Federal Practitioner

Some degree of pain is inevitable in older individuals, and as people pass 80 years of age, the harms of medications used to control chronic pain increase. Pain-reducing medication use in this age group may cause inflammation, gastric bleeding, kidney damage, or constipation.

These risks may lead some clinicians to avoid aggressive pain treatment in their eldest patients, resulting in unnecessary suffering.

“Pain causes harm beyond just the physical suffering associated with it,” said Diane Meier, MD, a geriatrician and palliative care specialist at Mount Sinai Medicine in New York City who treats many people in their 80s and 90s.

Downstream effects of untreated pain could include a loss of mobility and isolation, Dr. Meier said. And, as these harms are mounting, some clinicians may avoid using an analgesic that could bring great relief: buprenorphine.

“People think about buprenorphine like they think about methadone,” Dr. Meier said, as something prescribed to treat substance use disorder. In reality, it is an effective analgesic in other situations.

Buprenorphine is better at treating chronic pain than other opioids that carry a higher addiction risk and often cause constipation in elderly patients. Buprenorphine is easier on the kidneys and has a lower addiction risk than opioids like oxycodone.

The transdermal patch form of buprenorphine (Butrans, PurduePharma) is changed weekly and starts at low doses.

“There’s an adage in geriatrics: start low and go slow,” said Jessica Merlin, MD, PhD, a palliative care and addiction medicine physician at the University of Pittsburgh Medical Center in Pittsburgh, Pennsylvania.

Dr. Merlin recommends beginning elderly patients with chronic pain on a 10-microgram/hour dose of Butrans, among the lowest doses available. Physicians could monitor side effects, which will generally be mild, with the aim of never increasing the dose if pain is managed.
 

Nonpharmacologic Remedies, Drug Considerations

“Nonpharmacologic therapy is very underutilized,” Dr. Merlin said, even though multiple alternatives to medications can improve chronic pain symptoms at any age.

Cognitive-behavioral therapy or acceptance and commitment therapy can both help people reduce the impact of pain, Dr. Merlin said. And for people who can do so, physical therapy programs, yoga, or tai chi are all ways to strengthen the body’s defenses against pain, Dr. Merlin added.

Sometimes medication is necessary, however.

“You can’t get an older person to participate in rehab if they are in severe pain,” Dr. Meier said, adding that judicious use of medications should go hand in hand with nonpharmacologic treatment.

When medications are unavoidable, internist Douglas S. Paauw, MD, starts with topical injections at the site of the pain — a troublesome joint, for example — rather than systemic medications that affect multiple organs and the brain.

“We try not to flood their body with meds” for localized problems, Dr. Paauw said, whose goal when treating elderly patients with pain is to improve their daily functioning and quality of life.

Dr. Paauw works at the University of Washington in Seattle and treats people who are approaching 100 years old. As some of his patients have grown older, Dr. Paauw’s interest in effective pain management has grown; he thinks that all internists and family medicine physician need to know how to manage chronic pain in their eldest patients.

“Were you able to play with your grandkid? Were you able to go grocery shopping? Were you able to take a walk outside?” These are the kinds of improvements Dr. Paauw hopes to see in older patients, recognizing that the wear and tear of life — orthopedic stresses or healed fractures that cause lingering pain — make it impossible for many older people to be pain free.

Pain is often spread throughout the body rather than focusing at one point, which requires systemic medications if physical therapy and similar approaches have not reduced pain. Per American Geriatrics Society (AGS) guidelines, in this situation Dr. Paauw starts with acetaminophen (Tylenol) as the lowest-risk systemic pain treatment.

Dr. Pauuw often counsels older patients to begin with 2 grams/day of acetaminophen and then progress to 3 grams if the lower dose has manageable side effects, rather than the standard dose of 4 grams that he feels is geared toward younger patients.

When acetaminophen doesn’t reduce pain sufficiently, or aggravates inflammation, Dr. Paauw may use the nerve pain medication pregabalin, or the antidepressant duloxetine — especially if the pain appears to be neuropathic.

Tricyclic antidepressants used to be recommended for neuropathic pain in older adults, but are now on the AGS’s Beers Criteria of drugs to avoid in elderly patients due to risk of causing dizziness or cardiac stress. Dr. Paauw might still use a tricyclic, but only after a careful risk-benefit analysis.

Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen (Motrin) or naproxen (Aleve) could work in short bursts, Dr. Paauw said, although they may cause stomach bleeding or kidney damage in older patients.

This is why NSAIDs are not recommended by the AGS for chronic pain management. And opioids like oxycodone don’t work long at low doses, often leading to dose escalation and addiction.

“The American Geriatrics Society really puts opioids down at the bottom of the list,” Dr. Paauw said, to be used “judiciously and rarely.”

Opioids may interact with other drugs to increase risk of a fall, Dr. Meier added, making them inadvisable for older patients who live alone.

“That’s why knowing something about buprenorphine is so important,” Dr. Meier said.

Dr. Meier and Dr. Paauw are on the editorial board for Internal Medicine News. Dr. Merlin is a trainer for the Center to Advance Palliative Care, which Dr. Meier founded.
 

Some degree of pain is inevitable in older individuals, and as people pass 80 years of age, the harms of medications used to control chronic pain increase. Pain-reducing medication use in this age group may cause inflammation, gastric bleeding, kidney damage, or constipation.

These risks may lead some clinicians to avoid aggressive pain treatment in their eldest patients, resulting in unnecessary suffering.

“Pain causes harm beyond just the physical suffering associated with it,” said Diane Meier, MD, a geriatrician and palliative care specialist at Mount Sinai Medicine in New York City who treats many people in their 80s and 90s.

Downstream effects of untreated pain could include a loss of mobility and isolation, Dr. Meier said. And, as these harms are mounting, some clinicians may avoid using an analgesic that could bring great relief: buprenorphine.

“People think about buprenorphine like they think about methadone,” Dr. Meier said, as something prescribed to treat substance use disorder. In reality, it is an effective analgesic in other situations.

Buprenorphine is better at treating chronic pain than other opioids that carry a higher addiction risk and often cause constipation in elderly patients. Buprenorphine is easier on the kidneys and has a lower addiction risk than opioids like oxycodone.

The transdermal patch form of buprenorphine (Butrans, PurduePharma) is changed weekly and starts at low doses.

“There’s an adage in geriatrics: start low and go slow,” said Jessica Merlin, MD, PhD, a palliative care and addiction medicine physician at the University of Pittsburgh Medical Center in Pittsburgh, Pennsylvania.

Dr. Merlin recommends beginning elderly patients with chronic pain on a 10-microgram/hour dose of Butrans, among the lowest doses available. Physicians could monitor side effects, which will generally be mild, with the aim of never increasing the dose if pain is managed.
 

Nonpharmacologic Remedies, Drug Considerations

“Nonpharmacologic therapy is very underutilized,” Dr. Merlin said, even though multiple alternatives to medications can improve chronic pain symptoms at any age.

Cognitive-behavioral therapy or acceptance and commitment therapy can both help people reduce the impact of pain, Dr. Merlin said. And for people who can do so, physical therapy programs, yoga, or tai chi are all ways to strengthen the body’s defenses against pain, Dr. Merlin added.

Sometimes medication is necessary, however.

“You can’t get an older person to participate in rehab if they are in severe pain,” Dr. Meier said, adding that judicious use of medications should go hand in hand with nonpharmacologic treatment.

When medications are unavoidable, internist Douglas S. Paauw, MD, starts with topical injections at the site of the pain — a troublesome joint, for example — rather than systemic medications that affect multiple organs and the brain.

“We try not to flood their body with meds” for localized problems, Dr. Paauw said, whose goal when treating elderly patients with pain is to improve their daily functioning and quality of life.

Dr. Paauw works at the University of Washington in Seattle and treats people who are approaching 100 years old. As some of his patients have grown older, Dr. Paauw’s interest in effective pain management has grown; he thinks that all internists and family medicine physician need to know how to manage chronic pain in their eldest patients.

“Were you able to play with your grandkid? Were you able to go grocery shopping? Were you able to take a walk outside?” These are the kinds of improvements Dr. Paauw hopes to see in older patients, recognizing that the wear and tear of life — orthopedic stresses or healed fractures that cause lingering pain — make it impossible for many older people to be pain free.

Pain is often spread throughout the body rather than focusing at one point, which requires systemic medications if physical therapy and similar approaches have not reduced pain. Per American Geriatrics Society (AGS) guidelines, in this situation Dr. Paauw starts with acetaminophen (Tylenol) as the lowest-risk systemic pain treatment.

Dr. Pauuw often counsels older patients to begin with 2 grams/day of acetaminophen and then progress to 3 grams if the lower dose has manageable side effects, rather than the standard dose of 4 grams that he feels is geared toward younger patients.

When acetaminophen doesn’t reduce pain sufficiently, or aggravates inflammation, Dr. Paauw may use the nerve pain medication pregabalin, or the antidepressant duloxetine — especially if the pain appears to be neuropathic.

Tricyclic antidepressants used to be recommended for neuropathic pain in older adults, but are now on the AGS’s Beers Criteria of drugs to avoid in elderly patients due to risk of causing dizziness or cardiac stress. Dr. Paauw might still use a tricyclic, but only after a careful risk-benefit analysis.

Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen (Motrin) or naproxen (Aleve) could work in short bursts, Dr. Paauw said, although they may cause stomach bleeding or kidney damage in older patients.

This is why NSAIDs are not recommended by the AGS for chronic pain management. And opioids like oxycodone don’t work long at low doses, often leading to dose escalation and addiction.

“The American Geriatrics Society really puts opioids down at the bottom of the list,” Dr. Paauw said, to be used “judiciously and rarely.”

Opioids may interact with other drugs to increase risk of a fall, Dr. Meier added, making them inadvisable for older patients who live alone.

“That’s why knowing something about buprenorphine is so important,” Dr. Meier said.

Dr. Meier and Dr. Paauw are on the editorial board for Internal Medicine News. Dr. Merlin is a trainer for the Center to Advance Palliative Care, which Dr. Meier founded.
 

Some degree of pain is inevitable in older individuals, and as people pass 80 years of age, the harms of medications used to control chronic pain increase. Pain-reducing medication use in this age group may cause inflammation, gastric bleeding, kidney damage, or constipation.

These risks may lead some clinicians to avoid aggressive pain treatment in their eldest patients, resulting in unnecessary suffering.

“Pain causes harm beyond just the physical suffering associated with it,” said Diane Meier, MD, a geriatrician and palliative care specialist at Mount Sinai Medicine in New York City who treats many people in their 80s and 90s.

Downstream effects of untreated pain could include a loss of mobility and isolation, Dr. Meier said. And, as these harms are mounting, some clinicians may avoid using an analgesic that could bring great relief: buprenorphine.

“People think about buprenorphine like they think about methadone,” Dr. Meier said, as something prescribed to treat substance use disorder. In reality, it is an effective analgesic in other situations.

Buprenorphine is better at treating chronic pain than other opioids that carry a higher addiction risk and often cause constipation in elderly patients. Buprenorphine is easier on the kidneys and has a lower addiction risk than opioids like oxycodone.

The transdermal patch form of buprenorphine (Butrans, PurduePharma) is changed weekly and starts at low doses.

“There’s an adage in geriatrics: start low and go slow,” said Jessica Merlin, MD, PhD, a palliative care and addiction medicine physician at the University of Pittsburgh Medical Center in Pittsburgh, Pennsylvania.

Dr. Merlin recommends beginning elderly patients with chronic pain on a 10-microgram/hour dose of Butrans, among the lowest doses available. Physicians could monitor side effects, which will generally be mild, with the aim of never increasing the dose if pain is managed.
 

