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Two suspected cases of Nipah virus reported from a second Indian state

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May 23, 2018 / 6:41 AM / Updated 11 minutes ago

Two suspected cases of Nipah virus reported from a second Indian state

MUMBAI (Reuters) – Two people suspected to be infected with the brain-damaging Nipah virus are under treatment in India’s Karnataka state, a health official said on Wednesday, after an outbreak of the rare virus in neighboring Kerala state killed 10.

Symptoms of the virus were seen in a 20-year old woman and a 75-year-old man in Karnataka’s port city of Mangalore after they traveled to Kerala and came into contact with infected patients there, Rajesh B.V., a district surveillance officer said by phone.

“They are not confirmed Nipah cases yet, so there is no need to panic … the situation is under control,” he said, adding that blood samples of the two people have been sent to Manipal Centre for Virus Research and results are awaited by Thursday.

Reporting by Zeba Siddiqui in Mumbai; Editing by Sanjeev Miglani




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Irish PM urges voters to see through last minute abortion 'tactics'

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May 23, 2018 / 2:51 AM / Updated 25 minutes ago

Irish PM urges voters to see through last minute abortion 'tactics'

DUBLIN (Reuters) – Irish Prime Minister Leo Varadkar accused campaigners opposing a referendum on liberalizing Ireland’s abortion regime of trying to dupe voters into thinking the government could still change the laws even if they voted ‘No’.

A woman walks past a new Pro-Choice mural by a graffiti artist collective called ‘Subset’ ahead of a 25th May referendum on abortion law, in Dublin, Ireland May 22, 2018. REUTERS/Clodagh Kilcoyne

Voters will be asked on Friday if they wish to repeal a constitutional amendment inserted following a 1983 referendum that enshrined the equal right to life of the mother and her unborn child, and to enable parliament to set the laws.

Some politicians appealing for a ‘No’ vote have suggested in recent days that if the referendum fails, the constitution could instead be amended again to allow for abortions in cases such as rape, incest and fatal foetal abnormality.

A complete ban was lifted in Ireland five years ago for cases where the mother’s life is in danger.

A woman walks past a pro-life poster in the city centre of Dublin, Ireland, May 22, 2018. REUTERS/Max Rossi

“What I see now in the final days of this campaign is a tactic by the ‘No’ campaign to try and make out that there is some sort of alternative amendment that we could put into our constitution,” Varadkar, who is campaigning for a ‘Yes’ vote, told parliament.

“I would ask those people 30 years after that amendment was put into our constitution, why has nobody put forward an alternative that would deal with all these hard cases? Why only three days from the vote are people only suddenly raising that?”

Slideshow (10 Images)

“It’s not a realistic alternative. It is just a tactic and I believe the Irish people will see through that.”

While not on the ballot paper, much of the campaign has focused on the legislation Varadkar intends to bring forward if the referendum is carried, which calls for terminations with no restrictions to be allowed up to 12 weeks into a pregnancy.

That was in line with recommendations made by an all-party parliamentary committee, which came to a more liberal position than some had anticipated after concluding that legislating for termination for reasons of rape and incest was too complex.

The leaders of Fianna Fail and Sinn Fein, the two largest opposition parties, backed Varadkar in saying amending the constitution for such cases was impossible.

However ‘No’ campaigners, which include more than half of the Fianna Fail parliamentary party, say the government’s proposals go too far.

“The government has used difficult, tragic cases to push through extreme abortion on demand.┬áThis is why people are increasingly voting “NO” to abortion this Friday,” Clare McCarthy, a spokeswoman for the LoveBoth group said in a statement.

Opinion polls have put those who favor liberalizing one of the world’s most restrictive regimes in a clear lead and while there has been some tightening in the margin, two surveys on Sunday showed the ‘Yes’ side pulling further ahead.

Reporting by Padraic Halpin; Editing by Alison Williams




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Most Preclinical AD Doesn't Progress to Dementia

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Medpage Today

Most Preclinical AD Doesn’t Progress to Dementia

Model is the first to include biomarkers in lifetime Alzheimer’s dementia risk

MedpageToday

  • by Contributing Writer, MedPage Today

Most people with preclinical Alzheimer’s disease will not develop Alzheimer’s dementia during their lifetimes, according to a mathematical analysis based on several large cohort longitudinal studies.

Based on a multistate model for the Alzheimer’s disease process, the risks of Alzheimer’s dementia varied by age and sex, as well as by preclinical biomarker results and clinical symptoms, reported Ron Brookmeyer, PhD, and Nada Abdalla, both of the University of California Los Angeles, in Alzheimer’s & Dementia.

“This is the first paper to calculate the lifetime risks of Alzheimer’s disease taking early preclinical signs from biomarker test results into account,” Brookmeyer told MedPage Today.

There were some surprising results, he noted. For instance, a 70-year old male with only amyloid has a lifetime risk of only 20%. “It’s more likely that he won’t get Alzheimer’s disease dementia than he will, even though he has amyloid in his brain,” Brookmeyer stated.

But if that same 70-year-old male also has neurodegeneration, his risk climbs to 31%. Brookmeyer noted that “if has mild cognitive impairment, plus neurodegeneration and amyloid, his lifetime risk rises to 86%. That’s quite a range.”

This “methodologically sound study” provides “hope to most with preclinical Alzheimer’s that they might live dementia-free even when very old,” observed Constantine Lyketsos, MD, MHS, of Johns Hopkins School of Medicine in Baltimore, who was not involved in the study.

“What’s encouraging here is that people with preclinical Alzheimer’s are not destined to develop dementia,” Lyketsos told MedPage Today.

Brookmeyer and Abdalla used two large published epidemiological cohort studies that had measured biomarkers for amyloidosis and neurodegeneration: the Mayo Clinic Study of Aging, which analyzed 1,541 participants, and a study based on 13 cohorts in Europe and the U.S., which evaluated 353 people with mild cognitive impairment (MCI) as well as amyloidosis and neurodegeneration, plus another 222 individuals with MCI and neurodegeneration.

Using the transition rates from the published studies and U.S. death rates data based on age and sex, the researchers created a model to determine the likelihood of lifetime progression along the continuum of the disease.

“The preclinical period of Alzheimer’s dementia is very long and variable,” Brookmeyer said. “In elderly populations, many will likely die of other causes before the disease actually expresses itself clinically.”

Sex plays a role, too, he added. “Females generally will have higher risk because of their longer life expectancy. A 90-year-old female who has just amyloid, nothing else, has a lifetime risk of only 8% of developing Alzheimer’s dementia.”

