MDedge Endocrinology

People with rheumatic and musculoskeletal diseases (RMDs) who contract the SARS-CoV-2 virus appear more likely to die from COVID-19 if their rheumatologic condition is not being well controlled at the time of their infection.

New data from the COVID-19 Global Rheumatology Alliance (GRA) physician registry reported in Annals of the Rheumatic Diseases have found that the odds of dying from COVID-19 were 87% higher in individuals recorded as having moderate to high disease activity versus those reported to be in remission or having low disease activity.

“I think this really highlights the importance of continuing to appropriately, and actively, treat our patients, and the importance of controlling their disease,” Pedro Machado, MD, PhD, said in an interview. Dr. Machado, an associate professor in rheumatology and muscle diseases at University College London and a consultant rheumatologist at several U.K. hospitals, has been involved in the GRA physician registry from the start, and sits on the GRA steering committee.

Alongside higher disease activity, several other important factors were found to be associated with increased odds of dying from COVID-19 – older age, male gender, and the presence of one or more comorbidities, such as hypertension combined with cardiovascular disease or chronic lung disease.

These demographic and disease-based factors have been linked to an increased risk for COVID-19–related hospitalization before, both in people with RMDs and in the general population, but the latest GRA physician registry data now take that a step further, and link them also to an increased risk for death, together with several other factors more specific to RMDs.
 

Logging COVID-19 rheumatologic cases

Since the start of the global pandemic, the potential effects that SARS-CoV-2 infection might have on people with RMDs in particular has concerned the rheumatology community. The main worries being that, either because of the underlying RMD itself or to its treatment, there may be immunoregulatory deficits or other risk factors that would make individuals more susceptible to not only infection but also to developing more severe COVID-19 than the general population.

These concerns led to the rapid formation of the GRA and the COVID-19 GRA physician registry in March 2020 to collect and analyze data on adults with rheumatic disease and confirmed or presumptive COVID-19. Entries into the registry are made by or under the direction of rheumatologists, and this is a voluntary process.

“This population cannot ever be entirely representative of the population of patients with rheumatic diseases,” Dr. Machado acknowledged. There will be selection and other biases that affect the reported data. That said, it’s the largest database of reported COVID-19 cases in adult rheumatology patients across the world, with more than 9,000 cases so far included from multiple registries, including those based in Europe and North and South America. Data from one of these – the French RMD cohort – have also recently been published in Annals of the Rheumatic Diseases, showing much the same findings but on a national level.

Hospitalization was the focus of a previous report because “you need large sample sizes” to look at endpoints that occur less frequently. When the first analysis was done, there were around 600 cases from 40 countries in the registry with sufficient data that could be used. Now, with a greater number of recorded cases, factors influencing the risk for death could be examined.

Death rate and risk factors found

Data on 3,729 COVID-19 cases in people with RMDs were included in the current analysis, all recorded in the first few months of the registry being open and up until July 1, 2020. In all, 390 (10.5%) of people died. While this is “clearly higher” than reported in the general population in most countries, the analysis was not designed to calculate a precise estimate.

“It should not be taken as an estimate of the overall death rate among patients with rheumatic diseases and COVID-19,” Dr. Machado and coauthors have been keen to point out.

“Age is always the biggest risk factor,” Dr. Machado explained. “There’s always a gradient: the older the patient, the worse the outcome.”

Indeed, there was a threefold increased risk for death among those aged 66-75 years versus those who were 65 years or younger (odds ratio, 3.00), and a sixfold increased risk for patients older than 75, compared with the younger age group (OR, 6.18).

Having both hypertension and cardiovascular disease was associated with an OR of 1.89, and coexisting chronic lung disease also significantly increased the chances of dying from COVID-19 (OR, 1.68).

Being of male sex was associated with a 46% increased risk for death from COVID-19 versus being of female sex.

The risk for COVID-19 death also rose with the use of corticosteroids. Compared with no steroid use, there was a 69% increased risk for with death at doses of 10 mg or more prednisolone equivalent per day.

“The finding about moderate to high doses of steroids being associated with a worse outcome is consistent with the first report; it was the same for hospitalization,” Dr. Machado observed.

The general consensus on steroid use in the COVID-19 setting is that they should be continued as needed, but at the lowest possible dose, as outlined in provisional recommendations set out by the recently renamed European Alliance of Associations for Rheumatology.

The GRA physician registry findings provide further support for this, suggesting that disease control should be optimized with disease-modifying antirheumatic drugs, ideally without increasing the dose of steroids.

Surprise over sulfasalazine risk

“Taking all medications into account – such as methotrexate, leflunomide, hydroxychloroquine, [tumor necrosis factor] blockers, interleukin-6 blockers, and [Janus kinase] inhibitors – it is quite reassuring because we did not see an association with worse outcome with those drugs overall,” Dr. Machado said.

However, treatment with rituximab (OR, 4.0), sulfasalazine (OR, 3.6), and immunosuppressive agents such as azathioprine, cyclophosphamide, cyclosporine, mycophenolate, or tacrolimus (OR, 2.2), were associated with higher odds of dying from COVID-19 when compared with treatment with methotrexate alone.

The findings for rituximab and immunosuppressant use were perhaps not unexpected, but the possible association between sulfasalazine and COVID-19 death was “a bit intriguing,” Dr. Machado observed. “Sulfasalazine is believed to have low immunosuppressive effect.”

This warrants further investigation, but there are likely a range of confounding factors at play. One could be that people considered to be at higher risk may have been more often prescribed sulfasalazine because it was thought to be less immunosuppressive. Another might be because people taking sulfasalazine were more likely to be smokers, and they were also not advised to protect themselves from exposure to the virus (shielding) during the first wave of the pandemic, at least not in the United Kingdom.
 

Rituximab caution and vaccination

“Rituximab is a concern,” Dr. Machado acknowledged. “It is a concern that rheumatologists are now aware of and they are addressing, but then it’s a concern for a very specific subgroup of patients.”

While rheumatologists are, and will continue to prescribe it, there will be even more careful consideration over when, in whom, and how to use it during, and possibly even after, the pandemic.

“COVID is here to stay, it will become endemic, and it’s going to be part of our lives like the flu virus is,” Dr. Machado predicted.

Then there is the issue on vaccinating people against COVID-19, should those on rituximab still receive it? The answer is a yes, but, as with other vaccinations it’s all about the timing of when the vaccination is given.

Societies such as the British Society for Rheumatology have already begun to include guidance on this, recommending one of the available COVID-19 vaccines is given at least a month before the next or first dose of rituximab is due. As rituximab is given every few months, with doses sometimes spaced as much as 9 months or even a year apart, this should not be too much of a problem, but it is “better to have the vaccine first,” Dr. Machado said.
 

Has COVID-19 care improved in RMDs?

In separate research published in The Lancet Rheumatology, April Jorge, MD, of Massachusetts General Hospital and Harvard Medical School, both in Boston, and associates found that the risks of severe COVID-19 outcomes have improved over time, although they still “remain substantial.”

Dr. Jorge and colleagues looked at temporal trends in COVID-19 outcomes in patients with RMDs over the course of the first 6 months of the pandemic in 2020, using data from a large, multicenter, electronic health record network (TriNetX).

They formed two patient cohorts – a late (diagnosed from April 20 to July 20) and an early (diagnosed from January 20 to April 20) cohort – to see if outcomes had improved and discovered lower relative risks among patients in the late cohort for hospitalization (0.67), admission to the ICU (0.56), mechanical ventilation (0.39), acute kidney injury (0.66), renal replacement (0.53), and death (0.39).

“These results are encouraging,” but it’s difficult to match these different populations of patients, Dr. Machado said. “There are always factors that you cannot match for” and were not included in the U.S. analysis.

While there are important caveats in how the analysis was performed and thus in interpreting these data, they do “suggest that one of the reasons why outcomes have improved is because we have become better at treating these patients,” Dr. Machado added.

“Our treatment has improved, and our capacity to treat the complications has improved. We understand better how the disease behaves – we know that they can have thromboembolic complications that we can manage, and we are now able to manage ventilation issues better.”

Moreover, Dr. Machado said that, not only were clinicians more aware of what they should or should not do, there were treatments that were being used routinely or in some cases based on recent clinical trial results. “I think we are indeed treating these patients better.”

The COVID-19 GRA physician registry is financially supported by the American College of Rheumatology and EULAR. Dr. Machado had no relevant conflicts of interest.

People with rheumatic and musculoskeletal diseases (RMDs) who contract the SARS-CoV-2 virus appear more likely to die from COVID-19 if their rheumatologic condition is not being well controlled at the time of their infection.

New data from the COVID-19 Global Rheumatology Alliance (GRA) physician registry reported in Annals of the Rheumatic Diseases have found that the odds of dying from COVID-19 were 87% higher in individuals recorded as having moderate to high disease activity versus those reported to be in remission or having low disease activity.

“I think this really highlights the importance of continuing to appropriately, and actively, treat our patients, and the importance of controlling their disease,” Pedro Machado, MD, PhD, said in an interview. Dr. Machado, an associate professor in rheumatology and muscle diseases at University College London and a consultant rheumatologist at several U.K. hospitals, has been involved in the GRA physician registry from the start, and sits on the GRA steering committee.

Alongside higher disease activity, several other important factors were found to be associated with increased odds of dying from COVID-19 – older age, male gender, and the presence of one or more comorbidities, such as hypertension combined with cardiovascular disease or chronic lung disease.

These demographic and disease-based factors have been linked to an increased risk for COVID-19–related hospitalization before, both in people with RMDs and in the general population, but the latest GRA physician registry data now take that a step further, and link them also to an increased risk for death, together with several other factors more specific to RMDs.
 

Logging COVID-19 rheumatologic cases

Since the start of the global pandemic, the potential effects that SARS-CoV-2 infection might have on people with RMDs in particular has concerned the rheumatology community. The main worries being that, either because of the underlying RMD itself or to its treatment, there may be immunoregulatory deficits or other risk factors that would make individuals more susceptible to not only infection but also to developing more severe COVID-19 than the general population.

These concerns led to the rapid formation of the GRA and the COVID-19 GRA physician registry in March 2020 to collect and analyze data on adults with rheumatic disease and confirmed or presumptive COVID-19. Entries into the registry are made by or under the direction of rheumatologists, and this is a voluntary process.

“This population cannot ever be entirely representative of the population of patients with rheumatic diseases,” Dr. Machado acknowledged. There will be selection and other biases that affect the reported data. That said, it’s the largest database of reported COVID-19 cases in adult rheumatology patients across the world, with more than 9,000 cases so far included from multiple registries, including those based in Europe and North and South America. Data from one of these – the French RMD cohort – have also recently been published in Annals of the Rheumatic Diseases, showing much the same findings but on a national level.

Hospitalization was the focus of a previous report because “you need large sample sizes” to look at endpoints that occur less frequently. When the first analysis was done, there were around 600 cases from 40 countries in the registry with sufficient data that could be used. Now, with a greater number of recorded cases, factors influencing the risk for death could be examined.

Death rate and risk factors found

Data on 3,729 COVID-19 cases in people with RMDs were included in the current analysis, all recorded in the first few months of the registry being open and up until July 1, 2020. In all, 390 (10.5%) of people died. While this is “clearly higher” than reported in the general population in most countries, the analysis was not designed to calculate a precise estimate.

“It should not be taken as an estimate of the overall death rate among patients with rheumatic diseases and COVID-19,” Dr. Machado and coauthors have been keen to point out.

“Age is always the biggest risk factor,” Dr. Machado explained. “There’s always a gradient: the older the patient, the worse the outcome.”

Indeed, there was a threefold increased risk for death among those aged 66-75 years versus those who were 65 years or younger (odds ratio, 3.00), and a sixfold increased risk for patients older than 75, compared with the younger age group (OR, 6.18).

Having both hypertension and cardiovascular disease was associated with an OR of 1.89, and coexisting chronic lung disease also significantly increased the chances of dying from COVID-19 (OR, 1.68).

Being of male sex was associated with a 46% increased risk for death from COVID-19 versus being of female sex.

The risk for COVID-19 death also rose with the use of corticosteroids. Compared with no steroid use, there was a 69% increased risk for with death at doses of 10 mg or more prednisolone equivalent per day.

“The finding about moderate to high doses of steroids being associated with a worse outcome is consistent with the first report; it was the same for hospitalization,” Dr. Machado observed.

The general consensus on steroid use in the COVID-19 setting is that they should be continued as needed, but at the lowest possible dose, as outlined in provisional recommendations set out by the recently renamed European Alliance of Associations for Rheumatology.

The GRA physician registry findings provide further support for this, suggesting that disease control should be optimized with disease-modifying antirheumatic drugs, ideally without increasing the dose of steroids.

Surprise over sulfasalazine risk

“Taking all medications into account – such as methotrexate, leflunomide, hydroxychloroquine, [tumor necrosis factor] blockers, interleukin-6 blockers, and [Janus kinase] inhibitors – it is quite reassuring because we did not see an association with worse outcome with those drugs overall,” Dr. Machado said.

However, treatment with rituximab (OR, 4.0), sulfasalazine (OR, 3.6), and immunosuppressive agents such as azathioprine, cyclophosphamide, cyclosporine, mycophenolate, or tacrolimus (OR, 2.2), were associated with higher odds of dying from COVID-19 when compared with treatment with methotrexate alone.

The findings for rituximab and immunosuppressant use were perhaps not unexpected, but the possible association between sulfasalazine and COVID-19 death was “a bit intriguing,” Dr. Machado observed. “Sulfasalazine is believed to have low immunosuppressive effect.”

This warrants further investigation, but there are likely a range of confounding factors at play. One could be that people considered to be at higher risk may have been more often prescribed sulfasalazine because it was thought to be less immunosuppressive. Another might be because people taking sulfasalazine were more likely to be smokers, and they were also not advised to protect themselves from exposure to the virus (shielding) during the first wave of the pandemic, at least not in the United Kingdom.
 

Rituximab caution and vaccination

“Rituximab is a concern,” Dr. Machado acknowledged. “It is a concern that rheumatologists are now aware of and they are addressing, but then it’s a concern for a very specific subgroup of patients.”

While rheumatologists are, and will continue to prescribe it, there will be even more careful consideration over when, in whom, and how to use it during, and possibly even after, the pandemic.

“COVID is here to stay, it will become endemic, and it’s going to be part of our lives like the flu virus is,” Dr. Machado predicted.

Then there is the issue on vaccinating people against COVID-19, should those on rituximab still receive it? The answer is a yes, but, as with other vaccinations it’s all about the timing of when the vaccination is given.

Societies such as the British Society for Rheumatology have already begun to include guidance on this, recommending one of the available COVID-19 vaccines is given at least a month before the next or first dose of rituximab is due. As rituximab is given every few months, with doses sometimes spaced as much as 9 months or even a year apart, this should not be too much of a problem, but it is “better to have the vaccine first,” Dr. Machado said.
 

Has COVID-19 care improved in RMDs?

In separate research published in The Lancet Rheumatology, April Jorge, MD, of Massachusetts General Hospital and Harvard Medical School, both in Boston, and associates found that the risks of severe COVID-19 outcomes have improved over time, although they still “remain substantial.”

Dr. Jorge and colleagues looked at temporal trends in COVID-19 outcomes in patients with RMDs over the course of the first 6 months of the pandemic in 2020, using data from a large, multicenter, electronic health record network (TriNetX).

They formed two patient cohorts – a late (diagnosed from April 20 to July 20) and an early (diagnosed from January 20 to April 20) cohort – to see if outcomes had improved and discovered lower relative risks among patients in the late cohort for hospitalization (0.67), admission to the ICU (0.56), mechanical ventilation (0.39), acute kidney injury (0.66), renal replacement (0.53), and death (0.39).

“These results are encouraging,” but it’s difficult to match these different populations of patients, Dr. Machado said. “There are always factors that you cannot match for” and were not included in the U.S. analysis.

While there are important caveats in how the analysis was performed and thus in interpreting these data, they do “suggest that one of the reasons why outcomes have improved is because we have become better at treating these patients,” Dr. Machado added.

“Our treatment has improved, and our capacity to treat the complications has improved. We understand better how the disease behaves – we know that they can have thromboembolic complications that we can manage, and we are now able to manage ventilation issues better.”

Moreover, Dr. Machado said that, not only were clinicians more aware of what they should or should not do, there were treatments that were being used routinely or in some cases based on recent clinical trial results. “I think we are indeed treating these patients better.”

The COVID-19 GRA physician registry is financially supported by the American College of Rheumatology and EULAR. Dr. Machado had no relevant conflicts of interest.

People with rheumatic and musculoskeletal diseases (RMDs) who contract the SARS-CoV-2 virus appear more likely to die from COVID-19 if their rheumatologic condition is not being well controlled at the time of their infection.

New data from the COVID-19 Global Rheumatology Alliance (GRA) physician registry reported in Annals of the Rheumatic Diseases have found that the odds of dying from COVID-19 were 87% higher in individuals recorded as having moderate to high disease activity versus those reported to be in remission or having low disease activity.

“I think this really highlights the importance of continuing to appropriately, and actively, treat our patients, and the importance of controlling their disease,” Pedro Machado, MD, PhD, said in an interview. Dr. Machado, an associate professor in rheumatology and muscle diseases at University College London and a consultant rheumatologist at several U.K. hospitals, has been involved in the GRA physician registry from the start, and sits on the GRA steering committee.

Alongside higher disease activity, several other important factors were found to be associated with increased odds of dying from COVID-19 – older age, male gender, and the presence of one or more comorbidities, such as hypertension combined with cardiovascular disease or chronic lung disease.

These demographic and disease-based factors have been linked to an increased risk for COVID-19–related hospitalization before, both in people with RMDs and in the general population, but the latest GRA physician registry data now take that a step further, and link them also to an increased risk for death, together with several other factors more specific to RMDs.
 

Logging COVID-19 rheumatologic cases

Since the start of the global pandemic, the potential effects that SARS-CoV-2 infection might have on people with RMDs in particular has concerned the rheumatology community. The main worries being that, either because of the underlying RMD itself or to its treatment, there may be immunoregulatory deficits or other risk factors that would make individuals more susceptible to not only infection but also to developing more severe COVID-19 than the general population.

These concerns led to the rapid formation of the GRA and the COVID-19 GRA physician registry in March 2020 to collect and analyze data on adults with rheumatic disease and confirmed or presumptive COVID-19. Entries into the registry are made by or under the direction of rheumatologists, and this is a voluntary process.

“This population cannot ever be entirely representative of the population of patients with rheumatic diseases,” Dr. Machado acknowledged. There will be selection and other biases that affect the reported data. That said, it’s the largest database of reported COVID-19 cases in adult rheumatology patients across the world, with more than 9,000 cases so far included from multiple registries, including those based in Europe and North and South America. Data from one of these – the French RMD cohort – have also recently been published in Annals of the Rheumatic Diseases, showing much the same findings but on a national level.

Hospitalization was the focus of a previous report because “you need large sample sizes” to look at endpoints that occur less frequently. When the first analysis was done, there were around 600 cases from 40 countries in the registry with sufficient data that could be used. Now, with a greater number of recorded cases, factors influencing the risk for death could be examined.

Death rate and risk factors found

Data on 3,729 COVID-19 cases in people with RMDs were included in the current analysis, all recorded in the first few months of the registry being open and up until July 1, 2020. In all, 390 (10.5%) of people died. While this is “clearly higher” than reported in the general population in most countries, the analysis was not designed to calculate a precise estimate.

“It should not be taken as an estimate of the overall death rate among patients with rheumatic diseases and COVID-19,” Dr. Machado and coauthors have been keen to point out.

“Age is always the biggest risk factor,” Dr. Machado explained. “There’s always a gradient: the older the patient, the worse the outcome.”