Nonpharmacologic Remedies, Drug Considerations

“Nonpharmacologic therapy is very underutilized,” Dr. Merlin said, even though multiple alternatives to medications can improve chronic pain symptoms at any age.

Cognitive-behavioral therapy or acceptance and commitment therapy can both help people reduce the impact of pain, Dr. Merlin said. And for people who can do so, physical therapy programs, yoga, or tai chi are all ways to strengthen the body’s defenses against pain, Dr. Merlin added.

Sometimes medication is necessary, however.

“You can’t get an older person to participate in rehab if they are in severe pain,” Dr. Meier said, adding that judicious use of medications should go hand in hand with nonpharmacologic treatment.

When medications are unavoidable, internist Douglas S. Paauw, MD, starts with topical injections at the site of the pain — a troublesome joint, for example — rather than systemic medications that affect multiple organs and the brain.

“We try not to flood their body with meds” for localized problems, Dr. Paauw said, whose goal when treating elderly patients with pain is to improve their daily functioning and quality of life.

Dr. Paauw works at the University of Washington in Seattle and treats people who are approaching 100 years old. As some of his patients have grown older, Dr. Paauw’s interest in effective pain management has grown; he thinks that all internists and family medicine physician need to know how to manage chronic pain in their eldest patients.

“Were you able to play with your grandkid? Were you able to go grocery shopping? Were you able to take a walk outside?” These are the kinds of improvements Dr. Paauw hopes to see in older patients, recognizing that the wear and tear of life — orthopedic stresses or healed fractures that cause lingering pain — make it impossible for many older people to be pain free.

Pain is often spread throughout the body rather than focusing at one point, which requires systemic medications if physical therapy and similar approaches have not reduced pain. Per American Geriatrics Society (AGS) guidelines, in this situation Dr. Paauw starts with acetaminophen (Tylenol) as the lowest-risk systemic pain treatment.

Dr. Pauuw often counsels older patients to begin with 2 grams/day of acetaminophen and then progress to 3 grams if the lower dose has manageable side effects, rather than the standard dose of 4 grams that he feels is geared toward younger patients.

When acetaminophen doesn’t reduce pain sufficiently, or aggravates inflammation, Dr. Paauw may use the nerve pain medication pregabalin, or the antidepressant duloxetine — especially if the pain appears to be neuropathic.

Tricyclic antidepressants used to be recommended for neuropathic pain in older adults, but are now on the AGS’s Beers Criteria of drugs to avoid in elderly patients due to risk of causing dizziness or cardiac stress. Dr. Paauw might still use a tricyclic, but only after a careful risk-benefit analysis.

Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen (Motrin) or naproxen (Aleve) could work in short bursts, Dr. Paauw said, although they may cause stomach bleeding or kidney damage in older patients.

This is why NSAIDs are not recommended by the AGS for chronic pain management. And opioids like oxycodone don’t work long at low doses, often leading to dose escalation and addiction.

“The American Geriatrics Society really puts opioids down at the bottom of the list,” Dr. Paauw said, to be used “judiciously and rarely.”

Opioids may interact with other drugs to increase risk of a fall, Dr. Meier added, making them inadvisable for older patients who live alone.

“That’s why knowing something about buprenorphine is so important,” Dr. Meier said.

Dr. Meier and Dr. Paauw are on the editorial board for Internal Medicine News. Dr. Merlin is a trainer for the Center to Advance Palliative Care, which Dr. Meier founded.
 

In this special supplement to Federal Practitioner, Dr. Jameel Muzaffar, MD shares insights into a second-line treatment option for previously treated radioiodine-refractory differentiated thyroid cancer (DTC), along with an exploratory analysis of BRAF mutation status. It discusses the challenges associated with metastatic DTC and the significance of understanding factors like BRAF mutation status in treatment decisions. Additionally, it highlights the efficacy and safety profiles of the treatment option.

Click here to Read More

CA-3326

In this special supplement to Federal Practitioner, Dr. Jameel Muzaffar, MD shares insights into a second-line treatment option for previously treated radioiodine-refractory differentiated thyroid cancer (DTC), along with an exploratory analysis of BRAF mutation status. It discusses the challenges associated with metastatic DTC and the significance of understanding factors like BRAF mutation status in treatment decisions. Additionally, it highlights the efficacy and safety profiles of the treatment option.

Click here to Read More

CA-3326

In this special supplement to Federal Practitioner, Dr. Jameel Muzaffar, MD shares insights into a second-line treatment option for previously treated radioiodine-refractory differentiated thyroid cancer (DTC), along with an exploratory analysis of BRAF mutation status. It discusses the challenges associated with metastatic DTC and the significance of understanding factors like BRAF mutation status in treatment decisions. Additionally, it highlights the efficacy and safety profiles of the treatment option.

Click here to Read More

CA-3326

The effectiveness of massage therapy for a range of painful adult health conditions remains uncertain. Despite hundreds of randomized clinical trials and dozens of systematic reviews, few studies have offered conclusions based on more than low-certainty evidence, a systematic review in JAMA Network Open has shown (doi: 10.1001/jamanetworkopen.2024.22259).

Some moderate-certainty evidence, however, suggested massage therapy may alleviate pain related to such conditions as low-back problems, labor, and breast cancer surgery, concluded a group led by Selene Mak, PhD, MPH, program manager in the Evidence Synthesis Program at the Veterans Health Administration Greater Los Angeles Healthcare System in Los Angeles, California.

“More high-quality randomized clinical trials are needed to provide a stronger evidence base to assess the effect of massage therapy on pain,” Dr. Mak and colleagues wrote.

The review updates a previous Veterans Affairs evidence map covering reviews of massage therapy for pain published through 2018.

To categorize the evidence base for decision-making by policymakers and practitioners, the VA requested an updated evidence map of reviews to answer the question: “What is the certainty of evidence in systematic reviews of massage therapy for pain?”
 

The Analysis

The current review included studies published from 2018 to 2023 with formal ratings of evidence quality or certainty, excluding other nonpharmacologic techniques such as sports massage therapy, osteopathy, dry cupping, dry needling, and internal massage therapy, and self-administered techniques such as foam rolling.

Of 129 systematic reviews, only 41 formally rated evidence quality, and 17 were evidence-mapped for pain across 13 health states: cancer, back, neck and mechanical neck issues, fibromyalgia, labor, myofascial, palliative care need, plantar fasciitis, postoperative, post breast cancer surgery, and post cesarean/postpartum.

The investigators found no conclusions based on a high certainty of evidence, while seven based conclusions on moderate-certainty evidence. All remaining conclusions were rated as having low- or very-low-certainty evidence.

The priority, they added, should be studies comparing massage therapy with other recommended, accepted, and active therapies for pain and should have sufficiently long follow-up to allow any nonspecific outcomes to dissipate, At least 6 months’ follow-up has been suggested for studies of chronic pain.

While massage therapy is considered safe, in patients with central sensitizations more aggressive treatments may cause a flare of myofascial pain.

This study was funded by the Department of Veterans Affairs Health Services Research and Development. The authors had no conflicts of interest to disclose.

The effectiveness of massage therapy for a range of painful adult health conditions remains uncertain. Despite hundreds of randomized clinical trials and dozens of systematic reviews, few studies have offered conclusions based on more than low-certainty evidence, a systematic review in JAMA Network Open has shown (doi: 10.1001/jamanetworkopen.2024.22259).

Some moderate-certainty evidence, however, suggested massage therapy may alleviate pain related to such conditions as low-back problems, labor, and breast cancer surgery, concluded a group led by Selene Mak, PhD, MPH, program manager in the Evidence Synthesis Program at the Veterans Health Administration Greater Los Angeles Healthcare System in Los Angeles, California.

“More high-quality randomized clinical trials are needed to provide a stronger evidence base to assess the effect of massage therapy on pain,” Dr. Mak and colleagues wrote.

The review updates a previous Veterans Affairs evidence map covering reviews of massage therapy for pain published through 2018.

To categorize the evidence base for decision-making by policymakers and practitioners, the VA requested an updated evidence map of reviews to answer the question: “What is the certainty of evidence in systematic reviews of massage therapy for pain?”
 

The Analysis

The current review included studies published from 2018 to 2023 with formal ratings of evidence quality or certainty, excluding other nonpharmacologic techniques such as sports massage therapy, osteopathy, dry cupping, dry needling, and internal massage therapy, and self-administered techniques such as foam rolling.

Of 129 systematic reviews, only 41 formally rated evidence quality, and 17 were evidence-mapped for pain across 13 health states: cancer, back, neck and mechanical neck issues, fibromyalgia, labor, myofascial, palliative care need, plantar fasciitis, postoperative, post breast cancer surgery, and post cesarean/postpartum.

The investigators found no conclusions based on a high certainty of evidence, while seven based conclusions on moderate-certainty evidence. All remaining conclusions were rated as having low- or very-low-certainty evidence.

The priority, they added, should be studies comparing massage therapy with other recommended, accepted, and active therapies for pain and should have sufficiently long follow-up to allow any nonspecific outcomes to dissipate, At least 6 months’ follow-up has been suggested for studies of chronic pain.

While massage therapy is considered safe, in patients with central sensitizations more aggressive treatments may cause a flare of myofascial pain.

This study was funded by the Department of Veterans Affairs Health Services Research and Development. The authors had no conflicts of interest to disclose.

The effectiveness of massage therapy for a range of painful adult health conditions remains uncertain. Despite hundreds of randomized clinical trials and dozens of systematic reviews, few studies have offered conclusions based on more than low-certainty evidence, a systematic review in JAMA Network Open has shown (doi: 10.1001/jamanetworkopen.2024.22259).

Some moderate-certainty evidence, however, suggested massage therapy may alleviate pain related to such conditions as low-back problems, labor, and breast cancer surgery, concluded a group led by Selene Mak, PhD, MPH, program manager in the Evidence Synthesis Program at the Veterans Health Administration Greater Los Angeles Healthcare System in Los Angeles, California.

“More high-quality randomized clinical trials are needed to provide a stronger evidence base to assess the effect of massage therapy on pain,” Dr. Mak and colleagues wrote.

The review updates a previous Veterans Affairs evidence map covering reviews of massage therapy for pain published through 2018.

To categorize the evidence base for decision-making by policymakers and practitioners, the VA requested an updated evidence map of reviews to answer the question: “What is the certainty of evidence in systematic reviews of massage therapy for pain?”
 

The Analysis

The current review included studies published from 2018 to 2023 with formal ratings of evidence quality or certainty, excluding other nonpharmacologic techniques such as sports massage therapy, osteopathy, dry cupping, dry needling, and internal massage therapy, and self-administered techniques such as foam rolling.

Of 129 systematic reviews, only 41 formally rated evidence quality, and 17 were evidence-mapped for pain across 13 health states: cancer, back, neck and mechanical neck issues, fibromyalgia, labor, myofascial, palliative care need, plantar fasciitis, postoperative, post breast cancer surgery, and post cesarean/postpartum.

The investigators found no conclusions based on a high certainty of evidence, while seven based conclusions on moderate-certainty evidence. All remaining conclusions were rated as having low- or very-low-certainty evidence.

The priority, they added, should be studies comparing massage therapy with other recommended, accepted, and active therapies for pain and should have sufficiently long follow-up to allow any nonspecific outcomes to dissipate, At least 6 months’ follow-up has been suggested for studies of chronic pain.

While massage therapy is considered safe, in patients with central sensitizations more aggressive treatments may cause a flare of myofascial pain.

This study was funded by the Department of Veterans Affairs Health Services Research and Development. The authors had no conflicts of interest to disclose.

A growing body of evidence has shown that people who regularly take aspirin have a lower risk for colorectal cancer (CRC) and are less likely to die if they do develop the disease.

