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Patient Navigators for Serious Illnesses Can Now Bill Under New Medicare Codes
In a move that acknowledges the gauntlet the US health system poses for people facing serious and fatal illnesses, Medicare will pay for a new class of workers to help patients manage treatments for conditions like cancer and heart failure.
The 2024 Medicare physician fee schedule includes new billing codes, including G0023, to pay for 60 minutes a month of care coordination by certified or trained auxiliary personnel working under the direction of a clinician.
A diagnosis of cancer or another serious illness takes a toll beyond the physical effects of the disease. Patients often scramble to make adjustments in family and work schedules to manage treatment, said Samyukta Mullangi, MD, MBA, medical director of oncology at Thyme Care, a Nashville, Tennessee–based firm that provides navigation and coordination services to oncology practices and insurers.
“It just really does create a bit of a pressure cooker for patients,” Dr. Mullangi told this news organization.
Medicare has for many years paid for medical professionals to help patients cope with the complexities of disease, such as chronic care management (CCM) provided by physicians, nurses, and physician assistants.
The new principal illness navigation (PIN) payments are intended to pay for work that to date typically has been done by people without medical degrees, including those involved in peer support networks and community health programs. The US Centers for Medicare and Medicaid Services(CMS) expects these navigators will undergo training and work under the supervision of clinicians.
The new navigators may coordinate care transitions between medical settings, follow up with patients after emergency department (ED) visits, or communicate with skilled nursing facilities regarding the psychosocial needs and functional deficits of a patient, among other functions.
CMS expects the new navigators may:
- Conduct assessments to understand a patient’s life story, strengths, needs, goals, preferences, and desired outcomes, including understanding cultural and linguistic factors.
- Provide support to accomplish the clinician’s treatment plan.
- Coordinate the receipt of needed services from healthcare facilities, home- and community-based service providers, and caregivers.
Peers as Navigators
The new navigators can be former patients who have undergone similar treatments for serious diseases, CMS said. This approach sets the new program apart from other care management services Medicare already covers, program officials wrote in the 2024 physician fee schedule.
“For some conditions, patients are best able to engage with the healthcare system and access care if they have assistance from a single, dedicated individual who has ‘lived experience,’ ” according to the rule.
The agency has taken a broad initial approach in defining what kinds of illnesses a patient may have to qualify for services. Patients must have a serious condition that is expected to last at least 3 months, such as cancer, heart failure, or substance use disorder.
But those without a definitive diagnosis may also qualify to receive navigator services.
In the rule, CMS cited a case in which a CT scan identified a suspicious mass in a patient’s colon. A clinician might decide this person would benefit from navigation services due to the potential risks for an undiagnosed illness.
“Regardless of the definitive diagnosis of the mass, presence of a colonic mass for that patient may be a serious high-risk condition that could, for example, cause obstruction and lead the patient to present to the emergency department, as well as be potentially indicative of an underlying life-threatening illness such as colon cancer,” CMS wrote in the rule.
Navigators often start their work when cancer patients are screened and guide them through initial diagnosis, potential surgery, radiation, or chemotherapy, said Sharon Gentry, MSN, RN, a former nurse navigator who is now the editor in chief of the Journal of the Academy of Oncology Nurse & Patient Navigators.
The navigators are meant to be a trusted and continual presence for patients, who otherwise might be left to start anew in finding help at each phase of care.
The navigators “see the whole picture. They see the whole journey the patient takes, from pre-diagnosis all the way through diagnosis care out through survival,” Ms. Gentry said.
Gaining a special Medicare payment for these kinds of services will elevate this work, she said.
Many newer drugs can target specific mechanisms and proteins of cancer. Often, oncology treatment involves testing to find out if mutations are allowing the cancer cells to evade a patient’s immune system.
Checking these biomarkers takes time, however. Patients sometimes become frustrated because they are anxious to begin treatment. Patients may receive inaccurate information from friends or family who went through treatment previously. Navigators can provide knowledge on the current state of care for a patient’s disease, helping them better manage anxieties.
“You have to explain to them that things have changed since the guy you drink coffee with was diagnosed with cancer, and there may be a drug that could target that,” Ms. Gentry said.
Potential Challenges
Initial uptake of the new PIN codes may be slow going, however, as clinicians and health systems may already use well-established codes. These include CCM and principal care management services, which may pay higher rates, Mullangi said.
“There might be sensitivity around not wanting to cannibalize existing programs with a new program,” Dr. Mullangi said.
In addition, many patients will have a copay for the services of principal illness navigators, Dr. Mullangi said.
While many patients have additional insurance that would cover the service, not all do. People with traditional Medicare coverage can sometimes pay 20% of the cost of some medical services.
“I think that may give patients pause, particularly if they’re already feeling the financial burden of a cancer treatment journey,” Dr. Mullangi said.
Pay rates for PIN services involve calculations of regional price differences, which are posted publicly by CMS, and potential added fees for services provided by hospital-affiliated organizations.
Consider payments for code G0023, covering 60 minutes of principal navigation services provided in a single month.
A set reimbursement for patients cared for in independent medical practices exists, with variation for local costs. Medicare’s non-facility price for G0023 would be $102.41 in some parts of Silicon Valley in California, including San Jose. In Arkansas, where costs are lower, reimbursement would be $73.14 for this same service.
Patients who get services covered by code G0023 in independent medical practices would have monthly copays of about $15-$20, depending on where they live.
The tab for patients tends to be higher for these same services if delivered through a medical practice owned by a hospital, as this would trigger the addition of facility fees to the payments made to cover the services. Facility fees are difficult for the public to ascertain before getting a treatment or service.
Dr. Mullangi and Ms. Gentry reported no relevant financial disclosures outside of their employers.
A version of this article first appeared on Medscape.com.
In a move that acknowledges the gauntlet the US health system poses for people facing serious and fatal illnesses, Medicare will pay for a new class of workers to help patients manage treatments for conditions like cancer and heart failure.
The 2024 Medicare physician fee schedule includes new billing codes, including G0023, to pay for 60 minutes a month of care coordination by certified or trained auxiliary personnel working under the direction of a clinician.
A diagnosis of cancer or another serious illness takes a toll beyond the physical effects of the disease. Patients often scramble to make adjustments in family and work schedules to manage treatment, said Samyukta Mullangi, MD, MBA, medical director of oncology at Thyme Care, a Nashville, Tennessee–based firm that provides navigation and coordination services to oncology practices and insurers.
“It just really does create a bit of a pressure cooker for patients,” Dr. Mullangi told this news organization.
Medicare has for many years paid for medical professionals to help patients cope with the complexities of disease, such as chronic care management (CCM) provided by physicians, nurses, and physician assistants.
The new principal illness navigation (PIN) payments are intended to pay for work that to date typically has been done by people without medical degrees, including those involved in peer support networks and community health programs. The US Centers for Medicare and Medicaid Services(CMS) expects these navigators will undergo training and work under the supervision of clinicians.
The new navigators may coordinate care transitions between medical settings, follow up with patients after emergency department (ED) visits, or communicate with skilled nursing facilities regarding the psychosocial needs and functional deficits of a patient, among other functions.
CMS expects the new navigators may:
- Conduct assessments to understand a patient’s life story, strengths, needs, goals, preferences, and desired outcomes, including understanding cultural and linguistic factors.
- Provide support to accomplish the clinician’s treatment plan.
- Coordinate the receipt of needed services from healthcare facilities, home- and community-based service providers, and caregivers.
Peers as Navigators
The new navigators can be former patients who have undergone similar treatments for serious diseases, CMS said. This approach sets the new program apart from other care management services Medicare already covers, program officials wrote in the 2024 physician fee schedule.
“For some conditions, patients are best able to engage with the healthcare system and access care if they have assistance from a single, dedicated individual who has ‘lived experience,’ ” according to the rule.
The agency has taken a broad initial approach in defining what kinds of illnesses a patient may have to qualify for services. Patients must have a serious condition that is expected to last at least 3 months, such as cancer, heart failure, or substance use disorder.
But those without a definitive diagnosis may also qualify to receive navigator services.
In the rule, CMS cited a case in which a CT scan identified a suspicious mass in a patient’s colon. A clinician might decide this person would benefit from navigation services due to the potential risks for an undiagnosed illness.
“Regardless of the definitive diagnosis of the mass, presence of a colonic mass for that patient may be a serious high-risk condition that could, for example, cause obstruction and lead the patient to present to the emergency department, as well as be potentially indicative of an underlying life-threatening illness such as colon cancer,” CMS wrote in the rule.
Navigators often start their work when cancer patients are screened and guide them through initial diagnosis, potential surgery, radiation, or chemotherapy, said Sharon Gentry, MSN, RN, a former nurse navigator who is now the editor in chief of the Journal of the Academy of Oncology Nurse & Patient Navigators.
The navigators are meant to be a trusted and continual presence for patients, who otherwise might be left to start anew in finding help at each phase of care.
The navigators “see the whole picture. They see the whole journey the patient takes, from pre-diagnosis all the way through diagnosis care out through survival,” Ms. Gentry said.
Gaining a special Medicare payment for these kinds of services will elevate this work, she said.
Many newer drugs can target specific mechanisms and proteins of cancer. Often, oncology treatment involves testing to find out if mutations are allowing the cancer cells to evade a patient’s immune system.
Checking these biomarkers takes time, however. Patients sometimes become frustrated because they are anxious to begin treatment. Patients may receive inaccurate information from friends or family who went through treatment previously. Navigators can provide knowledge on the current state of care for a patient’s disease, helping them better manage anxieties.
“You have to explain to them that things have changed since the guy you drink coffee with was diagnosed with cancer, and there may be a drug that could target that,” Ms. Gentry said.
Potential Challenges
Initial uptake of the new PIN codes may be slow going, however, as clinicians and health systems may already use well-established codes. These include CCM and principal care management services, which may pay higher rates, Mullangi said.
“There might be sensitivity around not wanting to cannibalize existing programs with a new program,” Dr. Mullangi said.
In addition, many patients will have a copay for the services of principal illness navigators, Dr. Mullangi said.
While many patients have additional insurance that would cover the service, not all do. People with traditional Medicare coverage can sometimes pay 20% of the cost of some medical services.
“I think that may give patients pause, particularly if they’re already feeling the financial burden of a cancer treatment journey,” Dr. Mullangi said.
Pay rates for PIN services involve calculations of regional price differences, which are posted publicly by CMS, and potential added fees for services provided by hospital-affiliated organizations.
Consider payments for code G0023, covering 60 minutes of principal navigation services provided in a single month.
A set reimbursement for patients cared for in independent medical practices exists, with variation for local costs. Medicare’s non-facility price for G0023 would be $102.41 in some parts of Silicon Valley in California, including San Jose. In Arkansas, where costs are lower, reimbursement would be $73.14 for this same service.
Patients who get services covered by code G0023 in independent medical practices would have monthly copays of about $15-$20, depending on where they live.
The tab for patients tends to be higher for these same services if delivered through a medical practice owned by a hospital, as this would trigger the addition of facility fees to the payments made to cover the services. Facility fees are difficult for the public to ascertain before getting a treatment or service.
Dr. Mullangi and Ms. Gentry reported no relevant financial disclosures outside of their employers.
A version of this article first appeared on Medscape.com.
In a move that acknowledges the gauntlet the US health system poses for people facing serious and fatal illnesses, Medicare will pay for a new class of workers to help patients manage treatments for conditions like cancer and heart failure.
The 2024 Medicare physician fee schedule includes new billing codes, including G0023, to pay for 60 minutes a month of care coordination by certified or trained auxiliary personnel working under the direction of a clinician.
A diagnosis of cancer or another serious illness takes a toll beyond the physical effects of the disease. Patients often scramble to make adjustments in family and work schedules to manage treatment, said Samyukta Mullangi, MD, MBA, medical director of oncology at Thyme Care, a Nashville, Tennessee–based firm that provides navigation and coordination services to oncology practices and insurers.
“It just really does create a bit of a pressure cooker for patients,” Dr. Mullangi told this news organization.
Medicare has for many years paid for medical professionals to help patients cope with the complexities of disease, such as chronic care management (CCM) provided by physicians, nurses, and physician assistants.
The new principal illness navigation (PIN) payments are intended to pay for work that to date typically has been done by people without medical degrees, including those involved in peer support networks and community health programs. The US Centers for Medicare and Medicaid Services(CMS) expects these navigators will undergo training and work under the supervision of clinicians.
The new navigators may coordinate care transitions between medical settings, follow up with patients after emergency department (ED) visits, or communicate with skilled nursing facilities regarding the psychosocial needs and functional deficits of a patient, among other functions.
CMS expects the new navigators may:
- Conduct assessments to understand a patient’s life story, strengths, needs, goals, preferences, and desired outcomes, including understanding cultural and linguistic factors.
- Provide support to accomplish the clinician’s treatment plan.
- Coordinate the receipt of needed services from healthcare facilities, home- and community-based service providers, and caregivers.
Peers as Navigators
The new navigators can be former patients who have undergone similar treatments for serious diseases, CMS said. This approach sets the new program apart from other care management services Medicare already covers, program officials wrote in the 2024 physician fee schedule.
“For some conditions, patients are best able to engage with the healthcare system and access care if they have assistance from a single, dedicated individual who has ‘lived experience,’ ” according to the rule.
The agency has taken a broad initial approach in defining what kinds of illnesses a patient may have to qualify for services. Patients must have a serious condition that is expected to last at least 3 months, such as cancer, heart failure, or substance use disorder.
But those without a definitive diagnosis may also qualify to receive navigator services.
In the rule, CMS cited a case in which a CT scan identified a suspicious mass in a patient’s colon. A clinician might decide this person would benefit from navigation services due to the potential risks for an undiagnosed illness.
“Regardless of the definitive diagnosis of the mass, presence of a colonic mass for that patient may be a serious high-risk condition that could, for example, cause obstruction and lead the patient to present to the emergency department, as well as be potentially indicative of an underlying life-threatening illness such as colon cancer,” CMS wrote in the rule.
Navigators often start their work when cancer patients are screened and guide them through initial diagnosis, potential surgery, radiation, or chemotherapy, said Sharon Gentry, MSN, RN, a former nurse navigator who is now the editor in chief of the Journal of the Academy of Oncology Nurse & Patient Navigators.
The navigators are meant to be a trusted and continual presence for patients, who otherwise might be left to start anew in finding help at each phase of care.
The navigators “see the whole picture. They see the whole journey the patient takes, from pre-diagnosis all the way through diagnosis care out through survival,” Ms. Gentry said.
Gaining a special Medicare payment for these kinds of services will elevate this work, she said.
Many newer drugs can target specific mechanisms and proteins of cancer. Often, oncology treatment involves testing to find out if mutations are allowing the cancer cells to evade a patient’s immune system.
