Federal Practitioner

LAS VEGAS — Measuring disease status in inflammatory bowel disease (IBD) patients generally requires invasive blood draws or procedures, but a novel wearable device shows initial promise at providing similar information from perspiration.

The device, in development by EnLiSense, can rapidly detect calprotectin, C-reactive protein (CRP), and interleukin-6 (IL-6), using miniaturized versions of biochemical lab tests.

Patient monitoring relies on identifying trends, whether biomarker levels are increasing or decreasing, according to Shalini Prasad, PhD, who presented the study during a poster session at the annual Crohn’s & Colitis Congress^®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “In a blood test you don’t get that unless you’re willing to sample every month. That’s the benefit [of the device],” said Dr. Prasad, professor of bioengineering at University of Texas at Dallas and a cofounder of EnLiSense.

University of Texas at Dallas

The project grew out of the involvement of EnLiSense with the Biomedical Advanced Research Development Authority (BARDA). “We were tracking infections, and we were looking at inflammatory markers associated with infections: Cytokines and chemokines. We thought it was a natural pivot for us because the disease of inflammation is IBD,” said Dr. Prasad.

The device need only be worn when the physician determines the disease is in a variable state. The patient “will wear it for the duration of time as determined by the clinician,” said Dr. Prasad.

The watch face–sized device, typically worn on the forearm, absorbs sweat and performs automated biochemical analysis independently, then beams its findings to the cloud. “What you get back is concentration [of inflammatory biomarkers]. It is essentially trend line reporting of how the concentration is fluctuating over time for markers,” said Dr. Prasad.

The Crohn’s and Colitis Foundation is supporting the company through its IBD Ventures program. EnLiSense is currently conducting a study tracking patients over 4 weeks to correlate biomarker concentrations in sweat with concentrations in stool.

A key remaining question is how long the device should be worn and during what clinical periods. The technology has the potential to provide too much information. “Just figuring the balance. We’re trying to find the right spot where it makes sense for both the clinician and the patient. This is something that is a work in progress. We don’t want this to be just like any other consumer wearable which gives you something but you’re not sure what it means,” said Dr. Prasad.

The study included 33 patients with IBD who were monitored between 40 and 130 minutes. The device measured levels of CRP, IL-6, and calprotectin. Serum samples were also measured the same day.

The researchers found higher levels of calprotectin among patients with active disease in perspiration (P = .0260), serum (P = .022), and in fecal samples (P = .0411). There were no significant differences between patients who are active and those in remission with respect to CRP levels in perspiration or serum, or IL-6 in perspiration. Serum Il-6 levels were higher in those with active disease.

There was no significant difference between serum and sweat calprotectin levels among patients who were active or in remission, but the median expression of IL-6 in perspiration was higher in the active group (P = .0016). In the active group, calprotectin was elevated in sweat, serum, and stool.

Levels of calprotectin measured in perspiration correlated with levels in the serum (R2 = 0.7195), as did CRP (R2 = 0.615) and IL-6 (R2 = 0.5411).
 

Treating to Target

The poster caught the interest of Jeremiah Faith, PhD, who attended the session and was asked to comment. “I think patients want to know what’s happening [with their disease], and we could probably give better care if we know day to day the status of someone, especially because every time we test them we get a point in time, but the reality is probably that people are kind of wavy, and knowing the wave is much better,” he said.

He noted that there was not a strong separation between mean perspiration calprotectin values, but he said the ability to take frequent measurements could overcome that weakness. “The difference between active and remission is not as drastic as what you’d see from blood, for example. But it’s the same thing with your watch. Your watch is a really poor sensor of what your heartbeat is doing, but if you measure it every few seconds, and you average over a long period of time, it can actually more be more [accurate]. So there’s a lot of potential for this,” said Dr. Faith, associate professor of genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai in New York.

If perfected, the device could help efforts at treating to target, in which therapies are adjusted to achieve minimal disease. Currently, physicians are forced to adjust doses or change therapies based on infrequent testing. “If this is accurate ... maybe at some point we will have the tools to be smarter about it,” said Dr. Faith.

Dr. Prasad is a cofounder of EnLiSense. Dr. Faith has no relevant financial disclosures.

LAS VEGAS — Measuring disease status in inflammatory bowel disease (IBD) patients generally requires invasive blood draws or procedures, but a novel wearable device shows initial promise at providing similar information from perspiration.

The device, in development by EnLiSense, can rapidly detect calprotectin, C-reactive protein (CRP), and interleukin-6 (IL-6), using miniaturized versions of biochemical lab tests.

Patient monitoring relies on identifying trends, whether biomarker levels are increasing or decreasing, according to Shalini Prasad, PhD, who presented the study during a poster session at the annual Crohn’s & Colitis Congress^®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “In a blood test you don’t get that unless you’re willing to sample every month. That’s the benefit [of the device],” said Dr. Prasad, professor of bioengineering at University of Texas at Dallas and a cofounder of EnLiSense.

University of Texas at Dallas

The project grew out of the involvement of EnLiSense with the Biomedical Advanced Research Development Authority (BARDA). “We were tracking infections, and we were looking at inflammatory markers associated with infections: Cytokines and chemokines. We thought it was a natural pivot for us because the disease of inflammation is IBD,” said Dr. Prasad.

The device need only be worn when the physician determines the disease is in a variable state. The patient “will wear it for the duration of time as determined by the clinician,” said Dr. Prasad.

The watch face–sized device, typically worn on the forearm, absorbs sweat and performs automated biochemical analysis independently, then beams its findings to the cloud. “What you get back is concentration [of inflammatory biomarkers]. It is essentially trend line reporting of how the concentration is fluctuating over time for markers,” said Dr. Prasad.

The Crohn’s and Colitis Foundation is supporting the company through its IBD Ventures program. EnLiSense is currently conducting a study tracking patients over 4 weeks to correlate biomarker concentrations in sweat with concentrations in stool.

A key remaining question is how long the device should be worn and during what clinical periods. The technology has the potential to provide too much information. “Just figuring the balance. We’re trying to find the right spot where it makes sense for both the clinician and the patient. This is something that is a work in progress. We don’t want this to be just like any other consumer wearable which gives you something but you’re not sure what it means,” said Dr. Prasad.

The study included 33 patients with IBD who were monitored between 40 and 130 minutes. The device measured levels of CRP, IL-6, and calprotectin. Serum samples were also measured the same day.

The researchers found higher levels of calprotectin among patients with active disease in perspiration (P = .0260), serum (P = .022), and in fecal samples (P = .0411). There were no significant differences between patients who are active and those in remission with respect to CRP levels in perspiration or serum, or IL-6 in perspiration. Serum Il-6 levels were higher in those with active disease.

There was no significant difference between serum and sweat calprotectin levels among patients who were active or in remission, but the median expression of IL-6 in perspiration was higher in the active group (P = .0016). In the active group, calprotectin was elevated in sweat, serum, and stool.

Levels of calprotectin measured in perspiration correlated with levels in the serum (R2 = 0.7195), as did CRP (R2 = 0.615) and IL-6 (R2 = 0.5411).
 

Treating to Target

The poster caught the interest of Jeremiah Faith, PhD, who attended the session and was asked to comment. “I think patients want to know what’s happening [with their disease], and we could probably give better care if we know day to day the status of someone, especially because every time we test them we get a point in time, but the reality is probably that people are kind of wavy, and knowing the wave is much better,” he said.

He noted that there was not a strong separation between mean perspiration calprotectin values, but he said the ability to take frequent measurements could overcome that weakness. “The difference between active and remission is not as drastic as what you’d see from blood, for example. But it’s the same thing with your watch. Your watch is a really poor sensor of what your heartbeat is doing, but if you measure it every few seconds, and you average over a long period of time, it can actually more be more [accurate]. So there’s a lot of potential for this,” said Dr. Faith, associate professor of genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai in New York.

If perfected, the device could help efforts at treating to target, in which therapies are adjusted to achieve minimal disease. Currently, physicians are forced to adjust doses or change therapies based on infrequent testing. “If this is accurate ... maybe at some point we will have the tools to be smarter about it,” said Dr. Faith.

Dr. Prasad is a cofounder of EnLiSense. Dr. Faith has no relevant financial disclosures.

LAS VEGAS — Measuring disease status in inflammatory bowel disease (IBD) patients generally requires invasive blood draws or procedures, but a novel wearable device shows initial promise at providing similar information from perspiration.

The device, in development by EnLiSense, can rapidly detect calprotectin, C-reactive protein (CRP), and interleukin-6 (IL-6), using miniaturized versions of biochemical lab tests.

Patient monitoring relies on identifying trends, whether biomarker levels are increasing or decreasing, according to Shalini Prasad, PhD, who presented the study during a poster session at the annual Crohn’s & Colitis Congress^®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “In a blood test you don’t get that unless you’re willing to sample every month. That’s the benefit [of the device],” said Dr. Prasad, professor of bioengineering at University of Texas at Dallas and a cofounder of EnLiSense.

University of Texas at Dallas

The project grew out of the involvement of EnLiSense with the Biomedical Advanced Research Development Authority (BARDA). “We were tracking infections, and we were looking at inflammatory markers associated with infections: Cytokines and chemokines. We thought it was a natural pivot for us because the disease of inflammation is IBD,” said Dr. Prasad.

The device need only be worn when the physician determines the disease is in a variable state. The patient “will wear it for the duration of time as determined by the clinician,” said Dr. Prasad.

The watch face–sized device, typically worn on the forearm, absorbs sweat and performs automated biochemical analysis independently, then beams its findings to the cloud. “What you get back is concentration [of inflammatory biomarkers]. It is essentially trend line reporting of how the concentration is fluctuating over time for markers,” said Dr. Prasad.

The Crohn’s and Colitis Foundation is supporting the company through its IBD Ventures program. EnLiSense is currently conducting a study tracking patients over 4 weeks to correlate biomarker concentrations in sweat with concentrations in stool.

A key remaining question is how long the device should be worn and during what clinical periods. The technology has the potential to provide too much information. “Just figuring the balance. We’re trying to find the right spot where it makes sense for both the clinician and the patient. This is something that is a work in progress. We don’t want this to be just like any other consumer wearable which gives you something but you’re not sure what it means,” said Dr. Prasad.

The study included 33 patients with IBD who were monitored between 40 and 130 minutes. The device measured levels of CRP, IL-6, and calprotectin. Serum samples were also measured the same day.

The researchers found higher levels of calprotectin among patients with active disease in perspiration (P = .0260), serum (P = .022), and in fecal samples (P = .0411). There were no significant differences between patients who are active and those in remission with respect to CRP levels in perspiration or serum, or IL-6 in perspiration. Serum Il-6 levels were higher in those with active disease.

There was no significant difference between serum and sweat calprotectin levels among patients who were active or in remission, but the median expression of IL-6 in perspiration was higher in the active group (P = .0016). In the active group, calprotectin was elevated in sweat, serum, and stool.

Levels of calprotectin measured in perspiration correlated with levels in the serum (R2 = 0.7195), as did CRP (R2 = 0.615) and IL-6 (R2 = 0.5411).
 

Treating to Target

The poster caught the interest of Jeremiah Faith, PhD, who attended the session and was asked to comment. “I think patients want to know what’s happening [with their disease], and we could probably give better care if we know day to day the status of someone, especially because every time we test them we get a point in time, but the reality is probably that people are kind of wavy, and knowing the wave is much better,” he said.

He noted that there was not a strong separation between mean perspiration calprotectin values, but he said the ability to take frequent measurements could overcome that weakness. “The difference between active and remission is not as drastic as what you’d see from blood, for example. But it’s the same thing with your watch. Your watch is a really poor sensor of what your heartbeat is doing, but if you measure it every few seconds, and you average over a long period of time, it can actually more be more [accurate]. So there’s a lot of potential for this,” said Dr. Faith, associate professor of genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai in New York.

If perfected, the device could help efforts at treating to target, in which therapies are adjusted to achieve minimal disease. Currently, physicians are forced to adjust doses or change therapies based on infrequent testing. “If this is accurate ... maybe at some point we will have the tools to be smarter about it,” said Dr. Faith.

Dr. Prasad is a cofounder of EnLiSense. Dr. Faith has no relevant financial disclosures.

Some Robitussin cough syrup products are being recalled nationwide due to potentially deadly microbial contamination. 

The company that makes Robitussin syrups did not specify which microorganisms may be in the products. The recall announcement from the global consumer health products company Haleon stated that the contamination could lead to fungal infections or the presence of fungi or yeasts in a person’s blood. So far, the company has not received any reports of people being sickened by the recalled products.

The recall applies to bottles of Robitussin Honey CF Max Day and Robitussin Honey CF Max Nighttime. Both varieties are for adults. Affected products were sold nationwide and have specific lot numbers printed at the bottom of the back of the bottles. Consumers can view the lot numbers on the FDA’s recall webpage.

People with weakened immune systems have a higher risk of life-threatening health problems due to the cough syrup, the company warned.

“In non-immunocompromised consumers, the population most likely to use the product, life-threatening infections are not likely to occur,” the recall notice from Haleon stated. “However, the occurrence of an infection that may necessitate medical intervention cannot be completely ruled out.”

People who have affected products should stop using them immediately. The company asked that anyone with the products email Haleon at [email protected], or call the company at 800-245-1040 Monday through Friday from 8 a.m. to 6 p.m. Eastern time. 
 

A version of this article appeared on WebMD.com.

Some Robitussin cough syrup products are being recalled nationwide due to potentially deadly microbial contamination. 

The company that makes Robitussin syrups did not specify which microorganisms may be in the products. The recall announcement from the global consumer health products company Haleon stated that the contamination could lead to fungal infections or the presence of fungi or yeasts in a person’s blood. So far, the company has not received any reports of people being sickened by the recalled products.

The recall applies to bottles of Robitussin Honey CF Max Day and Robitussin Honey CF Max Nighttime. Both varieties are for adults. Affected products were sold nationwide and have specific lot numbers printed at the bottom of the back of the bottles. Consumers can view the lot numbers on the FDA’s recall webpage.

People with weakened immune systems have a higher risk of life-threatening health problems due to the cough syrup, the company warned.

“In non-immunocompromised consumers, the population most likely to use the product, life-threatening infections are not likely to occur,” the recall notice from Haleon stated. “However, the occurrence of an infection that may necessitate medical intervention cannot be completely ruled out.”