A 2020 meta-analysis, for instance, found that 325 mg of daily aspirin — the typical dose in a single tablet — conferred a 35% reduced risk of developing CRC, and a highly cited The Lancet study from 2010 found that a low dose of daily aspirin reduced the incidence of colon cancer by 24% and colon cancer deaths by 35% over 20 years.

The evidence surrounding aspirin and CRC is so intriguing that more than 70,000 people are currently participating in more than two dozen clinical studies worldwide, putting aspirin through its paces as an intervention in CRC.

But what, exactly, is aspirin doing?

We know that aspirin inhibits cyclooxygenase (COX) enzymes — COX-1 and COX-2, specifically — and that the COX-2 pathway is implicated in the development and progression of CRC, explained Marco Scarpa, MD, PhD, staff surgeon at the University of Padova in Padova, Italy.

“However, the new thing we’ve found is that aspirin may have a direct role in enhancing immunosurveillance,” Dr. Scarpa said in an interview.

In April, Dr. Scarpa’s team published a paper in Cancer describing a mechanism that provides deeper insight into the aspirin-CRC connection.

Dr. Scarpa heads up the IMMUNOREACT study group, a collaboration of dozens of researchers across Italy running studies on immunosurveillance in rectal cancer. In the baseline study, IMMUNOREACT 1, the team created and analyzed a database of records from 238 patients who underwent surgery for CRC at the Azienda Ospedale Università di Padova, Padova, Italy, from 2015 to 2019.

Using the same database, the latest findings from IMMUNOREACT 7 focused on the fate of the 31 patients (13%) who used aspirin regularly.

The researchers found that regular aspirin use did not appear to affect colorectal tumor stage at diagnosis, but tumor grading was significantly lower overall, especially in patients with BRAF mutations. Regular aspirin users were also less likely to have nodal metastases and metastatic lymph nodes, and this effect was more pronounced in patients with proximal (right-sided) colon cancer vs distal (left-sided).

Most notably, IMMUNOREACT 7 revealed that aspirin has beneficial effects on the CRC immune microenvironment.

The team found that aspirin directly boosts the presence of antigens on gastrointestinal epithelial tumor cells, which can direct the body’s immune response to combat the cancer.

At a macro level, the aspirin users in the study were more likely to have high levels of tumor-infiltrating lymphocytes (TILs). Dr. Scarpa’s team had previously shown that high levels of CD8+ and CD3+ TILs were predictive of successful neoadjuvant therapy in rectal cancer.

Cytotoxic CD8+ T cells are central to the anticancer immune response, and in the latest study, a high ratio of CD8+/CD3+ T cells was more common in aspirin users, suggesting a stronger presence of cancer-killing CD8+ cells. Expression of CD8 beta+, an activation marker of CD8+ cells, was also enhanced in aspirin users.

The most significant discovery, according to Dr. Scarpa, was that aspirin users were more likely to show high expression of CD80 on the surface of their rectal epithelial cells.

CD80 is a molecule that allows T cells to identify the tumor cell as foreign and kill it. Although cancer cells can downregulate their CD80 to avoid detection by T cells, the study suggests that aspirin appears to help foil this strategy by boosting the production of CD80 on the surface of the tumor cells.

The researchers confirmed the clinical findings by showing that aspirin increased CD80 gene expression in lab-cultivated CRC cells.

“We didn’t expect the activation through CD80,” said Dr. Scarpa. “This means that aspirin can act on this very first interaction between the epithelial cell and the CD8+ lymphocyte.”

Overall, these new data suggest that aspirin helps activate the immune system, which helps explain its potential chemopreventive effect in CRC.

However, one puzzling result was that aspirin boosted expression of PD-L1 genes in the CRC cells, said Joanna Davies, DPhil, an immunologist who heads up the San Diego Biomedical Research Institute, San Diego, California, and was not involved in the study.

PD-L1 serves as an “off” switch for patrolling T cells, which protects the tumor cell from being recognized.

“If aspirin is inducing PD-L1 on cancer cells, that is a potential problem,” said Dr. Davies. “An ideal therapy might be the combination of aspirin to enhance the CD8 T cells in the tumor and immune checkpoint blockade to block PD-L1.”

David Kerr, CBE, MD, DSc, agreed that high-dose aspirin plus immunotherapy might be “a wee bit more effective.” However, the combination would be blocked by the economics of drug development: “Will anybody ever do a trial of 10,000 patients to prove that? Not on your nelly,” said Dr. Kerr, professor of cancer medicine at the University of Oxford, Oxford, England.

Despite the small patient numbers in the study, Dr. Kerr felt encouraged by the IMMUNOREACT analysis. “It’s a plausible piece of science and some quite promising work on the tumor immune microenvironment and the effects of aspirin on it,” Dr. Kerr said in a recent commentary for this news organization.

Dr. Scarpa and Dr. Davies had no conflicts of interest to declare.

A version of this article appeared on Medscape.com .

A growing body of evidence has shown that people who regularly take aspirin have a lower risk for colorectal cancer (CRC) and are less likely to die if they do develop the disease.

A 2020 meta-analysis, for instance, found that 325 mg of daily aspirin — the typical dose in a single tablet — conferred a 35% reduced risk of developing CRC, and a highly cited The Lancet study from 2010 found that a low dose of daily aspirin reduced the incidence of colon cancer by 24% and colon cancer deaths by 35% over 20 years.

The evidence surrounding aspirin and CRC is so intriguing that more than 70,000 people are currently participating in more than two dozen clinical studies worldwide, putting aspirin through its paces as an intervention in CRC.

But what, exactly, is aspirin doing?

We know that aspirin inhibits cyclooxygenase (COX) enzymes — COX-1 and COX-2, specifically — and that the COX-2 pathway is implicated in the development and progression of CRC, explained Marco Scarpa, MD, PhD, staff surgeon at the University of Padova in Padova, Italy.

“However, the new thing we’ve found is that aspirin may have a direct role in enhancing immunosurveillance,” Dr. Scarpa said in an interview.

In April, Dr. Scarpa’s team published a paper in Cancer describing a mechanism that provides deeper insight into the aspirin-CRC connection.

Dr. Scarpa heads up the IMMUNOREACT study group, a collaboration of dozens of researchers across Italy running studies on immunosurveillance in rectal cancer. In the baseline study, IMMUNOREACT 1, the team created and analyzed a database of records from 238 patients who underwent surgery for CRC at the Azienda Ospedale Università di Padova, Padova, Italy, from 2015 to 2019.

Using the same database, the latest findings from IMMUNOREACT 7 focused on the fate of the 31 patients (13%) who used aspirin regularly.

The researchers found that regular aspirin use did not appear to affect colorectal tumor stage at diagnosis, but tumor grading was significantly lower overall, especially in patients with BRAF mutations. Regular aspirin users were also less likely to have nodal metastases and metastatic lymph nodes, and this effect was more pronounced in patients with proximal (right-sided) colon cancer vs distal (left-sided).

Most notably, IMMUNOREACT 7 revealed that aspirin has beneficial effects on the CRC immune microenvironment.

The team found that aspirin directly boosts the presence of antigens on gastrointestinal epithelial tumor cells, which can direct the body’s immune response to combat the cancer.

At a macro level, the aspirin users in the study were more likely to have high levels of tumor-infiltrating lymphocytes (TILs). Dr. Scarpa’s team had previously shown that high levels of CD8+ and CD3+ TILs were predictive of successful neoadjuvant therapy in rectal cancer.

Cytotoxic CD8+ T cells are central to the anticancer immune response, and in the latest study, a high ratio of CD8+/CD3+ T cells was more common in aspirin users, suggesting a stronger presence of cancer-killing CD8+ cells. Expression of CD8 beta+, an activation marker of CD8+ cells, was also enhanced in aspirin users.

The most significant discovery, according to Dr. Scarpa, was that aspirin users were more likely to show high expression of CD80 on the surface of their rectal epithelial cells.

CD80 is a molecule that allows T cells to identify the tumor cell as foreign and kill it. Although cancer cells can downregulate their CD80 to avoid detection by T cells, the study suggests that aspirin appears to help foil this strategy by boosting the production of CD80 on the surface of the tumor cells.

The researchers confirmed the clinical findings by showing that aspirin increased CD80 gene expression in lab-cultivated CRC cells.

“We didn’t expect the activation through CD80,” said Dr. Scarpa. “This means that aspirin can act on this very first interaction between the epithelial cell and the CD8+ lymphocyte.”

Overall, these new data suggest that aspirin helps activate the immune system, which helps explain its potential chemopreventive effect in CRC.

However, one puzzling result was that aspirin boosted expression of PD-L1 genes in the CRC cells, said Joanna Davies, DPhil, an immunologist who heads up the San Diego Biomedical Research Institute, San Diego, California, and was not involved in the study.

PD-L1 serves as an “off” switch for patrolling T cells, which protects the tumor cell from being recognized.

“If aspirin is inducing PD-L1 on cancer cells, that is a potential problem,” said Dr. Davies. “An ideal therapy might be the combination of aspirin to enhance the CD8 T cells in the tumor and immune checkpoint blockade to block PD-L1.”

David Kerr, CBE, MD, DSc, agreed that high-dose aspirin plus immunotherapy might be “a wee bit more effective.” However, the combination would be blocked by the economics of drug development: “Will anybody ever do a trial of 10,000 patients to prove that? Not on your nelly,” said Dr. Kerr, professor of cancer medicine at the University of Oxford, Oxford, England.

Despite the small patient numbers in the study, Dr. Kerr felt encouraged by the IMMUNOREACT analysis. “It’s a plausible piece of science and some quite promising work on the tumor immune microenvironment and the effects of aspirin on it,” Dr. Kerr said in a recent commentary for this news organization.

Dr. Scarpa and Dr. Davies had no conflicts of interest to declare.

A version of this article appeared on Medscape.com .

A growing body of evidence has shown that people who regularly take aspirin have a lower risk for colorectal cancer (CRC) and are less likely to die if they do develop the disease.

A 2020 meta-analysis, for instance, found that 325 mg of daily aspirin — the typical dose in a single tablet — conferred a 35% reduced risk of developing CRC, and a highly cited The Lancet study from 2010 found that a low dose of daily aspirin reduced the incidence of colon cancer by 24% and colon cancer deaths by 35% over 20 years.

The evidence surrounding aspirin and CRC is so intriguing that more than 70,000 people are currently participating in more than two dozen clinical studies worldwide, putting aspirin through its paces as an intervention in CRC.

But what, exactly, is aspirin doing?

We know that aspirin inhibits cyclooxygenase (COX) enzymes — COX-1 and COX-2, specifically — and that the COX-2 pathway is implicated in the development and progression of CRC, explained Marco Scarpa, MD, PhD, staff surgeon at the University of Padova in Padova, Italy.

“However, the new thing we’ve found is that aspirin may have a direct role in enhancing immunosurveillance,” Dr. Scarpa said in an interview.

In April, Dr. Scarpa’s team published a paper in Cancer describing a mechanism that provides deeper insight into the aspirin-CRC connection.

Dr. Scarpa heads up the IMMUNOREACT study group, a collaboration of dozens of researchers across Italy running studies on immunosurveillance in rectal cancer. In the baseline study, IMMUNOREACT 1, the team created and analyzed a database of records from 238 patients who underwent surgery for CRC at the Azienda Ospedale Università di Padova, Padova, Italy, from 2015 to 2019.

Using the same database, the latest findings from IMMUNOREACT 7 focused on the fate of the 31 patients (13%) who used aspirin regularly.

The researchers found that regular aspirin use did not appear to affect colorectal tumor stage at diagnosis, but tumor grading was significantly lower overall, especially in patients with BRAF mutations. Regular aspirin users were also less likely to have nodal metastases and metastatic lymph nodes, and this effect was more pronounced in patients with proximal (right-sided) colon cancer vs distal (left-sided).