Checking these biomarkers takes time, however. Patients sometimes become frustrated because they are anxious to begin treatment. Patients may receive inaccurate information from friends or family who went through treatment previously. Navigators can provide knowledge on the current state of care for a patient’s disease, helping them better manage anxieties.
“You have to explain to them that things have changed since the guy you drink coffee with was diagnosed with cancer, and there may be a drug that could target that,” Ms. Gentry said.
Potential Challenges
Initial uptake of the new PIN codes may be slow going, however, as clinicians and health systems may already use well-established codes. These include CCM and principal care management services, which may pay higher rates, Mullangi said.
“There might be sensitivity around not wanting to cannibalize existing programs with a new program,” Dr. Mullangi said.
In addition, many patients will have a copay for the services of principal illness navigators, Dr. Mullangi said.
While many patients have additional insurance that would cover the service, not all do. People with traditional Medicare coverage can sometimes pay 20% of the cost of some medical services.
“I think that may give patients pause, particularly if they’re already feeling the financial burden of a cancer treatment journey,” Dr. Mullangi said.
Pay rates for PIN services involve calculations of regional price differences, which are posted publicly by CMS, and potential added fees for services provided by hospital-affiliated organizations.
Consider payments for code G0023, covering 60 minutes of principal navigation services provided in a single month.
A set reimbursement for patients cared for in independent medical practices exists, with variation for local costs. Medicare’s non-facility price for G0023 would be $102.41 in some parts of Silicon Valley in California, including San Jose. In Arkansas, where costs are lower, reimbursement would be $73.14 for this same service.
Patients who get services covered by code G0023 in independent medical practices would have monthly copays of about $15-$20, depending on where they live.
The tab for patients tends to be higher for these same services if delivered through a medical practice owned by a hospital, as this would trigger the addition of facility fees to the payments made to cover the services. Facility fees are difficult for the public to ascertain before getting a treatment or service.
Dr. Mullangi and Ms. Gentry reported no relevant financial disclosures outside of their employers.
A version of this article first appeared on Medscape.com.
‘No Hint of Benefit’ in Large Colchicine Trial
WASHINGTON —
The CLEAR SYNERGY (OASIS 9) study, called “the largest trial ever of colchicine in acute MI,” showed no hint of benefit in an adverse event curve for colchicine relative to placebo over 5 years, which suggests that the role of this drug after myocardial infarction (MI) “is uncertain,” Sanjit Jolly, MD, an interventional cardiologist at Hamilton Health Sciences and a professor of medicine at McMaster University in Hamilton, Ontario, Canada, reported at Transcatheter Cardiovascular Therapeutics (TCT) 2024.
For the primary composite outcome — cardiovascular death, MI, stroke, and ischemia-driven revascularization — the event curves in the colchicine and placebo groups remained essentially superimposed over 5 years of follow-up, with only a slight separation after 4 years. The hazard ratio for the primary endpoint showed a 1% difference in favor of colchicine (hazard ratio [HR], 0.99; P = .93).
There were no meaningful differences in any of the individual endpoint components; all 95% CIs straddled the line of unity. Rates of cardiovascular death (3.3% vs 3.2%) and stroke (1.4% vs 1.2%) were numerically higher in the colchicine group than in the placebo group. Rates of MI (2.9% vs 3.1%) and ischemia-driven revascularization (4.6% vs 4.7%) were numerically lower in the colchicine group.
No Difference
No adverse outcomes, including all-cause death (4.6% vs 5.1%), approached significance, with the exception of noncardiovascular death (13.0% vs 1.9%). For this outcome, the 95% CI stopped just short of the line of unity (HR, 0.68; 95% CI, 0.46-0.99).
Rates of adverse events (31.9% vs 31.7%; P = .86), serious adverse events (6.7% vs 7.4%; P = .22), and serious infections (2.5% vs 2.9%; P = .85) were similar in the colchicine and placebo groups, but diarrhea, a known side effect of colchicine, was higher in the colchicine group (10.2% vs 6.6%; P < .001).
Given these results, a panelist questioned the use of the word “uncertain” to describe the findings during the late-breaker session in which these results were presented.
“I think you are selling yourself short,” said J. Dawn Abbott, MD, director of the Interventional Cardiology Fellowship Training Program at the Lifespan Cardiovascular Institute, Brown University in Providence, Rhode Island. Based on the size and conduct of this trial, she called the results “definitive” and suggested that the guidelines should be adjusted.
The OASIS 9 Trial
In OASIS 9, 3528 patients were randomized to colchicine, and 3534 were randomized to placebo. A second randomization in both groups was to spironolactone or placebo; these results will be presented at the upcoming American Heart Association (AHA) 2024 meeting. Both analyses will be published in The New England Journal of Medicine at that time, Jolly reported.
The study involved 104 sites in Australia, Egypt, Europe, Nepal, and North America. Follow-up in both groups exceeded 99%. Most patients had an ST-elevation MI (STEMI), but about 5% of those enrolled had a non-STEMI. Less than 10% of patients had experienced a previous MI.
Less than 5% of patients were discharged on sodium-glucose cotransporter 2 therapy, and more than 95% were discharged on aspirin and a statin. Nearly 80% were discharged on an angiotensin-converting enzyme inhibitor, and most patients received an anticoagulant. More than 95% of patients were implanted with a drug-eluting stent.
At month 3, C-reactive protein levels were significantly lower in the colchicine group than in the placebo group. C-reactive protein is a biomarker for the anti-inflammatory effect that is considered to be colchicine’s primary mechanism of action. An anti-inflammatory effect has been cited as the probable explanation for the positive results shown in the COLCOT and LODOCO2 trials, published in 2019 and 2020, respectively.
In COLCOT, which randomized 4745 patients who experienced an acute MI in the previous 30 days, colchicine was associated with a 23% reduction in a composite major cardiovascular adverse events endpoint relative to placebo (HR, 0.77; P = .02). In LODOCO2, which randomized 5522 patients with chronic coronary disease, colchicine was associated with a 31% reduction in an adverse event composite endpoint (HR, 0.68; P < .0001).
However, two more recent trials — CONVINCE and CHANCE-3 — showed no difference between colchicine and placebo for the endpoint of recurrent stroke at 90 days. CONVINCE, with approximately 3000 patients, was relatively small, whereas CHANCE-3 randomized more than 8000 patients and showed no effect on the risk for stroke (HR, 0.98; 95% CI, 0.83-1.16).
New Data Challenge Guidelines
Of these trials, COLCOT was the most similar to OASIS 9, according to Jolly. Among the differences, OASIS 9 was initiated earlier and was larger than the other trials, so it had more power to address the study question.
Given the absence of benefit, Jolly indicated that OASIS 9 might disrupt both the joint American College of Cardiology and AHA guidelines, which gave colchicine a class 2b recommendation in 2023, and the European Society of Cardiology guidelines, which gave colchicine a 2a recommendation.
“This is a big deal for me,” said Ajay J. Kirtane, director of the Interventional Cardiovascular Care program at Columbia University in New York City. As someone who is now using colchicine routinely, these data have changed his opinion.
The previous data supporting the use of colchicine “were just so-so,” he explained. “Now I have a good rationale” for foregoing the routine use of this therapy.
Jolly said that he had put his own father on colchicine after an acute MI on the basis of the guidelines, but immediately took him off this therapy when the data from OASIS 9 were unblinded.
“The only signal from this trial was an increased risk of diarrhea,” Jolly said. The results, at the very least, suggest that colchicine “is not for everyone” after an acute MI, although he emphasized that these results do not rule out the potential for benefit from anti-inflammatory therapy. Ongoing trials, including one targeting interleukin 6, a cytokine associated with inflammation, remain of interest, he added.
A version of this article first appeared on Medscape.com.
WASHINGTON —
The CLEAR SYNERGY (OASIS 9) study, called “the largest trial ever of colchicine in acute MI,” showed no hint of benefit in an adverse event curve for colchicine relative to placebo over 5 years, which suggests that the role of this drug after myocardial infarction (MI) “is uncertain,” Sanjit Jolly, MD, an interventional cardiologist at Hamilton Health Sciences and a professor of medicine at McMaster University in Hamilton, Ontario, Canada, reported at Transcatheter Cardiovascular Therapeutics (TCT) 2024.
For the primary composite outcome — cardiovascular death, MI, stroke, and ischemia-driven revascularization — the event curves in the colchicine and placebo groups remained essentially superimposed over 5 years of follow-up, with only a slight separation after 4 years. The hazard ratio for the primary endpoint showed a 1% difference in favor of colchicine (hazard ratio [HR], 0.99; P = .93).
There were no meaningful differences in any of the individual endpoint components; all 95% CIs straddled the line of unity. Rates of cardiovascular death (3.3% vs 3.2%) and stroke (1.4% vs 1.2%) were numerically higher in the colchicine group than in the placebo group. Rates of MI (2.9% vs 3.1%) and ischemia-driven revascularization (4.6% vs 4.7%) were numerically lower in the colchicine group.
No Difference
No adverse outcomes, including all-cause death (4.6% vs 5.1%), approached significance, with the exception of noncardiovascular death (13.0% vs 1.9%). For this outcome, the 95% CI stopped just short of the line of unity (HR, 0.68; 95% CI, 0.46-0.99).
Rates of adverse events (31.9% vs 31.7%; P = .86), serious adverse events (6.7% vs 7.4%; P = .22), and serious infections (2.5% vs 2.9%; P = .85) were similar in the colchicine and placebo groups, but diarrhea, a known side effect of colchicine, was higher in the colchicine group (10.2% vs 6.6%; P < .001).
Given these results, a panelist questioned the use of the word “uncertain” to describe the findings during the late-breaker session in which these results were presented.
“I think you are selling yourself short,” said J. Dawn Abbott, MD, director of the Interventional Cardiology Fellowship Training Program at the Lifespan Cardiovascular Institute, Brown University in Providence, Rhode Island. Based on the size and conduct of this trial, she called the results “definitive” and suggested that the guidelines should be adjusted.
The OASIS 9 Trial
In OASIS 9, 3528 patients were randomized to colchicine, and 3534 were randomized to placebo. A second randomization in both groups was to spironolactone or placebo; these results will be presented at the upcoming American Heart Association (AHA) 2024 meeting. Both analyses will be published in The New England Journal of Medicine at that time, Jolly reported.
The study involved 104 sites in Australia, Egypt, Europe, Nepal, and North America. Follow-up in both groups exceeded 99%. Most patients had an ST-elevation MI (STEMI), but about 5% of those enrolled had a non-STEMI. Less than 10% of patients had experienced a previous MI.
Less than 5% of patients were discharged on sodium-glucose cotransporter 2 therapy, and more than 95% were discharged on aspirin and a statin. Nearly 80% were discharged on an angiotensin-converting enzyme inhibitor, and most patients received an anticoagulant. More than 95% of patients were implanted with a drug-eluting stent.
At month 3, C-reactive protein levels were significantly lower in the colchicine group than in the placebo group. C-reactive protein is a biomarker for the anti-inflammatory effect that is considered to be colchicine’s primary mechanism of action. An anti-inflammatory effect has been cited as the probable explanation for the positive results shown in the COLCOT and LODOCO2 trials, published in 2019 and 2020, respectively.
In COLCOT, which randomized 4745 patients who experienced an acute MI in the previous 30 days, colchicine was associated with a 23% reduction in a composite major cardiovascular adverse events endpoint relative to placebo (HR, 0.77; P = .02). In LODOCO2, which randomized 5522 patients with chronic coronary disease, colchicine was associated with a 31% reduction in an adverse event composite endpoint (HR, 0.68; P < .0001).
However, two more recent trials — CONVINCE and CHANCE-3 — showed no difference between colchicine and placebo for the endpoint of recurrent stroke at 90 days. CONVINCE, with approximately 3000 patients, was relatively small, whereas CHANCE-3 randomized more than 8000 patients and showed no effect on the risk for stroke (HR, 0.98; 95% CI, 0.83-1.16).
New Data Challenge Guidelines
Of these trials, COLCOT was the most similar to OASIS 9, according to Jolly. Among the differences, OASIS 9 was initiated earlier and was larger than the other trials, so it had more power to address the study question.
Given the absence of benefit, Jolly indicated that OASIS 9 might disrupt both the joint American College of Cardiology and AHA guidelines, which gave colchicine a class 2b recommendation in 2023, and the European Society of Cardiology guidelines, which gave colchicine a 2a recommendation.
“This is a big deal for me,” said Ajay J. Kirtane, director of the Interventional Cardiovascular Care program at Columbia University in New York City. As someone who is now using colchicine routinely, these data have changed his opinion.
The previous data supporting the use of colchicine “were just so-so,” he explained. “Now I have a good rationale” for foregoing the routine use of this therapy.
Jolly said that he had put his own father on colchicine after an acute MI on the basis of the guidelines, but immediately took him off this therapy when the data from OASIS 9 were unblinded.
“The only signal from this trial was an increased risk of diarrhea,” Jolly said. The results, at the very least, suggest that colchicine “is not for everyone” after an acute MI, although he emphasized that these results do not rule out the potential for benefit from anti-inflammatory therapy. Ongoing trials, including one targeting interleukin 6, a cytokine associated with inflammation, remain of interest, he added.
A version of this article first appeared on Medscape.com.
WASHINGTON —
The CLEAR SYNERGY (OASIS 9) study, called “the largest trial ever of colchicine in acute MI,” showed no hint of benefit in an adverse event curve for colchicine relative to placebo over 5 years, which suggests that the role of this drug after myocardial infarction (MI) “is uncertain,” Sanjit Jolly, MD, an interventional cardiologist at Hamilton Health Sciences and a professor of medicine at McMaster University in Hamilton, Ontario, Canada, reported at Transcatheter Cardiovascular Therapeutics (TCT) 2024.
For the primary composite outcome — cardiovascular death, MI, stroke, and ischemia-driven revascularization — the event curves in the colchicine and placebo groups remained essentially superimposed over 5 years of follow-up, with only a slight separation after 4 years. The hazard ratio for the primary endpoint showed a 1% difference in favor of colchicine (hazard ratio [HR], 0.99; P = .93).
There were no meaningful differences in any of the individual endpoint components; all 95% CIs straddled the line of unity. Rates of cardiovascular death (3.3% vs 3.2%) and stroke (1.4% vs 1.2%) were numerically higher in the colchicine group than in the placebo group. Rates of MI (2.9% vs 3.1%) and ischemia-driven revascularization (4.6% vs 4.7%) were numerically lower in the colchicine group.
No Difference
No adverse outcomes, including all-cause death (4.6% vs 5.1%), approached significance, with the exception of noncardiovascular death (13.0% vs 1.9%). For this outcome, the 95% CI stopped just short of the line of unity (HR, 0.68; 95% CI, 0.46-0.99).
