The hemophilia A treatment paradigm has shifted away from simply maintaining a prophylaxis trough level of 1% towards a focus on patient outcomes and leading healthy, active lives, according to a recent report in The Journal of Medicine in Life.

To get there, the World Federation of Hemophilia (WFH) has recognized that physicians need to aim for higher trough levels so patients can lead as normal a life as possible, but there’s debate about which levels are ideal.

“There is increasing recognition and evidence from the literature that factor trough levels of 1%-3% are insufficient to prevent bleeds in all patients with hemophilia. It has also been suggested that maintaining higher factor levels (above 10%) may be optimal to prevent subclinical bleeding and the gradual progression of joint disease over a lifespan in very active patients,” according to the report.

The paper was a summary of expert opinion on the issue and a range of other current and future challenges in hemophilia care. Switzerland-based Sobi surveyed nine hemophilia experts in central Europe for their insights, then convened an advisory panel to flesh out their responses.

They were asked for their thoughts on the efficacy of factor versus non-factor replacement therapy when aiming for a 3%-5% target trough for hemophilia A prophylaxis.

About half said non-factor therapy was more effective, while the other half favored factor therapy because it has similar efficacy and allows the tailoring of treatment to individual pharmacokinetic data, physical activity, and the condition of the musculoskeletal system.

However, “if the new treatment aim for [prophylaxis] is to increase the trough level, existing and future prophylactic regimens are likely to require adjustment. Maintaining such high trough levels in some patients may lead to the re-shortening of longer treatment intervals and, consequently, an increase of previously reduced factor consumption, which has been an important benefit of [extended half-life] products,” the report noted.

“This creates space for next-generation FVIII replacement therapy,” such as Sobi’s efanesoctocog alfa, which has been granted fast-track designation in the United States for hemophilia treatment, the report notes.

There was also a split in opinion on whether factor therapy offered similar or improved efficacy, compared with non-factor therapy when prophylaxis is intensified to aim for a 10% trough in very active patients. Factor prophylaxis “may be preferable for active hemophilia A” because of the greater personalization, it said.

The experts noted that trough levels are just one aspect of patient care; the overall aim is a better quality of life. The panel was asked about how quality of life could be enhanced in the future. More than half said that the move towards personalized treatment is key, including greater use of telemedicine applications such as Sobi’s florio HAEMO and Takeda’s MyPKFit.

“In addition, most of the experts agreed that novel therapies such as the new class of FVIII replacement therapy, efanesoctocog alfa (BIVV001), would become another mainstream therapy due to its potential to achieve personalized, extended protection against all bleeding types in patients with severe hemophilia A,” the report said.

In the meantime, the advent of extended half-life products and novel non-factor therapies such as emicizumab; subcutaneous siRNA prophylactic therapies such as fitusiran; and anti-tissue factor pathway inhibitors such as marstacimab – each with different mechanisms of action – has led to new challenges in laboratory monitoring.

For more personalized treatment to happen, “it will be necessary for specialized clinical laboratories to be fully equipped with the required equipment, product-specific reagents, and expertise to perform appropriate assays and monitor levels of coagulation activity,” the report noted.

Thrombin generation assays to measure the dynamics of blood coagulation are promising. “There’s significant potential for monitoring the efficacy” of prophylaxis across various established and novel hemophilia treatments, but the approach “is still in its infancy,” the report noted.

Overall, “new and emerging therapies such as novel [extended half-life] factor concentrates and non-factor treatments will likely reshape hemophilia care within the next decade, providing more efficacious and convenient management options and possibly curative therapies,” it said.

The work was funded by Sobi. Most of the panelists disclosed speaker/advisor fees and/or research funding from the company, as well as many others.

The hemophilia A treatment paradigm has shifted away from simply maintaining a prophylaxis trough level of 1% towards a focus on patient outcomes and leading healthy, active lives, according to a recent report in The Journal of Medicine in Life.

To get there, the World Federation of Hemophilia (WFH) has recognized that physicians need to aim for higher trough levels so patients can lead as normal a life as possible, but there’s debate about which levels are ideal.

“There is increasing recognition and evidence from the literature that factor trough levels of 1%-3% are insufficient to prevent bleeds in all patients with hemophilia. It has also been suggested that maintaining higher factor levels (above 10%) may be optimal to prevent subclinical bleeding and the gradual progression of joint disease over a lifespan in very active patients,” according to the report.

The paper was a summary of expert opinion on the issue and a range of other current and future challenges in hemophilia care. Switzerland-based Sobi surveyed nine hemophilia experts in central Europe for their insights, then convened an advisory panel to flesh out their responses.

They were asked for their thoughts on the efficacy of factor versus non-factor replacement therapy when aiming for a 3%-5% target trough for hemophilia A prophylaxis.

About half said non-factor therapy was more effective, while the other half favored factor therapy because it has similar efficacy and allows the tailoring of treatment to individual pharmacokinetic data, physical activity, and the condition of the musculoskeletal system.

However, “if the new treatment aim for [prophylaxis] is to increase the trough level, existing and future prophylactic regimens are likely to require adjustment. Maintaining such high trough levels in some patients may lead to the re-shortening of longer treatment intervals and, consequently, an increase of previously reduced factor consumption, which has been an important benefit of [extended half-life] products,” the report noted.

“This creates space for next-generation FVIII replacement therapy,” such as Sobi’s efanesoctocog alfa, which has been granted fast-track designation in the United States for hemophilia treatment, the report notes.

There was also a split in opinion on whether factor therapy offered similar or improved efficacy, compared with non-factor therapy when prophylaxis is intensified to aim for a 10% trough in very active patients. Factor prophylaxis “may be preferable for active hemophilia A” because of the greater personalization, it said.

The experts noted that trough levels are just one aspect of patient care; the overall aim is a better quality of life. The panel was asked about how quality of life could be enhanced in the future. More than half said that the move towards personalized treatment is key, including greater use of telemedicine applications such as Sobi’s florio HAEMO and Takeda’s MyPKFit.

“In addition, most of the experts agreed that novel therapies such as the new class of FVIII replacement therapy, efanesoctocog alfa (BIVV001), would become another mainstream therapy due to its potential to achieve personalized, extended protection against all bleeding types in patients with severe hemophilia A,” the report said.

In the meantime, the advent of extended half-life products and novel non-factor therapies such as emicizumab; subcutaneous siRNA prophylactic therapies such as fitusiran; and anti-tissue factor pathway inhibitors such as marstacimab – each with different mechanisms of action – has led to new challenges in laboratory monitoring.

For more personalized treatment to happen, “it will be necessary for specialized clinical laboratories to be fully equipped with the required equipment, product-specific reagents, and expertise to perform appropriate assays and monitor levels of coagulation activity,” the report noted.

Thrombin generation assays to measure the dynamics of blood coagulation are promising. “There’s significant potential for monitoring the efficacy” of prophylaxis across various established and novel hemophilia treatments, but the approach “is still in its infancy,” the report noted.

Overall, “new and emerging therapies such as novel [extended half-life] factor concentrates and non-factor treatments will likely reshape hemophilia care within the next decade, providing more efficacious and convenient management options and possibly curative therapies,” it said.

The work was funded by Sobi. Most of the panelists disclosed speaker/advisor fees and/or research funding from the company, as well as many others.

The hemophilia A treatment paradigm has shifted away from simply maintaining a prophylaxis trough level of 1% towards a focus on patient outcomes and leading healthy, active lives, according to a recent report in The Journal of Medicine in Life.

To get there, the World Federation of Hemophilia (WFH) has recognized that physicians need to aim for higher trough levels so patients can lead as normal a life as possible, but there’s debate about which levels are ideal.

“There is increasing recognition and evidence from the literature that factor trough levels of 1%-3% are insufficient to prevent bleeds in all patients with hemophilia. It has also been suggested that maintaining higher factor levels (above 10%) may be optimal to prevent subclinical bleeding and the gradual progression of joint disease over a lifespan in very active patients,” according to the report.

The paper was a summary of expert opinion on the issue and a range of other current and future challenges in hemophilia care. Switzerland-based Sobi surveyed nine hemophilia experts in central Europe for their insights, then convened an advisory panel to flesh out their responses.

They were asked for their thoughts on the efficacy of factor versus non-factor replacement therapy when aiming for a 3%-5% target trough for hemophilia A prophylaxis.

About half said non-factor therapy was more effective, while the other half favored factor therapy because it has similar efficacy and allows the tailoring of treatment to individual pharmacokinetic data, physical activity, and the condition of the musculoskeletal system.

However, “if the new treatment aim for [prophylaxis] is to increase the trough level, existing and future prophylactic regimens are likely to require adjustment. Maintaining such high trough levels in some patients may lead to the re-shortening of longer treatment intervals and, consequently, an increase of previously reduced factor consumption, which has been an important benefit of [extended half-life] products,” the report noted.

“This creates space for next-generation FVIII replacement therapy,” such as Sobi’s efanesoctocog alfa, which has been granted fast-track designation in the United States for hemophilia treatment, the report notes.

There was also a split in opinion on whether factor therapy offered similar or improved efficacy, compared with non-factor therapy when prophylaxis is intensified to aim for a 10% trough in very active patients. Factor prophylaxis “may be preferable for active hemophilia A” because of the greater personalization, it said.

The experts noted that trough levels are just one aspect of patient care; the overall aim is a better quality of life. The panel was asked about how quality of life could be enhanced in the future. More than half said that the move towards personalized treatment is key, including greater use of telemedicine applications such as Sobi’s florio HAEMO and Takeda’s MyPKFit.

“In addition, most of the experts agreed that novel therapies such as the new class of FVIII replacement therapy, efanesoctocog alfa (BIVV001), would become another mainstream therapy due to its potential to achieve personalized, extended protection against all bleeding types in patients with severe hemophilia A,” the report said.

In the meantime, the advent of extended half-life products and novel non-factor therapies such as emicizumab; subcutaneous siRNA prophylactic therapies such as fitusiran; and anti-tissue factor pathway inhibitors such as marstacimab – each with different mechanisms of action – has led to new challenges in laboratory monitoring.

For more personalized treatment to happen, “it will be necessary for specialized clinical laboratories to be fully equipped with the required equipment, product-specific reagents, and expertise to perform appropriate assays and monitor levels of coagulation activity,” the report noted.

Thrombin generation assays to measure the dynamics of blood coagulation are promising. “There’s significant potential for monitoring the efficacy” of prophylaxis across various established and novel hemophilia treatments, but the approach “is still in its infancy,” the report noted.

Overall, “new and emerging therapies such as novel [extended half-life] factor concentrates and non-factor treatments will likely reshape hemophilia care within the next decade, providing more efficacious and convenient management options and possibly curative therapies,” it said.

The work was funded by Sobi. Most of the panelists disclosed speaker/advisor fees and/or research funding from the company, as well as many others.

Over the past decade, the U.S. Food and Drug Administration has approved new cancer drugs twice as fast as the European Medicines Agency (EMA), often using accelerated pathways, a new analysis shows.

Between 2010 and 2019, the FDA approved almost all oncology therapies ahead of the EMA. Drugs entered the United States market about 8 months (241 days) before European market authorization.

But do quicker review times translate to wins for patients?

“The faster FDA approval process potentially provides earlier access to potentially life-prolonging medications for patients with cancer in the United States,” Ali Raza Khaki, MD, department of oncology, Stanford (Calif.) University School of Medicine, told this news organization. “On the surface, this is a good thing. However, it comes with limitations.”

Earlier drug approval often means greater uncertainty about an agent’s benefit – most notably, whether it will improve a patient’s survival or quality of life. Dr. Khaki pointed to a study published in JAMA Internal Medicine, which found that only 19 of 93 (20%) cancer drugs that had been recently approved through the FDA’s accelerated approval pathway demonstrated an improvement in overall survival.

In the new study, published online in JAMA Network Open, Dr. Khaki and colleagues found that among the 89 cancer drugs approved in the United States and Europe between January 2010 and December 2019, the FDA approved 85 (95%) before European authorization and four (5%) after.

The researchers found that the median FDA review time was half that of the EMA’s (200 vs. 426 days). Furthermore, 64 new drug applications (72%) were submitted to the FDA first, compared with 21 (23%) to the EMA.

Of the drugs approved through an accelerated pathway, three were ultimately pulled from the U.S. market, compared with one in Europe.

“These early drug approvals that later lead to withdrawal expose many more patients to toxicity, including financial toxicity, given the high cost of cancer medications,” Dr. Khaki commented.

In addition, 35 oncology therapies (39%) were approved by the FDA before trial results were published, compared with only eight (9%) by the EMA. Although FDA drug labels contain some information about efficacy and toxicity, scientific publications often have much more, including details about study populations and toxicities.

“Without this information, providers may be limited in their knowledge about patient selection, clinical benefit, and optimal toxicity management,” Dr. Khaki said.

Jeff Allen PhD, president and CEO of the nonprofit Friends of Cancer Research, who wasn’t involved in the study, believes that an FDA approval before publication shouldn’t be “particularly concerning.”

“Peer-reviewed publication is an important component of validating and communicating scientific findings, but the processes and time lines for individual journals can be highly variable,” he said. “I don’t think we would want to see a situation where potential beneficial treatments are held up due to unrelated publication processes.”

The author of an invited commentary in JAMA Network Open had a different take on the study findings.

“A tempting interpretation” of this study is that the FDA is a “superior agency for expedited review times that bring cancer drugs to patients earlier,” Kristina Jenei, BSN, MSc, with the University of British Columbia School of Population and Public Health, writes. In addition, the fact that more drugs were pulled from the market after approval in the United States than in Europe could be interpreted to mean that the system is working as it should.

Although the speed of FDA reviews and the number of subsequent approvals have increased over time, the proportion of cancer drugs that improve survival has declined. In addition, because the FDA’s follow-up of postmarketing studies has been “inconsistent,” a substantial number of cancer drugs that were approved through accelerated pathways have remained on the market for years without confirmation of their benefit.

Although regulatory agencies must balance earlier patient access to novel treatments with evidence that the therapies are effective and safe, “faster review times and approvals are not cause for celebration; better patient outcomes are,” Ms. Jenei writes. “In other words, quality over quantity.”

The study was supported by the National Cancer Institute. Dr. Khaki reported stock ownership from Merck and stock ownership from Sanofi outside the submitted work. Dr. Allen and Ms. Jenei have disclosed no relevant financial relationships.

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

Over the past decade, the U.S. Food and Drug Administration has approved new cancer drugs twice as fast as the European Medicines Agency (EMA), often using accelerated pathways, a new analysis shows.

Between 2010 and 2019, the FDA approved almost all oncology therapies ahead of the EMA. Drugs entered the United States market about 8 months (241 days) before European market authorization.

But do quicker review times translate to wins for patients?

“The faster FDA approval process potentially provides earlier access to potentially life-prolonging medications for patients with cancer in the United States,” Ali Raza Khaki, MD, department of oncology, Stanford (Calif.) University School of Medicine, told this news organization. “On the surface, this is a good thing. However, it comes with limitations.”

Earlier drug approval often means greater uncertainty about an agent’s benefit – most notably, whether it will improve a patient’s survival or quality of life. Dr. Khaki pointed to a study published in JAMA Internal Medicine, which found that only 19 of 93 (20%) cancer drugs that had been recently approved through the FDA’s accelerated approval pathway demonstrated an improvement in overall survival.

In the new study, published online in JAMA Network Open, Dr. Khaki and colleagues found that among the 89 cancer drugs approved in the United States and Europe between January 2010 and December 2019, the FDA approved 85 (95%) before European authorization and four (5%) after.

The researchers found that the median FDA review time was half that of the EMA’s (200 vs. 426 days). Furthermore, 64 new drug applications (72%) were submitted to the FDA first, compared with 21 (23%) to the EMA.

Of the drugs approved through an accelerated pathway, three were ultimately pulled from the U.S. market, compared with one in Europe.

“These early drug approvals that later lead to withdrawal expose many more patients to toxicity, including financial toxicity, given the high cost of cancer medications,” Dr. Khaki commented.

In addition, 35 oncology therapies (39%) were approved by the FDA before trial results were published, compared with only eight (9%) by the EMA. Although FDA drug labels contain some information about efficacy and toxicity, scientific publications often have much more, including details about study populations and toxicities.

“Without this information, providers may be limited in their knowledge about patient selection, clinical benefit, and optimal toxicity management,” Dr. Khaki said.

Jeff Allen PhD, president and CEO of the nonprofit Friends of Cancer Research, who wasn’t involved in the study, believes that an FDA approval before publication shouldn’t be “particularly concerning.”

“Peer-reviewed publication is an important component of validating and communicating scientific findings, but the processes and time lines for individual journals can be highly variable,” he said. “I don’t think we would want to see a situation where potential beneficial treatments are held up due to unrelated publication processes.”

The author of an invited commentary in JAMA Network Open had a different take on the study findings.

