University of Sydney.
 

‘All carbohydrates are not the same’

“What we’re saying is that all carbohydrates are not the same. Some seem to increase the risk for CVD, and others seem protective. This is not new, but worth restating in an era of low-carb and no-carb diets,” said Dr. Jenkins.

Low-glycemic-index foods are generally unprocessed foods in their native state, including fruits, vegetables, legumes, and unrefined whole grains. High-glycemic-index foods contain processed and refined carbohydrates that deliver jolts of glucose soon after eating, as the sugar in these carbohydrates quickly moves from the gut to the bloodstream.

An association between a diet with a lower glycemic index and better outcomes had appeared in prior reports from other studies, but not as unambiguously as in the new data from PURE, likely because of fewer study participants in previous studies.

Another feature of PURE that adds to the generalizability of the findings is the diversity of adults included in the study, from 20 countries on five continents.

“This clinches it,” Dr. Jenkins declared in an interview.
 

New PURE data tip the evidence balance

The NEJM article includes a new meta-analysis that adds the PURE findings to data from two large prior reports that were each less conclusive. The new calculation with the PURE numbers helps establish a clearer association between a diet with a higher glycemic index and the endpoint of CVD death, showing an overall 26% increase in the outcome.

The PURE data are especially informative because the investigators collected additional information on a range of potential confounders they incorporated into their analyses.

“We were able to include a lot of documentation on many potential confounders. That’s a strength of our data,” noted Dr. Jenkins, a professor of nutritional science and medicine at the University of Toronto.

Higher BMI associated with greater glycemic index effect

Another important analysis in the new report calculated the impact of a higher glycemic index diet among people with a body mass index (BMI) of less than 25 kg/m2 as well as higher BMIs.

Among people in the lower BMI subgroup, greater intake of high-glycemic-index foods showed slightly more incident primary outcome events. In contrast, people with a BMI of 25 or greater showed a steady increment in primary outcome events as the glycemic index of their diet increased.

People with higher BMIs in the quartile that ate the greatest amount of high-glycemic =-index foods had a significant 38% higher rate of primary outcome events, compared with people with similar BMIs in the lowest quartile for high-glycemic-index intake.

However, the study showed no impact on the primary association of high glycemic index and increased adverse outcomes by exercise habits, smoking, use of blood pressure medications, or use of statins. 

The new report complements a separate analysis from PURE published just a few weeks earlier in the BMJ that established a significant association between increased consumption of whole grains and fewer CVD events, compared with people who had more refined grains in their diet, as reported by this news organization.

This prior report on whole versus refined grains, which Dr. Jenkins coauthored, looked at carbohydrate quality using a two-pronged approach, while glycemic index is a continuous variable that provides more nuance and takes into account carbohydrates from sources other than grains, Dr. Jenkins said.

PURE enrolled roughly 225,000 people aged 35-70 years at entry. The glycemic index analysis focused on 119,575 people who had data available for the primary outcome. During a median follow-up of 9.5 years, these people had 14,075 primary outcome events, including 8,780 deaths.

Analyses that looked at the individual outcomes that comprised the composite endpoint showed significant associations between a high-glycemic-index diet and total mortality, CVD death, non-CVD death, and stroke, but showed no significant link with myocardial infarction or heart failure. These findings are consistent with prior results of other studies that showed a stronger link between stroke and a high glycemic index diet, compared with other nonfatal CVD events.

Dr. Jenkins suggested that the significant excess of non-CVD deaths linked with a high-glycemic-index diet may stem from the impact of this type of diet on cancer-associated mortality.

PURE received partial funding through unrestricted grants from several drug companies. Dr. Jenkins has reported receiving gifts from several food-related trade associations and food companies, as well as research grants from two legume-oriented trade associations.

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

People who mostly ate foods with a low glycemic index had a lower likelihood of premature death and major cardiovascular disease (CVD) events, compared with those whose diet included more “poor-quality” food with a high glycemic index.

The results from the global PURE study of nearly 120,000 people provide evidence that helps cement glycemic index as a key measure of dietary health.

This new analysis from PURE (Prospective Urban and Rural Epidemiological Study) – a massive prospective epidemiologic study – shows people with a diet in the highest quintile of glycemic index had a significant 25% higher rate of combined total deaths and major CVD events during a median follow-up of nearly 10 years, compared with those with a diet in the lowest glycemic index quintile, in the report published online on Feb. 24, 2021, in the New England Journal of Medicine.

David J.A. Jenkins, MD, PhD, DSc, lead author, said people do not necessarily need to closely track the glycemic index of what they eat to follow the guidance that lower is better.

The link between lower glycemic load and fewer CVD events was even stronger among people with an established history of CVD at study entry. In this subset, which included 9% of the total cohort, people in the highest quintile for glycemic index consumption had a 51% higher rate of the composite primary endpoint, compared with those in the lowest quintile, in an analysis that adjusted for several potential confounders.

A simple but accurate and effective public health message is to follow existing dietary recommendations to eat better-quality food – more unprocessed fruits, vegetables, legumes, and whole grains – Dr. Jenkins advised. Those who prefer a more detailed approach could use the comprehensive glycemic index tables compiled by researchers at the University of Sydney.
 

‘All carbohydrates are not the same’

“What we’re saying is that all carbohydrates are not the same. Some seem to increase the risk for CVD, and others seem protective. This is not new, but worth restating in an era of low-carb and no-carb diets,” said Dr. Jenkins.

Low-glycemic-index foods are generally unprocessed foods in their native state, including fruits, vegetables, legumes, and unrefined whole grains. High-glycemic-index foods contain processed and refined carbohydrates that deliver jolts of glucose soon after eating, as the sugar in these carbohydrates quickly moves from the gut to the bloodstream.

An association between a diet with a lower glycemic index and better outcomes had appeared in prior reports from other studies, but not as unambiguously as in the new data from PURE, likely because of fewer study participants in previous studies.

Another feature of PURE that adds to the generalizability of the findings is the diversity of adults included in the study, from 20 countries on five continents.

“This clinches it,” Dr. Jenkins declared in an interview.
 

New PURE data tip the evidence balance

The NEJM article includes a new meta-analysis that adds the PURE findings to data from two large prior reports that were each less conclusive. The new calculation with the PURE numbers helps establish a clearer association between a diet with a higher glycemic index and the endpoint of CVD death, showing an overall 26% increase in the outcome.

The PURE data are especially informative because the investigators collected additional information on a range of potential confounders they incorporated into their analyses.

“We were able to include a lot of documentation on many potential confounders. That’s a strength of our data,” noted Dr. Jenkins, a professor of nutritional science and medicine at the University of Toronto.

Higher BMI associated with greater glycemic index effect

Another important analysis in the new report calculated the impact of a higher glycemic index diet among people with a body mass index (BMI) of less than 25 kg/m2 as well as higher BMIs.

Among people in the lower BMI subgroup, greater intake of high-glycemic-index foods showed slightly more incident primary outcome events. In contrast, people with a BMI of 25 or greater showed a steady increment in primary outcome events as the glycemic index of their diet increased.

People with higher BMIs in the quartile that ate the greatest amount of high-glycemic =-index foods had a significant 38% higher rate of primary outcome events, compared with people with similar BMIs in the lowest quartile for high-glycemic-index intake.

However, the study showed no impact on the primary association of high glycemic index and increased adverse outcomes by exercise habits, smoking, use of blood pressure medications, or use of statins. 

The new report complements a separate analysis from PURE published just a few weeks earlier in the BMJ that established a significant association between increased consumption of whole grains and fewer CVD events, compared with people who had more refined grains in their diet, as reported by this news organization.

This prior report on whole versus refined grains, which Dr. Jenkins coauthored, looked at carbohydrate quality using a two-pronged approach, while glycemic index is a continuous variable that provides more nuance and takes into account carbohydrates from sources other than grains, Dr. Jenkins said.

PURE enrolled roughly 225,000 people aged 35-70 years at entry. The glycemic index analysis focused on 119,575 people who had data available for the primary outcome. During a median follow-up of 9.5 years, these people had 14,075 primary outcome events, including 8,780 deaths.

Analyses that looked at the individual outcomes that comprised the composite endpoint showed significant associations between a high-glycemic-index diet and total mortality, CVD death, non-CVD death, and stroke, but showed no significant link with myocardial infarction or heart failure. These findings are consistent with prior results of other studies that showed a stronger link between stroke and a high glycemic index diet, compared with other nonfatal CVD events.

Dr. Jenkins suggested that the significant excess of non-CVD deaths linked with a high-glycemic-index diet may stem from the impact of this type of diet on cancer-associated mortality.

PURE received partial funding through unrestricted grants from several drug companies. Dr. Jenkins has reported receiving gifts from several food-related trade associations and food companies, as well as research grants from two legume-oriented trade associations.

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

A study of post–COVID-19 patients in the United Kingdom who developed severe lung inflammation after they left the hospital may provide greater clarity on which patients are most likely to have persistent lung dysfunction.

In addition to pinpointing those most at risk, the findings showed that conventional corticosteroid treatment is highly effective in improving lung function and reducing symptoms.

Researchers from Guy’s and St. Thomas’ National Health Foundation Trust in London reported that a small percentage of patients – 4.8%, or 35 of 837 patients in the study – had severe persistent interstitial lung disease (ILD), mostly organizing pneumonia, 4 weeks after discharge. Of these patients, 30 received steroid treatment, all of whom showed improvement in lung function.

Lead author Katherine Jane Myall, MRCP, and colleagues wrote that the most common radiologic finding in acute COVID-19 is bilateral ground-glass opacification, and findings of organizing pneumonia are common. However, no reports exist of the role of inflammatory infiltrates during recovery from COVID-19 or of the effectiveness of treatments for persistent ILD. “The long-term respiratory morbidity remains unclear,” Dr. Myall and colleagues wrote.

The study findings are significant because they quantify the degree of lung disease that patients have after COVID-19, said Sachin Gupta, MD, FCCP, a pulmonologist and critical care specialist at Alameda Health System in Oakland, Calif. He added that the disease course and presentation followed the pattern of organizing pneumonia in some patients, and traditional corticosteroid therapy seemed to resolve symptoms and improve lung function.

“This is a really important piece to get out there because it describes what a lot of us are worried about in patients with post-COVID lung disease and about what type of lung disease they have. It offers a potential treatment,” he said.

Dr. Myall and colleagues noted that even a “relatively small proportion” of patients with persistent, severe ILD – as reported in this study – pose “a significant disease burden.” They added: “Prompt therapy may avoid potentially permanent fibrosis and functional impairment.”

The single-center, prospective, observational study followed discharged patients with telephone calls 4 weeks after discharge to determine their status. At that point, 39% of the study cohort (n = 325) reported ongoing symptoms.

The patients had outpatient examinations at 6 weeks post discharge, at which time 42.9% (n = 138) had no signs or symptoms of persistent disease; 33.8% (n = 110) had symptoms but no radiologic findings and received referrals to other departments; and 24% (n = 77) were referred to the post-COVID lung disease multidisciplinary team. A total of 59 were diagnosed with persistent post-COVID interstitial change, 35 of whom had organizing pneumonia, hence the rationale for using steroids in this group, Dr. Myall and colleagues stated.

The 30 patients treated with corticosteroids received a maximum initial dose of 0.5 mg/kg prednisolone, which was rapidly weaned over 3 weeks. Some patients received lower doses depending on their comorbidities.

Treatment resulted in an average relative increase in transfer factor of 31.6% (P < .001) and forced vital capacity of 9.6% (P = .014), along with significant improvement in symptoms and x-ray signs.

The study identified some key characteristics of the patients who had persistent post–COVID-19 inflammatory ILD. They were mostly male (71.5%) and overweight with an average body mass index of 28.3, but only 26% were obese. Most had at least one comorbidity, with the most common being diabetes and asthma (22.9%). Their average hospital stay was 16.9 days, 82.9% required oxygen, 55% were in the ICU, and 46% needed invasive mechanical ventilation.

The patients most vulnerable to ILD and organizing pneumonia were the “sicker” of the whole cohort, Dr. Gupta said. “In one sense, it’s reassuring that this is not just happening in anyone; this is happening in patients who had the worst course and were hospitalized in the ICU for the most part.”

The study shows that identifying these patients early on and initiating steroid therapy could avoid persistent lung injury and scarring, Dr. Gupta said.

The London researchers noted that theirs wasn’t a radiologic study, so CT scans weren’t formally scored before and after treatment. They also acknowledged vagueness about imaging and clinical findings representing “nothing other than slow ongoing recovery.”

Patients with post–COVID-19 ILD will require ongoing follow-up to better understand the disease course, Dr. Myall and colleagues stated, although they predicted organizing pneumonia is unlikely to recur once it resolves.

Dr. Myall and coauthors had no relevant relationships to disclose. Dr. Gupta disclosed he is also an employee and shareholder at Genentech.

A study of post–COVID-19 patients in the United Kingdom who developed severe lung inflammation after they left the hospital may provide greater clarity on which patients are most likely to have persistent lung dysfunction.

In addition to pinpointing those most at risk, the findings showed that conventional corticosteroid treatment is highly effective in improving lung function and reducing symptoms.

Researchers from Guy’s and St. Thomas’ National Health Foundation Trust in London reported that a small percentage of patients – 4.8%, or 35 of 837 patients in the study – had severe persistent interstitial lung disease (ILD), mostly organizing pneumonia, 4 weeks after discharge. Of these patients, 30 received steroid treatment, all of whom showed improvement in lung function.

Lead author Katherine Jane Myall, MRCP, and colleagues wrote that the most common radiologic finding in acute COVID-19 is bilateral ground-glass opacification, and findings of organizing pneumonia are common. However, no reports exist of the role of inflammatory infiltrates during recovery from COVID-19 or of the effectiveness of treatments for persistent ILD. “The long-term respiratory morbidity remains unclear,” Dr. Myall and colleagues wrote.

The study findings are significant because they quantify the degree of lung disease that patients have after COVID-19, said Sachin Gupta, MD, FCCP, a pulmonologist and critical care specialist at Alameda Health System in Oakland, Calif. He added that the disease course and presentation followed the pattern of organizing pneumonia in some patients, and traditional corticosteroid therapy seemed to resolve symptoms and improve lung function.

“This is a really important piece to get out there because it describes what a lot of us are worried about in patients with post-COVID lung disease and about what type of lung disease they have. It offers a potential treatment,” he said.

Dr. Myall and colleagues noted that even a “relatively small proportion” of patients with persistent, severe ILD – as reported in this study – pose “a significant disease burden.” They added: “Prompt therapy may avoid potentially permanent fibrosis and functional impairment.”