While these calculations may reassure some patients who test positive on amyloid, the risks may change considerably as the disease progresses. “Once patients have MCI, our calculations show the rates go up quite a lot,” Brookmeyer noted. “But based only on preclinical conditions, these calculations may help guide clinicians in interpreting what biomarker results might mean for a patient. Is the risk low? Is it moderate? That’s its utility.”

The results also may have implications for research and clinical trials. “One of the things we also calculated were 10-year-risks to help show who might be a priority for entering clinical trials, and what kinds of people are most likely to progress to dementia,” Brookmeyer said.

There’s more work to be done, including factoring in APOE4 to see how that might interact with preclinical states, he said. While the analysis included some of the largest cohort longitudinal studies that have been published, the populations assessed were not ethnically diverse.

Brookmeyer and Abdalla’s model differs from the new Alzheimer’s definition for research recently proposed by the National Institute on Aging (NIA) and the Alzheimer’s Association (AA), said Maria Carrillo, PhD, chief science officer for AA.

Under the proposed NIA-AA definition, a person who does not have amyloid plaques does not have Alzheimer’s pathology. In Brookmeyer and Abdalla’s model, two states of Alzheimer’s disease progression do not include amyloid.

Brookmeyer disclosed support from the NIH and relevant relationships with Takeda. Abdalla disclosed no relevant relationships with industry.

2018-05-22T16:45:00-0400
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Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.

Medpage Today

Most Preclinical AD Doesn't Progress to Dementia

Model is the first to include biomarkers in lifetime Alzheimer's dementia risk

MedpageToday

  • by Contributing Writer, MedPage Today

Most people with preclinical Alzheimer's disease will not develop Alzheimer's dementia during their lifetimes, according to a mathematical analysis based on several large cohort longitudinal studies.

Based on a multistate model for the Alzheimer's disease process, the risks of Alzheimer's dementia varied by age and sex, as well as by preclinical biomarker results and clinical symptoms, reported Ron Brookmeyer, PhD, and Nada Abdalla, both of the University of California Los Angeles, in Alzheimer's & Dementia.

"This is the first paper to calculate the lifetime risks of Alzheimer's disease taking early preclinical signs from biomarker test results into account," Brookmeyer told MedPage Today.

There were some surprising results, he noted. For instance, a 70-year old male with only amyloid has a lifetime risk of only 20%. "It's more likely that he won't get Alzheimer's disease dementia than he will, even though he has amyloid in his brain," Brookmeyer stated.

But if that same 70-year-old male also has neurodegeneration, his risk climbs to 31%. Brookmeyer noted that "if has mild cognitive impairment, plus neurodegeneration and amyloid, his lifetime risk rises to 86%. That's quite a range."

This "methodologically sound study" provides "hope to most with preclinical Alzheimer's that they might live dementia-free even when very old," observed Constantine Lyketsos, MD, MHS, of Johns Hopkins School of Medicine in Baltimore, who was not involved in the study.

"What's encouraging here is that people with preclinical Alzheimer's are not destined to develop dementia," Lyketsos told MedPage Today.

Brookmeyer and Abdalla used two large published epidemiological cohort studies that had measured biomarkers for amyloidosis and neurodegeneration: the Mayo Clinic Study of Aging, which analyzed 1,541 participants, and a study based on 13 cohorts in Europe and the U.S., which evaluated 353 people with mild cognitive impairment (MCI) as well as amyloidosis and neurodegeneration, plus another 222 individuals with MCI and neurodegeneration.

Using the transition rates from the published studies and U.S. death rates data based on age and sex, the researchers created a model to determine the likelihood of lifetime progression along the continuum of the disease.

"The preclinical period of Alzheimer's dementia is very long and variable," Brookmeyer said. "In elderly populations, many will likely die of other causes before the disease actually expresses itself clinically."

Sex plays a role, too, he added. "Females generally will have higher risk because of their longer life expectancy. A 90-year-old female who has just amyloid, nothing else, has a lifetime risk of only 8% of developing Alzheimer's dementia."

While these calculations may reassure some patients who test positive on amyloid, the risks may change considerably as the disease progresses. "Once patients have MCI, our calculations show the rates go up quite a lot," Brookmeyer noted. "But based only on preclinical conditions, these calculations may help guide clinicians in interpreting what biomarker results might mean for a patient. Is the risk low? Is it moderate? That's its utility."

The results also may have implications for research and clinical trials. "One of the things we also calculated were 10-year-risks to help show who might be a priority for entering clinical trials, and what kinds of people are most likely to progress to dementia," Brookmeyer said.

There's more work to be done, including factoring in APOE4 to see how that might interact with preclinical states, he said. While the analysis included some of the largest cohort longitudinal studies that have been published, the populations assessed were not ethnically diverse.

Brookmeyer and Abdalla's model differs from the new Alzheimer's definition for research recently proposed by the National Institute on Aging (NIA) and the Alzheimer's Association (AA), said Maria Carrillo, PhD, chief science officer for AA.

Under the proposed NIA-AA definition, a person who does not have amyloid plaques does not have Alzheimer's pathology. In Brookmeyer and Abdalla's model, two states of Alzheimer's disease progression do not include amyloid.

Brookmeyer disclosed support from the NIH and relevant relationships with Takeda. Abdalla disclosed no relevant relationships with industry.

2018-05-22T16:45:00-0400
Comments

Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.



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Better Specificity with Next-Gen Thyroid Gene Sequence Test

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Medpage Today

Better Specificity with Next-Gen Thyroid Gene Sequence Test

Afirma GCS seems to send fewer patients for surgical intervention

MedpageToday

  • by Staff Writer, MedPage Today
  • This article is a collaboration between MedPage Today® and:

    Medpage Today

Action Points

  • Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

BOSTON — Fewer thyroid nodules were deemed suspicious with the Afirma gene classifier technology, according to researchers here.

Compared with their first generation technology available since early 2011, the gene expression classifier (GEC), the next generation Afirma (Veracyte) genetic sequence classifier (GSC) showed improved specificity in determining thyroid nodule cytology marked by a 21% reduction in Bethesda 3 and 4 nodules classified as suspicious, reported R. Mack Harrell, MD, of Memorial Healthcare System in Hollywood, Florida, and colleagues:

  • Afirma GEC: 39.3% (200) benign versus 53.9% (274) suspicious
  • Afirma GSC: 60% (48) benign versus 32.5% (26) suspicious

The study was one of several late-breaking posters from Veracyte on the RNA sequencing-based test presented at the American Association of Clinical Endocrinologists (AACE) annual meeting.