Rates of adverse events (31.9% vs 31.7%; P = .86), serious adverse events (6.7% vs 7.4%; P = .22), and serious infections (2.5% vs 2.9%; P = .85) were similar in the colchicine and placebo groups, but diarrhea, a known side effect of colchicine, was higher in the colchicine group (10.2% vs 6.6%; P < .001).
Given these results, a panelist questioned the use of the word “uncertain” to describe the findings during the late-breaker session in which these results were presented.
“I think you are selling yourself short,” said J. Dawn Abbott, MD, director of the Interventional Cardiology Fellowship Training Program at the Lifespan Cardiovascular Institute, Brown University in Providence, Rhode Island. Based on the size and conduct of this trial, she called the results “definitive” and suggested that the guidelines should be adjusted.
The OASIS 9 Trial
In OASIS 9, 3528 patients were randomized to colchicine, and 3534 were randomized to placebo. A second randomization in both groups was to spironolactone or placebo; these results will be presented at the upcoming American Heart Association (AHA) 2024 meeting. Both analyses will be published in The New England Journal of Medicine at that time, Jolly reported.
The study involved 104 sites in Australia, Egypt, Europe, Nepal, and North America. Follow-up in both groups exceeded 99%. Most patients had an ST-elevation MI (STEMI), but about 5% of those enrolled had a non-STEMI. Less than 10% of patients had experienced a previous MI.
Less than 5% of patients were discharged on sodium-glucose cotransporter 2 therapy, and more than 95% were discharged on aspirin and a statin. Nearly 80% were discharged on an angiotensin-converting enzyme inhibitor, and most patients received an anticoagulant. More than 95% of patients were implanted with a drug-eluting stent.
At month 3, C-reactive protein levels were significantly lower in the colchicine group than in the placebo group. C-reactive protein is a biomarker for the anti-inflammatory effect that is considered to be colchicine’s primary mechanism of action. An anti-inflammatory effect has been cited as the probable explanation for the positive results shown in the COLCOT and LODOCO2 trials, published in 2019 and 2020, respectively.
In COLCOT, which randomized 4745 patients who experienced an acute MI in the previous 30 days, colchicine was associated with a 23% reduction in a composite major cardiovascular adverse events endpoint relative to placebo (HR, 0.77; P = .02). In LODOCO2, which randomized 5522 patients with chronic coronary disease, colchicine was associated with a 31% reduction in an adverse event composite endpoint (HR, 0.68; P < .0001).
However, two more recent trials — CONVINCE and CHANCE-3 — showed no difference between colchicine and placebo for the endpoint of recurrent stroke at 90 days. CONVINCE, with approximately 3000 patients, was relatively small, whereas CHANCE-3 randomized more than 8000 patients and showed no effect on the risk for stroke (HR, 0.98; 95% CI, 0.83-1.16).
New Data Challenge Guidelines
Of these trials, COLCOT was the most similar to OASIS 9, according to Jolly. Among the differences, OASIS 9 was initiated earlier and was larger than the other trials, so it had more power to address the study question.
Given the absence of benefit, Jolly indicated that OASIS 9 might disrupt both the joint American College of Cardiology and AHA guidelines, which gave colchicine a class 2b recommendation in 2023, and the European Society of Cardiology guidelines, which gave colchicine a 2a recommendation.
“This is a big deal for me,” said Ajay J. Kirtane, director of the Interventional Cardiovascular Care program at Columbia University in New York City. As someone who is now using colchicine routinely, these data have changed his opinion.
The previous data supporting the use of colchicine “were just so-so,” he explained. “Now I have a good rationale” for foregoing the routine use of this therapy.
Jolly said that he had put his own father on colchicine after an acute MI on the basis of the guidelines, but immediately took him off this therapy when the data from OASIS 9 were unblinded.
“The only signal from this trial was an increased risk of diarrhea,” Jolly said. The results, at the very least, suggest that colchicine “is not for everyone” after an acute MI, although he emphasized that these results do not rule out the potential for benefit from anti-inflammatory therapy. Ongoing trials, including one targeting interleukin 6, a cytokine associated with inflammation, remain of interest, he added.
A version of this article first appeared on Medscape.com.
FROM TCT 2024
A New and Early Predictor of Dementia?
, in new findings that may provide a potential opportunity to identify high-risk populations for targeted enrollment in clinical trials of dementia prevention and treatment.
Results of an international study assessing frailty trajectories showed frailty levels notably increased in the 4-9 years before dementia diagnosis. Even among study participants whose baseline frailty measurement was taken prior to that acceleration period, frailty was still positively associated with dementia risk, the investigators noted.
“We found that with every four to five additional health problems, there is on average a 40% higher risk of developing dementia, while the risk is lower for people who are more physically fit,” said study investigator David Ward, PhD, of the Centre for Health Services Research, The University of Queensland, Brisbane, Australia.
The findings were published online in JAMA Neurology.
A Promising Biomarker
An accessible biomarker for both biologic age and dementia risk is essential for advancing dementia prevention and treatment strategies, the investigators noted, adding that growing evidence suggests frailty may be a promising candidate for this role.
To learn more about the association between frailty and dementia, Ward and his team analyzed data on 29,849 participants aged 60 years or above (mean age, 71.6 years; 62% women) who participated in four cohort studies: the English Longitudinal Study of Ageing (ELSA; n = 6771), the Health and Retirement Study (HRS; n = 9045), the Rush Memory and Aging Project (MAP; n = 1451), and the National Alzheimer’s Coordinating Center (NACC; n = 12,582).
The primary outcome was all-cause dementia. Depending on the cohort, dementia diagnoses were determined through cognitive testing, self- or family report of physician diagnosis, or a diagnosis by the study physician. Participants were excluded if they had cognitive impairment at baseline.
Investigators retrospectively determined frailty index scores by gathering information on health and functional outcomes for participants from each cohort. Only participants with frailty data on at least 30 deficits were included.
Commonly included deficits included high blood pressure, cancer, and chronic pain, as well as functional problems such as hearing impairment, difficulty with mobility, and challenges managing finances.
Investigators conducted follow-up visits with participants until they developed dementia or until the study ended, with follow-up periods varying across cohorts.
After adjustment for potential confounders, frailty scores were modeled using backward time scales.
Among participants who developed incident dementia (n = 3154), covariate-adjusted expected frailty index scores were, on average, higher in women than in men by 18.5% in ELSA, 20.9% in HRS, and 16.2% in MAP. There were no differences in frailty scores between sexes in the NACC cohort.
When measured on a timeline, as compared with those who didn’t develop dementia, frailty scores were significantly and consistently higher in the dementia groups 8-20 before dementia onset (20 years in HRS; 13 in MAP; 12 in ELSA; 8 in NACC).
Increases in the rates of frailty index scores began accelerating 4-9 years before dementia onset for the various cohorts, investigators noted.
In all four cohorts, each 0.1 increase in frailty scores was positively associated with increased dementia risk.
Adjusted hazard ratios [aHRs] ranged from 1.18 in the HRS cohort to 1.73 in the NACC cohort, which showed the strongest association.
In participants whose baseline frailty measurement was conducted before the predementia acceleration period began, the association of frailty scores and dementia risk was positive. These aHRs ranged from 1.18 in the HRS cohort to 1.43 in the NACC cohort.
The ‘Four Pillars’ of Prevention
The good news, investigators said, is that the long trajectory of frailty symptoms preceding dementia onset provides plenty of opportunity for intervention.
To slow the development of frailty, Ward suggested adhering to the “four pillars of frailty prevention and management,” which include good nutrition with plenty of protein, exercise, optimizing medications for chronic conditions, and maintaining a strong social network.
Ward suggested neurologists track frailty in their patients and pointed to a recent article focused on helping neurologists use frailty measures to influence care planning.
Study limitations include the possibility of reverse causality and the fact that investigators could not adjust for genetic risk for dementia.
Unclear Pathway
Commenting on the findings, Lycia Neumann, PhD, senior director of Health Services Research at the Alzheimer’s Association, noted that many studies over the years have shown a link between frailty and dementia. However, she cautioned that a link does not imply causation.
The pathway from frailty to dementia is not 100% clear, and both are complex conditions, said Neumann, who was not part of the study.
“Adopting healthy lifestyle behaviors early and consistently can help decrease the risk of — or postpone the onset of — both frailty and cognitive decline,” she said. Neumann added that physical activity, a healthy diet, social engagement, and controlling diabetes and blood pressure can also reduce the risk for dementia as well as cardiovascular disease.
The study was funded in part by the Deep Dementia Phenotyping Network through the Frailty and Dementia Special Interest Group. Ward and Neumann reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
, in new findings that may provide a potential opportunity to identify high-risk populations for targeted enrollment in clinical trials of dementia prevention and treatment.
Results of an international study assessing frailty trajectories showed frailty levels notably increased in the 4-9 years before dementia diagnosis. Even among study participants whose baseline frailty measurement was taken prior to that acceleration period, frailty was still positively associated with dementia risk, the investigators noted.
“We found that with every four to five additional health problems, there is on average a 40% higher risk of developing dementia, while the risk is lower for people who are more physically fit,” said study investigator David Ward, PhD, of the Centre for Health Services Research, The University of Queensland, Brisbane, Australia.
The findings were published online in JAMA Neurology.
A Promising Biomarker
An accessible biomarker for both biologic age and dementia risk is essential for advancing dementia prevention and treatment strategies, the investigators noted, adding that growing evidence suggests frailty may be a promising candidate for this role.
To learn more about the association between frailty and dementia, Ward and his team analyzed data on 29,849 participants aged 60 years or above (mean age, 71.6 years; 62% women) who participated in four cohort studies: the English Longitudinal Study of Ageing (ELSA; n = 6771), the Health and Retirement Study (HRS; n = 9045), the Rush Memory and Aging Project (MAP; n = 1451), and the National Alzheimer’s Coordinating Center (NACC; n = 12,582).
The primary outcome was all-cause dementia. Depending on the cohort, dementia diagnoses were determined through cognitive testing, self- or family report of physician diagnosis, or a diagnosis by the study physician. Participants were excluded if they had cognitive impairment at baseline.
Investigators retrospectively determined frailty index scores by gathering information on health and functional outcomes for participants from each cohort. Only participants with frailty data on at least 30 deficits were included.
Commonly included deficits included high blood pressure, cancer, and chronic pain, as well as functional problems such as hearing impairment, difficulty with mobility, and challenges managing finances.
Investigators conducted follow-up visits with participants until they developed dementia or until the study ended, with follow-up periods varying across cohorts.
After adjustment for potential confounders, frailty scores were modeled using backward time scales.
Among participants who developed incident dementia (n = 3154), covariate-adjusted expected frailty index scores were, on average, higher in women than in men by 18.5% in ELSA, 20.9% in HRS, and 16.2% in MAP. There were no differences in frailty scores between sexes in the NACC cohort.
When measured on a timeline, as compared with those who didn’t develop dementia, frailty scores were significantly and consistently higher in the dementia groups 8-20 before dementia onset (20 years in HRS; 13 in MAP; 12 in ELSA; 8 in NACC).
Increases in the rates of frailty index scores began accelerating 4-9 years before dementia onset for the various cohorts, investigators noted.
In all four cohorts, each 0.1 increase in frailty scores was positively associated with increased dementia risk.
Adjusted hazard ratios [aHRs] ranged from 1.18 in the HRS cohort to 1.73 in the NACC cohort, which showed the strongest association.
In participants whose baseline frailty measurement was conducted before the predementia acceleration period began, the association of frailty scores and dementia risk was positive. These aHRs ranged from 1.18 in the HRS cohort to 1.43 in the NACC cohort.
The ‘Four Pillars’ of Prevention
The good news, investigators said, is that the long trajectory of frailty symptoms preceding dementia onset provides plenty of opportunity for intervention.
To slow the development of frailty, Ward suggested adhering to the “four pillars of frailty prevention and management,” which include good nutrition with plenty of protein, exercise, optimizing medications for chronic conditions, and maintaining a strong social network.
Ward suggested neurologists track frailty in their patients and pointed to a recent article focused on helping neurologists use frailty measures to influence care planning.
Study limitations include the possibility of reverse causality and the fact that investigators could not adjust for genetic risk for dementia.
Unclear Pathway
Commenting on the findings, Lycia Neumann, PhD, senior director of Health Services Research at the Alzheimer’s Association, noted that many studies over the years have shown a link between frailty and dementia. However, she cautioned that a link does not imply causation.
The pathway from frailty to dementia is not 100% clear, and both are complex conditions, said Neumann, who was not part of the study.
“Adopting healthy lifestyle behaviors early and consistently can help decrease the risk of — or postpone the onset of — both frailty and cognitive decline,” she said. Neumann added that physical activity, a healthy diet, social engagement, and controlling diabetes and blood pressure can also reduce the risk for dementia as well as cardiovascular disease.
The study was funded in part by the Deep Dementia Phenotyping Network through the Frailty and Dementia Special Interest Group. Ward and Neumann reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
, in new findings that may provide a potential opportunity to identify high-risk populations for targeted enrollment in clinical trials of dementia prevention and treatment.
Results of an international study assessing frailty trajectories showed frailty levels notably increased in the 4-9 years before dementia diagnosis. Even among study participants whose baseline frailty measurement was taken prior to that acceleration period, frailty was still positively associated with dementia risk, the investigators noted.
“We found that with every four to five additional health problems, there is on average a 40% higher risk of developing dementia, while the risk is lower for people who are more physically fit,” said study investigator David Ward, PhD, of the Centre for Health Services Research, The University of Queensland, Brisbane, Australia.
The findings were published online in JAMA Neurology.
A Promising Biomarker
An accessible biomarker for both biologic age and dementia risk is essential for advancing dementia prevention and treatment strategies, the investigators noted, adding that growing evidence suggests frailty may be a promising candidate for this role.
To learn more about the association between frailty and dementia, Ward and his team analyzed data on 29,849 participants aged 60 years or above (mean age, 71.6 years; 62% women) who participated in four cohort studies: the English Longitudinal Study of Ageing (ELSA; n = 6771), the Health and Retirement Study (HRS; n = 9045), the Rush Memory and Aging Project (MAP; n = 1451), and the National Alzheimer’s Coordinating Center (NACC; n = 12,582).
The primary outcome was all-cause dementia. Depending on the cohort, dementia diagnoses were determined through cognitive testing, self- or family report of physician diagnosis, or a diagnosis by the study physician. Participants were excluded if they had cognitive impairment at baseline.
Investigators retrospectively determined frailty index scores by gathering information on health and functional outcomes for participants from each cohort. Only participants with frailty data on at least 30 deficits were included.