The single-center, prospective, observational study followed discharged patients with telephone calls 4 weeks after discharge to determine their status. At that point, 39% of the study cohort (n = 325) reported ongoing symptoms.

The patients had outpatient examinations at 6 weeks post discharge, at which time 42.9% (n = 138) had no signs or symptoms of persistent disease; 33.8% (n = 110) had symptoms but no radiologic findings and received referrals to other departments; and 24% (n = 77) were referred to the post-COVID lung disease multidisciplinary team. A total of 59 were diagnosed with persistent post-COVID interstitial change, 35 of whom had organizing pneumonia, hence the rationale for using steroids in this group, Dr. Myall and colleagues stated.

The 30 patients treated with corticosteroids received a maximum initial dose of 0.5 mg/kg prednisolone, which was rapidly weaned over 3 weeks. Some patients received lower doses depending on their comorbidities.

Treatment resulted in an average relative increase in transfer factor of 31.6% (P < .001) and forced vital capacity of 9.6% (P = .014), along with significant improvement in symptoms and x-ray signs.

The study identified some key characteristics of the patients who had persistent post–COVID-19 inflammatory ILD. They were mostly male (71.5%) and overweight with an average body mass index of 28.3, but only 26% were obese. Most had at least one comorbidity, with the most common being diabetes and asthma (22.9%). Their average hospital stay was 16.9 days, 82.9% required oxygen, 55% were in the ICU, and 46% needed invasive mechanical ventilation.

The patients most vulnerable to ILD and organizing pneumonia were the “sicker” of the whole cohort, Dr. Gupta said. “In one sense, it’s reassuring that this is not just happening in anyone; this is happening in patients who had the worst course and were hospitalized in the ICU for the most part.”

The study shows that identifying these patients early on and initiating steroid therapy could avoid persistent lung injury and scarring, Dr. Gupta said.

The London researchers noted that theirs wasn’t a radiologic study, so CT scans weren’t formally scored before and after treatment. They also acknowledged vagueness about imaging and clinical findings representing “nothing other than slow ongoing recovery.”

Patients with post–COVID-19 ILD will require ongoing follow-up to better understand the disease course, Dr. Myall and colleagues stated, although they predicted organizing pneumonia is unlikely to recur once it resolves.

Dr. Myall and coauthors had no relevant relationships to disclose. Dr. Gupta disclosed he is also an employee and shareholder at Genentech.

A study of post–COVID-19 patients in the United Kingdom who developed severe lung inflammation after they left the hospital may provide greater clarity on which patients are most likely to have persistent lung dysfunction.

In addition to pinpointing those most at risk, the findings showed that conventional corticosteroid treatment is highly effective in improving lung function and reducing symptoms.

Researchers from Guy’s and St. Thomas’ National Health Foundation Trust in London reported that a small percentage of patients – 4.8%, or 35 of 837 patients in the study – had severe persistent interstitial lung disease (ILD), mostly organizing pneumonia, 4 weeks after discharge. Of these patients, 30 received steroid treatment, all of whom showed improvement in lung function.

Lead author Katherine Jane Myall, MRCP, and colleagues wrote that the most common radiologic finding in acute COVID-19 is bilateral ground-glass opacification, and findings of organizing pneumonia are common. However, no reports exist of the role of inflammatory infiltrates during recovery from COVID-19 or of the effectiveness of treatments for persistent ILD. “The long-term respiratory morbidity remains unclear,” Dr. Myall and colleagues wrote.

The study findings are significant because they quantify the degree of lung disease that patients have after COVID-19, said Sachin Gupta, MD, FCCP, a pulmonologist and critical care specialist at Alameda Health System in Oakland, Calif. He added that the disease course and presentation followed the pattern of organizing pneumonia in some patients, and traditional corticosteroid therapy seemed to resolve symptoms and improve lung function.

“This is a really important piece to get out there because it describes what a lot of us are worried about in patients with post-COVID lung disease and about what type of lung disease they have. It offers a potential treatment,” he said.

Dr. Myall and colleagues noted that even a “relatively small proportion” of patients with persistent, severe ILD – as reported in this study – pose “a significant disease burden.” They added: “Prompt therapy may avoid potentially permanent fibrosis and functional impairment.”

The single-center, prospective, observational study followed discharged patients with telephone calls 4 weeks after discharge to determine their status. At that point, 39% of the study cohort (n = 325) reported ongoing symptoms.

The patients had outpatient examinations at 6 weeks post discharge, at which time 42.9% (n = 138) had no signs or symptoms of persistent disease; 33.8% (n = 110) had symptoms but no radiologic findings and received referrals to other departments; and 24% (n = 77) were referred to the post-COVID lung disease multidisciplinary team. A total of 59 were diagnosed with persistent post-COVID interstitial change, 35 of whom had organizing pneumonia, hence the rationale for using steroids in this group, Dr. Myall and colleagues stated.

The 30 patients treated with corticosteroids received a maximum initial dose of 0.5 mg/kg prednisolone, which was rapidly weaned over 3 weeks. Some patients received lower doses depending on their comorbidities.

Treatment resulted in an average relative increase in transfer factor of 31.6% (P < .001) and forced vital capacity of 9.6% (P = .014), along with significant improvement in symptoms and x-ray signs.

The study identified some key characteristics of the patients who had persistent post–COVID-19 inflammatory ILD. They were mostly male (71.5%) and overweight with an average body mass index of 28.3, but only 26% were obese. Most had at least one comorbidity, with the most common being diabetes and asthma (22.9%). Their average hospital stay was 16.9 days, 82.9% required oxygen, 55% were in the ICU, and 46% needed invasive mechanical ventilation.

The patients most vulnerable to ILD and organizing pneumonia were the “sicker” of the whole cohort, Dr. Gupta said. “In one sense, it’s reassuring that this is not just happening in anyone; this is happening in patients who had the worst course and were hospitalized in the ICU for the most part.”

The study shows that identifying these patients early on and initiating steroid therapy could avoid persistent lung injury and scarring, Dr. Gupta said.

The London researchers noted that theirs wasn’t a radiologic study, so CT scans weren’t formally scored before and after treatment. They also acknowledged vagueness about imaging and clinical findings representing “nothing other than slow ongoing recovery.”

Patients with post–COVID-19 ILD will require ongoing follow-up to better understand the disease course, Dr. Myall and colleagues stated, although they predicted organizing pneumonia is unlikely to recur once it resolves.

Dr. Myall and coauthors had no relevant relationships to disclose. Dr. Gupta disclosed he is also an employee and shareholder at Genentech.

New guidelines from the American Society of Hematology “strongly recommend” using no thromboprophylaxis over using parenteral thromboprophylaxis in ambulatory patients receiving cancer chemotherapy who have low venous thromboembolism (VTE) risk, and using no thromboprophylaxis over oral thromboprophylaxis with vitamin K antagonists in those at any VTE risk level.

The evidence-based guidelines for the prevention and treatment of VTE in patient with cancer, published online in Blood Advances, also include a “conditional recommendation” for using either thromboprophylaxis with the direct oral anticoagulants (DOACs) apixaban or rivaroxaban or using no thromboprophylaxis in ambulatory patients with intermediate risk and using the DOACs over no thromboprophylaxis in those with high VTE risk.

The purpose of the guidelines, which also address VTE prophylaxis in hospitalized patients with cancer and the use of anticoagulation for VTE treatment in patients with cancer, is to provide clinical decision support for shared decision-making by patients and clinicians, Gary H. Lyman, MD, of Fred Hutchinson Cancer Research Center, Seattle and Marc Carrier, MD, of the University of Ottawa, and their colleagues from the multidisciplinary guidelines panel explained.

“The recommendations take into consideration the strength of the evidence, risks of mortality, VTE, and bleeding, as well as quality of life, acceptability, and cost considerations,” they wrote, noting that VTE is a common complication in patients with cancer, who are at markedly increased risk for morbidity and mortality from VTE.
 

Levels of evidence

The panel members relied on updated and original systematic evidence reviews. Conditional recommendations, as opposed to strong recommendations, are defined by the panel as “suggestions,” and all 33 recommendations that make up the guidelines include a statement on the strength of the relevant evidence.

For example, the thromboprophylaxis recommendations for low, intermediate, and high VTE risk are made based on “moderate certainty in the evidence of effects,” and the recommendation for no thromboprophylaxis over oral thromboprophylaxis with vitamin K antagonists is a strong recommendation based on “very low certainty in the evidence of benefits, but high certainty about the harms.”

The guidelines panel also strongly recommends, based on moderate certainty in the evidence of effects, using low-molecular-weight heparin over unfractionated heparin for the initial treatment of VTE in patients with cancer, and suggests, based on “very low certainty in the evidence of effects,” using LMWH over fondaparinux in this setting.

In addition to primary prophylaxis in ambulatory and hospitalized patients and initial VTE treatment, they also address primary prophylaxis for patients with cancer who have a central venous catheter, VTE treatment in surgical patients with cancer, short-term VTE treatment, and long-term VTE treatment.

For example, the guidelines panel conditionally recommends:

• Not using parenteral or oral thromboprophylaxis in patients with cancer and a central venous catheter
• Using LMWH or fondaparinux for surgical patients with cancer
• Using DOACS for the short-term treatment of VTE, and LMWH or DOACs for the long-term treatment of VTE in patients with cancer.

The perils of VTE

VTE in patients with cancer can interfere with treatment, increase mortality risk, and increase costs, the authors noted, adding that VTE can also adversely affect cancer patients’ quality of life.

“Some have even reported the experience of VTE to be more upsetting than that of the cancer,” they wrote. “More than 50% of thrombotic events occur within 3 months of the cancer diagnosis, a time when most cancer treatments will be underway. Patients, who are still coming to terms with a recent cancer diagnosis, often view the occurrence of VTE as a further threat to life, confirmation of the severity of their condition, and a poor prognostic sign.”

Therefore, the new guidelines aim to reduce VTE frequency, risk of bleeding complications, morbidity, and costs, thereby improving quality of life and the patient experience, the authors said, noting that three other recent guidelines on VTEs in patients with cancer have been published: the 2019 American Society of Clinical Oncology guidelines, the 2019 International Initiative on Thrombosis and Cancer guidelines, and the 2020 National Comprehensive Cancer Network guidelines.

The ASH guidelines are similar in many ways to the other guidelines, but differ in some ways, as well. An example is the timing of initiation of pharmacological thromboprophylaxis in patients undergoing cancer-related major abdominal surgery. The ASCO and ITAC guidelines advise starting thromboprophylaxis preoperatively, whereas the ASH guidelines recommend initiating thromboprophylaxis postoperatively, citing “the limited advantages to initiating thromboprophylaxis preoperatively, in addition to the potential bleeding and logistical considerations associated with neuraxial anesthesia.”

These differences highlight a lack of data in that setting and the need for additional studies, the authors said.
 

ASH vs. ASCO

James Douketis, MD, a practicing clinician and professor of medicine at McMaster University, Hamilton, Ont., highlighted another difference between the ASH and ASCO guidelines.

“For the treatment of [cancer-associated thrombosis], ASCO gives a strong recommendation to use LMWH or DOACs (with some caveats), which is easy to follow. ASH, on the other hand, suggests LMWH or a DOAC for the first 7-10 days, DOACs for the first 3-6 months, and back to LMWH or DOACs after 6 months,” he said in an interview.

The recommendation is “very evidence based but ambiguous and not helpful for the practicing clinician,” added Dr. Douketis, who helped develop the ITAC guidelines, but was not part of the ASH or ASCO guideline panels.

ASCO also provides a clear recommendation for giving VTE prophylaxis for 4 weeks after cancer surgery in patients with high VTE risk, whereas ASH gives “a somewhat vague recommendation” for thromboprophylaxis after hospital discharge.

The guidelines are “pretty well aligned” with respect to recommendations on VTE prophylaxis in medical cancer patients receiving chemotherapy, and although the “extremely academic” ASH guidelines were developed by “a superb team using the same evidence and excellent methodology,” they are interpreted in slightly different ways and fall short when it comes to being clinician friendly, Dr. Douketis said.

“At the end of day, for practicing clinicians, the ASH guidelines don’t provide a message that’s easy to digest,” he added.

ASH has, however, provided a resource page that includes tools and information for implementing the guidelines in clinical practice, and will maintain the guidelines “through surveillance for new evidence, ongoing review by experts, and regular revisions,” the authors said.

[email protected]

New guidelines from the American Society of Hematology “strongly recommend” using no thromboprophylaxis over using parenteral thromboprophylaxis in ambulatory patients receiving cancer chemotherapy who have low venous thromboembolism (VTE) risk, and using no thromboprophylaxis over oral thromboprophylaxis with vitamin K antagonists in those at any VTE risk level.

The evidence-based guidelines for the prevention and treatment of VTE in patient with cancer, published online in Blood Advances, also include a “conditional recommendation” for using either thromboprophylaxis with the direct oral anticoagulants (DOACs) apixaban or rivaroxaban or using no thromboprophylaxis in ambulatory patients with intermediate risk and using the DOACs over no thromboprophylaxis in those with high VTE risk.

The purpose of the guidelines, which also address VTE prophylaxis in hospitalized patients with cancer and the use of anticoagulation for VTE treatment in patients with cancer, is to provide clinical decision support for shared decision-making by patients and clinicians, Gary H. Lyman, MD, of Fred Hutchinson Cancer Research Center, Seattle and Marc Carrier, MD, of the University of Ottawa, and their colleagues from the multidisciplinary guidelines panel explained.

“The recommendations take into consideration the strength of the evidence, risks of mortality, VTE, and bleeding, as well as quality of life, acceptability, and cost considerations,” they wrote, noting that VTE is a common complication in patients with cancer, who are at markedly increased risk for morbidity and mortality from VTE.
 

Levels of evidence

The panel members relied on updated and original systematic evidence reviews. Conditional recommendations, as opposed to strong recommendations, are defined by the panel as “suggestions,” and all 33 recommendations that make up the guidelines include a statement on the strength of the relevant evidence.

For example, the thromboprophylaxis recommendations for low, intermediate, and high VTE risk are made based on “moderate certainty in the evidence of effects,” and the recommendation for no thromboprophylaxis over oral thromboprophylaxis with vitamin K antagonists is a strong recommendation based on “very low certainty in the evidence of benefits, but high certainty about the harms.”

The guidelines panel also strongly recommends, based on moderate certainty in the evidence of effects, using low-molecular-weight heparin over unfractionated heparin for the initial treatment of VTE in patients with cancer, and suggests, based on “very low certainty in the evidence of effects,” using LMWH over fondaparinux in this setting.