People who have affected products should stop using them immediately. The company asked that anyone with the products email Haleon at [email protected], or call the company at 800-245-1040 Monday through Friday from 8 a.m. to 6 p.m. Eastern time. 
 

A version of this article appeared on WebMD.com.

Some Robitussin cough syrup products are being recalled nationwide due to potentially deadly microbial contamination. 

The company that makes Robitussin syrups did not specify which microorganisms may be in the products. The recall announcement from the global consumer health products company Haleon stated that the contamination could lead to fungal infections or the presence of fungi or yeasts in a person’s blood. So far, the company has not received any reports of people being sickened by the recalled products.

The recall applies to bottles of Robitussin Honey CF Max Day and Robitussin Honey CF Max Nighttime. Both varieties are for adults. Affected products were sold nationwide and have specific lot numbers printed at the bottom of the back of the bottles. Consumers can view the lot numbers on the FDA’s recall webpage.

People with weakened immune systems have a higher risk of life-threatening health problems due to the cough syrup, the company warned.

“In non-immunocompromised consumers, the population most likely to use the product, life-threatening infections are not likely to occur,” the recall notice from Haleon stated. “However, the occurrence of an infection that may necessitate medical intervention cannot be completely ruled out.”

People who have affected products should stop using them immediately. The company asked that anyone with the products email Haleon at [email protected], or call the company at 800-245-1040 Monday through Friday from 8 a.m. to 6 p.m. Eastern time. 
 

A version of this article appeared on WebMD.com.

TOPLINE:

While low-density lipoprotein (LDL) particles are much more abundant than lipoprotein(a) [Lp(a)] particles and carry the greatest overall risk for coronary heart disease (CHD), on a per-particle basis, Lp(a) is associated with about six times the atherogenic risk for LDL, new observational research suggested.

METHODOLOGY:

• To compare the atherogenicity of Lp(a) relative to LDL on a per-particle basis, researchers used a genetic analysis because Lp(a) and LDL both contain one apolipoprotein B (apoB) per particle.
• In a genome-wide association study of 502,413 UK Biobank participants, they identified genetic variants uniquely affecting plasma levels of either Lp(a) or LDL particles.
• For these two genetic clusters, they related the change in apoB to the respective change in CHD risk, which allowed them to directly compare the atherogenicity of LDL and Lp(a), particle to particle.

TAKEAWAY:

• The odds ratio for CHD for a 50 nmol/L higher Lp(a)-apoB was 1.28 (95% CI, 1.24-1.33) compared with 1.04 (95% CI, 1.03-1.05) for the same increment in LDL-apoB.
• Additional supporting evidence was provided by using polygenic scores to rank participants according to the difference in Lp(a)-apoB vs LDL-apoB, which revealed a greater risk for CHD per 50 nmol/L apoB for the Lp(a) cluster (hazard ratio [HR], 1.47; 95% CI, 1.36-1.58) than the LDL cluster (HR, 1.04; 95% CI, 1.02-1.05).
• Based on the data, the researchers estimate that the atherogenicity of Lp(a) is roughly sixfold greater (point estimate of 6.6; 95% CI, 5.1-8.8) than that of LDL on a per-particle basis.

IN PRACTICE:

“There are two clinical implications. First, to completely characterize atherosclerotic cardiovascular disease risk, it is imperative to measure Lp(a) in all adult patients at least once. Second, these studies provide a rationale that targeting Lp(a) with potent and specific drugs may lead to clinically meaningful benefit,” wrote the authors of an accompanying commentary on the study.

SOURCE:

The study, with first author Elias Björnson, PhD, University of Gothenburg, Gothenburg, Sweden, and an editorial by Sotirios Tsimikas, MD, University of California, San Diego, and Vera Bittner, MD, University of Alabama at Birmingham, was published in the Journal of the American College of Cardiology.

LIMITATIONS:

The UK Biobank consists primarily of a Caucasian population, and confirmatory studies in more diverse samples are needed. The working range for the Lp(a) assay used in the study did not cover the full range of Lp(a) values seen in the population. Variations in Lp(a)-apoB and LDL-apoB were estimated from genetic analysis and not measured specifically in biochemical assays.

DISCLOSURES:

The study had no commercial funding. Some authors received honoraria from the pharmaceutical industry. A complete list of author disclosures is available with the original article.

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

TOPLINE:

While low-density lipoprotein (LDL) particles are much more abundant than lipoprotein(a) [Lp(a)] particles and carry the greatest overall risk for coronary heart disease (CHD), on a per-particle basis, Lp(a) is associated with about six times the atherogenic risk for LDL, new observational research suggested.

METHODOLOGY:

• To compare the atherogenicity of Lp(a) relative to LDL on a per-particle basis, researchers used a genetic analysis because Lp(a) and LDL both contain one apolipoprotein B (apoB) per particle.
• In a genome-wide association study of 502,413 UK Biobank participants, they identified genetic variants uniquely affecting plasma levels of either Lp(a) or LDL particles.
• For these two genetic clusters, they related the change in apoB to the respective change in CHD risk, which allowed them to directly compare the atherogenicity of LDL and Lp(a), particle to particle.

TAKEAWAY:

• The odds ratio for CHD for a 50 nmol/L higher Lp(a)-apoB was 1.28 (95% CI, 1.24-1.33) compared with 1.04 (95% CI, 1.03-1.05) for the same increment in LDL-apoB.
• Additional supporting evidence was provided by using polygenic scores to rank participants according to the difference in Lp(a)-apoB vs LDL-apoB, which revealed a greater risk for CHD per 50 nmol/L apoB for the Lp(a) cluster (hazard ratio [HR], 1.47; 95% CI, 1.36-1.58) than the LDL cluster (HR, 1.04; 95% CI, 1.02-1.05).
• Based on the data, the researchers estimate that the atherogenicity of Lp(a) is roughly sixfold greater (point estimate of 6.6; 95% CI, 5.1-8.8) than that of LDL on a per-particle basis.

IN PRACTICE:

“There are two clinical implications. First, to completely characterize atherosclerotic cardiovascular disease risk, it is imperative to measure Lp(a) in all adult patients at least once. Second, these studies provide a rationale that targeting Lp(a) with potent and specific drugs may lead to clinically meaningful benefit,” wrote the authors of an accompanying commentary on the study.

SOURCE:

The study, with first author Elias Björnson, PhD, University of Gothenburg, Gothenburg, Sweden, and an editorial by Sotirios Tsimikas, MD, University of California, San Diego, and Vera Bittner, MD, University of Alabama at Birmingham, was published in the Journal of the American College of Cardiology.

LIMITATIONS:

The UK Biobank consists primarily of a Caucasian population, and confirmatory studies in more diverse samples are needed. The working range for the Lp(a) assay used in the study did not cover the full range of Lp(a) values seen in the population. Variations in Lp(a)-apoB and LDL-apoB were estimated from genetic analysis and not measured specifically in biochemical assays.

DISCLOSURES:

The study had no commercial funding. Some authors received honoraria from the pharmaceutical industry. A complete list of author disclosures is available with the original article.

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

TOPLINE:

While low-density lipoprotein (LDL) particles are much more abundant than lipoprotein(a) [Lp(a)] particles and carry the greatest overall risk for coronary heart disease (CHD), on a per-particle basis, Lp(a) is associated with about six times the atherogenic risk for LDL, new observational research suggested.

METHODOLOGY:

• To compare the atherogenicity of Lp(a) relative to LDL on a per-particle basis, researchers used a genetic analysis because Lp(a) and LDL both contain one apolipoprotein B (apoB) per particle.
• In a genome-wide association study of 502,413 UK Biobank participants, they identified genetic variants uniquely affecting plasma levels of either Lp(a) or LDL particles.
• For these two genetic clusters, they related the change in apoB to the respective change in CHD risk, which allowed them to directly compare the atherogenicity of LDL and Lp(a), particle to particle.

TAKEAWAY:

• The odds ratio for CHD for a 50 nmol/L higher Lp(a)-apoB was 1.28 (95% CI, 1.24-1.33) compared with 1.04 (95% CI, 1.03-1.05) for the same increment in LDL-apoB.
• Additional supporting evidence was provided by using polygenic scores to rank participants according to the difference in Lp(a)-apoB vs LDL-apoB, which revealed a greater risk for CHD per 50 nmol/L apoB for the Lp(a) cluster (hazard ratio [HR], 1.47; 95% CI, 1.36-1.58) than the LDL cluster (HR, 1.04; 95% CI, 1.02-1.05).
• Based on the data, the researchers estimate that the atherogenicity of Lp(a) is roughly sixfold greater (point estimate of 6.6; 95% CI, 5.1-8.8) than that of LDL on a per-particle basis.

IN PRACTICE:

“There are two clinical implications. First, to completely characterize atherosclerotic cardiovascular disease risk, it is imperative to measure Lp(a) in all adult patients at least once. Second, these studies provide a rationale that targeting Lp(a) with potent and specific drugs may lead to clinically meaningful benefit,” wrote the authors of an accompanying commentary on the study.

SOURCE:

The study, with first author Elias Björnson, PhD, University of Gothenburg, Gothenburg, Sweden, and an editorial by Sotirios Tsimikas, MD, University of California, San Diego, and Vera Bittner, MD, University of Alabama at Birmingham, was published in the Journal of the American College of Cardiology.

LIMITATIONS:

The UK Biobank consists primarily of a Caucasian population, and confirmatory studies in more diverse samples are needed. The working range for the Lp(a) assay used in the study did not cover the full range of Lp(a) values seen in the population. Variations in Lp(a)-apoB and LDL-apoB were estimated from genetic analysis and not measured specifically in biochemical assays.

DISCLOSURES:

The study had no commercial funding. Some authors received honoraria from the pharmaceutical industry. A complete list of author disclosures is available with the original article.

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

Once the standard treatment for adult patients with acute lymphocytic leukemia (ALL), stem cell transplants have fallen out of favor somewhat in recent years, with immunotherapy and pediatric-inspired chemotherapy regimens moving to the forefront. But hematologists differ on how to treat relapsed/refractory patients with Philadelphia-chromosome negative (Ph-negative) ALL who are minimal residual disease (MRD)-negative.

Allogeneic hematopoietic stem cell transplants (HSCT) are still part of the hematology armamentarium for relapsed/refractory (R/R) patients with Ph-negative ALL who are MRD positive. However, when asked about the best treatment strategy for patients who are MRD-negative, hematologist Mark R. Litzow, MD, of the Mayo Clinic in Rochester, Minnesota, said in an interview, “There is no firm consensus about that.”

Discussing how medicine has evolved over the past 20 to 30 years, Dr. Litzow recalled that HSCT used to be standard treatment for adult patients with ALL. “We felt that in most instances, chemotherapy alone was not going to be effective in curing them. A vast majority would relapse,” he said. Nowadays, however, specialists differ on the use of HSCT in patients with Ph-negative, MRD-negative ALL.

A pair of commentaries in the January issue of The Lancet Hematology tackle this topic from different perspectives. On one hand, hematologist Patrice Chevallier, MD, of the University of Nantes in France, argues that for such patients, HSCT “remains a valid option,”and MRD status shouldn’t be the sole factor used for a decision.

However, hematologist Nicolas Boissel, MD, PhD, of Paris Cité University, contends that detectable early MRD is the “only robust predictor” of HSCT benefit in patients under 60 with Ph-negative ALL, and it has “unproven” benefit in older patients.

As Dr. Chevallier notes, “allogeneic HSCT is indicated in patients defined as having a high risk of relapse. Currently, a high level of residual leukemic cells after treatment is recognized as the strongest, and sometimes sole, criterion defining high-risk patients.”

As first- and second-line therapy in pediatric patients and as first-line therapy in adults, the “rule” is to offer HSCT to MRD-positive patients but not MRD-negative ones, he writes. “In older patients and those who are relapsed or refractory, the recent demonstration of efficient immunotherapies and cell therapies has launched the debate on the role of MRD status and the question of whether or not to transplant patients who are MRD-negative in both settings.”

Dr. Chevallier notes that “there is no standard definition of an MRD-negative status,” and the best timing for evaluation is unknown. Further, he adds, a “variable proportion of MRD-negative patients still relapse after treatment — up to 25% of patients who respond early and more than 50% of patients who respond late.”

He also points out that there’s an 80% chance that patients will convert from MRD negative to MRD positive after blinatumomab therapy, and he highlights the low long-term survival rate (20%) after brexucabtagene autoleucel (Tecartus), a CAR T-cell therapy.

As for older patients, Dr. Chevallier observes that improved chemo-immunotherapy and conditioning regimens could spark a rethinking of the feasibility of HSCT. However, for now, in those patients, “MRD is not decisional, and allogeneic HSCT is not a routine practice,” he writes.

In his commentary, Dr. Boissel points out that there have been no controlled studies of HSCT in the first-remission setting, although he writes that some data suggests that HSCT may be helpful for patients in high-risk genetic subgroups, regardless of MRD status. On the other hand, “converging observations suggest no benefit of HSCT in MRD-positive patients treated with blinatumomab in the front-line setting.”

If MRD monitoring is unavailable, Dr. Boissel adds, “it seems reasonable to use early blast clearance or other baseline high-risk features to indicate HSCT.”

How can hematologists make the best decision about HSCT?

In an interview, City of Hope Medical Center (Duarte, California) hematologist-oncologist Ibrahim T. Aldoss, MD, said that chemotherapy — with or without immunotherapy — can often be enough to treat younger patients without high-risk genetic factors. “Potentially, these patients can be spared from transplants,” he said, although patients with resistant MRD “clearly need transplants.”

The risks of transplants are significant, he noted. While they can reduce the risk of relapse, the risk of dying during remission is higher vs chemotherapy. “So you have to balance the risks that you’re willing to take,” he said, keeping in mind that some patients can be cured with chemotherapy.

In addition, Dr. Aldoss said, acute graft-versus-host disease in the first few months after transplant can become chronic. “Many years later, patients can be struggling to where it actually impacts their daily activity. And unfortunately, patients can die from it.”

In the big picture, “you cannot have a generalized statement about whether you shouldn’t do transplants in every MRD-negative patient,” he said. However, “if you do achieve MRD negativity, most patients likely don’t need transplants.”

The Mayo Clinic’s Dr. Litzow urged colleagues to consider several factors when making decisions. Do patients have a high level of comorbidities that would raise the risk of death from HSCT? He noted that there’s nearly a 20% risk of death from HSCT, and comorbidities can boost the risk to 40%-50%.

