Federal Practitioner

N95 masks began arriving at grocery stores and pharmacies on. Jan. 28, and consumers will be able to pick them up for free while supplies last.

The first batches are expected to arrive in some stores on Jan. 27, and many locations will begin offering them to customers on Jan. 28, according to NPR.

Meijer, which operates more than 250 groceries and pharmacies throughout the Midwest, has received about 3 million masks. Customers can pick up masks from the greeter stand at the store entrance.

More than 2,200 Kroger stores with pharmacies will give out free masks, with the first shipment expected to arrive on Jan. 27, a spokeswoman told NPR.

Walgreens will likely begin offering masks in some stores on Jan. 28, which will continue “on a rolling basis in the days and weeks following,” a spokesman told NPR.

Masks should arrive by Jan. 28 at Southeastern Grocers locations with in-store pharmacies, including Fresco y Mas, Harveys, and Winn-Dixie, according to CNN.

Hy-Vee received and began giving out masks on Jan. 21, and most stores with pharmacies were giving them out Jan. 26, according to Today.

CVS Pharmacy locations will offer free masks as early as Jan. 27, a spokesman told Today. That will include CVS Pharmacy locations inside Target and Schnucks.

Albertsons is “currently working to finalize details regarding inventory and distribution,” the chain told Today.

Rite Aid will have free masks in some stores at the end of the week, with all stores receiving them by early February, Today reported.

Walmart and Sam’s Club will offer free masks late next week at the earliest, according to NBC Chicago.

The Biden administration is sending out 400 million N95 masks from the Strategic National Stockpile. Each person can take up to three free masks, if they’re available, the Department of Health and Human Services has said.

The distribution of masks is meant to align with the CDC’s latest recommendation to wear an N95 or KN95 mask to prevent the spread of the highly transmissible Omicron variant. When worn correctly over the mouth and nose, the high-filtration masks are made to filter out 95% or more of airborne particles.

The Biden administration is also sending masks to community health centers and COVID-19 test kits directly to Americans. The programs are ramping up now and should be fully running by early February, NPR reported.

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

N95 masks began arriving at grocery stores and pharmacies on. Jan. 28, and consumers will be able to pick them up for free while supplies last.

The first batches are expected to arrive in some stores on Jan. 27, and many locations will begin offering them to customers on Jan. 28, according to NPR.

Meijer, which operates more than 250 groceries and pharmacies throughout the Midwest, has received about 3 million masks. Customers can pick up masks from the greeter stand at the store entrance.

More than 2,200 Kroger stores with pharmacies will give out free masks, with the first shipment expected to arrive on Jan. 27, a spokeswoman told NPR.

Walgreens will likely begin offering masks in some stores on Jan. 28, which will continue “on a rolling basis in the days and weeks following,” a spokesman told NPR.

Masks should arrive by Jan. 28 at Southeastern Grocers locations with in-store pharmacies, including Fresco y Mas, Harveys, and Winn-Dixie, according to CNN.

Hy-Vee received and began giving out masks on Jan. 21, and most stores with pharmacies were giving them out Jan. 26, according to Today.

CVS Pharmacy locations will offer free masks as early as Jan. 27, a spokesman told Today. That will include CVS Pharmacy locations inside Target and Schnucks.

Albertsons is “currently working to finalize details regarding inventory and distribution,” the chain told Today.

Rite Aid will have free masks in some stores at the end of the week, with all stores receiving them by early February, Today reported.

Walmart and Sam’s Club will offer free masks late next week at the earliest, according to NBC Chicago.

The Biden administration is sending out 400 million N95 masks from the Strategic National Stockpile. Each person can take up to three free masks, if they’re available, the Department of Health and Human Services has said.

The distribution of masks is meant to align with the CDC’s latest recommendation to wear an N95 or KN95 mask to prevent the spread of the highly transmissible Omicron variant. When worn correctly over the mouth and nose, the high-filtration masks are made to filter out 95% or more of airborne particles.

The Biden administration is also sending masks to community health centers and COVID-19 test kits directly to Americans. The programs are ramping up now and should be fully running by early February, NPR reported.

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

N95 masks began arriving at grocery stores and pharmacies on. Jan. 28, and consumers will be able to pick them up for free while supplies last.

The first batches are expected to arrive in some stores on Jan. 27, and many locations will begin offering them to customers on Jan. 28, according to NPR.

Meijer, which operates more than 250 groceries and pharmacies throughout the Midwest, has received about 3 million masks. Customers can pick up masks from the greeter stand at the store entrance.

More than 2,200 Kroger stores with pharmacies will give out free masks, with the first shipment expected to arrive on Jan. 27, a spokeswoman told NPR.

Walgreens will likely begin offering masks in some stores on Jan. 28, which will continue “on a rolling basis in the days and weeks following,” a spokesman told NPR.

Masks should arrive by Jan. 28 at Southeastern Grocers locations with in-store pharmacies, including Fresco y Mas, Harveys, and Winn-Dixie, according to CNN.

Hy-Vee received and began giving out masks on Jan. 21, and most stores with pharmacies were giving them out Jan. 26, according to Today.

CVS Pharmacy locations will offer free masks as early as Jan. 27, a spokesman told Today. That will include CVS Pharmacy locations inside Target and Schnucks.

Albertsons is “currently working to finalize details regarding inventory and distribution,” the chain told Today.

Rite Aid will have free masks in some stores at the end of the week, with all stores receiving them by early February, Today reported.

Walmart and Sam’s Club will offer free masks late next week at the earliest, according to NBC Chicago.

The Biden administration is sending out 400 million N95 masks from the Strategic National Stockpile. Each person can take up to three free masks, if they’re available, the Department of Health and Human Services has said.

The distribution of masks is meant to align with the CDC’s latest recommendation to wear an N95 or KN95 mask to prevent the spread of the highly transmissible Omicron variant. When worn correctly over the mouth and nose, the high-filtration masks are made to filter out 95% or more of airborne particles.

The Biden administration is also sending masks to community health centers and COVID-19 test kits directly to Americans. The programs are ramping up now and should be fully running by early February, NPR reported.

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

Here we are. Again. It’s cold and it’s gray. The sun rises late and sets early, so that it feels like midnight by 8 p.m. Indoor venues are risky with the highly contagious Omicron variant, and I feel like we are all pushing the replay button on 2021’s miserable winter.

In some ways, it’s worse: In 2021 we had the hope that vaccines would pull us out of the pandemic and we had guidance on all that we should not be doing. In January, we were gaming the various Internet sites to get a coveted vaccine for ourselves or our family and friends, then lining up to get jabbed. We did not yet know that it wouldn’t be enough – that we’d need boosters, that Delta and Omicron would defy the vaccines. Yes, the vaccines work miracles to prevent severe disease and death, but the worry of passing the virus to someone who is vulnerable or unvaccinated(!), or both, remains – and now we can wonder how we’ll ever get out of this mess with hopeful talk of an endemic, while we wait on the next variant. I like certainty, and this pandemic is one big screaming reminder that certainty about anything is just a pleasant notion, death and taxes excluded, of course.

PeopleImages/E+/Getty Images

Kris Lukish, vice president of human resources at Johns Hopkins Hospital in Baltimore, started an update to the hospital employees with: “As we begin 2022, it feels like we are experiencing dejà vu, or ‘Groundhog Day,’ or ‘50 First Dates.’ In ‘50 First Dates,’ Drew Barrymore wakes up each day reliving one specific day. It never changes. I realize our world may seem a little like that right now. We thought we’d turned a corner with COVID, and instead we saw a rapid rise in cases and hospitalizations due to the Omicron variant, higher than in previous surges.”

In 2021, many of us skipped holiday travel and ate outdoors. My morning coffee group moved to Zoom and it wasn’t until late spring, when community rates of COVID nose-dived, that I began seeing patients in my office for the first time in over a year. Since many of my patients are over 60, I tested myself with a home antigen test before going into the office. I changed my schedule so sessions began on the half-hour to be sure the suite’s waiting room would be empty, and I purchased an air purifier, cracked the window open, and figured everyone was as safe as we could reasonably be.

By the first Monday in January 2022, the positivity rate in Maryland was just shy of 30%. Twitter circulated anecdotes about false negatives with the home antigen test kits, and I decided it was safest to return to all-virtual appointments.

Mona Masood, DO, is cofounder of the Physician Support Line, a call-in service for doctors that started in March 2020. She has noted a change in the problems physicians face.

“We’re seeing a lot of empathy fatigue,” Dr. Masood said. “It’s not unexpected with a prolonged situation like this – the trauma has doctors in survival mode and they need to be present for themselves, their families, and their patients. People are emotionally drained, and we’re stretching them to the limit. Now at the front lines, doctors are getting a lot of backlash. There are the conspiracy theories, and people who challenge their knowledge and training and it leads them to ask if they should be doing this work. Some callers are thinking about leaving medicine and asking: ‘Is this what I signed up for?’ and these are large decisions that are being made in a specific context.

“The other thing we’re hearing is from trainees – residents and fellows – who are expected to carry a lot of work on the COVID units. Some are being told that they can’t graduate because they haven’t finished their other training requirements. This type of systemic issue produces moral injury.”

Dr. Masood talked about what running the support line has been like for her. “I know people want to give more in a catastrophe, and I was realistic that the enthusiasm might die off. I would go as long as psychiatrists volunteer, and the most incredible thing is that it hasn’t stopped. Some of the original people are no longer with us, but others have come aboard, and it’s been incredible to be a part of this.”

In her Jan. 26, 2022, newsletter, epidemiologist Katelyn Jetelina, PhD, MPH, tried to be reassuring about the future. “In order to know how this will end, we need to look at how other pandemics ended,” Dr. Jetelina wrote. “First, recognize the last part of that sentence ... pandemics end. Every epi curve comes down. This pandemic will end, too. Hold that fact close to you.”

She wrote about the three ways that pandemics end. The SARS pandemic of 2002 lasted 1.5 years as public health measures were effective, in large part because the disease was spread only by symptomatic patients. Vaccines offer a second way to end pandemics, as they have for polio and smallpox. “If the globe works together, we could possibly eradicate SARS-CoV-2 with vaccines. [Now that we have numerous animal reservoirs, though, this is close to impossible.]”

Finally, Dr. Jetelina noted that the 1918 flu changed from a pandemic situation to being endemic. “Over time, the virus attenuated, it became less severe.” Society acclimates to a virus with a low mortality rate. “The vast majority of scientists think an endemic state is the future of SARS-CoV-2. I agree.” And she goes on to define endemic as a steady state, but not the absence of suffering. She likens it to malaria and tuberculosis, illnesses with high global mortality.

“An endemic will come without an announcement or headlines, we won’t know we’re there until well after we’ve arrived.” She wrote of the uncertainty that faces us moving forward: We don’t know how much, or how long, immunity from Omicron infections will last, or if future variants will cause more or less severe disease. She casted her vote for global vaccinations, boosters, masks, better ventilation, communication, empathy, and tolerance to end the pandemic.

In Maryland, hospitalizations and positivity are starting to decline from the postholiday surge. I have figured out that I am not good at predicting what will happen next, and the experts don’t seem to be much better. I’d like a headline ending, the kind we looked to be heading toward last June.

I’ve told my patients who want to come in person that I will reassess in March. We have written our own rules, and mine are somewhere in the middle – I don’t go to public indoor spaces unmasked, but I do see vaccinated family and friends in our homes without masks. I don’t want to be responsible for transmitting a potentially fatal illness to a vulnerable patient. Honestly, this makes no sense, but since there is a video option, I feel I should not risk passing a potentially lethal virus to my patients. I just hope I’m not writing this same article again in January 2023.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins. Dr. Miller has no conflicts of interest.

Here we are. Again. It’s cold and it’s gray. The sun rises late and sets early, so that it feels like midnight by 8 p.m. Indoor venues are risky with the highly contagious Omicron variant, and I feel like we are all pushing the replay button on 2021’s miserable winter.

In some ways, it’s worse: In 2021 we had the hope that vaccines would pull us out of the pandemic and we had guidance on all that we should not be doing. In January, we were gaming the various Internet sites to get a coveted vaccine for ourselves or our family and friends, then lining up to get jabbed. We did not yet know that it wouldn’t be enough – that we’d need boosters, that Delta and Omicron would defy the vaccines. Yes, the vaccines work miracles to prevent severe disease and death, but the worry of passing the virus to someone who is vulnerable or unvaccinated(!), or both, remains – and now we can wonder how we’ll ever get out of this mess with hopeful talk of an endemic, while we wait on the next variant. I like certainty, and this pandemic is one big screaming reminder that certainty about anything is just a pleasant notion, death and taxes excluded, of course.

PeopleImages/E+/Getty Images

Kris Lukish, vice president of human resources at Johns Hopkins Hospital in Baltimore, started an update to the hospital employees with: “As we begin 2022, it feels like we are experiencing dejà vu, or ‘Groundhog Day,’ or ‘50 First Dates.’ In ‘50 First Dates,’ Drew Barrymore wakes up each day reliving one specific day. It never changes. I realize our world may seem a little like that right now. We thought we’d turned a corner with COVID, and instead we saw a rapid rise in cases and hospitalizations due to the Omicron variant, higher than in previous surges.”

In 2021, many of us skipped holiday travel and ate outdoors. My morning coffee group moved to Zoom and it wasn’t until late spring, when community rates of COVID nose-dived, that I began seeing patients in my office for the first time in over a year. Since many of my patients are over 60, I tested myself with a home antigen test before going into the office. I changed my schedule so sessions began on the half-hour to be sure the suite’s waiting room would be empty, and I purchased an air purifier, cracked the window open, and figured everyone was as safe as we could reasonably be.

By the first Monday in January 2022, the positivity rate in Maryland was just shy of 30%. Twitter circulated anecdotes about false negatives with the home antigen test kits, and I decided it was safest to return to all-virtual appointments.

Mona Masood, DO, is cofounder of the Physician Support Line, a call-in service for doctors that started in March 2020. She has noted a change in the problems physicians face.

“We’re seeing a lot of empathy fatigue,” Dr. Masood said. “It’s not unexpected with a prolonged situation like this – the trauma has doctors in survival mode and they need to be present for themselves, their families, and their patients. People are emotionally drained, and we’re stretching them to the limit. Now at the front lines, doctors are getting a lot of backlash. There are the conspiracy theories, and people who challenge their knowledge and training and it leads them to ask if they should be doing this work. Some callers are thinking about leaving medicine and asking: ‘Is this what I signed up for?’ and these are large decisions that are being made in a specific context.