Indeed, there was a threefold increased risk for death among those aged 66-75 years versus those who were 65 years or younger (odds ratio, 3.00), and a sixfold increased risk for patients older than 75, compared with the younger age group (OR, 6.18).

Having both hypertension and cardiovascular disease was associated with an OR of 1.89, and coexisting chronic lung disease also significantly increased the chances of dying from COVID-19 (OR, 1.68).

Being of male sex was associated with a 46% increased risk for death from COVID-19 versus being of female sex.

The risk for COVID-19 death also rose with the use of corticosteroids. Compared with no steroid use, there was a 69% increased risk for with death at doses of 10 mg or more prednisolone equivalent per day.

“The finding about moderate to high doses of steroids being associated with a worse outcome is consistent with the first report; it was the same for hospitalization,” Dr. Machado observed.

The general consensus on steroid use in the COVID-19 setting is that they should be continued as needed, but at the lowest possible dose, as outlined in provisional recommendations set out by the recently renamed European Alliance of Associations for Rheumatology.

The GRA physician registry findings provide further support for this, suggesting that disease control should be optimized with disease-modifying antirheumatic drugs, ideally without increasing the dose of steroids.

Surprise over sulfasalazine risk

“Taking all medications into account – such as methotrexate, leflunomide, hydroxychloroquine, [tumor necrosis factor] blockers, interleukin-6 blockers, and [Janus kinase] inhibitors – it is quite reassuring because we did not see an association with worse outcome with those drugs overall,” Dr. Machado said.

However, treatment with rituximab (OR, 4.0), sulfasalazine (OR, 3.6), and immunosuppressive agents such as azathioprine, cyclophosphamide, cyclosporine, mycophenolate, or tacrolimus (OR, 2.2), were associated with higher odds of dying from COVID-19 when compared with treatment with methotrexate alone.

The findings for rituximab and immunosuppressant use were perhaps not unexpected, but the possible association between sulfasalazine and COVID-19 death was “a bit intriguing,” Dr. Machado observed. “Sulfasalazine is believed to have low immunosuppressive effect.”

This warrants further investigation, but there are likely a range of confounding factors at play. One could be that people considered to be at higher risk may have been more often prescribed sulfasalazine because it was thought to be less immunosuppressive. Another might be because people taking sulfasalazine were more likely to be smokers, and they were also not advised to protect themselves from exposure to the virus (shielding) during the first wave of the pandemic, at least not in the United Kingdom.
 

Rituximab caution and vaccination

“Rituximab is a concern,” Dr. Machado acknowledged. “It is a concern that rheumatologists are now aware of and they are addressing, but then it’s a concern for a very specific subgroup of patients.”

While rheumatologists are, and will continue to prescribe it, there will be even more careful consideration over when, in whom, and how to use it during, and possibly even after, the pandemic.

“COVID is here to stay, it will become endemic, and it’s going to be part of our lives like the flu virus is,” Dr. Machado predicted.

Then there is the issue on vaccinating people against COVID-19, should those on rituximab still receive it? The answer is a yes, but, as with other vaccinations it’s all about the timing of when the vaccination is given.

Societies such as the British Society for Rheumatology have already begun to include guidance on this, recommending one of the available COVID-19 vaccines is given at least a month before the next or first dose of rituximab is due. As rituximab is given every few months, with doses sometimes spaced as much as 9 months or even a year apart, this should not be too much of a problem, but it is “better to have the vaccine first,” Dr. Machado said.
 

Has COVID-19 care improved in RMDs?

In separate research published in The Lancet Rheumatology, April Jorge, MD, of Massachusetts General Hospital and Harvard Medical School, both in Boston, and associates found that the risks of severe COVID-19 outcomes have improved over time, although they still “remain substantial.”

Dr. Jorge and colleagues looked at temporal trends in COVID-19 outcomes in patients with RMDs over the course of the first 6 months of the pandemic in 2020, using data from a large, multicenter, electronic health record network (TriNetX).

They formed two patient cohorts – a late (diagnosed from April 20 to July 20) and an early (diagnosed from January 20 to April 20) cohort – to see if outcomes had improved and discovered lower relative risks among patients in the late cohort for hospitalization (0.67), admission to the ICU (0.56), mechanical ventilation (0.39), acute kidney injury (0.66), renal replacement (0.53), and death (0.39).

“These results are encouraging,” but it’s difficult to match these different populations of patients, Dr. Machado said. “There are always factors that you cannot match for” and were not included in the U.S. analysis.

While there are important caveats in how the analysis was performed and thus in interpreting these data, they do “suggest that one of the reasons why outcomes have improved is because we have become better at treating these patients,” Dr. Machado added.

“Our treatment has improved, and our capacity to treat the complications has improved. We understand better how the disease behaves – we know that they can have thromboembolic complications that we can manage, and we are now able to manage ventilation issues better.”

Moreover, Dr. Machado said that, not only were clinicians more aware of what they should or should not do, there were treatments that were being used routinely or in some cases based on recent clinical trial results. “I think we are indeed treating these patients better.”

The COVID-19 GRA physician registry is financially supported by the American College of Rheumatology and EULAR. Dr. Machado had no relevant conflicts of interest.

The gout drug colchicine appears to lower the severity of COVID-19, a small new Brazilian study finds, adding to evidence that the familiar medication holds promise as a treatment for hospitalized patients.

Patients who received colchicine in this randomized, double-blinded, placebo-controlled clinical trial presented better evolution in terms of the need for supplemental oxygen and the length of hospitalisation. ... Colchicine was safe and well tolerated,” the study authors wrote in RMD Open. However, deaths were rare in the trial, they added, and it is impossible to “evaluate the capacity of colchicine to avoid admission to ICU and reduce mortality.”

The oral anti-inflammatory colchicine, widely used as treatment in rheumatic disease, was first approved in the United States 60 years ago. Researchers began to explore its potential as a COVID-19 treatment in the early months of the pandemic.

On Jan. 25, an international team of researchers reported in a press release – but not yet a published paper – that the drug seemed to reduce hospitalizations, mechanical ventilation, and deaths in the ColCORONA trial. Earlier, a much-smaller, randomized, open-label, Greek trial linked the drug to reduced time to clinical deterioration and hospital stay.

The Brazilian authors of the new study, led by Maria Isabel Lopes of the University of São Paulo’s Ribeirão Preto Medical School, randomly assigned 75 hospitalized patients with moderate to severe COVID-19 to colchicine or placebo. A total of 72 subjects completed the April-August 2020 trial: 36 received colchicine (typically 0.5 mg three times for 5 days, then 0.5 mg twice daily for 5 days; doses were adjusted in low-weight patients and those with chronic kidney disease). The other 36 received the placebo.

(In the United States, 0.6-mg tablets of generic colchicine cost as little as $1.90 each with free coupons, according to goodrx.com.)

The median age in the groups was similar (55 years); and the placebo group had more women (61% vs. 47% in the colchicine group, P = .34). All 72 patients received the same COVID-19 treatment at the time of the trial: azithromycin, hydroxychloroquine, and unfractionated heparin. Most patients, about two-thirds in both groups, also received methylprednisolone because they needed higher amounts of supplemental oxygen.

Patients in the colchicine group needed supplemental oxygen for less time: Their median time of need was 4.0 days (interquartile range [IQR], 2.0-6.0) vs. 6.5 days (IQR, 4.0-9.0) for the placebo group (P < .001). The median time for hospitalization was also lower at 7.0 days (IQR, 5.0–9.0) for the colchicine group vs. 9.0 (IQR, 7.0–12.0) for the placebo group (log rank test, 10.6; P = .001).

The researchers also reported the percentage of patients who needed supplemental oxygen at day 2 as 67% with colchicine vs. 86% with placebo, and at day 7 as 9% vs. 42% (log rank test, 10.6; P = .001). Two patients in the placebo group died, both from ventilator-associated pneumonia.

As for side effects, new or worsened diarrhea was reported more often in the colchicine group (17% vs. 6% with placebo), but the difference was not statistically significant (P = .26), and diarrhea was controlled via medication.

The researchers reported that limitations include the exclusion criteria and their inability to link colchicine to rates of ICU admissions and death.

The drug appears to help patients with COVID-19, the study authors wrote, by “inhibiting inflammasome, reducing neutrophil migration and activation, or preventing endothelial damage.”

A “well-conceived and well-designed” study

In an interview, NYU Langone Health rheumatologist Michael H. Pillinger, MD – an investigator with the ColCORONA trial – praised the Brazilian study. It “appears well-conceived and well-designed, and was enrolled at a rate that was greater than the sample size that was estimated to be needed based on power analysis,” he said.

The Brazilian study is small, he noted. (In contrast, the ColCORONA trial had 4,488 outpatient participants.) “This study differs from ColCORONA in several ways – the most important being that it is a study of inpatients with moderate to severe COVID (really mostly moderate),” he added. “ColCORONA is looking at a target audience that is much larger – outpatients with mild to moderate COVID with risk factors for hospitalization. Both questions are really important and certainly not mutually exclusive, since our care remains inadequate in both venues. This study also adds value in that several other studies have been conducted in hospital patients with enrollment criteria relatively similar to this one, and all showed benefit, but those were open-label or retrospective, and this is blinded and placebo-controlled.”
 

Using colchicine in patients with COVID-19

Should physicians turn to colchicine in patients with COVID-19? “I would rather that it still be used in the context of research until formal recommendations can be made by bodies like the NIH and CDC,” Dr. Pillinger said. “But certainly, there may be times when physicians feel compelled to treat patients off label.”

He cautioned, however, that colchicine should never be used with some other drugs. Its interaction with the antibiotic clarithromycin can be fatal, he noted. And, he said, the drug must be monitored in general since it can cause rare, severe problems.

“Overall, colchicine probably works on the overabundant inflammatory response to COVID, and it may be that it can be combined with other drugs that affect viral replication or promote immunity – e.g. vaccines,” Dr. Pillinger said. “So far, it seems as if there is no safety problem with combining colchicine with other approaches, but this has not been studied in a rigorous manner.”

Moving forward, he said, the drug’s very low price outside of the United States “could provide resource-poor countries with a way to help keep patients out of precious hospital beds – or help them go home sooner once admitted.” For now, however, “we need a large-scale inpatient study, and one is currently going on in Great Britain. We also need validation of the outpatient ColCORONA study, and studies to look at whether colchicine can work in conjunction with other strategies.”

The study was funded by grants from the São Paulo Research Foundation, Brazilian National Council for Scientific and Technological Development, and CAPES Foundation. No disclosures are reported. Dr. Pillinger reports serving as an investigator for the ColCORONA trial and receiving a unrelated investigator-initiated grant from Hikma, a colchicine manufacturer.

The gout drug colchicine appears to lower the severity of COVID-19, a small new Brazilian study finds, adding to evidence that the familiar medication holds promise as a treatment for hospitalized patients.

Patients who received colchicine in this randomized, double-blinded, placebo-controlled clinical trial presented better evolution in terms of the need for supplemental oxygen and the length of hospitalisation. ... Colchicine was safe and well tolerated,” the study authors wrote in RMD Open. However, deaths were rare in the trial, they added, and it is impossible to “evaluate the capacity of colchicine to avoid admission to ICU and reduce mortality.”

The oral anti-inflammatory colchicine, widely used as treatment in rheumatic disease, was first approved in the United States 60 years ago. Researchers began to explore its potential as a COVID-19 treatment in the early months of the pandemic.

On Jan. 25, an international team of researchers reported in a press release – but not yet a published paper – that the drug seemed to reduce hospitalizations, mechanical ventilation, and deaths in the ColCORONA trial. Earlier, a much-smaller, randomized, open-label, Greek trial linked the drug to reduced time to clinical deterioration and hospital stay.

The Brazilian authors of the new study, led by Maria Isabel Lopes of the University of São Paulo’s Ribeirão Preto Medical School, randomly assigned 75 hospitalized patients with moderate to severe COVID-19 to colchicine or placebo. A total of 72 subjects completed the April-August 2020 trial: 36 received colchicine (typically 0.5 mg three times for 5 days, then 0.5 mg twice daily for 5 days; doses were adjusted in low-weight patients and those with chronic kidney disease). The other 36 received the placebo.

(In the United States, 0.6-mg tablets of generic colchicine cost as little as $1.90 each with free coupons, according to goodrx.com.)

The median age in the groups was similar (55 years); and the placebo group had more women (61% vs. 47% in the colchicine group, P = .34). All 72 patients received the same COVID-19 treatment at the time of the trial: azithromycin, hydroxychloroquine, and unfractionated heparin. Most patients, about two-thirds in both groups, also received methylprednisolone because they needed higher amounts of supplemental oxygen.

Patients in the colchicine group needed supplemental oxygen for less time: Their median time of need was 4.0 days (interquartile range [IQR], 2.0-6.0) vs. 6.5 days (IQR, 4.0-9.0) for the placebo group (P < .001). The median time for hospitalization was also lower at 7.0 days (IQR, 5.0–9.0) for the colchicine group vs. 9.0 (IQR, 7.0–12.0) for the placebo group (log rank test, 10.6; P = .001).

The researchers also reported the percentage of patients who needed supplemental oxygen at day 2 as 67% with colchicine vs. 86% with placebo, and at day 7 as 9% vs. 42% (log rank test, 10.6; P = .001). Two patients in the placebo group died, both from ventilator-associated pneumonia.

As for side effects, new or worsened diarrhea was reported more often in the colchicine group (17% vs. 6% with placebo), but the difference was not statistically significant (P = .26), and diarrhea was controlled via medication.

The researchers reported that limitations include the exclusion criteria and their inability to link colchicine to rates of ICU admissions and death.

The drug appears to help patients with COVID-19, the study authors wrote, by “inhibiting inflammasome, reducing neutrophil migration and activation, or preventing endothelial damage.”

A “well-conceived and well-designed” study

In an interview, NYU Langone Health rheumatologist Michael H. Pillinger, MD – an investigator with the ColCORONA trial – praised the Brazilian study. It “appears well-conceived and well-designed, and was enrolled at a rate that was greater than the sample size that was estimated to be needed based on power analysis,” he said.

The Brazilian study is small, he noted. (In contrast, the ColCORONA trial had 4,488 outpatient participants.) “This study differs from ColCORONA in several ways – the most important being that it is a study of inpatients with moderate to severe COVID (really mostly moderate),” he added. “ColCORONA is looking at a target audience that is much larger – outpatients with mild to moderate COVID with risk factors for hospitalization. Both questions are really important and certainly not mutually exclusive, since our care remains inadequate in both venues. This study also adds value in that several other studies have been conducted in hospital patients with enrollment criteria relatively similar to this one, and all showed benefit, but those were open-label or retrospective, and this is blinded and placebo-controlled.”
 

Using colchicine in patients with COVID-19

Should physicians turn to colchicine in patients with COVID-19? “I would rather that it still be used in the context of research until formal recommendations can be made by bodies like the NIH and CDC,” Dr. Pillinger said. “But certainly, there may be times when physicians feel compelled to treat patients off label.”

He cautioned, however, that colchicine should never be used with some other drugs. Its interaction with the antibiotic clarithromycin can be fatal, he noted. And, he said, the drug must be monitored in general since it can cause rare, severe problems.

“Overall, colchicine probably works on the overabundant inflammatory response to COVID, and it may be that it can be combined with other drugs that affect viral replication or promote immunity – e.g. vaccines,” Dr. Pillinger said. “So far, it seems as if there is no safety problem with combining colchicine with other approaches, but this has not been studied in a rigorous manner.”

Moving forward, he said, the drug’s very low price outside of the United States “could provide resource-poor countries with a way to help keep patients out of precious hospital beds – or help them go home sooner once admitted.” For now, however, “we need a large-scale inpatient study, and one is currently going on in Great Britain. We also need validation of the outpatient ColCORONA study, and studies to look at whether colchicine can work in conjunction with other strategies.”

The study was funded by grants from the São Paulo Research Foundation, Brazilian National Council for Scientific and Technological Development, and CAPES Foundation. No disclosures are reported. Dr. Pillinger reports serving as an investigator for the ColCORONA trial and receiving a unrelated investigator-initiated grant from Hikma, a colchicine manufacturer.

The gout drug colchicine appears to lower the severity of COVID-19, a small new Brazilian study finds, adding to evidence that the familiar medication holds promise as a treatment for hospitalized patients.

Patients who received colchicine in this randomized, double-blinded, placebo-controlled clinical trial presented better evolution in terms of the need for supplemental oxygen and the length of hospitalisation. ... Colchicine was safe and well tolerated,” the study authors wrote in RMD Open. However, deaths were rare in the trial, they added, and it is impossible to “evaluate the capacity of colchicine to avoid admission to ICU and reduce mortality.”

The oral anti-inflammatory colchicine, widely used as treatment in rheumatic disease, was first approved in the United States 60 years ago. Researchers began to explore its potential as a COVID-19 treatment in the early months of the pandemic.

On Jan. 25, an international team of researchers reported in a press release – but not yet a published paper – that the drug seemed to reduce hospitalizations, mechanical ventilation, and deaths in the ColCORONA trial. Earlier, a much-smaller, randomized, open-label, Greek trial linked the drug to reduced time to clinical deterioration and hospital stay.

The Brazilian authors of the new study, led by Maria Isabel Lopes of the University of São Paulo’s Ribeirão Preto Medical School, randomly assigned 75 hospitalized patients with moderate to severe COVID-19 to colchicine or placebo. A total of 72 subjects completed the April-August 2020 trial: 36 received colchicine (typically 0.5 mg three times for 5 days, then 0.5 mg twice daily for 5 days; doses were adjusted in low-weight patients and those with chronic kidney disease). The other 36 received the placebo.

(In the United States, 0.6-mg tablets of generic colchicine cost as little as $1.90 each with free coupons, according to goodrx.com.)

The median age in the groups was similar (55 years); and the placebo group had more women (61% vs. 47% in the colchicine group, P = .34). All 72 patients received the same COVID-19 treatment at the time of the trial: azithromycin, hydroxychloroquine, and unfractionated heparin. Most patients, about two-thirds in both groups, also received methylprednisolone because they needed higher amounts of supplemental oxygen.

Patients in the colchicine group needed supplemental oxygen for less time: Their median time of need was 4.0 days (interquartile range [IQR], 2.0-6.0) vs. 6.5 days (IQR, 4.0-9.0) for the placebo group (P < .001). The median time for hospitalization was also lower at 7.0 days (IQR, 5.0–9.0) for the colchicine group vs. 9.0 (IQR, 7.0–12.0) for the placebo group (log rank test, 10.6; P = .001).

The researchers also reported the percentage of patients who needed supplemental oxygen at day 2 as 67% with colchicine vs. 86% with placebo, and at day 7 as 9% vs. 42% (log rank test, 10.6; P = .001). Two patients in the placebo group died, both from ventilator-associated pneumonia.

As for side effects, new or worsened diarrhea was reported more often in the colchicine group (17% vs. 6% with placebo), but the difference was not statistically significant (P = .26), and diarrhea was controlled via medication.

The researchers reported that limitations include the exclusion criteria and their inability to link colchicine to rates of ICU admissions and death.

The drug appears to help patients with COVID-19, the study authors wrote, by “inhibiting inflammasome, reducing neutrophil migration and activation, or preventing endothelial damage.”

A “well-conceived and well-designed” study

In an interview, NYU Langone Health rheumatologist Michael H. Pillinger, MD – an investigator with the ColCORONA trial – praised the Brazilian study. It “appears well-conceived and well-designed, and was enrolled at a rate that was greater than the sample size that was estimated to be needed based on power analysis,” he said.