Also, does the patient have a suitable donor? While advances have boosted the number of eligible donors, he said, “not everybody has an ideal donor.”

If a patient is MRD-negative but not a good candidate for a transplant, Dr. Litzow said consolidation therapy followed by maintenance therapy may be indicated. “Continue to check their bone marrow and their blood periodically as they’re going through treatment and reassess their MRD status to make sure they’re staying negative. If they turn MRD-positive during the course of their therapy, then we have to step back and rethink the role of transplant.”

As for cost, Dr. Litzow points out that HSCT is very expensive, although ALL is an accepted indication for HSCT. However, “if someone doesn’t have medical insurance, then it can be difficult to consider them having a transplant.”

What’s next? In his commentary, Dr. Boissel writes that his team aims to study whether HSCT is helpful in patients with high-risk B-cell ALL “who reach MRD negativity after a consolidation phase including blinatumomab.”

Dr. Aldoss discloses relationships with Amgen, Kite, Pfizer, Jazz, AbbVie, Sobi, Agios, Autolus, and MacroGenics. Dr. Litzow reports ties with Amgen. Dr. Boissel declares relationships with Amgen, Pfizer, Novartis, and Servier. Dr. Chevallier has no disclosures.

Once the standard treatment for adult patients with acute lymphocytic leukemia (ALL), stem cell transplants have fallen out of favor somewhat in recent years, with immunotherapy and pediatric-inspired chemotherapy regimens moving to the forefront. But hematologists differ on how to treat relapsed/refractory patients with Philadelphia-chromosome negative (Ph-negative) ALL who are minimal residual disease (MRD)-negative.

Allogeneic hematopoietic stem cell transplants (HSCT) are still part of the hematology armamentarium for relapsed/refractory (R/R) patients with Ph-negative ALL who are MRD positive. However, when asked about the best treatment strategy for patients who are MRD-negative, hematologist Mark R. Litzow, MD, of the Mayo Clinic in Rochester, Minnesota, said in an interview, “There is no firm consensus about that.”

Discussing how medicine has evolved over the past 20 to 30 years, Dr. Litzow recalled that HSCT used to be standard treatment for adult patients with ALL. “We felt that in most instances, chemotherapy alone was not going to be effective in curing them. A vast majority would relapse,” he said. Nowadays, however, specialists differ on the use of HSCT in patients with Ph-negative, MRD-negative ALL.

A pair of commentaries in the January issue of The Lancet Hematology tackle this topic from different perspectives. On one hand, hematologist Patrice Chevallier, MD, of the University of Nantes in France, argues that for such patients, HSCT “remains a valid option,”and MRD status shouldn’t be the sole factor used for a decision.

However, hematologist Nicolas Boissel, MD, PhD, of Paris Cité University, contends that detectable early MRD is the “only robust predictor” of HSCT benefit in patients under 60 with Ph-negative ALL, and it has “unproven” benefit in older patients.

As Dr. Chevallier notes, “allogeneic HSCT is indicated in patients defined as having a high risk of relapse. Currently, a high level of residual leukemic cells after treatment is recognized as the strongest, and sometimes sole, criterion defining high-risk patients.”

As first- and second-line therapy in pediatric patients and as first-line therapy in adults, the “rule” is to offer HSCT to MRD-positive patients but not MRD-negative ones, he writes. “In older patients and those who are relapsed or refractory, the recent demonstration of efficient immunotherapies and cell therapies has launched the debate on the role of MRD status and the question of whether or not to transplant patients who are MRD-negative in both settings.”

Dr. Chevallier notes that “there is no standard definition of an MRD-negative status,” and the best timing for evaluation is unknown. Further, he adds, a “variable proportion of MRD-negative patients still relapse after treatment — up to 25% of patients who respond early and more than 50% of patients who respond late.”

He also points out that there’s an 80% chance that patients will convert from MRD negative to MRD positive after blinatumomab therapy, and he highlights the low long-term survival rate (20%) after brexucabtagene autoleucel (Tecartus), a CAR T-cell therapy.

As for older patients, Dr. Chevallier observes that improved chemo-immunotherapy and conditioning regimens could spark a rethinking of the feasibility of HSCT. However, for now, in those patients, “MRD is not decisional, and allogeneic HSCT is not a routine practice,” he writes.

In his commentary, Dr. Boissel points out that there have been no controlled studies of HSCT in the first-remission setting, although he writes that some data suggests that HSCT may be helpful for patients in high-risk genetic subgroups, regardless of MRD status. On the other hand, “converging observations suggest no benefit of HSCT in MRD-positive patients treated with blinatumomab in the front-line setting.”

If MRD monitoring is unavailable, Dr. Boissel adds, “it seems reasonable to use early blast clearance or other baseline high-risk features to indicate HSCT.”

How can hematologists make the best decision about HSCT?

In an interview, City of Hope Medical Center (Duarte, California) hematologist-oncologist Ibrahim T. Aldoss, MD, said that chemotherapy — with or without immunotherapy — can often be enough to treat younger patients without high-risk genetic factors. “Potentially, these patients can be spared from transplants,” he said, although patients with resistant MRD “clearly need transplants.”

The risks of transplants are significant, he noted. While they can reduce the risk of relapse, the risk of dying during remission is higher vs chemotherapy. “So you have to balance the risks that you’re willing to take,” he said, keeping in mind that some patients can be cured with chemotherapy.

In addition, Dr. Aldoss said, acute graft-versus-host disease in the first few months after transplant can become chronic. “Many years later, patients can be struggling to where it actually impacts their daily activity. And unfortunately, patients can die from it.”

In the big picture, “you cannot have a generalized statement about whether you shouldn’t do transplants in every MRD-negative patient,” he said. However, “if you do achieve MRD negativity, most patients likely don’t need transplants.”

The Mayo Clinic’s Dr. Litzow urged colleagues to consider several factors when making decisions. Do patients have a high level of comorbidities that would raise the risk of death from HSCT? He noted that there’s nearly a 20% risk of death from HSCT, and comorbidities can boost the risk to 40%-50%.

Also, does the patient have a suitable donor? While advances have boosted the number of eligible donors, he said, “not everybody has an ideal donor.”

If a patient is MRD-negative but not a good candidate for a transplant, Dr. Litzow said consolidation therapy followed by maintenance therapy may be indicated. “Continue to check their bone marrow and their blood periodically as they’re going through treatment and reassess their MRD status to make sure they’re staying negative. If they turn MRD-positive during the course of their therapy, then we have to step back and rethink the role of transplant.”

As for cost, Dr. Litzow points out that HSCT is very expensive, although ALL is an accepted indication for HSCT. However, “if someone doesn’t have medical insurance, then it can be difficult to consider them having a transplant.”

What’s next? In his commentary, Dr. Boissel writes that his team aims to study whether HSCT is helpful in patients with high-risk B-cell ALL “who reach MRD negativity after a consolidation phase including blinatumomab.”

Dr. Aldoss discloses relationships with Amgen, Kite, Pfizer, Jazz, AbbVie, Sobi, Agios, Autolus, and MacroGenics. Dr. Litzow reports ties with Amgen. Dr. Boissel declares relationships with Amgen, Pfizer, Novartis, and Servier. Dr. Chevallier has no disclosures.

Once the standard treatment for adult patients with acute lymphocytic leukemia (ALL), stem cell transplants have fallen out of favor somewhat in recent years, with immunotherapy and pediatric-inspired chemotherapy regimens moving to the forefront. But hematologists differ on how to treat relapsed/refractory patients with Philadelphia-chromosome negative (Ph-negative) ALL who are minimal residual disease (MRD)-negative.

Allogeneic hematopoietic stem cell transplants (HSCT) are still part of the hematology armamentarium for relapsed/refractory (R/R) patients with Ph-negative ALL who are MRD positive. However, when asked about the best treatment strategy for patients who are MRD-negative, hematologist Mark R. Litzow, MD, of the Mayo Clinic in Rochester, Minnesota, said in an interview, “There is no firm consensus about that.”

Discussing how medicine has evolved over the past 20 to 30 years, Dr. Litzow recalled that HSCT used to be standard treatment for adult patients with ALL. “We felt that in most instances, chemotherapy alone was not going to be effective in curing them. A vast majority would relapse,” he said. Nowadays, however, specialists differ on the use of HSCT in patients with Ph-negative, MRD-negative ALL.

A pair of commentaries in the January issue of The Lancet Hematology tackle this topic from different perspectives. On one hand, hematologist Patrice Chevallier, MD, of the University of Nantes in France, argues that for such patients, HSCT “remains a valid option,”and MRD status shouldn’t be the sole factor used for a decision.

However, hematologist Nicolas Boissel, MD, PhD, of Paris Cité University, contends that detectable early MRD is the “only robust predictor” of HSCT benefit in patients under 60 with Ph-negative ALL, and it has “unproven” benefit in older patients.

As Dr. Chevallier notes, “allogeneic HSCT is indicated in patients defined as having a high risk of relapse. Currently, a high level of residual leukemic cells after treatment is recognized as the strongest, and sometimes sole, criterion defining high-risk patients.”

As first- and second-line therapy in pediatric patients and as first-line therapy in adults, the “rule” is to offer HSCT to MRD-positive patients but not MRD-negative ones, he writes. “In older patients and those who are relapsed or refractory, the recent demonstration of efficient immunotherapies and cell therapies has launched the debate on the role of MRD status and the question of whether or not to transplant patients who are MRD-negative in both settings.”

Dr. Chevallier notes that “there is no standard definition of an MRD-negative status,” and the best timing for evaluation is unknown. Further, he adds, a “variable proportion of MRD-negative patients still relapse after treatment — up to 25% of patients who respond early and more than 50% of patients who respond late.”

He also points out that there’s an 80% chance that patients will convert from MRD negative to MRD positive after blinatumomab therapy, and he highlights the low long-term survival rate (20%) after brexucabtagene autoleucel (Tecartus), a CAR T-cell therapy.

As for older patients, Dr. Chevallier observes that improved chemo-immunotherapy and conditioning regimens could spark a rethinking of the feasibility of HSCT. However, for now, in those patients, “MRD is not decisional, and allogeneic HSCT is not a routine practice,” he writes.

In his commentary, Dr. Boissel points out that there have been no controlled studies of HSCT in the first-remission setting, although he writes that some data suggests that HSCT may be helpful for patients in high-risk genetic subgroups, regardless of MRD status. On the other hand, “converging observations suggest no benefit of HSCT in MRD-positive patients treated with blinatumomab in the front-line setting.”

If MRD monitoring is unavailable, Dr. Boissel adds, “it seems reasonable to use early blast clearance or other baseline high-risk features to indicate HSCT.”

How can hematologists make the best decision about HSCT?

In an interview, City of Hope Medical Center (Duarte, California) hematologist-oncologist Ibrahim T. Aldoss, MD, said that chemotherapy — with or without immunotherapy — can often be enough to treat younger patients without high-risk genetic factors. “Potentially, these patients can be spared from transplants,” he said, although patients with resistant MRD “clearly need transplants.”

The risks of transplants are significant, he noted. While they can reduce the risk of relapse, the risk of dying during remission is higher vs chemotherapy. “So you have to balance the risks that you’re willing to take,” he said, keeping in mind that some patients can be cured with chemotherapy.

In addition, Dr. Aldoss said, acute graft-versus-host disease in the first few months after transplant can become chronic. “Many years later, patients can be struggling to where it actually impacts their daily activity. And unfortunately, patients can die from it.”

In the big picture, “you cannot have a generalized statement about whether you shouldn’t do transplants in every MRD-negative patient,” he said. However, “if you do achieve MRD negativity, most patients likely don’t need transplants.”

The Mayo Clinic’s Dr. Litzow urged colleagues to consider several factors when making decisions. Do patients have a high level of comorbidities that would raise the risk of death from HSCT? He noted that there’s nearly a 20% risk of death from HSCT, and comorbidities can boost the risk to 40%-50%.

Also, does the patient have a suitable donor? While advances have boosted the number of eligible donors, he said, “not everybody has an ideal donor.”

If a patient is MRD-negative but not a good candidate for a transplant, Dr. Litzow said consolidation therapy followed by maintenance therapy may be indicated. “Continue to check their bone marrow and their blood periodically as they’re going through treatment and reassess their MRD status to make sure they’re staying negative. If they turn MRD-positive during the course of their therapy, then we have to step back and rethink the role of transplant.”

As for cost, Dr. Litzow points out that HSCT is very expensive, although ALL is an accepted indication for HSCT. However, “if someone doesn’t have medical insurance, then it can be difficult to consider them having a transplant.”

What’s next? In his commentary, Dr. Boissel writes that his team aims to study whether HSCT is helpful in patients with high-risk B-cell ALL “who reach MRD negativity after a consolidation phase including blinatumomab.”

Dr. Aldoss discloses relationships with Amgen, Kite, Pfizer, Jazz, AbbVie, Sobi, Agios, Autolus, and MacroGenics. Dr. Litzow reports ties with Amgen. Dr. Boissel declares relationships with Amgen, Pfizer, Novartis, and Servier. Dr. Chevallier has no disclosures.

Five people in the United Kingdom have been diagnosed with Alzheimer’s disease resulting from a medical treatment they received decades earlier, new research shows. 

Investigators say they are the first known cases of medically acquired AD in living people, but outside experts say the findings should be interpreted cautiously.

The individuals received treatment as children with human growth hormone extracted from pituitary glands of cadavers (c-hGH). Between 1958-1985, an estimated 30,000 people worldwide, mostly children, were treated with c-hGH for genetic disorders and growth hormone deficiencies. 

The therapy was halted in 1985 after three patients in the US who received the treatment later died of Creutzfeldt-Jakob disease (CJD) transmitted through batches of c-hGH that were contaminated with disease-causing prions. 

The new study builds on the investigators’ earlier work that showed the batches of c-hGH also contained amyloid-beta protein and that the protein could be transmitted decades later. These five cases were referred to or reviewed by researchers and clinicians at a prion clinic led by one of the lead researchers.

There are no reports of amyloid-beta transmission through any other medical or surgical procedures, researchers stress, and there is no evidence that amyloid-beta can be passed on during routine patient care or in daily activities. 

“However, the recognition of transmission of amyloid-beta pathology in these rare situations should lead us to review measures to prevent accidental transmission via other medical or surgical procedures, in order to prevent such cases occurring in future,” lead author John Collinge, MD, director of the University of College London Institute of Prion Diseases, London, England, and leader of the UK’s National Prion Clinic, said in a press release. 