Harrell’s group also reported that the percentage of oncocytic Bethesda 3 and 4 nodules was generally similar between the GEC and GSC groups, at 21% and 22% of indeterminate cytology thyroid nodules, respectively.

However, there was a significant decrease of around 50% in the percentage of oncocytic patients classified as having a suspicious nodule with the GSC technology:

  • Afirma GEC: 17.8% (19) benign versus 77.6% (83) suspicious
  • Afirma GSC: 66.7% (12) benign versus 27.8% (5) suspicious

Both technologies serve as an aid in determining which Bethesda 3 and 4 fine-needle aspiration biopsied nodules were suspicious and in need of surgical removal, or which nodules were benign and could undergo observation.

Harrell told MedPage Today that this second-generation technology, which was released for clinical use in August 2017, was the “rule out cancer molecular technology,” designed to “decrease the percentage of falsely positive Afirma GEC tested patients who were sent to surgery.”

Harrell, who is also past president of AACE and current president of the American College of Endocrinology (ACE), said that at his endocrine surgical practice, use of the Afirma GSC increased benign calls, and reduced the amount of surgeries in patients with Bethesda 3 and 4 nodules by around 19% over roughly 7 months.

“Much of this improvement could be attributed to improved specificity in Hürthle Cell dominant biopsies,” he said. “Afirma GSC appears to be a better choice than the GEC in practices that have substantial numbers of Hürthle Cell dominant Bethesda 3-4 nodules in their thyroid biopsy population. Hürthle Cell dominant Bethesda 3-4 nodules account for 21% our indeterminate cytologies.”

Giulia Kennedy, PhD, chief scientific and medical officer for Veracyte in South San Francisco, explained the difference between Afirma GEC and GSC to MedPage Today.

“The original Afirma Gene Expression Classifier used RNA-based gene expression, which was measured on a microarray platform, with machine learning algorithms to recognize benign thyroid nodules among those diagnosed indeterminate by cytology. The rates of transcription from expressed genes are the ‘features’ that feed into the algorithm, which uses a form of pattern recognition to determine if a nodule is benign,” she said.

“With the next-generation Afirma Genomic Sequencing Classifier, we are combining RNA sequencing and newer machine learning techniques to leverage more enriched, previously undetectable genomic information. This includes not only gene expression, but also the presence of DNA variants, RNA fusions, copy number variants, and other information that may be predictive of thyroid cancer.”

As a result, the clinician receives a “richer genomic content that enhances the classifier’s ability to distinguish benign from malignant nodules,” she stated.

“Think of it as going from standard- to high-definition television — we’re producing a much higher-resolution genomic picture of thyroid nodules,” said Kennedy.

Harrell disclosed no relevant relationships with industry.

2018-05-22T16:52:56-0400
Comments

Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.

Medpage Today

Better Specificity with Next-Gen Thyroid Gene Sequence Test

Afirma GCS seems to send fewer patients for surgical intervention

MedpageToday

  • by Staff Writer, MedPage Today
  • This article is a collaboration between MedPage Today® and:

    Medpage Today

Action Points

  • Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

BOSTON -- Fewer thyroid nodules were deemed suspicious with the Afirma gene classifier technology, according to researchers here.

Compared with their first generation technology available since early 2011, the gene expression classifier (GEC), the next generation Afirma (Veracyte) genetic sequence classifier (GSC) showed improved specificity in determining thyroid nodule cytology marked by a 21% reduction in Bethesda 3 and 4 nodules classified as suspicious, reported R. Mack Harrell, MD, of Memorial Healthcare System in Hollywood, Florida, and colleagues:

  • Afirma GEC: 39.3% (200) benign versus 53.9% (274) suspicious
  • Afirma GSC: 60% (48) benign versus 32.5% (26) suspicious

The study was one of several late-breaking posters from Veracyte on the RNA sequencing-based test presented at the American Association of Clinical Endocrinologists (AACE) annual meeting.

Harrell's group also reported that the percentage of oncocytic Bethesda 3 and 4 nodules was generally similar between the GEC and GSC groups, at 21% and 22% of indeterminate cytology thyroid nodules, respectively.

However, there was a significant decrease of around 50% in the percentage of oncocytic patients classified as having a suspicious nodule with the GSC technology:

  • Afirma GEC: 17.8% (19) benign versus 77.6% (83) suspicious
  • Afirma GSC: 66.7% (12) benign versus 27.8% (5) suspicious

Both technologies serve as an aid in determining which Bethesda 3 and 4 fine-needle aspiration biopsied nodules were suspicious and in need of surgical removal, or which nodules were benign and could undergo observation.

Harrell told MedPage Today that this second-generation technology, which was released for clinical use in August 2017, was the "rule out cancer molecular technology," designed to "decrease the percentage of falsely positive Afirma GEC tested patients who were sent to surgery."

Harrell, who is also past president of AACE and current president of the American College of Endocrinology (ACE), said that at his endocrine surgical practice, use of the Afirma GSC increased benign calls, and reduced the amount of surgeries in patients with Bethesda 3 and 4 nodules by around 19% over roughly 7 months.

"Much of this improvement could be attributed to improved specificity in Hürthle Cell dominant biopsies," he said. "Afirma GSC appears to be a better choice than the GEC in practices that have substantial numbers of Hürthle Cell dominant Bethesda 3-4 nodules in their thyroid biopsy population. Hürthle Cell dominant Bethesda 3-4 nodules account for 21% our indeterminate cytologies."

Giulia Kennedy, PhD, chief scientific and medical officer for Veracyte in South San Francisco, explained the difference between Afirma GEC and GSC to MedPage Today.

"The original Afirma Gene Expression Classifier used RNA-based gene expression, which was measured on a microarray platform, with machine learning algorithms to recognize benign thyroid nodules among those diagnosed indeterminate by cytology. The rates of transcription from expressed genes are the 'features' that feed into the algorithm, which uses a form of pattern recognition to determine if a nodule is benign," she said.

"With the next-generation Afirma Genomic Sequencing Classifier, we are combining RNA sequencing and newer machine learning techniques to leverage more enriched, previously undetectable genomic information. This includes not only gene expression, but also the presence of DNA variants, RNA fusions, copy number variants, and other information that may be predictive of thyroid cancer."

As a result, the clinician receives a "richer genomic content that enhances the classifier's ability to distinguish benign from malignant nodules," she stated.