“A tempting interpretation” of this study is that the FDA is a “superior agency for expedited review times that bring cancer drugs to patients earlier,” Kristina Jenei, BSN, MSc, with the University of British Columbia School of Population and Public Health, writes. In addition, the fact that more drugs were pulled from the market after approval in the United States than in Europe could be interpreted to mean that the system is working as it should.

Although the speed of FDA reviews and the number of subsequent approvals have increased over time, the proportion of cancer drugs that improve survival has declined. In addition, because the FDA’s follow-up of postmarketing studies has been “inconsistent,” a substantial number of cancer drugs that were approved through accelerated pathways have remained on the market for years without confirmation of their benefit.

Although regulatory agencies must balance earlier patient access to novel treatments with evidence that the therapies are effective and safe, “faster review times and approvals are not cause for celebration; better patient outcomes are,” Ms. Jenei writes. “In other words, quality over quantity.”

The study was supported by the National Cancer Institute. Dr. Khaki reported stock ownership from Merck and stock ownership from Sanofi outside the submitted work. Dr. Allen and Ms. Jenei have disclosed no relevant financial relationships.

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

Over the past decade, the U.S. Food and Drug Administration has approved new cancer drugs twice as fast as the European Medicines Agency (EMA), often using accelerated pathways, a new analysis shows.

Between 2010 and 2019, the FDA approved almost all oncology therapies ahead of the EMA. Drugs entered the United States market about 8 months (241 days) before European market authorization.

But do quicker review times translate to wins for patients?

“The faster FDA approval process potentially provides earlier access to potentially life-prolonging medications for patients with cancer in the United States,” Ali Raza Khaki, MD, department of oncology, Stanford (Calif.) University School of Medicine, told this news organization. “On the surface, this is a good thing. However, it comes with limitations.”

Earlier drug approval often means greater uncertainty about an agent’s benefit – most notably, whether it will improve a patient’s survival or quality of life. Dr. Khaki pointed to a study published in JAMA Internal Medicine, which found that only 19 of 93 (20%) cancer drugs that had been recently approved through the FDA’s accelerated approval pathway demonstrated an improvement in overall survival.

In the new study, published online in JAMA Network Open, Dr. Khaki and colleagues found that among the 89 cancer drugs approved in the United States and Europe between January 2010 and December 2019, the FDA approved 85 (95%) before European authorization and four (5%) after.

The researchers found that the median FDA review time was half that of the EMA’s (200 vs. 426 days). Furthermore, 64 new drug applications (72%) were submitted to the FDA first, compared with 21 (23%) to the EMA.

Of the drugs approved through an accelerated pathway, three were ultimately pulled from the U.S. market, compared with one in Europe.

“These early drug approvals that later lead to withdrawal expose many more patients to toxicity, including financial toxicity, given the high cost of cancer medications,” Dr. Khaki commented.

In addition, 35 oncology therapies (39%) were approved by the FDA before trial results were published, compared with only eight (9%) by the EMA. Although FDA drug labels contain some information about efficacy and toxicity, scientific publications often have much more, including details about study populations and toxicities.

“Without this information, providers may be limited in their knowledge about patient selection, clinical benefit, and optimal toxicity management,” Dr. Khaki said.

Jeff Allen PhD, president and CEO of the nonprofit Friends of Cancer Research, who wasn’t involved in the study, believes that an FDA approval before publication shouldn’t be “particularly concerning.”

“Peer-reviewed publication is an important component of validating and communicating scientific findings, but the processes and time lines for individual journals can be highly variable,” he said. “I don’t think we would want to see a situation where potential beneficial treatments are held up due to unrelated publication processes.”

The author of an invited commentary in JAMA Network Open had a different take on the study findings.

“A tempting interpretation” of this study is that the FDA is a “superior agency for expedited review times that bring cancer drugs to patients earlier,” Kristina Jenei, BSN, MSc, with the University of British Columbia School of Population and Public Health, writes. In addition, the fact that more drugs were pulled from the market after approval in the United States than in Europe could be interpreted to mean that the system is working as it should.

Although the speed of FDA reviews and the number of subsequent approvals have increased over time, the proportion of cancer drugs that improve survival has declined. In addition, because the FDA’s follow-up of postmarketing studies has been “inconsistent,” a substantial number of cancer drugs that were approved through accelerated pathways have remained on the market for years without confirmation of their benefit.

Although regulatory agencies must balance earlier patient access to novel treatments with evidence that the therapies are effective and safe, “faster review times and approvals are not cause for celebration; better patient outcomes are,” Ms. Jenei writes. “In other words, quality over quantity.”

The study was supported by the National Cancer Institute. Dr. Khaki reported stock ownership from Merck and stock ownership from Sanofi outside the submitted work. Dr. Allen and Ms. Jenei have disclosed no relevant financial relationships.

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

Adults in the United States increasingly perceive electronic cigarettes, or e-cigarettes, as “more harmful” than traditional cigarettes, according to a new study published in the American Journal of Preventive Medicine.

In addition, the percentage of people who exclusively used traditional cigarettes almost doubled between 2019 and 2020 among those who perceived e-cigarettes as more harmful, jumping from 8.4% in 2019 to 16.3% in 2020.

“We were able to show that these changes in perception potentially changed behaviors on a population level,” said Priti Bandi, PhD, principal scientist at the American Cancer Society in Atlanta and lead author of the study.

Since e-cigarettes entered the U.S. market in 2006, public health experts have questioned claims from manufacturers that the products work as a harm reduction tool to help traditional cigarette smokers to quit. Public perceptions have generally been that e-cigarettes are safer for a person’s health. While the research is still emerging on the long-term health outcomes of users, public opinion has shifted since the introduction of the devices.

The new study showed a sharp change in public perception of e-cigarettes following media coverage of cases of users who presented to emergency rooms with mysterious lung symptoms in 2019. The Centers for Disease Control and Prevention eventually found that what are now called e-cigarette or vaping product use–associated lung injuries were linked to vitamin E acetate, an additive to tetrahydrocannabinol-containing products but not nicotine.

The last update from the CDC came in February 2020, shortly before the COVID-19 pandemic swept through the United States, prompting a sharp shift to investigate the new virus among both health care providers and researchers.

Dr. Bandi and colleagues gathered 2018-2020 data from a National Institutes of Health database called the Health Information National Trends Survey, a mail-based, nationally representative, cross-sectional survey of U.S. adults and their attitudes of cancer and health-related information. More than 3,000 people each year responded to questions about e-cigarettes.

The study found that the percentage of people who believed e-cigarettes to be more harmful than traditional cigarettes more than tripled from 6.8% in 2018 to 28.3% in 2020. Fewer people also viewed e-cigarettes as less harmful than traditional cigarettes, falling from 17.6% in 2018 to 11.4% in 2020. Fewer people also said they were unsure about which product was more harmful.

Among those who believed e-cigarettes were “relatively” less harmful than traditional cigarettes, use of e-cigarettes jumped from 15.3% in 2019 to 26.7% in 2020.
 

The implications

The main finding that people started smoking cigarettes when they thought e-cigarettes were more harmful should be a wake-up to public health officials and doctors who communicate health risks to patients, according to Dr. Bandi and other experts.

Messaging should be more nuanced, Dr. Bandi said. Many adults use e-cigarettes as a cessation tool, and she and other experts point to research that shows the products are, at least in the short-term, less harmful especially as a smoking cessation tool. Vapes are among the most popular tools people use when they want to quit smoking – with the majority of U.S. adults using vapes either partially or fully to quit, according to the CDC.

Some countries, such as England, are moving to allow doctors to prescribe e-cigarettes to help reduce smoking rates. United Kingdom regulatory authorities in 2021 said they’re considering allowing licensing the devices for use in smoking cessation.

“There is an absolute need for ongoing, accurate communication from public health authorities targeted toward the appropriate audiences,” Bandi said.

Ashley Brooks-Russell, PhD, MPH, associate professor at the University of Colorado at Denver, Aurora, said the finding that perceptions can change behavior is good news. However, the bad news is that adults overcorrected and switched to cigarettes, which are proven to cause cancer and other health conditions.

“We’re good in public health about messaging that cigarettes are bad, that tobacco is broadly harmful,” Dr. Brooks-Russell said in an interview. “We’re really bad at talking about lesser options, like if you’re going to smoke, e-cigarettes are less harmful.” 

But other health leaders warn that e-cigarettes might produce the same adverse health outcomes, or worse, as cigarettes. The only way researchers will gain a conclusive answer is decades into a patient’s life. Until then, it’s not clear if any potential benefit from smoking cessation will outweigh the risks.

“This research should remind healthcare providers to find out what products patients are using, how much, and if those patients experience health issues later on,” said Kevin McQueen, MHA, lead respiratory director at University of Colorado Health System and president of the Colorado Respiratory Care Society.

“My concern is that while people are starting to think e-cigarettes are more dangerous, some people still think they are safe – and we don’t know how much safer they are,” he said. “And we aren’t going to know until 10, 15, 20 years from now.”

All authors were employed by the American Cancer Society at the time of the study, which receives grants from private and corporate foundations, including foundations associated with companies in the health sector for research outside of the submitted work. The authors are not funded by or key personnel for any of these grants, and their salaries are solely funded through American Cancer Society funds. No other financial disclosures were reported.

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

Adults in the United States increasingly perceive electronic cigarettes, or e-cigarettes, as “more harmful” than traditional cigarettes, according to a new study published in the American Journal of Preventive Medicine.

In addition, the percentage of people who exclusively used traditional cigarettes almost doubled between 2019 and 2020 among those who perceived e-cigarettes as more harmful, jumping from 8.4% in 2019 to 16.3% in 2020.

“We were able to show that these changes in perception potentially changed behaviors on a population level,” said Priti Bandi, PhD, principal scientist at the American Cancer Society in Atlanta and lead author of the study.

Since e-cigarettes entered the U.S. market in 2006, public health experts have questioned claims from manufacturers that the products work as a harm reduction tool to help traditional cigarette smokers to quit. Public perceptions have generally been that e-cigarettes are safer for a person’s health. While the research is still emerging on the long-term health outcomes of users, public opinion has shifted since the introduction of the devices.

The new study showed a sharp change in public perception of e-cigarettes following media coverage of cases of users who presented to emergency rooms with mysterious lung symptoms in 2019. The Centers for Disease Control and Prevention eventually found that what are now called e-cigarette or vaping product use–associated lung injuries were linked to vitamin E acetate, an additive to tetrahydrocannabinol-containing products but not nicotine.

The last update from the CDC came in February 2020, shortly before the COVID-19 pandemic swept through the United States, prompting a sharp shift to investigate the new virus among both health care providers and researchers.

Dr. Bandi and colleagues gathered 2018-2020 data from a National Institutes of Health database called the Health Information National Trends Survey, a mail-based, nationally representative, cross-sectional survey of U.S. adults and their attitudes of cancer and health-related information. More than 3,000 people each year responded to questions about e-cigarettes.

The study found that the percentage of people who believed e-cigarettes to be more harmful than traditional cigarettes more than tripled from 6.8% in 2018 to 28.3% in 2020. Fewer people also viewed e-cigarettes as less harmful than traditional cigarettes, falling from 17.6% in 2018 to 11.4% in 2020. Fewer people also said they were unsure about which product was more harmful.

Among those who believed e-cigarettes were “relatively” less harmful than traditional cigarettes, use of e-cigarettes jumped from 15.3% in 2019 to 26.7% in 2020.
 

The implications

The main finding that people started smoking cigarettes when they thought e-cigarettes were more harmful should be a wake-up to public health officials and doctors who communicate health risks to patients, according to Dr. Bandi and other experts.

Messaging should be more nuanced, Dr. Bandi said. Many adults use e-cigarettes as a cessation tool, and she and other experts point to research that shows the products are, at least in the short-term, less harmful especially as a smoking cessation tool. Vapes are among the most popular tools people use when they want to quit smoking – with the majority of U.S. adults using vapes either partially or fully to quit, according to the CDC.

Some countries, such as England, are moving to allow doctors to prescribe e-cigarettes to help reduce smoking rates. United Kingdom regulatory authorities in 2021 said they’re considering allowing licensing the devices for use in smoking cessation.

“There is an absolute need for ongoing, accurate communication from public health authorities targeted toward the appropriate audiences,” Bandi said.

Ashley Brooks-Russell, PhD, MPH, associate professor at the University of Colorado at Denver, Aurora, said the finding that perceptions can change behavior is good news. However, the bad news is that adults overcorrected and switched to cigarettes, which are proven to cause cancer and other health conditions.

“We’re good in public health about messaging that cigarettes are bad, that tobacco is broadly harmful,” Dr. Brooks-Russell said in an interview. “We’re really bad at talking about lesser options, like if you’re going to smoke, e-cigarettes are less harmful.” 

But other health leaders warn that e-cigarettes might produce the same adverse health outcomes, or worse, as cigarettes. The only way researchers will gain a conclusive answer is decades into a patient’s life. Until then, it’s not clear if any potential benefit from smoking cessation will outweigh the risks.

“This research should remind healthcare providers to find out what products patients are using, how much, and if those patients experience health issues later on,” said Kevin McQueen, MHA, lead respiratory director at University of Colorado Health System and president of the Colorado Respiratory Care Society.

“My concern is that while people are starting to think e-cigarettes are more dangerous, some people still think they are safe – and we don’t know how much safer they are,” he said. “And we aren’t going to know until 10, 15, 20 years from now.”

All authors were employed by the American Cancer Society at the time of the study, which receives grants from private and corporate foundations, including foundations associated with companies in the health sector for research outside of the submitted work. The authors are not funded by or key personnel for any of these grants, and their salaries are solely funded through American Cancer Society funds. No other financial disclosures were reported.

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

Adults in the United States increasingly perceive electronic cigarettes, or e-cigarettes, as “more harmful” than traditional cigarettes, according to a new study published in the American Journal of Preventive Medicine.

In addition, the percentage of people who exclusively used traditional cigarettes almost doubled between 2019 and 2020 among those who perceived e-cigarettes as more harmful, jumping from 8.4% in 2019 to 16.3% in 2020.

“We were able to show that these changes in perception potentially changed behaviors on a population level,” said Priti Bandi, PhD, principal scientist at the American Cancer Society in Atlanta and lead author of the study.

Since e-cigarettes entered the U.S. market in 2006, public health experts have questioned claims from manufacturers that the products work as a harm reduction tool to help traditional cigarette smokers to quit. Public perceptions have generally been that e-cigarettes are safer for a person’s health. While the research is still emerging on the long-term health outcomes of users, public opinion has shifted since the introduction of the devices.

The new study showed a sharp change in public perception of e-cigarettes following media coverage of cases of users who presented to emergency rooms with mysterious lung symptoms in 2019. The Centers for Disease Control and Prevention eventually found that what are now called e-cigarette or vaping product use–associated lung injuries were linked to vitamin E acetate, an additive to tetrahydrocannabinol-containing products but not nicotine.

The last update from the CDC came in February 2020, shortly before the COVID-19 pandemic swept through the United States, prompting a sharp shift to investigate the new virus among both health care providers and researchers.

Dr. Bandi and colleagues gathered 2018-2020 data from a National Institutes of Health database called the Health Information National Trends Survey, a mail-based, nationally representative, cross-sectional survey of U.S. adults and their attitudes of cancer and health-related information. More than 3,000 people each year responded to questions about e-cigarettes.

The study found that the percentage of people who believed e-cigarettes to be more harmful than traditional cigarettes more than tripled from 6.8% in 2018 to 28.3% in 2020. Fewer people also viewed e-cigarettes as less harmful than traditional cigarettes, falling from 17.6% in 2018 to 11.4% in 2020. Fewer people also said they were unsure about which product was more harmful.

Among those who believed e-cigarettes were “relatively” less harmful than traditional cigarettes, use of e-cigarettes jumped from 15.3% in 2019 to 26.7% in 2020.
 

The implications

The main finding that people started smoking cigarettes when they thought e-cigarettes were more harmful should be a wake-up to public health officials and doctors who communicate health risks to patients, according to Dr. Bandi and other experts.

Messaging should be more nuanced, Dr. Bandi said. Many adults use e-cigarettes as a cessation tool, and she and other experts point to research that shows the products are, at least in the short-term, less harmful especially as a smoking cessation tool. Vapes are among the most popular tools people use when they want to quit smoking – with the majority of U.S. adults using vapes either partially or fully to quit, according to the CDC.

Some countries, such as England, are moving to allow doctors to prescribe e-cigarettes to help reduce smoking rates. United Kingdom regulatory authorities in 2021 said they’re considering allowing licensing the devices for use in smoking cessation.

“There is an absolute need for ongoing, accurate communication from public health authorities targeted toward the appropriate audiences,” Bandi said.