“Importantly, our findings also suggest that Alzheimer’s and some other neurological conditions share similar disease processes to CJD, and this may have important implications for understanding and treating Alzheimer’s disease in the future,” Dr. Collinge continued.

The findings were published online January 29 in Nature Medicine. 
 

Building on Earlier Work

The research builds on investigators’ previous 2015 work that found archived samples of c-hGH were also contaminated with amyloid-beta protein. In 2018, mouse studies showed that c-hGH samples stored for decades could still transmit amyloid-beta via injection. 

Researchers said the findings suggested that individuals exposed to contaminated c-hGH who did not die from CJD might eventually develop AD.

Patients in the new study developed neurological symptoms consistent with AD between the ages of 38 and 55 years. The individual cases were either referred to or reviewed by experts in the National Prion Clinic in the UK between 2017 and 2022. The clinic coordinates the National Prion Monitoring Cohort, a longitudinal study of individuals with confirmed prion diseases. 

Of the eight cases, three were diagnosed with AD before referral to the clinic; two others met criteria for an AD diagnosis; and three did not meet the criteria. Three of the patients — two of whom had AD — are now deceased. 

All patients in the study received c-hGH prepared using a method called Wilhelmi or Hartree-modified Wilhelmi preparation (HWP).

Biomarker analyses confirmed the AD diagnosis in two patients. Other cases showed either progressive brain volume loss on brain imaging or elevated cerebrospinal fluid total tau and phosphorylated tau, or evidence of amyloid-beta deposits on autopsy. 
 

‘Potentially Transmissible’

The cases offered diverse presentations. Some were not symptomatic and some failed to meet current diagnostic criteria for sporadic Alzheimer’s disease. Treatment duration and frequency differed among those in the study, as did their age at treatment onset and completion. That and other factors could contribute to the diverse phenotype recorded in individuals, investigators note. 

Investigators examined and ruled out other factors that might explain the individuals’ cognitive symptoms, including childhood intellectual disability, which has been linked to dementia risk, the underlying condition that prompted their treatment with c-hGH, growth hormone deficiency, and cranial radiotherapy, which four of the individuals had received. They also ruled out inherited disease in all five of the cases with samples available for testing. 

“Taken together, the only factor common to all of the patients whom we describe is treatment with the HWP subtype of c-hGH,” the authors write. “Given the strong experimental evidence for A-beta transmission from relevant archived HWP c-hGH batches, we conclude that this is the most plausible explanation for the findings observed.”

Investigators say the findings show that, like other prion diseases, AD has three etiologies: sporadic, inherited, and rare acquired forms, or iatrogenic AD. 

“The clinical syndrome developed by these individuals can, therefore, be termed iatrogenic Alzheimer’s disease, and Alzheimer’s disease should now be recognized as a potentially transmissible disorder,” the authors write. 

“Our cases suggest that, similarly to what is observed in human prion diseases, iatrogenic forms of Alzheimer’s disease differ phenotypically from sporadic and inherited forms, with some individuals remaining asymptomatic despite exposure to A-beta seeds due to protective factors that, at present, are unknown,” they continue
 

‘Measure of Skepticism’

In an accompanying editorial, Mathias Jucker, PhD, of the Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany, and Lary C. Walker, PhD, in the Department of Neurology at Emory University, Atlanta, write that the findings should be considered “with a measure of skepticism.”

“The cases presented are diverse and complicated; the individuals had undergone a variety of medical interventions for various disorders earlier in life, and it is difficult to exclude a contribution of these circumstances to the complex disease phenotypes that appeared many years later,” they write. 

However, they continue, “there is good reason to take the findings seriously.”

“From a practical standpoint, this report reinforces the potential of amyloid-beta seeds as targets for early prevention, and it underscores the importance of informed caution in the preparation of surgical instruments, handling of tissues, and implementation of therapeutic biologics, particularly those derived from human sources,” Dr. Jucker and Dr. Walker write. 

Commenting on the findings for this news organization, Christopher Weber, PhD, director of global science initiatives for the Alzheimer’s Association, says the idea that amyloid-beta is transmissible between individuals has been shown before. 

“We’ve known for a long time that it is possible to create abnormal amyloid buildup — similar to that seen in Alzheimer’s – in the brain of an animal by injecting it with amyloid-beta. We also transfer human Alzheimer’s genes into animals to initiate abnormal, Alzheimer’s-like processes in their brains,” he said. “Thus, the idea that amyloid is transferable between individuals is not so novel as implied in the new paper.”

However, the study does highlight the importance of safety measures to prevent the accidental transmission of amyloid-beta, Weber added. 

“It is a reasonable and actionable caution that the scientific and clinical communities must understand the possible risks and ensure that all methods of transmission are eliminated — for example, with complete and conscientious sterilization of surgical instruments,” he said. “Bottom line: We shouldn’t put amyloid-beta into people’s brains, either accidentally or on purpose, and appropriate measures should be in place to ensure that doesn’t happen.”

The study was supported by the Medical Research Council, the National Institute for Health and Care Research (NIHR), the NIHR University College of London Hospital Biomedical Research Centre, Alzheimer’s Research UK, and the Stroke Association. Dr. Collinge is a shareholder and director of D-Gen, Ltd., an academic spin-out company working in the field of prion disease diagnosis, decontamination and therapeutics. Dr. Jucker and Dr. Walker report no conflicts of interest. 

A version of this article appeared on Medscape.com.

Five people in the United Kingdom have been diagnosed with Alzheimer’s disease resulting from a medical treatment they received decades earlier, new research shows. 

Investigators say they are the first known cases of medically acquired AD in living people, but outside experts say the findings should be interpreted cautiously.

The individuals received treatment as children with human growth hormone extracted from pituitary glands of cadavers (c-hGH). Between 1958-1985, an estimated 30,000 people worldwide, mostly children, were treated with c-hGH for genetic disorders and growth hormone deficiencies. 

The therapy was halted in 1985 after three patients in the US who received the treatment later died of Creutzfeldt-Jakob disease (CJD) transmitted through batches of c-hGH that were contaminated with disease-causing prions. 

The new study builds on the investigators’ earlier work that showed the batches of c-hGH also contained amyloid-beta protein and that the protein could be transmitted decades later. These five cases were referred to or reviewed by researchers and clinicians at a prion clinic led by one of the lead researchers.

There are no reports of amyloid-beta transmission through any other medical or surgical procedures, researchers stress, and there is no evidence that amyloid-beta can be passed on during routine patient care or in daily activities. 

“However, the recognition of transmission of amyloid-beta pathology in these rare situations should lead us to review measures to prevent accidental transmission via other medical or surgical procedures, in order to prevent such cases occurring in future,” lead author John Collinge, MD, director of the University of College London Institute of Prion Diseases, London, England, and leader of the UK’s National Prion Clinic, said in a press release. 

“Importantly, our findings also suggest that Alzheimer’s and some other neurological conditions share similar disease processes to CJD, and this may have important implications for understanding and treating Alzheimer’s disease in the future,” Dr. Collinge continued.

The findings were published online January 29 in Nature Medicine. 
 

Building on Earlier Work

The research builds on investigators’ previous 2015 work that found archived samples of c-hGH were also contaminated with amyloid-beta protein. In 2018, mouse studies showed that c-hGH samples stored for decades could still transmit amyloid-beta via injection. 

Researchers said the findings suggested that individuals exposed to contaminated c-hGH who did not die from CJD might eventually develop AD.

Patients in the new study developed neurological symptoms consistent with AD between the ages of 38 and 55 years. The individual cases were either referred to or reviewed by experts in the National Prion Clinic in the UK between 2017 and 2022. The clinic coordinates the National Prion Monitoring Cohort, a longitudinal study of individuals with confirmed prion diseases. 

Of the eight cases, three were diagnosed with AD before referral to the clinic; two others met criteria for an AD diagnosis; and three did not meet the criteria. Three of the patients — two of whom had AD — are now deceased. 

All patients in the study received c-hGH prepared using a method called Wilhelmi or Hartree-modified Wilhelmi preparation (HWP).

Biomarker analyses confirmed the AD diagnosis in two patients. Other cases showed either progressive brain volume loss on brain imaging or elevated cerebrospinal fluid total tau and phosphorylated tau, or evidence of amyloid-beta deposits on autopsy. 
 

‘Potentially Transmissible’

The cases offered diverse presentations. Some were not symptomatic and some failed to meet current diagnostic criteria for sporadic Alzheimer’s disease. Treatment duration and frequency differed among those in the study, as did their age at treatment onset and completion. That and other factors could contribute to the diverse phenotype recorded in individuals, investigators note. 

Investigators examined and ruled out other factors that might explain the individuals’ cognitive symptoms, including childhood intellectual disability, which has been linked to dementia risk, the underlying condition that prompted their treatment with c-hGH, growth hormone deficiency, and cranial radiotherapy, which four of the individuals had received. They also ruled out inherited disease in all five of the cases with samples available for testing. 

“Taken together, the only factor common to all of the patients whom we describe is treatment with the HWP subtype of c-hGH,” the authors write. “Given the strong experimental evidence for A-beta transmission from relevant archived HWP c-hGH batches, we conclude that this is the most plausible explanation for the findings observed.”

Investigators say the findings show that, like other prion diseases, AD has three etiologies: sporadic, inherited, and rare acquired forms, or iatrogenic AD. 

“The clinical syndrome developed by these individuals can, therefore, be termed iatrogenic Alzheimer’s disease, and Alzheimer’s disease should now be recognized as a potentially transmissible disorder,” the authors write. 

“Our cases suggest that, similarly to what is observed in human prion diseases, iatrogenic forms of Alzheimer’s disease differ phenotypically from sporadic and inherited forms, with some individuals remaining asymptomatic despite exposure to A-beta seeds due to protective factors that, at present, are unknown,” they continue
 

‘Measure of Skepticism’

In an accompanying editorial, Mathias Jucker, PhD, of the Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany, and Lary C. Walker, PhD, in the Department of Neurology at Emory University, Atlanta, write that the findings should be considered “with a measure of skepticism.”

“The cases presented are diverse and complicated; the individuals had undergone a variety of medical interventions for various disorders earlier in life, and it is difficult to exclude a contribution of these circumstances to the complex disease phenotypes that appeared many years later,” they write. 

However, they continue, “there is good reason to take the findings seriously.”

“From a practical standpoint, this report reinforces the potential of amyloid-beta seeds as targets for early prevention, and it underscores the importance of informed caution in the preparation of surgical instruments, handling of tissues, and implementation of therapeutic biologics, particularly those derived from human sources,” Dr. Jucker and Dr. Walker write. 

Commenting on the findings for this news organization, Christopher Weber, PhD, director of global science initiatives for the Alzheimer’s Association, says the idea that amyloid-beta is transmissible between individuals has been shown before. 

“We’ve known for a long time that it is possible to create abnormal amyloid buildup — similar to that seen in Alzheimer’s – in the brain of an animal by injecting it with amyloid-beta. We also transfer human Alzheimer’s genes into animals to initiate abnormal, Alzheimer’s-like processes in their brains,” he said. “Thus, the idea that amyloid is transferable between individuals is not so novel as implied in the new paper.”

However, the study does highlight the importance of safety measures to prevent the accidental transmission of amyloid-beta, Weber added. 

“It is a reasonable and actionable caution that the scientific and clinical communities must understand the possible risks and ensure that all methods of transmission are eliminated — for example, with complete and conscientious sterilization of surgical instruments,” he said. “Bottom line: We shouldn’t put amyloid-beta into people’s brains, either accidentally or on purpose, and appropriate measures should be in place to ensure that doesn’t happen.”

The study was supported by the Medical Research Council, the National Institute for Health and Care Research (NIHR), the NIHR University College of London Hospital Biomedical Research Centre, Alzheimer’s Research UK, and the Stroke Association. Dr. Collinge is a shareholder and director of D-Gen, Ltd., an academic spin-out company working in the field of prion disease diagnosis, decontamination and therapeutics. Dr. Jucker and Dr. Walker report no conflicts of interest. 

A version of this article appeared on Medscape.com.

Five people in the United Kingdom have been diagnosed with Alzheimer’s disease resulting from a medical treatment they received decades earlier, new research shows. 

Investigators say they are the first known cases of medically acquired AD in living people, but outside experts say the findings should be interpreted cautiously.

The individuals received treatment as children with human growth hormone extracted from pituitary glands of cadavers (c-hGH). Between 1958-1985, an estimated 30,000 people worldwide, mostly children, were treated with c-hGH for genetic disorders and growth hormone deficiencies. 

The therapy was halted in 1985 after three patients in the US who received the treatment later died of Creutzfeldt-Jakob disease (CJD) transmitted through batches of c-hGH that were contaminated with disease-causing prions. 

The new study builds on the investigators’ earlier work that showed the batches of c-hGH also contained amyloid-beta protein and that the protein could be transmitted decades later. These five cases were referred to or reviewed by researchers and clinicians at a prion clinic led by one of the lead researchers.

There are no reports of amyloid-beta transmission through any other medical or surgical procedures, researchers stress, and there is no evidence that amyloid-beta can be passed on during routine patient care or in daily activities. 

“However, the recognition of transmission of amyloid-beta pathology in these rare situations should lead us to review measures to prevent accidental transmission via other medical or surgical procedures, in order to prevent such cases occurring in future,” lead author John Collinge, MD, director of the University of College London Institute of Prion Diseases, London, England, and leader of the UK’s National Prion Clinic, said in a press release. 

“Importantly, our findings also suggest that Alzheimer’s and some other neurological conditions share similar disease processes to CJD, and this may have important implications for understanding and treating Alzheimer’s disease in the future,” Dr. Collinge continued.

The findings were published online January 29 in Nature Medicine. 
 

Building on Earlier Work

The research builds on investigators’ previous 2015 work that found archived samples of c-hGH were also contaminated with amyloid-beta protein. In 2018, mouse studies showed that c-hGH samples stored for decades could still transmit amyloid-beta via injection. 

Researchers said the findings suggested that individuals exposed to contaminated c-hGH who did not die from CJD might eventually develop AD.

Patients in the new study developed neurological symptoms consistent with AD between the ages of 38 and 55 years. The individual cases were either referred to or reviewed by experts in the National Prion Clinic in the UK between 2017 and 2022. The clinic coordinates the National Prion Monitoring Cohort, a longitudinal study of individuals with confirmed prion diseases. 

