Clinician Reviews

The liquid form of the antibiotic amoxicillin often used to treat ear infections and strep throat in children is in short supply, just as Americans head into the season when they use the bacteria-fighting drug the most.

The FDA officially listed the shortage Oct. 28, but pharmacists, hospitals, and a supply tracking database sounded alarms earlier this month.

“The scary part is, we’re coming into the time of the year where you have the greatest need,” independent pharmacy owner Hugh Chancy, PharmD, of Georgia, told NBC News. 

Thus far, reports indicate the impact of the shortages is not widespread but does affect some pharmacies, and at least one hospital has published an algorithm for offering treatment alternatives. 

CVS told Bloomberg News that some stores are experiencing shortages of certain doses of amoxicillin, but a Walmart spokesperson said its diverse supply chain meant none of its pharmacies were affected.

“Hypothetically, if amoxicillin doesn’t come into stock for some time, then we’re potentially having to use less effective antibiotics with more side effects,” said Ohio pediatrician Sean Gallagher, MD, according to Bloomberg.

The shortage impacts three of the four largest amoxicillin manufacturers worldwide, according to the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota. The FDA listed the reason for the shortage as “demand increase for drug,” except in the case of manufacturer Sandoz, for which the reason listed read “information pending.”

A company spokesperson told Bloomberg the reasons were complex.

“The combination in rapid succession of the pandemic impact and consequent demand swings, manufacturing capacity constraints, scarcity of raw materials, and the current energy crisis means we face a uniquely difficult situation in the short term,” Sandoz spokesperson Leslie Pott told Bloomberg.

According to Bloomberg, other major manufacturers are still delivering the product, but limiting new orders.

The American Society of Health-System Pharmacists issued an alert for the shortage last week via its real time drug shortage database.

“Amoxicillin comes in many forms – including capsules, powders and chewable tablets – but the most common type children take is the liquid form, which makes up at least 19 products that are part of the” shortage, Becker’s Hospital Review summarized of the database reports.

The pediatric health system Children’s Minnesota told CIDRAP that supplies are low and that alternatives are being prescribed “when appropriate.”

“As a final step, we temporarily discontinued our standard procedure of dispensing the entire bottle of amoxicillin (which comes in multiple sizes),” a spokesperson told CIDRAP. “We are instead mixing and pouring the exact amount for each course of therapy, to eliminate waste.” 

The Minnesota pediatric clinic and others are particularly on alert because of the surge nationwide of a respiratory virus that particularly impacts children known as RSV.

“We have certainly observed an increase in recent use most likely correlating with the surge in RSV and other respiratory viruses with concern for superimposed bacterial infection in our critically ill and hospitalized patient population,” Laura Bio, PharmD, a clinical pharmacy specialist at Stanford Medicine Children’s Health told CIDRAP.

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

The liquid form of the antibiotic amoxicillin often used to treat ear infections and strep throat in children is in short supply, just as Americans head into the season when they use the bacteria-fighting drug the most.

The FDA officially listed the shortage Oct. 28, but pharmacists, hospitals, and a supply tracking database sounded alarms earlier this month.

“The scary part is, we’re coming into the time of the year where you have the greatest need,” independent pharmacy owner Hugh Chancy, PharmD, of Georgia, told NBC News. 

Thus far, reports indicate the impact of the shortages is not widespread but does affect some pharmacies, and at least one hospital has published an algorithm for offering treatment alternatives. 

CVS told Bloomberg News that some stores are experiencing shortages of certain doses of amoxicillin, but a Walmart spokesperson said its diverse supply chain meant none of its pharmacies were affected.

“Hypothetically, if amoxicillin doesn’t come into stock for some time, then we’re potentially having to use less effective antibiotics with more side effects,” said Ohio pediatrician Sean Gallagher, MD, according to Bloomberg.

The shortage impacts three of the four largest amoxicillin manufacturers worldwide, according to the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota. The FDA listed the reason for the shortage as “demand increase for drug,” except in the case of manufacturer Sandoz, for which the reason listed read “information pending.”

A company spokesperson told Bloomberg the reasons were complex.

“The combination in rapid succession of the pandemic impact and consequent demand swings, manufacturing capacity constraints, scarcity of raw materials, and the current energy crisis means we face a uniquely difficult situation in the short term,” Sandoz spokesperson Leslie Pott told Bloomberg.

According to Bloomberg, other major manufacturers are still delivering the product, but limiting new orders.

The American Society of Health-System Pharmacists issued an alert for the shortage last week via its real time drug shortage database.

“Amoxicillin comes in many forms – including capsules, powders and chewable tablets – but the most common type children take is the liquid form, which makes up at least 19 products that are part of the” shortage, Becker’s Hospital Review summarized of the database reports.

The pediatric health system Children’s Minnesota told CIDRAP that supplies are low and that alternatives are being prescribed “when appropriate.”

“As a final step, we temporarily discontinued our standard procedure of dispensing the entire bottle of amoxicillin (which comes in multiple sizes),” a spokesperson told CIDRAP. “We are instead mixing and pouring the exact amount for each course of therapy, to eliminate waste.” 

The Minnesota pediatric clinic and others are particularly on alert because of the surge nationwide of a respiratory virus that particularly impacts children known as RSV.

“We have certainly observed an increase in recent use most likely correlating with the surge in RSV and other respiratory viruses with concern for superimposed bacterial infection in our critically ill and hospitalized patient population,” Laura Bio, PharmD, a clinical pharmacy specialist at Stanford Medicine Children’s Health told CIDRAP.

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

The liquid form of the antibiotic amoxicillin often used to treat ear infections and strep throat in children is in short supply, just as Americans head into the season when they use the bacteria-fighting drug the most.

The FDA officially listed the shortage Oct. 28, but pharmacists, hospitals, and a supply tracking database sounded alarms earlier this month.

“The scary part is, we’re coming into the time of the year where you have the greatest need,” independent pharmacy owner Hugh Chancy, PharmD, of Georgia, told NBC News. 

Thus far, reports indicate the impact of the shortages is not widespread but does affect some pharmacies, and at least one hospital has published an algorithm for offering treatment alternatives. 

CVS told Bloomberg News that some stores are experiencing shortages of certain doses of amoxicillin, but a Walmart spokesperson said its diverse supply chain meant none of its pharmacies were affected.

“Hypothetically, if amoxicillin doesn’t come into stock for some time, then we’re potentially having to use less effective antibiotics with more side effects,” said Ohio pediatrician Sean Gallagher, MD, according to Bloomberg.

The shortage impacts three of the four largest amoxicillin manufacturers worldwide, according to the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota. The FDA listed the reason for the shortage as “demand increase for drug,” except in the case of manufacturer Sandoz, for which the reason listed read “information pending.”

A company spokesperson told Bloomberg the reasons were complex.

“The combination in rapid succession of the pandemic impact and consequent demand swings, manufacturing capacity constraints, scarcity of raw materials, and the current energy crisis means we face a uniquely difficult situation in the short term,” Sandoz spokesperson Leslie Pott told Bloomberg.

According to Bloomberg, other major manufacturers are still delivering the product, but limiting new orders.

The American Society of Health-System Pharmacists issued an alert for the shortage last week via its real time drug shortage database.

“Amoxicillin comes in many forms – including capsules, powders and chewable tablets – but the most common type children take is the liquid form, which makes up at least 19 products that are part of the” shortage, Becker’s Hospital Review summarized of the database reports.

The pediatric health system Children’s Minnesota told CIDRAP that supplies are low and that alternatives are being prescribed “when appropriate.”

“As a final step, we temporarily discontinued our standard procedure of dispensing the entire bottle of amoxicillin (which comes in multiple sizes),” a spokesperson told CIDRAP. “We are instead mixing and pouring the exact amount for each course of therapy, to eliminate waste.” 

The Minnesota pediatric clinic and others are particularly on alert because of the surge nationwide of a respiratory virus that particularly impacts children known as RSV.

“We have certainly observed an increase in recent use most likely correlating with the surge in RSV and other respiratory viruses with concern for superimposed bacterial infection in our critically ill and hospitalized patient population,” Laura Bio, PharmD, a clinical pharmacy specialist at Stanford Medicine Children’s Health told CIDRAP.

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

Only about one in three patients seen in the emergency department of an academic health system for acute gout had a follow-up visit that addressed this condition, Lesley Jackson, MD, of the University of Alabama at Birmingham, reported at the annual research symposium of the Gout, Hyperuricemia, and Crystal Associated Disease Network (G-CAN).

Dr. Jackson presented research done on patients seen within her university’s health system, looking at 72 patients seen in the ED between September 2021 and February 2022. Medications prescribed at discharge from the ED included corticosteroids (46 patients, or 64%), opioids (45 patients, 63%), NSAIDs (31 patients, 43%), and colchicine (23 patients, 32%).

Only 26 patients, or about 36%, had a subsequent outpatient visit in the UAB health system addressing gout, she said. Of 33 patients with any outpatient follow-up visit within the UAB system, 21 were within 1 month after the index ED visit, followed by 3 more prior to 3 months, and 9 more after 3 months.

The limitations of the study includes its collection of data from a single institution. But the results highlight the need for improved quality of care for gout, with too many people being treated for this condition primarily in the ED, she said.

In an email exchange arranged by the Arthritis Foundation, Herbert S. B. Baraf, MD, said he agreed that patients too often limit their treatment for gout to seeking care for acute attacks in the ED.

Because of competing demands, physicians working there are more to take a “Band-Aid” approach and not impress upon patients that gout is a lifelong condition that needs follow-up and monitoring, said Dr. Baraf, clinical professor of medicine at George Washington University, Washington, and an associate clinical professor at the University of Maryland, Baltimore. He retired from private practice in 2022.

“This problem is akin to the patient who has a hip fracture due to osteoporosis who gets a surgical repair but is never referred for osteoporotic management,” wrote Dr. Baraf, who is a former board member of the Arthritis Foundation.

He suggested viewing gout as a form of arthritis that has two components.

“The first, that which brings the patient to seek medical care, is the often exquisitely painful attack of pain and swelling in a joint or joints that comes on acutely,” he wrote. “Calming these attacks are the focus of the patient and the doctor, who does the evaluation as relief of pain and inflammation is the most pressing task at hand.”

But equally important is the second element, addressing the cause of these flare ups of arthritis, he wrote. Elevated uric acid leads to crystalline deposits of urate in the joints, particularly in the feet, ankles, knees, and hands. Over time, these deposits generate seemingly random flare ups of acute joint pain in one or more of these areas.

“Thus, when a patient presents to an emergency room with a first or second attack of gout, pain relief is the primary focus of the visit,” Dr. Baraf wrote. “But if over time that is the only focus, and the elevation of serum uric acid is not addressed, deposits will continue to mount and flare ups will occur with increasing frequency and severity.”

This study was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Jackson has no relevant financial disclosures.

Only about one in three patients seen in the emergency department of an academic health system for acute gout had a follow-up visit that addressed this condition, Lesley Jackson, MD, of the University of Alabama at Birmingham, reported at the annual research symposium of the Gout, Hyperuricemia, and Crystal Associated Disease Network (G-CAN).

Dr. Jackson presented research done on patients seen within her university’s health system, looking at 72 patients seen in the ED between September 2021 and February 2022. Medications prescribed at discharge from the ED included corticosteroids (46 patients, or 64%), opioids (45 patients, 63%), NSAIDs (31 patients, 43%), and colchicine (23 patients, 32%).

Only 26 patients, or about 36%, had a subsequent outpatient visit in the UAB health system addressing gout, she said. Of 33 patients with any outpatient follow-up visit within the UAB system, 21 were within 1 month after the index ED visit, followed by 3 more prior to 3 months, and 9 more after 3 months.

The limitations of the study includes its collection of data from a single institution. But the results highlight the need for improved quality of care for gout, with too many people being treated for this condition primarily in the ED, she said.

In an email exchange arranged by the Arthritis Foundation, Herbert S. B. Baraf, MD, said he agreed that patients too often limit their treatment for gout to seeking care for acute attacks in the ED.

Because of competing demands, physicians working there are more to take a “Band-Aid” approach and not impress upon patients that gout is a lifelong condition that needs follow-up and monitoring, said Dr. Baraf, clinical professor of medicine at George Washington University, Washington, and an associate clinical professor at the University of Maryland, Baltimore. He retired from private practice in 2022.

“This problem is akin to the patient who has a hip fracture due to osteoporosis who gets a surgical repair but is never referred for osteoporotic management,” wrote Dr. Baraf, who is a former board member of the Arthritis Foundation.

He suggested viewing gout as a form of arthritis that has two components.

“The first, that which brings the patient to seek medical care, is the often exquisitely painful attack of pain and swelling in a joint or joints that comes on acutely,” he wrote. “Calming these attacks are the focus of the patient and the doctor, who does the evaluation as relief of pain and inflammation is the most pressing task at hand.”

But equally important is the second element, addressing the cause of these flare ups of arthritis, he wrote. Elevated uric acid leads to crystalline deposits of urate in the joints, particularly in the feet, ankles, knees, and hands. Over time, these deposits generate seemingly random flare ups of acute joint pain in one or more of these areas.

“Thus, when a patient presents to an emergency room with a first or second attack of gout, pain relief is the primary focus of the visit,” Dr. Baraf wrote. “But if over time that is the only focus, and the elevation of serum uric acid is not addressed, deposits will continue to mount and flare ups will occur with increasing frequency and severity.”

This study was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Jackson has no relevant financial disclosures.

Only about one in three patients seen in the emergency department of an academic health system for acute gout had a follow-up visit that addressed this condition, Lesley Jackson, MD, of the University of Alabama at Birmingham, reported at the annual research symposium of the Gout, Hyperuricemia, and Crystal Associated Disease Network (G-CAN).

Dr. Jackson presented research done on patients seen within her university’s health system, looking at 72 patients seen in the ED between September 2021 and February 2022. Medications prescribed at discharge from the ED included corticosteroids (46 patients, or 64%), opioids (45 patients, 63%), NSAIDs (31 patients, 43%), and colchicine (23 patients, 32%).

Only 26 patients, or about 36%, had a subsequent outpatient visit in the UAB health system addressing gout, she said. Of 33 patients with any outpatient follow-up visit within the UAB system, 21 were within 1 month after the index ED visit, followed by 3 more prior to 3 months, and 9 more after 3 months.

The limitations of the study includes its collection of data from a single institution. But the results highlight the need for improved quality of care for gout, with too many people being treated for this condition primarily in the ED, she said.

In an email exchange arranged by the Arthritis Foundation, Herbert S. B. Baraf, MD, said he agreed that patients too often limit their treatment for gout to seeking care for acute attacks in the ED.

Because of competing demands, physicians working there are more to take a “Band-Aid” approach and not impress upon patients that gout is a lifelong condition that needs follow-up and monitoring, said Dr. Baraf, clinical professor of medicine at George Washington University, Washington, and an associate clinical professor at the University of Maryland, Baltimore. He retired from private practice in 2022.

“This problem is akin to the patient who has a hip fracture due to osteoporosis who gets a surgical repair but is never referred for osteoporotic management,” wrote Dr. Baraf, who is a former board member of the Arthritis Foundation.