In addition to primary prophylaxis in ambulatory and hospitalized patients and initial VTE treatment, they also address primary prophylaxis for patients with cancer who have a central venous catheter, VTE treatment in surgical patients with cancer, short-term VTE treatment, and long-term VTE treatment.

For example, the guidelines panel conditionally recommends:

• Not using parenteral or oral thromboprophylaxis in patients with cancer and a central venous catheter
• Using LMWH or fondaparinux for surgical patients with cancer
• Using DOACS for the short-term treatment of VTE, and LMWH or DOACs for the long-term treatment of VTE in patients with cancer.

The perils of VTE

VTE in patients with cancer can interfere with treatment, increase mortality risk, and increase costs, the authors noted, adding that VTE can also adversely affect cancer patients’ quality of life.

“Some have even reported the experience of VTE to be more upsetting than that of the cancer,” they wrote. “More than 50% of thrombotic events occur within 3 months of the cancer diagnosis, a time when most cancer treatments will be underway. Patients, who are still coming to terms with a recent cancer diagnosis, often view the occurrence of VTE as a further threat to life, confirmation of the severity of their condition, and a poor prognostic sign.”

Therefore, the new guidelines aim to reduce VTE frequency, risk of bleeding complications, morbidity, and costs, thereby improving quality of life and the patient experience, the authors said, noting that three other recent guidelines on VTEs in patients with cancer have been published: the 2019 American Society of Clinical Oncology guidelines, the 2019 International Initiative on Thrombosis and Cancer guidelines, and the 2020 National Comprehensive Cancer Network guidelines.

The ASH guidelines are similar in many ways to the other guidelines, but differ in some ways, as well. An example is the timing of initiation of pharmacological thromboprophylaxis in patients undergoing cancer-related major abdominal surgery. The ASCO and ITAC guidelines advise starting thromboprophylaxis preoperatively, whereas the ASH guidelines recommend initiating thromboprophylaxis postoperatively, citing “the limited advantages to initiating thromboprophylaxis preoperatively, in addition to the potential bleeding and logistical considerations associated with neuraxial anesthesia.”

These differences highlight a lack of data in that setting and the need for additional studies, the authors said.
 

ASH vs. ASCO

James Douketis, MD, a practicing clinician and professor of medicine at McMaster University, Hamilton, Ont., highlighted another difference between the ASH and ASCO guidelines.

“For the treatment of [cancer-associated thrombosis], ASCO gives a strong recommendation to use LMWH or DOACs (with some caveats), which is easy to follow. ASH, on the other hand, suggests LMWH or a DOAC for the first 7-10 days, DOACs for the first 3-6 months, and back to LMWH or DOACs after 6 months,” he said in an interview.

The recommendation is “very evidence based but ambiguous and not helpful for the practicing clinician,” added Dr. Douketis, who helped develop the ITAC guidelines, but was not part of the ASH or ASCO guideline panels.

ASCO also provides a clear recommendation for giving VTE prophylaxis for 4 weeks after cancer surgery in patients with high VTE risk, whereas ASH gives “a somewhat vague recommendation” for thromboprophylaxis after hospital discharge.

The guidelines are “pretty well aligned” with respect to recommendations on VTE prophylaxis in medical cancer patients receiving chemotherapy, and although the “extremely academic” ASH guidelines were developed by “a superb team using the same evidence and excellent methodology,” they are interpreted in slightly different ways and fall short when it comes to being clinician friendly, Dr. Douketis said.

“At the end of day, for practicing clinicians, the ASH guidelines don’t provide a message that’s easy to digest,” he added.

ASH has, however, provided a resource page that includes tools and information for implementing the guidelines in clinical practice, and will maintain the guidelines “through surveillance for new evidence, ongoing review by experts, and regular revisions,” the authors said.

[email protected]

New guidelines from the American Society of Hematology “strongly recommend” using no thromboprophylaxis over using parenteral thromboprophylaxis in ambulatory patients receiving cancer chemotherapy who have low venous thromboembolism (VTE) risk, and using no thromboprophylaxis over oral thromboprophylaxis with vitamin K antagonists in those at any VTE risk level.

The evidence-based guidelines for the prevention and treatment of VTE in patient with cancer, published online in Blood Advances, also include a “conditional recommendation” for using either thromboprophylaxis with the direct oral anticoagulants (DOACs) apixaban or rivaroxaban or using no thromboprophylaxis in ambulatory patients with intermediate risk and using the DOACs over no thromboprophylaxis in those with high VTE risk.

The purpose of the guidelines, which also address VTE prophylaxis in hospitalized patients with cancer and the use of anticoagulation for VTE treatment in patients with cancer, is to provide clinical decision support for shared decision-making by patients and clinicians, Gary H. Lyman, MD, of Fred Hutchinson Cancer Research Center, Seattle and Marc Carrier, MD, of the University of Ottawa, and their colleagues from the multidisciplinary guidelines panel explained.

“The recommendations take into consideration the strength of the evidence, risks of mortality, VTE, and bleeding, as well as quality of life, acceptability, and cost considerations,” they wrote, noting that VTE is a common complication in patients with cancer, who are at markedly increased risk for morbidity and mortality from VTE.
 

Levels of evidence

The panel members relied on updated and original systematic evidence reviews. Conditional recommendations, as opposed to strong recommendations, are defined by the panel as “suggestions,” and all 33 recommendations that make up the guidelines include a statement on the strength of the relevant evidence.

For example, the thromboprophylaxis recommendations for low, intermediate, and high VTE risk are made based on “moderate certainty in the evidence of effects,” and the recommendation for no thromboprophylaxis over oral thromboprophylaxis with vitamin K antagonists is a strong recommendation based on “very low certainty in the evidence of benefits, but high certainty about the harms.”

The guidelines panel also strongly recommends, based on moderate certainty in the evidence of effects, using low-molecular-weight heparin over unfractionated heparin for the initial treatment of VTE in patients with cancer, and suggests, based on “very low certainty in the evidence of effects,” using LMWH over fondaparinux in this setting.

In addition to primary prophylaxis in ambulatory and hospitalized patients and initial VTE treatment, they also address primary prophylaxis for patients with cancer who have a central venous catheter, VTE treatment in surgical patients with cancer, short-term VTE treatment, and long-term VTE treatment.

For example, the guidelines panel conditionally recommends:

• Not using parenteral or oral thromboprophylaxis in patients with cancer and a central venous catheter
• Using LMWH or fondaparinux for surgical patients with cancer
• Using DOACS for the short-term treatment of VTE, and LMWH or DOACs for the long-term treatment of VTE in patients with cancer.

The perils of VTE

VTE in patients with cancer can interfere with treatment, increase mortality risk, and increase costs, the authors noted, adding that VTE can also adversely affect cancer patients’ quality of life.

“Some have even reported the experience of VTE to be more upsetting than that of the cancer,” they wrote. “More than 50% of thrombotic events occur within 3 months of the cancer diagnosis, a time when most cancer treatments will be underway. Patients, who are still coming to terms with a recent cancer diagnosis, often view the occurrence of VTE as a further threat to life, confirmation of the severity of their condition, and a poor prognostic sign.”

Therefore, the new guidelines aim to reduce VTE frequency, risk of bleeding complications, morbidity, and costs, thereby improving quality of life and the patient experience, the authors said, noting that three other recent guidelines on VTEs in patients with cancer have been published: the 2019 American Society of Clinical Oncology guidelines, the 2019 International Initiative on Thrombosis and Cancer guidelines, and the 2020 National Comprehensive Cancer Network guidelines.

The ASH guidelines are similar in many ways to the other guidelines, but differ in some ways, as well. An example is the timing of initiation of pharmacological thromboprophylaxis in patients undergoing cancer-related major abdominal surgery. The ASCO and ITAC guidelines advise starting thromboprophylaxis preoperatively, whereas the ASH guidelines recommend initiating thromboprophylaxis postoperatively, citing “the limited advantages to initiating thromboprophylaxis preoperatively, in addition to the potential bleeding and logistical considerations associated with neuraxial anesthesia.”

These differences highlight a lack of data in that setting and the need for additional studies, the authors said.
 

ASH vs. ASCO

James Douketis, MD, a practicing clinician and professor of medicine at McMaster University, Hamilton, Ont., highlighted another difference between the ASH and ASCO guidelines.

“For the treatment of [cancer-associated thrombosis], ASCO gives a strong recommendation to use LMWH or DOACs (with some caveats), which is easy to follow. ASH, on the other hand, suggests LMWH or a DOAC for the first 7-10 days, DOACs for the first 3-6 months, and back to LMWH or DOACs after 6 months,” he said in an interview.

The recommendation is “very evidence based but ambiguous and not helpful for the practicing clinician,” added Dr. Douketis, who helped develop the ITAC guidelines, but was not part of the ASH or ASCO guideline panels.

ASCO also provides a clear recommendation for giving VTE prophylaxis for 4 weeks after cancer surgery in patients with high VTE risk, whereas ASH gives “a somewhat vague recommendation” for thromboprophylaxis after hospital discharge.

The guidelines are “pretty well aligned” with respect to recommendations on VTE prophylaxis in medical cancer patients receiving chemotherapy, and although the “extremely academic” ASH guidelines were developed by “a superb team using the same evidence and excellent methodology,” they are interpreted in slightly different ways and fall short when it comes to being clinician friendly, Dr. Douketis said.

“At the end of day, for practicing clinicians, the ASH guidelines don’t provide a message that’s easy to digest,” he added.

ASH has, however, provided a resource page that includes tools and information for implementing the guidelines in clinical practice, and will maintain the guidelines “through surveillance for new evidence, ongoing review by experts, and regular revisions,” the authors said.

[email protected]

Major ECG abnormalities were found in 13% of more than 8,000 unselected patients with type 2 diabetes, including a 9% prevalence in the subgroup of these patients without identified cardiovascular disease (CVD) in a community-based Dutch cohort. Minor ECG abnormalities were even more prevalent.

enot-poloskun/Getty Images

These prevalence rates were consistent with prior findings from patients with type 2 diabetes, but the current report is notable because “it provides the most thorough description of the prevalence of ECG abnormalities in people with type 2 diabetes,” and used an “unselected and large population with comprehensive measurements,” including many without a history of CVD, said Peter P. Harms, MSc, and associates noted in a recent report in the Journal of Diabetes and Its Complications.

The analysis also identified several parameters that significantly linked with the presence of a major ECG abnormality including hypertension, male sex, older age, and higher levels of hemoglobin A1c.

“Resting ECG abnormalities might be a useful tool for CVD screening in people with type 2 diabetes,” concluded Mr. Harms, a researcher at the Amsterdam University Medical Center, and coauthors.
 

Findings “not unexpected”

Patients with diabetes have a higher prevalence of ECG abnormalities “because of their higher likelihood of having hypertension and other CVD risk factors,” as well as potentially having subclinical CVD, said Fred M. Kusumoto, MD, so these findings are “not unexpected. The more risk factors a patient has for structural heart disease, atrial fibrillation (AFib), or stroke from AFib, the more a physician must consider whether a baseline ECG and future surveillance is appropriate,” Dr. Kusumoto said in an interview.

But he cautioned against seeing these findings as a rationale to routinely run a resting ECG examination on every adult with diabetes.

“Patients with diabetes are very heterogeneous,” which makes it “difficult to come up with a ‘one size fits all’ recommendation” for ECG screening of patients with diabetes, he said.

While a task force of the European Society of Cardiology and the European Association for the Study of Diabetes set a class I level C guideline for resting ECG screening of patients with diabetes if they also have either hypertension or suspected CVD, the American Diabetes Association has no specific recommendations on which patients with diabetes should receive ECG screening.

“The current absence of U.S. recommendations is reasonable, as it allows patients and physicians to discuss the issues and decide on the utility of an ECG in their specific situation,” said Dr. Kusumoto, director of heart rhythm services at the Mayo Clinic in Jacksonville, Fla. But he also suggested that “the more risk factors that a patient with diabetes has for structural heart disease, AFib, or stroke from AFib the more a physician must consider whether a baseline ECG and future surveillance is appropriate.”

Data from a Dutch prospective cohort

The new study used data collected from 8,068 patients with type 2 diabetes and enrolled in the prospective Hoorn Diabetes Care System cohort, which enrolled patients newly diagnosed with type 2 diabetes in the West Friesland region of the Netherlands starting in 1996. The study includes most of these patients in the region who are under regular care of a general practitioner, and the study protocol calls for an annual resting ECG examination.

The investigators used standard, 12-lead ECG readings taken for each patient during 2018, and classified abnormalities by the Minnesota Code criteria. They divided the abnormalities into major or minor groups “in accordance with consensus between previous studies who categorised abnormalities according to perceived importance and/or severity.” The major subgroup included major QS pattern abnormalities, major ST-segment abnormalities, complete left bundle branch block or intraventricular block, or atrial fibrillation or flutter. Minor abnormalities included minor QS pattern abnormalities, minor ST-segment abnormalities, complete right bundle branch block, or premature atrial or ventricular contractions.

The prevalence of a major abnormality in the entire cohort examined was 13%, and another 16% had a minor abnormality. The most common types of abnormalities were ventricular conduction defects, in 14%; and arrhythmias, in 11%. In the subgroup of 6,494 of these patients with no history of CVD, 9% had a major abnormality and 15% a minor abnormality. Within this subgroup, 23% also had no hypertension, and their prevalence of a major abnormality was 4%, while 9% had a minor abnormality.

A multivariable analysis of potential risk factors among the entire study cohort showed that patients with hypertension had nearly triple the prevalence of a major ECG abnormality as those without hypertension, and men had double the prevalence of a major abnormality compared with women. Other markers that significantly linked with a higher rate of a major abnormality were older age, higher body mass index, higher A1c levels, and moderately depressed renal function.

“While the criteria the authors used for differentiating major and minor criteria are reasonable, in an asymptomatic patient even the presence of frequent premature atrial contractions on a baseline ECG has been associated with the development of AFib and a higher risk for stroke. The presence of left or right bundle branch block could spur additional evaluation with an echocardiogram,” said Dr. Kusumoto, president-elect of the Heart Rhythm Society.

“Generally an ECG abnormality is supplemental to clinical data in deciding the choice and timing of next therapeutic steps or additional testing. Physicians should have a fairly low threshold for obtaining ECG in patients with diabetes since it is inexpensive and can provide supplemental and potentially actionable information,” he said. “The presence of ECG abnormalities increases the possibility of underlying cardiovascular disease. When taking care of patients with diabetes at initial evaluation or without prior cardiac history or symptoms referable to the heart, two main issues are identifying the likelihood of coronary artery disease and atrial fibrillation.”