Of the eight cases, three were diagnosed with AD before referral to the clinic; two others met criteria for an AD diagnosis; and three did not meet the criteria. Three of the patients — two of whom had AD — are now deceased. 

All patients in the study received c-hGH prepared using a method called Wilhelmi or Hartree-modified Wilhelmi preparation (HWP).

Biomarker analyses confirmed the AD diagnosis in two patients. Other cases showed either progressive brain volume loss on brain imaging or elevated cerebrospinal fluid total tau and phosphorylated tau, or evidence of amyloid-beta deposits on autopsy. 
 

‘Potentially Transmissible’

The cases offered diverse presentations. Some were not symptomatic and some failed to meet current diagnostic criteria for sporadic Alzheimer’s disease. Treatment duration and frequency differed among those in the study, as did their age at treatment onset and completion. That and other factors could contribute to the diverse phenotype recorded in individuals, investigators note. 

Investigators examined and ruled out other factors that might explain the individuals’ cognitive symptoms, including childhood intellectual disability, which has been linked to dementia risk, the underlying condition that prompted their treatment with c-hGH, growth hormone deficiency, and cranial radiotherapy, which four of the individuals had received. They also ruled out inherited disease in all five of the cases with samples available for testing. 

“Taken together, the only factor common to all of the patients whom we describe is treatment with the HWP subtype of c-hGH,” the authors write. “Given the strong experimental evidence for A-beta transmission from relevant archived HWP c-hGH batches, we conclude that this is the most plausible explanation for the findings observed.”

Investigators say the findings show that, like other prion diseases, AD has three etiologies: sporadic, inherited, and rare acquired forms, or iatrogenic AD. 

“The clinical syndrome developed by these individuals can, therefore, be termed iatrogenic Alzheimer’s disease, and Alzheimer’s disease should now be recognized as a potentially transmissible disorder,” the authors write. 

“Our cases suggest that, similarly to what is observed in human prion diseases, iatrogenic forms of Alzheimer’s disease differ phenotypically from sporadic and inherited forms, with some individuals remaining asymptomatic despite exposure to A-beta seeds due to protective factors that, at present, are unknown,” they continue
 

‘Measure of Skepticism’

In an accompanying editorial, Mathias Jucker, PhD, of the Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany, and Lary C. Walker, PhD, in the Department of Neurology at Emory University, Atlanta, write that the findings should be considered “with a measure of skepticism.”

“The cases presented are diverse and complicated; the individuals had undergone a variety of medical interventions for various disorders earlier in life, and it is difficult to exclude a contribution of these circumstances to the complex disease phenotypes that appeared many years later,” they write. 

However, they continue, “there is good reason to take the findings seriously.”

“From a practical standpoint, this report reinforces the potential of amyloid-beta seeds as targets for early prevention, and it underscores the importance of informed caution in the preparation of surgical instruments, handling of tissues, and implementation of therapeutic biologics, particularly those derived from human sources,” Dr. Jucker and Dr. Walker write. 

Commenting on the findings for this news organization, Christopher Weber, PhD, director of global science initiatives for the Alzheimer’s Association, says the idea that amyloid-beta is transmissible between individuals has been shown before. 

“We’ve known for a long time that it is possible to create abnormal amyloid buildup — similar to that seen in Alzheimer’s – in the brain of an animal by injecting it with amyloid-beta. We also transfer human Alzheimer’s genes into animals to initiate abnormal, Alzheimer’s-like processes in their brains,” he said. “Thus, the idea that amyloid is transferable between individuals is not so novel as implied in the new paper.”

However, the study does highlight the importance of safety measures to prevent the accidental transmission of amyloid-beta, Weber added. 

“It is a reasonable and actionable caution that the scientific and clinical communities must understand the possible risks and ensure that all methods of transmission are eliminated — for example, with complete and conscientious sterilization of surgical instruments,” he said. “Bottom line: We shouldn’t put amyloid-beta into people’s brains, either accidentally or on purpose, and appropriate measures should be in place to ensure that doesn’t happen.”

The study was supported by the Medical Research Council, the National Institute for Health and Care Research (NIHR), the NIHR University College of London Hospital Biomedical Research Centre, Alzheimer’s Research UK, and the Stroke Association. Dr. Collinge is a shareholder and director of D-Gen, Ltd., an academic spin-out company working in the field of prion disease diagnosis, decontamination and therapeutics. Dr. Jucker and Dr. Walker report no conflicts of interest. 

A version of this article appeared on Medscape.com.

Veterans Administration (VA) hospitals are a stepchild in the bizarre mishmash of the U.S. healthcare system. They’re best known (often justifiably so) for rather cantankerous patients, rigid rules, and other oddities (such as patients being able to go on leave and come back).

The majority of American doctors, including myself, did at least part of our training at a VA and have no shortage of stories about them. One I worked at (Omaha VA) was powered by its own nuclear reactor in the basement (no, really, it was, though sadly it’s since been taken out).

VA hospitals, in general, are no-frills — linoleum floors, no piano player in the lobby, very few private rooms, and occasionally in the news for scandals like the one at my hometown Carl T. Hayden VA hospital (I trained there, too).

Yet, a recent study found VA hospitals to be surprisingly efficient compared with the private sector. Their focus on patient care, rather than profits, allows them to run with 8% fewer administrative staff since they generally don’t have to deal with insurance billings, denials, and other paperwork (they also don’t have to deal with shareholders and investor demands or ridiculous CEO salaries, though the study didn’t address that).

On a national scale, this would mean roughly 900,000 fewer administrative jobs in the private sector. Granted, that also would mean those people would have to find other jobs, but let’s look at the patient side. If you had 900,000 fewer desk workers, you’d have the money to hire more nurses, respiratory techs, therapists, and other people directly involved in patient care. You’d also need a lot less office space, which further brings down overhead.

Part of the problem is that a lot of the current medical business is in marketing — how many ads do you see each day for different hospitals in your area? — and upcoding to extract more money from each billing. Neither of these has any clinical value on the patient side of things.

You don’t have to look back too far (2020) for the study that found U.S. healthcare spent four times as much money ($812 billion) per capita than our northern neighbors.

And, for all the jokes we make about the VA (myself included), a study last year found its care was on par (or even better than) most hospitals .

I’m not saying the VA is perfect. All of us who worked there can think of times it wasn’t. But we also remember plenty of issues we’ve had at other places we’ve practiced, too.

Maybe it’s time to stop laughing at the VA and realize they’re doing something right — and learn from it to make healthcare better at the other 6,000 or so hospitals in the U.S.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Veterans Administration (VA) hospitals are a stepchild in the bizarre mishmash of the U.S. healthcare system. They’re best known (often justifiably so) for rather cantankerous patients, rigid rules, and other oddities (such as patients being able to go on leave and come back).

The majority of American doctors, including myself, did at least part of our training at a VA and have no shortage of stories about them. One I worked at (Omaha VA) was powered by its own nuclear reactor in the basement (no, really, it was, though sadly it’s since been taken out).

VA hospitals, in general, are no-frills — linoleum floors, no piano player in the lobby, very few private rooms, and occasionally in the news for scandals like the one at my hometown Carl T. Hayden VA hospital (I trained there, too).

Yet, a recent study found VA hospitals to be surprisingly efficient compared with the private sector. Their focus on patient care, rather than profits, allows them to run with 8% fewer administrative staff since they generally don’t have to deal with insurance billings, denials, and other paperwork (they also don’t have to deal with shareholders and investor demands or ridiculous CEO salaries, though the study didn’t address that).

On a national scale, this would mean roughly 900,000 fewer administrative jobs in the private sector. Granted, that also would mean those people would have to find other jobs, but let’s look at the patient side. If you had 900,000 fewer desk workers, you’d have the money to hire more nurses, respiratory techs, therapists, and other people directly involved in patient care. You’d also need a lot less office space, which further brings down overhead.

Part of the problem is that a lot of the current medical business is in marketing — how many ads do you see each day for different hospitals in your area? — and upcoding to extract more money from each billing. Neither of these has any clinical value on the patient side of things.

You don’t have to look back too far (2020) for the study that found U.S. healthcare spent four times as much money ($812 billion) per capita than our northern neighbors.

And, for all the jokes we make about the VA (myself included), a study last year found its care was on par (or even better than) most hospitals .

I’m not saying the VA is perfect. All of us who worked there can think of times it wasn’t. But we also remember plenty of issues we’ve had at other places we’ve practiced, too.

Maybe it’s time to stop laughing at the VA and realize they’re doing something right — and learn from it to make healthcare better at the other 6,000 or so hospitals in the U.S.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Veterans Administration (VA) hospitals are a stepchild in the bizarre mishmash of the U.S. healthcare system. They’re best known (often justifiably so) for rather cantankerous patients, rigid rules, and other oddities (such as patients being able to go on leave and come back).

The majority of American doctors, including myself, did at least part of our training at a VA and have no shortage of stories about them. One I worked at (Omaha VA) was powered by its own nuclear reactor in the basement (no, really, it was, though sadly it’s since been taken out).

VA hospitals, in general, are no-frills — linoleum floors, no piano player in the lobby, very few private rooms, and occasionally in the news for scandals like the one at my hometown Carl T. Hayden VA hospital (I trained there, too).

Yet, a recent study found VA hospitals to be surprisingly efficient compared with the private sector. Their focus on patient care, rather than profits, allows them to run with 8% fewer administrative staff since they generally don’t have to deal with insurance billings, denials, and other paperwork (they also don’t have to deal with shareholders and investor demands or ridiculous CEO salaries, though the study didn’t address that).

On a national scale, this would mean roughly 900,000 fewer administrative jobs in the private sector. Granted, that also would mean those people would have to find other jobs, but let’s look at the patient side. If you had 900,000 fewer desk workers, you’d have the money to hire more nurses, respiratory techs, therapists, and other people directly involved in patient care. You’d also need a lot less office space, which further brings down overhead.

Part of the problem is that a lot of the current medical business is in marketing — how many ads do you see each day for different hospitals in your area? — and upcoding to extract more money from each billing. Neither of these has any clinical value on the patient side of things.

You don’t have to look back too far (2020) for the study that found U.S. healthcare spent four times as much money ($812 billion) per capita than our northern neighbors.

And, for all the jokes we make about the VA (myself included), a study last year found its care was on par (or even better than) most hospitals .

I’m not saying the VA is perfect. All of us who worked there can think of times it wasn’t. But we also remember plenty of issues we’ve had at other places we’ve practiced, too.

Maybe it’s time to stop laughing at the VA and realize they’re doing something right — and learn from it to make healthcare better at the other 6,000 or so hospitals in the U.S.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at the NYU Grossman School of Medicine. There has been an explosion of interest recently in bills that propose to extend medical assistance in dying to more Americans as states begin to contemplate legalization.

Right now, there are 10 states and the District of Columbia that have had some version of medical assistance in dying approved and on the books. That basically means that about 20% of Americans have access where they live to a physician who can prescribe a lethal dose of medication to them if they’re terminally ill and can ingest the medication themselves. That leaves many Americans not covered by this kind of access to this kind of service.

Many of you watching this may live in states where it is legal, like Oregon, Washington, New Jersey, Colorado, and Hawaii. I know many doctors say, “I’m not going to do that.” It’s not something that anyone is compelling a doctor to do. For some Americans, access is not just about where they live but whether there is a doctor willing to participate with them in bringing about their accelerated death, knowing that they’re inevitably going to die.

There’s not much we can do about that. It’s up to the conscience of each physician as to what they’re comfortable with. Certainly, there are other things that can be done to extend the possibility of having this available.

One thing that’s taking place is that, after lawsuits were filed, Vermont and Oregon have given up on their residency requirement, so you don’t have to be there 6 months or a year in order to use this opportunity. It’s legal now to move to the state or visit the state, and as soon as you get there, sign up for this kind of end-of-life intervention.

New Jersey is also being sued. I’ll predict that every state that has a residency requirement, when sued in court, is going to lose because we’ve long recognized the right of Americans to seek out healthcare in the United States, wherever they want to go.

If some states have made this a legitimate medical procedure, courts are going to say you can’t restrict it only to state residents. If someone wants to use a service, they’re entitled to show up from another state or another place and use it. I’m not sure about foreign nationals, but I’m very sure that Americans can go state to state in search of legitimate medical procedures.

The other bills that are out there, however, are basically saying they want to emulate Oregon, Washington, and the other states and say that the terminally ill, with severe restrictions, are going to be able to get this service without going anywhere.

The restrictions include a diagnosis of terminal illness and that you have to be deemed mentally competent. You can’t use this if you have Alzheimer’s or severe depression. You have to make a request twice with a week or two in between to make sure that your request is authentic. And obviously, everyone is on board to make sure that you’re not being coerced or pushed somehow into requesting a somewhat earlier death than you would have experienced without having the availability of the pills.

You also have to take the pills yourself or be able to pull a switch so that you could use a feeding tube–type administration. If you can’t do that, say due to ALS, you’re not eligible to use medical aid in dying. It’s a pretty restricted intervention.

Many people who get pills after going through these restrictions in the states that permit it don’t use it. As many as one third say they like having it there as a safety valve or a parachute, but once they know they could end their life sooner, then they’re going to stick it out.

Should states make this legal? New York, Massachusetts, Florida, and many other states have bills that are moving through. I’m going to say yes. We’ve had Oregon and Washington since the late 1990s with medical aid in dying on the books. There doesn’t seem to be any evidence of pushing people to use this, of bias against the disabled, or bigotry against particular ethnic or racial groups being used to encourage people to end their life sooner.

I think it is an option that Americans want. I think it’s an option that makes some sense. I’m well aware that we also have to make sure that people know about hospice. In some of these states, medical aid in dying is offered as a part of hospice — not all, but a few. Not everybody wants hospice once they realize that they’re dying and that it is coming relatively soon. They may want to leave with family present, with a ceremony, or with a quality of life that they desire.

Past experience says let’s continue to expand availability in each state. Let’s also realize that we have to keep the restrictions in place on how it’s used because they have protected us against abuse. Let’s understand that every doctor has an option to do this or not do this. It’s a matter of conscience and a matter of comfort.

I think legalization is the direction we’re going to be going in. Getting rid of the residency requirements that have been around, as I think courts are going to overturn them, also gives a push to the idea that once the service is in this many states, it’s something that should be available if there are doctors willing to do it.