He suggested viewing gout as a form of arthritis that has two components.

“The first, that which brings the patient to seek medical care, is the often exquisitely painful attack of pain and swelling in a joint or joints that comes on acutely,” he wrote. “Calming these attacks are the focus of the patient and the doctor, who does the evaluation as relief of pain and inflammation is the most pressing task at hand.”

But equally important is the second element, addressing the cause of these flare ups of arthritis, he wrote. Elevated uric acid leads to crystalline deposits of urate in the joints, particularly in the feet, ankles, knees, and hands. Over time, these deposits generate seemingly random flare ups of acute joint pain in one or more of these areas.

“Thus, when a patient presents to an emergency room with a first or second attack of gout, pain relief is the primary focus of the visit,” Dr. Baraf wrote. “But if over time that is the only focus, and the elevation of serum uric acid is not addressed, deposits will continue to mount and flare ups will occur with increasing frequency and severity.”

This study was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Jackson has no relevant financial disclosures.

Knee and hip replacements can improve how well patients get around and can significantly increase their quality of life. But if a bone near the new joint breaks, the injury can be a major setback for the patient’s mobility, and the consequences can be life-threatening.

The proportion of patients who experience a periprosthetic fracture within 5 years of total hip arthroplasty is 0.9%. After total knee arthroplasty (TKA), the proportion is 0.6%, research shows.

Those rates might seem low. But given that more than a million of these joint replacement surgeries are performed each year in the United States – they are the most common inpatient surgical procedures among people aged 65 and older – thousands of revision surgeries due to periprosthetic fractures occur each year.

Primary care physicians, surgeons, and researchers are trying to identify risk factors, medication regimens, and nondrug approaches to avoid these complications. Primary care clinicians who make their patients’ bone health a priority early on – years before surgery, ideally – may help patients enjoy the benefits of new joints long term.

At the 2022 annual Santa Fe Bone Symposium this summer, Susan V. Bukata, MD, professor and chair of orthopedics at the University of California, San Diego, showed an image of “what we’re trying to avoid” – a patient with a broken bone and infection. Unfortunately, Dr. Bukata said, the patient’s clinicians had not adequately addressed her skeletal health before the injury.

“This is a complete disaster for this person who went in having a total hip to improve their function and now will probably never walk normally on that leg,” Dr. Bukata said at the meeting.

The patient eventually underwent total femur replacement. Five surgeries were required to clear the infection.

Medical and surgical advances have allowed more people – including older patients and those with other medical conditions – to undergo joint replacement surgery, including replacement of knees, hips, and shoulders.

The surgeries often are performed for adults whose bones are thinning. Sometimes surgeons don’t realize just how thin a patient’s bone is until they are operating.
 

Prioritizing bone health

In patients with osteoporosis, the bone surrounding the new joint is weaker than the metal of the prosthesis, and the metal can rip out of the bone, Dr. Bukata told this news organization. A periprosthetic fracture should be recognized as an osteoporotic fracture, too, although these fractures have not typically been categorized that way, she said.

People live with total joints in place for as long as 40 years, and fractures around the implants are “one of the fastest growing injuries that we are seeing in older patients,” Dr. Bukata said. “People don’t think of those as osteoporotic fractures. But a 90-year-old who falls and breaks next to their total knee, if they didn’t have that total knee in place, everybody would be, like, ‘Oh, that’s an osteoporotic fracture.’ ”

Periprosthetic fractures tend not to occur right after surgery but rather after the bone continues to lose density as the patient ages, Dr. Bukata said.
 

Missed chances

One approach to preventing periprosthetic fractures could involve prioritizing bone health earlier in life and diagnosing and treating osteoporosis well before a patient is scheduled for surgery.

A patient’s initial visit to their primary care doctor because of joint pain is an opportunity to check on and promote their bone health, given that they might be a candidate for surgery in the future, Dr. Bukata said.

Ahead of a scheduled surgery, patients can see endocrinologists or rheumatologists to receive medication to try to strengthen bones. Doctors may be limited in how much of a difference they can make in a matter of several weeks or months with these drugs, however. These patients still likely will need to be treated as if they have osteoporosis, Dr. Bukata said.

When surgeons realize that a patient has weaker bones while they are in the middle of an operation, they should emphasize the importance of bone health after the procedure, Dr. Bukata said.

Strengthening, maintaining, and protecting bone should be seen as a long-term investment in the patient’s success after a joint replacement. That said, “There is no clear evidence or protocol for us to follow,” she said. “The mantra at UCSD now is, let’s keep it simple. Get the patient on track. And then we can always refine things as we continue to treat the patient.”

Health systems should establish routines in which bone health is discussed before surgery in the way patient education programs address smoking cessation, nutrition, and weight management, Dr. Bukata said. Another step in the right direction could involve setting electronic medical records to automatically order assessments of bone health when a surgeon books a case.

Linda A. Russell, MD, rheumatologist and director of perioperative medicine at the Hospital for Special Surgery in New York, said periprosthetic fractures are a “complication we fear.”

“It’s a big deal to try to repair it,” Dr. Russell said. “Sometimes you need to revise the joint, or sometimes you need to put lots more hardware in.” Surgeons increasingly appreciate the need to pay attention to the quality of the bone before they operate, she said.

Nevertheless, Dr. Russell does not necessarily say that such cases call for alarm or particularly aggressive treatment regimens – just regular bone health evaluations before and after surgery to see whether patients have osteoporosis and are candidates for treatment.
 

Lifelong effort

In some ways, to address bone health at the time of surgery may be too late.

Bone health “is not something that you can have as an afterthought when you’re 75 years old,” said Elizabeth Matzkin, MD, chief of women’s sports medicine at Brigham and Women’s Hospital, in Boston.

The chance of being able to rebuild bone mass at that age is slim. If patients maximize bone density when they are young, they can afford to lose some bone mass each year as they age.

To that end, a healthy diet, exercise, not smoking, and cutting back on alcohol can help, she said.

For Dr. Matzkin, a fragility fracture is a red flag that the patient’s bone density is probably not optimal. In such cases, she prepares for various scenarios during surgery, such as a screw not holding in a low-density bone.

Recently published research reflects that prior fragility fractures are a significant risk factor for complications after surgery, including periprosthetic fractures.

Edward J. Testa, MD, of Brown University, Providence, R.I., and colleagues analyzed insurance claims to compare outcomes for 24,398 patients who had experienced a fragility fracture – that is, a break caused by low-velocity trauma such as a fall – during the 3 years before their TKA procedure and a matched group of patients who were similar in many respects but who had not had a fragility fracture in the 3 years before surgery.

Dr. Testa’s group found that a history of fragility fracture was associated with higher rates of complications in the year after surgery, including hospital readmissions (hazard ratio = 1.30; 95% CI, 1.22-1.38), periprosthetic fractures (odds ratio = 2.72; 95% CI, 1.89-3.99), and secondary fragility fractures (OR = 4.62; 95% CI, 4.19-5.12). Patients who had previously experienced fragility fractures also experienced dislocated prostheses (OR = 1.76; 95% CI, 1.22-2.56) and periprosthetic infections (OR = 1.49; 95% CI, 1.29-1.71) at higher rates.

The rates of complications were similar regardless of whether patients had filled a prescription for medications used to treat osteoporosis, including bisphosphonates, vitamin D replacement, raloxifene, and denosumab, the researchers reported.

The lack of a clear association between these treatments and patient outcomes could be related to an insufficient duration of pharmacotherapy before or after TKA, poor medication adherence, or small sample sizes, Dr. Testa said.

Given the findings, which were published online in the Journal of Arthroplasty, “patients with a history of fragility fracture should be identified and counseled appropriately for a possible increased risk of the aforementioned complications, and optimized when possible, prior to undergoing TKA,” Dr. Testa told this news organization. “Ultimately, the decision to move forward with surgery is far more complex than the identification of this sole, yet important, risk factor for certain postoperative, implant-related complications.”
 

Treatment gaps

Prior research has shown that women aged 70 years and older are at higher risk for periprosthetic fractures. Many women in this age group who could receive treatment for osteoporosis do not, and major treatment gaps exist worldwide, noted Neil Binkley, MD, with the University of Wisconsin–Madison, in a separate talk at the Santa Fe Bone Symposium.

Ensuring adequate protein intake and addressing the risk of falling are other measures that clinicians can take to promote healthy bones, apart from prescribing drugs, he said.

Unpublished data from one group show that nearly 90% of periprosthetic fractures may result from falls, while about 8% may be spontaneous. “We need to be thinking about falls,” Dr. Binkley said.

Dr. Bukata has consulted for Amgen, Radius, and Solarea Bio and has served on a speakers bureau for Radius. She also is a board member for the Orthopaedic Research Society and the American Academy of Orthopaedic Surgeons Board of Specialty Societies. Dr. Binkley has received research support from Radius and has consulted for Amgen.

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

Knee and hip replacements can improve how well patients get around and can significantly increase their quality of life. But if a bone near the new joint breaks, the injury can be a major setback for the patient’s mobility, and the consequences can be life-threatening.

The proportion of patients who experience a periprosthetic fracture within 5 years of total hip arthroplasty is 0.9%. After total knee arthroplasty (TKA), the proportion is 0.6%, research shows.

Those rates might seem low. But given that more than a million of these joint replacement surgeries are performed each year in the United States – they are the most common inpatient surgical procedures among people aged 65 and older – thousands of revision surgeries due to periprosthetic fractures occur each year.

Primary care physicians, surgeons, and researchers are trying to identify risk factors, medication regimens, and nondrug approaches to avoid these complications. Primary care clinicians who make their patients’ bone health a priority early on – years before surgery, ideally – may help patients enjoy the benefits of new joints long term.

At the 2022 annual Santa Fe Bone Symposium this summer, Susan V. Bukata, MD, professor and chair of orthopedics at the University of California, San Diego, showed an image of “what we’re trying to avoid” – a patient with a broken bone and infection. Unfortunately, Dr. Bukata said, the patient’s clinicians had not adequately addressed her skeletal health before the injury.

“This is a complete disaster for this person who went in having a total hip to improve their function and now will probably never walk normally on that leg,” Dr. Bukata said at the meeting.

The patient eventually underwent total femur replacement. Five surgeries were required to clear the infection.

Medical and surgical advances have allowed more people – including older patients and those with other medical conditions – to undergo joint replacement surgery, including replacement of knees, hips, and shoulders.

The surgeries often are performed for adults whose bones are thinning. Sometimes surgeons don’t realize just how thin a patient’s bone is until they are operating.
 

Prioritizing bone health

In patients with osteoporosis, the bone surrounding the new joint is weaker than the metal of the prosthesis, and the metal can rip out of the bone, Dr. Bukata told this news organization. A periprosthetic fracture should be recognized as an osteoporotic fracture, too, although these fractures have not typically been categorized that way, she said.

People live with total joints in place for as long as 40 years, and fractures around the implants are “one of the fastest growing injuries that we are seeing in older patients,” Dr. Bukata said. “People don’t think of those as osteoporotic fractures. But a 90-year-old who falls and breaks next to their total knee, if they didn’t have that total knee in place, everybody would be, like, ‘Oh, that’s an osteoporotic fracture.’ ”

Periprosthetic fractures tend not to occur right after surgery but rather after the bone continues to lose density as the patient ages, Dr. Bukata said.
 

Missed chances

One approach to preventing periprosthetic fractures could involve prioritizing bone health earlier in life and diagnosing and treating osteoporosis well before a patient is scheduled for surgery.

A patient’s initial visit to their primary care doctor because of joint pain is an opportunity to check on and promote their bone health, given that they might be a candidate for surgery in the future, Dr. Bukata said.

Ahead of a scheduled surgery, patients can see endocrinologists or rheumatologists to receive medication to try to strengthen bones. Doctors may be limited in how much of a difference they can make in a matter of several weeks or months with these drugs, however. These patients still likely will need to be treated as if they have osteoporosis, Dr. Bukata said.

When surgeons realize that a patient has weaker bones while they are in the middle of an operation, they should emphasize the importance of bone health after the procedure, Dr. Bukata said.

Strengthening, maintaining, and protecting bone should be seen as a long-term investment in the patient’s success after a joint replacement. That said, “There is no clear evidence or protocol for us to follow,” she said. “The mantra at UCSD now is, let’s keep it simple. Get the patient on track. And then we can always refine things as we continue to treat the patient.”

Health systems should establish routines in which bone health is discussed before surgery in the way patient education programs address smoking cessation, nutrition, and weight management, Dr. Bukata said. Another step in the right direction could involve setting electronic medical records to automatically order assessments of bone health when a surgeon books a case.

Linda A. Russell, MD, rheumatologist and director of perioperative medicine at the Hospital for Special Surgery in New York, said periprosthetic fractures are a “complication we fear.”

“It’s a big deal to try to repair it,” Dr. Russell said. “Sometimes you need to revise the joint, or sometimes you need to put lots more hardware in.” Surgeons increasingly appreciate the need to pay attention to the quality of the bone before they operate, she said.

Nevertheless, Dr. Russell does not necessarily say that such cases call for alarm or particularly aggressive treatment regimens – just regular bone health evaluations before and after surgery to see whether patients have osteoporosis and are candidates for treatment.
 

Lifelong effort

In some ways, to address bone health at the time of surgery may be too late.

Bone health “is not something that you can have as an afterthought when you’re 75 years old,” said Elizabeth Matzkin, MD, chief of women’s sports medicine at Brigham and Women’s Hospital, in Boston.

The chance of being able to rebuild bone mass at that age is slim. If patients maximize bone density when they are young, they can afford to lose some bone mass each year as they age.

To that end, a healthy diet, exercise, not smoking, and cutting back on alcohol can help, she said.

For Dr. Matzkin, a fragility fracture is a red flag that the patient’s bone density is probably not optimal. In such cases, she prepares for various scenarios during surgery, such as a screw not holding in a low-density bone.

Recently published research reflects that prior fragility fractures are a significant risk factor for complications after surgery, including periprosthetic fractures.

Edward J. Testa, MD, of Brown University, Providence, R.I., and colleagues analyzed insurance claims to compare outcomes for 24,398 patients who had experienced a fragility fracture – that is, a break caused by low-velocity trauma such as a fall – during the 3 years before their TKA procedure and a matched group of patients who were similar in many respects but who had not had a fragility fracture in the 3 years before surgery.

Dr. Testa’s group found that a history of fragility fracture was associated with higher rates of complications in the year after surgery, including hospital readmissions (hazard ratio = 1.30; 95% CI, 1.22-1.38), periprosthetic fractures (odds ratio = 2.72; 95% CI, 1.89-3.99), and secondary fragility fractures (OR = 4.62; 95% CI, 4.19-5.12). Patients who had previously experienced fragility fractures also experienced dislocated prostheses (OR = 1.76; 95% CI, 1.22-2.56) and periprosthetic infections (OR = 1.49; 95% CI, 1.29-1.71) at higher rates.

The rates of complications were similar regardless of whether patients had filled a prescription for medications used to treat osteoporosis, including bisphosphonates, vitamin D replacement, raloxifene, and denosumab, the researchers reported.