"Think of it as going from standard- to high-definition television -- we're producing a much higher-resolution genomic picture of thyroid nodules," said Kennedy.

Harrell disclosed no relevant relationships with industry.

2018-05-22T16:52:56-0400
Comments

Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.



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When Preventive Care Becomes Upselling

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Medpage Today

When Preventive Care Becomes Upselling

It’s not fair to patients, says Hans Duvefelt, MD

MedpageToday

  • by

For many years, I’ve held a brief huddle with my team every morning to make sure we are ready for the day: Anybody with complex problems coming in today? Anybody who’s been in the ER? How is Mrs. Jones’s husband over at the nursing home; is she worried about his condition? Where can we squeeze in more add-ons?

Now other people have tried to hijack the word “huddle” for a completely different purpose. They want to use it to slow us down instead of helping get us get through the avalanche of issues we’re already expecting. In my other office, they call it pre-visit planning. It’s not about having the MRI result available or the recent ER note, but more about who is behind on some aspect of their health maintenance and (unsuspectingly) expecting just a sore throat visit, but consistently avoiding their diabetes followup visits?

My veterinarian colleagues handle this differently. They just send a postcard at random times or hand me a paper, usually part of my exit statement, as I recall, that says which critter is due for what. But in that case, I’m already safely close to the door, and nobody is expecting me to act on it in that instant.

In human medicine, our quality ratings, and soon our paycheck, will depend on how effectively we convince patients to get caught up on their prescribed health maintenance.

In the retail world, they call that upselling. When I stop at a 24-hour gas station and buy some coffee for my long trip between my two offices, they always ask if I want some donuts or chips with that, maybe a banana or whatever. It’s the same thing at the hardware store, if I buy a flashlight, they ask if I need spare batteries, and so on.

How fair is that to our patients?

I remember seeing a video about the hijacked kind of huddle, where the doctor and medical assistant almost gleefully talk about how to convince a noncompliant female patient to have her overdue Pap smear when she is only expecting something much less involved.

And all the while we are supposed to be patient-centered and respect each patient’s own agenda. Too bad not everyone else has to.

Hans Duvefelt, MD, is a family physician who blogs at acountrydoctorwrites.com. This post also appeared on KevinMD.

2018-05-22T17:00:00-0400
Comments

Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.

Medpage Today

When Preventive Care Becomes Upselling

It's not fair to patients, says Hans Duvefelt, MD

MedpageToday

  • by

For many years, I've held a brief huddle with my team every morning to make sure we are ready for the day: Anybody with complex problems coming in today? Anybody who's been in the ER? How is Mrs. Jones's husband over at the nursing home; is she worried about his condition? Where can we squeeze in more add-ons?

Now other people have tried to hijack the word "huddle" for a completely different purpose. They want to use it to slow us down instead of helping get us get through the avalanche of issues we're already expecting. In my other office, they call it pre-visit planning. It's not about having the MRI result available or the recent ER note, but more about who is behind on some aspect of their health maintenance and (unsuspectingly) expecting just a sore throat visit, but consistently avoiding their diabetes followup visits?

My veterinarian colleagues handle this differently. They just send a postcard at random times or hand me a paper, usually part of my exit statement, as I recall, that says which critter is due for what. But in that case, I'm already safely close to the door, and nobody is expecting me to act on it in that instant.

In human medicine, our quality ratings, and soon our paycheck, will depend on how effectively we convince patients to get caught up on their prescribed health maintenance.

In the retail world, they call that upselling. When I stop at a 24-hour gas station and buy some coffee for my long trip between my two offices, they always ask if I want some donuts or chips with that, maybe a banana or whatever. It's the same thing at the hardware store, if I buy a flashlight, they ask if I need spare batteries, and so on.

How fair is that to our patients?

I remember seeing a video about the hijacked kind of huddle, where the doctor and medical assistant almost gleefully talk about how to convince a noncompliant female patient to have her overdue Pap smear when she is only expecting something much less involved.

And all the while we are supposed to be patient-centered and respect each patient's own agenda. Too bad not everyone else has to.

Hans Duvefelt, MD, is a family physician who blogs at acountrydoctorwrites.com. This post also appeared on KevinMD.

2018-05-22T17:00:00-0400
Comments

Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.



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COPD: Combo Tx Promising for Rapid Bronchodilation

0


Medpage Today

COPD: Combo Tx Promising for Rapid Bronchodilation

Greater than 100 ml increase in peak FEV1 with RPL554 plus Spiriva

MedpageToday

  • by Contributing Writer, MedPage Today

Action Points

  • Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

SAN DIEGO — An investigational agent paired with tiotropium (Spiriva) therapy led to rapid additional bronchodilation in patients with moderate to severe chronic obstructive pulmonary disease (COPD), researchers said here.

In the dose-ranging study, the median time to onset, defined as a ≥10% improvement in forced expiratory volume in 1 second (FEV1) occurred in less than 5 minutes with one of two doses of RPL554 plus tiotropium, compared with 38 minutes to achieve that goal with tiotropium alone (P<0.001), according to Dave Singh, MD, of the University of Manchester in England, and colleagues.

“RPL554 represents a potentially first-in-class compound that combines bronchodilator and anti-inflammatory effects in a single molecule and has now been demonstrated to have additional bronchodilation on top of both short and long-acting bronchodilators,” Singh said at his poster presentation at the American Thoracic Society annual meeting.

RPL554 is an inhaled dual phosphodiesterase 3/4 inhibitor that has demonstrated bronchodilator, bronchoprotective, and anti-inflammatory effects in clinical studies, the researchers reported.

The early-phase study enrolled 30 individuals (17 men; 13 women; average age 62) with COPD who were studied in a three-way crossover fashion. The patients were eligible if they had a post-bronchodilator FEV1 that was ≤40% and ≤80% of predicted, and a FEV1 response to albuterol of <150 ml.

Each patients was treated with tiotropium once daily, and either 1.5 mg of RPL554 or 6 mg of RPL554 twice daily for 3 days in a randomized sequence. Treatment periods were separated by 7-21 days washout period. Singh reported that 26 of 30 patients completed the study.

Singh reported that the average FEV1 increase in day 3 was greater with tiotropium and the study agent at 6 mg versus tiotropium plus placebo (331 ml versus 266 ml, P=0.0009).

With RPL554 1.5 mg ,the increase was 317 ml (P=0.09 compared with the higher dose).