Most notably, IMMUNOREACT 7 revealed that aspirin has beneficial effects on the CRC immune microenvironment.

The team found that aspirin directly boosts the presence of antigens on gastrointestinal epithelial tumor cells, which can direct the body’s immune response to combat the cancer.

At a macro level, the aspirin users in the study were more likely to have high levels of tumor-infiltrating lymphocytes (TILs). Dr. Scarpa’s team had previously shown that high levels of CD8+ and CD3+ TILs were predictive of successful neoadjuvant therapy in rectal cancer.

Cytotoxic CD8+ T cells are central to the anticancer immune response, and in the latest study, a high ratio of CD8+/CD3+ T cells was more common in aspirin users, suggesting a stronger presence of cancer-killing CD8+ cells. Expression of CD8 beta+, an activation marker of CD8+ cells, was also enhanced in aspirin users.

The most significant discovery, according to Dr. Scarpa, was that aspirin users were more likely to show high expression of CD80 on the surface of their rectal epithelial cells.

CD80 is a molecule that allows T cells to identify the tumor cell as foreign and kill it. Although cancer cells can downregulate their CD80 to avoid detection by T cells, the study suggests that aspirin appears to help foil this strategy by boosting the production of CD80 on the surface of the tumor cells.

The researchers confirmed the clinical findings by showing that aspirin increased CD80 gene expression in lab-cultivated CRC cells.

“We didn’t expect the activation through CD80,” said Dr. Scarpa. “This means that aspirin can act on this very first interaction between the epithelial cell and the CD8+ lymphocyte.”

Overall, these new data suggest that aspirin helps activate the immune system, which helps explain its potential chemopreventive effect in CRC.

However, one puzzling result was that aspirin boosted expression of PD-L1 genes in the CRC cells, said Joanna Davies, DPhil, an immunologist who heads up the San Diego Biomedical Research Institute, San Diego, California, and was not involved in the study.

PD-L1 serves as an “off” switch for patrolling T cells, which protects the tumor cell from being recognized.

“If aspirin is inducing PD-L1 on cancer cells, that is a potential problem,” said Dr. Davies. “An ideal therapy might be the combination of aspirin to enhance the CD8 T cells in the tumor and immune checkpoint blockade to block PD-L1.”

David Kerr, CBE, MD, DSc, agreed that high-dose aspirin plus immunotherapy might be “a wee bit more effective.” However, the combination would be blocked by the economics of drug development: “Will anybody ever do a trial of 10,000 patients to prove that? Not on your nelly,” said Dr. Kerr, professor of cancer medicine at the University of Oxford, Oxford, England.

Despite the small patient numbers in the study, Dr. Kerr felt encouraged by the IMMUNOREACT analysis. “It’s a plausible piece of science and some quite promising work on the tumor immune microenvironment and the effects of aspirin on it,” Dr. Kerr said in a recent commentary for this news organization.

Dr. Scarpa and Dr. Davies had no conflicts of interest to declare.

A version of this article appeared on Medscape.com .

A recent report by this news organization of a vitamin D clinical practice guideline released by the Endocrine Society in June triggered an outpouring of objections in the comments section from doctors and other readers.

A society press release listed the key new recommendations on the use of vitamin D supplementation and screening to reduce disease risks in individuals without established indications for such treatment or testing:

• For healthy adults younger than 75, no supplementation at doses above the recommended dietary intakes.
• Populations that may benefit from higher doses include: children and adolescents 18 and younger to prevent rickets and to reduce risk for respiratory infection, individuals 75 and older to possibly lower mortality risk, “pregnant people” to potentially reduce various risks, and people with prediabetes to potentially reduce risk of progression.
• No routine testing for 25-hydroxyvitamin D levels because outcome-specific benefits based on those levels have not been identified (including screening in people with dark complexion or obesity).
• Based on insufficient evidence, the panel could not determine specific blood-level thresholds for 25-hydroxyvitamin D for adequacy or for target levels for disease prevention.

This news organization covered the guideline release and simultaneous presentation at the Endocrine Society annual meeting. In response to the coverage, more than 200 doctors and other readers expressed concerns about the guideline, and some said outright that they would not follow it (readers quoted below are identified by the usernames they registered with on the website).

One reader who posted as Dr. Joseph Destefano went so far as to call the guideline “dangerous” and “almost ... evil.” Ironically, some readers attacked this news organization, thinking that the coverage implied an endorsement, rather than a news report.
 

Ignores Potential Benefits

Although the guideline is said to be for people who are “otherwise healthy” (other than the exceptions noted above), many readers were concerned that the recommendations ignore the potential benefits of supplementation for other health conditions relevant to patients and other populations.

“They address issues dealing only with endocrinology and bone health for the most part,” Dr. Emilio Gonzalez wrote. “However, vitamin D insufficiency and deficiency are not rare, and they impact the treatment of autoimmune disorders, chronic pain control, immunosuppression, cancer prevention, cardiovascular health, etc. There is plenty of literature in this regard.”

“They make these claims as if quality studies contradicting their guidelines have not been out there for years,” Dr. Brian Batcheldor said. “What about the huge demographic with diseases that impact intestinal absorption, eg, Crohn’s and celiac disease, cystic fibrosis, and ulcerative colitis? What about the one in nine that now have autoimmune diseases still awaiting diagnosis? What about night workers or anyone with more restricted access to sun exposure? How about those whose cultural or religious dress code limit skin exposure?”

The latter group was also mentioned in a post from Dr. Eve Finkelstein who said, “They don’t take into account women who are totally covered for religious reasons. They have no skin other than part of their face exposed. It does not make sense not to supplement them. Ignoring women’s health needs seems to be the norm.”

“I don’t think they considered the oral health effects of vitamin D deficiency,” pointed out commenter Corie Lewis. “Excess dental calculus (tartar) from excess calcium/phosphate in saliva significantly increases an individual’s periodontal disease risks (gum disease), and low saliva calcium/phosphate increases dental caries (cavities) risks, which generally indicates an imbalance of the oral microbiome. Vitamin D can help create balance and reduce those oral health risks.”

Noted Kimberley Morris-Windisch, “Having worked in rheumatology and pain for most of my career, I have seen too many people benefit from correcting deficiency of vitamin D. To ignore this is to miss opportunities to improve patient health.” Furthermore, “I find it unlikely that it would only improve mortality after age 75. That makes no sense.”

“Also,” she added, “what is the number [needed] to harm? In my 25 years, I have seen vitamin D toxicity once and an excessively high level without symptoms one other time.”

“WHY? Just WHY?” lamented Anne Kinchen. “Low levels in pregnant women have long-term effects on the developing fetus — higher and earlier rates of osteopenia in female children, weaker immune systems overall. There are just SO many reasons to test. These guidelines for no testing are absurd!”
 

No Screening, No Need for Decision-Making?

Several readers questioned the society’s rationale for not screening, as expressed by session moderator Clifford J. Rosen, MD, director of Clinical and Translational Research and senior scientist at Maine Medical Center Research Institute, Scarborough, Maine.

“When clinicians measure vitamin D, then they’re forced to make a decision what to do about it,” Dr. Rosen said. “That’s where questions about the levels come in. And that’s a big problem. So what the panel’s saying is, don’t screen. ... This really gets to the heart of the issue, because we have no data that there’s anything about screening that allows us to improve quality of life. ... Screening is probably not worthwhile in any age group.”

Among the reader comments in this regard:

“So misguided. Don’t look because we don’t know what do to with data. That’s the message this article exposes. The recommendation is do nothing. But, doing nothing IS an action — not a default.” (Lisa Tracy)

“So now, you will not screen for vitamin D because you do not know what to do next? See a naturopathic doctor — we know what to do next!” (Dr. Joyce Roberson)

“Gee, how do we treat it? ... What to do? Sounds incompetent at minimum. I suspect it’s vital, easy, and inexpensive ... so hide it.” (Holly Kohley)

“Just because we do not know is not a rationale for not testing. The opposite should be done.” (Dr. JJ Gold)
 

Caters to Industry?

Many commentators intimated that pharma and/or insurance company considerations played a role in the recommendations. Their comments included the following:

“I have been under the impression people do routine checkups to verify there are no hidden problems. If only some testing is done, the probability of not finding a problem is huge. ... Preventive healthcare should be looking for something to prevent instead of waiting until they can cure it. Of course, it might come back to ‘follow the money.’ It is much more profitable to diagnose and treat than it is to prevent.” (Grace Kyser)

“The current irrational ‘recommendation’ gives insurance companies an excuse to deny ALL tests of vitamin D — even if the proper code is supplied. The result is — people suffer. This recommendation does harm!” (Dr JJ Gold)

“Essentially, they are saying let’s not screen ‘healthy’ individuals and ignore it altogether. Better to wait till they’re old, pregnant, or already sick and diagnosed with a disease. This is the problem with the healthcare in this country.” (Brittney Lesher)

“Until allopathic medicine stops waiting for severe symptoms to develop before even screening for potential health problems, the most expensive healthcare (aka, sick care) system in the world will continue to be content to focus on medical emergencies and ignore prevention. ...” (Dean Raffelock)

“Don’t test? Are you kidding me? Especially when people are supplementing? That is akin to taking a blood pressure medication without measuring blood pressures! ... Don’t test? Don’t supplement? ... I have only one explanation for such nonsense: Pharma lives off sick people, not healthy ones.” (Georg Schlomka)

On a somewhat conciliatory and pointed note, Dr Francesca Luna-Rudin commented, “I would like to remind all of my fellow physicians that recommendations should be regarded as just that, a ‘recommendation.’ As doctors, we can use guidelines and recommendations in our practice, but if a new one is presented that does not make sense or would lead to harm based on our education and training, then we are not bound to follow it!”

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

A recent report by this news organization of a vitamin D clinical practice guideline released by the Endocrine Society in June triggered an outpouring of objections in the comments section from doctors and other readers.

A society press release listed the key new recommendations on the use of vitamin D supplementation and screening to reduce disease risks in individuals without established indications for such treatment or testing:

• For healthy adults younger than 75, no supplementation at doses above the recommended dietary intakes.
• Populations that may benefit from higher doses include: children and adolescents 18 and younger to prevent rickets and to reduce risk for respiratory infection, individuals 75 and older to possibly lower mortality risk, “pregnant people” to potentially reduce various risks, and people with prediabetes to potentially reduce risk of progression.
• No routine testing for 25-hydroxyvitamin D levels because outcome-specific benefits based on those levels have not been identified (including screening in people with dark complexion or obesity).
• Based on insufficient evidence, the panel could not determine specific blood-level thresholds for 25-hydroxyvitamin D for adequacy or for target levels for disease prevention.

This news organization covered the guideline release and simultaneous presentation at the Endocrine Society annual meeting. In response to the coverage, more than 200 doctors and other readers expressed concerns about the guideline, and some said outright that they would not follow it (readers quoted below are identified by the usernames they registered with on the website).

One reader who posted as Dr. Joseph Destefano went so far as to call the guideline “dangerous” and “almost ... evil.” Ironically, some readers attacked this news organization, thinking that the coverage implied an endorsement, rather than a news report.
 

Ignores Potential Benefits

Although the guideline is said to be for people who are “otherwise healthy” (other than the exceptions noted above), many readers were concerned that the recommendations ignore the potential benefits of supplementation for other health conditions relevant to patients and other populations.

“They address issues dealing only with endocrinology and bone health for the most part,” Dr. Emilio Gonzalez wrote. “However, vitamin D insufficiency and deficiency are not rare, and they impact the treatment of autoimmune disorders, chronic pain control, immunosuppression, cancer prevention, cardiovascular health, etc. There is plenty of literature in this regard.”