Ashley Brooks-Russell, PhD, MPH, associate professor at the University of Colorado at Denver, Aurora, said the finding that perceptions can change behavior is good news. However, the bad news is that adults overcorrected and switched to cigarettes, which are proven to cause cancer and other health conditions.

“We’re good in public health about messaging that cigarettes are bad, that tobacco is broadly harmful,” Dr. Brooks-Russell said in an interview. “We’re really bad at talking about lesser options, like if you’re going to smoke, e-cigarettes are less harmful.” 

But other health leaders warn that e-cigarettes might produce the same adverse health outcomes, or worse, as cigarettes. The only way researchers will gain a conclusive answer is decades into a patient’s life. Until then, it’s not clear if any potential benefit from smoking cessation will outweigh the risks.

“This research should remind healthcare providers to find out what products patients are using, how much, and if those patients experience health issues later on,” said Kevin McQueen, MHA, lead respiratory director at University of Colorado Health System and president of the Colorado Respiratory Care Society.

“My concern is that while people are starting to think e-cigarettes are more dangerous, some people still think they are safe – and we don’t know how much safer they are,” he said. “And we aren’t going to know until 10, 15, 20 years from now.”

All authors were employed by the American Cancer Society at the time of the study, which receives grants from private and corporate foundations, including foundations associated with companies in the health sector for research outside of the submitted work. The authors are not funded by or key personnel for any of these grants, and their salaries are solely funded through American Cancer Society funds. No other financial disclosures were reported.

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

ATLANTA – Disturbances in ovulation that didn’t produce any actual changes in the menstrual cycle of women were extremely common during the first year of the COVID-19 pandemic and were linked to emotional stress, according to the findings of an “experiment of nature” that allowed for comparison with women a decade earlier.

Findings from two studies of reproductive-age women, one conducted in 2006-2008 and the other in 2020-2021, were presented by Jerilynn C. Prior, MD, at the annual meeting of the Endocrine Society.

The comparison of the two time periods yielded several novel findings. “I was taught in medical school that when women don’t eat enough they lose their period. But what we now understand is there’s a graded response to various stressors, acting through the hypothalamus in a common pathway. There is a gradation of disturbances, some of which are subclinical or not obvious,” said Dr. Prior, professor of endocrinology and metabolism at the University of British Columbia, Vancouver.

Moreover, women’s menstrual cycle lengths didn’t differ across the two time periods, despite a dramatic 63% decrement in normal ovulatory function related to increased depression, anxiety, and outside stresses that the women reported in diaries.

“Assuming that regular cycles need normal ovulation is something we should just get out of our minds. It changes our concept about what’s normal if we only know about the cycle length,” she observed.

It will be critical going forward to see whether the ovulatory disturbances have resolved as the pandemic has shifted “because there’s strong evidence that ovulatory disturbances, even with normal cycle length, are related to bone loss and some evidence it’s related to early heart attacks, breast and endometrial cancers,” Dr. Prior said during a press conference.

Lisa Nainggolan/MDedge News

Asked to comment, session moderator Genevieve Neal-Perry, MD, PhD, told this news organization: “I think what we can take away is that stress itself is a modifier of the way the brain and the gonads communicate with each other, and that then has an impact on ovulatory function.”

Dr. Neal-Perry noted that the association of stress and ovulatory disruption has been reported in various ways previously, but “clearly it doesn’t affect everyone. What we don’t know is who is most susceptible. There have been some studies showing a genetic predisposition and a genetic anomaly that actually makes them more susceptible to the impact of stress on the reproductive system.”

But the lack of data on weight change in the study cohorts is a limitation. “To me one of the more important questions was what was going on with weight. Just looking at a static number doesn’t tell you whether there were changes. We know that weight gain or weight loss can stress the reproductive axis,” noted Dr. Neal-Parry of the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill.
 

‘Experiment of nature’ revealed invisible effect of pandemic stress

The women in both cohorts of the Menstruation Ovulation Study (MOS) were healthy volunteers aged 19-35 years recruited from the metropolitan Vancouver region. All were menstruating monthly and none were taking hormonal birth control. Recruitment for the second cohort had begun just prior to the March 2020 COVID-19 pandemic lockdown.

Interviewer-administered questionnaires (CaMos) covering demographics, socioeconomic status, and reproductive history, and daily diaries kept by the women (menstrual cycle diary) were identical for both cohorts.

Assessments of ovulation differed for the two studies but were cross-validated. For the earlier time period, ovulation was assessed by a threefold increase in follicular-to-luteal urinary progesterone (PdG). For the pandemic-era study, the validated quantitative basal temperature (QBT) method was used.

There were 301 women in the earlier cohort and 125 during the pandemic. Both were an average age of about 29 years and had a body mass index of about 24.3 kg/m² (within the normal range). The pandemic cohort was more racially/ethnically diverse than the earlier one and more in-line with recent census data.

More of the women were nulliparous during the pandemic than earlier (92.7% vs. 80.4%; P = .002).

The distribution of menstrual cycle lengths didn’t differ, with both cohorts averaging about 30 days (P = .893). However, while 90% of the women in the earlier cohort ovulated normally, only 37% did during the pandemic, a highly significant difference (P < .0001).

Thus, during the pandemic, 63% of women had “silent ovulatory disturbances,” either with short luteal phases after ovulation or no ovulation, compared with just 10% in the earlier cohort, “which is remarkable, unbelievable actually,” Dr. Prior remarked.  

The difference wasn’t explained by any of the demographic information collected either, including socioeconomic status, lifestyle, or reproductive history variables.

And it wasn’t because of COVID-19 vaccination, as the vaccine wasn’t available when most of the women were recruited, and of the 79 who were recruited during vaccine availability, only two received a COVID-19 vaccine during the study (and both had normal ovulation).

Employment changes, caring responsibilities, and worry likely causes

The information from the diaries was more revealing. Several diary components were far more common during the pandemic, including negative mood (feeling depressed or anxious, sleep problems, and outside stresses), self-worth, interest in sex, energy level, and appetite. All were significantly different between the two cohorts (P < .001) and between those with and without ovulatory disturbances.

“So menstrual cycle lengths and long cycles didn’t differ, but there was a much higher prevalence of silent or subclinical ovulatory disturbances, and these were related to the increased stresses that women recorded in their diaries. This means that the estrogen levels were pretty close to normal but the progesterone levels were remarkably decreased,” Dr. Prior said.

Interestingly, reported menstrual cramps were also significantly more common during the pandemic and associated with ovulatory disruption.

“That is a new observation because previously we’ve always thought that you needed to ovulate in order to even have cramps,” she commented.

Asked whether COVID-19 itself might have played a role, Dr. Prior said no woman in the study tested positive for the virus or had long COVID.

“As far as I’m aware, it was the changes in employment … and caring for elders and worry about illness in somebody you loved that was related,” she said.

Asked what she thinks the result would be if the study were conducted now, she said: “I don’t know. We’re still in a stressful time with inflation and not complete recovery, so probably the issue is still very present.”

Dr. Prior and Dr. Neal-Perry have reported no relevant financial relationships.

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

ATLANTA – Disturbances in ovulation that didn’t produce any actual changes in the menstrual cycle of women were extremely common during the first year of the COVID-19 pandemic and were linked to emotional stress, according to the findings of an “experiment of nature” that allowed for comparison with women a decade earlier.

Findings from two studies of reproductive-age women, one conducted in 2006-2008 and the other in 2020-2021, were presented by Jerilynn C. Prior, MD, at the annual meeting of the Endocrine Society.

The comparison of the two time periods yielded several novel findings. “I was taught in medical school that when women don’t eat enough they lose their period. But what we now understand is there’s a graded response to various stressors, acting through the hypothalamus in a common pathway. There is a gradation of disturbances, some of which are subclinical or not obvious,” said Dr. Prior, professor of endocrinology and metabolism at the University of British Columbia, Vancouver.

Moreover, women’s menstrual cycle lengths didn’t differ across the two time periods, despite a dramatic 63% decrement in normal ovulatory function related to increased depression, anxiety, and outside stresses that the women reported in diaries.

“Assuming that regular cycles need normal ovulation is something we should just get out of our minds. It changes our concept about what’s normal if we only know about the cycle length,” she observed.

It will be critical going forward to see whether the ovulatory disturbances have resolved as the pandemic has shifted “because there’s strong evidence that ovulatory disturbances, even with normal cycle length, are related to bone loss and some evidence it’s related to early heart attacks, breast and endometrial cancers,” Dr. Prior said during a press conference.

Lisa Nainggolan/MDedge News

Asked to comment, session moderator Genevieve Neal-Perry, MD, PhD, told this news organization: “I think what we can take away is that stress itself is a modifier of the way the brain and the gonads communicate with each other, and that then has an impact on ovulatory function.”

Dr. Neal-Perry noted that the association of stress and ovulatory disruption has been reported in various ways previously, but “clearly it doesn’t affect everyone. What we don’t know is who is most susceptible. There have been some studies showing a genetic predisposition and a genetic anomaly that actually makes them more susceptible to the impact of stress on the reproductive system.”

But the lack of data on weight change in the study cohorts is a limitation. “To me one of the more important questions was what was going on with weight. Just looking at a static number doesn’t tell you whether there were changes. We know that weight gain or weight loss can stress the reproductive axis,” noted Dr. Neal-Parry of the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill.
 

‘Experiment of nature’ revealed invisible effect of pandemic stress

The women in both cohorts of the Menstruation Ovulation Study (MOS) were healthy volunteers aged 19-35 years recruited from the metropolitan Vancouver region. All were menstruating monthly and none were taking hormonal birth control. Recruitment for the second cohort had begun just prior to the March 2020 COVID-19 pandemic lockdown.

Interviewer-administered questionnaires (CaMos) covering demographics, socioeconomic status, and reproductive history, and daily diaries kept by the women (menstrual cycle diary) were identical for both cohorts.

Assessments of ovulation differed for the two studies but were cross-validated. For the earlier time period, ovulation was assessed by a threefold increase in follicular-to-luteal urinary progesterone (PdG). For the pandemic-era study, the validated quantitative basal temperature (QBT) method was used.

There were 301 women in the earlier cohort and 125 during the pandemic. Both were an average age of about 29 years and had a body mass index of about 24.3 kg/m² (within the normal range). The pandemic cohort was more racially/ethnically diverse than the earlier one and more in-line with recent census data.

More of the women were nulliparous during the pandemic than earlier (92.7% vs. 80.4%; P = .002).

The distribution of menstrual cycle lengths didn’t differ, with both cohorts averaging about 30 days (P = .893). However, while 90% of the women in the earlier cohort ovulated normally, only 37% did during the pandemic, a highly significant difference (P < .0001).

Thus, during the pandemic, 63% of women had “silent ovulatory disturbances,” either with short luteal phases after ovulation or no ovulation, compared with just 10% in the earlier cohort, “which is remarkable, unbelievable actually,” Dr. Prior remarked.  

The difference wasn’t explained by any of the demographic information collected either, including socioeconomic status, lifestyle, or reproductive history variables.

And it wasn’t because of COVID-19 vaccination, as the vaccine wasn’t available when most of the women were recruited, and of the 79 who were recruited during vaccine availability, only two received a COVID-19 vaccine during the study (and both had normal ovulation).

Employment changes, caring responsibilities, and worry likely causes

The information from the diaries was more revealing. Several diary components were far more common during the pandemic, including negative mood (feeling depressed or anxious, sleep problems, and outside stresses), self-worth, interest in sex, energy level, and appetite. All were significantly different between the two cohorts (P < .001) and between those with and without ovulatory disturbances.

“So menstrual cycle lengths and long cycles didn’t differ, but there was a much higher prevalence of silent or subclinical ovulatory disturbances, and these were related to the increased stresses that women recorded in their diaries. This means that the estrogen levels were pretty close to normal but the progesterone levels were remarkably decreased,” Dr. Prior said.

Interestingly, reported menstrual cramps were also significantly more common during the pandemic and associated with ovulatory disruption.

“That is a new observation because previously we’ve always thought that you needed to ovulate in order to even have cramps,” she commented.

Asked whether COVID-19 itself might have played a role, Dr. Prior said no woman in the study tested positive for the virus or had long COVID.

“As far as I’m aware, it was the changes in employment … and caring for elders and worry about illness in somebody you loved that was related,” she said.

Asked what she thinks the result would be if the study were conducted now, she said: “I don’t know. We’re still in a stressful time with inflation and not complete recovery, so probably the issue is still very present.”

Dr. Prior and Dr. Neal-Perry have reported no relevant financial relationships.

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

ATLANTA – Disturbances in ovulation that didn’t produce any actual changes in the menstrual cycle of women were extremely common during the first year of the COVID-19 pandemic and were linked to emotional stress, according to the findings of an “experiment of nature” that allowed for comparison with women a decade earlier.

Findings from two studies of reproductive-age women, one conducted in 2006-2008 and the other in 2020-2021, were presented by Jerilynn C. Prior, MD, at the annual meeting of the Endocrine Society.

The comparison of the two time periods yielded several novel findings. “I was taught in medical school that when women don’t eat enough they lose their period. But what we now understand is there’s a graded response to various stressors, acting through the hypothalamus in a common pathway. There is a gradation of disturbances, some of which are subclinical or not obvious,” said Dr. Prior, professor of endocrinology and metabolism at the University of British Columbia, Vancouver.

Moreover, women’s menstrual cycle lengths didn’t differ across the two time periods, despite a dramatic 63% decrement in normal ovulatory function related to increased depression, anxiety, and outside stresses that the women reported in diaries.

“Assuming that regular cycles need normal ovulation is something we should just get out of our minds. It changes our concept about what’s normal if we only know about the cycle length,” she observed.

It will be critical going forward to see whether the ovulatory disturbances have resolved as the pandemic has shifted “because there’s strong evidence that ovulatory disturbances, even with normal cycle length, are related to bone loss and some evidence it’s related to early heart attacks, breast and endometrial cancers,” Dr. Prior said during a press conference.

Lisa Nainggolan/MDedge News

Asked to comment, session moderator Genevieve Neal-Perry, MD, PhD, told this news organization: “I think what we can take away is that stress itself is a modifier of the way the brain and the gonads communicate with each other, and that then has an impact on ovulatory function.”

Dr. Neal-Perry noted that the association of stress and ovulatory disruption has been reported in various ways previously, but “clearly it doesn’t affect everyone. What we don’t know is who is most susceptible. There have been some studies showing a genetic predisposition and a genetic anomaly that actually makes them more susceptible to the impact of stress on the reproductive system.”

But the lack of data on weight change in the study cohorts is a limitation. “To me one of the more important questions was what was going on with weight. Just looking at a static number doesn’t tell you whether there were changes. We know that weight gain or weight loss can stress the reproductive axis,” noted Dr. Neal-Parry of the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill.
 

‘Experiment of nature’ revealed invisible effect of pandemic stress

The women in both cohorts of the Menstruation Ovulation Study (MOS) were healthy volunteers aged 19-35 years recruited from the metropolitan Vancouver region. All were menstruating monthly and none were taking hormonal birth control. Recruitment for the second cohort had begun just prior to the March 2020 COVID-19 pandemic lockdown.

Interviewer-administered questionnaires (CaMos) covering demographics, socioeconomic status, and reproductive history, and daily diaries kept by the women (menstrual cycle diary) were identical for both cohorts.

Assessments of ovulation differed for the two studies but were cross-validated. For the earlier time period, ovulation was assessed by a threefold increase in follicular-to-luteal urinary progesterone (PdG). For the pandemic-era study, the validated quantitative basal temperature (QBT) method was used.

There were 301 women in the earlier cohort and 125 during the pandemic. Both were an average age of about 29 years and had a body mass index of about 24.3 kg/m² (within the normal range). The pandemic cohort was more racially/ethnically diverse than the earlier one and more in-line with recent census data.

More of the women were nulliparous during the pandemic than earlier (92.7% vs. 80.4%; P = .002).

The distribution of menstrual cycle lengths didn’t differ, with both cohorts averaging about 30 days (P = .893). However, while 90% of the women in the earlier cohort ovulated normally, only 37% did during the pandemic, a highly significant difference (P < .0001).

Thus, during the pandemic, 63% of women had “silent ovulatory disturbances,” either with short luteal phases after ovulation or no ovulation, compared with just 10% in the earlier cohort, “which is remarkable, unbelievable actually,” Dr. Prior remarked.  

The difference wasn’t explained by any of the demographic information collected either, including socioeconomic status, lifestyle, or reproductive history variables.

And it wasn’t because of COVID-19 vaccination, as the vaccine wasn’t available when most of the women were recruited, and of the 79 who were recruited during vaccine availability, only two received a COVID-19 vaccine during the study (and both had normal ovulation).

Employment changes, caring responsibilities, and worry likely causes

The information from the diaries was more revealing. Several diary components were far more common during the pandemic, including negative mood (feeling depressed or anxious, sleep problems, and outside stresses), self-worth, interest in sex, energy level, and appetite. All were significantly different between the two cohorts (P < .001) and between those with and without ovulatory disturbances.