Peak FEV1 was greater for RPL554 1.5 mg compared with tiotropium plus placebo (P=0.002) and for RPL554 6 mg versus tiotropium plus placebo (P<0.0001). Singh said this demonstrates a clinically meaningful effect as well as a statistically significant change.

Morning trough FEV1 was increased 54 ml more than tiotropium plus placebo with the low dose of RPL554 plus tiotropium, and was increased 116 mg with the higher dose (both P<0.001).

Plethysmography showed a significant reduction in residual volume and functional residual capacity with RPL554 plus tiotropium compared with tiotropium plus placebo, Singh reported.

“RPL554 was well tolerated without any gastrointestinal side effects,” Singh added, noting that the side effect profile of RPL554 plus tiotropium was similar to the profile of tiotropium plus placebo.

Antonio Anzueta, MD, of the University of Texas Health Science Center in San Antonio, commented that “With these new medications, I really think we need to wait. With RPL554, we need to see if these effects are sustainable.”

Anzueta told MedPage Today that RPL554 remains far from being ready for prime time. “We have seen many, many compounds that look interesting in early-stage studies, but then many of them do not go forward from there,” he said.” It is important that we wait for the next studies with this agent.”

Singh noted that “This was a 3-day study, and we are now doing a 1-month dose ranging study in 400 patients.”

The study was sponsored by Verona Pharma London.

Singh disclosed multiple relevant relationships with industry including Verona Pharma.

Anzueta disclosed relevant relationships with C. R. Bard, Boehringer Ingelheim Pharmaceuticals, GlaxoSmithKline, ALTANA AG, Bayer Pharma, Pfizer, and sanofi-aventis.

2018-05-22T17:10:00-0400
Comments

Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.

Medpage Today

COPD: Combo Tx Promising for Rapid Bronchodilation

Greater than 100 ml increase in peak FEV1 with RPL554 plus Spiriva

MedpageToday

  • by Contributing Writer, MedPage Today

Action Points

  • Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

SAN DIEGO -- An investigational agent paired with tiotropium (Spiriva) therapy led to rapid additional bronchodilation in patients with moderate to severe chronic obstructive pulmonary disease (COPD), researchers said here.

In the dose-ranging study, the median time to onset, defined as a ≥10% improvement in forced expiratory volume in 1 second (FEV1) occurred in less than 5 minutes with one of two doses of RPL554 plus tiotropium, compared with 38 minutes to achieve that goal with tiotropium alone (P<0.001), according to Dave Singh, MD, of the University of Manchester in England, and colleagues.

"RPL554 represents a potentially first-in-class compound that combines bronchodilator and anti-inflammatory effects in a single molecule and has now been demonstrated to have additional bronchodilation on top of both short and long-acting bronchodilators," Singh said at his poster presentation at the American Thoracic Society annual meeting.

RPL554 is an inhaled dual phosphodiesterase 3/4 inhibitor that has demonstrated bronchodilator, bronchoprotective, and anti-inflammatory effects in clinical studies, the researchers reported.

The early-phase study enrolled 30 individuals (17 men; 13 women; average age 62) with COPD who were studied in a three-way crossover fashion. The patients were eligible if they had a post-bronchodilator FEV1 that was ≤40% and ≤80% of predicted, and a FEV1 response to albuterol of <150 ml.

Each patients was treated with tiotropium once daily, and either 1.5 mg of RPL554 or 6 mg of RPL554 twice daily for 3 days in a randomized sequence. Treatment periods were separated by 7-21 days washout period. Singh reported that 26 of 30 patients completed the study.

Singh reported that the average FEV1 increase in day 3 was greater with tiotropium and the study agent at 6 mg versus tiotropium plus placebo (331 ml versus 266 ml, P=0.0009).

With RPL554 1.5 mg ,the increase was 317 ml (P=0.09 compared with the higher dose).

Peak FEV1 was greater for RPL554 1.5 mg compared with tiotropium plus placebo (P=0.002) and for RPL554 6 mg versus tiotropium plus placebo (P<0.0001). Singh said this demonstrates a clinically meaningful effect as well as a statistically significant change.

Morning trough FEV1 was increased 54 ml more than tiotropium plus placebo with the low dose of RPL554 plus tiotropium, and was increased 116 mg with the higher dose (both P<0.001).

Plethysmography showed a significant reduction in residual volume and functional residual capacity with RPL554 plus tiotropium compared with tiotropium plus placebo, Singh reported.

"RPL554 was well tolerated without any gastrointestinal side effects," Singh added, noting that the side effect profile of RPL554 plus tiotropium was similar to the profile of tiotropium plus placebo.

Antonio Anzueta, MD, of the University of Texas Health Science Center in San Antonio, commented that "With these new medications, I really think we need to wait. With RPL554, we need to see if these effects are sustainable."

Anzueta told MedPage Today that RPL554 remains far from being ready for prime time. "We have seen many, many compounds that look interesting in early-stage studies, but then many of them do not go forward from there," he said." It is important that we wait for the next studies with this agent."

Singh noted that "This was a 3-day study, and we are now doing a 1-month dose ranging study in 400 patients."

The study was sponsored by Verona Pharma London.

Singh disclosed multiple relevant relationships with industry including Verona Pharma.

Anzueta disclosed relevant relationships with C. R. Bard, Boehringer Ingelheim Pharmaceuticals, GlaxoSmithKline, ALTANA AG, Bayer Pharma, Pfizer, and sanofi-aventis.

2018-05-22T17:10:00-0400
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Deadly Black Lung Disease Resurgent Among Coal Miners

0


Medpage Today

Deadly Black Lung Disease Resurgent Among Coal Miners

More than 2,000 cases of progressive massive fibrosis in last 2 decades

MedpageToday

SAN DIEGO — Despite stricter rules aimed at reducing dust levels from coal extraction, there has been an increase in incidence of a particularly deadly form of black lung disease among the nation’s coal miners, researchers reported here.

The confirmation of an increase in progressive massive fibrosis (PMF) across the coal mining industry follows several reports of outbreaks in isolated coal mining regions, including a 2016 CDC report of 60 PMF cases identified at a single radiology clinic in eastern Kentucky.

Earlier this year, the National Institute for Occupational Safety and Health reported more than 550 cases of PMF occurring in three clinics in southwestern Virginia since 2013 — the largest cluster of advanced black lung disease ever reported in the U.S.

The newly reported analysis of U.S. Department of Labor data on coal miners collected since 1970 identified 4,679 cases of PMF, with half occurring among miners presenting for evaluation after 2000.