“They make these claims as if quality studies contradicting their guidelines have not been out there for years,” Dr. Brian Batcheldor said. “What about the huge demographic with diseases that impact intestinal absorption, eg, Crohn’s and celiac disease, cystic fibrosis, and ulcerative colitis? What about the one in nine that now have autoimmune diseases still awaiting diagnosis? What about night workers or anyone with more restricted access to sun exposure? How about those whose cultural or religious dress code limit skin exposure?”

The latter group was also mentioned in a post from Dr. Eve Finkelstein who said, “They don’t take into account women who are totally covered for religious reasons. They have no skin other than part of their face exposed. It does not make sense not to supplement them. Ignoring women’s health needs seems to be the norm.”

“I don’t think they considered the oral health effects of vitamin D deficiency,” pointed out commenter Corie Lewis. “Excess dental calculus (tartar) from excess calcium/phosphate in saliva significantly increases an individual’s periodontal disease risks (gum disease), and low saliva calcium/phosphate increases dental caries (cavities) risks, which generally indicates an imbalance of the oral microbiome. Vitamin D can help create balance and reduce those oral health risks.”

Noted Kimberley Morris-Windisch, “Having worked in rheumatology and pain for most of my career, I have seen too many people benefit from correcting deficiency of vitamin D. To ignore this is to miss opportunities to improve patient health.” Furthermore, “I find it unlikely that it would only improve mortality after age 75. That makes no sense.”

“Also,” she added, “what is the number [needed] to harm? In my 25 years, I have seen vitamin D toxicity once and an excessively high level without symptoms one other time.”

“WHY? Just WHY?” lamented Anne Kinchen. “Low levels in pregnant women have long-term effects on the developing fetus — higher and earlier rates of osteopenia in female children, weaker immune systems overall. There are just SO many reasons to test. These guidelines for no testing are absurd!”
 

No Screening, No Need for Decision-Making?

Several readers questioned the society’s rationale for not screening, as expressed by session moderator Clifford J. Rosen, MD, director of Clinical and Translational Research and senior scientist at Maine Medical Center Research Institute, Scarborough, Maine.

“When clinicians measure vitamin D, then they’re forced to make a decision what to do about it,” Dr. Rosen said. “That’s where questions about the levels come in. And that’s a big problem. So what the panel’s saying is, don’t screen. ... This really gets to the heart of the issue, because we have no data that there’s anything about screening that allows us to improve quality of life. ... Screening is probably not worthwhile in any age group.”

Among the reader comments in this regard:

“So misguided. Don’t look because we don’t know what do to with data. That’s the message this article exposes. The recommendation is do nothing. But, doing nothing IS an action — not a default.” (Lisa Tracy)

“So now, you will not screen for vitamin D because you do not know what to do next? See a naturopathic doctor — we know what to do next!” (Dr. Joyce Roberson)

“Gee, how do we treat it? ... What to do? Sounds incompetent at minimum. I suspect it’s vital, easy, and inexpensive ... so hide it.” (Holly Kohley)

“Just because we do not know is not a rationale for not testing. The opposite should be done.” (Dr. JJ Gold)
 

Caters to Industry?

Many commentators intimated that pharma and/or insurance company considerations played a role in the recommendations. Their comments included the following:

“I have been under the impression people do routine checkups to verify there are no hidden problems. If only some testing is done, the probability of not finding a problem is huge. ... Preventive healthcare should be looking for something to prevent instead of waiting until they can cure it. Of course, it might come back to ‘follow the money.’ It is much more profitable to diagnose and treat than it is to prevent.” (Grace Kyser)

“The current irrational ‘recommendation’ gives insurance companies an excuse to deny ALL tests of vitamin D — even if the proper code is supplied. The result is — people suffer. This recommendation does harm!” (Dr JJ Gold)

“Essentially, they are saying let’s not screen ‘healthy’ individuals and ignore it altogether. Better to wait till they’re old, pregnant, or already sick and diagnosed with a disease. This is the problem with the healthcare in this country.” (Brittney Lesher)

“Until allopathic medicine stops waiting for severe symptoms to develop before even screening for potential health problems, the most expensive healthcare (aka, sick care) system in the world will continue to be content to focus on medical emergencies and ignore prevention. ...” (Dean Raffelock)

“Don’t test? Are you kidding me? Especially when people are supplementing? That is akin to taking a blood pressure medication without measuring blood pressures! ... Don’t test? Don’t supplement? ... I have only one explanation for such nonsense: Pharma lives off sick people, not healthy ones.” (Georg Schlomka)

On a somewhat conciliatory and pointed note, Dr Francesca Luna-Rudin commented, “I would like to remind all of my fellow physicians that recommendations should be regarded as just that, a ‘recommendation.’ As doctors, we can use guidelines and recommendations in our practice, but if a new one is presented that does not make sense or would lead to harm based on our education and training, then we are not bound to follow it!”

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

A recent report by this news organization of a vitamin D clinical practice guideline released by the Endocrine Society in June triggered an outpouring of objections in the comments section from doctors and other readers.

A society press release listed the key new recommendations on the use of vitamin D supplementation and screening to reduce disease risks in individuals without established indications for such treatment or testing:

• For healthy adults younger than 75, no supplementation at doses above the recommended dietary intakes.
• Populations that may benefit from higher doses include: children and adolescents 18 and younger to prevent rickets and to reduce risk for respiratory infection, individuals 75 and older to possibly lower mortality risk, “pregnant people” to potentially reduce various risks, and people with prediabetes to potentially reduce risk of progression.
• No routine testing for 25-hydroxyvitamin D levels because outcome-specific benefits based on those levels have not been identified (including screening in people with dark complexion or obesity).
• Based on insufficient evidence, the panel could not determine specific blood-level thresholds for 25-hydroxyvitamin D for adequacy or for target levels for disease prevention.

This news organization covered the guideline release and simultaneous presentation at the Endocrine Society annual meeting. In response to the coverage, more than 200 doctors and other readers expressed concerns about the guideline, and some said outright that they would not follow it (readers quoted below are identified by the usernames they registered with on the website).

One reader who posted as Dr. Joseph Destefano went so far as to call the guideline “dangerous” and “almost ... evil.” Ironically, some readers attacked this news organization, thinking that the coverage implied an endorsement, rather than a news report.
 

Ignores Potential Benefits

Although the guideline is said to be for people who are “otherwise healthy” (other than the exceptions noted above), many readers were concerned that the recommendations ignore the potential benefits of supplementation for other health conditions relevant to patients and other populations.

“They address issues dealing only with endocrinology and bone health for the most part,” Dr. Emilio Gonzalez wrote. “However, vitamin D insufficiency and deficiency are not rare, and they impact the treatment of autoimmune disorders, chronic pain control, immunosuppression, cancer prevention, cardiovascular health, etc. There is plenty of literature in this regard.”

“They make these claims as if quality studies contradicting their guidelines have not been out there for years,” Dr. Brian Batcheldor said. “What about the huge demographic with diseases that impact intestinal absorption, eg, Crohn’s and celiac disease, cystic fibrosis, and ulcerative colitis? What about the one in nine that now have autoimmune diseases still awaiting diagnosis? What about night workers or anyone with more restricted access to sun exposure? How about those whose cultural or religious dress code limit skin exposure?”

The latter group was also mentioned in a post from Dr. Eve Finkelstein who said, “They don’t take into account women who are totally covered for religious reasons. They have no skin other than part of their face exposed. It does not make sense not to supplement them. Ignoring women’s health needs seems to be the norm.”

“I don’t think they considered the oral health effects of vitamin D deficiency,” pointed out commenter Corie Lewis. “Excess dental calculus (tartar) from excess calcium/phosphate in saliva significantly increases an individual’s periodontal disease risks (gum disease), and low saliva calcium/phosphate increases dental caries (cavities) risks, which generally indicates an imbalance of the oral microbiome. Vitamin D can help create balance and reduce those oral health risks.”

Noted Kimberley Morris-Windisch, “Having worked in rheumatology and pain for most of my career, I have seen too many people benefit from correcting deficiency of vitamin D. To ignore this is to miss opportunities to improve patient health.” Furthermore, “I find it unlikely that it would only improve mortality after age 75. That makes no sense.”

“Also,” she added, “what is the number [needed] to harm? In my 25 years, I have seen vitamin D toxicity once and an excessively high level without symptoms one other time.”

“WHY? Just WHY?” lamented Anne Kinchen. “Low levels in pregnant women have long-term effects on the developing fetus — higher and earlier rates of osteopenia in female children, weaker immune systems overall. There are just SO many reasons to test. These guidelines for no testing are absurd!”
 

No Screening, No Need for Decision-Making?

Several readers questioned the society’s rationale for not screening, as expressed by session moderator Clifford J. Rosen, MD, director of Clinical and Translational Research and senior scientist at Maine Medical Center Research Institute, Scarborough, Maine.

“When clinicians measure vitamin D, then they’re forced to make a decision what to do about it,” Dr. Rosen said. “That’s where questions about the levels come in. And that’s a big problem. So what the panel’s saying is, don’t screen. ... This really gets to the heart of the issue, because we have no data that there’s anything about screening that allows us to improve quality of life. ... Screening is probably not worthwhile in any age group.”

Among the reader comments in this regard:

“So misguided. Don’t look because we don’t know what do to with data. That’s the message this article exposes. The recommendation is do nothing. But, doing nothing IS an action — not a default.” (Lisa Tracy)

“So now, you will not screen for vitamin D because you do not know what to do next? See a naturopathic doctor — we know what to do next!” (Dr. Joyce Roberson)

“Gee, how do we treat it? ... What to do? Sounds incompetent at minimum. I suspect it’s vital, easy, and inexpensive ... so hide it.” (Holly Kohley)

“Just because we do not know is not a rationale for not testing. The opposite should be done.” (Dr. JJ Gold)
 

Caters to Industry?

Many commentators intimated that pharma and/or insurance company considerations played a role in the recommendations. Their comments included the following:

“I have been under the impression people do routine checkups to verify there are no hidden problems. If only some testing is done, the probability of not finding a problem is huge. ... Preventive healthcare should be looking for something to prevent instead of waiting until they can cure it. Of course, it might come back to ‘follow the money.’ It is much more profitable to diagnose and treat than it is to prevent.” (Grace Kyser)

“The current irrational ‘recommendation’ gives insurance companies an excuse to deny ALL tests of vitamin D — even if the proper code is supplied. The result is — people suffer. This recommendation does harm!” (Dr JJ Gold)

“Essentially, they are saying let’s not screen ‘healthy’ individuals and ignore it altogether. Better to wait till they’re old, pregnant, or already sick and diagnosed with a disease. This is the problem with the healthcare in this country.” (Brittney Lesher)

“Until allopathic medicine stops waiting for severe symptoms to develop before even screening for potential health problems, the most expensive healthcare (aka, sick care) system in the world will continue to be content to focus on medical emergencies and ignore prevention. ...” (Dean Raffelock)

“Don’t test? Are you kidding me? Especially when people are supplementing? That is akin to taking a blood pressure medication without measuring blood pressures! ... Don’t test? Don’t supplement? ... I have only one explanation for such nonsense: Pharma lives off sick people, not healthy ones.” (Georg Schlomka)

On a somewhat conciliatory and pointed note, Dr Francesca Luna-Rudin commented, “I would like to remind all of my fellow physicians that recommendations should be regarded as just that, a ‘recommendation.’ As doctors, we can use guidelines and recommendations in our practice, but if a new one is presented that does not make sense or would lead to harm based on our education and training, then we are not bound to follow it!”