“So menstrual cycle lengths and long cycles didn’t differ, but there was a much higher prevalence of silent or subclinical ovulatory disturbances, and these were related to the increased stresses that women recorded in their diaries. This means that the estrogen levels were pretty close to normal but the progesterone levels were remarkably decreased,” Dr. Prior said.

Interestingly, reported menstrual cramps were also significantly more common during the pandemic and associated with ovulatory disruption.

“That is a new observation because previously we’ve always thought that you needed to ovulate in order to even have cramps,” she commented.

Asked whether COVID-19 itself might have played a role, Dr. Prior said no woman in the study tested positive for the virus or had long COVID.

“As far as I’m aware, it was the changes in employment … and caring for elders and worry about illness in somebody you loved that was related,” she said.

Asked what she thinks the result would be if the study were conducted now, she said: “I don’t know. We’re still in a stressful time with inflation and not complete recovery, so probably the issue is still very present.”

Dr. Prior and Dr. Neal-Perry have reported no relevant financial relationships.

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

COPENHAGEN – Chronic exposure to high levels of particulate matter (PM) air pollution 2.5 mcm (PM2.5) or larger, and 10 mcm (PM10) or larger, in size is associated with a significantly higher likelihood of having osteoporosis, according to research presented at the annual European Congress of Rheumatology.

The results of the 7-year longitudinal study carried out across Italy from 2013 to 2019 dovetail with other recent published accounts from the same team of Italian researchers, led by Giovanni Adami, MD, of the rheumatology unit at the University of Verona (Italy). In addition to the current report presented at EULAR 2022, Dr. Adami and associates have reported an increased risk of flares of both rheumatoid arthritis and psoriasis following periods of elevated pollution, as well as an overall elevated risk for autoimmune diseases with higher concentrations of PM2.5 and PM10.

The pathogenesis of osteoporosis is thought to involve both genetic and environmental input, such as smoking, which is itself environmental air pollution, Dr. Adami said. The biological rationale for why air pollution might contribute to risk for osteoporosis comes from studies showing that exposure to indoor air pollution from biomass combustion raises serum levels of RANKL (receptor activator of nuclear factor-kappa ligand 1) but lowers serum osteoprotegerin – suggesting an increased risk of bone resorption – and that toxic metals such as lead, cadmium, mercury, and aluminum accumulate in the skeleton and negatively affect bone health.

In their study, Dr. Adami and colleagues found that, overall, the average exposure during the period 2013-2019 across Italy was 16.0 mcg/m³ for PM2.5 and 25.0 mcg/m³ for PM10.

“I can tell you that [25.0 mcg/m3 for PM10] is a very high exposure. It’s not very good for your health,” Dr. Adami said.

Data on more than 59,000 Italian women

Dr. Adami and colleagues used clinical characteristics and densitometric data from Italy’s osteoporosis fracture risk and osteoporosis screening reimbursement tool known as DeFRAcalc79, which has amassed variables from more than 59,000 women across the country. They used long-term average PM concentrations across Italy during 2013-2019 that were obtained from the Italian Institute for Environmental Protection and Research’s 617 air quality stations in 110 Italian provinces. The researchers linked individuals to a PM exposure value determined from the average concentration of urban, rural, and near-traffic stations in each person’s province of residence.

For 59,950 women across Italy who were at high risk for fracture, the researchers found 64.5% with bone mineral density that was defined as osteoporotic. At PM10 concentrations of 30 mcg/m³ or greater, there was a significantly higher likelihood of osteoporosis at both the femoral neck (odds ratio, 1.15) and lumbar spine (OR, 1.17).

The likelihood of osteoporosis was slightly greater with PM2.5 at concentrations of 25 mcg/m³ or more at the femoral neck (OR, 1.22) and lumbar spine (OR, 1.18). These comparisons were adjusted for age, body mass index (BMI), presence of prevalent fragility fractures, family history of osteoporosis, menopause, glucocorticoid use, comorbidities, and for residency in northern, central, or southern Italy.

Both thresholds of PM10 > 30 mcg/m³ and PM2.5 > 25 mcg/m³ “are considered safe … by the World Health Organization,” Dr. Adami pointed out.

“If you live in a place where the chronic exposure is less than 30 mcg/m³, you probably have slightly lower risk of osteoporosis as compared to those who live in a highly industrialized, polluted zone,” he explained.

“The cortical bone – femoral neck – seemed to be more susceptible, compared to trabecular bone, which is the lumbar spine. We have no idea why this is true, but we might speculate that somehow chronic inflammation like the [kind] seen in rheumatoid arthritis might be responsible for cortical bone impairment and not trabecular bone impairment,” Dr. Adami said.

One audience member, Kenneth Poole, BM, PhD, senior lecturer and honorary consultant in Metabolic Bone Disease and Rheumatology at the University of Cambridge (England), asked whether it was possible to account for the possibility of confounding caused by areas with dense housing in places where the particulate matter would be highest, and where residents may be less active and use stairs less often.

Dr. Adami noted that confounding is indeed a possibility, but he said Italy is unique in that its most polluted area – the Po River valley – is also its most wealthy area and in general has less crowded living situations with a healthier population, which could have attenuated, rather than reinforced, the results.

Does air pollution have an immunologic effect?

In interviews with this news organization, session comoderators Filipe Araújo, MD, and Irene Bultink, MD, PhD, said that the growth in evidence for the impact of air pollution on risk for, and severity of, various diseases suggests air pollution might have an immunologic effect.

“I think it’s very important to point this out. I also think it’s very hard to rule out confounding, because when you’re living in a city with crowded housing you may not walk or ride your bike but instead go by car or metro, and [the lifestyle is different],” said Dr. Bultink of Amsterdam University Medical Centers.

“It stresses that these diseases [that are associated with air pollution] although they are different in their pathophysiology, it points toward the systemic nature of rheumatic diseases, including osteoporosis,” said Dr. Araújo of Hospital Cuf Cascais (Portugal) and Hospital Ortopédico de Sant’Ana, Parede, Portugal.

The study was independently supported.Dr. Adami disclosed being a shareholder of Galapagos and Theramex.

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

COPENHAGEN – Chronic exposure to high levels of particulate matter (PM) air pollution 2.5 mcm (PM2.5) or larger, and 10 mcm (PM10) or larger, in size is associated with a significantly higher likelihood of having osteoporosis, according to research presented at the annual European Congress of Rheumatology.

The results of the 7-year longitudinal study carried out across Italy from 2013 to 2019 dovetail with other recent published accounts from the same team of Italian researchers, led by Giovanni Adami, MD, of the rheumatology unit at the University of Verona (Italy). In addition to the current report presented at EULAR 2022, Dr. Adami and associates have reported an increased risk of flares of both rheumatoid arthritis and psoriasis following periods of elevated pollution, as well as an overall elevated risk for autoimmune diseases with higher concentrations of PM2.5 and PM10.

The pathogenesis of osteoporosis is thought to involve both genetic and environmental input, such as smoking, which is itself environmental air pollution, Dr. Adami said. The biological rationale for why air pollution might contribute to risk for osteoporosis comes from studies showing that exposure to indoor air pollution from biomass combustion raises serum levels of RANKL (receptor activator of nuclear factor-kappa ligand 1) but lowers serum osteoprotegerin – suggesting an increased risk of bone resorption – and that toxic metals such as lead, cadmium, mercury, and aluminum accumulate in the skeleton and negatively affect bone health.

In their study, Dr. Adami and colleagues found that, overall, the average exposure during the period 2013-2019 across Italy was 16.0 mcg/m³ for PM2.5 and 25.0 mcg/m³ for PM10.

“I can tell you that [25.0 mcg/m3 for PM10] is a very high exposure. It’s not very good for your health,” Dr. Adami said.

Data on more than 59,000 Italian women

Dr. Adami and colleagues used clinical characteristics and densitometric data from Italy’s osteoporosis fracture risk and osteoporosis screening reimbursement tool known as DeFRAcalc79, which has amassed variables from more than 59,000 women across the country. They used long-term average PM concentrations across Italy during 2013-2019 that were obtained from the Italian Institute for Environmental Protection and Research’s 617 air quality stations in 110 Italian provinces. The researchers linked individuals to a PM exposure value determined from the average concentration of urban, rural, and near-traffic stations in each person’s province of residence.

For 59,950 women across Italy who were at high risk for fracture, the researchers found 64.5% with bone mineral density that was defined as osteoporotic. At PM10 concentrations of 30 mcg/m³ or greater, there was a significantly higher likelihood of osteoporosis at both the femoral neck (odds ratio, 1.15) and lumbar spine (OR, 1.17).

The likelihood of osteoporosis was slightly greater with PM2.5 at concentrations of 25 mcg/m³ or more at the femoral neck (OR, 1.22) and lumbar spine (OR, 1.18). These comparisons were adjusted for age, body mass index (BMI), presence of prevalent fragility fractures, family history of osteoporosis, menopause, glucocorticoid use, comorbidities, and for residency in northern, central, or southern Italy.

Both thresholds of PM10 > 30 mcg/m³ and PM2.5 > 25 mcg/m³ “are considered safe … by the World Health Organization,” Dr. Adami pointed out.

“If you live in a place where the chronic exposure is less than 30 mcg/m³, you probably have slightly lower risk of osteoporosis as compared to those who live in a highly industrialized, polluted zone,” he explained.

“The cortical bone – femoral neck – seemed to be more susceptible, compared to trabecular bone, which is the lumbar spine. We have no idea why this is true, but we might speculate that somehow chronic inflammation like the [kind] seen in rheumatoid arthritis might be responsible for cortical bone impairment and not trabecular bone impairment,” Dr. Adami said.

One audience member, Kenneth Poole, BM, PhD, senior lecturer and honorary consultant in Metabolic Bone Disease and Rheumatology at the University of Cambridge (England), asked whether it was possible to account for the possibility of confounding caused by areas with dense housing in places where the particulate matter would be highest, and where residents may be less active and use stairs less often.

Dr. Adami noted that confounding is indeed a possibility, but he said Italy is unique in that its most polluted area – the Po River valley – is also its most wealthy area and in general has less crowded living situations with a healthier population, which could have attenuated, rather than reinforced, the results.

Does air pollution have an immunologic effect?

In interviews with this news organization, session comoderators Filipe Araújo, MD, and Irene Bultink, MD, PhD, said that the growth in evidence for the impact of air pollution on risk for, and severity of, various diseases suggests air pollution might have an immunologic effect.

“I think it’s very important to point this out. I also think it’s very hard to rule out confounding, because when you’re living in a city with crowded housing you may not walk or ride your bike but instead go by car or metro, and [the lifestyle is different],” said Dr. Bultink of Amsterdam University Medical Centers.

“It stresses that these diseases [that are associated with air pollution] although they are different in their pathophysiology, it points toward the systemic nature of rheumatic diseases, including osteoporosis,” said Dr. Araújo of Hospital Cuf Cascais (Portugal) and Hospital Ortopédico de Sant’Ana, Parede, Portugal.

The study was independently supported.Dr. Adami disclosed being a shareholder of Galapagos and Theramex.

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

COPENHAGEN – Chronic exposure to high levels of particulate matter (PM) air pollution 2.5 mcm (PM2.5) or larger, and 10 mcm (PM10) or larger, in size is associated with a significantly higher likelihood of having osteoporosis, according to research presented at the annual European Congress of Rheumatology.

The results of the 7-year longitudinal study carried out across Italy from 2013 to 2019 dovetail with other recent published accounts from the same team of Italian researchers, led by Giovanni Adami, MD, of the rheumatology unit at the University of Verona (Italy). In addition to the current report presented at EULAR 2022, Dr. Adami and associates have reported an increased risk of flares of both rheumatoid arthritis and psoriasis following periods of elevated pollution, as well as an overall elevated risk for autoimmune diseases with higher concentrations of PM2.5 and PM10.

The pathogenesis of osteoporosis is thought to involve both genetic and environmental input, such as smoking, which is itself environmental air pollution, Dr. Adami said. The biological rationale for why air pollution might contribute to risk for osteoporosis comes from studies showing that exposure to indoor air pollution from biomass combustion raises serum levels of RANKL (receptor activator of nuclear factor-kappa ligand 1) but lowers serum osteoprotegerin – suggesting an increased risk of bone resorption – and that toxic metals such as lead, cadmium, mercury, and aluminum accumulate in the skeleton and negatively affect bone health.

In their study, Dr. Adami and colleagues found that, overall, the average exposure during the period 2013-2019 across Italy was 16.0 mcg/m³ for PM2.5 and 25.0 mcg/m³ for PM10.

“I can tell you that [25.0 mcg/m3 for PM10] is a very high exposure. It’s not very good for your health,” Dr. Adami said.

Data on more than 59,000 Italian women

Dr. Adami and colleagues used clinical characteristics and densitometric data from Italy’s osteoporosis fracture risk and osteoporosis screening reimbursement tool known as DeFRAcalc79, which has amassed variables from more than 59,000 women across the country. They used long-term average PM concentrations across Italy during 2013-2019 that were obtained from the Italian Institute for Environmental Protection and Research’s 617 air quality stations in 110 Italian provinces. The researchers linked individuals to a PM exposure value determined from the average concentration of urban, rural, and near-traffic stations in each person’s province of residence.

For 59,950 women across Italy who were at high risk for fracture, the researchers found 64.5% with bone mineral density that was defined as osteoporotic. At PM10 concentrations of 30 mcg/m³ or greater, there was a significantly higher likelihood of osteoporosis at both the femoral neck (odds ratio, 1.15) and lumbar spine (OR, 1.17).

The likelihood of osteoporosis was slightly greater with PM2.5 at concentrations of 25 mcg/m³ or more at the femoral neck (OR, 1.22) and lumbar spine (OR, 1.18). These comparisons were adjusted for age, body mass index (BMI), presence of prevalent fragility fractures, family history of osteoporosis, menopause, glucocorticoid use, comorbidities, and for residency in northern, central, or southern Italy.

Both thresholds of PM10 > 30 mcg/m³ and PM2.5 > 25 mcg/m³ “are considered safe … by the World Health Organization,” Dr. Adami pointed out.

“If you live in a place where the chronic exposure is less than 30 mcg/m³, you probably have slightly lower risk of osteoporosis as compared to those who live in a highly industrialized, polluted zone,” he explained.

“The cortical bone – femoral neck – seemed to be more susceptible, compared to trabecular bone, which is the lumbar spine. We have no idea why this is true, but we might speculate that somehow chronic inflammation like the [kind] seen in rheumatoid arthritis might be responsible for cortical bone impairment and not trabecular bone impairment,” Dr. Adami said.

One audience member, Kenneth Poole, BM, PhD, senior lecturer and honorary consultant in Metabolic Bone Disease and Rheumatology at the University of Cambridge (England), asked whether it was possible to account for the possibility of confounding caused by areas with dense housing in places where the particulate matter would be highest, and where residents may be less active and use stairs less often.

Dr. Adami noted that confounding is indeed a possibility, but he said Italy is unique in that its most polluted area – the Po River valley – is also its most wealthy area and in general has less crowded living situations with a healthier population, which could have attenuated, rather than reinforced, the results.

Does air pollution have an immunologic effect?

In interviews with this news organization, session comoderators Filipe Araújo, MD, and Irene Bultink, MD, PhD, said that the growth in evidence for the impact of air pollution on risk for, and severity of, various diseases suggests air pollution might have an immunologic effect.

“I think it’s very important to point this out. I also think it’s very hard to rule out confounding, because when you’re living in a city with crowded housing you may not walk or ride your bike but instead go by car or metro, and [the lifestyle is different],” said Dr. Bultink of Amsterdam University Medical Centers.

“It stresses that these diseases [that are associated with air pollution] although they are different in their pathophysiology, it points toward the systemic nature of rheumatic diseases, including osteoporosis,” said Dr. Araújo of Hospital Cuf Cascais (Portugal) and Hospital Ortopédico de Sant’Ana, Parede, Portugal.

The study was independently supported.Dr. Adami disclosed being a shareholder of Galapagos and Theramex.

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

The long-term health consequences of COVID-19 have refocused our attention on post–acute infection syndromes (PAIS), starting a discussion on the need for a complete understanding of multisystemic pathophysiology, clinical indicators, and the epidemiology of these syndromes, representing a significant blind spot in the field of medicine. A better understanding of these persistent symptom profiles, not only for post-acute sequelae of SARS-CoV-2 infection (PASC), better known as long COVID, but also for other diseases with unexplainable post-acute sequelae, would allow doctors to fine tune the diagnostic criteria. Having a clear definition and better understanding of post–acute infection symptoms is a necessary step toward developing an evidence-based, multidisciplinary management approach.

PAIS, PASC, or long COVID

The observation of unexplained chronic sequelae after SARS-CoV-2 is known as PASC or long COVID.