Commonly included deficits included high blood pressure, cancer, and chronic pain, as well as functional problems such as hearing impairment, difficulty with mobility, and challenges managing finances.
Investigators conducted follow-up visits with participants until they developed dementia or until the study ended, with follow-up periods varying across cohorts.
After adjustment for potential confounders, frailty scores were modeled using backward time scales.
Among participants who developed incident dementia (n = 3154), covariate-adjusted expected frailty index scores were, on average, higher in women than in men by 18.5% in ELSA, 20.9% in HRS, and 16.2% in MAP. There were no differences in frailty scores between sexes in the NACC cohort.
When measured on a timeline, as compared with those who didn’t develop dementia, frailty scores were significantly and consistently higher in the dementia groups 8-20 before dementia onset (20 years in HRS; 13 in MAP; 12 in ELSA; 8 in NACC).
Increases in the rates of frailty index scores began accelerating 4-9 years before dementia onset for the various cohorts, investigators noted.
In all four cohorts, each 0.1 increase in frailty scores was positively associated with increased dementia risk.
Adjusted hazard ratios [aHRs] ranged from 1.18 in the HRS cohort to 1.73 in the NACC cohort, which showed the strongest association.
In participants whose baseline frailty measurement was conducted before the predementia acceleration period began, the association of frailty scores and dementia risk was positive. These aHRs ranged from 1.18 in the HRS cohort to 1.43 in the NACC cohort.
The ‘Four Pillars’ of Prevention
The good news, investigators said, is that the long trajectory of frailty symptoms preceding dementia onset provides plenty of opportunity for intervention.
To slow the development of frailty, Ward suggested adhering to the “four pillars of frailty prevention and management,” which include good nutrition with plenty of protein, exercise, optimizing medications for chronic conditions, and maintaining a strong social network.
Ward suggested neurologists track frailty in their patients and pointed to a recent article focused on helping neurologists use frailty measures to influence care planning.
Study limitations include the possibility of reverse causality and the fact that investigators could not adjust for genetic risk for dementia.
Unclear Pathway
Commenting on the findings, Lycia Neumann, PhD, senior director of Health Services Research at the Alzheimer’s Association, noted that many studies over the years have shown a link between frailty and dementia. However, she cautioned that a link does not imply causation.
The pathway from frailty to dementia is not 100% clear, and both are complex conditions, said Neumann, who was not part of the study.
“Adopting healthy lifestyle behaviors early and consistently can help decrease the risk of — or postpone the onset of — both frailty and cognitive decline,” she said. Neumann added that physical activity, a healthy diet, social engagement, and controlling diabetes and blood pressure can also reduce the risk for dementia as well as cardiovascular disease.
The study was funded in part by the Deep Dementia Phenotyping Network through the Frailty and Dementia Special Interest Group. Ward and Neumann reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Smoldering MS May Warrant Unique Diagnosis, Treatment, and Research Strategies
Smoldering-associated worsening (SAW) of multiple sclerosis (MS) deserves a broader, more comprehensive approach to diagnosis, treatment, and research that goes beyond neurologists’ understanding of progression independent of relapse activity (PIRA), according to a recently published international consensus. However, an outside expert said that promulgating the “smoldering” concept may stoke patient and provider confusion.
Although current disease-modifying therapies (DMTs) for MS exclusively target focal white matter (WM) inflammation, wrote authors lead by Antonio Scalfari, MD, PhD, of Charing Cross Hospital, Imperial College London in England, many people with MS experience worsening disability in a more indolent fashion — despite stable inflammatory markers.
“The gradual accumulation of physical and cognitive disability is driven by smoldering pathological processes via biological substrates, which are different from those of acute focal damage, remain an important unmet therapeutic target,” they wrote.
The same research team first described smoldering MS in a 2022 publication. In the present paper, Scalfari and colleagues reviewed emerging clinical, radiological, and pathological evidence and presented 29 consensus statements in areas ranging from the definition, pathology, and clinical manifestations of smoldering MS to appropriate biomarkers and best clinical practices.
Definition
By definition, the authors wrote, SAW encompasses PIRA but also includes a range of gradually worsening, relapse-independent symptoms that remain undetectable on standard assessments, including the Expanded Disability Status Scale (EDSS) or EDSS-Plus, especially in early disease. To capture symptoms such as subtle motor impairment, cognitive slowing, and fatigue, Scalfari and colleagues recommend tools such as neurological stress tests, fatigue/mood scales, wearable devices, and patient reported outcomes.
Disease Mechanisms
Pathologically, the authors wrote, smoldering MS may stem from intrinsic central nervous system processes that likely incorporate various glial, immune, and neural cells. Smoldering MS also could contribute to aging, and vice versa, the latter possibly through dynamics such as age-related exhaustion of compensatory mechanisms, reduction in remyelination efficiency, and telomere shortening, they added.
Clinical Implementation
Current MS management rests on crude estimates of physical disability and overemphasizes identifying relapses and new MRI lesions as the principal markers of disease activity, wrote Scalfari and colleagues. Instead, they suggested combining motor-associated assessments such as EDSS-Plus with cognitive gauges such as the Brief International Cognitive Assessment for Multiple Sclerosis.
Providers are uncomfortable identifying and discussing smoldering MS, authors allowed, because no licensed treatments target SAW. However, the authors wrote, a principal reason for discussing smoldering MS with patients is to help manage their expectations of current DMTs, which may have little effect on SAW.
‘More Than Lesions’
Bruce Cree, MD, PhD, MAS, professor of neurology at the University of California, San Francisco, said that it is extremely important to raise awareness of physicians’ emerging understanding that “there is more going on in MS than lesions and relapses,” a concept that has been a work in progress for several years. He was not involved with the study but was asked to comment.
A 2019 report on the EPIC cohort coauthored by Cree labeled the disconnect between disability accumulation and relapse occurrence “silent progression.” The observation that disability accumulates in early relapsing MS independent of relapsing activity has been replicated in virtually every dataset worldwide, he added.
“What I don’t like about this article is the reliance on the term ‘smoldering’ and the acceptance that this is an actual phenomenon supported by data.” And authors’ leveraging “smoldering” into additional acronyms such as SAW likely will confuse rather than clarify physicians’ and patients’ understanding of the situation, Cree added. “Clinicians don’t need yet another snappy acronym.” Many are still trying to grasp the PIRA concept in relapsing MS, he said.
“One of the reasons this topic has become so important is that we recognize that even when we have very good control of relapsing disease activity — clinical relapses as well as radiographic large lesion formation on MRI — some patients still develop insidious worsening of disability. And the reasons for that are not well understood,” said Cree.
Accumulating disability absent relapse activity could stem from any number of microscopic inflammatory processes, possibly involving abnormal microglial activation, fibrinogen deposition, microscopic inflammatory infiltrates of CD8-positive T cells, or mitochondrial damage from iron deposition, he said. Or the processes driving PIRA may not even involve inflammation, he added. “We still don’t have a unifying way of understanding how these processes work.”
Cree suspects that, despite investigators’ good intentions, the study’s sponsor, Sanofi, may have influenced the resultant messaging. The company’s tolebrutinib recently completed phase 3 trials in secondary progressive MS and relapsing MS, and a phase 3 trial in primary progressive MS is scheduled for completion in 2025. “A hallmark of Sanofi’s messaging has been this idea that there is smoldering inflammation occurring in MS that tolebrutinib is going to address,” he said.
If clinicians really knew what drove progressive MS, said Cree, “we would be keen on developing therapies targeting that fundamental process. But because we don’t know what’s driving it, we don’t know what to go after.”
The study was supported by Sanofi. Cree is a coauthor of the GEMINI 1 and GEMINI 2 tolebrutinib studies.
A version of this article first appeared on Medscape.com.
Smoldering-associated worsening (SAW) of multiple sclerosis (MS) deserves a broader, more comprehensive approach to diagnosis, treatment, and research that goes beyond neurologists’ understanding of progression independent of relapse activity (PIRA), according to a recently published international consensus. However, an outside expert said that promulgating the “smoldering” concept may stoke patient and provider confusion.
Although current disease-modifying therapies (DMTs) for MS exclusively target focal white matter (WM) inflammation, wrote authors lead by Antonio Scalfari, MD, PhD, of Charing Cross Hospital, Imperial College London in England, many people with MS experience worsening disability in a more indolent fashion — despite stable inflammatory markers.
“The gradual accumulation of physical and cognitive disability is driven by smoldering pathological processes via biological substrates, which are different from those of acute focal damage, remain an important unmet therapeutic target,” they wrote.
The same research team first described smoldering MS in a 2022 publication. In the present paper, Scalfari and colleagues reviewed emerging clinical, radiological, and pathological evidence and presented 29 consensus statements in areas ranging from the definition, pathology, and clinical manifestations of smoldering MS to appropriate biomarkers and best clinical practices.
Definition
By definition, the authors wrote, SAW encompasses PIRA but also includes a range of gradually worsening, relapse-independent symptoms that remain undetectable on standard assessments, including the Expanded Disability Status Scale (EDSS) or EDSS-Plus, especially in early disease. To capture symptoms such as subtle motor impairment, cognitive slowing, and fatigue, Scalfari and colleagues recommend tools such as neurological stress tests, fatigue/mood scales, wearable devices, and patient reported outcomes.
Disease Mechanisms
Pathologically, the authors wrote, smoldering MS may stem from intrinsic central nervous system processes that likely incorporate various glial, immune, and neural cells. Smoldering MS also could contribute to aging, and vice versa, the latter possibly through dynamics such as age-related exhaustion of compensatory mechanisms, reduction in remyelination efficiency, and telomere shortening, they added.
Clinical Implementation
Current MS management rests on crude estimates of physical disability and overemphasizes identifying relapses and new MRI lesions as the principal markers of disease activity, wrote Scalfari and colleagues. Instead, they suggested combining motor-associated assessments such as EDSS-Plus with cognitive gauges such as the Brief International Cognitive Assessment for Multiple Sclerosis.
Providers are uncomfortable identifying and discussing smoldering MS, authors allowed, because no licensed treatments target SAW. However, the authors wrote, a principal reason for discussing smoldering MS with patients is to help manage their expectations of current DMTs, which may have little effect on SAW.
‘More Than Lesions’
Bruce Cree, MD, PhD, MAS, professor of neurology at the University of California, San Francisco, said that it is extremely important to raise awareness of physicians’ emerging understanding that “there is more going on in MS than lesions and relapses,” a concept that has been a work in progress for several years. He was not involved with the study but was asked to comment.
A 2019 report on the EPIC cohort coauthored by Cree labeled the disconnect between disability accumulation and relapse occurrence “silent progression.” The observation that disability accumulates in early relapsing MS independent of relapsing activity has been replicated in virtually every dataset worldwide, he added.
“What I don’t like about this article is the reliance on the term ‘smoldering’ and the acceptance that this is an actual phenomenon supported by data.” And authors’ leveraging “smoldering” into additional acronyms such as SAW likely will confuse rather than clarify physicians’ and patients’ understanding of the situation, Cree added. “Clinicians don’t need yet another snappy acronym.” Many are still trying to grasp the PIRA concept in relapsing MS, he said.
“One of the reasons this topic has become so important is that we recognize that even when we have very good control of relapsing disease activity — clinical relapses as well as radiographic large lesion formation on MRI — some patients still develop insidious worsening of disability. And the reasons for that are not well understood,” said Cree.
Accumulating disability absent relapse activity could stem from any number of microscopic inflammatory processes, possibly involving abnormal microglial activation, fibrinogen deposition, microscopic inflammatory infiltrates of CD8-positive T cells, or mitochondrial damage from iron deposition, he said. Or the processes driving PIRA may not even involve inflammation, he added. “We still don’t have a unifying way of understanding how these processes work.”
Cree suspects that, despite investigators’ good intentions, the study’s sponsor, Sanofi, may have influenced the resultant messaging. The company’s tolebrutinib recently completed phase 3 trials in secondary progressive MS and relapsing MS, and a phase 3 trial in primary progressive MS is scheduled for completion in 2025. “A hallmark of Sanofi’s messaging has been this idea that there is smoldering inflammation occurring in MS that tolebrutinib is going to address,” he said.
If clinicians really knew what drove progressive MS, said Cree, “we would be keen on developing therapies targeting that fundamental process. But because we don’t know what’s driving it, we don’t know what to go after.”
The study was supported by Sanofi. Cree is a coauthor of the GEMINI 1 and GEMINI 2 tolebrutinib studies.
A version of this article first appeared on Medscape.com.
Smoldering-associated worsening (SAW) of multiple sclerosis (MS) deserves a broader, more comprehensive approach to diagnosis, treatment, and research that goes beyond neurologists’ understanding of progression independent of relapse activity (PIRA), according to a recently published international consensus. However, an outside expert said that promulgating the “smoldering” concept may stoke patient and provider confusion.
Although current disease-modifying therapies (DMTs) for MS exclusively target focal white matter (WM) inflammation, wrote authors lead by Antonio Scalfari, MD, PhD, of Charing Cross Hospital, Imperial College London in England, many people with MS experience worsening disability in a more indolent fashion — despite stable inflammatory markers.
“The gradual accumulation of physical and cognitive disability is driven by smoldering pathological processes via biological substrates, which are different from those of acute focal damage, remain an important unmet therapeutic target,” they wrote.
The same research team first described smoldering MS in a 2022 publication. In the present paper, Scalfari and colleagues reviewed emerging clinical, radiological, and pathological evidence and presented 29 consensus statements in areas ranging from the definition, pathology, and clinical manifestations of smoldering MS to appropriate biomarkers and best clinical practices.
Definition
By definition, the authors wrote, SAW encompasses PIRA but also includes a range of gradually worsening, relapse-independent symptoms that remain undetectable on standard assessments, including the Expanded Disability Status Scale (EDSS) or EDSS-Plus, especially in early disease. To capture symptoms such as subtle motor impairment, cognitive slowing, and fatigue, Scalfari and colleagues recommend tools such as neurological stress tests, fatigue/mood scales, wearable devices, and patient reported outcomes.
Disease Mechanisms
Pathologically, the authors wrote, smoldering MS may stem from intrinsic central nervous system processes that likely incorporate various glial, immune, and neural cells. Smoldering MS also could contribute to aging, and vice versa, the latter possibly through dynamics such as age-related exhaustion of compensatory mechanisms, reduction in remyelination efficiency, and telomere shortening, they added.
Clinical Implementation
Current MS management rests on crude estimates of physical disability and overemphasizes identifying relapses and new MRI lesions as the principal markers of disease activity, wrote Scalfari and colleagues. Instead, they suggested combining motor-associated assessments such as EDSS-Plus with cognitive gauges such as the Brief International Cognitive Assessment for Multiple Sclerosis.