Mr. Harms and coauthors, and Dr. Kusumoto, had no disclosures.

[email protected]

Major ECG abnormalities were found in 13% of more than 8,000 unselected patients with type 2 diabetes, including a 9% prevalence in the subgroup of these patients without identified cardiovascular disease (CVD) in a community-based Dutch cohort. Minor ECG abnormalities were even more prevalent.

enot-poloskun/Getty Images

These prevalence rates were consistent with prior findings from patients with type 2 diabetes, but the current report is notable because “it provides the most thorough description of the prevalence of ECG abnormalities in people with type 2 diabetes,” and used an “unselected and large population with comprehensive measurements,” including many without a history of CVD, said Peter P. Harms, MSc, and associates noted in a recent report in the Journal of Diabetes and Its Complications.

The analysis also identified several parameters that significantly linked with the presence of a major ECG abnormality including hypertension, male sex, older age, and higher levels of hemoglobin A1c.

“Resting ECG abnormalities might be a useful tool for CVD screening in people with type 2 diabetes,” concluded Mr. Harms, a researcher at the Amsterdam University Medical Center, and coauthors.
 

Findings “not unexpected”

Patients with diabetes have a higher prevalence of ECG abnormalities “because of their higher likelihood of having hypertension and other CVD risk factors,” as well as potentially having subclinical CVD, said Fred M. Kusumoto, MD, so these findings are “not unexpected. The more risk factors a patient has for structural heart disease, atrial fibrillation (AFib), or stroke from AFib, the more a physician must consider whether a baseline ECG and future surveillance is appropriate,” Dr. Kusumoto said in an interview.

But he cautioned against seeing these findings as a rationale to routinely run a resting ECG examination on every adult with diabetes.

“Patients with diabetes are very heterogeneous,” which makes it “difficult to come up with a ‘one size fits all’ recommendation” for ECG screening of patients with diabetes, he said.

While a task force of the European Society of Cardiology and the European Association for the Study of Diabetes set a class I level C guideline for resting ECG screening of patients with diabetes if they also have either hypertension or suspected CVD, the American Diabetes Association has no specific recommendations on which patients with diabetes should receive ECG screening.

“The current absence of U.S. recommendations is reasonable, as it allows patients and physicians to discuss the issues and decide on the utility of an ECG in their specific situation,” said Dr. Kusumoto, director of heart rhythm services at the Mayo Clinic in Jacksonville, Fla. But he also suggested that “the more risk factors that a patient with diabetes has for structural heart disease, AFib, or stroke from AFib the more a physician must consider whether a baseline ECG and future surveillance is appropriate.”

Data from a Dutch prospective cohort

The new study used data collected from 8,068 patients with type 2 diabetes and enrolled in the prospective Hoorn Diabetes Care System cohort, which enrolled patients newly diagnosed with type 2 diabetes in the West Friesland region of the Netherlands starting in 1996. The study includes most of these patients in the region who are under regular care of a general practitioner, and the study protocol calls for an annual resting ECG examination.

The investigators used standard, 12-lead ECG readings taken for each patient during 2018, and classified abnormalities by the Minnesota Code criteria. They divided the abnormalities into major or minor groups “in accordance with consensus between previous studies who categorised abnormalities according to perceived importance and/or severity.” The major subgroup included major QS pattern abnormalities, major ST-segment abnormalities, complete left bundle branch block or intraventricular block, or atrial fibrillation or flutter. Minor abnormalities included minor QS pattern abnormalities, minor ST-segment abnormalities, complete right bundle branch block, or premature atrial or ventricular contractions.

The prevalence of a major abnormality in the entire cohort examined was 13%, and another 16% had a minor abnormality. The most common types of abnormalities were ventricular conduction defects, in 14%; and arrhythmias, in 11%. In the subgroup of 6,494 of these patients with no history of CVD, 9% had a major abnormality and 15% a minor abnormality. Within this subgroup, 23% also had no hypertension, and their prevalence of a major abnormality was 4%, while 9% had a minor abnormality.

A multivariable analysis of potential risk factors among the entire study cohort showed that patients with hypertension had nearly triple the prevalence of a major ECG abnormality as those without hypertension, and men had double the prevalence of a major abnormality compared with women. Other markers that significantly linked with a higher rate of a major abnormality were older age, higher body mass index, higher A1c levels, and moderately depressed renal function.

“While the criteria the authors used for differentiating major and minor criteria are reasonable, in an asymptomatic patient even the presence of frequent premature atrial contractions on a baseline ECG has been associated with the development of AFib and a higher risk for stroke. The presence of left or right bundle branch block could spur additional evaluation with an echocardiogram,” said Dr. Kusumoto, president-elect of the Heart Rhythm Society.

“Generally an ECG abnormality is supplemental to clinical data in deciding the choice and timing of next therapeutic steps or additional testing. Physicians should have a fairly low threshold for obtaining ECG in patients with diabetes since it is inexpensive and can provide supplemental and potentially actionable information,” he said. “The presence of ECG abnormalities increases the possibility of underlying cardiovascular disease. When taking care of patients with diabetes at initial evaluation or without prior cardiac history or symptoms referable to the heart, two main issues are identifying the likelihood of coronary artery disease and atrial fibrillation.”

Mr. Harms and coauthors, and Dr. Kusumoto, had no disclosures.

[email protected]

Major ECG abnormalities were found in 13% of more than 8,000 unselected patients with type 2 diabetes, including a 9% prevalence in the subgroup of these patients without identified cardiovascular disease (CVD) in a community-based Dutch cohort. Minor ECG abnormalities were even more prevalent.

enot-poloskun/Getty Images

These prevalence rates were consistent with prior findings from patients with type 2 diabetes, but the current report is notable because “it provides the most thorough description of the prevalence of ECG abnormalities in people with type 2 diabetes,” and used an “unselected and large population with comprehensive measurements,” including many without a history of CVD, said Peter P. Harms, MSc, and associates noted in a recent report in the Journal of Diabetes and Its Complications.

The analysis also identified several parameters that significantly linked with the presence of a major ECG abnormality including hypertension, male sex, older age, and higher levels of hemoglobin A1c.

“Resting ECG abnormalities might be a useful tool for CVD screening in people with type 2 diabetes,” concluded Mr. Harms, a researcher at the Amsterdam University Medical Center, and coauthors.
 

Findings “not unexpected”

Patients with diabetes have a higher prevalence of ECG abnormalities “because of their higher likelihood of having hypertension and other CVD risk factors,” as well as potentially having subclinical CVD, said Fred M. Kusumoto, MD, so these findings are “not unexpected. The more risk factors a patient has for structural heart disease, atrial fibrillation (AFib), or stroke from AFib, the more a physician must consider whether a baseline ECG and future surveillance is appropriate,” Dr. Kusumoto said in an interview.

But he cautioned against seeing these findings as a rationale to routinely run a resting ECG examination on every adult with diabetes.

“Patients with diabetes are very heterogeneous,” which makes it “difficult to come up with a ‘one size fits all’ recommendation” for ECG screening of patients with diabetes, he said.

While a task force of the European Society of Cardiology and the European Association for the Study of Diabetes set a class I level C guideline for resting ECG screening of patients with diabetes if they also have either hypertension or suspected CVD, the American Diabetes Association has no specific recommendations on which patients with diabetes should receive ECG screening.

“The current absence of U.S. recommendations is reasonable, as it allows patients and physicians to discuss the issues and decide on the utility of an ECG in their specific situation,” said Dr. Kusumoto, director of heart rhythm services at the Mayo Clinic in Jacksonville, Fla. But he also suggested that “the more risk factors that a patient with diabetes has for structural heart disease, AFib, or stroke from AFib the more a physician must consider whether a baseline ECG and future surveillance is appropriate.”

Data from a Dutch prospective cohort

The new study used data collected from 8,068 patients with type 2 diabetes and enrolled in the prospective Hoorn Diabetes Care System cohort, which enrolled patients newly diagnosed with type 2 diabetes in the West Friesland region of the Netherlands starting in 1996. The study includes most of these patients in the region who are under regular care of a general practitioner, and the study protocol calls for an annual resting ECG examination.

The investigators used standard, 12-lead ECG readings taken for each patient during 2018, and classified abnormalities by the Minnesota Code criteria. They divided the abnormalities into major or minor groups “in accordance with consensus between previous studies who categorised abnormalities according to perceived importance and/or severity.” The major subgroup included major QS pattern abnormalities, major ST-segment abnormalities, complete left bundle branch block or intraventricular block, or atrial fibrillation or flutter. Minor abnormalities included minor QS pattern abnormalities, minor ST-segment abnormalities, complete right bundle branch block, or premature atrial or ventricular contractions.

The prevalence of a major abnormality in the entire cohort examined was 13%, and another 16% had a minor abnormality. The most common types of abnormalities were ventricular conduction defects, in 14%; and arrhythmias, in 11%. In the subgroup of 6,494 of these patients with no history of CVD, 9% had a major abnormality and 15% a minor abnormality. Within this subgroup, 23% also had no hypertension, and their prevalence of a major abnormality was 4%, while 9% had a minor abnormality.

A multivariable analysis of potential risk factors among the entire study cohort showed that patients with hypertension had nearly triple the prevalence of a major ECG abnormality as those without hypertension, and men had double the prevalence of a major abnormality compared with women. Other markers that significantly linked with a higher rate of a major abnormality were older age, higher body mass index, higher A1c levels, and moderately depressed renal function.

“While the criteria the authors used for differentiating major and minor criteria are reasonable, in an asymptomatic patient even the presence of frequent premature atrial contractions on a baseline ECG has been associated with the development of AFib and a higher risk for stroke. The presence of left or right bundle branch block could spur additional evaluation with an echocardiogram,” said Dr. Kusumoto, president-elect of the Heart Rhythm Society.

“Generally an ECG abnormality is supplemental to clinical data in deciding the choice and timing of next therapeutic steps or additional testing. Physicians should have a fairly low threshold for obtaining ECG in patients with diabetes since it is inexpensive and can provide supplemental and potentially actionable information,” he said. “The presence of ECG abnormalities increases the possibility of underlying cardiovascular disease. When taking care of patients with diabetes at initial evaluation or without prior cardiac history or symptoms referable to the heart, two main issues are identifying the likelihood of coronary artery disease and atrial fibrillation.”

Mr. Harms and coauthors, and Dr. Kusumoto, had no disclosures.

[email protected]

What happened to Hasan Gokal, MD, should stick painfully in the craws of all physicians. It should serve as a call to action, because Dr. Gokal is sitting at home today without a job and under threat of further legal action while we continue about our day.

Dr. Gokal’s “crime” is that he vaccinated 10 strangers and acquaintances with soon-to-expire doses of the Moderna COVID-19 vaccine. He drove to the homes of some in the dark of night and injected others on his Sugar Land, Texas, lawn. He spent hours in a frantic search for willing recipients to beat the expiration clock. With minutes to spare, he gave the last dose to his at-risk wife, who has symptomatic pulmonary sarcoidosis, but whose age meant she did not fall into a vaccine priority tier.

According to the New York Times, Dr. Gokal’s wife was hesitant, afraid he might get into trouble. But why would she be hesitant? He wasn’t doing anything immoral. Perhaps she knew how far physicians have fallen and how bitterly they both could suffer.

In Barren County, Ky., where I live, a state of emergency was declared by our judge executive because of inclement weather. This directive allows our emergency management to “waive procedures and formalities otherwise required by the law.” It’s too bad that the same courtesy was not afforded to Dr. Gokal in Texas. It’s a shame that ice and snow didn’t drive his actions. Perhaps that would have protected him against the harsh criticism. Rather, it was his oath to patients and dedication to his fellow humans that motivated him, and for that, he was made to suffer.

Dr. Gokal was right to think that pouring the last 10 vaccine doses down the toilet would be an egregious act. But he was wrong in thinking his decision to find takers for the vaccine would be viewed as expedient. Instead, he was accused of graft and even nepotism. And there is the rub. That he was fired and charged with the theft of $137 worth of vaccines says everything about how physicians are treated in the year 2021. Dr. Gokal’s lawyer says the charge carried a maximum penalty of 1 year in prison and a fine of nearly $4,000.

Thank God a sage judge threw out the case and “rebuked” the office of District Attorney Kim Ogg. That hasn’t stopped her from threatening to bring the case to a grand jury. That threat invites anyone faced with the same scenario to flush the extra vaccine doses into the septic system. It encourages us to choose the toilet handle to avoid a mug shot.

And we can’t ignore the racial slant to this story. The Times reported that Dr. Gokal asked the officials, “Are you suggesting that there were too many Indian names in this group?”

“Exactly” was the answer. Let that sink in.

None of this would have happened 20 years ago. Back then, no one would have questioned the wisdom a physician gains from all our years of training and residency. In an age when anyone who conducts an office visit is now called “doctor,” respect for the letters “MD” has been leveled. We physicians have lost our autonomy and been cowed into submission.

But whatever his profession, Hasan Gokal was fired for being a good human. Today, the sun rose on 10 individuals who now enjoy better protection against a deadly pandemic. They include a bed-bound nonagenarian. A woman in her 80s with dementia. A mother with a child who uses a ventilator. All now have antibodies against SARS-CoV2 because of the tireless actions of Dr. Gokal.

Yet Dr. Gokal’s future is uncertain. Will we help him, or will we leave him to the wolves? In an email exchange with his lawyer’s office, I learned that Dr. Gokal has received offers of employment but is unable to entertain them because the actions by the Harris County District Attorney triggered an automatic review by the Texas Medical Board. A GoFundMe page was launched, but an appreciative Dr. Gokal stated publicly that he’d rather the money go to a needy charity.

 In the last paragraph of the Times article, Dr. Gokal asks, “How can I take it back?” referencing stories about “the Pakistani doctor in Houston who stole all those vaccines.”

Let’s help him take back his story. In helping him, perhaps we can take back a little control. We could start with letters of support that could be mailed to his lawyer, Paul Doyle, Esq., of Houston, or tweet, respectfully of course, to the district attorney @Kimoggforda.

We can also let the Harris County Public Health Department in Houston know what we think of their actions.

On Martin Luther King Day, Kim Ogg, the district attorney who charged Dr. Gokal, tweeted MLK’s famous quote: “Injustice anywhere is a threat to justice everywhere.”

Let that motivate us to action.