The lack of a clear association between these treatments and patient outcomes could be related to an insufficient duration of pharmacotherapy before or after TKA, poor medication adherence, or small sample sizes, Dr. Testa said.

Given the findings, which were published online in the Journal of Arthroplasty, “patients with a history of fragility fracture should be identified and counseled appropriately for a possible increased risk of the aforementioned complications, and optimized when possible, prior to undergoing TKA,” Dr. Testa told this news organization. “Ultimately, the decision to move forward with surgery is far more complex than the identification of this sole, yet important, risk factor for certain postoperative, implant-related complications.”
 

Treatment gaps

Prior research has shown that women aged 70 years and older are at higher risk for periprosthetic fractures. Many women in this age group who could receive treatment for osteoporosis do not, and major treatment gaps exist worldwide, noted Neil Binkley, MD, with the University of Wisconsin–Madison, in a separate talk at the Santa Fe Bone Symposium.

Ensuring adequate protein intake and addressing the risk of falling are other measures that clinicians can take to promote healthy bones, apart from prescribing drugs, he said.

Unpublished data from one group show that nearly 90% of periprosthetic fractures may result from falls, while about 8% may be spontaneous. “We need to be thinking about falls,” Dr. Binkley said.

Dr. Bukata has consulted for Amgen, Radius, and Solarea Bio and has served on a speakers bureau for Radius. She also is a board member for the Orthopaedic Research Society and the American Academy of Orthopaedic Surgeons Board of Specialty Societies. Dr. Binkley has received research support from Radius and has consulted for Amgen.

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

Knee and hip replacements can improve how well patients get around and can significantly increase their quality of life. But if a bone near the new joint breaks, the injury can be a major setback for the patient’s mobility, and the consequences can be life-threatening.

The proportion of patients who experience a periprosthetic fracture within 5 years of total hip arthroplasty is 0.9%. After total knee arthroplasty (TKA), the proportion is 0.6%, research shows.

Those rates might seem low. But given that more than a million of these joint replacement surgeries are performed each year in the United States – they are the most common inpatient surgical procedures among people aged 65 and older – thousands of revision surgeries due to periprosthetic fractures occur each year.

Primary care physicians, surgeons, and researchers are trying to identify risk factors, medication regimens, and nondrug approaches to avoid these complications. Primary care clinicians who make their patients’ bone health a priority early on – years before surgery, ideally – may help patients enjoy the benefits of new joints long term.

At the 2022 annual Santa Fe Bone Symposium this summer, Susan V. Bukata, MD, professor and chair of orthopedics at the University of California, San Diego, showed an image of “what we’re trying to avoid” – a patient with a broken bone and infection. Unfortunately, Dr. Bukata said, the patient’s clinicians had not adequately addressed her skeletal health before the injury.

“This is a complete disaster for this person who went in having a total hip to improve their function and now will probably never walk normally on that leg,” Dr. Bukata said at the meeting.

The patient eventually underwent total femur replacement. Five surgeries were required to clear the infection.

Medical and surgical advances have allowed more people – including older patients and those with other medical conditions – to undergo joint replacement surgery, including replacement of knees, hips, and shoulders.

The surgeries often are performed for adults whose bones are thinning. Sometimes surgeons don’t realize just how thin a patient’s bone is until they are operating.
 

Prioritizing bone health

In patients with osteoporosis, the bone surrounding the new joint is weaker than the metal of the prosthesis, and the metal can rip out of the bone, Dr. Bukata told this news organization. A periprosthetic fracture should be recognized as an osteoporotic fracture, too, although these fractures have not typically been categorized that way, she said.

People live with total joints in place for as long as 40 years, and fractures around the implants are “one of the fastest growing injuries that we are seeing in older patients,” Dr. Bukata said. “People don’t think of those as osteoporotic fractures. But a 90-year-old who falls and breaks next to their total knee, if they didn’t have that total knee in place, everybody would be, like, ‘Oh, that’s an osteoporotic fracture.’ ”

Periprosthetic fractures tend not to occur right after surgery but rather after the bone continues to lose density as the patient ages, Dr. Bukata said.
 

Missed chances

One approach to preventing periprosthetic fractures could involve prioritizing bone health earlier in life and diagnosing and treating osteoporosis well before a patient is scheduled for surgery.

A patient’s initial visit to their primary care doctor because of joint pain is an opportunity to check on and promote their bone health, given that they might be a candidate for surgery in the future, Dr. Bukata said.

Ahead of a scheduled surgery, patients can see endocrinologists or rheumatologists to receive medication to try to strengthen bones. Doctors may be limited in how much of a difference they can make in a matter of several weeks or months with these drugs, however. These patients still likely will need to be treated as if they have osteoporosis, Dr. Bukata said.

When surgeons realize that a patient has weaker bones while they are in the middle of an operation, they should emphasize the importance of bone health after the procedure, Dr. Bukata said.

Strengthening, maintaining, and protecting bone should be seen as a long-term investment in the patient’s success after a joint replacement. That said, “There is no clear evidence or protocol for us to follow,” she said. “The mantra at UCSD now is, let’s keep it simple. Get the patient on track. And then we can always refine things as we continue to treat the patient.”

Health systems should establish routines in which bone health is discussed before surgery in the way patient education programs address smoking cessation, nutrition, and weight management, Dr. Bukata said. Another step in the right direction could involve setting electronic medical records to automatically order assessments of bone health when a surgeon books a case.

Linda A. Russell, MD, rheumatologist and director of perioperative medicine at the Hospital for Special Surgery in New York, said periprosthetic fractures are a “complication we fear.”

“It’s a big deal to try to repair it,” Dr. Russell said. “Sometimes you need to revise the joint, or sometimes you need to put lots more hardware in.” Surgeons increasingly appreciate the need to pay attention to the quality of the bone before they operate, she said.

Nevertheless, Dr. Russell does not necessarily say that such cases call for alarm or particularly aggressive treatment regimens – just regular bone health evaluations before and after surgery to see whether patients have osteoporosis and are candidates for treatment.
 

Lifelong effort

In some ways, to address bone health at the time of surgery may be too late.

Bone health “is not something that you can have as an afterthought when you’re 75 years old,” said Elizabeth Matzkin, MD, chief of women’s sports medicine at Brigham and Women’s Hospital, in Boston.

The chance of being able to rebuild bone mass at that age is slim. If patients maximize bone density when they are young, they can afford to lose some bone mass each year as they age.

To that end, a healthy diet, exercise, not smoking, and cutting back on alcohol can help, she said.

For Dr. Matzkin, a fragility fracture is a red flag that the patient’s bone density is probably not optimal. In such cases, she prepares for various scenarios during surgery, such as a screw not holding in a low-density bone.

Recently published research reflects that prior fragility fractures are a significant risk factor for complications after surgery, including periprosthetic fractures.

Edward J. Testa, MD, of Brown University, Providence, R.I., and colleagues analyzed insurance claims to compare outcomes for 24,398 patients who had experienced a fragility fracture – that is, a break caused by low-velocity trauma such as a fall – during the 3 years before their TKA procedure and a matched group of patients who were similar in many respects but who had not had a fragility fracture in the 3 years before surgery.

Dr. Testa’s group found that a history of fragility fracture was associated with higher rates of complications in the year after surgery, including hospital readmissions (hazard ratio = 1.30; 95% CI, 1.22-1.38), periprosthetic fractures (odds ratio = 2.72; 95% CI, 1.89-3.99), and secondary fragility fractures (OR = 4.62; 95% CI, 4.19-5.12). Patients who had previously experienced fragility fractures also experienced dislocated prostheses (OR = 1.76; 95% CI, 1.22-2.56) and periprosthetic infections (OR = 1.49; 95% CI, 1.29-1.71) at higher rates.

The rates of complications were similar regardless of whether patients had filled a prescription for medications used to treat osteoporosis, including bisphosphonates, vitamin D replacement, raloxifene, and denosumab, the researchers reported.

The lack of a clear association between these treatments and patient outcomes could be related to an insufficient duration of pharmacotherapy before or after TKA, poor medication adherence, or small sample sizes, Dr. Testa said.

Given the findings, which were published online in the Journal of Arthroplasty, “patients with a history of fragility fracture should be identified and counseled appropriately for a possible increased risk of the aforementioned complications, and optimized when possible, prior to undergoing TKA,” Dr. Testa told this news organization. “Ultimately, the decision to move forward with surgery is far more complex than the identification of this sole, yet important, risk factor for certain postoperative, implant-related complications.”
 

Treatment gaps

Prior research has shown that women aged 70 years and older are at higher risk for periprosthetic fractures. Many women in this age group who could receive treatment for osteoporosis do not, and major treatment gaps exist worldwide, noted Neil Binkley, MD, with the University of Wisconsin–Madison, in a separate talk at the Santa Fe Bone Symposium.

Ensuring adequate protein intake and addressing the risk of falling are other measures that clinicians can take to promote healthy bones, apart from prescribing drugs, he said.

Unpublished data from one group show that nearly 90% of periprosthetic fractures may result from falls, while about 8% may be spontaneous. “We need to be thinking about falls,” Dr. Binkley said.

Dr. Bukata has consulted for Amgen, Radius, and Solarea Bio and has served on a speakers bureau for Radius. She also is a board member for the Orthopaedic Research Society and the American Academy of Orthopaedic Surgeons Board of Specialty Societies. Dr. Binkley has received research support from Radius and has consulted for Amgen.

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

Just 3 weeks into the 2022-2023 flu season, the latest data from the Centers for Disease Control and Prevention’s Influenza Division suggest that the flu and respiratory syncytial virus are more than making up for the recent decline in COVID activity.

Outpatient visits for influenzalike illness (ILI), which includes influenza, SARS-CoV-2, and RSV, were higher after 3 weeks than for any of the previous five flu seasons: 3.3% of visits reported through the CDC’s Outpatient Influenza-like Illness Surveillance Network involved ILI as of Oct. 22. The highest comparable rate in the previous 5 years was the 1.9% recorded in late October of 2021, shortly after the definition of ILI was changed to also include illnesses other than influenza.

This season’s higher flu activity is in contrast to the previous two, which were unusually mild. The change, however, is not unexpected, as William Schaffner, MD, an infectious disease expert and professor of preventive medicine at Vanderbilt University, recently told CNN.

“Here we are in the middle of October – not the middle of November – we’re already seeing scattered influenza cases, even hospitalized influenza cases, around the country,” he said. “So we know that this virus is now spreading out in the community already. It’s gathering speed already. It looks to me to be about a month early.”

One indication of the mildness of the previous two flu seasons was the number of deaths, both pediatric and overall. Influenza-associated pediatric deaths had averaged about 110 per season over the previous eight seasons, compared with just 1 for 2020-2021 and 43 in 2021-2022. Overall flu deaths never reached 1% of all weekly deaths for either season, well below baseline levels for the flu, which range from 5.5% to 6.8%, CDC data show.
 

Other indicators of early severity

This season’s early rise in viral activity also can be seen in hospitalizations. The cumulative rate of flu-related admissions was 1.5 per 100,000 population as of Oct. 22, higher than the rate observed in the comparable week of previous seasons going back to 2010-2011, according to the CDC’s Influenza Hospitalization Surveillance Network.

A look at state reports of ILI outpatient visit rates shows that the District of Columbia and South Carolina are already in the very high range of the CDC’s severity scale, while 11 states are in the high range. Again going back to 2010-2011, no jurisdiction has ever been in the very high range this early in the season, based on data from the Outpatient Influenza-like Illness Surveillance Network.

Just 3 weeks into the 2022-2023 flu season, the latest data from the Centers for Disease Control and Prevention’s Influenza Division suggest that the flu and respiratory syncytial virus are more than making up for the recent decline in COVID activity.

Outpatient visits for influenzalike illness (ILI), which includes influenza, SARS-CoV-2, and RSV, were higher after 3 weeks than for any of the previous five flu seasons: 3.3% of visits reported through the CDC’s Outpatient Influenza-like Illness Surveillance Network involved ILI as of Oct. 22. The highest comparable rate in the previous 5 years was the 1.9% recorded in late October of 2021, shortly after the definition of ILI was changed to also include illnesses other than influenza.

This season’s higher flu activity is in contrast to the previous two, which were unusually mild. The change, however, is not unexpected, as William Schaffner, MD, an infectious disease expert and professor of preventive medicine at Vanderbilt University, recently told CNN.

“Here we are in the middle of October – not the middle of November – we’re already seeing scattered influenza cases, even hospitalized influenza cases, around the country,” he said. “So we know that this virus is now spreading out in the community already. It’s gathering speed already. It looks to me to be about a month early.”

One indication of the mildness of the previous two flu seasons was the number of deaths, both pediatric and overall. Influenza-associated pediatric deaths had averaged about 110 per season over the previous eight seasons, compared with just 1 for 2020-2021 and 43 in 2021-2022. Overall flu deaths never reached 1% of all weekly deaths for either season, well below baseline levels for the flu, which range from 5.5% to 6.8%, CDC data show.
 

Other indicators of early severity

This season’s early rise in viral activity also can be seen in hospitalizations. The cumulative rate of flu-related admissions was 1.5 per 100,000 population as of Oct. 22, higher than the rate observed in the comparable week of previous seasons going back to 2010-2011, according to the CDC’s Influenza Hospitalization Surveillance Network.

A look at state reports of ILI outpatient visit rates shows that the District of Columbia and South Carolina are already in the very high range of the CDC’s severity scale, while 11 states are in the high range. Again going back to 2010-2011, no jurisdiction has ever been in the very high range this early in the season, based on data from the Outpatient Influenza-like Illness Surveillance Network.

Just 3 weeks into the 2022-2023 flu season, the latest data from the Centers for Disease Control and Prevention’s Influenza Division suggest that the flu and respiratory syncytial virus are more than making up for the recent decline in COVID activity.

Outpatient visits for influenzalike illness (ILI), which includes influenza, SARS-CoV-2, and RSV, were higher after 3 weeks than for any of the previous five flu seasons: 3.3% of visits reported through the CDC’s Outpatient Influenza-like Illness Surveillance Network involved ILI as of Oct. 22. The highest comparable rate in the previous 5 years was the 1.9% recorded in late October of 2021, shortly after the definition of ILI was changed to also include illnesses other than influenza.

This season’s higher flu activity is in contrast to the previous two, which were unusually mild. The change, however, is not unexpected, as William Schaffner, MD, an infectious disease expert and professor of preventive medicine at Vanderbilt University, recently told CNN.

“Here we are in the middle of October – not the middle of November – we’re already seeing scattered influenza cases, even hospitalized influenza cases, around the country,” he said. “So we know that this virus is now spreading out in the community already. It’s gathering speed already. It looks to me to be about a month early.”

One indication of the mildness of the previous two flu seasons was the number of deaths, both pediatric and overall. Influenza-associated pediatric deaths had averaged about 110 per season over the previous eight seasons, compared with just 1 for 2020-2021 and 43 in 2021-2022. Overall flu deaths never reached 1% of all weekly deaths for either season, well below baseline levels for the flu, which range from 5.5% to 6.8%, CDC data show.
 