The analysis was presented May 22 at ATS 2018, the annual international conference of the American Thoracic Society.

“We have known about the clusters of PMF cases, but this study represents the first systematic attempt to assess the burden of PMF in former miners,” the study’s lead researcher, Kirsten Almberg, PhD, of the University of Illinois at Chicago, told MedPage Today.

The data show a significant increase in cases during the past 2 decades, relative to the previous 20 to 30 years, her team found.

In 2014, the Mine Safety Health Administration lowered acceptable breathable dust levels at coal mines from 2.0 to 1.5 per cubic meter of air. Almberg said the resurgence in PMF may reflect mine conditions before these stricter standards went into effect.

The change may also be influenced by changes in mining practices in recent decades, she said. Current mining practices, such as surface mining, typically expose miner to high levels of rock dust, including crystalline silica dust. “Silica is much more toxic to the lung than coal dust. And it is now profitable to sort out coal from rock, so that is increasingly part of the process.”

In an effort to better understand the impact of silica dust exposure on the PMF resurgence, Almberg and colleagues are now conducting a study to compare the mineral composition of lung dust from biopsied or extracted tissue of contemporary miners with PMF with stored lung autopsy samples from miners who died of black lung disease 40 or 50 years ago.

“Once we start analyzing the samples, we should be able to see if the silica levels are significantly higher.”

Despite the cause, the resurgence in PMF is alarming: “This is a totally preventable disease,” Almberg said. “If you don’t have the dust exposure, you won’t get the disease. So every case of PMF is a failure of the system to protect these coal miners.”

Another of the co-authors, Robert Cohen, MD, of the University of Chicago, discussed recent clusters of PMF among coal miners in a separate session at the conference devoted to lung disease risks associated with energy extraction.

“We are seeing resurgent coal mine lung disease, and it’s not a relic of the past or something we learned about in medical school,” he said.

Active surveillance has not been particularly effective in identifying PMF cases, in part because participation in federally mandated surveillance programs is low among active coal miners, he noted.

“We are finding many of these cases after people have been laid off or after the mine in their area has closed. People don’t participate because of fear of job loss and fear of knowing. And sometimes there is a certain amount of mistrust of the government and government programs.”

The researchers recently linked black lung compensation claims to surveillance data from the Coal Workers Health Surveillance Program to see if people who applied f0r benefits at the end of their careers had participated in the surveillance program while they were still working in the mines. The results showed that 39% of miners who applied for black lung benefits had never participated in surveillance during their careers.

Also at the session, a fourth-generation coal miner, William “Cotton” Jarrell of Peabody Energy, a Fortune 500 coal company, who now works in mining safety, addressed the challenge of getting miners to seek medical attention: “We don’t want to know, so a lot of us just don’t go to doctors,” he said.

“You can help us by not letting us cancel appointments. Instead of having a receptionist do it, the doctor should pick up the phone and call us with a simple ‘Hey buddy, I need you to get in for this appointment.’ That would make a huge difference. And if that doesn’t work call our wife. She’ll get us in there. And as a last resort, call and tell us you’re disappointed. We hate to disappoint people. If you tell us you’re disappointed that we missed an appointment, I guarantee you we will make the next one.”

2018-05-22T17:15:00-0400
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Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.

Medpage Today

Deadly Black Lung Disease Resurgent Among Coal Miners

More than 2,000 cases of progressive massive fibrosis in last 2 decades

MedpageToday

SAN DIEGO -- Despite stricter rules aimed at reducing dust levels from coal extraction, there has been an increase in incidence of a particularly deadly form of black lung disease among the nation's coal miners, researchers reported here.

The confirmation of an increase in progressive massive fibrosis (PMF) across the coal mining industry follows several reports of outbreaks in isolated coal mining regions, including a 2016 CDC report of 60 PMF cases identified at a single radiology clinic in eastern Kentucky.

Earlier this year, the National Institute for Occupational Safety and Health reported more than 550 cases of PMF occurring in three clinics in southwestern Virginia since 2013 -- the largest cluster of advanced black lung disease ever reported in the U.S.

The newly reported analysis of U.S. Department of Labor data on coal miners collected since 1970 identified 4,679 cases of PMF, with half occurring among miners presenting for evaluation after 2000.

The analysis was presented May 22 at ATS 2018, the annual international conference of the American Thoracic Society.

"We have known about the clusters of PMF cases, but this study represents the first systematic attempt to assess the burden of PMF in former miners," the study's lead researcher, Kirsten Almberg, PhD, of the University of Illinois at Chicago, told MedPage Today.

The data show a significant increase in cases during the past 2 decades, relative to the previous 20 to 30 years, her team found.

In 2014, the Mine Safety Health Administration lowered acceptable breathable dust levels at coal mines from 2.0 to 1.5 per cubic meter of air. Almberg said the resurgence in PMF may reflect mine conditions before these stricter standards went into effect.

The change may also be influenced by changes in mining practices in recent decades, she said. Current mining practices, such as surface mining, typically expose miner to high levels of rock dust, including crystalline silica dust. "Silica is much more toxic to the lung than coal dust. And it is now profitable to sort out coal from rock, so that is increasingly part of the process."

In an effort to better understand the impact of silica dust exposure on the PMF resurgence, Almberg and colleagues are now conducting a study to compare the mineral composition of lung dust from biopsied or extracted tissue of contemporary miners with PMF with stored lung autopsy samples from miners who died of black lung disease 40 or 50 years ago.

"Once we start analyzing the samples, we should be able to see if the silica levels are significantly higher."

Despite the cause, the resurgence in PMF is alarming: "This is a totally preventable disease," Almberg said. "If you don't have the dust exposure, you won't get the disease. So every case of PMF is a failure of the system to protect these coal miners."

Another of the co-authors, Robert Cohen, MD, of the University of Chicago, discussed recent clusters of PMF among coal miners in a separate session at the conference devoted to lung disease risks associated with energy extraction.

"We are seeing resurgent coal mine lung disease, and it's not a relic of the past or something we learned about in medical school," he said.

Active surveillance has not been particularly effective in identifying PMF cases, in part because participation in federally mandated surveillance programs is low among active coal miners, he noted.

"We are finding many of these cases after people have been laid off or after the mine in their area has closed. People don't participate because of fear of job loss and fear of knowing. And sometimes there is a certain amount of mistrust of the government and government programs."