Melissa Walton-Shirley, MD, is a native Kentuckian who retired from full-time invasive cardiology. She enjoys locums work in Montana and is a champion of physician rights and patient safety. In addition to opinion writing, she enjoys spending time with her husband, daughters and parents, and sidelines as a backing vocalist for local rock bands. A version of this article first appeared on Medscape.com.

What happened to Hasan Gokal, MD, should stick painfully in the craws of all physicians. It should serve as a call to action, because Dr. Gokal is sitting at home today without a job and under threat of further legal action while we continue about our day.

Dr. Gokal’s “crime” is that he vaccinated 10 strangers and acquaintances with soon-to-expire doses of the Moderna COVID-19 vaccine. He drove to the homes of some in the dark of night and injected others on his Sugar Land, Texas, lawn. He spent hours in a frantic search for willing recipients to beat the expiration clock. With minutes to spare, he gave the last dose to his at-risk wife, who has symptomatic pulmonary sarcoidosis, but whose age meant she did not fall into a vaccine priority tier.

According to the New York Times, Dr. Gokal’s wife was hesitant, afraid he might get into trouble. But why would she be hesitant? He wasn’t doing anything immoral. Perhaps she knew how far physicians have fallen and how bitterly they both could suffer.

In Barren County, Ky., where I live, a state of emergency was declared by our judge executive because of inclement weather. This directive allows our emergency management to “waive procedures and formalities otherwise required by the law.” It’s too bad that the same courtesy was not afforded to Dr. Gokal in Texas. It’s a shame that ice and snow didn’t drive his actions. Perhaps that would have protected him against the harsh criticism. Rather, it was his oath to patients and dedication to his fellow humans that motivated him, and for that, he was made to suffer.

Dr. Gokal was right to think that pouring the last 10 vaccine doses down the toilet would be an egregious act. But he was wrong in thinking his decision to find takers for the vaccine would be viewed as expedient. Instead, he was accused of graft and even nepotism. And there is the rub. That he was fired and charged with the theft of $137 worth of vaccines says everything about how physicians are treated in the year 2021. Dr. Gokal’s lawyer says the charge carried a maximum penalty of 1 year in prison and a fine of nearly $4,000.

Thank God a sage judge threw out the case and “rebuked” the office of District Attorney Kim Ogg. That hasn’t stopped her from threatening to bring the case to a grand jury. That threat invites anyone faced with the same scenario to flush the extra vaccine doses into the septic system. It encourages us to choose the toilet handle to avoid a mug shot.

And we can’t ignore the racial slant to this story. The Times reported that Dr. Gokal asked the officials, “Are you suggesting that there were too many Indian names in this group?”

“Exactly” was the answer. Let that sink in.

None of this would have happened 20 years ago. Back then, no one would have questioned the wisdom a physician gains from all our years of training and residency. In an age when anyone who conducts an office visit is now called “doctor,” respect for the letters “MD” has been leveled. We physicians have lost our autonomy and been cowed into submission.

But whatever his profession, Hasan Gokal was fired for being a good human. Today, the sun rose on 10 individuals who now enjoy better protection against a deadly pandemic. They include a bed-bound nonagenarian. A woman in her 80s with dementia. A mother with a child who uses a ventilator. All now have antibodies against SARS-CoV2 because of the tireless actions of Dr. Gokal.

Yet Dr. Gokal’s future is uncertain. Will we help him, or will we leave him to the wolves? In an email exchange with his lawyer’s office, I learned that Dr. Gokal has received offers of employment but is unable to entertain them because the actions by the Harris County District Attorney triggered an automatic review by the Texas Medical Board. A GoFundMe page was launched, but an appreciative Dr. Gokal stated publicly that he’d rather the money go to a needy charity.

 In the last paragraph of the Times article, Dr. Gokal asks, “How can I take it back?” referencing stories about “the Pakistani doctor in Houston who stole all those vaccines.”

Let’s help him take back his story. In helping him, perhaps we can take back a little control. We could start with letters of support that could be mailed to his lawyer, Paul Doyle, Esq., of Houston, or tweet, respectfully of course, to the district attorney @Kimoggforda.

We can also let the Harris County Public Health Department in Houston know what we think of their actions.

On Martin Luther King Day, Kim Ogg, the district attorney who charged Dr. Gokal, tweeted MLK’s famous quote: “Injustice anywhere is a threat to justice everywhere.”

Let that motivate us to action.

Melissa Walton-Shirley, MD, is a native Kentuckian who retired from full-time invasive cardiology. She enjoys locums work in Montana and is a champion of physician rights and patient safety. In addition to opinion writing, she enjoys spending time with her husband, daughters and parents, and sidelines as a backing vocalist for local rock bands. A version of this article first appeared on Medscape.com.

What happened to Hasan Gokal, MD, should stick painfully in the craws of all physicians. It should serve as a call to action, because Dr. Gokal is sitting at home today without a job and under threat of further legal action while we continue about our day.

Dr. Gokal’s “crime” is that he vaccinated 10 strangers and acquaintances with soon-to-expire doses of the Moderna COVID-19 vaccine. He drove to the homes of some in the dark of night and injected others on his Sugar Land, Texas, lawn. He spent hours in a frantic search for willing recipients to beat the expiration clock. With minutes to spare, he gave the last dose to his at-risk wife, who has symptomatic pulmonary sarcoidosis, but whose age meant she did not fall into a vaccine priority tier.

According to the New York Times, Dr. Gokal’s wife was hesitant, afraid he might get into trouble. But why would she be hesitant? He wasn’t doing anything immoral. Perhaps she knew how far physicians have fallen and how bitterly they both could suffer.

In Barren County, Ky., where I live, a state of emergency was declared by our judge executive because of inclement weather. This directive allows our emergency management to “waive procedures and formalities otherwise required by the law.” It’s too bad that the same courtesy was not afforded to Dr. Gokal in Texas. It’s a shame that ice and snow didn’t drive his actions. Perhaps that would have protected him against the harsh criticism. Rather, it was his oath to patients and dedication to his fellow humans that motivated him, and for that, he was made to suffer.

Dr. Gokal was right to think that pouring the last 10 vaccine doses down the toilet would be an egregious act. But he was wrong in thinking his decision to find takers for the vaccine would be viewed as expedient. Instead, he was accused of graft and even nepotism. And there is the rub. That he was fired and charged with the theft of $137 worth of vaccines says everything about how physicians are treated in the year 2021. Dr. Gokal’s lawyer says the charge carried a maximum penalty of 1 year in prison and a fine of nearly $4,000.

Thank God a sage judge threw out the case and “rebuked” the office of District Attorney Kim Ogg. That hasn’t stopped her from threatening to bring the case to a grand jury. That threat invites anyone faced with the same scenario to flush the extra vaccine doses into the septic system. It encourages us to choose the toilet handle to avoid a mug shot.

And we can’t ignore the racial slant to this story. The Times reported that Dr. Gokal asked the officials, “Are you suggesting that there were too many Indian names in this group?”

“Exactly” was the answer. Let that sink in.

None of this would have happened 20 years ago. Back then, no one would have questioned the wisdom a physician gains from all our years of training and residency. In an age when anyone who conducts an office visit is now called “doctor,” respect for the letters “MD” has been leveled. We physicians have lost our autonomy and been cowed into submission.

But whatever his profession, Hasan Gokal was fired for being a good human. Today, the sun rose on 10 individuals who now enjoy better protection against a deadly pandemic. They include a bed-bound nonagenarian. A woman in her 80s with dementia. A mother with a child who uses a ventilator. All now have antibodies against SARS-CoV2 because of the tireless actions of Dr. Gokal.

Yet Dr. Gokal’s future is uncertain. Will we help him, or will we leave him to the wolves? In an email exchange with his lawyer’s office, I learned that Dr. Gokal has received offers of employment but is unable to entertain them because the actions by the Harris County District Attorney triggered an automatic review by the Texas Medical Board. A GoFundMe page was launched, but an appreciative Dr. Gokal stated publicly that he’d rather the money go to a needy charity.

 In the last paragraph of the Times article, Dr. Gokal asks, “How can I take it back?” referencing stories about “the Pakistani doctor in Houston who stole all those vaccines.”

Let’s help him take back his story. In helping him, perhaps we can take back a little control. We could start with letters of support that could be mailed to his lawyer, Paul Doyle, Esq., of Houston, or tweet, respectfully of course, to the district attorney @Kimoggforda.

We can also let the Harris County Public Health Department in Houston know what we think of their actions.

On Martin Luther King Day, Kim Ogg, the district attorney who charged Dr. Gokal, tweeted MLK’s famous quote: “Injustice anywhere is a threat to justice everywhere.”

Let that motivate us to action.

Melissa Walton-Shirley, MD, is a native Kentuckian who retired from full-time invasive cardiology. She enjoys locums work in Montana and is a champion of physician rights and patient safety. In addition to opinion writing, she enjoys spending time with her husband, daughters and parents, and sidelines as a backing vocalist for local rock bands. A version of this article first appeared on Medscape.com.

Immunization of people 70 and older with the Pfizer/BioNTech COVID-19 vaccine in Israel was associated with a precipitous drop in need for mechanical ventilation, new evidence reveals.

Compared with residents younger than 50 – so far vaccinated at lower rates than those of the higher-risk older people – Israelis 70 and older were 67% less likely to require mechanical ventilation for SARS-CoV-2 infection in February 2021 compared with October-December 2020.

“This study provides preliminary evidence at the population level for the reduction in risk for severe COVID-19, as manifested by need for mechanical ventilation, after vaccination with the Pfizer-BioNTech COVID-19 vaccine,” wrote lead author Ehud Rinott, department of public health, faculty of health sciences, Ben-Gurion University of the Negev in Beer-Sheva, Israel, and colleagues.

The study was published online Feb. 26, 2021, in Morbidity and Mortality Weekly Report.

The progress of COVID-19 vaccination across Israel presents researchers with a unique opportunity to study effectiveness on a population level. In this study, 84% of residents 70 and older received two-dose vaccinations. In contrast, only 10% of people in Israel younger than 50 received the same vaccine coverage.

Along with senior author Yair Lewis, MD, PhD, and coauthor Ilan Youngster, MD, Mr. Rinott compared mechanical ventilation rates between Oct. 2, 2020, and Feb. 9, 2021. They found that the ratio of people 70 and older compared with those younger than 50 requiring mechanical ventilation changed from 5.8:1 to 1.9:1 between these periods. This translates to the 67% decrease.

The study offers a “real-world” look at vaccination effectiveness, adding to more controlled evidence from clinical trials. “Achieving high vaccination coverage through intensive vaccination campaigns has the potential to substantially reduce COVID-19-associated morbidity and mortality,” the researchers wrote.

Israel started a national vaccination program on Dec. 20, 2020, targeting high-risk residents including people 60 and older, health care workers, and those with relevant comorbidities. At the same time, in addition to immunization, Israel has used strategies like stay-at-home orders, school closures, mask mandates, and more.

Potential limitations include a limited ability to account for the effect of the stay-at-home orders, spread of virus variants, and other concomitant factors; a potential for a delayed reporting of cases; and variability in mitigation measures by age group.

Dr. Youngster reported receipt of consulting fees from MyBiotix Ltd.

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

Immunization of people 70 and older with the Pfizer/BioNTech COVID-19 vaccine in Israel was associated with a precipitous drop in need for mechanical ventilation, new evidence reveals.

Compared with residents younger than 50 – so far vaccinated at lower rates than those of the higher-risk older people – Israelis 70 and older were 67% less likely to require mechanical ventilation for SARS-CoV-2 infection in February 2021 compared with October-December 2020.

“This study provides preliminary evidence at the population level for the reduction in risk for severe COVID-19, as manifested by need for mechanical ventilation, after vaccination with the Pfizer-BioNTech COVID-19 vaccine,” wrote lead author Ehud Rinott, department of public health, faculty of health sciences, Ben-Gurion University of the Negev in Beer-Sheva, Israel, and colleagues.

The study was published online Feb. 26, 2021, in Morbidity and Mortality Weekly Report.

The progress of COVID-19 vaccination across Israel presents researchers with a unique opportunity to study effectiveness on a population level. In this study, 84% of residents 70 and older received two-dose vaccinations. In contrast, only 10% of people in Israel younger than 50 received the same vaccine coverage.

Along with senior author Yair Lewis, MD, PhD, and coauthor Ilan Youngster, MD, Mr. Rinott compared mechanical ventilation rates between Oct. 2, 2020, and Feb. 9, 2021. They found that the ratio of people 70 and older compared with those younger than 50 requiring mechanical ventilation changed from 5.8:1 to 1.9:1 between these periods. This translates to the 67% decrease.

The study offers a “real-world” look at vaccination effectiveness, adding to more controlled evidence from clinical trials. “Achieving high vaccination coverage through intensive vaccination campaigns has the potential to substantially reduce COVID-19-associated morbidity and mortality,” the researchers wrote.

Israel started a national vaccination program on Dec. 20, 2020, targeting high-risk residents including people 60 and older, health care workers, and those with relevant comorbidities. At the same time, in addition to immunization, Israel has used strategies like stay-at-home orders, school closures, mask mandates, and more.

Potential limitations include a limited ability to account for the effect of the stay-at-home orders, spread of virus variants, and other concomitant factors; a potential for a delayed reporting of cases; and variability in mitigation measures by age group.

Dr. Youngster reported receipt of consulting fees from MyBiotix Ltd.

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

Immunization of people 70 and older with the Pfizer/BioNTech COVID-19 vaccine in Israel was associated with a precipitous drop in need for mechanical ventilation, new evidence reveals.

Compared with residents younger than 50 – so far vaccinated at lower rates than those of the higher-risk older people – Israelis 70 and older were 67% less likely to require mechanical ventilation for SARS-CoV-2 infection in February 2021 compared with October-December 2020.

“This study provides preliminary evidence at the population level for the reduction in risk for severe COVID-19, as manifested by need for mechanical ventilation, after vaccination with the Pfizer-BioNTech COVID-19 vaccine,” wrote lead author Ehud Rinott, department of public health, faculty of health sciences, Ben-Gurion University of the Negev in Beer-Sheva, Israel, and colleagues.

The study was published online Feb. 26, 2021, in Morbidity and Mortality Weekly Report.

The progress of COVID-19 vaccination across Israel presents researchers with a unique opportunity to study effectiveness on a population level. In this study, 84% of residents 70 and older received two-dose vaccinations. In contrast, only 10% of people in Israel younger than 50 received the same vaccine coverage.

Along with senior author Yair Lewis, MD, PhD, and coauthor Ilan Youngster, MD, Mr. Rinott compared mechanical ventilation rates between Oct. 2, 2020, and Feb. 9, 2021. They found that the ratio of people 70 and older compared with those younger than 50 requiring mechanical ventilation changed from 5.8:1 to 1.9:1 between these periods. This translates to the 67% decrease.