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

Parkinson’s disease (PD) and dementia with Lewy bodies are currently defined by clinical features, which can be heterogeneous and do not capture the presymptomatic phase of neurodegeneration.

Recent advances have enabled the detection of misfolded and aggregated alpha-synuclein protein (synucleinopathy) — a key pathologic feature of these diseases — allowing for earlier and more accurate diagnosis. This has led two international research groups to propose a major shift from a clinical to a biological definition of the disease.

Both groups emphasized the detection of alpha-synuclein through recently developed seed amplification assays as a key diagnostic and staging tool, although they differ in their approaches and criteria.
 

NSD-ISS

A team led by Tanya Simuni, MD, with Northwestern University, Chicago, proposed a biological definition that combines PD and dementia with Lewy bodies under the term neuronal alpha-synuclein disease (NSD).

NSD is defined by the presence during life of pathologic neuronal alpha-synuclein (S, the first biological anchor) in cerebrospinal fluid (CSF), regardless of the presence of any specific clinical syndrome. Individuals with pathologic neuronal alpha-synuclein aggregates are at a high risk for dopaminergic neuronal dysfunction (D, the second key biological anchor).

Dr. Simuni and colleagues also proposed the NSD integrated staging system (NSD-ISS) rooted in the S and D biological anchors coupled with the degree of functional impairment caused by clinical signs or symptoms.

Stages 0-1 occur without signs or symptoms and are defined by the presence of pathogenic variants in the SNCA gene (stage 0), S alone (stage 1A), or S and D (stage 1B).

The presence of clinical manifestations marks the transition to stage 2 and beyond, with stage 2 characterized by subtle signs or symptoms but without functional impairment. Stages 2B-6 require both S and D and stage-specific increases in functional impairment.

“An advantage of the NSD-ISS will be to reduce heterogeneity in clinical trials by requiring biological consistency within the study cohort rather than identifying study participants on the basis of clinical criteria for Parkinson’s disease and dementia with Lewy bodies,” Dr. Simuni and colleagues pointed out in a position paper describing the NSD-ISS published online earlier this year in The Lancet Neurology.

The NSD-ISS will “evolve to include the incorporation of data-driven definitions of stage-specific functional anchors and additional biomarkers as they emerge and are validated.”

For now, the NSD-ISS is intended for research use only and not in the clinic.
 

The SynNeurGe Research Diagnostic Criteria

Separately, a team led by Anthony Lang, MD, with the Krembil Brain Institute at Toronto Western Hospital, Toronto, Ontario, Canada, proposed the SynNeurGe biological classification of PD.

Described in a companion paper published online in The Lancet Neurology, their “S-N-G” classification emphasizes the important interactions between three biological factors that contribute to disease: The presence or absence of pathologic alpha-synuclein (S) in tissues or CSF, an evidence of underlying neurodegeneration (N) defined by neuroimaging procedures, and the documentation of pathogenic gene variants (G) that cause or strongly predispose to PD.

These three components link to a clinical component, defined either by a single high-specificity clinical feature or by multiple lower-specificity clinical features.

As with the NSD-ISS, the SynNeurGe model is intended for research purposes only and is not ready for immediate application in the clinic.

Both groups acknowledged the need for studies to test and validate the proposed classification systems.
 

Caveats, Cautionary Notes

Adopting a biological definition of PD would represent a shift as the field has prompted considerable discussion and healthy debate.

Commenting for this news organization, James Beck, PhD, chief scientific officer at the Parkinson’s Foundation, said the principle behind the proposed classifications is where “the field needs to go.”

“Right now, people with Parkinson’s take too long to get a confirmed diagnosis of their disease, and despite best efforts, clinicians can get it wrong, not diagnosing people or maybe misdiagnosing people,” Dr. Beck said. “Moving to a biological basis, where we have better certainty, is going to be really important.”

Beck noted that the NSD-ISS “goes all in on alpha-synuclein,” which does play a big role in PD, but added, “I don’t know if I want to declare a winner after the first heat. There are other biomarkers that are coming to fruition but still need validation, and alpha-synuclein may be just one of many to help determine whether someone has Parkinson’s disease or not.”

Un Kang, MD, director of translational research at the Fresco Institute for Parkinson’s & Movement Disorders at NYU Langone Health, New York City, told this news organization that alpha-synuclein has “very high diagnostic accuracy” but cautioned that the adoption of a biological definition for PD would not usurp a clinical diagnosis.

“We need both,” Dr. Kang said. “But knowing the underlying pathology is important for earlier diagnosis and testing of potential therapies to treat the molecular pathology. If a patient doesn’t have abnormal synuclein, you may be treating the wrong disease.”

The coauthors of recent JAMA Neurology perspective said the biological definitions are “exciting, but there is “wisdom” in tapping the brakes when attempting to establish a biological definition and classification system for PD.

“Although these two proposals represent significant steps forward, a sprint toward the finish line may not be wise,” wrote Njideka U. Okubadejo, MD, with University of Lagos, Nigeria; Joseph Jankovic, MD, with Baylor College of Medicine, Houston; and Michael S. Okun, MD, with University of Florida Health, Gainesville, Florida.

“A process that embraces inclusivity and weaves in evolving technological advancements will be important. Who benefits if implementation of a biologically based staging system for PD is hurried?” they continued.

The proposals rely heavily on alpha-synuclein assays, they noted, which currently require subjective interpretation and lack extensive validation. They also worry that the need for expensive and, in some regions, unattainable biological fluids (CSF) or imaging studies (dopamine transporter scan) may limit global access to both PD trials and future therapeutics.

They also worry about retiring the name Parkinson’s disease.

“Beyond the historical importance of the term Parkinson disease, any classification that proposes abandoning the two words in either clinical or research descriptions could have unintended global repercussions,” Dr. Okubadejo, Dr. Jankovic, and Dr. Okun cautioned.

Dr. Beck told this news organization he’s spoken to clinicians at meetings about this and “no one really likes the idea” of retiring the term Parkinson’s disease.

Frederick Ketchum, MD, and Nathaniel Chin, MD, with University of Wisconsin–Madison, worry about the “lived” experience of the asymptomatic patient after receiving a biological diagnosis.

“Biological diagnosis might enable effective prognostication and treatment in the future but will substantially change the experience of illness for patients now as new frameworks are slowly adopted and knowledge is gained,” they said in a correspondence in The Lancet Neurology.

“Understanding and addressing this lived experience remains a core task for health professionals and must be made central as we begin an era in which neurological diseases are redefined on a biological basis,” Dr. Ketchum and Dr. Chin advised.

A complete list of agencies that supported this work and author disclosures are available with the original articles. Dr. Beck and Dr. Kang had no relevant disclosures.

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

Parkinson’s disease (PD) and dementia with Lewy bodies are currently defined by clinical features, which can be heterogeneous and do not capture the presymptomatic phase of neurodegeneration.

Recent advances have enabled the detection of misfolded and aggregated alpha-synuclein protein (synucleinopathy) — a key pathologic feature of these diseases — allowing for earlier and more accurate diagnosis. This has led two international research groups to propose a major shift from a clinical to a biological definition of the disease.

Both groups emphasized the detection of alpha-synuclein through recently developed seed amplification assays as a key diagnostic and staging tool, although they differ in their approaches and criteria.
 

NSD-ISS

A team led by Tanya Simuni, MD, with Northwestern University, Chicago, proposed a biological definition that combines PD and dementia with Lewy bodies under the term neuronal alpha-synuclein disease (NSD).

NSD is defined by the presence during life of pathologic neuronal alpha-synuclein (S, the first biological anchor) in cerebrospinal fluid (CSF), regardless of the presence of any specific clinical syndrome. Individuals with pathologic neuronal alpha-synuclein aggregates are at a high risk for dopaminergic neuronal dysfunction (D, the second key biological anchor).

Dr. Simuni and colleagues also proposed the NSD integrated staging system (NSD-ISS) rooted in the S and D biological anchors coupled with the degree of functional impairment caused by clinical signs or symptoms.

Stages 0-1 occur without signs or symptoms and are defined by the presence of pathogenic variants in the SNCA gene (stage 0), S alone (stage 1A), or S and D (stage 1B).

The presence of clinical manifestations marks the transition to stage 2 and beyond, with stage 2 characterized by subtle signs or symptoms but without functional impairment. Stages 2B-6 require both S and D and stage-specific increases in functional impairment.

“An advantage of the NSD-ISS will be to reduce heterogeneity in clinical trials by requiring biological consistency within the study cohort rather than identifying study participants on the basis of clinical criteria for Parkinson’s disease and dementia with Lewy bodies,” Dr. Simuni and colleagues pointed out in a position paper describing the NSD-ISS published online earlier this year in The Lancet Neurology.

The NSD-ISS will “evolve to include the incorporation of data-driven definitions of stage-specific functional anchors and additional biomarkers as they emerge and are validated.”

For now, the NSD-ISS is intended for research use only and not in the clinic.
 

The SynNeurGe Research Diagnostic Criteria

Separately, a team led by Anthony Lang, MD, with the Krembil Brain Institute at Toronto Western Hospital, Toronto, Ontario, Canada, proposed the SynNeurGe biological classification of PD.

Described in a companion paper published online in The Lancet Neurology, their “S-N-G” classification emphasizes the important interactions between three biological factors that contribute to disease: The presence or absence of pathologic alpha-synuclein (S) in tissues or CSF, an evidence of underlying neurodegeneration (N) defined by neuroimaging procedures, and the documentation of pathogenic gene variants (G) that cause or strongly predispose to PD.

These three components link to a clinical component, defined either by a single high-specificity clinical feature or by multiple lower-specificity clinical features.

As with the NSD-ISS, the SynNeurGe model is intended for research purposes only and is not ready for immediate application in the clinic.

Both groups acknowledged the need for studies to test and validate the proposed classification systems.
 

Caveats, Cautionary Notes

Adopting a biological definition of PD would represent a shift as the field has prompted considerable discussion and healthy debate.

Commenting for this news organization, James Beck, PhD, chief scientific officer at the Parkinson’s Foundation, said the principle behind the proposed classifications is where “the field needs to go.”

“Right now, people with Parkinson’s take too long to get a confirmed diagnosis of their disease, and despite best efforts, clinicians can get it wrong, not diagnosing people or maybe misdiagnosing people,” Dr. Beck said. “Moving to a biological basis, where we have better certainty, is going to be really important.”

Beck noted that the NSD-ISS “goes all in on alpha-synuclein,” which does play a big role in PD, but added, “I don’t know if I want to declare a winner after the first heat. There are other biomarkers that are coming to fruition but still need validation, and alpha-synuclein may be just one of many to help determine whether someone has Parkinson’s disease or not.”

Un Kang, MD, director of translational research at the Fresco Institute for Parkinson’s & Movement Disorders at NYU Langone Health, New York City, told this news organization that alpha-synuclein has “very high diagnostic accuracy” but cautioned that the adoption of a biological definition for PD would not usurp a clinical diagnosis.

“We need both,” Dr. Kang said. “But knowing the underlying pathology is important for earlier diagnosis and testing of potential therapies to treat the molecular pathology. If a patient doesn’t have abnormal synuclein, you may be treating the wrong disease.”

The coauthors of recent JAMA Neurology perspective said the biological definitions are “exciting, but there is “wisdom” in tapping the brakes when attempting to establish a biological definition and classification system for PD.

“Although these two proposals represent significant steps forward, a sprint toward the finish line may not be wise,” wrote Njideka U. Okubadejo, MD, with University of Lagos, Nigeria; Joseph Jankovic, MD, with Baylor College of Medicine, Houston; and Michael S. Okun, MD, with University of Florida Health, Gainesville, Florida.

“A process that embraces inclusivity and weaves in evolving technological advancements will be important. Who benefits if implementation of a biologically based staging system for PD is hurried?” they continued.