Providers are uncomfortable identifying and discussing smoldering MS, authors allowed, because no licensed treatments target SAW. However, the authors wrote, a principal reason for discussing smoldering MS with patients is to help manage their expectations of current DMTs, which may have little effect on SAW.
‘More Than Lesions’
Bruce Cree, MD, PhD, MAS, professor of neurology at the University of California, San Francisco, said that it is extremely important to raise awareness of physicians’ emerging understanding that “there is more going on in MS than lesions and relapses,” a concept that has been a work in progress for several years. He was not involved with the study but was asked to comment.
A 2019 report on the EPIC cohort coauthored by Cree labeled the disconnect between disability accumulation and relapse occurrence “silent progression.” The observation that disability accumulates in early relapsing MS independent of relapsing activity has been replicated in virtually every dataset worldwide, he added.
“What I don’t like about this article is the reliance on the term ‘smoldering’ and the acceptance that this is an actual phenomenon supported by data.” And authors’ leveraging “smoldering” into additional acronyms such as SAW likely will confuse rather than clarify physicians’ and patients’ understanding of the situation, Cree added. “Clinicians don’t need yet another snappy acronym.” Many are still trying to grasp the PIRA concept in relapsing MS, he said.
“One of the reasons this topic has become so important is that we recognize that even when we have very good control of relapsing disease activity — clinical relapses as well as radiographic large lesion formation on MRI — some patients still develop insidious worsening of disability. And the reasons for that are not well understood,” said Cree.
Accumulating disability absent relapse activity could stem from any number of microscopic inflammatory processes, possibly involving abnormal microglial activation, fibrinogen deposition, microscopic inflammatory infiltrates of CD8-positive T cells, or mitochondrial damage from iron deposition, he said. Or the processes driving PIRA may not even involve inflammation, he added. “We still don’t have a unifying way of understanding how these processes work.”
Cree suspects that, despite investigators’ good intentions, the study’s sponsor, Sanofi, may have influenced the resultant messaging. The company’s tolebrutinib recently completed phase 3 trials in secondary progressive MS and relapsing MS, and a phase 3 trial in primary progressive MS is scheduled for completion in 2025. “A hallmark of Sanofi’s messaging has been this idea that there is smoldering inflammation occurring in MS that tolebrutinib is going to address,” he said.
If clinicians really knew what drove progressive MS, said Cree, “we would be keen on developing therapies targeting that fundamental process. But because we don’t know what’s driving it, we don’t know what to go after.”
The study was supported by Sanofi. Cree is a coauthor of the GEMINI 1 and GEMINI 2 tolebrutinib studies.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF NEUROLOGY
Faster Brain Atrophy Linked to MCI
While some brain atrophy is expected in aging, high levels of atrophy in the white matter and high enlargement in the ventricles are associated with earlier progression from normal cognition to MCI, the study found. The researchers also identified diabetes and atypical levels of amyloid beta protein in the cerebrospinal fluid as risk factors for brain atrophy and MCI.
For their research, published online on JAMA Network Open, Yuto Uchida, MD, PhD, and his colleagues at the Johns Hopkins University School of Medicine in Baltimore, Maryland, looked at data for 185 individuals (mean age, 55.4 years; 63% women) who were cognitively normal at baseline and followed for a median of 20 years.
All had been enrolled in a longitudinal cohort study on biomarkers of cognitive decline conducted at Johns Hopkins. Each participant underwent a median of five structural MRI studies during the follow-up period as well as annual cognitive testing. Altogether 60 individuals developed MCI, with eight of them progressing to dementia.
“We hypothesized that annual rates of change of segmental brain volumes would be associated with vascular risk factors among middle-aged and older adults and that these trends would be associated with the progression from normal cognition to MCI,” Uchida and colleagues wrote.
Uniquely Long Follow-Up
Most longitudinal studies using structural MRI count a decade or less of follow-up, the study authors noted. This makes it difficult to discern whether the annual rates of change of brain volumes are affected by vascular risk factors or are useful in predicting MCI, they said. Individual differences in brain aging make population-based studies less informative.
This study’s long timeframe allowed for tracking of brain changes “on an individual basis, which facilitates the differentiation between interindividual and intraindividual variations and leads to more accurate estimations of rates of brain atrophy,” Uchida and colleagues wrote.
People with high levels of atrophy in the white matter and enlargement in the ventricles saw earlier progression to MCI (hazard ratio [HR], 1.86; 95% CI, 1.24-2.49; P = .001). Diabetes mellitus was associated with progression to MCI (HR, 1.41; 95% CI, 1.06-1.76; P = .04), as was a low CSF Abeta42:Abeta40 ratio (HR, 1.48; 95% CI, 1.09-1.88; P = .04).
People with both diabetes and an abnormal amyloid profile were even more vulnerable to developing MCI (HR, 1.55; 95% CI, 1.13-1.98; P = .03). This indicated “a synergic association of diabetes and amyloid pathology with MCI progression,” Uchida and colleagues wrote, noting that insulin resistance has been shown to promote the formation of amyloid plaques, a hallmark of Alzheimer’s disease.
The findings also underscore that “white matter volume changes are closely associated with cognitive function in aging, suggesting that white matter degeneration may play a crucial role in cognitive decline,” the authors noted.
Uchida and colleagues acknowledged the modest size and imbalanced sex ratio of their study cohort as potential weaknesses, as well as the fact that the imaging technologies had changed over the course of the study. Most of the participants were White with family histories of dementia.
Findings May Lead to Targeted Interventions
In an editorial comment accompanying Uchida and colleagues’ study, Shohei Fujita, MD, PhD, of Massachusetts General Hospital, Boston, said that, while a more diverse population sample would be desirable and should be sought for future studies, the results nonetheless highlight “the potential of long-term longitudinal brain MRI datasets in elucidating the interplay of risk factors underlying cognitive decline and the potential benefits of controlling diabetes to reduce the risk of progression” along the Alzheimer’s disease continuum.
The findings may prove informative, Fujita said, in developing “targeted interventions for those most susceptible to progressive brain changes, potentially combining lifestyle modifications and pharmacological treatments.”
Uchida and colleagues’ study was funded by the Alzheimer’s Association, the National Alzheimer’s Coordinating Center, and the National Institutes of Health. The study’s corresponding author, Kenichi Oishi, disclosed funding from the Richman Family Foundation, Richman, the Sharp Family Foundation, and others. Uchida and Fujita reported no relevant financial conflicts of interest.
A version of this article first appeared on Medscape.com.
While some brain atrophy is expected in aging, high levels of atrophy in the white matter and high enlargement in the ventricles are associated with earlier progression from normal cognition to MCI, the study found. The researchers also identified diabetes and atypical levels of amyloid beta protein in the cerebrospinal fluid as risk factors for brain atrophy and MCI.
For their research, published online on JAMA Network Open, Yuto Uchida, MD, PhD, and his colleagues at the Johns Hopkins University School of Medicine in Baltimore, Maryland, looked at data for 185 individuals (mean age, 55.4 years; 63% women) who were cognitively normal at baseline and followed for a median of 20 years.
All had been enrolled in a longitudinal cohort study on biomarkers of cognitive decline conducted at Johns Hopkins. Each participant underwent a median of five structural MRI studies during the follow-up period as well as annual cognitive testing. Altogether 60 individuals developed MCI, with eight of them progressing to dementia.
“We hypothesized that annual rates of change of segmental brain volumes would be associated with vascular risk factors among middle-aged and older adults and that these trends would be associated with the progression from normal cognition to MCI,” Uchida and colleagues wrote.
Uniquely Long Follow-Up
Most longitudinal studies using structural MRI count a decade or less of follow-up, the study authors noted. This makes it difficult to discern whether the annual rates of change of brain volumes are affected by vascular risk factors or are useful in predicting MCI, they said. Individual differences in brain aging make population-based studies less informative.
This study’s long timeframe allowed for tracking of brain changes “on an individual basis, which facilitates the differentiation between interindividual and intraindividual variations and leads to more accurate estimations of rates of brain atrophy,” Uchida and colleagues wrote.
People with high levels of atrophy in the white matter and enlargement in the ventricles saw earlier progression to MCI (hazard ratio [HR], 1.86; 95% CI, 1.24-2.49; P = .001). Diabetes mellitus was associated with progression to MCI (HR, 1.41; 95% CI, 1.06-1.76; P = .04), as was a low CSF Abeta42:Abeta40 ratio (HR, 1.48; 95% CI, 1.09-1.88; P = .04).
People with both diabetes and an abnormal amyloid profile were even more vulnerable to developing MCI (HR, 1.55; 95% CI, 1.13-1.98; P = .03). This indicated “a synergic association of diabetes and amyloid pathology with MCI progression,” Uchida and colleagues wrote, noting that insulin resistance has been shown to promote the formation of amyloid plaques, a hallmark of Alzheimer’s disease.
The findings also underscore that “white matter volume changes are closely associated with cognitive function in aging, suggesting that white matter degeneration may play a crucial role in cognitive decline,” the authors noted.
Uchida and colleagues acknowledged the modest size and imbalanced sex ratio of their study cohort as potential weaknesses, as well as the fact that the imaging technologies had changed over the course of the study. Most of the participants were White with family histories of dementia.
Findings May Lead to Targeted Interventions
In an editorial comment accompanying Uchida and colleagues’ study, Shohei Fujita, MD, PhD, of Massachusetts General Hospital, Boston, said that, while a more diverse population sample would be desirable and should be sought for future studies, the results nonetheless highlight “the potential of long-term longitudinal brain MRI datasets in elucidating the interplay of risk factors underlying cognitive decline and the potential benefits of controlling diabetes to reduce the risk of progression” along the Alzheimer’s disease continuum.
The findings may prove informative, Fujita said, in developing “targeted interventions for those most susceptible to progressive brain changes, potentially combining lifestyle modifications and pharmacological treatments.”
Uchida and colleagues’ study was funded by the Alzheimer’s Association, the National Alzheimer’s Coordinating Center, and the National Institutes of Health. The study’s corresponding author, Kenichi Oishi, disclosed funding from the Richman Family Foundation, Richman, the Sharp Family Foundation, and others. Uchida and Fujita reported no relevant financial conflicts of interest.
A version of this article first appeared on Medscape.com.
While some brain atrophy is expected in aging, high levels of atrophy in the white matter and high enlargement in the ventricles are associated with earlier progression from normal cognition to MCI, the study found. The researchers also identified diabetes and atypical levels of amyloid beta protein in the cerebrospinal fluid as risk factors for brain atrophy and MCI.
For their research, published online on JAMA Network Open, Yuto Uchida, MD, PhD, and his colleagues at the Johns Hopkins University School of Medicine in Baltimore, Maryland, looked at data for 185 individuals (mean age, 55.4 years; 63% women) who were cognitively normal at baseline and followed for a median of 20 years.
All had been enrolled in a longitudinal cohort study on biomarkers of cognitive decline conducted at Johns Hopkins. Each participant underwent a median of five structural MRI studies during the follow-up period as well as annual cognitive testing. Altogether 60 individuals developed MCI, with eight of them progressing to dementia.
“We hypothesized that annual rates of change of segmental brain volumes would be associated with vascular risk factors among middle-aged and older adults and that these trends would be associated with the progression from normal cognition to MCI,” Uchida and colleagues wrote.
Uniquely Long Follow-Up
Most longitudinal studies using structural MRI count a decade or less of follow-up, the study authors noted. This makes it difficult to discern whether the annual rates of change of brain volumes are affected by vascular risk factors or are useful in predicting MCI, they said. Individual differences in brain aging make population-based studies less informative.
This study’s long timeframe allowed for tracking of brain changes “on an individual basis, which facilitates the differentiation between interindividual and intraindividual variations and leads to more accurate estimations of rates of brain atrophy,” Uchida and colleagues wrote.
People with high levels of atrophy in the white matter and enlargement in the ventricles saw earlier progression to MCI (hazard ratio [HR], 1.86; 95% CI, 1.24-2.49; P = .001). Diabetes mellitus was associated with progression to MCI (HR, 1.41; 95% CI, 1.06-1.76; P = .04), as was a low CSF Abeta42:Abeta40 ratio (HR, 1.48; 95% CI, 1.09-1.88; P = .04).
People with both diabetes and an abnormal amyloid profile were even more vulnerable to developing MCI (HR, 1.55; 95% CI, 1.13-1.98; P = .03). This indicated “a synergic association of diabetes and amyloid pathology with MCI progression,” Uchida and colleagues wrote, noting that insulin resistance has been shown to promote the formation of amyloid plaques, a hallmark of Alzheimer’s disease.
The findings also underscore that “white matter volume changes are closely associated with cognitive function in aging, suggesting that white matter degeneration may play a crucial role in cognitive decline,” the authors noted.
Uchida and colleagues acknowledged the modest size and imbalanced sex ratio of their study cohort as potential weaknesses, as well as the fact that the imaging technologies had changed over the course of the study. Most of the participants were White with family histories of dementia.
Findings May Lead to Targeted Interventions
In an editorial comment accompanying Uchida and colleagues’ study, Shohei Fujita, MD, PhD, of Massachusetts General Hospital, Boston, said that, while a more diverse population sample would be desirable and should be sought for future studies, the results nonetheless highlight “the potential of long-term longitudinal brain MRI datasets in elucidating the interplay of risk factors underlying cognitive decline and the potential benefits of controlling diabetes to reduce the risk of progression” along the Alzheimer’s disease continuum.
The findings may prove informative, Fujita said, in developing “targeted interventions for those most susceptible to progressive brain changes, potentially combining lifestyle modifications and pharmacological treatments.”
Uchida and colleagues’ study was funded by the Alzheimer’s Association, the National Alzheimer’s Coordinating Center, and the National Institutes of Health. The study’s corresponding author, Kenichi Oishi, disclosed funding from the Richman Family Foundation, Richman, the Sharp Family Foundation, and others. Uchida and Fujita reported no relevant financial conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Vitamin K Supplementation Reduces Nocturnal Leg Cramps in Older Adults
TOPLINE:
Vitamin K supplementation significantly reduced the frequency, intensity, and duration of nocturnal leg cramps in older adults. No adverse events related to vitamin K were identified.
METHODOLOGY:
- Researchers conducted a multicenter, double-blind, placebo-controlled randomized clinical trial in China from September 2022 to December 2023.
- A total of 199 participants aged ≥ 65 years with at least two documented episodes of nocturnal leg cramps during a 2-week screening period were included.
- Participants were randomized in a 1:1 ratio to receive either 180 μg of vitamin K (menaquinone 7) or a placebo daily for 8 weeks.
- The primary outcome was the mean number of nocturnal leg cramps per week, while secondary outcomes were the duration and severity of muscle cramps.
- The ethics committees of Third People’s Hospital of Chengdu and Affiliated Hospital of North Sichuan Medical College approved the study, and all participants provided written informed consent.