The study offers a “real-world” look at vaccination effectiveness, adding to more controlled evidence from clinical trials. “Achieving high vaccination coverage through intensive vaccination campaigns has the potential to substantially reduce COVID-19-associated morbidity and mortality,” the researchers wrote.

Israel started a national vaccination program on Dec. 20, 2020, targeting high-risk residents including people 60 and older, health care workers, and those with relevant comorbidities. At the same time, in addition to immunization, Israel has used strategies like stay-at-home orders, school closures, mask mandates, and more.

Potential limitations include a limited ability to account for the effect of the stay-at-home orders, spread of virus variants, and other concomitant factors; a potential for a delayed reporting of cases; and variability in mitigation measures by age group.

Dr. Youngster reported receipt of consulting fees from MyBiotix Ltd.

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

And then there were three. The U.S. Food and Drug Administration (FDA) on Feb. 27 granted emergency use authorization (EUA) to the Ad26.COV2.S vaccine from Janssen/Johnson & Johnson (J&J) for people 18 and older after reviewing its safety and efficacy data.

More vaccine availability at a time of high demand and limited supply could help officials vaccinate more Americans, more quickly. In addition, the J&J vaccine offers one-dose convenience and storage at conventional refrigeration temperatures.

Initial reactions to the EUA for the J&J vaccine have been positive.

“The advantages of having a third vaccine, especially one that is a single shot and can be stored without special refrigeration requirements, will be a major contribution in getting the general public vaccinated sooner, both in the U.S. and around the world,” Phyllis Tien, MD, professor of medicine in the division of infectious diseases at the University of California, San Francisco, told Medscape Medical News.

“It’s great news. We have yet a third vaccine that is highly effective at preventing COVID, and even more effective at preventing severe COVID,” said Paul Goepfert, MD. It’s a “tremendous boon for our country and other countries as well.”

“This vaccine has also been shown to be effective against the B.1.351 strain that was first described in South Africa,” added Dr. Goepfert, director of the Alabama Vaccine Research Clinic and infectious disease specialist at the University of Alabama at Birmingham.

The EUA “is indeed exciting news,” Colleen Kraft, MD, associate chief medical officer at Emory University Hospital and associate professor at Emory University School of Medicine in Atlanta, said during a February 25 media briefing.

One recent concern centers on people aged 60 years and older. Documents the FDA released earlier this week suggest a lower efficacy, 42%, for the J&J immunization among people in this age group with certain relevant comorbidities. In contrast, without underlying conditions like heart disease or diabetes, efficacy in this cohort was 72%.

The more the merrier

The scope and urgency of the COVID-19 pandemic necessitates as many protective measures as possible, said Raj Shah, MD, geriatrician, and associate professor of family medicine and codirector of the Center for Community Health Equity at Rush University in Chicago.

“Trying to vaccinate as many individuals living in the United States to prevent the spread of COVID is such a big project that no one company or one vaccine was going to be able to ramp up fast enough on its own,” Dr. Shah told Medscape Medical News.“This has been the hope for us,” he added, “to get to multiple vaccines with slightly different properties that will provide more options.”

Experience with the J&J vaccine so far suggests reactions are less severe. “The nice thing about the Johnson and Johnson [vaccine] is that it definitely has less side effects,” Dr. Kraft said.

On the other hand, low-grade fever, chills, or fatigue after vaccination can be considered a positive because they can reflect how well the immune system is responding, she added.

One and done?

Single-dose administration could be more than a convenience — it could also help clinicians vaccinate members of underserved communities and rural locations, where returning for a second dose could be more difficult for some people.

“In a controlled setting, in a clinical trial, we do a lot to make sure people get all the treatment they need,” Dr. Shah said. “We’re not seeing it right now, but we’re always worried when we have more than one dose that has to be administered, that some people will drop off and not come back for the second vaccine.”

This group could include the needle-phobic, he added. “For them, having it done once alleviates a lot of the anxiety.”

Looking beyond the numbers

The phase 3 ENSEMBLE study of the J&J vaccine revealed a 72% efficacy for preventing moderate-to-severe COVID-19 among U.S. participants. In contrast, researchers reported 94% to 95% efficacy for the Pfizer/BioNTech and Moderna vaccines.

However, experts agreed that focusing solely on these numbers can miss more important points. For example, no participants who received the J&J vaccine in the phase 3 trial died from COVID-19-related illness. There were five such deaths in the placebo cohort.

“One of the things that these vaccines do very well is they minimize severe disease,” Dr. Kraft said. “As somebody that has spent an inordinate time in the hospital taking care of patients with severe disease from COVID, this is very much a welcome addition to our armamentarium to fight this virus.”

“If you can give something that prevents people from dying, that is a true path to normalcy,” Dr. Goepfert added.

More work to do

“The demand is strong from all groups right now. We just have to work on getting more vaccines out there,” Dr. Shah said.

“We are at a point in this country where we are getting better with the distribution of the vaccine,” he added, “but we are nowhere close to achieving that distribution of vaccines to get to everybody.”

Dr. Goepfert, Dr. Shah, and Dr. Kraft disclosed no relevant financial relationships. Dr. Tien received support from Johnson & Johnson to conduct the J&J COVID-19 vaccine trial in the San Francisco VA Health Care System.

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

And then there were three. The U.S. Food and Drug Administration (FDA) on Feb. 27 granted emergency use authorization (EUA) to the Ad26.COV2.S vaccine from Janssen/Johnson & Johnson (J&J) for people 18 and older after reviewing its safety and efficacy data.

More vaccine availability at a time of high demand and limited supply could help officials vaccinate more Americans, more quickly. In addition, the J&J vaccine offers one-dose convenience and storage at conventional refrigeration temperatures.

Initial reactions to the EUA for the J&J vaccine have been positive.

“The advantages of having a third vaccine, especially one that is a single shot and can be stored without special refrigeration requirements, will be a major contribution in getting the general public vaccinated sooner, both in the U.S. and around the world,” Phyllis Tien, MD, professor of medicine in the division of infectious diseases at the University of California, San Francisco, told Medscape Medical News.

“It’s great news. We have yet a third vaccine that is highly effective at preventing COVID, and even more effective at preventing severe COVID,” said Paul Goepfert, MD. It’s a “tremendous boon for our country and other countries as well.”

“This vaccine has also been shown to be effective against the B.1.351 strain that was first described in South Africa,” added Dr. Goepfert, director of the Alabama Vaccine Research Clinic and infectious disease specialist at the University of Alabama at Birmingham.

The EUA “is indeed exciting news,” Colleen Kraft, MD, associate chief medical officer at Emory University Hospital and associate professor at Emory University School of Medicine in Atlanta, said during a February 25 media briefing.

One recent concern centers on people aged 60 years and older. Documents the FDA released earlier this week suggest a lower efficacy, 42%, for the J&J immunization among people in this age group with certain relevant comorbidities. In contrast, without underlying conditions like heart disease or diabetes, efficacy in this cohort was 72%.

The more the merrier

The scope and urgency of the COVID-19 pandemic necessitates as many protective measures as possible, said Raj Shah, MD, geriatrician, and associate professor of family medicine and codirector of the Center for Community Health Equity at Rush University in Chicago.

“Trying to vaccinate as many individuals living in the United States to prevent the spread of COVID is such a big project that no one company or one vaccine was going to be able to ramp up fast enough on its own,” Dr. Shah told Medscape Medical News.“This has been the hope for us,” he added, “to get to multiple vaccines with slightly different properties that will provide more options.”

Experience with the J&J vaccine so far suggests reactions are less severe. “The nice thing about the Johnson and Johnson [vaccine] is that it definitely has less side effects,” Dr. Kraft said.

On the other hand, low-grade fever, chills, or fatigue after vaccination can be considered a positive because they can reflect how well the immune system is responding, she added.

One and done?

Single-dose administration could be more than a convenience — it could also help clinicians vaccinate members of underserved communities and rural locations, where returning for a second dose could be more difficult for some people.

“In a controlled setting, in a clinical trial, we do a lot to make sure people get all the treatment they need,” Dr. Shah said. “We’re not seeing it right now, but we’re always worried when we have more than one dose that has to be administered, that some people will drop off and not come back for the second vaccine.”

This group could include the needle-phobic, he added. “For them, having it done once alleviates a lot of the anxiety.”

Looking beyond the numbers

The phase 3 ENSEMBLE study of the J&J vaccine revealed a 72% efficacy for preventing moderate-to-severe COVID-19 among U.S. participants. In contrast, researchers reported 94% to 95% efficacy for the Pfizer/BioNTech and Moderna vaccines.

However, experts agreed that focusing solely on these numbers can miss more important points. For example, no participants who received the J&J vaccine in the phase 3 trial died from COVID-19-related illness. There were five such deaths in the placebo cohort.

“One of the things that these vaccines do very well is they minimize severe disease,” Dr. Kraft said. “As somebody that has spent an inordinate time in the hospital taking care of patients with severe disease from COVID, this is very much a welcome addition to our armamentarium to fight this virus.”

“If you can give something that prevents people from dying, that is a true path to normalcy,” Dr. Goepfert added.

More work to do

“The demand is strong from all groups right now. We just have to work on getting more vaccines out there,” Dr. Shah said.

“We are at a point in this country where we are getting better with the distribution of the vaccine,” he added, “but we are nowhere close to achieving that distribution of vaccines to get to everybody.”

Dr. Goepfert, Dr. Shah, and Dr. Kraft disclosed no relevant financial relationships. Dr. Tien received support from Johnson & Johnson to conduct the J&J COVID-19 vaccine trial in the San Francisco VA Health Care System.

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

And then there were three. The U.S. Food and Drug Administration (FDA) on Feb. 27 granted emergency use authorization (EUA) to the Ad26.COV2.S vaccine from Janssen/Johnson & Johnson (J&J) for people 18 and older after reviewing its safety and efficacy data.

More vaccine availability at a time of high demand and limited supply could help officials vaccinate more Americans, more quickly. In addition, the J&J vaccine offers one-dose convenience and storage at conventional refrigeration temperatures.

Initial reactions to the EUA for the J&J vaccine have been positive.

“The advantages of having a third vaccine, especially one that is a single shot and can be stored without special refrigeration requirements, will be a major contribution in getting the general public vaccinated sooner, both in the U.S. and around the world,” Phyllis Tien, MD, professor of medicine in the division of infectious diseases at the University of California, San Francisco, told Medscape Medical News.

“It’s great news. We have yet a third vaccine that is highly effective at preventing COVID, and even more effective at preventing severe COVID,” said Paul Goepfert, MD. It’s a “tremendous boon for our country and other countries as well.”

“This vaccine has also been shown to be effective against the B.1.351 strain that was first described in South Africa,” added Dr. Goepfert, director of the Alabama Vaccine Research Clinic and infectious disease specialist at the University of Alabama at Birmingham.

The EUA “is indeed exciting news,” Colleen Kraft, MD, associate chief medical officer at Emory University Hospital and associate professor at Emory University School of Medicine in Atlanta, said during a February 25 media briefing.

One recent concern centers on people aged 60 years and older. Documents the FDA released earlier this week suggest a lower efficacy, 42%, for the J&J immunization among people in this age group with certain relevant comorbidities. In contrast, without underlying conditions like heart disease or diabetes, efficacy in this cohort was 72%.

The more the merrier

The scope and urgency of the COVID-19 pandemic necessitates as many protective measures as possible, said Raj Shah, MD, geriatrician, and associate professor of family medicine and codirector of the Center for Community Health Equity at Rush University in Chicago.

“Trying to vaccinate as many individuals living in the United States to prevent the spread of COVID is such a big project that no one company or one vaccine was going to be able to ramp up fast enough on its own,” Dr. Shah told Medscape Medical News.“This has been the hope for us,” he added, “to get to multiple vaccines with slightly different properties that will provide more options.”

Experience with the J&J vaccine so far suggests reactions are less severe. “The nice thing about the Johnson and Johnson [vaccine] is that it definitely has less side effects,” Dr. Kraft said.

On the other hand, low-grade fever, chills, or fatigue after vaccination can be considered a positive because they can reflect how well the immune system is responding, she added.

One and done?

Single-dose administration could be more than a convenience — it could also help clinicians vaccinate members of underserved communities and rural locations, where returning for a second dose could be more difficult for some people.

“In a controlled setting, in a clinical trial, we do a lot to make sure people get all the treatment they need,” Dr. Shah said. “We’re not seeing it right now, but we’re always worried when we have more than one dose that has to be administered, that some people will drop off and not come back for the second vaccine.”

This group could include the needle-phobic, he added. “For them, having it done once alleviates a lot of the anxiety.”

Looking beyond the numbers

The phase 3 ENSEMBLE study of the J&J vaccine revealed a 72% efficacy for preventing moderate-to-severe COVID-19 among U.S. participants. In contrast, researchers reported 94% to 95% efficacy for the Pfizer/BioNTech and Moderna vaccines.

However, experts agreed that focusing solely on these numbers can miss more important points. For example, no participants who received the J&J vaccine in the phase 3 trial died from COVID-19-related illness. There were five such deaths in the placebo cohort.

“One of the things that these vaccines do very well is they minimize severe disease,” Dr. Kraft said. “As somebody that has spent an inordinate time in the hospital taking care of patients with severe disease from COVID, this is very much a welcome addition to our armamentarium to fight this virus.”

“If you can give something that prevents people from dying, that is a true path to normalcy,” Dr. Goepfert added.

More work to do

“The demand is strong from all groups right now. We just have to work on getting more vaccines out there,” Dr. Shah said.

“We are at a point in this country where we are getting better with the distribution of the vaccine,” he added, “but we are nowhere close to achieving that distribution of vaccines to get to everybody.”

Dr. Goepfert, Dr. Shah, and Dr. Kraft disclosed no relevant financial relationships. Dr. Tien received support from Johnson & Johnson to conduct the J&J COVID-19 vaccine trial in the San Francisco VA Health Care System.

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

An FDA advisory panel lent their support Feb. 26 to a rapid clearance for Janssen/Johnson & Johnson’s COVID-19 vaccine.

The Food and Drug Administration (FDA) is expected to quickly provide an emergency use authorization (EUA) for the vaccine following the recommendation by the panel. The FDA’s Vaccines and Related Biological Products Advisory Committee voted 22-0 on this question: Based on the totality of scientific evidence available, do the benefits of the Johnson & Johnson COVID-19 Vaccine outweigh its risks for use in individuals 18 years of age and older?