The proposals rely heavily on alpha-synuclein assays, they noted, which currently require subjective interpretation and lack extensive validation. They also worry that the need for expensive and, in some regions, unattainable biological fluids (CSF) or imaging studies (dopamine transporter scan) may limit global access to both PD trials and future therapeutics.

They also worry about retiring the name Parkinson’s disease.

“Beyond the historical importance of the term Parkinson disease, any classification that proposes abandoning the two words in either clinical or research descriptions could have unintended global repercussions,” Dr. Okubadejo, Dr. Jankovic, and Dr. Okun cautioned.

Dr. Beck told this news organization he’s spoken to clinicians at meetings about this and “no one really likes the idea” of retiring the term Parkinson’s disease.

Frederick Ketchum, MD, and Nathaniel Chin, MD, with University of Wisconsin–Madison, worry about the “lived” experience of the asymptomatic patient after receiving a biological diagnosis.

“Biological diagnosis might enable effective prognostication and treatment in the future but will substantially change the experience of illness for patients now as new frameworks are slowly adopted and knowledge is gained,” they said in a correspondence in The Lancet Neurology.

“Understanding and addressing this lived experience remains a core task for health professionals and must be made central as we begin an era in which neurological diseases are redefined on a biological basis,” Dr. Ketchum and Dr. Chin advised.

A complete list of agencies that supported this work and author disclosures are available with the original articles. Dr. Beck and Dr. Kang had no relevant disclosures.

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

Parkinson’s disease (PD) and dementia with Lewy bodies are currently defined by clinical features, which can be heterogeneous and do not capture the presymptomatic phase of neurodegeneration.

Recent advances have enabled the detection of misfolded and aggregated alpha-synuclein protein (synucleinopathy) — a key pathologic feature of these diseases — allowing for earlier and more accurate diagnosis. This has led two international research groups to propose a major shift from a clinical to a biological definition of the disease.

Both groups emphasized the detection of alpha-synuclein through recently developed seed amplification assays as a key diagnostic and staging tool, although they differ in their approaches and criteria.
 

NSD-ISS

A team led by Tanya Simuni, MD, with Northwestern University, Chicago, proposed a biological definition that combines PD and dementia with Lewy bodies under the term neuronal alpha-synuclein disease (NSD).

NSD is defined by the presence during life of pathologic neuronal alpha-synuclein (S, the first biological anchor) in cerebrospinal fluid (CSF), regardless of the presence of any specific clinical syndrome. Individuals with pathologic neuronal alpha-synuclein aggregates are at a high risk for dopaminergic neuronal dysfunction (D, the second key biological anchor).

Dr. Simuni and colleagues also proposed the NSD integrated staging system (NSD-ISS) rooted in the S and D biological anchors coupled with the degree of functional impairment caused by clinical signs or symptoms.

Stages 0-1 occur without signs or symptoms and are defined by the presence of pathogenic variants in the SNCA gene (stage 0), S alone (stage 1A), or S and D (stage 1B).

The presence of clinical manifestations marks the transition to stage 2 and beyond, with stage 2 characterized by subtle signs or symptoms but without functional impairment. Stages 2B-6 require both S and D and stage-specific increases in functional impairment.

“An advantage of the NSD-ISS will be to reduce heterogeneity in clinical trials by requiring biological consistency within the study cohort rather than identifying study participants on the basis of clinical criteria for Parkinson’s disease and dementia with Lewy bodies,” Dr. Simuni and colleagues pointed out in a position paper describing the NSD-ISS published online earlier this year in The Lancet Neurology.

The NSD-ISS will “evolve to include the incorporation of data-driven definitions of stage-specific functional anchors and additional biomarkers as they emerge and are validated.”

For now, the NSD-ISS is intended for research use only and not in the clinic.
 

The SynNeurGe Research Diagnostic Criteria

Separately, a team led by Anthony Lang, MD, with the Krembil Brain Institute at Toronto Western Hospital, Toronto, Ontario, Canada, proposed the SynNeurGe biological classification of PD.

Described in a companion paper published online in The Lancet Neurology, their “S-N-G” classification emphasizes the important interactions between three biological factors that contribute to disease: The presence or absence of pathologic alpha-synuclein (S) in tissues or CSF, an evidence of underlying neurodegeneration (N) defined by neuroimaging procedures, and the documentation of pathogenic gene variants (G) that cause or strongly predispose to PD.

These three components link to a clinical component, defined either by a single high-specificity clinical feature or by multiple lower-specificity clinical features.

As with the NSD-ISS, the SynNeurGe model is intended for research purposes only and is not ready for immediate application in the clinic.

Both groups acknowledged the need for studies to test and validate the proposed classification systems.
 

Caveats, Cautionary Notes

Adopting a biological definition of PD would represent a shift as the field has prompted considerable discussion and healthy debate.

Commenting for this news organization, James Beck, PhD, chief scientific officer at the Parkinson’s Foundation, said the principle behind the proposed classifications is where “the field needs to go.”

“Right now, people with Parkinson’s take too long to get a confirmed diagnosis of their disease, and despite best efforts, clinicians can get it wrong, not diagnosing people or maybe misdiagnosing people,” Dr. Beck said. “Moving to a biological basis, where we have better certainty, is going to be really important.”

Beck noted that the NSD-ISS “goes all in on alpha-synuclein,” which does play a big role in PD, but added, “I don’t know if I want to declare a winner after the first heat. There are other biomarkers that are coming to fruition but still need validation, and alpha-synuclein may be just one of many to help determine whether someone has Parkinson’s disease or not.”

Un Kang, MD, director of translational research at the Fresco Institute for Parkinson’s & Movement Disorders at NYU Langone Health, New York City, told this news organization that alpha-synuclein has “very high diagnostic accuracy” but cautioned that the adoption of a biological definition for PD would not usurp a clinical diagnosis.

“We need both,” Dr. Kang said. “But knowing the underlying pathology is important for earlier diagnosis and testing of potential therapies to treat the molecular pathology. If a patient doesn’t have abnormal synuclein, you may be treating the wrong disease.”

The coauthors of recent JAMA Neurology perspective said the biological definitions are “exciting, but there is “wisdom” in tapping the brakes when attempting to establish a biological definition and classification system for PD.

“Although these two proposals represent significant steps forward, a sprint toward the finish line may not be wise,” wrote Njideka U. Okubadejo, MD, with University of Lagos, Nigeria; Joseph Jankovic, MD, with Baylor College of Medicine, Houston; and Michael S. Okun, MD, with University of Florida Health, Gainesville, Florida.

“A process that embraces inclusivity and weaves in evolving technological advancements will be important. Who benefits if implementation of a biologically based staging system for PD is hurried?” they continued.

The proposals rely heavily on alpha-synuclein assays, they noted, which currently require subjective interpretation and lack extensive validation. They also worry that the need for expensive and, in some regions, unattainable biological fluids (CSF) or imaging studies (dopamine transporter scan) may limit global access to both PD trials and future therapeutics.

They also worry about retiring the name Parkinson’s disease.

“Beyond the historical importance of the term Parkinson disease, any classification that proposes abandoning the two words in either clinical or research descriptions could have unintended global repercussions,” Dr. Okubadejo, Dr. Jankovic, and Dr. Okun cautioned.

Dr. Beck told this news organization he’s spoken to clinicians at meetings about this and “no one really likes the idea” of retiring the term Parkinson’s disease.

Frederick Ketchum, MD, and Nathaniel Chin, MD, with University of Wisconsin–Madison, worry about the “lived” experience of the asymptomatic patient after receiving a biological diagnosis.

“Biological diagnosis might enable effective prognostication and treatment in the future but will substantially change the experience of illness for patients now as new frameworks are slowly adopted and knowledge is gained,” they said in a correspondence in The Lancet Neurology.

“Understanding and addressing this lived experience remains a core task for health professionals and must be made central as we begin an era in which neurological diseases are redefined on a biological basis,” Dr. Ketchum and Dr. Chin advised.

A complete list of agencies that supported this work and author disclosures are available with the original articles. Dr. Beck and Dr. Kang had no relevant disclosures.

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

TOPLINE:

Combat exposure is strongly associated with chronic pain in active-duty servicewomen and female civilian dependents of military personnel on active duty; a lower socioeconomic status and mental health conditions further increased the likelihood of chronic pain.

METHODOLOGY:

• Researchers analyzed claims data from the Military Health System to identify chronic pain diagnoses among active-duty servicewomen and civilian dependents of individuals on active duty.
• A total of 3,473,401 individuals (median age, 29 years) were included in the study, with 644,478 active-duty servicewomen and 2,828,923 civilian dependents.
• The study compared the incidence of chronic pain during 2006-2013, a period of heightened deployment intensity, with 2014-2020, a period of reduced deployment intensity.
• The primary outcome was the diagnosis of chronic pain.

TAKEAWAY:

• Active-duty servicewomen in the years 2006-2013 had a 53% increase in the odds of reporting chronic pain compared with those in the period between 2014 and 2020 (odds ratio [OR], 1.53; 95% CI, 1.48-1.58).
• Civilian dependents in the years 2006-2013 had a 96% increase in the odds of chronic pain compared with those in the later interval (OR, 1.96; 95% CI, 1.93-1.99).
• In 2006-2013, junior enlisted active-duty servicewomen had nearly a twofold increase in the odds of chronic pain (OR, 1.95; 95% CI, 1.83-2.09), while junior enlisted dependents had more than a threefold increase in the odds of chronic pain (OR, 3.05; 95% CI, 2.87-3.25) compared with senior officers.
• Comorbid mental conditions also were associated with an increased odds of reporting chronic pain (OR, 1.67; 95% CI, 1.65-1.69).

IN PRACTICE:

“The potential for higher rates of chronic pain in women veterans has been theorized to result from differences in support structures, family conflict, coping strategies, stress regulation, and exposure to military sexual trauma,” the authors wrote. “Our results suggest that these contributing factors may carry over to the women dependents of combat veterans in addition, indicating a line of research that requires urgent further exploration.”

SOURCE:

The study was led by Andrew J. Schoenfeld, MD, MSc, of the Center for Surgery and Public Health, Department of Orthopaedic Surgery at Brigham and Women’s Hospital and Harvard Medical School, in Boston. It was published online on July 5, 2024, in JAMA Network Open.

LIMITATIONS:

This study relied on claims-based data, which may have issues with coding accuracy and limited clinical granularity. The population size reduced over time owing to military downsizing, which could impact the findings. The prevalence of chronic pain in the population was likely underestimated because individuals who did not report symptoms or were diagnosed after separation from service were not identified.

DISCLOSURES:

This study was funded by the US Department of Defense. The lead author reported receiving grants and personal fees, serving as the editor-in-chief for Spine, acting as a consultant, and having other ties with various sources outside the submitted work.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Combat exposure is strongly associated with chronic pain in active-duty servicewomen and female civilian dependents of military personnel on active duty; a lower socioeconomic status and mental health conditions further increased the likelihood of chronic pain.

METHODOLOGY:

• Researchers analyzed claims data from the Military Health System to identify chronic pain diagnoses among active-duty servicewomen and civilian dependents of individuals on active duty.
• A total of 3,473,401 individuals (median age, 29 years) were included in the study, with 644,478 active-duty servicewomen and 2,828,923 civilian dependents.
• The study compared the incidence of chronic pain during 2006-2013, a period of heightened deployment intensity, with 2014-2020, a period of reduced deployment intensity.
• The primary outcome was the diagnosis of chronic pain.