“The other thing we’re hearing is from trainees – residents and fellows – who are expected to carry a lot of work on the COVID units. Some are being told that they can’t graduate because they haven’t finished their other training requirements. This type of systemic issue produces moral injury.”

Dr. Masood talked about what running the support line has been like for her. “I know people want to give more in a catastrophe, and I was realistic that the enthusiasm might die off. I would go as long as psychiatrists volunteer, and the most incredible thing is that it hasn’t stopped. Some of the original people are no longer with us, but others have come aboard, and it’s been incredible to be a part of this.”

In her Jan. 26, 2022, newsletter, epidemiologist Katelyn Jetelina, PhD, MPH, tried to be reassuring about the future. “In order to know how this will end, we need to look at how other pandemics ended,” Dr. Jetelina wrote. “First, recognize the last part of that sentence ... pandemics end. Every epi curve comes down. This pandemic will end, too. Hold that fact close to you.”

She wrote about the three ways that pandemics end. The SARS pandemic of 2002 lasted 1.5 years as public health measures were effective, in large part because the disease was spread only by symptomatic patients. Vaccines offer a second way to end pandemics, as they have for polio and smallpox. “If the globe works together, we could possibly eradicate SARS-CoV-2 with vaccines. [Now that we have numerous animal reservoirs, though, this is close to impossible.]”

Finally, Dr. Jetelina noted that the 1918 flu changed from a pandemic situation to being endemic. “Over time, the virus attenuated, it became less severe.” Society acclimates to a virus with a low mortality rate. “The vast majority of scientists think an endemic state is the future of SARS-CoV-2. I agree.” And she goes on to define endemic as a steady state, but not the absence of suffering. She likens it to malaria and tuberculosis, illnesses with high global mortality.

“An endemic will come without an announcement or headlines, we won’t know we’re there until well after we’ve arrived.” She wrote of the uncertainty that faces us moving forward: We don’t know how much, or how long, immunity from Omicron infections will last, or if future variants will cause more or less severe disease. She casted her vote for global vaccinations, boosters, masks, better ventilation, communication, empathy, and tolerance to end the pandemic.

In Maryland, hospitalizations and positivity are starting to decline from the postholiday surge. I have figured out that I am not good at predicting what will happen next, and the experts don’t seem to be much better. I’d like a headline ending, the kind we looked to be heading toward last June.

I’ve told my patients who want to come in person that I will reassess in March. We have written our own rules, and mine are somewhere in the middle – I don’t go to public indoor spaces unmasked, but I do see vaccinated family and friends in our homes without masks. I don’t want to be responsible for transmitting a potentially fatal illness to a vulnerable patient. Honestly, this makes no sense, but since there is a video option, I feel I should not risk passing a potentially lethal virus to my patients. I just hope I’m not writing this same article again in January 2023.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins. Dr. Miller has no conflicts of interest.

Here we are. Again. It’s cold and it’s gray. The sun rises late and sets early, so that it feels like midnight by 8 p.m. Indoor venues are risky with the highly contagious Omicron variant, and I feel like we are all pushing the replay button on 2021’s miserable winter.

In some ways, it’s worse: In 2021 we had the hope that vaccines would pull us out of the pandemic and we had guidance on all that we should not be doing. In January, we were gaming the various Internet sites to get a coveted vaccine for ourselves or our family and friends, then lining up to get jabbed. We did not yet know that it wouldn’t be enough – that we’d need boosters, that Delta and Omicron would defy the vaccines. Yes, the vaccines work miracles to prevent severe disease and death, but the worry of passing the virus to someone who is vulnerable or unvaccinated(!), or both, remains – and now we can wonder how we’ll ever get out of this mess with hopeful talk of an endemic, while we wait on the next variant. I like certainty, and this pandemic is one big screaming reminder that certainty about anything is just a pleasant notion, death and taxes excluded, of course.

PeopleImages/E+/Getty Images

Kris Lukish, vice president of human resources at Johns Hopkins Hospital in Baltimore, started an update to the hospital employees with: “As we begin 2022, it feels like we are experiencing dejà vu, or ‘Groundhog Day,’ or ‘50 First Dates.’ In ‘50 First Dates,’ Drew Barrymore wakes up each day reliving one specific day. It never changes. I realize our world may seem a little like that right now. We thought we’d turned a corner with COVID, and instead we saw a rapid rise in cases and hospitalizations due to the Omicron variant, higher than in previous surges.”

In 2021, many of us skipped holiday travel and ate outdoors. My morning coffee group moved to Zoom and it wasn’t until late spring, when community rates of COVID nose-dived, that I began seeing patients in my office for the first time in over a year. Since many of my patients are over 60, I tested myself with a home antigen test before going into the office. I changed my schedule so sessions began on the half-hour to be sure the suite’s waiting room would be empty, and I purchased an air purifier, cracked the window open, and figured everyone was as safe as we could reasonably be.

By the first Monday in January 2022, the positivity rate in Maryland was just shy of 30%. Twitter circulated anecdotes about false negatives with the home antigen test kits, and I decided it was safest to return to all-virtual appointments.

Mona Masood, DO, is cofounder of the Physician Support Line, a call-in service for doctors that started in March 2020. She has noted a change in the problems physicians face.

“We’re seeing a lot of empathy fatigue,” Dr. Masood said. “It’s not unexpected with a prolonged situation like this – the trauma has doctors in survival mode and they need to be present for themselves, their families, and their patients. People are emotionally drained, and we’re stretching them to the limit. Now at the front lines, doctors are getting a lot of backlash. There are the conspiracy theories, and people who challenge their knowledge and training and it leads them to ask if they should be doing this work. Some callers are thinking about leaving medicine and asking: ‘Is this what I signed up for?’ and these are large decisions that are being made in a specific context.

“The other thing we’re hearing is from trainees – residents and fellows – who are expected to carry a lot of work on the COVID units. Some are being told that they can’t graduate because they haven’t finished their other training requirements. This type of systemic issue produces moral injury.”

Dr. Masood talked about what running the support line has been like for her. “I know people want to give more in a catastrophe, and I was realistic that the enthusiasm might die off. I would go as long as psychiatrists volunteer, and the most incredible thing is that it hasn’t stopped. Some of the original people are no longer with us, but others have come aboard, and it’s been incredible to be a part of this.”

In her Jan. 26, 2022, newsletter, epidemiologist Katelyn Jetelina, PhD, MPH, tried to be reassuring about the future. “In order to know how this will end, we need to look at how other pandemics ended,” Dr. Jetelina wrote. “First, recognize the last part of that sentence ... pandemics end. Every epi curve comes down. This pandemic will end, too. Hold that fact close to you.”

She wrote about the three ways that pandemics end. The SARS pandemic of 2002 lasted 1.5 years as public health measures were effective, in large part because the disease was spread only by symptomatic patients. Vaccines offer a second way to end pandemics, as they have for polio and smallpox. “If the globe works together, we could possibly eradicate SARS-CoV-2 with vaccines. [Now that we have numerous animal reservoirs, though, this is close to impossible.]”

Finally, Dr. Jetelina noted that the 1918 flu changed from a pandemic situation to being endemic. “Over time, the virus attenuated, it became less severe.” Society acclimates to a virus with a low mortality rate. “The vast majority of scientists think an endemic state is the future of SARS-CoV-2. I agree.” And she goes on to define endemic as a steady state, but not the absence of suffering. She likens it to malaria and tuberculosis, illnesses with high global mortality.

“An endemic will come without an announcement or headlines, we won’t know we’re there until well after we’ve arrived.” She wrote of the uncertainty that faces us moving forward: We don’t know how much, or how long, immunity from Omicron infections will last, or if future variants will cause more or less severe disease. She casted her vote for global vaccinations, boosters, masks, better ventilation, communication, empathy, and tolerance to end the pandemic.

In Maryland, hospitalizations and positivity are starting to decline from the postholiday surge. I have figured out that I am not good at predicting what will happen next, and the experts don’t seem to be much better. I’d like a headline ending, the kind we looked to be heading toward last June.

I’ve told my patients who want to come in person that I will reassess in March. We have written our own rules, and mine are somewhere in the middle – I don’t go to public indoor spaces unmasked, but I do see vaccinated family and friends in our homes without masks. I don’t want to be responsible for transmitting a potentially fatal illness to a vulnerable patient. Honestly, this makes no sense, but since there is a video option, I feel I should not risk passing a potentially lethal virus to my patients. I just hope I’m not writing this same article again in January 2023.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins. Dr. Miller has no conflicts of interest.

A recent STAT article by Usha Lee McFarling identified orthopedic surgery as “the whitest specialty.” That’s a problem many, perhaps most, orthopedic surgeons are aware of. But seeing it stated so bluntly is jolting. It’s disconcerting to think that the orthopedic community is making so little progress toward achieving the principal ideal articulated in our country’s fundamental declaration of moral values: that all people are created equal and that they have inalienable rights – in our case, that everyone, Black, brown, as well as White, has the right to the same high level of medical care.

Unfortunately, as study after study has shown, minorities do not enjoy the right to equitable care. Instead, they are subject to disparities in treatment and outcomes that speak to the prejudices that are built into the health care system and are present – sometimes consciously, but most often subconsciously – in the minds of physicians. One important contributing element to these disparities is the paucity of minority practitioners. Studies have also shown that Black patients, for example, respond better to Black physicians, who so often share a psychological and cultural sympathy unavailable to most White physicians. It’s for that reason that being identified as “the whitest specialty” is so immensely troubling.

In researching her STAT article, Ms. McFarling spoke with American Academy of Orthopaedic Surgeons leaders, practicing surgeons, residents, and med students about the dearth of minority and female orthopedic surgeons. What she heard was perplexity and frustration about why better progress hasn’t been made toward correcting the gross underrepresentation of everyone other than White men. The AAOS, she noted, was one of the first specialties to recognize the lack of diversity and over the years has put in great effort to address the problem, creating task forces, committees, and diversity awards and sponsoring conferences and discussions. Yet progress has been glacial, at best.

From her respondents, Ms. McFarling heard an array of reasons for this. Black, Hispanic, and Native American persons are underrepresented in medical schools, so the pool of potential applicants for orthopedic residencies is shallow to begin with. STEM studies are notoriously inadequate in poorer primary and secondary schools, in which so many minority students are educated. The MCAT and USMLE Step 1 test, which play a role in acceptance to residencies, have been shown to be biased. The specialty has few Black or brown role models and, consequently, few advocates and a lack of mentorship. Overt bias may be fairly rare (though microaggressions are still a common and ongoing problem), but most minority and female orthopedic surgeons feel strongly that implicit or subconscious bias is entrenched and works against acceptance to residencies, success in residencies, and advancement in the field.

One of this article’s authors (AW) saw all these factors at work as a resident, then as an admissions committee member at both Yale and Harvard. But the fact is that other medical specialties face exactly these problems and barriers, and yet have been substantially more successful in overcoming them.

What seems to be distinctive about orthopedics is that the mindset which perpetuated (and still perpetuates) the old, lily-white, male predominance in medicine seems stronger, more ingrained, and more resistant to change than it is among physicians in other specialties. In this regard, Kristy Weber, MD, the first female president of the AAOS, told Ms. McFarling that the critical first step to bringing in more women or people of color is changing the culture. There seems to be a consensus about that.

So, what does that mean, given that the AAOS has made serious efforts in that regard that have clearly been less than effective?

The answer, as we see it, is first – to not give in to frustration. The time frames involved in changing customary states of mind are typically elongated, and the deeper the habituation, the longer transformation takes. Deep changes always mean a long, hard slog. For transformations of this sort to take place, the requirements are a general agreement on the value of the transformation, exposure to the destructive consequences of the customary modus operandi, and persuasion for why change needs to happen.

In orthopedics, the first requirement has been met. The AAOS espouses diversity and inclusion as a high-level value. In terms of the second two requirements – exposure and persuasion – orthopedic surgeons have been witness to events, campaigns, conferences, et cetera. But these have not been enough, which means that efforts need to be focused, enlarged, sustained, determined, and innovative.

Does the orthopedic surgery community have the ability to do that?

The answer is: Yes, it does.

Currently the orthopedic surgeon community boasts a number of organizations, groups, and individuals pushing for change, in addition to the AAOS’s Diversity Advisory Board. The predominantly African American J. Robert Gladden Orthopaedic Society, the Ruth Jackson Orthopaedic Society of female orthopedic physicians, and the Association of Latino Orthopaedic Surgeons are all energetic advocates, as is Nth Dimensions, the Perry Initiative, and various ad hoc and individual endeavors.

These are all strong proponents for their own groups in their own way. But history has shown in so many cases that concerted rather than individual action empowers advocacy, and what orthopedic surgery needs in its current situation of gross underrepresentation of minorities and women is an enhanced campaign to raise awareness and redouble persuasion.

One of many examples of the power of collective action is the Association of Minority Health Professions Schools founded by Dr. Louis Sullivan in 1977.* Dr. Sullivan (later secretary of the Department of Health & Human Services) was at that time the founding dean of Morehouse School of Medicine. Morehouse had been launched on a shoestring and needed funding urgently. Other Black health schools, such as Meharry Medical College and Tuskegee College of Veterinary Medicine, were in even more pressing financial need. The coalition of schools that Dr. Sullivan organized became a powerful force in Congress and the National Institutes of Health, magnitudes more effective in raising funds from government and other sources than the best individual efforts of the separate institutions.

Dr. Sullivan’s association is only one of a multitude of historical examples of the effectiveness of unified action. AAOS currently has no single officer charged with bringing together the efforts of the change assets that already exist. It could, perhaps should, have someone in that position. AAOS could invest that same office with a mandate to survey the other medical specialties and bring to bear the most effective diversity, equity, and inclusion (DEI) practices in their arsenals.

Finally, despite the attention AAOS has brought to DEI needs, a look at the organization’s strategic goals, its core values, and its “key enablers” finds not a single mention of diversity or inclusion. Given the country’s current focus on the need for equality, given the poor performance of the orthopedic surgery specialty in terms of inclusion, the obvious question is: Should there not be an official declaration positing diversity as a primary AAOS desideratum?