The Brazilian study is small, he noted. (In contrast, the ColCORONA trial had 4,488 outpatient participants.) “This study differs from ColCORONA in several ways – the most important being that it is a study of inpatients with moderate to severe COVID (really mostly moderate),” he added. “ColCORONA is looking at a target audience that is much larger – outpatients with mild to moderate COVID with risk factors for hospitalization. Both questions are really important and certainly not mutually exclusive, since our care remains inadequate in both venues. This study also adds value in that several other studies have been conducted in hospital patients with enrollment criteria relatively similar to this one, and all showed benefit, but those were open-label or retrospective, and this is blinded and placebo-controlled.”
 

Using colchicine in patients with COVID-19

Should physicians turn to colchicine in patients with COVID-19? “I would rather that it still be used in the context of research until formal recommendations can be made by bodies like the NIH and CDC,” Dr. Pillinger said. “But certainly, there may be times when physicians feel compelled to treat patients off label.”

He cautioned, however, that colchicine should never be used with some other drugs. Its interaction with the antibiotic clarithromycin can be fatal, he noted. And, he said, the drug must be monitored in general since it can cause rare, severe problems.

“Overall, colchicine probably works on the overabundant inflammatory response to COVID, and it may be that it can be combined with other drugs that affect viral replication or promote immunity – e.g. vaccines,” Dr. Pillinger said. “So far, it seems as if there is no safety problem with combining colchicine with other approaches, but this has not been studied in a rigorous manner.”

Moving forward, he said, the drug’s very low price outside of the United States “could provide resource-poor countries with a way to help keep patients out of precious hospital beds – or help them go home sooner once admitted.” For now, however, “we need a large-scale inpatient study, and one is currently going on in Great Britain. We also need validation of the outpatient ColCORONA study, and studies to look at whether colchicine can work in conjunction with other strategies.”

The study was funded by grants from the São Paulo Research Foundation, Brazilian National Council for Scientific and Technological Development, and CAPES Foundation. No disclosures are reported. Dr. Pillinger reports serving as an investigator for the ColCORONA trial and receiving a unrelated investigator-initiated grant from Hikma, a colchicine manufacturer.

The United States has now reported more than 450,000 COVID-19 deaths during the pandemic, adding 3,912 more on Wednesday, according to data from Johns Hopkins University.

Daily COVID-19 deaths still remain high in the United States, though they’ve decreased slightly from the peak of 4,466 deaths on Jan. 12.

The United States also reported more than 121,000 new COVID-19 cases on Wednesday, which is down from a peak of more than 300,000 new cases on Tuesday. In total, more than 26.5 million people in the United States have been diagnosed with COVID-19, making up a quarter of the 104.5 million cases reported worldwide.

The 7-day average for COVID-19 hospitalizations and deaths continues to decline, according to the COVID Tracking Project. The 7-day average for hospitalizations is around 96,500, and the 7-day average for deaths is about 3,000. With the exception of Vermont, all states and territories have reported declines or no changes in their hospitalizations and deaths.

“We have seen the 7-day average for new deaths decrease for over a week. At the same time, states are reporting an average of 3,000 people dying per day,” the COVID Tracking Project wrote in a post on Twitter. “The data is hopeful and devastating.”

More than 2.2 million COVID-19 deaths have been reported worldwide. The United States continues to report the most deaths, followed by Brazil with 227,500, Mexico with 161,200, and India with 154,700 deaths.

The U.S. COVID-19 death toll could reach 496,000-534,000 by the end of February, according to a new forecast by the CDC, which includes models from 36 national groups. Deaths will likely decrease during the next 4 weeks, with about 11,300-22,600 deaths possibly reported during the last week of February.

The 534,000 total would equal about 1 death for every minute of the pandemic, according to CNN, given that the first U.S. death was reported on Feb. 29 last year.

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

The United States has now reported more than 450,000 COVID-19 deaths during the pandemic, adding 3,912 more on Wednesday, according to data from Johns Hopkins University.

Daily COVID-19 deaths still remain high in the United States, though they’ve decreased slightly from the peak of 4,466 deaths on Jan. 12.

The United States also reported more than 121,000 new COVID-19 cases on Wednesday, which is down from a peak of more than 300,000 new cases on Tuesday. In total, more than 26.5 million people in the United States have been diagnosed with COVID-19, making up a quarter of the 104.5 million cases reported worldwide.

The 7-day average for COVID-19 hospitalizations and deaths continues to decline, according to the COVID Tracking Project. The 7-day average for hospitalizations is around 96,500, and the 7-day average for deaths is about 3,000. With the exception of Vermont, all states and territories have reported declines or no changes in their hospitalizations and deaths.

“We have seen the 7-day average for new deaths decrease for over a week. At the same time, states are reporting an average of 3,000 people dying per day,” the COVID Tracking Project wrote in a post on Twitter. “The data is hopeful and devastating.”

More than 2.2 million COVID-19 deaths have been reported worldwide. The United States continues to report the most deaths, followed by Brazil with 227,500, Mexico with 161,200, and India with 154,700 deaths.

The U.S. COVID-19 death toll could reach 496,000-534,000 by the end of February, according to a new forecast by the CDC, which includes models from 36 national groups. Deaths will likely decrease during the next 4 weeks, with about 11,300-22,600 deaths possibly reported during the last week of February.

The 534,000 total would equal about 1 death for every minute of the pandemic, according to CNN, given that the first U.S. death was reported on Feb. 29 last year.

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

The United States has now reported more than 450,000 COVID-19 deaths during the pandemic, adding 3,912 more on Wednesday, according to data from Johns Hopkins University.

Daily COVID-19 deaths still remain high in the United States, though they’ve decreased slightly from the peak of 4,466 deaths on Jan. 12.

The United States also reported more than 121,000 new COVID-19 cases on Wednesday, which is down from a peak of more than 300,000 new cases on Tuesday. In total, more than 26.5 million people in the United States have been diagnosed with COVID-19, making up a quarter of the 104.5 million cases reported worldwide.

The 7-day average for COVID-19 hospitalizations and deaths continues to decline, according to the COVID Tracking Project. The 7-day average for hospitalizations is around 96,500, and the 7-day average for deaths is about 3,000. With the exception of Vermont, all states and territories have reported declines or no changes in their hospitalizations and deaths.

“We have seen the 7-day average for new deaths decrease for over a week. At the same time, states are reporting an average of 3,000 people dying per day,” the COVID Tracking Project wrote in a post on Twitter. “The data is hopeful and devastating.”

More than 2.2 million COVID-19 deaths have been reported worldwide. The United States continues to report the most deaths, followed by Brazil with 227,500, Mexico with 161,200, and India with 154,700 deaths.

The U.S. COVID-19 death toll could reach 496,000-534,000 by the end of February, according to a new forecast by the CDC, which includes models from 36 national groups. Deaths will likely decrease during the next 4 weeks, with about 11,300-22,600 deaths possibly reported during the last week of February.

The 534,000 total would equal about 1 death for every minute of the pandemic, according to CNN, given that the first U.S. death was reported on Feb. 29 last year.

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

Metformin extended gestation by nearly a week in women with preterm preeclampsia and was also linked to a shorter neonatal hospital stay, according to findings from a study presented Jan. 28 at the virtual Society for Maternal-Fetal Medicine 2021 Annual Pregnancy Meeting.

The causes of preeclampsia have continued to elude researchers, but most agree the placenta plays a key role, explained Cathy Cluver, PhD, director of the preeclampsia research unit and an associate professor at Stellenbosch University, Cape Town. Past trials have tested sildenafil, antithrombin, pravastatin, and esomeprazole, but the drugs either did not show promise, had unacceptable side effects, or need further study.

“This trial provides proof of concept that preterm preeclampsia can be treated and that we can slow the progression of preterm preeclampsia,” Dr. Cluver said.

In this trial, the researchers enrolled 180 women with preterm preeclampsia between 26 and 31 weeks of gestation. All the women were taking hypertensives. They were randomly assigned to receive 3 g oral metformin XR or placebo daily. The intention-to-treat analysis included 87 women who received metformin and 84 who received placebo, with baseline characteristics similar in both groups.

Women in the metformin group gave birth a median 16.2 days after randomization, which was 6.7 days longer than the 9.5 days postrandomization delivery of women in the placebo group. The differences, however, narrowly missed statistical significance (P =.056).

But when the researchers took compliance and dose into account, the effect of the metformin increased, showing a dose-dependent effect, and did reach statistical significance. Among the 147 women who continued treatment until delivery, those in the metformin group delivered a median 8.4 days later than those in the placebo group (16.2 vs. 7.4 days; P =.026). Further, when the analysis was further restricted to just the 100 women who continued taking the full dose until delivery, the difference was even greater (16.2 vs. 4.8 days; P =.008). In accordance with the safety profile of metformin, women taking the drug had more diarrhea and a trend toward more nausea than those taking the placebo.

There were no differences between the groups in composite maternal or neonatal outcomes, but the infants were an average 136 g (4.8 ounces) heavier in the metformin group, albeit the difference did not reach statistical significance. The 6-day–shorter neonatal stay at the study site facility for infants of the metformin group also did not reach statistical significance, but there was a significant difference between the groups on overall stay, including transfers to other facilities. Infants in the metformin group averaged 26 days vs. 34 days for infants in the placebo group (P =.007).

“We have shown that metformin XR may be a treatment for preterm preeclampsia. We now plan to do a larger study to hopefully confirm these findings, which will be powered to both prolongation of pregnancy and neonatal outcomes,” Dr. Cluver told this news organization. “We have also shown that one can prolong pregnancy in preterm preeclampsia, and we hope that this will encourage others in our field to continue researching therapeutics for preterm preeclampsia.”

In response to questions from attendees, Dr. Cluver reported that her team did not collect histological data from placentas in this study, and lack of funding is limiting their ability to evaluate longer-term outcomes.

The findings of prolonged gestation were certainly exciting, but they warrant caution before any changes in clinical practice, Michelle Y. Owens, MD, professor and chief of maternal-fetal medicine at the University of Mississippi Medical Center, Jackson, said in an interview.

“While the findings of this study are promising, the sample size was small, the dosing exceeds what we typically use in the U.S., and this was undertaken in Cape Town, South Africa, all of which may render this study less generalizable to our population and others across the globe,” said Dr. Owens, who moderated the oral abstract session.

She also pointed out a possible conflicting effect on birth weight brought on by using metformin to extend gestation.

“If larger studies are undertaken, I believe it is quite possible that, with extended gestation, there will be bigger babies,” she said. “However, metformin also helps control blood glucose and in so doing, may contribute to lower birth weights over time, compared with women not exposed to the drug.”

Dr. Cluver and Dr. Owens have disclosed no relevant financial relationships.

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

*This story was updated on 2/9/2021. 

Metformin extended gestation by nearly a week in women with preterm preeclampsia and was also linked to a shorter neonatal hospital stay, according to findings from a study presented Jan. 28 at the virtual Society for Maternal-Fetal Medicine 2021 Annual Pregnancy Meeting.

The causes of preeclampsia have continued to elude researchers, but most agree the placenta plays a key role, explained Cathy Cluver, PhD, director of the preeclampsia research unit and an associate professor at Stellenbosch University, Cape Town. Past trials have tested sildenafil, antithrombin, pravastatin, and esomeprazole, but the drugs either did not show promise, had unacceptable side effects, or need further study.

“This trial provides proof of concept that preterm preeclampsia can be treated and that we can slow the progression of preterm preeclampsia,” Dr. Cluver said.

In this trial, the researchers enrolled 180 women with preterm preeclampsia between 26 and 31 weeks of gestation. All the women were taking hypertensives. They were randomly assigned to receive 3 g oral metformin XR or placebo daily. The intention-to-treat analysis included 87 women who received metformin and 84 who received placebo, with baseline characteristics similar in both groups.

Women in the metformin group gave birth a median 16.2 days after randomization, which was 6.7 days longer than the 9.5 days postrandomization delivery of women in the placebo group. The differences, however, narrowly missed statistical significance (P =.056).

But when the researchers took compliance and dose into account, the effect of the metformin increased, showing a dose-dependent effect, and did reach statistical significance. Among the 147 women who continued treatment until delivery, those in the metformin group delivered a median 8.4 days later than those in the placebo group (16.2 vs. 7.4 days; P =.026). Further, when the analysis was further restricted to just the 100 women who continued taking the full dose until delivery, the difference was even greater (16.2 vs. 4.8 days; P =.008). In accordance with the safety profile of metformin, women taking the drug had more diarrhea and a trend toward more nausea than those taking the placebo.

There were no differences between the groups in composite maternal or neonatal outcomes, but the infants were an average 136 g (4.8 ounces) heavier in the metformin group, albeit the difference did not reach statistical significance. The 6-day–shorter neonatal stay at the study site facility for infants of the metformin group also did not reach statistical significance, but there was a significant difference between the groups on overall stay, including transfers to other facilities. Infants in the metformin group averaged 26 days vs. 34 days for infants in the placebo group (P =.007).

“We have shown that metformin XR may be a treatment for preterm preeclampsia. We now plan to do a larger study to hopefully confirm these findings, which will be powered to both prolongation of pregnancy and neonatal outcomes,” Dr. Cluver told this news organization. “We have also shown that one can prolong pregnancy in preterm preeclampsia, and we hope that this will encourage others in our field to continue researching therapeutics for preterm preeclampsia.”

In response to questions from attendees, Dr. Cluver reported that her team did not collect histological data from placentas in this study, and lack of funding is limiting their ability to evaluate longer-term outcomes.

The findings of prolonged gestation were certainly exciting, but they warrant caution before any changes in clinical practice, Michelle Y. Owens, MD, professor and chief of maternal-fetal medicine at the University of Mississippi Medical Center, Jackson, said in an interview.

“While the findings of this study are promising, the sample size was small, the dosing exceeds what we typically use in the U.S., and this was undertaken in Cape Town, South Africa, all of which may render this study less generalizable to our population and others across the globe,” said Dr. Owens, who moderated the oral abstract session.

She also pointed out a possible conflicting effect on birth weight brought on by using metformin to extend gestation.

“If larger studies are undertaken, I believe it is quite possible that, with extended gestation, there will be bigger babies,” she said. “However, metformin also helps control blood glucose and in so doing, may contribute to lower birth weights over time, compared with women not exposed to the drug.”

Dr. Cluver and Dr. Owens have disclosed no relevant financial relationships.

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

*This story was updated on 2/9/2021. 

Metformin extended gestation by nearly a week in women with preterm preeclampsia and was also linked to a shorter neonatal hospital stay, according to findings from a study presented Jan. 28 at the virtual Society for Maternal-Fetal Medicine 2021 Annual Pregnancy Meeting.

The causes of preeclampsia have continued to elude researchers, but most agree the placenta plays a key role, explained Cathy Cluver, PhD, director of the preeclampsia research unit and an associate professor at Stellenbosch University, Cape Town. Past trials have tested sildenafil, antithrombin, pravastatin, and esomeprazole, but the drugs either did not show promise, had unacceptable side effects, or need further study.

“This trial provides proof of concept that preterm preeclampsia can be treated and that we can slow the progression of preterm preeclampsia,” Dr. Cluver said.

In this trial, the researchers enrolled 180 women with preterm preeclampsia between 26 and 31 weeks of gestation. All the women were taking hypertensives. They were randomly assigned to receive 3 g oral metformin XR or placebo daily. The intention-to-treat analysis included 87 women who received metformin and 84 who received placebo, with baseline characteristics similar in both groups.

Women in the metformin group gave birth a median 16.2 days after randomization, which was 6.7 days longer than the 9.5 days postrandomization delivery of women in the placebo group. The differences, however, narrowly missed statistical significance (P =.056).

But when the researchers took compliance and dose into account, the effect of the metformin increased, showing a dose-dependent effect, and did reach statistical significance. Among the 147 women who continued treatment until delivery, those in the metformin group delivered a median 8.4 days later than those in the placebo group (16.2 vs. 7.4 days; P =.026). Further, when the analysis was further restricted to just the 100 women who continued taking the full dose until delivery, the difference was even greater (16.2 vs. 4.8 days; P =.008). In accordance with the safety profile of metformin, women taking the drug had more diarrhea and a trend toward more nausea than those taking the placebo.

There were no differences between the groups in composite maternal or neonatal outcomes, but the infants were an average 136 g (4.8 ounces) heavier in the metformin group, albeit the difference did not reach statistical significance. The 6-day–shorter neonatal stay at the study site facility for infants of the metformin group also did not reach statistical significance, but there was a significant difference between the groups on overall stay, including transfers to other facilities. Infants in the metformin group averaged 26 days vs. 34 days for infants in the placebo group (P =.007).

“We have shown that metformin XR may be a treatment for preterm preeclampsia. We now plan to do a larger study to hopefully confirm these findings, which will be powered to both prolongation of pregnancy and neonatal outcomes,” Dr. Cluver told this news organization. “We have also shown that one can prolong pregnancy in preterm preeclampsia, and we hope that this will encourage others in our field to continue researching therapeutics for preterm preeclampsia.”

In response to questions from attendees, Dr. Cluver reported that her team did not collect histological data from placentas in this study, and lack of funding is limiting their ability to evaluate longer-term outcomes.

The findings of prolonged gestation were certainly exciting, but they warrant caution before any changes in clinical practice, Michelle Y. Owens, MD, professor and chief of maternal-fetal medicine at the University of Mississippi Medical Center, Jackson, said in an interview.

“While the findings of this study are promising, the sample size was small, the dosing exceeds what we typically use in the U.S., and this was undertaken in Cape Town, South Africa, all of which may render this study less generalizable to our population and others across the globe,” said Dr. Owens, who moderated the oral abstract session.

She also pointed out a possible conflicting effect on birth weight brought on by using metformin to extend gestation.

“If larger studies are undertaken, I believe it is quite possible that, with extended gestation, there will be bigger babies,” she said. “However, metformin also helps control blood glucose and in so doing, may contribute to lower birth weights over time, compared with women not exposed to the drug.”

Dr. Cluver and Dr. Owens have disclosed no relevant financial relationships.

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

*This story was updated on 2/9/2021. 

People who report regularly eating oily fish had a significantly reduced risk for developing type 2 diabetes in a prospective, observational study of nearly 400,000 UK residents.

Dmitriy Danilchenko/Shutterstock

The results also show a significant, but weaker, positive link between regular use of fish oil supplements and a drop in the incidence of type 2 diabetes, Qibin Qi, PhD, and colleagues wrote in a report published in Diabetes Care. Their analysis failed to show a significant link between consumption of non-oily fish and type 2 diabetes onset.

The study is notable for being “the largest so far” to examine the link between fish consumption and type 2 diabetes incidence, and the first to establish a clear, significant association between regularly eating oily fish and a drop in the incidence of diabetes, said Dr. Qi, an epidemiologist at Albert Einstein College of Medicine in New York.

“At present, it is prudent to recommend fresh oily fish as a part of a healthy dietary pattern instead of fish oil supplements for diabetes prevention,” said Dr. Qi and coauthors.

The study included just over 392,000 adults without type 2 diabetes or cardiovascular disease at baseline enrolled in the UK Biobank. Median follow-up was just over 10 years, during which 7,262 participants developed diabetes.

Participants who ate either one, or two or more, servings of oily fish weekly each had a significant 22% lower rate of incident type 2 diabetes than that of those who ate no oily fish, after adjustment for multiple confounders. Those who reported regularly taking a fish oil supplement had a significant 9% lower incidence of type 2 diabetes than that of those who didn’t.
 

Evidence growing to add oily fish to diet to prevent type 2 diabetes

“Many current dietary guidelines recommend consumption of two servings of fish, preferably oily, per week, primarily based on cardiovascular benefits,” Dr. Qi said in an interview.

“No prior statements recommended oily fish for prevention of type 2 diabetes,” he explained, adding: “Our findings support future recommendations, but the evidence is not strong enough to make a [formal] recommendation now. We need evidence from clinical trials.”