Other indicators of early severity

This season’s early rise in viral activity also can be seen in hospitalizations. The cumulative rate of flu-related admissions was 1.5 per 100,000 population as of Oct. 22, higher than the rate observed in the comparable week of previous seasons going back to 2010-2011, according to the CDC’s Influenza Hospitalization Surveillance Network.

A look at state reports of ILI outpatient visit rates shows that the District of Columbia and South Carolina are already in the very high range of the CDC’s severity scale, while 11 states are in the high range. Again going back to 2010-2011, no jurisdiction has ever been in the very high range this early in the season, based on data from the Outpatient Influenza-like Illness Surveillance Network.

Courtesy of Jon Karnes, MD

The physician used a curette to perform a shave biopsy; pathology results indicated this was a poorly differentiated squamous cell carcinoma (SCC). Cutaneous SCC is the second most common skin cancer in the United States (after basal cell carcinoma) and increases in frequency with age and cumulative sun damage. It is the most common skin cancer in patients who are Black.

SCC is frequently found on the head and neck, including the ear, but is less commonly found within the conchal bowl (as seen here). Often, SCC manifests as a rough plaque or dome-shaped papule in a sun damaged location, but it may occasionally manifest as an ulcer. While most patients are cured with outpatient surgery, an estimated 8000 patients will develop nodal metastasis and 3000 patients will die from the disease in the United States annually.¹ Chronically immunosuppressed patients, such as organ transplant recipients, are at high risk.

This patient underwent Mohs microsurgery (MMS) and clear margins were achieved after 2 stages. The resulting defect was repaired with a full-thickness graft from the postauricular fold. MMS is an excellent technique for keratinocyte carcinomas (SCC and basal cell carcinomas) of the head and neck, recurrent skin cancers on the trunk and extremities, high-risk cancer subtypes, and tumors with indistinct clinical borders. Follow-up for patients with SCCs includes full skin exams every 6 months for 2 years.

The American Academy of Dermatology offers a complimentary Mohs Surgery Appropriate Use Criteria App that assists in determining when Mohs surgery is appropriate, based on multiple tumor characteristics.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

Courtesy of Jon Karnes, MD

The physician used a curette to perform a shave biopsy; pathology results indicated this was a poorly differentiated squamous cell carcinoma (SCC). Cutaneous SCC is the second most common skin cancer in the United States (after basal cell carcinoma) and increases in frequency with age and cumulative sun damage. It is the most common skin cancer in patients who are Black.

SCC is frequently found on the head and neck, including the ear, but is less commonly found within the conchal bowl (as seen here). Often, SCC manifests as a rough plaque or dome-shaped papule in a sun damaged location, but it may occasionally manifest as an ulcer. While most patients are cured with outpatient surgery, an estimated 8000 patients will develop nodal metastasis and 3000 patients will die from the disease in the United States annually.¹ Chronically immunosuppressed patients, such as organ transplant recipients, are at high risk.

This patient underwent Mohs microsurgery (MMS) and clear margins were achieved after 2 stages. The resulting defect was repaired with a full-thickness graft from the postauricular fold. MMS is an excellent technique for keratinocyte carcinomas (SCC and basal cell carcinomas) of the head and neck, recurrent skin cancers on the trunk and extremities, high-risk cancer subtypes, and tumors with indistinct clinical borders. Follow-up for patients with SCCs includes full skin exams every 6 months for 2 years.

The American Academy of Dermatology offers a complimentary Mohs Surgery Appropriate Use Criteria App that assists in determining when Mohs surgery is appropriate, based on multiple tumor characteristics.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

Courtesy of Jon Karnes, MD

The physician used a curette to perform a shave biopsy; pathology results indicated this was a poorly differentiated squamous cell carcinoma (SCC). Cutaneous SCC is the second most common skin cancer in the United States (after basal cell carcinoma) and increases in frequency with age and cumulative sun damage. It is the most common skin cancer in patients who are Black.

SCC is frequently found on the head and neck, including the ear, but is less commonly found within the conchal bowl (as seen here). Often, SCC manifests as a rough plaque or dome-shaped papule in a sun damaged location, but it may occasionally manifest as an ulcer. While most patients are cured with outpatient surgery, an estimated 8000 patients will develop nodal metastasis and 3000 patients will die from the disease in the United States annually.¹ Chronically immunosuppressed patients, such as organ transplant recipients, are at high risk.

This patient underwent Mohs microsurgery (MMS) and clear margins were achieved after 2 stages. The resulting defect was repaired with a full-thickness graft from the postauricular fold. MMS is an excellent technique for keratinocyte carcinomas (SCC and basal cell carcinomas) of the head and neck, recurrent skin cancers on the trunk and extremities, high-risk cancer subtypes, and tumors with indistinct clinical borders. Follow-up for patients with SCCs includes full skin exams every 6 months for 2 years.

The American Academy of Dermatology offers a complimentary Mohs Surgery Appropriate Use Criteria App that assists in determining when Mohs surgery is appropriate, based on multiple tumor characteristics.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

Performing moderate to vigorous activity (MVPA) in the afternoon or evening may improve blood glucose control to a greater extent than exercising evenly throughout the day, new research suggests.

The data come from 775 participants with a mean body mass index (BMI) of 26.2 kg/m² in the observational Netherlands Epidemiology of Obesity (NEO) study. Use of activity monitors for four consecutive days showed that performance of MVPA (defined as activity with intensity of > 3 metabolic equivalents of task) in the afternoon or evening was associated with up to 25% reduced insulin resistance compared with an even distribution of activity during the day.

“This is one of the first studies where in humans the relation between timing of physical activity and insulin resistance was examined,” lead author Jeroen van der Velde of the department of clinical epidemiology, Leiden (the Netherlands) University Medical Center, said in an interview.

Moreover, he noted that, while previous intervention studies have shown greater blood glucose reduction with high-intensity exercise performed in the afternoon, compared with the morning, in people with impaired glucose metabolism or type 2 diabetes, “as far as I am aware, we were the first to use a population-based study in a general population to study this.”

Katarina Kos, MD, PhD, senior lecturer in diabetes and obesity, University of Exeter (England), said: “This study is novel in that it relates the timing of physical activity if performed in the morning, afternoon, or evening to insulin resistance and fat content. This is from a cohort of middle-aged Dutch people between ages 45-65 studied 10 years ago and based on self-reports of weight and eating behavior and who were found to be generally overweight.”
 

Is it down to circadian rhythm?

“The results are of interest in that if the chosen timing was in the afternoon [63% of studied population] or evening (8% of the studied population), it seemed to relate with improved metabolism when compared to the morning exercising [16% of population]. ... Whether this was due to the (timing) of activity is yet to be shown,” Dr. Kos told the UK Science Media Centre.

Mr. van der Velde agrees that the effect may be explained at least in part by the circadian rhythm of the body. “Physical activity may act as ... a cue for the activation of clock genes. Previous research has suggested that our body’s muscular system and oxidative system are also affected by our circadian rhythm and their peak activity seems to be in the late afternoon. So, being mostly active in this time period ... may elicit greater metabolic responses compared to being active in the morning.”

But, he cautioned, “I think it is important to realize that we are just beginning to understand the potential impact of physical activity timing. At this stage, I believe it is most important to be physically active in general. So ... if the morning is the only time of the day to go for a walk or a run, certainly do this.”

Dr. Kos concurred: “As this is not an intervention study, further research is needed to explain the cause of the observed association.”

Mr. van der Velde also added that it’s not yet clear which individuals or subgroups might experience additional benefits from timed activities. That’s the current research focus of a large consortium of several research institutes in the Netherlands and Canada.
 

Timed exercise reduces insulin resistance but not liver fat

The findings were published online in Diabetologia.

The study population included men and women living in the greater Leiden area in the western Netherlands who were aged 45-65 years and self-reported a BMI of 27 or higher. A second cohort included inhabitants of one municipality who were invited to participate regardless of their BMI. All wore the activity monitors for 4 consecutive days and nights during their usual activities.

Neither sedentary time nor breaks in sedentary time (defined as a period of activity with an acceleration greater than 0.75 m/s2 following a sedentary period) were associated with lower insulin resistance, as calculated by blood sampling.

However, the number of breaks in sedentary time was associated with a significant 22% higher liver fat content, assessed with proton magnetic resonance spectroscopy.

One reason for the lack of effect of breaks on insulin resistance, the authors theorized, is that this was a real-world observational study where regular breaks aren’t common. Alternatively, people might not have been intensively active enough during breaks to make a difference.

After adjustment for total body fat, an additional hour of MVPA was associated with a 5% drop in insulin resistance. An additional hour of MVPA in 5-minute bouts was associated with 9% lower insulin resistance.

Also after adjustments, insulin resistance was reduced significantly in participants who were most active in the afternoon, by 18%, or evening, by 25%, whereas insulin resistance was not affected among those who were most active in the morning (–3%), all compared with people who distributed their MVPA throughout the day.

Timing of MVPA was not associated with liver fat content, and there were no significant differences in liver fat content and insulin resistance between groups based on timing of light physical activity.

“This is just speculation, but perhaps for fat accumulation in the liver the circadian system is less involved. Or perhaps timing of other lifestyle variables are more important here, such as dietary intake,” Mr. van der Velde said.

Finally, he observed, “timing of physical activity is most likely just a piece of the puzzle. Timing of other lifestyle behavior, such as sleep, and food intake are important cues for our circadian system as well, and it is likely that all these behaviors interact with each other.”

The NEO study is supported by Leiden University Medical Center, the Netherlands Cardiovascular Research Initiative, an initiative supported by the Dutch Heart Foundation, and the Netherlands Organisation for Health Research and Development/Partnership Diabetes/Dutch Diabetes foundation Breakthrough. Mr. van der Velde has reported no further disclosures.

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

Performing moderate to vigorous activity (MVPA) in the afternoon or evening may improve blood glucose control to a greater extent than exercising evenly throughout the day, new research suggests.

The data come from 775 participants with a mean body mass index (BMI) of 26.2 kg/m² in the observational Netherlands Epidemiology of Obesity (NEO) study. Use of activity monitors for four consecutive days showed that performance of MVPA (defined as activity with intensity of > 3 metabolic equivalents of task) in the afternoon or evening was associated with up to 25% reduced insulin resistance compared with an even distribution of activity during the day.

“This is one of the first studies where in humans the relation between timing of physical activity and insulin resistance was examined,” lead author Jeroen van der Velde of the department of clinical epidemiology, Leiden (the Netherlands) University Medical Center, said in an interview.

Moreover, he noted that, while previous intervention studies have shown greater blood glucose reduction with high-intensity exercise performed in the afternoon, compared with the morning, in people with impaired glucose metabolism or type 2 diabetes, “as far as I am aware, we were the first to use a population-based study in a general population to study this.”

Katarina Kos, MD, PhD, senior lecturer in diabetes and obesity, University of Exeter (England), said: “This study is novel in that it relates the timing of physical activity if performed in the morning, afternoon, or evening to insulin resistance and fat content. This is from a cohort of middle-aged Dutch people between ages 45-65 studied 10 years ago and based on self-reports of weight and eating behavior and who were found to be generally overweight.”
 

Is it down to circadian rhythm?

“The results are of interest in that if the chosen timing was in the afternoon [63% of studied population] or evening (8% of the studied population), it seemed to relate with improved metabolism when compared to the morning exercising [16% of population]. ... Whether this was due to the (timing) of activity is yet to be shown,” Dr. Kos told the UK Science Media Centre.

Mr. van der Velde agrees that the effect may be explained at least in part by the circadian rhythm of the body. “Physical activity may act as ... a cue for the activation of clock genes. Previous research has suggested that our body’s muscular system and oxidative system are also affected by our circadian rhythm and their peak activity seems to be in the late afternoon. So, being mostly active in this time period ... may elicit greater metabolic responses compared to being active in the morning.”

But, he cautioned, “I think it is important to realize that we are just beginning to understand the potential impact of physical activity timing. At this stage, I believe it is most important to be physically active in general. So ... if the morning is the only time of the day to go for a walk or a run, certainly do this.”

Dr. Kos concurred: “As this is not an intervention study, further research is needed to explain the cause of the observed association.”

Mr. van der Velde also added that it’s not yet clear which individuals or subgroups might experience additional benefits from timed activities. That’s the current research focus of a large consortium of several research institutes in the Netherlands and Canada.
 

Timed exercise reduces insulin resistance but not liver fat

The findings were published online in Diabetologia.

The study population included men and women living in the greater Leiden area in the western Netherlands who were aged 45-65 years and self-reported a BMI of 27 or higher. A second cohort included inhabitants of one municipality who were invited to participate regardless of their BMI. All wore the activity monitors for 4 consecutive days and nights during their usual activities.

Neither sedentary time nor breaks in sedentary time (defined as a period of activity with an acceleration greater than 0.75 m/s2 following a sedentary period) were associated with lower insulin resistance, as calculated by blood sampling.

However, the number of breaks in sedentary time was associated with a significant 22% higher liver fat content, assessed with proton magnetic resonance spectroscopy.

One reason for the lack of effect of breaks on insulin resistance, the authors theorized, is that this was a real-world observational study where regular breaks aren’t common. Alternatively, people might not have been intensively active enough during breaks to make a difference.

After adjustment for total body fat, an additional hour of MVPA was associated with a 5% drop in insulin resistance. An additional hour of MVPA in 5-minute bouts was associated with 9% lower insulin resistance.

Also after adjustments, insulin resistance was reduced significantly in participants who were most active in the afternoon, by 18%, or evening, by 25%, whereas insulin resistance was not affected among those who were most active in the morning (–3%), all compared with people who distributed their MVPA throughout the day.

Timing of MVPA was not associated with liver fat content, and there were no significant differences in liver fat content and insulin resistance between groups based on timing of light physical activity.

“This is just speculation, but perhaps for fat accumulation in the liver the circadian system is less involved. Or perhaps timing of other lifestyle variables are more important here, such as dietary intake,” Mr. van der Velde said.

Finally, he observed, “timing of physical activity is most likely just a piece of the puzzle. Timing of other lifestyle behavior, such as sleep, and food intake are important cues for our circadian system as well, and it is likely that all these behaviors interact with each other.”

The NEO study is supported by Leiden University Medical Center, the Netherlands Cardiovascular Research Initiative, an initiative supported by the Dutch Heart Foundation, and the Netherlands Organisation for Health Research and Development/Partnership Diabetes/Dutch Diabetes foundation Breakthrough. Mr. van der Velde has reported no further disclosures.

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

Performing moderate to vigorous activity (MVPA) in the afternoon or evening may improve blood glucose control to a greater extent than exercising evenly throughout the day, new research suggests.

The data come from 775 participants with a mean body mass index (BMI) of 26.2 kg/m² in the observational Netherlands Epidemiology of Obesity (NEO) study. Use of activity monitors for four consecutive days showed that performance of MVPA (defined as activity with intensity of > 3 metabolic equivalents of task) in the afternoon or evening was associated with up to 25% reduced insulin resistance compared with an even distribution of activity during the day.