There is recent precedent for this in the American College of Physicians/American Board of Internal Medicine’s Physician Charter on Professionalism, which includes “social justice” as a primary goal of medical practice. This highlights and reinforces the humanitarian strivings of the profession. In light of the paralysis illuminated by Ms. McFarling’s STAT article, a clear, concise declaration by the AAOS of the value and need for DEI as a central component of the organization’s values should be high on the AAOS order of business. A commitment in that form would serve as a powerful catalyst for bringing orthopedic surgery into step with its sister specialties, as well as affirming the core egalitarian principle that underlies all of medical care.

Dr. White is the Ellen and Melvin Gordon Distinguished Professor of Medical Education and Professor of Orthopedic Surgery at Harvard Medical School, Boston. Dr. Chanoff is a founding board member of the Augustus A. White III Institute for Healthcare Equity. Neither Dr. White nor Dr. Chanoff reported any conflicts of interest. A version of this article first appeared on Medscape.com.

Correction, 2/1/22: An earlier version of this article omitted the title of "Dr." before Dr. Louis Sullivan's name.

A recent STAT article by Usha Lee McFarling identified orthopedic surgery as “the whitest specialty.” That’s a problem many, perhaps most, orthopedic surgeons are aware of. But seeing it stated so bluntly is jolting. It’s disconcerting to think that the orthopedic community is making so little progress toward achieving the principal ideal articulated in our country’s fundamental declaration of moral values: that all people are created equal and that they have inalienable rights – in our case, that everyone, Black, brown, as well as White, has the right to the same high level of medical care.

Unfortunately, as study after study has shown, minorities do not enjoy the right to equitable care. Instead, they are subject to disparities in treatment and outcomes that speak to the prejudices that are built into the health care system and are present – sometimes consciously, but most often subconsciously – in the minds of physicians. One important contributing element to these disparities is the paucity of minority practitioners. Studies have also shown that Black patients, for example, respond better to Black physicians, who so often share a psychological and cultural sympathy unavailable to most White physicians. It’s for that reason that being identified as “the whitest specialty” is so immensely troubling.

In researching her STAT article, Ms. McFarling spoke with American Academy of Orthopaedic Surgeons leaders, practicing surgeons, residents, and med students about the dearth of minority and female orthopedic surgeons. What she heard was perplexity and frustration about why better progress hasn’t been made toward correcting the gross underrepresentation of everyone other than White men. The AAOS, she noted, was one of the first specialties to recognize the lack of diversity and over the years has put in great effort to address the problem, creating task forces, committees, and diversity awards and sponsoring conferences and discussions. Yet progress has been glacial, at best.

From her respondents, Ms. McFarling heard an array of reasons for this. Black, Hispanic, and Native American persons are underrepresented in medical schools, so the pool of potential applicants for orthopedic residencies is shallow to begin with. STEM studies are notoriously inadequate in poorer primary and secondary schools, in which so many minority students are educated. The MCAT and USMLE Step 1 test, which play a role in acceptance to residencies, have been shown to be biased. The specialty has few Black or brown role models and, consequently, few advocates and a lack of mentorship. Overt bias may be fairly rare (though microaggressions are still a common and ongoing problem), but most minority and female orthopedic surgeons feel strongly that implicit or subconscious bias is entrenched and works against acceptance to residencies, success in residencies, and advancement in the field.

One of this article’s authors (AW) saw all these factors at work as a resident, then as an admissions committee member at both Yale and Harvard. But the fact is that other medical specialties face exactly these problems and barriers, and yet have been substantially more successful in overcoming them.

What seems to be distinctive about orthopedics is that the mindset which perpetuated (and still perpetuates) the old, lily-white, male predominance in medicine seems stronger, more ingrained, and more resistant to change than it is among physicians in other specialties. In this regard, Kristy Weber, MD, the first female president of the AAOS, told Ms. McFarling that the critical first step to bringing in more women or people of color is changing the culture. There seems to be a consensus about that.

So, what does that mean, given that the AAOS has made serious efforts in that regard that have clearly been less than effective?

The answer, as we see it, is first – to not give in to frustration. The time frames involved in changing customary states of mind are typically elongated, and the deeper the habituation, the longer transformation takes. Deep changes always mean a long, hard slog. For transformations of this sort to take place, the requirements are a general agreement on the value of the transformation, exposure to the destructive consequences of the customary modus operandi, and persuasion for why change needs to happen.

In orthopedics, the first requirement has been met. The AAOS espouses diversity and inclusion as a high-level value. In terms of the second two requirements – exposure and persuasion – orthopedic surgeons have been witness to events, campaigns, conferences, et cetera. But these have not been enough, which means that efforts need to be focused, enlarged, sustained, determined, and innovative.

Does the orthopedic surgery community have the ability to do that?

The answer is: Yes, it does.

Currently the orthopedic surgeon community boasts a number of organizations, groups, and individuals pushing for change, in addition to the AAOS’s Diversity Advisory Board. The predominantly African American J. Robert Gladden Orthopaedic Society, the Ruth Jackson Orthopaedic Society of female orthopedic physicians, and the Association of Latino Orthopaedic Surgeons are all energetic advocates, as is Nth Dimensions, the Perry Initiative, and various ad hoc and individual endeavors.

These are all strong proponents for their own groups in their own way. But history has shown in so many cases that concerted rather than individual action empowers advocacy, and what orthopedic surgery needs in its current situation of gross underrepresentation of minorities and women is an enhanced campaign to raise awareness and redouble persuasion.

One of many examples of the power of collective action is the Association of Minority Health Professions Schools founded by Dr. Louis Sullivan in 1977.* Dr. Sullivan (later secretary of the Department of Health & Human Services) was at that time the founding dean of Morehouse School of Medicine. Morehouse had been launched on a shoestring and needed funding urgently. Other Black health schools, such as Meharry Medical College and Tuskegee College of Veterinary Medicine, were in even more pressing financial need. The coalition of schools that Dr. Sullivan organized became a powerful force in Congress and the National Institutes of Health, magnitudes more effective in raising funds from government and other sources than the best individual efforts of the separate institutions.

Dr. Sullivan’s association is only one of a multitude of historical examples of the effectiveness of unified action. AAOS currently has no single officer charged with bringing together the efforts of the change assets that already exist. It could, perhaps should, have someone in that position. AAOS could invest that same office with a mandate to survey the other medical specialties and bring to bear the most effective diversity, equity, and inclusion (DEI) practices in their arsenals.

Finally, despite the attention AAOS has brought to DEI needs, a look at the organization’s strategic goals, its core values, and its “key enablers” finds not a single mention of diversity or inclusion. Given the country’s current focus on the need for equality, given the poor performance of the orthopedic surgery specialty in terms of inclusion, the obvious question is: Should there not be an official declaration positing diversity as a primary AAOS desideratum?

There is recent precedent for this in the American College of Physicians/American Board of Internal Medicine’s Physician Charter on Professionalism, which includes “social justice” as a primary goal of medical practice. This highlights and reinforces the humanitarian strivings of the profession. In light of the paralysis illuminated by Ms. McFarling’s STAT article, a clear, concise declaration by the AAOS of the value and need for DEI as a central component of the organization’s values should be high on the AAOS order of business. A commitment in that form would serve as a powerful catalyst for bringing orthopedic surgery into step with its sister specialties, as well as affirming the core egalitarian principle that underlies all of medical care.

Dr. White is the Ellen and Melvin Gordon Distinguished Professor of Medical Education and Professor of Orthopedic Surgery at Harvard Medical School, Boston. Dr. Chanoff is a founding board member of the Augustus A. White III Institute for Healthcare Equity. Neither Dr. White nor Dr. Chanoff reported any conflicts of interest. A version of this article first appeared on Medscape.com.

Correction, 2/1/22: An earlier version of this article omitted the title of "Dr." before Dr. Louis Sullivan's name.

A recent STAT article by Usha Lee McFarling identified orthopedic surgery as “the whitest specialty.” That’s a problem many, perhaps most, orthopedic surgeons are aware of. But seeing it stated so bluntly is jolting. It’s disconcerting to think that the orthopedic community is making so little progress toward achieving the principal ideal articulated in our country’s fundamental declaration of moral values: that all people are created equal and that they have inalienable rights – in our case, that everyone, Black, brown, as well as White, has the right to the same high level of medical care.

Unfortunately, as study after study has shown, minorities do not enjoy the right to equitable care. Instead, they are subject to disparities in treatment and outcomes that speak to the prejudices that are built into the health care system and are present – sometimes consciously, but most often subconsciously – in the minds of physicians. One important contributing element to these disparities is the paucity of minority practitioners. Studies have also shown that Black patients, for example, respond better to Black physicians, who so often share a psychological and cultural sympathy unavailable to most White physicians. It’s for that reason that being identified as “the whitest specialty” is so immensely troubling.

In researching her STAT article, Ms. McFarling spoke with American Academy of Orthopaedic Surgeons leaders, practicing surgeons, residents, and med students about the dearth of minority and female orthopedic surgeons. What she heard was perplexity and frustration about why better progress hasn’t been made toward correcting the gross underrepresentation of everyone other than White men. The AAOS, she noted, was one of the first specialties to recognize the lack of diversity and over the years has put in great effort to address the problem, creating task forces, committees, and diversity awards and sponsoring conferences and discussions. Yet progress has been glacial, at best.

From her respondents, Ms. McFarling heard an array of reasons for this. Black, Hispanic, and Native American persons are underrepresented in medical schools, so the pool of potential applicants for orthopedic residencies is shallow to begin with. STEM studies are notoriously inadequate in poorer primary and secondary schools, in which so many minority students are educated. The MCAT and USMLE Step 1 test, which play a role in acceptance to residencies, have been shown to be biased. The specialty has few Black or brown role models and, consequently, few advocates and a lack of mentorship. Overt bias may be fairly rare (though microaggressions are still a common and ongoing problem), but most minority and female orthopedic surgeons feel strongly that implicit or subconscious bias is entrenched and works against acceptance to residencies, success in residencies, and advancement in the field.

One of this article’s authors (AW) saw all these factors at work as a resident, then as an admissions committee member at both Yale and Harvard. But the fact is that other medical specialties face exactly these problems and barriers, and yet have been substantially more successful in overcoming them.

What seems to be distinctive about orthopedics is that the mindset which perpetuated (and still perpetuates) the old, lily-white, male predominance in medicine seems stronger, more ingrained, and more resistant to change than it is among physicians in other specialties. In this regard, Kristy Weber, MD, the first female president of the AAOS, told Ms. McFarling that the critical first step to bringing in more women or people of color is changing the culture. There seems to be a consensus about that.

So, what does that mean, given that the AAOS has made serious efforts in that regard that have clearly been less than effective?

The answer, as we see it, is first – to not give in to frustration. The time frames involved in changing customary states of mind are typically elongated, and the deeper the habituation, the longer transformation takes. Deep changes always mean a long, hard slog. For transformations of this sort to take place, the requirements are a general agreement on the value of the transformation, exposure to the destructive consequences of the customary modus operandi, and persuasion for why change needs to happen.

In orthopedics, the first requirement has been met. The AAOS espouses diversity and inclusion as a high-level value. In terms of the second two requirements – exposure and persuasion – orthopedic surgeons have been witness to events, campaigns, conferences, et cetera. But these have not been enough, which means that efforts need to be focused, enlarged, sustained, determined, and innovative.

Does the orthopedic surgery community have the ability to do that?

The answer is: Yes, it does.

Currently the orthopedic surgeon community boasts a number of organizations, groups, and individuals pushing for change, in addition to the AAOS’s Diversity Advisory Board. The predominantly African American J. Robert Gladden Orthopaedic Society, the Ruth Jackson Orthopaedic Society of female orthopedic physicians, and the Association of Latino Orthopaedic Surgeons are all energetic advocates, as is Nth Dimensions, the Perry Initiative, and various ad hoc and individual endeavors.

These are all strong proponents for their own groups in their own way. But history has shown in so many cases that concerted rather than individual action empowers advocacy, and what orthopedic surgery needs in its current situation of gross underrepresentation of minorities and women is an enhanced campaign to raise awareness and redouble persuasion.

One of many examples of the power of collective action is the Association of Minority Health Professions Schools founded by Dr. Louis Sullivan in 1977.* Dr. Sullivan (later secretary of the Department of Health & Human Services) was at that time the founding dean of Morehouse School of Medicine. Morehouse had been launched on a shoestring and needed funding urgently. Other Black health schools, such as Meharry Medical College and Tuskegee College of Veterinary Medicine, were in even more pressing financial need. The coalition of schools that Dr. Sullivan organized became a powerful force in Congress and the National Institutes of Health, magnitudes more effective in raising funds from government and other sources than the best individual efforts of the separate institutions.

Dr. Sullivan’s association is only one of a multitude of historical examples of the effectiveness of unified action. AAOS currently has no single officer charged with bringing together the efforts of the change assets that already exist. It could, perhaps should, have someone in that position. AAOS could invest that same office with a mandate to survey the other medical specialties and bring to bear the most effective diversity, equity, and inclusion (DEI) practices in their arsenals.

Finally, despite the attention AAOS has brought to DEI needs, a look at the organization’s strategic goals, its core values, and its “key enablers” finds not a single mention of diversity or inclusion. Given the country’s current focus on the need for equality, given the poor performance of the orthopedic surgery specialty in terms of inclusion, the obvious question is: Should there not be an official declaration positing diversity as a primary AAOS desideratum?

There is recent precedent for this in the American College of Physicians/American Board of Internal Medicine’s Physician Charter on Professionalism, which includes “social justice” as a primary goal of medical practice. This highlights and reinforces the humanitarian strivings of the profession. In light of the paralysis illuminated by Ms. McFarling’s STAT article, a clear, concise declaration by the AAOS of the value and need for DEI as a central component of the organization’s values should be high on the AAOS order of business. A commitment in that form would serve as a powerful catalyst for bringing orthopedic surgery into step with its sister specialties, as well as affirming the core egalitarian principle that underlies all of medical care.

Dr. White is the Ellen and Melvin Gordon Distinguished Professor of Medical Education and Professor of Orthopedic Surgery at Harvard Medical School, Boston. Dr. Chanoff is a founding board member of the Augustus A. White III Institute for Healthcare Equity. Neither Dr. White nor Dr. Chanoff reported any conflicts of interest. A version of this article first appeared on Medscape.com.

Correction, 2/1/22: An earlier version of this article omitted the title of "Dr." before Dr. Louis Sullivan's name.