Long COVID has been reported as a syndrome in survivors of serious and critical disease, but the effects also persist over time for subjects who experienced a mild infection that did not require admission to hospital. This means that PASC, especially when occurring after a mild or moderate COVID-19 infection, shares many of the same characteristics as chronic diseases triggered by other pathogenic organisms, many of which have not been sufficiently clarified.

PAIS are characterized by a set of core symptoms centering on the following:

• Exertion intolerance
• Disproportionate levels of fatigue
• Neurocognitive and sensory impairment
• Flu-like symptoms
• Unrefreshing sleep
• Myalgia/arthralgia

A plethora of nonspecific symptoms are often present to various degrees.

These similarities suggest a unifying pathophysiology that needs to be elucidated to properly understand and manage postinfectious chronic disability.
 

Overview of PAIS

A detailed revision on what is currently known about PAIS was published in Nature Medicine. It provided various useful pieces of information to assist with the poor recognition of these conditions in clinical practice, a result of which is that patients might experience delayed or a complete lack of clinical care.

The following consolidated postinfection sequelae are mentioned:

• Q fever fatigue syndrome, which follows infection by the intracellular bacterium Coxiella burnetii
• Post-dengue fatigue syndrome, which can follow infection by the mosquito-borne dengue virus
• Fatiguing and rheumatic symptoms in a subset of individuals infected with chikungunya virus, a mosquito-borne virus that causes fever and joint pain in the acute phase
• Post-polio syndrome, which can emerge as many as 15-40 years after an initial poliomyelitis attack (similarly, some other neurotropic microbes, such as West Nile virus, might lead to persistent effects)
• Prolonged, debilitating, chronic symptoms have long been reported in a subset of patients after common and typically nonserious infections. For example, after mononucleosis, a condition generally caused by Epstein-Barr virus (EBV), and after an outbreak of Giardia lamblia, an intestinal parasite that usually causes acute intestinal illness. In fact, several studies identified the association of this outbreak of giardiasis with chronic fatigue, irritable bowel syndrome (IBS), and fibromyalgia persisting for many years.
• Views expressed in the literature regarding the frequency and the validity of posttreatment Lyme disease syndrome are divided. Although substantial evidence points to persistence of arthralgia, fatigue, and subjective neurocognitive impairments in a minority of patients with Lyme disease after the recommended antibiotic treatment, some of the early studies have failed to characterize the initial Lyme disease episode with sufficient rigor.

Symptoms and signs

The symptoms and signs which, based on the evidence available, are seen more frequently in health care checks may be characterized as the following:

• Exertion intolerance, fatigue
• Flu-like and ‘sickness behavior’ symptoms: fever, feverishness, muscle pain, feeling sick, malaise, sweating, irritability
• Neurological/neurocognitive symptoms: brain fog, impaired concentration or memory, trouble finding words
• Rheumatologic symptoms: chronic or recurrent joint pain
• Trigger-specific symptoms: for example, eye problems post Ebola, IBS post Giardia, anosmia and ageusia post COVID-19, motor disturbances post polio and post West Nile virus

Myalgic encephalomyelitis/chronic fatigue syndrome

Patients with this disorder experience worsening of symptoms following physical, cognitive, or emotional exertion above their (very low) tolerated limit. Other prominent features frequently observed in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are neurocognitive impairments (colloquially referred to as brain fog), unrefreshing sleep, pain, sensory disturbances, gastrointestinal issues, and various forms of dysautonomia. Up to 75% of ME/CFS cases report an infection-like episode preceding the onset of their illness. Postinfectious and postviral fatigue syndromes were originally postulated as subsets of chronic fatigue syndrome. However, there appears to be no clear consensus at present about whether these terms should be considered synonymous to the ME/CFS label or any of its subsets, or include a wider range of postinfectious fatigue conditions.

Practical diagnostic criteria

From a revision of the available criteria, it emerges that the diagnostic criteria for a PAIS should include not only the presence of symptoms, but ideally also the intensity, course, and constellation of symptoms within an individual, as the individual symptoms and symptom trajectories of PAIS vary over time, rendering a mere comparison of symptom presence at a single time point misleading. Furthermore, when a diagnosis of ME/CFS is made, attention should be given to the choice of diagnostic criteria, with preference given to the more conservative criteria, so as not to run the risk of overestimating the syndrome.

Asthenia is the cornerstone symptom for most epidemiological studies on PAIS, but it would be reductive to concentrate only on this rather than the other characteristics, such as the exacerbation of symptoms following exertion, together with other characteristic symptoms and signs that may allow for better identification of the overall, observable clinical picture in these postinfection syndromes, which have significant impacts on a patient’s quality of life.

This article was translated from Univadis Italy. A version of this article appeared on Medscape.com.

The long-term health consequences of COVID-19 have refocused our attention on post–acute infection syndromes (PAIS), starting a discussion on the need for a complete understanding of multisystemic pathophysiology, clinical indicators, and the epidemiology of these syndromes, representing a significant blind spot in the field of medicine. A better understanding of these persistent symptom profiles, not only for post-acute sequelae of SARS-CoV-2 infection (PASC), better known as long COVID, but also for other diseases with unexplainable post-acute sequelae, would allow doctors to fine tune the diagnostic criteria. Having a clear definition and better understanding of post–acute infection symptoms is a necessary step toward developing an evidence-based, multidisciplinary management approach.

PAIS, PASC, or long COVID

The observation of unexplained chronic sequelae after SARS-CoV-2 is known as PASC or long COVID.

Long COVID has been reported as a syndrome in survivors of serious and critical disease, but the effects also persist over time for subjects who experienced a mild infection that did not require admission to hospital. This means that PASC, especially when occurring after a mild or moderate COVID-19 infection, shares many of the same characteristics as chronic diseases triggered by other pathogenic organisms, many of which have not been sufficiently clarified.

PAIS are characterized by a set of core symptoms centering on the following:

• Exertion intolerance
• Disproportionate levels of fatigue
• Neurocognitive and sensory impairment
• Flu-like symptoms
• Unrefreshing sleep
• Myalgia/arthralgia

A plethora of nonspecific symptoms are often present to various degrees.

These similarities suggest a unifying pathophysiology that needs to be elucidated to properly understand and manage postinfectious chronic disability.
 

Overview of PAIS

A detailed revision on what is currently known about PAIS was published in Nature Medicine. It provided various useful pieces of information to assist with the poor recognition of these conditions in clinical practice, a result of which is that patients might experience delayed or a complete lack of clinical care.

The following consolidated postinfection sequelae are mentioned:

• Q fever fatigue syndrome, which follows infection by the intracellular bacterium Coxiella burnetii
• Post-dengue fatigue syndrome, which can follow infection by the mosquito-borne dengue virus
• Fatiguing and rheumatic symptoms in a subset of individuals infected with chikungunya virus, a mosquito-borne virus that causes fever and joint pain in the acute phase
• Post-polio syndrome, which can emerge as many as 15-40 years after an initial poliomyelitis attack (similarly, some other neurotropic microbes, such as West Nile virus, might lead to persistent effects)
• Prolonged, debilitating, chronic symptoms have long been reported in a subset of patients after common and typically nonserious infections. For example, after mononucleosis, a condition generally caused by Epstein-Barr virus (EBV), and after an outbreak of Giardia lamblia, an intestinal parasite that usually causes acute intestinal illness. In fact, several studies identified the association of this outbreak of giardiasis with chronic fatigue, irritable bowel syndrome (IBS), and fibromyalgia persisting for many years.
• Views expressed in the literature regarding the frequency and the validity of posttreatment Lyme disease syndrome are divided. Although substantial evidence points to persistence of arthralgia, fatigue, and subjective neurocognitive impairments in a minority of patients with Lyme disease after the recommended antibiotic treatment, some of the early studies have failed to characterize the initial Lyme disease episode with sufficient rigor.

Symptoms and signs

The symptoms and signs which, based on the evidence available, are seen more frequently in health care checks may be characterized as the following:

• Exertion intolerance, fatigue
• Flu-like and ‘sickness behavior’ symptoms: fever, feverishness, muscle pain, feeling sick, malaise, sweating, irritability
• Neurological/neurocognitive symptoms: brain fog, impaired concentration or memory, trouble finding words
• Rheumatologic symptoms: chronic or recurrent joint pain
• Trigger-specific symptoms: for example, eye problems post Ebola, IBS post Giardia, anosmia and ageusia post COVID-19, motor disturbances post polio and post West Nile virus

Myalgic encephalomyelitis/chronic fatigue syndrome

Patients with this disorder experience worsening of symptoms following physical, cognitive, or emotional exertion above their (very low) tolerated limit. Other prominent features frequently observed in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are neurocognitive impairments (colloquially referred to as brain fog), unrefreshing sleep, pain, sensory disturbances, gastrointestinal issues, and various forms of dysautonomia. Up to 75% of ME/CFS cases report an infection-like episode preceding the onset of their illness. Postinfectious and postviral fatigue syndromes were originally postulated as subsets of chronic fatigue syndrome. However, there appears to be no clear consensus at present about whether these terms should be considered synonymous to the ME/CFS label or any of its subsets, or include a wider range of postinfectious fatigue conditions.

Practical diagnostic criteria

From a revision of the available criteria, it emerges that the diagnostic criteria for a PAIS should include not only the presence of symptoms, but ideally also the intensity, course, and constellation of symptoms within an individual, as the individual symptoms and symptom trajectories of PAIS vary over time, rendering a mere comparison of symptom presence at a single time point misleading. Furthermore, when a diagnosis of ME/CFS is made, attention should be given to the choice of diagnostic criteria, with preference given to the more conservative criteria, so as not to run the risk of overestimating the syndrome.

Asthenia is the cornerstone symptom for most epidemiological studies on PAIS, but it would be reductive to concentrate only on this rather than the other characteristics, such as the exacerbation of symptoms following exertion, together with other characteristic symptoms and signs that may allow for better identification of the overall, observable clinical picture in these postinfection syndromes, which have significant impacts on a patient’s quality of life.

This article was translated from Univadis Italy. A version of this article appeared on Medscape.com.

The long-term health consequences of COVID-19 have refocused our attention on post–acute infection syndromes (PAIS), starting a discussion on the need for a complete understanding of multisystemic pathophysiology, clinical indicators, and the epidemiology of these syndromes, representing a significant blind spot in the field of medicine. A better understanding of these persistent symptom profiles, not only for post-acute sequelae of SARS-CoV-2 infection (PASC), better known as long COVID, but also for other diseases with unexplainable post-acute sequelae, would allow doctors to fine tune the diagnostic criteria. Having a clear definition and better understanding of post–acute infection symptoms is a necessary step toward developing an evidence-based, multidisciplinary management approach.

PAIS, PASC, or long COVID

The observation of unexplained chronic sequelae after SARS-CoV-2 is known as PASC or long COVID.

Long COVID has been reported as a syndrome in survivors of serious and critical disease, but the effects also persist over time for subjects who experienced a mild infection that did not require admission to hospital. This means that PASC, especially when occurring after a mild or moderate COVID-19 infection, shares many of the same characteristics as chronic diseases triggered by other pathogenic organisms, many of which have not been sufficiently clarified.

PAIS are characterized by a set of core symptoms centering on the following:

• Exertion intolerance
• Disproportionate levels of fatigue
• Neurocognitive and sensory impairment
• Flu-like symptoms
• Unrefreshing sleep
• Myalgia/arthralgia

A plethora of nonspecific symptoms are often present to various degrees.

These similarities suggest a unifying pathophysiology that needs to be elucidated to properly understand and manage postinfectious chronic disability.
 

Overview of PAIS

A detailed revision on what is currently known about PAIS was published in Nature Medicine. It provided various useful pieces of information to assist with the poor recognition of these conditions in clinical practice, a result of which is that patients might experience delayed or a complete lack of clinical care.

The following consolidated postinfection sequelae are mentioned:

• Q fever fatigue syndrome, which follows infection by the intracellular bacterium Coxiella burnetii
• Post-dengue fatigue syndrome, which can follow infection by the mosquito-borne dengue virus
• Fatiguing and rheumatic symptoms in a subset of individuals infected with chikungunya virus, a mosquito-borne virus that causes fever and joint pain in the acute phase
• Post-polio syndrome, which can emerge as many as 15-40 years after an initial poliomyelitis attack (similarly, some other neurotropic microbes, such as West Nile virus, might lead to persistent effects)
• Prolonged, debilitating, chronic symptoms have long been reported in a subset of patients after common and typically nonserious infections. For example, after mononucleosis, a condition generally caused by Epstein-Barr virus (EBV), and after an outbreak of Giardia lamblia, an intestinal parasite that usually causes acute intestinal illness. In fact, several studies identified the association of this outbreak of giardiasis with chronic fatigue, irritable bowel syndrome (IBS), and fibromyalgia persisting for many years.
• Views expressed in the literature regarding the frequency and the validity of posttreatment Lyme disease syndrome are divided. Although substantial evidence points to persistence of arthralgia, fatigue, and subjective neurocognitive impairments in a minority of patients with Lyme disease after the recommended antibiotic treatment, some of the early studies have failed to characterize the initial Lyme disease episode with sufficient rigor.

Symptoms and signs

The symptoms and signs which, based on the evidence available, are seen more frequently in health care checks may be characterized as the following:

• Exertion intolerance, fatigue
• Flu-like and ‘sickness behavior’ symptoms: fever, feverishness, muscle pain, feeling sick, malaise, sweating, irritability
• Neurological/neurocognitive symptoms: brain fog, impaired concentration or memory, trouble finding words
• Rheumatologic symptoms: chronic or recurrent joint pain
• Trigger-specific symptoms: for example, eye problems post Ebola, IBS post Giardia, anosmia and ageusia post COVID-19, motor disturbances post polio and post West Nile virus

Myalgic encephalomyelitis/chronic fatigue syndrome

Patients with this disorder experience worsening of symptoms following physical, cognitive, or emotional exertion above their (very low) tolerated limit. Other prominent features frequently observed in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are neurocognitive impairments (colloquially referred to as brain fog), unrefreshing sleep, pain, sensory disturbances, gastrointestinal issues, and various forms of dysautonomia. Up to 75% of ME/CFS cases report an infection-like episode preceding the onset of their illness. Postinfectious and postviral fatigue syndromes were originally postulated as subsets of chronic fatigue syndrome. However, there appears to be no clear consensus at present about whether these terms should be considered synonymous to the ME/CFS label or any of its subsets, or include a wider range of postinfectious fatigue conditions.

Practical diagnostic criteria

From a revision of the available criteria, it emerges that the diagnostic criteria for a PAIS should include not only the presence of symptoms, but ideally also the intensity, course, and constellation of symptoms within an individual, as the individual symptoms and symptom trajectories of PAIS vary over time, rendering a mere comparison of symptom presence at a single time point misleading. Furthermore, when a diagnosis of ME/CFS is made, attention should be given to the choice of diagnostic criteria, with preference given to the more conservative criteria, so as not to run the risk of overestimating the syndrome.

Asthenia is the cornerstone symptom for most epidemiological studies on PAIS, but it would be reductive to concentrate only on this rather than the other characteristics, such as the exacerbation of symptoms following exertion, together with other characteristic symptoms and signs that may allow for better identification of the overall, observable clinical picture in these postinfection syndromes, which have significant impacts on a patient’s quality of life.

This article was translated from Univadis Italy. A version of this article appeared on Medscape.com.

Vaccines against human papillomavirus have been hailed as a success: they have been shown to decrease the incidence of cervical lesions associated with the HPV types that are in the vaccine.

However, new evidence suggests that HPV vaccination makes women more susceptible than their nonvaccinated peers to HPV genotypes not covered by the vaccine.

An expert not involved in the research said the new data “tell us to be a little bit careful.” Although the HPV types not included in the vaccine are rarer and less aggressive, they can still cause cancer.

The data come from the Costa Rica HPV Vaccine Trial, which involved more than 10,000 women aged 18-25 years. The HPV vaccine used in the trial was Cervarix, from GlaxoSmithKline. It covers the two leading causes of cervical cancer, HPV-16 and -18, and provides partial protection against three other genotypes.

After a follow-up of 11 years, among vaccinated women, there was an excess of precancerous cervical lesions caused by genotypes not included in the vaccine, resulting in negative vaccine efficacy for those HPV variants.

The increase wasn’t enough to offset the overall benefit of vaccination when all genotypes were considered, said the researchers, led by Jaimie Shing, PhD, a postdoctoral research fellow at the National Cancer Institute in Bethesda, Md.

Vaccinated women “still had long-term absolute reductions in high-grade lesions,” they pointed out.

The net protection “remained considerable, emphasizing the importance of HPV vaccination for cervical cancer prevention,” the team concluded.

The findings were published online in The Lancet Oncology.

The results are likely the first evidence to date of “clinical unmasking” with HPV vaccination, meaning that protection against the strains covered by the vaccine leaves women more prone to attack from other carcinogenic HPV variants.