Jason Wu, PhD, an epidemiologist at the University of New South Wales in Sydney, Australia, who specializes in this field but was not involved with the current study, said it “is a very well-conducted study, and certainly generates important new evidence supporting the potential benefits of regular consumption of oily fish.”

But he agrees that the evidence remains too preliminary for any official recommendations on eating oily fish for preventing the development of type 2 diabetes, including targeting advice to high-risk subgroups such as those with prediabetes or people who are obese.

Before any groups make recommendations, “we need to thoroughly review all the literature in this space to appraise the overall body of evidence,” Dr. Wu noted in an interview.
 

Oily fish: Solid evidence for prevention of CVD events

In contrast, the case for including oily fish in the diet to prevent CVD events seems settled. In 2018, a panel assembled by the American Heart Association to address the issue released a statement that concluded: “Current scientific evidence strongly supports the recommendation that seafood be an integral component of a heart-healthy dietary pattern.” It added that “a large body of evidence supports the recommendation to consume nonfried seafood, especially species higher in long-chain n-3 fatty acids, one to two times per week for cardiovascular benefits, including reduced risk of cardiac death, coronary heart disease, and ischemic stroke.”

The statement highlighted that “cold-water oily fish such as salmon, anchovies, herring, mackerel (Atlantic and Pacific), tuna (bluefin and albacore), and sardines have the highest levels” of long-chain n-3 fatty acids, notably eicosapentaenoic acid and docosahexaenoic acid, also collectively known as omega-3 fatty acids.

These fish types were among the oily fishes tallied in the UK Biobank data used by Dr. Qi and colleagues.

The case for fish oil supplements for preventing CVD events is much rockier, as summarized in a 2019 editorial, with some studies reporting no discernible effect while others indicate efficacy.

A second commentary from December 2020 highlighted how results from the REDUCE-IT trial showed clear benefit for preventing CVD using a highly purified form of fish oil, icosapent ethyl (Vascepa, Amarin). However, findings from two other recent reports, the STRENGTH and OMENI studies, failed to show CVD benefits from more conventional fish oil formulations.
 

Composite CVD and diabetes prevention effects?

The new findings by Dr. Qi and colleagues “highlight the need to specifically test the effect of fish oil supplements on glucose metabolism in people who cannot or choose not to regularly eat oily fish,” said Dr. Wu, a researcher at the George Institute for Global Health in Newtown, Australia.

“If eventually there is really strong evidence that fish, fish oil, or both have independent effects on both CVD and type 2 diabetes” it would be reasonable to integrate both outcomes into a single, composite, efficacy endpoint for the purpose of future studies, he added.

Dr. Qi agreed on both points. “A randomized, controlled trial of fish oil on type 2 diabetes as a primary outcome is needed. Most existing data are based on secondary analyses in the randomized trials for CVD,” he explained.

But, he added, “our results suggest a potential beneficial effect from fish oil supplements,” which implies that these may be “better than nothing” for people who can’t add oily fish to their regular diet.

The means by which fish and fish oil might slow or stop progression to type 2 diabetes remains uncertain.

The mechanisms for preventing both diabetes and CVD events may overlap, Dr. Qi noted, such as anti-inflammatory effects and improved insulin sensitivity, both of which have been observed in animal studies.

Evidence is “still lacking from human studies,” he explained, but if such mechanisms were at play, Dr. Wu said that would “add biologic plausibility” to a possible causal link between oily fish consumption and diabetes prevention. 

“But we can’t assume that omega-3 fatty acids alone will have the same effect as oily fish, which obviously contains many other components.”

The study received no commercial funding. Dr. Qi and Dr. Wu have reported no relevant financial relationships.

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

People who report regularly eating oily fish had a significantly reduced risk for developing type 2 diabetes in a prospective, observational study of nearly 400,000 UK residents.

Dmitriy Danilchenko/Shutterstock

The results also show a significant, but weaker, positive link between regular use of fish oil supplements and a drop in the incidence of type 2 diabetes, Qibin Qi, PhD, and colleagues wrote in a report published in Diabetes Care. Their analysis failed to show a significant link between consumption of non-oily fish and type 2 diabetes onset.

The study is notable for being “the largest so far” to examine the link between fish consumption and type 2 diabetes incidence, and the first to establish a clear, significant association between regularly eating oily fish and a drop in the incidence of diabetes, said Dr. Qi, an epidemiologist at Albert Einstein College of Medicine in New York.

“At present, it is prudent to recommend fresh oily fish as a part of a healthy dietary pattern instead of fish oil supplements for diabetes prevention,” said Dr. Qi and coauthors.

The study included just over 392,000 adults without type 2 diabetes or cardiovascular disease at baseline enrolled in the UK Biobank. Median follow-up was just over 10 years, during which 7,262 participants developed diabetes.

Participants who ate either one, or two or more, servings of oily fish weekly each had a significant 22% lower rate of incident type 2 diabetes than that of those who ate no oily fish, after adjustment for multiple confounders. Those who reported regularly taking a fish oil supplement had a significant 9% lower incidence of type 2 diabetes than that of those who didn’t.
 

Evidence growing to add oily fish to diet to prevent type 2 diabetes

“Many current dietary guidelines recommend consumption of two servings of fish, preferably oily, per week, primarily based on cardiovascular benefits,” Dr. Qi said in an interview.

“No prior statements recommended oily fish for prevention of type 2 diabetes,” he explained, adding: “Our findings support future recommendations, but the evidence is not strong enough to make a [formal] recommendation now. We need evidence from clinical trials.”

Jason Wu, PhD, an epidemiologist at the University of New South Wales in Sydney, Australia, who specializes in this field but was not involved with the current study, said it “is a very well-conducted study, and certainly generates important new evidence supporting the potential benefits of regular consumption of oily fish.”

But he agrees that the evidence remains too preliminary for any official recommendations on eating oily fish for preventing the development of type 2 diabetes, including targeting advice to high-risk subgroups such as those with prediabetes or people who are obese.

Before any groups make recommendations, “we need to thoroughly review all the literature in this space to appraise the overall body of evidence,” Dr. Wu noted in an interview.
 

Oily fish: Solid evidence for prevention of CVD events

In contrast, the case for including oily fish in the diet to prevent CVD events seems settled. In 2018, a panel assembled by the American Heart Association to address the issue released a statement that concluded: “Current scientific evidence strongly supports the recommendation that seafood be an integral component of a heart-healthy dietary pattern.” It added that “a large body of evidence supports the recommendation to consume nonfried seafood, especially species higher in long-chain n-3 fatty acids, one to two times per week for cardiovascular benefits, including reduced risk of cardiac death, coronary heart disease, and ischemic stroke.”

The statement highlighted that “cold-water oily fish such as salmon, anchovies, herring, mackerel (Atlantic and Pacific), tuna (bluefin and albacore), and sardines have the highest levels” of long-chain n-3 fatty acids, notably eicosapentaenoic acid and docosahexaenoic acid, also collectively known as omega-3 fatty acids.

These fish types were among the oily fishes tallied in the UK Biobank data used by Dr. Qi and colleagues.

The case for fish oil supplements for preventing CVD events is much rockier, as summarized in a 2019 editorial, with some studies reporting no discernible effect while others indicate efficacy.

A second commentary from December 2020 highlighted how results from the REDUCE-IT trial showed clear benefit for preventing CVD using a highly purified form of fish oil, icosapent ethyl (Vascepa, Amarin). However, findings from two other recent reports, the STRENGTH and OMENI studies, failed to show CVD benefits from more conventional fish oil formulations.
 

Composite CVD and diabetes prevention effects?

The new findings by Dr. Qi and colleagues “highlight the need to specifically test the effect of fish oil supplements on glucose metabolism in people who cannot or choose not to regularly eat oily fish,” said Dr. Wu, a researcher at the George Institute for Global Health in Newtown, Australia.

“If eventually there is really strong evidence that fish, fish oil, or both have independent effects on both CVD and type 2 diabetes” it would be reasonable to integrate both outcomes into a single, composite, efficacy endpoint for the purpose of future studies, he added.

Dr. Qi agreed on both points. “A randomized, controlled trial of fish oil on type 2 diabetes as a primary outcome is needed. Most existing data are based on secondary analyses in the randomized trials for CVD,” he explained.

But, he added, “our results suggest a potential beneficial effect from fish oil supplements,” which implies that these may be “better than nothing” for people who can’t add oily fish to their regular diet.

The means by which fish and fish oil might slow or stop progression to type 2 diabetes remains uncertain.

The mechanisms for preventing both diabetes and CVD events may overlap, Dr. Qi noted, such as anti-inflammatory effects and improved insulin sensitivity, both of which have been observed in animal studies.

Evidence is “still lacking from human studies,” he explained, but if such mechanisms were at play, Dr. Wu said that would “add biologic plausibility” to a possible causal link between oily fish consumption and diabetes prevention. 

“But we can’t assume that omega-3 fatty acids alone will have the same effect as oily fish, which obviously contains many other components.”

The study received no commercial funding. Dr. Qi and Dr. Wu have reported no relevant financial relationships.

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

People who report regularly eating oily fish had a significantly reduced risk for developing type 2 diabetes in a prospective, observational study of nearly 400,000 UK residents.

Dmitriy Danilchenko/Shutterstock

The results also show a significant, but weaker, positive link between regular use of fish oil supplements and a drop in the incidence of type 2 diabetes, Qibin Qi, PhD, and colleagues wrote in a report published in Diabetes Care. Their analysis failed to show a significant link between consumption of non-oily fish and type 2 diabetes onset.

The study is notable for being “the largest so far” to examine the link between fish consumption and type 2 diabetes incidence, and the first to establish a clear, significant association between regularly eating oily fish and a drop in the incidence of diabetes, said Dr. Qi, an epidemiologist at Albert Einstein College of Medicine in New York.

“At present, it is prudent to recommend fresh oily fish as a part of a healthy dietary pattern instead of fish oil supplements for diabetes prevention,” said Dr. Qi and coauthors.

The study included just over 392,000 adults without type 2 diabetes or cardiovascular disease at baseline enrolled in the UK Biobank. Median follow-up was just over 10 years, during which 7,262 participants developed diabetes.

Participants who ate either one, or two or more, servings of oily fish weekly each had a significant 22% lower rate of incident type 2 diabetes than that of those who ate no oily fish, after adjustment for multiple confounders. Those who reported regularly taking a fish oil supplement had a significant 9% lower incidence of type 2 diabetes than that of those who didn’t.
 

Evidence growing to add oily fish to diet to prevent type 2 diabetes

“Many current dietary guidelines recommend consumption of two servings of fish, preferably oily, per week, primarily based on cardiovascular benefits,” Dr. Qi said in an interview.

“No prior statements recommended oily fish for prevention of type 2 diabetes,” he explained, adding: “Our findings support future recommendations, but the evidence is not strong enough to make a [formal] recommendation now. We need evidence from clinical trials.”

Jason Wu, PhD, an epidemiologist at the University of New South Wales in Sydney, Australia, who specializes in this field but was not involved with the current study, said it “is a very well-conducted study, and certainly generates important new evidence supporting the potential benefits of regular consumption of oily fish.”

But he agrees that the evidence remains too preliminary for any official recommendations on eating oily fish for preventing the development of type 2 diabetes, including targeting advice to high-risk subgroups such as those with prediabetes or people who are obese.

Before any groups make recommendations, “we need to thoroughly review all the literature in this space to appraise the overall body of evidence,” Dr. Wu noted in an interview.
 

Oily fish: Solid evidence for prevention of CVD events

In contrast, the case for including oily fish in the diet to prevent CVD events seems settled. In 2018, a panel assembled by the American Heart Association to address the issue released a statement that concluded: “Current scientific evidence strongly supports the recommendation that seafood be an integral component of a heart-healthy dietary pattern.” It added that “a large body of evidence supports the recommendation to consume nonfried seafood, especially species higher in long-chain n-3 fatty acids, one to two times per week for cardiovascular benefits, including reduced risk of cardiac death, coronary heart disease, and ischemic stroke.”

The statement highlighted that “cold-water oily fish such as salmon, anchovies, herring, mackerel (Atlantic and Pacific), tuna (bluefin and albacore), and sardines have the highest levels” of long-chain n-3 fatty acids, notably eicosapentaenoic acid and docosahexaenoic acid, also collectively known as omega-3 fatty acids.

These fish types were among the oily fishes tallied in the UK Biobank data used by Dr. Qi and colleagues.

The case for fish oil supplements for preventing CVD events is much rockier, as summarized in a 2019 editorial, with some studies reporting no discernible effect while others indicate efficacy.

A second commentary from December 2020 highlighted how results from the REDUCE-IT trial showed clear benefit for preventing CVD using a highly purified form of fish oil, icosapent ethyl (Vascepa, Amarin). However, findings from two other recent reports, the STRENGTH and OMENI studies, failed to show CVD benefits from more conventional fish oil formulations.
 

Composite CVD and diabetes prevention effects?

The new findings by Dr. Qi and colleagues “highlight the need to specifically test the effect of fish oil supplements on glucose metabolism in people who cannot or choose not to regularly eat oily fish,” said Dr. Wu, a researcher at the George Institute for Global Health in Newtown, Australia.

“If eventually there is really strong evidence that fish, fish oil, or both have independent effects on both CVD and type 2 diabetes” it would be reasonable to integrate both outcomes into a single, composite, efficacy endpoint for the purpose of future studies, he added.

Dr. Qi agreed on both points. “A randomized, controlled trial of fish oil on type 2 diabetes as a primary outcome is needed. Most existing data are based on secondary analyses in the randomized trials for CVD,” he explained.

But, he added, “our results suggest a potential beneficial effect from fish oil supplements,” which implies that these may be “better than nothing” for people who can’t add oily fish to their regular diet.

The means by which fish and fish oil might slow or stop progression to type 2 diabetes remains uncertain.

The mechanisms for preventing both diabetes and CVD events may overlap, Dr. Qi noted, such as anti-inflammatory effects and improved insulin sensitivity, both of which have been observed in animal studies.

Evidence is “still lacking from human studies,” he explained, but if such mechanisms were at play, Dr. Wu said that would “add biologic plausibility” to a possible causal link between oily fish consumption and diabetes prevention. 

“But we can’t assume that omega-3 fatty acids alone will have the same effect as oily fish, which obviously contains many other components.”

The study received no commercial funding. Dr. Qi and Dr. Wu have reported no relevant financial relationships.

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

The final numbers won’t look much different, but the 2021 Match results will be unlike any before. As of mid-January, only 16 more institutions were confirmed to be participating in Match Day this year, resulting in about 800 more positions, said Donna Lamb, president and CEO of the National Resident Matching Program (NRMP). The Electronic Residency Application Service reported about 50,000 individual applicant submissions, a slight increase from prior years.

The stats may be similar, but the current residency application cycle may lead to wildly different results after the pandemic forced interviews to be conducted virtually and caused the cancellation of most away clinical rotations. Troy Amen, a fifth-year MD-MBA student at Harvard Medical School, Boston, and copresident of his student class, says the lack of on-campus, in-person experiences means students feel more in the dark than ever. The same is true for institutions. “The programs are also suffering because now they don’t know which students are a good ‘cultural fit’ for them,” he said.

Standing out has always been a concern for prospective residents, but Mr. Amen says fears are even higher this year. “[Institutions are] struggling to vet out 850 applicants, and they have no connection to us.”

Organizations have scrambled to keep the process as fair and informative as possible. “Everyone is trying to do the right thing here,” said Alison J. Whelan, MD, chief academic officer of the Association of American Medical Colleges (AAMC). She says that although the process has significantly changed, the heart of it remains the same. “The bottom line is directors really want to fill their intern class, and schools and students really want to match.”

Since the NRMP was established in 1952, it has never had to contend with a pandemic of this scale. The unprecedented circumstances have led to some much-feared and some unexpected changes, like top candidates “stealing” interview slots, “swag bags” sent to entice residents, beefed-up online profiles, as well as “Zoom fatigue,” a spike in home-field advantage for institutions, and massive anxiety for those students staking their future to a city they may have never seen in person.
 

What was lost and what was gained

“It’s really hard to get a real feel for the program when you’ve not been there in person,” said Christopher Smith, MD, director of the internal medicine residency program at Beth Israel Deaconess Medical Center in Boston. Dr. Smith recalled interviewing for residencies 25 years ago. His wife, a teacher, took time off to travel with him.

“She would ‘interview the town’ while I interviewed the program, and we compared notes at night,” he said. Because of COVID-19-related travel restrictions, just physically seeing the city in which they may live for years wasn’t an option for many. “I have a lot of sympathy for students applying right now,” Dr. Smith said.

For the residency class of 2021, the first shoe really dropped last March, when the AAMC issued guidance strongly recommending that programs pause clinical rotations away from their home schools. As established doctors know well, and as graduating medical students confirmed, these rotations are crucial to understanding a program’s culture and gaining experience that can boost candidacy. “I’m applying to orthopedic surgery, where away rotations are the gold standard for impressing attendees and residents at institutions away from home,” said Mr. Amen.

The pandemic completely cut off that key source of information to determine the right fit. It also meant applicants couldn’t have as diverse a portfolio of recommendation letters, something many worry may be detrimental to their soon-to-be-released Match rankings.

Unlike the loss of away rotations, the forced shift from in-person to virtual interviews had some meaningful benefits. Students no longer incurred expenses for airline flights, hotel rooms, and rental cars. Many organizations and programs have been trying for years to figure out how to lower the financial burden of interviews to make the process more equitable for those at economic or other disadvantage.

“The equity piece of this is huge – decreasing barriers and leveling the field a little bit is a really huge advantage,” said Kate Shaw, MD, residency program director and associate chair of education for the obstetrics and gynecology program at Stanford (Calif.) University. In some ways, this latest change is an extension of a strategy Dr. Shaw and others had already begun implementing.

“Over the last 5 to 10 years, we’ve been working to address the implicit bias in the application process, so we’ve gone to a holistic review of applicants, where we don’t have score cutoffs. We look at the whole person,” she said. “And we did that in an effort to increase diversity and equity.” Dr. Shaw and others hope that the accidental positive changes from COVID restrictions may be intentionally preserved long after the pandemic ends.
 

Home-field advantage vs. swag bags

Many medical students applying to residencies this year say they have given greater weight to their home programs than they might have without the pandemic. “I didn’t get a sense of anyone’s culture other than my home institution,” said Alex Skidmore, a fourth-year medical student at Washington University in St. Louis. “I definitely am ranking Wash-U higher.”

The desire to emphasize the known quality of a student’s home institution isn’t surprising to program directors. Dr. Shaw said she thinks this year’s Match could well end with a higher percentage of students matching either in their home programs or in programs close to loved ones. “The value of being close to family has come up in our conversations, where students are considering the right program for them but also the other life factors,” she said.

To overcome this home-field advantage, many programs have beefed up their websites, including providing video tours of their facilities. They also “upped their social media game” and encouraged residents to create online groups for prospective residents to share information about programs and life outside of work. Some residents even offered video tours of their personal apartments to applicants.

Without in-person access to facilities and staff, a program’s online presence became a deciding factor, applicants said. “If you have a bad website, it’s like having a dirty building to interview applicants in,” Mr. Skidmore said. For many prospective residents, an institution’s Internet presence was a “make or break” factor. “It’s the only thing I saw for many programs, and when we are doing the amount of research we are doing remotely, when I saw a program with a bad website, it made me not like the program as much,” he said.

Some programs, hoping to woo candidates as well as to provide them with more insight into what they and their cities have to offer, sent “swag bags” to candidates. These included things like gift cards for food delivery and offerings from local businesses. Washington University’s pediatrics residency program sent gooey butter cakes – a St. Louis staple – along with other treats from small businesses and copies of magazines that showcased the city’s dining and entertainment scene.