It is indisputable that patients with newly diagnosed advanced non–small cell lung cancer (NSCLC) bearing mutations in the epidermal growth factor receptor (EGFR) pathway may benefit from targeted therapy with a tyrosine kinase inhibitor (TKI) directed against EGFR.

What’s less clear is whether monotherapy with an EGFR TKI or combination therapy with a TKI and chemotherapy, immunotherapy, monoclonal antibodies or other targeted agents is the preferred frontline strategy.

NSCLC guidelines from the National Comprehensive Cancer Network, for example, recommend that patients with EFGR mutations such as exon 19 deletion, discovered prior to first-line systemic therapy, should preferably received osimertinib (Tagrisso) or another TKI, such as erlotinib (Tarceva), afatinib (Gilotrif), gefitinib (Iressa) or dacomitinib (Vizimpro), or erlotinib with a VEGF inhibitor. For patients with EGFR mutations identified during first-line systemic therapy, NCCN recommends complete systemic therapy or interrupting it, followed by osimertinib as the preferred agent, or another TKI with or without a VEGF inhibitors.

Similarly, guidelines from the American Society of Clinical Oncology and Ontario Health recommend osimertinib monotherapy as a preferred first-line option for patients with L858R/exon 19 deletion EGFR mutations. Alternatives for patients for whom osimertinib is not available include gefitinib plus platinum/pemetrexed chemotherapy with maintenance pemetrexed, monotherapy with dacomitinib, or other targeted agents with or without VEGF inhibitors.

Combination or go it alone?

The guidelines are largely mute on the question of chemotherapy in this population, primarily because they have not caught up to clinical trial evidence, said Paul Wheatley-Price, MBChB, FRCP, MD, from the University of Ottawa Hospital Research Institute.

“There is recent data that looks quite promising on combining EGFR inhibitors with either chemotherapy or antiangiogenic drugs, but it’s too soon, I think, and while the trials are promising, there are still too many question marks over it to make it into the guidelines,” he said in an interview.

The question of frontline combinations vs. monotherapy in patients with advanced EGFR-mutated NSCLC was the subject of a recent “controversies in thoracic oncology” feature in the Journal of Thoracic Oncology, with Dr. Wheatley-Price and University of Ottawa colleague Sara Moore, MD, FRCPC, arguing that combining EGFR TKIs with either cytotoxic chemotherapy or antiangiogenic monoclonal antibodies targeting the vascular endothelial growth factor (VEGF) receptor has been shown consistently to improve progression-free survival (PFS) and in some cases overall survival (OS).

“There is a consistent drop-off in patients who receive second-line therapy, highlighting the importance of using combination therapy in the first-line setting to ensure patients will be exposed to multiple available therapies that may prolong survival. Chemotherapy-based combinations lead to improved response rates which may be especially helpful in patients with a significant burden of disease,” they wrote.

The authors noted that, compared with patients with wild-type EGFR, patients with EGFR-mutated NSCLC had a doubling of response rates to chemotherapy with a platinum-based doublet in the IPASS trial, suggesting that EGFR-mutated tumors may be more chemosensitive.
 

Promising trials, old drug

“Chemotherapy and EGFR TKIs may have a synergistic effect through combined reduction in vascular endothelial growth factor (VEGF)–mediated angiogenesis, and with EGFR TKIs counteracting chemotherapy-induced up-regulation of downstream EGFR signaling,” they wrote.

The authors cited two studies, one from Japan, and one from India, both of which showed significant improvements in response rates, PFS, and OS with the combination of gefitinib plus carboplatin and pemetrexed chemotherapy with pemetrexed maintenance vs. carboplatin alone,

“Now of course we don’t use gefitinib as our first-line treatment. In Canada and the United States, we use osimertinib, so certainly the chemotherapy/TKI combination, while it looks quite promising, was compared to an old control arm,” Dr. Wheatley-Price said.

He noted that the phase 3 FLAURA2 trial, currently underway, will address the question of whether adding osimertinib to a chemotherapy doublet with pemetrexed plus either carboplatin or cisplatin can improve PFS in patients with EGFR-positive locally advanced or metastatic NSCLC, compared with osimertinib alone.

The authors acknowledged that chemotherapy adds toxicities, compared with the use of TKI monotherapy, but added that, “even with the use of first-line osimertinib monotherapy, patients may still be exposed to chemotherapy with later lines of treatment. Therefore, combination therapy does not expose patients to new toxicity, it simply changes when they will be exposed to that toxicity during their treatment course.”

VEGF plus EGFR

Adding a VEGF-targeted monoclonal antibody or TKI to and EGFR TKI has shown consistent PFS benefits in the NEJ026, ARTEMIS, RELAY, and ACTIVE trials, Dr. Moore and Dr. Wheatley-Price noted.

“In all four trials, resistance testing at the time of progression revealed similar rates of T790M mutation in both arms, highlighting the potential role of optimizing the sequence of therapy with use of second-line osimertinib among those with a T790M resistance mutation,” they wrote.

All four trials also showed higher rates of adverse events in the combination arms, but most, except for hypertension, were low grade, and in the RELAY trial the added toxicities did not significantly affect patient quality of life, they said.
 

Monotherapy advocated

Although in agreement that the combination of gefitinib and chemotherapy has both PFS and OS benefits compared with monotherapy alone, “these combinations are not applicable to real-life practice given their use of first-generation EGFR TKIs rather than third-generation EGFR TKI osimertinib,” wrote Sophie Stock-Martineau, MD, FRCPC from Hôpital Maisonneuve-Rosemont and the University of Montreal, and Frances A. Shepherd, MD, FRCPC from the Princess Margaret Cancer Centre in Toronto, in an article touting EGFR monotherapy.

They stated that until the results of FLAURA2 are available “osimertinib alone remains the current standard first-line therapy in metastatic EGFRm+ NSCLC.”

“The addition of an antiangiogenic agent to an EGFR TKI mildly prolongs PFS; however, it does not yet translate into survival benefit. Not only does it add more toxicity to patients, but it also adds cost, which is far from negligible,” they wrote.

Dr. Stock-Martineau and Dr. Shepherd also noted that two phase 2 trials comparing afatinib with the EGFR monoclonal antibody cetuximab (Erbitux) showed no PFS or OS benefits in patients with untreated EGFR-mutated NSCLC and were terminated for lack of efficacy.

In addition, clinical trials of combinations of EGFR TKIs with immune checkpoint inhibitors ­or MET inhibitors have failed to date to demonstrate survival benefits, the authors said.

“No trials have yet revealed PFS or OS benefit with osimertinib combinations. Adding virtually all agents to EGFR TKIs has been associated with more toxicity to patients and a significant financial burden to the health care system. Combinations could potentially also worsen quality of life given their heightened toxicity profiles. Therefore, single-agent EGFR TKI, such as osimertinib, remains for now the standard of care in the first-line setting for advanced EGFRm+ NSCLC,” they concluded.

No funding sources for the articles were reported. All authors declared no conflicts of interest to disclose.

It is indisputable that patients with newly diagnosed advanced non–small cell lung cancer (NSCLC) bearing mutations in the epidermal growth factor receptor (EGFR) pathway may benefit from targeted therapy with a tyrosine kinase inhibitor (TKI) directed against EGFR.

What’s less clear is whether monotherapy with an EGFR TKI or combination therapy with a TKI and chemotherapy, immunotherapy, monoclonal antibodies or other targeted agents is the preferred frontline strategy.

NSCLC guidelines from the National Comprehensive Cancer Network, for example, recommend that patients with EFGR mutations such as exon 19 deletion, discovered prior to first-line systemic therapy, should preferably received osimertinib (Tagrisso) or another TKI, such as erlotinib (Tarceva), afatinib (Gilotrif), gefitinib (Iressa) or dacomitinib (Vizimpro), or erlotinib with a VEGF inhibitor. For patients with EGFR mutations identified during first-line systemic therapy, NCCN recommends complete systemic therapy or interrupting it, followed by osimertinib as the preferred agent, or another TKI with or without a VEGF inhibitors.

Similarly, guidelines from the American Society of Clinical Oncology and Ontario Health recommend osimertinib monotherapy as a preferred first-line option for patients with L858R/exon 19 deletion EGFR mutations. Alternatives for patients for whom osimertinib is not available include gefitinib plus platinum/pemetrexed chemotherapy with maintenance pemetrexed, monotherapy with dacomitinib, or other targeted agents with or without VEGF inhibitors.

Combination or go it alone?

The guidelines are largely mute on the question of chemotherapy in this population, primarily because they have not caught up to clinical trial evidence, said Paul Wheatley-Price, MBChB, FRCP, MD, from the University of Ottawa Hospital Research Institute.

“There is recent data that looks quite promising on combining EGFR inhibitors with either chemotherapy or antiangiogenic drugs, but it’s too soon, I think, and while the trials are promising, there are still too many question marks over it to make it into the guidelines,” he said in an interview.

The question of frontline combinations vs. monotherapy in patients with advanced EGFR-mutated NSCLC was the subject of a recent “controversies in thoracic oncology” feature in the Journal of Thoracic Oncology, with Dr. Wheatley-Price and University of Ottawa colleague Sara Moore, MD, FRCPC, arguing that combining EGFR TKIs with either cytotoxic chemotherapy or antiangiogenic monoclonal antibodies targeting the vascular endothelial growth factor (VEGF) receptor has been shown consistently to improve progression-free survival (PFS) and in some cases overall survival (OS).

“There is a consistent drop-off in patients who receive second-line therapy, highlighting the importance of using combination therapy in the first-line setting to ensure patients will be exposed to multiple available therapies that may prolong survival. Chemotherapy-based combinations lead to improved response rates which may be especially helpful in patients with a significant burden of disease,” they wrote.

The authors noted that, compared with patients with wild-type EGFR, patients with EGFR-mutated NSCLC had a doubling of response rates to chemotherapy with a platinum-based doublet in the IPASS trial, suggesting that EGFR-mutated tumors may be more chemosensitive.
 

Promising trials, old drug

“Chemotherapy and EGFR TKIs may have a synergistic effect through combined reduction in vascular endothelial growth factor (VEGF)–mediated angiogenesis, and with EGFR TKIs counteracting chemotherapy-induced up-regulation of downstream EGFR signaling,” they wrote.

The authors cited two studies, one from Japan, and one from India, both of which showed significant improvements in response rates, PFS, and OS with the combination of gefitinib plus carboplatin and pemetrexed chemotherapy with pemetrexed maintenance vs. carboplatin alone,

“Now of course we don’t use gefitinib as our first-line treatment. In Canada and the United States, we use osimertinib, so certainly the chemotherapy/TKI combination, while it looks quite promising, was compared to an old control arm,” Dr. Wheatley-Price said.

He noted that the phase 3 FLAURA2 trial, currently underway, will address the question of whether adding osimertinib to a chemotherapy doublet with pemetrexed plus either carboplatin or cisplatin can improve PFS in patients with EGFR-positive locally advanced or metastatic NSCLC, compared with osimertinib alone.

The authors acknowledged that chemotherapy adds toxicities, compared with the use of TKI monotherapy, but added that, “even with the use of first-line osimertinib monotherapy, patients may still be exposed to chemotherapy with later lines of treatment. Therefore, combination therapy does not expose patients to new toxicity, it simply changes when they will be exposed to that toxicity during their treatment course.”

VEGF plus EGFR

Adding a VEGF-targeted monoclonal antibody or TKI to and EGFR TKI has shown consistent PFS benefits in the NEJ026, ARTEMIS, RELAY, and ACTIVE trials, Dr. Moore and Dr. Wheatley-Price noted.

“In all four trials, resistance testing at the time of progression revealed similar rates of T790M mutation in both arms, highlighting the potential role of optimizing the sequence of therapy with use of second-line osimertinib among those with a T790M resistance mutation,” they wrote.

All four trials also showed higher rates of adverse events in the combination arms, but most, except for hypertension, were low grade, and in the RELAY trial the added toxicities did not significantly affect patient quality of life, they said.
 

Monotherapy advocated

Although in agreement that the combination of gefitinib and chemotherapy has both PFS and OS benefits compared with monotherapy alone, “these combinations are not applicable to real-life practice given their use of first-generation EGFR TKIs rather than third-generation EGFR TKI osimertinib,” wrote Sophie Stock-Martineau, MD, FRCPC from Hôpital Maisonneuve-Rosemont and the University of Montreal, and Frances A. Shepherd, MD, FRCPC from the Princess Margaret Cancer Centre in Toronto, in an article touting EGFR monotherapy.

They stated that until the results of FLAURA2 are available “osimertinib alone remains the current standard first-line therapy in metastatic EGFRm+ NSCLC.”

“The addition of an antiangiogenic agent to an EGFR TKI mildly prolongs PFS; however, it does not yet translate into survival benefit. Not only does it add more toxicity to patients, but it also adds cost, which is far from negligible,” they wrote.

Dr. Stock-Martineau and Dr. Shepherd also noted that two phase 2 trials comparing afatinib with the EGFR monoclonal antibody cetuximab (Erbitux) showed no PFS or OS benefits in patients with untreated EGFR-mutated NSCLC and were terminated for lack of efficacy.

In addition, clinical trials of combinations of EGFR TKIs with immune checkpoint inhibitors ­or MET inhibitors have failed to date to demonstrate survival benefits, the authors said.

“No trials have yet revealed PFS or OS benefit with osimertinib combinations. Adding virtually all agents to EGFR TKIs has been associated with more toxicity to patients and a significant financial burden to the health care system. Combinations could potentially also worsen quality of life given their heightened toxicity profiles. Therefore, single-agent EGFR TKI, such as osimertinib, remains for now the standard of care in the first-line setting for advanced EGFRm+ NSCLC,” they concluded.

No funding sources for the articles were reported. All authors declared no conflicts of interest to disclose.

It is indisputable that patients with newly diagnosed advanced non–small cell lung cancer (NSCLC) bearing mutations in the epidermal growth factor receptor (EGFR) pathway may benefit from targeted therapy with a tyrosine kinase inhibitor (TKI) directed against EGFR.

What’s less clear is whether monotherapy with an EGFR TKI or combination therapy with a TKI and chemotherapy, immunotherapy, monoclonal antibodies or other targeted agents is the preferred frontline strategy.