TAKEAWAY:
- Vitamin K group experienced a significant reduction in the mean weekly frequency of cramps (mean difference, 2.60 [SD, 0.81] to 0.96 [SD, 1.41]) compared with the placebo group, which maintained a mean weekly frequency of 3.63 (SD, 2.20) (P < .001).
- The severity of nocturnal leg cramps decreased more in the vitamin K group (mean difference, −2.55 [SD, 2.12] points) than in the placebo group (mean difference, −1.24 [SD, 1.16] points).
- The duration of nocturnal leg cramps also decreased more in the vitamin K group (mean difference, −0.90 [SD, 0.88] minutes) than in the placebo group (mean difference, −0.32 [SD, 0.78] minutes).
- No adverse events related to vitamin K use were identified, indicating a good safety profile for the supplementation.
IN PRACTICE:
“Given the generally benign characteristics of NLCs, treatment modality must be both effective and safe, thus minimizing the risk of iatrogenic harm,” the study authors wrote.
SOURCE:
This study was led by Jing Tan, MD, the Third People’s Hospital of Chengdu in Chengdu, China. It was published online on October 28 in JAMA Internal Medicine.
LIMITATIONS:
This study did not investigate the quality of life or sleep, which could have provided additional insights into the impact of vitamin K on nocturnal leg cramps. The relatively mild nature of nocturnal leg cramps experienced by the participants may limit the generalizability of the findings to populations with more severe symptoms.
DISCLOSURES:
This study was supported by grants from China Health Promotion Foundation and the Third People’s Hospital of Chengdu Scientific Research Project. Tan disclosed receiving personal fees from BeiGene, AbbVie, Pfizer, Xian Janssen Pharmaceutical, and Takeda Pharmaceutical 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 first appeared on Medscape.com.
TOPLINE:
Vitamin K supplementation significantly reduced the frequency, intensity, and duration of nocturnal leg cramps in older adults. No adverse events related to vitamin K were identified.
METHODOLOGY:
- Researchers conducted a multicenter, double-blind, placebo-controlled randomized clinical trial in China from September 2022 to December 2023.
- A total of 199 participants aged ≥ 65 years with at least two documented episodes of nocturnal leg cramps during a 2-week screening period were included.
- Participants were randomized in a 1:1 ratio to receive either 180 μg of vitamin K (menaquinone 7) or a placebo daily for 8 weeks.
- The primary outcome was the mean number of nocturnal leg cramps per week, while secondary outcomes were the duration and severity of muscle cramps.
- The ethics committees of Third People’s Hospital of Chengdu and Affiliated Hospital of North Sichuan Medical College approved the study, and all participants provided written informed consent.
TAKEAWAY:
- Vitamin K group experienced a significant reduction in the mean weekly frequency of cramps (mean difference, 2.60 [SD, 0.81] to 0.96 [SD, 1.41]) compared with the placebo group, which maintained a mean weekly frequency of 3.63 (SD, 2.20) (P < .001).
- The severity of nocturnal leg cramps decreased more in the vitamin K group (mean difference, −2.55 [SD, 2.12] points) than in the placebo group (mean difference, −1.24 [SD, 1.16] points).
- The duration of nocturnal leg cramps also decreased more in the vitamin K group (mean difference, −0.90 [SD, 0.88] minutes) than in the placebo group (mean difference, −0.32 [SD, 0.78] minutes).
- No adverse events related to vitamin K use were identified, indicating a good safety profile for the supplementation.
IN PRACTICE:
“Given the generally benign characteristics of NLCs, treatment modality must be both effective and safe, thus minimizing the risk of iatrogenic harm,” the study authors wrote.
SOURCE:
This study was led by Jing Tan, MD, the Third People’s Hospital of Chengdu in Chengdu, China. It was published online on October 28 in JAMA Internal Medicine.
LIMITATIONS:
This study did not investigate the quality of life or sleep, which could have provided additional insights into the impact of vitamin K on nocturnal leg cramps. The relatively mild nature of nocturnal leg cramps experienced by the participants may limit the generalizability of the findings to populations with more severe symptoms.
DISCLOSURES:
This study was supported by grants from China Health Promotion Foundation and the Third People’s Hospital of Chengdu Scientific Research Project. Tan disclosed receiving personal fees from BeiGene, AbbVie, Pfizer, Xian Janssen Pharmaceutical, and Takeda Pharmaceutical 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 first appeared on Medscape.com.
TOPLINE:
Vitamin K supplementation significantly reduced the frequency, intensity, and duration of nocturnal leg cramps in older adults. No adverse events related to vitamin K were identified.
METHODOLOGY:
- Researchers conducted a multicenter, double-blind, placebo-controlled randomized clinical trial in China from September 2022 to December 2023.
- A total of 199 participants aged ≥ 65 years with at least two documented episodes of nocturnal leg cramps during a 2-week screening period were included.
- Participants were randomized in a 1:1 ratio to receive either 180 μg of vitamin K (menaquinone 7) or a placebo daily for 8 weeks.
- The primary outcome was the mean number of nocturnal leg cramps per week, while secondary outcomes were the duration and severity of muscle cramps.
- The ethics committees of Third People’s Hospital of Chengdu and Affiliated Hospital of North Sichuan Medical College approved the study, and all participants provided written informed consent.
TAKEAWAY:
- Vitamin K group experienced a significant reduction in the mean weekly frequency of cramps (mean difference, 2.60 [SD, 0.81] to 0.96 [SD, 1.41]) compared with the placebo group, which maintained a mean weekly frequency of 3.63 (SD, 2.20) (P < .001).
- The severity of nocturnal leg cramps decreased more in the vitamin K group (mean difference, −2.55 [SD, 2.12] points) than in the placebo group (mean difference, −1.24 [SD, 1.16] points).
- The duration of nocturnal leg cramps also decreased more in the vitamin K group (mean difference, −0.90 [SD, 0.88] minutes) than in the placebo group (mean difference, −0.32 [SD, 0.78] minutes).
- No adverse events related to vitamin K use were identified, indicating a good safety profile for the supplementation.
IN PRACTICE:
“Given the generally benign characteristics of NLCs, treatment modality must be both effective and safe, thus minimizing the risk of iatrogenic harm,” the study authors wrote.
SOURCE:
This study was led by Jing Tan, MD, the Third People’s Hospital of Chengdu in Chengdu, China. It was published online on October 28 in JAMA Internal Medicine.
LIMITATIONS:
This study did not investigate the quality of life or sleep, which could have provided additional insights into the impact of vitamin K on nocturnal leg cramps. The relatively mild nature of nocturnal leg cramps experienced by the participants may limit the generalizability of the findings to populations with more severe symptoms.
DISCLOSURES:
This study was supported by grants from China Health Promotion Foundation and the Third People’s Hospital of Chengdu Scientific Research Project. Tan disclosed receiving personal fees from BeiGene, AbbVie, Pfizer, Xian Janssen Pharmaceutical, and Takeda Pharmaceutical 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 first appeared on Medscape.com.
Solo Vs McDoctors Inc.
STAT News recently ran a series on UnitedHealthcare (UHC) and its growing physician empire. This includes the corporation pressuring its employed physicians to see more patients, work weekends, upcode visits, add in diagnoses that will increase reimbursement, yadda, yadda, yadda.
For legal disclaimer purposes, I’m not saying UHC did any of this, nor am I saying they didn’t. But the series on STAT is worth reading.
Reading the articles brings back memories of the last time I was an employed physician, 24 years ago. I didn’t have people telling me to upcode visits, but I do remember hearing terms such as “dollars per physician per square foot” bandied about concerning my performance. At least back then no one was going to yell at me about a 1-star online review from a disgruntled patient.
After a little over 2 years I’d had enough and went solo.
I have no desire at this point to go back to that. I certainly make a lot less money than my employed counterparts, but I also have time and a degree of peace, which are worth something.
I’m not paying for anyone else’s overhead. I don’t slack off, but at least I know what I’m working for, and where the money is going when I write out a check. I can work my schedule around having to take my dog to the vet, or pick a kid up at the airport, or whatever.
I can spend more time with the patients who need it. Isn’t that part of why I’m here?
Wearing Hawaiian shirts and shorts to the office everyday is also a plus (at least I think so).
It surprises me that more physicians aren’t willing to go into solo or small group practice. The big advantage is freedom, only needing to pay the overhead and your salary, and cover for others when needed.
The downside is financial. Like our hunting and gathering ancestors, you eat what you kill. If there’s a shortfall in cash flow, I’m the one who doesn’t get paid. It’s always good to have a line of credit available to fall back on in a pinch.
I can see why it’s daunting. Coming out of training you have loans to pay off. You may have a young family, and your first mortgage. You sure don’t want to take out another loan to start a private practice. The security of a guaranteed paycheck and no start-up costs is attractive. I was there, too, and I also took the first job I was offered back then.
There’s also the fear of suddenly working without a net for the first time in your career. It’s reassuring to get some added experience while being able to bounce a challenging case off another doctor. (I still do that, too, and always will.)
But no one tells me to upcode visits or add diagnostic codes just to get more money. Patients don’t call in panicked that they have an ICD-10 code for a condition no one told them they had.
At the end of the day I can tell the guy in the mirror that I’m doing my best.
Medicine has changed a lot over time ... but being a doctor hasn’t. The spark that led us all here is still there, somewhere, I hope. Go back and read Neighbor Rosicky by Willa Cather, and The Doctor Stories by William Carlos Williams.
In an age when technology is moving us forward, I think the practice of medicine should move backward, away from McDoctors Inc. A small, even solo, medical practice isn’t incompatible with the shiny toys of 2024 medicine. You can make good patient care happen with both.
I freely admit that it’s not for everyone.
But I wish more people would see it as a realistic option, and take the road less traveled.
Dr. Block has a solo neurology practice in Scottsdale, Arizona.
STAT News recently ran a series on UnitedHealthcare (UHC) and its growing physician empire. This includes the corporation pressuring its employed physicians to see more patients, work weekends, upcode visits, add in diagnoses that will increase reimbursement, yadda, yadda, yadda.
For legal disclaimer purposes, I’m not saying UHC did any of this, nor am I saying they didn’t. But the series on STAT is worth reading.
Reading the articles brings back memories of the last time I was an employed physician, 24 years ago. I didn’t have people telling me to upcode visits, but I do remember hearing terms such as “dollars per physician per square foot” bandied about concerning my performance. At least back then no one was going to yell at me about a 1-star online review from a disgruntled patient.
After a little over 2 years I’d had enough and went solo.
I have no desire at this point to go back to that. I certainly make a lot less money than my employed counterparts, but I also have time and a degree of peace, which are worth something.
I’m not paying for anyone else’s overhead. I don’t slack off, but at least I know what I’m working for, and where the money is going when I write out a check. I can work my schedule around having to take my dog to the vet, or pick a kid up at the airport, or whatever.
I can spend more time with the patients who need it. Isn’t that part of why I’m here?
Wearing Hawaiian shirts and shorts to the office everyday is also a plus (at least I think so).
It surprises me that more physicians aren’t willing to go into solo or small group practice. The big advantage is freedom, only needing to pay the overhead and your salary, and cover for others when needed.
The downside is financial. Like our hunting and gathering ancestors, you eat what you kill. If there’s a shortfall in cash flow, I’m the one who doesn’t get paid. It’s always good to have a line of credit available to fall back on in a pinch.
I can see why it’s daunting. Coming out of training you have loans to pay off. You may have a young family, and your first mortgage. You sure don’t want to take out another loan to start a private practice. The security of a guaranteed paycheck and no start-up costs is attractive. I was there, too, and I also took the first job I was offered back then.
There’s also the fear of suddenly working without a net for the first time in your career. It’s reassuring to get some added experience while being able to bounce a challenging case off another doctor. (I still do that, too, and always will.)
But no one tells me to upcode visits or add diagnostic codes just to get more money. Patients don’t call in panicked that they have an ICD-10 code for a condition no one told them they had.
At the end of the day I can tell the guy in the mirror that I’m doing my best.
Medicine has changed a lot over time ... but being a doctor hasn’t. The spark that led us all here is still there, somewhere, I hope. Go back and read Neighbor Rosicky by Willa Cather, and The Doctor Stories by William Carlos Williams.
In an age when technology is moving us forward, I think the practice of medicine should move backward, away from McDoctors Inc. A small, even solo, medical practice isn’t incompatible with the shiny toys of 2024 medicine. You can make good patient care happen with both.
I freely admit that it’s not for everyone.
But I wish more people would see it as a realistic option, and take the road less traveled.
Dr. Block has a solo neurology practice in Scottsdale, Arizona.
STAT News recently ran a series on UnitedHealthcare (UHC) and its growing physician empire. This includes the corporation pressuring its employed physicians to see more patients, work weekends, upcode visits, add in diagnoses that will increase reimbursement, yadda, yadda, yadda.
For legal disclaimer purposes, I’m not saying UHC did any of this, nor am I saying they didn’t. But the series on STAT is worth reading.
Reading the articles brings back memories of the last time I was an employed physician, 24 years ago. I didn’t have people telling me to upcode visits, but I do remember hearing terms such as “dollars per physician per square foot” bandied about concerning my performance. At least back then no one was going to yell at me about a 1-star online review from a disgruntled patient.
After a little over 2 years I’d had enough and went solo.
I have no desire at this point to go back to that. I certainly make a lot less money than my employed counterparts, but I also have time and a degree of peace, which are worth something.
I’m not paying for anyone else’s overhead. I don’t slack off, but at least I know what I’m working for, and where the money is going when I write out a check. I can work my schedule around having to take my dog to the vet, or pick a kid up at the airport, or whatever.
I can spend more time with the patients who need it. Isn’t that part of why I’m here?
Wearing Hawaiian shirts and shorts to the office everyday is also a plus (at least I think so).
It surprises me that more physicians aren’t willing to go into solo or small group practice. The big advantage is freedom, only needing to pay the overhead and your salary, and cover for others when needed.
The downside is financial. Like our hunting and gathering ancestors, you eat what you kill. If there’s a shortfall in cash flow, I’m the one who doesn’t get paid. It’s always good to have a line of credit available to fall back on in a pinch.
I can see why it’s daunting. Coming out of training you have loans to pay off. You may have a young family, and your first mortgage. You sure don’t want to take out another loan to start a private practice. The security of a guaranteed paycheck and no start-up costs is attractive. I was there, too, and I also took the first job I was offered back then.
There’s also the fear of suddenly working without a net for the first time in your career. It’s reassuring to get some added experience while being able to bounce a challenging case off another doctor. (I still do that, too, and always will.)
But no one tells me to upcode visits or add diagnostic codes just to get more money. Patients don’t call in panicked that they have an ICD-10 code for a condition no one told them they had.