“This is one of the first studies where in humans the relation between timing of physical activity and insulin resistance was examined,” lead author Jeroen van der Velde of the department of clinical epidemiology, Leiden (the Netherlands) University Medical Center, said in an interview.

Moreover, he noted that, while previous intervention studies have shown greater blood glucose reduction with high-intensity exercise performed in the afternoon, compared with the morning, in people with impaired glucose metabolism or type 2 diabetes, “as far as I am aware, we were the first to use a population-based study in a general population to study this.”

Katarina Kos, MD, PhD, senior lecturer in diabetes and obesity, University of Exeter (England), said: “This study is novel in that it relates the timing of physical activity if performed in the morning, afternoon, or evening to insulin resistance and fat content. This is from a cohort of middle-aged Dutch people between ages 45-65 studied 10 years ago and based on self-reports of weight and eating behavior and who were found to be generally overweight.”
 

Is it down to circadian rhythm?

“The results are of interest in that if the chosen timing was in the afternoon [63% of studied population] or evening (8% of the studied population), it seemed to relate with improved metabolism when compared to the morning exercising [16% of population]. ... Whether this was due to the (timing) of activity is yet to be shown,” Dr. Kos told the UK Science Media Centre.

Mr. van der Velde agrees that the effect may be explained at least in part by the circadian rhythm of the body. “Physical activity may act as ... a cue for the activation of clock genes. Previous research has suggested that our body’s muscular system and oxidative system are also affected by our circadian rhythm and their peak activity seems to be in the late afternoon. So, being mostly active in this time period ... may elicit greater metabolic responses compared to being active in the morning.”

But, he cautioned, “I think it is important to realize that we are just beginning to understand the potential impact of physical activity timing. At this stage, I believe it is most important to be physically active in general. So ... if the morning is the only time of the day to go for a walk or a run, certainly do this.”

Dr. Kos concurred: “As this is not an intervention study, further research is needed to explain the cause of the observed association.”

Mr. van der Velde also added that it’s not yet clear which individuals or subgroups might experience additional benefits from timed activities. That’s the current research focus of a large consortium of several research institutes in the Netherlands and Canada.
 

Timed exercise reduces insulin resistance but not liver fat

The findings were published online in Diabetologia.

The study population included men and women living in the greater Leiden area in the western Netherlands who were aged 45-65 years and self-reported a BMI of 27 or higher. A second cohort included inhabitants of one municipality who were invited to participate regardless of their BMI. All wore the activity monitors for 4 consecutive days and nights during their usual activities.

Neither sedentary time nor breaks in sedentary time (defined as a period of activity with an acceleration greater than 0.75 m/s2 following a sedentary period) were associated with lower insulin resistance, as calculated by blood sampling.

However, the number of breaks in sedentary time was associated with a significant 22% higher liver fat content, assessed with proton magnetic resonance spectroscopy.

One reason for the lack of effect of breaks on insulin resistance, the authors theorized, is that this was a real-world observational study where regular breaks aren’t common. Alternatively, people might not have been intensively active enough during breaks to make a difference.

After adjustment for total body fat, an additional hour of MVPA was associated with a 5% drop in insulin resistance. An additional hour of MVPA in 5-minute bouts was associated with 9% lower insulin resistance.

Also after adjustments, insulin resistance was reduced significantly in participants who were most active in the afternoon, by 18%, or evening, by 25%, whereas insulin resistance was not affected among those who were most active in the morning (–3%), all compared with people who distributed their MVPA throughout the day.

Timing of MVPA was not associated with liver fat content, and there were no significant differences in liver fat content and insulin resistance between groups based on timing of light physical activity.

“This is just speculation, but perhaps for fat accumulation in the liver the circadian system is less involved. Or perhaps timing of other lifestyle variables are more important here, such as dietary intake,” Mr. van der Velde said.

Finally, he observed, “timing of physical activity is most likely just a piece of the puzzle. Timing of other lifestyle behavior, such as sleep, and food intake are important cues for our circadian system as well, and it is likely that all these behaviors interact with each other.”

The NEO study is supported by Leiden University Medical Center, the Netherlands Cardiovascular Research Initiative, an initiative supported by the Dutch Heart Foundation, and the Netherlands Organisation for Health Research and Development/Partnership Diabetes/Dutch Diabetes foundation Breakthrough. Mr. van der Velde has reported no further disclosures.

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

The SARS-CoV-2 infection disrupts the normal mix of gut bacteria, allowing harmful bacteria to enter the bloodstream and raising the risk for potentially life-threatening secondary bloodstream infections (BSIs), new research suggests.

“Collectively, these results reveal an unappreciated link between SARS-CoV-2 infection, gut microbiome dysbiosis, and a severe complication of COVID-19, BSIs,” the study team reported in Nature Communications.

“Our findings suggest that coronavirus infection directly interferes with the healthy balance of microbes in the gut, further endangering patients in the process,” microbiologist and co–senior author Ken Cadwell, PhD, New York University, added in a news release. “Now that we have uncovered the source of this bacterial imbalance, physicians can better identify those coronavirus patients most at risk of a secondary bloodstream infection.”

In a mouse model, the researchers first demonstrated that the SARS-CoV-2 infection alone induces gut microbiome dysbiosis and gut epithelial cell alterations, which correlate with markers of gut barrier permeability.

Next, they analyzed the bacterial composition of stool samples from 96 adults hospitalized with COVID-19 in 2020 in New York and New Haven, Conn.

In line with their observations in mice, they found that the SARS-CoV-2 infection is associated with “severe microbiome injury,” characterized by the loss of gut microbiome diversity.

They also observed an increase in populations of several microbes known to include antibiotic-resistant species. An analysis of stool samples paired with blood cultures found that antibiotic-resistant bacteria in the gut migrated to the bloodstream in 20% of patients.

This migration could be caused by a combination of the immune-compromising effects of the viral infection and the antibiotic-driven depletion of commensal gut microbes, the researchers said.

However, COVID-19 patients are also uniquely exposed to other potential factors predisposing them to bacteremia, including immunosuppressive drugs, long hospital stays, and catheters, the investigators noted. The study is limited in its ability to investigate the individual effects of these factors.

“Our findings support a scenario in which gut-to-blood translocation of microorganisms following microbiome dysbiosis leads to dangerous BSIs during COVID-19, a complication seen in other immunocompromised patients, including patients with cancer, acute respiratory distress syndrome, and in ICU patients receiving probiotics,” the researchers wrote.

Investigating the underlying mechanism behind their observations could help inform “the judicious application of antibiotics and immunosuppressives in patients with respiratory viral infections and increase our resilience to pandemics,” they added.

Funding for the study was provided by the National Institutes of Health, the Yale School of Public Health, and numerous other sources. Dr. Cadwell has received research support from Pfizer, Takeda, Pacific Biosciences, Genentech, and AbbVie; consulted for or received an honoraria from PureTech Health, Genentech, and AbbVie; and is named as an inventor on US patent 10,722,600 and provisional patents 62/935,035 and 63/157,225.

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

The SARS-CoV-2 infection disrupts the normal mix of gut bacteria, allowing harmful bacteria to enter the bloodstream and raising the risk for potentially life-threatening secondary bloodstream infections (BSIs), new research suggests.

“Collectively, these results reveal an unappreciated link between SARS-CoV-2 infection, gut microbiome dysbiosis, and a severe complication of COVID-19, BSIs,” the study team reported in Nature Communications.

“Our findings suggest that coronavirus infection directly interferes with the healthy balance of microbes in the gut, further endangering patients in the process,” microbiologist and co–senior author Ken Cadwell, PhD, New York University, added in a news release. “Now that we have uncovered the source of this bacterial imbalance, physicians can better identify those coronavirus patients most at risk of a secondary bloodstream infection.”

In a mouse model, the researchers first demonstrated that the SARS-CoV-2 infection alone induces gut microbiome dysbiosis and gut epithelial cell alterations, which correlate with markers of gut barrier permeability.

Next, they analyzed the bacterial composition of stool samples from 96 adults hospitalized with COVID-19 in 2020 in New York and New Haven, Conn.

In line with their observations in mice, they found that the SARS-CoV-2 infection is associated with “severe microbiome injury,” characterized by the loss of gut microbiome diversity.

They also observed an increase in populations of several microbes known to include antibiotic-resistant species. An analysis of stool samples paired with blood cultures found that antibiotic-resistant bacteria in the gut migrated to the bloodstream in 20% of patients.

This migration could be caused by a combination of the immune-compromising effects of the viral infection and the antibiotic-driven depletion of commensal gut microbes, the researchers said.

However, COVID-19 patients are also uniquely exposed to other potential factors predisposing them to bacteremia, including immunosuppressive drugs, long hospital stays, and catheters, the investigators noted. The study is limited in its ability to investigate the individual effects of these factors.

“Our findings support a scenario in which gut-to-blood translocation of microorganisms following microbiome dysbiosis leads to dangerous BSIs during COVID-19, a complication seen in other immunocompromised patients, including patients with cancer, acute respiratory distress syndrome, and in ICU patients receiving probiotics,” the researchers wrote.

Investigating the underlying mechanism behind their observations could help inform “the judicious application of antibiotics and immunosuppressives in patients with respiratory viral infections and increase our resilience to pandemics,” they added.

Funding for the study was provided by the National Institutes of Health, the Yale School of Public Health, and numerous other sources. Dr. Cadwell has received research support from Pfizer, Takeda, Pacific Biosciences, Genentech, and AbbVie; consulted for or received an honoraria from PureTech Health, Genentech, and AbbVie; and is named as an inventor on US patent 10,722,600 and provisional patents 62/935,035 and 63/157,225.

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

The SARS-CoV-2 infection disrupts the normal mix of gut bacteria, allowing harmful bacteria to enter the bloodstream and raising the risk for potentially life-threatening secondary bloodstream infections (BSIs), new research suggests.

“Collectively, these results reveal an unappreciated link between SARS-CoV-2 infection, gut microbiome dysbiosis, and a severe complication of COVID-19, BSIs,” the study team reported in Nature Communications.

“Our findings suggest that coronavirus infection directly interferes with the healthy balance of microbes in the gut, further endangering patients in the process,” microbiologist and co–senior author Ken Cadwell, PhD, New York University, added in a news release. “Now that we have uncovered the source of this bacterial imbalance, physicians can better identify those coronavirus patients most at risk of a secondary bloodstream infection.”

In a mouse model, the researchers first demonstrated that the SARS-CoV-2 infection alone induces gut microbiome dysbiosis and gut epithelial cell alterations, which correlate with markers of gut barrier permeability.

Next, they analyzed the bacterial composition of stool samples from 96 adults hospitalized with COVID-19 in 2020 in New York and New Haven, Conn.

In line with their observations in mice, they found that the SARS-CoV-2 infection is associated with “severe microbiome injury,” characterized by the loss of gut microbiome diversity.

They also observed an increase in populations of several microbes known to include antibiotic-resistant species. An analysis of stool samples paired with blood cultures found that antibiotic-resistant bacteria in the gut migrated to the bloodstream in 20% of patients.

This migration could be caused by a combination of the immune-compromising effects of the viral infection and the antibiotic-driven depletion of commensal gut microbes, the researchers said.

However, COVID-19 patients are also uniquely exposed to other potential factors predisposing them to bacteremia, including immunosuppressive drugs, long hospital stays, and catheters, the investigators noted. The study is limited in its ability to investigate the individual effects of these factors.

“Our findings support a scenario in which gut-to-blood translocation of microorganisms following microbiome dysbiosis leads to dangerous BSIs during COVID-19, a complication seen in other immunocompromised patients, including patients with cancer, acute respiratory distress syndrome, and in ICU patients receiving probiotics,” the researchers wrote.

Investigating the underlying mechanism behind their observations could help inform “the judicious application of antibiotics and immunosuppressives in patients with respiratory viral infections and increase our resilience to pandemics,” they added.

Funding for the study was provided by the National Institutes of Health, the Yale School of Public Health, and numerous other sources. Dr. Cadwell has received research support from Pfizer, Takeda, Pacific Biosciences, Genentech, and AbbVie; consulted for or received an honoraria from PureTech Health, Genentech, and AbbVie; and is named as an inventor on US patent 10,722,600 and provisional patents 62/935,035 and 63/157,225.

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

Shedding of genital herpes simplex virus was frequent soon after first-time infection but declined significantly during the first year, based on data from 82 individuals.

Genital herpes simplex virus (HSV) infections remain common and incurable; consequently, the population with residual infection continues to rise, Christine Johnston, MD, of the University of Washington, Seattle, and colleagues wrote. However, data on the viral shedding trajectory of genital HSV-1 are limited, although HSV-1 accounts for an increasing number of infections.

In a study published in JAMA the researchers recruited 82 women with first-episode genital HSV-1 infections from sexual health and primary care clinics in Seattle, between 2013 and 2018. The participants supplied self-collected oral and genital swabs for daily HSV polymerase chain reaction testing for two 30-day periods at 2 months and 11 months after their initial symptoms. The study population was not pregnant and did not have HIV infection. The median age of the participants was 26 years, 54 were women, and 42 had primary HSV-1 infections. Primary HSV-1 infection was defined as the lack of HSV antibody at baseline or an evolving antibody profile, based on the University of Washington HSV Western Blot.

The primary outcome was the rates of genital and oral HSV shedding and lesions at 2 and 11 months and up to 2 years after an initial HSV-1 infection.

At 2 months, approximately two-thirds (64.6%) of the participants had HSV-1 in the genital tract and 29.3% had virus in the mouth. Genital shedding of HSV-1 was detected in 12.1% of 2,264 total testing days at 2 months, but this rate declined to 7.1% of 1,719 testing days at 11 months (relative risk, 0.52).

The researchers identified oral HSV-1 shedding on 3.9% of 2,247 testing days at 2 months, with a slight increase to 5.1% of 1,714 testing days at 11 months.

Both genital and oral lesions were rare, with reports of 2.6% and 0.4%, respectively, at 2 months and 3.8% and 0.5%, respectively, at 11 months.

The risk of genital shedding was significantly higher in individuals with primary HSV-1, compared with those with nonprimary infections (7.9% vs. 2.9%; RR, 2.75). The overall rate of genital shedding was 17.2% for those with primary HSV-1, of which 15.2% was asymptomatic. Oral shedding was similar for individuals with primary and nonprimary HSV in a multivariate analysis.

In addition, HSV-specific CD4+ and CD8+ T-cell responses were identified in all participants, and these remained stable during the study period. No association appeared between rates of genital and oral shedding and the proportion of cells that expressed two, three, or four cytokines.

The current study is the first known to comprehensively assess genital and oral HSV-1 viral shedding using polymerase chain reaction, the researchers wrote. “Characterizing shedding rates is clinically important because patients with genital herpes are often concerned about transmission to sexual partners, which usually occurs in the absence of lesions.”

The study findings were limited by several factors including the 22% loss of participants to follow-up by the end of the first year, and the use of data from a single location with a primarily White population, the researchers noted. Another limitation was reliance on self-reports and the potential underestimation of recurrences because of the possible use of antiviral medications between swabbing periods.