NSCLC guidelines from the National Comprehensive Cancer Network, for example, recommend that patients with EFGR mutations such as exon 19 deletion, discovered prior to first-line systemic therapy, should preferably received osimertinib (Tagrisso) or another TKI, such as erlotinib (Tarceva), afatinib (Gilotrif), gefitinib (Iressa) or dacomitinib (Vizimpro), or erlotinib with a VEGF inhibitor. For patients with EGFR mutations identified during first-line systemic therapy, NCCN recommends complete systemic therapy or interrupting it, followed by osimertinib as the preferred agent, or another TKI with or without a VEGF inhibitors.

Similarly, guidelines from the American Society of Clinical Oncology and Ontario Health recommend osimertinib monotherapy as a preferred first-line option for patients with L858R/exon 19 deletion EGFR mutations. Alternatives for patients for whom osimertinib is not available include gefitinib plus platinum/pemetrexed chemotherapy with maintenance pemetrexed, monotherapy with dacomitinib, or other targeted agents with or without VEGF inhibitors.

Combination or go it alone?

The guidelines are largely mute on the question of chemotherapy in this population, primarily because they have not caught up to clinical trial evidence, said Paul Wheatley-Price, MBChB, FRCP, MD, from the University of Ottawa Hospital Research Institute.

“There is recent data that looks quite promising on combining EGFR inhibitors with either chemotherapy or antiangiogenic drugs, but it’s too soon, I think, and while the trials are promising, there are still too many question marks over it to make it into the guidelines,” he said in an interview.

The question of frontline combinations vs. monotherapy in patients with advanced EGFR-mutated NSCLC was the subject of a recent “controversies in thoracic oncology” feature in the Journal of Thoracic Oncology, with Dr. Wheatley-Price and University of Ottawa colleague Sara Moore, MD, FRCPC, arguing that combining EGFR TKIs with either cytotoxic chemotherapy or antiangiogenic monoclonal antibodies targeting the vascular endothelial growth factor (VEGF) receptor has been shown consistently to improve progression-free survival (PFS) and in some cases overall survival (OS).

“There is a consistent drop-off in patients who receive second-line therapy, highlighting the importance of using combination therapy in the first-line setting to ensure patients will be exposed to multiple available therapies that may prolong survival. Chemotherapy-based combinations lead to improved response rates which may be especially helpful in patients with a significant burden of disease,” they wrote.

The authors noted that, compared with patients with wild-type EGFR, patients with EGFR-mutated NSCLC had a doubling of response rates to chemotherapy with a platinum-based doublet in the IPASS trial, suggesting that EGFR-mutated tumors may be more chemosensitive.
 

Promising trials, old drug

“Chemotherapy and EGFR TKIs may have a synergistic effect through combined reduction in vascular endothelial growth factor (VEGF)–mediated angiogenesis, and with EGFR TKIs counteracting chemotherapy-induced up-regulation of downstream EGFR signaling,” they wrote.

The authors cited two studies, one from Japan, and one from India, both of which showed significant improvements in response rates, PFS, and OS with the combination of gefitinib plus carboplatin and pemetrexed chemotherapy with pemetrexed maintenance vs. carboplatin alone,

“Now of course we don’t use gefitinib as our first-line treatment. In Canada and the United States, we use osimertinib, so certainly the chemotherapy/TKI combination, while it looks quite promising, was compared to an old control arm,” Dr. Wheatley-Price said.

He noted that the phase 3 FLAURA2 trial, currently underway, will address the question of whether adding osimertinib to a chemotherapy doublet with pemetrexed plus either carboplatin or cisplatin can improve PFS in patients with EGFR-positive locally advanced or metastatic NSCLC, compared with osimertinib alone.

The authors acknowledged that chemotherapy adds toxicities, compared with the use of TKI monotherapy, but added that, “even with the use of first-line osimertinib monotherapy, patients may still be exposed to chemotherapy with later lines of treatment. Therefore, combination therapy does not expose patients to new toxicity, it simply changes when they will be exposed to that toxicity during their treatment course.”

VEGF plus EGFR

Adding a VEGF-targeted monoclonal antibody or TKI to and EGFR TKI has shown consistent PFS benefits in the NEJ026, ARTEMIS, RELAY, and ACTIVE trials, Dr. Moore and Dr. Wheatley-Price noted.

“In all four trials, resistance testing at the time of progression revealed similar rates of T790M mutation in both arms, highlighting the potential role of optimizing the sequence of therapy with use of second-line osimertinib among those with a T790M resistance mutation,” they wrote.

All four trials also showed higher rates of adverse events in the combination arms, but most, except for hypertension, were low grade, and in the RELAY trial the added toxicities did not significantly affect patient quality of life, they said.
 

Monotherapy advocated

Although in agreement that the combination of gefitinib and chemotherapy has both PFS and OS benefits compared with monotherapy alone, “these combinations are not applicable to real-life practice given their use of first-generation EGFR TKIs rather than third-generation EGFR TKI osimertinib,” wrote Sophie Stock-Martineau, MD, FRCPC from Hôpital Maisonneuve-Rosemont and the University of Montreal, and Frances A. Shepherd, MD, FRCPC from the Princess Margaret Cancer Centre in Toronto, in an article touting EGFR monotherapy.

They stated that until the results of FLAURA2 are available “osimertinib alone remains the current standard first-line therapy in metastatic EGFRm+ NSCLC.”

“The addition of an antiangiogenic agent to an EGFR TKI mildly prolongs PFS; however, it does not yet translate into survival benefit. Not only does it add more toxicity to patients, but it also adds cost, which is far from negligible,” they wrote.

Dr. Stock-Martineau and Dr. Shepherd also noted that two phase 2 trials comparing afatinib with the EGFR monoclonal antibody cetuximab (Erbitux) showed no PFS or OS benefits in patients with untreated EGFR-mutated NSCLC and were terminated for lack of efficacy.

In addition, clinical trials of combinations of EGFR TKIs with immune checkpoint inhibitors ­or MET inhibitors have failed to date to demonstrate survival benefits, the authors said.

“No trials have yet revealed PFS or OS benefit with osimertinib combinations. Adding virtually all agents to EGFR TKIs has been associated with more toxicity to patients and a significant financial burden to the health care system. Combinations could potentially also worsen quality of life given their heightened toxicity profiles. Therefore, single-agent EGFR TKI, such as osimertinib, remains for now the standard of care in the first-line setting for advanced EGFRm+ NSCLC,” they concluded.

No funding sources for the articles were reported. All authors declared no conflicts of interest to disclose.

Berries, red wine, and other foods rich in flavonoids are associated with a lower risk for death in patients with Parkinson’s disease (PD), new research suggests.

In a prospective analysis of more than 1,200 participants with an eventual PD diagnosis, those who ate three or more servings of flavonoid-rich foods a week had a 70% lower mortality versus those consuming one or fewer servings of such foods per month.

“Adopting a healthy dietary pattern that is high in colorful fruits and veggies like berries, even after a Parkinson diagnosis, could slow disease progression and improve survival rate,” study investigator Xiang Gao, MD, PhD, professor and director, Nutritional Epidemiology Lab, department of nutritional sciences, Penn State University, University Park, said in an interview.

The findings were published online Jan. 26, 2022, in Neurology.

First evidence of survival advantage

Flavonoids are plant-derived polyphenolic molecules found in fruits such as berries, apples, and oranges; vegetables such as kale and broccoli; and beverages, including tea and red wine. They are the dietary components that give many foods their vibrant color.

Certain flavonoids have been shown previously to have antioxidant and anti-inflammatory properties.

A previous study by Dr. Gao and colleagues showed that flavonoids were associated with a lower future risk for developing PD. However, it did not provide evidence these nutrients improved survival rates among PD patients.

The new analysis included participants from the ongoing Nurses’ Health Study (NHS) of female registered nurses, which began in 1976, and male participants from the ongoing Health Professionals Follow-up Study (HPFS), which began in 1986.

All participants answered questionnaires at baseline and then biennially to update information on demographics, lifestyle, medical history, and occurrence of chronic disease.

Using validated food-frequency questionnaires completed every 4 years, researchers assessed dietary intakes of total flavonoid, six flavonoid subclasses, and flavonoid-rich foods such as tea, apples, berries, oranges and orange juice, and red wine.

They examined flavonoid intake both before and after a PD diagnosis to minimize the potential for reverse causality. The investigators noted that patients with PD have difficulty swallowing and handling food and cutlery, which could impact their consumption of flavonoid-rich foods.

Frequency of consumption of flavonoid-rich foods was categorized into four groups: one or less servings per month (the reference group), one to three servings per month, one to two servings per week, and three or more servings per week.

The analysis included 599 women and 652 men who were newly diagnosed with PD. The mean age at PD diagnosis was 72 years, and the mean time between the last prediagnosis dietary assessment and PD diagnosis was 32 months.

The primary outcome measure was all-cause mortality. There were 528 deaths in men and 416 deaths in women during an average of 33 years of follow-up.
 

Neuroprotective pathway?

After controlling for age, lifestyle behaviors, medical history, and total energy and caffeine intake, results showed that higher total flavonoid intake before PD diagnosis was associated with a lower risk for all-cause mortality after diagnosis in men, with a hazard ratio of 0.53 (95% confidence interval, 0.39-0.71) when comparing the highest and lowest quartiles (P for trend < .001).

However, this association was not found in women (HR, 0.93; 95% CI, 0.68-1.28; P for trend = .69).

The pooled HR was 0.70 (95% CI, 0.40-1.22; P for trend = .25) with significant heterogeneity (P = .01).

There were significant associations between a higher prediagnosis intake of certain flavonoids and lower mortality risk. The pooled HR comparing the highest versus lowest intake quartiles was 0.66 for anthocyanin, 0.78 for flavones, and 0.69 for flavan-3-ols (P < .05 for all).

Compared with participants who consumed less than one serving a month, those consuming more than three servings a week prediagnosis of berries or red wine had a lower mortality risk (pooled HR, 0.77; 95% CI, 0.58-1.02 for berries and HR, 0.68; 95% CI, 0.51-0.91 for red wine).

After PD diagnosis, higher flavonoid consumption was associated with better survival rates in both men and women.

It’s unclear why there was a gender difference in the association between prediagnosis flavonoid intake and mortality but not for postdiagnosis flavonoid intakes, Dr. Gao said.

A potential neuroprotective pathway by which flavonoids reduce mortality in PD involves direct radical scavenging, which lowers oxidative stress and chronic neuroinflammation levels, he noted.

“Certain flavonoids, for example, anthocyanins, have been shown to exert antiapoptosis effects and protect cognition and motor functions. They could also increase dopamine release,” Dr. Gao added.

Study limitations included not having detailed information on participants’ PD disease severity and that both the NHS and HPFS include predominantly White health care professionals, which limits the generalizability of the results, the investigators noted.
 

No direct link

Commenting on the findings, Michael S. Okun, MD, medical advisor at the Parkinson’s Foundation and director of the Norman Fixel Institute for Neurological Diseases, University of Florida Health, Gainesville, said the study adds to growing evidence suggesting “subsets of flavonoids and especially berries and wine will have benefits pre- and post–Parkinson’s disease diagnosis.”

However, he emphasized that patients should not take up drinking red wine just to improve survival.

“We don’t recommend that folks who are already diagnosed with Parkinson’s drink alcohol, especially without physician supervision,” said Dr. Okun, who was not involved with the research.

Also commenting for this article, Gunter Kuhnle, PhD, professor of nutrition and food science, University of Reading (England), said because the study doesn’t appear to adjust for socioeconomic status, the results may be driven by factors such as income and education and not food intake.

The study found a beneficial association with anthocyanins, which are mainly found in expensive berries, and with flavan-3-ols found mainly in tea, which in the United States is often a marker of higher income, said Dr. Kuhnle.

The advantage of assessing dietary intake of flavonoids using a food-frequency questionnaire, as was done in this study, is that it captures long-term patterns. However, the disadvantage is a loss in “resolution” by combining similar foods, Dr. Kuhnle noted.

Since flavonoids are found in most fruits and vegetables, high flavonoid intake “might simply be a marker of fruit and vegetable intake and therefore a ‘healthy’ dietary pattern,” he concluded.

The study received funding from the National Institute of Neurological Disorders and Stroke. Dr. Gao and Dr. Okun reported no relevant financial relationships. Dr. Kuhnle has conducted research into the associations between flavanol and health, some of which has been funded by Mars.

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

Berries, red wine, and other foods rich in flavonoids are associated with a lower risk for death in patients with Parkinson’s disease (PD), new research suggests.

In a prospective analysis of more than 1,200 participants with an eventual PD diagnosis, those who ate three or more servings of flavonoid-rich foods a week had a 70% lower mortality versus those consuming one or fewer servings of such foods per month.

“Adopting a healthy dietary pattern that is high in colorful fruits and veggies like berries, even after a Parkinson diagnosis, could slow disease progression and improve survival rate,” study investigator Xiang Gao, MD, PhD, professor and director, Nutritional Epidemiology Lab, department of nutritional sciences, Penn State University, University Park, said in an interview.

The findings were published online Jan. 26, 2022, in Neurology.

First evidence of survival advantage

Flavonoids are plant-derived polyphenolic molecules found in fruits such as berries, apples, and oranges; vegetables such as kale and broccoli; and beverages, including tea and red wine. They are the dietary components that give many foods their vibrant color.

Certain flavonoids have been shown previously to have antioxidant and anti-inflammatory properties.

A previous study by Dr. Gao and colleagues showed that flavonoids were associated with a lower future risk for developing PD. However, it did not provide evidence these nutrients improved survival rates among PD patients.

The new analysis included participants from the ongoing Nurses’ Health Study (NHS) of female registered nurses, which began in 1976, and male participants from the ongoing Health Professionals Follow-up Study (HPFS), which began in 1986.

All participants answered questionnaires at baseline and then biennially to update information on demographics, lifestyle, medical history, and occurrence of chronic disease.

Using validated food-frequency questionnaires completed every 4 years, researchers assessed dietary intakes of total flavonoid, six flavonoid subclasses, and flavonoid-rich foods such as tea, apples, berries, oranges and orange juice, and red wine.

They examined flavonoid intake both before and after a PD diagnosis to minimize the potential for reverse causality. The investigators noted that patients with PD have difficulty swallowing and handling food and cutlery, which could impact their consumption of flavonoid-rich foods.