The Johnson & Johnson vaccine is expected to offer more convenient dosing and be easier to distribute than the two rival products already available in the United States. Janssen’s vaccine is intended to be given in a single dose. In December, the FDA granted EUAs for the Pfizer/BioNTech and Moderna COVID-19 vaccines, which are each two-dose regimens.

Johnson & Johnson’s vaccine can be stored for at least 3 months at normal refrigerator temperatures of 2°C to 8°C (36°F to 46°F). Its shipping and storage fits into the existing medical supply infrastructure, the company said in its briefing materials for the FDA advisory committee meeting. In contrast, Pfizer’s vaccine is stored in ultracold freezers at temperatures between -80°C and -60°C (-112°F and -76°F), according to the Centers for Disease Control and Prevention. Moderna’s vaccine may be stored in a freezer between -25°C and -15°C (-13°F and 5°F).

But FDA advisers focused more in their deliberations on concerns about Janssen’s vaccine, including emerging reports of allergic reactions.

The advisers also discussed how patients might respond to the widely reported gap between Johnson & Johnson’s topline efficacy rates compared with rivals. The company’s initial unveiling last month of key results for its vaccine caused an initial wave of disappointment, with its overall efficacy against moderate-to-severe COVID-19 28 days postvaccination first reported at about 66% globally. By contrast, results for the Pfizer and Moderna vaccines suggest they have efficacy rates of 95% and 94%.

But in concluding, the advisers spoke of the Janssen vaccine as a much-needed tool to address the COVID-19 pandemic. The death toll in the United States attributed to the virus has reached 501,414, according to the World Health Organization.

“Despite the concerns that were raised during the discussion. I think what we have to keep in mind is that we’re still in the midst of this deadly pandemic,” said FDA adviser Archana Chatterjee, MD, PhD, from Rosalind Franklin University. “There is a shortage of vaccines that are currently authorized, and I think authorization of this vaccine will help meet the needs at the moment.”

The FDA is not bound to accept the recommendations of its advisers, but it often does so.

Anaphylaxis case

FDA advisers raised only a few questions for Johnson & Johnson and FDA staff ahead of their vote. The committee’s deliberations were less contentious and heated than had been during its December reviews of the Pfizer and Moderna vaccines. In those meetings, the panel voted 17-4, with one abstention, in favor of Pfizer’s vaccine and  20-0, with one abstention, on the Moderna vaccine.

“We are very comfortable now with the procedure, as well as the vaccines,” said Arnold Monto, MD, after the Feb. 26 vote on the Janssen vaccine. Dr. Monto, from the University of Michigan School of Public Health in Ann Arbor, has served as the chairman of the FDA panel through its review of all three COVID-19 vaccines.

Among the issues noted in the deliberations was the emergence of a concern about anaphylaxis with the vaccine.

This serious allergic reaction has been seen in people who have taken the Pfizer and Moderna vaccines. Before the week of the panel meeting, though, there had not been reports of anaphylaxis with the Johnson & Johnson vaccine, said Macaya Douoguih, MD, MPH, head of clinical development and medical affairs for Janssen/ Johnson & Johnson’s vaccines division.

However, on February 24, Johnson & Johnson received preliminary reports about two cases of severe allergic reaction from an open-label study in South Africa, with one of these being anaphylaxis, Dr. Douoguih said. The company will continue to closely monitor for these events as outlined in their pharmacovigilance plan, Dr. Douoguih said.

Federal health officials have sought to make clinicians aware of the rare risk for anaphylaxis with COVID vaccines, while reminding the public that this reaction can be managed.

The FDA had Tom Shimabukuro, MD, MPH, MBA, from the CDC, give an update on postmarketing surveillance for the Pfizer and Moderna vaccines as part of the review of the Johnson & Johnson application. Dr. Shimabukuro and CDC colleagues published a report in JAMA on February 14 that looked at an anaphylaxis case reported connected with COVID vaccines between December 14, 2020, and January 18, 2021.

The CDC identified 66 case reports received that met Brighton Collaboration case definition criteria for anaphylaxis (levels 1, 2, or 3): 47 following Pfizer/BioNTech vaccine, for a reporting rate of 4.7 cases/million doses administered, and 19 following Moderna vaccine, for a reporting rate of 2.5 cases/million doses administered, Dr. Shimabukuro and CDC colleagues wrote.

The CDC has published materials to help clinicians prepare for the possibility of this rare event, Dr. Shimabukuro told the FDA advisers.

“The take-home message here is that these are rare events and anaphylaxis, although clinically serious, is treatable,” Dr. Shimabukuro said.

At the conclusion of the meeting, FDA panelist Patrick Moore, MD, MPH, from the University of Pittsburgh in Pennsylvania, stressed the need to convey to the public that the COVID vaccines appear so far to be safe. Many people earlier had doubts about how the FDA could both safely and quickly review the applications for EUAs for these products.

“As of February 26, things are looking good. That could change tomorrow,” Dr. Moore said. But “this whole EUA process does seem to have worked, despite my own personal concerns about it.”

No second-class vaccines

The Johnson & Johnson vaccine, known as Ad26.COV2.S, is composed of a recombinant, replication-incompetent human adenovirus type 26 (Ad26) vector. It’s intended to encode a stabilized form of SARS-CoV-2 spike (S) protein. The Pfizer and Moderna vaccines use a different mechanism. They rely on mRNA.

The FDA advisers also discussed how patients might respond to the widely reported gap between Janssen’s topline efficacy rates compared with rivals. They urged against people parsing study details too finely and seeking to pick and choose their shots.

“It’s important that people do not think that one vaccine is better than another,” said FDA adviser H. Cody Meissner, MD, from Tufts University School of Medicine in Boston.

Dr. Monto agreed, noting that many people in the United States are still waiting for their turn to get COVID vaccines because of the limited early supply.

Trying to game the system to get one vaccine instead of another would not be wise. “In this environment, whatever you can get, get,” Dr. Monto said.

During an open public hearing, Sarah Christopherson, policy advocacy director of the National Women’s Health Network, said that press reports are fueling a damaging impression in the public that there are “first and second-class” vaccines.

“That has the potential to exacerbate existing mistrust” in vaccines, she said. “Public health authorities must address these perceptions head on.”

She urged against attempts to compare the Janssen vaccine to others, noting the potential effects of emerging variants of the virus.

“It’s difficult to make an apples-to-apples comparison between vaccines,” she said.

Johnson & Johnson’s efficacy results, which are lower than those of the mRNA vaccines, may be a reflection of the ways in which SARS-Co-V-2 is mutating and thus becoming more of a threat, according to the company. A key study of the new vaccine, involving about 44,000 people, coincided with the emergence of new SARS-CoV-2 variants, which were emerging in some of the countries where the pivotal COV3001 study was being conducted, the company said.

At least 14 days after vaccination, the Johnson & Johnson COVID vaccine efficacy (95% confidence interval) was 72.0% (58.2, 81.7) in the United States, 68.1% (48.8, 80.7) in Brazil, and 64.0% (41.2, 78.7) in South Africa.

Weakened standards?

Several researchers called on the FDA to maintain a critical attitude when assessing Johnson & Johnson’s application for the EUA, warning of a potential for a permanent erosion of agency rules due to hasty action on COVID vaccines.

They raised concerns about the FDA demanding too little in terms of follow-up studies on COVID vaccines and with persisting murkiness resulting in attempts to determine how well these treatments work beyond the initial study period.

“I worry about FDA lowering its approval standards,” said Peter Doshi, PhD, from The BMJ and a faculty member at the University of Maryland School of Medicine in Baltimore, during an open public hearing at the meeting.

“There’s a real urgency to stand back right now and look at the forest here, as well as the trees, and I urge the committee to consider the effects FDA decisions may have on the entire regulatory approval process,” Dr. Doshi said.

Dr. Doshi asked why Johnson & Johnson did not seek a standard full approval — a biologics license application (BLA) — instead of aiming for the lower bar of an EUA. The FDA already has allowed wide distribution of the Pfizer/BioNTech and Moderna vaccines through EUAs. That removes the sense of urgency that FDA faced last year in his view.

The FDA’s June 2020 guidance on the development of COVID vaccines had asked drugmakers to plan on following participants in COVID vaccine trials for “ideally at least one to two years.” Yet people who got placebo in Moderna and Pfizer trials already are being vaccinated, Dr. Doshi said. And Johnson & Johnson said in its presentation to the FDA that if the Ad26.COV2.S vaccine were granted an EUA, the COV3001 study design would be amended to “facilitate cross-over of placebo participants in all participating countries to receive one dose of active study vaccine as fast as operationally feasible.”

“I’m nervous about the prospect of there never being a COVID vaccine that meets the FDA’s approval standard” for a BLA instead of the more limited EUA, Dr. Doshi said.

Diana Zuckerman, PhD, president of the nonprofit National Center for Health Research, noted that the FDA’s subsequent guidance tailored for EUAs for COVID vaccines “drastically shortened” the follow-up time to a median of 2 months. Dr. Zuckerman said that a crossover design would be “a reasonable compromise, but only if the placebo group has at least 6 months of data.” Dr. Zuckerman opened her remarks in the open public hearing by saying she had inherited Johnson & Johnson stock, so was speaking at the meeting against her own financial interest.

“As soon as a vaccine is authorized, we start losing the placebo group. If FDA lets that happen, that’s a huge loss for public health and a huge loss of information about how we can all stay safe,” Dr. Zuckerman said.



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

An FDA advisory panel lent their support Feb. 26 to a rapid clearance for Janssen/Johnson & Johnson’s COVID-19 vaccine.

The Food and Drug Administration (FDA) is expected to quickly provide an emergency use authorization (EUA) for the vaccine following the recommendation by the panel. The FDA’s Vaccines and Related Biological Products Advisory Committee voted 22-0 on this question: Based on the totality of scientific evidence available, do the benefits of the Johnson & Johnson COVID-19 Vaccine outweigh its risks for use in individuals 18 years of age and older?

The Johnson & Johnson vaccine is expected to offer more convenient dosing and be easier to distribute than the two rival products already available in the United States. Janssen’s vaccine is intended to be given in a single dose. In December, the FDA granted EUAs for the Pfizer/BioNTech and Moderna COVID-19 vaccines, which are each two-dose regimens.

Johnson & Johnson’s vaccine can be stored for at least 3 months at normal refrigerator temperatures of 2°C to 8°C (36°F to 46°F). Its shipping and storage fits into the existing medical supply infrastructure, the company said in its briefing materials for the FDA advisory committee meeting. In contrast, Pfizer’s vaccine is stored in ultracold freezers at temperatures between -80°C and -60°C (-112°F and -76°F), according to the Centers for Disease Control and Prevention. Moderna’s vaccine may be stored in a freezer between -25°C and -15°C (-13°F and 5°F).

But FDA advisers focused more in their deliberations on concerns about Janssen’s vaccine, including emerging reports of allergic reactions.

The advisers also discussed how patients might respond to the widely reported gap between Johnson & Johnson’s topline efficacy rates compared with rivals. The company’s initial unveiling last month of key results for its vaccine caused an initial wave of disappointment, with its overall efficacy against moderate-to-severe COVID-19 28 days postvaccination first reported at about 66% globally. By contrast, results for the Pfizer and Moderna vaccines suggest they have efficacy rates of 95% and 94%.

But in concluding, the advisers spoke of the Janssen vaccine as a much-needed tool to address the COVID-19 pandemic. The death toll in the United States attributed to the virus has reached 501,414, according to the World Health Organization.

“Despite the concerns that were raised during the discussion. I think what we have to keep in mind is that we’re still in the midst of this deadly pandemic,” said FDA adviser Archana Chatterjee, MD, PhD, from Rosalind Franklin University. “There is a shortage of vaccines that are currently authorized, and I think authorization of this vaccine will help meet the needs at the moment.”

The FDA is not bound to accept the recommendations of its advisers, but it often does so.

Anaphylaxis case

FDA advisers raised only a few questions for Johnson & Johnson and FDA staff ahead of their vote. The committee’s deliberations were less contentious and heated than had been during its December reviews of the Pfizer and Moderna vaccines. In those meetings, the panel voted 17-4, with one abstention, in favor of Pfizer’s vaccine and  20-0, with one abstention, on the Moderna vaccine.

“We are very comfortable now with the procedure, as well as the vaccines,” said Arnold Monto, MD, after the Feb. 26 vote on the Janssen vaccine. Dr. Monto, from the University of Michigan School of Public Health in Ann Arbor, has served as the chairman of the FDA panel through its review of all three COVID-19 vaccines.

Among the issues noted in the deliberations was the emergence of a concern about anaphylaxis with the vaccine.

This serious allergic reaction has been seen in people who have taken the Pfizer and Moderna vaccines. Before the week of the panel meeting, though, there had not been reports of anaphylaxis with the Johnson & Johnson vaccine, said Macaya Douoguih, MD, MPH, head of clinical development and medical affairs for Janssen/ Johnson & Johnson’s vaccines division.

However, on February 24, Johnson & Johnson received preliminary reports about two cases of severe allergic reaction from an open-label study in South Africa, with one of these being anaphylaxis, Dr. Douoguih said. The company will continue to closely monitor for these events as outlined in their pharmacovigilance plan, Dr. Douoguih said.

Federal health officials have sought to make clinicians aware of the rare risk for anaphylaxis with COVID vaccines, while reminding the public that this reaction can be managed.

The FDA had Tom Shimabukuro, MD, MPH, MBA, from the CDC, give an update on postmarketing surveillance for the Pfizer and Moderna vaccines as part of the review of the Johnson & Johnson application. Dr. Shimabukuro and CDC colleagues published a report in JAMA on February 14 that looked at an anaphylaxis case reported connected with COVID vaccines between December 14, 2020, and January 18, 2021.

The CDC identified 66 case reports received that met Brighton Collaboration case definition criteria for anaphylaxis (levels 1, 2, or 3): 47 following Pfizer/BioNTech vaccine, for a reporting rate of 4.7 cases/million doses administered, and 19 following Moderna vaccine, for a reporting rate of 2.5 cases/million doses administered, Dr. Shimabukuro and CDC colleagues wrote.

The CDC has published materials to help clinicians prepare for the possibility of this rare event, Dr. Shimabukuro told the FDA advisers.

“The take-home message here is that these are rare events and anaphylaxis, although clinically serious, is treatable,” Dr. Shimabukuro said.

At the conclusion of the meeting, FDA panelist Patrick Moore, MD, MPH, from the University of Pittsburgh in Pennsylvania, stressed the need to convey to the public that the COVID vaccines appear so far to be safe. Many people earlier had doubts about how the FDA could both safely and quickly review the applications for EUAs for these products.