Other programs, even those at the same medical institution, felt quite strongly that those types of packages shouldn’t be sent. “We interviewed almost 500 applicants, so there was no way we could have afforded that,” said Dominique Cosco, MD, director of Washington University’s internal medicine residency program. “Our normal recruitment budget is almost $100,000 in a normal year, and that got cut because of COVID. For us, it was thinking about allocations of resources.”
 

Interview slot theft and zoom fatigue

Remote interviewing also meant that applicants could accept more interviews, something that raised a big concern. Without expenses or travel time, would top-tier candidates take more interviews than normal and thus take limited interview spots from other qualified candidates? Maybe so, says the AAMC’s Dr. Whelan.

“We didn’t have systematic data, but we heard from enough schools and programs ... that students who were maybe not the top-top ranked students in the class but in every way solid were receiving fewer interviews than previous years,” Dr. Whelan said. This is despite guidance that recommended programs add interview slots to serve as a counterbalance.

Some students say they accepted more interview slots in the beginning of the interview season, partly because they could, and partly because some thought of early interviews as “practice” for later interviews. However, as video interviews piled up, some of them described feeling “Zoom fatigue” and said they later canceled interviews with programs they didn’t anticipate joining.
 

More SOAP, less clarity

As for what comes next, the NRMP is preparing for a longer-than-normal Supplemental Offer and Acceptance Program (SOAP) than in years past. SOAP usually offers three rounds of matches after the initial Match Day; Ms. Lamb said things are different this year.

“SOAP will be the same number of days, but we’ve added an additional round on Thursday afternoon,” she said. Will it be unnecessary or not enough? Nobody knows. “How big SOAP actually is going to be is one of the things that we really don’t have a sense of right now and probably aren’t going to have a sense of until the Match.”

Uncertainty is the name of the game. More than any other Match before, programs and applicants won’t know how results from this pandemic year stack up for a few months at the very least. “I really want to see what this looks like on the other side,” Dr. Smith said. “Are applicants happy with the way it looks when they come here? Do they feel like they matched with the right place?”

Whether this unprecedented year will be remembered more for positive changes moving forward, including more flexibility on remote interviews, or for less-informed decisions that result in dissatisfied participants is also unclear.

“I think after the Match is over, we’ll be talking to everyone to get more perspective on what people who are applying now would tell the next class, and how programs can adjust,” said Kathy Diemer, MD, assistant dean for career counseling at Washington University. At the very least, those who are involved in this year after year can start thinking about what the future should look like.

“We’re going to need to do some kind of debriefing after this is over, both program directors and our students as well, so we can determine how to move forward next year and beyond.”

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

The final numbers won’t look much different, but the 2021 Match results will be unlike any before. As of mid-January, only 16 more institutions were confirmed to be participating in Match Day this year, resulting in about 800 more positions, said Donna Lamb, president and CEO of the National Resident Matching Program (NRMP). The Electronic Residency Application Service reported about 50,000 individual applicant submissions, a slight increase from prior years.

The stats may be similar, but the current residency application cycle may lead to wildly different results after the pandemic forced interviews to be conducted virtually and caused the cancellation of most away clinical rotations. Troy Amen, a fifth-year MD-MBA student at Harvard Medical School, Boston, and copresident of his student class, says the lack of on-campus, in-person experiences means students feel more in the dark than ever. The same is true for institutions. “The programs are also suffering because now they don’t know which students are a good ‘cultural fit’ for them,” he said.

Standing out has always been a concern for prospective residents, but Mr. Amen says fears are even higher this year. “[Institutions are] struggling to vet out 850 applicants, and they have no connection to us.”

Organizations have scrambled to keep the process as fair and informative as possible. “Everyone is trying to do the right thing here,” said Alison J. Whelan, MD, chief academic officer of the Association of American Medical Colleges (AAMC). She says that although the process has significantly changed, the heart of it remains the same. “The bottom line is directors really want to fill their intern class, and schools and students really want to match.”

Since the NRMP was established in 1952, it has never had to contend with a pandemic of this scale. The unprecedented circumstances have led to some much-feared and some unexpected changes, like top candidates “stealing” interview slots, “swag bags” sent to entice residents, beefed-up online profiles, as well as “Zoom fatigue,” a spike in home-field advantage for institutions, and massive anxiety for those students staking their future to a city they may have never seen in person.
 

What was lost and what was gained

“It’s really hard to get a real feel for the program when you’ve not been there in person,” said Christopher Smith, MD, director of the internal medicine residency program at Beth Israel Deaconess Medical Center in Boston. Dr. Smith recalled interviewing for residencies 25 years ago. His wife, a teacher, took time off to travel with him.

“She would ‘interview the town’ while I interviewed the program, and we compared notes at night,” he said. Because of COVID-19-related travel restrictions, just physically seeing the city in which they may live for years wasn’t an option for many. “I have a lot of sympathy for students applying right now,” Dr. Smith said.

For the residency class of 2021, the first shoe really dropped last March, when the AAMC issued guidance strongly recommending that programs pause clinical rotations away from their home schools. As established doctors know well, and as graduating medical students confirmed, these rotations are crucial to understanding a program’s culture and gaining experience that can boost candidacy. “I’m applying to orthopedic surgery, where away rotations are the gold standard for impressing attendees and residents at institutions away from home,” said Mr. Amen.

The pandemic completely cut off that key source of information to determine the right fit. It also meant applicants couldn’t have as diverse a portfolio of recommendation letters, something many worry may be detrimental to their soon-to-be-released Match rankings.

Unlike the loss of away rotations, the forced shift from in-person to virtual interviews had some meaningful benefits. Students no longer incurred expenses for airline flights, hotel rooms, and rental cars. Many organizations and programs have been trying for years to figure out how to lower the financial burden of interviews to make the process more equitable for those at economic or other disadvantage.

“The equity piece of this is huge – decreasing barriers and leveling the field a little bit is a really huge advantage,” said Kate Shaw, MD, residency program director and associate chair of education for the obstetrics and gynecology program at Stanford (Calif.) University. In some ways, this latest change is an extension of a strategy Dr. Shaw and others had already begun implementing.

“Over the last 5 to 10 years, we’ve been working to address the implicit bias in the application process, so we’ve gone to a holistic review of applicants, where we don’t have score cutoffs. We look at the whole person,” she said. “And we did that in an effort to increase diversity and equity.” Dr. Shaw and others hope that the accidental positive changes from COVID restrictions may be intentionally preserved long after the pandemic ends.
 

Home-field advantage vs. swag bags

Many medical students applying to residencies this year say they have given greater weight to their home programs than they might have without the pandemic. “I didn’t get a sense of anyone’s culture other than my home institution,” said Alex Skidmore, a fourth-year medical student at Washington University in St. Louis. “I definitely am ranking Wash-U higher.”

The desire to emphasize the known quality of a student’s home institution isn’t surprising to program directors. Dr. Shaw said she thinks this year’s Match could well end with a higher percentage of students matching either in their home programs or in programs close to loved ones. “The value of being close to family has come up in our conversations, where students are considering the right program for them but also the other life factors,” she said.

To overcome this home-field advantage, many programs have beefed up their websites, including providing video tours of their facilities. They also “upped their social media game” and encouraged residents to create online groups for prospective residents to share information about programs and life outside of work. Some residents even offered video tours of their personal apartments to applicants.

Without in-person access to facilities and staff, a program’s online presence became a deciding factor, applicants said. “If you have a bad website, it’s like having a dirty building to interview applicants in,” Mr. Skidmore said. For many prospective residents, an institution’s Internet presence was a “make or break” factor. “It’s the only thing I saw for many programs, and when we are doing the amount of research we are doing remotely, when I saw a program with a bad website, it made me not like the program as much,” he said.

Some programs, hoping to woo candidates as well as to provide them with more insight into what they and their cities have to offer, sent “swag bags” to candidates. These included things like gift cards for food delivery and offerings from local businesses. Washington University’s pediatrics residency program sent gooey butter cakes – a St. Louis staple – along with other treats from small businesses and copies of magazines that showcased the city’s dining and entertainment scene.

Other programs, even those at the same medical institution, felt quite strongly that those types of packages shouldn’t be sent. “We interviewed almost 500 applicants, so there was no way we could have afforded that,” said Dominique Cosco, MD, director of Washington University’s internal medicine residency program. “Our normal recruitment budget is almost $100,000 in a normal year, and that got cut because of COVID. For us, it was thinking about allocations of resources.”
 

Interview slot theft and zoom fatigue

Remote interviewing also meant that applicants could accept more interviews, something that raised a big concern. Without expenses or travel time, would top-tier candidates take more interviews than normal and thus take limited interview spots from other qualified candidates? Maybe so, says the AAMC’s Dr. Whelan.

“We didn’t have systematic data, but we heard from enough schools and programs ... that students who were maybe not the top-top ranked students in the class but in every way solid were receiving fewer interviews than previous years,” Dr. Whelan said. This is despite guidance that recommended programs add interview slots to serve as a counterbalance.

Some students say they accepted more interview slots in the beginning of the interview season, partly because they could, and partly because some thought of early interviews as “practice” for later interviews. However, as video interviews piled up, some of them described feeling “Zoom fatigue” and said they later canceled interviews with programs they didn’t anticipate joining.
 

More SOAP, less clarity

As for what comes next, the NRMP is preparing for a longer-than-normal Supplemental Offer and Acceptance Program (SOAP) than in years past. SOAP usually offers three rounds of matches after the initial Match Day; Ms. Lamb said things are different this year.

“SOAP will be the same number of days, but we’ve added an additional round on Thursday afternoon,” she said. Will it be unnecessary or not enough? Nobody knows. “How big SOAP actually is going to be is one of the things that we really don’t have a sense of right now and probably aren’t going to have a sense of until the Match.”

Uncertainty is the name of the game. More than any other Match before, programs and applicants won’t know how results from this pandemic year stack up for a few months at the very least. “I really want to see what this looks like on the other side,” Dr. Smith said. “Are applicants happy with the way it looks when they come here? Do they feel like they matched with the right place?”

Whether this unprecedented year will be remembered more for positive changes moving forward, including more flexibility on remote interviews, or for less-informed decisions that result in dissatisfied participants is also unclear.

“I think after the Match is over, we’ll be talking to everyone to get more perspective on what people who are applying now would tell the next class, and how programs can adjust,” said Kathy Diemer, MD, assistant dean for career counseling at Washington University. At the very least, those who are involved in this year after year can start thinking about what the future should look like.

“We’re going to need to do some kind of debriefing after this is over, both program directors and our students as well, so we can determine how to move forward next year and beyond.”

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

The final numbers won’t look much different, but the 2021 Match results will be unlike any before. As of mid-January, only 16 more institutions were confirmed to be participating in Match Day this year, resulting in about 800 more positions, said Donna Lamb, president and CEO of the National Resident Matching Program (NRMP). The Electronic Residency Application Service reported about 50,000 individual applicant submissions, a slight increase from prior years.

The stats may be similar, but the current residency application cycle may lead to wildly different results after the pandemic forced interviews to be conducted virtually and caused the cancellation of most away clinical rotations. Troy Amen, a fifth-year MD-MBA student at Harvard Medical School, Boston, and copresident of his student class, says the lack of on-campus, in-person experiences means students feel more in the dark than ever. The same is true for institutions. “The programs are also suffering because now they don’t know which students are a good ‘cultural fit’ for them,” he said.

Standing out has always been a concern for prospective residents, but Mr. Amen says fears are even higher this year. “[Institutions are] struggling to vet out 850 applicants, and they have no connection to us.”

Organizations have scrambled to keep the process as fair and informative as possible. “Everyone is trying to do the right thing here,” said Alison J. Whelan, MD, chief academic officer of the Association of American Medical Colleges (AAMC). She says that although the process has significantly changed, the heart of it remains the same. “The bottom line is directors really want to fill their intern class, and schools and students really want to match.”

Since the NRMP was established in 1952, it has never had to contend with a pandemic of this scale. The unprecedented circumstances have led to some much-feared and some unexpected changes, like top candidates “stealing” interview slots, “swag bags” sent to entice residents, beefed-up online profiles, as well as “Zoom fatigue,” a spike in home-field advantage for institutions, and massive anxiety for those students staking their future to a city they may have never seen in person.
 

What was lost and what was gained

“It’s really hard to get a real feel for the program when you’ve not been there in person,” said Christopher Smith, MD, director of the internal medicine residency program at Beth Israel Deaconess Medical Center in Boston. Dr. Smith recalled interviewing for residencies 25 years ago. His wife, a teacher, took time off to travel with him.

“She would ‘interview the town’ while I interviewed the program, and we compared notes at night,” he said. Because of COVID-19-related travel restrictions, just physically seeing the city in which they may live for years wasn’t an option for many. “I have a lot of sympathy for students applying right now,” Dr. Smith said.

For the residency class of 2021, the first shoe really dropped last March, when the AAMC issued guidance strongly recommending that programs pause clinical rotations away from their home schools. As established doctors know well, and as graduating medical students confirmed, these rotations are crucial to understanding a program’s culture and gaining experience that can boost candidacy. “I’m applying to orthopedic surgery, where away rotations are the gold standard for impressing attendees and residents at institutions away from home,” said Mr. Amen.

The pandemic completely cut off that key source of information to determine the right fit. It also meant applicants couldn’t have as diverse a portfolio of recommendation letters, something many worry may be detrimental to their soon-to-be-released Match rankings.

Unlike the loss of away rotations, the forced shift from in-person to virtual interviews had some meaningful benefits. Students no longer incurred expenses for airline flights, hotel rooms, and rental cars. Many organizations and programs have been trying for years to figure out how to lower the financial burden of interviews to make the process more equitable for those at economic or other disadvantage.

“The equity piece of this is huge – decreasing barriers and leveling the field a little bit is a really huge advantage,” said Kate Shaw, MD, residency program director and associate chair of education for the obstetrics and gynecology program at Stanford (Calif.) University. In some ways, this latest change is an extension of a strategy Dr. Shaw and others had already begun implementing.

“Over the last 5 to 10 years, we’ve been working to address the implicit bias in the application process, so we’ve gone to a holistic review of applicants, where we don’t have score cutoffs. We look at the whole person,” she said. “And we did that in an effort to increase diversity and equity.” Dr. Shaw and others hope that the accidental positive changes from COVID restrictions may be intentionally preserved long after the pandemic ends.
 

Home-field advantage vs. swag bags

Many medical students applying to residencies this year say they have given greater weight to their home programs than they might have without the pandemic. “I didn’t get a sense of anyone’s culture other than my home institution,” said Alex Skidmore, a fourth-year medical student at Washington University in St. Louis. “I definitely am ranking Wash-U higher.”

The desire to emphasize the known quality of a student’s home institution isn’t surprising to program directors. Dr. Shaw said she thinks this year’s Match could well end with a higher percentage of students matching either in their home programs or in programs close to loved ones. “The value of being close to family has come up in our conversations, where students are considering the right program for them but also the other life factors,” she said.

To overcome this home-field advantage, many programs have beefed up their websites, including providing video tours of their facilities. They also “upped their social media game” and encouraged residents to create online groups for prospective residents to share information about programs and life outside of work. Some residents even offered video tours of their personal apartments to applicants.

Without in-person access to facilities and staff, a program’s online presence became a deciding factor, applicants said. “If you have a bad website, it’s like having a dirty building to interview applicants in,” Mr. Skidmore said. For many prospective residents, an institution’s Internet presence was a “make or break” factor. “It’s the only thing I saw for many programs, and when we are doing the amount of research we are doing remotely, when I saw a program with a bad website, it made me not like the program as much,” he said.

Some programs, hoping to woo candidates as well as to provide them with more insight into what they and their cities have to offer, sent “swag bags” to candidates. These included things like gift cards for food delivery and offerings from local businesses. Washington University’s pediatrics residency program sent gooey butter cakes – a St. Louis staple – along with other treats from small businesses and copies of magazines that showcased the city’s dining and entertainment scene.

Other programs, even those at the same medical institution, felt quite strongly that those types of packages shouldn’t be sent. “We interviewed almost 500 applicants, so there was no way we could have afforded that,” said Dominique Cosco, MD, director of Washington University’s internal medicine residency program. “Our normal recruitment budget is almost $100,000 in a normal year, and that got cut because of COVID. For us, it was thinking about allocations of resources.”
 

Interview slot theft and zoom fatigue

Remote interviewing also meant that applicants could accept more interviews, something that raised a big concern. Without expenses or travel time, would top-tier candidates take more interviews than normal and thus take limited interview spots from other qualified candidates? Maybe so, says the AAMC’s Dr. Whelan.

“We didn’t have systematic data, but we heard from enough schools and programs ... that students who were maybe not the top-top ranked students in the class but in every way solid were receiving fewer interviews than previous years,” Dr. Whelan said. This is despite guidance that recommended programs add interview slots to serve as a counterbalance.

Some students say they accepted more interview slots in the beginning of the interview season, partly because they could, and partly because some thought of early interviews as “practice” for later interviews. However, as video interviews piled up, some of them described feeling “Zoom fatigue” and said they later canceled interviews with programs they didn’t anticipate joining.
 

More SOAP, less clarity

As for what comes next, the NRMP is preparing for a longer-than-normal Supplemental Offer and Acceptance Program (SOAP) than in years past. SOAP usually offers three rounds of matches after the initial Match Day; Ms. Lamb said things are different this year.

“SOAP will be the same number of days, but we’ve added an additional round on Thursday afternoon,” she said. Will it be unnecessary or not enough? Nobody knows. “How big SOAP actually is going to be is one of the things that we really don’t have a sense of right now and probably aren’t going to have a sense of until the Match.”

Uncertainty is the name of the game. More than any other Match before, programs and applicants won’t know how results from this pandemic year stack up for a few months at the very least. “I really want to see what this looks like on the other side,” Dr. Smith said. “Are applicants happy with the way it looks when they come here? Do they feel like they matched with the right place?”

Whether this unprecedented year will be remembered more for positive changes moving forward, including more flexibility on remote interviews, or for less-informed decisions that result in dissatisfied participants is also unclear.

“I think after the Match is over, we’ll be talking to everyone to get more perspective on what people who are applying now would tell the next class, and how programs can adjust,” said Kathy Diemer, MD, assistant dean for career counseling at Washington University. At the very least, those who are involved in this year after year can start thinking about what the future should look like.

“We’re going to need to do some kind of debriefing after this is over, both program directors and our students as well, so we can determine how to move forward next year and beyond.”

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

Adults who eat three slices of white bread daily have a significantly increased risk for dying from cardiovascular causes.

MikeyGen73/Getty Images

That’s one finding from an assessment of a more than 137,000 people in 21 countries that documented a clear link between a high level of consumption of refined grains and a significantly increased risk for death from any cause or major cardiovascular disease (CVD) event during a median follow-up of 9.5 years.

The results showed that people who reported eating at least 350 g (seven servings) of refined grain daily had a significant 29% increased risk of either death or a major CVD event (MI, stroke, or heart failure), compared with those who consumed less than one serving per day (fewer than 50 g) of refined grain after adjustment for multiple potential confounders, according to a report from the Prospective Urban Rural Epidemiology (PURE) study published in the BMJ on Feb. 3, 2021.

The analysis also showed no significant association between levels of whole grains or white rice in the diet and CVD events. Rice was considered a separate grain in the analysis because nearly two-thirds of the PURE study population reside in Asia, where rice is a staple food.

The findings show that “reduction in the quantity of refined grains and sugar, and improvement in the quality of carbohydrates is essential for better health outcomes, although we do not suggest complete elimination of refined grains,” said Mahshid Dehghan, PhD, lead investigator for this report and a researcher in nutrition epidemiology at the Population Health Research Institute of McMaster University, Hamilton, Ont.
 