This phenomenon “could attenuate long-term reductions in high-grade disease following successful implementation of HPV vaccination programs,” the investigators commented.
 

Highlighting a need for caution

The take-home message from the trial is that “we have to be careful,” said Marc Steben, MD, co-President of HPV Global Action and a professor at the University of Montreal.

He noted that the Cervarix HPV vaccine used in the trial is not the vaccine that is used now in developed nations.

The current standard HPV vaccine is Gardasil 9 (Merck), which offers broader coverage against nine HPV types (types 6, 11, 16, 18, 31, 33, 45, 52, and 58).

There are 12 main carcinogenic HPV genotypes, so unmasking of other strains is still possible with Gardasil 9, he said.

There is another issue, Dr. Steben added. The success of HPV vaccinations - a nearly 90% reduction in invasive cervical cancer in women who are vaccinated at a young age – has led to questions about the future role of routine cervical cancer screening.

“Some people are saying that if we achieve 90% coverage, we might” eliminate community transmission and no longer need to screen, he said.

These trial results “tell us to be a little bit careful,” Dr. Steben continued. Those HPV types that are less aggressive and rarer than HPV-16 and -18 “can still cause cancer and might be there and surprise us. It could take more time than we thought” to get to the point where screening can be eliminated.

“There might be a little problem if we stop too early,” he said.
 

Study details

During the period 2004-2005, the investigators randomly assigned 3,727 women aged 18-25 years to receive Cervarix and 3,739 to a control group that received the hepatitis A vaccine; after 4 years, the control group also received Cervarix and exited the study. They were replaced by an unvaccinated control group of 2,836 women. The new control group and the original HPV vaccine group were followed for an additional 7 years.

In years 7-11 of the trial, the investigators found 9.2 additional cervical intraepithelial neoplasias of grade 2 or worse (CIN2+) from HPV types not covered by Cervarix per 1,000 vaccinated women in comparison with unvaccinated participants. This corresponds to –71.2% negative vaccine efficacy against CIN2+ lesions of HPV types not covered by the vaccine.

There were 8.3 additional CIN3+ lesions from nontargeted HPV strains per 1,000 vaccinated women in comparison with unvaccinated participants, which corresponds to –135% negative vaccine efficacy.

Overall, however, there was a net benefit of vaccination, with 27 fewer CIN2+ lesions when all HPV genotypes – vaccine covered or not – were considered per 1,000 vaccinated women over the entire 11 years of follow-up.

There were also 8.7 fewer CIN3+ lesions across all genotypes per 1,000 vaccinated women, but the benefit was not statistically significant.

Among the study limits, the team was unable to evaluate the effect of clinical unmasking on cervical cancer, because women were treated for high-grade cervical lesions before cases could progress to cervical cancer.

The trial was funded by the National Cancer Institute and the National Institutes of Health Office of Research on Women’s Health. GlaxoSmithKline provided the Cervarix vaccine and supported aspects of the trial. Two authors are named inventors on U.S. government–owned HPV vaccine patents with expired licenses to GlaxoSmithKline and Merck. Dr. Steben is an adviser/speaker for many companies, including GlaxoSmithKline and Merck.

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

Vaccines against human papillomavirus have been hailed as a success: they have been shown to decrease the incidence of cervical lesions associated with the HPV types that are in the vaccine.

However, new evidence suggests that HPV vaccination makes women more susceptible than their nonvaccinated peers to HPV genotypes not covered by the vaccine.

An expert not involved in the research said the new data “tell us to be a little bit careful.” Although the HPV types not included in the vaccine are rarer and less aggressive, they can still cause cancer.

The data come from the Costa Rica HPV Vaccine Trial, which involved more than 10,000 women aged 18-25 years. The HPV vaccine used in the trial was Cervarix, from GlaxoSmithKline. It covers the two leading causes of cervical cancer, HPV-16 and -18, and provides partial protection against three other genotypes.

After a follow-up of 11 years, among vaccinated women, there was an excess of precancerous cervical lesions caused by genotypes not included in the vaccine, resulting in negative vaccine efficacy for those HPV variants.

The increase wasn’t enough to offset the overall benefit of vaccination when all genotypes were considered, said the researchers, led by Jaimie Shing, PhD, a postdoctoral research fellow at the National Cancer Institute in Bethesda, Md.

Vaccinated women “still had long-term absolute reductions in high-grade lesions,” they pointed out.

The net protection “remained considerable, emphasizing the importance of HPV vaccination for cervical cancer prevention,” the team concluded.

The findings were published online in The Lancet Oncology.

The results are likely the first evidence to date of “clinical unmasking” with HPV vaccination, meaning that protection against the strains covered by the vaccine leaves women more prone to attack from other carcinogenic HPV variants.

This phenomenon “could attenuate long-term reductions in high-grade disease following successful implementation of HPV vaccination programs,” the investigators commented.
 

Highlighting a need for caution

The take-home message from the trial is that “we have to be careful,” said Marc Steben, MD, co-President of HPV Global Action and a professor at the University of Montreal.

He noted that the Cervarix HPV vaccine used in the trial is not the vaccine that is used now in developed nations.

The current standard HPV vaccine is Gardasil 9 (Merck), which offers broader coverage against nine HPV types (types 6, 11, 16, 18, 31, 33, 45, 52, and 58).

There are 12 main carcinogenic HPV genotypes, so unmasking of other strains is still possible with Gardasil 9, he said.

There is another issue, Dr. Steben added. The success of HPV vaccinations - a nearly 90% reduction in invasive cervical cancer in women who are vaccinated at a young age – has led to questions about the future role of routine cervical cancer screening.

“Some people are saying that if we achieve 90% coverage, we might” eliminate community transmission and no longer need to screen, he said.

These trial results “tell us to be a little bit careful,” Dr. Steben continued. Those HPV types that are less aggressive and rarer than HPV-16 and -18 “can still cause cancer and might be there and surprise us. It could take more time than we thought” to get to the point where screening can be eliminated.

“There might be a little problem if we stop too early,” he said.
 

Study details

During the period 2004-2005, the investigators randomly assigned 3,727 women aged 18-25 years to receive Cervarix and 3,739 to a control group that received the hepatitis A vaccine; after 4 years, the control group also received Cervarix and exited the study. They were replaced by an unvaccinated control group of 2,836 women. The new control group and the original HPV vaccine group were followed for an additional 7 years.

In years 7-11 of the trial, the investigators found 9.2 additional cervical intraepithelial neoplasias of grade 2 or worse (CIN2+) from HPV types not covered by Cervarix per 1,000 vaccinated women in comparison with unvaccinated participants. This corresponds to –71.2% negative vaccine efficacy against CIN2+ lesions of HPV types not covered by the vaccine.

There were 8.3 additional CIN3+ lesions from nontargeted HPV strains per 1,000 vaccinated women in comparison with unvaccinated participants, which corresponds to –135% negative vaccine efficacy.

Overall, however, there was a net benefit of vaccination, with 27 fewer CIN2+ lesions when all HPV genotypes – vaccine covered or not – were considered per 1,000 vaccinated women over the entire 11 years of follow-up.

There were also 8.7 fewer CIN3+ lesions across all genotypes per 1,000 vaccinated women, but the benefit was not statistically significant.

Among the study limits, the team was unable to evaluate the effect of clinical unmasking on cervical cancer, because women were treated for high-grade cervical lesions before cases could progress to cervical cancer.

The trial was funded by the National Cancer Institute and the National Institutes of Health Office of Research on Women’s Health. GlaxoSmithKline provided the Cervarix vaccine and supported aspects of the trial. Two authors are named inventors on U.S. government–owned HPV vaccine patents with expired licenses to GlaxoSmithKline and Merck. Dr. Steben is an adviser/speaker for many companies, including GlaxoSmithKline and Merck.

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

Vaccines against human papillomavirus have been hailed as a success: they have been shown to decrease the incidence of cervical lesions associated with the HPV types that are in the vaccine.

However, new evidence suggests that HPV vaccination makes women more susceptible than their nonvaccinated peers to HPV genotypes not covered by the vaccine.

An expert not involved in the research said the new data “tell us to be a little bit careful.” Although the HPV types not included in the vaccine are rarer and less aggressive, they can still cause cancer.

The data come from the Costa Rica HPV Vaccine Trial, which involved more than 10,000 women aged 18-25 years. The HPV vaccine used in the trial was Cervarix, from GlaxoSmithKline. It covers the two leading causes of cervical cancer, HPV-16 and -18, and provides partial protection against three other genotypes.

After a follow-up of 11 years, among vaccinated women, there was an excess of precancerous cervical lesions caused by genotypes not included in the vaccine, resulting in negative vaccine efficacy for those HPV variants.

The increase wasn’t enough to offset the overall benefit of vaccination when all genotypes were considered, said the researchers, led by Jaimie Shing, PhD, a postdoctoral research fellow at the National Cancer Institute in Bethesda, Md.

Vaccinated women “still had long-term absolute reductions in high-grade lesions,” they pointed out.

The net protection “remained considerable, emphasizing the importance of HPV vaccination for cervical cancer prevention,” the team concluded.

The findings were published online in The Lancet Oncology.

The results are likely the first evidence to date of “clinical unmasking” with HPV vaccination, meaning that protection against the strains covered by the vaccine leaves women more prone to attack from other carcinogenic HPV variants.

This phenomenon “could attenuate long-term reductions in high-grade disease following successful implementation of HPV vaccination programs,” the investigators commented.
 

Highlighting a need for caution

The take-home message from the trial is that “we have to be careful,” said Marc Steben, MD, co-President of HPV Global Action and a professor at the University of Montreal.

He noted that the Cervarix HPV vaccine used in the trial is not the vaccine that is used now in developed nations.

The current standard HPV vaccine is Gardasil 9 (Merck), which offers broader coverage against nine HPV types (types 6, 11, 16, 18, 31, 33, 45, 52, and 58).

There are 12 main carcinogenic HPV genotypes, so unmasking of other strains is still possible with Gardasil 9, he said.

There is another issue, Dr. Steben added. The success of HPV vaccinations - a nearly 90% reduction in invasive cervical cancer in women who are vaccinated at a young age – has led to questions about the future role of routine cervical cancer screening.

“Some people are saying that if we achieve 90% coverage, we might” eliminate community transmission and no longer need to screen, he said.

These trial results “tell us to be a little bit careful,” Dr. Steben continued. Those HPV types that are less aggressive and rarer than HPV-16 and -18 “can still cause cancer and might be there and surprise us. It could take more time than we thought” to get to the point where screening can be eliminated.

“There might be a little problem if we stop too early,” he said.
 

Study details

During the period 2004-2005, the investigators randomly assigned 3,727 women aged 18-25 years to receive Cervarix and 3,739 to a control group that received the hepatitis A vaccine; after 4 years, the control group also received Cervarix and exited the study. They were replaced by an unvaccinated control group of 2,836 women. The new control group and the original HPV vaccine group were followed for an additional 7 years.

In years 7-11 of the trial, the investigators found 9.2 additional cervical intraepithelial neoplasias of grade 2 or worse (CIN2+) from HPV types not covered by Cervarix per 1,000 vaccinated women in comparison with unvaccinated participants. This corresponds to –71.2% negative vaccine efficacy against CIN2+ lesions of HPV types not covered by the vaccine.

There were 8.3 additional CIN3+ lesions from nontargeted HPV strains per 1,000 vaccinated women in comparison with unvaccinated participants, which corresponds to –135% negative vaccine efficacy.

Overall, however, there was a net benefit of vaccination, with 27 fewer CIN2+ lesions when all HPV genotypes – vaccine covered or not – were considered per 1,000 vaccinated women over the entire 11 years of follow-up.

There were also 8.7 fewer CIN3+ lesions across all genotypes per 1,000 vaccinated women, but the benefit was not statistically significant.

Among the study limits, the team was unable to evaluate the effect of clinical unmasking on cervical cancer, because women were treated for high-grade cervical lesions before cases could progress to cervical cancer.

The trial was funded by the National Cancer Institute and the National Institutes of Health Office of Research on Women’s Health. GlaxoSmithKline provided the Cervarix vaccine and supported aspects of the trial. Two authors are named inventors on U.S. government–owned HPV vaccine patents with expired licenses to GlaxoSmithKline and Merck. Dr. Steben is an adviser/speaker for many companies, including GlaxoSmithKline and Merck.

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

Patients with type 2 diabetes who received empagliflozin, a sodium glucose cotransporter-2 (SGLT2) inhibitor, were almost 40% less likely to have a kidney stone than patients who received placebo during a median 1.5 years of treatment.

These findings are from an analysis of pooled data from phase 1-4 clinical trials of empagliflozin for blood glucose control in 15,081 patients with type 2 diabetes.  

Priyadarshini Balasubramanian, MD, presented the study as a poster at the annual meeting of the Endocrine Society; the study also was published online in the Journal of Clinical Endocrinology & Metabolism.

The researchers acknowledge this was a retrospective, post-hoc analysis and that urolithiasis – a stone in the urinary tract, which includes nephrolithiasis, a kidney stone – was an adverse event, not a primary or secondary outcome.

Also, the stone composition, which might help explain how the drug may affect stone formation, is unknown.

Therefore, “dedicated randomized prospective clinical trials are needed to confirm these initial observations in patients both with and without type 2 diabetes,” said Dr. Balasubramanian, a clinical fellow in the section of endocrinology & metabolism, department of internal medicine at Yale University, New Haven, Conn.

However, “if this association is proven, empagliflozin may be used to decrease the risk of kidney stones at least in those with type 2 diabetes, but maybe also in those without diabetes,” Dr. Balasubramanian said in an interview.

Further trials are also needed to determine if this is a class effect, which is likely, she speculated, and to unravel the potential mechanism.

This is important because of the prevalence of kidney stones, which affect up to 15% of the general population and 15%-20% of patients with diabetes, she explained.
 

‘Provocative’ earlier findings

The current study was prompted by a recent observational study by Kasper B. Kristensen, MD, PhD, and colleagues.

Because SGLT2 inhibitors increase urinary glucose excretion through reduced renal reabsorption of glucose leading to osmotic diuresis and increased urinary flow, they hypothesized that these therapies “may reduce the risk of upper urinary tract stones (nephrolithiasis) by reducing the concentration of lithogenic substances in urine.” 

Using data from Danish Health registries, they matched 12,325 individuals newly prescribed an SGLT2 inhibitor 1:1 with patients newly prescribed a glucagonlike peptide-1 (GLP1) agonist, another new class of drugs for treating type 2 diabetes.

They found a hazard ratio of 0.51 (95% confidence interval, 0.37-0.71) for incident nephrolithiasis and a hazard ratio of 0.68 (95% CI, 0.48-0.97) for recurrent nephrolithiasis for patients taking SGLT2 inhibitors versus GLP-1 agonists.

These findings are “striking,” according to Dr. Balasubramanian and colleagues. However, “these data, while provocative, were entirely retrospective and therefore possibly prone to bias,” they add.
 

Pooled data from 20 trials

The current study analyzed data from 20 randomized controlled trials of glycemic control in type 2 diabetes, in which 10,177 patients had received empagliflozin 10 mg or 25 mg and 4,904 patients had received placebo.

Most patients (46.5%) had participated in the EMPA-REG OUTCOMES trial, which also had the longest follow-up (2.6 years).

The researchers identified patients with a new stone from the urinary tract (including the kidney, ureter, and urethra). Patients had received either the study drug for a median of 543 days or placebo for a median of 549 days.

During treatment, 104 of 10,177 patients in the pooled empagliflozin groups and 79 of 4,904 patients in the pooled placebo groups developed a stone in the urinary tract.

This was equivalent to 0.63 new urinary-tract stones per 100 patient-years in the pooled empagliflozin groups versus 1.01 new urinary-tract stones per 100 patient-years in the pooled placebo groups.

The incidence rate ratio was 0.64 (95% CI, 0.48-0.86), in favor of empagliflozin.

When the analysis was restricted to new kidney stones, the results were similar: 75 of 10,177 patients in the pooled empagliflozin groups and 57 of 4,904 patients in the pooled placebo groups developed a kidney stone.

This was equivalent to 0.45 new kidney stones per 100 patient-years in the pooled empagliflozin groups versus 0.72 new kidney stones per 100 patient-years in the pooled placebo groups.

The IRR was 0.65 (95% CI, 0.46-0.92), in favor of empagliflozin.
 

Upcoming small RCT in adults without diabetes

Invited to comment on the new study, Dr. Kristensen said: “The reduced risk of SGLT2 inhibitors towards nephrolithiasis is now reported in at least two studies with different methodology, different populations, and different exposure and outcome definitions.”

“I agree that randomized clinical trials designed specifically to confirm these findings appear warranted,” added Dr. Kristensen, from the Institute of Public Health, Clinical Pharmacology, Pharmacy, and Environmental Medicine, University of Southern Denmark in Odense.