The researchers recently linked black lung compensation claims to surveillance data from the Coal Workers Health Surveillance Program to see if people who applied f0r benefits at the end of their careers had participated in the surveillance program while they were still working in the mines. The results showed that 39% of miners who applied for black lung benefits had never participated in surveillance during their careers.

Also at the session, a fourth-generation coal miner, William "Cotton" Jarrell of Peabody Energy, a Fortune 500 coal company, who now works in mining safety, addressed the challenge of getting miners to seek medical attention: "We don't want to know, so a lot of us just don't go to doctors," he said.

"You can help us by not letting us cancel appointments. Instead of having a receptionist do it, the doctor should pick up the phone and call us with a simple 'Hey buddy, I need you to get in for this appointment.' That would make a huge difference. And if that doesn't work call our wife. She'll get us in there. And as a last resort, call and tell us you're disappointed. We hate to disappoint people. If you tell us you're disappointed that we missed an appointment, I guarantee you we will make the next one."

2018-05-22T17:15:00-0400
Comments

Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.



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Europeans Stand Behind FFR-, iFR-Guided PCI for Stable CAD

0


Medpage Today

Europeans Stand Behind FFR-, iFR-Guided PCI for Stable CAD

EAPCI backs it as studies signals benefit in soft and hard outcomes

MedpageToday

  • by Reporter, MedPage Today/CRTonline.org

PARIS — For the treatment of stable coronary artery disease (CAD), medical therapy alone is no match for percutaneous coronary intervention (PCI) guided by physiological assessment, researchers here suggested.

Stenting guided by fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) was associated with better clinical outcomes over medical therapy alone when patients present with stable CAD or non-culprit lesions in stabilized acute coronary syndrome (ACS) in three studies presented in a late-breaking trial session at the annual EuroPCR meeting.

In turn, the PCR conference group and the sponsoring society for EuroPCR, the European Association of Percutaneous Cardiovascular Interventions (EAPCI), released a statement advocating FFR- and iFR-guided PCI as the treatment of choice for stable angina. This will officially be reflected in future European guidelines to come, Michael Haude, MD, PhD, of Germany’s Städtische Kliniken Neuss, said at a press conference.

FAME-2

One such study supporting stenting in stable CAD with abnormal FFR in at least one stenosis was FAME-2. In a 5-year analysis presented at the session, PCI with drug-eluting stents (DES) was associated with lower odds of urgent revascularization and spontaneous MI at that point than was medical therapy alone for this population.

Randomization to receive a drug-eluting stent (DES) was associated with a lower primary combined endpoint of death, MI, and urgent revascularization versus medical therapy (13.9% versus 27%, HR 0.46, 95% CI 0.34 to 0.63) at 5 years in the 19 of 28 sites still participating in follow-up at that point.

Moreover, rates of these events in PCI recipients were low enough to be comparable to what was experienced by the 332 individuals who had normal-range FFR and were put on medical therapy from the start (15.7%, HR 0.88, 95% CI 0.55 to 1.39).

The advantage of stenting was driven by urgent revascularization (6.3% versus 21.1%, HR 0.27, 95% CI 0.18 to 0.41), along with a trend for reduced MI (8.1% versus 12%, HR 0.66, 95% CI 0.43 to 1.00) and a greater impact on spontaneous MIs (HR 0.62, 95% CI 0.39 to 0.99).

Panagiotis Xaplanteris, MD, PhD, of OLV-Clinic in Aalst, Belgium, and colleagues had their study simultaneously published online in the New England Journal of Medicine.

It’s often said that PCI has no impact on hard endpoints in stable angina except for ischemia, according to session panelist Martin Leon, MD, of Columbia University Medical Center/New York-Presbyterian Hospital in New York City. A reduction in the “hard and important” endpoint of spontaneous MI “gives credence to the understanding that PCI improves not only ischemia but hard endpoints,” Leon said.

However, the NEJM paper cautioned that this secondary endpoint of non-periprocedural MIs was not adjusted for multiple testing, “and any inferences drawn from the intervals as reported may not be reproducible.”

All participants in the open-label FAME-2 trial got standardized medical therapy consisting of aspirin, ACE inhibitors, statins, and P2Y12 inhibitors. Most patients were highly compliant to their medications, Xaplanteris said, as 80% were still on their assigned drugs after 5 years without a significant difference in adherence between groups.

GZ-FFR Trial

Separately, PCI was associated with better improvement in anginal frequency and quality of life even when stable CAD patients started with grey-zone FFR measurements, according to the GZ-FFR trial presented during the same session.

Outcomes of the Seattle Angina Questionnaire (SAQ) favored those who were randomized to PCI over medical therapy such that at 3 months, these patients had a lower anginal frequency (+20.58 versus +9.39 points for domain score, P=0.035) and a better quality of life (+24.04 versus +10.54 points, P=0.012).

Participants in this prospective single-center trial (n=110) all had FFR in the 0.75-0.82 range and lacked other PCI target vessels or residual ischemia, said presenter Barry Hennigan, MB BCh BAO, of the Mater Private Hospital and Cork University Hospital in Ireland.

Hennigan’s group also had the study population undergo 3T perfusion MRI for the purposes of the study and showed that before randomization, rates of major ischemia and any ischemia were 17.4% and 24.4%, respectively, which fell to 7.3% and 12.2% after PCI.

Although stenting therefore only halved ischemia on repeat MRI, patients who started off with ischemia were especially likely to gain a 10-point boost in the SAQ quality of life domain (89% versus 53% for those who didn’t have ischemia, P=0.046).

Meta-Analysis

Finally, FFR-guided PCI was tied to lower odds of cardiac death or MI in stable CAD compared with medical therapy in pooled analysis of the FAME 2, DANAMI-3-PRIMULTI, and Compare-Acute studies (n=2,400).

Over 35 months of follow-up, there was a reduction in these hard outcomes (HR 0.72, 95% CI 0.54 to 0.96) that turned out to be driven by MI (HR 0.71, 95% CI 0.51 to 0.97), according to Frederik Zimmermann, MD, of Catharina Hospital Eindhoven in the Netherlands.

While the benefit of PCI tended to be more pronounced in those with at least one FFR-positive lesion, this wasn’t a statistically significant interaction (P=0.065).

“These findings imply that appropriately-selected patients have a prognostic benefit from PCI independent of its impact on symptoms,” Zimmermann told the audience.

Unlike FAME 2, the DANAMI and Compare-Acute studies enrolled patients that had a prior ST-segment elevation MI but had the culprit lesion treated and were hemodynamically stable at the time of randomization. Even so, “all trials were pointing in the same direction” in terms of the main findings, according to the author.