At the end of the day I can tell the guy in the mirror that I’m doing my best.
Medicine has changed a lot over time ... but being a doctor hasn’t. The spark that led us all here is still there, somewhere, I hope. Go back and read Neighbor Rosicky by Willa Cather, and The Doctor Stories by William Carlos Williams.
In an age when technology is moving us forward, I think the practice of medicine should move backward, away from McDoctors Inc. A small, even solo, medical practice isn’t incompatible with the shiny toys of 2024 medicine. You can make good patient care happen with both.
I freely admit that it’s not for everyone.
But I wish more people would see it as a realistic option, and take the road less traveled.
Dr. Block has a solo neurology practice in Scottsdale, Arizona.
Many Patients With Cancer Visit EDs Before Diagnosis
Researchers examined Institute for Clinical Evaluative Sciences (ICES) data that had been gathered from January 1, 2014, to December 31, 2021. The study focused on patients aged 18 years or older with confirmed primary cancer diagnoses.
Factors associated with an increased likelihood of an ED visit ahead of diagnosis included having certain cancers, living in rural areas, and having less access to primary care, according to study author Keerat Grewal, MD, an emergency physician and clinician scientist at the Schwartz/Reisman Emergency Medicine Institute at Sinai Health in Toronto, Ontario, Canada, and coauthors.
“The ED is a distressing environment for patients to receive a possible cancer diagnosis,” the authors wrote. “Moreover, it is frequently ill equipped to provide ongoing continuity of care, which can lead patients down a poorly defined diagnostic pathway before receiving a confirmed diagnosis based on tissue and a subsequent treatment plan.”
The findings were published online on November 4 in CMAJ).
Neurologic Cancers Prominent
In an interview, Grewal said in an interview that the study reflects her desire as an emergency room physician to understand why so many patients with cancer get the initial reports about their disease from clinicians whom they often have just met for the first time.
Among patients with an ED visit before cancer diagnosis, 51.4% were admitted to hospital from the most recent visit.
Compared with patients with a family physician on whom they could rely for routine care, those who had no outpatient visits (odds ratio [OR], 2.09) or fewer than three outpatient visits (OR, 1.41) in the 6-30 months before cancer diagnosis were more likely to have an ED visit before their cancer diagnosis.
Other factors associated with increased odds of ED use before cancer diagnosis included rurality (OR, 1.15), residence in northern Ontario (northeast region: OR, 1.14 and northwest region: OR, 1.27 vs Toronto region), and living in the most marginalized areas (material resource deprivation: OR, 1.37 and housing stability: OR, 1.09 vs least marginalized area).
The researchers also found that patients with certain cancers were more likely to have sought care in the ED. They compared these cancers with breast cancer, which is often detected through screening.
“Patients with neurologic cancers had extremely high odds of ED use before cancer diagnosis,” the authors wrote. “This is likely because of the emergent nature of presentation, with acute neurologic symptoms such as weakness, confusion, or seizures, which require urgent assessment.” On the other hand, pancreatic, liver, or thoracic cancer can trigger nonspecific symptoms that may be ignored until they reach a crisis level that prompts an ED visit.
The limitations of the study included its inability to identify cancer-related ED visits and its narrow focus on patients in Ontario, according to the researchers. But the use of the ICES databases also allowed researchers access to a broader pool of data than are available in many other cases.
The findings in the new paper echo those of previous research, the authors noted. Research in the United Kingdom found that 24%-31% of cancer diagnoses involved the ED. In addition, a study of people enrolled in the US Medicare program, which serves patients aged 65 years or older, found that 23% were seen in the ED in the 30 days before diagnosis.
‘Unpacking the Data’
The current findings also are consistent with those of an International Cancer Benchmarking Partnership study that was published in 2022 in The Lancet Oncology, said Erika Nicholson, MHS, vice president of cancer systems and innovation at the Canadian Partnership Against Cancer. The latter study analyzed cancer registration and linked hospital admissions data from 14 jurisdictions in Australia, Canada, Denmark, New Zealand, Norway, and the United Kingdom.
“We see similar trends in terms of people visiting EDs and being diagnosed through EDs internationally,” Nicholson said. “We’re working with partners to put in place different strategies to address the challenges” that this phenomenon presents in terms of improving screening and follow-up care.
“Cancer is not one disease, but many diseases,” she said. “They present differently. We’re focused on really unpacking the data and understanding them.”
All this research highlights the need for more services and personnel to address cancer, including people who are trained to help patients cope after getting concerning news through emergency care, she said.
“That means having a system that fully supports you and helps you navigate through that diagnostic process,” Nicholson said. Addressing the added challenges for patients who don’t have secure housing is a special need, she added.
This study was supported by the Canadian Institutes of Health Research (CIHR). Grewal reported receiving grants from CIHR and the Canadian Association of Emergency Physicians. Nicholson reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Researchers examined Institute for Clinical Evaluative Sciences (ICES) data that had been gathered from January 1, 2014, to December 31, 2021. The study focused on patients aged 18 years or older with confirmed primary cancer diagnoses.
Factors associated with an increased likelihood of an ED visit ahead of diagnosis included having certain cancers, living in rural areas, and having less access to primary care, according to study author Keerat Grewal, MD, an emergency physician and clinician scientist at the Schwartz/Reisman Emergency Medicine Institute at Sinai Health in Toronto, Ontario, Canada, and coauthors.
“The ED is a distressing environment for patients to receive a possible cancer diagnosis,” the authors wrote. “Moreover, it is frequently ill equipped to provide ongoing continuity of care, which can lead patients down a poorly defined diagnostic pathway before receiving a confirmed diagnosis based on tissue and a subsequent treatment plan.”
The findings were published online on November 4 in CMAJ).
Neurologic Cancers Prominent
In an interview, Grewal said in an interview that the study reflects her desire as an emergency room physician to understand why so many patients with cancer get the initial reports about their disease from clinicians whom they often have just met for the first time.
Among patients with an ED visit before cancer diagnosis, 51.4% were admitted to hospital from the most recent visit.
Compared with patients with a family physician on whom they could rely for routine care, those who had no outpatient visits (odds ratio [OR], 2.09) or fewer than three outpatient visits (OR, 1.41) in the 6-30 months before cancer diagnosis were more likely to have an ED visit before their cancer diagnosis.
Other factors associated with increased odds of ED use before cancer diagnosis included rurality (OR, 1.15), residence in northern Ontario (northeast region: OR, 1.14 and northwest region: OR, 1.27 vs Toronto region), and living in the most marginalized areas (material resource deprivation: OR, 1.37 and housing stability: OR, 1.09 vs least marginalized area).
The researchers also found that patients with certain cancers were more likely to have sought care in the ED. They compared these cancers with breast cancer, which is often detected through screening.
“Patients with neurologic cancers had extremely high odds of ED use before cancer diagnosis,” the authors wrote. “This is likely because of the emergent nature of presentation, with acute neurologic symptoms such as weakness, confusion, or seizures, which require urgent assessment.” On the other hand, pancreatic, liver, or thoracic cancer can trigger nonspecific symptoms that may be ignored until they reach a crisis level that prompts an ED visit.
The limitations of the study included its inability to identify cancer-related ED visits and its narrow focus on patients in Ontario, according to the researchers. But the use of the ICES databases also allowed researchers access to a broader pool of data than are available in many other cases.
The findings in the new paper echo those of previous research, the authors noted. Research in the United Kingdom found that 24%-31% of cancer diagnoses involved the ED. In addition, a study of people enrolled in the US Medicare program, which serves patients aged 65 years or older, found that 23% were seen in the ED in the 30 days before diagnosis.
‘Unpacking the Data’
The current findings also are consistent with those of an International Cancer Benchmarking Partnership study that was published in 2022 in The Lancet Oncology, said Erika Nicholson, MHS, vice president of cancer systems and innovation at the Canadian Partnership Against Cancer. The latter study analyzed cancer registration and linked hospital admissions data from 14 jurisdictions in Australia, Canada, Denmark, New Zealand, Norway, and the United Kingdom.
“We see similar trends in terms of people visiting EDs and being diagnosed through EDs internationally,” Nicholson said. “We’re working with partners to put in place different strategies to address the challenges” that this phenomenon presents in terms of improving screening and follow-up care.
“Cancer is not one disease, but many diseases,” she said. “They present differently. We’re focused on really unpacking the data and understanding them.”
All this research highlights the need for more services and personnel to address cancer, including people who are trained to help patients cope after getting concerning news through emergency care, she said.
“That means having a system that fully supports you and helps you navigate through that diagnostic process,” Nicholson said. Addressing the added challenges for patients who don’t have secure housing is a special need, she added.
This study was supported by the Canadian Institutes of Health Research (CIHR). Grewal reported receiving grants from CIHR and the Canadian Association of Emergency Physicians. Nicholson reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Researchers examined Institute for Clinical Evaluative Sciences (ICES) data that had been gathered from January 1, 2014, to December 31, 2021. The study focused on patients aged 18 years or older with confirmed primary cancer diagnoses.
Factors associated with an increased likelihood of an ED visit ahead of diagnosis included having certain cancers, living in rural areas, and having less access to primary care, according to study author Keerat Grewal, MD, an emergency physician and clinician scientist at the Schwartz/Reisman Emergency Medicine Institute at Sinai Health in Toronto, Ontario, Canada, and coauthors.
“The ED is a distressing environment for patients to receive a possible cancer diagnosis,” the authors wrote. “Moreover, it is frequently ill equipped to provide ongoing continuity of care, which can lead patients down a poorly defined diagnostic pathway before receiving a confirmed diagnosis based on tissue and a subsequent treatment plan.”
The findings were published online on November 4 in CMAJ).
Neurologic Cancers Prominent
In an interview, Grewal said in an interview that the study reflects her desire as an emergency room physician to understand why so many patients with cancer get the initial reports about their disease from clinicians whom they often have just met for the first time.
Among patients with an ED visit before cancer diagnosis, 51.4% were admitted to hospital from the most recent visit.
Compared with patients with a family physician on whom they could rely for routine care, those who had no outpatient visits (odds ratio [OR], 2.09) or fewer than three outpatient visits (OR, 1.41) in the 6-30 months before cancer diagnosis were more likely to have an ED visit before their cancer diagnosis.
Other factors associated with increased odds of ED use before cancer diagnosis included rurality (OR, 1.15), residence in northern Ontario (northeast region: OR, 1.14 and northwest region: OR, 1.27 vs Toronto region), and living in the most marginalized areas (material resource deprivation: OR, 1.37 and housing stability: OR, 1.09 vs least marginalized area).
The researchers also found that patients with certain cancers were more likely to have sought care in the ED. They compared these cancers with breast cancer, which is often detected through screening.
“Patients with neurologic cancers had extremely high odds of ED use before cancer diagnosis,” the authors wrote. “This is likely because of the emergent nature of presentation, with acute neurologic symptoms such as weakness, confusion, or seizures, which require urgent assessment.” On the other hand, pancreatic, liver, or thoracic cancer can trigger nonspecific symptoms that may be ignored until they reach a crisis level that prompts an ED visit.
The limitations of the study included its inability to identify cancer-related ED visits and its narrow focus on patients in Ontario, according to the researchers. But the use of the ICES databases also allowed researchers access to a broader pool of data than are available in many other cases.
The findings in the new paper echo those of previous research, the authors noted. Research in the United Kingdom found that 24%-31% of cancer diagnoses involved the ED. In addition, a study of people enrolled in the US Medicare program, which serves patients aged 65 years or older, found that 23% were seen in the ED in the 30 days before diagnosis.
‘Unpacking the Data’
The current findings also are consistent with those of an International Cancer Benchmarking Partnership study that was published in 2022 in The Lancet Oncology, said Erika Nicholson, MHS, vice president of cancer systems and innovation at the Canadian Partnership Against Cancer. The latter study analyzed cancer registration and linked hospital admissions data from 14 jurisdictions in Australia, Canada, Denmark, New Zealand, Norway, and the United Kingdom.
“We see similar trends in terms of people visiting EDs and being diagnosed through EDs internationally,” Nicholson said. “We’re working with partners to put in place different strategies to address the challenges” that this phenomenon presents in terms of improving screening and follow-up care.
“Cancer is not one disease, but many diseases,” she said. “They present differently. We’re focused on really unpacking the data and understanding them.”
All this research highlights the need for more services and personnel to address cancer, including people who are trained to help patients cope after getting concerning news through emergency care, she said.
“That means having a system that fully supports you and helps you navigate through that diagnostic process,” Nicholson said. Addressing the added challenges for patients who don’t have secure housing is a special need, she added.
This study was supported by the Canadian Institutes of Health Research (CIHR). Grewal reported receiving grants from CIHR and the Canadian Association of Emergency Physicians. Nicholson reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM CMAJ
Scurvy: A Diagnosis Still Relevant Today
“Petechial rash often prompts further investigation into hematological, dermatological, or vasculitis causes. However, if the above investigations are negative and skin biopsy has not revealed a cause, there is a Renaissance-era diagnosis that is often overlooked but is easily investigated and treated,” wrote Andrew Dermawan, MD, and colleagues from Sir Charles Gairdner Hospital in Nedlands, Australia, in BMJ Case Reports. The diagnosis they highlight is scurvy, a disease that has faded from common medical concern but is reemerging, partly because of the rise in bariatric surgery.
Diagnosing Scurvy in the 2020s
In their article, Dermawan and colleagues present the case of a 50-year-old man with a bilateral petechial rash on his lower limbs, without any history of trauma. The patient, who exhibited no infectious symptoms, also had gross hematuria, microcytic anemia, mild neutropenia, and lymphopenia. Tests for autoimmune and hematological diseases were negative, as were abdominal and leg CT scans, ruling out abdominal hemorrhage and vasculitis. Additionally, a skin biopsy showed no causative findings.
The doctors noted that the patient had undergone sleeve gastrectomy, prompting them to inquire about his diet. They discovered that, because of financial difficulties, his diet primarily consisted of processed foods with little to no fruits or vegetables, and he had stopped taking supplements recommended by his gastroenterologist. Further tests revealed a vitamin D deficiency and a severe deficiency in vitamin C. With the diagnosis of scurvy confirmed, the doctors treated the patient with 1000 mg of ascorbic acid daily, along with cholecalciferol, folic acid, and a multivitamin complex, leading to a complete resolution of his symptoms.
Risk Factors Then and Now
It can cause mucosal and gastric hemorrhages, and if left untreated, it can lead to fatal bleeding.
Historically known as “sailors’ disease,” scurvy plagued men on long voyages who lacked access to fresh fruits or vegetables and thus did not get enough vitamin C. In 1747, James Lind, a British physician in the Royal Navy, demonstrated that the consumption of oranges and lemons could combat scurvy.