However, the results indicate the early frequency of HSV-1 shedding and suggest that suppressive therapy might benefit individuals with primary HSV-1 during their first year of infection, the researchers said.
 

Findings may improve HSV management

The current study helps fill a knowledge gap regarding the natural history of genital HSV-1 infections, Richard J. Whitley, MD, and Edward W. Hook III, MD, both of the University of Alabama at Birmingham, wrote in an accompanying editorial. Despite the small study population, the data represent the largest cohort to date of individuals with first-episode infection and up to 2 years’ follow-up.

Although HSV-2 shedding is greater and associated with more symptoms, seroprevalence of HSV-2 in the United States is declining, they noted. Therefore, the findings can inform patient counseling and recommendations for antiviral therapy that may extend to managing HSV-1 in pregnant women as well, although no pregnant women were included in the study.

“For clinicians, these data emphasize the importance of determining the HSV viral type in persons presenting with initial episodes of genital herpes to accurately counsel patients regarding risk of clinical recurrence, the likelihood of asymptomatic shedding of virus and hence transmission, and antiviral prophylaxis,” the editorialists emphasized. For investigators, the results should prompt additional studies of the host defense against HSV and improved serological testing.
 

Study supports need for attention to HSV-1

“Genital herpes is an extremely common sexually transmitted infection, and often only HSV-2 is measured,” Sarah W. Prager, MD, of the University of Washington, Seattle, said in an interview. “This study shows that HSV-1 also accounts for a significant amount of genital disease, and should also be considered when determining prevalence of genital herpes.

“I was not surprised to see that viral shedding decreased significantly over the first year after diagnosis, and similarly not surprised that lesions were rare after the initial infection,” said Dr. Prager, who was not involved in the study. “I was somewhat surprised to see that genital HSV-1 shedding was more common than oral shedding.”

Dr. Prager said that she would advise clinicians against serum HSV testing unless someone has an active genital lesion. “Testing after a lesion will often reveal HSV-1, and patients should be counseled that shedding will decrease over the first year. Subsequent genital lesions are uncommon, but certainly possible, and oral lesions and shedding are both rare.” ]

More research is needed in a more diverse population, Dr. Prager emphasized. Following patients for more than a year and learning more about the use of antiviral medications also would be useful.

The study was supported in part by the National Institutes of Health/National Institute of Allergy and Infectious Diseases through grants to several authors, including lead author Dr. Johnston. Dr. Johnston also disclosed personal fees from AbbVie, grants from Gilead, royalties from UpToDate, and personal fees from GlaxoSmithKline unrelated to the current study. Dr. Whitley disclosed personal fees from Virios Therapeutics as a board member and shareholder during the conduct of the study, royalties from Aettis unrelated to the submitted work, and serving on an advisory board for Visby Diagnostics. Dr. Hook disclosed serving on an advisory board for Visby Diagnostics unrelated to the submitted work. Dr. Prager had no conflicts to disclose and serves on the editorial advisory board of Ob.Gyn News.
 

Shedding of genital herpes simplex virus was frequent soon after first-time infection but declined significantly during the first year, based on data from 82 individuals.

Genital herpes simplex virus (HSV) infections remain common and incurable; consequently, the population with residual infection continues to rise, Christine Johnston, MD, of the University of Washington, Seattle, and colleagues wrote. However, data on the viral shedding trajectory of genital HSV-1 are limited, although HSV-1 accounts for an increasing number of infections.

In a study published in JAMA the researchers recruited 82 women with first-episode genital HSV-1 infections from sexual health and primary care clinics in Seattle, between 2013 and 2018. The participants supplied self-collected oral and genital swabs for daily HSV polymerase chain reaction testing for two 30-day periods at 2 months and 11 months after their initial symptoms. The study population was not pregnant and did not have HIV infection. The median age of the participants was 26 years, 54 were women, and 42 had primary HSV-1 infections. Primary HSV-1 infection was defined as the lack of HSV antibody at baseline or an evolving antibody profile, based on the University of Washington HSV Western Blot.

The primary outcome was the rates of genital and oral HSV shedding and lesions at 2 and 11 months and up to 2 years after an initial HSV-1 infection.

At 2 months, approximately two-thirds (64.6%) of the participants had HSV-1 in the genital tract and 29.3% had virus in the mouth. Genital shedding of HSV-1 was detected in 12.1% of 2,264 total testing days at 2 months, but this rate declined to 7.1% of 1,719 testing days at 11 months (relative risk, 0.52).

The researchers identified oral HSV-1 shedding on 3.9% of 2,247 testing days at 2 months, with a slight increase to 5.1% of 1,714 testing days at 11 months.

Both genital and oral lesions were rare, with reports of 2.6% and 0.4%, respectively, at 2 months and 3.8% and 0.5%, respectively, at 11 months.

The risk of genital shedding was significantly higher in individuals with primary HSV-1, compared with those with nonprimary infections (7.9% vs. 2.9%; RR, 2.75). The overall rate of genital shedding was 17.2% for those with primary HSV-1, of which 15.2% was asymptomatic. Oral shedding was similar for individuals with primary and nonprimary HSV in a multivariate analysis.

In addition, HSV-specific CD4+ and CD8+ T-cell responses were identified in all participants, and these remained stable during the study period. No association appeared between rates of genital and oral shedding and the proportion of cells that expressed two, three, or four cytokines.

The current study is the first known to comprehensively assess genital and oral HSV-1 viral shedding using polymerase chain reaction, the researchers wrote. “Characterizing shedding rates is clinically important because patients with genital herpes are often concerned about transmission to sexual partners, which usually occurs in the absence of lesions.”

The study findings were limited by several factors including the 22% loss of participants to follow-up by the end of the first year, and the use of data from a single location with a primarily White population, the researchers noted. Another limitation was reliance on self-reports and the potential underestimation of recurrences because of the possible use of antiviral medications between swabbing periods.

However, the results indicate the early frequency of HSV-1 shedding and suggest that suppressive therapy might benefit individuals with primary HSV-1 during their first year of infection, the researchers said.
 

Findings may improve HSV management

The current study helps fill a knowledge gap regarding the natural history of genital HSV-1 infections, Richard J. Whitley, MD, and Edward W. Hook III, MD, both of the University of Alabama at Birmingham, wrote in an accompanying editorial. Despite the small study population, the data represent the largest cohort to date of individuals with first-episode infection and up to 2 years’ follow-up.

Although HSV-2 shedding is greater and associated with more symptoms, seroprevalence of HSV-2 in the United States is declining, they noted. Therefore, the findings can inform patient counseling and recommendations for antiviral therapy that may extend to managing HSV-1 in pregnant women as well, although no pregnant women were included in the study.

“For clinicians, these data emphasize the importance of determining the HSV viral type in persons presenting with initial episodes of genital herpes to accurately counsel patients regarding risk of clinical recurrence, the likelihood of asymptomatic shedding of virus and hence transmission, and antiviral prophylaxis,” the editorialists emphasized. For investigators, the results should prompt additional studies of the host defense against HSV and improved serological testing.
 

Study supports need for attention to HSV-1

“Genital herpes is an extremely common sexually transmitted infection, and often only HSV-2 is measured,” Sarah W. Prager, MD, of the University of Washington, Seattle, said in an interview. “This study shows that HSV-1 also accounts for a significant amount of genital disease, and should also be considered when determining prevalence of genital herpes.

“I was not surprised to see that viral shedding decreased significantly over the first year after diagnosis, and similarly not surprised that lesions were rare after the initial infection,” said Dr. Prager, who was not involved in the study. “I was somewhat surprised to see that genital HSV-1 shedding was more common than oral shedding.”

Dr. Prager said that she would advise clinicians against serum HSV testing unless someone has an active genital lesion. “Testing after a lesion will often reveal HSV-1, and patients should be counseled that shedding will decrease over the first year. Subsequent genital lesions are uncommon, but certainly possible, and oral lesions and shedding are both rare.” ]

More research is needed in a more diverse population, Dr. Prager emphasized. Following patients for more than a year and learning more about the use of antiviral medications also would be useful.

The study was supported in part by the National Institutes of Health/National Institute of Allergy and Infectious Diseases through grants to several authors, including lead author Dr. Johnston. Dr. Johnston also disclosed personal fees from AbbVie, grants from Gilead, royalties from UpToDate, and personal fees from GlaxoSmithKline unrelated to the current study. Dr. Whitley disclosed personal fees from Virios Therapeutics as a board member and shareholder during the conduct of the study, royalties from Aettis unrelated to the submitted work, and serving on an advisory board for Visby Diagnostics. Dr. Hook disclosed serving on an advisory board for Visby Diagnostics unrelated to the submitted work. Dr. Prager had no conflicts to disclose and serves on the editorial advisory board of Ob.Gyn News.
 

Shedding of genital herpes simplex virus was frequent soon after first-time infection but declined significantly during the first year, based on data from 82 individuals.

Genital herpes simplex virus (HSV) infections remain common and incurable; consequently, the population with residual infection continues to rise, Christine Johnston, MD, of the University of Washington, Seattle, and colleagues wrote. However, data on the viral shedding trajectory of genital HSV-1 are limited, although HSV-1 accounts for an increasing number of infections.

In a study published in JAMA the researchers recruited 82 women with first-episode genital HSV-1 infections from sexual health and primary care clinics in Seattle, between 2013 and 2018. The participants supplied self-collected oral and genital swabs for daily HSV polymerase chain reaction testing for two 30-day periods at 2 months and 11 months after their initial symptoms. The study population was not pregnant and did not have HIV infection. The median age of the participants was 26 years, 54 were women, and 42 had primary HSV-1 infections. Primary HSV-1 infection was defined as the lack of HSV antibody at baseline or an evolving antibody profile, based on the University of Washington HSV Western Blot.

The primary outcome was the rates of genital and oral HSV shedding and lesions at 2 and 11 months and up to 2 years after an initial HSV-1 infection.

At 2 months, approximately two-thirds (64.6%) of the participants had HSV-1 in the genital tract and 29.3% had virus in the mouth. Genital shedding of HSV-1 was detected in 12.1% of 2,264 total testing days at 2 months, but this rate declined to 7.1% of 1,719 testing days at 11 months (relative risk, 0.52).

The researchers identified oral HSV-1 shedding on 3.9% of 2,247 testing days at 2 months, with a slight increase to 5.1% of 1,714 testing days at 11 months.

Both genital and oral lesions were rare, with reports of 2.6% and 0.4%, respectively, at 2 months and 3.8% and 0.5%, respectively, at 11 months.

The risk of genital shedding was significantly higher in individuals with primary HSV-1, compared with those with nonprimary infections (7.9% vs. 2.9%; RR, 2.75). The overall rate of genital shedding was 17.2% for those with primary HSV-1, of which 15.2% was asymptomatic. Oral shedding was similar for individuals with primary and nonprimary HSV in a multivariate analysis.

In addition, HSV-specific CD4+ and CD8+ T-cell responses were identified in all participants, and these remained stable during the study period. No association appeared between rates of genital and oral shedding and the proportion of cells that expressed two, three, or four cytokines.

The current study is the first known to comprehensively assess genital and oral HSV-1 viral shedding using polymerase chain reaction, the researchers wrote. “Characterizing shedding rates is clinically important because patients with genital herpes are often concerned about transmission to sexual partners, which usually occurs in the absence of lesions.”

The study findings were limited by several factors including the 22% loss of participants to follow-up by the end of the first year, and the use of data from a single location with a primarily White population, the researchers noted. Another limitation was reliance on self-reports and the potential underestimation of recurrences because of the possible use of antiviral medications between swabbing periods.

However, the results indicate the early frequency of HSV-1 shedding and suggest that suppressive therapy might benefit individuals with primary HSV-1 during their first year of infection, the researchers said.
 

Findings may improve HSV management

The current study helps fill a knowledge gap regarding the natural history of genital HSV-1 infections, Richard J. Whitley, MD, and Edward W. Hook III, MD, both of the University of Alabama at Birmingham, wrote in an accompanying editorial. Despite the small study population, the data represent the largest cohort to date of individuals with first-episode infection and up to 2 years’ follow-up.

Although HSV-2 shedding is greater and associated with more symptoms, seroprevalence of HSV-2 in the United States is declining, they noted. Therefore, the findings can inform patient counseling and recommendations for antiviral therapy that may extend to managing HSV-1 in pregnant women as well, although no pregnant women were included in the study.

“For clinicians, these data emphasize the importance of determining the HSV viral type in persons presenting with initial episodes of genital herpes to accurately counsel patients regarding risk of clinical recurrence, the likelihood of asymptomatic shedding of virus and hence transmission, and antiviral prophylaxis,” the editorialists emphasized. For investigators, the results should prompt additional studies of the host defense against HSV and improved serological testing.
 

Study supports need for attention to HSV-1

“Genital herpes is an extremely common sexually transmitted infection, and often only HSV-2 is measured,” Sarah W. Prager, MD, of the University of Washington, Seattle, said in an interview. “This study shows that HSV-1 also accounts for a significant amount of genital disease, and should also be considered when determining prevalence of genital herpes.

“I was not surprised to see that viral shedding decreased significantly over the first year after diagnosis, and similarly not surprised that lesions were rare after the initial infection,” said Dr. Prager, who was not involved in the study. “I was somewhat surprised to see that genital HSV-1 shedding was more common than oral shedding.”

Dr. Prager said that she would advise clinicians against serum HSV testing unless someone has an active genital lesion. “Testing after a lesion will often reveal HSV-1, and patients should be counseled that shedding will decrease over the first year. Subsequent genital lesions are uncommon, but certainly possible, and oral lesions and shedding are both rare.” ]

More research is needed in a more diverse population, Dr. Prager emphasized. Following patients for more than a year and learning more about the use of antiviral medications also would be useful.

The study was supported in part by the National Institutes of Health/National Institute of Allergy and Infectious Diseases through grants to several authors, including lead author Dr. Johnston. Dr. Johnston also disclosed personal fees from AbbVie, grants from Gilead, royalties from UpToDate, and personal fees from GlaxoSmithKline unrelated to the current study. Dr. Whitley disclosed personal fees from Virios Therapeutics as a board member and shareholder during the conduct of the study, royalties from Aettis unrelated to the submitted work, and serving on an advisory board for Visby Diagnostics. Dr. Hook disclosed serving on an advisory board for Visby Diagnostics unrelated to the submitted work. Dr. Prager had no conflicts to disclose and serves on the editorial advisory board of Ob.Gyn News.
 

The U.S. Preventive Services Task Force moved forward their recommendations for using hormone therapy to prevent chronic conditions in postmenopausal women by keeping them the same.

The central message of the new recommendations, released on Nov. 1 as a statement published in JAMA, remains unchanged from the last update in 2017.

The message also remains simple: Don’t use hormone therapy for preventing chronic conditions, such as cardiovascular disease, cancer, and osteoporosis, or bone fracture.

The USPSTF summarized its recommendations in two brief statements: the group “recommends against the use of combined estrogen and progestin for the primary prevention of chronic conditions in postmenopausal persons” and “recommends against the use of estrogen alone for the primary prevention of chronic conditions in postmenopausal persons who have had a hysterectomy.”