I’m Art Caplan at the Division of Medical Ethics at NYU Grossman School of Medicine. New York, NY. Thank you for watching.

Arthur L. Caplan, PhD, has disclosed the following relevant financial relationships:

• Served as a director, officer, partner, employee, advisor, consultant, or trustee for: Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position)
• Serves as a contributing author and adviser for: Medscape

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at the NYU Grossman School of Medicine. There has been an explosion of interest recently in bills that propose to extend medical assistance in dying to more Americans as states begin to contemplate legalization.

Right now, there are 10 states and the District of Columbia that have had some version of medical assistance in dying approved and on the books. That basically means that about 20% of Americans have access where they live to a physician who can prescribe a lethal dose of medication to them if they’re terminally ill and can ingest the medication themselves. That leaves many Americans not covered by this kind of access to this kind of service.

Many of you watching this may live in states where it is legal, like Oregon, Washington, New Jersey, Colorado, and Hawaii. I know many doctors say, “I’m not going to do that.” It’s not something that anyone is compelling a doctor to do. For some Americans, access is not just about where they live but whether there is a doctor willing to participate with them in bringing about their accelerated death, knowing that they’re inevitably going to die.

There’s not much we can do about that. It’s up to the conscience of each physician as to what they’re comfortable with. Certainly, there are other things that can be done to extend the possibility of having this available.

One thing that’s taking place is that, after lawsuits were filed, Vermont and Oregon have given up on their residency requirement, so you don’t have to be there 6 months or a year in order to use this opportunity. It’s legal now to move to the state or visit the state, and as soon as you get there, sign up for this kind of end-of-life intervention.

New Jersey is also being sued. I’ll predict that every state that has a residency requirement, when sued in court, is going to lose because we’ve long recognized the right of Americans to seek out healthcare in the United States, wherever they want to go.

If some states have made this a legitimate medical procedure, courts are going to say you can’t restrict it only to state residents. If someone wants to use a service, they’re entitled to show up from another state or another place and use it. I’m not sure about foreign nationals, but I’m very sure that Americans can go state to state in search of legitimate medical procedures.

The other bills that are out there, however, are basically saying they want to emulate Oregon, Washington, and the other states and say that the terminally ill, with severe restrictions, are going to be able to get this service without going anywhere.

The restrictions include a diagnosis of terminal illness and that you have to be deemed mentally competent. You can’t use this if you have Alzheimer’s or severe depression. You have to make a request twice with a week or two in between to make sure that your request is authentic. And obviously, everyone is on board to make sure that you’re not being coerced or pushed somehow into requesting a somewhat earlier death than you would have experienced without having the availability of the pills.

You also have to take the pills yourself or be able to pull a switch so that you could use a feeding tube–type administration. If you can’t do that, say due to ALS, you’re not eligible to use medical aid in dying. It’s a pretty restricted intervention.

Many people who get pills after going through these restrictions in the states that permit it don’t use it. As many as one third say they like having it there as a safety valve or a parachute, but once they know they could end their life sooner, then they’re going to stick it out.

Should states make this legal? New York, Massachusetts, Florida, and many other states have bills that are moving through. I’m going to say yes. We’ve had Oregon and Washington since the late 1990s with medical aid in dying on the books. There doesn’t seem to be any evidence of pushing people to use this, of bias against the disabled, or bigotry against particular ethnic or racial groups being used to encourage people to end their life sooner.

I think it is an option that Americans want. I think it’s an option that makes some sense. I’m well aware that we also have to make sure that people know about hospice. In some of these states, medical aid in dying is offered as a part of hospice — not all, but a few. Not everybody wants hospice once they realize that they’re dying and that it is coming relatively soon. They may want to leave with family present, with a ceremony, or with a quality of life that they desire.

Past experience says let’s continue to expand availability in each state. Let’s also realize that we have to keep the restrictions in place on how it’s used because they have protected us against abuse. Let’s understand that every doctor has an option to do this or not do this. It’s a matter of conscience and a matter of comfort.

I think legalization is the direction we’re going to be going in. Getting rid of the residency requirements that have been around, as I think courts are going to overturn them, also gives a push to the idea that once the service is in this many states, it’s something that should be available if there are doctors willing to do it.

I’m Art Caplan at the Division of Medical Ethics at NYU Grossman School of Medicine. New York, NY. Thank you for watching.

Arthur L. Caplan, PhD, has disclosed the following relevant financial relationships:

• Served as a director, officer, partner, employee, advisor, consultant, or trustee for: Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position)
• Serves as a contributing author and adviser for: Medscape

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at the NYU Grossman School of Medicine. There has been an explosion of interest recently in bills that propose to extend medical assistance in dying to more Americans as states begin to contemplate legalization.

Right now, there are 10 states and the District of Columbia that have had some version of medical assistance in dying approved and on the books. That basically means that about 20% of Americans have access where they live to a physician who can prescribe a lethal dose of medication to them if they’re terminally ill and can ingest the medication themselves. That leaves many Americans not covered by this kind of access to this kind of service.

Many of you watching this may live in states where it is legal, like Oregon, Washington, New Jersey, Colorado, and Hawaii. I know many doctors say, “I’m not going to do that.” It’s not something that anyone is compelling a doctor to do. For some Americans, access is not just about where they live but whether there is a doctor willing to participate with them in bringing about their accelerated death, knowing that they’re inevitably going to die.

There’s not much we can do about that. It’s up to the conscience of each physician as to what they’re comfortable with. Certainly, there are other things that can be done to extend the possibility of having this available.

One thing that’s taking place is that, after lawsuits were filed, Vermont and Oregon have given up on their residency requirement, so you don’t have to be there 6 months or a year in order to use this opportunity. It’s legal now to move to the state or visit the state, and as soon as you get there, sign up for this kind of end-of-life intervention.

New Jersey is also being sued. I’ll predict that every state that has a residency requirement, when sued in court, is going to lose because we’ve long recognized the right of Americans to seek out healthcare in the United States, wherever they want to go.

If some states have made this a legitimate medical procedure, courts are going to say you can’t restrict it only to state residents. If someone wants to use a service, they’re entitled to show up from another state or another place and use it. I’m not sure about foreign nationals, but I’m very sure that Americans can go state to state in search of legitimate medical procedures.

The other bills that are out there, however, are basically saying they want to emulate Oregon, Washington, and the other states and say that the terminally ill, with severe restrictions, are going to be able to get this service without going anywhere.

The restrictions include a diagnosis of terminal illness and that you have to be deemed mentally competent. You can’t use this if you have Alzheimer’s or severe depression. You have to make a request twice with a week or two in between to make sure that your request is authentic. And obviously, everyone is on board to make sure that you’re not being coerced or pushed somehow into requesting a somewhat earlier death than you would have experienced without having the availability of the pills.

You also have to take the pills yourself or be able to pull a switch so that you could use a feeding tube–type administration. If you can’t do that, say due to ALS, you’re not eligible to use medical aid in dying. It’s a pretty restricted intervention.

Many people who get pills after going through these restrictions in the states that permit it don’t use it. As many as one third say they like having it there as a safety valve or a parachute, but once they know they could end their life sooner, then they’re going to stick it out.

Should states make this legal? New York, Massachusetts, Florida, and many other states have bills that are moving through. I’m going to say yes. We’ve had Oregon and Washington since the late 1990s with medical aid in dying on the books. There doesn’t seem to be any evidence of pushing people to use this, of bias against the disabled, or bigotry against particular ethnic or racial groups being used to encourage people to end their life sooner.

I think it is an option that Americans want. I think it’s an option that makes some sense. I’m well aware that we also have to make sure that people know about hospice. In some of these states, medical aid in dying is offered as a part of hospice — not all, but a few. Not everybody wants hospice once they realize that they’re dying and that it is coming relatively soon. They may want to leave with family present, with a ceremony, or with a quality of life that they desire.

Past experience says let’s continue to expand availability in each state. Let’s also realize that we have to keep the restrictions in place on how it’s used because they have protected us against abuse. Let’s understand that every doctor has an option to do this or not do this. It’s a matter of conscience and a matter of comfort.

I think legalization is the direction we’re going to be going in. Getting rid of the residency requirements that have been around, as I think courts are going to overturn them, also gives a push to the idea that once the service is in this many states, it’s something that should be available if there are doctors willing to do it.

I’m Art Caplan at the Division of Medical Ethics at NYU Grossman School of Medicine. New York, NY. Thank you for watching.

Arthur L. Caplan, PhD, has disclosed the following relevant financial relationships:

• Served as a director, officer, partner, employee, advisor, consultant, or trustee for: Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position)
• Serves as a contributing author and adviser for: Medscape

A version of this article appeared on Medscape.com.

Recent reporting has shown that the number of physician-scientists — doctors who both practice medicine and perform scientific research — in the United States is dropping rapidly. That’s a problem, because physician-scientists are uniquely equipped to make scientific discoveries in the laboratory and translate them to the clinic. Indeed, many of the discoveries that have transformed medicine for the better were made by physician-scientists. For example, Jonas Salk developed the polio vaccine, Timothy Ley sequenced the first cancer genome, and Anthony Fauci coordinated public health responses to both the HIV/AIDS and COVID-19 pandemics. Indicative of their sheer impact, at least a third and as many as half of all Nobel Prizes and Lasker Awards in physiology/medicine have gone to physician-scientists.

So why is the supply of physician-scientists shrinking so precipitously at a time when medical discoveries are being made at a record-high rate? Immunotherapy and proton therapy are transforming cancer care; RNA technology led to COVID vaccines; CRISPR is facilitating gene editing and treatment of diseases like sickle cell anemia. Yet, as exciting as medical science has become, only 1.5% of American doctors work as physician-scientists, more than a threefold drop compared with 30 years ago when the figure was a more robust 4.7%. What’s going on?

Residency training programs at prestigious academic medical centers have standard infolded research years; for example, neurosurgery residents at academic medical centers will often get 2 years of protected research time. And the National Institutes of Health has training grants dedicated to physician-scientists, such as the K08 award program. Several foundations are also dedicated to supporting early-career physician-scientists. Yet, the number of physicians deciding to become physician-scientists remains low, and, more troubling, the attrition rate of those who do decide to go this route is quite high.

The underlying issue is multifold. First, funding rates from the federal government for grants have become competitive to the point of being unrealistic. For example, the current funding rate for the flagship R01 program from the National Cancer Institute is only 12%. Promotions are typically tied to these grant awards, which means physician-scientists who are unable to acquire substantial grant funding are unable to pay for their research or win promotion — and often exit the physician-scientist track altogether.

Compounding this issue is a lack of mentorship for early-career physician-scientists. With the rise of “careerism” in medicine, senior-level physician-scientists may have less incentive to mentor those who are earlier in their careers. Rather, there seems to be greater reward to “managing up” — that is, spending time to please hospital administrators and departmental leadership. Being involved in countless committees appears to carry more value in advancing an established investigator’s career than does mentorship.

Finally, physician-scientists typically earn less than their clinician colleagues, despite juggling both scientific and clinical responsibilities. While many are comfortable with this arrangement when embarking on this track, the disparity may become untenable after a while, especially as departmental leadership will often turn to physician-scientists to fill clinical coverage gaps when faculty leave the department, or as the medical center expands to satellite centers outside the primary hospital. Indeed, physician-scientists get pulled in several directions, which can lead to burnout and attrition, with many who are highly equipped for this track ultimately hanging up their cleats and seeking more clinical or private industry–oriented opportunities.

Every academic medical center operates differently. Some clearly have done a better job than others promoting and fostering physician-scientists. What we find in the centers that manage to retain physician-scientists is leadership plays a major role: If a medical center values the importance of physician-scientists, they will do things to foster the success of those people, such as assembling mentorship committees, establishing clear criteria for promotion and career advancement, protecting research time while maintaining some level of pay equity, advocating for team science approaches, and supporting investigators in cases of gaps in federal funding. Different countries also have different models for physician-scientist training, with Germany, for example, allowing medical residents to have 3 years of protected time to engage in research after their second year of residency.

The stakes here are high. If we can’t address the physician-scientist recruitment and retention crisis in America now, we risk falling behind other countries in our ability to innovate and deliver world-class care.

Dr Chaudhuri is a tenure-track physician-scientist at Washington University in St. Louis, a Paul and Daisy Soros Fellow, and a Public Voices Fellow of The OpEd Project.

Aadel Chaudhuri, MD, PhD, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Recent reporting has shown that the number of physician-scientists — doctors who both practice medicine and perform scientific research — in the United States is dropping rapidly. That’s a problem, because physician-scientists are uniquely equipped to make scientific discoveries in the laboratory and translate them to the clinic. Indeed, many of the discoveries that have transformed medicine for the better were made by physician-scientists. For example, Jonas Salk developed the polio vaccine, Timothy Ley sequenced the first cancer genome, and Anthony Fauci coordinated public health responses to both the HIV/AIDS and COVID-19 pandemics. Indicative of their sheer impact, at least a third and as many as half of all Nobel Prizes and Lasker Awards in physiology/medicine have gone to physician-scientists.

So why is the supply of physician-scientists shrinking so precipitously at a time when medical discoveries are being made at a record-high rate? Immunotherapy and proton therapy are transforming cancer care; RNA technology led to COVID vaccines; CRISPR is facilitating gene editing and treatment of diseases like sickle cell anemia. Yet, as exciting as medical science has become, only 1.5% of American doctors work as physician-scientists, more than a threefold drop compared with 30 years ago when the figure was a more robust 4.7%. What’s going on?

Residency training programs at prestigious academic medical centers have standard infolded research years; for example, neurosurgery residents at academic medical centers will often get 2 years of protected research time. And the National Institutes of Health has training grants dedicated to physician-scientists, such as the K08 award program. Several foundations are also dedicated to supporting early-career physician-scientists. Yet, the number of physicians deciding to become physician-scientists remains low, and, more troubling, the attrition rate of those who do decide to go this route is quite high.

The underlying issue is multifold. First, funding rates from the federal government for grants have become competitive to the point of being unrealistic. For example, the current funding rate for the flagship R01 program from the National Cancer Institute is only 12%. Promotions are typically tied to these grant awards, which means physician-scientists who are unable to acquire substantial grant funding are unable to pay for their research or win promotion — and often exit the physician-scientist track altogether.