There is a need for studies in patients with and without diabetes, he added, especially ones that focus on prevention of nephrolithiasis in patients with kidney stone disease.

A new trial should shed further light on this.

Results are expected by the end of 2022 for SWEETSTONE (Impact of the SGLT2 Inhibitor Empagliflozin on Urinary Supersaturations in Kidney Stone Formers), a randomized, double-blind crossover exploratory study in 46 patients without diabetes.

This should provide preliminary data to “establish the relevance for larger trials assessing the prophylactic potential of empagliflozin in kidney stone disease,” according to an article on the trial protocol recently published in BMJ.

The trials included in the pooled dataset were funded by Boehringer Ingelheim or the Boehringer Ingelheim and Eli Lilly Diabetes Alliance. Dr. Balasubramanian has reported no relevant financial relationships.

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

Patients with type 2 diabetes who received empagliflozin, a sodium glucose cotransporter-2 (SGLT2) inhibitor, were almost 40% less likely to have a kidney stone than patients who received placebo during a median 1.5 years of treatment.

These findings are from an analysis of pooled data from phase 1-4 clinical trials of empagliflozin for blood glucose control in 15,081 patients with type 2 diabetes.  

Priyadarshini Balasubramanian, MD, presented the study as a poster at the annual meeting of the Endocrine Society; the study also was published online in the Journal of Clinical Endocrinology & Metabolism.

The researchers acknowledge this was a retrospective, post-hoc analysis and that urolithiasis – a stone in the urinary tract, which includes nephrolithiasis, a kidney stone – was an adverse event, not a primary or secondary outcome.

Also, the stone composition, which might help explain how the drug may affect stone formation, is unknown.

Therefore, “dedicated randomized prospective clinical trials are needed to confirm these initial observations in patients both with and without type 2 diabetes,” said Dr. Balasubramanian, a clinical fellow in the section of endocrinology & metabolism, department of internal medicine at Yale University, New Haven, Conn.

However, “if this association is proven, empagliflozin may be used to decrease the risk of kidney stones at least in those with type 2 diabetes, but maybe also in those without diabetes,” Dr. Balasubramanian said in an interview.

Further trials are also needed to determine if this is a class effect, which is likely, she speculated, and to unravel the potential mechanism.

This is important because of the prevalence of kidney stones, which affect up to 15% of the general population and 15%-20% of patients with diabetes, she explained.
 

‘Provocative’ earlier findings

The current study was prompted by a recent observational study by Kasper B. Kristensen, MD, PhD, and colleagues.

Because SGLT2 inhibitors increase urinary glucose excretion through reduced renal reabsorption of glucose leading to osmotic diuresis and increased urinary flow, they hypothesized that these therapies “may reduce the risk of upper urinary tract stones (nephrolithiasis) by reducing the concentration of lithogenic substances in urine.” 

Using data from Danish Health registries, they matched 12,325 individuals newly prescribed an SGLT2 inhibitor 1:1 with patients newly prescribed a glucagonlike peptide-1 (GLP1) agonist, another new class of drugs for treating type 2 diabetes.

They found a hazard ratio of 0.51 (95% confidence interval, 0.37-0.71) for incident nephrolithiasis and a hazard ratio of 0.68 (95% CI, 0.48-0.97) for recurrent nephrolithiasis for patients taking SGLT2 inhibitors versus GLP-1 agonists.

These findings are “striking,” according to Dr. Balasubramanian and colleagues. However, “these data, while provocative, were entirely retrospective and therefore possibly prone to bias,” they add.
 

Pooled data from 20 trials

The current study analyzed data from 20 randomized controlled trials of glycemic control in type 2 diabetes, in which 10,177 patients had received empagliflozin 10 mg or 25 mg and 4,904 patients had received placebo.

Most patients (46.5%) had participated in the EMPA-REG OUTCOMES trial, which also had the longest follow-up (2.6 years).

The researchers identified patients with a new stone from the urinary tract (including the kidney, ureter, and urethra). Patients had received either the study drug for a median of 543 days or placebo for a median of 549 days.

During treatment, 104 of 10,177 patients in the pooled empagliflozin groups and 79 of 4,904 patients in the pooled placebo groups developed a stone in the urinary tract.

This was equivalent to 0.63 new urinary-tract stones per 100 patient-years in the pooled empagliflozin groups versus 1.01 new urinary-tract stones per 100 patient-years in the pooled placebo groups.

The incidence rate ratio was 0.64 (95% CI, 0.48-0.86), in favor of empagliflozin.

When the analysis was restricted to new kidney stones, the results were similar: 75 of 10,177 patients in the pooled empagliflozin groups and 57 of 4,904 patients in the pooled placebo groups developed a kidney stone.

This was equivalent to 0.45 new kidney stones per 100 patient-years in the pooled empagliflozin groups versus 0.72 new kidney stones per 100 patient-years in the pooled placebo groups.

The IRR was 0.65 (95% CI, 0.46-0.92), in favor of empagliflozin.
 

Upcoming small RCT in adults without diabetes

Invited to comment on the new study, Dr. Kristensen said: “The reduced risk of SGLT2 inhibitors towards nephrolithiasis is now reported in at least two studies with different methodology, different populations, and different exposure and outcome definitions.”

“I agree that randomized clinical trials designed specifically to confirm these findings appear warranted,” added Dr. Kristensen, from the Institute of Public Health, Clinical Pharmacology, Pharmacy, and Environmental Medicine, University of Southern Denmark in Odense.

There is a need for studies in patients with and without diabetes, he added, especially ones that focus on prevention of nephrolithiasis in patients with kidney stone disease.

A new trial should shed further light on this.

Results are expected by the end of 2022 for SWEETSTONE (Impact of the SGLT2 Inhibitor Empagliflozin on Urinary Supersaturations in Kidney Stone Formers), a randomized, double-blind crossover exploratory study in 46 patients without diabetes.

This should provide preliminary data to “establish the relevance for larger trials assessing the prophylactic potential of empagliflozin in kidney stone disease,” according to an article on the trial protocol recently published in BMJ.

The trials included in the pooled dataset were funded by Boehringer Ingelheim or the Boehringer Ingelheim and Eli Lilly Diabetes Alliance. Dr. Balasubramanian has reported no relevant financial relationships.

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

Patients with type 2 diabetes who received empagliflozin, a sodium glucose cotransporter-2 (SGLT2) inhibitor, were almost 40% less likely to have a kidney stone than patients who received placebo during a median 1.5 years of treatment.

These findings are from an analysis of pooled data from phase 1-4 clinical trials of empagliflozin for blood glucose control in 15,081 patients with type 2 diabetes.  

Priyadarshini Balasubramanian, MD, presented the study as a poster at the annual meeting of the Endocrine Society; the study also was published online in the Journal of Clinical Endocrinology & Metabolism.

The researchers acknowledge this was a retrospective, post-hoc analysis and that urolithiasis – a stone in the urinary tract, which includes nephrolithiasis, a kidney stone – was an adverse event, not a primary or secondary outcome.

Also, the stone composition, which might help explain how the drug may affect stone formation, is unknown.

Therefore, “dedicated randomized prospective clinical trials are needed to confirm these initial observations in patients both with and without type 2 diabetes,” said Dr. Balasubramanian, a clinical fellow in the section of endocrinology & metabolism, department of internal medicine at Yale University, New Haven, Conn.

However, “if this association is proven, empagliflozin may be used to decrease the risk of kidney stones at least in those with type 2 diabetes, but maybe also in those without diabetes,” Dr. Balasubramanian said in an interview.

Further trials are also needed to determine if this is a class effect, which is likely, she speculated, and to unravel the potential mechanism.

This is important because of the prevalence of kidney stones, which affect up to 15% of the general population and 15%-20% of patients with diabetes, she explained.
 

‘Provocative’ earlier findings

The current study was prompted by a recent observational study by Kasper B. Kristensen, MD, PhD, and colleagues.

Because SGLT2 inhibitors increase urinary glucose excretion through reduced renal reabsorption of glucose leading to osmotic diuresis and increased urinary flow, they hypothesized that these therapies “may reduce the risk of upper urinary tract stones (nephrolithiasis) by reducing the concentration of lithogenic substances in urine.” 

Using data from Danish Health registries, they matched 12,325 individuals newly prescribed an SGLT2 inhibitor 1:1 with patients newly prescribed a glucagonlike peptide-1 (GLP1) agonist, another new class of drugs for treating type 2 diabetes.

They found a hazard ratio of 0.51 (95% confidence interval, 0.37-0.71) for incident nephrolithiasis and a hazard ratio of 0.68 (95% CI, 0.48-0.97) for recurrent nephrolithiasis for patients taking SGLT2 inhibitors versus GLP-1 agonists.

These findings are “striking,” according to Dr. Balasubramanian and colleagues. However, “these data, while provocative, were entirely retrospective and therefore possibly prone to bias,” they add.
 

Pooled data from 20 trials

The current study analyzed data from 20 randomized controlled trials of glycemic control in type 2 diabetes, in which 10,177 patients had received empagliflozin 10 mg or 25 mg and 4,904 patients had received placebo.

Most patients (46.5%) had participated in the EMPA-REG OUTCOMES trial, which also had the longest follow-up (2.6 years).

The researchers identified patients with a new stone from the urinary tract (including the kidney, ureter, and urethra). Patients had received either the study drug for a median of 543 days or placebo for a median of 549 days.

During treatment, 104 of 10,177 patients in the pooled empagliflozin groups and 79 of 4,904 patients in the pooled placebo groups developed a stone in the urinary tract.

This was equivalent to 0.63 new urinary-tract stones per 100 patient-years in the pooled empagliflozin groups versus 1.01 new urinary-tract stones per 100 patient-years in the pooled placebo groups.

The incidence rate ratio was 0.64 (95% CI, 0.48-0.86), in favor of empagliflozin.

When the analysis was restricted to new kidney stones, the results were similar: 75 of 10,177 patients in the pooled empagliflozin groups and 57 of 4,904 patients in the pooled placebo groups developed a kidney stone.

This was equivalent to 0.45 new kidney stones per 100 patient-years in the pooled empagliflozin groups versus 0.72 new kidney stones per 100 patient-years in the pooled placebo groups.

The IRR was 0.65 (95% CI, 0.46-0.92), in favor of empagliflozin.
 

Upcoming small RCT in adults without diabetes

Invited to comment on the new study, Dr. Kristensen said: “The reduced risk of SGLT2 inhibitors towards nephrolithiasis is now reported in at least two studies with different methodology, different populations, and different exposure and outcome definitions.”

“I agree that randomized clinical trials designed specifically to confirm these findings appear warranted,” added Dr. Kristensen, from the Institute of Public Health, Clinical Pharmacology, Pharmacy, and Environmental Medicine, University of Southern Denmark in Odense.

There is a need for studies in patients with and without diabetes, he added, especially ones that focus on prevention of nephrolithiasis in patients with kidney stone disease.

A new trial should shed further light on this.

Results are expected by the end of 2022 for SWEETSTONE (Impact of the SGLT2 Inhibitor Empagliflozin on Urinary Supersaturations in Kidney Stone Formers), a randomized, double-blind crossover exploratory study in 46 patients without diabetes.

This should provide preliminary data to “establish the relevance for larger trials assessing the prophylactic potential of empagliflozin in kidney stone disease,” according to an article on the trial protocol recently published in BMJ.

The trials included in the pooled dataset were funded by Boehringer Ingelheim or the Boehringer Ingelheim and Eli Lilly Diabetes Alliance. Dr. Balasubramanian has reported no relevant financial relationships.

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

For most of us, the “best” time of day to work out is simple: When we can.

Maybe that’s before or after work. Or when the gym offers free daycare. Or when our favorite instructor teaches our favorite class.

That’s why we call it a “routine.” And if the results are the same, it’s hard to imagine changing it up.

But what if the results aren’t the same?

pojoslaw/Thinkstock

They may not be, according to a new study from a research team at Skidmore College in Saratoga Springs, N.Y. The results of a 12-week exercise program were different for morning versus evening workouts.

Women who worked out in the morning lost more fat, while those who trained in the evening gained more upper-body strength and power. As for men, the performance improvements were similar no matter when they exercised. But those who did so in the evening had a significant drop in blood pressure, among other benefits.

The study is part of a growing body of research showing different results for different times of day among different populations. As it turns out, when you exercise can ultimately have a big effect, not just on strength and fat loss, but also heart health, mood, and quality of sleep.
 

An accidental discovery

The original goal of the Skidmore study was to test a unique fitness program with a group of healthy, fit, and extremely active adults in early middle age.

The program includes four workouts a week, each with a different focus: strength, steady-pace endurance, high-intensity intervals, and flexibility (traditional stretching combined with yoga and Pilates exercises).

But because the group was so large – 27 women and 20 men completed the 3-month program – they had to split them into morning and evening workout groups.

It wasn’t until researchers looked at the results that they saw the differences between morning and evening exercise, says lead author Paul Arciero, PhD.

Dr. Arciero stressed that participants in every group got leaner and stronger. But the women who worked out in the morning got much bigger reductions in body fat and body-fat percentage than the evening group. Meanwhile, women in the evening group got much bigger gains in upper-body strength, power, and muscular endurance than their morning counterparts.

Among the men, the evening group had significantly larger improvements in blood pressure, cholesterol levels, and the percentage of fat they burned for energy, along with a bigger drop in feelings of fatigue.
 

Strategic timing for powerful results

Some of these findings are consistent with previous research. For example, a study published in 2021 showed that the ability to exert high effort and express strength and power peaks in the late afternoon, about the same time that your core body temperature is at its highest point.

On the other hand, you’ll probably perform better in the morning when the activity requires a lot of skill and coordination or depends on strategic decision-making.

The findings apply to both men and women.

Performance aside, exercise timing might offer strong health benefits for men with type 2 diabetes, or at high risk for it.

A study showed that men who exercised between 3 p.m. and 6 p.m. saw dramatic improvements in blood sugar management and insulin sensitivity, compared to a group that worked out between 8 a.m. and 10 a.m.

They also lost more fat during the 12-week program, even though they were doing the exact same workouts.
 

Train consistently, sleep well

When you exercise can affect your sleep quality in many ways, said neuroscientist Jennifer Heisz, PhD, of McMaster University, Hamilton, Ont.

First, she said, “exercise helps you fall asleep faster and sleep deeper at night.” (The only exception is if you exercise so intensely or so close to bedtime that your heart rate is still elevated.)

Second, “exercising at a consistent time every day helps regulate the body’s circadian rhythms.” It doesn’t matter if the exercise is in the morning, evening, or anywhere in between. As long as it’s predictable, it will help you fall asleep and wake up at the same times.

Outdoor exercise is even better, she said. The sun is the most powerful regulator of the circadian clock and works in tandem with physical activity.

Third, exercising at specific times can help you overcome jet lag or adjust to an earlier or later shift at work.

“Exercising at 7 a.m. or between 1 and 4 p.m. helps your circadian clock to ‘fall back’ in time, making it easier to wake up earlier,” Dr. Heisz said. If you need to train your body to wake up later in the morning, try working out between 7 p.m. and 10 p.m.
 

All exercise is good, but the right timing can make it even better

“The best time to exercise is when you can fit it in,” Dr. Arciero said. “You’ve got to choose the time that fits your lifestyle best.”

But context matters, he noted.

“For someone needing to achieve an improvement in their risk for cardiometabolic disease,” his study shows an advantage to working out later in the day, especially for men. If you’re more focused on building upper-body strength and power, you’ll probably get better results from training in the afternoon or evening.

And for fat loss, the Skidmore study shows better results for women who did morning workouts.

And if you’re still not sure? Try sleeping on it – preferably after your workout.

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

For most of us, the “best” time of day to work out is simple: When we can.

Maybe that’s before or after work. Or when the gym offers free daycare. Or when our favorite instructor teaches our favorite class.

That’s why we call it a “routine.” And if the results are the same, it’s hard to imagine changing it up.

But what if the results aren’t the same?

pojoslaw/Thinkstock

They may not be, according to a new study from a research team at Skidmore College in Saratoga Springs, N.Y. The results of a 12-week exercise program were different for morning versus evening workouts.

Women who worked out in the morning lost more fat, while those who trained in the evening gained more upper-body strength and power. As for men, the performance improvements were similar no matter when they exercised. But those who did so in the evening had a significant drop in blood pressure, among other benefits.

The study is part of a growing body of research showing different results for different times of day among different populations. As it turns out, when you exercise can ultimately have a big effect, not just on strength and fat loss, but also heart health, mood, and quality of sleep.
 

An accidental discovery

The original goal of the Skidmore study was to test a unique fitness program with a group of healthy, fit, and extremely active adults in early middle age.

The program includes four workouts a week, each with a different focus: strength, steady-pace endurance, high-intensity intervals, and flexibility (traditional stretching combined with yoga and Pilates exercises).