This wording is identical to that used in the 2017 guidance (except it now refers to postmenopausal persons instead of specifically women). The recommendation against use of estrogen and progestin for prevention of chronic conditions in postmenopausal women was first made by the USPSTF in 2002.

An editorial accompanying the 2022 revision notes that the evidence cited by the USPSTF includes “only two additional, modest-sized trials” (that focused on the effects of hormone therapy on cognition and brain structure) compared with 2017, “as well as ancillary analyses of previous trials.”
 

A standard 5-year update

The 2022 revision and revisiting of the evidence base by the Task Force regarding the benefits and risks of postmenopausal hormone therapy occurred “as part of the Task Force’s standard approach, which includes updating each recommendation approximately every 5 years,” explained Carol M. Mangione, MD, who is USPSTF chair and chief of the division of general internal medicine and health services research at the University of California, Los Angeles.

“In our review we again found that while hormone therapy may reduce the risk of some conditions, it can also lead to serious harms such as an increase in the risk of blood clots and stroke,” Dr. Mangione said in an interview. “The harms cancel out any potential benefits overall.”

This new statement only applies to using menopausal hormone treatment for preventing chronic conditions in asymptomatic people but does not speak to using this treatment in managing people with perimenopausal symptoms such as hot flashes or vaginal dryness or treating people with premature or surgical menopause, Dr. Mangione highlighted.
 

No review for treating menopausal symptoms

“The Task Force encourages people who are experiencing symptoms of menopause to talk with their health care professional about the best treatment for them,” explained Dr. Mangione. “The Task Force did not review the evidence on the use of hormone therapy to treat symptoms of menopause.”

Osteoporosis and increased risk for bone fracture were among the conditions that accompany menopause reviewed by the USPSTF. The Task Force concluded that while “hormone therapy was associated with decreased risk of fractures,” after weighing the benefits and harms for preventing this condition, “there is no net benefit at the population level.”

This conclusion seems to contrast with the 2022 hormone therapy position statement of the North American Menopause Society (NAMS), released in July, which states: “For women aged younger than 60 years or who are within 10 years of menopause onset and have no contraindications, the benefit-risk ratio is favorable for treatment of bothersome vasomotor symptoms and prevention of bone loss.”
 

USPSTF, NAMS are ‘completely consistent’

However, Stephanie S. Faubion, MD, medical director of NAMS and director of the women’s health clinic at Mayo Clinic, Rochester, Minn., said the new USPSTF recommendations “are completely consistent” with the recent NAMS statement.

“We are entirely aligned with the recommendation to use hormone therapy for management of menopausal symptoms and not for chronic disease prevention or as an anti-aging strategy,” Dr. Faubion commented in an interview.

Dr. Faubion also stressed that “menopausal hormone therapy remains the most effective treatment for menopausal symptoms,” and that “women should not be reflexively directed to other pharmacologic therapies for management of menopausal symptoms.”

The distinction the USPSTF makes between its recommendations against using hormone therapy to prevent chronic conditions and its deferral of comment on use of the same treatment to manage perimenopausal symptoms is often forgotten, note Alison J. Huang, MD, and Deborah Grady, MD, in their editorial.
 

A problem of conflation

“Many patients and clinicians conflate these two different indications,” they write.

The notion that the net harms of menopausal hormone therapy outweigh the benefits “is now widely adopted as a rationale for foregoing menopausal hormone therapy for symptomatic treatment,” even though “nonhormonal treatments that are as effective as menopausal hormone therapy have not yet been identified,” say Dr. Huang and Dr. Grady, both physicians at the University of California, San Francisco.

In addition, alternative, nonhormonal options for treating perimenopausal symptoms have not received the same level of scrutiny as hormonal treatment, they say.

“It is arguably problematic to avoid menopausal hormone therapy and favor potentially less effective treatments, when the longer-term implications of those treatments for health have not been evaluated,” Dr. Huang and Dr. Grady write in their editorial.

In short, during menopause, people are at risk of being “frightened away from considering using menopausal hormone therapy for distressing symptoms,” they say.

“We can’t speak to whether or how often clinicians might be conflating the role of hormone therapy in treating symptoms and preventing chronic conditions,” answered Dr. Mangione.

“We hope to ensure that health professionals know that hormone therapy is not a beneficial way to reduce the risk of chronic conditions such as heart disease, cancer, and strokes,” she added. The new recommendations are an effort to “raise awareness about the value of considering other safe and effective ways for people to reduce their risk of chronic health problems as they age.”
 

The issue of timing

Another critique offered by Dr. Huang and Dr. Grady in their editorial is that “the scientific and medical community should let go of the past,” and should no longer invest additional resources in “trying to parse out subsets of menopausal patients who may derive some preventive benefit from menopausal hormone therapy for a limited amount of time.”

But Dr. Mangione disagreed.

The USPSTF “calls for more research that can help us understand whether health outcomes – both benefits and harms – differ depending on a person’s age or when they started hormone therapy related to when they went through menopause,” she said.

Dr. Mangione also highlighted the need for additional research on whether the benefits and risks of menopausal hormone therapy vary across racial and ethnic groups.

USPSTF receives no commercial funding. Dr. Mangione, Dr. Huang, and Dr. Grady have reported no relevant financial relationships.

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

The U.S. Preventive Services Task Force moved forward their recommendations for using hormone therapy to prevent chronic conditions in postmenopausal women by keeping them the same.

The central message of the new recommendations, released on Nov. 1 as a statement published in JAMA, remains unchanged from the last update in 2017.

The message also remains simple: Don’t use hormone therapy for preventing chronic conditions, such as cardiovascular disease, cancer, and osteoporosis, or bone fracture.

The USPSTF summarized its recommendations in two brief statements: the group “recommends against the use of combined estrogen and progestin for the primary prevention of chronic conditions in postmenopausal persons” and “recommends against the use of estrogen alone for the primary prevention of chronic conditions in postmenopausal persons who have had a hysterectomy.”

This wording is identical to that used in the 2017 guidance (except it now refers to postmenopausal persons instead of specifically women). The recommendation against use of estrogen and progestin for prevention of chronic conditions in postmenopausal women was first made by the USPSTF in 2002.

An editorial accompanying the 2022 revision notes that the evidence cited by the USPSTF includes “only two additional, modest-sized trials” (that focused on the effects of hormone therapy on cognition and brain structure) compared with 2017, “as well as ancillary analyses of previous trials.”
 

A standard 5-year update

The 2022 revision and revisiting of the evidence base by the Task Force regarding the benefits and risks of postmenopausal hormone therapy occurred “as part of the Task Force’s standard approach, which includes updating each recommendation approximately every 5 years,” explained Carol M. Mangione, MD, who is USPSTF chair and chief of the division of general internal medicine and health services research at the University of California, Los Angeles.

“In our review we again found that while hormone therapy may reduce the risk of some conditions, it can also lead to serious harms such as an increase in the risk of blood clots and stroke,” Dr. Mangione said in an interview. “The harms cancel out any potential benefits overall.”

This new statement only applies to using menopausal hormone treatment for preventing chronic conditions in asymptomatic people but does not speak to using this treatment in managing people with perimenopausal symptoms such as hot flashes or vaginal dryness or treating people with premature or surgical menopause, Dr. Mangione highlighted.
 

No review for treating menopausal symptoms

“The Task Force encourages people who are experiencing symptoms of menopause to talk with their health care professional about the best treatment for them,” explained Dr. Mangione. “The Task Force did not review the evidence on the use of hormone therapy to treat symptoms of menopause.”

Osteoporosis and increased risk for bone fracture were among the conditions that accompany menopause reviewed by the USPSTF. The Task Force concluded that while “hormone therapy was associated with decreased risk of fractures,” after weighing the benefits and harms for preventing this condition, “there is no net benefit at the population level.”

This conclusion seems to contrast with the 2022 hormone therapy position statement of the North American Menopause Society (NAMS), released in July, which states: “For women aged younger than 60 years or who are within 10 years of menopause onset and have no contraindications, the benefit-risk ratio is favorable for treatment of bothersome vasomotor symptoms and prevention of bone loss.”
 

USPSTF, NAMS are ‘completely consistent’

However, Stephanie S. Faubion, MD, medical director of NAMS and director of the women’s health clinic at Mayo Clinic, Rochester, Minn., said the new USPSTF recommendations “are completely consistent” with the recent NAMS statement.

“We are entirely aligned with the recommendation to use hormone therapy for management of menopausal symptoms and not for chronic disease prevention or as an anti-aging strategy,” Dr. Faubion commented in an interview.

Dr. Faubion also stressed that “menopausal hormone therapy remains the most effective treatment for menopausal symptoms,” and that “women should not be reflexively directed to other pharmacologic therapies for management of menopausal symptoms.”

The distinction the USPSTF makes between its recommendations against using hormone therapy to prevent chronic conditions and its deferral of comment on use of the same treatment to manage perimenopausal symptoms is often forgotten, note Alison J. Huang, MD, and Deborah Grady, MD, in their editorial.
 

A problem of conflation

“Many patients and clinicians conflate these two different indications,” they write.

The notion that the net harms of menopausal hormone therapy outweigh the benefits “is now widely adopted as a rationale for foregoing menopausal hormone therapy for symptomatic treatment,” even though “nonhormonal treatments that are as effective as menopausal hormone therapy have not yet been identified,” say Dr. Huang and Dr. Grady, both physicians at the University of California, San Francisco.

In addition, alternative, nonhormonal options for treating perimenopausal symptoms have not received the same level of scrutiny as hormonal treatment, they say.

“It is arguably problematic to avoid menopausal hormone therapy and favor potentially less effective treatments, when the longer-term implications of those treatments for health have not been evaluated,” Dr. Huang and Dr. Grady write in their editorial.

In short, during menopause, people are at risk of being “frightened away from considering using menopausal hormone therapy for distressing symptoms,” they say.

“We can’t speak to whether or how often clinicians might be conflating the role of hormone therapy in treating symptoms and preventing chronic conditions,” answered Dr. Mangione.

“We hope to ensure that health professionals know that hormone therapy is not a beneficial way to reduce the risk of chronic conditions such as heart disease, cancer, and strokes,” she added. The new recommendations are an effort to “raise awareness about the value of considering other safe and effective ways for people to reduce their risk of chronic health problems as they age.”
 

The issue of timing

Another critique offered by Dr. Huang and Dr. Grady in their editorial is that “the scientific and medical community should let go of the past,” and should no longer invest additional resources in “trying to parse out subsets of menopausal patients who may derive some preventive benefit from menopausal hormone therapy for a limited amount of time.”

But Dr. Mangione disagreed.

The USPSTF “calls for more research that can help us understand whether health outcomes – both benefits and harms – differ depending on a person’s age or when they started hormone therapy related to when they went through menopause,” she said.

Dr. Mangione also highlighted the need for additional research on whether the benefits and risks of menopausal hormone therapy vary across racial and ethnic groups.

USPSTF receives no commercial funding. Dr. Mangione, Dr. Huang, and Dr. Grady have reported no relevant financial relationships.

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

The U.S. Preventive Services Task Force moved forward their recommendations for using hormone therapy to prevent chronic conditions in postmenopausal women by keeping them the same.

The central message of the new recommendations, released on Nov. 1 as a statement published in JAMA, remains unchanged from the last update in 2017.

The message also remains simple: Don’t use hormone therapy for preventing chronic conditions, such as cardiovascular disease, cancer, and osteoporosis, or bone fracture.

The USPSTF summarized its recommendations in two brief statements: the group “recommends against the use of combined estrogen and progestin for the primary prevention of chronic conditions in postmenopausal persons” and “recommends against the use of estrogen alone for the primary prevention of chronic conditions in postmenopausal persons who have had a hysterectomy.”

This wording is identical to that used in the 2017 guidance (except it now refers to postmenopausal persons instead of specifically women). The recommendation against use of estrogen and progestin for prevention of chronic conditions in postmenopausal women was first made by the USPSTF in 2002.

An editorial accompanying the 2022 revision notes that the evidence cited by the USPSTF includes “only two additional, modest-sized trials” (that focused on the effects of hormone therapy on cognition and brain structure) compared with 2017, “as well as ancillary analyses of previous trials.”
 

A standard 5-year update

The 2022 revision and revisiting of the evidence base by the Task Force regarding the benefits and risks of postmenopausal hormone therapy occurred “as part of the Task Force’s standard approach, which includes updating each recommendation approximately every 5 years,” explained Carol M. Mangione, MD, who is USPSTF chair and chief of the division of general internal medicine and health services research at the University of California, Los Angeles.

“In our review we again found that while hormone therapy may reduce the risk of some conditions, it can also lead to serious harms such as an increase in the risk of blood clots and stroke,” Dr. Mangione said in an interview. “The harms cancel out any potential benefits overall.”

This new statement only applies to using menopausal hormone treatment for preventing chronic conditions in asymptomatic people but does not speak to using this treatment in managing people with perimenopausal symptoms such as hot flashes or vaginal dryness or treating people with premature or surgical menopause, Dr. Mangione highlighted.
 

No review for treating menopausal symptoms

“The Task Force encourages people who are experiencing symptoms of menopause to talk with their health care professional about the best treatment for them,” explained Dr. Mangione. “The Task Force did not review the evidence on the use of hormone therapy to treat symptoms of menopause.”

Osteoporosis and increased risk for bone fracture were among the conditions that accompany menopause reviewed by the USPSTF. The Task Force concluded that while “hormone therapy was associated with decreased risk of fractures,” after weighing the benefits and harms for preventing this condition, “there is no net benefit at the population level.”

This conclusion seems to contrast with the 2022 hormone therapy position statement of the North American Menopause Society (NAMS), released in July, which states: “For women aged younger than 60 years or who are within 10 years of menopause onset and have no contraindications, the benefit-risk ratio is favorable for treatment of bothersome vasomotor symptoms and prevention of bone loss.”
 

USPSTF, NAMS are ‘completely consistent’

However, Stephanie S. Faubion, MD, medical director of NAMS and director of the women’s health clinic at Mayo Clinic, Rochester, Minn., said the new USPSTF recommendations “are completely consistent” with the recent NAMS statement.

“We are entirely aligned with the recommendation to use hormone therapy for management of menopausal symptoms and not for chronic disease prevention or as an anti-aging strategy,” Dr. Faubion commented in an interview.

Dr. Faubion also stressed that “menopausal hormone therapy remains the most effective treatment for menopausal symptoms,” and that “women should not be reflexively directed to other pharmacologic therapies for management of menopausal symptoms.”

The distinction the USPSTF makes between its recommendations against using hormone therapy to prevent chronic conditions and its deferral of comment on use of the same treatment to manage perimenopausal symptoms is often forgotten, note Alison J. Huang, MD, and Deborah Grady, MD, in their editorial.
 

A problem of conflation

“Many patients and clinicians conflate these two different indications,” they write.

The notion that the net harms of menopausal hormone therapy outweigh the benefits “is now widely adopted as a rationale for foregoing menopausal hormone therapy for symptomatic treatment,” even though “nonhormonal treatments that are as effective as menopausal hormone therapy have not yet been identified,” say Dr. Huang and Dr. Grady, both physicians at the University of California, San Francisco.