Compounding this issue is a lack of mentorship for early-career physician-scientists. With the rise of “careerism” in medicine, senior-level physician-scientists may have less incentive to mentor those who are earlier in their careers. Rather, there seems to be greater reward to “managing up” — that is, spending time to please hospital administrators and departmental leadership. Being involved in countless committees appears to carry more value in advancing an established investigator’s career than does mentorship.

Finally, physician-scientists typically earn less than their clinician colleagues, despite juggling both scientific and clinical responsibilities. While many are comfortable with this arrangement when embarking on this track, the disparity may become untenable after a while, especially as departmental leadership will often turn to physician-scientists to fill clinical coverage gaps when faculty leave the department, or as the medical center expands to satellite centers outside the primary hospital. Indeed, physician-scientists get pulled in several directions, which can lead to burnout and attrition, with many who are highly equipped for this track ultimately hanging up their cleats and seeking more clinical or private industry–oriented opportunities.

Every academic medical center operates differently. Some clearly have done a better job than others promoting and fostering physician-scientists. What we find in the centers that manage to retain physician-scientists is leadership plays a major role: If a medical center values the importance of physician-scientists, they will do things to foster the success of those people, such as assembling mentorship committees, establishing clear criteria for promotion and career advancement, protecting research time while maintaining some level of pay equity, advocating for team science approaches, and supporting investigators in cases of gaps in federal funding. Different countries also have different models for physician-scientist training, with Germany, for example, allowing medical residents to have 3 years of protected time to engage in research after their second year of residency.

The stakes here are high. If we can’t address the physician-scientist recruitment and retention crisis in America now, we risk falling behind other countries in our ability to innovate and deliver world-class care.

Dr Chaudhuri is a tenure-track physician-scientist at Washington University in St. Louis, a Paul and Daisy Soros Fellow, and a Public Voices Fellow of The OpEd Project.

Aadel Chaudhuri, MD, PhD, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Recent reporting has shown that the number of physician-scientists — doctors who both practice medicine and perform scientific research — in the United States is dropping rapidly. That’s a problem, because physician-scientists are uniquely equipped to make scientific discoveries in the laboratory and translate them to the clinic. Indeed, many of the discoveries that have transformed medicine for the better were made by physician-scientists. For example, Jonas Salk developed the polio vaccine, Timothy Ley sequenced the first cancer genome, and Anthony Fauci coordinated public health responses to both the HIV/AIDS and COVID-19 pandemics. Indicative of their sheer impact, at least a third and as many as half of all Nobel Prizes and Lasker Awards in physiology/medicine have gone to physician-scientists.

So why is the supply of physician-scientists shrinking so precipitously at a time when medical discoveries are being made at a record-high rate? Immunotherapy and proton therapy are transforming cancer care; RNA technology led to COVID vaccines; CRISPR is facilitating gene editing and treatment of diseases like sickle cell anemia. Yet, as exciting as medical science has become, only 1.5% of American doctors work as physician-scientists, more than a threefold drop compared with 30 years ago when the figure was a more robust 4.7%. What’s going on?

Residency training programs at prestigious academic medical centers have standard infolded research years; for example, neurosurgery residents at academic medical centers will often get 2 years of protected research time. And the National Institutes of Health has training grants dedicated to physician-scientists, such as the K08 award program. Several foundations are also dedicated to supporting early-career physician-scientists. Yet, the number of physicians deciding to become physician-scientists remains low, and, more troubling, the attrition rate of those who do decide to go this route is quite high.

The underlying issue is multifold. First, funding rates from the federal government for grants have become competitive to the point of being unrealistic. For example, the current funding rate for the flagship R01 program from the National Cancer Institute is only 12%. Promotions are typically tied to these grant awards, which means physician-scientists who are unable to acquire substantial grant funding are unable to pay for their research or win promotion — and often exit the physician-scientist track altogether.

Compounding this issue is a lack of mentorship for early-career physician-scientists. With the rise of “careerism” in medicine, senior-level physician-scientists may have less incentive to mentor those who are earlier in their careers. Rather, there seems to be greater reward to “managing up” — that is, spending time to please hospital administrators and departmental leadership. Being involved in countless committees appears to carry more value in advancing an established investigator’s career than does mentorship.

Finally, physician-scientists typically earn less than their clinician colleagues, despite juggling both scientific and clinical responsibilities. While many are comfortable with this arrangement when embarking on this track, the disparity may become untenable after a while, especially as departmental leadership will often turn to physician-scientists to fill clinical coverage gaps when faculty leave the department, or as the medical center expands to satellite centers outside the primary hospital. Indeed, physician-scientists get pulled in several directions, which can lead to burnout and attrition, with many who are highly equipped for this track ultimately hanging up their cleats and seeking more clinical or private industry–oriented opportunities.

Every academic medical center operates differently. Some clearly have done a better job than others promoting and fostering physician-scientists. What we find in the centers that manage to retain physician-scientists is leadership plays a major role: If a medical center values the importance of physician-scientists, they will do things to foster the success of those people, such as assembling mentorship committees, establishing clear criteria for promotion and career advancement, protecting research time while maintaining some level of pay equity, advocating for team science approaches, and supporting investigators in cases of gaps in federal funding. Different countries also have different models for physician-scientist training, with Germany, for example, allowing medical residents to have 3 years of protected time to engage in research after their second year of residency.

The stakes here are high. If we can’t address the physician-scientist recruitment and retention crisis in America now, we risk falling behind other countries in our ability to innovate and deliver world-class care.

Dr Chaudhuri is a tenure-track physician-scientist at Washington University in St. Louis, a Paul and Daisy Soros Fellow, and a Public Voices Fellow of The OpEd Project.

Aadel Chaudhuri, MD, PhD, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

A two-step screening strategy in postmenopausal women demonstrated a high specificity, sensitivity, and positive predictive value for detecting ovarian and borderline cancer, with most identified as stage I or II disease, a new analysis with a 21-year follow-up found.

METHODOLOGY:

• Detecting ovarian cancer at stage I or II could significantly reduce ovarian cancer-related deaths, but only 25%-30% of patients are diagnosed at an early stage.
• In this single-arm prospective analysis, 7,856 healthy postmenopausal women received annual screening for ovarian cancer between 2011 and 2022. Screening involved an annual blood test to detect levels of cancer antigen 125 and track these levels over time.
• Investigators used the Risk of Ovarian Cancer Algorithm (ROCA) to determine whether ovarian cancer risk was normal, intermediate, or high. Those with elevated ROCA scores were referred for transvaginal sonography; those with intermediate scores received follow-up blood tests every 3 months.
• Overall, 92.3% of women were normal risk, 5.7% were intermediate, and 2% were high risk and recommended for transvaginal sonography.

TAKEAWAY:

• Most women (95.5%) referred for transvaginal ultrasound had one. Of these ultrasounds, most (90%) were negative or revealed benign findings, 5.2% required a repeat ultrasound, and 4.8% (34 patients) showed suspicious findings.
• Of 34 patients with suspicious findings and recommended for surgery, 15 had ovarian cancer and two had borderline tumors, indicating a positive predictive value of 50% (17 of 34 patients) for ovarian cancer. Of these 17 patients, 12 (70.6%) had stage I or II disease.
• Following abnormal ROCA results, seven other women were diagnosed with endometrial tumors (six of which were stage I), indicating a positive predictive value of 74% (25 of 34) for any cancer.
• The specificity for elevated risk ROCA prompting ultrasound was 98%, and the specificity of the ROCA and ultrasound prompting surgery was 99.8%. The sensitivity for detecting ovarian and borderline cancer was 74% (17 of 23).

IN PRACTICE:

“Remarkably, 70% of ovarian cancers detected by the ROCA” were early stage,” the authors concluded. Although the trial was not powered to detect reduced mortality, the high specificity, positive predictive value, and shift to identifying earlier-stage cancers “support further development of this strategy,” the investigators said.

LIMITATIONS:

This trial was not powered to detect mortality benefit. Six ovarian cancers and borderline tumors were missed. Only 80% of ovarian cancers express cancer antigen 125, potentially limiting the sensitivity of the algorithm.

SOURCE:

This study, led by Chae Young Han from the University of Texas MD Anderson Cancer Center, Houston, was published online on January 12 in the Journal of Clinical Oncology.

DISCLOSURES:

This study was supported by funds from the NCI Early Detection Research Network, the MD Anderson Ovarian SPOREs, the National Cancer Institute, the Department of Health and Human Services, and others. The authors reported receiving research funding, grants, consulting, and personal fees from various companies, including Curio Science, Fujirebio Diagnostics, GlaxoSmithKline, AstraZeneca, and Genentech.

A version of this article appeared on Medscape.com.

TOPLINE:

A two-step screening strategy in postmenopausal women demonstrated a high specificity, sensitivity, and positive predictive value for detecting ovarian and borderline cancer, with most identified as stage I or II disease, a new analysis with a 21-year follow-up found.

METHODOLOGY:

• Detecting ovarian cancer at stage I or II could significantly reduce ovarian cancer-related deaths, but only 25%-30% of patients are diagnosed at an early stage.
• In this single-arm prospective analysis, 7,856 healthy postmenopausal women received annual screening for ovarian cancer between 2011 and 2022. Screening involved an annual blood test to detect levels of cancer antigen 125 and track these levels over time.
• Investigators used the Risk of Ovarian Cancer Algorithm (ROCA) to determine whether ovarian cancer risk was normal, intermediate, or high. Those with elevated ROCA scores were referred for transvaginal sonography; those with intermediate scores received follow-up blood tests every 3 months.
• Overall, 92.3% of women were normal risk, 5.7% were intermediate, and 2% were high risk and recommended for transvaginal sonography.

TAKEAWAY:

• Most women (95.5%) referred for transvaginal ultrasound had one. Of these ultrasounds, most (90%) were negative or revealed benign findings, 5.2% required a repeat ultrasound, and 4.8% (34 patients) showed suspicious findings.
• Of 34 patients with suspicious findings and recommended for surgery, 15 had ovarian cancer and two had borderline tumors, indicating a positive predictive value of 50% (17 of 34 patients) for ovarian cancer. Of these 17 patients, 12 (70.6%) had stage I or II disease.
• Following abnormal ROCA results, seven other women were diagnosed with endometrial tumors (six of which were stage I), indicating a positive predictive value of 74% (25 of 34) for any cancer.
• The specificity for elevated risk ROCA prompting ultrasound was 98%, and the specificity of the ROCA and ultrasound prompting surgery was 99.8%. The sensitivity for detecting ovarian and borderline cancer was 74% (17 of 23).

IN PRACTICE:

“Remarkably, 70% of ovarian cancers detected by the ROCA” were early stage,” the authors concluded. Although the trial was not powered to detect reduced mortality, the high specificity, positive predictive value, and shift to identifying earlier-stage cancers “support further development of this strategy,” the investigators said.

LIMITATIONS:

This trial was not powered to detect mortality benefit. Six ovarian cancers and borderline tumors were missed. Only 80% of ovarian cancers express cancer antigen 125, potentially limiting the sensitivity of the algorithm.

SOURCE:

This study, led by Chae Young Han from the University of Texas MD Anderson Cancer Center, Houston, was published online on January 12 in the Journal of Clinical Oncology.

DISCLOSURES:

This study was supported by funds from the NCI Early Detection Research Network, the MD Anderson Ovarian SPOREs, the National Cancer Institute, the Department of Health and Human Services, and others. The authors reported receiving research funding, grants, consulting, and personal fees from various companies, including Curio Science, Fujirebio Diagnostics, GlaxoSmithKline, AstraZeneca, and Genentech.

A version of this article appeared on Medscape.com.

TOPLINE:

A two-step screening strategy in postmenopausal women demonstrated a high specificity, sensitivity, and positive predictive value for detecting ovarian and borderline cancer, with most identified as stage I or II disease, a new analysis with a 21-year follow-up found.

METHODOLOGY:

• Detecting ovarian cancer at stage I or II could significantly reduce ovarian cancer-related deaths, but only 25%-30% of patients are diagnosed at an early stage.
• In this single-arm prospective analysis, 7,856 healthy postmenopausal women received annual screening for ovarian cancer between 2011 and 2022. Screening involved an annual blood test to detect levels of cancer antigen 125 and track these levels over time.
• Investigators used the Risk of Ovarian Cancer Algorithm (ROCA) to determine whether ovarian cancer risk was normal, intermediate, or high. Those with elevated ROCA scores were referred for transvaginal sonography; those with intermediate scores received follow-up blood tests every 3 months.
• Overall, 92.3% of women were normal risk, 5.7% were intermediate, and 2% were high risk and recommended for transvaginal sonography.

TAKEAWAY:

• Most women (95.5%) referred for transvaginal ultrasound had one. Of these ultrasounds, most (90%) were negative or revealed benign findings, 5.2% required a repeat ultrasound, and 4.8% (34 patients) showed suspicious findings.
• Of 34 patients with suspicious findings and recommended for surgery, 15 had ovarian cancer and two had borderline tumors, indicating a positive predictive value of 50% (17 of 34 patients) for ovarian cancer. Of these 17 patients, 12 (70.6%) had stage I or II disease.
• Following abnormal ROCA results, seven other women were diagnosed with endometrial tumors (six of which were stage I), indicating a positive predictive value of 74% (25 of 34) for any cancer.
• The specificity for elevated risk ROCA prompting ultrasound was 98%, and the specificity of the ROCA and ultrasound prompting surgery was 99.8%. The sensitivity for detecting ovarian and borderline cancer was 74% (17 of 23).

IN PRACTICE:

“Remarkably, 70% of ovarian cancers detected by the ROCA” were early stage,” the authors concluded. Although the trial was not powered to detect reduced mortality, the high specificity, positive predictive value, and shift to identifying earlier-stage cancers “support further development of this strategy,” the investigators said.

LIMITATIONS:

This trial was not powered to detect mortality benefit. Six ovarian cancers and borderline tumors were missed. Only 80% of ovarian cancers express cancer antigen 125, potentially limiting the sensitivity of the algorithm.

SOURCE:

This study, led by Chae Young Han from the University of Texas MD Anderson Cancer Center, Houston, was published online on January 12 in the Journal of Clinical Oncology.

DISCLOSURES:

This study was supported by funds from the NCI Early Detection Research Network, the MD Anderson Ovarian SPOREs, the National Cancer Institute, the Department of Health and Human Services, and others. The authors reported receiving research funding, grants, consulting, and personal fees from various companies, including Curio Science, Fujirebio Diagnostics, GlaxoSmithKline, AstraZeneca, and Genentech.

A version of this article appeared on Medscape.com.