Today’s risk factors for scurvy include malnutrition, gastrointestinal disorders (eg, chronic inflammatory bowel diseases), alcohol and tobacco use, eating disorders, psychiatric illnesses, dialysis, and the use of medications that reduce the absorption of ascorbic acid (such as corticosteroids and proton pump inhibitors).
Scurvy remains more common among individuals with unfavorable socioeconomic conditions. The authors of the study emphasize how the rising cost of living — specifically in Australia but applicable elsewhere — is changing eating habits, leading to a high consumption of low-cost, nutritionally poor foods.
Poverty has always been a risk factor for scurvy, but today there may be an additional cause: bariatric surgery. Patients undergoing these procedures are at a risk for deficiencies in fat-soluble vitamins A, D, E, and K, and if their diet is inadequate, they may also experience a vitamin C deficiency. Awareness of this can facilitate the timely diagnosis of scurvy in these patients.
This story was translated from Univadis Italy 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.
“Petechial rash often prompts further investigation into hematological, dermatological, or vasculitis causes. However, if the above investigations are negative and skin biopsy has not revealed a cause, there is a Renaissance-era diagnosis that is often overlooked but is easily investigated and treated,” wrote Andrew Dermawan, MD, and colleagues from Sir Charles Gairdner Hospital in Nedlands, Australia, in BMJ Case Reports. The diagnosis they highlight is scurvy, a disease that has faded from common medical concern but is reemerging, partly because of the rise in bariatric surgery.
Diagnosing Scurvy in the 2020s
In their article, Dermawan and colleagues present the case of a 50-year-old man with a bilateral petechial rash on his lower limbs, without any history of trauma. The patient, who exhibited no infectious symptoms, also had gross hematuria, microcytic anemia, mild neutropenia, and lymphopenia. Tests for autoimmune and hematological diseases were negative, as were abdominal and leg CT scans, ruling out abdominal hemorrhage and vasculitis. Additionally, a skin biopsy showed no causative findings.
The doctors noted that the patient had undergone sleeve gastrectomy, prompting them to inquire about his diet. They discovered that, because of financial difficulties, his diet primarily consisted of processed foods with little to no fruits or vegetables, and he had stopped taking supplements recommended by his gastroenterologist. Further tests revealed a vitamin D deficiency and a severe deficiency in vitamin C. With the diagnosis of scurvy confirmed, the doctors treated the patient with 1000 mg of ascorbic acid daily, along with cholecalciferol, folic acid, and a multivitamin complex, leading to a complete resolution of his symptoms.
Risk Factors Then and Now
It can cause mucosal and gastric hemorrhages, and if left untreated, it can lead to fatal bleeding.
Historically known as “sailors’ disease,” scurvy plagued men on long voyages who lacked access to fresh fruits or vegetables and thus did not get enough vitamin C. In 1747, James Lind, a British physician in the Royal Navy, demonstrated that the consumption of oranges and lemons could combat scurvy.
Today’s risk factors for scurvy include malnutrition, gastrointestinal disorders (eg, chronic inflammatory bowel diseases), alcohol and tobacco use, eating disorders, psychiatric illnesses, dialysis, and the use of medications that reduce the absorption of ascorbic acid (such as corticosteroids and proton pump inhibitors).
Scurvy remains more common among individuals with unfavorable socioeconomic conditions. The authors of the study emphasize how the rising cost of living — specifically in Australia but applicable elsewhere — is changing eating habits, leading to a high consumption of low-cost, nutritionally poor foods.
Poverty has always been a risk factor for scurvy, but today there may be an additional cause: bariatric surgery. Patients undergoing these procedures are at a risk for deficiencies in fat-soluble vitamins A, D, E, and K, and if their diet is inadequate, they may also experience a vitamin C deficiency. Awareness of this can facilitate the timely diagnosis of scurvy in these patients.
This story was translated from Univadis Italy 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.
“Petechial rash often prompts further investigation into hematological, dermatological, or vasculitis causes. However, if the above investigations are negative and skin biopsy has not revealed a cause, there is a Renaissance-era diagnosis that is often overlooked but is easily investigated and treated,” wrote Andrew Dermawan, MD, and colleagues from Sir Charles Gairdner Hospital in Nedlands, Australia, in BMJ Case Reports. The diagnosis they highlight is scurvy, a disease that has faded from common medical concern but is reemerging, partly because of the rise in bariatric surgery.
Diagnosing Scurvy in the 2020s
In their article, Dermawan and colleagues present the case of a 50-year-old man with a bilateral petechial rash on his lower limbs, without any history of trauma. The patient, who exhibited no infectious symptoms, also had gross hematuria, microcytic anemia, mild neutropenia, and lymphopenia. Tests for autoimmune and hematological diseases were negative, as were abdominal and leg CT scans, ruling out abdominal hemorrhage and vasculitis. Additionally, a skin biopsy showed no causative findings.
The doctors noted that the patient had undergone sleeve gastrectomy, prompting them to inquire about his diet. They discovered that, because of financial difficulties, his diet primarily consisted of processed foods with little to no fruits or vegetables, and he had stopped taking supplements recommended by his gastroenterologist. Further tests revealed a vitamin D deficiency and a severe deficiency in vitamin C. With the diagnosis of scurvy confirmed, the doctors treated the patient with 1000 mg of ascorbic acid daily, along with cholecalciferol, folic acid, and a multivitamin complex, leading to a complete resolution of his symptoms.
Risk Factors Then and Now
It can cause mucosal and gastric hemorrhages, and if left untreated, it can lead to fatal bleeding.
Historically known as “sailors’ disease,” scurvy plagued men on long voyages who lacked access to fresh fruits or vegetables and thus did not get enough vitamin C. In 1747, James Lind, a British physician in the Royal Navy, demonstrated that the consumption of oranges and lemons could combat scurvy.
Today’s risk factors for scurvy include malnutrition, gastrointestinal disorders (eg, chronic inflammatory bowel diseases), alcohol and tobacco use, eating disorders, psychiatric illnesses, dialysis, and the use of medications that reduce the absorption of ascorbic acid (such as corticosteroids and proton pump inhibitors).
Scurvy remains more common among individuals with unfavorable socioeconomic conditions. The authors of the study emphasize how the rising cost of living — specifically in Australia but applicable elsewhere — is changing eating habits, leading to a high consumption of low-cost, nutritionally poor foods.
Poverty has always been a risk factor for scurvy, but today there may be an additional cause: bariatric surgery. Patients undergoing these procedures are at a risk for deficiencies in fat-soluble vitamins A, D, E, and K, and if their diet is inadequate, they may also experience a vitamin C deficiency. Awareness of this can facilitate the timely diagnosis of scurvy in these patients.
This story was translated from Univadis Italy 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.
Plasma Omega-6 and Omega-3 Fatty Acids Inversely Associated With Cancer
TOPLINE:
Higher plasma levels of omega-6 and omega-3 fatty acids are associated with a lower incidence of cancer. However, omega-3 fatty acids are linked to an increased risk for prostate cancer, specifically.
METHODOLOGY:
- Researchers looked for associations of plasma omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) with the incidence of cancer overall and 19 site-specific cancers in the large population-based prospective UK Biobank cohort.
- They included 253,138 participants aged 37-73 years who were followed for an average of 12.9 years, with 29,838 diagnosed with cancer.
- Plasma levels of omega-3 and omega-6 fatty acids were measured using nuclear magnetic resonance and expressed as percentages of total fatty acids.
- Participants with cancer diagnoses at baseline, those who withdrew from the study, and those with missing data on plasma PUFAs were excluded.
- The study adjusted for multiple covariates, including age, sex, ethnicity, socioeconomic status, lifestyle behaviors, and family history of diseases.
TAKEAWAY:
- Higher plasma levels of omega-6 and omega-3 fatty acids were associated with a 2% and 1% reduction in overall cancer risk per SD increase, respectively (P = .001 and P = .03).
- Omega-6 fatty acids were inversely associated with 14 site-specific cancers, whereas omega-3 fatty acids were inversely associated with five site-specific cancers.
- Prostate cancer was positively associated with omega-3 fatty acids, with a 3% increased risk per SD increase (P = .049).
- A higher omega-6/omega-3 ratio was associated with an increased risk for overall cancer, and three site-specific cancers showed positive associations with the ratio. “Each standard deviation increase, corresponding to a 13.13 increase in the omega ratio, was associated with a 2% increase in the risk of rectum cancer,” for example, the authors wrote.
IN PRACTICE:
“Overall, our findings provide support for possible small net protective roles of omega-3 and omega-6 PUFAs in the development of new cancer incidence. Our study also suggests that the usage of circulating blood biomarkers captures different aspects of dietary intake, reduces measurement errors, and thus enhances statistical power. The differential effects of omega-6% and omega-3% in age and sex subgroups warrant future investigation,” wrote the authors of the study.
SOURCE:
The study was led by Yuchen Zhang of the University of Georgia in Athens, Georgia. It was published online in the International Journal of Cancer.
LIMITATIONS:
The study’s potential for selective bias persists due to the participant sample skewing heavily toward European ancestry and White ethnicity. The number of events was small for some specific cancer sites, which may have limited the statistical power. The study focused on total omega-3 and omega-6 PUFAs, with only two individual fatty acids measured. Future studies are needed to examine the roles of other individual PUFAs and specific genetic variants.
DISCLOSURES:
This study was supported by grants from the National Institute of General Medical Sciences of the National Institutes of Health. No relevant conflicts of interest were disclosed by the authors.
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:
Higher plasma levels of omega-6 and omega-3 fatty acids are associated with a lower incidence of cancer. However, omega-3 fatty acids are linked to an increased risk for prostate cancer, specifically.
METHODOLOGY:
- Researchers looked for associations of plasma omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) with the incidence of cancer overall and 19 site-specific cancers in the large population-based prospective UK Biobank cohort.
- They included 253,138 participants aged 37-73 years who were followed for an average of 12.9 years, with 29,838 diagnosed with cancer.
- Plasma levels of omega-3 and omega-6 fatty acids were measured using nuclear magnetic resonance and expressed as percentages of total fatty acids.
- Participants with cancer diagnoses at baseline, those who withdrew from the study, and those with missing data on plasma PUFAs were excluded.
- The study adjusted for multiple covariates, including age, sex, ethnicity, socioeconomic status, lifestyle behaviors, and family history of diseases.
TAKEAWAY:
- Higher plasma levels of omega-6 and omega-3 fatty acids were associated with a 2% and 1% reduction in overall cancer risk per SD increase, respectively (P = .001 and P = .03).
- Omega-6 fatty acids were inversely associated with 14 site-specific cancers, whereas omega-3 fatty acids were inversely associated with five site-specific cancers.
- Prostate cancer was positively associated with omega-3 fatty acids, with a 3% increased risk per SD increase (P = .049).
- A higher omega-6/omega-3 ratio was associated with an increased risk for overall cancer, and three site-specific cancers showed positive associations with the ratio. “Each standard deviation increase, corresponding to a 13.13 increase in the omega ratio, was associated with a 2% increase in the risk of rectum cancer,” for example, the authors wrote.
IN PRACTICE:
“Overall, our findings provide support for possible small net protective roles of omega-3 and omega-6 PUFAs in the development of new cancer incidence. Our study also suggests that the usage of circulating blood biomarkers captures different aspects of dietary intake, reduces measurement errors, and thus enhances statistical power. The differential effects of omega-6% and omega-3% in age and sex subgroups warrant future investigation,” wrote the authors of the study.
SOURCE:
The study was led by Yuchen Zhang of the University of Georgia in Athens, Georgia. It was published online in the International Journal of Cancer.
LIMITATIONS:
The study’s potential for selective bias persists due to the participant sample skewing heavily toward European ancestry and White ethnicity. The number of events was small for some specific cancer sites, which may have limited the statistical power. The study focused on total omega-3 and omega-6 PUFAs, with only two individual fatty acids measured. Future studies are needed to examine the roles of other individual PUFAs and specific genetic variants.
DISCLOSURES:
This study was supported by grants from the National Institute of General Medical Sciences of the National Institutes of Health. No relevant conflicts of interest were disclosed by the authors.
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:
Higher plasma levels of omega-6 and omega-3 fatty acids are associated with a lower incidence of cancer. However, omega-3 fatty acids are linked to an increased risk for prostate cancer, specifically.
METHODOLOGY:
- Researchers looked for associations of plasma omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) with the incidence of cancer overall and 19 site-specific cancers in the large population-based prospective UK Biobank cohort.
- They included 253,138 participants aged 37-73 years who were followed for an average of 12.9 years, with 29,838 diagnosed with cancer.
- Plasma levels of omega-3 and omega-6 fatty acids were measured using nuclear magnetic resonance and expressed as percentages of total fatty acids.
- Participants with cancer diagnoses at baseline, those who withdrew from the study, and those with missing data on plasma PUFAs were excluded.
- The study adjusted for multiple covariates, including age, sex, ethnicity, socioeconomic status, lifestyle behaviors, and family history of diseases.
TAKEAWAY:
- Higher plasma levels of omega-6 and omega-3 fatty acids were associated with a 2% and 1% reduction in overall cancer risk per SD increase, respectively (P = .001 and P = .03).
- Omega-6 fatty acids were inversely associated with 14 site-specific cancers, whereas omega-3 fatty acids were inversely associated with five site-specific cancers.
- Prostate cancer was positively associated with omega-3 fatty acids, with a 3% increased risk per SD increase (P = .049).
- A higher omega-6/omega-3 ratio was associated with an increased risk for overall cancer, and three site-specific cancers showed positive associations with the ratio. “Each standard deviation increase, corresponding to a 13.13 increase in the omega ratio, was associated with a 2% increase in the risk of rectum cancer,” for example, the authors wrote.
IN PRACTICE:
“Overall, our findings provide support for possible small net protective roles of omega-3 and omega-6 PUFAs in the development of new cancer incidence. Our study also suggests that the usage of circulating blood biomarkers captures different aspects of dietary intake, reduces measurement errors, and thus enhances statistical power. The differential effects of omega-6% and omega-3% in age and sex subgroups warrant future investigation,” wrote the authors of the study.
SOURCE:
The study was led by Yuchen Zhang of the University of Georgia in Athens, Georgia. It was published online in the International Journal of Cancer.
LIMITATIONS:
The study’s potential for selective bias persists due to the participant sample skewing heavily toward European ancestry and White ethnicity. The number of events was small for some specific cancer sites, which may have limited the statistical power. The study focused on total omega-3 and omega-6 PUFAs, with only two individual fatty acids measured. Future studies are needed to examine the roles of other individual PUFAs and specific genetic variants.
DISCLOSURES:
This study was supported by grants from the National Institute of General Medical Sciences of the National Institutes of Health. No relevant conflicts of interest were disclosed by the authors.
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.