In addition, alternative, nonhormonal options for treating perimenopausal symptoms have not received the same level of scrutiny as hormonal treatment, they say.

“It is arguably problematic to avoid menopausal hormone therapy and favor potentially less effective treatments, when the longer-term implications of those treatments for health have not been evaluated,” Dr. Huang and Dr. Grady write in their editorial.

In short, during menopause, people are at risk of being “frightened away from considering using menopausal hormone therapy for distressing symptoms,” they say.

“We can’t speak to whether or how often clinicians might be conflating the role of hormone therapy in treating symptoms and preventing chronic conditions,” answered Dr. Mangione.

“We hope to ensure that health professionals know that hormone therapy is not a beneficial way to reduce the risk of chronic conditions such as heart disease, cancer, and strokes,” she added. The new recommendations are an effort to “raise awareness about the value of considering other safe and effective ways for people to reduce their risk of chronic health problems as they age.”
 

The issue of timing

Another critique offered by Dr. Huang and Dr. Grady in their editorial is that “the scientific and medical community should let go of the past,” and should no longer invest additional resources in “trying to parse out subsets of menopausal patients who may derive some preventive benefit from menopausal hormone therapy for a limited amount of time.”

But Dr. Mangione disagreed.

The USPSTF “calls for more research that can help us understand whether health outcomes – both benefits and harms – differ depending on a person’s age or when they started hormone therapy related to when they went through menopause,” she said.

Dr. Mangione also highlighted the need for additional research on whether the benefits and risks of menopausal hormone therapy vary across racial and ethnic groups.

USPSTF receives no commercial funding. Dr. Mangione, Dr. Huang, and Dr. Grady have reported no relevant financial relationships.

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

MONTREAL – Children and young people with severe atopic dermatitis had a more rapid treatment response with ciclosporin, but more sustained disease control with methotrexate in the TREAT study, investigators reported at the annual meeting of the International Society of Atopic Dermatitis.

The findings are important, since many regulatory bodies require patients to have tried such first-line conventional systemic therapies before moving on to novel therapeutics, explained Carsten Flohr, MD, PhD, research and development lead at St John’s Institute of Dermatology, Guy’s and St Thomas’ NHS Foundation Trust London.

“We don’t really have much pediatric trial data; very often the pediatric data that we have is buried in adult trials and when it comes to an adequately powered randomized controlled trial with conventional systemic medication in pediatric patients, we don’t have one – so we’re lacking that gold standard,” said Dr. Flohr, chair in dermatology and population health sciences at King’s College London.

In the TREAT trial, 103 patients with AD (mean age, 10 years) who had not responded to topical treatment, were randomly assigned to oral ciclosporin (4 mg/kg daily) or methotrexate (0.4 mg/kg weekly) for 36 weeks and then followed for another 24 weeks off therapy for the co-primary outcomes of change in objective Scoring Atopic Dermatitis (o-SCORAD) at 12 weeks, as well as time to first significant flare after treatment cessation, defined as returning to baseline o-SCORAD, or restarting a systemic treatment.

Secondary outcomes included disease severity and quality of life (QOL) measures, as well as safety. At baseline, the mean o-SCORAD was 46.81, with mean Eczema Area and Severity Index (EASI) and Patient Oriented Eczema Measure (POEM) scores of 28.05 and 20.62 respectively. The mean Children’s Dermatology Life Quality Index (CDLQI) score was 14.96.

Looking at change in eczema severity measured by o-SCORAD at 12 weeks, ciclosporin was superior to methotrexate, with a mean difference in o-SCORAD change of -5.69 (P =.01). For the co-primary endpoint of time to first significant flare during the 24 weeks after treatment cessation, “there was a trend toward more flare activity in the ciclosporin group, although with a hazard ratio of 1.55, this was statistically not significant,” Dr. Flohr said.

On a graph showing mean EASI scores from baseline through the 60-week study period, Dr. Flohr explained how the score first dropped more precipitously in patients treated with ciclosporin compared with those treated with methotrexate, reaching a statistically significant difference between the groups by 12 weeks (–3.13, P = .0145).

However, after that time, while the EASI score among those on methotrexate continued to drop, the ciclosporin score evened out, so that by 20 weeks, methotrexate EASI scores were better, and remained so until the end of treatment and further, out to 60 weeks (mean difference -6.36, P < .001). “The most interesting bit of this graph is [that] the curve is pointing downwards for methotrexate up to the 9-month point, suggesting these people had not reached their full therapeutic potential yet, whereas if you’re on ciclosporin you plateau and there’s not much additional improvement, if at all, and then people [on ciclosporin] start going up in their disease activity off therapy,” he said.

The same pattern was seen with all the other outcome measures, including o-SCORAD and POEM.

Quality of life significantly improved by about 8 points in both treatment groups, with no significant differences between groups, and this improvement was sustained through the 24 weeks following cessation of therapy. However, during this treatment-free phase, patients on methotrexate had fewer parent-reported flares compared with those on ciclosporin (mean 6.19 vs 5.40 flares, P =.0251), although there was no difference between groups in time to first flare.

Describing the treatment safety as “overall reassuring,” Dr. Flohr said there were slightly more nonserious adverse events in the methotrexate arm (407 vs. 369), with nausea occurring more often in this group (43.1% vs. 17.6%).

“I think we were seeing this clinically, but to see it in a clinical trial gives us more confidence in discussing with parents,” said session moderator Melinda Gooderham, MD, assistant professor at Queens University, Kingston, Ont., and medical director at the SKiN Centre for Dermatology in Peterborough.

What she also took away from the study was safety of these treatments. “The discontinuation rate was not different with either drug, so it’s not like ciclosporin works fast but all these people have problems and discontinue,” Dr. Gooderham told this news organization. “That’s also reassuring.”

Asked which treatment she prefers, Dr. Gooderham, a consultant physician at Peterborough Regional Health Centre, picked methotrexate “because of the lasting effect. But there are times when you may need more rapid control ... where I might choose ciclosporin first, but for me it’s maybe 90% methotrexate first, 10% ciclosporin.”

Dr. Flohr and Dr. Gooderham report no relevant financial relationships. The study was funded by the National Institute for Health and Care Research.

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

MONTREAL – Children and young people with severe atopic dermatitis had a more rapid treatment response with ciclosporin, but more sustained disease control with methotrexate in the TREAT study, investigators reported at the annual meeting of the International Society of Atopic Dermatitis.

The findings are important, since many regulatory bodies require patients to have tried such first-line conventional systemic therapies before moving on to novel therapeutics, explained Carsten Flohr, MD, PhD, research and development lead at St John’s Institute of Dermatology, Guy’s and St Thomas’ NHS Foundation Trust London.

“We don’t really have much pediatric trial data; very often the pediatric data that we have is buried in adult trials and when it comes to an adequately powered randomized controlled trial with conventional systemic medication in pediatric patients, we don’t have one – so we’re lacking that gold standard,” said Dr. Flohr, chair in dermatology and population health sciences at King’s College London.

In the TREAT trial, 103 patients with AD (mean age, 10 years) who had not responded to topical treatment, were randomly assigned to oral ciclosporin (4 mg/kg daily) or methotrexate (0.4 mg/kg weekly) for 36 weeks and then followed for another 24 weeks off therapy for the co-primary outcomes of change in objective Scoring Atopic Dermatitis (o-SCORAD) at 12 weeks, as well as time to first significant flare after treatment cessation, defined as returning to baseline o-SCORAD, or restarting a systemic treatment.

Secondary outcomes included disease severity and quality of life (QOL) measures, as well as safety. At baseline, the mean o-SCORAD was 46.81, with mean Eczema Area and Severity Index (EASI) and Patient Oriented Eczema Measure (POEM) scores of 28.05 and 20.62 respectively. The mean Children’s Dermatology Life Quality Index (CDLQI) score was 14.96.

Looking at change in eczema severity measured by o-SCORAD at 12 weeks, ciclosporin was superior to methotrexate, with a mean difference in o-SCORAD change of -5.69 (P =.01). For the co-primary endpoint of time to first significant flare during the 24 weeks after treatment cessation, “there was a trend toward more flare activity in the ciclosporin group, although with a hazard ratio of 1.55, this was statistically not significant,” Dr. Flohr said.

On a graph showing mean EASI scores from baseline through the 60-week study period, Dr. Flohr explained how the score first dropped more precipitously in patients treated with ciclosporin compared with those treated with methotrexate, reaching a statistically significant difference between the groups by 12 weeks (–3.13, P = .0145).

However, after that time, while the EASI score among those on methotrexate continued to drop, the ciclosporin score evened out, so that by 20 weeks, methotrexate EASI scores were better, and remained so until the end of treatment and further, out to 60 weeks (mean difference -6.36, P < .001). “The most interesting bit of this graph is [that] the curve is pointing downwards for methotrexate up to the 9-month point, suggesting these people had not reached their full therapeutic potential yet, whereas if you’re on ciclosporin you plateau and there’s not much additional improvement, if at all, and then people [on ciclosporin] start going up in their disease activity off therapy,” he said.

The same pattern was seen with all the other outcome measures, including o-SCORAD and POEM.

Quality of life significantly improved by about 8 points in both treatment groups, with no significant differences between groups, and this improvement was sustained through the 24 weeks following cessation of therapy. However, during this treatment-free phase, patients on methotrexate had fewer parent-reported flares compared with those on ciclosporin (mean 6.19 vs 5.40 flares, P =.0251), although there was no difference between groups in time to first flare.

Describing the treatment safety as “overall reassuring,” Dr. Flohr said there were slightly more nonserious adverse events in the methotrexate arm (407 vs. 369), with nausea occurring more often in this group (43.1% vs. 17.6%).

“I think we were seeing this clinically, but to see it in a clinical trial gives us more confidence in discussing with parents,” said session moderator Melinda Gooderham, MD, assistant professor at Queens University, Kingston, Ont., and medical director at the SKiN Centre for Dermatology in Peterborough.

What she also took away from the study was safety of these treatments. “The discontinuation rate was not different with either drug, so it’s not like ciclosporin works fast but all these people have problems and discontinue,” Dr. Gooderham told this news organization. “That’s also reassuring.”

Asked which treatment she prefers, Dr. Gooderham, a consultant physician at Peterborough Regional Health Centre, picked methotrexate “because of the lasting effect. But there are times when you may need more rapid control ... where I might choose ciclosporin first, but for me it’s maybe 90% methotrexate first, 10% ciclosporin.”

Dr. Flohr and Dr. Gooderham report no relevant financial relationships. The study was funded by the National Institute for Health and Care Research.

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

MONTREAL – Children and young people with severe atopic dermatitis had a more rapid treatment response with ciclosporin, but more sustained disease control with methotrexate in the TREAT study, investigators reported at the annual meeting of the International Society of Atopic Dermatitis.

The findings are important, since many regulatory bodies require patients to have tried such first-line conventional systemic therapies before moving on to novel therapeutics, explained Carsten Flohr, MD, PhD, research and development lead at St John’s Institute of Dermatology, Guy’s and St Thomas’ NHS Foundation Trust London.

“We don’t really have much pediatric trial data; very often the pediatric data that we have is buried in adult trials and when it comes to an adequately powered randomized controlled trial with conventional systemic medication in pediatric patients, we don’t have one – so we’re lacking that gold standard,” said Dr. Flohr, chair in dermatology and population health sciences at King’s College London.

In the TREAT trial, 103 patients with AD (mean age, 10 years) who had not responded to topical treatment, were randomly assigned to oral ciclosporin (4 mg/kg daily) or methotrexate (0.4 mg/kg weekly) for 36 weeks and then followed for another 24 weeks off therapy for the co-primary outcomes of change in objective Scoring Atopic Dermatitis (o-SCORAD) at 12 weeks, as well as time to first significant flare after treatment cessation, defined as returning to baseline o-SCORAD, or restarting a systemic treatment.

Secondary outcomes included disease severity and quality of life (QOL) measures, as well as safety. At baseline, the mean o-SCORAD was 46.81, with mean Eczema Area and Severity Index (EASI) and Patient Oriented Eczema Measure (POEM) scores of 28.05 and 20.62 respectively. The mean Children’s Dermatology Life Quality Index (CDLQI) score was 14.96.

Looking at change in eczema severity measured by o-SCORAD at 12 weeks, ciclosporin was superior to methotrexate, with a mean difference in o-SCORAD change of -5.69 (P =.01). For the co-primary endpoint of time to first significant flare during the 24 weeks after treatment cessation, “there was a trend toward more flare activity in the ciclosporin group, although with a hazard ratio of 1.55, this was statistically not significant,” Dr. Flohr said.

On a graph showing mean EASI scores from baseline through the 60-week study period, Dr. Flohr explained how the score first dropped more precipitously in patients treated with ciclosporin compared with those treated with methotrexate, reaching a statistically significant difference between the groups by 12 weeks (–3.13, P = .0145).

However, after that time, while the EASI score among those on methotrexate continued to drop, the ciclosporin score evened out, so that by 20 weeks, methotrexate EASI scores were better, and remained so until the end of treatment and further, out to 60 weeks (mean difference -6.36, P < .001). “The most interesting bit of this graph is [that] the curve is pointing downwards for methotrexate up to the 9-month point, suggesting these people had not reached their full therapeutic potential yet, whereas if you’re on ciclosporin you plateau and there’s not much additional improvement, if at all, and then people [on ciclosporin] start going up in their disease activity off therapy,” he said.

The same pattern was seen with all the other outcome measures, including o-SCORAD and POEM.

Quality of life significantly improved by about 8 points in both treatment groups, with no significant differences between groups, and this improvement was sustained through the 24 weeks following cessation of therapy. However, during this treatment-free phase, patients on methotrexate had fewer parent-reported flares compared with those on ciclosporin (mean 6.19 vs 5.40 flares, P =.0251), although there was no difference between groups in time to first flare.

Describing the treatment safety as “overall reassuring,” Dr. Flohr said there were slightly more nonserious adverse events in the methotrexate arm (407 vs. 369), with nausea occurring more often in this group (43.1% vs. 17.6%).

“I think we were seeing this clinically, but to see it in a clinical trial gives us more confidence in discussing with parents,” said session moderator Melinda Gooderham, MD, assistant professor at Queens University, Kingston, Ont., and medical director at the SKiN Centre for Dermatology in Peterborough.

What she also took away from the study was safety of these treatments. “The discontinuation rate was not different with either drug, so it’s not like ciclosporin works fast but all these people have problems and discontinue,” Dr. Gooderham told this news organization. “That’s also reassuring.”

Asked which treatment she prefers, Dr. Gooderham, a consultant physician at Peterborough Regional Health Centre, picked methotrexate “because of the lasting effect. But there are times when you may need more rapid control ... where I might choose ciclosporin first, but for me it’s maybe 90% methotrexate first, 10% ciclosporin.”

Dr. Flohr and Dr. Gooderham report no relevant financial relationships. The study was funded by the National Institute for Health and Care Research.

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