TAKEAWAY:

• Active-duty servicewomen in the years 2006-2013 had a 53% increase in the odds of reporting chronic pain compared with those in the period between 2014 and 2020 (odds ratio [OR], 1.53; 95% CI, 1.48-1.58).
• Civilian dependents in the years 2006-2013 had a 96% increase in the odds of chronic pain compared with those in the later interval (OR, 1.96; 95% CI, 1.93-1.99).
• In 2006-2013, junior enlisted active-duty servicewomen had nearly a twofold increase in the odds of chronic pain (OR, 1.95; 95% CI, 1.83-2.09), while junior enlisted dependents had more than a threefold increase in the odds of chronic pain (OR, 3.05; 95% CI, 2.87-3.25) compared with senior officers.
• Comorbid mental conditions also were associated with an increased odds of reporting chronic pain (OR, 1.67; 95% CI, 1.65-1.69).

IN PRACTICE:

“The potential for higher rates of chronic pain in women veterans has been theorized to result from differences in support structures, family conflict, coping strategies, stress regulation, and exposure to military sexual trauma,” the authors wrote. “Our results suggest that these contributing factors may carry over to the women dependents of combat veterans in addition, indicating a line of research that requires urgent further exploration.”

SOURCE:

The study was led by Andrew J. Schoenfeld, MD, MSc, of the Center for Surgery and Public Health, Department of Orthopaedic Surgery at Brigham and Women’s Hospital and Harvard Medical School, in Boston. It was published online on July 5, 2024, in JAMA Network Open.

LIMITATIONS:

This study relied on claims-based data, which may have issues with coding accuracy and limited clinical granularity. The population size reduced over time owing to military downsizing, which could impact the findings. The prevalence of chronic pain in the population was likely underestimated because individuals who did not report symptoms or were diagnosed after separation from service were not identified.

DISCLOSURES:

This study was funded by the US Department of Defense. The lead author reported receiving grants and personal fees, serving as the editor-in-chief for Spine, acting as a consultant, and having other ties with various sources outside the submitted work.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Combat exposure is strongly associated with chronic pain in active-duty servicewomen and female civilian dependents of military personnel on active duty; a lower socioeconomic status and mental health conditions further increased the likelihood of chronic pain.

METHODOLOGY:

• Researchers analyzed claims data from the Military Health System to identify chronic pain diagnoses among active-duty servicewomen and civilian dependents of individuals on active duty.
• A total of 3,473,401 individuals (median age, 29 years) were included in the study, with 644,478 active-duty servicewomen and 2,828,923 civilian dependents.
• The study compared the incidence of chronic pain during 2006-2013, a period of heightened deployment intensity, with 2014-2020, a period of reduced deployment intensity.
• The primary outcome was the diagnosis of chronic pain.

TAKEAWAY:

• Active-duty servicewomen in the years 2006-2013 had a 53% increase in the odds of reporting chronic pain compared with those in the period between 2014 and 2020 (odds ratio [OR], 1.53; 95% CI, 1.48-1.58).
• Civilian dependents in the years 2006-2013 had a 96% increase in the odds of chronic pain compared with those in the later interval (OR, 1.96; 95% CI, 1.93-1.99).
• In 2006-2013, junior enlisted active-duty servicewomen had nearly a twofold increase in the odds of chronic pain (OR, 1.95; 95% CI, 1.83-2.09), while junior enlisted dependents had more than a threefold increase in the odds of chronic pain (OR, 3.05; 95% CI, 2.87-3.25) compared with senior officers.
• Comorbid mental conditions also were associated with an increased odds of reporting chronic pain (OR, 1.67; 95% CI, 1.65-1.69).

IN PRACTICE:

“The potential for higher rates of chronic pain in women veterans has been theorized to result from differences in support structures, family conflict, coping strategies, stress regulation, and exposure to military sexual trauma,” the authors wrote. “Our results suggest that these contributing factors may carry over to the women dependents of combat veterans in addition, indicating a line of research that requires urgent further exploration.”

SOURCE:

The study was led by Andrew J. Schoenfeld, MD, MSc, of the Center for Surgery and Public Health, Department of Orthopaedic Surgery at Brigham and Women’s Hospital and Harvard Medical School, in Boston. It was published online on July 5, 2024, in JAMA Network Open.

LIMITATIONS:

This study relied on claims-based data, which may have issues with coding accuracy and limited clinical granularity. The population size reduced over time owing to military downsizing, which could impact the findings. The prevalence of chronic pain in the population was likely underestimated because individuals who did not report symptoms or were diagnosed after separation from service were not identified.

DISCLOSURES:

This study was funded by the US Department of Defense. The lead author reported receiving grants and personal fees, serving as the editor-in-chief for Spine, acting as a consultant, and having other ties with various sources outside the submitted work.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Patients taking a glucagon-like peptide 1 receptor agonist (GLP-1 RA) experience only a modest delay in gastric emptying of solid foods and no significant delay for liquids, compared with those receiving placebo, indicating that patients may not need to discontinue these medications before surgery.

METHODOLOGY:

• GLP-1 RAs, while effective in managing diabetes and obesity, are linked to delayed gastric emptying, which may pose risks during procedures requiring anesthesia or sedation due to potential aspiration of gastric contents.
• Researchers conducted a meta-analysis to quantify the duration of delay in gastric emptying caused by GLP-1 RAs in patients with diabetes and/or excessive body weight, which could guide periprocedural management decisions in the future.
• The primary outcome was halftime, the time required for 50% of solid gastric contents to empty, measured using scintigraphy. This analysis included data from five studies involving 247 patients who received either a GLP-1 RA or placebo.
• The secondary outcome was gastric emptying of liquids measured using the acetaminophen absorption test. Ten studies including 411 patients who received either a GLP-1 RA or placebo were included in this analysis.

TAKEAWAY:

• The mean gastric emptying halftime for solid foods was 138.4 minutes with a GLP-1 RA and 95.0 minutes with placebo, resulting in a pooled mean difference of 36.0 minutes (P < .01).
• No significant difference was found in the gastric emptying time for liquids between the GLP-1 RA and placebo groups. Furthermore, the amount of gastric emptying noted at 4 or 5 hours on the acetaminophen absorption test was comparable between these groups.
• The gastric emptying time for both solids and liquids did not differ between GLP-1 RA formulations or between short-acting or long-acting GLP-1 RAs.

IN PRACTICE:

“Based on current evidence, a conservative approach with a liquid diet on the day before procedures while continuing GLP-1 RA therapy would represent the most sensible approach until more conclusive data on a solid diet are available,” the authors wrote.

SOURCE:

The study, led by Brent Hiramoto, MD, MPH, of the Center for Gastrointestinal Motility at Brigham and Women’s Hospital and Harvard Medical School, Boston, was published online in The American Journal of Gastroenterology.

LIMITATIONS:

The small number of studies utilizing some diagnostic modalities, such as breath testing, precluded a formal meta-analysis of these subgroups. The results could not be stratified by indication for GLP-1 RA (diabetes or obesity) because of insufficient studies in each category.

DISCLOSURES:

The lead author was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. One author declared serving on the advisory boards of three pharmaceutical companies.

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

TOPLINE:

Patients taking a glucagon-like peptide 1 receptor agonist (GLP-1 RA) experience only a modest delay in gastric emptying of solid foods and no significant delay for liquids, compared with those receiving placebo, indicating that patients may not need to discontinue these medications before surgery.

METHODOLOGY:

• GLP-1 RAs, while effective in managing diabetes and obesity, are linked to delayed gastric emptying, which may pose risks during procedures requiring anesthesia or sedation due to potential aspiration of gastric contents.
• Researchers conducted a meta-analysis to quantify the duration of delay in gastric emptying caused by GLP-1 RAs in patients with diabetes and/or excessive body weight, which could guide periprocedural management decisions in the future.
• The primary outcome was halftime, the time required for 50% of solid gastric contents to empty, measured using scintigraphy. This analysis included data from five studies involving 247 patients who received either a GLP-1 RA or placebo.
• The secondary outcome was gastric emptying of liquids measured using the acetaminophen absorption test. Ten studies including 411 patients who received either a GLP-1 RA or placebo were included in this analysis.

TAKEAWAY:

• The mean gastric emptying halftime for solid foods was 138.4 minutes with a GLP-1 RA and 95.0 minutes with placebo, resulting in a pooled mean difference of 36.0 minutes (P < .01).
• No significant difference was found in the gastric emptying time for liquids between the GLP-1 RA and placebo groups. Furthermore, the amount of gastric emptying noted at 4 or 5 hours on the acetaminophen absorption test was comparable between these groups.
• The gastric emptying time for both solids and liquids did not differ between GLP-1 RA formulations or between short-acting or long-acting GLP-1 RAs.

IN PRACTICE:

“Based on current evidence, a conservative approach with a liquid diet on the day before procedures while continuing GLP-1 RA therapy would represent the most sensible approach until more conclusive data on a solid diet are available,” the authors wrote.

SOURCE:

The study, led by Brent Hiramoto, MD, MPH, of the Center for Gastrointestinal Motility at Brigham and Women’s Hospital and Harvard Medical School, Boston, was published online in The American Journal of Gastroenterology.

LIMITATIONS:

The small number of studies utilizing some diagnostic modalities, such as breath testing, precluded a formal meta-analysis of these subgroups. The results could not be stratified by indication for GLP-1 RA (diabetes or obesity) because of insufficient studies in each category.

DISCLOSURES:

The lead author was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. One author declared serving on the advisory boards of three pharmaceutical companies.

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

TOPLINE:

Patients taking a glucagon-like peptide 1 receptor agonist (GLP-1 RA) experience only a modest delay in gastric emptying of solid foods and no significant delay for liquids, compared with those receiving placebo, indicating that patients may not need to discontinue these medications before surgery.

METHODOLOGY:

• GLP-1 RAs, while effective in managing diabetes and obesity, are linked to delayed gastric emptying, which may pose risks during procedures requiring anesthesia or sedation due to potential aspiration of gastric contents.
• Researchers conducted a meta-analysis to quantify the duration of delay in gastric emptying caused by GLP-1 RAs in patients with diabetes and/or excessive body weight, which could guide periprocedural management decisions in the future.
• The primary outcome was halftime, the time required for 50% of solid gastric contents to empty, measured using scintigraphy. This analysis included data from five studies involving 247 patients who received either a GLP-1 RA or placebo.
• The secondary outcome was gastric emptying of liquids measured using the acetaminophen absorption test. Ten studies including 411 patients who received either a GLP-1 RA or placebo were included in this analysis.

TAKEAWAY:

• The mean gastric emptying halftime for solid foods was 138.4 minutes with a GLP-1 RA and 95.0 minutes with placebo, resulting in a pooled mean difference of 36.0 minutes (P < .01).
• No significant difference was found in the gastric emptying time for liquids between the GLP-1 RA and placebo groups. Furthermore, the amount of gastric emptying noted at 4 or 5 hours on the acetaminophen absorption test was comparable between these groups.
• The gastric emptying time for both solids and liquids did not differ between GLP-1 RA formulations or between short-acting or long-acting GLP-1 RAs.

IN PRACTICE:

“Based on current evidence, a conservative approach with a liquid diet on the day before procedures while continuing GLP-1 RA therapy would represent the most sensible approach until more conclusive data on a solid diet are available,” the authors wrote.

SOURCE:

The study, led by Brent Hiramoto, MD, MPH, of the Center for Gastrointestinal Motility at Brigham and Women’s Hospital and Harvard Medical School, Boston, was published online in The American Journal of Gastroenterology.

LIMITATIONS:

The small number of studies utilizing some diagnostic modalities, such as breath testing, precluded a formal meta-analysis of these subgroups. The results could not be stratified by indication for GLP-1 RA (diabetes or obesity) because of insufficient studies in each category.

DISCLOSURES:

The lead author was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. One author declared serving on the advisory boards of three pharmaceutical companies.

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