‘Widely applicable’ results from large, diverse study

Although prior evidence had already shown the CVD risk from eating larger amounts of refined grains, “our findings are robust and more widely applicable because our large study recorded over 9,000 deaths and 3,500 major CVD events across a broad range of refined grain intake, and in a variety of different settings and cultures with varying dietary patterns,” Dr. Dehghan said in an interview.

“This is an important paper, with the strength of data from diverse countries. The associations are robust,” commented Dariush Mozaffarian, MD, DrPH, professor and dean of the Friedman School of Nutrition Science and Policy at Tufts University, Boston, who was not involved in the new report.

“The public and the public health community think about added sugar in food as harmful, but starch has gotten a free pass,” he said in an interview. Recently revised U.S. dietary guidelines recommend that refined grains constitute less than half of a person’s carbohydrate consumption, but that limitation remains set too high, Dr. Mozaffarian cautioned. A much safer daily consumption limit would cap refined grains to no more than one serving a day.

The data for the current PURE analysis came from more than 148,000 people aged 35-70 years at entry in 21 geographically and economically diverse countries. Excluding patients with known CVD at baseline left a cohort of 137,130 people.

The results showed no significant association between the quantity of whole grains consumed and the main outcome, nor a link between higher amounts of white rice consumption and the main outcome.

“Our findings suggest that intake of up to 350 g of cooked rice daily may not pose a significant health risk,” said Dr. Dehghan.

Refined grains produce a glucose surge

Dr. Dehghan and associates speculated that possible explanations for their findings are that “varieties of rice such as long-grain rice and especially parboiled white rice may have both a definite glycemic advantage and an overall nutritional advantage over refined wheat products. Also, depending on the culture and the nature of the rice eaten, rice may be displacing less desirable foods.”

In contrast, refined grains undergo “rapid action by digestive enzymes and quick absorption from the small intestines [that] could lead to an increase in postprandial blood glucose concentrations. The rise in glucose concentrations increases the insulin concentrations, which leads to hypoglycemia, lipolysis, and the stimulation of hunger and food intake,” the authors wrote.

“It’s similar to eating sugar, or candy,” noted Dr. Mozaffarian, as refined grain “is 100% glucose.” Whole grains differ by entering the gut packaged in cell structures that slow digestion and avoid delivering sugar in an unnaturally rapid way.

“We are providing new evidence, and we hope that dietary guidelines in North America encourage individuals to lower their refined grain and sugar intake,” Dr. Dehghan said.

PURE has received partial funding with unrestricted grants from several drug companies. Dr. Dehghan had no disclosures. Dr. Mozaffarian has been an adviser to or has received personal fees from several food companies, but had no relevant disclosures.

mzoler@mdedge.com
 

Adults who eat three slices of white bread daily have a significantly increased risk for dying from cardiovascular causes.

MikeyGen73/Getty Images

That’s one finding from an assessment of a more than 137,000 people in 21 countries that documented a clear link between a high level of consumption of refined grains and a significantly increased risk for death from any cause or major cardiovascular disease (CVD) event during a median follow-up of 9.5 years.

The results showed that people who reported eating at least 350 g (seven servings) of refined grain daily had a significant 29% increased risk of either death or a major CVD event (MI, stroke, or heart failure), compared with those who consumed less than one serving per day (fewer than 50 g) of refined grain after adjustment for multiple potential confounders, according to a report from the Prospective Urban Rural Epidemiology (PURE) study published in the BMJ on Feb. 3, 2021.

The analysis also showed no significant association between levels of whole grains or white rice in the diet and CVD events. Rice was considered a separate grain in the analysis because nearly two-thirds of the PURE study population reside in Asia, where rice is a staple food.

The findings show that “reduction in the quantity of refined grains and sugar, and improvement in the quality of carbohydrates is essential for better health outcomes, although we do not suggest complete elimination of refined grains,” said Mahshid Dehghan, PhD, lead investigator for this report and a researcher in nutrition epidemiology at the Population Health Research Institute of McMaster University, Hamilton, Ont.
 

‘Widely applicable’ results from large, diverse study

Although prior evidence had already shown the CVD risk from eating larger amounts of refined grains, “our findings are robust and more widely applicable because our large study recorded over 9,000 deaths and 3,500 major CVD events across a broad range of refined grain intake, and in a variety of different settings and cultures with varying dietary patterns,” Dr. Dehghan said in an interview.

“This is an important paper, with the strength of data from diverse countries. The associations are robust,” commented Dariush Mozaffarian, MD, DrPH, professor and dean of the Friedman School of Nutrition Science and Policy at Tufts University, Boston, who was not involved in the new report.

“The public and the public health community think about added sugar in food as harmful, but starch has gotten a free pass,” he said in an interview. Recently revised U.S. dietary guidelines recommend that refined grains constitute less than half of a person’s carbohydrate consumption, but that limitation remains set too high, Dr. Mozaffarian cautioned. A much safer daily consumption limit would cap refined grains to no more than one serving a day.

The data for the current PURE analysis came from more than 148,000 people aged 35-70 years at entry in 21 geographically and economically diverse countries. Excluding patients with known CVD at baseline left a cohort of 137,130 people.

The results showed no significant association between the quantity of whole grains consumed and the main outcome, nor a link between higher amounts of white rice consumption and the main outcome.

“Our findings suggest that intake of up to 350 g of cooked rice daily may not pose a significant health risk,” said Dr. Dehghan.

Refined grains produce a glucose surge

Dr. Dehghan and associates speculated that possible explanations for their findings are that “varieties of rice such as long-grain rice and especially parboiled white rice may have both a definite glycemic advantage and an overall nutritional advantage over refined wheat products. Also, depending on the culture and the nature of the rice eaten, rice may be displacing less desirable foods.”

In contrast, refined grains undergo “rapid action by digestive enzymes and quick absorption from the small intestines [that] could lead to an increase in postprandial blood glucose concentrations. The rise in glucose concentrations increases the insulin concentrations, which leads to hypoglycemia, lipolysis, and the stimulation of hunger and food intake,” the authors wrote.

“It’s similar to eating sugar, or candy,” noted Dr. Mozaffarian, as refined grain “is 100% glucose.” Whole grains differ by entering the gut packaged in cell structures that slow digestion and avoid delivering sugar in an unnaturally rapid way.

“We are providing new evidence, and we hope that dietary guidelines in North America encourage individuals to lower their refined grain and sugar intake,” Dr. Dehghan said.

PURE has received partial funding with unrestricted grants from several drug companies. Dr. Dehghan had no disclosures. Dr. Mozaffarian has been an adviser to or has received personal fees from several food companies, but had no relevant disclosures.

mzoler@mdedge.com
 

Adults who eat three slices of white bread daily have a significantly increased risk for dying from cardiovascular causes.

MikeyGen73/Getty Images

That’s one finding from an assessment of a more than 137,000 people in 21 countries that documented a clear link between a high level of consumption of refined grains and a significantly increased risk for death from any cause or major cardiovascular disease (CVD) event during a median follow-up of 9.5 years.

The results showed that people who reported eating at least 350 g (seven servings) of refined grain daily had a significant 29% increased risk of either death or a major CVD event (MI, stroke, or heart failure), compared with those who consumed less than one serving per day (fewer than 50 g) of refined grain after adjustment for multiple potential confounders, according to a report from the Prospective Urban Rural Epidemiology (PURE) study published in the BMJ on Feb. 3, 2021.

The analysis also showed no significant association between levels of whole grains or white rice in the diet and CVD events. Rice was considered a separate grain in the analysis because nearly two-thirds of the PURE study population reside in Asia, where rice is a staple food.

The findings show that “reduction in the quantity of refined grains and sugar, and improvement in the quality of carbohydrates is essential for better health outcomes, although we do not suggest complete elimination of refined grains,” said Mahshid Dehghan, PhD, lead investigator for this report and a researcher in nutrition epidemiology at the Population Health Research Institute of McMaster University, Hamilton, Ont.
 

‘Widely applicable’ results from large, diverse study

Although prior evidence had already shown the CVD risk from eating larger amounts of refined grains, “our findings are robust and more widely applicable because our large study recorded over 9,000 deaths and 3,500 major CVD events across a broad range of refined grain intake, and in a variety of different settings and cultures with varying dietary patterns,” Dr. Dehghan said in an interview.

“This is an important paper, with the strength of data from diverse countries. The associations are robust,” commented Dariush Mozaffarian, MD, DrPH, professor and dean of the Friedman School of Nutrition Science and Policy at Tufts University, Boston, who was not involved in the new report.

“The public and the public health community think about added sugar in food as harmful, but starch has gotten a free pass,” he said in an interview. Recently revised U.S. dietary guidelines recommend that refined grains constitute less than half of a person’s carbohydrate consumption, but that limitation remains set too high, Dr. Mozaffarian cautioned. A much safer daily consumption limit would cap refined grains to no more than one serving a day.

The data for the current PURE analysis came from more than 148,000 people aged 35-70 years at entry in 21 geographically and economically diverse countries. Excluding patients with known CVD at baseline left a cohort of 137,130 people.

The results showed no significant association between the quantity of whole grains consumed and the main outcome, nor a link between higher amounts of white rice consumption and the main outcome.

“Our findings suggest that intake of up to 350 g of cooked rice daily may not pose a significant health risk,” said Dr. Dehghan.

Refined grains produce a glucose surge

Dr. Dehghan and associates speculated that possible explanations for their findings are that “varieties of rice such as long-grain rice and especially parboiled white rice may have both a definite glycemic advantage and an overall nutritional advantage over refined wheat products. Also, depending on the culture and the nature of the rice eaten, rice may be displacing less desirable foods.”

In contrast, refined grains undergo “rapid action by digestive enzymes and quick absorption from the small intestines [that] could lead to an increase in postprandial blood glucose concentrations. The rise in glucose concentrations increases the insulin concentrations, which leads to hypoglycemia, lipolysis, and the stimulation of hunger and food intake,” the authors wrote.

“It’s similar to eating sugar, or candy,” noted Dr. Mozaffarian, as refined grain “is 100% glucose.” Whole grains differ by entering the gut packaged in cell structures that slow digestion and avoid delivering sugar in an unnaturally rapid way.

“We are providing new evidence, and we hope that dietary guidelines in North America encourage individuals to lower their refined grain and sugar intake,” Dr. Dehghan said.

PURE has received partial funding with unrestricted grants from several drug companies. Dr. Dehghan had no disclosures. Dr. Mozaffarian has been an adviser to or has received personal fees from several food companies, but had no relevant disclosures.

mzoler@mdedge.com
 

Younger adolescents who underwent metabolic and bariatric surgery had outcomes similar to those of older adolescents undergoing the same procedure, according to recent research in Pediatrics.

Five years after metabolic and bariatric surgery (MBS), adolescents between ages 13 and 15 years had similar outcomes with regard to reduction in body mass index percentage, hypertension and dyslipidemia, and improved quality of life, compared with adolescents between ages 16 and 19 years, according to Sarah B. Ogle, DO, MS, of Children’s Hospital Colorado at the University of Colorado at Denver, Aurora, and colleagues.

“These results appear promising for the treatment of severe obesity in young patients,” Dr. Ogle and colleagues wrote, “however, further controlled studies are needed to fully evaluate the timing of surgery and extended long-term durability.”

The researchers analyzed the outcomes of adolescents enrolled in the Teen–Longitudinal Assessment of Bariatric Surgery who were aged 19 years or younger and underwent MBS between March 2007 and December 2011 at five U.S. centers. In the group of younger adolescents (66 participants), the mean age at surgery was 15.1 years, while the group of older adolescents (162 participants) had a mean age of 17.7 years at the time of surgery. Both groups consisted mostly of White (71.6%-72.7%) girls (72.7%-75.9%) who were morbidly obese (mean BMI, 52.4-53.1 kg/m²). With regard to baseline comorbidities, about three-quarters of participants in the younger (72.4%) and older (77.0%) adolescent groups had dyslipidemia. More than one-quarter of younger adolescents had hypertension (27.3%) compared with more than one-third of older adolescents (37.1%). The prevalence of type 2 diabetes was 10.6% in the younger adolescent group and 13.6% among older adolescents.

At 5-year follow-up, there was a similar BMI reduction maintained from baseline in the younger adolescent group (–22.2%; 95% confidence interval, –26.2% to –18.2%) and the older adolescent group (–24.6%; 95% CI, –27.7% to –22.5%; P = .59). There was a similar number of participants who had remission of dyslipidemia at 5 years in the younger adolescent group (61%; 95% CI, 46.3%-81.1%) and older adolescent group (58%; 95% CI, 48.0%-68.9%; P = .74). In participants with hypertension, 77% of younger adolescents (95% CI, 57.1%-100.0%) and 67% of older adolescents (95% CI, 54.5%-81.5%) achieved remission at 5 years after MBS, which showed no significant differences after adjustment (P = .84). For participants with type 2 diabetes at baseline, 83% of younger adolescents (6 participants) and 87% of older adolescents (15 participants) experienced remission by 5 years after surgery. Participants in both younger and older adolescent groups had similar quality of life scores at 5 years after surgery. When analyzing nutritional abnormalities, the researchers found younger adolescents in the group were less at risk for elevated transferrin levels (prevalence ratio, 0.52; P = .048) as well as less likely to have low vitamin D levels (prevalence ratio, 0.8; P = .034).
 

Pediatricians still concerned about safety

In an interview, Kelly A. Curran, MD, MA, assistant professor of pediatrics at University of Oklahoma Children’s Hospital in Oklahoma City, said that the findings by Dr. Ogle and colleagues add to a “growing body of literature about the importance of bariatric surgery for both younger and older adolescents.

“While many often see bariatric surgery as a ‘last resort,’ this study shows good outcomes in resolving obesity-related health conditions in both young and older teens over time – and something that should be considered more frequently than it is currently being used,” she said.

Guidelines from the American Society for Metabolic and Bariatric Surgery removed a restriction for younger age before a patient undergoes MBS, and a policy statement from the American Academy of Pediatrics encouraged increased use and access to MBS for younger adolescents. However, Dr. Curran noted that many pediatricians are still concerned about performing MBS on younger adolescents.

“Despite growing evidence of safety, I think many pediatricians worry about the potential for unintended consequences and potential impact on adolescent development or for lifelong micronutrition deficiencies – especially as there are no longitudinal studies over a lifetime,” she said.

“[W]ith the growing obesity epidemic and the long-term consequences of obesity on health and quality of life – the potential to help impact adolescents’ lives – for now and for the future – is impressive,” Dr. Curran said, acknowledging the ethical challenges involved with performing MBS on a patient who may be too young to understand the full risks and benefits of surgery.

“There are always inherent ethical challenges in providing surgery for patients too young to understand – we are asking parents to act in their child’s best interests, which may be murky to elucidate,” she explained. “While there is [a] growing body of literature around the safety and efficacy in bariatric surgery for children and adolescents, there are still many unanswered questions that remain – especially for parents. Parents can feel trapped in between these two choices – have children undergo surgery or stick with potentially less effective medical management.”

The limitations of the study include its observational nature, small sample size of some comorbidities, and a lack of diversity among participants, most of whom were White and female. In addition, “long-term studies examining the impact of bariatric surgery during adolescence would be important to give more perspective and guidance on the risks and benefits for teens,” Dr. Curran said.

The study was funded by the National Institutes of Health and grants from the National Institute of Diabetes and Digestive and Kidney Diseases as well as grants from Cincinnati Children’s Hospital Medical Center, Nationwide Children’s Hospital, Texas Children’s Hospital and Baylor College of Medicine, University of Pittsburgh, and the University of Alabama at Birmingham. The authors and Dr. Curran reported no conflicts of interest.
 

Younger adolescents who underwent metabolic and bariatric surgery had outcomes similar to those of older adolescents undergoing the same procedure, according to recent research in Pediatrics.

Five years after metabolic and bariatric surgery (MBS), adolescents between ages 13 and 15 years had similar outcomes with regard to reduction in body mass index percentage, hypertension and dyslipidemia, and improved quality of life, compared with adolescents between ages 16 and 19 years, according to Sarah B. Ogle, DO, MS, of Children’s Hospital Colorado at the University of Colorado at Denver, Aurora, and colleagues.

“These results appear promising for the treatment of severe obesity in young patients,” Dr. Ogle and colleagues wrote, “however, further controlled studies are needed to fully evaluate the timing of surgery and extended long-term durability.”

The researchers analyzed the outcomes of adolescents enrolled in the Teen–Longitudinal Assessment of Bariatric Surgery who were aged 19 years or younger and underwent MBS between March 2007 and December 2011 at five U.S. centers. In the group of younger adolescents (66 participants), the mean age at surgery was 15.1 years, while the group of older adolescents (162 participants) had a mean age of 17.7 years at the time of surgery. Both groups consisted mostly of White (71.6%-72.7%) girls (72.7%-75.9%) who were morbidly obese (mean BMI, 52.4-53.1 kg/m²). With regard to baseline comorbidities, about three-quarters of participants in the younger (72.4%) and older (77.0%) adolescent groups had dyslipidemia. More than one-quarter of younger adolescents had hypertension (27.3%) compared with more than one-third of older adolescents (37.1%). The prevalence of type 2 diabetes was 10.6% in the younger adolescent group and 13.6% among older adolescents.

At 5-year follow-up, there was a similar BMI reduction maintained from baseline in the younger adolescent group (–22.2%; 95% confidence interval, –26.2% to –18.2%) and the older adolescent group (–24.6%; 95% CI, –27.7% to –22.5%; P = .59). There was a similar number of participants who had remission of dyslipidemia at 5 years in the younger adolescent group (61%; 95% CI, 46.3%-81.1%) and older adolescent group (58%; 95% CI, 48.0%-68.9%; P = .74). In participants with hypertension, 77% of younger adolescents (95% CI, 57.1%-100.0%) and 67% of older adolescents (95% CI, 54.5%-81.5%) achieved remission at 5 years after MBS, which showed no significant differences after adjustment (P = .84). For participants with type 2 diabetes at baseline, 83% of younger adolescents (6 participants) and 87% of older adolescents (15 participants) experienced remission by 5 years after surgery. Participants in both younger and older adolescent groups had similar quality of life scores at 5 years after surgery. When analyzing nutritional abnormalities, the researchers found younger adolescents in the group were less at risk for elevated transferrin levels (prevalence ratio, 0.52; P = .048) as well as less likely to have low vitamin D levels (prevalence ratio, 0.8; P = .034).
 

Pediatricians still concerned about safety

In an interview, Kelly A. Curran, MD, MA, assistant professor of pediatrics at University of Oklahoma Children’s Hospital in Oklahoma City, said that the findings by Dr. Ogle and colleagues add to a “growing body of literature about the importance of bariatric surgery for both younger and older adolescents.

“While many often see bariatric surgery as a ‘last resort,’ this study shows good outcomes in resolving obesity-related health conditions in both young and older teens over time – and something that should be considered more frequently than it is currently being used,” she said.

Guidelines from the American Society for Metabolic and Bariatric Surgery removed a restriction for younger age before a patient undergoes MBS, and a policy statement from the American Academy of Pediatrics encouraged increased use and access to MBS for younger adolescents. However, Dr. Curran noted that many pediatricians are still concerned about performing MBS on younger adolescents.

“Despite growing evidence of safety, I think many pediatricians worry about the potential for unintended consequences and potential impact on adolescent development or for lifelong micronutrition deficiencies – especially as there are no longitudinal studies over a lifetime,” she said.

“[W]ith the growing obesity epidemic and the long-term consequences of obesity on health and quality of life – the potential to help impact adolescents’ lives – for now and for the future – is impressive,” Dr. Curran said, acknowledging the ethical challenges involved with performing MBS on a patient who may be too young to understand the full risks and benefits of surgery.

“There are always inherent ethical challenges in providing surgery for patients too young to understand – we are asking parents to act in their child’s best interests, which may be murky to elucidate,” she explained. “While there is [a] growing body of literature around the safety and efficacy in bariatric surgery for children and adolescents, there are still many unanswered questions that remain – especially for parents. Parents can feel trapped in between these two choices – have children undergo surgery or stick with potentially less effective medical management.”