“As of February 26, things are looking good. That could change tomorrow,” Dr. Moore said. But “this whole EUA process does seem to have worked, despite my own personal concerns about it.”

No second-class vaccines

The Johnson & Johnson vaccine, known as Ad26.COV2.S, is composed of a recombinant, replication-incompetent human adenovirus type 26 (Ad26) vector. It’s intended to encode a stabilized form of SARS-CoV-2 spike (S) protein. The Pfizer and Moderna vaccines use a different mechanism. They rely on mRNA.

The FDA advisers also discussed how patients might respond to the widely reported gap between Janssen’s topline efficacy rates compared with rivals. They urged against people parsing study details too finely and seeking to pick and choose their shots.

“It’s important that people do not think that one vaccine is better than another,” said FDA adviser H. Cody Meissner, MD, from Tufts University School of Medicine in Boston.

Dr. Monto agreed, noting that many people in the United States are still waiting for their turn to get COVID vaccines because of the limited early supply.

Trying to game the system to get one vaccine instead of another would not be wise. “In this environment, whatever you can get, get,” Dr. Monto said.

During an open public hearing, Sarah Christopherson, policy advocacy director of the National Women’s Health Network, said that press reports are fueling a damaging impression in the public that there are “first and second-class” vaccines.

“That has the potential to exacerbate existing mistrust” in vaccines, she said. “Public health authorities must address these perceptions head on.”

She urged against attempts to compare the Janssen vaccine to others, noting the potential effects of emerging variants of the virus.

“It’s difficult to make an apples-to-apples comparison between vaccines,” she said.

Johnson & Johnson’s efficacy results, which are lower than those of the mRNA vaccines, may be a reflection of the ways in which SARS-Co-V-2 is mutating and thus becoming more of a threat, according to the company. A key study of the new vaccine, involving about 44,000 people, coincided with the emergence of new SARS-CoV-2 variants, which were emerging in some of the countries where the pivotal COV3001 study was being conducted, the company said.

At least 14 days after vaccination, the Johnson & Johnson COVID vaccine efficacy (95% confidence interval) was 72.0% (58.2, 81.7) in the United States, 68.1% (48.8, 80.7) in Brazil, and 64.0% (41.2, 78.7) in South Africa.

Weakened standards?

Several researchers called on the FDA to maintain a critical attitude when assessing Johnson & Johnson’s application for the EUA, warning of a potential for a permanent erosion of agency rules due to hasty action on COVID vaccines.

They raised concerns about the FDA demanding too little in terms of follow-up studies on COVID vaccines and with persisting murkiness resulting in attempts to determine how well these treatments work beyond the initial study period.

“I worry about FDA lowering its approval standards,” said Peter Doshi, PhD, from The BMJ and a faculty member at the University of Maryland School of Medicine in Baltimore, during an open public hearing at the meeting.

“There’s a real urgency to stand back right now and look at the forest here, as well as the trees, and I urge the committee to consider the effects FDA decisions may have on the entire regulatory approval process,” Dr. Doshi said.

Dr. Doshi asked why Johnson & Johnson did not seek a standard full approval — a biologics license application (BLA) — instead of aiming for the lower bar of an EUA. The FDA already has allowed wide distribution of the Pfizer/BioNTech and Moderna vaccines through EUAs. That removes the sense of urgency that FDA faced last year in his view.

The FDA’s June 2020 guidance on the development of COVID vaccines had asked drugmakers to plan on following participants in COVID vaccine trials for “ideally at least one to two years.” Yet people who got placebo in Moderna and Pfizer trials already are being vaccinated, Dr. Doshi said. And Johnson & Johnson said in its presentation to the FDA that if the Ad26.COV2.S vaccine were granted an EUA, the COV3001 study design would be amended to “facilitate cross-over of placebo participants in all participating countries to receive one dose of active study vaccine as fast as operationally feasible.”

“I’m nervous about the prospect of there never being a COVID vaccine that meets the FDA’s approval standard” for a BLA instead of the more limited EUA, Dr. Doshi said.

Diana Zuckerman, PhD, president of the nonprofit National Center for Health Research, noted that the FDA’s subsequent guidance tailored for EUAs for COVID vaccines “drastically shortened” the follow-up time to a median of 2 months. Dr. Zuckerman said that a crossover design would be “a reasonable compromise, but only if the placebo group has at least 6 months of data.” Dr. Zuckerman opened her remarks in the open public hearing by saying she had inherited Johnson & Johnson stock, so was speaking at the meeting against her own financial interest.

“As soon as a vaccine is authorized, we start losing the placebo group. If FDA lets that happen, that’s a huge loss for public health and a huge loss of information about how we can all stay safe,” Dr. Zuckerman said.



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

An FDA advisory panel lent their support Feb. 26 to a rapid clearance for Janssen/Johnson & Johnson’s COVID-19 vaccine.

The Food and Drug Administration (FDA) is expected to quickly provide an emergency use authorization (EUA) for the vaccine following the recommendation by the panel. The FDA’s Vaccines and Related Biological Products Advisory Committee voted 22-0 on this question: Based on the totality of scientific evidence available, do the benefits of the Johnson & Johnson COVID-19 Vaccine outweigh its risks for use in individuals 18 years of age and older?

The Johnson & Johnson vaccine is expected to offer more convenient dosing and be easier to distribute than the two rival products already available in the United States. Janssen’s vaccine is intended to be given in a single dose. In December, the FDA granted EUAs for the Pfizer/BioNTech and Moderna COVID-19 vaccines, which are each two-dose regimens.

Johnson & Johnson’s vaccine can be stored for at least 3 months at normal refrigerator temperatures of 2°C to 8°C (36°F to 46°F). Its shipping and storage fits into the existing medical supply infrastructure, the company said in its briefing materials for the FDA advisory committee meeting. In contrast, Pfizer’s vaccine is stored in ultracold freezers at temperatures between -80°C and -60°C (-112°F and -76°F), according to the Centers for Disease Control and Prevention. Moderna’s vaccine may be stored in a freezer between -25°C and -15°C (-13°F and 5°F).

But FDA advisers focused more in their deliberations on concerns about Janssen’s vaccine, including emerging reports of allergic reactions.

The advisers also discussed how patients might respond to the widely reported gap between Johnson & Johnson’s topline efficacy rates compared with rivals. The company’s initial unveiling last month of key results for its vaccine caused an initial wave of disappointment, with its overall efficacy against moderate-to-severe COVID-19 28 days postvaccination first reported at about 66% globally. By contrast, results for the Pfizer and Moderna vaccines suggest they have efficacy rates of 95% and 94%.

But in concluding, the advisers spoke of the Janssen vaccine as a much-needed tool to address the COVID-19 pandemic. The death toll in the United States attributed to the virus has reached 501,414, according to the World Health Organization.

“Despite the concerns that were raised during the discussion. I think what we have to keep in mind is that we’re still in the midst of this deadly pandemic,” said FDA adviser Archana Chatterjee, MD, PhD, from Rosalind Franklin University. “There is a shortage of vaccines that are currently authorized, and I think authorization of this vaccine will help meet the needs at the moment.”

The FDA is not bound to accept the recommendations of its advisers, but it often does so.

Anaphylaxis case

FDA advisers raised only a few questions for Johnson & Johnson and FDA staff ahead of their vote. The committee’s deliberations were less contentious and heated than had been during its December reviews of the Pfizer and Moderna vaccines. In those meetings, the panel voted 17-4, with one abstention, in favor of Pfizer’s vaccine and  20-0, with one abstention, on the Moderna vaccine.

“We are very comfortable now with the procedure, as well as the vaccines,” said Arnold Monto, MD, after the Feb. 26 vote on the Janssen vaccine. Dr. Monto, from the University of Michigan School of Public Health in Ann Arbor, has served as the chairman of the FDA panel through its review of all three COVID-19 vaccines.

Among the issues noted in the deliberations was the emergence of a concern about anaphylaxis with the vaccine.

This serious allergic reaction has been seen in people who have taken the Pfizer and Moderna vaccines. Before the week of the panel meeting, though, there had not been reports of anaphylaxis with the Johnson & Johnson vaccine, said Macaya Douoguih, MD, MPH, head of clinical development and medical affairs for Janssen/ Johnson & Johnson’s vaccines division.

However, on February 24, Johnson & Johnson received preliminary reports about two cases of severe allergic reaction from an open-label study in South Africa, with one of these being anaphylaxis, Dr. Douoguih said. The company will continue to closely monitor for these events as outlined in their pharmacovigilance plan, Dr. Douoguih said.

Federal health officials have sought to make clinicians aware of the rare risk for anaphylaxis with COVID vaccines, while reminding the public that this reaction can be managed.

The FDA had Tom Shimabukuro, MD, MPH, MBA, from the CDC, give an update on postmarketing surveillance for the Pfizer and Moderna vaccines as part of the review of the Johnson & Johnson application. Dr. Shimabukuro and CDC colleagues published a report in JAMA on February 14 that looked at an anaphylaxis case reported connected with COVID vaccines between December 14, 2020, and January 18, 2021.

The CDC identified 66 case reports received that met Brighton Collaboration case definition criteria for anaphylaxis (levels 1, 2, or 3): 47 following Pfizer/BioNTech vaccine, for a reporting rate of 4.7 cases/million doses administered, and 19 following Moderna vaccine, for a reporting rate of 2.5 cases/million doses administered, Dr. Shimabukuro and CDC colleagues wrote.

The CDC has published materials to help clinicians prepare for the possibility of this rare event, Dr. Shimabukuro told the FDA advisers.

“The take-home message here is that these are rare events and anaphylaxis, although clinically serious, is treatable,” Dr. Shimabukuro said.

At the conclusion of the meeting, FDA panelist Patrick Moore, MD, MPH, from the University of Pittsburgh in Pennsylvania, stressed the need to convey to the public that the COVID vaccines appear so far to be safe. Many people earlier had doubts about how the FDA could both safely and quickly review the applications for EUAs for these products.

“As of February 26, things are looking good. That could change tomorrow,” Dr. Moore said. But “this whole EUA process does seem to have worked, despite my own personal concerns about it.”

No second-class vaccines

The Johnson & Johnson vaccine, known as Ad26.COV2.S, is composed of a recombinant, replication-incompetent human adenovirus type 26 (Ad26) vector. It’s intended to encode a stabilized form of SARS-CoV-2 spike (S) protein. The Pfizer and Moderna vaccines use a different mechanism. They rely on mRNA.

The FDA advisers also discussed how patients might respond to the widely reported gap between Janssen’s topline efficacy rates compared with rivals. They urged against people parsing study details too finely and seeking to pick and choose their shots.

“It’s important that people do not think that one vaccine is better than another,” said FDA adviser H. Cody Meissner, MD, from Tufts University School of Medicine in Boston.

Dr. Monto agreed, noting that many people in the United States are still waiting for their turn to get COVID vaccines because of the limited early supply.

Trying to game the system to get one vaccine instead of another would not be wise. “In this environment, whatever you can get, get,” Dr. Monto said.

During an open public hearing, Sarah Christopherson, policy advocacy director of the National Women’s Health Network, said that press reports are fueling a damaging impression in the public that there are “first and second-class” vaccines.

“That has the potential to exacerbate existing mistrust” in vaccines, she said. “Public health authorities must address these perceptions head on.”

She urged against attempts to compare the Janssen vaccine to others, noting the potential effects of emerging variants of the virus.

“It’s difficult to make an apples-to-apples comparison between vaccines,” she said.

Johnson & Johnson’s efficacy results, which are lower than those of the mRNA vaccines, may be a reflection of the ways in which SARS-Co-V-2 is mutating and thus becoming more of a threat, according to the company. A key study of the new vaccine, involving about 44,000 people, coincided with the emergence of new SARS-CoV-2 variants, which were emerging in some of the countries where the pivotal COV3001 study was being conducted, the company said.

At least 14 days after vaccination, the Johnson & Johnson COVID vaccine efficacy (95% confidence interval) was 72.0% (58.2, 81.7) in the United States, 68.1% (48.8, 80.7) in Brazil, and 64.0% (41.2, 78.7) in South Africa.

Weakened standards?

Several researchers called on the FDA to maintain a critical attitude when assessing Johnson & Johnson’s application for the EUA, warning of a potential for a permanent erosion of agency rules due to hasty action on COVID vaccines.

They raised concerns about the FDA demanding too little in terms of follow-up studies on COVID vaccines and with persisting murkiness resulting in attempts to determine how well these treatments work beyond the initial study period.

“I worry about FDA lowering its approval standards,” said Peter Doshi, PhD, from The BMJ and a faculty member at the University of Maryland School of Medicine in Baltimore, during an open public hearing at the meeting.

“There’s a real urgency to stand back right now and look at the forest here, as well as the trees, and I urge the committee to consider the effects FDA decisions may have on the entire regulatory approval process,” Dr. Doshi said.

Dr. Doshi asked why Johnson & Johnson did not seek a standard full approval — a biologics license application (BLA) — instead of aiming for the lower bar of an EUA. The FDA already has allowed wide distribution of the Pfizer/BioNTech and Moderna vaccines through EUAs. That removes the sense of urgency that FDA faced last year in his view.

The FDA’s June 2020 guidance on the development of COVID vaccines had asked drugmakers to plan on following participants in COVID vaccine trials for “ideally at least one to two years.” Yet people who got placebo in Moderna and Pfizer trials already are being vaccinated, Dr. Doshi said. And Johnson & Johnson said in its presentation to the FDA that if the Ad26.COV2.S vaccine were granted an EUA, the COV3001 study design would be amended to “facilitate cross-over of placebo participants in all participating countries to receive one dose of active study vaccine as fast as operationally feasible.”

“I’m nervous about the prospect of there never being a COVID vaccine that meets the FDA’s approval standard” for a BLA instead of the more limited EUA, Dr. Doshi said.

Diana Zuckerman, PhD, president of the nonprofit National Center for Health Research, noted that the FDA’s subsequent guidance tailored for EUAs for COVID vaccines “drastically shortened” the follow-up time to a median of 2 months. Dr. Zuckerman said that a crossover design would be “a reasonable compromise, but only if the placebo group has at least 6 months of data.” Dr. Zuckerman opened her remarks in the open public hearing by saying she had inherited Johnson & Johnson stock, so was speaking at the meeting against her own financial interest.

“As soon as a vaccine is authorized, we start losing the placebo group. If FDA lets that happen, that’s a huge loss for public health and a huge loss of information about how we can all stay safe,” Dr. Zuckerman said.



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