Prior to 2013, the backbone of hepatitis C virus (HCV) therapy was pegylated interferon (PEG) in combination with ribavirin (RBV). This year-long therapy was associated with significant side effects and abysmal cure rates. Although efficacy improved with the addition of first-generation protease inhibitors, cure rates remained suboptimal and treatment side effects continued to be significant.

Clinicians and patients needed better options and looked to the drug pipeline with hope. However, even among the most optimistic, the idea that HCV therapy could evolve into an all-oral option seemed a relative pipe dream.

The Sofosbuvir Revolution Begins

The Liver Meeting held in 2013 changed everything.

Several presentations featured compelling data with sofosbuvir, a new polymerase inhibitor that, when combined with RBV, offered an all-oral option to patients with genotypes 2 and 3, as well as improved efficacy for patients with genotypes 1, 4, 5, and 6 when it was combined with 12 weeks of PEG/RBV.

However, the glass ceiling of HCV care was truly shattered with the randomized COSMOS trial, a late-breaker abstract that revealed 12-week functional cure rates in patients receiving sofosbuvir in combination with the protease inhibitor simeprevir.

This phase 2a trial in treatment-naive and -experienced genotype 1 patients with and without cirrhosis showed that an all-oral option was not only viable for the most common strain of HCV but was also safe and efficacious, even in difficult-to-treat populations.

On December 6, 2013, the US Food and Drug Administration (FDA) approved sofosbuvir for the treatment of HCV, ushering in a new era of therapy.

Guidelines quickly changed to advocate for both expansive HCV screening and generous treatment. Yet, as this more permissive approach was being recommended, the high price tag and large anticipated volume of those seeking prescriptions were setting off alarms. The drug cost triggered extensive restrictions based on degree of fibrosis, sobriety, and provider type in an effort to prevent immediate healthcare expenditures.

Given its high cost, rules restricting a patient to only one course of sofosbuvir-based therapy also surfaced. Although treatment with first-generation protease inhibitors carried a hefty price of $161,813.49 per sustained virologic response (SVR), compared with $66,000-$100,000 for 12 weeks of all-oral therapy, its uptake was low and limited by side effects and comorbid conditions. All-oral treatment appeared to have few medical barriers, leading payers to find ways to slow utilization. These restrictions are now gradually being eliminated.

Because of high SVR rates and few contraindications to therapy, most patients who gained access to treatment achieved cure. This included patients who had previously not responded to treatment and prioritized those with more advanced disease.

This quickly led to a significant shift in the population in need of treatment. Prior to 2013, many patients with HCV had advanced disease and did not respond to prior treatment options. After uptake of all-oral therapy, individuals in need were typically treatment naive without advanced disease.

This shift also added new psychosocial dimensions, as many of the newly infected individuals were struggling with active substance abuse. HCV treatment providers needed to change, with increasing recruitment of advanced practice providers, primary care physicians, and addiction medication specialists.

Progress, but Far From Reaching Targets

Fast-forward to 2023.

Ten years after FDA approval, 13.2 million individuals infected with HCV have been treated globally, 82% with sofosbuvir-based regimens and most in lower-middle-income countries. This is absolutely cause for celebration, but not complacency.

In 2016, the World Health Assembly adopted a resolution of elimination of viral hepatitis by 2030. The World Health Organization (WHO) defined elimination of HCV as 90% reduction in new cases of infection, 90% diagnosis of those infected, 80% of eligible individuals treated, and 65% reduction of deaths by 2030.

Despite all the success thus far, the CDA Foundation estimates that the WHO elimination targets will not be achieved until after the year 2050. They also note that in 2020, over 50 million individuals were infected with HCV, of which only 20% were diagnosed and 1% annually treated.

The HCV care cascade, by which the patient journeys from screening to cure, is complicated, and a one-size-fits-all solution is not possible. Reflex testing (an automatic transition to HCV polymerase chain reaction [PCR] testing in the lab for those who are HCV antibody positive) has significantly improved diagnosis. However, communicating these results and linking a patient to curative therapy remain significant obstacles.

Models and real-life experience show that multiple strategies can be successful. They include leveraging the electronic medical record, simplified treatment algorithms, test-and-treat strategies (screening high-risk populations with a point-of-care test that allows treatment initiation at the same visit), and co-localizing HCV screening and treatment with addiction services and relinkage programs (finding those who are already diagnosed and linking them to treatment).

In addition, focusing on populations at high risk for HCV infection — such as people who inject drugs, men who have sex with men, and incarcerated individuals — allows for better resource utilization.

Though daunting, HCV elimination is not impossible. There are several examples of success, including in the countries of Georgia and Iceland. Although, comparatively, the United States remains behind the curve, the White House has asked Congress for $11 billion to fund HCV elimination domestically.

As we await action at the national level, clinicians are reminded that there are several things we can do in caring for patients with HCV:

• A one-time HCV screening is recommended in all individuals aged 18 or older, including pregnant people with each pregnancy.
• HCV antibody testing with reflex to PCR should be used as the screening test.
• Pan-genotypic all-oral therapy is recommended for patients with HCV. Cure rates are greater than 95%, and there are few contraindications to treatment.
• Most people are eligible for simplified treatment algorithms that allow minimal on-treatment monitoring.

Without increased screening and linkage to curative therapy, we will not meet the WHO goals for HCV elimination.

Dr. Reau is chief of the hepatology section at Rush University Medical Center in Chicago and a regular contributor to this news organization. She serves as editor of Clinical Liver Disease, a multimedia review journal, and recently as a member of HCVGuidelines.org, a web-based resource from the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America, as well as educational chair of the AASLD hepatitis C special interest group. She continues to have an active role in the hepatology interest group of the World Gastroenterology Organisation and the American Liver Foundation at the regional and national levels. She disclosed ties with AbbVie, Gilead, Arbutus, Intercept, and Salix.

A version of this article appeared on Medscape.com.

Prior to 2013, the backbone of hepatitis C virus (HCV) therapy was pegylated interferon (PEG) in combination with ribavirin (RBV). This year-long therapy was associated with significant side effects and abysmal cure rates. Although efficacy improved with the addition of first-generation protease inhibitors, cure rates remained suboptimal and treatment side effects continued to be significant.

Clinicians and patients needed better options and looked to the drug pipeline with hope. However, even among the most optimistic, the idea that HCV therapy could evolve into an all-oral option seemed a relative pipe dream.

The Sofosbuvir Revolution Begins

The Liver Meeting held in 2013 changed everything.

Several presentations featured compelling data with sofosbuvir, a new polymerase inhibitor that, when combined with RBV, offered an all-oral option to patients with genotypes 2 and 3, as well as improved efficacy for patients with genotypes 1, 4, 5, and 6 when it was combined with 12 weeks of PEG/RBV.

However, the glass ceiling of HCV care was truly shattered with the randomized COSMOS trial, a late-breaker abstract that revealed 12-week functional cure rates in patients receiving sofosbuvir in combination with the protease inhibitor simeprevir.

This phase 2a trial in treatment-naive and -experienced genotype 1 patients with and without cirrhosis showed that an all-oral option was not only viable for the most common strain of HCV but was also safe and efficacious, even in difficult-to-treat populations.

On December 6, 2013, the US Food and Drug Administration (FDA) approved sofosbuvir for the treatment of HCV, ushering in a new era of therapy.

Guidelines quickly changed to advocate for both expansive HCV screening and generous treatment. Yet, as this more permissive approach was being recommended, the high price tag and large anticipated volume of those seeking prescriptions were setting off alarms. The drug cost triggered extensive restrictions based on degree of fibrosis, sobriety, and provider type in an effort to prevent immediate healthcare expenditures.

Given its high cost, rules restricting a patient to only one course of sofosbuvir-based therapy also surfaced. Although treatment with first-generation protease inhibitors carried a hefty price of $161,813.49 per sustained virologic response (SVR), compared with $66,000-$100,000 for 12 weeks of all-oral therapy, its uptake was low and limited by side effects and comorbid conditions. All-oral treatment appeared to have few medical barriers, leading payers to find ways to slow utilization. These restrictions are now gradually being eliminated.

Because of high SVR rates and few contraindications to therapy, most patients who gained access to treatment achieved cure. This included patients who had previously not responded to treatment and prioritized those with more advanced disease.

This quickly led to a significant shift in the population in need of treatment. Prior to 2013, many patients with HCV had advanced disease and did not respond to prior treatment options. After uptake of all-oral therapy, individuals in need were typically treatment naive without advanced disease.

This shift also added new psychosocial dimensions, as many of the newly infected individuals were struggling with active substance abuse. HCV treatment providers needed to change, with increasing recruitment of advanced practice providers, primary care physicians, and addiction medication specialists.

Progress, but Far From Reaching Targets

Fast-forward to 2023.

Ten years after FDA approval, 13.2 million individuals infected with HCV have been treated globally, 82% with sofosbuvir-based regimens and most in lower-middle-income countries. This is absolutely cause for celebration, but not complacency.

In 2016, the World Health Assembly adopted a resolution of elimination of viral hepatitis by 2030. The World Health Organization (WHO) defined elimination of HCV as 90% reduction in new cases of infection, 90% diagnosis of those infected, 80% of eligible individuals treated, and 65% reduction of deaths by 2030.

Despite all the success thus far, the CDA Foundation estimates that the WHO elimination targets will not be achieved until after the year 2050. They also note that in 2020, over 50 million individuals were infected with HCV, of which only 20% were diagnosed and 1% annually treated.

The HCV care cascade, by which the patient journeys from screening to cure, is complicated, and a one-size-fits-all solution is not possible. Reflex testing (an automatic transition to HCV polymerase chain reaction [PCR] testing in the lab for those who are HCV antibody positive) has significantly improved diagnosis. However, communicating these results and linking a patient to curative therapy remain significant obstacles.

Models and real-life experience show that multiple strategies can be successful. They include leveraging the electronic medical record, simplified treatment algorithms, test-and-treat strategies (screening high-risk populations with a point-of-care test that allows treatment initiation at the same visit), and co-localizing HCV screening and treatment with addiction services and relinkage programs (finding those who are already diagnosed and linking them to treatment).

In addition, focusing on populations at high risk for HCV infection — such as people who inject drugs, men who have sex with men, and incarcerated individuals — allows for better resource utilization.

Though daunting, HCV elimination is not impossible. There are several examples of success, including in the countries of Georgia and Iceland. Although, comparatively, the United States remains behind the curve, the White House has asked Congress for $11 billion to fund HCV elimination domestically.

As we await action at the national level, clinicians are reminded that there are several things we can do in caring for patients with HCV:

• A one-time HCV screening is recommended in all individuals aged 18 or older, including pregnant people with each pregnancy.
• HCV antibody testing with reflex to PCR should be used as the screening test.
• Pan-genotypic all-oral therapy is recommended for patients with HCV. Cure rates are greater than 95%, and there are few contraindications to treatment.
• Most people are eligible for simplified treatment algorithms that allow minimal on-treatment monitoring.

Without increased screening and linkage to curative therapy, we will not meet the WHO goals for HCV elimination.

Dr. Reau is chief of the hepatology section at Rush University Medical Center in Chicago and a regular contributor to this news organization. She serves as editor of Clinical Liver Disease, a multimedia review journal, and recently as a member of HCVGuidelines.org, a web-based resource from the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America, as well as educational chair of the AASLD hepatitis C special interest group. She continues to have an active role in the hepatology interest group of the World Gastroenterology Organisation and the American Liver Foundation at the regional and national levels. She disclosed ties with AbbVie, Gilead, Arbutus, Intercept, and Salix.

A version of this article appeared on Medscape.com.

Prior to 2013, the backbone of hepatitis C virus (HCV) therapy was pegylated interferon (PEG) in combination with ribavirin (RBV). This year-long therapy was associated with significant side effects and abysmal cure rates. Although efficacy improved with the addition of first-generation protease inhibitors, cure rates remained suboptimal and treatment side effects continued to be significant.

Clinicians and patients needed better options and looked to the drug pipeline with hope. However, even among the most optimistic, the idea that HCV therapy could evolve into an all-oral option seemed a relative pipe dream.

The Sofosbuvir Revolution Begins

The Liver Meeting held in 2013 changed everything.

Several presentations featured compelling data with sofosbuvir, a new polymerase inhibitor that, when combined with RBV, offered an all-oral option to patients with genotypes 2 and 3, as well as improved efficacy for patients with genotypes 1, 4, 5, and 6 when it was combined with 12 weeks of PEG/RBV.

However, the glass ceiling of HCV care was truly shattered with the randomized COSMOS trial, a late-breaker abstract that revealed 12-week functional cure rates in patients receiving sofosbuvir in combination with the protease inhibitor simeprevir.

This phase 2a trial in treatment-naive and -experienced genotype 1 patients with and without cirrhosis showed that an all-oral option was not only viable for the most common strain of HCV but was also safe and efficacious, even in difficult-to-treat populations.

On December 6, 2013, the US Food and Drug Administration (FDA) approved sofosbuvir for the treatment of HCV, ushering in a new era of therapy.

Guidelines quickly changed to advocate for both expansive HCV screening and generous treatment. Yet, as this more permissive approach was being recommended, the high price tag and large anticipated volume of those seeking prescriptions were setting off alarms. The drug cost triggered extensive restrictions based on degree of fibrosis, sobriety, and provider type in an effort to prevent immediate healthcare expenditures.

Given its high cost, rules restricting a patient to only one course of sofosbuvir-based therapy also surfaced. Although treatment with first-generation protease inhibitors carried a hefty price of $161,813.49 per sustained virologic response (SVR), compared with $66,000-$100,000 for 12 weeks of all-oral therapy, its uptake was low and limited by side effects and comorbid conditions. All-oral treatment appeared to have few medical barriers, leading payers to find ways to slow utilization. These restrictions are now gradually being eliminated.

Because of high SVR rates and few contraindications to therapy, most patients who gained access to treatment achieved cure. This included patients who had previously not responded to treatment and prioritized those with more advanced disease.

This quickly led to a significant shift in the population in need of treatment. Prior to 2013, many patients with HCV had advanced disease and did not respond to prior treatment options. After uptake of all-oral therapy, individuals in need were typically treatment naive without advanced disease.

This shift also added new psychosocial dimensions, as many of the newly infected individuals were struggling with active substance abuse. HCV treatment providers needed to change, with increasing recruitment of advanced practice providers, primary care physicians, and addiction medication specialists.