The limitations of the study include its observational nature, small sample size of some comorbidities, and a lack of diversity among participants, most of whom were White and female. In addition, “long-term studies examining the impact of bariatric surgery during adolescence would be important to give more perspective and guidance on the risks and benefits for teens,” Dr. Curran said.

The study was funded by the National Institutes of Health and grants from the National Institute of Diabetes and Digestive and Kidney Diseases as well as grants from Cincinnati Children’s Hospital Medical Center, Nationwide Children’s Hospital, Texas Children’s Hospital and Baylor College of Medicine, University of Pittsburgh, and the University of Alabama at Birmingham. The authors and Dr. Curran reported no conflicts of interest.
 

Younger adolescents who underwent metabolic and bariatric surgery had outcomes similar to those of older adolescents undergoing the same procedure, according to recent research in Pediatrics.

Five years after metabolic and bariatric surgery (MBS), adolescents between ages 13 and 15 years had similar outcomes with regard to reduction in body mass index percentage, hypertension and dyslipidemia, and improved quality of life, compared with adolescents between ages 16 and 19 years, according to Sarah B. Ogle, DO, MS, of Children’s Hospital Colorado at the University of Colorado at Denver, Aurora, and colleagues.

“These results appear promising for the treatment of severe obesity in young patients,” Dr. Ogle and colleagues wrote, “however, further controlled studies are needed to fully evaluate the timing of surgery and extended long-term durability.”

The researchers analyzed the outcomes of adolescents enrolled in the Teen–Longitudinal Assessment of Bariatric Surgery who were aged 19 years or younger and underwent MBS between March 2007 and December 2011 at five U.S. centers. In the group of younger adolescents (66 participants), the mean age at surgery was 15.1 years, while the group of older adolescents (162 participants) had a mean age of 17.7 years at the time of surgery. Both groups consisted mostly of White (71.6%-72.7%) girls (72.7%-75.9%) who were morbidly obese (mean BMI, 52.4-53.1 kg/m²). With regard to baseline comorbidities, about three-quarters of participants in the younger (72.4%) and older (77.0%) adolescent groups had dyslipidemia. More than one-quarter of younger adolescents had hypertension (27.3%) compared with more than one-third of older adolescents (37.1%). The prevalence of type 2 diabetes was 10.6% in the younger adolescent group and 13.6% among older adolescents.

At 5-year follow-up, there was a similar BMI reduction maintained from baseline in the younger adolescent group (–22.2%; 95% confidence interval, –26.2% to –18.2%) and the older adolescent group (–24.6%; 95% CI, –27.7% to –22.5%; P = .59). There was a similar number of participants who had remission of dyslipidemia at 5 years in the younger adolescent group (61%; 95% CI, 46.3%-81.1%) and older adolescent group (58%; 95% CI, 48.0%-68.9%; P = .74). In participants with hypertension, 77% of younger adolescents (95% CI, 57.1%-100.0%) and 67% of older adolescents (95% CI, 54.5%-81.5%) achieved remission at 5 years after MBS, which showed no significant differences after adjustment (P = .84). For participants with type 2 diabetes at baseline, 83% of younger adolescents (6 participants) and 87% of older adolescents (15 participants) experienced remission by 5 years after surgery. Participants in both younger and older adolescent groups had similar quality of life scores at 5 years after surgery. When analyzing nutritional abnormalities, the researchers found younger adolescents in the group were less at risk for elevated transferrin levels (prevalence ratio, 0.52; P = .048) as well as less likely to have low vitamin D levels (prevalence ratio, 0.8; P = .034).
 

Pediatricians still concerned about safety

In an interview, Kelly A. Curran, MD, MA, assistant professor of pediatrics at University of Oklahoma Children’s Hospital in Oklahoma City, said that the findings by Dr. Ogle and colleagues add to a “growing body of literature about the importance of bariatric surgery for both younger and older adolescents.

“While many often see bariatric surgery as a ‘last resort,’ this study shows good outcomes in resolving obesity-related health conditions in both young and older teens over time – and something that should be considered more frequently than it is currently being used,” she said.

Guidelines from the American Society for Metabolic and Bariatric Surgery removed a restriction for younger age before a patient undergoes MBS, and a policy statement from the American Academy of Pediatrics encouraged increased use and access to MBS for younger adolescents. However, Dr. Curran noted that many pediatricians are still concerned about performing MBS on younger adolescents.

“Despite growing evidence of safety, I think many pediatricians worry about the potential for unintended consequences and potential impact on adolescent development or for lifelong micronutrition deficiencies – especially as there are no longitudinal studies over a lifetime,” she said.

“[W]ith the growing obesity epidemic and the long-term consequences of obesity on health and quality of life – the potential to help impact adolescents’ lives – for now and for the future – is impressive,” Dr. Curran said, acknowledging the ethical challenges involved with performing MBS on a patient who may be too young to understand the full risks and benefits of surgery.

“There are always inherent ethical challenges in providing surgery for patients too young to understand – we are asking parents to act in their child’s best interests, which may be murky to elucidate,” she explained. “While there is [a] growing body of literature around the safety and efficacy in bariatric surgery for children and adolescents, there are still many unanswered questions that remain – especially for parents. Parents can feel trapped in between these two choices – have children undergo surgery or stick with potentially less effective medical management.”

The limitations of the study include its observational nature, small sample size of some comorbidities, and a lack of diversity among participants, most of whom were White and female. In addition, “long-term studies examining the impact of bariatric surgery during adolescence would be important to give more perspective and guidance on the risks and benefits for teens,” Dr. Curran said.

The study was funded by the National Institutes of Health and grants from the National Institute of Diabetes and Digestive and Kidney Diseases as well as grants from Cincinnati Children’s Hospital Medical Center, Nationwide Children’s Hospital, Texas Children’s Hospital and Baylor College of Medicine, University of Pittsburgh, and the University of Alabama at Birmingham. The authors and Dr. Curran reported no conflicts of interest.
 

Autopsies on patients who died from COVID-19 are providing important clues on how to treat the disease. In an analysis of 40 hearts from COVID-19 patients who died early in the pandemic, myocyte necrosis was seen in 14 hearts, or 35%.

In the majority of these hearts, pathologists found both small areas of focal necrosis and cardiac thrombi, most of which were microthrombi in myocardial capillaries, arterioles, and small muscular cells.

In an interview, senior author Aloke V. Finn, MD, CVPath Institute, Gaithersburg, Md., stressed the importance of understanding what they saw, but also what they didn’t see.

“What we saw in the majority of patients with myocardial injury were these small areas of infarct and microthrombi in small vessels. What we didn’t see was any evidence of myocarditis and or huge infarcts in, like, the LAD artery,” he said.

“What we’re seeing here is not clinically detectable. ... There is no test that will tell you there are microthrombi and no imaging tests that will show these focal areas of necrosis, but that doesn’t mean it’s not there,” he added.

The finding of myocyte necrosis in about one-third of samples is consistent with another study that showed that 30%-40% of patients hospitalized with COVID-19 have elevated troponins, noted Dr. Finn. The investigators were unable to obtain troponin levels on their patients, which could limit the clinical translation of myocardial necrosis detected at autopsy.

Dr. Finn and colleagues, including first author Dario Pellegrini, MD, from Ospedale Papa Giovanni XXIII in Bergamo, Italy, published their findings online in Circulation on Jan. 22, 2020.

The report is a follow-up to another just published by Dr. Finn’s group in the Journal of the American College of Cardiology, which showed that myocarditis is a very rare finding in COVID-19 autopsies.

Only three of 14 individuals (21.4%) with evidence of myocyte necrosis showed evidence of acute MI, which Dr. Finn and colleagues define as an area of necrosis at least 1 cm² in size. The remaining 11 (78.6%) had only discrete areas of myocyte necrosis (>20 necrotic myocytes with an area of ≥0.05 mm², but <1 cm²).

“This makes sense when we saw what type of thrombus there was in these cases; it wasn’t thrombus in major epicardial vessels but microthombi in small vessels,” said Dr. Finn.

In those with necrosis, cardiac thrombi were present in 11 of 14 (78.6%) cases, with 2 of 14 (14.2%) having epicardial coronary artery thrombi and 0 of 14 (64.3%) having microthrombi in myocardial capillaries, arterioles, and small muscular arteries.

Further supporting the role of COVID-19–related hypercoagulability as the cause of myocardial injury in many patients, the investigators noted that the incidence of severe coronary artery disease (defined as >75% cross sectional narrowing) did not differ significantly between those with and without necrosis.
 

COVID-19 vs. non–COVID-19 thrombi

Going one step further, Dr. Finn’s team compared cardiac microthrombi from their COVID-19–positive autopsy cases with intramyocardial thromboemboli from COVID-19 cases. They also compared the samples with aspirated thrombi obtained during primary percutaneous coronary intervention from uninfected and COVID-19–infected patients presenting with ST-segment elevation MI (STEMI).

The autopsy-obtained microthrombi had significantly more fibrin and terminal complement C5b-9 immunostaining than intramyocardial thromboemboli from COVID-19–negative subjects and than aspirated thrombi from either COVID-positive or COVID-negative STEMI patients.

“Basically, what we’re seeing in these thrombi is evidence of an immune-mediated reaction,” said Dr. Finn, explaining that complement C5b-9 is an innate immune system protein that circulates in the blood in response to any kind of activation of the immune system. “It is nonspecific but can also lead to coagulation problems,” he said.
 

Anticoagulation, yes, but dose unclear

These findings clearly support the use of anticoagulation in hospitalized COVID patients, said Jeffrey Weitz, MD, director of the Thrombosis & Atherosclerosis Research Institute, McMaster University, Hamilton, Ont. But the details of how much anticoagulation, what kind, and for whom are still a moving target.

“I think what we can say at this point is that these autopsy findings fit with previous studies that have shown microthrombi in the lungs and thrombi in the legs and gut, and support the notion that these patients should receive prophylactic doses of anticoagulants if they’re sick enough to be hospitalized,” said Dr. Weitz.

“But it’s not as simple as to say that this study shows clots form in the heart of COVID patients and therefore more anticoagulation is going to be better than less anticoagulation,” he said in an interview.

Recent top-line findings from three linked clinical trials – REMAP-CAP, ACTIV-4, and ATTACC – show that full-dose anticoagulation was beneficial in moderately ill patients hospitalized for COVID-19 and reduced the need for mechanical ventilation.

Moderately ill patients are those not in intensive care and who did not require organ support, such as mechanical ventilation, at the time of enrollment.

However, the same group reported findings in December that showed that routine use of full-dose anticoagulation when started in the ICU in critically ill patients was not beneficial and possibly harmful.

Dr. Weitz was only a little bit surprised by this finding of potential harm in the sickest patients. “I figured everybody should get prophylaxis but I wasn’t sure that everybody should get intensified anticoagulant. But my assumption was that if anybody is going to benefit from it, it would be the ICU patients.”

It was notable, said Dr. Weitz, that levels of D-dimer, a fibrin degradation product, were not associated with outcomes. “So, it doesn’t seem to be that patients with evidence of more clotting are more likely to benefit, which might indicate that it’s not the anticoagulant effect of the heparin that’s helping, but maybe the anti-inflammatory effect. At this point, we just don’t know.”

All three studies have paused enrollment of the critically ill subgroup, but are continuing to enroll patients with moderate illness and expect to publish results in the coming months, according to previous coverage from this news organization.

The study was funded by CVPath, a nonprofit institute that receives funding from a number of different industry entities. Dr. Finn and Dr. Weitz reported no relevant conflicts of interest.

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

Autopsies on patients who died from COVID-19 are providing important clues on how to treat the disease. In an analysis of 40 hearts from COVID-19 patients who died early in the pandemic, myocyte necrosis was seen in 14 hearts, or 35%.

In the majority of these hearts, pathologists found both small areas of focal necrosis and cardiac thrombi, most of which were microthrombi in myocardial capillaries, arterioles, and small muscular cells.

In an interview, senior author Aloke V. Finn, MD, CVPath Institute, Gaithersburg, Md., stressed the importance of understanding what they saw, but also what they didn’t see.

“What we saw in the majority of patients with myocardial injury were these small areas of infarct and microthrombi in small vessels. What we didn’t see was any evidence of myocarditis and or huge infarcts in, like, the LAD artery,” he said.

“What we’re seeing here is not clinically detectable. ... There is no test that will tell you there are microthrombi and no imaging tests that will show these focal areas of necrosis, but that doesn’t mean it’s not there,” he added.

The finding of myocyte necrosis in about one-third of samples is consistent with another study that showed that 30%-40% of patients hospitalized with COVID-19 have elevated troponins, noted Dr. Finn. The investigators were unable to obtain troponin levels on their patients, which could limit the clinical translation of myocardial necrosis detected at autopsy.

Dr. Finn and colleagues, including first author Dario Pellegrini, MD, from Ospedale Papa Giovanni XXIII in Bergamo, Italy, published their findings online in Circulation on Jan. 22, 2020.

The report is a follow-up to another just published by Dr. Finn’s group in the Journal of the American College of Cardiology, which showed that myocarditis is a very rare finding in COVID-19 autopsies.

Only three of 14 individuals (21.4%) with evidence of myocyte necrosis showed evidence of acute MI, which Dr. Finn and colleagues define as an area of necrosis at least 1 cm² in size. The remaining 11 (78.6%) had only discrete areas of myocyte necrosis (>20 necrotic myocytes with an area of ≥0.05 mm², but <1 cm²).

“This makes sense when we saw what type of thrombus there was in these cases; it wasn’t thrombus in major epicardial vessels but microthombi in small vessels,” said Dr. Finn.

In those with necrosis, cardiac thrombi were present in 11 of 14 (78.6%) cases, with 2 of 14 (14.2%) having epicardial coronary artery thrombi and 0 of 14 (64.3%) having microthrombi in myocardial capillaries, arterioles, and small muscular arteries.

Further supporting the role of COVID-19–related hypercoagulability as the cause of myocardial injury in many patients, the investigators noted that the incidence of severe coronary artery disease (defined as >75% cross sectional narrowing) did not differ significantly between those with and without necrosis.
 

COVID-19 vs. non–COVID-19 thrombi

Going one step further, Dr. Finn’s team compared cardiac microthrombi from their COVID-19–positive autopsy cases with intramyocardial thromboemboli from COVID-19 cases. They also compared the samples with aspirated thrombi obtained during primary percutaneous coronary intervention from uninfected and COVID-19–infected patients presenting with ST-segment elevation MI (STEMI).

The autopsy-obtained microthrombi had significantly more fibrin and terminal complement C5b-9 immunostaining than intramyocardial thromboemboli from COVID-19–negative subjects and than aspirated thrombi from either COVID-positive or COVID-negative STEMI patients.

“Basically, what we’re seeing in these thrombi is evidence of an immune-mediated reaction,” said Dr. Finn, explaining that complement C5b-9 is an innate immune system protein that circulates in the blood in response to any kind of activation of the immune system. “It is nonspecific but can also lead to coagulation problems,” he said.
 

Anticoagulation, yes, but dose unclear

These findings clearly support the use of anticoagulation in hospitalized COVID patients, said Jeffrey Weitz, MD, director of the Thrombosis & Atherosclerosis Research Institute, McMaster University, Hamilton, Ont. But the details of how much anticoagulation, what kind, and for whom are still a moving target.

“I think what we can say at this point is that these autopsy findings fit with previous studies that have shown microthrombi in the lungs and thrombi in the legs and gut, and support the notion that these patients should receive prophylactic doses of anticoagulants if they’re sick enough to be hospitalized,” said Dr. Weitz.

“But it’s not as simple as to say that this study shows clots form in the heart of COVID patients and therefore more anticoagulation is going to be better than less anticoagulation,” he said in an interview.

Recent top-line findings from three linked clinical trials – REMAP-CAP, ACTIV-4, and ATTACC – show that full-dose anticoagulation was beneficial in moderately ill patients hospitalized for COVID-19 and reduced the need for mechanical ventilation.

Moderately ill patients are those not in intensive care and who did not require organ support, such as mechanical ventilation, at the time of enrollment.

However, the same group reported findings in December that showed that routine use of full-dose anticoagulation when started in the ICU in critically ill patients was not beneficial and possibly harmful.

Dr. Weitz was only a little bit surprised by this finding of potential harm in the sickest patients. “I figured everybody should get prophylaxis but I wasn’t sure that everybody should get intensified anticoagulant. But my assumption was that if anybody is going to benefit from it, it would be the ICU patients.”

It was notable, said Dr. Weitz, that levels of D-dimer, a fibrin degradation product, were not associated with outcomes. “So, it doesn’t seem to be that patients with evidence of more clotting are more likely to benefit, which might indicate that it’s not the anticoagulant effect of the heparin that’s helping, but maybe the anti-inflammatory effect. At this point, we just don’t know.”

All three studies have paused enrollment of the critically ill subgroup, but are continuing to enroll patients with moderate illness and expect to publish results in the coming months, according to previous coverage from this news organization.

The study was funded by CVPath, a nonprofit institute that receives funding from a number of different industry entities. Dr. Finn and Dr. Weitz reported no relevant conflicts of interest.

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

Autopsies on patients who died from COVID-19 are providing important clues on how to treat the disease. In an analysis of 40 hearts from COVID-19 patients who died early in the pandemic, myocyte necrosis was seen in 14 hearts, or 35%.

In the majority of these hearts, pathologists found both small areas of focal necrosis and cardiac thrombi, most of which were microthrombi in myocardial capillaries, arterioles, and small muscular cells.

In an interview, senior author Aloke V. Finn, MD, CVPath Institute, Gaithersburg, Md., stressed the importance of understanding what they saw, but also what they didn’t see.

“What we saw in the majority of patients with myocardial injury were these small areas of infarct and microthrombi in small vessels. What we didn’t see was any evidence of myocarditis and or huge infarcts in, like, the LAD artery,” he said.

“What we’re seeing here is not clinically detectable. ... There is no test that will tell you there are microthrombi and no imaging tests that will show these focal areas of necrosis, but that doesn’t mean it’s not there,” he added.

The finding of myocyte necrosis in about one-third of samples is consistent with another study that showed that 30%-40% of patients hospitalized with COVID-19 have elevated troponins, noted Dr. Finn. The investigators were unable to obtain troponin levels on their patients, which could limit the clinical translation of myocardial necrosis detected at autopsy.

Dr. Finn and colleagues, including first author Dario Pellegrini, MD, from Ospedale Papa Giovanni XXIII in Bergamo, Italy, published their findings online in Circulation on Jan. 22, 2020.

The report is a follow-up to another just published by Dr. Finn’s group in the Journal of the American College of Cardiology, which showed that myocarditis is a very rare finding in COVID-19 autopsies.

Only three of 14 individuals (21.4%) with evidence of myocyte necrosis showed evidence of acute MI, which Dr. Finn and colleagues define as an area of necrosis at least 1 cm² in size. The remaining 11 (78.6%) had only discrete areas of myocyte necrosis (>20 necrotic myocytes with an area of ≥0.05 mm², but <1 cm²).

“This makes sense when we saw what type of thrombus there was in these cases; it wasn’t thrombus in major epicardial vessels but microthombi in small vessels,” said Dr. Finn.

In those with necrosis, cardiac thrombi were present in 11 of 14 (78.6%) cases, with 2 of 14 (14.2%) having epicardial coronary artery thrombi and 0 of 14 (64.3%) having microthrombi in myocardial capillaries, arterioles, and small muscular arteries.

Further supporting the role of COVID-19–related hypercoagulability as the cause of myocardial injury in many patients, the investigators noted that the incidence of severe coronary artery disease (defined as >75% cross sectional narrowing) did not differ significantly between those with and without necrosis.
 