Frequency of consumption of flavonoid-rich foods was categorized into four groups: one or less servings per month (the reference group), one to three servings per month, one to two servings per week, and three or more servings per week.

The analysis included 599 women and 652 men who were newly diagnosed with PD. The mean age at PD diagnosis was 72 years, and the mean time between the last prediagnosis dietary assessment and PD diagnosis was 32 months.

The primary outcome measure was all-cause mortality. There were 528 deaths in men and 416 deaths in women during an average of 33 years of follow-up.
 

Neuroprotective pathway?

After controlling for age, lifestyle behaviors, medical history, and total energy and caffeine intake, results showed that higher total flavonoid intake before PD diagnosis was associated with a lower risk for all-cause mortality after diagnosis in men, with a hazard ratio of 0.53 (95% confidence interval, 0.39-0.71) when comparing the highest and lowest quartiles (P for trend < .001).

However, this association was not found in women (HR, 0.93; 95% CI, 0.68-1.28; P for trend = .69).

The pooled HR was 0.70 (95% CI, 0.40-1.22; P for trend = .25) with significant heterogeneity (P = .01).

There were significant associations between a higher prediagnosis intake of certain flavonoids and lower mortality risk. The pooled HR comparing the highest versus lowest intake quartiles was 0.66 for anthocyanin, 0.78 for flavones, and 0.69 for flavan-3-ols (P < .05 for all).

Compared with participants who consumed less than one serving a month, those consuming more than three servings a week prediagnosis of berries or red wine had a lower mortality risk (pooled HR, 0.77; 95% CI, 0.58-1.02 for berries and HR, 0.68; 95% CI, 0.51-0.91 for red wine).

After PD diagnosis, higher flavonoid consumption was associated with better survival rates in both men and women.

It’s unclear why there was a gender difference in the association between prediagnosis flavonoid intake and mortality but not for postdiagnosis flavonoid intakes, Dr. Gao said.

A potential neuroprotective pathway by which flavonoids reduce mortality in PD involves direct radical scavenging, which lowers oxidative stress and chronic neuroinflammation levels, he noted.

“Certain flavonoids, for example, anthocyanins, have been shown to exert antiapoptosis effects and protect cognition and motor functions. They could also increase dopamine release,” Dr. Gao added.

Study limitations included not having detailed information on participants’ PD disease severity and that both the NHS and HPFS include predominantly White health care professionals, which limits the generalizability of the results, the investigators noted.
 

No direct link

Commenting on the findings, Michael S. Okun, MD, medical advisor at the Parkinson’s Foundation and director of the Norman Fixel Institute for Neurological Diseases, University of Florida Health, Gainesville, said the study adds to growing evidence suggesting “subsets of flavonoids and especially berries and wine will have benefits pre- and post–Parkinson’s disease diagnosis.”

However, he emphasized that patients should not take up drinking red wine just to improve survival.

“We don’t recommend that folks who are already diagnosed with Parkinson’s drink alcohol, especially without physician supervision,” said Dr. Okun, who was not involved with the research.

Also commenting for this article, Gunter Kuhnle, PhD, professor of nutrition and food science, University of Reading (England), said because the study doesn’t appear to adjust for socioeconomic status, the results may be driven by factors such as income and education and not food intake.

The study found a beneficial association with anthocyanins, which are mainly found in expensive berries, and with flavan-3-ols found mainly in tea, which in the United States is often a marker of higher income, said Dr. Kuhnle.

The advantage of assessing dietary intake of flavonoids using a food-frequency questionnaire, as was done in this study, is that it captures long-term patterns. However, the disadvantage is a loss in “resolution” by combining similar foods, Dr. Kuhnle noted.

Since flavonoids are found in most fruits and vegetables, high flavonoid intake “might simply be a marker of fruit and vegetable intake and therefore a ‘healthy’ dietary pattern,” he concluded.

The study received funding from the National Institute of Neurological Disorders and Stroke. Dr. Gao and Dr. Okun reported no relevant financial relationships. Dr. Kuhnle has conducted research into the associations between flavanol and health, some of which has been funded by Mars.

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

Berries, red wine, and other foods rich in flavonoids are associated with a lower risk for death in patients with Parkinson’s disease (PD), new research suggests.

In a prospective analysis of more than 1,200 participants with an eventual PD diagnosis, those who ate three or more servings of flavonoid-rich foods a week had a 70% lower mortality versus those consuming one or fewer servings of such foods per month.

“Adopting a healthy dietary pattern that is high in colorful fruits and veggies like berries, even after a Parkinson diagnosis, could slow disease progression and improve survival rate,” study investigator Xiang Gao, MD, PhD, professor and director, Nutritional Epidemiology Lab, department of nutritional sciences, Penn State University, University Park, said in an interview.

The findings were published online Jan. 26, 2022, in Neurology.

First evidence of survival advantage

Flavonoids are plant-derived polyphenolic molecules found in fruits such as berries, apples, and oranges; vegetables such as kale and broccoli; and beverages, including tea and red wine. They are the dietary components that give many foods their vibrant color.

Certain flavonoids have been shown previously to have antioxidant and anti-inflammatory properties.

A previous study by Dr. Gao and colleagues showed that flavonoids were associated with a lower future risk for developing PD. However, it did not provide evidence these nutrients improved survival rates among PD patients.

The new analysis included participants from the ongoing Nurses’ Health Study (NHS) of female registered nurses, which began in 1976, and male participants from the ongoing Health Professionals Follow-up Study (HPFS), which began in 1986.

All participants answered questionnaires at baseline and then biennially to update information on demographics, lifestyle, medical history, and occurrence of chronic disease.

Using validated food-frequency questionnaires completed every 4 years, researchers assessed dietary intakes of total flavonoid, six flavonoid subclasses, and flavonoid-rich foods such as tea, apples, berries, oranges and orange juice, and red wine.

They examined flavonoid intake both before and after a PD diagnosis to minimize the potential for reverse causality. The investigators noted that patients with PD have difficulty swallowing and handling food and cutlery, which could impact their consumption of flavonoid-rich foods.

Frequency of consumption of flavonoid-rich foods was categorized into four groups: one or less servings per month (the reference group), one to three servings per month, one to two servings per week, and three or more servings per week.

The analysis included 599 women and 652 men who were newly diagnosed with PD. The mean age at PD diagnosis was 72 years, and the mean time between the last prediagnosis dietary assessment and PD diagnosis was 32 months.

The primary outcome measure was all-cause mortality. There were 528 deaths in men and 416 deaths in women during an average of 33 years of follow-up.
 

Neuroprotective pathway?

After controlling for age, lifestyle behaviors, medical history, and total energy and caffeine intake, results showed that higher total flavonoid intake before PD diagnosis was associated with a lower risk for all-cause mortality after diagnosis in men, with a hazard ratio of 0.53 (95% confidence interval, 0.39-0.71) when comparing the highest and lowest quartiles (P for trend < .001).

However, this association was not found in women (HR, 0.93; 95% CI, 0.68-1.28; P for trend = .69).

The pooled HR was 0.70 (95% CI, 0.40-1.22; P for trend = .25) with significant heterogeneity (P = .01).

There were significant associations between a higher prediagnosis intake of certain flavonoids and lower mortality risk. The pooled HR comparing the highest versus lowest intake quartiles was 0.66 for anthocyanin, 0.78 for flavones, and 0.69 for flavan-3-ols (P < .05 for all).

Compared with participants who consumed less than one serving a month, those consuming more than three servings a week prediagnosis of berries or red wine had a lower mortality risk (pooled HR, 0.77; 95% CI, 0.58-1.02 for berries and HR, 0.68; 95% CI, 0.51-0.91 for red wine).

After PD diagnosis, higher flavonoid consumption was associated with better survival rates in both men and women.

It’s unclear why there was a gender difference in the association between prediagnosis flavonoid intake and mortality but not for postdiagnosis flavonoid intakes, Dr. Gao said.

A potential neuroprotective pathway by which flavonoids reduce mortality in PD involves direct radical scavenging, which lowers oxidative stress and chronic neuroinflammation levels, he noted.

“Certain flavonoids, for example, anthocyanins, have been shown to exert antiapoptosis effects and protect cognition and motor functions. They could also increase dopamine release,” Dr. Gao added.

Study limitations included not having detailed information on participants’ PD disease severity and that both the NHS and HPFS include predominantly White health care professionals, which limits the generalizability of the results, the investigators noted.
 

No direct link

Commenting on the findings, Michael S. Okun, MD, medical advisor at the Parkinson’s Foundation and director of the Norman Fixel Institute for Neurological Diseases, University of Florida Health, Gainesville, said the study adds to growing evidence suggesting “subsets of flavonoids and especially berries and wine will have benefits pre- and post–Parkinson’s disease diagnosis.”

However, he emphasized that patients should not take up drinking red wine just to improve survival.

“We don’t recommend that folks who are already diagnosed with Parkinson’s drink alcohol, especially without physician supervision,” said Dr. Okun, who was not involved with the research.

Also commenting for this article, Gunter Kuhnle, PhD, professor of nutrition and food science, University of Reading (England), said because the study doesn’t appear to adjust for socioeconomic status, the results may be driven by factors such as income and education and not food intake.

The study found a beneficial association with anthocyanins, which are mainly found in expensive berries, and with flavan-3-ols found mainly in tea, which in the United States is often a marker of higher income, said Dr. Kuhnle.

The advantage of assessing dietary intake of flavonoids using a food-frequency questionnaire, as was done in this study, is that it captures long-term patterns. However, the disadvantage is a loss in “resolution” by combining similar foods, Dr. Kuhnle noted.

Since flavonoids are found in most fruits and vegetables, high flavonoid intake “might simply be a marker of fruit and vegetable intake and therefore a ‘healthy’ dietary pattern,” he concluded.

The study received funding from the National Institute of Neurological Disorders and Stroke. Dr. Gao and Dr. Okun reported no relevant financial relationships. Dr. Kuhnle has conducted research into the associations between flavanol and health, some of which has been funded by Mars.

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

More than 1 in 10 Americans have diabetes and over a third have prediabetes, according to updated statistics from the Centers for Disease Control and Prevention.

The National Diabetes Statistics Report includes data for 2017-2020 from several nationally representative sources on prevalence and incidence of diabetes and prediabetes, risk factors for complications, acute and long-term complications, and costs.

According to the new report, published on Jan. 25, a total of 37.3 million people in the United States have diabetes, or about 11.3% of the population. Of those, 28.7 million are diagnosed (including 28.5 million adults), while 8.5 million, or 23% of those with diabetes, are undiagnosed.

Another 96 million adults have prediabetes, comprising 38.0% of the adult U.S. population, of whom only 19% are aware of their prediabetes status.

In a statement, the American Diabetes Association said the new CDC data “show an alarming increase of diabetes in our nation among adults,” while the high number with prediabetes who don’t know that they have it “is fueling the diabetes epidemic.”

Regarding the total estimated 1.84 million with type 1 diabetes, the advocacy organization JDRF said in a statement: “These data and additional statistical research reinforces the urgency to accelerate life-changing breakthroughs to cure, prevent, and treat [type 1 diabetes] and its complications.”

Overall, the ADA said, “the National Diabetes Statistics Report reaffirms why the ADA is dedicated to innovative research to find a cure for diabetes once and for all.”
 

Notable increases since 2019

These new data represent notable increases since the CDC’s 2019 Report Card, which gave the U.S. population with diabetes in 2018 as 34.2 million, or 10.5% of the population, including 7.3 million undiagnosed. The prediabetes prevalence that year was 88 million.

Among children and adolescents younger than 20 years, 283,000, or 35 per 10,000 U.S. youths, had diagnosed diabetes in 2019. Of those, 244,000 had type 1 diabetes. Another 1.6 million adults aged 20 and older also reported having type 1 diabetes, comprising 5.7% of U.S. adults with diagnosed diabetes.

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

More than 1 in 10 Americans have diabetes and over a third have prediabetes, according to updated statistics from the Centers for Disease Control and Prevention.

The National Diabetes Statistics Report includes data for 2017-2020 from several nationally representative sources on prevalence and incidence of diabetes and prediabetes, risk factors for complications, acute and long-term complications, and costs.

According to the new report, published on Jan. 25, a total of 37.3 million people in the United States have diabetes, or about 11.3% of the population. Of those, 28.7 million are diagnosed (including 28.5 million adults), while 8.5 million, or 23% of those with diabetes, are undiagnosed.

Another 96 million adults have prediabetes, comprising 38.0% of the adult U.S. population, of whom only 19% are aware of their prediabetes status.

In a statement, the American Diabetes Association said the new CDC data “show an alarming increase of diabetes in our nation among adults,” while the high number with prediabetes who don’t know that they have it “is fueling the diabetes epidemic.”

Regarding the total estimated 1.84 million with type 1 diabetes, the advocacy organization JDRF said in a statement: “These data and additional statistical research reinforces the urgency to accelerate life-changing breakthroughs to cure, prevent, and treat [type 1 diabetes] and its complications.”

Overall, the ADA said, “the National Diabetes Statistics Report reaffirms why the ADA is dedicated to innovative research to find a cure for diabetes once and for all.”
 

Notable increases since 2019

These new data represent notable increases since the CDC’s 2019 Report Card, which gave the U.S. population with diabetes in 2018 as 34.2 million, or 10.5% of the population, including 7.3 million undiagnosed. The prediabetes prevalence that year was 88 million.

Among children and adolescents younger than 20 years, 283,000, or 35 per 10,000 U.S. youths, had diagnosed diabetes in 2019. Of those, 244,000 had type 1 diabetes. Another 1.6 million adults aged 20 and older also reported having type 1 diabetes, comprising 5.7% of U.S. adults with diagnosed diabetes.

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

More than 1 in 10 Americans have diabetes and over a third have prediabetes, according to updated statistics from the Centers for Disease Control and Prevention.

The National Diabetes Statistics Report includes data for 2017-2020 from several nationally representative sources on prevalence and incidence of diabetes and prediabetes, risk factors for complications, acute and long-term complications, and costs.

According to the new report, published on Jan. 25, a total of 37.3 million people in the United States have diabetes, or about 11.3% of the population. Of those, 28.7 million are diagnosed (including 28.5 million adults), while 8.5 million, or 23% of those with diabetes, are undiagnosed.

Another 96 million adults have prediabetes, comprising 38.0% of the adult U.S. population, of whom only 19% are aware of their prediabetes status.