GZ-FFR was supported by the British Heart Foundation.

Haude disclose receiving grants/research support from Biotronik, as well as honoraria/consultation fees from Abbott, Biotronik, Cardiac Dimensions, OrbusNeich, and Philips Healthcare.

Xaplanteris and Zimmermann disclosed no relevant conflicts of interest.

Hennigan reported receiving honoraria for consulting for Philips Volcano.

2018-05-22T17:20:00-0400
Comments

Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.

Medpage Today

Europeans Stand Behind FFR-, iFR-Guided PCI for Stable CAD

EAPCI backs it as studies signals benefit in soft and hard outcomes

MedpageToday

  • by Reporter, MedPage Today/CRTonline.org

PARIS -- For the treatment of stable coronary artery disease (CAD), medical therapy alone is no match for percutaneous coronary intervention (PCI) guided by physiological assessment, researchers here suggested.

Stenting guided by fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) was associated with better clinical outcomes over medical therapy alone when patients present with stable CAD or non-culprit lesions in stabilized acute coronary syndrome (ACS) in three studies presented in a late-breaking trial session at the annual EuroPCR meeting.

In turn, the PCR conference group and the sponsoring society for EuroPCR, the European Association of Percutaneous Cardiovascular Interventions (EAPCI), released a statement advocating FFR- and iFR-guided PCI as the treatment of choice for stable angina. This will officially be reflected in future European guidelines to come, Michael Haude, MD, PhD, of Germany's Städtische Kliniken Neuss, said at a press conference.

FAME-2

One such study supporting stenting in stable CAD with abnormal FFR in at least one stenosis was FAME-2. In a 5-year analysis presented at the session, PCI with drug-eluting stents (DES) was associated with lower odds of urgent revascularization and spontaneous MI at that point than was medical therapy alone for this population.

Randomization to receive a drug-eluting stent (DES) was associated with a lower primary combined endpoint of death, MI, and urgent revascularization versus medical therapy (13.9% versus 27%, HR 0.46, 95% CI 0.34 to 0.63) at 5 years in the 19 of 28 sites still participating in follow-up at that point.

Moreover, rates of these events in PCI recipients were low enough to be comparable to what was experienced by the 332 individuals who had normal-range FFR and were put on medical therapy from the start (15.7%, HR 0.88, 95% CI 0.55 to 1.39).

The advantage of stenting was driven by urgent revascularization (6.3% versus 21.1%, HR 0.27, 95% CI 0.18 to 0.41), along with a trend for reduced MI (8.1% versus 12%, HR 0.66, 95% CI 0.43 to 1.00) and a greater impact on spontaneous MIs (HR 0.62, 95% CI 0.39 to 0.99).

Panagiotis Xaplanteris, MD, PhD, of OLV-Clinic in Aalst, Belgium, and colleagues had their study simultaneously published online in the New England Journal of Medicine.

It's often said that PCI has no impact on hard endpoints in stable angina except for ischemia, according to session panelist Martin Leon, MD, of Columbia University Medical Center/New York-Presbyterian Hospital in New York City. A reduction in the "hard and important" endpoint of spontaneous MI "gives credence to the understanding that PCI improves not only ischemia but hard endpoints," Leon said.

However, the NEJM paper cautioned that this secondary endpoint of non-periprocedural MIs was not adjusted for multiple testing, "and any inferences drawn from the intervals as reported may not be reproducible."

All participants in the open-label FAME-2 trial got standardized medical therapy consisting of aspirin, ACE inhibitors, statins, and P2Y12 inhibitors. Most patients were highly compliant to their medications, Xaplanteris said, as 80% were still on their assigned drugs after 5 years without a significant difference in adherence between groups.

GZ-FFR Trial

Separately, PCI was associated with better improvement in anginal frequency and quality of life even when stable CAD patients started with grey-zone FFR measurements, according to the GZ-FFR trial presented during the same session.

Outcomes of the Seattle Angina Questionnaire (SAQ) favored those who were randomized to PCI over medical therapy such that at 3 months, these patients had a lower anginal frequency (+20.58 versus +9.39 points for domain score, P=0.035) and a better quality of life (+24.04 versus +10.54 points, P=0.012).

Participants in this prospective single-center trial (n=110) all had FFR in the 0.75-0.82 range and lacked other PCI target vessels or residual ischemia, said presenter Barry Hennigan, MB BCh BAO, of the Mater Private Hospital and Cork University Hospital in Ireland.

Hennigan's group also had the study population undergo 3T perfusion MRI for the purposes of the study and showed that before randomization, rates of major ischemia and any ischemia were 17.4% and 24.4%, respectively, which fell to 7.3% and 12.2% after PCI.

Although stenting therefore only halved ischemia on repeat MRI, patients who started off with ischemia were especially likely to gain a 10-point boost in the SAQ quality of life domain (89% versus 53% for those who didn't have ischemia, P=0.046).

Meta-Analysis

Finally, FFR-guided PCI was tied to lower odds of cardiac death or MI in stable CAD compared with medical therapy in pooled analysis of the FAME 2, DANAMI-3-PRIMULTI, and Compare-Acute studies (n=2,400).

Over 35 months of follow-up, there was a reduction in these hard outcomes (HR 0.72, 95% CI 0.54 to 0.96) that turned out to be driven by MI (HR 0.71, 95% CI 0.51 to 0.97), according to Frederik Zimmermann, MD, of Catharina Hospital Eindhoven in the Netherlands.

While the benefit of PCI tended to be more pronounced in those with at least one FFR-positive lesion, this wasn't a statistically significant interaction (P=0.065).

"These findings imply that appropriately-selected patients have a prognostic benefit from PCI independent of its impact on symptoms," Zimmermann told the audience.

Unlike FAME 2, the DANAMI and Compare-Acute studies enrolled patients that had a prior ST-segment elevation MI but had the culprit lesion treated and were hemodynamically stable at the time of randomization. Even so, "all trials were pointing in the same direction" in terms of the main findings, according to the author.

GZ-FFR was supported by the British Heart Foundation.

Haude disclose receiving grants/research support from Biotronik, as well as honoraria/consultation fees from Abbott, Biotronik, Cardiac Dimensions, OrbusNeich, and Philips Healthcare.

Xaplanteris and Zimmermann disclosed no relevant conflicts of interest.

Hennigan reported receiving honoraria for consulting for Philips Volcano.

2018-05-22T17:20:00-0400
Comments

Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.