COVID-19 vs. non–COVID-19 thrombi

Going one step further, Dr. Finn’s team compared cardiac microthrombi from their COVID-19–positive autopsy cases with intramyocardial thromboemboli from COVID-19 cases. They also compared the samples with aspirated thrombi obtained during primary percutaneous coronary intervention from uninfected and COVID-19–infected patients presenting with ST-segment elevation MI (STEMI).

The autopsy-obtained microthrombi had significantly more fibrin and terminal complement C5b-9 immunostaining than intramyocardial thromboemboli from COVID-19–negative subjects and than aspirated thrombi from either COVID-positive or COVID-negative STEMI patients.

“Basically, what we’re seeing in these thrombi is evidence of an immune-mediated reaction,” said Dr. Finn, explaining that complement C5b-9 is an innate immune system protein that circulates in the blood in response to any kind of activation of the immune system. “It is nonspecific but can also lead to coagulation problems,” he said.
 

Anticoagulation, yes, but dose unclear

These findings clearly support the use of anticoagulation in hospitalized COVID patients, said Jeffrey Weitz, MD, director of the Thrombosis & Atherosclerosis Research Institute, McMaster University, Hamilton, Ont. But the details of how much anticoagulation, what kind, and for whom are still a moving target.

“I think what we can say at this point is that these autopsy findings fit with previous studies that have shown microthrombi in the lungs and thrombi in the legs and gut, and support the notion that these patients should receive prophylactic doses of anticoagulants if they’re sick enough to be hospitalized,” said Dr. Weitz.

“But it’s not as simple as to say that this study shows clots form in the heart of COVID patients and therefore more anticoagulation is going to be better than less anticoagulation,” he said in an interview.

Recent top-line findings from three linked clinical trials – REMAP-CAP, ACTIV-4, and ATTACC – show that full-dose anticoagulation was beneficial in moderately ill patients hospitalized for COVID-19 and reduced the need for mechanical ventilation.

Moderately ill patients are those not in intensive care and who did not require organ support, such as mechanical ventilation, at the time of enrollment.

However, the same group reported findings in December that showed that routine use of full-dose anticoagulation when started in the ICU in critically ill patients was not beneficial and possibly harmful.

Dr. Weitz was only a little bit surprised by this finding of potential harm in the sickest patients. “I figured everybody should get prophylaxis but I wasn’t sure that everybody should get intensified anticoagulant. But my assumption was that if anybody is going to benefit from it, it would be the ICU patients.”

It was notable, said Dr. Weitz, that levels of D-dimer, a fibrin degradation product, were not associated with outcomes. “So, it doesn’t seem to be that patients with evidence of more clotting are more likely to benefit, which might indicate that it’s not the anticoagulant effect of the heparin that’s helping, but maybe the anti-inflammatory effect. At this point, we just don’t know.”

All three studies have paused enrollment of the critically ill subgroup, but are continuing to enroll patients with moderate illness and expect to publish results in the coming months, according to previous coverage from this news organization.

The study was funded by CVPath, a nonprofit institute that receives funding from a number of different industry entities. Dr. Finn and Dr. Weitz reported no relevant conflicts of interest.

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

A small, single-center randomized trial of patients with obesity and advanced type 2 diabetes, defined as diabetes for ≥ 5 years and A1c ≥ 7%, found that a quarter to a half of patients who had metabolic surgery had diabetes remission (cure) that lasted 5-9 years.

That is, of the 60 randomized patients, 50% who had biliopancreatic diversion and 25% who had Roux-en-Y gastric bypass – but none who had received current medical therapy – still had diabetes remission a decade later.

Until now, there had only been 5-year follow-up data from this and similar trials, Geltrude Mingrone, MD, PhD, and colleagues noted in the study published online Jan. 23 in The Lancet.

These results provide “the most robust scientific evidence yet that full-blown type 2 diabetes is a curable disease, not inevitably progressive, and irreversible,” senior author Francesco Rubino, MD, chair of bariatric and metabolic surgery at King’s College London, said in a statement from his institution.

“The results of this trial will make a noticeable difference in the field and convince even the most skeptical of clinicians about the role of metabolic surgery as part of optimal care for their patients with difficult to control type 2 diabetes,” predicted two editorialists.

Alexander D. Miras, PhD, section of metabolism, digestion, and reproduction, Imperial College London, and Carel le Roux, MBChB, PhD, of the Diabetes Complications Research Centre, University College Dublin, penned the accompanying commentary.

Patients who had metabolic surgery also had greater weight loss, reduced medication use, lower cardiovascular risk, better quality of life, and a lower incidence of diabetes-related complications compared with those who received medical therapy.

“Clinicians and policymakers should ensure that metabolic surgery is appropriately considered in the management of patients with obesity and type 2 diabetes,” advised Dr. Mingrone of King’s College London and the Catholic University of Rome, and colleagues.
 

“Reassuring results, will make a difference in the field”

“It is reassuring that we now have 10-year data showing greater efficacy of metabolic surgery than conventional medical therapy,” Dr. Miras and Dr. le Roux wrote in their commentary.

There were no unexpected risks associated with surgery, they noted, and the findings are consistent with those of 12 other randomized controlled trials in the past 12 years.

“New generations of diabetologists are now more open to the use of metabolic surgery for patients with suboptimal responses to medical treatments,” they wrote, rather than endlessly intensifying insulin and blaming poor response on poor compliance.

And Dr. Miras and Dr. le Roux “eagerly await” 10-year data from the 150-patient STAMPEDE trial – which is examining sleeve gastrectomy, currently the most widely performed bariatric procedure, as well as Roux-en-Y gastric bypass and medical therapy – following the 5-year results published in 2017.  
 

Diabetes for at least 5 years, mid 40s, half on insulin

Dr. Mingrone and colleagues previously reported 5-year findings from the 60 patients with obesity and advanced diabetes who were seen in a single center in Rome and randomized to three treatments (20 in each group) in 2009-2011.

Biliopancreatic diversion “remains infrequently performed but is still considered the best operation for glycemic control,” the researchers noted.

The primary endpoint was diabetes remission at 2 years (fasting plasma glucose < 100 mg/dL [5.6 mmol/L] and A1c < 6.5%) without the need for ongoing pharmacological treatment for at least 1 year.

Patients were a mean age of 44 years and had a mean body mass index of 44 kg/m^2. About half were men. They had diabetes for a mean of 5.8 years and an average A1c of 8.6%. About half were taking insulin.

Patient retention rate was high (95%) and trial outcomes were assessed by nonsurgeons.

At 10 years, patients’ mean A1c had dropped to 6.4%, 6.7%, and 7.6%, in the biliopancreatic diversion, Roux-en-Y gastric bypass, and medical therapy groups, respectively; only 2.5% of patients in the surgery groups, versus 53% in the medical therapy group, required insulin.

At study end, patients in the surgery groups had lost about 29% of their initial weight versus a weight loss of 4.2% in the medical therapy group.
 

First 2 years after surgery is key

“We also learnt that patients who do not go into remission after 2 years are very unlikely to ever do so,” Dr. Miras and Dr. le Roux observed, which “might help us to intensify modern and potent glucose-lowering therapies like SGLT2 inhibitors and GLP-1 receptor agonists earlier after metabolic surgery.”

Ten of 19 patients (53%) in the biliopancreatic diversion group and 10 of 15 patients (67%) in the Roux-en-Y gastric bypass group who had diabetes remission at 2 years had a diabetes relapse, but at 10 years, they all had adequate glycemic control (mean A1c 6.7%), despite drastically reduced use of diabetes medications.

The two patients who crossed over to surgery from the medical therapy group had postoperative diabetes remission, which was maintained at 10 years in one patient.
 

Better risk-to-benefit ratio with Roux-en-y gastric bypass

No patient in the medical therapy group had a serious adverse event, but one patient in each surgery group had deep vein thrombosis or pulmonary embolism, and one patient in the biliopancreatic diversion group had an episode of atrial fibrillation. There were no late surgical complications.

Iron deficiency and mild osteopenia occurred in both surgical groups, but were more common in the biliopancreatic diversion group. And osteoporosis, transient nyctalopia (night blindness) due to vitamin A deficiency, and kidney stones were observed only with biliopancreatic diversion.

This suggests that despite the greater antidiabetic potential of biliopancreatic diversion, Roux-en-Y gastric bypass might have a more favorable risk-to-benefit profile as a standard surgical option for the treatment of type 2 diabetes, Dr. Mingrone and colleagues concluded.

The authors and Dr. Miras have reported no relevant financial relationships. Dr. le Roux has reported receiving funding from the Science Foundation Ireland, the Health Research Board, and the Irish Research Council for type 2 diabetes research, and serves on several advisory boards outside of the scope of the current study.

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

A small, single-center randomized trial of patients with obesity and advanced type 2 diabetes, defined as diabetes for ≥ 5 years and A1c ≥ 7%, found that a quarter to a half of patients who had metabolic surgery had diabetes remission (cure) that lasted 5-9 years.

That is, of the 60 randomized patients, 50% who had biliopancreatic diversion and 25% who had Roux-en-Y gastric bypass – but none who had received current medical therapy – still had diabetes remission a decade later.

Until now, there had only been 5-year follow-up data from this and similar trials, Geltrude Mingrone, MD, PhD, and colleagues noted in the study published online Jan. 23 in The Lancet.

These results provide “the most robust scientific evidence yet that full-blown type 2 diabetes is a curable disease, not inevitably progressive, and irreversible,” senior author Francesco Rubino, MD, chair of bariatric and metabolic surgery at King’s College London, said in a statement from his institution.

“The results of this trial will make a noticeable difference in the field and convince even the most skeptical of clinicians about the role of metabolic surgery as part of optimal care for their patients with difficult to control type 2 diabetes,” predicted two editorialists.

Alexander D. Miras, PhD, section of metabolism, digestion, and reproduction, Imperial College London, and Carel le Roux, MBChB, PhD, of the Diabetes Complications Research Centre, University College Dublin, penned the accompanying commentary.

Patients who had metabolic surgery also had greater weight loss, reduced medication use, lower cardiovascular risk, better quality of life, and a lower incidence of diabetes-related complications compared with those who received medical therapy.

“Clinicians and policymakers should ensure that metabolic surgery is appropriately considered in the management of patients with obesity and type 2 diabetes,” advised Dr. Mingrone of King’s College London and the Catholic University of Rome, and colleagues.
 

“Reassuring results, will make a difference in the field”

“It is reassuring that we now have 10-year data showing greater efficacy of metabolic surgery than conventional medical therapy,” Dr. Miras and Dr. le Roux wrote in their commentary.

There were no unexpected risks associated with surgery, they noted, and the findings are consistent with those of 12 other randomized controlled trials in the past 12 years.

“New generations of diabetologists are now more open to the use of metabolic surgery for patients with suboptimal responses to medical treatments,” they wrote, rather than endlessly intensifying insulin and blaming poor response on poor compliance.

And Dr. Miras and Dr. le Roux “eagerly await” 10-year data from the 150-patient STAMPEDE trial – which is examining sleeve gastrectomy, currently the most widely performed bariatric procedure, as well as Roux-en-Y gastric bypass and medical therapy – following the 5-year results published in 2017.  
 

Diabetes for at least 5 years, mid 40s, half on insulin

Dr. Mingrone and colleagues previously reported 5-year findings from the 60 patients with obesity and advanced diabetes who were seen in a single center in Rome and randomized to three treatments (20 in each group) in 2009-2011.

Biliopancreatic diversion “remains infrequently performed but is still considered the best operation for glycemic control,” the researchers noted.

The primary endpoint was diabetes remission at 2 years (fasting plasma glucose < 100 mg/dL [5.6 mmol/L] and A1c < 6.5%) without the need for ongoing pharmacological treatment for at least 1 year.

Patients were a mean age of 44 years and had a mean body mass index of 44 kg/m^2. About half were men. They had diabetes for a mean of 5.8 years and an average A1c of 8.6%. About half were taking insulin.

Patient retention rate was high (95%) and trial outcomes were assessed by nonsurgeons.

At 10 years, patients’ mean A1c had dropped to 6.4%, 6.7%, and 7.6%, in the biliopancreatic diversion, Roux-en-Y gastric bypass, and medical therapy groups, respectively; only 2.5% of patients in the surgery groups, versus 53% in the medical therapy group, required insulin.

At study end, patients in the surgery groups had lost about 29% of their initial weight versus a weight loss of 4.2% in the medical therapy group.
 

First 2 years after surgery is key

“We also learnt that patients who do not go into remission after 2 years are very unlikely to ever do so,” Dr. Miras and Dr. le Roux observed, which “might help us to intensify modern and potent glucose-lowering therapies like SGLT2 inhibitors and GLP-1 receptor agonists earlier after metabolic surgery.”

Ten of 19 patients (53%) in the biliopancreatic diversion group and 10 of 15 patients (67%) in the Roux-en-Y gastric bypass group who had diabetes remission at 2 years had a diabetes relapse, but at 10 years, they all had adequate glycemic control (mean A1c 6.7%), despite drastically reduced use of diabetes medications.

The two patients who crossed over to surgery from the medical therapy group had postoperative diabetes remission, which was maintained at 10 years in one patient.
 

Better risk-to-benefit ratio with Roux-en-y gastric bypass

No patient in the medical therapy group had a serious adverse event, but one patient in each surgery group had deep vein thrombosis or pulmonary embolism, and one patient in the biliopancreatic diversion group had an episode of atrial fibrillation. There were no late surgical complications.

Iron deficiency and mild osteopenia occurred in both surgical groups, but were more common in the biliopancreatic diversion group. And osteoporosis, transient nyctalopia (night blindness) due to vitamin A deficiency, and kidney stones were observed only with biliopancreatic diversion.

This suggests that despite the greater antidiabetic potential of biliopancreatic diversion, Roux-en-Y gastric bypass might have a more favorable risk-to-benefit profile as a standard surgical option for the treatment of type 2 diabetes, Dr. Mingrone and colleagues concluded.

The authors and Dr. Miras have reported no relevant financial relationships. Dr. le Roux has reported receiving funding from the Science Foundation Ireland, the Health Research Board, and the Irish Research Council for type 2 diabetes research, and serves on several advisory boards outside of the scope of the current study.

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

A small, single-center randomized trial of patients with obesity and advanced type 2 diabetes, defined as diabetes for ≥ 5 years and A1c ≥ 7%, found that a quarter to a half of patients who had metabolic surgery had diabetes remission (cure) that lasted 5-9 years.

That is, of the 60 randomized patients, 50% who had biliopancreatic diversion and 25% who had Roux-en-Y gastric bypass – but none who had received current medical therapy – still had diabetes remission a decade later.

Until now, there had only been 5-year follow-up data from this and similar trials, Geltrude Mingrone, MD, PhD, and colleagues noted in the study published online Jan. 23 in The Lancet.

These results provide “the most robust scientific evidence yet that full-blown type 2 diabetes is a curable disease, not inevitably progressive, and irreversible,” senior author Francesco Rubino, MD, chair of bariatric and metabolic surgery at King’s College London, said in a statement from his institution.

“The results of this trial will make a noticeable difference in the field and convince even the most skeptical of clinicians about the role of metabolic surgery as part of optimal care for their patients with difficult to control type 2 diabetes,” predicted two editorialists.

Alexander D. Miras, PhD, section of metabolism, digestion, and reproduction, Imperial College London, and Carel le Roux, MBChB, PhD, of the Diabetes Complications Research Centre, University College Dublin, penned the accompanying commentary.

Patients who had metabolic surgery also had greater weight loss, reduced medication use, lower cardiovascular risk, better quality of life, and a lower incidence of diabetes-related complications compared with those who received medical therapy.

“Clinicians and policymakers should ensure that metabolic surgery is appropriately considered in the management of patients with obesity and type 2 diabetes,” advised Dr. Mingrone of King’s College London and the Catholic University of Rome, and colleagues.
 

“Reassuring results, will make a difference in the field”

“It is reassuring that we now have 10-year data showing greater efficacy of metabolic surgery than conventional medical therapy,” Dr. Miras and Dr. le Roux wrote in their commentary.

There were no unexpected risks associated with surgery, they noted, and the findings are consistent with those of 12 other randomized controlled trials in the past 12 years.

“New generations of diabetologists are now more open to the use of metabolic surgery for patients with suboptimal responses to medical treatments,” they wrote, rather than endlessly intensifying insulin and blaming poor response on poor compliance.

And Dr. Miras and Dr. le Roux “eagerly await” 10-year data from the 150-patient STAMPEDE trial – which is examining sleeve gastrectomy, currently the most widely performed bariatric procedure, as well as Roux-en-Y gastric bypass and medical therapy – following the 5-year results published in 2017.  
 

Diabetes for at least 5 years, mid 40s, half on insulin

Dr. Mingrone and colleagues previously reported 5-year findings from the 60 patients with obesity and advanced diabetes who were seen in a single center in Rome and randomized to three treatments (20 in each group) in 2009-2011.

Biliopancreatic diversion “remains infrequently performed but is still considered the best operation for glycemic control,” the researchers noted.

The primary endpoint was diabetes remission at 2 years (fasting plasma glucose < 100 mg/dL [5.6 mmol/L] and A1c < 6.5%) without the need for ongoing pharmacological treatment for at least 1 year.

Patients were a mean age of 44 years and had a mean body mass index of 44 kg/m^2. About half were men. They had diabetes for a mean of 5.8 years and an average A1c of 8.6%. About half were taking insulin.

Patient retention rate was high (95%) and trial outcomes were assessed by nonsurgeons.

At 10 years, patients’ mean A1c had dropped to 6.4%, 6.7%, and 7.6%, in the biliopancreatic diversion, Roux-en-Y gastric bypass, and medical therapy groups, respectively; only 2.5% of patients in the surgery groups, versus 53% in the medical therapy group, required insulin.

At study end, patients in the surgery groups had lost about 29% of their initial weight versus a weight loss of 4.2% in the medical therapy group.
 

First 2 years after surgery is key

“We also learnt that patients who do not go into remission after 2 years are very unlikely to ever do so,” Dr. Miras and Dr. le Roux observed, which “might help us to intensify modern and potent glucose-lowering therapies like SGLT2 inhibitors and GLP-1 receptor agonists earlier after metabolic surgery.”

Ten of 19 patients (53%) in the biliopancreatic diversion group and 10 of 15 patients (67%) in the Roux-en-Y gastric bypass group who had diabetes remission at 2 years had a diabetes relapse, but at 10 years, they all had adequate glycemic control (mean A1c 6.7%), despite drastically reduced use of diabetes medications.

The two patients who crossed over to surgery from the medical therapy group had postoperative diabetes remission, which was maintained at 10 years in one patient.
 

Better risk-to-benefit ratio with Roux-en-y gastric bypass

No patient in the medical therapy group had a serious adverse event, but one patient in each surgery group had deep vein thrombosis or pulmonary embolism, and one patient in the biliopancreatic diversion group had an episode of atrial fibrillation. There were no late surgical complications.

Iron deficiency and mild osteopenia occurred in both surgical groups, but were more common in the biliopancreatic diversion group. And osteoporosis, transient nyctalopia (night blindness) due to vitamin A deficiency, and kidney stones were observed only with biliopancreatic diversion.

This suggests that despite the greater antidiabetic potential of biliopancreatic diversion, Roux-en-Y gastric bypass might have a more favorable risk-to-benefit profile as a standard surgical option for the treatment of type 2 diabetes, Dr. Mingrone and colleagues concluded.

The authors and Dr. Miras have reported no relevant financial relationships. Dr. le Roux has reported receiving funding from the Science Foundation Ireland, the Health Research Board, and the Irish Research Council for type 2 diabetes research, and serves on several advisory boards outside of the scope of the current study.

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