In a statement, the American Diabetes Association said the new CDC data “show an alarming increase of diabetes in our nation among adults,” while the high number with prediabetes who don’t know that they have it “is fueling the diabetes epidemic.”

Regarding the total estimated 1.84 million with type 1 diabetes, the advocacy organization JDRF said in a statement: “These data and additional statistical research reinforces the urgency to accelerate life-changing breakthroughs to cure, prevent, and treat [type 1 diabetes] and its complications.”

Overall, the ADA said, “the National Diabetes Statistics Report reaffirms why the ADA is dedicated to innovative research to find a cure for diabetes once and for all.”
 

Notable increases since 2019

These new data represent notable increases since the CDC’s 2019 Report Card, which gave the U.S. population with diabetes in 2018 as 34.2 million, or 10.5% of the population, including 7.3 million undiagnosed. The prediabetes prevalence that year was 88 million.

Among children and adolescents younger than 20 years, 283,000, or 35 per 10,000 U.S. youths, had diagnosed diabetes in 2019. Of those, 244,000 had type 1 diabetes. Another 1.6 million adults aged 20 and older also reported having type 1 diabetes, comprising 5.7% of U.S. adults with diagnosed diabetes.

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

Japanese researchers say the Omicron variant survives longer on plastic and skin than other COVID-19 variants, one possible explanation for why Omicron has spread so rapidly around the world.

In a lab experiment, samples of different variants were applied to pieces of plastic and human skin collected from autopsies, researchers from Kyoto Prefectural University of Medicine wrote in bioRxiv. A variant “survived” until it could no longer be detected on the surface.

“This study showed that the Omicron variant also has the highest environmental stability among VOCs (variants of concern), which suggests that this high stability might also be one of the factors that have allowed the Omicron variant to replace the Delta variant and spread rapidly,” the researchers wrote.

On plastic, the Omicron variant samples survived an average of 193.5 hours, a little more than 8 days. By comparison, the other survival times on plastic were 56 hours for the original COVID strain, 191.3 hours for Alpha, 156.6 hours for Beta, 59.3 hours for Gamma, and 114 hours for Delta.

On skin samples, the Omicron samples survived an average of 21.1 hours. The other variants had these average survival times on skin: 8.6 hours for the original version, 19.6 hours for Alpha, 19.1 hours for Beta, 11 hours for Gamma, and 16.8 hours for Delta.

The study found that the variants had more resistance to ethanol than the original strain of COVID. That said, all COVID samples were inactivated after being exposed to alcohol-based hand sanitizers for 15 seconds.

“Therefore, it is highly recommended that current infection control (hand hygiene) practices use disinfectants ... as proposed by the World Health Organization,” the researchers said.

The study has not been peer-reviewed.

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

Japanese researchers say the Omicron variant survives longer on plastic and skin than other COVID-19 variants, one possible explanation for why Omicron has spread so rapidly around the world.

In a lab experiment, samples of different variants were applied to pieces of plastic and human skin collected from autopsies, researchers from Kyoto Prefectural University of Medicine wrote in bioRxiv. A variant “survived” until it could no longer be detected on the surface.

“This study showed that the Omicron variant also has the highest environmental stability among VOCs (variants of concern), which suggests that this high stability might also be one of the factors that have allowed the Omicron variant to replace the Delta variant and spread rapidly,” the researchers wrote.

On plastic, the Omicron variant samples survived an average of 193.5 hours, a little more than 8 days. By comparison, the other survival times on plastic were 56 hours for the original COVID strain, 191.3 hours for Alpha, 156.6 hours for Beta, 59.3 hours for Gamma, and 114 hours for Delta.

On skin samples, the Omicron samples survived an average of 21.1 hours. The other variants had these average survival times on skin: 8.6 hours for the original version, 19.6 hours for Alpha, 19.1 hours for Beta, 11 hours for Gamma, and 16.8 hours for Delta.

The study found that the variants had more resistance to ethanol than the original strain of COVID. That said, all COVID samples were inactivated after being exposed to alcohol-based hand sanitizers for 15 seconds.

“Therefore, it is highly recommended that current infection control (hand hygiene) practices use disinfectants ... as proposed by the World Health Organization,” the researchers said.

The study has not been peer-reviewed.

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

Japanese researchers say the Omicron variant survives longer on plastic and skin than other COVID-19 variants, one possible explanation for why Omicron has spread so rapidly around the world.

In a lab experiment, samples of different variants were applied to pieces of plastic and human skin collected from autopsies, researchers from Kyoto Prefectural University of Medicine wrote in bioRxiv. A variant “survived” until it could no longer be detected on the surface.

“This study showed that the Omicron variant also has the highest environmental stability among VOCs (variants of concern), which suggests that this high stability might also be one of the factors that have allowed the Omicron variant to replace the Delta variant and spread rapidly,” the researchers wrote.

On plastic, the Omicron variant samples survived an average of 193.5 hours, a little more than 8 days. By comparison, the other survival times on plastic were 56 hours for the original COVID strain, 191.3 hours for Alpha, 156.6 hours for Beta, 59.3 hours for Gamma, and 114 hours for Delta.

On skin samples, the Omicron samples survived an average of 21.1 hours. The other variants had these average survival times on skin: 8.6 hours for the original version, 19.6 hours for Alpha, 19.1 hours for Beta, 11 hours for Gamma, and 16.8 hours for Delta.

The study found that the variants had more resistance to ethanol than the original strain of COVID. That said, all COVID samples were inactivated after being exposed to alcohol-based hand sanitizers for 15 seconds.

“Therefore, it is highly recommended that current infection control (hand hygiene) practices use disinfectants ... as proposed by the World Health Organization,” the researchers said.

The study has not been peer-reviewed.

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

More steps per day, particularly at a higher intensity, may reduce the risk of type 2 diabetes in older women, based on a prospective cohort study.

The link between daily stepping and diabetes was not significantly modified by body mass index (BMI) or other common diabetes risk factors, suggesting that the relationship is highly generalizable, lead author Alexis C. Garduno, MPH, a PhD student at the University of California, San Diego, and colleagues reported.

“Physical activity is a key modifiable behavior for diabetes prevention and management,” the investigators wrote in Diabetes Care. “Many prevention studies have demonstrated that regular physical activity, along with improved diet, reduces the risk of diabetes in adults. ... To the best of our knowledge, there are few studies examining the association between objectively measured steps per day and incident diabetes in a community-based setting.”

To this end, the investigators analyzed data from 4,838 older, community-living women in the Objective Physical Activity and Cardiovascular Health Study. Upon enrollment, women were without physician-diagnosed diabetes and had a mean age of 78.9 years. For 1 week, participants wore ActiGraph GT3X+ accelerometers to measure steps per day, as well as step intensity, graded as light or moderate to vigorous.

The relationship between daily activity and diabetes was analyzed using three multivariate models: The first included race/ethnicity and age; the second also included family history of diabetes, education, physical functioning, self-rated health, smoking status, and alcohol consumption; and the third added BMI, “a potential mediator in the causal pathway between steps per day and diabetes,” the investigators wrote.

Participants took an average of 3,729 steps per day, divided roughly evenly between light and moderate to vigorous intensity.

After a median follow-up of 5.7 years, 8.1% of women developed diabetes. The least-adjusted model showed a 14% reduction in diabetes risk per 2,000 steps (hazard ratio, 0.86; 95% confidence interval, 0.80-0.92; P = .007), whereas the second model, adjusting for more confounding variables, showed a 12% reduction in diabetes risk per 2,000 steps (HR, 0.88; 95% CI, 0.78-1.00; P = .045).

The final model, which added BMI, showed a 10% reduction in risk, although it didn’t reach statistical significance (HR, 0.90; 95% CI, 0.80-1.02; P = .11). Furthermore, accelerated failure time models suggested that BMI did not significantly impact the link between steps and diabetes (proportion mediated, 17.7%;95% CI, –55.0 to 142.0; P = .09). Further analyses also found no significant interactions between BMI or other possible confounders.

“The steps per day–diabetes association was not modified by age, race/ethnicity, BMI, physical functioning, or family history of diabetes, which supports the generalizability of these findings to community-living older women,” the investigators wrote.

Increased stepping intensity also appeared to lower risk of diabetes. After adjusting for confounding variables, light stepping was not linked to reduced risk (HR, 0.97; 95% CI, 0.73-1.29; P = .83), whereas moderate to vigorous stepping reduced risk by 14% per 2,000 steps (HR, 0.86; 95% CI, 0.74-1.00; P = .04).

“This study provides evidence supporting an association between steps per day and lower incident diabetes,” the investigators concluded. “While further work is needed to identify whether there is a minimum number of steps per day that results in a clinically significant reduction of diabetes and to evaluate the role that step intensity plays in diabetes etiology for older adults, findings from this study suggest that moderate-vigorous–intensity steps may be more important than lower-intensity steps with respect to incident diabetes. Steps per day–based interventions are needed to advance diabetes prevention science in older adults.”

The study was supported by the National Institute on Aging, the National Institute of Diabetes and Digestive and Kidney Diseases, the Tobacco-Related Disease Research Program, and others. The investigators had no potential conflicts of interest.

More steps per day, particularly at a higher intensity, may reduce the risk of type 2 diabetes in older women, based on a prospective cohort study.

The link between daily stepping and diabetes was not significantly modified by body mass index (BMI) or other common diabetes risk factors, suggesting that the relationship is highly generalizable, lead author Alexis C. Garduno, MPH, a PhD student at the University of California, San Diego, and colleagues reported.

“Physical activity is a key modifiable behavior for diabetes prevention and management,” the investigators wrote in Diabetes Care. “Many prevention studies have demonstrated that regular physical activity, along with improved diet, reduces the risk of diabetes in adults. ... To the best of our knowledge, there are few studies examining the association between objectively measured steps per day and incident diabetes in a community-based setting.”

To this end, the investigators analyzed data from 4,838 older, community-living women in the Objective Physical Activity and Cardiovascular Health Study. Upon enrollment, women were without physician-diagnosed diabetes and had a mean age of 78.9 years. For 1 week, participants wore ActiGraph GT3X+ accelerometers to measure steps per day, as well as step intensity, graded as light or moderate to vigorous.

The relationship between daily activity and diabetes was analyzed using three multivariate models: The first included race/ethnicity and age; the second also included family history of diabetes, education, physical functioning, self-rated health, smoking status, and alcohol consumption; and the third added BMI, “a potential mediator in the causal pathway between steps per day and diabetes,” the investigators wrote.

Participants took an average of 3,729 steps per day, divided roughly evenly between light and moderate to vigorous intensity.

After a median follow-up of 5.7 years, 8.1% of women developed diabetes. The least-adjusted model showed a 14% reduction in diabetes risk per 2,000 steps (hazard ratio, 0.86; 95% confidence interval, 0.80-0.92; P = .007), whereas the second model, adjusting for more confounding variables, showed a 12% reduction in diabetes risk per 2,000 steps (HR, 0.88; 95% CI, 0.78-1.00; P = .045).

The final model, which added BMI, showed a 10% reduction in risk, although it didn’t reach statistical significance (HR, 0.90; 95% CI, 0.80-1.02; P = .11). Furthermore, accelerated failure time models suggested that BMI did not significantly impact the link between steps and diabetes (proportion mediated, 17.7%;95% CI, –55.0 to 142.0; P = .09). Further analyses also found no significant interactions between BMI or other possible confounders.

“The steps per day–diabetes association was not modified by age, race/ethnicity, BMI, physical functioning, or family history of diabetes, which supports the generalizability of these findings to community-living older women,” the investigators wrote.

Increased stepping intensity also appeared to lower risk of diabetes. After adjusting for confounding variables, light stepping was not linked to reduced risk (HR, 0.97; 95% CI, 0.73-1.29; P = .83), whereas moderate to vigorous stepping reduced risk by 14% per 2,000 steps (HR, 0.86; 95% CI, 0.74-1.00; P = .04).

“This study provides evidence supporting an association between steps per day and lower incident diabetes,” the investigators concluded. “While further work is needed to identify whether there is a minimum number of steps per day that results in a clinically significant reduction of diabetes and to evaluate the role that step intensity plays in diabetes etiology for older adults, findings from this study suggest that moderate-vigorous–intensity steps may be more important than lower-intensity steps with respect to incident diabetes. Steps per day–based interventions are needed to advance diabetes prevention science in older adults.”

The study was supported by the National Institute on Aging, the National Institute of Diabetes and Digestive and Kidney Diseases, the Tobacco-Related Disease Research Program, and others. The investigators had no potential conflicts of interest.

More steps per day, particularly at a higher intensity, may reduce the risk of type 2 diabetes in older women, based on a prospective cohort study.

The link between daily stepping and diabetes was not significantly modified by body mass index (BMI) or other common diabetes risk factors, suggesting that the relationship is highly generalizable, lead author Alexis C. Garduno, MPH, a PhD student at the University of California, San Diego, and colleagues reported.

“Physical activity is a key modifiable behavior for diabetes prevention and management,” the investigators wrote in Diabetes Care. “Many prevention studies have demonstrated that regular physical activity, along with improved diet, reduces the risk of diabetes in adults. ... To the best of our knowledge, there are few studies examining the association between objectively measured steps per day and incident diabetes in a community-based setting.”

To this end, the investigators analyzed data from 4,838 older, community-living women in the Objective Physical Activity and Cardiovascular Health Study. Upon enrollment, women were without physician-diagnosed diabetes and had a mean age of 78.9 years. For 1 week, participants wore ActiGraph GT3X+ accelerometers to measure steps per day, as well as step intensity, graded as light or moderate to vigorous.

The relationship between daily activity and diabetes was analyzed using three multivariate models: The first included race/ethnicity and age; the second also included family history of diabetes, education, physical functioning, self-rated health, smoking status, and alcohol consumption; and the third added BMI, “a potential mediator in the causal pathway between steps per day and diabetes,” the investigators wrote.

Participants took an average of 3,729 steps per day, divided roughly evenly between light and moderate to vigorous intensity.

After a median follow-up of 5.7 years, 8.1% of women developed diabetes. The least-adjusted model showed a 14% reduction in diabetes risk per 2,000 steps (hazard ratio, 0.86; 95% confidence interval, 0.80-0.92; P = .007), whereas the second model, adjusting for more confounding variables, showed a 12% reduction in diabetes risk per 2,000 steps (HR, 0.88; 95% CI, 0.78-1.00; P = .045).