But because the group was so large – 27 women and 20 men completed the 3-month program – they had to split them into morning and evening workout groups.

It wasn’t until researchers looked at the results that they saw the differences between morning and evening exercise, says lead author Paul Arciero, PhD.

Dr. Arciero stressed that participants in every group got leaner and stronger. But the women who worked out in the morning got much bigger reductions in body fat and body-fat percentage than the evening group. Meanwhile, women in the evening group got much bigger gains in upper-body strength, power, and muscular endurance than their morning counterparts.

Among the men, the evening group had significantly larger improvements in blood pressure, cholesterol levels, and the percentage of fat they burned for energy, along with a bigger drop in feelings of fatigue.
 

Strategic timing for powerful results

Some of these findings are consistent with previous research. For example, a study published in 2021 showed that the ability to exert high effort and express strength and power peaks in the late afternoon, about the same time that your core body temperature is at its highest point.

On the other hand, you’ll probably perform better in the morning when the activity requires a lot of skill and coordination or depends on strategic decision-making.

The findings apply to both men and women.

Performance aside, exercise timing might offer strong health benefits for men with type 2 diabetes, or at high risk for it.

A study showed that men who exercised between 3 p.m. and 6 p.m. saw dramatic improvements in blood sugar management and insulin sensitivity, compared to a group that worked out between 8 a.m. and 10 a.m.

They also lost more fat during the 12-week program, even though they were doing the exact same workouts.
 

Train consistently, sleep well

When you exercise can affect your sleep quality in many ways, said neuroscientist Jennifer Heisz, PhD, of McMaster University, Hamilton, Ont.

First, she said, “exercise helps you fall asleep faster and sleep deeper at night.” (The only exception is if you exercise so intensely or so close to bedtime that your heart rate is still elevated.)

Second, “exercising at a consistent time every day helps regulate the body’s circadian rhythms.” It doesn’t matter if the exercise is in the morning, evening, or anywhere in between. As long as it’s predictable, it will help you fall asleep and wake up at the same times.

Outdoor exercise is even better, she said. The sun is the most powerful regulator of the circadian clock and works in tandem with physical activity.

Third, exercising at specific times can help you overcome jet lag or adjust to an earlier or later shift at work.

“Exercising at 7 a.m. or between 1 and 4 p.m. helps your circadian clock to ‘fall back’ in time, making it easier to wake up earlier,” Dr. Heisz said. If you need to train your body to wake up later in the morning, try working out between 7 p.m. and 10 p.m.
 

All exercise is good, but the right timing can make it even better

“The best time to exercise is when you can fit it in,” Dr. Arciero said. “You’ve got to choose the time that fits your lifestyle best.”

But context matters, he noted.

“For someone needing to achieve an improvement in their risk for cardiometabolic disease,” his study shows an advantage to working out later in the day, especially for men. If you’re more focused on building upper-body strength and power, you’ll probably get better results from training in the afternoon or evening.

And for fat loss, the Skidmore study shows better results for women who did morning workouts.

And if you’re still not sure? Try sleeping on it – preferably after your workout.

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

For most of us, the “best” time of day to work out is simple: When we can.

Maybe that’s before or after work. Or when the gym offers free daycare. Or when our favorite instructor teaches our favorite class.

That’s why we call it a “routine.” And if the results are the same, it’s hard to imagine changing it up.

But what if the results aren’t the same?

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They may not be, according to a new study from a research team at Skidmore College in Saratoga Springs, N.Y. The results of a 12-week exercise program were different for morning versus evening workouts.

Women who worked out in the morning lost more fat, while those who trained in the evening gained more upper-body strength and power. As for men, the performance improvements were similar no matter when they exercised. But those who did so in the evening had a significant drop in blood pressure, among other benefits.

The study is part of a growing body of research showing different results for different times of day among different populations. As it turns out, when you exercise can ultimately have a big effect, not just on strength and fat loss, but also heart health, mood, and quality of sleep.
 

An accidental discovery

The original goal of the Skidmore study was to test a unique fitness program with a group of healthy, fit, and extremely active adults in early middle age.

The program includes four workouts a week, each with a different focus: strength, steady-pace endurance, high-intensity intervals, and flexibility (traditional stretching combined with yoga and Pilates exercises).

But because the group was so large – 27 women and 20 men completed the 3-month program – they had to split them into morning and evening workout groups.

It wasn’t until researchers looked at the results that they saw the differences between morning and evening exercise, says lead author Paul Arciero, PhD.

Dr. Arciero stressed that participants in every group got leaner and stronger. But the women who worked out in the morning got much bigger reductions in body fat and body-fat percentage than the evening group. Meanwhile, women in the evening group got much bigger gains in upper-body strength, power, and muscular endurance than their morning counterparts.

Among the men, the evening group had significantly larger improvements in blood pressure, cholesterol levels, and the percentage of fat they burned for energy, along with a bigger drop in feelings of fatigue.
 

Strategic timing for powerful results

Some of these findings are consistent with previous research. For example, a study published in 2021 showed that the ability to exert high effort and express strength and power peaks in the late afternoon, about the same time that your core body temperature is at its highest point.

On the other hand, you’ll probably perform better in the morning when the activity requires a lot of skill and coordination or depends on strategic decision-making.

The findings apply to both men and women.

Performance aside, exercise timing might offer strong health benefits for men with type 2 diabetes, or at high risk for it.

A study showed that men who exercised between 3 p.m. and 6 p.m. saw dramatic improvements in blood sugar management and insulin sensitivity, compared to a group that worked out between 8 a.m. and 10 a.m.

They also lost more fat during the 12-week program, even though they were doing the exact same workouts.
 

Train consistently, sleep well

When you exercise can affect your sleep quality in many ways, said neuroscientist Jennifer Heisz, PhD, of McMaster University, Hamilton, Ont.

First, she said, “exercise helps you fall asleep faster and sleep deeper at night.” (The only exception is if you exercise so intensely or so close to bedtime that your heart rate is still elevated.)

Second, “exercising at a consistent time every day helps regulate the body’s circadian rhythms.” It doesn’t matter if the exercise is in the morning, evening, or anywhere in between. As long as it’s predictable, it will help you fall asleep and wake up at the same times.

Outdoor exercise is even better, she said. The sun is the most powerful regulator of the circadian clock and works in tandem with physical activity.

Third, exercising at specific times can help you overcome jet lag or adjust to an earlier or later shift at work.

“Exercising at 7 a.m. or between 1 and 4 p.m. helps your circadian clock to ‘fall back’ in time, making it easier to wake up earlier,” Dr. Heisz said. If you need to train your body to wake up later in the morning, try working out between 7 p.m. and 10 p.m.
 

All exercise is good, but the right timing can make it even better

“The best time to exercise is when you can fit it in,” Dr. Arciero said. “You’ve got to choose the time that fits your lifestyle best.”

But context matters, he noted.

“For someone needing to achieve an improvement in their risk for cardiometabolic disease,” his study shows an advantage to working out later in the day, especially for men. If you’re more focused on building upper-body strength and power, you’ll probably get better results from training in the afternoon or evening.

And for fat loss, the Skidmore study shows better results for women who did morning workouts.

And if you’re still not sure? Try sleeping on it – preferably after your workout.

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

Although breast cancer occurs less frequently in Black women, compared with White women, they have a much higher risk of dying from the disease.

In the United States, age-adjusted breast cancer mortality between 2014 and 2018 was approximately 40% higher among Black women than among non-Hispanic White women.

This mortality gap likely reflects the fact that Black women face substantial barriers to obtaining timely, high-quality medical care, compared with White women, lead author Ismail Jatoi, MD, PhD, University of Texas Health Science Center, San Antonio, and colleagues suggest in a recent opinion piece.

The article was published online  in The New England Journal of Medicine.

When the team examined the statistics for breast cancer mortality, they found a surprise: The mortality gap between races only dates back to 1980.

Prior to 1980, mortality from breast cancer among Black women was slightly lower than White women, Dr. Jatoi and colleagues point out.

That year was a turning point in breast cancer management, as in 1980, both mammography screening and adjuvant endocrine therapy became available.

This was also when the mortality gap between the races started to show up.

It was disparities in access to the two new interventions that precipitated the divergence, as the authors suggest. Why this occurred is fairly self-evident, they comment.

“Black women are more likely than White women to lack health insurance or to have inadequate coverage, which has limited their access to mammography screening and adversely affected therapeutic decisionmaking,” researchers point out.

Moreover, both mammography screening and endocrine therapy primarily benefit patients with hormone receptor (HR)-positive breast cancer, which is equally common in Black and White patients. However, Black women have a 65% higher rate of HR-negative cancers than White women – and HR-negative tumors are often detected during the interval between mammography screening exams as palpable cancers.

Black women also have an 81% higher rate of triple-negative breast cancer, so they have benefited less from mammography screening and adjuvant endocrine therapy, both of which favor the detection and treatment of HR-positive breast cancer, the authors emphasize.

Some have suggested that the excess HR-negative breast cancer in Black women might be explained by hereditary factors. Yet as Dr. Jatoi and colleagues point out, the incidence of HR-negative breast cancer has actually been falling across all races in the United States since 1992.

However, the declines have been slower among Black women, and reductions in its incidence have been smaller among White women living in less affluent regions of the United States compared with White women from more affluent regions.

These patterns suggest that social determinants of health influence not only access to and quality of health care but also the development of HR-negative breast cancers, as the authors observe.

“If all people with breast cancer benefited equally from effective medical interventions, racial differences in mortality for individual tumor subtypes would largely reflect differences in incidence,” Dr. Jatoi and colleagues continue.

Yet the statistics show that the substantial racial disparities in mortality for both HR-positive and HR-negative cancers between Black and White women cannot be explained by differences in the incidence of either tumor alone, they write.

For example, mortality for HR-positive breast cancer is 19% higher among Black women than among White women, yet the incidence of HR-positive breast cancer is 22% lower among Black women.

Similarly, mortality from HR-negative breast cancer is over twice as high among Black women as it is among White women – a substantially larger disparity, compared with the 65% relative difference in the incidence of HR-negative breast cancer between the two races.

“Universal health care coverage could reduce disparities in treatment for cancers of all subtypes, including triple-negative breast cancer,” Dr. Jatoi and colleagues emphasize.

“Ensuring universal access to high-quality medical care can substantially narrow the racial disparity in U.S. breast-cancer mortality,” they conclude. 

The authors have reported no relevant financial relationships.

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

Although breast cancer occurs less frequently in Black women, compared with White women, they have a much higher risk of dying from the disease.

In the United States, age-adjusted breast cancer mortality between 2014 and 2018 was approximately 40% higher among Black women than among non-Hispanic White women.

This mortality gap likely reflects the fact that Black women face substantial barriers to obtaining timely, high-quality medical care, compared with White women, lead author Ismail Jatoi, MD, PhD, University of Texas Health Science Center, San Antonio, and colleagues suggest in a recent opinion piece.

The article was published online  in The New England Journal of Medicine.

When the team examined the statistics for breast cancer mortality, they found a surprise: The mortality gap between races only dates back to 1980.

Prior to 1980, mortality from breast cancer among Black women was slightly lower than White women, Dr. Jatoi and colleagues point out.

That year was a turning point in breast cancer management, as in 1980, both mammography screening and adjuvant endocrine therapy became available.

This was also when the mortality gap between the races started to show up.

It was disparities in access to the two new interventions that precipitated the divergence, as the authors suggest. Why this occurred is fairly self-evident, they comment.

“Black women are more likely than White women to lack health insurance or to have inadequate coverage, which has limited their access to mammography screening and adversely affected therapeutic decisionmaking,” researchers point out.

Moreover, both mammography screening and endocrine therapy primarily benefit patients with hormone receptor (HR)-positive breast cancer, which is equally common in Black and White patients. However, Black women have a 65% higher rate of HR-negative cancers than White women – and HR-negative tumors are often detected during the interval between mammography screening exams as palpable cancers.

Black women also have an 81% higher rate of triple-negative breast cancer, so they have benefited less from mammography screening and adjuvant endocrine therapy, both of which favor the detection and treatment of HR-positive breast cancer, the authors emphasize.

Some have suggested that the excess HR-negative breast cancer in Black women might be explained by hereditary factors. Yet as Dr. Jatoi and colleagues point out, the incidence of HR-negative breast cancer has actually been falling across all races in the United States since 1992.

However, the declines have been slower among Black women, and reductions in its incidence have been smaller among White women living in less affluent regions of the United States compared with White women from more affluent regions.

These patterns suggest that social determinants of health influence not only access to and quality of health care but also the development of HR-negative breast cancers, as the authors observe.

“If all people with breast cancer benefited equally from effective medical interventions, racial differences in mortality for individual tumor subtypes would largely reflect differences in incidence,” Dr. Jatoi and colleagues continue.

Yet the statistics show that the substantial racial disparities in mortality for both HR-positive and HR-negative cancers between Black and White women cannot be explained by differences in the incidence of either tumor alone, they write.

For example, mortality for HR-positive breast cancer is 19% higher among Black women than among White women, yet the incidence of HR-positive breast cancer is 22% lower among Black women.

Similarly, mortality from HR-negative breast cancer is over twice as high among Black women as it is among White women – a substantially larger disparity, compared with the 65% relative difference in the incidence of HR-negative breast cancer between the two races.

“Universal health care coverage could reduce disparities in treatment for cancers of all subtypes, including triple-negative breast cancer,” Dr. Jatoi and colleagues emphasize.

“Ensuring universal access to high-quality medical care can substantially narrow the racial disparity in U.S. breast-cancer mortality,” they conclude. 

The authors have reported no relevant financial relationships.

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

Although breast cancer occurs less frequently in Black women, compared with White women, they have a much higher risk of dying from the disease.

In the United States, age-adjusted breast cancer mortality between 2014 and 2018 was approximately 40% higher among Black women than among non-Hispanic White women.

This mortality gap likely reflects the fact that Black women face substantial barriers to obtaining timely, high-quality medical care, compared with White women, lead author Ismail Jatoi, MD, PhD, University of Texas Health Science Center, San Antonio, and colleagues suggest in a recent opinion piece.

The article was published online  in The New England Journal of Medicine.

When the team examined the statistics for breast cancer mortality, they found a surprise: The mortality gap between races only dates back to 1980.

Prior to 1980, mortality from breast cancer among Black women was slightly lower than White women, Dr. Jatoi and colleagues point out.

That year was a turning point in breast cancer management, as in 1980, both mammography screening and adjuvant endocrine therapy became available.

This was also when the mortality gap between the races started to show up.

It was disparities in access to the two new interventions that precipitated the divergence, as the authors suggest. Why this occurred is fairly self-evident, they comment.

“Black women are more likely than White women to lack health insurance or to have inadequate coverage, which has limited their access to mammography screening and adversely affected therapeutic decisionmaking,” researchers point out.

Moreover, both mammography screening and endocrine therapy primarily benefit patients with hormone receptor (HR)-positive breast cancer, which is equally common in Black and White patients. However, Black women have a 65% higher rate of HR-negative cancers than White women – and HR-negative tumors are often detected during the interval between mammography screening exams as palpable cancers.

Black women also have an 81% higher rate of triple-negative breast cancer, so they have benefited less from mammography screening and adjuvant endocrine therapy, both of which favor the detection and treatment of HR-positive breast cancer, the authors emphasize.

Some have suggested that the excess HR-negative breast cancer in Black women might be explained by hereditary factors. Yet as Dr. Jatoi and colleagues point out, the incidence of HR-negative breast cancer has actually been falling across all races in the United States since 1992.

However, the declines have been slower among Black women, and reductions in its incidence have been smaller among White women living in less affluent regions of the United States compared with White women from more affluent regions.

These patterns suggest that social determinants of health influence not only access to and quality of health care but also the development of HR-negative breast cancers, as the authors observe.

“If all people with breast cancer benefited equally from effective medical interventions, racial differences in mortality for individual tumor subtypes would largely reflect differences in incidence,” Dr. Jatoi and colleagues continue.

Yet the statistics show that the substantial racial disparities in mortality for both HR-positive and HR-negative cancers between Black and White women cannot be explained by differences in the incidence of either tumor alone, they write.

For example, mortality for HR-positive breast cancer is 19% higher among Black women than among White women, yet the incidence of HR-positive breast cancer is 22% lower among Black women.

Similarly, mortality from HR-negative breast cancer is over twice as high among Black women as it is among White women – a substantially larger disparity, compared with the 65% relative difference in the incidence of HR-negative breast cancer between the two races.

“Universal health care coverage could reduce disparities in treatment for cancers of all subtypes, including triple-negative breast cancer,” Dr. Jatoi and colleagues emphasize.

“Ensuring universal access to high-quality medical care can substantially narrow the racial disparity in U.S. breast-cancer mortality,” they conclude. 

The authors have reported no relevant financial relationships.

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