The final model, which added BMI, showed a 10% reduction in risk, although it didn’t reach statistical significance (HR, 0.90; 95% CI, 0.80-1.02; P = .11). Furthermore, accelerated failure time models suggested that BMI did not significantly impact the link between steps and diabetes (proportion mediated, 17.7%;95% CI, –55.0 to 142.0; P = .09). Further analyses also found no significant interactions between BMI or other possible confounders.

“The steps per day–diabetes association was not modified by age, race/ethnicity, BMI, physical functioning, or family history of diabetes, which supports the generalizability of these findings to community-living older women,” the investigators wrote.

Increased stepping intensity also appeared to lower risk of diabetes. After adjusting for confounding variables, light stepping was not linked to reduced risk (HR, 0.97; 95% CI, 0.73-1.29; P = .83), whereas moderate to vigorous stepping reduced risk by 14% per 2,000 steps (HR, 0.86; 95% CI, 0.74-1.00; P = .04).

“This study provides evidence supporting an association between steps per day and lower incident diabetes,” the investigators concluded. “While further work is needed to identify whether there is a minimum number of steps per day that results in a clinically significant reduction of diabetes and to evaluate the role that step intensity plays in diabetes etiology for older adults, findings from this study suggest that moderate-vigorous–intensity steps may be more important than lower-intensity steps with respect to incident diabetes. Steps per day–based interventions are needed to advance diabetes prevention science in older adults.”

The study was supported by the National Institute on Aging, the National Institute of Diabetes and Digestive and Kidney Diseases, the Tobacco-Related Disease Research Program, and others. The investigators had no potential conflicts of interest.

Three weekly infusions of the dissociative anesthetic ketamine coupled with mindfulness-based relapse prevention therapy may help adults with alcohol use disorder (AUD) maintain abstinence, new research suggests.

Preliminary results from a phase 2, double-blind, placebo-controlled trial show ketamine was well tolerated and, compared with placebo, associated with more days of abstinence from alcohol at 6 months.

The results suggest ketamine plus psychological therapy may be a “new, relatively brief treatment that has long lasting effects in AUD,” Celia Morgan, PhD, professor of psychopharmacology, University of Exeter, United Kingdom, told this news organization.

The study was published online Jan. 11 in the American Journal of Psychiatry.
 

Target depression

Depressive symptoms are common in patients under treatment for AUD and increase relapse risk.

“Ketamine may support alcohol abstinence by temporarily alleviating depressive symptoms during the high-risk relapse period in the weeks after detoxification,” the investigators note.

Ketamine may also provide a “temporary boost to synaptogenesis and neurogenesis, which may allow psychological therapies and new strategies for managing addiction to embed more readily,” they add.

To test these theories, the researchers recruited 96 adults (mean age, 44 years, 35 women) with severe AUD to participate in the trial.

All participants had to abstain from alcohol for at least 24 hours before the trial started and have a reading of 0.0 on a breath alcohol test at the baseline visit.

Participants were randomly allocated to one of four groups:

1. three weekly ketamine infusions of 0.8 mg/kg IV over 40 minutes plus psychological therapy

2. three saline infusions plus psychological therapy

3. three ketamine infusions plus alcohol education

4. three saline infusions plus alcohol education

The primary outcome was self-reported percentage of days abstinent, as well as confirmed alcohol relapse at 6-month follow-up.

At 6-month follow-up, ketamine was associated with a significantly greater number of days abstinent from alcohol (mean difference, 10.1%; 95% confidence interval, 1.1-19.0), “although confidence intervals were wide, consistent with a proof-of-concept study,” the authors note.

The greatest reduction in total days off alcohol occurred in the ketamine plus relapse-prevention therapy group compared with the saline plus alcohol education group (mean difference, 15.9%; 95% CI, 3.8-28.1).

There was no significant difference in relapse rate between the ketamine and placebo groups. No serious adverse effects were reported in any participant.
 

Growing evidence

These findings support some other studies that have also suggested a benefit of ketamine in AUD.

As reported by this news organization, one recent study found a single infusion of ketamine combined with counseling may help alcohol-dependent patients curb their drinking.

A separate study showed that a single dose of ketamine plus therapy that focused on reactivating drinking-related “maladaptive reward memories” reduced drinking urges and alcohol intake more than just ketamine or a placebo infusion alone.

“That ketamine can reduce both alcohol use and depression in AUD is encouraging therapeutically,” the researchers write.

“While a clear link between depression and AUD is acknowledged, alcohol and mental health services still struggle to meet the needs of dual-diagnosis patients, so ketamine may represent a solution to this long-standing comorbidity,” they add.

Dr. Morgan said in an interview that adjunctive ketamine with relapse-prevention therapy is “currently being delivered in Awakn Clinics in the U.K. and Norway, but we need to conduct the phase 3 trial in order to make the treatment more widely accessible.”
 

An ‘Intriguing new therapy’

Reached for comment, Timothy Brennan, MD, MPH, chief of clinical services, Addiction Institute of Mount Sinai, New York, said ketamine “continues to be an intriguing new therapy for a variety of mental health conditions.”

“Unfortunately, the study did not show any difference in rates of relapse to alcohol, though an improvement in days of abstinence is certainly noteworthy,” Dr. Brennan said in an interview.

“Because this was just a proof-of-concept study and did not compare ketamine to any FDA-approved pharmacotherapy for alcohol, it remains too early to recommend ketamine infusions to those suffering from alcohol use disorder,” he cautioned.

The study was supported by the Medical Research Council. Dr. Morgan has received royalties for KARE (Ketamine for Reduction of Alcoholic Relapse) therapy license distribution. KARE therapy is licensed from University of Exeter to Awakn Life Sciences. Dr. Morgan has received research funding from Awakn Life Sciences and has served as a consultant for Janssen Pharmaceuticals. Other coauthors have disclosed relationships with industry; the full list can be found with the original article. Dr. Brennan has disclosed no relevant financial relationships.

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

Three weekly infusions of the dissociative anesthetic ketamine coupled with mindfulness-based relapse prevention therapy may help adults with alcohol use disorder (AUD) maintain abstinence, new research suggests.

Preliminary results from a phase 2, double-blind, placebo-controlled trial show ketamine was well tolerated and, compared with placebo, associated with more days of abstinence from alcohol at 6 months.

The results suggest ketamine plus psychological therapy may be a “new, relatively brief treatment that has long lasting effects in AUD,” Celia Morgan, PhD, professor of psychopharmacology, University of Exeter, United Kingdom, told this news organization.

The study was published online Jan. 11 in the American Journal of Psychiatry.
 

Target depression

Depressive symptoms are common in patients under treatment for AUD and increase relapse risk.

“Ketamine may support alcohol abstinence by temporarily alleviating depressive symptoms during the high-risk relapse period in the weeks after detoxification,” the investigators note.

Ketamine may also provide a “temporary boost to synaptogenesis and neurogenesis, which may allow psychological therapies and new strategies for managing addiction to embed more readily,” they add.

To test these theories, the researchers recruited 96 adults (mean age, 44 years, 35 women) with severe AUD to participate in the trial.

All participants had to abstain from alcohol for at least 24 hours before the trial started and have a reading of 0.0 on a breath alcohol test at the baseline visit.

Participants were randomly allocated to one of four groups:

1. three weekly ketamine infusions of 0.8 mg/kg IV over 40 minutes plus psychological therapy

2. three saline infusions plus psychological therapy

3. three ketamine infusions plus alcohol education

4. three saline infusions plus alcohol education

The primary outcome was self-reported percentage of days abstinent, as well as confirmed alcohol relapse at 6-month follow-up.

At 6-month follow-up, ketamine was associated with a significantly greater number of days abstinent from alcohol (mean difference, 10.1%; 95% confidence interval, 1.1-19.0), “although confidence intervals were wide, consistent with a proof-of-concept study,” the authors note.

The greatest reduction in total days off alcohol occurred in the ketamine plus relapse-prevention therapy group compared with the saline plus alcohol education group (mean difference, 15.9%; 95% CI, 3.8-28.1).

There was no significant difference in relapse rate between the ketamine and placebo groups. No serious adverse effects were reported in any participant.
 

Growing evidence

These findings support some other studies that have also suggested a benefit of ketamine in AUD.

As reported by this news organization, one recent study found a single infusion of ketamine combined with counseling may help alcohol-dependent patients curb their drinking.

A separate study showed that a single dose of ketamine plus therapy that focused on reactivating drinking-related “maladaptive reward memories” reduced drinking urges and alcohol intake more than just ketamine or a placebo infusion alone.

“That ketamine can reduce both alcohol use and depression in AUD is encouraging therapeutically,” the researchers write.

“While a clear link between depression and AUD is acknowledged, alcohol and mental health services still struggle to meet the needs of dual-diagnosis patients, so ketamine may represent a solution to this long-standing comorbidity,” they add.

Dr. Morgan said in an interview that adjunctive ketamine with relapse-prevention therapy is “currently being delivered in Awakn Clinics in the U.K. and Norway, but we need to conduct the phase 3 trial in order to make the treatment more widely accessible.”
 

An ‘Intriguing new therapy’

Reached for comment, Timothy Brennan, MD, MPH, chief of clinical services, Addiction Institute of Mount Sinai, New York, said ketamine “continues to be an intriguing new therapy for a variety of mental health conditions.”

“Unfortunately, the study did not show any difference in rates of relapse to alcohol, though an improvement in days of abstinence is certainly noteworthy,” Dr. Brennan said in an interview.

“Because this was just a proof-of-concept study and did not compare ketamine to any FDA-approved pharmacotherapy for alcohol, it remains too early to recommend ketamine infusions to those suffering from alcohol use disorder,” he cautioned.

The study was supported by the Medical Research Council. Dr. Morgan has received royalties for KARE (Ketamine for Reduction of Alcoholic Relapse) therapy license distribution. KARE therapy is licensed from University of Exeter to Awakn Life Sciences. Dr. Morgan has received research funding from Awakn Life Sciences and has served as a consultant for Janssen Pharmaceuticals. Other coauthors have disclosed relationships with industry; the full list can be found with the original article. Dr. Brennan has disclosed no relevant financial relationships.

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

Three weekly infusions of the dissociative anesthetic ketamine coupled with mindfulness-based relapse prevention therapy may help adults with alcohol use disorder (AUD) maintain abstinence, new research suggests.

Preliminary results from a phase 2, double-blind, placebo-controlled trial show ketamine was well tolerated and, compared with placebo, associated with more days of abstinence from alcohol at 6 months.

The results suggest ketamine plus psychological therapy may be a “new, relatively brief treatment that has long lasting effects in AUD,” Celia Morgan, PhD, professor of psychopharmacology, University of Exeter, United Kingdom, told this news organization.

The study was published online Jan. 11 in the American Journal of Psychiatry.
 

Target depression

Depressive symptoms are common in patients under treatment for AUD and increase relapse risk.

“Ketamine may support alcohol abstinence by temporarily alleviating depressive symptoms during the high-risk relapse period in the weeks after detoxification,” the investigators note.

Ketamine may also provide a “temporary boost to synaptogenesis and neurogenesis, which may allow psychological therapies and new strategies for managing addiction to embed more readily,” they add.

To test these theories, the researchers recruited 96 adults (mean age, 44 years, 35 women) with severe AUD to participate in the trial.

All participants had to abstain from alcohol for at least 24 hours before the trial started and have a reading of 0.0 on a breath alcohol test at the baseline visit.

Participants were randomly allocated to one of four groups:

1. three weekly ketamine infusions of 0.8 mg/kg IV over 40 minutes plus psychological therapy

2. three saline infusions plus psychological therapy

3. three ketamine infusions plus alcohol education

4. three saline infusions plus alcohol education

The primary outcome was self-reported percentage of days abstinent, as well as confirmed alcohol relapse at 6-month follow-up.

At 6-month follow-up, ketamine was associated with a significantly greater number of days abstinent from alcohol (mean difference, 10.1%; 95% confidence interval, 1.1-19.0), “although confidence intervals were wide, consistent with a proof-of-concept study,” the authors note.

The greatest reduction in total days off alcohol occurred in the ketamine plus relapse-prevention therapy group compared with the saline plus alcohol education group (mean difference, 15.9%; 95% CI, 3.8-28.1).

There was no significant difference in relapse rate between the ketamine and placebo groups. No serious adverse effects were reported in any participant.
 

Growing evidence

These findings support some other studies that have also suggested a benefit of ketamine in AUD.

As reported by this news organization, one recent study found a single infusion of ketamine combined with counseling may help alcohol-dependent patients curb their drinking.

A separate study showed that a single dose of ketamine plus therapy that focused on reactivating drinking-related “maladaptive reward memories” reduced drinking urges and alcohol intake more than just ketamine or a placebo infusion alone.

“That ketamine can reduce both alcohol use and depression in AUD is encouraging therapeutically,” the researchers write.

“While a clear link between depression and AUD is acknowledged, alcohol and mental health services still struggle to meet the needs of dual-diagnosis patients, so ketamine may represent a solution to this long-standing comorbidity,” they add.

Dr. Morgan said in an interview that adjunctive ketamine with relapse-prevention therapy is “currently being delivered in Awakn Clinics in the U.K. and Norway, but we need to conduct the phase 3 trial in order to make the treatment more widely accessible.”
 

An ‘Intriguing new therapy’

Reached for comment, Timothy Brennan, MD, MPH, chief of clinical services, Addiction Institute of Mount Sinai, New York, said ketamine “continues to be an intriguing new therapy for a variety of mental health conditions.”

“Unfortunately, the study did not show any difference in rates of relapse to alcohol, though an improvement in days of abstinence is certainly noteworthy,” Dr. Brennan said in an interview.

“Because this was just a proof-of-concept study and did not compare ketamine to any FDA-approved pharmacotherapy for alcohol, it remains too early to recommend ketamine infusions to those suffering from alcohol use disorder,” he cautioned.

The study was supported by the Medical Research Council. Dr. Morgan has received royalties for KARE (Ketamine for Reduction of Alcoholic Relapse) therapy license distribution. KARE therapy is licensed from University of Exeter to Awakn Life Sciences. Dr. Morgan has received research funding from Awakn Life Sciences and has served as a consultant for Janssen Pharmaceuticals. Other coauthors have disclosed relationships with industry; the full list can be found with the original article. Dr. Brennan has disclosed no relevant financial relationships.

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